Noninvasive Mechanical Ventilation and Difficult Weaning in Critical Care

Antonio M.
Esquinas Editor
Noninvasive Mechanical
Ventilation and Difficult
Weaning in Critical Care
Key Topics and

Practical Approaches
123
Noninvasive Mechanical Ventilation

and Difficult Weaning in Critical Care
Antonio M. Esquinas
Editor
Noninvasive Mechanical
Ventilation and Difficult
Weaning in Critical Care
Key Topics and Practical Approaches
Editor
Antonio M. Esquinas
Hospital Morales Meseguer
Intensive Care Unit
Murcia
Spain
ISBN 978-3-319-04258-9
ISBN 978-3-319-04259-6
DOI 10.1007/978-3-319-04259-6
(eBook)
Library of Congress Control Number: 2015960386

Springer Cham Heidelberg New York Dordrecht London
Springer International Publishing Switzerland 2016
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To wife Rosario, my daughters and Rosana

Alba, inspiration and meaning
To the memory of my father
Preface
Ideally all strategies directed toward decreasing the duration of invasive mechanical
ventilation (IMV) and reducing or avoiding its complications are useful in patients
receiving IMV for different medical or surgical reasons. In the past decade advancement in protocols focusing on weaning from mechanical ventilation and new ventilation modes such as neutrally adjusted ventilatory assist (NAVA) and airway
pressure release ventilation (APRV) has been developed along with improving the
patient-ventilator interaction, advance monitoring, and strategies for early diagnosis
and prevention of ventilator-associated pneumonia. However, there still remain a
significant proportion of those who are dependent on IMV and develop difficulty in
weaning from it even after their underlying acute respiratory failure (ARF) and
other organ failure have resolved. This population represents weaning failure and
ventilator dependence.
More and more advanced surgical procedures and medical management in the
elderly population and those with multiple comorbidities also lead to failure to wean
from IMV and impact healthcare delivery both due to persistent long-term illness
and increasing cost of care.
Currently, noninvasive mechanical ventilation (NIV) is considered one of the
alternatives to endotracheal intubation in selected patients who develop ARF of
diverse etiology. Its establishment as a suitable, effective, and rational alternative is
based not only for its strong and positive action on the respiratory muscles and gas
exchange but also due to its positive influence on short- and long-term outcome in
critically patients. This influence is significant particularly in patients with exacerbation of COPD and acute cardiac pulmonary edema and who are immunodepressed.
In the past decade there has been significant development in NIV equipment and
interfaces and in the understanding of the patient-NIV interaction. This has led to
physicians considering NIV as an alternate to endotracheal intubation and IMV, in
the management of not only ARF but also failure to wean from IMV and extubation
failure. The latter is defined as a condition where the patient is unable to sustain
respiratory status postextubation from IMV. Is NIV a recognized alternative to IMV
in these conditions? Will this strategy change patient outcomes and IMV-related
complications? Will NIV influence healthcare delivery by improving quality of care
and reduce cost of care?
In this book, sections and chapters are structured in response to these questions
based on evidence, clinical practice, and expert recommendations.
vii
viii
Preface
The recognized chapters that we have contemplated on NIV have been divided
into clinical conditions such as persistent weaning failure from prolonged mechanical ventilation, extubation post acute respiratory failure, and unplanned extubation
and its use as alternative to short- and long-term IMV including those with tracheotomy. The use of NIV in these clinical conditions will look at the diverse medical
and surgical (thoracic, cardiac, abdominal, lung transplants) population.
Additionally, determinants of NIV response, comorbidities, equipments and interfaces, ventilatory modes, patient-ventilator interaction, and clinical monitoring will
also be covered in this book.
We consider that this book represents a valuable tool for a practical approach by
the rational use of NIV in prolonged mechanical ventilation, difficult weaning, and
postextubation failure.
Murcia, Spain
Antonio M. Esquinas, MD, PhD, FCCP
Contents
Part I
Weaning From Mechanical Ventilation.

Determinants of Prolonged Mechanical
Ventlation and Weaning
Physiologic Determinants of Prolonged Mechanical

Ventilation and Unweanable Patients. . . . . . . . . . . . . . . . . . . . . . . . . . . .
Dimitrios Lagonidis and Isaac Chouris
Prolonged Weaning from Mechanical Ventilation:
Pathophysiology and Weaning Strategies,
Key Major Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Vasilios Papaioannou and Ioannis Pneumatikos
Automated Weaning Modes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

F. Wallet, S. Ledochowski, C. Bernet, N. Mottard,
A. Friggeri, and V. Piriou
Neurally Adjusted Ventilatory Assist in Noninvasive

Ventilation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
B. Repusseau and H. Roz
Recommendations of Sedation and Anesthetic

Considerations During Weaning from Mechanical
Ventilation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ari Balofsky and Peter J. Papadakos
Weaning Protocols in Prolonged Mechanical
Ventilation: What Have We Learned? . . . . . . . . . . . . . . . . . . . . . . . . . .
Anna Magidova, Farhad Mazdisnian,
and Catherine S. Sassoon
Evaluation of Cough During Weaning
from Mechanical Ventilation: Influence
in Postextubation Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pascal Beuret
15
21
29
37
43
51
ix
Contents
Implications of Manual Chest Physiotherapy

and Technology in Preventing Respiratory
Failure after Extubation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Maria Lusa Soares, Margarida Torres Redondo,
and Miguel R. Gonalves
Nutrition in Ventilator-Dependent Patients. . . . . . . . . . . . . . . . . . . . . .

Militsa Bitzani
10
Predictive Models of Prolonged Mechanical

Ventilation and Difficult Weaning . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Juan B. Figueroa-Casas
Part II
11
12
13
14
15
16
57
63
73
Non Invasive Mechanical Ventilation

in Weaning From Mechanical
Ventilation General Considerations
Noninvasive Mechanical Ventilation in Difficult

Weaning in Critical Care: Key Topics
and Practical Approach. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Guniz M. Koksal and Emre Erbabacan
in Post-extubation Failure: Interfaces
and Equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Dirk Dinjus
Monitoring and Mechanical Ventilator Setting
During Noninvasive Mechanical Ventilation:
Key Determinants in Post-extubation
Respiratory Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
D. Chiumello, F. Di Marco, S. Centanni,
and Mietto Cristina
Noninvasive Ventilation Withdrawal Methodology
After Hypercapnic Respiratory Failure. . . . . . . . . . . . . . . . . . . . . . . .
Chung-Tat Lun and Chung-Ming Chu
Rational Bases and Approach of Noninvasive
Mechanical Ventilation in Difficult Weaning:
A Practical Vision and Key Determinants . . . . . . . . . . . . . . . . . . . . . .
Antonio M. Esquinas
Influence of Prevention Protocols on Respiratory
Complications: Ventilator-Associated Pneumonia
During Prolonged Mechanical Ventilation . . . . . . . . . . . . . . . . . . . . .
Bushra Mina and Christian Kyung
85
91
95
111
117
129
Contents
17
18
19
High-Flow Nasal Cannula Oxygen in Acute

Respiratory Failure After Extubation: Key Practical
Topics and Clinical Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Rachael L. Parke
Noninvasive Mechanical Ventilation in Difficult
Weaning in Critical Care: A Rationale Approach . . . . . . . . . . . . . . .
Dhruva Chaudhry and Rahul Roshan
Noninvasive Technique of Nasal Intermittent
Pressure Ventilation (NIPPV) in Patients
with Chronic Obstructive Lung Disease After
Failure to Wean from Conventional Intermittent
Positive-Pressure Ventilation (IPPV): Key Practical
Topic and Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Farouk-Mike Elkhatib and Mohamad Khatib
Part III
20
21
22
23
24
25
xi
139
147
159
Post Extubation Failure and Use

of Non Invasive Mechanical Ventilation
Use of Noninvasive Ventilation to Facilitate Weaning

from Mechanical Ventilation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Scott K. Epstein
Noninvasive Positive-Pressure Ventilation
in the Management of Respiratory Distress
in Cardiac Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Andrew L. Miller and Bushra Mina
Postoperative Continuous Positive Airway
Pressure (CPAP). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Elisabet Guerra Hernndez
and Zoraya Hussein Dib Gonzlez
Noninvasive Ventilation for Weaning, Avoiding
Reintubation After Extubation,
and in the Postoperative Period . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Alastair J. Glossop
Noninvasive Mechanical Ventilation in Treatment
of Acute Respiratory Failure After Cardiac
Surgery: Key Topics and Clinical Implications. . . . . . . . . . . . . . . . . .
Luca Salvatore De Santo, Donato Catapano,
and Sergio Maria Caparrotti
Noninvasive Ventilation in Postextubation Failure
in Thoracic Surgery (Excluding Lung Cancer). . . . . . . . . . . . . . . . . .
Dimitrios Paliouras, Thomas Rallis,
and Nikolaos Barbetakis
165
173
179
183
191
197
xii
26
27
28
Contents
Predictors of Prolonged Mechanical Ventilation

in Lung Cancer: Use of Noninvasive Ventilation . . . . . . . . . . . . . . . .
E. Antypa and N. Barbetakis
Use of Noninvasive Mechanical Ventilation
in Lung Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ana Hernandez Voth, Pedro Benavides Maas,
and Javier Sayas Cataln
Noninvasive Mechanical Ventilation in Postoperative
Spinal Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Eren Fatma Akcil, Ozlem Korkmaz Dilmen,
and Yusuf Tunali
207
213
221
29
Noninvasive Ventilation Following Abdominal Surgery. . . . . . . . . . .

Alastair J. Morgan and Alastair J. Glossop
30
Noninvasive Mechanical Ventilation in Postoperative

Bariatric Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Michele Carron and Anna Toniolo
233
Noninvasive Ventilation After Extubation in Obese

Critically Ill Subjects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Enrique Calvo-Ayala and Paul E. Marik
241
Noninvasive Mechanical Ventilation in Patients

with Neuromuscular Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Fabrizio Racca, Chiara Robba, and Maria Pia Dusio
247
31
32
33
34
35
36
37
Dysphagia in Post-extubation Respiratory Failure:

Potential Implications of Noninvasive Ventilation . . . . . . . . . . . . . . .
Alberto Fernndez Carmona, Aida Daz Redondo,
and Antonio M. Esquinas
Agitation During Prolonged Mechanical Ventilation
and Influence on Weaning Outcomes. . . . . . . . . . . . . . . . . . . . . . . . . .
Eduardo Tobar and Dimitri Gusmao-Flores
BiPAP for Preoxygenation During Reintubation
in Acute Postoperative Respiratory Failure . . . . . . . . . . . . . . . . . . . .
Farouk-Mike ElKhatib, Anis S. Baraka,
and Mohamad Khatib
225
259
265
275
Determinant Factors of Failed Extubation

and the Use of Noninvasive Ventilation
in Trauma Patients. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Eric Bui, Jayson Aydelotte, Ben Coopwood,
and Carlos V.R. Brown
281

in Tetraplegia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Michael A. Gaytant and Mike J. Kampelmacher
287
Contents
38
39

in Sleep-Related Breathing Disorders . . . . . . . . . . . . . . . . . . . . . . . . .
Stefanie Keymel, Volker Schulze,
and Stephan Steiner
Impact of Noninvasive Positive-Pressure
Ventilation in Unplanned Extubation . . . . . . . . . . . . . . . . . . . . . . . . .
Emel Eryksel and Turgay elikel
Part IV
40
41
42
43
45
297
305

and Decannulation in Tracheostomized Patients
Tracheostomy Decannulation: Key Practical

Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Antonello Nicolini, Ines Maria Grazia Piroddi,
Sofia Karamichali, Paolo Banfi, and Antonio M. Esquinas
Transfer to Noninvasive Ventilation as an Alternative
to Tracheostomy in Obstructive Pulmonary Disease:
Key Practical Topics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gerhard Laier-Groeneveld
313
321
Extubation and Decannulation of Unweanable

Patients with Neuromuscular Weakness . . . . . . . . . . . . . . . . . . . . . . .
John Robert Bach
331
Tracheostomy Decannulation
After Cervical Spinal Cord Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Erik J.A. Westermann and Mike J. Kampelmacher
341
Part V
44
xiii
Discharge Ventilator Depend Patients
Criteria for Discharging Patients with Prolonged

and Difficult Weaning from Intensive Care Unit
to Weaning Center . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gatan Beduneau, Christophe Girault, Dorothe Carpentier,
and Fabienne Tamion
Discharge Planning of Neuromuscular Patients
with Noninvasive Mechanical Ventilation After Difficult
Weaning from Invasive Mechanical Ventilation:
From ICU to Home Care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
E. Barrot-Corts, L. Jara-Palomares,
and C. Caballero-Eraso
Part VI
353
361
Weaning Units. Organization
46
Organization of a Weaning Unit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Enrico M. Clini, Gloria Montanari, Laura Ciobanu,
and Michele Vitacca
47
Difficult and Prolonged Weaning: The Italian

Experience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Raffaele Scala
373
383
xiv
Contents
Part VII
48
49
50
51
52
53
54
Noninvasive Ventilation Interfaces and Equipment

in Neonatology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Daniele De Luca, Anne Claire Servel, and Alan de Klerk
393
Noninvasive Ventilation Strategies to Prevent

Post-extubation Failure: Neonatology Perspective . . . . . . . . . . . . . . .
Erik A. Jensen and Georg M. Schmlzer
401
Application of Noninvasive Ventilation in Preventing

Extubation Failure in Children with Heart Disease:
Key Topics and Clinical Implications. . . . . . . . . . . . . . . . . . . . . . . . . .
Yolanda Lpez-Fernndez and F. Javier Pilar-Orive
Noninvasive Ventilation After Extubation
in Pediatric Patients: Determinants of Response
and Key Topics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Juan Mayordomo-Colunga, Alberto Medina,
Mart Pons-dena, Teresa Gili, and Mara Gonzlez
High-Flow Nasal Cannula Oxygen in Acute
Respiratory Post-extubation Failure in Pediatric
Patients: Key Practical Topics and Clinical Implications . . . . . . . . .
F. Javier Pilar and Yolanda M. Lopez Fernandez
Noninvasive Positive Pressure Ventilation
by Means of a Nasal Mask May Avoid Recannulation
After Decannulation in Pediatric Patients:
Key Practical Aspects and Implications. . . . . . . . . . . . . . . . . . . . . . . .
Brigitte Fauroux, Alessandro Amaddeo,
Marion Blanchard, and Nicolas Leboulanger
Home Mechanical Ventilation in Ventilator-Dependent
Children: Criteria, Outcome, and Health Organization . . . . . . . . . .
Amit Agarwal and Punkaj Gupta
Part VIII
55
Non Invasive Mechanical Ventilatio

in Neonatology and Pediatric
407
417
423
433
439

and Weaning. Outcome
Noninvasive Ventilation and Weaning Outcome . . . . . . . . . . . . . . . . .

Karen E.A. Burns and Neill K.J. Adhikari
451
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
463
Part I
Weaning From Mechanical Ventilation.
Determinants of Prolonged Mechanical
Ventlation and Weaning
Physiologic Determinants of Prolonged

Mechanical Ventilation and Unweanable
Patients
Dimitrios Lagonidis and Isaac Chouris
1.1
Introduction
Unfortunately, there is no broadly accepted definition of prolonged mechanical ventilation (PMV). According to a consensus conference held in 2004, PMV is defined
as 21 consecutive days of mechanical ventilation (MV) for 6 h/day [1]. This definition seems to have high sensitivity; most patients requiring MV for more than
21 days after acute critical illness or injury would meet the clinical phenotype of
chronic critical illness syndrome (CCIS). Patients with CCIS have survived acute
critical illness. Pathophysiologically, it consists of a metabolic, immuneneuroendocrine axis and nutritional derangements caused by the initial event
(trauma, sepsis, surgery) and then maintained with unresolved critical illness, PMV,
and chronic inflammation [3].
CCIS has been considered a distinct entity with a predictable constellation of
clinical features and a course characterized by ongoing chronic inflammation, slow
fluctuations in function and care needs, and slow (over weeks or months) progress
or deterioration, which may be interrupted by acute events such as sepsis or acute
heart failure [2, 3]. Apart from prolonged ventilator dependence, patients with CCIS
have profound weakness (caused by myopathy, neuropathy, or loss of lean body
mass); brain dysfunction (coma, delirium, depression, anxiety, cognitive impairment); distinctive neuroendocrine derangements (impaired secretion of anterior
pituitary hormones, impaired anabolism); increased vulnerability to infections
caused by multi-drug-resistant pathogens;, and skin disruption attributed to nutritional deficiencies, edema, and prolonged immobility.
CCSI has been considered a byproduct of medical technology and is increasingly
recognized as an important problem in modern medicine and one of the growing
D. Lagonidis (*) I. Chouris
Intensive Care Unit, General Hospital of Giannitsa, Giannitsa, Greece
e-mail: lagonidis@gmail.com; ischouris@yahoo.gr
A.M. Esquinas (ed.), Noninvasive Mechanical Ventilation and Difficult Weaning
in Critical Care: Key Topics and Practical Approaches,
DOI 10.1007/978-3-319-04259-6_1
D. Lagonidis and I. Chouris
challenges in health care [2, 3]. It is estimated that between 5 and 13 % of mechanically ventilated patients require PMV [4], and that about 50 % of these will be liberated from the ventilator. However, about 25 % of intensive care unit (ICU) survivors
with CCIS and PMV are not weaned at the end of first year [2]. CCIS patients have
poor prognosis and prolonged ICU and hospital stays (either in long-term acute care
facilities or in specialized weaning centers), contributing to increased costs. It has
also been estimated that 1-year mortality rates range from 48 to 68 % [3].
The ultimate goal for CCIS patients is liberation from a ventilator, because successful weaning is associated with improved survival, better quality of life, and less
financial burden on health-care systems. Therefore, this review is intended not only
to analyze the physiologic determinants of PMV and unweanable patients in the
context of CCIS but also to guide physicians managing these patients in a comprehensive and structured way.
1.2
Physiologic Determinants
The adequacy of the respiratory function depends on the balance between the respiratory requirements (the load) and the capability of the respiratory pump and its components (the respiratory motor drive and the neuromuscular system) to meet those
requirements. A practical and methodical approach to the problem of difficult-towean and unweanable patients is to consider the various factors with the ability to
tip the balance, thereby slowing down or even disallowing the weaning procedure.
1.2.1
Respiratory Physiological Determinants
1.2.1.1 Factors Determining Increased Respiratory Load

Control of Breathing
It has been long recognized that the hallmark of weaning failure is a rapid shallow
breathing pattern, the combination of elevated frequency ( f ) and decreased tidal
volume (VT) [57]. Weaning failure patients exhibit marked shortening of both
inspiratory and expiratory time, which results in increased breathing frequency. At
the same time, the combination of decreased inspiratory time (Ti) and normal mean
inspiratory flow leads to decreased VT [8].
Acute hypercapnia has been consistently observed in many patients who failed to
wean despite an increase, not a decrease, in respiratory drive, measured by using P0.1
or the mean inspiratory flow. The hypercapnia is not caused by decreased minute
ventilation. Instead, it is the consequence of the rapid shallow breathing pattern,
resulting in dead-space ventilation [6].
Assessment of respiratory drive is determined by P0.1, which is the airway occlusion pressure at the first 100 msec of inspiration (normal values: 0.51.5 cmH2O).
Although it is available with most ventilators, it is of limited value because of the
wide normal range. The value of P0.1 depends not only on respiratory drive but also
1 Physiologic Determinants of Prolonged Mechanical Ventilation and Unweanable Patients 5
on inspiratory muscle capacity. It is worthy of consideration that in patients on PMV,

the values of P0.1 measured at the end-expiratory lung volume may be affected by
further development of abnormal muscle length and chest wall distortion [11]. Values
within the normal range practically exclude respiratory drive disorders as the source
of difficult weaning, although considerable variability has been reported [11].
Nevertheless, P0.1 remains a useful index when these limitations are recognized.
Impaired respiratory drive is only infrequently the cause of difficulties in weaning [5, 6]. It may involve defects in the peripheral and central chemoreceptors
(carotid body dysfunction, prolonged hypoxia, metabolic alkalosis) or the brainstem respiratory centers (encephalitis, brainstem infarction, hemorrhage or trauma,
demyelination, drug side-effects, endocrine disturbances hypothyroidism or
hyperthyroidism). Conversely, respiratory motor drive is increased in most patients
who are unable to liberate from the ventilator [5, 6]. In ventilator-dependent patients,
high P0.1 associated with low VT indicates the poor conversion of high drive to adequate ventilatory output. Accordingly, the demonstration of high drive to breathe
has been found to predict weaning failure [11].
It is well known that the absence of high f/VT breathing pattern can predict weaning success (WS), not only in heterogeneous ICU patients [7, 12, 13] but also in
chronically ill patients [11]. Nevertheless, specific groups of patients on PMV, such
as those with severe COPD, deserve special consideration. These patients may
exhibit weaning failure (WF) despite a low f/VT (shallow but not rapid breathing)
during unassisted breathing [11]. The major mechanism responsible for WF is the
combination of abnormal lung mechanics, specifically increased intrinsic positive
end-expiratory pressure (PEEPi) and resistance, and the reduced pressure-generating
capacity of inspiratory muscles resulting from dynamic hyperinflation. Interestingly,
the respiratory drive is augmented to maintain adequate tidal volume but is poorly
transformed into inspiratory flow because of the impaired respiratory muscles. As a
result, the breathing effort leads to low VT. The diminished VT is therefore ineffective to meet metabolic demands and clear carbon dioxide. On the other hand, the
high motor output drive charges the inspiratory muscles and forces them to use a
significant amount (>40 %) of their maximal pressure-generating capacity to sustain spontaneous ventilation. Accordingly, unassisted breathing cannot be sustained
without excessive dyspnea [11].
Respiratory Mechanics
In an acute setting, Jubran and Tobin [7] demonstrated that, during a spontaneous
breathing trial (SBT), all passive respiratory mechanics (resistance, elastance,
PEEPi) became more abnormal in WF patients than in WS patients. More specifically, respiratory resistance increased up to seven times the normal value at the end
of the trial, whereas pulmonary elastance increased about five times the normal
value. Moreover, PEEPi almost doubled during the trial. The same findings were
also found by other investigators [9].
Airway resistance and respiratory load, that is, the work of breathing (WOB), are
directly related. Significantly increased airway resistance that hinders the weaning
procedure may arise from upper (obstruction of tracheotomy tube, secretions,
post-extubation tracheal injury) or lower airway pathology (bronchospasm, bronchial hyper-responsiveness, pulmonary edema). Increased elastance (decreased
compliance) of the respiratory system correlates with increased WOB. Low thoracic
wall compliance may arise from pathological states such as edema of the thoracic
wall, rib cage deformities, pleural effusions, morbid obesity, increased intra-abdominal pressure. Additionally, decreased lung compliance may be the result of lung
edema (cardiogenic or noncardiogenic), lung infections and atelectasis.
Expiratory flow limitation leads to inadequate expiratory time to achieve fully
deflated lungs, hindering the lungs to reach the elastic equilibrium point. The result
is the phenomenon of progressive air-trapping and dynamic lung hyperinflation,
which is associated with the development of PEEPi. Dynamic hyperinflation may
have hemodynamic consequences (decreased venous return and cardiac output) but
is also a major cause of increased WOB. The positive pressure thus generated means
that the threshold to initiate inspiratory flow is heightened and the patients inspiratory efforts may be ineffective, leading to ineffective ventilator triggering and
patient-ventilator asynchrony. Moreover, the presence of dynamic hyperinflation
detrimentally affects the diaphragmatic force-generating capacity by displacing it to
a suboptimal position of its length-tension curve.
In spontaneously breathing patients, dynamic measurement of PEEPi with an
esophageal balloon delivers more precise results and thus is preferable. Elevated
PEEPi may arise for the following reasons:
increased expiratory flow resistance (bronchospasm, compromised endotracheal
tube patency, heat and moisture exchange (HME) filters)
loss of lung elastic recoil (emphysema)
increased minute ventilation
inadequate expiratory time
Gas Exchange
Inadequate gas exchange (hypoxemia, hypercapnia) exerts an additional load on
the respiratory muscles because increased minute volume is required to restore
gas exchange disturbances, resulting in muscle fatigue and WF. Hypercapnia
results mainly from the following mechanisms: hypoventilation (e.g., neuromuscular diseases), severe low ventilation/perfusion mismatch (e.g., chronic obstructive pulmonary disease (COPD)), and, to a lesser extent, increased dead space
(rapid shallow breathing, heat and moisture exchangers, connectors to the Y-point
of the circuit).
Interestingly, studies using the multiple inert gas method showed that ventilation/perfusion maldistribution and hypercapnia were found in WF patients [10].
Specifically, acute hypercapnia was observed in many patients who failed to wean
despite an increased respiratory motor output, measured by P0.1 [7]. Acute hypercapnia is not caused by decreased minute ventilation. Instead, it is the consequence
of a rapid shallow breathing pattern resulting in dead-space ventilation. Only in a
minority of WF patients may hypercapnia be attributed to primary depression of
respiratory drive [7].
1.2.1.2 Factors Determining Reduced Respiratory Capacity

Respiratory Muscle Weakness or Dysfunction
Spontaneous breathing during a weaning trial imposes a substantial load on the
inspiratory muscles, which are considered the major part of the respiratory pump.
Dysfunction of the respiratory pump may result from a defect anywhere between
the respiratory centers in the medulla and the myocytes inside the respiratory muscles. Upon release of positive pressure ventilation and during unassisted breathing,
patients have to make a greater inspiratory effort to compensate for the deteriorating
respiratory mechanics. Using an esophageal balloon catheter, direct measurements
of WOB and pressure-time product consistently showed that WF patients exhibit a
greater effort compared with WS patients [7].
Respiratory muscle dysfunction is a major determinant of the degree of weaning
difficulty. Clinical signs suggestive of respiratory muscle dysfunction, and thus of
the respiratory pump, include tachypnea, dyspnea, and paradoxical respiratory movements. Respiratory muscle dysfunction may be caused by any condition that leads to:
Impaired neurotransmission (amyotrophic lateral sclerosis, Guillain-Barr, myasthenia gravis, drugs, phrenic nerve dysfunction, critical illness polyneuropathy)
Reduced muscle strength (malnutrition, sepsis-associated myopathy, acidosis,
electrolyte disturbances, hypoxemia, low cardiac output states)
Global evaluation of inspiratory muscle strength includes the static measurement
of maximal inspiratory pressure (MIP) during the Mueller maneuver, with lower
normal values 75 cmH2O in men and 50 cmH2O in women younger than 65 years
old. It can be measured either in mechanically ventilated or spontaneous breathing
patients. Values that are more negative than normal essentially exclude significant
inspiratory muscle weakness, whereas values that are more positive than normal do
not prove muscle weakness. MIP depends on patient cooperation (it is a voluntary
test) and lung volume and thus can falsely assess muscle weakness. Many studies
have shown that MIP does not discriminate between WF and WS patients, suggesting that muscle weakness may not be a major determinant of weaning outcome [10].
A more reliable assessment of diaphragmatic strength is taken by recording
transdiaphragmatic pressure (Pdi). Pdi is the difference between abdominal (gastric) and pleural (esophageal) pressure. It can be obtained after a forceful inspiration
against a closed airway or after sniffing and both gastric and esophageal balloons
are required. The energy expenditure of the diaphragm can be estimated by the
tension-time index and the pressure-time product. These indices are too complicated
for routine clinical use. Ideally, Pdi should be measured during a SBT, because it is
influenced by positive pressure of the ventilator [27]
The involuntary evaluation of diaphragm strength is obtained by the measurement of
twitch transdiaphragmatic pressure (Pditw) or twitch airway pressure (Pawtw) after magnetic phrenic nerve stimulation [25, 26]. These methods are not applicable in everyday
practice because they are fairly invasive and technically difficult in critically ill intubated
or tracheostomized patients [27]. Values of Pditw between 35 and 39 cmH2O are recorded
in normal subjects, whereas values below 10 cmH2O are obtained in WF patients [14].
Another important task of the ventilator pump is the ability to endure, that is, to
avoid muscle fatigue. The fatigue threshold of the diaphragm can be quantified
by the tension-time index of the diaphragm (TTIdi), derived by the formula
TTIdi = (Pdi/Pdimax) (Ti/Ttot), where Pdi is the tidal transdiaphragmatic pressure,
Pdimax is the maximum transdiaphragmatic pressure, Ti is the inspiratory time, and
Ttot is the total breath duration. This equation demonstrates the importance of both
the pressure-generating effort of the diaphragm and the relative duration of inspiration as determinants of diaphragmatic fatigue. Diminishing diaphragm strength
results in decreased Pdimax, whereas reduced compliance increases Pdi. Similarly,
tachypnea increases the Ti/Ttot index, thus promoting muscle fatigue.
In one study, it was reported that the majority of ICU patients had diaphragm muscle
weakness at the beginning of mechanical ventilation associated with sepsis and disease
severity [24]. The ability of the diaphragm to generate force was assessed by recording
occluded twitch tracheal pressure during twitch magnetic stimulation of bilateral phrenic
nerves. The twitch tracheal pressure (Ptawtw), measured at the proximal end of the endotracheal tube, was used as a surrogate of transdiaphragmatic pressure independent of
patient effort and cooperation. More specifically, 64 % of patients had a Ptawtw less than
11 cmH2O, a value that indicates diaphragm muscle weakness.
Hypercapnia is often considered an indirect sign of respiratory muscle fatigue,
but one must be careful to take into account other mechanisms leading to it.
Nevertheless, it is probably safe to conclude that lack of hypercapnia, combined
with absence of acidbase disturbances, practically rules out the possibility of
fatigue as a cause for weaning failure.
It has been suggested that the f/VT ratio gives an estimate of the capability of
sustaining unsupported breathing and could be a surrogate of the most-difficult to
measure TTIdi or Pdi/Pdimax.
For the first time, Jubran et al. [7] showed that, in patients with COPD, the major
determinant between a successful and failed weaning trial was a change in the
breathing pattern rather than an intrinsic derangement of pulmonary mechanics. In
another study, Vassilakopoulos et al. [9] reported that, compared with WS patients,
WF patients had greater total resistance, intrinsic PEEP, dynamic hyperinflation,
ratio of mean to maximum inspiratory pressure, less MIP, and a breathing pattern
that was more rapid and shallow. They also found that TTI and f/VT were the only
significant parameters that predicted weaning success. Finally, in a study by
Capdevila et al. [15], the WF was associated with high breathing frequency,
increased P0.1, minute ventilation, intrinsic PEEP, and persistent hypercapnia.
Although TTI and Pdi/Pdimax. are too difficult to measure in everyday practice,
they seem to be more accurate in determining the potential reserve of the patients
during the weaning trial. On the other hand, the f/VT ratio may not give a thorough
insight into the weaning capabilities of ventilator-dependent patients because it
could be affected either by their psychological burden resulting in tachypnea or by
their tendency not to increase f to avoid dynamic hyperinflation [16].
Carlucci et al. [16], by recording active respiratory mechanics in true ventilatordependent patients with multiple weaning failures in the past, showed that the major
determinant of WS was associated with the significant improvement of diaphragmatic
inotropism at the time of gaining liberation from the ventilator, as expressed by
increased Pdimax. They also found that these patients on PMV have increased
mechanical load/capacity balance, predominantly because of reduced Pdimax rather

than excessive load, so that once they are on unassisted breathing, they breathe above
the threshold of diaphragmatic fatigue. In both the WF and WS patients, a tension-time
index (TTI) above the fatigue threshold was noted at the first attempt of weaning trial.
Specifically, in PMV patients, the recovery of an inadequate respiratory muscle
force could be the major determinant of late weaning success, because this factor
allows them to breathe far below the diaphragm fatigue threshold. Many factors
contribute to the reduced Pdimax in ventilator-dependent patients (e.g., age, hypercapnia, hypoxia, malnutrition, inactivity, mechanical ventilationinduced atrophy,
sepsis, prolonged use of corticosteroids, and cardiovascular compromise). Purro
et al. [11] showed that the patients who could not be weaned had small tidal volume,
high neuromuscular drive, abnormal lung mechanics, and reduced inspiratory muscle strength as soon as they resumed spontaneous breathing.
For many years, electromyography (EMG) of the diaphragm has been a useful
research tool in evaluating respiratory muscle dysfunction. It can be obtained in
ICU patients using a special esophageal catheter with multiple electrodes [27]. The
signal that is taken is referred as the electrical activity of the diaphragm (EAdi) and
it is considered as a direct measure of neural respiratory drive. Thus, it is considered
the gold standard to detect the onset and duration of neural inspiration and expiration and thus patient-ventilator asynchronies [27].
The VT/EAdi ratio represents the neuroventilatory efficiency (NVE) of the diaphragm. An improved NVE indicates the capability of the patient to generate the same
VT with lower Eadi [27]. It was suggested as an index to discriminate between extubation success and failure in patients weaning from the ventilator. Another index is the
neuro-mechanical efficiency (NME), indicated by the ratio Pdi/EAdi; a gradual
decrease in NME suggests the development of diaphragmatic weakness [27]. Although
EMG of the diaphragm has some limitations, it seems to be a reasonable method for
monitoring respiratory muscles during the course of a weaning trial in PMV patients.
Ultrasonography has been used to investigate diaphragmatic atrophy or dysfunction in critical care settings. By using B-mode ultrasonography with a linear array
transducer, the diaphragm thickness at the zone of apposition could be precisely and
reproducibly measured in spontaneously breathing patients during a weaning trial
[28]. Kim et al. [29] evaluated diaphragmatic dysfunction during a SBT after
patients had been ventilated for more than 48 h. They found diaphragmatic dysfunction (defined as <10 mm vertical excursion) in 29 % of patients, and there was a
correlation with longer mechanical ventilation and WF. Moreover, this ultrasonographic criterion to predict WF was similar to the rapid shallow breathing index.
1.3
Cardiac Determinants
The transition from the positive pressure ventilation to spontaneous breathing exerts
an additional load on the cardiovascular system and can impose or unmask cardiac
dysfunction, either systolic or diastolic. These factors may thus be causes of unsuccessful weaning. The heart-lung interactions during the weaning procedure are
complex. Spontaneous breathing raises WOB and oxygen consumption by the
respiratory muscles and promotes adrenergic stress and negative swings in the
10
intrathoracic pressure. These alterations lead to increases in both preload and afterload of right and left ventricles through the augmented venous return, resulting in
weaning-induced cardiac dysfunction.
At the end of a weaning trial, oxygen consumption is equivalent in WS and WF
patients [17]. However, the response of the cardiovascular system to the oxygen
demand differs in the two groups. In WS patients, oxygen demand is met by the
augmented oxygen delivery mediated through the expected increase in cardiac output on release of positive pressure ventilation [17]. In WF patients, because they
have relatively decreased oxygen delivery, oxygen demand is met by the increase in
oxygen extraction. Under these circumstances, the greater oxygen extraction results
in a significant decrease in SvO2, contributing to hypoxemia [17].
In 2015, it was reported that, in acute critically ill patients, it was found that a
negative passive leg-raising test performed before SBT, suggesting preload independence, was associated with weaning-induced cardiac dysfunction [23].
Diastolic dysfunction is a common and underdiagnosed entity. More than 60 % of
people over 65 years of age experience diastolic dysfunction, and in more than 50 %
of patients with heart failure, it is of the diastolic type. Moreover, differentiation
between systolic and diastolic cardiac failure is clinically important because of distinct therapeutic approaches [21]. Diastolic dysfunction with relaxation impairment
has been found to predict weaning failure. The principal feature of LV diastolic failure
is reduced compliance of the ventricle due to various causes (e.g., coronary artery
disease, myocardial hypertrophy and fibrosis, infiltrative diseases, hypoxia, or
acidosis).
There is growing evidence to advocate that transthoracic echocardiography (TTE)
plays a key role in the evaluation of patients who are difficult to wean due to cardiac
origin. However, it is not possible to use it in every critically ill patient because of certain limitations (e.g., excessive pulmonary emphysema, or thoracic trauma). In tissue
Doppler imaging TTE, the ratio of mitral Doppler inflow E velocity to annular tissue
Doppler Ea wave velocity (E/Ea) provides an accurate estimate of the degree of diastolic dysfunction. Moreover, these echocardiographic measurements can also be performed on patients with atrial fibrillation with reasonable sensitivity and specificity.
In 2010, Gaille et al. [20], in an unselected cohort of patients, found that weaning
failure occurred more often in patients with systolic heart failure. More precisely, in
patients with ejection fraction (EF) <50 % they found signs of diastolic dysfunction
(decreased E/A and depressed acceleration time of E wave) during a SBT. Moreover,
Moscietto et al. [18] showed that in 68 patients with sinus rhythm and atrial fibrillation
on mechanical ventilation more than 48 h, the measurement of E/Ea with Doppler tissue imaging TTE could predict weaning failure as early as 10 min after the beginning
of the SBT. They also suggested that diastolic dysfunction with relaxation impairment
was strongly associated with weaning failure. Conversely, in the same study, the systolic dysfunction was not associated with weaning outcome. In another study with
similar findings [19], the authors suggested that an E/Ea >7.8 may indentify patients at
high risk of WF.
In conclusion, diastolic dysfunction of the left ventricle seems to be important in
the evolution of WF. By measuring E and Ea waves even in patients with atrial
fibrillation, TTE with Doppler tissue imaging measuring is a key examination that
can be easily applied before and after the weaning trial. It has also been demonstrated that the transition from mechanical ventilation to sustained breathing could
lead to myocardial ischemia in patients with coronary artery disease. Ischemia can
be detected by electrocardiogram before and at the end of the SBT and the significance of anemia as a precipitating factor should not be underestimated.
Mixed venous oxygen saturation (SvO2) can be used as a marker of cardiac performance, with superior vena cava oxygen saturation (ScvO2) serving as a reasonable
surrogate. In difficult-to-wean patients, a decrease in SvO2 during the weaning procedure should raise the suspicion about the presence of inadequate cardiac output.
Patients with cardiac dysfunction largely rely on increasing the oxygen extraction
ratio instead of raising the cardiac output, resulting in SvO2 reduction as demonstrated by Jubran et al. [17] in a study comparing 8 patients who failed at SBT with
11 patients who successfully completed the SBT. The decrease in SvO2 was related
to the inability to improve cardiac output and consequently oxygen transport.
Increased afterloads of the right and left ventricle were found in these patients.
It is imperative to note that reduction in ScvO2 is the normal response to increased
loading. In normal subjects on moderate exercise, it was found that ScvO2 decreases
below 50 %. Therefore, a reduction in ScvO2 should not necessarily be interpreted as a
marker of heart failure. Accordingly, in WF patients, without a reduction in ScvO2, heart
dysfunction is highly unlikely [21]. Conversely, in those patients who failed a weaning
trial and had reduced ScvO2, heart dysfunction could be a limiting factor and further
investigation with echocardiography and/or insertion of a Swan-Ganz catheter is warranted [21].
Brain natriuretic peptide (BNP) is a neurohormone synthesized in the cardiac
ventricles and released from the myocardium upon stretch. It is released by the
myocytes as pre-proBNP that is cleaved into proBNP and finally into BNP and the
inactive N terminal proBNP peptide (NT-proBNP). Its release into the circulation
is directly proportional to the ventricle expansion and volume overload of the ventricles. Thus, it serves as a marker of the systolic and diastolic left ventricular
dysfunction. The value of BNP or NT-proBNP as a predictor of weaning failure
due to cardiovascular reasons seems to be well established in the literature.
Nevertheless, the accepted cut-off values pose a clinical challenge for data
interpretation.
A study by Grasso et al. [22] demonstrated that serial measurements of
NT-proBNP could detect acute cardiac dysfunction during an unsuccessful weaning
trial in difficult-to-wean patients with COPD. Baseline NT-proBNP levels were significantly higher (median, 5,000; interquartile range, 4,218 pg/mL) in patients with
cardiac dysfunction. It was also shown that levels of NT-proBNP increased significantly at the end of the spontaneous breathing trial only in patients with acute cardiac dysfunction (median, 12,733; interquartile range, 16,456 pg/mL).
Conclusions
The ultimate goal for CCIS patients on PMV is liberation from the ventilator.
Repeated weaning failure has been associated with an imbalance between
increased load and reduced capacity of the respiratory muscles or, to a lesser
extent, with the cardiovascular impairment. A systematic approach to the problem
12

Impaired motor drive
(uncommon)
Impaired neurotransmission
(uncommon)
Increased motor drive (very

common)
rapid shallow breathing
index (f/VT)
Resistive loads
Lung Elastic loads
elastance, resistance,
PEEPi
Chest wall elastic loads
Cardiovascular impairment
systolic dysfunction
diastolic dysfunction
(E<A, E/Ea >11)
passive leg raising test
pro-BNP or NT-proBNP
SvO2 or ScvO2
Respiratory
load
Inspiratory muscle weakness or

dysfunction (very common)
rapid shallow breathing
index (f/VT)
maximal inspiratory
pressure (MIP)
transdiaphragmatic
pressure (Pdi)
Tension time index
(TIdi)
Pressure time product
of the diaphragm
Pdi/Pdimax
electrical activity of the
diaphragm (Eadi)
neuroventilatory
efficiency (NVE) of the
diaphragm
B-mode
ultrasonographic
evaluation of
diaphragm thickening
Respiratory
capacity
Fig. 1.1 Balance between load (motor drive, resistive, elastic, cardiovascular impairment) and
capacity (motor drive, neurotransmission, inspiratory muscle weakness) determines the ability
to sustain spontaneous ventilation
Key Points
In PMV and unweanable patients, the imbalance between inspiratory muscle work load and inspiratory muscle capacity is of paramount
importance.
The rapid shallow breathing pattern is the hallmark of weaning failure.
In PMV patients, the major determinant of prolonged weaning is inspiratory muscle weakness or dysfunction, as expressed by TTIdi that is above
the fatigue threshold.
During the course of a weaning trial, most WF patients significantly
increase respiratory load as a result of severe worsening of respiratory
mechanics (e.g., resistance, elastance, or PEEPi).
In PMV patients, the recovery of inadequate inspiratory muscle force
seems to be the major determinant of WS allowing them to breathe below
the diaphragmatic fatigue threshold.
A less common cause of WF is impairment of cardiovascular
performance.
of difficult-to-wean and unweanable patients is to understand in-depth the physiologic determinants characterizing the two sides of the balance (Fig. 1.1). This
approach may help identify the factors that play a role in the specific patient so
that appropriate therapeutic strategies can be applied.
References
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Prolonged Weaning from Mechanical

Ventilation: Pathophysiology
and Weaning Strategies, Key Major
Recommendations
Vasilios Papaioannou and Ioannis Pneumatikos
Abbreviations
APACHE
ARDS
BNP
CCI
CCIS
CINM
COPD
ICU
GCS
LTAC
MV
NAMDRC
NIV
PMV
PSV
RCT
RSBI
SBT
SWU
acute physiology and health evaluation

acute respiratory distress syndrome
B-type natriuretic peptide
chronically critically ill
chronic critical illness syndrome
critical illness neuromyopathy
chronic obstructive pulmonary disease
intensive care unit
Glasgow coma scale
long-term acute care
mechanical ventilation
National Association for Medical Direction of Respiratory Care
noninvasive ventilation
prolonged mechanical ventilation
pressure support ventilation
randomized controlled trial
rapid shallow breathing index
spontaneous breathing trial
specialized weaning units
V. Papaioannou, MD, MSc, PhD (*) I. Pneumatikos, MD, PhD, FCCP

Intensive Care Unit, Democritus University of Thrace, Alexandroupolis Hospital, Dragana,
Alexandroupolis, 68100, Greece
e-mail: vapapa@med.duth.gr; ipnevmat@med.duth.gr
DOI 10.1007/978-3-319-04259-6_2
15
16
2.1
V. Papaioannou and I. Pneumatikos
Introduction
Advances in the management of critically ill patients in intensive care unit (ICU)
have improved mortality and morbidity as well as reduced length of stay and,
subsequently, cost of treatment. However, despite improvements in short-term
mortality and stabilization of acute organ dysfunction, a small but substantial
population of critically ill patients who survive the initial critical illness continue
to suffer from prolonged dependence on life support or to need long-term therapeutic interventions. These patients have been grouped under the classification of
chronically critically ill (CCI) patients. Such a group is characterized by heterogeneity, prolonged need for high-cost interventions, and high long-term (around
1 year) mortality rate [1]. The best characterized component of the CCI population is patients on prolonged mechanical ventilation (PMV). In 2005, the National
Association for Medical Direction of Respiratory Care (NAMDRC) defined
PMV as the need for 21 consecutive days of mechanical ventilation (MV)
for 6 h/day [2]. According to the European Respiratory Society Task Force,
these patients constitute a particular group needing prolonged weaning from the
ventilator, defined as more than three spontaneous breathing trials (SBTs), or
more than 7 days from the first unsuccessful SBT [3]. Nevertheless, other investigators have favored Medicares definition of MV >96 h, with tracheostomy as
the marker of PMV [2].
Patients requiring PMV have clearly different needs and resource consumption
patterns in relation with patients during the acute phase of critical illness. Moreover,
these patients may represent as many as 14 % of patients admitted to the ICU for
intubation and MV, whereas it is estimated that they account for 37 % of all ICU
costs and are associated with in-hospital mortality up to 32 % [4, 5]. Finally, available data suggest that the global prevalence of PMV in Europe ranges from 2 to 30
per 100,000 population according to different countries [6], whereas different studies have demonstrated that as many as 20 % of medical ICU patients remained
dependent on ventilator support after 21 days [3].
2.2
Discontinuation of PMV
2.2.1
Pathophysiology of Weaning Failure
The successful weaning process from PMV is based on the understanding of the
complexity of different causes associated with the need for prolonged ventilatory
support. In this respect, it has been suggested that the major mechanisms of weaning
failure in this group of patients include either an isolated failure of the respiratory
system or respiratory failure occurring within the context of chronic critical illness
syndrome (CCIS) [2, 3, 7].
It is estimated that pulmonary disease accounts for approximately 50 % of causes
for PMV, associated with inspiratory muscle weakness, increased work of breathing,
and reduced respiratory drive [2, 7]. Pulmonary disease results in reduced lung
Prolonged Weaning from Mechanical Ventilation: Pathophysiology and Weaning
17
compliance and increased load upon respiratory muscles. In this respect, ventilatorassociated pneumonia and acute respiratory distress syndrome (ARDS) are considered the main pulmonary pathologies leading to prolonged weaning from the
ventilator. Airway disease in patients with chronic obstructive pulmonary disease
(COPD) may also increase work of breathing through air-flow limitation, dynamic
hyperinflation, and auto-positive end-expiratory pressure (PEEP). Furthermore, congestive heart disease has been reported in up to 26 % of patients hospitalized in longterm acute care (LTAC) hospitals in the United States [8]. Such cardiac dysfunction
can be uncovered during SBTs due to increased venous return, end-diastolic volume
augmentation, and increased metabolic demands. In these cases, performance of cardiac echocardiography and determination of B-type natriuretic peptide (BNP) serum
levels during SBTs can be of significant value for early diagnosis and prompt treatment of possible myocardial dysfunction and/or hypervolemia [79].
Critical illness neuromyopathy (CINM) can manifest itself as ICU-acquired
weakness and subsequent PMV, usually associated with multiple organ failure,
muscle inactivity, hyperglycemia, or use of corticosteroids and neuromuscular
blockers. As a result, early mobilization, minimizing the use of deep sedation and
steroids, and avoidance of hyperglycemia have been advocated as effective preventive strategies during the acute phase of critical illness [7, 10]. Ventilator-induced
diaphragm dysfunction constitutes a rapid form of skeletal muscle injury that may
occur within only 18 h of MV [7, 11]. Age, malnutrition, and continuous mandatory
ventilation have been found to promote such muscle weakness, whereas pressure
support ventilation (PSV) seems to minimize diaphragmatic ventilator-induced
injury [11]. In addition, optimal patient-ventilator synchrony through properly
adjusted ventilator settings, psychotropic medications, and delirium management
seems to reduce work of breathing and further promote earlier weaning from ventilatory support [7].
Finally, managing PMV patients requires careful consideration and management of all issues related to CCIS, such as severe nutritional deficits, endocrine
dysfunction, including loss of glycemic control and hypothyroidism, bone loss,
and immune and autonomic nervous system dysfunction, that usually arise between
7 and 14 days post acute illness, if the patients do not fully recover from the acute
episode [1].
2.2.2
Weaning Strategies in PMV Patients
Weaning rates in PMV patients vary significantly, ranging from 42 to 83 % across

different studies, due to the heterogeneity of the population requiring prolonged MV
[2, 3]. A prospective observational cohort study that was carried out in 23 LTACs in
the United States and included 1,419 patients remains the main source of weaning
data in patients with PMV [8]. In this study, 20 % failed to wean from PMV. From this
group, 80 % required full-time PMV, 18 % part-time, and 2 % were managed with
noninvasive ventilation (NIV). More than half of ventilator-dependent survivors from
critical illness were successfully separated from prolonged mechanical ventilation [8].
18
According to the 2005 NAMDRC report, successful weaning in PMV patients

was defined as breathing unassisted for 7 days [2]. In this respect, the recommendations included weaning the PMV patient to about 50 % of ventilator requirements
using PSV mode (1015 cmH2O) and, subsequently, respiratory therapist-driven
SBTs of increasing duration using tracheostomy or T-piece. Moreover, a rapid shallow breathing index (RSBI) of up to 97 was found to correlate with successful
1-hour tolerance of SBT in these patients, shortening the time to weaning by
approximately 12 days [2].
What have we learned since the NAMDRC report? It seems that different protocols combining gradual decrease of pressure support ventilation, SBTs in a stepwise
manner, daily RSBI measurements, and capping of the tracheostomy tube with NIV
could be effective in reducing weaning time in PMV patients [7]. In this respect, a
bundle of weaning approaches has also been suggested in the acute care setting for
reducing length of MV in survivors of critical illness [12]. Thus, the ABCDE
bundle, which includes daily Awakening, spontaneous Breathing trials, sedation
Choice, Delirium monitoring, and Exercise/early mobility, has been proposed in
patients with prolonged weaning. Recently, a randomized controlled trial (RCT)
that was conducted among 316 PMV patients in a single LTAC facility found that
unassisted breathing through a tracheostomy (trash collar) compared with PSV
resulted in shorter median weaning time, although weaning mode had no effect on
survival at 6 and 12 months [13].
In addition, increased age, severity of illness estimated with Acute Physiology
and Chronic Health Evaluation (APACHE) II score, elevated body-mass index and
blood urea nitrogen levels, lower Glasgow Coma Scale (GCS), serum albumin, and
maximal inspiratory pressure have been associated with failure to wean from PMV
[2, 7]. As a result, better identification of different groups of patients requiring prolonged MV is needed for individualizing different weaning strategies. Moreover,
the 3 M approach, including minimizing sedation, maintaining nutrition, and maximizing mobility, has been proposed as a simple approach to treating such a complex
medical condition [7]. Such efforts should take place in long-term acute care hospitals and specialized weaning units (SWUs), reducing cost of treatment and providing at the same time a multidisciplinary approach of early rehabilitation. These units
with specialized teams, including nurses, physiotherapists, and nutritionists, might
be an appropriate bridge-to-home environment for PMV patients [3]. It has been
suggested that SWUs could be of two types: (1) step-down or noninvasive respiratory units within acute care hospitals and (2) regional weaning centers separate from
hospitals, where different studies have demonstrated that 3460 % of patients can
be successfully weaned from ventilatory support [3, 8].
Another subset of patients includes those who remain ventilator dependent,
requiring long-term ventilator support, which could be provided as NIV in the home
setting. Thus, different studies in various groups of PMV patients have shown that
approximately 9 % were discharged home with partial ventilator support, with 1 %
using NIV and 8 % requiring MV via the tracheostomy [3, 14].
Prolonged Weaning from Mechanical Ventilation: Pathophysiology and Weaning
19
Conclusions
The NAMDRC report included 12 recommendations regarding early identification, management, and research priorities for patients requiring PMV [2]. Such
patients by definition have failed multiple SBTs and usually require the placement
of a tracheostomy tube. The first priority for the management of this subgroup of
critically ill patients is the optimization of any reversible factor contributing to
PMV. Thus, early mobilization, discontinuation of high doses of narcotics and
benzodiazepines, early recognition, and management of mental disorders, such as
delirium, are a few actions that can accelerate the weaning process, in association
with treatment of underlying causes of respiratory failure. Moreover, weekly
monitoring of proteins and albumin levels should be part of the plan to make sure
nutrition goals are met. Ensuring adequate nutrition in CCI patients improves
immune function and muscle strength, preventing excess breakdown of lean body
mass. Furthermore, a multidisciplinary rehabilitation program must be implemented on an individualized basis, either in the acute care hospital, or to a specialized weaning center, where a team of physiotherapists and nutritionists could
manage or even restore muscle weakness and atrophy. Such therapies apart from
muscle strengthening can also facilitate the resolution of inflammation, turn off
catabolic stimuli, and restore glycemic control [3, 15]. Another important issue is
the transition from PMV to long-term MV. It seems that patients with COPD and
neuromuscular diseases are more amenable to long-term MV, with 3-year mortality more than 50 % [14]. Furthermore, patients with age >65 with sacral ulcers
and abnormal renal function constitute the group with the worse prognosis [14,
15]. In such cases, better communication between caregivers, patients, and families and resetting of expectations regarding weaning failure can facilitate the management of such patients in different settings more effectively.
Key Major Recommendations
Patients who need ventilatory support for more than 21 days, have failed at
least 3 SBTs, or require mechanical ventilation for more than 7 days since
the first unsuccessful SBT and have a tracheostomy tube have been categorized in the group needing prolonged mechanical ventilation.
Such patients are usually chronically critically ill patients with many endocrine, metabolic, neuromuscular, and immunological disorders because the
self-adaptation to acute stress has been transformed to a self-defense
response, preventing restoration of normal physiology, despite apparent
resolution of the causes of acute illness.
The process of liberating these patients from the ventilator demands, first, the
treatment of underlying disease and, second, a multidisciplinary approach,
where a group of health-care professionals, such as physiotherapists and
nutritionists, apply early mobilization and nutritional support to restore neuromuscular, metabolic, and immunological functions toward normalcy.
20
Weaning protocols may accelerate the weaning process in the acute care
setting, however, the heterogeneity of PMV patients limits their diagnostic
accuracy, prompting an individualized approach, usually in specialized
weaning centers, separate from the acute care hospitals.
The better communication between caregivers, patients, and families,
along with an advanced palliative care system, will restore confidence
between health-care professionals and relatives, resetting possibly unrealistic expectations for those patients needing long-term ventilation, usually
with NIV even at home.
References
1. Nelson JE, Cox CE, Hope AA, et al. Chronic critical illness. Am J Respir Crit Care Med.
2010;182(4):44654.
2. MacIntyre MR, Epstein SK, Carson S, et al. Management of patients requiring prolonged
mechanical ventilation. Report of a NAMDRC consensus conference. Chest.
2005;128:393754.
3. Boles J-M, Bion J, Connors A, et al. Task force. Weaning from mechanical ventilation.
Statement of the sixth international Consensus Conference on Intensive Care Medicine. Eur
Respir J. 2007;29:103356.
4. Funk GC, Anders S, Breyer MK, et al. Incidence and outcome of weaning from mechanical
ventilation according to new categories. Eur Respir J. 2010;35:8894.
5. Cox CE, Carson SS, Govert A, et al. An economic evaluation of prolonged mechanical ventilation. Crit Care Med. 2007;35:191827.
6. Lloyd-Owen SJ, Donaldson GC, Ambrosino N, et al. Patterns of home mechanical ventilation
use in Europe: results from the EUROVENT survey. Eur Respir J. 2005;25:102531.
7. White AC. Long-term mechanical ventilation: management strategies. Respir Care.
2012;57(6):88997.
8. Scheinhorn D, Hassenpflug M, Votto J, et al. Ventilator-dependent survivors of catastrophic
illness transferred to 23 long term hospitals for weaning from prolonged mechanical ventilation. Chest. 2007;131(1):7684.
9. Zapata L, Vera P, Roglan A, et al. B-type natriuretic peptides for prediction and diagnosis of
weaning failure from cardiac origin. Intensive Care Med. 2011;37(3):47785.
10. De Jonghe B, Lacherade J-C, Sharshar T, et al. Intensive care unit-acquired weakness: risk
factors and prevention. Crit Care Med. 2009;37(10 Suppl):30915.
11. Haitsma JJ. Diaphragmatic dysfunction in mechanical ventilation. Curr Opin Anaesthesiol.
2011;24(2):2148.
12. Banerjee A, Girard TD, Pandharipande P. The complex interplay between delirium, sedation
and early mobility during critical illness: applications in the trauma unit. Curr Opin
Anaesthesiol. 2011;24(2):195201.
13. Jubran A, Brydon JB, Grant MD, et al. Effect of pressure support versus unassisted breathing
through a tracheostomy collar on weaning duration in patients requiring prolonged mechanical
ventilation: a randomized trial. JAMA. 2013;309(7):6717.
14. Seneff MG, Wagner D, Thompson D, et al. The impact of long-term acute care facilities on the
outcome and cost of care for patients undergoing prolonged mechanical ventilation. Crit Care
Med. 2000;28:34250.
15. Camhi SL, Mercado AF, Morrison RS, et al. Deciding in the dark: advance directives and
continuation of treatment in chronic critical illness. Crit Care Med. 2009;37(3):91925.
Automated Weaning Modes

F. Wallet, S. Ledochowski, C. Bernet, N. Mottard,
A. Friggeri, and V. Piriou
Mechanical ventilatory support (MV) management of critically ill patients has

undergone profound changes over the past 10 years. This practice has evolved from
deep sedation associated with a totally controlled ventilation mode for prolong periods to minimal sedation and the corollary use of spontaneous ventilation modes. By
reducing the duration and the depth of the sedation, the duration of invasive mechanical ventilation in intensive care units (ICUs) has been significantly shortened.
Evidence showing the benefit of such strategies is now clearly demonstrated [13].
Weaning is the process of decreasing ventilator support and allowing patients to
assume a progressively increasing part of their work of breathing or proportion of
their ventilation. It is essential and represents nearly 40 % of the total duration of
mechanical ventilation [4]. It has been shown in clinical practice that the use of
protocols or algorithms was safe and effective in reducing the time spent on MV [4].
The first step consists of assessing the readiness to wean, using objective criteria
screened daily by nurses or ventilatory therapists to look for contraindications to
spontaneous breathing (absence of vasopressors, patient awake, and ad hoc ventilation parameters) [5]. When they are present, a spontaneous breathing trial (SBT) is
made, after which the practitioner decides whether to extubate the patient [6]. There
is, therefore, a scientific, economic, and human rationale to reduce the duration of
ventilation (and sedation).
In fact, a prolonged duration of mechanical ventilation has a cost [7]. In the next
decade, the need for ventilation will increase, both because of the aging of patients
admitted to the ICU and global population growth [8, 9]. The availability of medical
and paramedical personnel will decrease, with a risk of burnout among caregivers
resulting from an increased workload [1013].
F. Wallet (*) S. Ledochowski C. Bernet N. Mottard A. Friggeri V. Piriou
Critical Care Unit, Department of Anesthesiology and Critical Care Medicine, CHU Lyon
Sud, 165 Chemin du Grand Revoyet, Pierre Bnite 69495, France
e-mail: florent.wallet@chu-lyon.fr
DOI 10.1007/978-3-319-04259-6_3
21
22
F. Wallet et al.
Intubation
Weaning
SBT
Extubation
Adaptive support ventilation (ASVTM)
SmartCare/PSTM
IntelliventTM
Fig. 3.1 Positionning of different automated weaning modes from intubation to extubation
In such dire times, technological advances helping in the automation of all, or part,
of mechanical ventilation and its weaning seem to be an attractive solution. Furthermore,
automation also allows a constant application of the recommended guidelines for
efficient mechanical ventilation, thus resulting in improved care [14, 15].
The automation of mechanical ventilation can be used from intubation to extubation or only in the weaning phase [16]. It uses artificial intelligence technology that
involves feedback loops [16]. There are currently three available systems: the
SmartCare/PS from Drger, and ASV and IntelliVent-ASV from Hamilton. We
will later explain how these systems work. Their use in the course of a patients
mechanical ventilatory management is described in Fig. 3.1.
3.1
ASV
Adaptive support ventilation (ASV) is the oldest automated MV technology and

probably the most studied [17, 18]. It is fully automated and can adapt from intubation to the SBT. Its algorithm is based on the clinical information set by the user on
the size and sex of the patient. The ventilator calculates the predicted body weight
based on patients height (PBW) and then defines an ideal minute volume equal to
0.1 L/min/kg ideal body weight (e.g., 6 l/min for 60 kg of PBW). Then, the system
initially uses the expiratory resistance and compliance to calculate the time constant. The ventilator uses the Otis and Mead equation [19] to provide specific minute ventilation (a combination of ideal tidal volume (Vt) and ventilatory rate (RR))
optimized for a minimal ventilatory work and the smallest energy expenditure. The
clinician may then adjust three supplementary parameters:
percentage of the ideal expired minute volume, ranging from 50 to 250 % (resulting in a greater or lesser alveolar ventilation)
level of PEEP
FiO2 level
When the patient is passive (deeply sedated with no spontaneous breathing), the
ventilator delivers pressure-controlled ventilation with Vt and RR previously
23
Vt
Target
Patient
Vt > Target
Vt > Target
RR < Target
RR > Target
Pinsp
RR
Pinsp
RR
1600
V
ml
Target
Current
1200
MinVol
6.6
I/min
800
400
f
b/min
0
0
RR < Target
RR > Target
Pinsp
RR
Pinsp
RR
10
fSpont
20
30
fControl
40
50
60
Pinsp
12
b/min
b/min
cmH2O
Vt < Target
Vt < Target
RR
Fig. 3.2 ASV simplified algorithm
calculated. Once the patient starts breathing and triggers the ventilator, the system
tries to bring the patient to the ideal Vt/RR combination, if necessary by completing
his or her ventilatory pattern with machine cycles. Spontaneous cycles triggered by
the patient are delivered in pressure support mode (PSV). Finally, when the patient
triggers spontaneously at a ventilatory rate greater than the targeted RR, the ventilator applies only pressure support. It gradually reduces the level of support it offers
to shift the patients spontaneous Vt/RR combination toward the ideal curve, which
represents all the possible ideal Vt/RR combinations. The principle is shown in
Fig. 3.2.
3.2
SmartCare/PS System
This system is a feedback loop centered on the weaning period. Its objective is to
gradually reduce the level of pressure support while maintaining the patient in a
comfort zone. It therefore requires the patient to be in PSV. It is based on the
NeoGanesh expert system (from the Hindu god of wisdom and intelligence,
Ganesh). The comfort zone is defined as
Vt > 300 mL
RR of 1230/min
PETCO2 < 55 mmHg
24
F. Wallet et al.
Hypoventilation
PS
PS
PS
Insufficient ventilation
Severe tachypnea
PS
PS
PS
Normal ventilation
Hyperventilation
Tachypnea
Unexplained
hyperventilation
PS
identical
35
30
15
RR
Fig. 3.3 Simplified algorithm of the SmartCare/PS system
SmartCare/PS has certain requirements; it needs information about patient

weight, type of airway humidification, type of tracheal prosthesis (intubation vs
tracheotomy), existence of COPD or head trauma, and possible obstructive apnea
syndrome. The ventilator must also be equipped with a capnograph. The ventilator
evaluates the patients ventilatory status every 25 min (thus tolerating periods of
transient worsening related to external stimuli). Patients are classified as shown in
Fig. 3.3. The system modifies the level of pressure support and its alarms according
to each diagnosed condition.
Once a period of stability is achieved with a level of pressure support that is low
enough (depending on the threshold settings of the SmartCare/PS) and if the
patient has a PEEP less than 5 cmH20, an SB) is started. After 12 h of SBT, depending on the level of assistance set at the beginning of the SmartCare/PS session, if
the patient remains in stable condition, the system suggests the patients disconnection from the ventilator.
3.3
IntelliVent-ASV System
The IntelliVent-ASV system is the latest development of ASV. It combines the

latter mode with multiple feedback loops for setting PEEP and FiO2, with the same
adjustment of a variable percentage of minute ventilation by collecting various
25
biological signals from the patient (e.g., SpO2, EtCO2). With this system, the setting
of PEEP and FiO2 is based on an algorithm defined by Hamilton. It is based on a
combination of the lower PEEP table of the acute respiratory management (ARMA)
of acute respiratory distress syndrome (ARDS) study for incremental PEEP and FiO2
situations, and the decremental scheme used in the Assessment of Low tidal Volume
and elevated End-expiratory volume to Obviate Lung Injury (ALVEOLI) study
(faster decrease of FiO2 than PEEP) when necessary [20, 21]. Furthermore, the continuous analysis of SpO2 changes induced by the MV provides another level of feedback. However, when preload dependency is suspected by the analysis of the SpO2
waveform, the optimization of the PEEP level can be limited to control hemodynamic effects of PEEP and increase safety [22]. Moreover, the measured level of
EtCO2 has a negative feedback on the level of minute ventilation applied (i.e., the
percentage of minute ventilation in the ASV setting). In addition, the latest version of
the IntelliVent-ASV has an automated SBT module (Quick Wean), which performs
an SBT according to predefined criteria by the user (as with the SmartCare/PS system) as soon as the level of assistance of the patient is low enough. This system thus
offers a fully automated ventilatory strategy, from intubation to the SBT.
3.4
Review of the Literature
These automated systems are still poorly evaluated when compared with older conventional ventilatory modes. Regarding ASV, a very modest benefit from a clinical
point of view in postoperative cardiac surgery has been identified [23, 24]. Some
studies show a reduction in the duration of ventilation ranging from 1 to 2 days in
ICU patients [25, 26]. If there is a benefit in terms of duration of MV, it seems modest and of limited interest in the populations studied. The most important benefit
would be to relieve medical and paramedical teams of the management of MV in the
most simple patients. These ventilatory modes could also help enforcing the
recommended guideline in the ICU by systematically applying them. However,
more formal data are needed to confirm this.
Regarding SmartCare/PS, data from the literature are conflicting. The results of
two large studies by the team of Laurent Brochard [27, 28] found a 48-h reduction
in the duration of ventilation and a 4-day reduction in ICU length of stay without
deleterious effect in terms of reintubation. On the other hand, a large Australian
study did not find any benefit of the SmartCare/PS system when compared with a
conventional weaning protocol [29]. However, the latter team had the benefit of a
nurse-to-patient ratio of 1:1. To push the debate further, another study did not find
any benefit over the use of a written weaning protocol in a population of surgical
ICU patients [30], whereas a metanalysis by Friedrich et al. [31] found that weaning
with SmartCare/PS significantly decreased weaning time, time to successful extubation, ICU length of stay, and proportion of patients receiving ventilation for
longer than 7 and 21 days.
Finally, concerning IntelliVent-ASV, clinical assessment remains poor. Two
recent studies have demonstrated the feasibility and safety of this ventilatory
26
F. Wallet et al.
modality [3133]. The authors found a much higher percentage of time spent in an
optimal range (90 % vs 12 %) in the IntelliVent-ASV group compared with management of the usual ventilation. These results were recently confirmed by
Clavieras et al. [34] in an unselected ICU population. Moreover, an abstract was
published in 2013 that included ARDS patients, thus confirming IntelliVent-ASVs
safety in critically ill patients [35].
Conclusion
Novel automated ventilatory modes in the ICU look promising. Beyond their performance, their acceptance by health-care teams has yet to be evaluated [28]. Totally
automated modes have initially focused on selected aspects of MV in ICU patients
(initiation of the weaning process, or even its conclusion). They have shown a significant reduction in the length of the weaning process and have led to a novel,
totally automated mode that needs further development and evaluation. The implementation of such modes in daily practice is a challenge for the future.
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5. Kollef MH, Shapiro SD, Silver P, St John RE, Prentice D, Sauer S, et al. A randomized, controlled trial of protocol-directed versus physician-directed weaning from mechanical ventilation. Crit Care Med. 1997;25(4):56774.
6. Esteban A, Alia I, Tobin MJ, Gil A, Gordo F, Vallverdu I, et al. Effect of spontaneous breathing
trial duration on outcome of attempts to discontinue mechanical ventilation. Spanish Lung
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7. Cox CE, Carson SS, Govert JA, Chelluri L, Sanders GD. An economic evaluation of prolonged
mechanical ventilation. Crit Care Med. 2007;35(8):191827.
8. Needham DM, Bronskill SE, Calinawan JR, Sibbald WJ, Pronovost PJ, Laupacis A. Projected
incidence of mechanical ventilation in Ontario to 2026: preparing for the aging baby boomers.
Crit Care Med. 2005;33(3):5749.
9. Zilberberg MD, de Wit M, Pirone JR, Shorr AF. Growth in adult prolonged acute mechanical
ventilation: implications for healthcare delivery. Crit Care Med. 2008;36(5):14515.
10. Donchin Y, Seagull FJ. The hostile environment of the intensive care unit. Curr Opin Crit Care.
2002;8(4):31620.
11. Scott LD, Rogers AE, Hwang WT, Zhang Y. Effects of critical care nurses work hours on vigilance and patients safety. Am J Crit Care. 2006;15(1):307.
12. Le Gall JR, Azoulay E, Embriaco N, Poncet MC, Pochard F. [Burn out syndrome among critical care workers]. Bull Acad Natl Med. 2011;195(2):38997; discussion 978.
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13. Scott LD, Hwang WT, Rogers AE. The impact of multiple care giving roles on fatigue, stress,
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14. McGlynn EA, Asch SM, Adams J, Keesey J, Hicks J, DeCristofaro A, et al. The quality of
health care delivered to adults in the United States. N Engl J Med. 2003;348(26):263545.
15. Pronovost PJ, Rinke ML, Emery K, Dennison C, Blackledge C, Berenholtz SM. Interventions
to reduce mortality among patients treated in intensive care units. J Crit Care.
2004;19(3):15864.
16. Lellouche F, Brochard L. Advanced closed loops during mechanical ventilation (PAV, NAVA,
ASV, SmartCare). Best Pract Res Clin Anaesthesiol. 2009;23(1):8193.
17. Laubscher TP, Frutiger A, Fanconi S, Jutzi H, Brunner JX. Automatic selection of tidal volume, respiratory frequency and minute ventilation in intubated ICU patients as start up procedure for closed-loop controlled ventilation. Int J Clin Monit Comput. 1994;11(1):1930.
18. Campbell RS, Branson RD, Johannigman JA. Adaptive support ventilation. Respir Care Clin
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19. Otis AB, Fenn WO, Rahn H. Mechanics of breathing in man. J Appl Physiol.
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20. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung
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21. Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, et al. Higher
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24. Gruber PC, Gomersall CD, Leung P, Joynt GM, Ng SK, Ho KM, et al. Randomized controlled
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Neurally Adjusted Ventilatory Assist

in Noninvasive Ventilation
4.1
Introduction
Noninvasive ventilation (NIV) is widely used today in both acute and chronic settings to avoid complications of invasive ventilation, such as infection [1, 2]. Despite
its increasing use, a significant number of patients fail NIV and require endotracheal
intubation. There are several indications for NIV, and patientventilator asynchronies play a crucial role in the tolerance and success of this technique. Vignaux et al.
[3] showed in a multicenter study that 43 % of patients suffering from acute respiratory failure and treated by NIV demonstrated severe asynchronies. In a pneumatically triggered NIV mode, optimal settings, including pressure support, positive
end-expiratory pressure, and inspiratory flow rate and expiratory cycling, achieving
the longest time of synchrony could be difficult (Fig. 4.1).
Neurally adjusted ventilatory assist (NAVA) is a new spontaneous ventilatory
mode, first described in 1999 by Sinderby et al. [4], based on electric triggering and
proportional ventilation. NAVA uses an esophageal catheter to collect the diaphragmatic electrical activity (EAdi) and to synchronize (in terms of timing and amount
of pressure) the assistance to the patients inspiratory effort. There has been increasing use of NAVA, and a limited number of physiological studies have pointed out
the clinical potential benefit of this new ventilatory mode. First, electric triggering,
replacing pneumatic triggering, allows better synchrony between the patient and the
ventilator. For example, in a subject with dynamic hyperinflation, synchronization
of the pressure support with EAdi could increase patientventilator interaction
(Fig. 4.2). In the same way, auto-triggering, which frequently occurs with leaks,
could be resolved with electrical triggering.
B. Repusseau, MD (*) H. Roz, MD, PhD
Thoracic Intensive Care Unit, Department of Anesthesia and Intensive Care 2, Bordeaux
University Hospital, Bordeaux, F-33000, France
e-mail: benjamin.repusseau@chu-bordeaux.fr
DOI 10.1007/978-3-319-04259-6_4
29
30
Fig. 4.1 Synchrony

between patients
inspiratory effort (bottom
curve) and pressure
support (upper curve). Paw
airway pressure, Pdi
transdiaphragmatic
pressure, TiV ventilators
inspiratory time, TiP
patients inspiratory time,
T sync time of synchrony,
Insp or Exp Tr inspiratory
or expiratory trigger
20
Insp Tr Delay
Paw
(cmH2O)
TiV
3
T Sync
12
Pdi
(cmH2O)
TiP
Exp Tr Delay
0
0
Times (s)
Studies have been published on the invasive application of NAVA mode and have
shown better synchronization between the patient and the ventilator [5, 6]. Therefore,
NAVA could be an interesting alternative to pressure support ventilation (PSV) in
NIV.
4.2
Noninvasive NAVA Studies (Table 4.1)
In 2008, Moerer et al. [7] studied seven healthy adult volunteers receiving NIV via
the Helmet device. They showed that, compared with pneumatically triggered
NIV, neurally triggered NIV offers better patient-ventilator synchrony, better breathing comfort, and less trigger effort during increasing levels of PSV and respiratory
rate.
Another clinical study by Cammarota et al. [8] used the Helmet interface to
compare NAVA versus PSV in 10 patients in acute respiratory failure (ARF). They
also showed a better synchrony in NAVA mode compared with PSV. However, the
severe asynchrony rate was relatively high in PSV mode (7080 %), which was
probably due to the interface [9].
In 2012, Piquilloud et al. [10] assessed 13 patients receiving NAVA and PSV
with an oro-nasal face mask. Without using a NIV algorithm, but with an optimized
setting in PSV, they reported a greater patient-ventilator interaction in NAVA compared with PSV, mainly due to the reduction of ineffective effort. More recently,
Bertrand et al. [11] showed similar results on 13 patients with ARF (without chronic
obstructive pulmonary disease (COPD)).
Schmidt et al. [12] particularly focused on the NIV algorithm. This dedicated
software has been developed by manufacturers to take leaks into account and to
Neurally Adjusted Ventilatory Assist in Noninvasive Ventilation
31
Pressure (cmH2O)
4
0
Flow (L/sec)
Pdi (cmH2O)
0.8
16
0
5
Time (sec)
Pressure (cmH2O)
10
5
0
Flow (L/sec)
Pdi (cmH2O)
16
0
5
Time (sec)
Fig. 4.2 Asynchronies with ineffective efforts. Pressure/time, flow/time and trans-diaphragmatic/
time curves in noninvasive pressure support ventilation (upper figure) and noninvasive neurally
adjusted ventilatory assist (bottom). Black arrows represent ineffective efforts
32
Table 4.1 Characteristics of studies comparing NAVA to PSV in NIV

No. of
Year, author patients
2008,
10
Camarota
2012,
Piquilloud
13
2012,
Schmidt
17
2013,
Bertrand
13
Patients
PSV settings
Leaks
ARF post
extubation
Helmet, NIV
algorithm, all
patients: PS
12 cmH2O, PEEP
10 cmH2O,
expiratory trig
50 %
Oro-nasal mask,
No NIV
algorithm
Optimized
settings for each
patients
Oro-nasal mask,
with and without
NIV algorithm,
All patients
PEEP 4cmH2O,
expiratory trig
30 %
Oro-nasal mask,
NIV algorithm,
PEEP
5-10 cmH2O,
expiratory trig
30 %
NAVA 43 %
PSV 5 %
5 ARF
8
prophylactic
post
extubation
6 COPD
Prophylactic
post
extubation
4 COPD
ARF (5 post
extubation,
7
pneumonia)
No COPD
NAVA 15 %
PSV 14 %
With NIV
algorithm :
NAVA 26 %
PSV 13 %
NAVA 13 %
PSV 14 %
NAVA benefits
Decrease
Inspiratory and
expiratory trig
delay, AI
Increase time of
synchrony
Decrease
inspiratory trig
delay, AI,
ineffective effort,
delayed cycling,
premature cycling
Decrease
inspiratory trig
delay, AI, delayed
cycling, premature
cycling
Decrease
inspiratory trig
delay, Ti excess,
ineffective effort,
delayed cycling, AI
ARF acute respiratory failure, COPD chronic obstructive pulmonary disease, NIV noninvasive
ventilation, PSV pressure support ventilation, PEEP positive end-expiratory pressure, cmH2O centimeters of water, Trig trigger, NAVA neurally adjusted ventilatory assist, AI asynchrony index
automatically adjust the flow and the inspiratory trigger. They compared, in 17
patients receiving prophylactic post-extubation NIV, NAVA versus PSV with and
without NIV algorithm. They found that NAVA with this software offers the best
synchrony between the patient and the ventilator. Interestingly, NAVA without NIVmode was more effective in reducing the asynchrony index (AI) than PSV with NIV
algorithm.
4.3
Discussion
All of these physiologic studies are concordant and seem to indicate that NAVA
increases patient-ventilator synchrony compared with PSV in NIV.
The use of neural triggering is particularly interesting in NIV. Leaks frequently
occur, even with the NIV algorithm, and can alter a pneumatic inspiratory trigger.
Leaks can generate auto-triggering, which is a main source of discomfort. Based on
33
neural triggering, NAVA does not prevent leaks but allows the reduction of the
inspiratory trigger delay and auto-triggering frequency [13]. Under NAVA, the trigger can also be pneumatic as the algorithm is first arrived, first served between
pneumatic and neural triggering. However inspiratory trigger delays are important
in patients with dynamic hyperinflation, and, in these patients, neural trigger starts
before pneumatic trigger.
Ineffective effort can also affect NIV, especially with obstructive patients.
Dynamic hyperinflation (increased by a high level of pressure support) involves
intrinsic positive end-expiratory pressure (PEEP), which increases the patients
inspiratory threshold load in a pneumatically triggered mode. In NAVA, assistance
is directly synchronized to the respiratory drive, thereby reducing asynchronies and
the inspiratory effort related to intrinsic PEEP [14]. Using an automated analysis of
patient-ventilator interaction [15], Dooduin et al. [16] demonstrated in 12 COPD
patients that noninvasive NAVA improves synchrony compared with PSV, delivered
either by a dedicated or ICU ventilator.
However, with the exception of severe obstructive patients, we do not know
whether an increased patient-ventilator interaction is clinically relevant. In all of
these physiologic studies, a better synchrony between the patient and the ventilator
did not lead to a better oxygenation index. Furthermore, our group compared NAVA
versus PSV in 10 patients receiving prophylactic post-extubation NIV [17]. We
found that, despite an increased patient-ventilator synchrony in NAVA, there was no
difference in the inspiratory effort (expressed by the transdiaphragmatic pressure
time product by minute) between the two modes.
Moreover, it is somewhat a paradox to use NAVA in NIV. The NAVA catheter
insertion is, in a way, an invasive procedure. It seems to be much easier to use NIV
NAVA after extubation than during acute respiratory failure. A significant number
of critically ill ventilated patients need a nasogastric tube, and in those cases the
choice of the catheter has to be anticipated with the aim of using NAVA. It is more
difficult to propose NAVA ventilation at the beginning of acute respiratory failure
because of the difficulties and poor tolerance of NAVA catheter insertion in that
situation. In other cases, the use of NAVA has to be carefully thought through. One
argument for the use of NAVA is the simplicity of the settings. Once the EAdi catheter is inserted and well positioned, NAVA ventilation can be easily started, with, in
most cases, a relatively good patient-ventilator interaction.
Another point of research is the clinical challenge represented by gastric distension under NIV. It has been highlighted that closure of the glottis with increasing
level of assist reduces the effective ventilation and diverts air toward the digestive
system [18]. In 2012, Hadj-Ahmed et al. [19] showed the absence of inspiratory
laryngeal constrictor muscle activity during NAVA in nonsedated lambs. This finding may allow the improvement of the patient-ventilator interaction under NIV.
In addition to being a new ventilatory mode, NAVA offers, for the first time, in
invasive and noninvasive ventilation, neural respiratory drive monitoring at the bedside. EAdi monitoring might allow optimizing settings for patient-ventilator interaction. In addition to the clinical relevance, the educational interest is obvious. With
NAVA-preview software, under PSV it is possible to see an estimation of the
34
pressure-time curve synchronized to EAdi on the screen. Thus, inspiratory or expiratory trigger delays can easily be detected and adapted to fit with this estimated
curve. Moreover, over-assistance occurs frequently in PSV and can lead to asynchronism [20]. The level of assist under NIV can be titrated according to the drive
represented by EAdi [21]. It could also be an interesting tool to monitor the effect
of active or residual sedation on diaphragmatic function [22]. Or to assess lung
hyperinflation [23] and the work of breath or its variation for different levels of
assist [24].
Conclusion
NAVA represents a new alternative to PSV in NIV. It might be an interesting

mode that improves synchrony between the patient and the ventilator. Further
studies are needed to assess whether this is clinically relevant. Moreover, NAVA
gives access to a new parameter at the bedside (EAdi), revealing a new era in
ventilation.
NAVA is an alternative to PSV in noninvasive ventilation.

In NIV, NAVA offers a better interaction between the patient and the ventilator than PSV.
In case of high intrinsic PEEP or major leakage, NAVA could be an easy
way to achieve NIV.
NAVA offers continuous bedside EAdi monitoring.
References
1. Crimi C, Noto A, Princi P, et al. A European survey of noninvasive ventilation practices. Eur
Respir J. 2010;36:3629.
2. Esteban A, Frutos-Vivar F, Muriel A, et al. Evolution of mortality over time in patients receiving mechanical ventilation. Am J Respir Crit Care Med. 2013;188:22030.
3. Vignaux L, Vargas F, Roeseler J, et al. Patientventilator asynchrony during non-invasive ventilation for acute respiratory failure: a multicenter study. Intensive Care Med. 2009;35:8406.
4. Sinderby C, Navalesi P, Beck J, et al. Neural control of mechanical ventilation in respiratory
failure. Nat Med. 1999;5:14336.
5. Terzi N, Pelieu I, Guittet L, et al. Neurally adjusted ventilatory assist in patients recovering
spontaneous breathing after acute respiratory distress syndrome: physiological evaluation. Crit
Care Med. 2010;38:18307.
6. Piquilloud L, Vignaux L, Bialais E, et al. Neurally adjusted ventilatory assist improves patientventilator interaction. Intensive Care Med. 2011;37:26371.
7. Moerer O, Beck J, Brander L, et al. Subjectventilator synchrony during neural versus pneumatically triggered non-invasive helmet ventilation. Intensive Care Med. 2008;34:161523.
8. Cammarota G, Olivieri C, Costa R, et al. Noninvasive ventilation through a helmet in postextubation hypoxemic patients: physiologic comparison between neurally adjusted ventilatory
assist and pressure support ventilation. Intensive Care Med. 2011;37:194350.
35
9. Navalesi P, Costa R, Ceriana P, et al. Non-invasive ventilation in chronic obstructive pulmonary disease patients: helmet versus facial mask. Intensive Care Med. 2007;33:7481.
10. Piquilloud L, Tassaux D, Bialais E, et al. Neurally adjusted ventilatory assist (NAVA) improves
patient-ventilator interaction during non-invasive ventilation delivered by face mask. Intensive
Care Med. 2012;38:162431.
11. Bertrand P-M, Futier E, Coisel Y, et al. Neurally adjusted ventilatory assist versus pressure
support ventilation for noninvasive ventilation during acute respiratory failure: a cross-over
physiological study. Chest. 2013;143(1):306.
12. Schmidt M, Dres M, Raux M, et al. Neurally adjusted ventilatory assist improves patientventilator interaction during postextubation prophylactic noninvasive ventilation. Crit Care
Med. 2012;40:173844.
13. Roz H, Ouattara A. Use of neural trigger during neurally adjusted ventilatory assist in a
patient with a large broncho-pleural fistula and air leakage. Intensive Care Med.
2012;38:9223.
14. Spahija J, de Marchie M, Albert M, et al. Patient-ventilator interaction during pressure support
ventilation and neurally adjusted ventilatory assist. Crit Care Med. 2010;38:51826.
15. Sinderby C, Liu S, Colombo D, et al. An automated and standardized neural index to quantify
patient-ventilator interaction. Crit Care. 2013;17:R239.
16. Doorduin J, Sinderby CA, Beck J, et al. Automated patient-ventilator interaction analysis during neurally adjusted non-invasive ventilation and pressure support ventilation in chronic
obstructive pulmonary disease. Crit Care. 2014;18:550.
17. Repusseau B, Vargas F, Laluque C, et al. Neurally adjusted ventilatory assist versus pressure
support ventilation with optimal settings for non invasive ventilation. Intensive Care Med.
2013;39:S357.
18. Parreira VF, Jounieaux V, Aubert G, et al. Nasal two-level positive-pressure ventilation in
normal subjects. Effects of the glottis and ventilation. Am J Respir Crit Care Med.
1996;153:161623.
19. Hadj-Ahmed MA, Samson N, Bussires M, et al. Absence of inspiratory laryngeal constrictor
muscle activity during nasal neurally adjusted ventilatory assist in newborn lambs. J Appl
Physiol (1985). 2012;113:6370.
20. Thille AW, Cabello B, Galia F, et al. Reduction of patient-ventilator asynchrony by reducing
tidal volume during pressure-support ventilation. Intensive Care Med. 2008;34:147786.
21. Roz H, Lafrikh A, Perrier V, et al. Daily titration of neurally adjusted ventilatory assist using
the diaphragm electrical activity. Intensive Care Med. 2011;37:108794.
22. Roz H, Germain A, Perrier V, et al. Effect of flumazenil on diaphragm electrical activation
during weaning from mechanical ventilation after acute respiratory distress syndrome. Br J
Anaesth. 2015;114:26975.
23. Bellani G, Coppadoro A, Patroniti N, et al. Clinical assessment of auto-positive end-expiratory
pressure by diaphragmatic electrical activity during pressure support and neurally adjusted
ventilatory assist. Anesthesiology. 2014;121(3):56371.
24. Bellani G, Mauri T, Coppadoro A, et al. Estimation of patients inspiratory effort from the
electrical activity of the diaphragm. Crit Care Med. 2013;41:148391.
Recommendations of Sedation
and Anesthetic Considerations During
Weaning from Mechanical Ventilation
Ari Balofsky and Peter J. Papadakos
Abbreviations
ETI
ICU
NIV
TCI
5.1
Endotracheal intubation
Intensive care unit
Noninvasive ventilation
Target-controlled infusion
Introduction
The use of noninvasive ventilation (NIV) has gained popularity in a variety of applications, including acute respiratory failure, and it has been shown to be beneficial in
the reduction of complications and improvement in outcomes [1]. A variety of factors can lead to failure to tolerate NIV, and the use of sedation can be effective in
keeping the patient comfortable, yet awake and arousable, so as to prevent distress
while providing a suitable level of sedation. A survey of the use of sedation in
patients receiving NIV revealed that practices vary widely, likely because of a lack
of evidence, and as such its application is underused [2]. There are inconsistencies
in how often sedation and analgesia are provided, which agents are used, methods
of administration, and determination of patient requirements. This lack of consistency sets up a situation in which the patient is exposed to circumstances that make
it more difficult to be successfully weaned from mechanical ventilation.
A. Balofsky, MD P.J. Papadakos, MD (*)

Department of Anesthesiology, University of Rochester, Rochester, NY 14642, USA
e-mail: Ari_Balofsky@URMC.Rochester.edu; Peter_Papadakos@URMC.Rochester.edu
DOI 10.1007/978-3-319-04259-6_5
37
38
5.2
A. Balofsky and P.J. Papadakos
Analysis of Main Topics
There are several considerations with regard to sedation and anesthetic use that are
essential to ensure optimal conditions for successfully weaning from mechanical
ventilation. While providing sedation, one must be cognizant of the numerous factors linked to failure of NIV. Such factors include weak cough reflex, excessive
secretions, intolerance and psychomotor agitation, patientventilator asynchrony,
oxygen impairment, increased respiratory rate and elevated rapid shallow breathing
index, hypercapnia, sleep disturbance, and delirium [3]. Failure to optimize these
factors makes it increasingly difficult to wean from mechanical ventilation. As such,
the goal is to provide adequate sedation and pain control while maintaining arousability, respiratory drive, cough reflex, and airway protection, all while retaining the
ability to quickly and safely wean the patient from both sedation and mechanical
ventilation. Techniques that are beneficial to improving these conditions include
delivering an appropriate level of sedation and analgesia, integrating protocols to
guide administration, utilizing sufficient monitoring, using the practice of intermittent sedation, and the proper selection of anesthetic agent.
5.3
Discussion
To maximize the likelihood of success during weaning, it is crucial to incorporate

the best practices in regards to the delivery of sedation and analgesia to increase
effectiveness while minimizing risks. Reduction of pain and agitation, avoidance of
exacerbating factors, and allowing the patient to easily interact with the ventilator
will encourage improvement and prevent complications, and ultimately facilitate
achieving the desired outcome.
By using methods to ensure that the patient experiences appropriate levels of
sedation and analgesia, optimal conditions can be provided to prevent the problems
that lead to difficulty in weaning from mechanical ventilation. There is evidence
that the use of protocols and algorithms for optimizing sedation and analgesia produces numerous positive effects, including the prevention of oversedation, decreased
pain and agitation, less patient-ventilator asynchrony, better detection of delirium,
and a reduction in duration of mechanical ventilation and intensive care unit (ICU)
and hospital stay [4].
One important consideration to bear in mind when weaning sedation from the
mechanically ventilated patient is the temporal manner in which the sedation is
delivered. Numerous studies have shown there are a variety of benefits to patients
who receive daily interruption of sedation. Such benefits include shorter duration of
mechanical ventilation, shorter length of stay, fewer diagnostic imaging tests for
mental status changes, better Psychosocial Adjustment to Illness Scale scores, lower
incidence of post-traumatic stress disorder, and the potential for reducing the risk of
delirium [5].
It is important to monitor depth of sedation to maintain an adequate level,
because prolonged and too deep sedation has been associated with worse
Recommendations of Sedation and Anesthetic Considerations
39
outcomes. Toward this end, there are several tools available to ensure adequate
levels of sedation. For example, the Ramsay Sedation Scale, the Sedation Agitation
Scale, and the Richmond Agitation-Sedation Scale can be used to monitor and
adjust the depth of sedation [5]. Although the Bispectral Index (BIS, Aspect
Medical Systems, Norwood, MA, USA) represents a novel method of measuring
depth of sedation through the use of electroencephalography, more research is
likely needed at this time before it sees routine use for this application. In addition
to sedation scales, there are also various pain scales that may be employed to guide
the administration of adequate analgesia, such as the Numeric Rating Scale, the
Behavioral Pain Scale, the Critical Care Pain Observation Tool, and the Nonverbal
Pain Scale [6].
Although the application of the above-discussed techniques creates desirable
conditions for successful weaning, ultimately, the choice of sedative and analgesic agents used may play the most important role in this process. There are
numerous medications used to achieve adequate and appropriate sedation and
analgesia in the mechanically ventilated patient with varying pharmacodynamics, pharmacokinetics, and physiological effects. The different properties of
these commonly used drugs (particularly the effects on respiration) will dictate
which is the best for providing the desired results, as the condition and comorbidities of the patient must be considered when tailoring the best therapy for the
specific situation.
Dexmedetomidine is a centrally acting agonist of the 2-adrenergic receptor that
is metabolized hepatically, and has an estimated terminal elimination half-life of
2 h. Compared with other agents, dexmedetomidine is unique in that it produces
sedation, analgesia, and anxiolysis without adverse effects on respiration, is associated with a low risk for delirium, and decreases the need for alternative sedatives
[5]. In a study done by Akada et al. [7], all 10 patients who received dexmedetomidine while undergoing NIV due to prior uncooperativeness achieved adequate sedation, had respiratory rates decreased as intended, had and improved PaO2/FiO2 ratio
and Paco2, and were successfully weaned from NIV with none requiring endotracheal intubation (ETI). The patients could cough and expectorate without assistance, and none developed pneumonia. Although the properties of the drug make it
an excellent choice for use in sedation during weaning, potential side effects of
administration include hypotension and bradycardia.
Benzodiazepines such as midazolam are commonly used sedative agents that act
via the GABAA receptor. Midazolam is metabolized hepatically with renal clearance of active metabolites, which can accumulate during prolonged infusion.
Benzodiazepines are strongly associated with delirium, which is in turn associated
with increased mortality, prolonged duration of mechanical ventilation, and
increased risk of cognitive impairment in critically ill patients [5]. Whereas both
midazolam and dexmedetomidine have been found to be effective in providing adequate sedation during NIV, one group found dexmedetomidine to have several
advantages including decreased percentage of NIV failure requiring ETI (21.2 % vs
44.8 %) and a more prolonged mean time to ETI, more rapid weaning, decreased
overall duration of mechanical ventilation and ICU hospitalization, easier
40
A. Balofsky and P.J. Papadakos
arousability while maintaining adequate sedation, and a decreased incidence of

respiratory infections and vomiting [8]. Another found that dexmedetomidine
required fewer dose adjustments to maintain adequate sedation and cooperation
with NIV when compared with midazolam [9]. These studies showed dexmedetomidine doses in the range of 0.20.7 g/kg/h to be effective in achieving the desired
results.
Remifentanil is an ultra-short-acting agonist of the -opioid receptor that provides analgesia and sedation. When compared with other opioids, remifentanil has
a rapid offset even after prolonged infusion, elimination is not significantly altered
with organ dysfunction due to its elimination via extrahepatic, nonspecific blood
and tissue esterases, and it does not accumulate [10]. Depression of respiratory
drive occurs at known infusion rates (>0.05 g/kg/min), and the predictable nature
of its onset and offset makes it easily titrated to effect. These properties make remifentanil an attractive candidate for achieving optimal conditions during weaning.
However, it should be noted that, due to its rapid elimination, patients can experience pain after the infusion is discontinued. In a pilot study utilizing remifentanil
analgosedation for NIV following prior intolerance, it was found that 22 of 36
patients were able to tolerate NIV and had appropriate decreases in respiratory rate
and an improved PaO2/FiO2 ratio. Fourteen of 36 patients failed to tolerate NIV,
mainly due to persistent discomfort with concurrent persistent dyspnea and lack of
improvement in PaO2/FiO2 ratio. The mean dose of remifentanil used was
0.07 0.03 g/kg/min, and patients did not experience a decrease in respiratory
drive [11]. A preliminary study assessing remifentanil sedation in 13 patients with
prior NIV intolerance found there to be an appropriate decrease in respiratory rate
and an improved PaO2/FiO2 ratio, with a mean dose of 0.1 0.03 g/kg/min remifentanil used. Three patients required propofol supplementation and 4 patients
required endotracheal intubation due to inability to maintain an acceptable PaO2/
FiO2 ratio [12].
Propofol is an anesthetic agent that acts via the GABAA receptor to produce sedation, anxiolysis, and amnesia without any analgesia. It is primarily metabolized
hepatically, with some extrahepatic metabolism occurring, and has a dose-dependent
duration of action. It can cause respiratory depression, hypotension, and may rarely
lead to propofol infusion syndrome, a syndrome of metabolic acidosis, bradycardia,
hyperkalemia, rhabdomyolysis, and hyperlipidemia, especially when used in high
doses for prolonged periods of time and in critically ill patients [5]. Although commonly used for sedation, there is little research regarding its use in NIV in the critically ill patient. Clouzea et al. [13] found that delivering propofol via target-controlled
infusion (TCI), a technique of administration utilizing a protocol with computer
assistance for calculation of drug concentration, is a viable method of sedation for
patients undergoing NIV. They found that TCI of propofol allowed for patient cooperation, did not affect respiratory function, improved PaO2/FiO2 ratio, did not increase
PaCO2, and that patients did not experience vomiting or aspiration. Of the ten patients
studied, two required endotracheal intubation due to evolution of the underlying disease and one due to a seizure disorder. As such, TIC of propofol may represent a
novel method of sedation for use during weaning from mechanical ventilation.
Recommendations of Sedation and Anesthetic Considerations
41
Protocols and algorithms should be used for sedation when weaning from
mechanical ventilation.
Patients should receive daily interruption of sedation.
Depth of sedation and pain levels must be constantly and appropriately
monitored.
Appropriate and patient-specific anesthetics must be utilized to preserve
hemodynamic stability while maintaining ventilation and arousability.
References
1. Hilbert G, Clouzeau B, Nam Bui H, et al. Sedation during non-invasive ventilation. Minerva
Anestesiol. 2012;78(7):8426.
2. Devlin JW, Nava S, Fong JJ, et al. Survey of sedation practices during noninvasive positivepressure ventilation to treat acute respiratory failure. Crit Care Med. 2007;35(10):2298302.
3. Ozyilmaz E, Ugurlu AO, Nava S. Timing of noninvasive ventilation failure: causes, risk factors, and potential remedies. BMC Pulm Med. 2014;14:19.
4. Sessler CN, Pedram S. Protocolized and target-based sedation and analgesia in the ICU. Crit
Care Clin. 2009;25(3):489513.
5. Roberts DJ, Haroon B, Hall RI. Sedation for critically ill or injured adults in the intensive care
unit: a shifting paradigm. Drugs. 2012;72(14):1881916.
6. Patel SB, Kress JP. Sedation and analgesia in the mechanically ventilated patient. Am J Respir
Crit Care Med. 2012;185(5):48697.
7. Akada S, Takeda S, Yoshida Y, et al. The efficacy of dexmedetomidine in patients with noninvasive ventilation: a preliminary study. Anesth Analg. 2008;107(1):16770.
8. Huang Z, Chen YS, Yang ZL, et al. Dexmedetomidine versus midazolam for the sedation of
patients with non-invasive ventilation failure. Intern Med. 2012;51(17):2299305.
9. Senoglu N, Oksuz H, Dogan Z, et al. Sedation during noninvasive mechanical ventilation with
dexmedetomidine or midazolam: A randomized, double-blind, prospective study. Curr Ther
Res Clin Exp. 2010;71(3):14153.
10. Battershill AJ, Keating GM. Remifentanil: a review of its analgesic and sedative use in the
intensive care unit. Drugs. 2006;66(3):36585.
11. Rocco M, Conti G, Alessandri E, et al. Rescue treatment for noninvasive ventilation failure due
to interface intolerance with remifentanil analgosedation: a pilot study. Intensive Care Med.
2010;36(12):20605.
12. Constantin JM, Schneider E, Cayot-Constantin S, et al. Remifentanil-based sedation to treat
noninvasive ventilation failure: a preliminary study. Intensive Care Med. 2007;33(1):827.
13. Clouzeau B, Bui HN, Vargas F, et al. Target-controlled infusion of propofol for sedation in
patients with non-invasive ventilation failure due to low tolerance: a preliminary study.
Intensive Care Med. 2010;36(10):167580.
Weaning Protocols in Prolonged

Mechanical Ventilation: What Have
We Learned?
Anna Magidova, Farhad Mazdisnian,
and Catherine S. Sassoon
Abbreviations
ICU
IMS
MIP
Pditw
PMV
SBT
TIPS
Intensive care unit

Inspiratory muscle strength
Maximal inspiratory pressure
Twitch transdiaphragmatic pressure
Prolonged mechanical ventilation
Spontaneous breathing trial
Therapist-implemented patient-specific weaning protocol
6.1
Introduction
Prolonged mechanical ventilation (PMV) is defined as a patients reliance on

mechanical ventilation for 21 or more consecutive days, with the necessity of a
minimum 6 hours on mechanical ventilation per day [1]. The reported incidence of
Supported in part by Southern California Institute for Research and Education.
A. Magidova, MD
Division of Pulmonary and Critical Care, Department of Medicine,
VA Long Beach Healthcare System, Long Beach, CA, USA
F. Mazdisnian, MD
VA Long Beach Healthcare System, Long Beach, CA, USA
University of California, Irvine, CA, USA
C.S. Sassoon, MD (*)
University of California, Irvine, CA, USA
Pulmonary, Critical Care and Sleep Medicine, VA Long Beach Healthcare System (11/111P),
5701 East 7th Street, Long Beach, CA, 90822, USA
e-mail: csassoon@uci.edu; catherine.sassoon@va.gov
DOI 10.1007/978-3-319-04259-6_6
43
44
A. Magidova et al.
PMV is 4.4 % of intensive care unit (ICU) admissions and 6.3 % of patients receiving mechanical ventilation [2]. Patients requiring PMV have adverse clinical outcome, prolonged ICU and hospital length of stay, and high mortality [3]. To conserve
resources, weaning is commonly performed or continued at a long-term acute care
hospital (LTAC), a facility dedicated to weaning patients from mechanical ventilation. The prevalence of successful weaning among these patients is approximately
50 % [4], regardless of the various definitions of weaning success, that is, the ability
to sustain spontaneous breathing for 5 [5], 7 [1, 6], or 11 [7] consecutive days. In
ICU patients, implementation of a weaning protocol by nonphysician staff (i.e.,
respiratory therapists) is effective in reducing the time spent on mechanical ventilation among patients with either simple or difficult weaning [8, 9]. The application
of a weaning protocol in patients requiring PMV results in a similar favorable outcome of increasing ventilator-free days [7]. Surprisingly, a weaning protocol is
available in only 48% of ICUs [6]. In this chapter, we discuss (1) the necessity of a
weaning protocol for patients requiring PMV; (2) integrated measures that can
potentially increase ventilator-free days and/or successful weaning rate; and (3)
what constitutes a weaning protocol for patients requiring PMV.
6.2
Discussion and Analysis
6.2.1
Necessity of a Weaning Protocol for Patients

Requiring PMV
Scheinhorn and coworkers [7] were the first to report a significantly shortened
weaning time when a therapist-implemented patient-specific (TIPS) weaning protocol was used for patients requiring PMV. Patients enrolled prospectively in the TIPS
group (n = 252) were compared with a historical control group (n = 238). Median
weaning time in the TIPS group was 17 days compared with 29 days in the control
group, although the rate of successful weaning, ventilator dependence, and mortality were similar in both groups. As in ICU patients, a weaning protocol expedited
discontinuation from mechanical ventilation [8, 10]. However, others did not support this practice when substantial physician staffing was available to pay close
attention to patients [11]. Furthermore, in a national survey of 215 Canadian ICUs
with 308 patients requiring PMV, 81 % of units used individualized plans for weaning. Of those units with protocols, only 25 % had a weaning protocol specific to
PMV [12].
To our knowledge, a comparison between individualized plans and protocolized
weaning on weaning duration in patients requiring PMV has not been reported.
Nevertheless, the mechanisms of successful weaning protocols are related to obligating medical personnel to pay close attention to patients, perform daily screening,
order daily spontaneous breathing trials (SBTs), and wean patients who demonstrate improvement without delay [13]. In addition, for patients who do not tolerate
SBT, a weaning protocol provides guidelines for trial termination, re-trial, and steps
to be taken to prevent overtaxing the respiratory muscles. Thus, a weaning protocol
Weaning Protocols in Prolonged Mechanical Ventilation: What Have We Learned?
45
is helpful in motivating medical personnel to pay close attention to patients and in

decision-making for discontinuation from mechanical ventilation when ample physician staffing is unavailable. Weaning protocols, however, have limitations. Poor
compliance has been documented, despite a priori knowledge that adherence to a
weaning protocol shortens weaning time [14]. Reinforcement of the protocol and
re-education of medical personnel are needed to maintain the promising results of a
weaning protocol. Conversely, without a weaning protocol, medical personnel may
become less aggressive in weaning patients from mechanical ventilation. In the
study of Jubran and coworkers [5], approximately 30 % of the cohort could have
been weaned before transfer to a LTAC.
A weaning protocol should adapted to the individual patient when special circumstances arise. Whether or not a weaning protocol is employed, a collaborative
multidisciplinary approach that includes respiratory therapists, nurses, nutritionists,
physiatrist, occupational therapists, psychiatrists or psychologists, and pharmacists
is crucial to ensuring the implementation of a successful weaning in patients requiring PMV. Review of the individual areas is beyond the scope of this chapter.
6.2.2
Integrated Measures That Can Potentially Increase

Successful Weaning Rate
A weaning protocol increases ventilator-free days but does not improve the successful weaning rate [7]. The balance between inspiratory muscle capacity and load
determines a successful weaning rate. In fact, severe diaphragm muscle weakness is
common in patients transferred to LTAC [15].
In a study of 57 patients with sepsis and receiving mechanical ventilation,
Supinski and Callahan [15] measured twitch transdiaphragmatic pressure (Pditw) in
response to magnetic stimulation of bilateral phrenic nerves. Patients with Pditw of
10 cm H2O or greater (28 %, n = 16) had a better outcome than those with less than
10 cm H2O (72 %, n = 41). Seven of 41 (17 %) patients with Pditw of less than 10 cm
H2O were admitted to a LTAC compared with only 1 of 16 patients (6 %) with Pditw
of 10 cm H2O or greater. Respiratory muscle load, reflected by respiratory system
compliance and resistance, was not significantly different among groups. Severe
diaphragm muscle weakness, defined as Pditw of less than 10 cm H2O, was an important determinant of prolonged mechanical ventilation [15]. Thus, measures to
improve diaphragm muscle strength and/or endurance would be expected to expedite discontinuation from mechanical ventilation. Indeed, in a single blind, randomized controlled trial, Martin and coworkers [16] tested the efficacy of inspiratory
muscle strength (IMS) training on weaning outcome in patients with PMV. Patients
had received mechanical ventilation for an average of 6.5 weeks and had failed
multiple SBTs. Patients were randomly allocated into Sham and IMS training
groups. In the IMS training group, inspiratory muscle training with a threshold
training device utilizing high pressure and low repetition training (four sets of 610
inspiratory efforts daily, 5 days per week at the maximal pressure tolerated) was
implemented until weaned or for 28 days. The IMS training group improved
46
A. Magidova et al.
maximal inspiratory pressure (MIP) by 22 %, and 71 % of the patients were weaned,

whereas in the Sham group, MIP did not change significantly, and 47 % of the
patients were weaned (approximately the same rate as that of Scheinhorn et al [4]).
This study demonstrated the utility of IMS training in patients who failed multiple
SBTs. The incorporation of IMS training in a weaning protocol on admission to a
LTAC has the potential to enhance the rate of weaning success, inasmuch as admission to a LTAC implies that the patient has failed multiple SBTs in the home ICU.
In addition to diaphragm muscle weakness, limb muscle weakness is also common in patients requiring PMV as a result of prolonged immobilization related to
neuromuscular blockade, sedation, and underlying illness. ICU-acquired muscle
weakness occurs in approximately 50 % of patients admitted to the ICU [17] and is
associated with dramatically prolonged mechanical ventilation, length of ICU and
hospital stay, and mortality. Evidence suggests that physiotherapy intervention
focusing on early progressive mobilization in mechanically ventilated patients is
feasible and safe [18], resulting in reduced ICU and hospital length of stay [19].
Despite the safety and beneficial effects of early mobilization, currently only a few
patients on mechanical ventilation receive physiotherapy with early ambulation [20,
21]. In a retrospective study of 49 patients requiring PMV, in which all patients were
bedridden with severe upper and lower limb muscle weakness, initiation of physical
therapy on admission to a LTAC, followed by aggressive whole-body rehabilitation
after successful SBT for 4 h or greater, resulted in significantly increased upper and
lower limb muscle strength [22]. Patients were able to stand and ambulate prior to
discharge. All patients were successfully weaned from mechanical ventilation,
however, 3 patients required subsequent intermittent support, and 6 patients died
prior to discharge. Fifteen patients (31 %) were weaned in less than 7 days. Stepwise
multiple regression analysis demonstrated that upper limb motor strength, prior
exposure to neuromuscular blockade, and systemic corticosteroid were determinants of weaning time. Although the study of Martin et al. [22] lacked a control
group, the results suggest that whole-body physical therapy on admission to a LTAC
improves weaning time and increases the successful weaning rate. The above findings remain to be confirmed with a prospective randomized-control study, particularly when whole-body rehabilitation is continued from an ICU setting to a
LTAC. Taken together, the studies of Martin [16] and Martin [22] suggest that augmentation of both inspiratory muscle capacity and limb muscle strength, respectively, must be an integral part of a weaning protocol.
6.2.3
Factors That Constitute Weaning Protocol for Patients

Requiring PMV
Although protocol-based ventilator weaning has a structured sequence of procedures, it should be adaptable to the individual patient as circumstances dictate. The
patient must have cardiopulmonary stability and a Glasgow Coma Scale greater
than 13 [5]. Table 6.1 provides an example of a weaning protocol for patients requiring PMV, incorporating IMS and whole-body rehabilitation evaluation and training
at the time of admission to a LTAC. Both IMS training and whole-body physical
47
Table 6.1 Approach to weaning for patients with prolonged mechanical ventilation
I. Pre-daily screening at time of admission:
Evaluate for clinical stability including sedatives, analgesics requirement and delirium [24]
Glasgow Coma Scale >13
Evaluate to begin inspiratory muscle strength training
Evaluate to begin whole-body physical therapy
II. Daily screening:
Hemodynamic variables
Heart rate between 50 and 120 beats/min
Systolic blood pressure between 90 and 180 mmHg
[All variables must be met]
Respiratory variables
FIO2 <50 % with SpO2 >90 %; PEEP <8 cm H2O
The following variables measured during spontaneous breathing:
Tidal volume >5 ml/kg
Respiratory rate <35 breaths/min
Rapid shallow breathing index (f/VT) <105 breaths/min/l
Maximum inspiratory pressure less than 20 cm H2O
[4 out of 5 variables must be met]
III. Spontaneous breathing trial (SBT)
One hour SBT via tracheostomy collar and humidified O2
Assess for respiratory distress
Heart rate increased or decreased >20 % of baseline
Systolic blood pressure <80 or >180 mmHg
SpO2 <90 %
Respiratory rate >35 breaths/min
Agitation
Anxiety
Diaphoresis
Patient request
If any of the above signs are present, return patient to previous ventilator settings and
reassess the following morning.
IV. Weaning method
Tracheostomy collar with humidified O2:
If patient tolerates 1 h of SBT, increase SBT (tracheostomy collar and humidified O2) to a
total of 2 h, progressing with an increment of 2 h daily (i.e., 4, 6, 8, 10, 12 h) divided in
two separate sessions (e.g., 2 h twice a day for a total of 4 h of SBT).
If patient tolerates 12 h of SBT, increase duration with an increment of 4 h daily (i.e., 16,
20, 24 h).
Return to previous ventilator settings for any intolerance.
Pressure support:
If patient does not tolerate within the first 12 h of SBT, may use pressure support (PS) as
alternative weaning method. PS level titrated until patient does not display signs of
respiratory distress (see above) for at least 6 h before attempts to decrease PS level, or
reassess the following morning.
For PS trial, reduce PS level daily at a decrement of 2 cm H2O twice a day until patient
tolerates PS of less than 6 cm H2O for 12 h, then progress to SBT via tracheostomy collar
and humidified O2 with an increment of 4 h daily as above (i.e., 16, 20, 24 h).
48
A. Magidova et al.
therapy are integral parts of a weaning protocol and need to commence early. Daily
screening is for assessment of hemodynamic and respiratory stability. Once hemodynamic and respiratory stability is achieved, a SBT, the gold standard assessment
of inspiratory muscle capacity and endurance, begins with increasing duration as
weaning progresses. Based on the study of Jubran et al. [5], a weaning method using
a tracheostomy collar with humidified O2 was superior to pressure support. Weaning
with a tracheostomy collar and humidified O2 resulted in shorter median weaning
time. However, in patients who had early weaning trial failure, defined as failed
weaning in less than 12 h, weaning time was equivalent with tracheostomy collar or
pressure support (PS). In those patients, an alternative weaning method with PS
may be employed.
6.3
Summary
A weaning protocol in patients requiring PMV leads to shortened weaning time and
expedient decision-making but not an increase in weaning success rate. Increasing
the successful weaning rate requires enhancement of inspiratory muscle capacity
and limb muscles strength. Overall weaning time is shortened with unsupported
breathing (tracheostomy collar). In patients with early weaning failure, weaning
time is similar using PS as an alternative weaning method.
6.4
Future Research
There exists a paucity of studies of the effects inspiratory muscle strength training
and whole-body rehabilitation in patients requiring PMV. During cardiothoracic
surgery, brief phrenic nerve stimulation has been shown to increase force generation
in diaphragm muscle single-fiber preparation compared with unstimulated contralateral hemidiaphragm [23]. This preliminary data suggests that intermittent phrenic
nerve stimulations have the potential to improve diaphragm muscle strength in
patients requiring PMV. Similarly, because upper limb muscle strength training
contributes to shorten weaning time [22], studies of physical therapy focusing on
upper limb muscle strengthening are needed.
References
1. MacIntyre NR, Epstein SK, Carson S, et al. Management of patients requiring prolonged
mechanical ventilation: report of a NAMDRC consensus conference. Chest. 2005;128:
393754.
2. Lone NI, Walsh TS. Prolonged mechanical ventilation in critically ill patients: epidemiology,
outcomes and modeling the potential cost consequences of establishing a regional weaning
unit. Crit Care. 2011;15:R102.
3. Leroy G, Devos P, Lambiotte F, et al. One-year mortality in patients requiring prolonged
mechanical ventilation: multicenter evaluation of the ProVent score. Crit Care. 2014;18:R155.
49
4. Scheinhorn DJ, Hassenpflug MS, Votto JJ, et al. Ventilation outcomes study group. Post-ICU
mechanical ventilation at 23 long-term care hospitals: a multicenter outcomes study. Chest.
2007;131:8593.
5. Jubran A, Grant BJ, Duffner LA, et al. Effect of pressure support vs unassisted breathing
through a tracheostomy collar on weaning duration in patients requiring prolonged mechanical
ventilation: a randomized trial. JAMA. 2013;309:6717.
6. Rose L, Fraser IM. Patient characteristics and outcomes of a provincial prolonged-ventilation
weaning centre: a retrospective cohort study. Can Respir J. 2012;19:21620.
7. Scheinhorn DJ, Chao DC, Stearn-Hassenpflug M, et al. Outcomes in post-ICU mechanical
ventilation: a therapist-implemented weaning protocol. Chest. 2001;119:23642.
8. Gupta P, Giehler K, Walters RW, et al. The effect of a mechanical ventilation discontinuation
protocol in patients with simple and difficult weaning: impact on clinical outcomes. Respir
Care. 2014;59:1707.
9. Blackwood B, Burns KE, Cardwell CR, et al. Protocolized versus non-protocolized weaning
for reducing the duration of mechanical ventilation in critically ill adult patients. Cochrane
Database Syst Rev. 2014;(11):CD006904.
10. Ely EW, Baker AM, Dunagan DP, et al. Effect on the duration of mechanical ventilation of
identifying patients capable of breathing spontaneously. N Engl J Med. 1996;335:18649.
11. Krishnan JA, Moore D, Robeson C, et al. A prospective, controlled trial of a protocol-based
strategy to discontinue mechanical ventilation. Am J Respir Crit Care Med. 2004;169:6738.
12. Rose L, Fowler RA, Fan E, et al. Prolonged mechanical ventilation in Canadian intensive care
units: a national survey. J Crit Care. 2015;30:2531.
13. Hill NS. Following protocol: weaning difficult-to-wean patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001;164:1867.
14. Ely EW, Bennett PA, Bowton DL, et al. Large scale implementation of a respiratory therapistdriven protocol for ventilator weaning. Am J Respir Crit Care Med. 1999;159:43946.
15. Supinski GS, Callahan LA. Diaphragm weakness in mechanically ventilated critically ill
patients. Crit Care. 2013;17:R120.
16. Martin AD, Smith BK, Davenport PD, et al. Inspiratory muscle strength training improves
weaning outcome in failure to wean patients: a randomized trial. Crit Care. 2011;15:R84.
17. Stevens RD, Dowdy DW, Michaels RK, et al. Neuromuscular dysfunction acquired in critical
illness: a systematic review. Intensive Care Med. 2007;33:187691.
18. Hodgson CL, Stiller K, Needham DM, et al. Expert consensus and recommendations on safety
criteria for active mobilization of mechanically ventilated critically ill adults. Crit Care.
2014;18:658.
19. Stiller K. Physiotherapy in intensive care: an updated systematic review. Chest. 2013;144:
82547.
20. Nydahl P, Ruhl AP, Bartoszek G, et al. Early mobilization of mechanically ventilated patients:
a 1-day point-prevalence study in Germany. Crit Care Med. 2014;42:117886.
21. Hodgson C, Bellomo R, Berney S, et al. Early mobilization and recovery in mechanically
ventilated patients in the ICU: a bi-national, multi-centre, prospective cohort study. Crit Care.
2015;19:81.
22. Martin UJ, Hincapie L, Nimchuk M, et al. Impact of whole-body rehabilitation in patients
receiving chronic mechanical ventilation. Crit Care Med. 2005;33:225965.
23. Ahn B, Beaver T, Martin T, et al. Phrenic nerve stimulation increases human diaphragm fiber
force after cardiothoracic surgery. Am J Respir Crit Care Med. 2014;190:8379.
24. Dale CR, Kannas DA, Fan VS, et al. Improved analgesia, sedation, and delirium protocol
associated with decreased duration of delirium and mechanical ventilation. Ann Am Thorac
Soc. 2014;11:36774.
Evaluation of Cough During Weaning

from Mechanical Ventilation: Influence
in Postextubation Failure
Pascal Beuret
Abbreviations
PCEF
NIV
MAC
MI
peak cough expiratory flow

noninvasive ventilation
manually assisted coughing
mechanical insufflation
The inability to clear respiratory secretions is a major cause of extubation failure [1],
causing an increase in the resistive load imposed on the respiratory muscles. The prediction before extubation of the ability of a patient to clear the secretions once extubated is challenging. The International Consensus Conference 2007 on weaning from
mechanical ventilation recommended that patients who successfully pass a spontaneous breathing trial should be extubated if neurological status, excessive secretions,
and airway obstruction are not issues [2]. The evaluation of cough strength is not
mentioned here, but some studies emphasize its impact on extubation outcome.
The occurrence of sputum retention after extubation results in excessive secretions present in the lower airway and ineffective cough. Secretions may be present
before extubation, notably in cases of bronchopulmonary infection under treatment.
However, excess secretions may also appear suddenly after extubation as a result of
glottis dysfunction caused by prolonged intubation or because of a coexisting neurologic disease. This latter mechanism is clearly difficult to predict. Evaluation of
the amount of respiratory secretions and of cough strength before extubation is
important.
P. Beuret, MD
Intensive Care Unit, Centre Hospitalier Roanne, 28 rue de Charlieu, Roanne 42328, France
e-mail: pascal.beuret@ch-roanne.fr
DOI 10.1007/978-3-319-04259-6_7
51
52
P. Beuret
7.1
Criteria of Evaluation
7.1.1
Amount of Secretions
Two criteria are used, one being the volume of secretions. This evaluation is usually
subjective mild, moderate, or copious [35] and inter-rater reliability is uncertain. A more rigorous version of the method uses the mean volume of suctioned
secretions collected per hour [6, 7]. A second criteria is the frequency of suctioning:
usually the number of tracheal aspirates during the 24 h before extubation [5, 8, 9].
This evaluation is easier and more reproducible, however, the method of suctioning
is not always the same (e.g., suctioning on demand or systematic).
7.1.2
Cough Strength
Cough strength is usually evaluated subjectively poor, moderate, or excellent

by asking the patient to cough through the endotracheal tube [35]. The white
card test has been proposed to optimize this evaluation [4, 7]. A white card is
placed in front of the proximal tip of the endotracheal tube and the cough strength
is judged adequate if the card is soiled by secretions when the patient coughs.
However, this test may be negative despite an adequate cough strength if secretions are absent.
Cough strength is evaluated objectively by the measurement of the peak cough
expiratory flow (PCEF), where the patient is asked to cough on demand (Fig. 7.1).
This measure is widely used as an indicator of an effective cough, especially in
neuromuscular disease [10]. In intubated patients, this measure may be performed with a mechanical peak flow meter [6, 7]. However, the accuracy of this
device for measuring low peak expiratory flows, as is the case in intubated
Fig. 7.1 Air flow during

the three steps of cough
effort: (1) deep inspiration,
(2) compression step with
glottis occlusion and
contraction of expiratory
muscles, and (3) exhalation
step with sudden glottis
opening and forced
expiration characterized by
the peak of expiratory flow
(PCEF)
Air flow (l/s)

3
PCEF
Time
(1)
(2)
(3)
Impact of the Evaluation of Cough on Extubation Outcome
53
patients, is uncertain. The PCEF has also been measured with an electronic flow
meter [8] (Fig. 7.2). Alternatively, involuntary PCEF may be measured after
inducing a cough reflex by dripping 2 ml of normal saline in the endotracheal
tube [11].
7.2
Predicting Extubation Outcome
Some studies found an association between the volume of secretions and extubation
outcome [4, 7], whereas others did not [3, 6]. In a study with a large sample size, the
frequency of secretions during the last 24 h was associated with extubation outcome
[5]. Moreover, when focusing on patients with excessive secretions, the patients
requiring suctioning every 2 h or more were at risk of extubation failure [4, 9].
When the evaluation of cough is subjective, the results are conflicting: in some
studies the efficacy of cough is associated with outcome of extubation [4], in other
studies not [3, 5]. Similarly, the white card test was either predictive of extubation
outcome [4] or not [7]. Conversely, all studies that objectively measured cough
strength by PCEF found a significant association with extubation outcome [68,
11]: a low PCEF before extubation increases the risk of extubation failure by five- to
sevenfold. The cut-off value of PCEF differed depending on the device used.
7.3
Impact on the Decision to Extubate
As stated by the International Consensus Conference 2007 on weaning from

mechanical ventilation [2], it is recommended that patients who successfully pass a
Fig. 7.2 Measure of the peak cough expiratory flow with the PiKo-1 (E-Ness, Aix-en-Provence,
France). The patient, who was in the semi-recumbent position, was instructed to inspire deeply
through a three-way connector positioned between the proximal tip of the tracheal tube and the
PiKo-1. The external port of the connector was then occluded, and the patient was instructed to
cough as strongly as possible through the tracheal tube
54
P. Beuret
spontaneous breathing trial should not be extubated if the amount of respiratory

secretions is excessive; the need to suction the patient every 2 h or less seems here
a reliable criteria.
Concerning the evaluation of cough strength by the measurement of PCEF, the
positive predictive value of the test was low in all studies. For example, in a study
using an electronic flowmeter, the risk of extubation failure was 3.5 % for the
patients with a PCEF > 35 l/min and 24 % for those who did not cough on demand
or with a low PCEF < 35 l/min (RR = 6.9, 95 % CI 224, p = 0.002) [8]. Therefore, a
low PCEF does not preclude extubation but selects patients who are at risk and
need specific management after extubation.
7.4
Management after Extubation
Noninvasive ventilation (NIV) has been proposed as a prophylactic measure

after extubation for patients who are at high risk for reintubation. Three studies
showed a beneficial effect, with one study showing a reduction of reintubation
rate [12] and the others a reduction in the rate of respiratory failure post-extubation, which was the primary end-point [13, 14]. In the study by Nava et al. [12],
a weak cough before extubation was one of the criteria for enrollment. In a
before-after study, our group evaluated the impact on extubation outcome of
identifying weak cough at extubation by the measure of PCEF and assisting
these patients with NIV [15]. Two cohorts of patients were compared: a historical cohort of 141 patients in 20052006, where the physician was blinded to the
value of PCEF (blinded cohort) and no prophylactic NIV was applied, and an
open cohort of 151 patients in 20122013, where prophylactic NIV was applied
to the patients with PCEF < 35 l/min or inability to cough on demand. Extubation
failure was defined by the need of reintubation within 48 h following extubation. The rate of extubation failure was significantly reduced: 11/55 (20 %) in
the blinded cohort versus 3/51 (6 %) for the open cohort (p = 0.043), without
increasing the total duration of ventilator assistance. This result suggests that
NIV could be useful when applied systematically after extubation to patients
with a weak cough before extubation.
If sputum retention occurs after extubation, chest physiotherapy is indicated.
In patients with neuromuscular disease, it has been shown that PCEF was significantly correlated with maximal inspiratory capacity and expiratory reserve volume, which contributed to 44 % and 13 %, respectively, of the variance [10]. This
study demonstrated that cough effectiveness assessed by the measure of PCEF
was similar during manually assisted coughing (MAC) or after mechanical insufflation with an intermittent positive-pressure breathing device (MI). The
combination of MI and MAC significantly increased PCEF when compared with
MAC or MI alone. When these techniques of physiotherapy fail to clear the airways of secretions, the increase of resistive load imposed on the respiratory muscles may lead to post-extubation respiratory failure. In this situation, reintubation
is recommended [2].
Impact of the Evaluation of Cough on Extubation Outcome
55
Patients who successfully pass a spontaneous breathing trial should not be

extubated if the amount of respiratory secretions is excessive; the need to
suction the patient every 2 h or more seems here a reliable criteria.
The evaluation of cough before extubation requires measurement of peak
cough expiratory flow.
The detection before extubation of a weak cough strength does not preclude extubation but selects patients who are at risk and require specific
management after extubation.
These patients seem to benefit from prophylactic noninvasive ventilation
after extubation.
When sputum retention occurs after extubation, physiotherapy is indicated, and, if it fails, reintubation is recommended.
References
1. Epstein SK. Decision to extubate. Intensive Care Med. 2002;28:53546.
2. Boles JM, Bion J, Connors A, et al. Weaning from mechanical ventilation. Statement of the
Sixth International Consensus Conference on Intensive Care Medicine. Eur Respir J.
2007;29:103356.
3. Frutos-Vivar F, Ferguson ND, Esteban A, et al. Risk factors for extubation failure in patients
following a successful spontaneous breathing trial. Chest. 2006;130:166471.
4. Khamiees M, Raju P, DeGirolamo A, et al. Predictors of extubation outcome in patients who
have successfully completed a spontaneous breathing trial. Chest. 2001;120:126270.
5. Miu T, Joffe AM, Yanez ND, et al. Predictors of reintubation in critically ill patients. Respir
Care. 2014;59(2):17885.
6. Smina M, Salam A, Khamiees M, et al. Cough peak flows and extubation outcomes. Chest.
2003;124:2628.
7. Salam A, Tilluckdharry L, Amaoteng-Adjepong Y, et al. Neurologic status, cough, secretions
and extubation outcomes. Intensive Care Med. 2004;30:13349.
8. Beuret P, Roux C, Auclair A, et al. Interest of an objective evaluation of cough during weaning
from mechanical ventilation. Intensive Care Med. 2009;35:10903.
9. Mokhlesi B, Tulaimat A, Gluckman TJ, et al. Predicting extubation failure after successful
completion of a spontaneous breathing trial. Respir Care. 2007;42(12):17107.
10. Trebbia G, Lacombe M, Fermanian C, et al. Cough determinants in patients with neuromuscular disease. Respir Physiol Neurobiol. 2005;146(23):291300.
11. Su WL, Chen YH, Chen CW, et al. Involuntary cough strength and extubation outcomes for
patients in an ICU. Chest. 2010;137(4):77782.
12. Nava S, Gregoretti C, Fanfulla F, et al. Noninvasive ventilation to prevent respiratory failure
after extubation in high-risk patients. Crit Care Med. 2005;33:246570.
13. Ferrer M, Valencia M, Nicolas JM, et al. Early noninvasive ventilation averts extubation failure
in patients at risk: a randomized trial. Am J Respir Crit Care Med. 2006;173:16470.
14. Ferrer M, Sellares J, Valencia M, et al. Non-invasive ventilation after extubation in hypercapnic patients with chronic respiratory disorders: randomized controlled trial. Lancet.
2009;374:10828.
15. Beuret P, Roux C, Pelletier N, et al. Detection and assistance of weak cough at extubation:
impact on outcome. Abstract ESICM Congress Intensive Care Med 2014;40(suppl 1): O114.
Implications of Manual Chest

Physiotherapy and Technology
in Preventing Respiratory Failure after
Extubation
Maria Lusa Soares, Margarida Torres Redondo,
and Miguel R. Gonalves
8.1
Introduction
The process of discontinuing mechanical ventilation must balance the risk of complications caused by unnecessary delays in extubation with the risk of complications resulting from early discontinuation and the need for reintubation [1].
Extubation failure occurs in 1020 % of patients who meet all weaning criteria [2]
and is associated with a higher mortality rate [3]. After extubation, if respiratory
failure happens, a reintubation must be performed. Therefore, strategies that can
prevent the development of respiratory failure after extubation and the need for
reintubation are necessary to reduce the percentage of extubation failure. Airway
secretion clearance and noninvasive ventilation (NIV) can be two of the most helpful approaches to addressing extubation failure.
Patients in the intensive care setting often have impaired airway clearance.
Studies show the importance of cough strength and the amount of secretions for a
successful extubation [4, 5]. Beuret et al. [6] showed that extubation failure was
more likely among patients who were unable to cough on command or who had a
peak expiratory flow rate during a cough of <35 l/min. Therefore, following extubation, all patients should be closely monitored and an early airway secretion clearance must be performed to prevent reintubation. This may include manual chest
M.L. Soares, PT M.T. Redondo, MD

Pulmonology Department, University Hospital of So Joo, Porto, Portugal
M.R. Gonalves, PT, PhD (*)
Pulmonology Department, University Hospital of So Joo, Porto, Portugal
Faculty of Medicine, University of Porto, Porto, Portugal
Instituto de Investigao e Inovao em Sude, Universidade do Porto, Porto, Portugal
e-mail: goncalvesmr@gmail.com
DOI 10.1007/978-3-319-04259-6_8
57
58
M.L. Soares et al.
physiotherapy techniques, intrapulmonary percussive ventilation, high-frequency

chest wall oscillation, and mechanical insufflation-exsufflation (MI-E).
NIV can be used in the period after extubation to prevent extubation failure [7].
Patients most likely to benefit from the early application of NIV following extubation
include those with chronic obstructive pulmonary disease (COPD), especially those who
have compensated hypercapnia during their spontaneous breathing trial before extubation. However, routine use of NIV immediately after extubation is not recommended.
8.2
Chest Physiotherapy
The effective elimination of airway mucus and other debris is one of the most
important factors that permits successful use of ventilation support (invasive and
noninvasive) for patients with either ventilator or oxygenation impairment.
Approaches to prevent airway secretion retention include pharmacotherapy to
reduce mucus hypersecretion or to liquefy secretions, and the application of chest
physiotherapy techniques. The goals of chest physiotherapy, in ventilator-dependent
patients, are to maintain lung compliance and normal alveolar ventilation at all
times and to maximize cough flows for adequate bronchopulmonary secretion clearance [8]. Further studies are needed to identify the patients and circumstances that
are at risk from complications or adverse effects of manual chest physiotherapy.
Airway clearance refers to two separate, but connected, mechanisms: mucociliary clearance and cough clearance.
8.3
Mucociliary Clearance
Positioning the patient to enable gravity to assist the flow of bronchial secretions
from the airways has been a standard treatment for some time in patients with
retained secretions [9]. The combination of positioning with breathing techniques
and manual chest physiotherapy increases the effectiveness of airway clearance in
patients with different etiologies. Breathing control techniques include autonomous
breathing exercises such as forced and deep expirations and diaphragmatic breathing to optimize airway mucus clearance. Positioning can also place the patient at
risk for skin and cardiac complications, cerebral blood flow or intracranial pressure
changes, and gastroesophageal reflux [8]. Manual chest percussion (clapping) and
chest wall vibration have been shown to increase in airflow obstruction and hypoxemia [9]. Guidebooks on manual thoracic techniques are available demonstrating
the hand placements and thrusting techniques in children and adults [10].
8.3.1
Intrapulmonary Percussive Ventilation
The intrapulmonary percussive ventilator is an airway clearance device that simultaneously delivers aerosolized solution and intrathoracic percussion. This modified
Respiratory Physiotherapy in Preventing Respiratory Failure After Extubation
59
method of intermittent positive pressure breathing superimposes high-frequency

minibursts of gas (at 50550 cycles/min) on the patients own respiration. This creates a global effect of internal percussion of the lungs, which can promote clearance
of the peripheral bronchial tree. The high-frequency gas pulses expand the lungs,
vibrate and enlarge the airways, and deliver gas into distal lung units, beyond the
accumulated mucus [11].
Intrapulmonary percussive ventilation can be delivered through a mouthpiece, a
face mask, or through endotracheal and tracheostomy tubes. The primary aims of
this technique are to reduce secretion viscosity, promote deep lung recruitment,
improve gas exchange, deliver a vascular massage, and protect the airway against
barotrauma. The main contraindications are the presence of diffuse alveolar hemorrhage with hemodynamic instability. Relative contraindications include active or
recent gross hemoptysis, pulmonary embolism, subcutaneous emphysema, bronchopleural fistula, esophageal surgery, recent spinal infusion, spinal anesthesia or
acute spinal injury, presence of a transvenous or subcutaneous pacemaker, increased
intracranial pressures, uncontrolled hypertension, suspected or confirmed pulmonary tuberculosis, bronchospasm, empyema or large pleural effusion and acute cardiogenic pulmonary edema [12].
8.3.2
High-Frequency Chest Wall Oscillation
During high-frequency chest wall oscillation, positive pressure air pulses are applied
to the chest wall through a vest or under a chest shell. This technique provides oscillation at 525 Hz. Mechanical vibration is performed at frequencies up to 40 Hz.
Vibration is applied during the entire breathing cycle or during expiration only. The
adjustable inspiratory/expiratory ratio permits asymmetrical inspiratory and expiratory pressure changes (e.g., +36 cmH20), which favors higher exsufflation flow
velocities to mobilize secretions. The average length of time spent in each treatment
session will vary according to patient tolerance, amount and consistency of secretions,
and the phase of the patients illness (acute or chronic). Simultaneous use of an aerosolized medication or saline is recommended throughout the treatment. This humidifies the air to counteract the drying effect of the increased airflow [13]. High-frequency
chest wall oscillation may act like a physical mucolytic, reducing both the spinnability
and viscoelasticity of mucus and enhancing clearance by coughing [9, 11].
Contraindications for this therapy are mostly the same as for intrapulmonary percussive ventilation, with the addition of head or unstable neck injury, burns, open
wounds, infection or recent thoracic skin grafts, osteoporosis, osteomyelitis, coagulopathy, rib fracture, lung contusion, distended abdomen, and chest wall pain [9, 13].
8.4
Cough Clearance
The forced expiratory technique (FET, also known as huffing) consists of an active,
passive, or assisted increase of the expiratory flow with the glottis open. Low lung
60
M.L. Soares et al.
volumes mobilize distal secretions and high lung volumes remove tracheal and
proximal bronchial secretions [14].
Manually assisted cough has been shown to increase peak cough flow about
2030 %. During a forced exhalation, a compression is held in the zone of the epigastrium with one hand while the other hand and arm are placed on the chest, preventing paradoxical thoracic expansion. Abdominal thrust and thoracic thrust are
variations of this technique. This technique can be combined with air stacking to
further increase the cough flow. Air stacking is a technique that consists of deep
lung insufflations to the maximum insufflation capacity performed with a manual
resuscitator or a volumetric ventilator [15].
8.4.1
Mechanical Insufflation-Exsufflation
Mechanical insufflation-exsufflation (MI-E) is a therapy in which the device gradually inflates the lungs (insufflation), followed by an immediate and abrupt change to
negative pressure, which produces a rapid exhalation (exsufflation) [16]. The rapid
change from positive to negative pressure is aimed at stimulating the airflow changes
that occur during a cough, thereby assisting sputum clearance. MI-E can be provided
via an oronasal mask, a simple mouthpiece, or via translaryngeal or tracheostomy
tube. When delivered via the latter, the cuff, when present, should be inflated [17]. The
device can be manually or automatically cycled, depending on the model. One treatment consists of 35 cycles of in-exsufflation (with or without an abdominal thrust
during exsufflation) followed by about 30 s of rest [16]. This is repeated several times
or until secretions have been sufficiently expelled. Contraindications of the technique
include previous barotrauma, the existence of bullae, emphysema, or bronchial hyperreactivity [18].
MI-E should not be used in hypotensive patients or those with significant hemoptysis. Contraindications of the technique include previous barotrauma, the existence
of bullae, emphysema, or bronchial hyperreactivity. Even when used following
abdominal surgery or extensive chest wall surgery, no disruption of recently sutured
wounds was noted. Secondary effects, such as pneumothorax, aspiration, or coughing up blood, are reduced considerably by treating the mentioned contraindications.
On the other hand, gurgling noises and abdominal distension are rare and can be
eliminated by lowering the insufflation pressure. The significant increase of forced
expiratory flows in periods immediately following post-exsufflation indicates that
MI-E does not provoke obstruction of the airways. In patients with spinal shock can
present bradycardias, MI-E should be carried out with caution, with gradual increase
in pressures or premedication with anticholinergics.
Whether via the upper airway or via indwelling airway tubes, routine airway
suctioning misses the left main stem bronchus about 90 % of the time. MI-E, on the
other hand, provides the same exsufflation flows in both left and right airways without the discomfort or airway trauma of tracheal suctioning, and it can be effective
when suctioning is not.
Respiratory Physiotherapy in Preventing Respiratory Failure After Extubation
61
MI-E has been shown to increase peak cough flow (PCF) in patients with neuromuscular disease [19]. An increase in PCF is thought to improve the efficacy of the
cough and thus assist in secretion removal. Therefore, MI-E has been described as
an efficient technique in the acute setting for neuromuscular disorders patients in
the treatment of respiratory failure resulting from upper respiratory tract infections
[20], to avoid intubation [21], to facilitate extubation and decannulation, and to
prevent post-extubation failure [22].
Gonalves et al. [23] found that secretion management with MI-E may work as
a useful complementary technique to prevent reintubation in patients in whom acute
respiratory failure develops in the first 48 h after extubation, suggesting that MI-E
is safe and efficient in ICU respiratory patients with indications for mechanical
ventilation.
Conclusions
Hypersecretion, reduced mucus transport, and airflow obstruction are impairments, while chronic coughing and expectoration of mucus or dyspnea can limit
the patient and can therefore be classified as disabilities.
There continues to be widespread debate as to which airway clearance regimen should be used and when. In most comparisons, bronchial hygiene physical
therapy produced no significant effects on pulmonary function, apart from clearing sputum in COPD and in bronchiectasis. There is not enough evidence to
support or refute the use of bronchial hygiene physical therapy in people with
COPD and bronchiectasis. However, there is strong evidence that supports the
use of respiratory physical therapy techniques for secretion clearance in neuromuscular disease to improve quality of life and survival.
If one or more of the techniques are proven to be significantly more effective
and efficient, consideration would still have to be given to the technique to which
a particular patient will adhere and, in todays world, to cost implications. Longterm studies (1 4 years) are much harder to set up and expensive, but necessary
to increase understanding of airway clearance. Efficacy studies should be performed in homogeneous groups of patients with well-described characteristics in
terms of age, sex, diagnosis, baseline pulmonary function tests, and, if possible,
compliance characteristics. The effects of secretion clearance techniques are
probably determined by special characteristics of subgroups, characterized by
lung mechanics, bronchial hyperreactivity, rheological properties of mucus, and
localization of mucus in the bronchial tree.
In patients with ventilator impairment, NIV is an efficient technique in respiratory management; however, in the majority of the cases, secretions are excessive and NIV alone is likely to fail. The role of respiratory physiotherapy in these
cases is crucial to permit an efficient treatment.
Disclosure Financial disclosure statements have been obtained, and no conflicts of interest have
been reported by the authors or by any individuals in control of the content of this chapter.
62
M.L. Soares et al.
References
1. Boles JM, Bion J, Connors A, Herridge M, Marsh B, Melot C, Pearl R, Silverman H, Stanchina
M, Vieillard-Baron A, Welte T. Weaning from mechanical ventilation. Eur Respir J.
2007;29:103356.
2. Thille AW, Richard JCM, Crochard L. The decision to extubate in the intensive care unit. Am
J Respir Crit Care Med. 2013;187(12):1294302.
3. Frutos-Vivar F, Esteban A, Apezteguia C, et al. Outcome of reintubated patients after scheduled extubation. J Crit Care. 2011;26:5029.
4. Coplin WM, Pierson DJ, Cooley KD, et al. Implications of extubation delay in brain-injured
patients meeting standard weaning criteria. Am J Respir Crit Care Med. 2000;161:1530.
5. Khamiees M, Raju P, DeGirolamo A, et al. Predictors of extubation outcome in patients who
have successfully completed a spontaneous breathing trial. Chest. 2001;120(4):1262.
6. Beuret P, Roux C, Auclair A, et al. Interest of an objective evaluation of cough during weaning
from mechanical ventilation. Intensive Care Med. 2009;35(6):1090.
7. Hess DR. Noninvasive ventilation for acute respiratory failure. Respir Care.
2013;58(6):95072.
8. Van der Schans C, Bach J, Rubin BK. Chest physiotherapy: mucus-mobilization techniques.
In: Bach JR, editor. Noninvasive mechanical ventilation. 1st ed. Philadelphia: Hanley & Belfus
Inc.; 2002. p. 25984.
9. Pryor JA. Physiotherapy for airway clearance in adults. Eur Respir J. 1999;14:141824.
10. Hubert J. Mobilisations du Thorax. Les edicions Medicales et Paramedicales de Charleroi,
Montignies-sur-Sambre. Belgium; 1989.
11. Hess DR. The evidence for secretion clearance techniques. Respir Care. 2001;46:127693.
12. Nava S, Barbarito N, Piaggi G, et al. Physiological response to intrapulmonary percussive
ventilation in stable COPD patients. Respir Med. 2006;100:152633.
13. Scherer TA, Barandun J, Martinez E, et al. Effect of high-frequency oral airway and chest wall
oscillation and conventional chest physical therapy on expectoration in patients with stable
cystic fibrosis. Chest. 1998;113:101927.
14. Fink JB. Forced expiratory technique, directed cough, and autogenic drainage. Respir Care.
2007;52(9):121021; discussion 213.
15. Bach JR, Goncalves MR, Paez S, Winck JC, Leitao S, Abreu P. Expiratory flow maneuvers in
patients with neuromuscular diseases. Am J Phys Med Rehabil. 2006;85(2):10511.
16. Homnick D. Mechanical insufflation-exsufflation for airway mucus clearance. Respir Care.
2011;56(6):888.
17. Gomez-Merino E, Sancho J, Marin E, et al. Mechanical insufflation-exsufflation: pressure,
volume, and flow relationships and the adequacy of the manufacturers guidelines. Am J Phys
Med Rehabil. 2002;81(8):57983.
18. Whitney J, Harden B, Keilty S. Assisted cough: a new technique. Physiotherapy.
2002;88(4):2017.
19. Chatwin M, Ross E, Hart N, et al. Cough augmentation with mechanical insufflation/exsufflation in patients with neuromuscular weakness. Eur Respir J. 2003;21:5028.
20. Vianello A, Corrado A, Arcaro G, et al. Mechanical insufflation-exsufflation improves outcomes for neuromuscular disease patients with respiratory tract infections. Am J Phys Med
Rehabil. 2005;84:838.
21. Severa E, Sancho J, Zafra MJ, et al. Alternatives to endotracheal intubation for patients with
neuromuscular diseases. Am J Phys Med Rehabil. 2005;84:8517.
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Med Rehabil. 2004;83:5608.
23. Gonalves MR, Honrado T, Winck JC, et al. Effects of mechanical insufflation-exsufflation in
preventing respiratory failure after extubation: a randomized controlled trial. Crit Care.
2012;16(2):R48.
Nutrition in Ventilator-Dependent
Patients
Militsa Bitzani
Abbreviations
ABW
ALS
BEE
BIA
BMI
BW
CCI
CCIP
CHO
COPD
CRP
DEXA
EE
EN
ESPEN
FFM
FRS
IBW
IC
LBM
LTMV
MNA
MRI
Actual body weight

Amyotrophic lateral sclerosis
Basal Energy Expenditure
Bioelectrical impedance
Body mass index
Body weight
Chronically critically ill
Chronically critically ill patients
Carbohydrates
Chronic obstructive pulmonary disease
C-reactive protein
Dual X-ray absorptiometry
Energy expenditure
Enteral nutrition
European Society for Clinical Nutrition and Metabolism
Fat free mass
Functional Rating Scale
Ideal body weight
Indirect calorimetry
Lean body mass
Long-term mechanical ventilation
Mini Nutritional Assessment
Magnetic resonance imaging
M. Bitzani, MD, PhD

Intensive Care Unit, G. Papanikolaou Hosp, Thessaloniki, Greece
e-mail: bitmilly@gmail.com
DOI 10.1007/978-3-319-04259-6_9
63
64
M. Bitzani
MV
MVV
NIV
NRS 2002
PEG
PEJ
REE
SCI
SGA
VC
9.1
Mechanical ventilation
Maximum voluntary ventilation
Nutritional Risk Screening 2002
Percutaneous endoscopic gastrostomy
Percutaneous endoscopic jejunostomy
Resting energy expenditure
Spinal cord injury
subjective global assessment
Vital capacity
Introduction
Although mechanical ventilation (MV) is a lifesaving treatment in intensive care units

(ICUs), weaning from it is a difficult experience for approximately 30 % of patients.
It is estimated that 510 % of these patients evolve to chronically critically ill (CCI),
requiring prolonged care, mainly because of their dependence on MV, either invasive
or noninvasive. Long-term MV (LTMV) may also be required in a substantial number
of patients with chronic respiratory insufficiency because of chronic obstructive pulmonary disease (COPD) or restrictive lung diseases, and in unweanable patients
suffering from severe stroke, high-level spinal cord injury, terminal stages of degenerating neurological diseases, myasthenia gravis, or Guillain-Barr syndrome. The incidence of ventilator-dependent patients in Europe ranges from 2 to 30/100,000
population, and this constitutes a significant clinical and socioeconomic problem.
The pathophysiology of weaning failure is complex and multifactorial.
Malnutrition can independently interfere with the pathophysiology of weaning failure by affecting both of its main determinants, ventilatory drive and respiratory
muscle function.
The impairment of muscle function occurs via increased protein catabolism, because
both starving and critically ill patients catabolize muscle protein for fuel production. It
is estimated that the muscle mass loss per day in starving and critically ill patients can
reach approximately 200300 g and 7501000 g, respectively. This process involves
skeletal muscles, including inspiratory and expiratory intercostals and the diaphragm.
A linear relationship between body weight (BW) and diaphragm muscle mass has been
recorded [1]. Moreover, diminished muscle strength was also related to malnutrition
[2]. As shown by Arora et al. [3], underweight patients have respiratory muscle
strength, maximum voluntary ventilation (MVV), and vital capacity (VC) reduced by
37 %, 41 %, and 63 %, respectively. In addition to protein catabolism, prolonged
underfeeding induces changes in the electrophysiological properties of skeletal muscles, including imbalance in the intracellular electrolyte composition that can compromise muscle contractility and endurance. The resultant muscle weakness affects
inspiratory and expiratory muscles equally and impairs their ability to manage increased
ventilatory loads resulting from pulmonary disease or the weaning process.
Nutrition in Ventilator-Dependent Patients
65
Nutrition support has an important modulatory activity in the interaction between

metabolic rate and ventilatory drive. Refeeding succeeded in reversing the depression of hypoxic drive in underfed healthy volunteers. In addition, the impact of
protein intake on the ventilatory sensitivity to CO2 was confirmed both in healthy
volunteers and in malnourished patients without impaired respiratory function, as
well as in ventilator-dependent patients. According to these findings, high protein
intake may facilitate weaning in mechanically ventilated patients provided there are
sufficient respiratory reserves [4, 5].
Following severe illness or trauma, patients may remain hypercatabolic for more
than 12 months. This may explain why malnutrition, in addition to being an early
problem in critical illness, is also frequent among patients on LTMV. It is estimated
that it affects approximately 3543 % of patients, reaching 5075 % in the subgroup
of septic patients. Consequent muscle dysfunction undermines the efforts of weaning from a ventilator and enhances the work of breathing and energy demands, leading finally to increased duration of MV, increased length of stay, and high
hospitalization costs.
In a study by Moisey et al. [6], low skeletal muscle mass was related with significantly fewer ventilator-free days. The preservation and recovery of lean body mass
(LBM) and muscle strength are crucial for the successful weaning and rehabilitation
of the patient. To achieve this, it is fundamental to implement appropriate nutritional therapy with adequate protein delivery. Studies in malnourished and COPD
patients proved that nutritional support has beneficial effect on respiratory function,
provided there is weight gain [7]. Unfortunately, in many CCIP optimal recovery of
LBM is not easily obtained, highlighting the need for muscle mass preservation at
the early stage of the disease by limiting protein catabolism through adequate early
nutritional support.
9.2
Discussion
9.2.1
Assessment
Nutritional assessment is considered essential for the long-term nutritional management of LTMV patients. The appropriate nutritional assessment should include
medical history and thorough physical examination. Medical history should emphasize changes in BW and eating habits before hospitalization, gastrointestinal tract
disorders, and ICU course.
Physical examination should assess for muscle wasting, micronutrient deficiencies, edema, nonhealing wounds and ulcers, and potential losses of nitrogen.
Laboratory data should provide information on electrolyte status, mainly K, P,
and Mg and visceral proteins [8]. Prealbumin correlates promptly with the adequacy
of nutritional support and nitrogen balance and therefore is considered the more
reliable metabolic marker among visceral proteins. Concomitant evaluation of
C-reactive protein (CRP) is mandatory to discriminate between inflammation and
underfeeding.
66
M. Bitzani
Anthropometric parameters are inaccurate in the critically ill and probably in

CCIP. On the other hand, fat free mass (FFM), body mass index (BMI) <20, and
serum albumin are considered sensitive in detecting malnutrition in LTMV patients
with chronic respiratory insufficiency, or without spontaneous breathing.
Screening tools such as subjective global assessment (SGA), Nutritional Risk
Screening 2002 (NRS 2002), and Mini Nutritional Assessment (MNA) have not
been validated in this patient population. Likewise, the determination of body composition with ultrasound, dual X-ray absorptiometry (DEXA), bioelectrical impedance (BIA), or magnetic resonance imaging (MRI), although useful and reliable, are
not easy or affordable in everyday practice [9].
9.2.2
Energy and Protein Requirements
The goals of nutrition support in ventilator-dependent patients should be the preservation of LBM and the provision of adequate energy and protein to expedite the
weaning process. Determination of energy expenditure in patients dependent on
MV is challenging. Energy intake based on physicians orders proved to be adequate only in 25 % of the patients, whereas the rest were over- or underfed. It is
important to mention that, apart from undernutrition, overnutrition also has a detrimental effect on respiratory function, because it is accompanied by increased CO2
production. This can precipitate respiratory failure, or lead to weaning failure, when
the respiratory reserves are not sufficient to sustain the increased amount of ventilation necessary to maintain steady state. Appropriate nutritional intervention is of
paramount importance in this patient population.
The gold standard for the determination of an optimal individualized energy
support in critically ill patients is indirect calorimetry (IC). The handicap of IC is
that metabolic computers are not widely available. According to ESPEN guidelines,
resting energy expenditure (REE) in critically ill patients should be measured by IC,
or estimated by the use of a predictive equation. There are more than 200 predictive
equations addressing different patient populations. More recently, equations specifically designed for critically ill patients have been developed, taking into account
parameters such as MV, fever, and abnormal physiological states that can affect
metabolic demands [8, 9] (Table. 9.1). There is no consensus about which of these
equations is the most accurate in critically ill patients, or appropriate in
CCIP. Likewise, there are no guidelines specifically addressing the metabolic
requirements of this latter group.
Energy requirements of hospitalized COPD patients were estimated at 30 kcal/kg/
day. A reduction in mechanically assisted patients is likely due to decreased work of
breathing [10]. For stable, high-level quadriplegic patients, the Evidence-Based
Nutrition Guidelines for Spinal Cord Injury recommend energy intake equal to
22.7 kcal/kg/day. Diminished metabolic requirements in these patients are attributed
to lower limb paralysis. It is difficult to define energy requirements in patients with
amyotrophic lateral sclerosis (ALS) because, although ALS leads to skeletal muscles atrophy, patients are hypermetabolic. A general approach is the following:
67
Table 9.1 Predictive equations for REE estimation in critically ill patients
Ireton-Jones
Energy
Equations
(IJEE) 1992
Mifflin-St. Jeor
Penn State
Equation
(PSU 2003b)
Penn State
Equation
(PSU 2010)
Fasy-Fagon
American
College of
Chest
Physicians
(ACCP)
ESPEN
Guidelines
SB: REE = 629 11(A) + 25(BW) 609(O)

VD: REE = 1925 10(A) + 5(BW) + 281(S) + 292(T) + 851(B)
S, sex (male = 1, female = 0), T, trauma (present = 1, absent = 0), B, burn
(present = 1, absent = 0),
(O) BMI > 27 kg/m2 (present = 1, absent = 0).
M: REE = (9.99 BW) + (6.25 H) (4.92 A) + 5
F: REE = (9.99 BW) + (6.25 H) (4.92 A) 161
REE = Mifflin (0.96) + VE (31) + Tmax (167) 6212
Used for patient of any age with BMI <30 or patients < 60 years with
BMI > 30.
REE = Mifflin (0.71) + VE (64) + Tmax (85) 3085
Used for patients with BMI > 30 and older than 60 years.
REE (kcal/d) = 8 BW + 14 H + 32 VE + 94 T 4,834
REE = 25 BW
If BMI 1625 kg/m2, use usual BW
If BMI > 25 kg/m2, use IBW
If BMI < 16 kg/m2, use ABW for the first 710 days, then use IBW
2025 kcal/kg BW/d during the acute and initial phase of critical illness
2530 kcal/kg BW/d during the anabolic recovery phase
SB spontaneously breathing, VD ventilator dependent, REE resting energy expenditure, BW body

weight in kg, A age in years, H height in cm, VE minute ventilation in l/min, Tmax maximum body
temperature in degrees Celsius, M male, F female
REE = BEE ( Harrisand Benedict ) + 10 % for hypermetabolism

+ 10 % for thermogenesis +10 % for physical activity.
Vaisman et al. [11] propose an equation that predicts the actual measurement of
REE in 86 % of its variability. It can be used only in malnourished patients with
documented reduced caloric intake compared with the predicted value and should
be recalculated along the disease course.
REE measured = 507 + 23, 65 FFM + 0,186 caloric intake ( kcal )
3, 6A 4,185 Functional Rating Scale ( FRS)
+ 195 ( only if female )
Obese patients deserve special attention. According to ESPEN and American

Society for Parenteral and Enteral Nutrition (ASPEN) guidelines, energy intake
should be restricted to 1114 kcal/kg of actual BW (ABW) or 2225 kcal/kg of
ideal BW (IBW).
Taking into consideration that all of the above equations may be inaccurate on an
individual basis, physicians need to continuously reassess patients metabolic
demands under close monitoring and readjust their prescriptions when signs of
harmful under- or overfeeding are recognized.
68
M. Bitzani
There is a growing interest in the importance of adequate protein supply on

patients outcomes. Adequate protein delivery was proved beneficial for patients by
reducing mortality, time on ventilator, and length of stay, and by improving quality of
life [12, 13]. There is some evidence that increased protein intake improves physical
function post ICU and the rate of discharge to home versus to a rehabilitation center
[14]. Protein should be administered in amounts ranging from 1.2 to 1.5 g/kg/day and
could be increased to 2 g/kg/day in case there is additional nitrogen loss, as in renal
replacement therapy, decubitus ulcers, or high-output drainage. For obese patients,
more than 2 g/kg of IBW is suggested. There are no studies proving that enrichment
of diets with specific amino acids has any beneficial effect in muscle protein synthesis
or the weaning process.
The interrelation between substrate oxidation and ventilation was the basis of the
controversy regarding the appropriate composition of the nonprotein calories of a
diet. Earlier studies supported the use of low-carbohydrate (CHO), high-lipid diets
to reduce CO2 production in MV patients, whereas later ones proved that hypercapnia was the consequence of the combination of overfeeding and CHO load rather
than the CHO load alone. In addition, high-lipid diets were found to cause delayed
gastric emptying and intolerance to enteral nutrition (EN). Because of these conflicting results and the impact of the high-lipid diets on gastric emptying, there are
no recommendations on the ordinary use of low-CHO, high-lipid diets in LTMV
patients [9, 15].
LTMV patients can be at risk for micronutrient deficiencies; however, because
there is no reported data on this prevalence, routine provision should be restricted to
recommend daily allowances, except when clinical signs of specific deficiencies are
diagnosed. Low levels of 25(OH) D have been reported in studies with LTMV
patients, raising concern about vitamin D. Investigators attributed the high rate of
bone hyper-resorption in 92 % of CCIP to low levels of 25(OH) D, along with
immobilization. Authors suggest that low levels of 25(OH) D should be treated with
a combination of calcitriol and pamidronate, together with the recommend daily
allowances for Ca [9]. Low serum P levels should be repleted, inasmuch as hypophosphatemia can lead to respiratory insufficiency and weaning failure.
There are no data proving any beneficial effect of the administration of immunomodulating nutrients in uncomplicated LTMV patients
9.2.3
Nutrition Intervention
EN is the primary choice for nutrition support in ventilator-dependent patients.

Feeding can be administered through a nasogastric or nasojejunal tube, depending
on gastric motility and the risk of aspiration. Percutaneous endoscopic gastrostomy
(PEG) or percutaneous endoscopic jejunostomy (PEJ) are performed when EN is
required for more than 4 weeks. PEG is the preferred method for providing enteral
nutrition in patients with neurological diseases and swallow disorders. It facilitates
discharge home, allows oral feeding, and operates as a bridge toward oral feeding in
case dysphagia is reversible.
69
In CCIP, during the early stage of the disease, EN is better tolerated if given as a
continuous drip infusion using a pump. In later stages, when the patient is stable,
EN can be provided intermittently during the day, or cycled overnight to facilitate
mobilization of the patient or transition to oral nutrition. There is no ideal EN formula for ventilator-dependent patients, as long as their protein and caloric needs are
covered. The choice of the formula is usually guided by the functional needs of the
individual patient and, as such, is under continuous reconsideration. Parenteral
nutrition is reserved for patients unable to meet their metabolic requirements with
EN, mainly due to gastrointestinal dysfunction. In most of cases it is complementary to EN and has a short duration.
Oral feeding is the ultimate goal, assuming that swallow function is intact.
Although the actual value is difficult to determine, incidence of swallow disorders
in patients requiring prolonged mechanical ventilation has been reported to range
from 29 to 34 %. Dysphagia is associated with nutrition deficiencies and weight loss
and, if misdiagnosed, exposes the patient to the risk of aspiration.
Before the initiation of oral feeding, LTMV patients should be checked for swallow disorders clinically and have a direct laryngoscopy. Barium swallow video fluoroscopy is usually ordered to confirm the diagnosis and to provide information for
the implementation of corrective measures by a multidisciplinary team.
Usually, there is a transition period from EN to oral feeding that maybe long and
challenging. The first step is to switch from continuous drip infusion to intermittent
administration, or continuous feeding only at night. ral feeding is attempted when
intermittent feeding is well tolerated. Initially, one to two oral meals per day are
attempted. Frequency and delivery amount increases gradually, with corresponding
decreases in tube feeding. Strict monitoring of oral intake is necessary to determine
whether supplemental tube feeding is warranted to ensure metabolic needs.
Various specialized products, both for liquids and solids, differing in texture and
consistency, are at the disposition of dysphagic patients so that the most appropriate
may be chosen according to individual needs. Powdered thickeners and prethickened liquids are also available. In severe stages of dysphagia, PEG is a good
solution.
Oral feeding alone maybe inadequate in patients with respiratory disease placed
on NIV. There are clinical observations that patients on NIV have inadequate nutrition support, because of the limited time available for eating between applications
of ventilation masks. Additionally, they have poor appetite, are breathless, and show
early chewing tiredness. Patients may benefit from a nutrition intervention in the
form of two to three portions of small-volume, high-caloric-value supplements, distributed during the day between meals. In some cases, tube feeding maybe more
appropriate.
9.2.4
Monitoring Nutrition Support
Close follow-up and monitoring of tolerance is mandatory for optimal metabolic

support. In the case of tube feeding, signs of abdominal distention, pain, vomiting,
70
M. Bitzani
or diarrhea should be assessed and treated promptly. Gastric residuals should be

checked three to four times per day and amounts up to 500 ml should be tolerated.
Weight, if possible, should be checked on regular basis. Efficiency of nutrition
support and evaluation of the inflammatory status of the patient is monitored by
prealbumin and CRP values. It is important to monitor closely glucose levels and
serum electrolytes, P, and Mg on a weekly basis.
Conclusion
The goals of nutrition support in ventilator-dependent patients should be the

preservation of LBM and the provision of the adequate energy and protein to
expedite the weaning process. The implementation of an adequate nutrition plan
in these patients is often challenging. Nevertheless, careful nutritional assessment and determination of an individualized nutrition plan, with appropriate
readjustments guided by close monitoring, will help patients to meet their medical and nutrition targets.
Careful assessment of nutrition status will help to recognize patients who

are malnourished or at risk of malnutrition.
Appropriate energy requirements should be determined by measurement
through IC, or by estimation through a predictive equation.
Adequate protein should be delivered in amounts ranging from 1.2 to
1.5 g/kg/day, increasing to 2 g/kg/day in cases of additional nitrogen
losses.
An individualized nutrition plan should be determined.
The nutrition plan should be reconsidered on the basis of close monitoring
guidance.
References
1. Arora NS, Rochester DF. Effect of body weight and muscularity on human diaphragm muscle
mass, thickness and area. J Appl Physiol Respir Environ Exerc Physiol. 1982;52:647.
2. Kelly SM, Rosa A, Field S, et al. Inspiratory muscle strength and body composition in patients
receiving total parenteral nutrition therapy. Am Rev Respir Dis. 1984;130(1):337.
3. Arora NS, Rochester DF. Respiratory muscle strength and maximal voluntary ventilation in
undernourished patients. Am Rev Respir Dis. 1982;126:58.
4. Van den Berg B, Stam H, Hop W. Effects of dietary protein content on weaning from the ventilator. Clin Nutr. 1989;8:20712.
5. Askanazi J, Weissman C, LaSala P, et al. Effect of protein intake on ventilatory drive.
Anesthesiology. 1984;60(2):10610.
6. Moisey L, Mourtzakis M, Cotton B, et al. Skeletal muscle predicts ventilator-free days, ICUfree days, and mortality in elderly ICU patients. Crit Care. 2013;17:R206.
7. Wilson DO, Rogers RM, Sander MH, et al. Nutritional intervention in malnourished patients
with emphysema. Am Rev Respir Dis. 1986;134:6727.
71
8. Schuman R, Mechanick J. Metabolic and nutritional support in the chronic critical illness
syndrome. Respir Care. 2012;57:95878.
9. Doley J, Mallampalli A, Sandberg M. Nutrition management for the patient requiring prolonged mechanical ventilation. Nutr Clin Pract. 2011;26:23241.
10. Pingleton S. Enteral nutrition in patients with respiratory disease. Eur Respir J.
1996;9:36470.
11. Vaisman N, Lusaus M, Nefussy B, et al. Do patients with amyotrophic lateral sclerosis (ALS)
have increased energy needs? J Neurol Sci. 2009;279(12):269.
12. Weijs PJ, Stapel SN, de Groot SD, et al. Optimal protein and energy nutrition decreases mortality in mechanically ventilated, critically ill patients: a prospective observational cohort
study. JPEN J Parenter Enteral Nutr. 2012;36:608.
13. Weijs PJ, Wischmeyerer P. Optimizing energy and protein balance in the ICU. Curr Opin Clin
Nutr Metab Care. 2013;16:194201.
14. Rice T, Hays M, et al. A randomized trial of initial trophic versus full-energy enteral nutrition
in mechanically ventilated patients with acute respiratory failure. Crit Care Med.
2011;39(5):96774.
15. Ambrosino N, Clini E. Long-term mechanical ventilation and nutrition. Respir Med.
2004;98:41320.
Predictive Models of Prolonged

Mechanical Ventilation and Difficult
Weaning
10
Juan B. Figueroa-Casas
Abbreviations
APACHE
APS
ARDS
AUC
BUN
COPD
CRP
GCS
ICU
LIS
OSFI
NIV
NPV
PEEP
PPV
ROC
SAPS
Se
Sp
SS
Acute Physiology and Chronic Health Evaluation

Acute Physiology Score
Acute Respiratory Distress Syndrome
Area Under the receiver operating characteristics Curve
Blood Urea Nitrogen
Chronic Obstructive Pulmonary Disease
C-reactive protein
Glasgow Coma Scale
Intensive Care Unit
Lung Injury Score
Number of organ system failures
Noninvasive Ventilation
Negative predictive value
Positive end-expiratory pressure
Positive predictive value
Receiver Operating Characteristics
Simplified Acute Physiology Score
Sensitivity
Specificity
Sepsis Score
J.B. Figueroa-Casas, MD
Division of Pulmonary and Critical Care Medicine, Texas Tech University Health Sciences
Center at El Paso, El Paso, TX, USA
e-mail: Juan.Figueroa@ttuhsc.edu
DOI 10.1007/978-3-319-04259-6_10
73
74
10.1
J.B. Figueroa-Casas
Importance of Predicting Mechanical Ventilation

and Weaning Duration
Clinical predictions about individual patients total duration of mechanical ventilation or their duration of weaning are routinely made by intensivists as part of care
of ventilated patients. Although these predictions may not be systematically elaborated or formally expressed, they influence important clinical decisions. The decision about whether and when to perform a tracheostomy is one of particular
importance. Weaning and other aspects of care might be facilitated by an early tracheostomy in patients who will need a lengthy course of invasive ventilation. Other
decisions that may also be influenced by such predictions include the initiation of
enteral nutrition, the use of intensive glycemic control, the inclusion of patients in
clinical trials, and the possible transfer of patients to referral centers for mechanical
ventilation or weaning. However, the accuracy of these clinical predictions by intensivists, either in the setting of clinical research [1] or practice [2], has been shown
to be quite limited. Therefore, objective tools that allow accurate predictions of
these outcomes, prolonged ventilation or difficult weaning, have been sought to
assist physicians with these decisions. These tools include the identification of risk
factors and the development of predictive models. In this case, predictive models are
mathematical tools that combine results of several variables assessed at an early
point in the course of mechanical ventilation to estimate either the probability that a
patient will require prolonged ventilation (or weaning), or its actual duration.
This chapter reviews studies aimed at identifying risk factors for and developing
predictive models of prolonged mechanical ventilation and weaning.
10.2
Obstacles to Predictive Models Development,

Comparison, and Generalization
Before reviewing results of published studies, several factors that limit the ability to
summarize, compare, and generalize their findings on this subject need to be mentioned. First, there has been incompleteness or significant heterogeneity among
studies in defining the different components involved in the development of the
predictive factors or models. The measurement of the outcome to be predicted,
duration of mechanical ventilation, has varied in the following several aspects: the
determination of the end-day of mechanical ventilation according to the number of
days of successful unassisted breathing to follow ventilator discontinuation; the
inclusion (or not) of subsequent days of ventilation and/or the interval days when
ventilation was discontinuous (reintubation or reinitiation of ventilation); and the
inclusion or not of days on noninvasive ventilation. The definition of prolonged
mechanical ventilation has ranged from more than 5 to more than 21 days. The
selection of candidate predictors (variables to be analyzed as potentially predictive)
and the point in time at which they were assessed (first day on mechanical ventilation, first day in intensive care unit [ICU] whether a patient is intubated or not, or
other) have also differed significantly among studies. Second, there has been great
10
Predictive Models of Prolonged Mechanical Ventilation and Difficult Weaning
75
variation in accounting for the main competing risk for duration of mechanical ventilation until successful liberation, which is death while still receiving mechanical
ventilation. Sicker patients may logically be at risk of requiring a longer duration of
ventilation and weaning, but they may also be at higher risk of dying early during
the course of ventilation, and some may therefore have a relatively short duration of
ventilatory support and/or never reach a weaning stage. These patients have variably
been included, excluded, or treated as a separate category in different studies.
Similar heterogeneity in the definition of duration of ventilation, here used as an
outcome to be predicted, has been described for clinical trials in which duration of
ventilation is used as outcome of an intervention [3, 4]. In addition to the abovementioned factors, differences in populations among studies and lack of external
validation of the predictive models published further limit their generalization.
10.3
Studies Aimed at Predicting Duration of Mechanical

Ventilation
Studies that have aimed at predicting mechanical ventilation duration have used different measures to test and inform the accuracy of their predictive tools. A summary
is shown in Table 10.1. In some studies, the analysis has been limited to identification of associated or predictive factors of mechanical ventilation duration.
Sapijaszko et al. [5] suggested that the diagnosis category leading to mechanical
ventilation might be a predictive factor. In their prospective study of 145 general
ICU patients ventilated for at least 72 h, mostly nonrespiratory variables (age, Acute
Physiology and Chronic Health Evaluation (APACHE) II score, albumin, and fluid
balance) on the first ICU day were analyzed as possible predictors of duration of
mechanical ventilation. None of these variables correlated with the actual duration
by univariate analysis. When the first three variables were incorporated into a multiple regression analysis along with five mutually exclusive diagnostic categories,
only the categories of Acute Lung Injury with other organ failure and Other
Medical (which included medical nonrespiratory and non-neurologic diagnoses)
were associated with a longer and a shorter duration of ventilation, respectively.
Estenssoro et al. [6], however, did not find diagnosis category but rather hemodynamic condition to be associated with ventilation duration. In this retrospective
study of 189 medical-surgical ICU patients that excluded those dying before day 21,
the authors aimed to identify predictors of prolonged mechanical ventilation (here
defined as > 21 days). From the candidate predictors (severity of illness scores,
demographic and physiologic variables, and cause for mechanical ventilation) that
were assessed on ICU admission, only the presence of shock on admission was
independently associated with the need for > 21 days of ventilation.
Other studies have identified factors associated with duration of ventilation, then
applied them as predictive criteria and analyzed their classic predictive performance
characteristics. With this methodology, Troche et al. [7] reported that the Lung
Injury Score may have high negative predictive value for surgical patients to need
prolonged ventilation. In a study limited to a surgical ICU population, they followed
195 derivation,
128 validation,
surgical ICU
99 medical ICU
Clark et al.
Subjects
145 med/surg,
3 days on
ventilation
189 med/surg,
intubated in ICU
Troche et al.
Estenssoro et al.
Authors
Sapijaszko et al.
Candidate predictors
Age, APACHE II, fluid
balance, albumin,
diagnosis category
Age, gender, diagnosis
category, APACHE II,
SAPS II, McCabe score,
TISS, shock
Age, BMI, emergent
admission, emergent
intubation, days
admission-intubation,
Altemeier group,
diagnosis category, SAPS,
GCS, SS, LIS, OSFI,
albumin
Demographic,
anthropometrics, vital
signs, arterial blood gases,
hematology, chemistry,
APACHE II, APS,
intubation in ICU
Intubation day
First ICU day

and intubation
day
First ICU day
Time point
candidate
predictors
assessed
First ICU day
Table 10.1 Summary of studies aimed at predicting duration of mechanical ventilation
Emergent intubation,
LIS on intubation day
Intubation in the ICU,

heart rate > 100/min,
BUN > 25 mg/dl,
creatinine > 2 mg/dl,
pH < 7.25 and
HCO3 < 20 mEq/l
14 days
Shock
Variables independently
associated with
outcome
Diagnosis category
>14 days
>21 days
Outcome to be
predicted
Number of days
on ventilation
4 criteria met:
Se 0.16,
Sp 1,
PPV 1,
NPV 0.72,
AUC 0.75
Emergent
intubation +
LIS 1:
Se 0.88,
Sp 0.28, PPV
0.24, NPV 0.91
Prediction
accuracy
measures
76
J.B. Figueroa-Casas
142 general ICU
1,289 derivation,
372 validation,
from 13 ICUs
Papuzinski et al.
Aon et al.
Operative status, location

and day prior to ICU,
diagnosis category, APS,
TISS, APACHE III and its
individual physiology
variables, age,
comorbidities, hospital
type, chronic lung disease
Age, vital signs,
comorbidities, APACHE
II, TISS, diagnosis
category, hematology,
chemistry, CRP
APACHE II, SOFA,
location prior to ICU, NIV
failure, comorbidities,
Barthel index,
vasopressors, diagnosis
category
Intubation day
Not reported
First ICU day
Diagnosis category,
APS, age, chronic lung
disease, albumin, PaO2/
FIO2, respiratory rate,
hospital type, disease
physiology, location
and days prior to ICU.
Age, hypernatremia,
COPD, PaO2/FiO2 < 200
Not reported
Number of days
on ventilation
7 days
7 days
Predictive model:
AUC 0.64 vs
death +
<7 days
AUC 0.74 vs
alive +
<7 days
Predictive model:
AUC 0.81
Predictive
equation:
R2 0.18 in
individual
patients
ICU intensive care unit, APACHE Acute Physiology and Chronic Health Evaluation, SAPS Simplified Acute Physiology Score, TISS Therapeutic Intervention
Scoring System, GCS Glasgow Coma Scale, SS sepsis score, LIS lung injury score, OSFI number of organ system failures, APS Acute Physiology Score,
CRP C-reactive protein, BUN blood urea nitrogen, NIV noninvasive ventilation, COPD chronic obstructive pulmonary disease, Se sensitivity, Sp specificity,
PPV positive predictive value, NPV negative predictive value, AUC area under the receiver operating characteristics curve
5,915 intubated
on first ICU day,
from 42 ICUs
Sennef et al.
10
77
78
J.B. Figueroa-Casas
195 patients and analyzed multiple candidate variables including diagnosis leading
to mechanical ventilation and severity of illness scores assessed at the time of
admission and intubation. Only the need for emergent intubation and the Lung
Injury Score were independently associated with duration of ventilation > 14 days.
In their subsequent validation cohort of 128 patients requiring emergent intubation,
a Lung Injury Score 1 predicted >14 days of ventilation with sensitivity of 0.88,
specificity of 0.28, positive predictive value of 0.24, and negative predictive value
of 0.91. In contrast, Clark et al. [8] found a high positive predictive value to require
prolonged ventilation for medical patients when four of their predictive criteria
were met. In their retrospective study of 99 medical ICU patients, excluding those
dying before day 14, 27 common clinical and laboratory variables (diagnosis not
included) were collected from the day of intubation. By multivariate analysis, intubation in the ICU, heart rate >100/min, blood urea nitrogen (BUN) > 25 mg/dl, creatinine> 2 mg/dl, pH < 7.25, and HCO3 < 20 mEq/l were each associated with a
duration of ventilation 14 days. A predictive model consisting of the number (04)
of these criteria met, applied to the same derivation sample, resulted on sensitivity
of 0.16, specificity of 1, positive predictive value of 1, and negative predictive value
of 0.72 when four criteria were met. Lower numbers of criteria met resulted in progressively higher sensitivity and lower specificities. The area under the receiver
operating characteristics (ROC) curve for this model was 0.75.
The largest study reported to date suggested that both diagnosis category and the
degree of physiologic derangement could be important predictors [9]. This study
not only aimed to identify predictive factors but also to use them to develop an equation to predict the precise duration of mechanical ventilation. In this retrospective
analysis of the APACHE III database prospectively collected from 40 hospitals
ICUs, 5,915 patients who were on mechanical ventilation on their first ICU day had
many variables extracted from that day. The total duration on the ventilator was
precisely measured for patients spending 7 days on the ventilator, while it was
estimated for patients with longer durations. Of 11 variables that were found to be
independently associated with mechanical ventilation duration, the primary reason
for ICU admission (selected from the 78 APACHE III disease categories) and the
Acute Physiology Score (a component of the APACHE III score) accounted for
most of the relative contributions to this association. An equation to predict precise
duration on mechanical ventilation was then developed by the authors. In internal
cross-validation, this equation was shown to be accurate (R2 0.94) to predict average
duration in patient groups classified by illness severity, but inaccurate (R2 0.18) in
individual patients.
More recent studies have used multivariate analyses to identify associated factors
and develop a model to quantify the probability of prolonged duration of ventilation
to then analyze the accuracy of its predictions, mainly by measuring the area under
the ROC curve. In a retrospective study of 142 ICU patients, Papuzinski et al. [10]
identified age, diagnosis of chronic obstructive pulmonary disease (COPD), hypernatremia, and PaO2/FiO2 < 200 on intubation day as associated with a duration of 7
days on the ventilator. A derived model to predict this prolonged duration indicated
an area under the ROC curve of 0.80 in this same derivation sample, but neither
10
79
other measures of accuracy nor validation of the model were reported. In a much
larger and prospective study including 1,661 patients from 13 general ICUs, An
et al. [11] assessed multiple variables on the first day of ventilation, including the
reason for mechanical ventilation. Accounting for early deaths as a competing event
for duration of ventilation, this study aimed at discriminating patients dying before
day 7 from those requiring 7 days of ventilation, as well as those surviving but
requiring < 7 days from those same ones requiring 7 days of ventilation. A derived
multivariate risk model, when applied to a validation subsample, yielded areas
under the ROC curve of 0.64 and 0.74 for those predictions, respectively. As commented by the authors, these levels of accuracy seem insufficient for individual
clinical application.
Some of the above-mentioned studies performed in mixed ICU populations suggest an influence of diagnosis category on duration of mechanical ventilation. In
addition, the factors that primarily determine the need of mechanical ventilation
might differ among its different etiologies. It would then be reasonable to speculate
that predictive models restricted to a diagnostic category could yield better results.
Studies that have focused on predicting prolonged ventilation duration in selected
ICU subpopulations, however, have generally reported insufficient accuracies.
These selected subpopulations by diagnosis category have been as broad as trauma,
acute respiratory distress syndrome (ARDS), and burns, and as narrow and specific
as Guillain-Barr syndrome and post-aortic arch repair. Sensitivities to predict prolonged ventilation in these studies have ranged from 0.56 to 0.82, always lower
than specificities. Models consisting of a point system by number of criteria met
have shown reasonable accuracy only for the minority of patients at the extremes of
the scale.
10.4
Studies Aimed at Predicting Difficult or Prolonged

Weaning
Predicting whether a patient is able to be weaned off mechanical ventilation on a

given day and predicting whether a patient will require a difficult or lengthy weaning process are two related but different predictions. Most studies on weaning prediction have focused on the former, trying to identify when a patient is ready to be
liberated from ventilatory support and/or be extubated. In contrast, predicting early
on that a patient will require multiple attempts and/or lengthy weaning has received
much less attention.
A significant proportion of the total duration of mechanical ventilation is spent
in the weaning process. A prediction for prolonged ventilation might therefore also
imply a prediction for difficult weaning. However, this may not always be the case.
Only about 30 % of general ICU patients spend more than 7 days on mechanical
ventilation [12], but 4045 % need several attempts at weaning before discontinuation [13, 14]. Furthermore, prolonged ventilation predictions, as reviewed, are very
limited and the definition of difficult weaning had not been uniform. Only recently
has a classification been proposed to grade the complexity of weaning [15]. In this
80
J.B. Figueroa-Casas
classification, simple weaning refers to patients successfully extubated after a

first spontaneous breathing trial. Difficult weaning refers to patients needing up to
3 trials or 7 days from the first unsuccessful breathing trial. Prolonged weaning
refers to those needing more than 3 trials or 7 days to be successfully liberated from
the ventilator. This classification, particularly the prolonged weaning category, has
been found to be associated with mortality [13, 14].
Investigations so far have not attempted to develop models to predict the weaning complexity a patient will have, but two that have evaluated factors associated
with these categories had no findings in common. It should be noted that these
assessments have been performed in patients who have survived and improved to
reach their first weaning attempt without previously undergoing a tracheostomy.
Any potential prediction using these results should be applied to this situation and
time point. Predicting prolonged weaning at this point (day of first spontaneous
breathing trial) could be useful due to the long expected duration of weaning still
remaining and its associated worse clinical outcome. Predicting difficult weaning
at this same point, when the diagnosis is near-simultaneously confirmed by a spontaneous breathing trial failure, seems of much lower clinical value.
In a prospective study of 181 patients in a respiratory ICU undergoing their first
spontaneous breathing trial, clinical characteristics on ICU admission and physiologic parameters before and during the trial were analyzed for their association with
prolonged weaning (versus simple or difficult) [16]. Only higher heart rate and
PaCO2 levels at the end of the spontaneous breathing trial were independently associated with prolonged weaning. In another study, a secondary analysis of a multinational prospective cohort, 2,714 patients that similarly had reached their first
weaning attempt without tracheostomy had their clinical and ventilator variables
from admission to the first trial analyzed [13]. In a multiple regression analysis, the
following variables were associated with both difficult and prolonged weaning: a
diagnosis of non-COPD chronic lung disease or pneumonia as reason for mechanical ventilation, Simplified Acute Physiology Score (SAPS) II on ICU admission,
number of days of ventilation and level of positive end-expiratory pressure, the latter two measured before the first attempt of weaning.
10.5
Summary
Early prediction of duration of mechanical ventilation, particularly the prediction of

a prolonged duration that a minority of patients will have, remains very difficult
for intensivists. Studies aimed at identifying predictors of duration of mechanical
ventilation have been quite heterogeneous in design and outcome to predict, and
have failed to yield consistent results. Two reported predictive models may be useful when applied to patient group level [9, 11]. However, there are so far no properly
tested prediction models with sufficient accuracy to be clinically useful in predicting the need for prolonged mechanical ventilation in individual patients. Early death
while on mechanical ventilation is an important competing risk that might impair
the identification of accurate predictive models for ventilation duration and needs to
10
81
be accounted for in order for the models to be clinically useful. The intended purpose and timing of the prediction need to be kept in mind in designing studies with
this aim. A recently published comprehensive review of development of predictive
models in critical care can be a useful guide for future studies [17].
Predictive models for the recently defined categories of difficult and prolonged
weaning have not been developed. A predictive tool to be used at an early point in
the course of mechanical ventilation would be most desirable but likely difficult to
find. A predictive tool to be applied at the onset of the weaning stage should focus
on the prolonged weaning category.
References
1. Young D, Harrison DA, Cuthbertson BH, et al. Effect of early vs. late tracheostomy placement
on survival in patients receiving mechanical ventilation: the TracMan randomized trial. JAMA.
2013;309:21219.
2. Figueroa-Casas JB, Connery SM, Montoya R, et al. Accuracy of early prediction of duration
of mechanical ventilation by intensivists. Ann Am Thorac Soc. 2013;11:1825.
3. Blackwood B, Clarke M, Mcauley DF, et al. How outcomes are defined in clinical trials of
mechanically ventilated adults and children. Am J Respir Crit Care Med. 2014;189:88693.
4. Contentin L, Ehrmann S, Giraudeau B. Heterogeneity in the definition of mechanical ventilation duration and ventilator-free days. Am J Respir Crit Care Med. 2014;189:9981002.
5. Sapijaszko MJA, Brant R, Sandham D, et al. Nonrespiratory predictor of mechanical ventilation dependency in intensive care unit patients. Crit Care Med. 1996;24:6017.
6. Estenssoro E, Gonzalez F, Laffaire E, et al. Shock on admission day is the best predictor of
prolonged mechanical ventilation in the ICU. Chest. 2005;127:598603.
7. Troche G, Moine P. Is the duration of mechanical ventilation predictable? Chest.
1997;112:74551.
8. Clark PA, Lettieri CJ. Clinical model for predicting prolonged mechanical ventilation. J Crit
Care. 2013;28:880e17.
9. Seneff MG, Zimmerman JE, Knaus WA, et al. Predicting the duration of mechanical ventilation. Chest. 1996;110:46979.
10. Papuzinski C, Durante M, Tobar C, et al. Predicting the need of tracheostomy amongst patients
admitted to an intensive care unit: a multivariate model. Am J Otolaryngol. 2013;34:51722.
11. An JM, Gomez-Tello V, Gonzalez-Higueras E, et al. Prolonged mechanical ventilation
probability model. Med Intensiva. 2012;36:48895.
12. Esteban A, Frutos-Vivar F, Muriel A, et al. Evolution of mortality over time in patients receiving mechanical ventilation. Am J Respir Crit Care Med. 2013;188:22030.
13. Peuelas O, Frutos-Vivar F, Fernandez C, et al. Characteristics and outcomes of ventilated
patients according to time to liberation from mechanical ventilation. Am J Respir Crit Care
Med. 2011;184:4307.
14. Funk G, Anders S, Breyer M, et al. Incidence and outcome of weaning from mechanical ventilation according to new categories. Eur Respir J. 2010;35:8894.
15. Boles JM, Bion J, Connors A, et al. Weaning from mechanical ventilation. Eur Respir J.
2007;29:103356.
16. Sellares J, Ferrer M, Cano E, et al. Predictors of prolonged weaning and survival during ventilator weaning in a respiratory ICU. Intensive Care Med. 2011;37:77584.
17. Labarre J, Bertrand R, Fine MJ. How to derive and validate clinical prediction models for use
in intensive care medicine. Intensive Care Med. 2014;40:51327.
Part II
in Weaning From Mechanical
Ventilation General Considerations

in Difficult Weaning in Critical Care: Key
Topics and Practical Approach
11
Guniz M. Koksal and Emre Erbabacan
11.1
Introduction
Intubation and mechanical ventilation (MV) administration for curative purposes

are safe and effective in patients receiving intensive care. However, prolonged MV
without weaning can harm patients as much as premature extubation and increases
mortality and morbidity by increasing risks such as bronchopulmonary infections,
barotrauma, and oxygen toxicity. Weaning is defined as withdrawal of MV or liberating the patient from MV [1]. The time needed for weaning is approximately 40 %
of the duration MV. It has been shown that weaning duration is prolonged in 15 %
of patients [2]. The prolonged weaning process may be classified into the following
three categories according to difficulty and duration [3]:
Simple weaning: Successful extubation after the first spontaneous breathing trial
(SBT)
Difficult weaning: Successful extubation after two or three SBTs, or weaning taking
fewer than 7 days from the first SBT to successful extubation
Prolonged weaning: Not weaned after more than three SBTs, or weaning taking
longer than 7 days
As stated in an international consensus conference on weaning from MV, approximately 69 % of patients are successfully extubated at the first weaning trial (simple
weaning), whereas the remaining patients experience difficult or prolonged weaning. However, in some reports, the incidence of patients classified as simple weaning
was lower than that estimated at the conference, ranging instead from 30 to 55 %.
G.M. Koksal, MD (*) E. Erbabacan, MD
Department of Anesthesiology and Reanimation, Istanbul University Cerrahpasa
Medical Faculty, Istanbul, Turkey
e-mail: gunizkoksal@hotmail.com; emreerbabacan@hotmail.com
DOI 10.1007/978-3-319-04259-6_11
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G.M. Koksal and E. Erbabacan
Noninvasive mechanical ventilation (NIMV) is a ventilation technique that has

become popular in recent years. Today, NIMV is used for two main purposes: as
a preventive measure to avoid intubation in an acute respiratory failure situation,
and after extubation in patients who have difficultly weaning. NIVM administered
following extubation both decreases reintubation rates and shortens weaning
duration [4].
11.2
Discussion
NIMV is theoretically able to counteract several physiological mechanisms associated with weaning difficulties. In ventilator-dependent chronic obstructive pulmonary disease (COPD) patients, NIMV has been shown to be as effective as invasive
ventilation in reducing inspiratory effort and improving arterial blood gasses. In
fact, following some uncontrolled clinical studies in which NIMV was used as a
bridge to weaning, Nava et al. [5] performed the first study of this strategy. They
randomized 50 COPD patients with hypercapnia into two groups and administered
SBT with a T-piece 48 h after mechanical ventilation. One group was extubated and
received pressure support ventilation (PSV) noninvasively, and the other group was
administered invasive PSV. Patients in the group that received NIMV had lower
weaning durations and nosocomial pneumonia incidence and higher 60-day survival rates. In addition, pH and PaCO2 levels were similar in the NIMV group compared with the invasive mechanical ventilation (IMV) group.
Jiang et al. [6] conducted a prospective study on 93 patients who were randomized either to receive NIMV or oxygen therapy after planned or unplanned extubation, and they found no differences in the reintubation rates between two groups.
Nava [7] and Ferrer et al. [8] performed two randomized trials to assess whether
NIMV is effective in preventing the occurrence of post-extubation failure in patients
at risk. Both of these studies showed that the groups treated with NIMV had a lower
rate of intubation than the groups in which standard therapy was used. Furthermore,
in one of the two studies, intensive care unit mortality was also reduced in the subgroup where patients with hypercapnia were treated with NIMV. Several randomized controlled trials, mainly conducted in patients with preexisting lung disease,
have shown that the use of NIMV to avoid extubation in patients with difficult and
prolonged weaning can result in reduced periods of endotracheal intubation, lower
complication rates, and improved survival. NIMV is effective in avoiding respiratory failure after extubation and improving survival in patients at risk for complications [9]. In their randomized, prospective, clinical trial on 33 patients receiving
IMV with acute respiratory failure diagnosis, Girault et al. [10] aimed to evaluate
the utility of NIVM on systematic extubation in the difficult weaning process and its
effects on weaning duration. They administered invasive PSV with decreasing pressure support levels until the extubation of all patients in both groups. Then they
extubated patients in one group and administered NIMV with 24 h durations.
Between NIVM administrations, they gave nasal oxygen. NIVM administration
was performed via nasal or facial mask suitable for the face structure of the patient.
11
Noninvasive Mechanical Ventilation in Difficult Weaning in Critical Care
87
In the other group, patients were extubated when invasive pressure support ventilation (IPSV) pressure suport levels were below 8 cmH2O by decreasing levels with
35 cmH2O, and they were given nasal oxygen following the extubation. The
authors showed that it is possible to use NIMV as an early extubation and weaning
technique and that it can reduce the duration of invasive mechanical ventilation (i.e.,
it permits earlier removal of the endotracheal tube) compared with invasive PSV in
weaning intubated patients who are difficult to wean.
Quinnell et al. [11] performed a study on 67 patients with COPD in which invasive mechanical ventilation treatment was administered. Their reason for choosing
this patient population was the greater possibility of difficult weaning. Invasive PSV
was administered to the patients during the weaning process. After patients were
extubated, NIVM was administered if they were not successful in spontaneous ventilation without any support (only oxygen administration via nasal or face mask).
NIVM was administered only during the daytime. However, at night, if peripheral
oxygen saturation values dropped below 80 %, NIMV was also administered. The
authors concluded that, following extubation, use of PSV with NIVM increases
weaning success in COPD patients with difficult weaning.
In a randomized, clinical, prospective study on 43 patients with persistent weaning failure (failed weaning attempts over 3 consecutive days), Ferrer et al. [12] extubated patients in one group and administered NIMV and used conventional weaning
techniques in the other group. They showed that earlier extubation with NIV results
in shorter mechanical ventilation and length of stay, less need for tracheotomy, lower
incidence of complications, and improved survival in these patients.
11.3
Analysis
Although in studies to date NIVM is reported to be essential in difficult weaning,

NIMV administration still has not been placed in a general weaning algorithm.
There are some reasons for this. For example, humidification and warming of the
oxygen-air mixture used during NIVM administration are still an issue. Passive
warming is inadequate and adjusting the humidity and temperature with active
humidifiers may be difficult. In addition, use of distilled water can be a source of
nosocomial infections, which increases cost. Supplying patients with appropriate
interfaces (e.g., masks, cannulas) for NIMV administration is difficult, and use of
inappropriate interfaces increases air leaks. Aerophagia, excessive air swallowing,
impairs patient-ventilator interaction. In addition, interfaces can cause pressure
sores on the face area. All these issues affect the patient comfort.
Early extubation and continuing the weaning process with NIMV eliminates the
patients need of sedation, and this provides hemodynamic stability. Respiratory
physiotherapy can be performed more effectively as the patient can be mobilized in
the bed easily and can contribute actively. In addition, as described in the studies
above, early extubation and NIVM administration can protect patients from endotracheal tube-related complications (e.g., upper airway injuries, nosocomial pneumonia, sedation, single lung ventilation).
88
G.M. Koksal and E. Erbabacan
Most studies on NIMV during the weaning process are performed with the PSV
mode and on COPD patients who are susceptible to difficult weaning. Results
revealed can differ in different ventilation modes and patient groups (such as postoperative or oncological). For example, use of positive-pressure NIMV in the postoperative period in patients who underwent upper abdominal surgery (gastric,
esophageal, etc.) with anastomosis can damage the anastomosis line. Thus, the use of
NIMV with lower pressure support levels may not prevent early respiratory failure
occurrence. This would increase the reintubation rate and cause loss of precious time.
There are no studies evaluating the difference between continuous positive airway
pressure (CPAP) and biphasic positive-pressure ventilation (BIPAP) administration.
The differences in these modes can affect weaning process in terms of patient comfort. Increasing patient cooperation in difficult weaning cases can assist the weaning.
Another point that needs further attention is the time and the intervals of NIMV
administration. NIVM administration during the daytime may be insufficient. At
night, patients are more immobile, and to protect their sleep, activities such as postural drainage and physiotherapy are preferred to be administered during the daytime. Hence, desaturation is observed more frequently at night. Regular use of
NIMV is also recommended during the night [11].
The study of Giraul et al. [9] showed that intermittent NIMV with 24 h episodes
(this being dependent on patient cooperation) is effective and comfortable.
Conclusions
NIMV may be safely and successfully used in difficult weaning in critical care to
shorten the process of liberation from mechanical ventilation in stable patients
recovering from an episode of acute respiratory failure who had previously failed
a weaning trial. Further studies are needed to assess the benefits of NIMV in
weaning in other forms of respiratory failure, such as acute respiratory distress
syndrome, postoperative respiratory failure, and cardiac impairment.
The time needed for weaning is approximately 40 % of the mechanical

ventilation duration. It has been shown that weaning duration is prolonged
in 15 % of patients.
NIMV is used for two main purposes: as a preventive measure to avoid
intubation in an acute respiratory failure situation, and after extubation in
patients with difficulty weaning.
NIMV is theoretically able to counteract several physiological mechanisms associated with weaning difficulties.
NIMV is effective in avoiding respiratory failure after extubation and
improving survival in patients at risk for complications.
Use of NIMV as an early extubation and weaning technique can reduce the
duration of invasive mechanical ventilation compared with invasive PSV
weaning in intubated patients who have difficulty weaning.
11
89
References
1. Koksal GM, Sayilgan C, Sen O, et al. The effects of different weaning modes on the endocrine
stress response. Crit Care. 2004;8:R314.
2. Jeong BH, Ko MG, Nam J, et al. Differences in clinical outcomes according to weaning classifications in medical intensive care units. PLoS One. 2015. doi:10.1371/journal.pone.0122810.
3. Tonnelier A, Tonnelier J-M, Nowak E, et al. Clinical relevance of classification according to
weaning difficulty. Respir Care. 2011;56:58390.
4. Ferrer M. Non-invasive ventilation in the weaning process. Minerva Anestesiol.
2008;74:3114.
5. Nava S, Ambrosino N, Clini E, et al. Noninvasive mechanical ventilation in the weaning of
patients with respiration failure due to chronic obstructive pulmonary disease. A randomized
controlled trial. Ann Intern Med. 1998;128:7218.
6. Jiang JS, Kao SJ, Wang SN. Effect of early application of biphasic positive airway pressure on
the outcome of extubation in ventilator weaning. Respirology. 1999;4:11165.
after extubation in high risk patients. Crit Care Med. 2005;33:246570.
8. Ferrer M, Valencia M, Nicolas JM, et al. Early non-invasive ventilation averts extubation failure in patients at risk: a randomized trial. Am J Respir Crit Care Med. 2006;173(2):16470.
9. Ferrer M, Sellares J, Torres A. Noninvasive ventilation in withdrawal from mechanical ventilation. Semin Respir Crit Care Med. 2014;35:50718.
10. Girault C, Daudenthun I, Chevron V, et al. Noninvasive ventilation as a systematic extubation
and weaning technique in acuteon-chronic respiratory failure: a prospective, randomized controlled study. Am J Respir Crit Care Med. 1999;160:8692.
11. Quinnell TG, Pilsworth S, Shneerson JM, et al. Prolonged invasive ventilation following acute
ventilatory failure in COPD. Weaning results, survival, and the role of noninvasive ventilation.
Chest. 2006;129:1339.
12. Ferrer M, Esquinas A, Arancibia F, et al. Noninvasive ventilation during persistent weaning
failure: a randomized controlled trial. Am J Respir Crit Care Med. 2003;168:706.

in Post-extubation Failure: Interfaces
and Equipment
12
Dirk Dinjus
12.1
Introduction
Invasive mechanical ventilation can reduce the mortality of patients with acute critical illnesses. However, the procedure itself puts patients at risk for a number of
device-associated complications such as ventilator-associated lung injury, ventilatorassociated infection [1], and weakening of the respiratory muscle pump. The need
to reintubate a patient occurs in as few as 0.42 % of neurosurgical patients [2] and
as many as 23 %, with the highest rates in medical intensive care units (ICUs).
The weaning procedure is an effort to achieve termination of dependent ventilation. The weaning period takes up to 50 % of the overall invasive ventilation time
[3]. Noninvasive ventilation (NIV) in intensive care medicine is a proven indication
to avoid intubation [4] and to advance extubation in the weaning procedure after
intubation [5] as well as in the treatment of post-extubation failure [6]. The use of
NIV can shorten the time on invasive ventilation [7].
12.2
NIV to Prevent Extubation Failure
Some randomized controlled trials (RCTs) have investigated the effects of preventive NIV in an unselected population immediately after extubation in comparison
with standard treatment. There was no statistical difference in patient outcome,
most likely because of the unselected candidates [8]. In early studies of unselected
patients, only a few patients had previously diagnosed chronic obstructive pulmonary disease (COPD), and hypercapnia was not an included criterion to define the
D. Dinjus, MD
Division of Cardiology, Pulmonology and Vascular Medicine, Department of Medicine,
University of Duesseldorf, Moorenstr. 5, Duesseldorf 40225, Germany
e-mail: dirk.dinjus@med.uni-duesseldorf.de
DOI 10.1007/978-3-319-04259-6_12
91
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D. Dinjus
indication for primary NIV use after extubation. In an RCT comparing NIV versus
standard medical treatment in patients with risk factors for weaning failure, the
reintubation rate was lower in the NIV group, but there was no difference between
groups in ICU and hospital length of stay and survival [9]. Patients with risk factors
for respiratory failure after extubation were randomized to receive NIV or oxygen
mask. NIV reduced the incidence of respiratory failure and improved the hospital
survival rate. However, overall mortality was reduced only in a subgroup of hypercapnic patients. A study of selected hypercapnic patients reported a decreased incidence of respiratory failure, reintubation, and mortality rate at 3 months [10]. This
demonstrates that preventive application of NIV in a specific targeted population is
beneficial.
Risk factors for post-extubation failure include the following [9]:
Chronic heart failure
Hypercapnia (>45 mmHg)
More than one comorbidity
Weak cough
More than one spontaneous breathing trial (SBT) failure
Upper-airway obstruction
Excessive respiratory secretions
Severe obesity
12.3
NIV to Manage Extubation Failure
NIV was considered a promising therapy after extubation failure to avoid reintubation at a 2001 International Consensus Conference in Intensive Care Medicine. This
consideration was mainly based on information from uncontrolled studies or comparison with matched historical patients collective [11]. The results of RCTs
addressing the use of NIV in the management of patients with respiratory failure
after extubation were not, however, as promising as expected. One trial with more
than 300 patients included defined respiratory distress (>30 bpm or respiratory rate
>50 % from baseline) in 81 patients. These patients were randomized to NIV or
standard treatment. The study showed no significant difference in reintubation, ICU
stay, or survival [12]. Another RCT also showed no difference in reintubation rate
or ICU stay and an increased mortality rate among the NIV group patients [13]. This
was related to a longer time to reintubation in the NIV group. Both of these studies
had a patient cohort with only about 10 % of patients having COPD. NIV in both
studies was performed with active exhalation valve systems. In one study, the ventilation mode was volume controlled [13].
Today, advanced devices with sophisticated algorithms using passive expiration
valves and pressure-controlled modes may have different results. The focus on ventilatory failure, seen most frequently in obstructive lung diseases such as COPD,
results in beneficial use of NIV in the weaning process [14].
12
Noninvasive Mechanical Ventilation in Post-extubation Failure
12.4
93
Interfaces and Equipment
To achieve NIV, the interface between the device and the patients airway is crucial.
Oronasal, nasal, and oral masks, mouthpiece nasal pillows, total face masks, and
helmets are commercially available. The oronasal mask is most often preferred in
studies. To perform NIV with good success, it is important to have a variety of different mask types available from different companies to achieve good comfort for
the patient. Special care should be given to the skin, with regular visual inspection
at least four times a day. Moderate leaks can be tolerated in NIV devices, but they
should not irritate the eyes. A ventilator with good leak compensation capacity
should be used.
Intensive care respirators usually do not work with a turbine but with compressed
air and valves. This results in a technical limitation with regard to leak compensation. NIV should be implicated with a specialized NIV-respirator. To improve
patient comfort and tolerance, a skilled and calm clinician at the bedside is
necessary.
Conclusion
Post-extubation failure is associated with an increased risk of reintubation, prolonged ICU and hospital stay, and mortality. Early application of NIV after extubation decreased ICU and hospital mortality rates but not the reintubation rate
[8]. However, there are also data that show an increased risk to the patients if
NIV is used in the management of post-extubation failure. To avoid harm to the
patient, the post-extubation failure risk should be assessed before extubation. All
patients at risk should be directly treated with NIV to prevent post-extubation
failure. The success of the NIV should be monitored closely to avoid delay if
NIV fails to keep the patient stable. NIV should not be used to treat post-extubation failure as it has shown no conclusive benefit in a mixed population and even
excess mortality in a large RCT [13].
Use a standardized weaning protocol.

Address risk factors for post-extubation failure.
Perform NIV application immediately after extubation.
Closely monitor the success of the NIV treatment.
Do not use NIV to treat post-extubation failure.
Disclosures The author received a 40,000 unrestricted research grant from Linde Gas
Therapeutics, Unterschleissheim, Germany.
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D. Dinjus
References
1. Torres A, Aznar R, Gatell JM, et al. Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis. 1990;142:5238.
2. Shalev D, Kamel H. Risk of reintubation in neurosurgical patients. Neurocrit Care.
2015;22(1):159.
3. Esteban A, Ferguson ND, Meade MO, et al. Evolution of mechanical ventilation in response
to clinical research. Am J Respir Crit Care Med. 2008;177:1707.
4. Meduri GU, Abou-Shala N, Fox RC, Jones CB, Leeper KV, Wunderink RG. Noninvasive face
mask mechanical ventilation in patients with acute hypercapnic respiratory failure. Chest.
1991;100(2):44554.
5. Hess DR. The role of noninvasive ventilation in the ventilator discontinuation process. Respir
Care. 2012;57(10):161925.
6. Olper L, Corbetta D, Cabrini L, Landoni G, Zangrillo A. Effects of non-invasive ventilation on
reintubation rate: a systematic review and meta-analysis of randomised studies of patients
undergoing cardiothoracic surgery. Crit Care Resusc. 2013;15(3):2207.
7. Burns KE, Adhikari NK, Keenan SP, et al. Use of non-invasive ventilation to wean critically ill
adults off invasive ventilation: meta-analysis and systematic review. BMJ. 2009;338:b1574.
8. Lin C, Yu H, Fan H, Li Z. The efficacy of noninvasive ventilation in managing postextubation
respiratory failure: a meta-analysis. Heart Lung. 2014;43(2):99104.
9. Nava S, Gregoretti C, Fanfulla F, Squadrone E, Grassi M, Carlucci A, et al. Noninvasive ventilation to prevent respiratory failure after extubation in high-risk patients. Crit Care Med.
2005;33:246570.
11. Hilbert G, Gruson D, Portel L, et al. Noninvasive pressure support ventilation in COPD
patients with postextubation hypercapnic respiratory insufficiency. Eur Respir J.
1998;11:134953.
12. Keenan SP, Powers C, McCormack DG, et al. Noninvasive positive-pressure ventilation for
postextubation respiratory distress: a randomized controlled trial. JAMA. 2002;287:323844.
13. Esteban A, Frutos-Vivar F, Ferguson ND, et al. Noninvasive positive-pressure ventilation for
respiratory failure after extubation. N Engl J Med. 2004;350:245260.
14. Ornico SR, Lobo SM, Sanches HS, et al. Noninvasive ventilation immediately after extubation
improves weaning outcome after acute respiratory failure: a randomized controlled trial. Crit
Care. 2013;17(2):R39.
Monitoring and Mechanical Ventilator

Setting During Noninvasive Mechanical
Ventilation: Key Determinants in
Post-extubation Respiratory Failure
13
D. Chiumello, F. Di Marco, S. Centanni, and Mietto Cristina
13.1
Respiratory Failure After Extubation
13.1.1 Definition and Epidemiology

Extubation failure is usually defined as the need for reintubation within 4872 h
following extubation [1]. Patients may be unable to maintain spontaneous breathing
for multiple reasons: increased workload of breathing, cardiovascular dysfunction,
airway obstruction, or excessive secretions. The incidence of post-extubation respiratory failure ranges between 10 and 20 % [2]. Patients who fail extubation have
higher mortality, consistently reported at about 2050 % in intensive care units
(ICUs), and longer ICU and hospital stays [3]. Reintubation is a risk factor for
ventilator-associated pneumonia [4] and is independently associated with ICU mortality [3, 5, 6]. A minority of reintubated patients die in the first 24 h after reintubation, whereas mortality increases with time to reintubation [7]. Moreover,
upper-airway obstruction is the reason for reintubation in about 515 % of cases,
but no increase in mortality has been reported in this population [7]. Thus, three
scenarios explain the higher mortality rate: (1) reintubation entails risks per se, (2)
it is a marker for severity of illness, or (3) it is a consequence of a new event occurring between extubation and reintubation.
D. Chiumello (*) M. Cristina

Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Dipartimento di Anestesia,
Rianimazione e Terapia del Dolore, Fondazione IRCCS Ca Granda-Ospedale
Maggiore Policlinico, Universit degli Studi di Milano, Milan, Italy
e-mail: chiumello@libero.it
F. Di Marco S. Centanni
Unit respiratoria, Ospedale San Paolo, Dipartimento Scienze della Salute, Universit degli
Studi di Milano, Milan, Italy
DOI 10.1007/978-3-319-04259-6_13
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D. Chiumello et al.
Post-extubation respiratory distress is defined by classical clinical signs of respiratory muscle fatigue and gas exchange impairment. Numerous risk factors for extubation failure have been reported, including abundant secretions and cough strength,
older age, chronic respiratory disease, severity of illness, cardiac or neurological
impairment, prolonged mechanical ventilation, lung derecruitment during a spontaneous breathing trial (SBT), and hypercapnia [5, 8]. Patients with underlying heart
or respiratory disease are particularly at risk for extubation failure [3].
Respiratory failure is a severe impairment in gas exchange and respiratory
mechanics that usually requires invasive mechanical ventilation. Noninvasive ventilation (NIV) has been shown to be effective in improving gas exchange and respiratory mechanics in select patients with acute respiratory failure [9, 10]. Although
NIV was initially advocated as a promising tool to avoid reintubation in the case of
post-extubation respiratory failure [9], randomized clinical trials found benefits
only in high-risk patients and in the postoperative period.
In this chapter, the main evidence on the efficacy of NIV to prevent or treat postextubation respiratory failure is reviewed. At the same time, NIV modes and settings are presented so that respiratory support can be tailored to the individual
patient.
13.1.2 Post-extubation Respiratory Failure in ICU Patients

Patient selection has been shown to be of paramount importance in the ICU setting.
Evidence supporting the use of NIV in a mixed population of patients with postextubation respiratory failure is scarce. Timing of NIV implementation is equally
important, because, after respiratory failure is fully established, no advantage in
outcome could be found. Conversely, prophylactic NIV use in high-risk patients
(i.e., chronic obstructive pulmonary disease (COPD) or hypercapnic patients)
entails the major benefit.
Two large, randomized studies were performed to test the efficacy of NIV in
patients with a diagnosis of respiratory failure within 48 h after elective extubation.
No advantage in reintubation rate or other clinical outcome was found [11, 12].
Although few COPD patients were enrolled in either study, this selected population
could benefit the most from NIV. A recent meta-analysis confirmed that, pooling
together the results of these two studies, the reintubation rate was not significantly
reduced by the use of NIV (relative risk (RR) 1.02, 95 % confidence interval (CI)
0.831.25) [2]. Esteban et al. [12] found a higher relative risk of death in the NIV
group of 1.78 (95 % CI 1.033.20). Time delay to reintubation was proposed as the
cause of the increased mortality [11, 12].
A different approach focused on the early use of NIV to prevent reintubation in
high-risk patients. Nava et al. [13] hypothesized that the early use of NIV was
effective in avoiding reintubation in patients with at least one of the following risk
factors: hypercapnia, congestive heart failure, ineffective cough and excessive tracheobronchial secretions, more than one failure of a weaning trial, more than one
comorbid condition, or upper airway obstruction. NIV determined a reduction of
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97
16 % in the risk for reintubation (p = 0.027) and a trend toward a reduced ICU
mortality, probably due to an increased risk of death of 60 % in the reintubated
patients. The results of this study differed from a previous trial that showed no difference in reintubation rate between NIV and conventional therapy [14]. Although
in the latter study there was a high rate of unplanned extubations and an unselected
ICU population was enrolled, similar to the studies of Keenan and Esteban [11,
12]. Ferrer et al. [15] conducted a similar study and found a reduction in postextubation respiratory failure in high-risk patients (p = 0.029), largely during the
first day post-extubation, and a significant benefit in mortality (p = 0.015). It is
noteworthy that NIV was continuously delivered for 24 h and a large proportion
(51 %) of COPD patients was included, thus enrolling the best responders to
NIV. Reintubation rate was not different between the two groups, but NIV was
allowed as rescue therapy and could prevent reintubation in 47 % of patients in the
control group. Later, the same group designed a new randomized, controlled trial
to confirm that early use of NIV is beneficial to prevent post-extubation failure in
COPD patients [16]. This study found similar results to the previous one. NIV
reduced the incidence of respiratory distress after extubation in high-risk patients,
but no difference in reintubation rate could be detected, probably as a consequence
of the high successful use of NIV as rescue therapy in the control group (15 patients
out of 20 overt cases of post-extubation respiratory failure avoided intubation after
NIV implementation). Other studies found similar results, supporting the early
post-extubation use of NIV in patients with planned extubation and risk factors for
extubation failure [1719].
13.1.3 Post-extubation Respiratory Failure

in the Postoperative Period
Acute respiratory failure in the postoperative period is one of the most severe respiratory complications that can occur in the postoperative period. Postoperative reintubation entails a higher mortality and morbidity. Continuous positive airway
pressure (CPAP) and NIV have been shown to be beneficial during the postoperative
period to prevent or treat pulmonary complications [20]. NIV increases lung volumes and alveolar ventilation, decreases work of breathing, and counterbalances
diaphragmatic dysfunction to relieve the respiratory system modifications occurring
after anesthesia, surgery, and pain. Thus, postoperative NIV was shown to improve
gas exchange, minimize atelectasis formation, and increase functional residual
capacity [21].
Two different approaches have been proposed: (1) the prophylactic use of NIV to
prevent respiratory modification, thus avoiding the development of acute respiratory
failure and therefore the need for reintubation, and (2) the therapeutic use of NIV in
patients once respiratory failure is already established.
Squadrone et al. [22] studied the effects of early CPAP in hypoxemic patients
who underwent abdominal surgery. Severely hypercapnic patients were excluded.
Patients were randomized to a control group or to CPAP until resolution of
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D. Chiumello et al.
hypoxemia. The primary outcome was reintubation within 7 days after surgery. The
study was stopped at the interim analysis because of the lower rate of reintubation
in the CPAP group (p = 0.005). Intubation occurred in 10 % of patients in the control
group versus 1 % in the treatment group, with a RR of 0.099 (95 % CI 0.010.76).
Another study assessed the prophylactic use of CPAP after thoracoabdominal surgery, finding a similar reduction in reintubation rate (19 % vs. 3 %, p < 0.05) [23].
Several studies evaluated the effects of NIV in preventing respiratory failure during
the postoperative period after different kinds of surgery, often considering reintubation rate as part of a composite outcome [2426]. Evidence suggests the efficacy of
NIV in patients with postoperative respiratory failure, especially in abdominal and
thoracic surgery.
Antonelli et al. [27] studied NIV as a treatment strategy for respiratory distress
after solid organ transplantation. The primary endpoint was reintubation rate, and
20 % of patients in the NIV group versus 70 % in the control group were reintubated
(p = 0.002). NIV was used for a median time of 50 h. The benefits of NIV in immunocompromised patients were reinforced by Rocco et al. [28], who enrolled patients
with lung bilateral transplant. Twenty-one patients who developed respiratory failure postoperatively were treated with NIV and intubation was prevented in 86 % of
them. Otherwise, this is a special population in which the use of immunosuppressant drugs increases morbidity and mortality associated with pulmonary
infections.
Over a 2-year period, Jaber et al. [29] reported that 20 % of patients had postextubation respiratory failure after abdominal surgery and that 68 % of the patients
who were treated with NIV avoided reintubation. Numerous observational studies
found similar results in a mixed population of surgical patients [3032]. Among the
others, Varon et al. [30] successfully treated postoperative respiratory distress in
70 % of cases. Auriant et al. [33] used NIV after lung resection, and 50 % of patients
in the control group versus 21 % in the interventional group required reintubation
(p = 0.035). Similar results were obtained by Michelet et al. [34] in patients after
esophagectomy. Reintubation was lower in the NIV group (9/36 vs. 23/36, p = 0.008).
No differences in surgical complications, such as anastomosis air leakage, were
recorded.
NIV is a feasible and useful treatment in cases of postoperative respiratory failure. Note that NIV delivered though a helmet was associated with lower failure,
mainly because of better tolerability [35]. Moreover, different NIV techniques and
settings were used in these studies. A comprehensive knowledge of interfaces and
NIV settings is important to tailor the support to the individual patient.
13.2
Setting Up the NIV Support
13.2.1 Patient Selection

Other aspects of NIV use, including patient cooperation after extubation, absence of
deteriorating mental status, absence of hemodynamic instability, and ability to
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99
protect airways, are crucial to the application and success of NIV. NIV presents both
absolute (e.g., facial trauma or severe upper gastrointestinal bleeding or hemoptysis) and relative contraindications. Finally, primarily in cases of curative (i.e., for
respiratory failure treatment) NIV or CPAP and also in cases of prophylactic (i.e.,
for respiratory failure prevention) use, tracheal intubation should never be delayed
if respiratory status worsens because delayed reintubation may increase mortality
[7, 12].
Randomized controlled trials (RCTs) suggest benefit from NIV after extubation in patients at high risk of deterioration [13, 15, 16]. In general, high-risk
patients were defined differently among the RCTs: (1) age greater than 65 years,
cardiac failure as the cause of intubation, or Acute Physiology and Chronic
Health Evaluation (APACHE) II score greater than 12 at the time of extubation;
(2) more than one of the following: failure of consecutive weaning trials, chronic
cardiac failure, arterial pressure of CO2 >45 mmHg after extubation, more than
one noncardiac comorbidity, weak cough or stridor after extubation not requiring immediate intubation; and (3) history of chronic respiratory disease with
ventilation for more than 48 h and hypercapnia during the spontaneous breathing
trial. In an initial meta-analysis, the results for all patients combined showed
statistically significant reduced rates of reintubation (RR 0.42, 95 % CI 0.25
0.70), ICU mortality (RR 0.35, 95 % CI 0.160.78), and a nonsignificant reduction in the risk of hospital mortality (RR 0.66, 95 % CI 0.421.04) [36]. A more
recent meta-analysis, which included more studies, did not find a statistically
significant effect of NIV after extubation in decreasing reintubation rate (RR
0.75, 95 % CI 0.451.15) [2]; however, the same authors found NIV effective in
reducing reintubation rate, ICU mortality, and hospital mortality rate compared
with standard medical treatment in the planned extubation subgroup (i.e.,
patients who tolerated SBT). So, although controversial, accumulating evidence
suggests that this technique has a role in prevention of acute respiratory failure
after extubation, but mainly in patients with hypercapnic and congestive heart
failure who are at high risk for extubation failure and who tolerated a SBT, and
in centers with extensive experience both in the use of NIV and invasive airway
management.
13.2.2 Ventilation Mode and Setting, Ventilators, and Interfaces

For preventive and curative approaches, both CPAP and NIV have been used.
For NIV, pressure support ventilation (PSV) is the mode of ventilation most often
used. CPAP and PSV setting recommendations in post-extubation respiratory
failure prevention or treatment are based solely on clinical experience, without
any formal data to support the superiority of one technique over another. The
same is true for the type of ventilator: both ICU and portable ventilators can be
used. In the case of ICU ventilators, however, a specific NIV module is needed to
manage the presence of air leaks always present in case of a noninvasive interface use.
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In general, the studies that evaluated the use of PSV and positive end-expiratory pressure (PEEP) after extubation do not suggest a specific approach in this
setting. Usually, PEEP is started at 35 cmH2O and increased as needed to
improve oxygenation, without adverse hemodynamic effect and with particular
caution in COPD patients to avoid the worsening of hyperinflation. Rarely does
the level of PEEP exceed 10 cmH2O. Pressure support is started at the same level
(35 cmH2O) and increased in increments of 2 cmH2O to achieve 610 ml/kg
expiratory tidal volume, a decrease in the patients respiratory rate, and a comfort improvement; the average pressure support level is 1215 cmH2O. The slope
of delivered pressure (i.e., speed of pressurization) is set up as maximum tolerated, inspiratory and expiratory trigger of 5 l/min, and 50 % of peak inspiratory
flow. FiO2 is set to achieve arterial saturation between 92 and 95 %, with an average initial level of 5060 %. It has been demonstrated that the analysis of the
waveforms generated by ventilators for the optimization of ventilator setup has a
significant positive effect on physiological and patient-centered outcomes during
acute exacerbation of COPD. Thus, in the post-extubation setting, this approach
is probably convenient, and the acquisition of specific skills in this field should
be encouraged [37].
For CPAP, a pressure of 710 cmH2O is required to keep tracheal pressure positive during the entire respiratory cycle. In the study of Squadrone et al. [22], which
demonstrated that CPAP may decrease the incidence of endotracheal intubation and
other severe complications in patients who develop hypoxemia after elective major
abdominal surgery, CPAP was generated using a flow generator with adjustable
inspiratory oxygen fraction set to deliver a flow of up to 140 l/min and a springloaded expiratory pressure valve and applied using a polyvinyl chloride transparent
helmet. The CPAP level used was 7.5 cmH2O.
In the postoperative setting, Jaber et al. [21] proposed a protocol for NIV,
mainly for curative reasons. This protocol suggests the use of PSV, starting
with low pressures and gradually increasing pressure support (usually 1015
cmH2O) and PEEP (510 cmH2O) as tolerated, without major leaks, to achieve
alleviation of dyspnea, decreased respiratory rate, increased expiratory tidal volume (to achieve 610 ml/kg), and good patient-ventilator synchrony. An increase
of total inspiratory pressure (PEEP + PS) of more than 25 cmH2O is never recommended [21].
As in other areas of NIV use, in the post-extubation setting there have been no
specific recommendations for NIV weaning/duration published in guidelines to
date. So far, there are three different weaning/duration approaches: (1) gradual
decrease in duration of NIV, (2) gradual decrease in ventilator support level and
duration, and (3) abrupt discontinuation of NIV when clinical and gas exchange/
pH targets have been achieved. In many cases, the approach used in the postextubation trials is not described; however, in clinical practice, the second approach,
gradual decrease in ventilator support level and duration, is probably most often
used.
13
101
The interface is the defining element of NIV. Today, different types of interfaces, which differ in terms of shape, mechanical properties, and comfort, are
available, and their choice and fitting is a key element of NIV success [38].
Interfaces for NIV that deliver positive pressure both through the mouth and nose
(i.e., oronasal masks) are the most widely used, because patients with respiratory
failure often have a high respiratory drive and are generally mouth-breathers. In
the last decade, larger masks covering the entire face (i.e., full-face mask) and
specifically designed helmets have been developed for delivering NIV, theoretically improving comfort and patient tolerance. The full-face or total face mask
covers the entire face, including the eyes; thus, this interface has a large inner
volume that could increase dead space. The main advantage of a full-face mask is
that, through its large perimeter, it avoids pressure over the nasal bridge, which is
frequently exposed to pressure sores as the skin is thin and directly on the nasal
bone. However, a full-face mask is generally more expensive than an oronasal
mask, and it is single use. It is noteworthy that recent studies have shown that,
despite marked heterogeneity in mask internal volume and compliance, the
dynamic dead space and, above all, the clinical efficacy of different masks is, on
average, very similar. The helmet, originally used to deliver the desired oxygen
fraction during hyperbaric oxygen therapy, was first proposed for delivery of CPAP
and subsequently for NIV. For CPAP delivery, in some cases this interface may be
preferred, as in the study of Squadrone et al. [22]. Because it has no contact with
the face, the helmet allows the patient to cough, see, and talk with supposedly better comfort and tolerance. However, specific problems may arise, such as the possible occurrence of axillary decubitus.
With the exception of the nasal mask and the mouthpiece, a variety of interfaces
for NIV can be used in the acute care setting. For the reasons previously discussed,
an oronasal mask is usually the first choice, and a hydrocolloid dressing can be used
to prevent nasal-bridge damage [38]. Moreover, in case of prolonged NIV, the socalled mask rotation approach (a planned sequential utilization of different interfaces) can be used. This approach can reduce pressure effects by alternating the
points of highest pressure and is also useful to improve the tolerance and efficacy of
NIV [39].
In 2012, the American Association for Respiratory Care published a guideline
for humidification during invasive and noninvasive mechanical ventilation [40].
This clinical practice guideline was based on 184 clinical trials and systematic
reviews, and 10 articles, and used the Grading of Recommendations Assessment,
Development, and Evaluation (GRADE) scoring system. Authors concluded that
active humidification is suggested for noninvasive mechanical ventilation, as it
may improve adherence and comfort. Passive humidification with heat and moisture exchangers (HME) was not recommended for noninvasive mechanical ventilation, inasmuch as they can increase the work of breathing, decrease alveolar
ventilation, and deliver less humidity in comparison with heated humidifiers
(HH). However a randomized controlled multicenter study [41], which tested the
102
D. Chiumello et al.
hypothesis that NIV delivered via ICU ventilators with HH is associated with a
reduced rate of intubation in comparison with HME, failed to show a short-term
physiological benefit of HH in comparison with HME, and no difference in intubation rate was found. It is noteworthy the NIV with ICU ventilators can be particularly challenging for HME because of the specific setting (e.g., inspiratory
gases are dry, respiratory rate is high, and mouth breathing is frequent during
NIV). Thus, in the post-extubation setting, airway humidification is suggested
with both HHs or HMEs with low internal volume to avoid excess dead space.
However, it is noteworthy that HMEs must provide a minimum of 30 mg H2O/l
and are contraindicated for patients with frank bloody or thick, copious secretions
and for patients with an expired tidal volume less than 70 % of the delivered tidal
volume (e.g., those with large bronchopleurocutaneous fistulas or in cases of
intentional or unintentional large mask leaks, because the patient does not exhale
enough tidal volume to replenish heat and moisture to adequately condition the
inspired gas) [40].
13.3
Monitoring
Monitoring is essential to ensure safety and efficacy of any treatment. Standard

monitoring for patients on NIV includes clinical evaluation, peripheral pulse oximetry (SpO2), and arterial blood gas analysis (ABG). Additional vital parameters and
ventilation parameters (e.g., tidal volume, pressures, air leak, and asynchrony) are
required for a comprehensive evaluation of delivered support. Moreover, the analysis of pressure and flow waveforms have proved to determine a faster response in
CO2 decrease and patient tolerance of NIV support [37]. This basic monitoring must
be always take place within the actual environment where the patient is treated. In
fact, NIV support can be safely performed outside of the ICU, where routine monitoring and the patients/health-care providers ratio are more limited, for example,
emergency departments or general wards [4244]. Having staff trained and expert
in NIV support available 24 h a day is more important than location to ensure safety
and efficacy of the treatment [44, 45]. Factors such as severity of respiratory distress, underling etiology, and the patients co-morbidity principally influence the
location of admission.
Bedside clinical evaluation is mandatory because it offers a direct assessment of
the patients work of breathing, recruitment of accessory muscles, abdominal paradox breathing, respiratory rate, patient comfort, and level of consciousness.
Evaluation of ventilation asynchrony should not rely on the patients queries but
always through the assessment of ventilator parameters and any signs of discomfort.
Improvement in physical examination usually occurs within 12 h in patients who
benefit from NIV.
Guidelines recommend continuous SpO2 monitoring, although it does not replace
ABG analysis [45]. Transcutaneous CO2 is advocated as useful to follow patients
13
103
response to NIV support but it is rarely reported in studies. Arterial blood gases
should be check within 12 h after NIV establishment to assess initial NIV response.
Studies consistently reported that early improvements in terms of oxygenation, pH,
or PaCO2 are good predictors of NIV success [4648]. Subsequent timing of ABGs
is determined by patients clinical course. If little improvements are shown after 1 h
of treatment, a second tight control is advisable to avoid any delay in reassessment
of patient status and possible intubation. Commonly, a second ABG analysis is
performed 46 h after the patient starts NIV and is a reasonable time to reach gas
exchange stability. Obviously, a new evaluation must be performed after any ventilator setting change. Other criteria suggesting NIV failure are worse encephalopathy or agitation, inability to clear secretions, inability to tolerate any of the interfaces,
and hemodynamic instability [48].
Numerous studies have evaluated the predictors of NIV failure, finding that more
severely ill patients, those with poor nutritional status or altered mental status, and
patients with evidence of pneumonia, abundant secretions, or with large air leaks
should be monitored more closely because they are at higher risk of NIV failure [5].
In general, the ability of clinicians to select patients with a high likelihood of success is poor and NIV failure rates are high [42, 48]. Two observational studies found
that approximately one-third of patients who received a trial of NIV failed [47, 49]
(Tables 13.1 and 13.2).
Table 13.1 Potential risk factors for extubation failure [5]

Study
Thille et al. (2011) [3]
Epstein et al. (1997) [50]
Frutos-Vivar et al. (2006) [51]
Vallverd et al. (1998) [52]
Namen et al. (2001) [53]
Mokhlesi et al. (2007) [54]
Smina et al. (2003) [55]
Khamiees et al. (2001) [56]
Chien et al. (2008) [57]
Teixeira et al. (2010) [58]
Risk factors for extubation failure

Age >65 years or underlying chronic cardiorespiratory disease
Age, APACHE II at time of weaning, and acute respiratory
failure of cardiac origin
Pneumonia as the reason for intubation, high rapid shallow
breathing index (f/VT), and positive fluid balance
Neurological patients
Rapid shallow breathing index (f/VT) >105, PaO2/FIO2
<200 mmHg, Glasgow Coma Scale score <8
Abundant endotracheal secretions, Glasgow Coma Scale score
10, PaCO2 44 mmHg during spontaneous breathing trial
Peak expiratory flow 60 l/min and rapid shallow breathing
index 100
Moderate or abundant endotracheal secretions, cough absent
or weak, hemoglobin 10 g/dl
Increase in B-type natriuretic peptide during a spontaneous
breathing trial
>4.5 % reduction in central venous saturation 30 min after
spontaneous breathing trial initiation
ICU
RCT
RCT
RCT
RCT
General ICU
General ICU
High-risk
High-risk
COPD
COPD
COPD
General ICU
Treatment
Treatment
Preventive
Preventive
Preventive
Preventive
Girault
et al. (2011)
[17]
Khilnani
Preventive
et al. (2011)
[18]
Preventive
Su et al.
(2012) [19]
RCT
RCT
RCT
RCT
Study type
RCT
Intervention Population
Preventive
General ICU
Author
Jiang
et al. (1999)
[14]
Keenan
et al. (2002)
[11]
Esteban
et al. (2004)
[12]
Nava et al.
(2005) [13]
Ferrer
et al. (2006)
[15]
Ferrer et al.
(2009) [16]
Table 13.2 Trials of NIV use for post-extubation respiratory failure
406
40
208
106
162
97
221
81
NPPV
NPPV
NPPV
NPPV
NPPV
NPPV
NPPV
NPPV
Face mask No difference in intubation rate
Face mask Lower incidence of post-extubation

respiratory failure in the NPPV
group
Face mask Lower intubation rate in the NPPV

group
Face mask Lower incidence of post-extubation
respiratory failure in the NPPV group
N of
Type of
patients ventilation Interface
Conclusion
93
NPPV
104
D. Chiumello et al.
Solid organ
transplant
Thoracoabdominal
surgery
Bilateral lung
transplant
Thoracic surgery
Thoracoabdominal
surgery
Abdominal surgery
Abdominal surgery
Thoracoabdominal
surgery
Cardiac surgery
Thoracoabdominal
surgery
Thoracoabdominal
surgery
Treatment
Treatment
Treatment
Preventive
Treatment
Preventive
Preventive
Treatment
Treatment
Preventive
Treatment
Cancer patients
Treatment
Observational
Observational
RCT
RCT
RCT
RCT
RCT
RCT
Observational
Observational
RCT
Observational
36
72
500
50
209
204
70
48
21
20
40
60
NPPV/
CPAP
NPPV
CPAP
CPAP
CPAP
CPAP
CPAP
NPPV
NPPV
CPAP
NPPV
NPPV
NPPV prevented intubation in 90 % of

patients
Lower incidence of post-extubation

respiratory complications in the CPAP
group
Nasal
mask
respiratory complications in the CPAP
group
Facial
NPPV/CPAP prevented intubation in
mask
56 % of patients
group
Nasal
mask
Face mask NPPV prevented intubation in 86 % of

patients
Nasal
Lower intubation rate in the NPPV
mask
group
Face mask Lower intubation rate in the CPAP
group
Nasal
mask
respiratory failure in the CPAP group
Helmet
Lower intubation rate in the CPAP
group
Nasal
mask
Face mask NPPV prevented intubation in 70 % of

patients
group
ICU intensive care unit, RCT randomized controlled trial, NPPV noninvasive positive pressure ventilation, CPAP continuous positive pressure ventilation
Postoperative Varon et al.

(1998) [30]
Antonelli
et al. (2000)
[27]
KindgenMilles et al.
(2000) [31]
Rocco et al.
(2001) [28]
Auriant et al.
(2001) [33]
Fagevik et al.
(2002) [23]
Bhner et al.
(2002) [24]
Squadrone
et al. (2005)
[22]
KindgenMilles et al.
(2005) [25]
Zarbock
et al. (2009)
[26]
Wallet et al.
(2010) [32]
Michelet et al.
(2009) [34]
13
105
106
D. Chiumello et al.
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Noninvasive Ventilation Withdrawal

Methodology After Hypercapnic
Respiratory Failure
14
Chung-Tat Lun and Chung-Ming Chu
Abbreviations
AHcRF
ARF
BTS
COPD
NIV
OSA
RCT
14.1
Acute hypercapnic respiratory failure

Acute respiratory failure
British Thoracic Society
Obstructive sleep apnea
Randomized controlled trial
Introduction
Noninvasive ventilation (NIV) has been shown to be effective in treating acute

respiratory failure (ARF) due to a variety of causes [1, 2], including chronic obstructive pulmonary disease (COPD) [3], neuromuscular diseases [4], and obesityhypoventilation syndrome [5, 6]. NIV can augment ventilation and unloading of
respiratory muscles, reduce atelectasis, and splint the upper airway in obstructive
sleep apnea.
Despite the effectiveness of NIV as a treatment, there has been no study of the
withdrawal method of NIV after recovery from ARF. The Royal College of
Physicians (United Kingdom) and the British Thoracic Society (BTS) published
C.-T. Lun, MBChB, MRCP (UK) C.-M. Chu, MD, MSc, FRCP, FCCP (*)
Division of Respiratory Medicine, Department of Medicine and Geriatrics,
United Christian Hospital, Hong Kong, China
e-mail: lunfrankie@yahoo.com; chucm@ha.org.hk
DOI 10.1007/978-3-319-04259-6_14
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C.-T. Lun and C.-M. Chu
guidelines on the use of NIV in the management of patients with COPD admitted to
hospital with acute hypercapnic respiratory failure (AHcRF) in 2008 [7]. The guideline suggested a 4-day weaning strategy, starting with reduction of NIV use during
the daytime. The BTS guideline adopted the above weaning strategy from a multicenter randomized controlled trial that was planned to compare the effect of NIV
and standard medical treatment instead of comparing different methods of NIV
withdrawal [8].
In contrast to the paucity of data in NIV withdrawal, an RCT was performed in
1995 comparing different methods of weaning in patients receiving invasive
mechanical ventilation [9]. A once-daily spontaneous breathing trial led to extubation about three times more quickly than intermittent mandatory ventilation and
about twice as quickly as pressure-support ventilation.
It is important to determine the best time and the best schedule to withdraw NIV
after ARF. Premature NIV withdrawal may be followed by early recurrence of
ARF. On the other hand, NIV is labor intensive, occupies high-dependency beds, is
sometimes uncomfortable for patients, and is costly. A reduction of NIV duration
may reduce nursing care, free up NIV machines and beds, reduce patient discomfort, reduce cost, and facilitate early discharge. This chapter reviews the available
evidence in relation to NIV withdrawal after resolution of ARF.
14.2
Analysis
14.2.1 Duration of NIV at Initiation

There is no comparative study on the duration of NIV at initiation. As patients suffering from ARF are at life-threatening risk, it seems reasonable to have long hours
of NIV to improve their gas exchange at the beginning of treatment. The BTS guideline recommends the patient have NIV fir as long as they can tolerate at the beginning of treatment [7]. Many clinical trial protocols also encourage patients to use
NIV for as long as they can tolerate [1, 2, 8].
14.2.2 Time to Consider NIV Withdrawal

The aim of NIV in AHcRF in COPD is to reduce PaCO2 by augmenting ventilation
and unloading respiratory muscles. Physicians may consider NIV withdrawal after
patients have achieved clinical stability with improvement in blood gases. The BTS
recommends considering NIV withdrawal after 24 h of commencement, if NIV is
successful, which is defined as pH 7.35, resolution of underlying cause or symptoms, and normalization of respiratory rate. Studies of NIV in COPD have similar
criteria for NIV withdrawal [7]. Kramer et al. [2] attempted withdrawal when the
respiratory rate was less than 24 breaths/min, heart rate less than 110 beats/min, pH
7.35 and adequate oxygenation with 90 % saturation with oxygen flow less than
3 L/min.
14 Noninvasive Ventilation Withdrawal Methodology
113
14.2.3 NIV Withdrawal Methods

There are a number of NIV withdrawal methods being practiced. Plant et al. [8]
described a stepwise withdrawal method for AHcRF in COPD, in which patients
were encouraged to use NIV as much as possible on day 1, for 16 h on day 2,
12 h on day 3, and NIV was discontinued on day 4. Kramer et al. [2] described
immediate discontinuation of NIV once arterial blood gases were normalized
and clinical stability was achieved, with resumption of NIV if deterioration
occurred. Martin [1] described NIV withdrawal by either gradual reduction in
the levels of ventilatory support or by initiating brief periods without
NIV. However, these studies were not designed to compare different methods of
NIV withdrawal.
The BTS guideline in 2008 adopted the withdrawal method described by Plant
et al. [7, 8]. It recommends gradual withdrawal of NIV over a period for 4 days, with
an extended period of NIV-free time during daytime initially. However, BTS also
allows earlier withdrawal of NIV if patients improve rapidly and it allows some
patients to have self-determined withdrawal.
At the time of writing, there have been three clinical trials assessing NIV withdrawal methods in COPD patients recovering from AHcRF. Damas et al. [10]
treated 78 COPD patients with AHcRF with NIV and gradually withdrew NIV if
patients were stabilized. During the first 24 h of withdrawal, patients had 1 h without NIV in each 3-h period, except at night time. On the second day, they had 2 h
without NIV in each 3-h period. On the third day, they had only a night period of
NIV treatment. NIV was discontinued on day 4. In this study, all patients completed
the withdrawal protocol with no reinstitution of NIV. However, this study did not
have a comparison arm.
Sellares et al. [11] published an RCT in abstract form, comparing immediate
withdrawal of NIV with conventional oxygen therapy versus 3 additional nights of
NIV in 128 patients with AHcRF. The majority of studied subjects were COPD
patients (74 %). No statistically significant differences between immediate versus
gradual NIV withdrawal were observed, in terms of respiratory failure after NIV
withdrawal, long-term ventilator dependency, hospital stay, readmission rate, or
mortality. The authors concluded that prolongation of NIV after resolution of
AHcRF does not improve outcomes, and NIV can be directly withdrawn when
AHcRF is resolved and the patient tolerates spontaneous breathing.
Lun et al. [12] compared immediate versus stepwise withdrawal of NIV (16 h on
day 1, 12 h on day 2, 8 h nocturnal NIV on day 3) in an RCT of 60 COPD patients
recovering from AHcRF. There was no statistically significant difference in the success rate, with NIV successfully stopped in 74.3 and 56 % in the stepwise and
immediate withdrawal groups, respectively. However, the number of subjects
recruited in this study is small, and a type II error with a false-negative result was
possible.
There has not been a study to assess whether NIV withdrawal can be accomplished through reduction in pressure support. There is also no study evaluating
different withdrawal methods in ARF caused by non-COPD conditions.
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C.-T. Lun and C.-M. Chu
14.2.4 Long-Term NIV Dependency

It is not uncommon that patients with AHcRF being treated with NIV cannot achieve
complete weaning from NIV. Cuvelier et al. [13] observed that up to 39 % nonCOPD patients and 19 % COPD patients who were treated for AHcRF by NIV were
unable to have their NIV stopped for 8 consecutive days afterwards, and they
became dependent on long-term NIV. In addition, COPD patients recovering from
AHcRF after NIV treatment have high rates of recurrence [14], and long-term domiciliary nocturnal NIV may reduce the recurrence rate by about 20 % [15]. Therefore,
the decision to completely withdraw NIV needs to be individualized.
There is a diversity of NIV withdrawal methods after resolution of ARF

being practiced, including gradual reduction in time on NIV, gradual
reduction in pressure settings, and immediate discontinuation. No withdrawal method has been demonstrated to be clearly superior by RCT. An
adequately sized, multicenter RCT is required to compare different withdrawal methods in different diseases causing ARF.
It reasonable to discontinue NIV immediately in patients who have recovered from ARF rapidly, with a readiness to resume NIV if they fail
withdrawal.
For slowly recovering patients, a more gradual NIV withdrawal schedule
should be adopted.
Selected patients may require long-term NIV, and complete withdrawal
may not be appropriate in all patients.
References
1. Martin TJ, Hovis JD, Costantino JP, et al. A randomized, prospective evaluation of noninvasive
ventilation for acute respiratory failure. Am J Respir Crit Care Med. 2000;161:80713.
2. Kramer N, Meyer TJ, Meharg J, et al. Randomised, prospective trial of noninvasive positive
pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med. 1995;151:
1799806.
3. Lightlower JV, Wedzicha JA, Elliott MW, et al. Non-invasive positive pressure ventilation to
treat respiratory failure resulting from exacerbation of chronic obstructive pulmonary disease:
Cochrane systematic review and meta-analysis. BMJ. 2003;326:18590.
4. McKim DA, Griller N, Leblanc C, et al. Twenty-four hour noninvasive ventilation in Duchenne
muscular dystrophy: a safe alternative to tracheostomy. Can Respir J. 2013;20:e59.
5. Perez LA, Golpe R, Piquer MO, et al. Short-term and long-term effects of nasal intermittent
positive pressure ventilation in patients with obesity-hypoventilation syndrome. Chest. 2005;
128:58794.
6. Carrillo A, Ferrer M, Gonzalez-Diaz G, et al. Noninvasive ventilation in acute hypercapnic
respiratory failure caused by obesity hypoventilation syndrome and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;186:127985.
14 Noninvasive Ventilation Withdrawal Methodology
115
7. BTS/RCP London/Intensive Care Society. The use of non-invasive ventilation in the management of patients with chronic obstructive pulmonary disease admitted to hospital with acute
type II respiratory failure (with particular reference to bilevel positive pressure ventilation).
http://www.brit-thoracic.org.uk/guidelines/nippv-%E2%80%93-niv-in-acute-respiratoryfailure-guideline.aspx. Date last updated Oct 2008.
8. Plant PK, Owen JL, Elliot MW. Early use of non-invasive ventilation for acute exacerbations
of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Lancet. 2000;355:19315.
9. Esteban A, Frutos F, Tobin MJ, et al. A comparison of four methods of weaning patients from
mechanical ventilation. N Engl J Med. 1995;332:34550.
10. Damas C, Andrade C, Araujo JP, et al. Weaning from non-invasive positive pressure ventilation: experience with progressive periods of withdraw. Rev Port Pneumol. 2008;14:4953.
11. Sellares J, Ferrer M, Bencosme C, et al. Withdrawal of non-invasive ventilation in acute hypercapnic respiratory failure: randomized controlled trial. Am J Respir Crit Care Med.
2012;185:A6489.
12. Lun CT, Chan VL, Leung WS, et al. A pilot randomized study comparing two methods of noninvasive ventilation withdrawal after acute respiratory failure in chronic obstructive pulmonary
disease. Respirology. 2013;18:8149.
13. Cuvelier A, Viacroze C, Benichou J, et al. Dependency on mask ventilation after acute respiratory failure in the intermediate care unit. Eur Respir J. 2005;26:28997.
14. Chu CM, Chan VL, Lin AWN, et al. Readmission rates and life-threatening events in COPD
survivors treated with non-invasive ventilation for acute hypercapnic respiratory failure.
Thorax. 2004;59:10205.
15. Cheung AP, Chan VL, Liong JT, et al. A pilot trial of home non-invasive ventilation after acidotic respiratory failure in COPD. Int J Tuberc Lung Dis. 2010;14:6429.
Rational Bases and Approach

of Noninvasive Mechanical Ventilation
in Difficult Weaning: A Practical Vision
and Key Determinants
15
Antonio M. Esquinas
Traditionally, we understand mechanical ventilation as the principal tool of life support in critical patients for diverse forms of respiratory insufficiency in the intensive
care unit (ICU) [1]. From the first descriptions of its benefits in patients undergoing
surgical or medical procedures, it has demonstrated its effectiveness as a tool in the
control of alterations of gas exchange and in achieving muscular resting until the
initial process can be controlled [2]. Nevertheless, a considerable number of complications associated with invasive mechanical ventilation (IMV) deriving from endotracheal intubation (ETI), tracheotomy, and the prolongation of IMV are important
aspects to be considered and determine the short- and long-term prognosis [3].
Traditionally, the approach to this problem is based on the application of strict
protocols directed at the prevention of the complications associated with mechanical ventilation and on measures focused on reduction of the periods of mechanical
ventilation in patients [4]. In a percentage of patients, however, the alterations in gas
exchange and muscular fatigue cannot be controlled or reverted in a complete form,
prolonging the duration of mechanical ventilation [4, 5]. The number of cases that
are dependent on mechanical ventilation is variable, based on the published studies,
country, and weaning protocols [5]. Weaning protocols are oriented toward strengthening muscular weakness, improving control of bronchial secretions, early discontinuation of sedation, optimization of the ventilatory mechanics, and ability to reach
spontaneous breathing (SB) [5].
From a therapeutic point of view, we can classify prolonged mechanical ventilation (PMV) and the response to disconnection or weaning in different clinical
scenes. The first difficulty is the absence of consensus about the concept of PMV,
with different authors establishing different periods for its classification. This limits
A.M. Esquinas, MD, PhD, FCCP
Intensive Care and Non Invasive Ventilatory Unit, Hospital Morales Meseguer,
Murcia, Spain
e-mail: antmesquinas@gmail.com
DOI 10.1007/978-3-319-04259-6_15
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A.M. Esquinas
effective comparison of the published studies and the capacity to define a suitable
strategy for the problem. When this process is established, a classical form emerges
that we define as prolonged mechanical ventilation condition.
Its clinical presentation can be revealed by two main conditions: (a) the procedure
of the type of isolation of the patient airway (orotracheal intubation or tracheostomy)
or (b) it is temporarily revealed in the immediate or precocious period (extubation or
decannulation) as acute post-extubation respiratory insufficiency (APRF) or failed
decannulation. In both instances, the majority of patients have received a basic number of variable tests evaluating their capacity for SB, from a gradual reduction of
pressure support ventilation (PSV) to periods of oxygenation using a T tube [2, 4].
Patients who are unable to overcome their incapacity for spontaneous breathing
(PSV or T tube) are described as ventilatory-dependent or unweanable [6]. The
proportion and incidence are variable according to epidemiology studies, and the
protocols and strategies used to for disconnection or weaning from mechanical ventilation are also variable.
A variable proportion of unweanable patients, after a period of months or years,
can be disconnected from mechanical ventilation in special units (weaning units)
dedicated to difficult weaning. As an alternative, selected patients, such as those
with tracheostomy, can, after a prolonged tracheostomy period, become candidates
for programmed decannulation with the contribution of therapeutic or preventive
application of noninvasive mechanical ventilation [7]. A small subgroup of patients
can develop APRF in an accidental scenario (not programmed extubation) or autoextubation can be used [8]. Although protocols have been developed for IMV oriented to shortening the duration of mechanical ventilation and to ensure the success
for disconnection, there is still a subgroup of patients for whom it is impossible to
undergo disconnection of IMV [8, 9].
15.1
Current Use of Noninvasive Mechanical Ventilation
In patients who need prolonged mechanical ventilation or reintubation, there

can be established or considered other treatment measures, such as noninvasive
mechanical ventilation, that can diminish the incidence of complications associated with prolonged ventilation or the failure of extubation, decannulation, and
improvement of prognosis [10]. In these scenarios, two forms can be considered, one using NIV preventive measures, which identify the causes that contribute to post-extubation respiratory insufficiency or decannulation failure or,
on the contrary, therapeutic action once pathologies are present to restore
mechanical ventilation by means of reintubation or recannulation of the
patient [10, 11].
The latter situation affects in an unfavorable way the short- and long-term prognosis, specifically because of a greater risk of infections associated with mechanical
ventilation, muscular atrophy, undernourishment, and hospitalization costs [12, 13].
There is a complex approach to these patients and a challenge for the involved team:
doctors, nurses, and respiratory therapists in the intensive care unit [14]. In the
15
Rational Bases and Approach of Noninvasive Mechanical Ventilation
119
protocols for weaning there should be suitable daily planning for evaluation of the
capacity of spontaneous breathing, and identification and precocious treatment of
responsible factors that maintain dependency on mechanical ventilation.
With these possible scenarios, from the first descriptions of the development of
noninvasive mechanical ventilation (NIV), we have seen in the last decade the
development of studies with different variations in their design and results that have
enabled application of NIV, in a preventive or therapeutic form, in diverse clinical
situations in medical or post-surgery patients [10]. These studies, with variations
according to their design, scenario, and criteria of indications or contraindications
of NIV, continue to present a challenge for medical staff.
15.2
Potential Aims of NIV During Weaning

from Mechanical Ventilation
Although an international consensus does not exist on the ideal profile of patients
who are candidates for NIV use, we can define the criteria of its application, following the general recommendations for NIV [11, 15]. In a general way, the published
studies base the use of NIV on two larger objectives
(a) To improve gas exchange and muscular resting.
(b) To shorten the time of IMV and indirectly eliminate or ease the development of
complications airway associated injuries, infectious complications (mechanical
ventilation associated pneumonia) or noninfectious complications (muscular
atrophy, undernourishment, etc.). The frequency with which these results are
obtained is variable, as is described in the other chapters of this book.
15.3
Practical Determinants of NIV Efficacy
The improvement of gas exchange and muscular resting, independent of the causes
of the initial indication of IMV [15], is one of the larger objectives. The objectives
on which we plan the NIV are summarized below.
15.3.1 Respiratory Muscular Weakness

In our opinion, respiratory muscular weakness is one of the key causes of prolonged
IMV or post-extubation acute respiratory failure. From its initial descriptions, there
exists consolidated information that NIV can reverse the mechanisms of muscular
fatigue of diverse origins in hypercapnic or hypoxemic acute respiratory insufficiency [10, 15, 16]. The use of NIV in patients with different forms of associated
respiratory insufficiency due to weaning from mechanical ventilation requires multidicisciplinary therapeuctic approach.
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A.M. Esquinas
15.3.2 Nonmuscular Factors: Lung Mechanics, Airways,

and Prolonged Mechanical Ventilation
We can consider determinant factors associated with the characteristics of mechanical ventilation: (1) physiopathology characteristics that precede and are present in
prolonged IMV, (2) type of airway (orotracheal intubation or tracheotomy), and (3)
duration of mechanical ventilation (prolonged >72 h or not), (4) influence of residual effects of sedation/analgesia, (5) level of patient-NIV interaction (equipment
interface, device for mechanical ventilation, ventilatory mode), and (6) specialized
weaning unit and skills [2, 5, 7, 15]. Additionally, the potential uses and results
present specific determinants related to difficult weaning, such as extubation or
decannulation, or previous mechanical ventilation [1518]. In my opinion, there is
still not a descriptive predictive model based on physiopathology of difficult weaning and the possibilities that NIV that allows us regarding the diverse possible scenarios, indications, and prevention of NIV response. Our international network is
currently working in this project.
In the literature published in the last decade, NIV has shown efficacy in the
prevention or treatment of post-extubation respiratory insufficiency in hypercapnic patients (COPD) [1722] and in decannulation in neuromuscular patients
[2327].
15.3.3 Patient Comorbidities and Gas Exchange (Hypercapnic

Versus Hypoxemic)
These are major determinants of prolonged IMV or extubation acute respiratory
failure [20]. On this point, in published studies of patients with previous chronic
respiratory diseases, COPD, neuromuscular disease, chest wall deformity, obesity
hypoventilation, hypercapnia, and previous cardiac disease are the most frequent
comorbidities for which the application NIV during weaning application has been
evaluated [20, 21]. More recently, associated breathing sleep disorders have been
considered as potential risk factors, specially in patients with obstructive sleep
apnea (OSA) and obstructive hypoventilation sndrome [28].
15.3.3.1 Dependent Factors in Mechanical Ventilation

The existence of increased airway resistance (COPD), functional residual capacity
(FRC), neuromuscular disease, or low compliance (obesity hypoventilation syndrome) [28]. The best results are associated with NIV in preventive post-extubation
in hypercapnic patients [22].
15.3.4 Age and Weight

There are other factors that need to be taken into account in the NIV response [3, 7,
29, 30].
15
121
15.3.4.1 Age
Most studies exclude older patients, and this factor is usually more associated with
a greater number of comorbidities (respiratory and cardiac disease). It is not considered a limiting factor [3, 6, 7].
15.3.4.2 Weight (or Underweight)

Overall, weight is a relevant factor. Low weight is associated with decreased muscular response to fatigue and varying degrees of muscular weakness. Patients with
obesity (BMI >30) are considered at high risk, especially when associated with
hypercapnia, as shown in patients with obesity hypoventilation [31].
15.3.5 Anatomical Factors

Anatomical factors such as upper airway resistance should be considered, especially in patients who have basic obstruction of the upper respiratory tract, most
commonly patients with OSA [32]. Decreased cough reflex, especially in patients
with neurological or neuromuscular disease, or the effects of sedation and prolonged relaxation are factors to consider, especially in poor control of bronchial
secretions [33].
15.3.6 Airway Secretions

Airway secretions may be involved in the failure of NIV. Complementary techniques such as assisted coughing, an oscillatory vest, and use of humidification may
be used [33].
15.3.7 Nutritional and Psychological Factors

Nutritional and psychological factors are associated with mechanical ventilation
and its duration and can affect the interaction of the patient with the use of NIV [34].
From a practical point of view, patients and the factors described above need adequate identification at an early stage to apply effective strategies for successful
implementation of NIV. Although there are only a small number of published studies on nutritional and psychological factors, it is necessary to take them into account
during NIV.
15.3.8 NIV Equipment

Appropriate selection of equipmentinterface (face mask, helmet), mechanical ventilator, and ventilation modeand the experience and training of the ICU or weaning
unit team are determinants of a favorable response of the patient to NIV [10, 11].
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A.M. Esquinas
15.3.9 Weaning Scenario

It is important to define scenario and strategy for NIV indications. The scenarios
might include such situations as (a) extubation without prolonged IMV, (b) extubation with prolonged IMV, (c) self-extubation, (d) programmed decannulation, and (e)
accidental decannulation. Details of these situations are summarized in Fig. 15.2 [35].
15.4
Protocol of NIV During Weaning from Mechanical

Ventilation
The factors discussed above are essential to developing NIV extubation protocols
for the use of NIV in the weaning process. However, there remains much heterogeneity and few protocols focus on this topic. A review analysis of the literature on
NIV extubation protocols is summarized Table 15.1 and Fig. 15.1.
Table 15.1 Noninvasive ventilation during the extubation process: steps and practical approach
Before extubation:
1. Patient selection and timing of extubation:
Age and body mass index (BMI)
Nutritional status (both over- and underweight)
Underlying diseases (cardiac and pulmonary conditions), previous use of NIV, home
mechanical ventilation and CPAP (continuous positive airway pressure) use
Record and assessment of ventilator parameters, PSV pressure setting
Thorough evaluation of upper airway and assessment of potential airway difficulty
Thorough evaluation of lower airways (fluid, secretions, sputum load) and cough strength
Information regarding mechanical ventilation parameters during weaning period, i.e.,
airway compliance and resistance, tidal volume, minute volume, PEEP (positive endexpiratory pressure), and inspiratory oxygen fraction
Evaluation of respiratory muscle strength and endurance, evaluation of accessory muscle use
Early detection and recognition of high-risk extubation (warning signs present)a
Day 1. NIV extubation: immediate period
1. NIV setting and ventilatory mode
(a) Bilevel positive airway pressure (BiPAP)b
IPAP (inspiratory positive airway pressure) level: start at pressure equal to PS (Pressure Support)
before extubation; aims are to control dyspnea, respiratory rate, and accessory muscle activity
EPAP (end-expiratory positive airway pressure) level: start at pressure equal to PEEP before
extubation; aims are maintenance of adequate oxygenation and SaO2
(b) CPAP: recommended in hypoxemic respiratory failure
CPAP level: start at pressure equal to PEEP before extubation; aims are maintenance of
adequate oxygenation and SaO2
2. Interface: face mask or helmet,c nasal mask, or other interface (pipe)
3. Humidification: Heated humidifiere
4. Use of complementary respiratory techniques:
15
123
Table 15.1 (continued)

Complementary techniques may be an essential aspect to the success of NIV applied either
post-extubation (NIV extubation) or post decannulation (NIV decannulation). We recommend
early use for at least 3 days before extubation to ensure airway permeability and improve
airway resistance and compliance before extubation.
Available devices and techniques:
(a) Mechanical insufflation-exsufflation increases cough reflex after NIV and before extubation
Useful in patients with primary neuromuscular disorders and also acquired muscular weakness
due to prolonged mechanical ventilation
(b) High-frequency oscillatory devices
Improve mobilization of bronchial secretions clearance by oscillation of airflow within
dependent areas of lung. We recommended application of either high-frequency chest wall
oscillation or intrapulmonary percussion. The key to success with these techniques is early
application at the start of weaning (PSV or T tube) and continuation until at least the later
stages of withdrawal of NIV (nocturnal application only). Oscillatory device usage may be
extended into the oxygen-only period (via face or nasal mask) following ICU discharge.
5. Monitoring and assessment after NIV response:
(a) Clinical parameters such as respiratory rate, dyspnea, patient comfort, Glasgow Coma Score,
heart rate and hemodynamic stability, evidence of muscle fatigue, and accessory muscle usage
(b) Ventilatory parameters such as TV (tidal volumen), MV (mechanical ventilation),
leakage, flow, pressure and volume curve, and patient ventilator synchronization
(c) Monitoring of mask pressure areas and vigilance for the development of skin lesions.
(d) Chest X-ray (24 h)
6. Duration of NIV: In cases where NIV is being utilized as a strategy for early IMV
disconnection and the prevention of extubation failure, it is essential to use NIV continuously
during the first day post-extubation (i.e., at least 24 h continuous use).
In cases where NIV is applied as a prophylactic measure following routine extubation, it
should be used during the first day post-extubation for at least 18 h.
II. Day 2 of NIV extubation
NIV disconnections and positive pressure withdrawal
(a) Aim to reduce IPAP / EPAP levels to at least 50 % of initial pressures; aim to reduce
inspired oxygen fraction as tolerated by the patient
In patients with sleep-related breathing disorders or high risk of hypoventilation, we
recommend nocturnal NIV application.
(b) Gradual reduction of the levels of IPAP
This is especially important in patients with moderate to severe restrictive pathology (obesity
hypoventilation syndrome, kyphoscoliosis, neuromuscular disorders).
Maintain initial mask or alternate with other more comfortable interface during more stable
conditions (i.e., face or helmet to nasal mask or pipe) depending on type of respiratory failure,
patient comorbidities, and tolerance.
a
It is important to identify this population, especially before extubation, as the risk of failure and
reintubation is associated with a significantly increased morbidity and mortality
b
Use of bilevel positive airway pressure (IPAP/EPAP) is recommended in patients with: (a) pCO2
>45, (b) chronic respiratory comorbidity (COPD/obesity hypoventilation syndrome, OSA)
c
Recommended in patients with nasogastric tube in situ, hypoxemia, difficult anatomy, facemask
intolerance, and prolonged NIV
d
Neuromuscular/kyphoscoliosis, severe COPD patients in ICU, and after ICU discharge
e
Early use strongly recommended in high-risk extubation, i.e., known difficult airway, excessive
secretions, prolonged mechanical ventilation, chronic respiratory failure, and poor cough reflex
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A.M. Esquinas
Fig. 15.1 Practical details and steps of non invasive mechanical ventilation before and after extubation. These are critical for safe and effective response
Conclusion
In summary, protocols for NIV extubation require validation in a specific scenario (extubation or decannulation, planned or accidental, preventive or therapeutic). Decisions and responses are influenced by determinant factors before
extubation (e.g., lung mechanics, underlying diseases,), appropriate interaction
among physicians and the respiratory team (i.e., nurses, respiratory therapists),
and thorough evaluation of the factors in the failure of NIV (e.g., secretions,
cough reflex, neurologic disease, and muscular weakness). In real-world practice, however, proper patient selection, weaning time (short or prolonged
mechanical ventilation stages), equipment, strict monitoring, early detection of
favorable or failure responses, and a goal of prevention and early treatment of
possible complications are accepted as essential. Training, a multidisciplinary
approach, and specific weaning units are a crucial cornerstone to successful NIV
extubation. Further large prospective clinical trials are needed to evaluate respiratory and nonrespiratory determinants that influence potential impacts of NIV
in prolonged mechanical ventilation and all difficult weaning scenarios. A rationale practical approach to understand how NIV may interact during weaning
process is summarized in Fig. 15.2.
15
125
Fig. 15.2 NIV during differents steps of weaning from mechanical ventilation
Key Major Conclusions
Noninvasive mechanical ventilation could be a rational alternative for

improving acute respiratory failure during extubation or decannulation
after a variable previous period of IMV.
Noninvasive mechanical ventilation may impact complications associated
with reintubation and prolonged invasive ventilation (by endotracheal tube
or tracheostomy).
Noninvasive mechanical ventilation should be applied by a closed key
flow strategy if the physician considers it a safe alternative.
Noninvasive mechanical ventilation requires support with respiratory techniques that control airway secretions and expands the lungs before and
after extubation and decannulation.
Further large prospective clinical trials are needed to evaluate respiratory
and nonrespiratory determinants that influence potential impacts of NIV in
prolonged mechanical ventilation and all difficult weaning scenarios.
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A.M. Esquinas
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2. Jubran A, Tobin MJ. Pathophysiologic basis of acute respiratory distress in patients who fail a
trial of weaning from mechanical ventilation. Am J Respir Crit Care Med. 1997;155:90615.
3. BouAkl I, Bou-Khalil P, Kanazi G, Ayoub C, El-Khatib M. Weaning from mechanical ventilation. Curr Opin Anaesthesiol. 2012;25:427.
4. Thille AW, Corts-Puch I, Esteban A. Weaning from the ventilator and extubation in ICU. Curr
Opin Crit Care. 2013;19:5764.
5. Blackwood B, Burns KE, Cardwell CR, OHalloran P. Protocolized versus non-protocolized
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decannulation using a tracheostomy retainer in patients with prolonged weaning and persisting
respiratory failure. Respiration. 2012;84:46976.
9. Rothaar RC, Epstein SK. Extubation failure: magnitude of the problem, impact on outcomes,
and prevention. Curr Opin Crit Care. 2003;9:5966.
10. Hess DR. The role of noninvasive ventilation in the ventilator discontinuation process. Respir
Care. 2012;57:161925.
11. Epstein SK. Noninvasive ventilation to shorten the duration of mechanical ventilation. Respir
Care. 2009;54:198208.
12. Powers SK, Wiggs MP, Sollanek KJ, Smuder AJ. Ventilator-induced diaphragm dysfunction:
cause and effect. Am J Physiol Regul Integr Comp Physiol. 2013;305:R46477.
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Care. 2012;57:86786.
14. Henneman E, Dracup K, Ganz T, Molayeme O, Cooper CB. Using a collaborative weaning
plan to decrease duration of mechanical ventilation and length of stay in the intensive care unit
for patients receiving long-term ventilation. Am J Crit Care. 2002;11:13240.
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weaning strategy for intubated adults with respiratory failure. Cochrane Database Syst Rev.
2013;(12):CD004127. doi:10.1002/14651858.
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ventilation dependency in intensive care unit patients. Crit Care Med. 1996;24:6017.
17. Nava S, Ambrosino N, Clini E, Prato M, Orlando G, Vitacca M, Brigada P, Fracchia C, Rubini
F. Noninvasive mechanical ventilation in the weaning of patients with respiratory failure due
to chronic obstructive pulmonary disease. A randomized, controlled trial. Ann Intern Med.
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18. Ferrer M, Esquinas A, Arancibia F, Bauer TT, Gonzalez G, Carrillo A, Rodriguez-Roisin R,
Torres A. Noninvasive ventilation during persistent weaning failure: a randomized controlled
trial. Am J Respir Crit Care Med. 2003;168:706.
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P. Noninvasive ventilation to prevent respiratory failure after extubation in high-risk patients.
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20. Mati I, Dani D, Majeri-Kogler V, Jurjevi M, Mirkovi I, Mrzljak Vucini N. Chronic
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22. Ferrer M, Valencia M, Nicolas JM, Bernadich O, Badia JR, Torres A. Early noninvasive ventilation averts extubation failure in patients at risk: a randomized trial. Am J Respir Crit Care
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23. Racca F, Del Sorbo L, Capello EC, Ranieri VM. Neuromuscular patients as candidates for non
invasive ventilation during the weaning process. Minerva Anestesiol. 2012;78:391.
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Salvador V. Prevention of extubation failure in high-risk patients with neuromuscular disease.
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trends in the management of end-stage neuromuscular respiratory muscle failure: recommendations of an international consensus. Am J Phys Med Rehabil. 2013;92:26777.
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Influence of Prevention Protocols

on Respiratory Complications:
Ventilator-Associated Pneumonia During
Prolonged Mechanical Ventilation
16
Bushra Mina and Christian Kyung
16.1
Introduction
Ventilator-associated pneumonia (VAP) is a form of nosocomial infection that is

generally defined as a pneumonia that presents 4872 h after invasive mechanical
ventilation with an endotracheal tube or tracheostomy. VAP results from the invasion of the lower respiratory tract and lung parenchyma by microorganisms.
However, there has never been a reliable, collaborative definition of VAP, as some
organizations include radiographic imaging, symptoms (sputum production, fevers),
and laboratory findings (leukocytosis/leukopenia) as part of the definition as well.
Because of the lack of a true definition of VAP, it is difficult to identify the exact
percentage of mechanically ventilated patients who develop this condition. However,
historically, the incidence of VAP is 22.8 % among patients receiving mechanical
ventilation, and patients receiving ventilator support account for 86 % of the cases
of nosocomial pneumonia, with a mortality rate of 27 %, although it may reach as
high as 43 % when the causative agent is antibiotic resistant. The cost of VAP is
estimated to be an additional $40,000 per hospital admission per patient and an
estimated $1.2 billion per year in the United States.
The Centers for Disease Control and Prevention (CDC) in the United States have
created an umbrella term for events that occur during mechanical ventilation,
ventilator-associated events (VAEs), which include VAP as well as other conditions.
This new, broader terminology emphasizes all events and complications of
B. Mina, MD C. Kyung, MD
Department of Medicine, Division of Pulmonary and Critical Care Medicine,
Lenox Hill Hospital, New York, NY, USA
e-mail: bmina@mindspring.com; kriskyung@gmail.com
DOI 10.1007/978-3-319-04259-6_16
129
130
B. Mina and C. Kyung
mechanical ventilation as opposed to just VAP alone. The CDC identifies VAP
using a combination of several factors, including the following:
Deterioration of respiratory status after a period of stability or improvement on
the ventilator
Evidence of infection or inflammation
Laboratory evidence of respiratory infection
This new terminology states that mechanical ventilation must take place for at
least 2 days to be considered a VAE. The mechanically ventilated patient must also
be stable for 2 or more days and must not have increasing requirements of positive
end-expiratory pressure (PEEP) or fraction of inspired oxygen (FiO2). After a stable
period of unchanged oxygen requirements (no change in PEEP or FiO2) for 2 or
more days, if there is an increase in the requirements of oxygen, either:
Increase in FiO2 0.20 over the baseline stable FiO2
Increase in PEEP 3 over the baseline stable PEEP
Day 2
Day 1
Day 3
Day 4
Ventilator associated event (VAE)
Stable
Stable
Change in status
A change in PEEP within values of 05 cmH2O is not considered an increasing

requirement of oxygen. For example, a change in PEEP from 0 to 3 cmH2O is not
considered an increasing requirement of oxygen because it stayed within the
05 cmH2O value. Baseline stable FiO2 or PEEP is the lowest value of oxygenation
maintained for at least 1 h. If these requirements are met, then it is categorized as a
ventilator-associated condition (VAC), such as the following:
Pneumonia
Acute respiratory distress syndrome (ARDS)
Lobar atelectasis
Pulmonary edema
In the setting of a VAC, if the patient has been on mechanical ventilation for 3 or
more days or is within 2 days of worsening oxygenation, as described above, with
the following added criteria below, then it considered an infection-related ventilatorassociated complication (IVAC):
16
Influence of Prevention Protocols on Respiratory Complications
131
Temperature >38 or <36 C or white blood cell count 12 or 4 and

A new antibiotic is used and continued for 4 or more days
After all these events, if there is Gram stain evidence, inflammatory cells or culture above a certain threshold from the lungs, bronchi, or trachea, or cultures direct
from bronchoscopy, then it is classified as possible VAP. If the culture shows growth
surpassing specific thresholds or there are specific positive test findings or histopathology, then VAP is considered probable.
16.2
Interventions and Practices Considered

for Prevention of VAE
Following is a list of interventions and practices considered for prevention of

VAE:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Elevate the head of the bed

Maintain cuff pressure in the endotracheal tube between 20 and 25 mmHg
Circuit changes
Use heated humidifiers and heat and moisture exchangers
Provide oral care with chlorhexidine and water-soluble mouth moisturizer
Secretion removal with specially designed endotracheal tubes
Closed, in-line suctioning (no recommendation made)
Evaluation for kinetic bed therapy
Sedation reduction
Assessment of weaning readiness with brief weaning trials
Stress ulcer disease prophylaxis
Deep vein thrombosis prophylaxis
In 2014, the Society of Healthcare Epidemiology (SHEA) and the Infectious

Disease Society of America (IDSA) released a newly updated guideline for
Strategies to Prevent VAP in the Acute Care Hospitals [1]. The Basic Practices
Guidelines are listed as below:
Avoid intubation
Minimize sedation
Provide physical conditioning
Minimize secretions above the endotracheal tube cuff
Elevate the head of the bed
Maintain ventilator circuits
132
16.2.1 Intubate Only If Necessary and Utilize Noninvasive

Mechanical Ventilation Strategies
The presence of an endotracheal tube (ETT) can interfere with the protective mechanism of cough, which results in pooling of secretions in the upper airways, promoting micro-aspiration. Studies have shown that use of noninvasive ventilation (using
devices such as BiPAP) has decreased the need for invasive mechanical ventilation, and ultimately the incidence of VAP, with a resulting decrease in length of stay
in the intensive care unit (ICU). Noninvasive mechanical ventilation can assist in
liberation from mechanical ventilation and prevent reintubation, especially in
patients with chronic obstructive lung disease (COPD). Attempts to reduce the
number of ventilation days and need for reintubation will decrease the incidence of
VAP. Strategies to avoid premature and unplanned extubation should be in place.
16.2.2 Minimize Sedation

Strategies and development of approaches to limit the use of sedation in the ICU
have been associated with successful spontaneous breathing trials and early extubation. Efforts should be made to limit the need for sedation and should follow the
guidelines for analgesia and sedation. Other helpful tips include:
Use of shorter-acting sedative agents. Use of antipsychotics, dexmedetomidine,
propofol, and other shorter-acting agents rather than benzodiazepines
Sedation holidays. Stopping sedation infusions to allow the patient to be fully
awake. Randomized control trials have shown that daily sedation holidays can
decrease the average time of intubation by 24 days, thus minimizing the risk of
developing VAP
Daily spontaneous breathing trials
Daily assessment of extubation
16.2.3 Physical Conditioning

Early exercise and mobilization can prevent the development of critical muscle
weakness, expedite extubation, and improve overall quality of life for the patient.
16.2.4 Patient Positioning

The head of the bed should be elevated to 3045. Most meta-analyses and studies
have shown that patients whose beds are elevated to 3045 are have less risk of
aspiration compared with patients placed in a fully supine position [1]. However,
although incidence is lower, there has been no proven mortality benefit.
16
133
16.2.5 Subglottic Drainage

ETTs with specialized capabilities to provide subglottic secretion drainage (SSD)
are available but are costly. These devices can provide either continuous drainage or
intermittent drainage of the secretions and fluids near the subglottis, thus decreasing
the risk of aspiration and VAP [7].
A 2011 meta-analysis of 13 randomized controlled studies with 2442 patients
compared standard ETT and ETT with SSD capabilities. Twelve of the 13 studies
showed a decrease in rates of VAP. There were associations with decrease in length
of days of intubation, decrease in length of days spent in the ICU, and increased
length to first episode of VAP. However, despite these positive findings, there was
no difference in adverse events and mortality in patients with predicted prolonged
mechanical ventilation (>4872 h).
16.3
Ventilator Circuit Maintenance
Routine change of the circulatory circuit is not required unless contaminated with
soiled secretions or if it is malfunctioning.
The following strategies may assist in the prevention of VAP but the evidence is
not as concrete.
16.4
Oral Care
Chan et al. performed a meta-analysis that included 11 studies comparing use of

oral antiseptics or antibiotics with none. Four of the 11 trials did not show a significant reduction in the rate of VAP when comparing the two protocols. Seven of
the trials that assessed the use of oral antiseptic cleanses showed a significant
reduction in the rate of VAP. However, similar to the studies of the use of ETT
with SSD, there were no changes in mortality, ICU stay duration, or days of intubation [3].
Labeau et al. performed a similar meta-analysis of 14 studies comparing the use
of chlorhexidine and povidone-iodine as antiseptic agents with no prophylaxis.
Twelve of those studies that included chlorhexidine as the primary antiseptic showed
a reduction in VAP. However, the two studies using povidone-iodine showed unclear
results. In the same study, a subset analysis was performed that showed better outcomes with higher concentrations of chlorhexidine of 2 %, but there is no guideline
for the best solution strength [6].
Other meta-analyses and randomized controlled trials have shown benefits that
favor cardiac-surgical patients with high reduction rates. Its value in medical
patients it not as pronounced [6]. A meta-analysis of mechanical tooth brushing did
not show a significant impact on incidence, duration of mechanical ventilation, ICU
stay, or mortality [1].
134
16.5
Gastrointestinal Decontamination
A meta-analysis has shown that decontamination of the gastrointestinal tract can

reduce rates of VAP. de Smet et al. [10] performed a trial that included 5939 patients
in 13 participating ICUs in the Netherlands comparing the standard of care against
gastrointestinal decontamination with intravenous and topical antibiotics and oropharynx decontamination with antibiotics. The results showed a small mortality
benefit in both the gastrointestinal and oropharynx arms.
Despite the small mortality benefit, these practices are not performed in North
America secondary to concerns of resistant microorganisms, particularly Clostridium
difficile and vancomycin-resistant Enterococcus. Additionally, the benefits may
have been seen in the Netherlands due to lower incidence of resistant organisms.
The long-term effects of selective decontamination of the gastrointestinal tract also
remain to be seen.
16.6
Polyurethane Endotracheal Cuff
Polyurethane-coated cuffs allow better sealing around the tracheal wall and theoretically decrease the incidence of micro-aspiration into the lungs. Small studies
performed by Lorente et al. [11] (n = 280 patients) and Poelaert et al. [12] (n = 134
patients post cardiac surgery) showed decreased incidence, but the studies are too
small to extrapolate the effectiveness.
16.6.1 VAP Prevention Bundles

A VAP prevention bundle is a group of interventions that are performed for a highrisk patient with the goal of preventing VAP. A study by Bouadma et al. [2] compared the use of a VAP bundle before and after implementation that included:
Hand hygiene
Glove and gown use
Elevation of head of bed
Oral septic prophylaxis (four times daily)
ETT cuff pressure >20 cmH2O
Use of Orogastric tube over nasogastric tube
Gastric distention prevention
Decreased tracheal suctioning (nonessential)
The results of this study showed that episodes of VAP at baseline compared with
intervention with the bundle were, respectively, 22.6 and 13.1 total episodes per
1000 ventilator days, showing statistical significance. Despite the decrease in incidence and shorter length of ICU stay, there was no mortality benefit or change in
total duration of mechanical ventilation. Similar studies using different VAP prevention bundles have been evaluated showing reduction in incidence, however,
these have only been cohort studies [2].
16
135
16.6.2 Other Interventions

Other interventions that are not generally recommended or for which there is poor
data include use of silver-coated ETTs (specialized ETTs to prevent bacterial biofilm and colonization), kinetic beds (specialized beds that continuously rotate,) and
prone positioning. However, despite the decrease in incidence of VAP, there has
been no change in mortality or duration of mechanical ventilation.
16.6.3 Early Tracheotomy

A meta-analysis of intervention with early tracheostomy (within 7 days) has not
shown overall a direct reduction in incidence of VAP or mortality [1]. However, it
has been shown to reduce the length of mechanical ventilation and ICU stay. Some
studies have shown no change in mortality, but the number of studies focusing on
this intervention is small and there are no current guidelines set for this particular
intervention [1].
16.7
Implementing Guidelines
The SHEA/IDSA recommendation guidelines also emphasize the four Es to

effectively deliver care that will help prevent VAP: engage, educate, execute, and
evaluate. Multidisciplinary teams should be formed to help develop and implement plans to prevent VAP. Educational material should be provided to caregivers,
and VAP monitoring and prevention plans should be effectively executed through
guidelines, bundles, and redundancy. Information regarding the local epidemiology, risk factors, and outcomes should be readily available for health-care providers as well. With these educational tools, preventive measures and plans should
be executed and implemented. Specific measures, plans, or bundles, as mentioned before, such as hand-washing, bed-positioning, halting sedation, weaning
assessment, and oral care should be put into place. Observational tools and surveillance of the measures and outcomes should be implemented. This includes
measuring the incidence of VAP, VAP rates, and monitoring that particular patient
population. The effectiveness of these preventive measures should then be
evaluated.
16.8
Updates and Further Controversy
In the October 2014 issue of Chest, Hurley performed an analysis of the use of topical antibiotics in selective gastric decontamination. The results of this analysis
showed that the effects of the topical antibiotics on the incidence of VAP are confusing and even paradoxical [4]. Kollef, in an editorial to the article in the same issue,
pointed out that these effects of VAP incidence were different when using different
analysis methods. Kollef points out that there could still be a role for topical antibiotics and even aerosolized antibiotics in VAP prevention, however, more research
136
and information on their cost-effectiveness are required [9]. As we learn more about
these novel methods, it is important to remain focused on the basics methods for
VAP prevention: (1) VAP prevention bundles and prevention programs, (2) the practice of antibiotic stewardship, and (3) more research on VAP prevention and
treatment.
Conclusion
Ventilator-associated pneumonia is a preventable complication related to

mechanical ventilation. Morbidity and mortality related to VAP have a considerable economic impact on the health-care system. Although the data and research
on the methods of VAP prevention are not concrete, studies have shown that
there are various preventive measures aimed at decreasing the incidence of
VAP. The majority of these methods are generally cost-effective and easy to
implement. A summary of the recommendations is provided in Table 16.1.
The following key recommendations provide the best benefit against VAP
and are cost-effective and feasible to implement: avoid intubation if possible, decrease length of intubation, daily spontaneous breathing trials,
assess for extubation, bed elevation to 3045, early immobilizations, and
minimize sedation
Endotracheal tube with subglottic draining capabilities in patients with
likely prolonged intubation
Selective oral decontamination with chlorhexidine
Consider VAP bundle protocols
Develop a multidisciplinary team-based approach to prevention of VAP
and other complications.
Table 16.1 Recommendations for prevention of VAP

Key major recommendations
Avoid intubations and decrease length of
intubation Spontaneous breathing trials,
assess for extubation
Elevation to 3045 position
Early immobilization
Minimize sedation
ETT with SSD in prolonged mechanical
ventilation (4872 h)
Possible
Selective oral/digestive
decontamination
Chlorhexidine oral care
Specialized ETT
Cuff pressure
Aggressive oral care,
including dental care
Not
recommended
Silver-coated
ETT
Kinetic beds
Prone positioning
16
137
References
Review Article
1. Klompas M, et al. Strategies to prevent ventilator associated pneumonia in acute care hospitals. Infect Control Hosp Epidemiol. 2014;(35)8:91536.
Journal Article
2. Bouadma L, et al. Long-term impact of a multifaceted prevention program on ventilatorassociated pneumonia in a medical intensive care unit. Clin Infect Dis. 2010;51(10):111522.
3. Chan EY, et al. Oral decontamination for prevention of pneumonia in mechanically ventilated
adults: systematic review and meta-analysis. BMJ. 2007;334(7599):889.
4. Hurley JC, et al. Ventilator-associated pneumonia prevention methods using topic antibiotics:
herd protection or herd peril? Chest. 2014;146(4):8908. doi:10.1378/chest.13-2926.
5. Kalanuria AA, et al. Ventilator associated pneumonia in the ICU. Crit Care. 2014 18:208.
http://ccforum.com/content/18/2/208.
6. Labeau SO, et al. Prevention of ventilator-associated pneumonia with oral antiseptics: a systemic review and meta-analysis. Lancet. 2011;11(11):84554.
7. Muscedere J, et al. Subglottic secretion drainage for the prevention of ventilator-associated
pneumonia: a systemic review and meta-analysis. Crit Care Med. 2011;39(8):198591.
Protocols
8. Ventilator-Associated Event (VAE) protocol. http://www.cdc.gov/nhsn/pdfs/pscmanual/
10-vae_final.pdf
Editorial
9. Kollef MH. Ventilator-associated pneumonia prevention: we still have a long way to go! Chest.
2014;146(4):8734. doi:10.1378/chest.14-1066.
10. de Smet AM, Kluytmans JA, Cooper BS, et al. Decontamination of the digestive tract and
oropharynx in ICU patients. N Engl J Med. 2009;360(1):2031.
11. Lorente L, Lecuona M, Jimenez A, Mora ML, Sierra A. Influence of an endotracheal tube with
polyurethane cuff and subglottic secretion drainage on pneumonia. Am J Respir Crit Care
Med. 2007;176(11):107983.
12. Poelaert J, Depuydt P, De Wolf A, Van de Velde S, Herck I, Blot S. Polyurethane cuffed endotracheal tubes to prevent early postoperative pneumonia after cardiac surgery: a pilot study.
J Thorac Cardiovasc Surg. 2008;135(4):7716.
High-Flow Nasal Cannula Oxygen

in Acute Respiratory Failure After
Extubation: Key Practical Topics
and Clinical Implications
17
Rachael L. Parke
Abbreviations
BMI
EELI
EELV
EIT
FiO2
NHF
Body mass index

End-expiratory lung impedance
End-expiratory lung volume
Electrical impedance tomography
Fraction of inspired oxygen
Nasal high flow
17.1
Introduction
Traditionally, oxygen therapy has been provided by way of a range of devices such
as nasal prongs, face masks, and nose masks, the design of which has changed little
since the initial versions were developed more than 80 years ago. Limitations to the
provision of oxygen by conventional systems exist, including patient discomfort
and intolerance, inaccurate delivery of oxygen, failure to provide flow equivalent to
inspiratory demand, drying of the airway, and treatment failure requiring escalation
of respiratory support. Nasal high-flow oxygen therapy (NHF) has come to be used
widely in the treatment of acute respiratory failure. NHF has been demonstrated to
be easy to institute, is comfortable to the patient, and achieves excellent adherence
to therapy [1].
R.L. Parke, MHSc (Hons), PhD

Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital,
Auckland, New Zealand
e-mail: rparke@adhb.govt.nz
DOI 10.1007/978-3-319-04259-6_17
139
140
R.L. Parke
17.1.1 Nasal High-Flow Oxygen Therapy

Commercially available NHF systems have rapidly gained popularity among the
range of respiratory support devices and oxygen administration systems available to
clinicians. Advances in the design of heated delivery tubing and the development of
uniquely designed nasal interfaces have allowed the development of systems capable of delivering high-flow rates of heated, humidified, blended air and oxygen
directly into the nares, allowing delivery of optimally conditioned gas. Systems
comprise an air-oxygen blender (capable of delivering 21100 % fraction of inspired
oxygen (FiO2)), an active heated humidifier chamber, heated single-limb inspiratory
delivery tubing (which avoids heat loss and development of condensate in the circuit), and a uniquely designed large-bore nasal interface. This allows delivery of
blended air and oxygen at flows up to 60 l/min, heated to 37 C and optimally
humidified to 44 mgH2O/l.
NHF has been suggested as an intermediate form of respiratory support positioned between traditional methods of oxygen delivery such as low-flow nasal cannulas and noninvasive ventilation [2]. It can be used as part of a continuum of
respiratory support, either as a tool for escalation of respiratory support in the acute
phase of illness or as a means of moving from higher support to lower support when
used during the weaning phase. NHF has been shown to reduce respiratory rate,
improve oxygenation, reduce carbon dioxide concentrations, and reduce the need
for intubation and escalation of respiratory support therapy.
17.2
Mechanisms of Action
17.2.1 Delivery of an Accurate FiO2 to Meet or Exceed

the Patients Peak Inspiratory Flow Demand
The improvement in oxygenation seen with NHF may, in part, be due to less dilution of delivered oxygen. Oxygen dilution occurs in acute respiratory failure as
patients breathe with high peak inspiratory flows. As higher gas flows are achieved
with NHF, meeting or exceeding patient inspiratory demand, less entrainment of
room air and resultant dilution of oxygen concentration occurs. Studies have shown
that in healthy volunteers, the oxygen delivered by NHF systems approaches that
prescribed when the delivered gas flow rates were greater than the subjects peak
inspiratory flow rate [3, 4].
17.2.2 Washout of the Nasopharyngeal Dead Space

NHF removes the air contained in the nasopharyngeal cavity, reducing anatomic
dead space and enhancing alveolar ventilation and oxygenation [5, 6]. This dead
space washout also may result in higher resting oxygen saturation and potentially
enhances CO2 clearance [7]. Experiments suggest that a steady flow assumption
17
High-Flow Nasal Cannula Oxygen in Acute Respiratory Failure After Extubation
141
within the nasal cavity is invalid during natural breathing; however, it appears valid
with NHF. This may support the argument that NHF continuously flushes the nasopharyngeal dead space, which may enhance washout of carbon dioxide [8].
17.2.3 Provision of Optimal Humidity

Respiratory mechanics may be improved by the delivery of heated humidified gas
[6]. Mucosal function is impaired if gas is delivered above or below the optimum
level of temperature or humidity [3]. NHF provides conditioned gas that is optimally humidified to 37 C, 44 mgH2O/l. Improved mucociliary clearance has
been found in bronchiectatic patients using NHF for 7 days [9]. Active humidification improves mucociliary function, facilitates secretion clearance, and
decreases atelectasis formation, which may improve the ventilation-perfusion
ratio and oxygenation [10].
17.2.4 Provision of a Flow-Dependent Positive

Airway Pressure Effect
Studies have demonstrated a degree of positive airway pressure is generated by the
provision of NHF. This positive pressure ranges from 2.7 to 7.4 cmH2O at flows of
3550 l/min and correlates directly with the flow administered; that is, increasing the
flow increases the pressure generated. Higher pressure levels were found in female
participants and when participants breathed with mouth closed [1, 11]. The degree of
positive airway pressure is dependent on the flow delivered, the geometry of the
upper airways, lung compliance and resistance, whether the patient is breathing
through their mouth or nose, and the absence of significant leak around the nares.
Mean (SD) airway pressures of 1.93 (1.25), 2.58 (1.54), and 3.31 (1.05) cmH2O
were generated when patients breathed with their mouth closed while receiving 30,
40 and 50 l/min of NHF, respectively [12]. Furthermore, a positive linear relationship
was found between the flow delivered and the airway pressure generated. Regression
analysis of the mean airway pressure (Fig. 17.1) demonstrated that, for every 10 l/
min increase in flow, the mean airway pressure increased by 0.69 cmH2O in the
mouth-closed position and by 0.35 cmH2O in the mouth-open position [12].
17.2.5 Increase in End-Expiratory Lung Volumes

Electrical impedance tomography (EIT) has demonstrated that NHF increases both
end-expiratory lung volume (EELV) and tidal volume [13, 14]. Increases in endexpiratory lung impedance (EELI) were significantly influenced by body mass
index (BMI), with larger increases associated with higher BMIs. Increases in EELV
may result in a reduction in the work of breathing, assist in prevention of small
airway closure, and lead to improved oxygenation due to reduced shunting [13].
142
R.L. Parke
Plot of regression models*
4
Mean pressure generated (cmH2O)
Fig. 17.1 Regression

analysis of mean
nasopharyngeal pressure
during NHF therapy with
mouth open or closed
Mouth closed
y = 0.1507 + 0.0689* x
3
1
Mouth open
y = 0.5050 + 0.0347* x
*Where mean pressure generated is the response (y) and

Optiflow gas flow delivered is the predictor (x)
1
0
10
20
30
40
Gas flow delivered (L/min)
50
60
NHF was found to increase global EELI in both the prone and supine position,
which may represent an increase in functional residual capacity [14].
17.2.6 Enhanced Patient Comfort and Compliance

One of the perceived benefits of NHF is the enhanced patient comfort and tolerability leading to improved compliance with the therapy [10, 15]. Tolerance of NHF has
been demonstrated in several studies and is presumed to be due to the provision of
optimal heat and humidity during the therapy to patients [10, 16, 17]. The optimal
humidity delivered by the system has been shown to reduce mouth and nasal dryness when compared with dry oxygen therapy [10, 18, 19]. Also, because a nasal
interface is utilized as opposed to a face mask, patients can eat, drink, sleep, and
communicate more easily without removing the device. This has led to improved
patient comfort, fewer removals of the interface, and less oxygen desaturation when
compared with face mask oxygen therapy [20].
17.3
Clinical Outcomes and Indications
NHF offers a fast and sustained improvement in respiratory parameters in patients with
hypoxemic respiratory failure, ensures patient comfort over extended periods of time,
and has been shown to reduce respiratory rate, alleviate dyspnea, and improve oxygen
saturation in adult patients presenting to the emergency department and the intensive
care unit (ICU) [19, 21]. NHF can effectively be used to manage patients with mild to
moderate levels of hypoxemic respiratory failure, may prevent the need for intubation,
and can be used to provide respiratory support following extubation [22, 23].
17
143
Table 17.1 Indications, cautions, and contraindications for NHF use

Indications for NHF include:
Acute hypoxemic respiratory failure
Patients in mild/moderate respiratory distress (whether hypoxic or not)
Patients who may benefit from optimal humidification
Poor compliance with oxygen therapy via a mask
To facilitate weaning from invasive or noninvasive ventilation
Patients requiring high FiO2
As an early alternative to noninvasive ventilation
During clinical investigations, e.g., bronchoscopy
Pre-oxygenation for intubation
Postoperative respiratory support
Exacerbation of chronic obstructive pulmonary disease, pneumonia, pulmonary edema,
or asthma
As part of palliative care and in do-not-intubate patients
Contraindications for NHF include:
Inability to protect airway, e.g., reduced level of consciousness
Presence of base-of-skull fracture
Maxillofacial trauma
Nasal obstruction, e.g., choanal atresia, nasal polyps, adenoids.
Life-threatening hypoxia
Foreign body aspiration
Use NHF with caution:
Severe agitation, inability to follow commands
Respiratory acidosis
Swallowing impairment
Recent upper gastrointestinal, airway, or neurosurgery
Facial burns
NHF is a useful treatment in patients with acute respiratory failure due to a

variety of causes [6, 10, 17, 19]. Evidence suggests NHF may avoid the need for
intubation in patients with acute lung injury and acute respiratory distress syndrome as well as hypoxemic respiratory failure. Oxygen therapy after extubation
is used to correct residual oxygen impairment. Several studies have demonstrated
the use of NHF post extubation to improve gas exchange, reduce respiratory rate,
improve comfort, and reduce the need for noninvasive ventilation and reintubation
[15, 23, 24].
Patients who are hypoxemic, show signs of increased work of breathing, or
require optimal humidity for secretion mobilization may all benefit from a trial of
NHF. Patients may be electively extubated to NHF if deemed to be at increased risk
for respiratory failure, for example, because of increased BMI, or NHF may be used
in alternating cycles with noninvasive ventilation to rest the patient from a face
mask and to provide periods for nutrition and oral care. Other indications are
described in Table 17.1.
144
R.L. Parke
17.3.1 Instituting Nasal High-Flow Therapy

17.3.1.1 When Commencing NHF Therapy
Explain to the patient that the system will deliver higher flows of warmed air/
oxygen by way of the nose. Give them the interface to feel the generated flow and
temperature. It may be useful to commence flows at a lower rate to allow the
patient to adjust to the sensation of heat, humidity, and flow and then slowly
increase flow to desired levels as tolerated. Most commercial systems have a
range of interfaces available that must be sized appropriately for the patient to
ensure success. All NHF must be adequately warmed to 3437 to assist with
patient comfort and provision of humidity. Ensure tubing is supported so it does
not pull on the nasal cannula.
Commence at 3035 l/min and an appropriate FiO2 as determined by need based
on oxygen saturations. FiO2 can be set at 21100 % dependent on measured
oxygen saturation and goals for the patient.
Encourage patient to breathe in and out through the nose with their mouth closed
if possible, thereby slowing inspiratory and expiratory time and maintaining
optimum pressure.
Increase flow in 5 l/min increments to a maximum of 5060 l/min, depending on
patient need.
When weaning, decrease NHF oxygen first to 40 %, then decrease flow in 5 l/min
steps to baseline. In practice, patients often self-wean when their condition
improves.
17.3.1.2 Monitoring
It is preferable to have continuous monitoring of heart rate, respiratory rate, and
oxygen saturations. Blood gas measurements may be undertaken as per local protocol or as clinical need dictates.
17.3.1.3 Documentation
Staff should ensure that regular documentation of therapy includes the flow and
FiO2 delivered, respiratory rate, heart rate, and oxygen saturations. Acceptable
parameters should be prescribed describing target oxygen saturations and allowable
flow and FiO2.
17.3.2 Other
Provide regular oral care as per local protocol. Nebulizer spacers or a T piece can
be used in conjunction with NHF to deliver aerosol therapy. Patients may also be
successfully managed on some wards with NHF either in the case of deterioration
in respiratory function or following transfer from the ICU where therapy has already
been instituted. Care must be taken, however, to set realistic limits on the flow that
can be delivered in a ward environment, the FiO2 that is appropriate for ward use,
17
145
and at what point further advice and management should be sought from specialist
ICU teams. For example, call intensive care for further advice if >50 % FiO2 and/or
>40 l/min flow.
It is important to recognize that NHF may not be successful in all situations and
that an escalation protocol should be made available to staff that encourages higherlevel respiratory support in the case of increased respiratory distress, desaturation/
apnea, increased PCO2, or further clinical deterioration.
17.4
Discussion
The utilization of NHF has expanded rapidly since its introduction, and NHF is now
seen as a useful treatment option in patients with acute respiratory failure, improving oxygenation and patient comfort and reducing respiratory rate. There is growing
evidence that NHF is associated with a number of beneficial mechanisms not typically seen with traditional oxygen therapies.
Further research will help to define appropriate boundaries between nasal high
flow and traditional forms of respiratory support such as noninvasive ventilation.
Further work is also required to determine optimal patient selection, reliable indicators of success and/or failure, and its place and therapeutic value in novel patient
groups such as rapid sequence induction, bronchoscopy, transesophageal echocardiography, and other procedures where sedation is required.
References
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respiratory cycle. Respir Care. 2013;58:16214.
2. Chatila W, Nugent T, Vance G, Gaughan J, Criner GJ. The effects of high-flow vs low-flow
oxygen on exercise in advanced obstructive airways disease. Chest. 2004;126:110815.
3. Ritchie JE, Williams AB, Gerard C, Hockey H. Evaluation of a humidified nasal high-flow
oxygen system, using oxygraphy, capnography and measurement of upper airway pressures.
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4. Sim MA, Dean P, Kinsella J, Black R, Carter R, Hughes M. Performance of oxygen delivery
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2008;63:93840.
5. Ricard J. The high flow nasal oxygen in acute respiratory failure. Minerva Anestesiol.
2012;78(7):83641.
6. Masclans JR, Roca O. High-flow oxygen therapy in acute respiratory failure. Clin Pulm Med.
2012;19:12730.
7. Lee JH, Rehder K, Williford L, Cheifetz I, Turner D. Use of high flow nasal cannula in critically ill infants, children, and adults: a critical review of the literature. Intensive Care Med.
2013;39:24757.
8. Spence C, Buchmann N, Jermy M. Unsteady flow in the nasal cavity with high flow therapy
measured by stereoscopic PIV. Exp Fluids. 2012;52:56979.
9. Hasani A, Chapman T, McCool D, Smith R, Dilwroth J, Agnew J. Domiciliary humidification
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10. Roca O, Riera J, Torres F, Masclans J. High-flow oxygen therapy in acute respiratory failure.
Respir Care. 2010;55:40813.
11. Groves N, Tobin A. High flow nasal oxygen generates positive airway pressure in adult volunteers. Aust Crit Care. 2007;20:12631.
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high-flow oxygen therapy. Respir Care. 2011;56:11515.
13. Corley A, Caruana L, Barnett A, Tronstad O, Fraser JF. Oxygen delivery through high-flow
nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac
surgical patients. Br J Anaesth. 2011;107:9981004.
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and body position on end-expiratory lung volume: a cohort study using electrical impedance
tomography. Respir Care. 2013;58:58996.
15. Tiruvoipati R, Lewis D, Haji K, Botha J. High-flow nasal oxygen vs high-flow face mask: a
randomized crossover trial in extubated patients. J Crit Care. 2010;25:4638.
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17. Sztrymf B, Messika J, Bertrand F, et al. Beneficial effects of humidified high flow nasal oxygen in critical care patients: a prospective pilot study. Intensive Care Med. 2011;37:17806.
18. Nicolet J, Poulard F, Baneton D, Rigal JC, Blanloeil Y. High-flow nasal oxygen for severe
hypoxemia after cardiac surgery. Ann Fr Anesth Reanim. 2011;30:3314.
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2012;57:15717.
20. Parke RL, McGuinness SP, Eccleston ML. A preliminary randomized controlled trial to assess
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oxygen during respiratory failure in the emergency department: feasibility and efficacy. Respir
Care. 2012;57:18738.
22. Ward JJ. High-flow oxygen administration by nasal cannula for adult and perinatal patients.
Respir Care. 2013;58:98122.
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oxygen therapy in cardiac surgical patients. Br J Anaesth. 2013;111:92531.

in Difficult Weaning in Critical Care:
A Rationale Approach
18
Dhruva Chaudhry and Rahul Roshan
18.1
Introduction
Weaning, that is, withdrawal of ventilatory support, is a critical and vital step in the
care of intubated patients on mechanical ventilation. Forty to 50 % of the total duration of mechanical ventilation is the average time spent during weaning. Weaning
techniques vary among intensivists, with spontaneous breathing trials (SBTs) being
used as a diagnostic tool to estimate the probability of successful extubation.
Noninvasive ventilation (NIV) can act as bridge and facilitate the weaning process.
A patient must pass through different stages, from initiation of mechanical ventilation to weaning. The process includes (1) management of acute respiratory failure,
(2) suspicion of readiness to wean, (3) assessment of readiness to wean, (4) SBT, (5)
extubation, and (6) reintubation if needed. Patients are classified into three groups
on the basis of difficulty and duration of weaning process: (1) simple weaning, (2)
difficult weaning, and (3) prolonged weaning.
D. Chaudhry, MD, DNB, DM, FICCM, FICP (*)

Department of Pulmonary and Critical Care Medicine,
Pt. B.D. Sharma PGIMS, Rohtak 124001, India
Pt. B.D. Sharma University of Health Sciences Rohtak,
Rohtak, Haryana, India
e-mail: dhruvachaudhry@yahoo.co.in
R. Roshan, MD, DNB, FCCP
Department of Pulmonary Medicine, Maulana Azad Medical College and LN Hospital,
Delhi University, Delhi 110002, India
e-mail: rahul.roshan81@gmail.com
DOI 10.1007/978-3-319-04259-6_18
147
148
18.2
D. Chaudhry and R. Roshan
Terminologies (European Respiratory Society/

American Thoracic Society Definition) [1]
Simple weaning [1]: Successful extubation in first attempt from start of weaning
with no difficulty.
Difficult weaning [1]: Initial weaning failure and requiring up to three SBTs or as
many as 7 days from initial SBT to attain successful weaning.
Prolonged weaning [1]: Three or more weaning failures or >7 days of weaning from
initial SBT.
SBT [1]: A T-tube trial or a low-level pressure support trial (8 cmH2O).
Weaning failure [1]: Failure of an SBT or the need for reintubation following extubation within 48 h. There are various subjective and objective criteria for determining failure of an SBT (Table 18.1).
18.3
Etiology and Pathogenesis of Difficult Weaning
Difficult weaning occurs in around 25 % of intensive care patients and in 4060 %

of patients with chronic obstructive pulmonary disease (COPD). Reintubation may
be needed within 4872 h in 525 % of elective extubations, even after a successful
SBT. Reintubation is an independent factor in nosocomial pneumonia, mortality,
and intensive care unit (ICU) and hospital stay.
A wide number of reasons are attributed to difficult weaning (Fig. 18.1). It
includes partial resolution of the initial pathology leading to intubation or the
development of a new disease. Respiratory (28 %) and cardiac failure (23 %) have
been cited as among the commonest causes of reintubation. Aspiration and excessive secretions account for nearly 16 % of causes. Anemia and neuropsychological, metabolic, and nutritional factors may also contribute to a delay in weaning.
Patients with difficult weaning usually develop a rapid and shallow breathing
during the SBT. Prediction of successful SBT is most commonly assessed by calculating the rapid shallow breathing index (RSBI). It is the ratio of respiratory rate per
minute to tidal volume generated by patient in liters. A value of less than 105
breaths/min/l has a sensitivity of 0.97 and a specificity of 0.65. In patients with
chronic obstructive airway disease, a shift from positive pressure ventilation to
spontaneous breathing leads to increased stress on the respiratory muscles, with a
progressive rise in dynamic elastance and inspiratory resistance of lung. This leads
to development of auto-positive end-expiratory pressure (auto-PEEP) and increased
work of breathing. Due to progressive increase in dynamic hyperinflation, the respiratory muscles work at greater mechanical disadvantage with subsequent fall in
capacity, which can decrease further by the development of acidosis. The cardiac
stress during the transition of the positive pressure ventilation to spontaneous
breathing is vital to avert weaning failure. There occurs a rise in venous return to the
right ventricle, leading to displacement of interventricular septum to left side due to
ventricular interdependence. An increase in negative intrathoracic pressure due to
raised inspiratory threshold leads to a subsequent rise in left ventricular afterload.
18
149
Table 18.1 Criteria for

spontaneous breathing trial
failure
Spontaneous breathing trial (SBT) failure

Clinical assessment subjective tools
Agitation and anxiety
Depressed mental status
Cyanosis, diaphoresis
Evidence of increased breathing effort
Nasal flaring
Excessive use of accessory muscles of respiration
Intercostals recession
Objective parameters
PaO2 5060 mmHg on FiO2 0.5 or SaO2 <90 %
PaCO2 >50 mmHg or an increase in PaCO2 >8 mmHg
pH <7.32 or a decrease in pH 0.07
Respiratory rate/Tidal volume (RSBI) >105 breaths/min/l
RR >35/min or increased by 50 %
Heart rate >140/min or increased by 20 %
Systolic BP >180 mmHg or increased by 20 % or
<90 mmHg
Cardiac arrhythmias
1 mmHg = 0.133 kPa
PaO2 arterial oxygen tension, FiO2 inspiratory oxygen fraction,
SaO2 arterial oxygen saturation, PaCO2 arterial carbon dioxide
tension, RSBI rapid shallow breathing index, RR respiratory rate,
BP blood pressure
Reduced central drive

Sedative drugs
Coma
Raised intracranial pressure
Reduced respiratory muscle

strength
Hypophosphatemia
Hypomagnesemia
Steroid therapy
Disuse atrophy
Upper airway obstruction

Laryngospasm
Subglottic stenosis
Difficult
weaning
Increased cardiac load

Myocardial dysfunction
Increased pulmonary vascular
resistance
Reduction of right ventricular
filling
Left ventricular ischemia
Disease realted factors

Partial resolution of underlying
disease
Ventilator associated pneumonia
Undiagnosed co-morbid
condition
Fig. 18.1 Determinants of difficult weaning
Increased respiratory load

Bronchospasm
Excessive secretions
Hyperinflation
Obesity
Nutritional
Obesity
Malnutrition
Neuromuscular
Critical care illness related
neuropathy
Critical care illness related
myopathy
Diaphgramatic dysfunction
150
Inadequate cardiovascular response to these alterations leads to left ventricular failure, raised pulmonary artery occlusion pressure, and elevated brain natriuretic peptides, resulting in weaning failure.
Noninvasive ventilation is a mode of positive pressure ventilation that administers ventilatory support to the patients upper airway using a mask or similar device.
It is increasingly advocated for the weaning of patients from mechanical ventilation
and post-extubation respiratory failure. In patients with difficult weaning, NIV can
be used as
1. Alternative mode of weaning in cases of unsuccessful conventional weaning
2. Treatment of acute respiratory failure following extubation (post- extubation
failure)
3. Preventive measure for reintubation following extubation
18.4
Physiologic Rationale for NIV in Weaning (Table 18.2)
Noninvasive positive pressure ventilation (NIPPV) has positive effects on respiratory physiology and gas exchange. The improvement in hypoxemia and hypercapnia with NIPPV in patients with COPD is due to improved alveolar ventilation
secondary to attainment of a slower and deeper breathing pattern with no alterations
Table 18.2 Physiologic effects of noninvasive ventilation in difficult weaning

IPAP/PSV
Airway diseases
Alveolar ventilation
Inspiratory airway pressure
Slow and deep breathing pattern
Transdiaphragmatic pressures
Chronic neuromuscular diseases
Inspiratory support
Central responsiveness to CO2
Improved sleep architecture
Transdiaphragmatic pressures
EPAP
Decrease work of breathing
Inspiratory threshold
DHI/auto-PEEP
Dynamic airway collapse
Rebreathing of CO2
Improves oxygenation
FRC
Alveoli recruitment
V/Q mismatch
Lung compliance
Redistribution of lung water
Improves cardiac dysfunction
Left ventricular workload
Ejection fraction
Coronary artery oxygen content
IPAP inspiratory positive airway pressure, PSV pressure support ventilation, CO2 carbon dioxide,
EPAP expiratory positive airway pressure, DHI dynamic hyperinflation, auto-PEEP auto-positive
end-expiratory pressure, FRC functional residual capacity, V/Q ventilation/perfusion
18
151
in ventilation-perfusion mismatch. NIV attenuates the fall in intrathoracic pressure,

work of breathing with additive effects of positive pressure ventilation, and external
PEEP. A reduction in diaphragmatic effort indices (transdiaphragmatic pressures
and the pressure time product of diaphragm) is also seen after application of
NIV. Thus, NIV is associated with attenuation of rapid shallow breathing, better gas
exchange, augmented tidal volume, improved ventilation of alveoli, and reduced
work of breathing. PEEP counteracts the auto-PEEP, which decreases work of
breathing and alleviates the raised inspiratory threshold often present in patients
with obstructive airway diseases and in patients with dynamic hyperinflation. It also
improves oxygenation and prevents rebreathing of CO2. Putting a patient on T-tube
as a part of weaning results in an immediate rise in transpulmonary arterial occlusion pressure. Noninvasive ventilation-induced positive intrathoracic pressure can
avoid this by reduction in cardiac preload and afterload.
18.5
Use of NIV as an Alternative Mode in Conventional

Difficult Weaning (Fig. 18.2)
Numerous studies have suggested that NIV could assist in weaning patients from
invasive ventilation. A short weaning time and prevention of reintubation could be
primary end points where NIV is indicated in patients with failed weaning efforts
from mechanical ventilation. Udwadia et al. [2] evaluated the role of NIV in 22
patients with difficult weaning. Nine patients had primary lung pathology or chest
wall disease, and six had neuromuscular pathology. With nasal NIV, after a median
of 11 days, 18 patients were successfully weaned from invasive ventilation. The first
randomized controlled trial (RCT) for evaluation of NIV in weaning in patients with
acute exacerbation of COPD with severe type II respiratory failure who had recovered within 48 h of mechanical ventilation, but had failed SBT, randomized the
patients into two groups [3]. The first group continued to be intubated with weaning
by pressure support ventilation mode while the second group was extubated and put
on NIV. Patient on NIV had a significantly shorter duration of ventilation, a lower
incidence of nosocomial pneumonia, increase in survival by 60 days, and were more
likely to be successfully weaned (88 % vs 68 %). The authors concluded that shortening the duration of endotracheal intubation was the main cause of reduced incidence of ventilation-associated complications and mortality.
Another prospective randomized controlled trial evaluated the role of NIV in
patients on mechanical ventilation with persistent weaning failure who failed spontaneous breathing trials for 3 consecutive days [4]. Seventy-seven percent (n = 33) of
patients had chronic pulmonary diseases. Randomization was done and patients
were either extubated with noninvasive ventilation support or remained intubated
following a conventional weaning approach. The NIV group had reduced days of
invasive ventilation, shorter ICU and hospital stay, reduction in need for tracheostomy to facilitate weaning, and a decrease in incidence of nosocomial pneumonia
and septic shock. An improvement in 90-day survival and ICU survival was also
152
Readiness to wean
SBT
Success
Extubation
4872
h
Weaning
success
criteria
Met
Failure
Facilitation
of weaning
COPD
hypercapnic RF
Prevention*
Post
extubation
respiratory
failure
NIV
Inconclusive
evidence
Treatment
Fig. 18.2 Noninvasive ventilation: current status in weaning from invasive ventilation. SBT spontaneous breathing trial, COPD chronic obstructive pulmonary disease, NIV noninvasive ventilation, RF respiratory failure. *NIV can be applied in patients with chronic pulmonary disease,
chronic cardiac failure, old age >65 years, PaCO2 >45 mmHg, morbid obesity. Criteria for postextubation respiratory failure: RR >25/min for 2 h; heart rate >140/min or fall by >20 %; signs of
respiratory distress: SaO2 <90 %, PaO2 <80 mmHg on FiO2 0.5; PaCO2 >45 mmHg or 20 %
from pre-extubation; pH < .33. Weaning success criteria: SaO2 >90 %; FiO2 >0.4; pH >7.35; RR
<25/min, conscious
noted. As patients with failed weaning are likely to develop a rapid and shallow
breathing pattern, the ability of NIV to overcome hypoxemia and hypercapnia by
improving such an abnormal respiratory pattern might explain the efficacy of NIV
in these patients. Thus, NIV can be a good tool to assist the return of spontaneous
breath and alleviate the ICU requirement in patients with hypercapnic respiratory
failure requiring intubation.
Vaschetto et al. [5] evaluated role of NIV in weaning in patients of hypoxemic
respiratory failure. Twenty patients with hypoxemic failure were randomized into
two groups: weaning by conventional medical care or by NIV. In both groups, no
difference was observed in arterial blood gas after 1, 12, 24, and 48 h of NIV application. The total number of invasive-ventilation-free days at 4 weeks was higher in
the NIV group compared with conventional weaning (20 8 vs 10 6 days). No
significant difference was present in the rate of failed extubation, ICU and hospital
mortality, ICU and hospital stay, need for tracheostomy, sepsis, and use of sedation
18
153
in both groups. In this study, around 40 % of the patients in the NIV group and
50 % in the conventional group had respiratory failure due to trauma, while the rest
had pneumonia and acute lung injury. The beneficial results of NIV in this study
may be due to the predominance of trauma patients, as they can have a good
response with NIV.
Few case reports are available regarding the use of bi-level positive pressure non
invasive ventilation in children in weaning from invasive ventilation with neuromuscular diseases such as Guillain-Barr syndrome and Duchene muscular dystrophy [6]. It can be an alternative method to tracheostomy in such patients with
neuromuscular paralysis needing prolonged ventilation.
In our experience in patients with COPD with acute or chronic hypercapnic
respiratory failure who had failed T-piece weaning trial, after randomization of
patients to receive either pressure support ventilation (PSV) or NIV as the weaning
mode, NIV was found to be equally useful as PSV. Thirty patients with acute exacerbation of COPD on mechanical ventilation were included in this study. No significant difference in total duration of mechanical ventilation or ICU stay was present.
Fewer deaths among patients weaned with NIV at the time of discharge from ICU
and at 30 days were seen, though the number was not significant. Incidence of nosocomial pneumonia was lower in the NIV compared with the PSV group (6.66 % vs
33.33 %). It was concluded that NIV is a better tool in difficult weaning, especially
in COPD, and may lead to a reduction in complications and mortality [7].
18.6
NIV in Management of Post-extubation Respiratory

Failure
Two RCTs have shown some benefit from noninvasive positive pressure ventilation
in patients who had high risk of extubation failure [8, 9]. The risk factors were different between the two trials: (a) failure of more than one consecutive weaning
trial, chronic heart failure, PaCO2 45 mmHg after extubation, more than one
comorbidity, poor cough, and excessive tracheobronchial secretions [8]; and (b)
age greater than 65 years, heart failure, and APACHE (Acute Physiology and
Chronic Health Evaluation) II score greater than 12 at the time of extubation [9].
Both the trials showed a trend toward a fall in the rate of reintubation and lower
ICU mortality but minimal or no benefit in hospital mortality. Ferrer et al. [9] analyzed patients with and without CO2 retention during the spontaneous breathing
trial and reported that application of NIV lead to a drop in ICU mortality and
greater 90-day survival in hypercapnic patients only. Ornico et al. [10] did a randomized controlled trial to determine the benefit of NIV applied immediately after
extubation that showed that NIV led to a reduction in intubation and hospital mortality. There is still no clear-cut evidence regarding routine use of NIV to prevent
extubation failure except probably in patients with COPD. It is mandatory to monitor the extubated patient after application of NIV as no sign of improvement in the
respiratory parameters warrants reintubation.
154
18.7
NIV in Prevention of Post-extubation

Respiratory Failure
The benefits of NIV in the treatment of patients developing respiratory failure after
extubation is inconclusive. Few RCTs have been done that reported almost no
advantage of application of NIV in management of post-extubation respiratory failure. Esteban et al. [11] assessed the effect of NIV on mortality in patients who were
extubated after 48 h of mechanical ventilation and developed respiratory failure in
the next 48 h in a randomized controlled trial. In 221 patients, randomization was
done and they were either given NIV support (n = 114) or standard medical treatment (n = 107). No difference in the rate of reintubation was reported. Mortality was
higher in the NIV group (25 % vs 14 %), with median time from onset of respiratory
distress to reintubation significantly longer in NIV group. In a post hoc analysis of
a subset of patients with COPD (n = 23), the rate of reintubation was lower in
patients who had received NIV compared with standard therapy (50 % vs 67 %).
The authors concluded that NIV is not helpful in avoiding reintubation, does not
increase the survival, and can be harmful.
Another RCT done by Keenan et al. [12] on role of NIV in patients with postextubation failure compared with standard medical therapy showed that there were
no differences in rate of reintubation (72 % vs 69 %), occurrence of pneumonia
(47 % vs 41 %), ICU survival (83 % vs 74 %), or hospital survival (69 % vs 67 %).
Only 11 % of patients included in this study had a diagnosis of COPD, and the
patients with COPD were excluded after 1 year of study.
Lin et al. [13] did a meta-analysis of 10 trials involving 1,382 patients on the
efficacy of NIV in treatment of post-extubation failure and reported that use of NIV
did not reduce the reintubation rate or ICU mortality compared with standard treatment. Early NIV support also did not lead to a significant reduction in reintubation
rate after extubation. In the planned extubation subgroup, there was a significant
decrease in the rate of reintubation and ICU and hospital mortality rate. The authors
advocated for early use of NIV and vigilant monitoring of the patient during NIV
application in treatment of post-extubation respiratory failure.
Glossop et al. [14] analyzed the utility of NIV for weaning and prevention of
reintubation after extubation and reported that NIV reduced the duration of stay in
ICU by 5.12 days and hospital stay by 6.45 days during its use for weaning but not
post-extubation. Risk of pneumonia with NIV was also lower in weaning but not
post-extubation. No reduction in risk of reintubation or any increase in ICU survival
was seen when NIV was applied for weaning or post-extubation. Hospital survival
was greater with NIV during weaning but not post-extubation.
Burns et al. [15] performed a systematic review of the use of NIV in weaning of
mechanically ventilated critically ill patients. It included 12 trials with 530 patients,
most having COPD. Mortality, ventilator-associated pneumonia, duration of ICU
and hospital stay, and total time period of ventilation were significantly reduced
18
155
when weaned via NIV compared with invasive weaning. Weaning failure or weaning time were the same, irrespective of mode of weaning. In patients with underlying COPD compared with the general population, impact on the reduction in
mortality and weaning failure was relatively higher.
18.8
Weaning Protocol (Fig. 18.3)
I. Assess patients readiness to wean.

II. Perform SBT for 120 min.
III. Extubate if:
(a) Conscious
(b) Can protect the airway
(c) Good cough
(d) SBT well tolerated
IV. Monitor for the next 4872 h for post-extubation respiratory failure.
V. If the SBT fails
(a) Volume control mode: Measure the plateau pressure (Pplat) and monitor
PEEP.
(b) Pressure support/control mode: Measure the pressure support (PS) above
PEEP and monitor PEEP.
VI. Extubate the patient and apply BiPAP (bilevel positive airway pressure)
(a) IPAP (inspiratory positive airway pressure): Equivalent to the Pplat or up to
5 cm H2O less than Pplat or sum of PS above PEEP and PEEP on
ventilator
(b) EPAP (expiratory positive airway pressure): Equivalent to PEEP on the
ventilator [(BiPAP (Bilevel positive airway pressure machine): IPAP is
equal to pressure support above PEEP + PEEP on ventilator NIV mode on
ICU ventilator: PS/PC is equivalent to PS/PC on ventilators) EPAP (expiratory positive airway pressure): Equal to PEEP on the ventilator)]
IV.
Monitor (a) tidal volume, (b) respiratory rate, and (c) use of accessory muscles of respiration.
V.
Gradually decrease the IPAP and EPAP by 12 cm H2O in the daytime every
46 h.
VI. Bring IPAP to 8 cm H2O and EPAP to 4 cm H2O.
VII. Remove the NIV initially in the daytime during feeding and for short durations of time (12 h) intermittently.
VIII. Gradually take the patient off from NIV in the daytime, followed by its
removal in night.
IX. Monitor the predictors of failure during weaning through NIV carefully.
X.
Failure of NIV warrants invasive mechanical ventilation.
NIV failure
Measure PEEP and PS above PEEP
IPAP: Sum of PS above PEEP and PEEP* (NIV ventilator)

EPAP: Equivalent to PEEP
Take the patient off from NIV in the daytime, followed by its removal in night
Remove the NIV initially in the daytime during feeding and for short durations of time (12 h) intermittently
Bring IPAP to 8 cmH2O and EPAP to 4 cmH2O
Gradually decrease the IPAP and EPAP by 12 cmH2O in the daytime every 46 h
Monitor tidal volume, respiratory rate, use of accessory muscles of respiration
IPAP: Pplat or up to 5 cmH2O less than Pplat*

EPAP: Equivalent to PEEP on the ventilator
Extubation NIV
Fig. 18.3 Weaning protocol by Non-invasive ventilation in difficult weaning. SBT Spontaneous breathing trial, Pplat Plateau pressure, PEEP Positive end
expiratory pressure, PS Pressure support, IPAP Inspiratory positive airway pressure, EPAP Expiratory positive airway pressure, NIV Non-invasive ventilation,
MV Mechanical ventilation. *IPAP and EPAP are terminologies of BiPAP (Bilevel positive airway pressure) machine. In ICU ventilators: Pressure support
above PEEP is equivalent of IPAP; PEEP is equivalent of EPAP. Set PS above PEEP = Pplat or up to 5 cmH2O less than Pplat or pre extubation PS above PEEP.
Set PEEP =pre extubation PEEP
Intubation and MV
NIV
post-extubation respiratory failure
Measure Pplat and PEEP
Monitor for the next 4872 h for postextubation respiratory failure
Pressure support/Control
Ventilator mode
Volume control
No
conscious
can protect the airway
good cough
SBT well tolerated
Extubation
Yes
a.
b.
c.
d.
Perform SBT for 120 min
Assess patients readiness to wean
156
18
18.9
157
Advantages of NIV in Difficult Weaning
Several benefits occur when extubation is allowed for application of NIV, such as
minimal use of sedation, early removal of the endotracheal tube, decrease in the
incidence of ventilator-associated pneumonia, improved mucociliary clearance
with reduced incidence of sinusitis, better compliance with chest physiotherapy,
and better patient comfort and communication. It improves left ventricular dysfunction and reduces cardiac failure. Also, as the duration of stay in the hospital
may be reduced, it can lead to a reduction in morbidity and is more cost effective.
18.10 Determinants of NIV Failure in Weaning

NIV can be detrimental in patients where excessive secretions are present with poor
cough reflex and suctioning of the airways is needed. Chest physiotherapy and use
of mechanical insufflation/exsufflation devices can help in expectorating the secretions. It can be difficult to manage agitated patients and NIV does not guarantee
mechanical ventilation. The main reasons behind the failure of NIV are the inability
of the patient to cooperate, poor tolerance, patient-ventilator asynchrony, excessive
tracheobronchial secretions, severe strength-load imbalance, hemodynamic alterations, and cardiac arrhythmias. Application of NIV in patients with facial trauma or
deformity, excessive gastrointestinal bleeding, and multi-organ failure can be difficult and hazardous. Mask discomfort, skin ulceration or irritation, or claustrophobia
can be the additional factors leading to NIV failure. Persistent generation of adequate tidal volume without fatigue of the respiratory pump can be difficult in patients
with critical care illness myopathy and nutritional deficiencies.
Conclusion
Increased workload on respiratory muscle, leading to fatigue, is an important determinant in patients with difficult weaning from a ventilator along with cardiac and
other nutritional and biochemical factors. Ability to protect the airway and adequate consciousness of the patient is vital for the success of NIV. Noninvasive
ventilation can act as a bridge between weaning failure and successful weaning. It
can be a promising tool in critically ill patients with difficult weaning. Current
evidence suggest that it should not be used routinely for patients with weaning
failure. The exception is COPD patients having hypercapnic respiratory failure,
where it can reduce the mortality and prevent ventilator-associated complications.
Early use of NIV may avert post-extubation respiratory failure in a selected group
of patients. In patients with weaning from hypoxemic respiratory failure with high
PaO2/FiO2 ratio of 200250 mmHg at FiO2 of <0.6 and mild to moderate restrictive
mechanics, a trial of positive pressure ventilation can be given, but the outcome
still remains to be determined. In selected patients with neuromuscular diseases, it
can be tried with an eye over delivery of adequate tidal volume and avoidance of
hypoventilation. Proper monitoring of the patient during a trial of NIV in weaning
is mandatory to predict the failure of NIV. Excessive secretions, asynchrony, and
strength-load imbalance are common factors for NIV failure. Clear criteria for
termination of NIV support in weaning still need to be evaluated.
158
A trial of NIV is worthwhile in patients with hypercapnic respiratory failure with difficult weaning.
Strict monitoring of subjective and objective parameters is mandatory during NIV application.
Early recognition of predictors of failure of NIV is vital to prevent delay in
reintubation or mortality.
Following a weaning protocol will be helpful in the path of successful
weaning.
References
1. Boles JM, Bion J, Connors A, et al. Weaning from mechanical ventilation. Eur Respir
J. 2007;29(5):103356.
2. Udwadia ZF, Santis GK, Steven MH, et al. Nasal ventilation to facilitate weaning in patients
with chronic respiratory insufficiency. Thorax. 1992;47(9):7158.
patients with respiratory failure due to chronic obstructive pulmonary disease. A randomized,
controlled trial. Ann Intern Med. 1998;128(9):7218.
failure: a randomized controlled trial. Am J Respir Crit Care Med. 2003;168(1):706.
5. Vaschetto R, Turucz E, Dellapiazza F, et al. Noninvasive ventilation after early extubation in
patients recovering from hypoxemic acute respiratory failure: a single-centre feasibility study.
Intensive Care Med. 2012;38(10):1599606.
6. Reddy VG, Nair MP, Bataclan F. Role of non-invasive ventilation in difficult-to-wean children
with acute neuromuscular disease. Singapore Med J. 2004;45(5):2324.
7. Prasad SB, Chaudhry D, Khanna R. Role of noninvasive ventilation in weaning from mechanical ventilation in patients of chronic obstructive pulmonary disease: an Indian experience.
Indian J Crit Care Med. 2009;13(4):20712.
after extubation in high-risk patients. Crit Care Med. 2005;33(11):246570.
in patients at risk: a randomized trial. Am J Respir Crit Care Med. 2006;173(2):16470.
10. Ornico SR, Lobo SM, Sanches HS, et al. Noninvasive ventilation immediately after extubation
improves weaning outcome after acute respiratory failure: a randomized controlled trial. Crit
Care. 2013;17(2):R39.
respiratory failure after extubation. N Engl J Med. 2004;350(24):245260.
12. Keenan SP, Powers C, McCormack DG, et al. Noninvasive positive pressure ventilation for
postextubation respiratory distress: a randomized controlled trial. JAMA. 2002;287(24):
323844.
13. Lin C, Yuh H, Fan H, et al. The efficacy of non invasive ventilation in managing postextubation
respiratory failure: a meta-analysis. Heart Lung. 2014;43(2):99104.
14. Glossop AJ, Shephard N, Bryden DC, et al. Non-invasive ventilation for weaning, avoiding
reintubation after extubation and in the postoperative period: a meta-analysis. Br J Anaesth.
2012;109(3):30514.
15. Burns KE, Adhikari NK, Keenan SP, et al. Use of non-invasive ventilation to wean critically ill
adults off invasive ventilation: meta-analysis and systematic review. BMJ. 2009;338:b1574.
Noninvasive Technique of Nasal

Intermittent Pressure Ventilation
(NIPPV) in Patients with Chronic
Obstructive Lung Disease After Failure
to Wean from Conventional Intermittent
Positive-Pressure Ventilation (IPPV):
Key Practical Topic and Implications
19
Farouk-Mike Elkhatib and Mohamad Khatib
19.1
Introduction
Endotracheal intubation and invasive mechanical ventilation of patients with acute

exacerbation of chronic obstructive pulmonary disease (COPD) are often associated
with several complications [1]. As such, early weaning from invasive mechanical
ventilation and extubation is a paramount objective for clinicians. Usually this is a
simple process that necessitates switching patients from an assisted/controlled
mode of ventilatory support to an intermittent positive-pressure ventilation (IPPV)
mode and the subsequent gradual reduction of the IPPV mandatory rate to the level
that the clinician deems enough to attempt extubation and resumption of full spontaneous breathing. However, this process can be cumbersome and even detrimental
to patients in terms of prolonging duration of mechanical ventilation, increasing
intensive care unit (ICU) and hospital stays, and increasing risks of nosocomial
infections and at times mortality and/or morbidity [1]. Furthermore, during this
weaning process, some patients might display signs and symptoms of respiratory
distress and deranged gas exchange that lead to the termination of the weaning process and resumption of full ventilatory support.
F.-M. Elkhatib
School of Medicine, American University of Beirut, Beirut, Lebanon
e-mail: fme21@aub.edu.lb
M. Khatib (*)
Department of Anesthesiology, American University of Beirut Medical Center,
P.O. Box: 110236, Beirut 1107-2020, Lebanon
e-mail: mk05@aub.edu.lb
DOI 10.1007/978-3-319-04259-6_19
159
160
F.-M. Elkhatib and M. Khatib
Noninvasive ventilation (NIV) is a form of ventilatory support that can facilitate

early extubation and improves the outcome of invasive mechanical ventilation. It
has been shown to significantly reduce duration of mechanical ventilation, the duration of ICU and hospital stays, risks of infection, and cost [2].
19.2
Nasal Intermittent Positive-Pressure Ventilation
Nasal intermittent positive-pressure ventilation (NIPPV) is a form of noninvasive

positive-pressure ventilation that can be used in the weaning of patients with COPD
needing mechanical ventilation [3]. NIPPV is usually provided with a bi-level positive airway pressure (BiPAP) generator, a single-limb breathing circuit, and a patient
interface (e.g., nasal, oronasal, or a full facemask), and an exhalation port that can
be either attached to the breathing circuit or, most commonly, incorporated within
the patients interface. There are several factors that contribute for the success of
NIPPV for patients who fail weaning from invasive mechanical ventilation
(Table 19.1). The two most important factors are the appropriate patient selection
and the proper use and settings of the NIPPV.
In a randomized, controlled trial, Ferrer et al. [4] assessed the efficacy of NIPPV
in patients with persistent weaning failure. In 43 mechanically ventilated patients,
with the majority being ventilated secondary to exacerbation of COPD and who had
failed a conventional weaning trial for 3 consecutive days, NIPPV led to earlier
extubation, shorter mechanical ventilation and length of ICU and hospital stay, less
need for tracheostomy, lower incidence of complications, and improved ICU survival [4]. A meta-analysis of five studies and 171 patients reported that the use of
NPPV facilitates weaning with a consistent positive effect of noninvasive weaning
on mortality [5]. A large body of clinical evidence suggests that NIPPV can be beneficial for weaning COPD patients who fail weaning from invasive mechanical ventilation. In a randomized, controlled study of 50 patients invasively ventilated for
acute exacerbation of COPD and who failed a spontaneous breathing trial, Nava
et al. [6] showed that NIPPV facilitated extubation within 48 h, shortened the length
of stay in the ICU, decreased the incidence of nosocomial pneumonia, and improved
the 60-day survival rates. Trevisan et al. [7] assessed the use of NIPPV during weaning from mechanical ventilation. The majority of their patients (35 %) were patients
COPD patients. They showed that in patients who failed spontaneous ventilation
Table 19.1 Factors
contributing to the success of
NIPPV during weaning
COPD patients
1. Timing of intervention with NIPPV

2. Selection and adjustment of IPAP
3. Selection and adjustment of EPAP
4. Selection and adjustment of back-up rate
5. Selection and adjustment of FiO2
6. Selection of appropriate patient interface
7. Location of treatment
8. Expertise of clinicians with NIPPV
19 Noninvasive Technique of Nasal Intermittent Pressure Ventilation (NIPPV)
161
trial when weaning was attempted, NPPV is a good alternative that resulted in better
outcome, fewer complications, and less need for tracheostomy [7]. In a prospective,
randomized and controlled study, Prasad et al. [8] evaluated the effectiveness of
NIPPV as a weaning method in patients with COPD receiving invasive mechanical
ventilation. Thirty COPD patients were randomized to be weaned with either
NIPPV or invasive pressure support ventilation (PSV). In patients who failed a
weaning trial, NIPPV resulted in faster weaning and a decrease in ICU stay, complications, and mortality [8]. Mishra et al. [9] evaluated the usefulness of NIPPV in
weaning COPD patients from invasive mechanical ventilation in a prospective, randomized, and controlled study. They included 50 patients who failed an initial
weaning trial and subsequently were either extubated to be weaned with NIPPV (25
patients) or remained on invasive mechanical ventilation for further weaning with
PSV. NIPPV resulted in shorter duration of weaning and ventilation, shorter ICU
stay, less incidence of nosocomial pneumonia, and lower ICU mortality [9].
Another factor for the success of NIPPV in weaning COPD patients is the proper
utilization and adjustment of the device providing NIPPV. The mode of NIPPV as
well as other relevant parameters (i.e., inspiratory positive airway pressure (IPAP),
expiratory positive airway pressure (EPAP), back-up rate (RR) as well as fraction of
inspired oxygen (FiO2)) are parameters and variables that need to be adjusted
dynamically according to the patients needs. In general, most COPD patients are
managed with BiPAP in the spontaneous/timed (S/T) mode where the patient is triggering the device except during apneas/hypopneas, where the preset back-up RR
(usually 1214 breaths/min) guarantees adequate ventilatory support [69]. Initial
levels of IPAP (1025 cmH2O) and EPAP (510 cmH2O) are usually decided on
achieving adequate tidal (approximately 56 ml/kg), total respiratory rate less than
25 breaths/min, acceptable arterial blood gas values, and patient tolerance and comfort. When managing and adjusting IPAP and EPAP levels during the course of
ventilatory support, clinicians should consider the difference between IPAP and
EPAP as well as their individual values. The difference between IPAP and EPAP
(sometimes referred to as PSV) per se and not the absolute values has a direct effect
on the delivered tidal volume [10]. Increasing the difference between IPAP and
EPAP usually results in an increase in tidal volume and vice versa. EPAP, however,
has a similar physiological effect as positive end-expiratory pressure (PEEP). It has
a direct effect on oxygenation by restoring functional residual capacity and partially
recruits collapsed alveoli. In addition, EPAP can stabilize recruited alveoli and prevent derecruitment [10]. For patients with COPD, EPAP decreases the work of
breathing by minimizing the effect of auto-PEEP that is frequently seen and manifested in COPD patients [10]. With the emerging technologies of NIPPV, clinicians
can provide accurate and adequate FiO2 with the use of oxygen-air blenders incorporated in the new BiPAP machines. With the old BiPAP technologies where the
FiO2 was a result of air and oxygen flows mixing, it was always a challenge to provide adequate, accurate, and stable FiO2 best suited to COPD patients.
In conclusion, NIPPV has been shown to be beneficial in the weaning of patients
with obstructive pulmonary disease. COPD patients who fail initial weaning trials
with conventional weaning techniques as well as COPD patients who are immediately
162
F.-M. Elkhatib and M. Khatib
shifted for weaning with NIPPV show shorter duration of weaning, ICU stay, less
need for tracheostomy, lower incidence of nosocomial pneumonia, lower health-care
costs, and better outcomes with NIPPV. It is essential for the success of NIPPV therapy that clinicians are versed in the use and management of NIPPV.
NIPPV is a useful and safe alternative for ventilation and weaning in

COPD patients who fail initial weaning attempts.
The success of NIPPV for weaning COPD patients depends on appropriate
implementation of the therapy that involves dynamic adjustment and control of its main components (e.g., mode, IPAP, EPAP, FiO2, and back-up
respiratory rate).
Clinicians caring for COPD patients should be well versed in the initiation,
management, and discontinuation of NIPPV therapy.
References
1. Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med.
2013;369(22):212636.
2. Burns KE, Meade MO, Premji A, Adhikari NK. Noninvasive ventilation as a weaning strategy
for mechanical ventilation in adults with respiratory failure: a Cochrane systematic review.
CMAJ. 2014;186(3):E11222.
3. Khilnani GC, Banga A. Noninvasive ventilation in patients with chronic obstructive airway
disease. Int J Chron Obstruct Pulmon Dis. 2008;3(3):3517.
4. Ferrer M, Esquinas A, Aranciba F, et al. Noninvasive ventilation during persistent weaning
failure. Am J Respir Crit Care Med. 2003;168:706.
5. Burns KE, Adhikari NK, Meade MO. A meta-analysis of noninvasive weaning to facilitate
liberation from mechanical ventilation. Can J Anaesth. 2006;53:30515.
7. Trevisan C, Vieira S; The Research Group in Mechanical Ventilation Weaning. Noninvasive
mechanical ventilation may be useful in treating patients who fail weaning from invasive
mechanical ventilation: a randomized clinical trial. Crit Care. 2008;12:R518.
8. Prasad S, Chaudhry D, Khanna R. Role of noninvasive ventilation in weaning from mechanical
ventilation in patients of chronic obstructive pulmonary disease: an Indian experience. Indian
J Crit Care Med. 2009;13:20712.
9. Mishra M, Chaudhri S, Tripathi V, et al. Weaning of mechanically ventilated chronic obstructive pulmonary disease patients by using non-invasive positive pressure ventilation: a prospective study. Lung India. 2014;31:12733.
10. Hess DR. Noninvasive ventilation for acute respiratory failure. Respir Care. 2013;58(6):
95072.
Part III
Post Extubation Failure and Use of Non
Invasive Mechanical Ventilation
Use of Noninvasive Ventilation

to Facilitate Weaning from
Mechanical Ventilation
20
Scott K. Epstein
20.1
Introduction
Noninvasive positive-pressure ventilation (NIV), applied through various mask

interfaces, improves outcomes in patients with acute respiratory failure secondary
to acute exacerbation of chronic obstructive pulmonary disease (COPD), acute cardiogenic pulmonary edema, and hypoxemic respiratory failure with pulmonary
infiltrates in immunocompromised patients. NIV has also been used to prevent, or
treat, respiratory failure in patients undergoing planned extubation from mechanical
ventilation [1]. Randomized controlled trials suggest that NIV may not be effective
when applied to a heterogeneous group of patients with extubation failure, although
a case control study suggests this therapy may be effective for patients with COPD
with extubation failure [2, 3]. Similarly, NIV seems not to prevent extubation failure
(defined as the need for reintubation) when it is applied nonselectively to all extubated patients [4]. By contrast, NIV improves outcome (decreased reintubation,
decreased pneumonia, shorter duration or mechanical ventilation and length of stay,
improved survival) when it is used as preventive therapy in cohorts of patients
deemed to be at high risk for extubation failure [5, 6]. With the exception of some
patients in the Jiang study, NIV was used in these investigations only when a patient
had successfully passed a spontaneous breathing trial (SBT), indicating that
mechanical ventilatory support was no longer required. These studies raise the
question of whether NIV can be used in the patient who is ready to initiate weaning
but who is not yet able to tolerate an SBT. In other words, can NIV be used to facilitate weaning?
S.K. Epstein, MD
Division of Pulmonary, Critical Care, and Sleep Medicine, Tufts Medical Center,
Tufts University School of Medicine, Boston, MA, USA
e-mail: Scott.Epstein@tufts.edu
DOI 10.1007/978-3-319-04259-6_20
165
166
20.2
S.K. Epstein
Rationale for Using NIV
Patients who are intubated and mechanically ventilated for acute respiratory failure
are at increased risk for complications, including upper airway injury, respiratory
muscle weakness, gastrointestinal bleeding, thromboembolism, sinusitis, and
ventilator-associated pneumonia. The latter is particularly important given its association with increased morbidity and possibly increased mortality. The risk for complications and the risk of mortality rise with increasing duration of mechanical
ventilation. Needlessly delaying extubation in a patient who otherwise seems to be
ready also causes harm, as such patients experience increased risk for pneumonia,
length of stay, and mortality compared with patients expeditiously extubated. On
the other hand, numerous studies have found that patients who pass an SBT and
undergo planned extubation but require reintubation (extubation failure) have
increased risk for complications, prolonged hospital stay, and significantly increased
mortality [7].
Therefore, an essential task for ICU clinicians is trying to wean and successfully
extubate patients as expeditiously (and safely) as possible. A series of studies published in the 1990s indicated that between 15 and 35 % of patients mechanically
ventilated with acute respiratory failure fail an initial trial of spontaneous breathing
and will require a more prolonged weaning process. These studies, for the most
part, relied on clinician intuition for determining readiness for weaning. More
recently, investigators have noted that, depending on the patient population studied,
4070 % of patients do not tolerate their initial SBT. This observation is likely
related to the more aggressive screening criteria used to identify the earliest time
when spontaneous breathing can be undertaken.
Given the similarities between the pathophysiology of weaning failure and that
of acute respiratory failure, NIV may have a role to play in facilitating weaning.
As with acute respiratory failure, weaning failure is often characterized by an
imbalance between respiratory muscle capacity and the respiratory load confronted by those muscles (i.e., the work of breathing). The latter can result from
increased resistive or elastic work of breathing, the effects of intrinsic positive
end-expiratory pressure (PEEP), and abnormal gas exchange. When used to treat
patients with acute respiratory failure, NIV is capable of reducing the work of
breathing, providing respiratory muscle unloading (including offsetting the
effects of intrinsic PEEP), improving alveolar ventilation, and increasing oxygenation. In so doing, NIV decreases the risk for intubation, reduces important complications such as pneumonia, and improves survival. There is increasing
recognition that weaning failure may result from cardiovascular abnormalities
including ischemia, increased preload and afterload resulting from the negative
intrathoracic pressure that occurs during spontaneous breathing, and an inability
to adequately increase cardiac output to meet the metabolic demands of the
SBT. As demonstrated in studies of acute cardiogenic pulmonary edema, NIV can
counteract these factors and result in improved cardiac performance and decreased
cardiogenic pulmonary edema.
20
Use of Noninvasive Ventilation to Facilitate Weaning from Mechanical Ventilation
167
By exchanging the endotracheal tube for a noninvasive interface, NIV may have
additional benefits. With the removal of the endotracheal tube, any increased work
of breathing imposed by the artificial airway is eliminated. Removal of the endotracheal tube improves patient comfort and the ability to communicate, reduces the
need for sedation, and restores the capacity for effective cough; all factors that could
contribute to successful weaning and extubation.
20.3
Preliminary Studies
Based on the rationale above, NIV has the potential to facilitate the weaning process
in patients who are ready for spontaneous breathing but who cannot yet pass a
SBT. Observational studies, reported in the 1990s, indicated the potential of NIV to
promote successful weaning. Udwadia et al. [8] reported that 82 % of 22 difficult to
wean patients (mean duration of ventilation, 31 days), with various causes for respiratory failure, could be successfully liberated from mechanical ventilation by the
use of nasal NIV. Similarly, Restrick and colleagues [9] found the use of NIV
resulted in 93 % weaning success in 14 weaning failure patients, including 8 with
COPD. In a third study, 13 of 15 patients were successfully extubated to NIV after
satisfying criteria not typically associated with satisfactory completion of an SBT
(PaO2 40 mmHg on a fraction of inspired oxygen (FiO2) of 0.21, PaCO2 55 mmHg,
pH >7.32, respiratory rate 40 breaths/min, frequency/tidal volume ratio of 190
breaths/l/min) [10].
20.4
Randomized Controlled Trials
Over the last two decades, a number of randomized controlled trials have
addressed whether NIV, when compared with invasive weaning with the endotracheal tube in place, can successfully facilitate weaning in patients who are not
tolerating SBTs.
Nava and colleagues [11] randomized 50 COPD patients (40 % of whom had
failed NIV prior to intubation) with acute-on-chronic respiratory failure who had
failed a 2-h SBT to weaning with the endotracheal tube in place (using pressure
support) or direct extubation to NIV delivered with an oronasal mask. Patients
randomized to NIV experienced shorter time on mechanical ventilation,
decreased ICU stay, higher likelihood of successful weaning, and improved
60-day survival.
Using a similar study design, Girault et al. [12] randomized 33 patients with
acute-on-chronic respiratory failure and found that NIV reduced the duration of
intubation while other outcomes were unchanged. Interestingly, total mechanical
ventilation time (time intubated plus time on NIV) was more than a week greater
in the NIV group.
168
S.K. Epstein
Ferrer and coworkers [13] randomized 43 patients, including 77 % with chronic

lung diseases, after they had failed a minimum of three SBTs. This study was
terminated at the first interim analysis because of the overwhelming benefits
associated with weaning facilitated by NIV. NIV, compared with weaning performed while the patient remained intubated, was associated with reductions in
the duration of intubation, ICU and hospital stay, need for tracheostomy, and
development of pneumonia. NIV was associated with increased ICU and 90-day
survival.
In a small study of patients intubated for hypoxemic respiratory failure, Vaschetto
and co-investigators [14] randomized 20 patients to invasive weaning or
NIV. Patients randomized to NIV had a greater number of invasive-ventilationfree days at day 28. In contrast, no differences were found in the rate of extubation failure, ICU and hospital mortality, tracheotomies, septic complications, and
ICU length of stay.
Rabie Agmy and colleagues [15] randomized 264 patients with an acute exacerbation of COPD who failed a 120-min SBT. Patients extubated to NIV experienced decreased ventilator-associated pneumonia, increased weaning success,
and reduced mortality.
Prasad et al. [16] randomized 30 patients with COPD and acute hypercapnic
respiratory failure after they had failed a 2-h SBT. When comparing those weaned
invasively with those extubated to NIV, no statistically significant differences
were found in ventilator-associated pneumonia, duration of weaning, duration of
mechanical ventilation, length of stay, or survival.
Trevisan et al. [17] randomized 65 patients (35 % with obstructive lung disease)
who failed to tolerate a 30-min SBT. When compared with patients who remained
intubated for weaning, those extubated to NIV experienced fewer complications
but no differences in length of stay, duration of mechanical ventilation, or survival. Twenty-one percent of NIV patients required reintubation.
Tawfeek et al. [18] studied 42 patients, with various etiologies of acute respiratory failure, who had been invasively ventilated for greater than 48 h and failed
a 2-h SBT. Patients randomized to continued intubation were weaned using
Synchronized Intermittent Mandatory Ventilation (SIMV), whereas those in
the intervention group were randomized to extubation with NIV using proportional assist ventilation. Those in the NIV arm experienced greater weaning
success and reduced ventilator-associated pneumonia, but without a decrease in
mortality.
In the literature of NIV to facilitate weaning, the second study by Girault and
coworkers [19] is unique in that a third arm was included where patients were
extubated to oxygen, with NIV only applied as rescue therapy, if needed. In this
multicenter study of 208 acute-on-chronic respiratory failure patients, randomization occurred after failure of an SBT trial lasting from 5 to 120 min. When the
three groups were compared, no differences were found in likelihood of weaning
failure (including reintubation), length of stay, or hospital survival. Of note, NIV
was used as salvage therapy in 45 % of patients weaned invasively (45 % successfully) and 57 % of patients extubated to oxygen (58 % successfully).
20
20.5
169
Systematic Review of Randomized Controlled Trials
To further analyze these randomized controlled trials, Burns and colleagues [20]
have conducted a series of systematic reviews, the most recent of which considered 16 trials (including one with a quasi-randomized approach), totaling 994
patients, who had acute respiratory failure requiring invasive mechanical ventilation for a minimum of 24 h. The majority of patients in these studies had COPD;
of the 16 trials, 9 were restricted to patients with COPD and 7 studied mixed
patient populations. This analysis included the nine trials discussed above in addition to two abstracts and four investigations published in Chinese. Three of the
latter and one additional study differed significantly from the other studies analyzed in their focus on COPD patients with pneumonia. Importantly, in these studies the point of randomization was when the patient met criteria indicating control
of infection rather than after the patient had failed one or more SBTs. Four of
these additional studies also employed an SIMV weaning strategy (with or without pressure support) for those in the invasive groups while NIV was delivered
using pressure mode bi-level ventilation or pressure support. In this instance, any
superiority demonstrated by the NIV groups could be attributable to the approach
to weaning (e.g., a reduction of pressure or bi-level support) rather than factors
related to the removal of the endotracheal tube or the other potential beneficial
effects of NIV.
When all 16 trials were analyzed, Burns et al. [20] found that, compared with
invasive weaning, patients weaned with NIV had reduced mortality, greater weaning success, less ventilator-associated pneumonia, shorter length of stay in the ICU
and in the hospital, less need for tracheostomy, fewer episodes of reintubation, and
a shorter duration of mechanical ventilation. The reduction in mortality experienced
by patients weaning with NIV was greatest in trials that primarily or exclusively
enrolled patients with COPD.
20.6
Mechanism of Effect
The individual studies discussed above and the systemic review indicate that NIV
can successfully facilitate weaning, principally in patients with COPD. None of the
randomized controlled studies found NIV to be inferior to weaning with the endotracheal tube in place. The reason for NIVs benefit may be attributable to the associated reduction in complications, especially pneumonia, or the reduced need for
sedation. NIV may also improve the capacity of clinicians to detect the patients
ability to breathe spontaneously. By allowing the endotracheal tube to be removed,
any excess work of breathing imposed by that tube is alleviated. Psychological distress caused by tube discomfort, which may be misinterpreted as intolerance for
spontaneous breathing, can be alleviated by tube removal. In these cases, NIV does
not directly facilitate weaning; rather, it allows removal of the endotracheal tube
that was the proximate cause of weaning failure. The results of the second Girault
study would tend to support this hypothesis.
170
S.K. Epstein
Noninvasive ventilation can be used to facilitate weaning in a select group

of COPD patients who have been intubated for at least 24 h secondary to
an acute exacerbation and who have failed one or more trials of spontaneous breathing.
It must be remembered that NIV should only be used in a patient who has
satisfied the criteria to undertake a SBT. This strategy should be restricted
to patients who demonstrate some degree of recovery from the acute process that led to intubation and exhibit adequate oxygenation (e.g., PaO2/
FiO2 120150 on PEEP 58 cmH2O), hemodynamic stability (adequate
blood pressure with little or no vasopressor support), and some spontaneous breathing efforts.
The patient must be a good candidate for NIV. They must be able to tolerate the mask chosen to deliver NIV. The patient must be capable of spontaneous breathing for at least 510 min to allow for fitting and adjustment of
the mask and the fine-tuning of the ventilator required to ensure optimal
noninvasive support. NIV in this setting may be contraindicated in patients
deemed to be technically difficult to reintubate; this group should be considered for tracheostomy.
Once extubated to NIV, patients must be observed closely, and health-care
providers with expertise in airway management should be readily available. If signs of respiratory distress are present, despite NIV, and do not
resolve (or worsen) within 4 h of extubation, reintubation should occur
without delay.
References
1. Epstein SK. Noninvasive ventilation to shorten the duration of mechanical ventilation. Respir
Care. 2009;54:198208.
3. Hilbert G, Gruson D, Portel L, et al. Noninvasive pressure support ventilation in COPD
patients with postextubation hypercapnic respiratory insufficiency. Eur Respir J.
1998;11:134953.
after extubation in high-risk patients. Crit Care Med. 2005;33:246570.
8. Udwadia ZF, Santis GK, Steven MH, Simonds AK. Nasal ventilation to facilitate weaning in
patients with chronic respiratory insufficiency. Thorax. 1992;47:7158.
20
171
9. Restrick LJ, Scott AD, Ward EM, et al. Nasal intermittent positive-pressure ventilation in
weaning intubated patients with chronic respiratory disease from assisted intermittent,
positive-pressure ventilation. Respir Med. 1993;87:199204.
10. Kilger E, Briegel J, Haller M, et al. Effects of noninvasive positive pressure ventilatory support
in non-COPD patients with acute respiratory insufficiency after early extubation. Intensive
Care Med. 1999;25:137480.
12. Girault C, Daudenthun I, Chevron V, et al. Noninvasive ventilation as a systematic extubation
and weaning technique in acute-on-chronic respiratory failure: a prospective, randomized controlled study. Am J Respir Crit Care Med. 1999;160:8692.
failure: a randomized controlled trial. Am J Respir Crit Care Med. 2003;168:706.
14. Vaschetto R, Turucz E, Dellapiazza F, et al. Noninvasive ventilation after early extubation in
patients recovering from hypoxemic acute respiratory failure: a single-centre feasibility study.
15. Rabie Agmy GM, Metwally MM. Noninvasive ventilation in the weaning of patients with
acute-on-chronic respiratory failure due to COPD. Egypt J Chest Dis Tuberc. 2012;61:8491.
16. Prasad SB, Chaudhry D, Khanna R. Role of noninvasive ventilation in weaning from mechanical ventilation in patients of chronic obstructive pulmonary disease: an Indian experience.
Indian J Crit Care Med. 2009;13:20712.
17. Trevisan CE, Vieira SR. Noninvasive mechanical ventilation may be useful in treating patients
who fail weaning from invasive mechanical ventilation: a randomized clinical trial. Crit Care.
2008;12:R51.
18. Tawfeek MM, Ali-Elnabtity AM. Noninvasive proportional assist ventilation may be useful in
weaning patients who failed a spontaneous breathing trial. Egypt J Anaesth. 2012;28:8994.
19. Girault C, Bubenheim M, Abroug F, et al. Noninvasive ventilation and weaning in patients
with chronic hypercapnic respiratory failure. Am J Respir Crit Care Med. 2011;184:6729.
20. Burns KEA, Meade MO, Premji A, Adhikari NKJ. Noninvasive ventilation as a weaning strategy for mechanical ventilation in adults with respiratory failure: a Cochrane systematic review.
CMAJ. 2014;186:E11222.
Noninvasive Positive-Pressure
Ventilation in the Management
of Respiratory Distress in Cardiac
Diseases
21
Andrew L. Miller and Bushra Mina
21.1
Introduction
Noninvasive positive-pressure ventilation (NIPPV) is the application of respiratory

support (pressurized air and oxygen) without the use of an artificial airway such as
endotracheal intubation (ETI) or a tracheostomy tube. NIPPV exists as two main
types, NIPPV with bi-level positive airway pressure (BPAP) and NIPPV with continuous positive airway pressure (CPAP). Over the past 30 years, NIPPV has shown
well-studied efficacy for the treatment of respiratory distress caused by multiple
etiologies.
The beneficial treatment effects of NIPPV occur in multiple pathophysiologic
states. Acidosis and hypercapnia are treated by improved alveolar ventilation,
hypoxia is reversed through improved alveolar recruitment and therapeutic concentrations of fraction of inspired oxygen (FiO2), work of breathing is improved with
unloading of the diaphragm and accessory muscles as well as by reducing inspiratory energy expenditure, and cardiac function is modulated secondary to a reduction
in afterload.
Through the above actions, and with proper patient selection, ventilator type,
settings, and with close monitoring, NIPPV can often avoid a patient progressing
from respiratory distress to respiratory arrest and the need for invasive methods of
ventilation such as ETI and all of its noted sequelae. Indeed, NIPPV may be the
preferred method of ventilatory support in many cases [1].
The general contraindications to NIPPV are well described, although what precisely constitutes a relative versus an absolute contraindication is a topic of some
debate. Relative contraindications may include a need for full-time ventilatory
A.L. Miller, MD (*) B. Mina, MD
Department of Internal Medicine Lenox Hill Hospital,
NSLIJ/Lenox Hill Hospital, New York, NY, USA
e-mail: AMiller12@nshs.edu; BMina@nshs.edu
DOI 10.1007/978-3-319-04259-6_21
173
174
A.L. Miller and B. Mina
support, insufficient caregiver support, and severe dysphagia. Absolute contraindications require clinical judgment, but may include upper airway obstruction, lack of
adequate cough, poor ability of the patient to handle secretions, inability of the
patient to sync with the selected settings, and significant air leakage caused by poor
mask fit.
NIPPV has been best studied in the setting of acute respiratory distress secondary to pulmonary diseases such as asthma, chronic obstructive pulmonary disease,
and pneumonia. The evidence for its efficacy in respiratory distress resulting from
cardiac causes, however, is somewhat less well defined. As will be discussed, its
utility has been best shown in the setting of acute cardiogenic pulmonary edema
(ACPE) and congestive heart failure (CHF).
While the role of NIPPV in respiratory failure after general surgical procedures
has been examined, the evidence for its efficacy after surgical and percutaneous
procedures such as coronary artery bypass graft (CABG), valvular procedures, and
percutaneous coronary intervention (PCI) is far more limited.
21.2
Discussion
21.2.1 ACPE and CHF

Acute heart failure exacerbation is one of the main causes of hospitalization in the
United States, responsible for more than one million hospital admissions per year.
At least 25 % of these patients present with ACPE and a significant portion of those
require some form of ventilatory support [2].
There is strong evidence to support the use of both CPAP and BPAP in the setting of respiratory distress secondary to ACPE [3, 4]. Various guidelines recommend a trial of NIPPV in these patients [2]. Gray et al. [5] stated, CPAP and BPAP
safely provide earlier improvement and resolution of breathlessness, respiratory
distress, and metabolic abnormalities in severe ACPE. We recommend that noninvasive ventilation (CPAP or NIPPV) should be considered as adjunctive therapy in
patients with severe ACPE in the presence of severe respiratory distress or when
there is a failure to improve with pharmacological therapy. Other meta-analyses
have found that, although neither method is superior in terms of mortality when
compared against each other, BPAP is associated with more rapid resolution of
dyspnea and better oxygenation than CPAP or standard oxygen therapy with nasal
cannula [2].
The safety and efficacy of NIPPV to limit the need for ETI is well documented.
However, many, though not all, studies fail to show a decrease in 30-day mortality
among all manner of NIV compared with ETI. However, a recent meta-analysis suggests that the failure of more studies to show improved 30-day mortality is a consequence of their low power to detect this outcome [3]. Of note, NIV has been shown
to significantly decrease the risk of mortality when compared with medical management alone in the form of standard oxygen therapy [3]. Importantly, historical reports
of an increased risk of acute myocardial infarction with NIPPV use in the CHF and
ACPE populations has not been shown in multiple study populations [2, 3, 6].
21
Noninvasive Positive-Pressure Ventilation in Cardiac Diseases
175
CPAP should be started at 1015 cmH2O and titrated by 5 cmH2O every 5 min
based on the patients clinical status. If BPAP is selected, inspiratory positive airway
pressure (IPAP)/expiratory positive airway pressure (EPAP) should be started at
10/5 and titrated as for CPAP. Arterial blood gas monitoring, although not absolutely required in all cases, should be performed for any patient who does not show
appropriate clinical improvement after ~10 min of therapy. A rising PaCO2 after
treatment has begun should alert the physician that the patient may be failing NIPPV
and is in danger of imminent respiratory arrest. More aggressive treatment with
ventilatory support in the form of BPAP (if CPAP had been used) or ETI (if BPAP
had been attempted) must be urgently considered in these cases. Continuous endtidal CO2 monitoring may also be used where available. In all cases, close monitoring of patients is a necessity and transfer of these patients to a monitored unit is the
norm [5].
21.2.2 Surgery and Invasive Procedures: CABG, Valvular, and PCI

Major surgical procedures and the associated use of general anesthesia induce dramatic alterations in a patients respiratory function. This is, of course, particularly
true for surgery involving the thorax and upper abdomen. Physiologic stressors that
can develop include a significant decrease in venous return, cardiac output, and
pulmonary volumes, and can create significant atelectasis and shunt. Importantly,
these stressors are not relieved merely by the completion of the surgical procedure.
They may, in fact, be prolonged or even worsened secondary to postoperative pain
and diaphragmatic dysfunction. Thus, operative and postoperative patients are at
significant risk for developing acute respiratory failure even after an otherwise successful surgery [7].
The data for NIPPV use in the cardiac surgical patient is far less robust than that
seen in ACPE/CHF [7]. Pinilla et al. [8] report that 4090 % of patients undergoing
cardiac surgery have pulmonary complications. Other investigators have found
corresponding rates of increased morbidity in any surgery involving cardiopulmonary bypass [9].
Overall, the evidence seems to support NIPPV being used for its benefit in
improving symptomatic hypoxia and mild hypercapnia as well as for its utility in
avoiding the need for ETI [7]. In one prospective cohort of 85 patients, postoperative NIPPV used to prevent or treat postoperative acute respiratory failure was useful when applied in the cardiac surgical ward with 83/85 patients discharged from
hospital without requiring a higher level of care [10]. Another study in CABG
patients showed that the prophylactic use of NIPPV for 30 min after extubation
improved oxygenation in the immediate postoperative period of heart surgery compared with nasal oxygen through 120 min [9].
In a large meta-analysis, CPAP reduced the incidence of pulmonary complications such as hypoxemia, pneumonia, and need for ETI compared with standard
therapy with oxygen. However, this study did not find a decrease in either intensive
care unit (ICU) or hospital length of stay. When NIPPV was studied for prophylactic use in patients with evidence of radiologic atelectasis but who were otherwise
176
asymptomatic, no benefit in terms of decreased hospital length of stay or mortality

was seen [8].
Multiple studies stress that, as with its use in other indications, close monitoring
of patients given a trial of NIPPV is vital, because there is strong correlation between
increased need for emergent ETI and mortality in patients who do not clinically
improve with NIV trials [10, 11].
NIPPV has been used during percutaneous valve placement for patients unable
to tolerate lying supine and, in these cases, showed excellent results [11]. The same
authors suggest having equally beneficial results in selected instances of
PCI. Another groups pilot study for the use of NIV in PCI created a homemade
NIPPV-TEE (Transesophageal echocardiography) Probe interface whereby the
ultrasound probe could be passed through a sealed port of the BPAP mask. This
group had very good results in their published case series [12].
Few studies have been performed in the use of NIV after weaning from invasive
ventilation for acute respiratory failure in the post-extubation cardiac surgical
patient. Those studies that have been performed generally show that, when used in
the post-extubation for periods of 30 min to 4 h, there is improvement in oxygenation, decrease in PaCO2, and reduction in the rate of reintubation. Other studies
also suggest decreased incidence of postoperative pulmonary edema when either
oral and nasal NIPPV (with BPAP showing a nonsignificant trend over CPAP) are
used in the post-extubation cardiac surgical patient when compared with standard
medical therapy with nasal oxygen alone [9].
Postoperative cardiac patients have been shown to remain at relatively high risk
for acute respiratory failure in the hours after discharge from the ICU [9]. However,
because of the high cost and limited availability of ICU beds, length of ICU admission and the total number of readmissions by cardiac and other surgical patients has
become an important and an increasingly reportable quality metric. Thus, although
the currently available evidence for the use of NIPPV in this population is limited,
having discussions and remaining up-to-date with the newest research about the
safe and effective use of NIPPV in the cardiac surgical patient should be an ongoing
process.
Conclusion
CPAP and BPAP are the two most commonly used modes of NIPPV. CPAP
applies a constant pressure to a spontaneously breathing patient and is physiologically equivalent to constant positive end-expiratory pressure. BPAP delivers
two pressure levels according to the respiratory cycle and improves ventilation,
oxygenation, and alveolar recruitment. BPAP provides both IPAP and EPAP. The
difference between these pressures is responsible for augmenting the volume of
air displaced during the respiratory cycle. Noninvasive positive airway pressure
ventilators differ among manufactures but can provide modes nearly identical to
standard ventilators used for ETI in the ICU.
Both CPAP and BPAP have been used in ACPE. High-quality data over the
last 30 years suggest that both CPAP and BPAP are superior to standard oxygen
21
Noninvasive Positive-Pressure Ventilation in Cardiac Diseases
177
therapy in improving gas exchange, patient symptoms, and reducing the need for
ETI as well as mortality in the CHF/ACPE population. Mortality benefit has not
been shown in the cardiothoracic surgical patient, although the available studies
are generally underpowered to detect this outcome. While trends exist, the superiority of BPAP over CPAP for mortality has also not been conclusively shown,
even after numerous studies and meta-analyses. However, BPAP may show faster
resolution of patient symptoms and the above markers than CPAP in all of the
above populations.
Although cardiac surgery is associated with major alteration of lung function,
relatively few studies performed have evaluated the benefits of NIPPV in this
population. Notably, most of these studies examined the immediate postoperative patient in the ICU soon after endotracheal extubation. While there is little
high-quality evidence examining the use of NIV in the postsurgical cardiac
patient outside of the ICU, this does not take away from its possible use and
likely benefits. However, in this setting, great care must be taken in proper patient
selection and disposition.
Before attempting use of NIV, severity of respiratory compromise and risk of
failure must be examined. The weight of evidence and long-term clinical experience make clear that treatment failure is associated with emergent need for ETI
and increased mortality. Prior to its selection as a treatment modality, thought
should be given to the patients degree of hypoxemia, hypercarbia, other comorbidities, as well as their degree of cooperativeness and current mental status; a
patient should be able to call for help if needed.
Used appropriately, NIPPV, in all its modalities, is a major tool in our armamentarium. With more data helping to further define its benefits, it seems clear
that the populations for whom its use has shown evidenced-based utility will
only continue to grow.
CPAP and BPAP are the two most commonly used modes of NIPPV.
High-quality data over the last 30 years suggest that both CPAP and BPAP
improve mortality compared with standard oxygen therapy in the CHF/
ACPE patient.
Although trends do exist, the superiority of BPAP over CPAP for mortality
in any population has not been conclusively shown after numerous highquality studies and meta-analyses.
BPAP may show faster resolution of patient symptoms than CPAP in CHF,
ACPE, and the cardiothoracic surgical patient.
Proper patient selection and close monitoring of patients are absolutely
necessary when utilizing NIPPV, as the weight of evidence and long-term
clinical experience show that failure is associated with emergent need for
ETI and increased mortality.
178
References
1. Reis MS, Sampaio LMM, Lacerda D, et al. Acute effects of different levels of continuous positive airway pressure on cardiac autonomic modulation in chronic heart failure and chronic
obstructive pulmonary disease. Arch Med Sci. 2010;6(5):71927.
2. Mariani J, Macchia A, Belziti C, et al. Noninvasive ventilation in acute cardiogenic pulmonary
edema: a meta-analysis of randomized controlled trials. J Card Fail. 2011;17(10):8509.
3. Winck L, Azevedo F, Costa-Pereira A, et al. Efficacy and safety of non invasive ventilation in
the treatment of acute cardiogenic pulmonary edema a systematic review and meta-analysis.
Crit Care. 2006;10:R69.
4. Pang P, Masood Z. Airway management and assessment of dyspnea in emergency department
patients with acute heart failure. Curr Emerg Hosp Med Rep. 2013;1:1225.
5. Gray AJ, Goodacre S, Newby DE, et al. A multicentre randomised controlled trial of the use
of continuous positive airway pressure and non-invasive positive pressure ventilation in the
early treatment of patients presenting to the emergency department with severe acute cardiogenic pulmonary oedema: the 3CPO trial. Health Technol Assess. 2009;13(33):1106.
6. Masip J, Roque M, Sanches B, et al. Noninvasive ventilation in acute cardiogenic pulmonary
edema systematic review and meta-analysis. JAMA. 2005;294(24):312430.
7. Cabrini L, Zangrillo A. Non-invasive ventilation after cardiac surgery. HSR Proc Intensive
Care Cardiovasc Anesth. 2011;3(1):57.
8. Chiumello D, Chevallard G, Gregoretti C. Non-invasive ventilation in postoperative patients:
a systematic review. Intensive Care Med. 2011;37:91829.
9. Lopes CR, Brandao CMdA, Nozawa E, et al. Benefits of non-invasive ventilation after extubation in the postoperative period of heart surgery. Rev Bras Cir Cardiovasc.
2008;23(3):34450.
10. Olper L, Cabrini L, Landomi G, et al. Non-invasive ventilation after cardiac surgery outside
the Intensive Care Unit. Minerva Anestesiol. 2010;77(1):4045.
11. Cabrini L, Plumari VP, Nobile L, et al. Non-invasive ventilation in cardiac surgery: a concise
review. Heart Lung Vessels. 2013;5(3):13741.
12. Guarracino F, Cabrini L, Baldassarri R, et al. Non-invasive ventilation-aided transoesophageal
echocardiography in high-risk patients: a pilot study. Eur J Echocardiogr. 2010;11:5546.
Postoperative Continuous Positive

Airway Pressure (CPAP)
22
Elisabet Guerra Hernndez

and Zoraya Hussein Dib Gonzlez
Abbreviations
COPD
CPAP
ICU
PPCs
22.1

Continuous positive airway pressure
Intensive care unit
Introduction
The combination of surgery and anesthesia can be associated with a number of serious complications that may impair patient recovery. In particular, postoperative pulmonary complications (PPCs), including respiratory complications such as
atelectasis, pneumonia, and reintubation, are the leading cause of prolonged hospital stay, morbidity, and mortality in surgical patients [1]. PPCs are common, serious,
and expensive. Health-care costs associated with the treatment of PPCs are 50 %
greater than costs for treating postoperative cardiac complications. The incidence of
PPCs varies depending on the clinical treatment setting, the kind of surgery studied,
and the definition of PPC used. For all these reasons, incidence rates vary from 2 to
40 % [2, 3]. The actual incidence of important PPCs seems to be 25 % in patients
undergoing thoracic or upper-abdominal surgery.
In a general sense, a PPC is any event that occurs in the postoperative period that
produces physiologic dysfunction or clinical disease. A PPC may be diagnosed
E.G. Hernndez (*) Z.H.D. Gonzlez

Servicio de Anestesiologa y Reanimacin, Hospital Universitario de Gran Canaria
Doctor Negrn, Las Palmas de Gran Canaria, Spain
e-mail: ecgh_7@hotmail.com; dazo7374@hotmail.com
DOI 10.1007/978-3-319-04259-6_22
179
180
E.G. Hernndez and Z.H.D. Gonzlez
based on symptoms (cough, fever, abnormal breath sounds), laboratory values

(hypoxemia, leukocytosis), or radiographic criteria (atelectasis or infiltrate). As a
result, a PPC can be defined as simply atelectasis on a chest radiograph or as respiratory failure necessitating intubation and mechanical ventilation [2]. Brooks-Brunn
[4] suggested a more specific definition that includes at least two of the following
findings documented at any time during the first 6 days following surgery: new
cough and sputum production, abnormal breath sounds compared with baseline,
temperature >38 C, chest radiograph demonstrating atelectasis or a new infiltrate,
and physician documentation of atelectasis or pneumonia.
Surgery and anesthesia involve risk of PPCs to a degree that depends on the
patient, anesthetic, and surgical factors [5]. Anesthesia changes the balance of
forces between the chest wall and the lungs, leading to reduction in lung volume and
compliance, which results in greater predisposition to alveolar collapse and the
development of atelectasis [6], especially in the dependent parts of the lung. On a
secondary plane, ventilation-perfusion mismatching is exacerbated, leading to
impaired gas exchange and hypoxemia. Anesthetic management strategies can contribute to either the development or attenuation of PPC risk. Administering oxygen
at a concentration over 80 %, for example, predisposes the patient to alveolar collapse, whereas some intraoperative ventilation strategies have been thought to play
a role in reducing the incidence of PPCs [7].
There are a number of risk factors that have been identified that increase the
likelihood of developing a PPC. The greatest preoperative risk factor are age
>50 years, American Society of Anesthesiologists score >2, chronic obstructive
pulmonary disease (COPD), congestive heart failure, functional dependence, and
smoking. Obstructive sleep apnea is new to the list, but results in only a minor
increase in the risk of PPC. Asthma and obesity do not appear to increase the risk
substantially. The intraoperative risk factors are surgical site, duration of surgery,
anesthetic technique, and emergency surgery. An upper-abdominal incision, close
to the diaphragm, is the greatest PPC risk factor. From a procedural perspective,
open aortic repair, thoracic surgery, head and neck surgery, and neurosurgery are
associated with increased risk. Surgery longer than 3 h, general anesthesia, use of
neuromuscular blocking agents, and emergency surgery are associated with more
frequent complications. Perioperative blood transfusion does not appear to increase
risk [8].
22.2
CPAP might have a potential role in reducing PPCs and facilitating lung reexpansion after anesthesia and surgery by constant positive airway pressure during
inspiration and expiration. The application of a CPAP mask increases end-expiratory
lung volume without deep breathing and might be associated with less pain and
discomfort, allow alveolar recruitment, improve oxygenation and the ventilationperfusion relation, reduce the work of the respiratory muscles and the diaphragm,
provide dyspnea relief, and permit respiratory system muscle unloading.
22
Postoperative Continuous Positive Airway Pressure (CPAP)
181
Noninvasive ventilation can be used as a prophylactic and/or therapeutic tool to

improve gas exchange postoperatively. CPAP may decrease the incidence of endotracheal intubation in patients who develop hypoxemia after elective major abdominal surgery or post extubation [9]. Many studies have evaluated the use of CPAP to
prevent PPCs and demonstrated a reduction in the rate of postoperative pneumonia
[10]. In one study using nasal CPAP following postoperative care of cardiac bypass
patients, hypoxemia was prevented and sleep was improved with the addition of
CPAP. Zarbock et al. [11] published a trial of prophylactic nasal CPAP following
elective cardiac surgery. This study of 500 subjects delivered nasal CPAP after extubation in the operating room or in the intensive care unit (ICU). The authors concluded that nasal CPAP following cardiac surgery improved arterial oxygenation,
reduced the incidence of PPCs, including pneumonia and reintubation, and reduced
the ICU readmission rate. Barbagallo et al. [12] found that CPAP provided by a
helmet following thoracic surgery and lobectomy improved oxygenation, compared
with a control group, for the first 24 h. Patients receiving CPAP had a significantly
shorter hospital stay, in comparison with controls. However, there were no differences in PPCs, ICU readmission, or mortality. This was a small study (n = 50) of
high-risk subjects. Kindgen-Milles et al. [13] published a prospective randomized
clinical trial to evaluate the prophylactic application of nasal CPAP at airway pressure of 10 cmH2O in patients following the surgical repair of thoracoabdominal
aortic aneurysms. They concluded that CPAP reduced pulmonary morbidity and
length of hospital stay.
CPAP in high-risk patients appears to improve oxygenation, increase functional
residual capacity, and reduce PPCs. The widespread use of CPAP in patients without preoperative risk factors cannot be recommended.
Conclusion
The application of a CPAP mask increases end-expiratory lung volume without

deep breathing and might be associated with less pain and discomfort. It allows
alveolar recruitment, improves oxygenation and the ventilation-perfusion relation, reduces the work of the respiratory muscles and the diaphragm, provides
dyspnea relief, and permits respiratory system muscle unloading.
Knowledge of the risk factors of PPCs is important for prevention, treatment,
and choosing the most appropriate method of the noninvasive mechanical
ventilation.
CPAP is recommended for treatment of hypoxemic nonhypercapnic acute

respiratory failure. The major benefits are observed in patients with COPD
and congestive heart failure.
Prophylactic CPAP following thoracic, aortic repair, and upper-abdominal
surgery decreases the incidence of acute respiratory failure, reintubation,
readmission to ICU, morbidity and mortality, and hospital stay.
182
E.G. Hernndez and Z.H.D. Gonzlez
References
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2. Branson RD. The scientific basis for postoperative respiratory care. Respir Care.
2013;58(11):197484.
3. Smetana GW, Lawrence VA, Cornell JE; American College of Physicians. Preoperative pulmonary risk stratification for noncardiothoracic surgery: systematic review for the American
College of Physicians. Ann Intern Med. 2006;144(8):58195.
4. Brooks-Brunn JA. Predictors of postoperative pulmonary complications following abdominal
surgery. Chest. 1997;111(3):56471.
5. Smetana GW. Postoperative pulmonary complications: an update on risk assessment and
reduction. Cleve Clin J Med. 2009;76 Suppl 4:S605.
6. Sasaki N, Meyer MJ, Eikermann M. Postoperative respiratory muscle dysfunction: pathophysiology and preventive strategies. Anesthesiology. 2013;118(4):96178.
7. Canet J, Gallart L. Predicting postoperative pulmonary complications in the general population. Curr Opin Anaesthesiol. 2013;26(2):10715.
8. Qaseem A, Snow V, Fitterman N, et al. Risk assessment for and strategies to reduce perioperative pulmonary complications for patients undergoing noncardiothoracic surgery: a guideline
from the American College of Physicians. Ann Intern Med. 2006;144(8):57580.
9. Tusman G, Bohm SH, Warner DO, et al. Atelectasis and perioperative pulmonary complications in high-risk patients. Curr Opin Anaesthesiol. 2012;25(1):110.
10. Squadrone V, Coha M, Cerutti E, et al. Continuous positive airway pressure for treatment of
postoperative hypoxemia: a randomized controlled trial. JAMA. 2005;293(5):58995.
11. Zarbock A, Mueller E, Netzer S, et al. Prophylactic nasal continuous positive airway pressure
following cardiac surgery protects from postoperative pulmonary complications: a prospective, randomized, controlled trial in 500 patients. Chest. 2009;135(5):12529.
12. Barbagallo M, Ortu A, Spadini E, et al. Prophylactic use of helmet CPAP after pulmonary
lobectomy: a prospective randomized controlled study. Respir Care. 2012;57(9):141824.
13. Kindgen-Milles D, Muller E, Buhl R, et al. Nasal-continuous positive airway pressure reduces
pulmonary morbidity and length of hospital stay following thoracoabdominal aortic surgery.
Chest. 2005;128(2):8218.
Noninvasive Ventilation for Weaning,

Avoiding Reintubation After Extubation,
and in the Postoperative Period
23
Alastair J. Glossop
23.1
Introduction
Endotracheal intubation and mechanical ventilation (MV) are supportive interventions that may be life saving in critically ill patients but also introduce significant risk
of morbidity and mortality, including volutrauma, barotrauma, ventilator-associated
pneumonia (VAP), and the complications associated with sedation. VAP is associated with poor clinical and economic outcomes, with a large data registry series from
the United States quoting rates of VAP in ventilated intensive care unit (ICU) patients
of 9.3 % and demonstrating associated increased morbidity and ICU length of stay
[1]. Timely extubation is one way of minimizing this morbidity, but premature or
inappropriate extubation may in itself be detrimental, and the need for reintubation is
associated with a hospital mortality of up to 40 % in some patient groups [2].
The term noninvasive ventilation (NIV) is often used to describe both continuous
positive airway pressure (CPAP) and noninvasive positive-pressure ventilation
(NPPV). By definition, NIV is delivery of ventilatory support via the patients upper
airway using a mask or similar device [3], and its use has increased considerably
over the past 20 years as a viable alternative to MV. NIV use in patients with acute
respiratory failure (ARF) is well established, and it has been demonstrated to reduce
intubation rates and mortality in patients with exacerbations of chronic obstructive
pulmonary disease (COPD) [4], cardiogenic pulmonary edema [5], and the immunocompromised [6].
NIV has been more recently utilized in ICU patients who are difficult to wean [7] or
have recently been extubated following a period of MV [8], and also in postoperative
A.J. Glossop, MRCP, FRCA, DICM, FFICM

Department of Critical Care, Sheffield Teaching Hospitals NHS Foundation Trust,
Herries Road, Sheffield S5 7AU, UK
e-mail: alastair.glossop@sth.nhs.uk
DOI 10.1007/978-3-319-04259-6_23
183
184
A.J. Glossop
surgical patients [9]. This population of recently extubated patients suffers increased
morbidity and mortality should they develop respiratory failure and require reintubation, and may therefore benefit from the use of NIV to prevent this progression. Several
studies examining the use of NIV in these situations have been either inconclusive or
produced conflicting results, and debate continues within the critical care community
regarding the optimal use of NIV following extubation.
This chapter reviews the evidence for use of NIV in the following groups of
patients who have recently been extubated:
Patients weaning from MV but who are not suitable for extubation
Patients who have been recently extubated in the ICU
Patients who have been extubated following major surgery
23.2
NIV for Patients Weaning from MV

Who Are Not Suitable for Extubation
Several studies have examined the use of NIV as an alternative to ongoing MV in

patients who are deemed fit enough to start the process of weaning from MV but
have failed a spontaneous breathing trial (SBT). The rationale for using NIV in this
situation is that the patient will continue to receive mechanical support via NIV as
their respiratory muscle strength and coordination recovers without being exposed
to the potentially harmful effects of sedative drugs and ongoing endotracheal intubation. It has been suggested that weaning in this way with NIV may reduce the
incidence of VAP and accelerate the weaning process compared with conventional
methods of invasive weaning.
Several studies have compared NIV with conventional weaning in patients who
have failed an SBT and then been randomized to either extubation onto NIV or
continued weaning via MV. In two notable studies, NIV weaning was demonstrated
to reduce time spent on MV, rates of VAP, and mortality when compared with invasive weaning [7, 10]. These studies predominantly included patients with underlying COPD, and the treatment groups received NIV for prolonged periods at high
levels of pressure support.
A large randomized, controlled trial RCT, published in 2011, reported no benefit
from NIV weaning compared with continued invasive weaning or extubation onto
high flow oxygen [11], leading to debate regarding the merits of using NIV to wean
patients from MV. However, a recent Cochrane review, which pooled data from 16
trials and 994 patients including the VENISE trial mentioned above concluded
that NIV weaning in patients who had failed an SBT reduced mortality, ICU and
hospital length of stay, and rates of VAP, and that these benefits were more pronounced in patients with underlying COPD [12].
Use of NIV to wean patients is perhaps underutilized by clinicians, as it requires
something of a leap of faith to extubate patients who have failed SBTs and therefore do not meet criteria for extubation. There has also been some conflict in the
literature as to the benefits to be gained by weaning patients using NIV. However, a
23
NIV for Weaning, Avoiding Reitubation and the Post Operative Period
185
number of studies suggest that in COPD patients NIV weaning will reduce rates of
VAP, ICU length of stay, and mortality. Therefore, the use of NIV weaning should
be considered in all patients with known COPD who are ready to wean from MV
but not suitable for extubation.
23.3
NIV for Avoiding Reintubation After Extubation
Extubation of ICU patients who have received MV for a period of time carries the
risk of extubation failure and the need for further MV. Although the reported rate of
extubation failure in the literature varies, it may be as high as 19 % [13]. It is also
widely acknowledged that failing an extubation is associated with worse outcomes
and increased risk of morbidity and mortality, although this may be a result of sicker
patients with more comorbidities having a higher risk of extubation failure rather
than a direct effect of reintubation per se. The use of NIV in recently extubated
patients is an attractive treatment option, as it has the potential to provide ongoing
respiratory support to recently extubated patients without the attendant risks of
endotracheal intubation and MV, and several studies have examined the use of NIV
in this setting.
NIV has been assessed as a preventative strategy in ventilated ICU patients who
have risk factors for post-extubation failure, such as age greater than 65, poor
cough, cardiac and respiratory comorbidity, and hypercapnia (while ventilated or
preexisting). The application of NIV immediately post-extubation for periods of
up to 48 h was demonstrated to reduce reintubation rates and mortality in one large
RCT [8]. NIV used prophylactically has also been demonstrated to reduce the incidence of respiratory failure post-extubation when used for up to 24 h post-extubation [14], and a later study of 106 patients with chronic respiratory disease
demonstrated that prophylactic NIV use for 24 h following extubation reduced
respiratory failure and 90-day mortality when compared with standard medical
therapy [15].
There have been several RCTs examining the use of NIV as a rescue treatment
for post-extubation respiratory distress. Early work suggested that application of
NIV to patients with premorbid cardiorespiratory disease who developed respiratory failure post-extubation did not reduce reintubation rates, duration of MV
(mechanical ventilation), hospital mortality, or length of stay compared with
standard therapy [16]. A subsequent multicenter RCT reported that patients who
had been extubated following a successful SBT but then developed post-extubation respiratory failure had an increased ICU mortality if then treated with NIV
compared with standard medical therapy [17]. There has been some criticism of
this trial, and it is important to note that the patients who failed on NIV and went
on to require intubation had received long periods of ineffective NIV before reintubation on average 9 h longer than the controls which is likely to have contributed to their worse outcomes. Additionally, post hoc analysis of patients with
COPD in this study suggested that use of NIV may still be warranted if used
judiciously in post-extubation respiratory distress. However, in general, the onset
186
A.J. Glossop
of post-extubation respiratory failure is an ominous development and delaying

reintubation by any means risks potential harm and detriment to the patient.
These findings have been largely echoed by a recent meta-analysis of studies that
pooled data from 10 trials and 1382 patients who received NIV following extubation to prevent the onset of post-extubation respiratory failure and reintubation [18].
The authors concluded that use of NIV as a prophylactic treatment post-extubation
conferred significant benefits in terms of mortality and reintubation rates that were
not seen if NIV was used as a treatment for post-extubation respiratory distress.
Therefore, it seems that NIV has an important role to play in the prevention of postextubation respiratory failure and requirement for reintubation, but that vigilance is
required for the onset of respiratory failure and caution must be taken to not allow
NIV to delay reintubation once post-extubation respiratory failure is established.
23.4
NIV in Postoperative Patients
Prolonged surgical procedures, especially those involving breach of the abdominal

or thoracic cavity, predispose patients to the development of postoperative respiratory complications. In addition, the surgical population is increasing in age and
frequently includes patients with significant respiratory and cardiac comorbidities
who are at an increased risk of developing postoperative respiratory complications.
NIV has been used following a wide range of surgical procedures to both prevent
and treat respiratory failure, and potentially reduce the need for reintubation or prolonged critical care therapy, following major surgery.
Following abdominal surgery, the development of basal atelectasis secondary to
prolonged supine positioning and diaphragmatic splinting contributes to the development of postoperative respiratory failure. The use of CPAP both prophylactically
and as a treatment for hypoxic respiratory failure has been demonstrated to reduce
reintubation rates and respiratory complications in patients following open abdominal visceral surgery [9]. The use of NIV in patients who have undergone upper
gastrointestinal procedures remains controversial, although there is early evidence
for the safe use of NPPV and CPAP to treat and prevent respiratory complications
following esophageal, gastric, and bariatric surgery [19, 20].
In cardiac surgery, there is RCT evidence that the postoperative use of CPAP in
coronary artery bypass patients may reduce postoperative complications such as
pneumonia, need for reintubation, and readmission to critical care [21]. Postoperative
prophylactic CPAP has also been demonstrated to improve oxygenation, reduce
pulmonary complications, and reduce reintubation rates following abdominal and
thoracic aortic aneurysm repair [22, 23].
In thoracic surgery, ARF following pneumonectomy or lobectomy confers a significant risk of poor outcome, with reintubation associated with a mortality of up to
60 %. There are theoretical risks from any form of positive-pressure ventilation in
this postoperative group, including bronchial stump disruption and air leakage.
However, evidence from an RCT suggests that NIV is safe, and that treatment with
23
187
NPPV may reduce both reintubation rates and mortality in patients who have undergone lung resection surgery and develop ARF in the postoperative period [24].
A recent meta-analysis of major RCTs looking at NIV as an intervention in a
mixed population of postoperative patients demonstrated an improvement in hospital mortality, rates of VAP, and reintubation rates in patients receiving NIV compared with standard medical therapy, suggesting a benefit if NIV is applied to
high-risk patients in the immediate postoperative period [25].
The use of NIV following major surgery is associated with a reduction in rates of
postoperative complications, although many of the trials utilize differing regimes
for varying periods of time, and thus debate continues as to timing, duration, and
modality of NIV that should be used. Although reductions in reintubation rates and
respiratory complications have frequently been demonstrated in the literature, there
is less evidence as to the impact of NIV use on patient mortality. Additionally, the
evidence supports using NIV in selected high-risk surgical populations and, as such,
currently we are unable to extrapolate these findings to the wider surgical
population.
23.5
Conclusions and Recommendations
Although some conflict within the literature exists, the use of NIV for weaning has
been found to reduce mortality, rates of VAP, and ICU and hospital length of stay
when compared with conventional invasive weaning methods in a large Cochrane
review of trials. The benefits are more convincing in patients with COPD, in whom
the potential benefits of using NIV in many different clinical settings has been demonstrated, and thus NIV weaning should be considered in all patients with COPD
who are ready to start the process of weaning from MV.
The area of use of NIV in post-ICU extubation remains a contentious area, with
earlier prophylactic use seemingly preferential to treatment of established respiratory failure in this group of patients. There is also no consensus regarding the
optimal time period to provide NIV following extubation, although a stronger signal
for beneficial effects with NIV was seen in a study that utilized NIV prophylactically for 48 h post-extubation, suggesting that this longer time period may be
optimal.
Studies of NIV use in postsurgical patients have suggested that NIV may be
beneficial in treating and preventing respiratory failure in patients who have recently
undergone major surgery, but they have been very specific in the patient populations
studied and provided little mortality data. A recent meta-analysis has demonstrated
the benefits of NIV in reducing morbidity and mortality in postsurgical patients
pooled from several different surgical specialties, and provided evidence to support
the theory that NIV is perhaps underutilized in postoperative populations. Future
work should focus on determining the optimal regime in terms of modality, timing,
and duration of NIV postoperatively and also address the impact of NIV on mortality in high-risk surgical patients.
188
A.J. Glossop
References
1. Rello J, Ollendorf DA, Oster G, et al. Epidemiology and outcomes of ventilator-associated
pneumonia in a large US database. Chest. 2002;122:211521.
2. Epstein SK, Ciubotaru RL. Independent effects of etiology of failure and time to reintubation
on outcome for patients failing extubation. Am J Respir Crit Care Med. 1998;158:48993.
respiratory failure. Thorax. 2002;57:192211.
4. Keenan SP, Kernerman PD, Cook DJ, Martin CM, McCormack D, Sibbald WJ. Effect of noninvasive positive pressure ventilation on mortality in patients admitted with acute respiratory
failure: a meta-analysis. Crit Care Med. 1997;25:168592.
5. Winck JC, Azevedo LF, Costa-Pereira A, Antonelli M, Wyatt JC. Efficacy and safety of noninvasive ventilation in the treatment of acute cardiogenic pulmonary edemaa systematic
review and meta-analysis. Crit Care. 2006;10:R69.
6. Kilger E, Briegel J, Haller M, et al. Noninvasive ventilation after lung transplantation. Med
Klin. 1995;90:268.
7. Ferrer M, Esquinas A, Arancibia F, et al. Noninvasive ventilation during persistent weaning failure: a randomized controlled trial. [see comment]. Am J Respir Crit Care Med. 2003;168:706.
after extubation in high-risk patients*. Crit Care Med. 2005;33:246570.
postoperative hypoxemia: a randomized controlled trial. JAMA. 2005;293:58995.
11. Girault C, Bubenheim M, Abroug F, et al. Noninvasive ventilation and weaning in patients
with chronic hypercapnic respiratory failure: a randomized multicenter trial. Am J Respir Crit
Care Med. 2011;184:6729.
12. Burns KE, Meade MO, Premji A, Adhikari NK. Noninvasive ventilation as a weaning strategy
for mechanical ventilation in adults with respiratory failure: a Cochrane systematic review.
CMAJ Can Med Assoc J J Assoc Med Can. 2014;186:E11222.
13. Thille AW, Harrois A, Schortgen F, Brun-Buisson C, Brochard L. Outcomes of extubation
failure in medical intensive care unit patients. Crit Care Med. 2011;39:26128.
14. Ferrer M, Valencia M, Nicolas JM, Bernadich O, Badia JR, Torres A. Early noninvasive ventilation averts extubation failure in patients at risk: a randomized trial. Am J Respir Crit Care
Med. 2006;173:16470.
15. Ferrer M, Sellares J, Valencia M, et al. Non-invasive ventilation after extubation in hypercapnic patients with chronic respiratory disorders: randomised controlled trial. Lancet. 2009;374:
10828.
16. Keenan SP. Noninvasive positive-pressure ventilation for postextubation respiratory distress: a
randomized controlled trial. JAMA J Am Med Assoc. 2002;287:323844.
respiratory failure after extubation. [see comment]. N Engl J Med. 2004;350:245260.
respiratory failure: a meta-analysis. Heart Lung J Crit Care. 2014;43:99104.
19. Michelet P, DJourno XB, Seinaye F, Forel JM, Papazian L, Thomas P. Non-invasive ventilation for treatment of postoperative respiratory failure after oesophagectomy. Br J Surg.
2009;96:5460.
20. Neligan PJ, Malhotra G, Fraser M, et al. Continuous positive airway pressure via the
Boussignac system immediately after extubation improves lung function in morbidly obese
patients with obstructive sleep apnea undergoing laparoscopic bariatric surgery. Anesthesiology.
2009;110:87884.
23
189
21. Zarbock A, Mueller E, Netzer S, Gabriel A, Feindt P, Kindgen-Milles D. Prophylactic nasal

continuous positive airway pressure following cardiac surgery protects from postoperative pulmonary complications: a prospective, randomized, controlled trial in 500 patients. Chest.
2009;135:12529.
pulmonary morbidity and length of hospital stay following thoracoabdominal aortic surgery.
Chest. 2005;128:8218.
23. Bohner H, Kindgen-Milles D, Grust A, et al. Prophylactic nasal continuous positive airway
pressure after major vascular surgery: results of a prospective randomized trial. Langenbeck
Arch Surg Dtsch Ges Chir. 2002;387:216.
24. Auriant I, Jallot A, Herve P, et al. Noninvasive ventilation reduces mortality in acute respiratory failure following lung resection. Am J Respir Crit Care Med. 2001;164:12315.
25. Glossop AJ, Shepherd N, Bryden DC, Mills GH. Non-invasive ventilation for weaning, avoiding reintubation after extubation and in the postoperative period: a meta-analysis. Br J Anaesth.
2012;109:30514.

in Treatment of Acute Respiratory
Failure After Cardiac Surgery: Key
Topics and Clinical Implications
24
Luca Salvatore De Santo, Donato Catapano,

and Sergio Maria Caparrotti
Since the early days of cardiac surgery, postoperative pulmonary dysfunction has
been the subject of a considerable amount of experimental and clinical research
because it affects virtually every treated patient [1]. Both anomalies in gas exchange
and lung mechanics contribute to the expression of postoperative respiratory dysfunction, which is clinically evidenced by increased work of breathing and respiratory rate, shallow respirations, ineffective cough, hypoxemia, and changes in chest
radiographs. Widening of the alveolar-arterial oxygen gradient, increased lung
microvascular permeability, and increased pulmonary vascular resistance and shunt
fraction are commonly observed after cardiac surgical procedures. Accordingly,
reductions in vital capacity, functional residual capacity, and static as well as
dynamic lung compliance are usually evident. Pathogenesis of these derangements
has been extensively studied [2, 3]. It stems from a complex interplay between
patients baseline end organ function; the type, extent, and urgency of underlying
cardiovascular pathology; and the distinct features of this surgical setting. This
operative approach encompasses general anesthesia, peculiar surgical trauma
(median sternotomy, pleural dissection), cardiopulmonary bypass, topical cooling
for myocardial protection (which may cause phrenic nerve dysfunction),
L.S. De Santo, MD (*)
Department of Medical and Surgical Sciences, Chair of Cardiac Surgery,
University of Foggia, Foggia, Italy
Division of Cardiac Surgery, Casa di Cura Montevergine, Mercogliano, AV, Italy
e-mail: luca.desanto@unifg.it
D. Catapano, MD
Intensive Care Unit, Casa di Cura Montevergine, Mercogliano, AV, Italy
S.M. Caparrotti
Department of Cardiac Surgery, Casa di Cura Montevergine, Division of Cardiac Surgery,
Mercogliano, AV, Italy
e-mail: sergiocaparrotti@libero.it
DOI 10.1007/978-3-319-04259-6_24
191
192
L.S. De Santo et al.
transfusion of blood products, and postoperative pain, which individually and synergistically affect respiratory performance.
24.1
The Burden of Pulmonary Complications

in Cardiac Surgery
Despite these data, the continuum between pulmonary dysfunction and overt complications has been poorly characterized. Because such complications considerably
jeopardize outcomes and imply increased health-care costs and resource utilization,
their prevention, early identification, and effective treatment is highly advisable.
Preventive measures have been authoritatively described elsewhere [4, 5].
Refinements of operative techniques and cardiopulmonary bypass and mechanical
ventilation strategies, meticulous application of ventilator care bundles, rational
and early use of antibiotics, early extubation, and judicious blood management have
all been advocated for a thorough preventive management algorithm. Acute respiratory distress syndrome, transfusion-related lung injury, and ventilation associated
pneumonia, though infrequent, are the most dreaded of these complications because
of inherent dismal outcomes.
24.2
Weaning from Mechanical Ventilation and Extubation

Failure in Cardiac Surgery
Weaning from mechanical ventilation is essential to the success of the cardiac surgical procedure and a key step toward recovery and rehabilitation. The combination of
several respiratory and cardiovascular parameters is known to improve the accuracy
of prediction of successful weaning from ventilator support. Nevertheless, the same
parameters perform poorly in the prediction of late extubation failure. Today, pulmonary complications account for 54.9 % of intensive care unit (ICU) recidivism
and reintubation is needed in at least 6.6 % of the patients [6]. Causes of postextubation failure include both airway (such as upper-airway obstruction, aspirations, and excess pulmonary secretions) and non-airway-related factors (including
cardiogenic dysfunction). Pathophysiology of post-extubation failure usually
includes two distinct pathways: (1) alveolar hypoventilation and ventilationperfusion mismatch, due to increased respiratory rate and decreased tidal volume,
and (2) a failure to increase cardiac output, which leads to an enhanced tissue oxygen extraction with critically low mixed venous oxygen saturation [7]. Reintubation
prolongs the duration of invasive mechanical ventilation and increases the need for
tracheostomy. Loss of airway-protecting mechanisms, airway trauma, intense sedation, and the potential for aspiration are some of the drawbacks of invasive ventilation that predispose to the development of ventilator-associated pneumonia and
extend the length of the ICU and hospital stay, implying higher morbidity and mortality. A pivotal study by Hein and coworkers [8] on a contemporary series of cardiac surgery patients disclosed that hospital mortality in the event of respiratory
failure is as high as 38 % and the chance of 3-year survival is lower than 45 %.
24
Noninvasive Mechanical Ventilation in Cardiac Surgery
24.3
193
Prevention of Extubation Failure
These findings emphasize the importance of both determining perioperative predictors of extubation failure and implementing new preventive and curative modalities
that avoid the constraints of conventional invasive ventilation. Studies on predictors
of reintubation and mechanical ventilation after prior successful weaning from ventilator support and extubation in the cardiac surgery setting are few. Back in 1999, a
study conducted at the Mayo Clinic elegantly disclosed that preoperative predictors
commonly occur either as single or multiple features in this patient subset, however,
the author demonstrated that it is the combination of adverse intraoperative events
with baseline disease process and laboratory and hemodynamic perturbations that
compounds the risk of extubation failure in the individual patient. Indeed, difficult
surgery (redo procedures, procedures involving the thoracic aorta or the placement
of ventricular assist devices, those implying lengthy cardiopulmonary bypass time
or massive transfusions of blood products) usually impact on the individual patient
frailty as portrayed by surrogate markers of inadequate baseline cardiorespiratory
reserve (chronic obstructive pulmonary disease, pulmonary hypertension, low left
ventricular ejection fraction) and preoperative hematological and biochemical
abnormalities (anemia, hypoalbuminemia, increased blood urea nitrogen and/or
creatinine) [9]. Studies that are more recent substantially added to this knowledge
and further stressed the role of prolonged primary intubation, because the longer the
initial ventilator support, the higher the chance of extubation failure [25]. The
clinical bottom line is that identification of patients at risk may, and, actually, should
take place as early as ICU admission and should prompt alternate management
algorithms.
24.4
Noninvasive Ventilation, Definition, Physiologic

Effects, and the Rationale for Usage
Noninvasive ventilation (NIV) refers to a form of mechanical support in which positive pressure delivers a mixture of air and oxygen throughout the respiratory tree via
a noninvasive interface. It encompasses both continuous positive airway pressure
(CPAP) and noninvasive positive pressure ventilation (NPPV) modalities. NPPV
can provide modes nearly identical to standard ICU ventilators, such as pressure,
volume, assist control, and even proportional assist ventilation. Patient-ventilator
interfaces include a face mask, nasal mask or plugs, or a helmet that covers the head.
Notably, NIV provides effective ventilator support (i.e., reduction in respiratory
rate, increase in tidal volume, and decrease in dyspnea) with reduction in transdiaphragmatic pressures and work of breathing and improvement in oxygenation with
a reduction in hypercapnia. It also improves cardiac performance by decreasing
both preload and afterload. All in all, its physiologic effects effectively address the
two pathways of post-extubation failure described above. The use of NIV is highly
attractive because it is simple and does not require deep sedation. Most importantly,
it is associated with few of the nosocomial complications recognized with endotracheal intubation, such as ventilator-associated pneumonia, critical illness-associated
194
weakness, pneumothorax, delirium, and infections associated with the invasive

monitoring that is typically required during invasive life support [10]. Accurate
patient selection is crucial, and resolution of any surgical complication before the
institution of ventilation is mandatory. Primary contraindications include the inability to protect ones airway, excessive secretions, agitation, recent upper-airway or
esophageal surgery, untreated pneumothorax, and hemodynamic instability. The
best predictors of success are a reduction in respiratory rate, improvement in pH,
improvement in oxygenation, and a reduction in PaCO2 within the first 12 h of
therapy. Lack of such improvement should mandate immediate reintubation, inasmuch as undue delay portends higher mortality rates [5].
24.5
NIV in the Postoperative Settings
Actually, NIV might be implemented according to two different strategies: (1) prophylactically, in patients who are deemed at increased risk of developing respiratory
failure, and (2) curative, as an alternative to invasive reintubation, in the event of
overt post-extubation failure. The role of NIV in the surgical post-extubation setting
is under active investigation. A meta-analysis involving patients treated after different types of major surgical procedures demonstrated that a judicious usage in
selected patients effectively reduces both morbidity, namely reintubation and pneumonia, and ICU stay. This review added to the currently available literature underscoring that earlier prophylactic use seems more effective than treatment of
established respiratory failure. Optimal timing and duration of NIV after extubation
is still uncertain. Although CPAP is being used more prominently after operation,
little is known about the individual merits of CPAP against NPPV [11].
24.6
NIV Practice Patterns and Current Evidence

in Cardiac Surgery
Despite an evident widespread adoption, there are few data on the real pattern of
NPPV usage in the cardiac surgery setting. An international survey tried to fill this gap
in knowledge. The lack of a standardized and homogeneous use is clearly reported.
Preventive prescription, especially in high-risk patients, proved the main indication
with satisfactory outcomes, while the curative approach, though increasingly
addressed, had success rate lower than 50 % for 68 % of the respondent centers [11].
Several authoritative reviews and one meta-analysis updated the current evidence in
this setting [1215]. A detailed analysis of individual studies is beyond the scope of
this chapter, and readers might refer to the above-mentioned papers. However, several
limits must be disclosed for a thorough comprehension of the inherent clinical bottom
line. Available studies are still few, usually involved small patient samples, only a
minority had a randomized design, and the overall quality might be rated from moderate to low. The heterogeneous mix of comparators and anomalies relating to therapeutic protocols, terminology, and reporting of results also represents a considerable bias.
24
Noninvasive Mechanical Ventilation in Cardiac Surgery
195
Overall, available data demonstrate that NIV significantly reduces the reintubation
rate, hospital length of stay, and mortality with a highly satisfactory safety profile. As
a preventive tool, NIV effectiveness was maximized by selection of highly vulnerable
patients, inasmuch as routine usage had no evident clinical impact on hard outcomes.
As a treatment tool in overt acute respiratory failure, success rate as high as 94 % may
be anticipated in correctly selected patients.
24.7
Recommendations for Successful Clinical NIV

Implementation
An in-depth reading of published data discloses several key steps for successful
NIV implementation:
1. Early detection of pulmonary dysfunction before the onset of overt complication
is crucial to maximize outcomes. A comprehensive evaluation of preoperative
features, namely cardiopulmonary and renal physiologic reserve, along with
indication, type, extent, and intraoperative course of surgery, is mandatory to
individuate those patients at increased risk.
2. Length of initial ventilation and early (<24 h of spontaneous breathing) onset of
respiratory failure are highly predictive of NIV failure. The duration of difficult
spontaneous breathing before the institution of NIV should be minimized as
much as possible to avoid the onset of poor oxygenation and fatigue that are
strong predictors of failure.
3. Close hemodynamic and respiratory monitoring is mandatory because lack of
early improvement after NIV institution and subsequent delayed intubation portends worse outcomes.
4. There is not enough evidence to support the preferential use of a particular NIV
modality over the others.
5. Once NIV institution has exerted satisfactory oxygenation and respiratory support, the major determinant of outcome is the response to medical therapy and
the resolution of underlying disease. Pneumonia has relatively slow onset but
requires a definite amount of time to heal after institution of proper antibiotic
therapy. Conventional invasive ventilation still seems best suited in this patient
subset.
24.8
Closing Remarks
In conclusion, there is enough evidence to support NIV as a safe and effective tool
in reducing the burden of post-extubation failure in cardiac surgery. Available evidence should be confirmed by large randomized trials. Optimization of patient
selection criteria, timing, modalities, and location of NIV along with evaluation of
cost-effectiveness are fields of future research.
196
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9. Rady MY, Ryan T. Perioperative predictors of extubation failure and the effect on clinical
outcome after cardiac surgery. Crit Care Med. 1999;27:3407.
10. Carron M, Freo U, BaHammam AS, et al. Complications of non-invasive ventilation techniques: a comprehensive qualitative review of randomized trials. Br J Anaesth.
2013;110:896914.
2012;109:30514.
12. Guarracino F, Cabrini L, Ferro B, et al. Noninvasive ventilation practice in cardiac surgery
patients: insights from a European survey. J Cardiothorac Vasc Anesth. 2013;27:e635.
13. Guarracino F, Ambrosino N. Non invasive ventilation in cardio-surgical patients. Minerva
Anestesiol. 2011;77:73441.
14. Cabrini L, Plumari VP, Nobile L, et al. Non-invasive ventilation in cardiac surgery: a concise
review. Heart Lung Vessel. 2013;5:13741.
15. Olper L, Corbetta D, Cabrini L, et al. Effects of non-invasive ventilation on reintubation rate:
a systematic review and meta-analysis of randomised studies of patients undergoing cardiothoracic surgery. Crit Care Resusc. 2013;15:2207.
Noninvasive Ventilation
in Postextubation Failure in Thoracic
Surgery (Excluding Lung Cancer)
25
Dimitrios Paliouras, Thomas Rallis,

and Nikolaos Barbetakis
Abbreviations
AHRF
ARDS
ARF
BPAP
CPAP
EPAP
ETI
HFNC
ICU
IPAP
NCPAP
NIPPV
NIV
NPPV
PEEP
VAP
VT
Acute hypoxemic respiratory failure

Acute respiratory distress syndrome
Bi-level positive airway pressure
Expiratory positive airway pressures
High-flow nasal cannula
Intensive care unit
Inspiratory positive airway pressures
Continuous-flow nasal CPAP
Noninvasive intermittent positive pressure ventilation
Noninvasive mechanical ventilation
Noninvasive positive pressure ventilation
Ventilation-associated pneumonia
Tidal volume
D. Paliouras, PhD (*) T. Rallis, MD N. Barbetakis, PhD

Thoracic Surgery Department, Anti-Cancer Hospital Theageneio,
Thessaloniki, Greece
e-mail: demtros@yahoo.gr; thrallis@gmail.com; nibarbet@yahoo.gr
DOI 10.1007/978-3-319-04259-6_25
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25.1
D. Paliouras et al.
Introduction
Thoracic surgery operations play a significant part and are a wide-range weapon
in the confrontation and treatment of serious lung and heart conditions, lung cancer,
or severe traumatic injuries involving the anatomy and integrity of the chest cavity
and the underlying vital organs and tissues, such as the trachea and esophagus. In
the past two decades, thoracic surgery has also evolved as an accurate diagnostic aid
in the histological identification of tumors or other granulomatous, autoimmune,
and inflectional diseases involving the organs of the thorax. Depending on the
access in the thoracic cavity, great progress has been achieved against serious diagnostic issues that previously prevented or delayed the desired therapeutic evolution
of the patient. Today, pleural biopsy, chest wall biopsy, and pleural effusion drainage are performed in everyday practice with a high percentage of success [1].
The evolution of thoracic surgery has led to the performance of operative procedures such as a radical video-assisted thoracic surgery, thymectomy, minimally
invasive excisions of mediastinal tumors, and even lung transplantation. On the
other hand, the demands against the management of the manifestation of an acute or
chronic cardiac disease, a situation that usually demands urgent attention, have
required such procedures as percutaneous transluminal coronary angioplasty and
coronary artery bypass grafting to be established as routine. These operations can be
performed through long chest incisions, such as thoracotomy or sternotomy, or
through one to three small chest incisions with the additional use of a camera (thoracoscope), a minimally invasive procedure called video-assisted thoracic surgery.
The level of difficulty, the usual presence of high-risk patients, and the need to
maintain constant focus and emphasis on every detail require optimum pre-, intra-,
and postoperative cooperation between the surgeon and anesthesiologist.
A patient who is undergoing this kind of an operation can be expected to present
a wide spectrum of medical history and additional chronic diseases, which may or
may not receive the proper treatment. This is a challenge that thoracic surgeons and
anesthesiologists must always confront with great responsibility and a degree of
vigilance, especially in terms of an emergency incident or during the admission of
the patient to an emergency department. Additional brief examination procedures,
such as a spirometry, can indicate the degree of an individuals respiratory functionality when the time potentiality is given. A detailed and careful documentation of
their medical record is a good start for the thoracic surgeon to anticipate and overcome possible undesirable complications along the way.
25.2
Discussion
25.2.1 Indications for Noninvasive Mechanical Ventilation

One of the most important issues that requires continuous observation and proper
management is the satisfaction of the patients respiratory needs. The regulation of
postoperative analgesia is an additional variable that must be managed efficiently. It is
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Noninvasive Ventilation in Postextubation Failure in Thoracic Surgery
199
well-recognized that, as long as postoperative pain is correctly regulated, the patients

respiration is carried out without relative complications (e.g., pulmonary atelectasis).
We must not forget that every case has a unique medical history, with greater respiratory and recovery needs according to its complexity and seriousness [2].
Postoperative respiratory needs notably depend on the type of the operation procedure and the type of excision of the pulmonary parenchyma. Lung excisions
include single or multiple wedge resections, segmentectomy, lobectomy or bilobectomy, and radical pneumonectomy. The wide variety of thoracic procedures includes
lung, pleural, mediastinal, or lymph node biopsies. A necessary preoperative control via spirometry provides an indicative image of pulmonary functionality.
Emergency cases, such as pulmonary empyema, a tension pneumothorax, or a traumatic hemothorax are, of course, excluded, as their intraoperative process depends
on the degree of damage. According to the latest guidelines, the following spirometry measures indicate the maximum degree of excision that a patient can bear postoperatively without presenting a permanent respiratory disorder. If the FEV1
measurement is above 2.00, the patient is capable of receiving a radical pneumonectomy; if it is above 1.80, a lobectomy can be performed; and readings below 1.60
allow only the performance of a lung biopsy. Lower readings, for example, below
1.00, show a poor performance status, which makes an eventual procedure
impossible.
The aggravation of the patients respiratory functionality is clinically manifested
via sudden desaturation, the inability for independent respiration with the analog
effect over the patients respiratory index, blood gas, disturbance of pO2, pCO2,
PaO2/FiO2, and so on.
A novel indication for noninvasive mechanical ventilation (NIV) is its use during
other invasive procedures, such as bronchoscopy, particularly in patients with a high
risk of endotracheal intubation (e.g., immune-compromised patients). The use of
NIV during bronchoscopy should be considered as an alternative to avoid the complications related to intubation and mechanical ventilation in patients with severe
conditions, particularly in those with chronic obstructive pulmonary disease with a
tendency to develop hypercapnia.
Other indications include transesophageal echocardiography, interventional cardiology, and pulmonology. NIV may reduce the need for deep sedation or general
anesthesia, preventing the respiratory depression that results from it.
Esophageal surgery may not be an absolute contraindication for NIV or noninvasive positive pressure ventilation (NPPV), although it is considered an effective
treatment option in many cases because it can minimize trauma to these patients [3].
A common and serious complication sometimes evolves as a result of the development of a pulmonary infection during the postoperative period in the intensive
care unit (ICU), which may clinically result in acute respiratory failure (ARF). ARF
may also be triggered by acute heart failure or pulmonary fibrosis. This serious
clinical disorder may require immediate endotracheal intubation (ETI) and mechanical ventilation for its management [4].
Acute respiratory distress syndrome (ARDS) is another serious clinical complex
and is characterized by alveolar capillary injury arising from various extra- and
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intrapulmonary contributing factors. This severe stage of acute lung injury is clinically presented as increased respiratory rate and respiratory distress, progressive
hypoxemia, and diffuse infiltrations on chest X-ray [5].
Chronic obstructive pulmonary disease (COPD) has been a major health problem
for many years, and its manifestation is the result of many and variable factors and
may lead to ARF. An early diagnosis (especially in female patients), along with the
recognition of the disease with the latest guidelines and approaches in mind, may
ensure the optimum preoperative preparation for these kinds of chronic patients [6, 7].
25.2.2 Noninvasive Mechanical Ventilation

The progressive inability of the patient to oxygenate, ventilate, or protect the airway, leading to weaning/postextubation failure, is a direct indication for applying
NIV as a first choice of response. The response to NIV varies from patient to patient
and with the operative procedure the patient has undergone.
A mechanical breath can be classified according to three factors: (i) The trigger: This refers to the mechanism that initiates respiration. Time is considered to
be the traditional trigger, where the mechanical breath is delivered at a specific set
rate and regular time intervals, making it possible to deliver it at any time during the
patient's spontaneous respiratory cycle. (ii) Pressure ventilation or volume limited:
Pressure ventilation delivers each breath until a certain amount of peak inspiratory
pressure is reached, no matter how much tidal volume (VT) corresponds to that pressure. VT can vary from mechanical breath to mechanical breath. On the contrary,
volume-limited (also called volume-controlled) ventilation delivers a set VT of air
with each mechanical breath, without the need to reach specific pressure to get that
breath in. As the lung compliance changes during the procedure, the pressure varies
from mechanical breath to mechanical breath. Nonetheless, the delivered volume of
gas always remains the same. (iii) The cycle: This is the mechanism responsible
for breath termination. Each cycle is regulated by different means, to be completed
after a set time or inhale:exhale ratio. When a certain pressure or volume is reached,
or the inspiratory flow decreases to a small percentage, the process is considered
complete.
By definition, the term NIV includes any means of ventilatory support that does
not require tracheal intubation of the patient. Although the use of NIV was introduced during the 20th century (severe polio epidemics in the 1950s are recorded as
the first example of NIV application), the development of modern NIV has been
registered after the late 1980s, with the application of positive or negative pressure
NIV via a nasal mask. The aim was the treatment of respiratory failure in patients
with advanced neuromuscular disease, respiratory restrictive conditions, or even
sleep apnea. NIV is currently considered the gold standard as a first-line treatment
against serious and life-threatening respiratory complications, especially those that
accompany thoracic surgery.
In recent decades, the indications for NIV have expanded in both acute and
chronic care. NIV has decreased the need for intubation and mortality, effects that
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have been consistently observed in ICUs and respiratory wards. Noninvasive ventilator assistance is usually delivered using masks or nasal prongs. The flow of gas
extends to both the respiratory and gastrointestinal tracts.
NIV is often chosen as a means to avoid intubation during ARF to reduce the risk
of other complications, such as ventilation-associated pneumonia (VAP), especially
in immune-suppressed patients. The goal is to reestablish the functionality of the
poorly ventilated alveoli, achieve the unloading of the respiratory muscles, attain a
favorable hemodynamic preexisting level, and restore the normal respiratory function. The efficacy of NIV treatment depends strictly on the etiology of the established ARF, whether or not a potentially reversible trigger (e.g., pneumonia/acute
heart failure) or an acute exacerbation of (e.g., pulmonary fibrosis) takes place.
It is generally accepted that improvement in gas exchange during the performance of NIV treatment depends on the etiology of the ARF displayed. The heterogeneity of the possible etiologies of ARF demonstrates the importance of patient
selection and management with NIV. For instance, it has been demonstrated that the
application of noninvasive continuous positive airway pressure (CPAP) reduces the
risk of needing to perform in patients with severe hypoxemic ARF due to pneumonia, compared with O2 therapy. It improves oxygenation in patients with pneumonia. In other cases, noninvasive CPAP has been successfully introduced during ARF
caused by pneumonia in patients who underwent lung transplantation for idiopathic
pulmonary fibrosis.
NPPV can be an effective technique to improve gas exchange in order to avoid
endotracheal intubation in selected patients with ARF due to ARDS. Nevertheless,
the need for ETI via endotracheal intubation or tracheostomy is quite often necessary. According to recent studies, trials and the latest guidelines, it has been registered that the success rate of the applied NPPV was measured about 50 %, and
evidently it has been suggested that NPPV can be safely be applied in specific cases
under close supervision.
It has also been concluded that the early use of NIV for mildly and moderately
COPD patients, after a thoracic surgery procedure and their return to the general
ward, results in a rapid improvement of their physiological variables. The need for
invasive mechanical ventilation, as well as in-hospital mortality, has been significantly reduced with the application of NIV, and it has also been demonstrated to be
cost-effective. After continuing trials, the clinical usefulness of NIV has been widely
accepted for treating acute hypercapnic respiratory failure or obstructive atelectasis
due to COPD in patients who underwent a thoracic operative procedure [8].
25.2.3 Equipment
Respiratory support is achieved through the application of NIV, without the need for
a tube in the tracheal lumen. The delivery of the necessary amount of mechanically
assisted breaths is performed without an artificial airway. NIV may be performed
via negative or positive pressure. The expiration is passive until the alveolar pressure reaches atmospheric level. The main goal is to improve the existing
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ventilation-perfusion mismatch that has emerged, decreasing the airway resistance

at the same time. The equipment that is most commonly used in everyday practice
includes facemasks, nasal masks, and short binasal prongs. NIV is accomplished via
the following means: high-flow nasal cannula of intermediate-size (HFNC), CPAP,
continuous-flow nasal CPAP (NCPAP), variable-flow NCPAP, noninvasive intermittent positive pressure ventilation (NIPPV), bi-level positive airway pressure
(BPAP), and a RAM nasal cannula for newborns (Neotech, Valencia, CA, USA).
25.2.3.1 High-Flow Nasal Cannula

The HFNC systems (Fischer and Paykel, Auckland, NZ) manage to deliver gas
flows that meet or may even exceed a patient's inspiratory flow demands. With highhumidity high-flow nasal cannulas, the constant gas flow (28 l/min) is delivered
through a narrow-diameter interface, with a high-velocity jet of gas into the nares.
The satisfaction of the respiratory needs is carried out through three different mechanisms: (1) the gas is heated and humidified; (2) the adverse effects of drying on the
airway mucosa are eliminated; and (3) it is important to prevent any potential thermal losses. The flow increases dead space washout and decreases inspiratory resistance. Positive end-expiratory pressure (PEEP) is generated, which is limited and
dependent on the prong diameter, the gas flow, even whether the patients mouth is
open (Locke 1993; Frey 2001; Sreenan 2001). High gas flow is defined as up to
60 l/min in adults. The difficulty of monitoring the positive pressure that HFNC
delivers to the patient is its most important limitation.
25.2.3.2 Continuous Positive Airway Pressure (CPAP)

A CPAP system provides increased pulmonary pressure, mainly during the expiratory phase, in patients who breathe spontaneously and must also initiate all breaths.
This form of ventilatory support has been shown to reduce intubation rates and
relieve symptoms of postoperative respiratory failure. The delivery of constant airway pressure improves the patients respiratory effort by (i) increasing functional
residual capacity, (ii) reducing airway resistance, (iii) decreasing the work of breathing, and (iv) improving diaphragmatic function and synchrony movement of the
chest and abdomen. CPAP is delivered through a ventilator or other CPAP systems
that utilize a flow generator, oxygen blender, and humidifier.
The most common CPAP system, used widely in the ICU or general ward, is the
Boussignac CPAP System (Vygon, Ecouen, France). The Boussignac valve takes
gas from a single source and splits it to create four high-flow jets, which converge
in the chamber, creating turbulence. It is the turbulence that creates a virtual valve,
providing resistance for the patient to breathe against. Increased gas flow causes
increased turbulence and thus creates a higher pressure. Unlike most CPAP devices,
this system requires no valves or moving parts.
There are two main types of CPAP based on gas flow: continuous flow or variable flow:
Continuous-flow nasal CPAP (NCPAP): Continuous flow is delivered by a
ventilator or a CPAP machine. The PEEP valve controls the flow delivery of
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independent pressure and there are no pressure oscillations. A specific flow

sensor is responsible for increasing the dead space, resistance, and work of
breathing. Pressure monitoring is located within the ventilator, distant from
the patient, thus making the system less responsive.
Bubble CPAP is the simplest method of CPAP deliver. Here, a CPAP generator
generates a constant flow into the inspiratory line and the gas is then delivered
into the patient. At expiration, the exhaled breath goes through the expiratory
limb, which is immediately immersed under water.
Variable-flow NCPAP: Variable-flow NCPAP generates CPAP at the airway
proximal to the nares via a dual-injector. The injector is responsible for causing
gas deceleration and maintaining constant pressure. As the patient requires more
inspiratory flow, according to his or her respiratory needs, the injector jets entrain
additional flow. During the expiratory effort, the air stream passes the wall of the
airways, and a turbulent gas flow causes an attachment of the stream to the wall.
During the entire respiratory cycle, a residual gas pressure is provided by the
constant gas flow. This condition enables stable gas delivery at a desired pressure. This fluid-flip mechanism leads to a fraction of the continuous-flow
CPAP, against which the patient has to exhale.
25.2.3.3 Noninvasive Intermittent Positive Pressure Ventilation

(NIPPV)
NIPPV is achieved through applied positive pressure cycles that are delivered on top
of NCPAP. Mechanical breaths are usually ventilator-generated, and the patient
interfaces are similar to NCPAP, excluding the variable-flow interfaces. NIPPV augments ventilation, increases mean airway pressure, decreases anatomic dead space,
and stimulates respiratory drive through intermitted cycling.
25.2.3.4 Bi-level Positive Airway Pressure (BPAP)
BPAP (Respironics, Inc., Murrysville, PA, USA) is used during NIPPV. It delivers inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP).
Finally, the VT delivered is determined by the difference between IPAP and EPAP.
The obvious advantage of NIV is the avoidance of the serious complications
associated with ETI, such as hypoxemia, possible pneumothorax, local edema, pulmonary infection, and VAP or even ventilator-associated lung injury. Additionally,
due to the noninvasive nature of this method of mechanical ventilation, its application or interruption can be performed with the simultaneous collaboration of the
patient, who maintains the ability to speak, feed, and cough, resulting in greater
comfort and future rehabilitation [9].
25.2.4 Location and Application

An important consideration is the optimal location at which NIV should be delivered. Because of the clinical stage of the operated patients requiring NIV, the
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progression of eventual gas exchange abnormalities, and the overall clinical conditions, the first few hours after the initial acute manifestation may determine their
clinical outcomes. NIV therapy of such patients requires a thorough knowledge of
both respiratory physiology (including respiratory mechanics and gas exchange
abnormalities) and existing ventilatory devices (e.g., interfaces, valves, etc.). A
minimum monitoring level is necessary for its use. In addition to traditional prognostic variables, inadequate use of NIV resulting from a lack of personnel training
is detected in many cases of patients presenting with NIV. The most common problems include (i) a lack of operating knowledge by the staff; (ii) improperly fitted
equipment (e.g., a mask with excessive leaks); and (iii) the inability of the personnel
to control oxygen therapy or manage the ventilator alarms. Thus, the improper use
of NIV in non-designated areas, combined with the absence of well-trained medical
and nursing staff, may result in increased patient mortality. The presence of a welltrained team, careful patient selection, continuous cooperation between thoracic
surgeons and anesthesiologists, and optimal choice of the impact NIV outcomes [9].
The question on where NIV should be applied during the patients postoperative
period, after their hospitalization, is currently related to the available resources of each
hospital and the knowledge and experience of the specialized staff. ICU care is complex and expensive, and it is not needed as a rule for all the patients requiring NIV. In
this regard, specific intermediate locations (between the ICU and the respiratory ward)
have been implemented for the application of NIV in postoperative patients. These are
called semi-critical, intermediate, or high-dependency units, and they have emerged
especially in industrialized countries as an alternative to ICUs. Their specific goal is
to provide noninvasive respiratory support without the complex environment and the
costs of an ICU. The efficacy and cost effectiveness of such units give them the ability
to provide an ideal location for ventilator support (equipped with adequate resources
and staff) and a more comfortable environment for patients [10].
25.2.5 Prediction
NIV is currently considered the gold standard for managing respiratory failure after
a thoracic operative procedure. Significant and continuous efforts have been made
to identify the main predictors of successful NIV. The British Thoracic Society
defines treatment failure via the following guidelines: (i) deterioration in the
patients clinical condition, (ii) lack of improvement or deterioration in arterial
blood gas parameters, (iii) development of new symptoms or complications that
require ETI or ICU admission, or (iv) a decrease in the level of consciousness. If an
effective NIV treatment is performed, patients should experience improvement
within a few hours after the initiation of the ventilation.
NIV treatment failures can be divided into early (within 148 h of NIV use, with
or without an initial success) and late (48 h after initiation of NIV, following an
initial successful response). The latest international guidelines always recommend
a second complete evaluation of the patient after a few hours of NIV use. When
there is no clinical improvement, the prognosis is uncertain. In the presence of NIV
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failure, a decision concerning intubation should always be made. Thus, the severity
of the underlying disease and the operative procedure that has taken place must
always be of first concern.
Conclusion
The purpose of NIV is to achieve of a successful clinical reaction to a patients postoperative respiratory complications, improvement of gas exchange and the work of
breathing, and, ultimately, avoid the need for ETI. NIV can be used as a first-line
treatment response because of its many advantages. Overall results have shown a
statistically significant decrease in the rate of ETI, mortality, and fatal complications
along with reduced ICU and hospital length of stay. We must not forget, however,
that it is a complementary ventilation technique and cannot replace ETI in all
instances. Although it is efficacious, the implementation of NIV remains suboptimal, and the availability of trained staff and sufficient resources to guarantee its
proper application must be ensured, especially for patients who have undergone a
major thoracic operation. NIV should be applied with close monitoring, and ETI
should be promptly available in possible cases of failure. An optimal team-training
experience, careful selection of patients, and special attention to the selection of
devices are critical for optimizing NIV outcomes in critically ill patients.
References
1. Jaber S, De Jong A, Castagnoli A, et al. Non-invasive ventilation after surgery. Ann Fr Anesth
Reanim. 2014;33:48791.
2. Beaussier M, Genty T, Lescot T, et al. Influence of pain on postoperative ventilator disturbances. Management and expected benefits. Ann Fr Anesth Reanim. 2014;33:4846.
3. Kai-Yan Y, Zhao L, Chen Z, et al. Noninvasive positive pressure ventilation for the treatment of
acute respiratory distress syndrome following esophagectomy for esophageal cancer: a clinical
comparative study. J Thorac Dis. 2013;5(6):77782. doi:10.3978/j.issn.2072-1439.2013.09.09.
4. Aliberti S, Messinesi G, Gamberini S, et al. Non-invasive mechanical ventilation in patients
with diffuse interstitial lung diseases. BMC Pulm Med. 2014;14:194. http://www.biomedcentral.com/1471-2466/14/194.
5. Claesson J, Freundlich M, Gunnarsson I, et al. Scandinavian clinical practice guideline on
mechanical ventilation in adults with the acute respiratory distress syndrome. Acta Anaesthesiol
Scand. 2015;59:28697.
6. Lopez-Campos JL, Jara-Palomares L, Muoz X, et al. Lights and shadows of non-invasive
mechanical ventilation for chronic obstructive pulmonary disease (COPD) exacerbations. Ann
Thorac Med. 2015;10(2):8793.
7. Lorut C, Lefebvre A, Planquette B, et al. Early postoperative prophylactic noninvasive ventilation after major lung resection in COPD patients: a randomized controlled trial. Intensive Care
Med. 2014;40(2):2207.
8. Diaz Lobato S, Mayoralas AS. Modern non-invasive mechanical ventilation turns 25. Arch
Bronconeumol. 2013;49:4759.
9. AlYami MA, AlAhmari MD, Alotaibi H, et al. Evaluation of efficacy of non-invasive ventilation in non-COPD and non-trauma patients with acute hypoxemic respiratory failure: a systematic review and meta-analysis. Ann Thorac Med. 2015;10(1):1624.
10. Lin F, Pan L, Huang B, Ruan L, et al. Pressure-controlled versus volume controlled ventilation
during one-lung ventilation in elderly patients with poor pulmonary function. Ann Thorac
Med. 2014;9(4):2038.
Predictors of Prolonged Mechanical

Ventilation in Lung Cancer: Use
of Noninvasive Ventilation
26
26.1
Introduction
Although dyspnea is a well-known symptom of tumors involving the lung or pleura,

shortness of breath is commonly present in patients with terminal cancer who do not
have lung or pleura involvement. Dyspnea in cancer patients may be caused by the
tumor itself, treatment of the tumor, medical complications of the debilitated state,
or underlying lung or cardiac disease.
26.2
Analysis
Considering that lung cancer is the leading cause of cancer death in both men and
women and that as many as 65 % of these patients experience dyspnea, the contribution of lung cancer to dyspnea in patients with terminal cancer is substantial. It is
estimated that 30 % of patients with malignant disease will develop pulmonary metastasis at some time during the clinical course of their disease. Mechanisms for acute
respiratory failure in patients with bronchogenic carcinoma include the following:
1. Replacement of lung tissue to the extent that a restrictive ventilator defect is
produced
2. Pneumonia, atelectasis, or whole-lung collapse occurring behind an occluded
primary or segmental bronchus
E. Antypa, MD, PhD

Intensive Care Unit, Gennimatas General Hospital, Thessaloniki, Greece
N. Barbetakis, MD, PhD (*)
Thoracic Surgery Department, Theagenio Cancer Hospital, Thessaloniki, Greece
e-mail: nibarbet@yahoo.gr
DOI 10.1007/978-3-319-04259-6_26
207
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3. Entrapment of the phrenic nerve by tumor-filled mediastinal nodes and resulting

diaphragmatic paralysis
4. Lymphatic spread or interstitial edema, reducing lung compliance
Acute respiratory failure in cancer patients with pulmonary or pleural involvement
may be related to treatment of the carcinoma, for example, postradiation pneumonitis, postradiation lung fibrosis, or postpneumonectomy. The main respiratory modifications after thoracic surgery mostly lead to atelectasis, hypoxemia, acute
respiratory failure, pneumonia, or bronchopulmonary fistula. Alternatively, acute
respiratory failure in terminally ill cancer patients, including patients with lung cancer, may be related to chronic obstructive pulmonary disease caused by cigarette
smoking. Furthermore, acute respiratory failure in terminally ill cancer patients may
be a manifestation of the debility of terminal cancer. Reported causes include anemia, pulmonary embolism, and congestive heart failure. Moreover, acute respiratory failure in these patients most likely represents the debility of terminal cancer,
which includes general muscle weakness and medical complications. These patients
may be intubated for a long time.
Prolonged mechanical ventilation (MV) may be caused by
1. Inadequate respiratory drive due to nutritional deficiencies, sedatives [1], central
nervous system abnormality, or sleep deprivation
2. Inability of the lungs to carry out gas exchange effectively
3. Inspiratory respiratory muscle fatigue/weakness [2]
4. Psychological dependency
The most common cause is inspiratory respiratory muscle fatigue [3, 4], which is
almost always multifactorial in etiology. Possible causes of inspiratory respiratory
muscle fatigue are
1. Nutritional and metabolic deficiencies resulting from hypokalemia, hypomagnesemia, hypocalcemia, hypophosphatemia, or hypothyroidism [5]
2. Corticosteroids
3. Chronic renal failure
4. Systemic diseases with decreased protein synthesis and increased degradation
and/or decreased glycogen stores
5. Hypoxemia and hypercapnia
6. Increased work of breathing due to disease, ventilator, or airway humidification
devices
7. Failure of the cardiovascular system
8. Neuromuscular dysfunction/disease caused by drugs or critical illness
polyneuropathy-myopathy [6]
9. A combination of the above causes [7]
The predictors of prolonged MV are based on the clinical judgment of the physicians, for example,
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Predictors of Prolonged Mechanical Ventilation in Lung Cancer
209
1. The patient who is unable to initiate spontaneous inspiratory efforts

2. Inadequate oxygenation (Pao2/Fio2 < 200)
3. The patient who is hemodynamically unstable
The rapid shallow breathing index as reflected by the respiratory frequency (f) to
tidal volume (Vt) ratio is the most accurate predictor of failure in weaning patients
from MV [8].
26.3
Discussion
Prolonged MV may be a consequence of persistent weaning failure and is associated with an increased morbidity and mortality. Because patients with unsuccessful
weaning are likely to develop a rapid and shallow breathing pattern, the ability of
noninvasive mechanical ventilation (NIV) to improve hypoxemia and hypercapnia
by correcting such an abnormal breathing pattern might explain the benefits of NIV
in these patients.
The aims of NIV [9] are (1) to partially compensate for the affected respiratory
function by reducing the work of breathing, (2) to improve alveolar recruitment
with better gas exchange (oxygenation and ventilation), and (3) to reduce left ventricular afterload, increasing cardiac output and improving hemodynamics. NIV is
effective in shortening the period of invasive ventilation in patients with persistent
weaning failure and, as a consequence, decreasing the incidence of nosocomially
acquired infections, mortality, and other parameters such as length of intensive care
unit (ICU) and hospital stay.
The physician should also consider the use of NIV to facilitate weaning after
early extubation or for patients who develop hypoxic respiratory failure after more
prolonged intubation [10]. A select group of patients with a higher risk of failing an
extubation trial may be good candidates to use NIV as a preventive measure for
reintubation. NIV could also be considered as a prophylactic and therapeutic tool to
improve gas exchange in postoperative patients [11].
The evidence is also strong for patients developing respiratory distress after surgery for lung resection [12]. Short-term NIV with a ventilator support system
improves the efficiency of the lung as a gas exchanger without noticeable nondesired side effects in patients submitted to lung resectional surgery. In a randomized
trial of postoperative lung resection patients [12], NIMV was shown to be safe and
effective in reducing reintubation and improving survival.
Prophylactic postoperative NIV did not reduce the rate of acute respiratory
events in COPD patients [13] undergoing lung resection surgery and did not influence other postoperative complication rates, mortality rates, or duration of ICU and
hospital stay.
NIV has been successfully used after thoracic surgery. However, NIV fails in
about 20 % of patients [14]. NIV failure is associated with higher mortality, but is
merely a marker of progression of a more severe disease. This may at least indicate
the need for caution in some patients. The selection of the appropriate patients who
210
may benefit from postoperative preventive NIV is a key issue. Interestingly,

increased use of fiber-optic bronchoscopies during noninvasive ventilation use was
identified as a risk factor for failure. The following variables were associated with
NIV failure following lung resection [14]: tachypnea, high Sequential Organ Failure
Assessment score, number of bronchoscopies performed, and number of hours
spent on NIV.
A general protocol would urge that patients appropriate for NIMV be

Dyspneic due to hypoxic, hypercapnic, or mixed respiratory failure
Displaying physical signs of respiratory muscle weakness (accessory muscle use or paradoxical thoracoabdominal movement)
Tachypneic (respiratory rate 25 or higher)
Hemodynamically stable
Able to protect the airway and without excessive secretion control
problems
Able to tolerate or submit to NIV use and adaptable to fitting with a wellsealed interface.
Patients who are hypercapnic [11] tend to have better results than those
who are only hypoxemic. Patients with severe acidosis (pH 7.22 or higher)
and higher degrees of hypercapnia (PaCO2 near 100 mmHg), however, have
worse prognosis. The faster the onset of treatment, the better the outcome is.
Furthermore, the faster the gas exchange and respiratory rate improves [11],
the better the outcome is.
In the postoperative period, it is sometimes difficult to separate preventive
from curative application of NIV [15]. Further studies are needed to better
identify patients who may benefit from NIV after thoracic surgery [15] and
the optimal NIV protocol delivered.
References
1. Arroliga A, Frutos Vivar F, Hall J, et al. Use of sedatives and neuromuscular blockers in a
cohort of patients receiving mechanical ventilation. Chest. 2005;128:496.
2. Vassilakopoulos T, Petrof BJ. Ventilator induced diaphragmatic dysfunction. Am J Respir Crit
Care Med. 2004;169:336.
3. Laghi F, Tobin MJ. Disorders of the respiratory muscles. Am J Respir Crit Care Med.
2003;168:10.
4. Laghi F, Cattapan SE, Jubran A, et al. Is weaning failure caused by low-frequency fatigue of
the diaphragm. Am J Respir Crit Care Med. 2003;167:120.
5. Datta D, Scalise P. Hypothyroidism and failure to wean in patients receiving prolonged
mechanical ventilation at a regional weaning center. Chest. 2004;126:1307.
6. Bolton CF. Neuromuscular manifestations of clinical illness. Muscle Nerve. 2005;32:140.
26
Predictors of Prolonged Mechanical Ventilation in Lung Cancer
211
7. Polkey MI, Moxham J. Clinical aspects of respiratory muscle dysfunction in the critically ill.
Chest. 2001;119:926.
8. Yang KL, Tobin MJ. A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. N Engl J Med. 1991;324:144550.
9. Cered M, et al. Noninvasive respiratory support in the perioperative period. Curr Opin
Anaesthesiol. 2013;26:13440.
10. Ferrer M, Esquinas A, Aranbica F, et al. Non invasive ventilation during persistent weaning
failure a randomized controlled trial. Am J Respir Crit Care Med. 2003;168(1):706.
11. Chiumello D, Chevallard G, Gregoretetti C. Non-invasive ventilation in postoperative patients:
a systematic review. Intensive Care Med. 2011;37(6):91829.
12. Auriant I, Jallot A, Herve P, et al. Non invasive ventilation reduces mortality in acute respiratory failure following lung resection. Am J Respir Crit Care Med. 2001;164:1231.
13. Lorut C, Lefevre A, Planquette B, et al. Early postoperative prophylactic noninvasive ventilation after major lung resection in COPD patients: a randomized controlled trial. Intensive Care
Med. 2014;40(2):2207.
14. Riviere S, Monconduit J, Zarka V, et al. Failure of noninvasive ventilation after lung surgery:
a comprehensive analysis of incidence and possible risk factors. Eur J Cardiothorac Surg.
2011;39(5):76976.
15. Jaber S, Antonelli M. Preventive or curative postoperative noninvasive ventilation after thoracic surgery: still a grey zone? Intensive Care Med. 2014;40:2803.
Use of Noninvasive Mechanical

Ventilation in Lung Transplantation
27
Ana Hernandez Voth, Pedro Benavides Maas,

and Javier Sayas Cataln
Abbreviations
CF
COPD
CPAP
ETI
FEV1
ICU
ILD
LT
NIV
27.1
Cystic fibrosis
Flow expiratory volume in the first second
Intensive care unit
Interstitial lung disease
Lung transplantation
Noninvasive mechanical ventilation
Introduction
Lung transplantation (LT) is a consolidated therapeutic strategy in cases of end-stage

pulmonary diseases such as chronic obstructive pulmonary disease (COPD), diffuse
interstitial diseases, or vascular diseases. Noninvasive mechanical ventilation (NIV)
is one of the ventilatory support techniques that has achieved greater use in recent
years, becoming available at most hospitals and being successfully implemented in
intensive care units (ICUs), intermediate care units, and recovery units. In this chapter, the role of NIV in the management of lung transplant patients in the pretransplant
period, in the early postoperative period, and with LT complications, or to carry out
diagnostic and therapeutic techniques in transplant patients, is reviewed.
A. Hernandez Voth, MD (*) P. Benavides Maas, MD J. Sayas Catalan, MD

Pulmonology Service, Hospital Universitario 12 de Octubre, Madrid, Spain
e-mail: anahvoth@gmail.com; pedrobenavides79@yahoo.es; jsayascat@gmail.com
DOI 10.1007/978-3-319-04259-6_27
213
214
27.2
A. Hernandez Voth et al.
27.2.1 NIV in LT Indication Diseases

Many candidates for LT have a chronic domiciliary NIV indication as part of their
underlying lung disease treatment. There is evidence of NIV benefit as a bridge to
LT in two obstructive pathologies: COPD and cystic fibrosis (CF).
COPD exacerbation is a situation where the use of NIV has a higher degree of
evidence, particularly in severe exacerbations that develop respiratory acidosis.
These exacerbations are frequent in patients with COPD on the waiting list for LT,
and NIV can decrease mortality in up to 50 % cases of COPD exacerbation with
respiratory acidosis when compared with standard treatment [1]. This impact on survival is much higher than that obtained from any of pharmacological treatments used
in COPD exacerbations, and it has a high degree of evidence to be recommended.
NIV usefulness in stable COPD is more controversial. In patients with chronic
hypercapnic respiratory failure, several studies with contradictory results have been
published. Some of them show a slight increase in survival of patients with COPD
with hypercapnic respiratory insufficiency, whereas others have not found any differences in terms of exacerbations or survival. Nevertheless, although there is no
conclusive scientific evidence about its usefulness in stable COPD, it is one of the
main indications of chronic domiciliary NIV in Europe.
Regarding the use of NIV in COPD as bridge to LT, an improvement in a pulmonary function parameter (an increase of 0.20 0.18 l (liters) in FEV1) has been
described, along with a small increase in survival while on the waiting list for LT
[2]. However, these are limited data because of the absence of a control group and
the presence of important selection bias in their results. Functional improvement
has been achieved in very severe COPD by using NIV prior to an oncologic thoracic
surgery, which can be extrapolated to very severe COPD patients on the waiting list
for LT.
NIV in CF patients has shown short-term improvement in oxygen saturation and in
pCO2 levels, as well as a decrease in the work of breathing, alveolar ventilation and
exercise tolerance improvement, and pulmonary function stabilization during rehabilitation [3, 4]. When these patients have a severe exacerbation that requires ventilatory support, invasive mechanical ventilation has a bad prognosis associated with
infectious complications from frequent bronchial colonization, as ventilator-associated
pneumonia. As a bridge to LT, NIV in CF can reduce mortality from this cause.
27.2.2 NIV in the LT Early Postoperative Period

Generally, after thoracic surgery there are strong effects on respiratory function that
relate to postoperative prolonged mechanical ventilation requirements. In the particular case of LT, there are also other associated factors: the usual myopathy that
terminal respiratory insufficiency patients present, functional alterations due to
clamshell incision in bilateral LT, and postoperative diaphragm involvement due to
phrenic nerve damage.
27
Use of Noninvasive Mechanical Ventilation in Lung Transplantation
215
NIV use has been considered in the LT early postoperative period with three
major objectives: to facilitate early extubation, to prevent reintubation due to postsurgery ventilatory failure, and to treat ventilatory failure once it is established [5].
27.2.2.1 NIV as a Tool in Early Extubation

Early extubation is of particular interest in immunosuppressed patients to avoid
infectious consequences of prolonged mechanical ventilation, but also to avoid airway complications. Prolonged mechanical ventilation can lead to barotrauma on the
sutures associated with air leakage, modifying pulmonary defense mechanisms and
leading to bronchial anastomosis infection.
Consequences of reintubation due to postsurgical ventilatory failure may result
in a remarkable increase of mortality.
Hypoxemia, hypercapnia and muscle fatigue due to an increase in breathing
work are the most common causes of failed extubation. Furthermore, at the time
of extubation, there is a loss of the intrathoracic positive pressure maintained so
far. This induces hemodynamic changes, increasing venous return to the right
ventricle, left cardiac septum displacement, and a possible increase in pulmonary
artery pressure and pulmonary capillary wedge pressure. All these events can
result in the development of interstitial pulmonary edema and in a higher expiratory work. Pressure support associated with some degree of positive end-expiratory pressure can offset these effects, even applying ventilation in the noninvasive
mode.
NIV can represent a helpful tool in extubation of patients who do not succeed a
T-tube trial. Thus, early weaning protocols have been developed in LT including
epidural analgesia, early seating position, intensive physiotherapy, and NIV [6].
In our experience, we have reviewed retrospectively NIV use in the early postoperative period of 54 lung transplant patients for three consecutive years. Postextubation NIV was indicated in case of high levels of pCO2 during a T-piece trial
or after extubation, ventilatory mechanisms alterations, or moderate respiratory
acidosis. A major indication for LT was COPD (48 %), and the other indications
were interstitial lung disease (ILD) (26 %), pulmonary arterial hypertension
(11 %), CF (7 %), and others (6 %). Three patients had chronic domiciliary NIV as
a bridge to LT (two had COPD, the other one had ILD). Fourteen patients (26 %)
constituted a NIV group having five endotracheal reintubations (three of them
ended in tracheostomy), whereas in the non-NIV group there were three endotracheal reintubations (all of them ended in tracheostomy). There were no complications observed in the NIV group related to NIV, as well as fewer hours of
endotracheal intubation (ETI) and shorter length of stay in the ICU compared with
non-NIV group (Table 27.1).
In our study, NIV was a useful tool in the LT early postoperative period, and it
was associated with absence of airway complications, less ETI time, and shorter
length of stay on the ICU.
Another circumstance that frequently motivates a prolonged time spent on invasive mechanical ventilation and prolonged ICU length of stay is postsurgical phrenic
paralysis. In these cases, NIV use can reduce time spent on invasive mechanical
ventilation and, hence, length of stay on the ICU.
216
Table 27.1 Variables analyzed in the early postoperative period in lung transplant patients.
Hospital Universitario 12 de Octubre
Variable
Arterial blood gases (early postoperative period)
[pH/PCO2 (mean)]
Time spent in endotracheal intubation (mean)
Length of stay (mean)
Non-NIV group
(N = 39)
7.36/45.9
NIV group
(N = 14)
7.33/49.5
53.52 h
10.53 days
43.68 h
7.10 days
NIV noninvasive mechanical ventilation, ICU intensive care unit, PCO2 carbon dioxide partial
pressure in blood
27.2.2.2 NIV as Prevention of Post-extubation Ventilatory Failure

Reintubation due to ventilatory failure is associated with high mortality, mainly
because of its association with infectious events, which increases prophylactic use
of NIV in patients at risk of reintubation. We do not provide concrete evidence in
LT, but there are several studies on intubated patients at risk of post-extubation ventilatory failure in comparable circumstances to lung transplant patients conditions
that have shown a decrease in post-extubation ventilatory failure rate in patients
using NIV after extubation, trying to maintain NIV as long as possible in the first
24 h, compared with patients who received standard treatment [7].
Along with this, early use of NIV could be considered in lung transplant patients
who do not pass a T-piece trial or have hypercapnia during this trial, looking for a
protective effect on further development of ventilatory failure.
27.2.2.3 NIV as a Treatment of Ventilatory Failure

In post-extubation ventilatory failure, the use of NIV seems attractive as a way to
avoid the need for reintubation. However, in this case, there are dissenting opinions
about its safety and usefulness. Once ventilatory failure is established, NIV may not
be as useful as we think; it can even have a deleterious effect on survival because it
may delay a needed intubation, increasing the overall mortality. However, in some
studies performed in ventilatory failure in the postoperative period in thoracic surgery, NIV allowed a reduction in the rate of respiratory complications and its associated mortality in a relevant way.
27.2.3 NIV in LT Complications That Present Ventilatory Failure

A major cause of readmission to the ICU in the late postoperative period of LT is
respiratory failure. This might be due to many circumstances, most commonly
infection, cardiogenic acute pulmonary edema, drug side effects, and acute rejection. These situations with higher ventilatory requirements are often worsened by
different circumstances related to LT: myopathy due to steroid use and ventilatory
mechanics alterations due to surgery. Thus, it is known that lung transplant patients
who require invasive mechanical ventilation have a worse prognosis than patients
admitted to the ICU due to diseases not derived from surgery [8].
27
217
Moreover, NIV has demonstrated its usefulness in treating patients with hypoxemic respiratory failure of different etiologies, reducing the need for ETI and
thereby decreasing infectious complications from it (nosocomial pneumonia and
septic shock) and decreasing global mortality [9].
Along with the evidence that NIV is safe and may be beneficial in hypoxemic
failure, this technique also has utility in ventilatory failure management in immunosuppressed patients. In these patients, when ventilatory failure requires ETI, mortality increases significantly, but NIV use enables to reduce reintubation rate and
mortality, compared with reintubated patients. Particularly in lung transplant
patients it has demonstrated an improvement in physiological parameters (arterial
blood gases analysis, breathing rate, etc.) after introducing NIV as acute respiratory
failure treatment. However, these results derive from a descriptive study without a
control group, so we can only conclude that the NIV option is safe and may be beneficial to these patients [10].
27.2.4 NIV in Diagnostic and Therapeutic Techniques in Lung

Transplant Patients
Frequently, lung transplant patients require performance of diagnostic or therapeutic techniques in the airway, particularly bronchoscopy. Bronchoscopy can reduce
tracheal lumen in 1015 % of patients and increases work of breathing, generating
a relevant hypoxemia. Procedures like bronchoalveolar lavage can cause a greater
decline of oxygenation, and aspiration of bronchial secretions during bronchoscopy performance may produce a pressure drop at the end of expiration that facilitates alveolar collapse. Frequently, these techniques should be performed in
patients with severe hypoxemia, making it necessary to assure adequate oxygenation. NIV use can allow the performance of these procedures, avoiding the need
for intubation and invasive ventilation. Bronchoscopy performance has been
described under continuous positive airway pressure (CPAP), a particularly useful
nonmechanical CPAP system designed by Boussignac, or the helmet, but there
are no randomized studies that compare bronchoscopy performance under NIV
versus ETI. In general, it is described that NIV can significantly improve oxygenation during bronchoscopy performance in patients with refractory hypoxemia
compared with conventional oxygen therapy. Nevertheless, it may present some
disadvantages, particularly in hemodynamically unstable patients, severely acidotic patients (pH < 7.20), or patients with no possibility of airway isolation with
bronchoaspiration or gastric distension as associated complications.
Conclusion
NIV is a useful tool in lung transplant patients, where avoiding intubation is crucial. It can also improve work of breathing, gas exchange, oxygenation, and exercise tolerance. Its applications include all the range of complications that may be
present in the pretransplant and post-transplant period (early and late ones).
218
In addition, NIV presents obvious advantages over invasive mechanical ventilation, especially related to the lack of infectious complications associated with
the latter. It also allows patient feeding, talking, and expectorating, can be used
intermittently, and its withdrawal or its restart is easy. However, its use is not free
of risk, as with the delay of a necessary intubation, and may have implications in
prognosis, which is why it is recommended that it be used under close surveillance and with skilled staff trained in its application.
NIV use in diseases that may require LT is clear. Numerous candidates for
LT have an indication of chronic domiciliary NIV as part of the underlying
disease treatment. There is evidence of NIVs benefit as a transition aid to
LT in two obstructive pathologies: COPD and CF.
NIV use in the early postoperative period after LT has three major objectives: to facilitate early extubation, to prevent reintubation due to postsurgery ventilatory failure, and to treat ventilatory failure once it is
established. In our experience, NIV can decrease the number of reintubations and length of stay in the ICU compared with patients in whom NIV
has not been used during their stay on the ICU.
NIV is safe and may be beneficial in hypoxemic failure. It is very useful in
ventilatory failure management of immunosuppressed patients. Particularly
in lung transplant patients, an improvement of physiological parameters
(arterial blood gases, breathing rate, etc.) has been observed after introduction of NIV as acute respiratory failure treatment in the late postoperative
period.
NIV can significantly improve oxygenation during diagnostic and therapeutic procedures in lung transplant patients, including bronchoscopy performance in patients with refractory hypoxemia to isolated oxygen
therapy.
References
1. Rabe KF, et al. Global strategy for the diagnosis, management, and prevention of chronic
obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med.
2007;176(6):53255.
2. Wiebel M, et al. Noninvasive self-ventilationsuccessful transition aid in the waiting period
before lung transplantation? Med Klin (Munich). 1995;90(1 Suppl 1):324.
3. Fauroux B, et al. Long-term noninvasive ventilation in patients with cystic fibrosis. Respiration.
2008;76(2):16874.
4. Serra A, et al. Non-invasive proportional assist and pressure support ventilation in patients
with cystic fibrosis and chronic respiratory failure. Thorax. 2002;57(1):504.
5. Feltracco P, et al. Noninvasive ventilation in postoperative care of lung transplant recipients.
Transplant Proc. 2009;41(4):133944.
27
219
6. Rocca GD, et al. Is very early extubation after lung transplantation feasible? J Cardiothorac
Vasc Anesth. 2003;17(1):2935.
7. Ferrer M, et al. Noninvasive ventilation during persistent weaning failure: a randomized controlled trial. Am J Respir Crit Care Med. 2003;168(1):706.
8. Hadjiliadis D, et al. Outcome of lung transplant patients admitted to the medical ICU. Chest.
2004;125(3):10405.
9. Ferrer M, et al. Noninvasive ventilation in severe hypoxemic respiratory failure: a randomized
clinical trial. Am J Respir Crit Care Med. 2003;168(12):143844.
10. Rocco M, et al. Non-invasive pressure support ventilation in patients with acute respiratory
failure after bilateral lung transplantation. Intensive Care Med. 2001;27(10):16226.

in Postoperative Spinal Surgery
28
Eren Fatma Akcil, Ozlem Korkmaz Dilmen,

and Yusuf Tunali
28.1
Introduction
Noninvasive mechanical ventilation (NIMV) is widely used in the treatment of acute

respiratory failure (ARF), and it is particularly effective in the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) and cardiogenic pulmonary edema [1]. Acute postoperative respiratory failure is another of the application
areas of NIMV [2]. Postoperative pulmonary complications (PPCs) are critical in the
postoperative period because they increase hospital length of stay (LOS), morbidity,
and mortality [2, 3]. Atelectasis, pneumonia, bronchospasm, pleural effusion, pulmonary edema, pulmonary embolism, and pneumothorax are the clinical forms of PPC
that occur most often. Many cases of postoperative ARF are short and can be treated
successfully with supplemental oxygen, reversal of neuromuscular blocking agents,
bronchodilators, deep-breathing exercises, and chest physiotherapy if no intubation or
mechanical ventilation is required. Postoperative reintubation and invasive mechanical ventilation themselves are also suggested as relating to PPCs. Therefore, because
it is a noninvasive method, NIMV can be properly used in postoperative ARF [4].
28.2
Discussion
The efficacy of NIMV has been demonstrated in postoperative ARF, including cardiac, thoracic, thoracoabdominal, and abdominal surgery [15]. Various complications may develop following spinal surgery; the most common are cardiac
E.F. Akcil, MD (*) O.K. Dilmen, MD Y. Tunali, MD

Department of Anaesthesiology and Intensive Care Medicine, Istanbul University Cerrahpasa
School of Medicine, Istanbul, Turkey
e-mail: erenfat@yahoo.com; ozlemkorkmaz1978@mynet.com; ytunali@yahoo.com
DOI 10.1007/978-3-319-04259-6_28
221
222
E.F. Akcil et al.
complications (3 %), pulmonary complications (1.2 %), and pneumonia (1.2 %).
Postoperative complications were reported to increase mortality; advanced age (>65),
comorbidities, and complexity of surgical interventions are contributing factors [6, 7].
It is obvious that scoliosis, trauma, and oncological spinal surgical interventions are
more invasive interventions than degenerative disc disease surgery, with higher perioperative morbidity and mortality rates. Moreover, in posterior lumbar fusion operations, mortality is lower than with anterior and thoracic approaches [6]. It has been
demonstrated that diabetes mellitus (particularly insulin-dependent), obesity, COPD,
and steroid use increase complications in lumbar stenosis surgery [7]. Thoracic disk
surgery is particularly associated with pulmonary complications (6.9 %) [8]. In those
undergoing anterior/anterolateral decompression and fusion, all complications and
pulmonary complications were reported to be greater than in those undergoing posterior/posterolateral decompression and only disc decompression with fusion.
Although we report high mortality and morbidity rates in scoliosis surgery, surgical interventions are needed to improve the quality of life of these patients and for
the correction of the vital functions. Irreversibly affected respiratory and cardiac
functions may complicate both anesthesia and surgery. Spinal deformity progression may cause deteriorated respiratory functions. Secondary scoliosis may develop
in children with muscular dystrophies and myopathies, and, hence, spinal fusion
surgery is required. There is alveolar hypoventilation and hypercapnia susceptibility
due to respiratory muscle weakness, and inability to cough in scoliosis accompanied by neuromuscular diseases.
Postoperative pulmonary function is seen to deteriorate further than preoperative
function. In a case series including eight patients, early pre- and postoperative
NIMV applications are effective in protecting the respiratory functions in these children with restrictive respiratory failure [9]. Pre- and postoperative biphasic positive
airway pressure was performed in children with forced vital capacity (FVC) 1 L,
those undergoing scoliosis surgery, and in a case of desaturation due to hypoventilation during the night, and no difference between preoperative and postoperative
respiratory functions was observed [9]. When NIMV is used in chronic respiratory
failure due to scoliosis, it may improve arterial oxygenation, increase the quality of
life, and reduce the hospital LOS. Following scoliosis surgery, acute respiratory
failure may develop, particularly in patients with poor respiratory functions in the
preoperative period. Atelectasis, depressant effects of opioids, and pain are the contributing factors to the risk of postoperative respiratory failure in these patients [10].
It is established that the application of mechanically assisted cough and nasal intermittent positive pressure ventilation before and after surgery ensures that extubation
will performed successfully and invasive mechanical ventilation will not be required
in patients undergoing scoliosis surgery with FVC values of < 40 % before the surgery [11]. In a study of 73 patients undergoing scoliosis surgery, NIMV was applied
in 28 patients in the perioperative period, and PPC developed less often in this group
than in those who did not undergo NIMV [12].
In the pulmonary function tests of the children with muscular dystrophy, assuming that the vital capacity decreases by 310 % per year and surgery is contraindicated without opening tracheostomy in cases with FVC values of below 40 %,
perioperative NIMV application and early surgery seem to be advantageous [13].
28
Noninvasive Mechanical Ventilation in Postoperative Spinal Surgery
223
Respiratory function tests guide us in determining the need of ventilator postoperatively and PPC progression in these patients. The use of short-acting anesthetic
drugs, methods reducing blood loss, and effective pain control may reduce postoperative ventilator requirements [14].
Conclusion
Spinal surgery particularly surgery for scoliosis could be complicated by respiratory

failure in the perioperative period, and NIMV is essential for its management.
Key Recommendations
Respiratory function tests should be evaluated in the preoperative period of

thoracic spinal and scoliosis surgery.
Short-acting anesthetic drugs should be preferred.
Postoperative pain management is essential for recovery.
References
1. Garcia-Delgado M, Navarrete I, Garcia-Palma MJ, et al. Postoperative respiratory failure after
cardiac surgery: use of noninvasive ventilation. J Cardiothorac Vasc Anesth. 2012;26:4437.
2. Pelosi P, Jaber S. Noninvasive respiratory support in the perioperative period. Curr Opin
3. Chiumello D, Chevallard G, Gregoretti C. Non-invasive ventilation in postoperative patients:
a systematic review. Intensive Care Med. 2011;37:91829.
2010;112:45361.
5. Albala MZ, Ferrignio M. Short term noninvasive ventilation in the postanesthesia care unit: a
case series. J Clin Anesth. 2005;17:6369.
6. Pumberger M, Chiu YL, Ma Y, et al. Perioperative mortality after lumbar spinal fusion surgery: an analysis of epidemiology and risk factors. Eur Spine J. 2012;21:16339.
7. Deyo RA, Hickam D, Duckard JP, et al. Complications after surgery for lumbar stenosis in a
veteran population. Spine. 2013;38:1695702.
8. Jain A, Menga EN, Hassanzadeh H, et al. Thoracic disc disorders with myelopathy. Spine.
2014;39:12338.
9. Gill I, Eagle M, Mehta JS, et al. Correction of neuromuscular scoliosis in patients with preexisting respiratory failure. Spine. 2006;31:247883.
10. Doherty MJ, Millner PA, Latham M, et al. Non-invasive ventilation in the treatment of ventilatory failure following corrective spinal surgery. Anaesthesia. 2001;56:23547.
11. Bach JR, Sabharwal S. High pulmonary risk scoliosis surgery: role of noninvasive ventilation
and related techniques. J Spinal Disord Tech. 2005;18:52730.
12. Chong HS, Padua MRA, Kim JS, et al. Usefulness of noninvasive positive-pressure ventilation
during surgery of flaccid neuromuscular scoliosis. J Spinal Disord Tech. 2015. doi:10.1097
BSD.0000000000000234.
13. Mills B, Bach JR, Zhao C, et al. Posterior spinal fusion in children with flaccid neuromuscular
scoliosis: the role of noninvasive positive pressure ventilatory support. J Pediatr Orthop.
2013;33:48893.
14. Almenrader N, Patel D. Spinal fusion surgery in children with non-idiopathic scoliosis: is there
a need for routine postoperative ventilation? Br J Anaesth. 2006;97(6):8517.
Noninvasive Ventilation Following

Abdominal Surgery
29
Alastair J. Morgan and Alastair J. Glossop
Abbreviations
CPAP
GI
ICU
MV
NIV
NPPV
PF
PPC
PRF
RCT

Gastrointestinal
Intensive care unit
Noninvasive positive-pressure ventilation
PaO2/FiO2 ratio
Postoperative pulmonary complications
Postoperative respiratory failure
29.1
Introduction
Patients undergoing abdominal surgery are at risk of developing postoperative

respiratory failure (PRF) and postoperative pulmonary complications (PPCs),
including hypoxemia, atelectasis, bronchospasm, pleural effusions, aspiration
Authors Disclosures Alastair Glossop has previously received a scholarship awarded by the
National Institute for Health and Clinical Excellence (NICE) but received no financial incentive.
A.J. Morgan, BSc, MRCP(Ed), FRCA, FFICM A.J. Glossop, MRCP, FRCA, DICM,
FFICM (*)
Department of Critical Care, Sheffield Teaching Hospitals NHS Foundation Trust,
Herries Road, Sheffield S5 7AU, UK
e-mail: alastair.glossop@sth.nhs.uk
DOI 10.1007/978-3-319-04259-6_29
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A.J. Morgan and A.J. Glossop
pneumonitis, sputum plugging, lobar collapse, pneumonia, and the requirement for
mechanical ventilation (MV). The incidences of PRF and PPCs are 0.23.4 and
7.240 %, respectively, following elective abdominal surgery, with even higher
rates following emergency surgery and in patients older than 80 years [1]. Depending
on patient characteristics and demographics, associated mortality can exceed 25 %,
with substantial associated increases in health-care costs [13].
Endotracheal reintubation is required in 810 % of patients secondary to PRF
following major abdominal surgery. Although often a necessary supportive intervention, endotracheal intubation is an independent predictor of hospital mortality,
prolonged intensive care, and hospital stay [15]. Noninvasive ventilation (NIV)
has been used as both a prophylactic and therapeutic treatment option in patients
with PRF after major abdominal surgery and may potentially reduce the significant
morbidity and mortality associated with reintubation. Early studies examining the
use of NIV in this patient group were inconclusive or produced conflicting results
[6, 7], but there is now growing evidence and enthusiasm for using NIV postoperatively to reduce the risk of complications following major surgery. This chapter
reviews the evidence for the use of NIV in open abdominal visceral surgery, thoracoabdominal surgery, vascular surgery, and transplant surgery.
29.2
Etiology of Respiratory Complications

following Abdominal Surgery
Pulmonary function deteriorates in all patients following major abdominal surgery,

with a reduction in lung volumes and the development of alveolar collapse and atelectasis in 8090 % of patients. Atelectasis leads to hypoxemia via ventilation perfusion mismatching. Its development significantly increases the risk of PRF and PPCs
and may trigger an inflammatory reaction promoting bacterial growth in the lungs
and bacterial translocation into the bloodstream. The main disruptions to normal
respiratory function are maximal in the first hours following surgery and generally
regress after 12 weeks.
29.3
NIV Following Abdominal Surgery
The use of NIV following major surgery is well established as both a prophylactic
and therapeutic treatment modality. Although oxygen therapy may be effective in
attenuating postoperative hypoxemia, it is only a symptomatic approach that does
not reverse the underlying pathophysiological process. There is evidence to suggest that lung expansion therapy using incentive spirometry and deep-breathing
exercises reduces PPCs after abdominal surgery [8]. Compared with standard positive pressure respiratory therapy, the application of continuous NIV is associated
with an increase in functional residual capacity and reduced atelectasis and left
ventricular afterload, with a subsequent increase in cardiac output and arterial
oxygenation.
29
Noninvasive Ventilation Following Abdominal Surgery
227
Studies comparing NIV with standard therapy have generally provided positive
results supporting the use of NIV postoperatively, but they are limited by small
sample sizes, with a large variation in the modality of NIV, technical implementation, and timing of application seen between studies. The small sample sizes in
these studies has meant that atelectasis and PaO2/FiO2 (PF) ratio are commonly
assessed, which may not translate into clinically relevant end points such as reintubation and mortality rates. Although reductions in rates of PPCs and reintubation
have been demonstrated in the literature, there is currently limited evidence regarding the impact of NIV on mortality.
A landmark multicenter, prospective, randomized control trial (RCT) of 209
patients published in 2005 by Squadrone et al. [9] demonstrated a significant reduction in reintubation, pneumonia, and sepsis rates following early hood continuous
positive airway pressure (CPAP) in hypoxemic patients after elective major abdominal surgery. ICU length of stay was lower in the CPAP group, but there was no difference in hospital length of stay or in-hospital mortality between groups. In a
prospective observational study involving 72 patients with severe PRF after abdominal surgery, reintubation was avoided in 67 % of patients treated with NIV [10].
A large meta-analysis of 654 patients pooled from nine studies of NIV use
following abdominal surgery demonstrated that NIV use was associated with a
significantly lower rate of PPCs, including atelectasis, when compared with standard medical therapy [11]. The pooled estimate of two studies using intubation as
an endpoint showed a beneficial effect of CPAP (risk reduction 0.85; 95 % confidence interval (CI) 0.340.97). Two of the studies included in the analysis assessed
the effect of postoperative CPAP on mortality following abdominal surgery; however, the number of deaths was too small to allow meaningful analysis. The studies included in this meta-analysis displayed marked heterogeneity, differing in
both application and duration of CPAP use, and only included preoperatively
healthy patients in five studies and may therefore underestimate the beneficial
effects of NIV.
CPAP may be of particular benefit for patients who cannot participate with
incentive spirometry or deep-breathing exercises. In patients with obstructive airways disease, CPAP decreases work of breathing by counterbalancing the inspiratory threshold load imposed by intrinsic positive-end expiratory pressure (PEEP).
Noninvasive positive pressure ventilation (NPPV) may be considered in patients in
whom hypercarbia coexists with hypoxemia, when there is a history of chronic
obstructive pulmonary disease, or in patients who are experiencing an increased
respiratory workload.
The optimum amount of PEEP and duration of NIV, particularly as a prophylactic treatment, remains controversial, with a lack of supporting evidence and trials in
which a benefit for NIV has not been evident [7, 12]. Some authors have suggested
that immediate application of NIV post extubation may be more beneficial in
recruiting alveoli than delayed or intermittent NIV, although current practice varies
widely and is often dictated by local preferences and protocols or the need to balance
continued alveolar recruitment with patient comfort, nursing availability, and
workload.
228
Upper gastrointestinal (GI) surgery in which a surgical anastomosis has been

formed has historically been considered a contraindication to NIV because of the
theoretical risk of NIV causing increased gastric luminal pressures and subsequent
disruption of the surgical anastomosis. In a prospective cohort study, 1,067 patients
undergoing a gastrojejunostomy as part of a gastric bypass procedure were assessed
[13], and no correlation was found between anastomotic leaks and use of CPAP. In
a retrospective review involving 91 patients receiving CPAP after laparoscopic
Roux-en-Y gastric bypass surgery, the incidence of anastomotic leakage was zero
[14]. Additionally, transmural gastric pressures have not been demonstrated to
increase following the application of CPAP after laparoscopic Roux-en-Y gastric
bypass [15]. Despite the lack of RCT data in this area, it would appear that NIV
usage is not associated with an increased risk of anastomotic failure and is safe to
use following upper GI surgery, although caution should be exercised to avoid high
airway pressures (>25 cmH2O). It would also seem prudent in NPPV use to limit the
maximum Pressure support ventilation (PSV) level to 8 cmH2O to prevent generation of excessively high pressures during inspiration.
29.4
NIV Following Thoracoabdominal Surgery
Esophageal surgery results in diaphragmatic disruption and a restrictive syndrome resulting in atelectasis, hypoxemia, and a high incidence of PPCs, and the
presence of a transposed gastric conduit may further compromise respiratory
function postoperatively. Maintenance of adequate postoperative oxygenation is
of importance in preventing impaired oxygen delivery and subsequent ischemia
of the gastric conduit, which are the main risk factors predisposing to anastomotic leakage.
Michelet et al. [16] compared the efficacy of NIV with conventional treatment in
72 patients who developed post-esophagectomy respiratory failure. This casecontrolled study, in which 36 patients were matched to 36 historical controls, demonstrated a reduction in reintubation, frequency of acute respiratory distress
syndrome, anastomotic leakage, and intensive care unit (ICU) length of stay in
patients treated with NIV compared with controls. No reduction in either hospital
mortality or length of stay was seen. In an RCT including 70 patients undergoing
thoracoabdominal gastroesophageal resection, Fagevik Olsn et al. [4] compared
standard therapy with prophylactic CPAP in the immediate postoperative period.
Significantly fewer patients in the CPAP group required reintubation and prolonged
MV. Clinical outcomes of ICU and hospital length of stay and 30-day mortality
were similar between groups.
In this group of patients with a propensity for developing PRF, who are often of
an increased age with multiple comorbidities, NIV support presents an attractive
option in the postoperative period to maintain adequate oxygenation and reduce the
complications associated with MV. The use of NIV does not appear to be associated
with anastomotic failure and NIV may be safely used following esophageal
surgery.
29
29.5
229
NIV Following Vascular Surgery
Repair of a thoracic or abdominal aortic aneurysm is high-risk surgical procedure,

with the risk of developing PRF as high as 60 % in some patient groups and MV
being required in about 8 % of these patients [17, 18]. Mortality rates increase fourfold if a patient requires reintubation following the development of PRF. Therefore,
prevention of respiratory complications in this group of high-risk patients may have
a significant impact on patient morbidity and mortality.
Several studies have examined the use of NIV following abdominal surgery and
included vascular patients, but only two examined NIV use following vascular surgery alone. Bhner et al. [19] applied continuous nasal CPAP for at least 12 h in 99
patients post extubation following laparotomy for vascular surgery. Supplemental
oxygen to maintain arterial oxygen saturations greater than 95 % was used in the
control group of 105 patients. Severe hypoxemia occurred significantly less frequently in the NIV group (5 % vs 16 %; p = 0.01), and nonstatistically significant
trends toward reductions in the incidence of pneumonia and reintubation were also
seen. In a prospective randomized trial of 50 patients, Kindgen-Milles et al. [20]
compared the application of continuous nasal CPAP at 10 cmH2O for a mean of 23 h
with standard therapy following thoracoabdominal aortic aneurysm repair. Nasal
CPAP was associated with significantly fewer pulmonary complications (PF ratio
<100 mmHg, atelectasis, pneumonia, reintubation); a nonsignificant reduction in
mean ICU stay and a significant reduction in mean hospital length of stay (p = 0.048,
8 1 vs 12 2 days) were also seen.
The use of NIV prophylactically following major vascular surgery has thus been
demonstrated in large RCTs to be beneficial in terms of preventing complications
that result in significant morbidity and burden on health-care resources. Although
there is no mortality data to support its use in this patient group, NIV use should be
strongly considered following major vascular surgery.
29.6
NIV Following Solid Organ Transplantation
Postoperative pulmonary complications following solid organ transplantation contribute substantially to morbidity and mortality in this group of patients.
Approximately 5 % of patients undergoing renal, hepatic, cardiac, or pulmonary
transplantation develop postoperative pneumonia. The concurrent use of immunosuppressive therapy to prevent transplant rejection increases the morbidity and mortality associated with pulmonary infection. In patients with PRF, the need to
reintubate is the major factor associated with the development of nosocomial
pneumonia.
Although the use of NIV to prevent intubation and MV is well established in
immunocompromised patients with acute respiratory failure, there is only one randomized trial of postoperative NIV use in patients following intra-abdominal organ
transplantation. Antonelli et al. [21] concluded from an RCT of 40 patients that NIV
compared with supplemental oxygen alone significantly improves PF ratios and
230
reduces rates of reintubation, fatal complications, and overall ICU mortality in

organ transplant recipients (lung, liver, and kidney) with hypoxemic PRF. Hospital
mortality rate did not differ between the groups. A subgroup analysis of the patients
undergoing only liver transplantation did not show a significant difference in reintubation and mortality rate, a finding supported by a subgroup analysis of an observational study by Jaber et al. [10].
29.7
Conclusions and Recommendations
Although few studies have examined different techniques to treat or prevent pulmonary complications and large RCTs in this area are lacking, early NIV is an attractive treatment option following major abdominal surgery because it may provide
ongoing respiratory support without the risks of endotracheal intubation and
MV. When NIV is effective in avoiding reintubation, the morbidity and mortality
associated with MV are reduced. NIV may also reduce ICU length of stay, which
has substantial associated cost benefits.
There is good evidence to support the early use of NIV (CPAP) in high-risk
patients with PRF or PPCs following elective major abdominal surgery, and its use
is recommended in this group to reduce reintubation risk. The use of a risk stratification score may assist in identifying the specific patient population for whom NIV
may be of most benefit and directing resources toward patients with the most need
[1]. When used as prophylaxis, based on limited current evidence, NIV should be
applied immediately post extubation and used continuously as tolerated by the
patient. Future research should focus on determining the optimal NIV regimen in
terms of modality, timing, and duration and also address the impact of NIV on mortality in high-risk patients.
The use of NIV after gastrointestinal surgery involving formation of an anastomosis is more controversial, although the available literature suggests that NIV is
safe to use in patients with respiratory failure following esophageal, gastric, and
bariatric surgery as it may reduce reintubation rates without increasing risk of anastomotic dehiscence. Further work is needed in this area to clarify the mode of delivery, timing, and duration of NIV that is most beneficial in this patient group.
The use of NIV as prophylaxis following major vascular surgery has been shown
to reduce the risks of hypoxia, respiratory failure, and need for reintubation, which
are all major causes of postoperative morbidity. Although evidence of mortality
benefit in this patient group is lacking, the use of NIV to prevent such complications
is recommended. There is a paucity of evidence for the use of NIV following transplant surgery, although the available evidence suggests that NIV use may be beneficial in patients who develop respiratory failure postoperatively to prevent the need
for reintubation and the attendant infective risks.
Overall, it is evident that the use of NIV in patients following major abdominal
surgery is beneficial, and although there is little data pertaining to mortality benefit,
there is evidence in all patient groups of reductions in major causes of postoperative
morbidity and complications, which has important implications for patient safety
29
231
and use of health-care resources. Debate continues as to whether NIV is best used
as prophylaxis or treatment in postoperative patients and also whether CPAP or
NPPV is the optimal mode of delivery to reduce postoperative complications. Future
research should focus on mortality as an endpoint, given that the morbidity benefits
are already well demonstrated, and also debate the optimum mode, timing, and
delivery of NIV in high-risk surgical patients.
References
1. Canet J, Gallert L, Gomar C, et al. Prediction of postoperative pulmonary complications in a
population-based surgical cohort. Anesthesiology. 2010;113:133850.
2. Arozullah AM, Daley J, Henderson WG, et al. Multifactorial risk index for predicting postoperative respiratory failure in men after major non cardiac surgery. The National Veterans
Administration Surgical Quality Improvement Program. Ann Surg. 2000;232:24253.
3. Johnson RG, Arozullah AM, Neumayer L, et al. Multivariable predictors of postoperative
respiratory failure after general and vascular surgery: results from the patient safety in surgery
study. J Am Coll Surg. 2007;204:118898.
4. Fagevik Olsn M, Wennberg E, Johnsson E, et al. Randomized clinical study of the prevention
of pulmonary complications after thoracoabdominal resection by two different breathing techniques. Br J Surg. 2002;89:122834.
5. Lawrence VA, Hilsenbeck SG, Mulrow CD, et al. Incidence and hospital stay for cardiac and
pulmonary complications after abdominal surgery. J Gen Intern Med. 1995;10:6718.
6. Stock M, Downs J, Gauer P, et al. Prevention of postoperative pulmonary complications with
CPAP, incentive spirometry, and conservative therapy. Chest. 1985;87:1517.
7. Carlsson C, Sonden B, Thylen U. Can postoperative continuous airway pressure (CPAP) prevent pulmonary complications after abdominal surgery? Intensive Care Med. 1981;7:2259.
8. Lawrence VA, Cornell JE, Smetana GW, et al. Strategies to reduce post-operative pulmonary
complications after non-cardiothoracic surgery: systematic review for the American College of
Physicians. Ann Intern Med. 2006;144:595608.
post-operative hypoxaemia: a randomized controlled trial. JAMA. 2005;293:58995.
10. Jaber S, Delay J, Sebbane M, et al. Outcomes of patients with acute respiratory failure after abdominal surgery treated with non-invasive positive-pressure ventilation. Chest. 2005;128:268895.
11. Ferrerya GP, Baussano I, Squadrone V, et al. Continuous positive airway pressure for treatment
of respiratory complications after abdominal surgery: a systematic review and meta-analysis.
Ann Surg. 2008;247:61726.
12. Denehy L, Carroll S, Ntoumenopoulos G, et al. A randomized controlled trial comparing periodic mask CPAP with physiotherapy after abdominal surgery. Physiother Res Int. 2001;6:
23650.
13. Huerta S, DeShields S, Shpiner R, et al. Safety and efficacy of post-operative continuous positive airway pressure to prevent pulmonary complications after Roux-en-Y gastric bypass.
J Gastrointest Surg. 2002;6:3548.
14. Ramirez A, Labor PF, Szomstein S, et al. Continuous positive airway pressure in immediate
postoperative period after laparoscopic Roux-en-Y gastric bypass: is it safe? Surg Obes Relat
Dis. 2009;5:5446.
15. Weingarten TN, Kendrick M, Swain JM, et al. Effects of CPAP on gastric pouch pressure after
bariatric surgery. Obes Surg. 2011;21:19005.
16. Michelet P, DJourno XB, Seinaye F, et al. Non-invasive ventilation for treatment of postoperative respiratory failure after oesophagectomy. Br J Surg. 2009;96:5460.
17. Money SR, Rice K, Crockett D, et al. Risk of respiratory failure after repair of thoracoabdominal aortic aneurysms. Am J Surg. 1994;168:1525.
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18. Svensson LG, Hess KR, Coselli JS, et al. A prospective study of respiratory failure after highrisk surgery on the thoracoabdominal aorta. J Vasc Surg. 1991;14:27182.
19. Bhner H, Kindgen-Milles D, Grust A, et al. Prophylactic nasal continuous positive airway
pressure after major vascular surgery: results of prospective randomised trial. Langenbecks
Arch Surg. 2002;387:216.
pulmonary morbidity and length of hospital stay following thoraco-abdominal surgery. Chest.
2005;128:8218.
21. Antonelli M, Conti G, Bufi M, et al. Noninvasive ventilation for treatment of acute respiratory
failure in patients undergoing solid organ transplantation. A randomized trial. JAMA.
2000;283:23541.

in Postoperative Bariatric Surgery
30
Michele Carron and Anna Toniolo
30.1
Introduction
Obesity has increased worldwide during the past few decades [1, 2]. Anesthesiologists
must provide care for an increasing number of obese patients in their clinical practice.
Anesthesiologists should consider that the specific respiratory problems associated
with obesity may increase the risk of postoperative respiratory complications.
Anesthesia, surgery, and postoperative pain further diminish respiratory function, predisposing the obese patient to hypoxemia and acute respiratory failure (ARF) [1, 2].
Noninvasive ventilation (NIV) may be an important tool for managing obese
patients after surgery. NIV may reduce the risk of ARF, reintubation, duration of
intensive care and hospital stays, morbidity, and mortality in postoperative patients
[3]. Major issues surrounding preoperative and postoperative respiratory changes
and postoperative application of NIV in obese patient are discussed in this
chapter.
30.2
30.2.1 Definition of Obesity

Obesity is a metabolic disease involving an excessive amount of adipose tissue
[1, 2]. The amount of fat tissue increases proportionally with the total body weight
in obese patients. Body mass index (BMI) is a measure of relative weight based
M. Carron, MD (*) A. Toniolo, MD

Department of Medicine, Anesthesiology and Intensive Care, University of Padova,
Via C. Battisti, 267, 35121 Padova, Italy
e-mail: michele.carron@unipd.it; anna.toniolo84@gmail.com
DOI 10.1007/978-3-319-04259-6_30
233
234
M. Carron and A. Toniolo
on the mass and height of an individual. Obesity is defined by a BMI exceeding

30 kg/m2 [1, 2].
However, BMI is not the ideal measurement of obesity because it fails to convey
an accurate account of the distribution of fat [1]. Fat distribution is very important
[1, 2], and can be classified as either android or gynecoid [1]. Although the terms
android and gynecoid refer to the typical male (centripetal) and female (peripheral)
fat distributions, both distributions are observed in both genders [1]. The android
type is of greater pathophysiological significance. Android fat distribution describes
a physique in which weight is carried on the trunk with a high intraperitoneal fat
content. By contrast, gynecoid fat describes a physique in which more weight is
carried on the arms, legs, and buttocks, and abdominal fat is predominantly extraperitoneal. Compared with the gynecoid fat distribution, the android distribution is
more frequently associated with obstructive sleep apnea (OSA) and respiratory
changes [1].
30.2.2 Upper Airway Changes in Obese Patients

Obese patients are predisposed to upper airway obstruction and respiratory failure
[1, 2]. Patency of the upper airway is maintained by the pharyngeal dilator muscles
during inspiration, although lung inflation may also contribute to patency [1, 2].
Postoperative muscle weakness and upper airway or pharyngeal dysfunction following anesthesia may predispose patients to upper airway obstruction, particularly
patients with OSA [13]. Fat deposition can promote airway collapse and narrowing of the upper airway. Magnetic resonance imaging studies indicate superficial fat
deposition at the neck and a greater amount of fat deposition in the lateral pharyngeal wall, including pharyngeal structures, such as the tongue, uvula, tonsils, tonsillar pillars, and aryepiglottic folds [1]. These findings are particularly evident in the
android obesity pattern.
30.2.3 Changes in Respiratory Function in Obese Patients

Obesity, particularly severe obesity, affects pulmonary function [15]. The accumulation of fat tissue in the chest wall, abdominal cavity, and intrathoracic space
decreases compliance and diminishes lung volume. Cephalic displacement of the
diaphragm increases abdominal content and pulmonary blood volume, further
reducing compliance and lung volume [15].
Resting tidal volume normalized to total body weight or lean body weight is
reduced by 50 % or 20 %, respectively, in comparison with that of patients with
normal weights [1, 2]. In addition, the respiratory rate may be 40 % higher in obese
patients than in nonobese subjects [1, 2]. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), functional residual capacity (FRC), expiratory reserve
volume (ERV), total lung capacity (TLC), and maximal voluntary ventilation are
reduced, particularly among morbidly obese patients [2]. Because both FEV1 and
30
Noninvasive Mechanical Ventilation in Postoperative Bariatric Surgery
235
FVC decrease, the FEV1 to FVC ratio often remains unchanged [1, 2]. TLC, FRC,
and ERV decline exponentially as BMI increases [1, 2]. FRC is usually reduced as
a consequence of reduced ERV, with residual volume remaining within normal limit
[1]. FVC is reduced by 1015 % in some obese patients and by 2550 % in morbidly obese patients [2].
Mechanical pulmonary function is further altered by physiological changes that
are present in the obese state [1, 2]. Increased lean body weight and fat tissue
increases oxygen consumption and carbon dioxide production to satisfy metabolic
requirements. These changes increase minute ventilation [1, 2]. Oxygen consumption is increased at rest by approximately 25 % in obese subjects [1, 2]. Despite
increased production of carbon dioxide, normocapnia is usually maintained by the
increased minute ventilation [1, 2]. Patients with chronic obstructive pulmonary
disease (COPD) or obesity hypoventilation syndrome are generally hypercapnic [1,
2]. Increased upper airway resistance, restrictive pulmonary pathophysiology,
increased minute ventilation, oxygen consumption, carbon dioxide production, and
respiratory muscle dysfunction due to increased cytokine levels and fatty infiltration
significantly increase the effort required to breathe [1, 2]. Normocapnic, morbidly
obese subjects exhibit increased breathing effort at rest by about 3070 %. In severe
obesity, effort required may increase up to 280 % of normal, leading to a 10-fold
increase in the energy cost of breathing [1, 2].
Altered pulmonary function in obese patients affects pulmonary gas exchange,
especially among those with BMIs that exceed 40 kg/m2 [1, 2]. Morbidly obese
patients may have reduced partial arterial oxygen concentrations (PaO2), increased
partial arterial carbon dioxide concentrations (PaCO2), and increased alveolar-toarterial oxygen partial pressure differences. The increased shunt fraction and the
ventilation-perfusion mismatch result in hypoxemia [1, 2].
30.2.4 Postoperative Changes in Respiratory Function

and Impact on Postoperative Outcome
Anesthesia, surgery, and postoperative pain further reduce respiratory function
[1, 2]. Airway resistance and respiratory system elastance increase up to 60 % and
50 %, respectively, whereas the FRC decreases by about 60 % [4, 5]. Reduced lung
volume, modified breathing patterns, diaphragm dysfunction, and postoperative
pain favor low tidal volume ventilation. These changes collectively promote alveolar hypoventilation, hypoxemia, hypercapnia, and increased atelectasis, which predispose the patient to pneumonia [13, 6].
The Nationwide Inpatient Sample database documents 304,515 patients as
receiving bariatric surgery between 2006 and 2008, with an overall ARF rate of
1.35 %. The greatest rate of ARF (4.10 %) was observed after open gastric bypass
surgery. The ARF rate was lower after laparoscopic surgery compared with that
after open surgery (0.94 % vs 3.87 %, p < 0.01) or after nongastric bypass versus
gastric bypass (0.82 % vs 1.54 %, p < 0.01) [7]. Age, BMI, ASA =American Society
of Anesthesiologists physical status, metabolic syndrome, and additional
236
comorbidities are associated with an increased risk of postoperative respiratory

complications (i.e., pneumonia, atelectasis, respiratory failure, adult respiratory distress syndrome) [13]. Despite a relatively low incidence, postoperative ARF may
represent a life-threatening event. A retrospective analysis of a large prospective
database from 1996 to 2006, including 13,871 bariatric surgical procedures, showed
that ARF was the fourth cause of mortality (11.8 %) [8].
30.2.5 Noninvasive Ventilation Techniques and Device

Continuous positive airway pressure (CPAP) and non-invasive positive pressure
ventilation (NPPV) have been proposed for use during the postoperative period in
obese patients [2, 3].
CPAP is a method that delivers constant positive airway pressure noninvasively
during both inspiration and expiration [3]. When CPAP is applied with positive
inspiratory ventilatory support (PSV), it is referred to as positive end-expiratory
pressure (PEEP) [3]. CPAP decreases upper airway obstruction and prevents airway
and alveolar collapse. This action reduces atelectasis and increases FRC by recruiting and stabilizing previously collapsed lung tissue, reducing ventilation/perfusion
mismatch and shunt fraction with improved gas exchange [2, 3]. CPAP counteracts
the effect of increased abdominal pressure on the diaphragm and decreases the work
of breathing, counterbalancing the inspiratory threshold load imposed by intrinsic
PEEP in some patients (i.e., COPD patients) [2, 3]. Furthermore, CPAP reduces left
ventricular afterload and increases cardiac output [2, 3].
NPPV refers to PSV with or without PEEP and BiPAP (bi-level positive airway
pressure) [3]. BiPAP is a technique that delivers two positive airway pressures [3].
In fact, BiPAP includes PSV plus PEEP and CPAP, in which the later delivers only
one positive airway pressure. In comparison to that achieved with CPAP, PSV above
PEEP achieves improved muscle unloading and relief from dyspnea during NIV [3].
PSV plus PEEP increases the alveolar ventilation obtained with CPAP alone [2, 3].
It is difficult to establish a standard recommendation for all obese patients. An
individual titration should be performed to find the best NIV setting to reduce dyspnea, unload respiratory muscles, increase oxygenation, and counteract the effect of
increased abdominal pressure on the diaphragm in obese patients after surgery [2, 3].
Patient selection and monitoring are crucial for reducing NIV failure [6]. NIV should
never be initiated in uncooperative and/or hemodynamically unstable patients [6].
Such patients need prompt tracheal intubation to allow conventional ventilation;
delayed ventilation is associated with increased morbidity and mortality [6].
During NIV, gas is delivered to the airway via an interface (nasal or facial mask or
helmet) [2, 6]. The appropriate selection and adequate management of a device are
crucial for minimizing the risk of complications and failure during NIV [2, 6]. It is
important to choose an interface that fits properly and minimizes air leaks and to allow
the patient to become familiar with the equipment in the first few minutes of NIV [2,
6]. In patients who feel claustrophobic, the use of different sizes or types of masks or
helmets may enhance patient comfort [2, 6]. To date, there is no evidence supporting
30
237
the use of a specific patient interface device in obese patients [2, 6]. However, the use
of a helmet may improve patient comfort and compliance. Helmets are better tolerated
than masks, resulting in longer use and lower NIV failure rates [6].
Prevention and management of gastric insufflation may be achieved by placing a
nasogastric tube for intermittent air and fluid aspiration prior to NIV [2, 6]. Antacid
prophylaxis should be considered for reducing gastric content and vomiting after
gastric insufflation to avoid serious complications (i.e., pulmonary aspiration, pneumonia, and possibly death) [2, 6].
30.2.6 Rationale for Postoperative NIV in Obese Patients

Postoperative NIV can be used in a prophylactic or curative manner during bariatric
surgery. Prophylactic use involves treating postoperative changes in respiratory
function to prevent postoperative ARF. Curative use occurs after ARF develops and
is aimed toward alleviating respiratory failure and avoiding tracheal intubation,
which is associated with increased morbidity and mortality [3].
30.2.6.1 Postoperative Prophylactic Use of NIV in Obese Patients

Gaszynski et al. [9] compared postoperative Boussignac CPAP delivered through a
facial mask with traditional oxygen delivery via nasal catheter in 19 morbidly obese
patients after open Roux-en-Y gastric bypass [9]. CPAP improved blood oxygenation compared with that achieved with standard treatment (PaO2 81.0 16.0 vs.
65.9 4.9 mmHg, p < 0.05) without influencing carbon dioxide clearance [9].
Neligan et al. [10] compared the effect of Boussignac CPAP (CPAP System;
Vitaid; Toronto, CA) on lung function to that of supplemental oxygen alone after
extubation of 40 morbidly obese patients with known OSA who received laparoscopic bariatric surgery [10]. FEV1, FVC, and peak expiratory flow were increased
by 35 % after administering CPAP immediately after extubation for the duration of
stay in the PACU (post-anesthesia care unit) and by 22 % after CPAP was applied
for at least 8 h overnight [10].
El-Solh et al. [11] evaluated NIV immediately after extubation of 62 consecutive
severely obese patients. NIV was delivered by the BiPAP mode (BiPAP S/T-D
Ventilatory Support System; Respironics Inc.; Murrysville, PA, USA) through a nasal
mask [11]. Compared with conventional therapy, BiPAP resulted in a 16 % absolute
risk reduction in the rate of respiratory failure [11]. There were significant differences
in the lengths of intensive care unit (ICU) and hospital stays between the two groups
[11]. Subgroup analysis of hypercapnic patients showed a reduced number of hospital
mortalities in the NIV group compared with that of the control group [11].
Joris et al. [12] investigated the effect of BiPAP (BiPAP System; Respironics Inc.;
Murrysville, PA, USA) delivered through a nasal mask on postoperative pulmonary
function in 33 morbidly obese patients after gastroplasty. Patients were assigned to
one of three types of ventilatory support during the first 24 h postoperatively: oxygen
via face mask, BiPAP 8/4, or BiPAP 12/4 [12]. Patients in the two BiPAP groups used
the mask at least 2 h out of every 3 h during the first 24 h postoperatively [12]. The
238
use of BiPAP 12/4, but not 8/4, allowed significant reduction in the magnitude of
pulmonary dysfunction after gastroplasty [12]. FVC and FEV1 were more than 50 %
greater in the BiPAP 12/4 group compared with those in the control group during 3
days of follow-up observation [12]. The peak expiratory flow rate was also increased
in the BiPAP 12/4 group (p = 0.10) [12]. Improved pulmonary function was associated with a significant increase in oxygenation in both BiPAP groups [12].
Zoremba et al. [13] prospectively studied 60 obese patients undergoing minor
peripheral surgery. Half were randomly assigned to receive short-term NPPV
(PSV + PEEP; Drger AG; Lbeck, Germany) through full face masks during their
PACU stays; the others received supplemental oxygen via Venturi masks [13].
Pulmonary function in the NPPV group was significantly better than that in the
control group (p < 0.0001) [13]. Blood gas levels and the alveolar to arterial oxygen
partial pressure difference were also improved (p < 0.03) [13]. These effects persisted for at least 24 h after surgery (p < 0.05) [13] (Fig. 30.1).
30.2.6.2 Postoperative Curative Use of NIV in Obese Patients

No data are available in the literature regarding the role of NIV for postoperative
treatment of ARF in obese patients.
In a study of 72 nonobese patients with ARF after abdominal surgery who
were treated with NPPV (PSV + PEEP; Servo-Ventilator 300; Siemens; Elema,
Sweden; or Evita 4; Drger Medical; Lbeck, Germany) via face mask, Jaber
et al. [14] found that 67 % of patients avoided intubation [14]. Within the first
NPPV observation period, a significant benefit was observed only in the NPPV
group, with increased PaO2/FiO2 (+36 29), decreased respiratory rate (from
28.2 3.4 to 23.1 3.8 breaths/min), reduced length of ICU stay, and reduced
mortality rate [14].
Fig. 30.1 Postoperative use of NIV in obese patients. (a) Prophylactic use of CPAP in an obese
patient after laparoscopic sleeve gastrectomy through a CPAP mask with integral Venturi flow
driver and adjustable PEEP valve (Ventumask; StarMed; Mirandola, Italy). (b) Therapeutic use of
NPPV (PSV + PEEP) in an obese patient with respiratory failure after gastric bypass surgery delivered by a helmet for NIV (CaStar R; StarMed; Mirandola, Italy). Written informed consent was
obtained from patients
30
239
One meta-analysis showed that NIV reduced reintubation rates (odds ratio (OR)
0.24), incidence of pneumonia (OR 0.27), and ICU length of stay (0.44 days) when
applied after major surgery [15]. There was insufficient evidence to suggest that
NIV improves ICU survival, but an increased hospital survival was observed when
NIV was used after surgery (OR 4.54) [15].
Conclusion
Obese patients present preoperative changes in respiratory function. Anesthesia

and surgery can profoundly impair respiratory function, increasing the risk of
postoperative respiratory complications and ARF. Evidence supports early
administration of NIV as a prophylactic and as a therapeutic tool after surgery in
obese patients for improving respiratory function and gas exchange. Selection of
the correct interface (face or nasal mask vs helmet) and the type of NIV (CPAP
vs NPPV) together with proper monitoring of the patient during NIV is fundamental for increasing the likelihood of success of NIV.
Obese patients have a restrictive pattern, which includes reduced lung volume and compromised respiratory system compliance. Obese patients may
be hypoxemic with increased at-rest consumption of oxygen. Carbon dioxide is usually close to normal.
Anesthesia, surgery, and postoperative pain further reduce lung volumes,
altering respiratory mechanics and gas exchange.
Early administration of NIV should be considered as a prophylactic and
therapeutic tool in obese patients after surgery to improve respiratory function and gas exchange and to avoid respiratory failure.
CPAP essentially decreases upper airway obstruction and increases oxygenation by recruiting and stabilizing previously collapsed lung tissue,
increasing lung volumes. NPPV unloads respiratory muscles, relieves dyspnea, and reduces the work required for breathing.
Conflict of Interest Disclosure The authors have no interests to disclose.
References
1. Adams JP, Murphy PG. Obesity in anaesthesia and intensive care. Br J Anaesth.
2000;85:91108.
2. Pelosi P, Gregoretti C. Perioperative management of obese patients. Best Pract Res Clin
2010;112:45361.
240
4. Pelosi P, Croci M, Ravagnan I, et al. Total respiratory system, lung, and chest wall mechanics
in sedated-paralyzed postoperative morbidly obese patients. Chest. 1996;109:14451.
5. Pelosi P, Croci M, Ravagnan I, et al. Respiratory system mechanics in sedated, paralyzed,
morbidly obese patients. J Appl Physiol. 1997;82:8118.
6. Carron M, Freo U, BaHammam AS, et al. Complications of non-invasive ventilation techniques:
a comprehensive qualitative review of randomized trials. Br J Anaesth. 2013;110:896914.
7. Masoomi H, Reavis KM, Smith BR, et al. Risk factors for acute respiratory failure in bariatric
surgery: data from the Nationwide Inpatient Sample, 20062008. Surg Obes Relat Dis.
2013;9:27781.
8. Morino M, Toppino M, Forestieri P, et al. Mortality after bariatric surgery: analysis of 13,871
morbidly obese patients from a national registry. Ann Surg. 2007;246:10027.
9. Gaszynski T, Tokarz A, Piotrowski D, et al. Boussignac CPAP in the postoperative period in
morbidly obese patients. Obes Surg. 2007;17:4526.
10. Neligan PJ, Malhotra G, Fraser M, et al. Continuous positive airway pressure via the
Boussignac system immediately after extubation improves lung function in morbidly obese
patients with obstructive sleep apnea undergoing laparoscopic bariatric surgery. Anesthesiology.
2009;110:87884.
11. El-Solh AA, Aquilina A, Pineda L, et al. Noninvasive ventilation for prevention of postextubation respiratory failure in obese patients. Eur Respir J. 2006;28:58895.
12. Joris JL, Sottiaux TM, Chiche JD, et al. Effect of bi-level positive airway pressure (BiPAP)
nasal ventilation on the postoperative pulmonary restrictive syndrome in obese patients undergoing gastroplasty. Chest. 1997;111:66570.
13. Zoremba M, Kalmus G, Begemann D, et al. Short term non-invasive ventilation post-surgery
improves arterial blood-gases in obese subjects compared to supplemental oxygen delivery a
randomized controlled trial. BMC Anesthesiol. 2011;11:10.
14. Jaber S, Delay JM, Chanques G, et al. Outcomes of patients with acute respiratory failure after
abdominal surgery treated with noninvasive positive pressure ventilation. Chest.
2005;128:268895.
2012;109:30514.
Noninvasive Ventilation After

Extubation in Obese Critically Ill
Subjects
31
Enrique Calvo-Ayala and Paul E. Marik
31.1
Introduction
Obesity has become a major public health problem, with recent data demonstrating
that about a third of the US population is obese [1]. The economic impact of obesity
is significant because of the associated comorbidities and the increased health-care
utilization of obese subjects [2]. This increasing proportion of obesity among the
overall population is reflected by the high proportion of obese subjects who are
admitted to intensive care units (ICUs). Some series have estimated that 1825 % of
critically ill subjects are obese [3, 4]. In this particular population, the most common reason for admission to an ICU is respiratory failure, and up to 55 % of obese
subjects who are admitted to an ICU require mechanical ventilatory support [5, 6].
This emphasizes the importance of understanding the mechanisms of respiratory
failure, ventilatory strategies, and the approach to weaning and extubation to
decrease the risk for reintubation and improve the outcomes in critically ill obese
patients. This last aspect is the focus of this chapter.
31.2
Effects of Obesity in the Respiratory System

and Physiologic Usefulness of Noninvasive Ventilation
Obese subjects have an increased oxygen demand as a consequence of the increased

body mass from excess adipose tissue [7]. Meeting this high oxygen demand is
challenging because obesity affects the respiratory system at different levels (lung
E. Calvo-Ayala, MD P.E. Marik, MD, FCCM, FCCP (*)

Division of Pulmonary and Critical Care Medicine, Department of Medicine, EVMS,
Eastern Virginia Medical School, 825 Fairfax Ave, Suite 410, Norfolk, VA 23507, USA
e-mail: marikpe@evms.edu
DOI 10.1007/978-3-319-04259-6_31
241
242
E. Calvo-Ayala and P.E. Marik
mechanics, lung ventilation/perfusion, respiratory muscles, and upper airways

obstruction) [8, 9]. Lung mechanics and lung volumes are significantly affected by
obesity. There is consensus that lung volumes are significantly reduced in obese
individuals, particularly functional residual capacity and expiratory reserve volume,
leading to a restrictive ventilatory defect [1012]. This restrictive defect is worsened by a generalized stiffness and low compliance of the respiratory system, which
has been attributed to increased blood volume within the lungs (caused by the augmented cardiac output from increased oxygen demand from excess adiposity), low
lung volumes, and an overall low chest wall compliance [8]. These changes are
exacerbated by a high airway resistance caused by parapharyngeal fat deposition in
the upper airway and low forced expiratory volume in 1 sec (FEV1) in these subjects, suggesting small airway remodeling.
Obese subjects also have a ventilation/perfusion mismatch. Although, in obesity,
the lower lung zones are well perfused, because of the aforementioned reasons,
there is closure of small airways in this region, making the lower zones relatively
hypoventilated. This closure of the small airways in the bases causes the ventilation
to be redistributed to the upper lobes, which are usually hypoperfused, resulting in
a ventilation-perfusion mismatch with subsequent hypoxemia. Lastly, obese subjects have respiratory muscle insufficiency from lack of endurance and fatigue from
increased work of breathing and relatively high oxygen consumption. These factors
all lead to increased risk of respiratory failure resulting from low respiratory reserve.
Noninvasive ventilation (NIV) helps overcome some of the aforementioned
effects of obesity by (a) stenting the upper airway; (b) unloading the respiratory
muscles, reducing the work of breathing; and (c) increasing the lung volume, augmenting alveolar ventilation and reversing atelectasis [13].
31.3
Weaning Mechanical Ventilation in the Obese Patient:

The Role of NIV
International guidelines and consensus statements recommend liberating patients

from mechanical ventilation as soon as possible while making every effort to
decrease the chances for reintubation [14, 15]. The steps required to achieve these
goals include assessment of readiness for extubation, performance of a spontaneous
breathing trial, and consideration of NIV after extubation. These basic principles
should be applied to obese critically ill subjects with some modifications.
Once the underlying triggering factor for respiratory failure has been identified
and adequately treated, clinical assessments are needed to determine the patients
readiness for discontinuation of ventilator support and extubation. Although there is
no consensus about the parameters that need to be met to deem a patient ready for
extubation, in general, there should be adequate oxygenation (SpO2 > 90 % or
PaO2 > 60 mmHg), adequate acid base status (pH of 7.40 0.05), hemodynamic stability, and adequate mental status. The first (and probably most important) consideration in obese subjects is that, because of their relatively high intrapleural pressure,
the level of positive end-expiratory pressure (PEEP) that is needed to keep the
31
Noninvasive Ventilation After Extubation in Obese Critically Ill Subjects
243
alveoli recruited may be higher than the level recommended by the guidelines to
deem the patient ready (usually the guidelines recommend a PEEP between 5 and
8 cmH2O) [14]. In general, because of the altered lung mechanics in obese subjects,
we advocate the measurement of esophageal pressures as a surrogate for the pleural
pressure, with titration of PEEP to maintain the transpulmonary pressure gradient
(pressure in the airway pleural pressure) between 0 and 5 cm H2O [16]. In our
experience, the mean end-expiratory esophageal pressure of severely morbidly
obese subjects is approximately 17 cmH2O [17], which means that these patients
should be kept on a relatively high PEEP even when considering extubation. This
requirement is one of the justifications to extubate these patients to NIV. If the
esophageal manometry is not available, it is reasonable to keep the PEEP between
10 and 15 cmH2O based on previously published observational studies [8]. These
data suggest that obese subjects can be deemed ready for extubation if they meet the
aforementioned criteria, even if the PEEP is relatively high.
Once the subject is ready for extubation, then the next step is to proceed with a
spontaneous breathing trial (SBT). Although the literature recommends the use of
either a T-piece trial or a trial under PEEP and some pressure support ventilation,
based on the lung mechanics of the obese subjects it is recommended that they
undergo a SBT maintaining the same level of PEEP used during the acute phase
with some pressure support. The criterion for failure of SBT in obese subjects does
not differ from the general population and includes tachypnea, hypoxemia, tachycardia, hemodynamic instability, or signs of respiratory distress (thoracoabdominal
paradox, use of accessory muscles for respiration). If none of the criteria for failure
are present during the SBT, then extubation should follow. If a high level of PEEP
has been maintained during the weaning process, it is reasonable to extubate to
NIV. Even if the PEEP is at a low level (<8 cmH2O), NIV should still be considered
in obese subjects being liberated from invasive mechanical ventilation.
31.4
Preparing for NIV After Extubation
As reviewed above, NIV overcomes many of the obesity-related physiologic abnormalities that affect the respiratory system. There are, however, no randomized controlled trials that have investigated the effects of NIV when used after extubation in
critically ill obese subjects. A single before-after study has shown a positive outcome (decreased length of ICU and hospital stays) with NIV in obese patients [18].
Studies performed in the postoperative period have shown beneficial outcomes
when NIV is used routinely after extubation [19, 20]. Because of the anticipated
need for high pressure, a facial mask is preferred in these cases. Adequate fitting of
the face mask is essential for optimal use of NIV. Face masks have the advantage of
achieving a better seal with less air leak and better minute ventilation [21]. Based on
previously published data and our experience, we recommend extubating obese
patients directly to bi-level positive airway pressure ventilation. The inspiratory
positive airway pressure (iPAP) should be titrated to optimize minute ventilation.
There is no consensus on the amount of iPAP that needs to be provided in this
244
E. Calvo-Ayala and P.E. Marik
particular setting, however, it is acceptable to start with a pressure difference

between iPAP and expiratory positive airway pressure (ePAP) of at least 67 cmH2O,
but higher pressures may be required to achieve the desired ventilation. With the
same rationale, ePAP should be high enough to overcome the high intrapleural pressure of these subjects and should be kept around the same level as the PEEP prior to
extubation.
There is no standard approach to weaning patients from NIV. In general, NIV is
discontinued for short periods of time to allow for facial hygiene, oral medications,
and small sips of fluid and enteral nutrition supplements. If there is immediate deterioration, then NIV is resumed, however, the goal should be to progressively increase
the periods of time where the patient is off NIV. We usually attempt to continue
intermittent NIV support indefinitely. At this point, we initiate a diagnostic workup
to document the presence of obesity hypoventilation syndrome (OHS), sleep apnea,
or both so that patients can be discharged with positive airway pressure therapy that
they can use at home.
Key Points
NIV is an option when considering extubation of obese subjects.

High PEEP and ePAP is recommended when using mechanical ventilation
in obese individuals. We strongly recommend the use of esophageal
manometry to guide this decision.
Because of the advantages of tidal volume delivery and less leakage, we
recommend the use of a full face mask when using NIV in obese
subjects.
There is no consensus on how to wean patients from NIV. We recommend
the use of intermittent NIV (with naps and during sleep) for an indefinite
period of time in patients who meet criteria for OHS or sleep apnea.
Conflict of Interest None
References
1. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US
adults, 19992008. JAMA. 2010;303(3):23541.
2. Finkelstein EA, Ruhm CJ, Kosa KM. Economic causes and consequences of obesity. Annu
Rev Public Health. 2005;26:23957.
3. Ray DE, Matchett SC, Baker K, Wasser T, Young MJ. The effect of body mass index on patient
outcomes in a medical ICU. Chest. 2005;127(6):212531.
4. Sakr Y, Madl C, Filipescu D, et al. Obesity is associated with increased morbidity but not
mortality in critically ill patients. Intensive Care Med. 2008;34(11):19992009.
5. Akinnusi ME, Pineda LA, El Solh AA. Effect of obesity on intensive care morbidity and mortality: a meta-analysis. Crit Care Med. 2008;36(1):1518.
6. Winkelman C, Maloney B. Obese ICU patients: resource utilization and outcomes. Clin Nurs
Res. 2005;14(4):30323; discussion 3246.
31
Noninvasive Ventilation After Extubation in Obese Critically Ill Subjects
245
7. Alpert MA. Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome.
Am J Med Sci. 2001;321(4):22536.
8. Ashburn DD, DeAntonio A, Reed MJ. Pulmonary system and obesity. Crit Care Clin.
2010;26(4):597602.
9. Bahammam AS, Al-Jawder SE. Managing acute respiratory decompensation in the morbidly
obese. Respirology. 2012;17(5):75971.
10. Jones RL, Nzekwu MM. The effects of body mass index on lung volumes. Chest.
2006;130(3):82733.
11. Pelosi P, Croci M, Ravagnan I, et al. The effects of body mass on lung volumes, respiratory
mechanics, and gas exchange during general anesthesia. Anesth Analg. 1998;87(3):65460.
12. Behazin N, Jones SB, Cohen RI, Loring SH. Respiratory restriction and elevated pleural and
esophageal pressures in morbid obesity. J Appl Physiol. 2010;108(1):2128.
13. Organized jointly by the American Thoracic Society, the European Respiratory Society, the
European Society of Intensive Care Medicine, and the Socit de Ranimation de Langue
Franaise, and approved by ATS Board of Directors, December 2000. International Consensus
Conferences in Intensive Care Medicine: noninvasive positive pressure ventilation in acute
Respiratory failure. Am J Respir Crit Care Med. 2001;163(1):28391.
14. MacIntyre NR, Cook DJ, Ely Jr EW, et al. Evidence-based guidelines for weaning and discontinuing ventilatory support: a collective task force facilitated by the American College of Chest
Physicians; the American Association for Respiratory Care; and the American College of
Critical Care Medicine. Chest. 2001;120(6 Suppl):375S95.
15. Boles JM, Bion J, Connors A, et al. Weaning from mechanical ventilation. Eur Respir J. 2007;
29(5):103356.
16. Akoumianaki E, Maggiore SM, Valenza F, et al. The application of esophageal pressure measurement in patients with respiratory failure. Am J Respir Crit Care Med. 2014;189(5):
52031.
17. Marik PE, Desai H. Characteristics of patients with the malignant obesity hypoventilation
syndrome admitted to an ICU. J Intensive Care Med. 2013;28(2):12430.
18. El-Solh AA, Aquilina A, Pineda L, Dhanvantri V, Grant B, Bouquin P. Noninvasive ventilation
for prevention of post-extubation respiratory failure in obese patients. Eur Respir J. 2006;
28(3):58895.
19. Pankow W, Hijjeh N, Schuttler F, et al. Influence of noninvasive positive pressure ventilation
on inspiratory muscle activity in obese subjects. Eur Respir J. 1997;10(12):284752.
20. Huerta S, DeShields S, Shpiner R, et al. Safety and efficacy of postoperative continuous positive airway pressure to prevent pulmonary complications after Roux-en-Y gastric bypass.
J Gastrointest Surg. 2002;6(3):3548.
21. Navalesi P, Fanfulla F, Frigerio P, Gregoretti C, Nava S. Physiologic evaluation of noninvasive
mechanical ventilation delivered with three types of masks in patients with chronic hypercapnic respiratory failure. Crit Care Med. 2000;28(6):178590.

in Patients with Neuromuscular Disease
32
Fabrizio Racca, Chiara Robba, and Maria Pia Dusio
32.1
Introduction
Respiratory failure is the most common cause of morbidity and mortality in patients
with progressive neuromuscular diseases (NMDs) [14]. The wide variety of NMDs
that can affect respiratory function are listed in Table 32.1. NMDs are often complicated by progressive involvement of the respiratory muscles and can lead to both
chronic and acute respiratory failure (ARF). Reduced inspiratory muscle strength
can result in ineffective alveolar ventilation, and weakness of expiratory muscles
can lead to inadequate clearance of airway secretions. Thus, these conditions can
cause chronic respiratory failure as well as potentially life-threatening problems
[510].
Once patients with NMDs develop respiratory failure, noninvasive mechanical
ventilation (NIV) combined with techniques of manually or mechanically assisted
coughing are the main therapeutic interventions to support their respiratory function
[510]. This chapter reviews the pathophysiological mechanisms responsible for
respiratory failure in patients with slowly progressive NMDs (e.g., amyotrophic
lateral sclerosis (ALS), spinal muscular atrophy (SMA), Duchenne muscular dystrophy (DMD)) and the issues concerning their respiratory care during ARF. We do
F. Racca, MD (*)
Anesthesiology and Intensive Care Unit, SS Antonio Biagio e Cesare Arrigo Hospital,
Alessandria, Italy
S.C. Anestesia e Rianimazione Pediatrica Azienda Ospedaliera SS Antonio Biagio e Cesare
Arrigo, Via Venezia 16, 15100 Alessandria, Italy
e-mail: fracca7766@gmail.com
C. Robba M.P. Dusio
Anesthesiology and Intensive Care Unit, SS Antonio Biagio e Cesare Arrigo Hospital,
Alessandria, Italy
DOI 10.1007/978-3-319-04259-6_32
247
F. Racca et al.
248
Table 32.1 Neuromuscular diseases affecting respiratory function in children
1. Motor neuron diseases: Spinal muscular atrophy (SMA), amyotrophic lateral sclerosis
(ALS)
2. Peripheral neuropathies: GuillainBarr syndrome (GBS), chronic inflammatory
demyelinating polyneuropathy (CIDP), critical illness polyneuropathy
3. Disorders of neuromuscular junction: Myasthenia gravis (MG)
4. Myopathies
4.1 Progressive muscular dystrophies: Duchenne muscular dystrophy (DMD),
facioscapulohumeral muscular dystrophy (FSHD), limb-girdle muscular dystrophies
(LGMD), myotonic dystrophies
4.2 Congenital myopathies (e.g., central core diseases, myotubular myopathy, nemaline
myopathy, myofibrillar myopathies)
4.3 Congenital muscular dystrophies (e.g., merosin-deficient CMD)
4.4 Metabolic myopathies (Mitochondrial myopathies, glycogen storage diseases)
not consider rapidly progressive NMDs (e.g., Guillain-Barr syndrome and myasthenic crises) because there is currently insufficient data to support the extensive use
of NIV in these patients, and clinical issues arising from their rapid clinical evolution deserve separate remarks.
32.2
Mechanisms Underlying Respiratory Failure in NMDs
Patients with NMDs can develop respiratory failure because of an imbalance

between respiratory load and muscle strength, resulting in ineffective alveolar ventilation and hypercapnia. The main determinant of this process is the respiratory
muscles weakness [3]. In addition, patients with slowly progressive NMD have a
chronically elevated respiratory load, which leads to increased work of breathing
[1113]. The main contributions to the increased mechanical load are as follows:
1. Inability to achieve an effective lung expansion, resulting in progressive occurrence of microatelectasis [12, 13]
2. Stiffening of the chest wall, caused by muscle atrophy, osteoporosis, and in some
cases extra-articular contractures and intra-articular adhesions, progressing to
the irreversible degeneration of the joint cartilage of the rib cage [14]
3. Spinal deformities (e.g., thoracic scoliosis), contributing to increased work of
breathing [11] and leading to mechanical embarrassment of the respiratory muscles, impairing their contractile function [12]
As the NMD progresses, nocturnal respiratory dysfunction becomes evident and
can result in hypercapnia that is initially limited to sleep. With the progression of the
NMD, hypoventilation becomes chronic, resulting in daytime hypercapnia.
Additionally, weakness of expiratory muscle leads to inadequate clearance of airway secretions.
32
Noninvasive Mechanical Ventilation in Patients with Neuromuscular Disease
249
Table 32.2 Causes of acute exacerbations of chronic respiratory failure in children with NMD
Upper respiratory tracts infections
Pneumonia
Atelectasis
Aspiration
Pneumothorax
Cardiac failure
Tracheal hemorrhage (patients with tracheostomy)
Acute gastric distension (patients under mechanical ventilation)
Abuse of sedative drugs
Postoperative respiratory failure
Pulmonary embolism
Patients with NMD may require intensive care because of the progressive respiratory muscle dysfunction. Their admission to the intensive care unit (ICU) is usually prompted by precipitating factors (Table 32.2). In particular, ARF usually
occurs in NMD patients as a consequence of otherwise benign upper respiratory
tract infections [1517] or as a result of more severe respiratory complications, such
as pneumonia, aspiration, atelectasis, and pneumothorax [18, 19]. During these
events, the inspiratory muscles strength cannot compensate for the increased respiratory load, resulting in impaired alveolar ventilation. Moreover, weakness of expiratory and bulbar muscle causes ineffective coughing and airway mucus
accumulation that further increases the work of breathing, leading to respiratory
distress [1517, 20].
Patients with NMD usually experience mild to moderate bulbar dysfunction,
with the exception of patients diagnosed with type 1 SMA and ALS, who may
develop a severe glottis functional impairment. Bulbar muscle weakness (facial,
oropharyngeal, and laryngeal muscles) can affect the ability to swallow, leading to
a risk of aspiration.
Additionally, several myopathies (DMD, limb-girdle muscular dystrophies,
myotonic dystrophies, myofibrillar myopathies, mitochondrial myopathies, and
glycogen storage diseases) are associated with cardiac dysfunctions (dilated cardiomyopathy and/or abnormalities of the conduction system) [21, 22], which may also
contribute to the development of ARF [23].
In NMD patients with compromised respiratory function, anesthetic agents
may further decrease respiratory muscles strength and can exacerbate hypoventilation, airway secretions retention, aspiration, and obstructive and central apneas
[5, 7, 24]. These conditions may lead to nosocomial infections, prolonged intubation, tracheotomy, and eventually death. Therefore, in all patients with NMDs,
preoperative pulmonary evaluation is strongly recommended to assess the risk of
respiratory complications and when respiratory function measurements and/or
sleep studies are abnormal, NIV and assisted cough techniques may be indicated
[5, 7, 24].
250
32.3
F. Racca et al.
Diagnostic Process
The early identification of precipitants to intensive care admission (Table 32.2) is

essential because they are more amenable to therapy than the NMD itself [10, 18,
2528]. The overall diagnostic process is summarized below [10].
History: rule out abuse of sedative drugs, aspiration, and anticipatory care plan
(i.e., a do not intubate order)
Physical examination: rule out signs and symptoms of:
Heart failure (pulmonary crackles, peripheral edema, elevated jugular venous
pressure, pleural effusion, hepatic congestion)
Clinical signs of pneumonia, aspiration, or atelectasis
Pneumothorax
Lab tests:
Serum B-natriuretic peptide and D-dimer (good negative predictive values for
heart failure and pulmonary embolism)
Blood and sputum culture with Gram stain if pneumonia is suspected
Imaging:
Electrocardiogram to rule out arrhythmias and conduction defects
Chest X-ray to rule out cardiomegaly, pulmonary congestion, new pulmonary
infiltrate, and pneumothorax (mandatory computed tomography (CT) scan in
case of suspected pneumothorax and non-conclusive chest X-ray)
Echocardiogram to evaluate ventricular function if heart failure is suspected
It is important to note that pneumothorax is a rare but serious and life-threatening
complication in NMD patients. Conventional chest X-ray has poor sensitivity for
the detection of pneumothoraces and thoracic CT may be required [18]
32.4
Respiratory Management
Respiratory management of NMD patients includes invasive or noninvasive

mechanical ventilation, assisted coughing techniques, and the extubation process.
32.4.1 Mechanical Ventilation

NIV combined with mechanically assisted coughing is an established standard technique in patients with NMDs without severe bulbar impairment who require
mechanical ventilation (MV) for ARF. This strategy may represent an effective lifesupport measure and a good alternative to invasive MV, either as an outpatient or in
the ICU [16, 17, 2629]. Mechanical ventilation should be considered in NMD
patients with acute exacerbation who have at least one of the following issues: (1)
dyspnea, as referred by the patient; (2) lethargy; and (3) acute respiratory acidosis
(i.e., arterial pH below 7.35 with PaCO2 greater than 45 mmHg) [27]. Most of these
32
251
patients benefit from NIV. For patients already using nocturnal NIV, daytime NIV
may be required during acute exacerbations [34, 35].
NIV is contraindicated in patients with severe inability to swallow; uncontrollable airway secretions; life-threatening hypoxemia; severely impaired mental status;
hemodynamic instability; recent facial, upper airway, or upper gastrointestinal tract
surgery; or bowel obstruction [26, 27, 36, 37].
Invasive ventilation should be considered if, despite 612 h of NIV with optimal
ventilator settings, it proves impossible to reduce dyspnea or lethargy, to decrease
the respiratory rate, or to improve blood gas exchange (i.e., refractory arterial pH
below 7.30 or below the value on admission or failure to maintain a PaO2 > 65 mmHg
with a FIO2 0.6) [27, 36].
Hospital admission can be disruptive for these patients [38], who can often be successfully managed at home by experienced and well-trained family members [30].
Bach and colleagues [16, 17, 29, 39] described a regimen for managing acute on
chronic neuromuscular respiratory failure at home. The patients received a 24-h NIV
during the exacerbation periods. Oxygen saturation of room air was monitored continuously and when it fell below 95 %, secretions were aggressively removed using
MI-E (mechanical insufflation-exsufflation) until oxygen saturation returned to the
95 % range. Although controlled studies establishing the efficacy of this approach are
lacking, the authors reported a dramatic reduction in the need for hospitalization and
a prolongation of life expectancy. Vianello et al. [40] showed that hospital at home
for NMD patients with respiratory tract infection for whom hospital admission had
been recommended after medical assessment is an effective alternative to hospital
admission. They treated these patients according to the following treatment protocol:
District nurses visited the subjects mornings and afternoons until recovery from
exacerbation. The nurse assessed the subjects adherence and response to treatment and could request a pulmonology visit if clinical progress was
unsatisfactory.
A pulmonologist visited the subjects each morning for the first 3 days, and thereafter at the discretion of the district nurses or subjects general practitioner, to
assess the response to therapy and eventually introduce changes.
Subject telephone access to the pulmonologists was ensured.
The subjects general practitioners were informed of the subjects being randomized to the hospital-at-home program.
Standard antibiotic therapy was used, following guidelines for the management
of acute bronchitis or community-acquired pneumonia.
The ventilator was readjusted to obtain a tidal volume of 1012 ml/kg and a
breathing frequency of <25 breaths/min and to maintain SpO2 95 %. NIV was
initially delivered continuously, except for 3060 min periods of rest to allow
the subject to receive liquid dietary supplements, drink water, and speak. After
the first 2448 h, if clinical conditions and blood gas exchange were satisfactory,
the application of NIV was interrupted by progressively longer intervals of
spontaneous breathing. In all cases, nocturnal ventilation via nasal mask was
continued until the end of the follow-up period.
252
F. Racca et al.
Manually and mechanically assisted cough were provided whenever SpO2

decreased, the ventilator peak inspiratory pressure increased, or the subject had
a respiratory deterioration or sense of retained secretions. Assisted cough treatments were usually repeated until one or more of the following factors were
observed: improving dyspnea, reduction in breathing frequency, sputum elimination, or increased SpO2. Manually and mechanically assisted cough were administered for the first 3 days of the home-care protocol by a respiratory therapist
who visited the subjects each morning, and by nonprofessional caregivers (i.e.,
the subjects home care attendant or a family member) trained in the application
of the device. Subsequently, assisted cough was independently administered by
home caregivers.
Hospital-at-home subjects received pulse oximeter monitoring, and their caregivers were instructed to perform assisted coughing, NIV, or both as needed to
return SpO2 95 %.
If home management fails, patients must be hospitalized and they should be
managed in an ICU, where a cough machine and NIV should be applied aggressively. NIV and assisted coughing techniques have become a standard therapy for
the treatment of acute on chronic neuromuscular respiratory failure also in the critical care setting [2628, 30, 36, 37]. The increased utilization of NIV has been
driven in large part by the need to reduce patient discomfort and to avoid sedation
and complications of invasive MV [41].
In particular, Vianello and colleagues [27] demonstrated that in the NIV group
compared with the invasive MV group, intrahospital mortality (14 % vs 57 %),
treatment failure (29 % vs 79 %), and duration of ICU stay (13.6 9.7 vs 47.1
51.9 days) were lower. Interestingly, superimposed or unresolved pneumonia with
septic shock was absent in individuals receiving nasal intermittent positive pressure
ventilation (NIPPV). These complications represented the cause of failure in 6 of
the 11 subjects unsuccessfully treated via translaryngeal tube. In addition, the
results of another prospective cohort study evaluating only NMD patients treated
with a noninvasive approach (NIV and MI-E) showed a low mortality rate (8.3 %)
and a short hospital stay (12.05 7.03 days) [26].
Moreover, Servera et al. [26] treated 24 consecutive episodes of ARF in 17
patients with neuromuscular disease using NIV and mechanical coughing aids.
They showed that noninvasive management was successful in averting death and
endotracheal intubation in 79.2 % of the acute episodes.
The role of NIV as a reliable alternative to intubation is indirectly supported by
two clinical studies conducted in patients with NMDs treated with invasive MV for
ARF [38, 42]. In these studies, the mortality rate was 29 % and 32.8 %, respectively.
Moreover, Bradley and colleagues [38] reported a median weaning time period
before being discharged to the community of 10 weeks among survivors.
Patient selection remains crucial for the success of this ventilatory strategy.
Bulbar dysfunction increases the patients risk for aspiration, hampers the elimination of airway secretions, and increases resistance to airflow [26, 41, 43]. Therefore,
it can decrease the possibilities of successful use of NIV and MI-E [44]. In addition,
32
253
patient training in NIV and assisted coughing before hospitalization is important to

the success of this therapeutic approach [45].
In conclusion, there are only few prospective studies concerning the management of patients with NMDs presenting acute on chronic respiratory failure [26
28]. This is probably because it is methodologically difficult to recruit patients with
NMDs presenting with ARF [41]. These trials and other retrospective studies [16,
17, 29, 3133, 39, 44, 46] reported the successful use of NIV in improving gas
exchange abnormalities and avoiding intubation in this group of patients. Therefore,
a noninvasive approach (e.g., NIPPV combined with assisted coughing) is always
preferred where feasible. If it fails or is contraindicated (e.g., because of severe
bulbar impairment), patients can require endotracheal intubation as a short-term
measure.
32.4.2 Assisted Coughing Techniques

Cough augmentation is a necessary part of the noninvasive respiratory management
of patients with NMD with respiratory insufficiency. Previous research has demonstrated that cough peak flows (CPFs) relate directly to the ability to clear secretions
from the respiratory tract. The normal CPF in adults exceeds 360 l/min. In NMDs,
patients with a CPF of >270 l/min are thought to have an adequate cough. Studies
have demonstrated that a CPF of <160 l/min is associated with diminished cough
effectiveness and that cough augmentation is required. Patients with a CPF between
160 and 270 l/min have an adequate cough when they are well. However, these
patients get weaker with the progression of the illness (e.g., upper respiratory tract
infections) and CPF can often drop below 160. Therefore, patients with CPF < 270 l/
min benefit from cough-assisted maneuvers during ARF [5, 47].
In patients with acute exacerbation of respiratory failure, techniques to improve
airway clearance and MV should always be considered as integrated first-line therapy. In particular, during acute illness, assisted coughing techniques should be used
in case of (1) oxygen desaturation, (2) increased dyspnea, (3) patient sense of
retained secretions, (4) presence of auscultatory rhonchi, and (5) increased ventilator peak airway pressure [16, 26, 28].
Effective secretion clearance is crucial for patients with NMD to prevent atelectasis, pneumonia, and ARF and to reduce hospitalization. Thus, in these patients, the
use of airway clearance techniques is strongly recommended and should be always
included in the noninvasive approach to treat respiratory tract infections [23, 34].
Mechanical coughing aids include techniques of manually or mechanically assisted
coughing.
Manual assisted coughing techniques include inspiratory assistance followed by
augmentation of the forced expiratory effort. An improvement of the inspiratory
capacity can be achieved by a series of tidal breaths without exhalation between
them (i.e., air stacking), obtained with the application of positive pressure with selfinflating bags or mechanical ventilators. Forced exhalation is augmented by pushing
on the upper abdomen (i.e., abdominal thrust) or chest wall (i.e., anterior chest
254
F. Racca et al.
compression) in synchrony with the subjects own cough effort [23]. Nevertheless,
manually assisted coughing requires patient cooperation.
The mechanical insufflator-exsufflator (MI-E or cough machine) is a device
that generates a deep insufflation by a positive pressure blower (i.e., + 3040 cm
H2O) followed immediately by a forced exsufflation in which high expiratory flow
rates are determined by a deep negative pressure (i.e., 30 to 40 cmH2O) [48]. A
range of insufflation of +15 to 40 cmH2O and exsufflation of 20 to 50 cmH2O have
been suggested for the application of MI-E for pediatric patients [49]. The MI-E
may be applied via a full face mask or via endotracheal or tracheostomy tube with
the cuff inflated. Cough flow rates delivered by MI-E were shown to be superior to
those generated by manual-assisted coughing techniques alone [50]. The use of a
MI-E via a face mask increases peak cough flow and aids airway clearance. This
device has been demonstrated to be more effective than other techniques to clear
secretions from the respiratory tract in patients with NMDs [28, 4951]. Treatment
with the MI-E can be required as frequently as every few minutes around the clock
until no further secretions are present [26, 27].
Bronchoscopy should be considered only in cases of persistent atelectasis after
all noninvasive airway clearance techniques have proven to be unsuccessful [23].
32.4.3 Extubation Process

After recovery from the acute illness, patients who do not have severe bulbar impairment should be promptly extubated and started immediately on NIV [10, 52, 53].
Unfortunately, because of the weakness of the inspiratory muscles, inadequate
cough, and inability to handle oropharyngeal secretions, a substantial proportion of
patients with NMD who undergo invasive mechanical ventilation fail to pass spontaneous breathing trials after recovery from the acute illness and are at high risk for
extubation failure [2, 38, 54, 55]. It should be emphasized that extubation failure is
an outcome to be avoided because it is independently associated with increased
hospital mortality, prolonged ICU and hospital stay, higher costs, and greater need
for care. Therefore, strategies preventing this occurrence are required.
NMD patients are considered at high risk of extubation failure in the presence of
one or more of the following conditions:
Ineffective cough, defined as peak cough expiratory flow less than 160 l/min
Hypercapnia during spontaneous breathing trials
History of extubation failure
Failed multiple spontaneous breathing trials
Early application of NIV combined with cough-assist techniques can increase

the possibility of successful extubation in these patients. Vianello et al. [56] demonstrated that patients with NMDs who received NIV combined with assisted cough
were less likely to require reintubation and tracheotomy compared with historical
controls who had received standard medical treatment consisting in supplemental
oxygen and conventional chest physical therapy. Moreover, Bach et al. [52] reported
32
255
Table 32.3 Extubation criteria for patients with NMD at high risk of extubation failure
Afebrile and normal white blood cells count
PaCO2 40 mmHg at peak inspiratory pressures < 35 cmH2O on full-setting assist/control
mode
SpO2 95 % for 12 h or more in ambient air
All oxyhemoglobin desaturations <95 % reversed by cough machine and suctioning via
translaryngeal tube
Fully alert and cooperative, receiving no sedative medications
Chest radiograph abnormalities cleared or clearing
Air leakage via upper airway sufficient for vocalization upon cuff deflation
SpO2 pulse oxyhemoglobin saturation
the results of a large uncontrolled study performed on a NMD population that also
included patients with acquired critical care myopathy, showing that the standardized use of NIV and cough assistance leads to successful extubation in almost all
cases of NMD patients.
Bach et al. [52] developed a NMD-specific extubation protocol and NMDspecific extubation criteria. While intubated, ventilatory support was used to maintain normocapnia and normal respiratory rates. A cough machine was used at 40
to + 40 cmH2O or greater with exsufflation-timed abdominal thrusts. The cough
machine sessions were up to every 20 min to maintain or return the pulse oxyhemoglobin saturation (SpO2) to 95 % in ambient air. Once extubation criteria
(Table 32.3) were met, the orogastric or nasogastric tube was removed to facilitate
post-extubation nasal NIV. The patient was then extubated directly to NIV on assist/
control on room air. NIV was provided via a combination of nasal, oronasal, and
mouthpiece interfaces. For episodes of SpO2 < 95 %, ventilator setting, interface air
leakage, CO2 retention, and cough machine were considered. The therapists, nurses,
and, in particular, the family and personal care attendants provided Mechanical
assisted cough via oronasal interfaces up to every 20 min until the SpO2 no longer
dipped below 95 % and the patients felt comfortable and clear of secretions.
Tracheostomy may be required, but it should not be considered in the acute
phase. Tracheotomy would be recommended if the extubation criteria (Table 32.3)
could not be met within 2 weeks of application of the protocol [52].
Conclusion
In conclusion, when patients with NMDs develop respiratory failure, a noninvasive approach is preferred where feasible. For patients who do not have severe
bulbar impairment, the use of NIV in combination with assisted coughing is an
effective alternative to invasive ventilation. Moreover, ARF is usually prompted
by precipitating factors, whose identification is essential because they are amenable to therapy. If a noninvasive approach fails, patients can be intubated and
mechanically ventilated as a short-term measure. After recovery from the acute
illness, patients without severe bulbar impairment should be promptly extubated
and treated with NIV combined with assisted coughing. Finally, tracheotomy can
be considered, but not as an acute intervention.
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F. Racca et al.
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Dysphagia in Post-extubation
Respiratory Failure: Potential
Implications of Noninvasive Ventilation
33
Alberto Fernndez Carmona, Aida Daz Redondo,

and Antonio M. Esquinas
33.1
Introduction
Dysphagia is defined as a patient-perceived difficulty in swallowing solid and liquid

foods. It can manifest in variable forms: from a delay in food bolus formation or
movement to pathological displacement with passage of the bolus into the airway.
The consequences of dysphagia can be serious and may involve important mortality
when dehydration, malnutrition, and/or tracheobronchial aspiration are produced.
The penetration and aspiration of oropharyngeal secretions, food, and gastric
contents in the upper bronchial tree give rise to an inflammatory response that stimulates mucosal secretion. This, in turn, gives rise to bronchorrhea and to a series of
respiratory alterations ranging from conditions characterized by a good prognosis,
such as atelectasis or chemical pneumonitis (Mendelsons syndrome), to severe
respiratory infections or acute respiratory distress syndrome (ARDS) in fragile
patients or individuals who are recovering from serious conditions. The risk of
bronchoaspiration in patients with oropharyngeal dysphagia is 11 times greater than
in patients without swallowing difficulties [7, 8].
The incidence of pharyngeal and laryngeal incompetence in patients with disorders of neuromuscular origin is high, with variations in its frequency of manifestation, severity, and treatment options. Series of patients with disorders as common as
A.Fernndez Carmona, MD (*)

Intensive Care Unit, Virgen de las Nieves Hospital, Granada, Spain
e-mail: albertofernandezcarmona@gmail.com
A.Daz Redondo, MD
Critical Care and Emergency Unit, San Cecilio Hospital, Granada, Spain
A.M. Esquinas, PhD, MD, FCCP
Intensive Care Unit, Morales Meseguer Hospital, Murcia, Spain
e-mail: antmesquinas@gmail.com
DOI 10.1007/978-3-319-04259-6_33
259
260
A.F. Carmona et al.
cerebrovascular stroke have been reported in which 94 % of the subjects were seen
to suffer some degree of dysphagia, in an important number of cases with a good
response to conventional rehabilitation therapy. The persistence of dysphagia in
these patients was associated with a poorer prognosis, a prolonged hospital stay, and
increased admission to homes for the elderly, worsening of quality of life, and
dependency for activities of daily living [1].
The incidence of pharyngeal and laryngeal incompetence (typically in the intraglottic/subglottic region) in patients requiring an artificial airway has not been
clearly established. Some studies suggest an incidence range from 3 to 62 % in
recently extubated patients, that is, post-extubation dysphagia (PED) [2-4]. In a
large cohort of critically ill patients, dysphagia (non-neurologic) was present in
84 % of patients and between 50 and 84 % of patients required tracheotomy [1, 2].
Translaryngeal intubation can affect the laryngeal structures as a result of direct
impact during intubation, in the course of prolonged intubation, in restless patients,
as a consequence of abrasion of the laryngeal mucosa, or secondary to the mere
presence of the orotracheal tube. Common findings are vocal cord edema and swelling of the supraglottic space (Fig. 33.1), with a less frequent observation of granulomas at this level. Other infrequent findings are arytenoid subluxation or luxation
(Fig. 33.2) or vocal cord paralysis secondary to direct damage or involvement of the
recurrent nerves. The orotracheal (translaryngeal) tube keeps the glottis open for
prolonged periods of time, abolishing the natural movements of the larynx and of
pharyngeal muscles. This, in turn, leads to muscle atrophy, weakness of the pharyngolaryngeal muscles, and stiffness of the tongue, pharynx, hypopharynx, and larynx. The intrinsic movements of the larynx, such as reflex glottic closure during
swallowing, are affected. The edema produced as a result of the indwelling foreign
Fig. 33.1 Vocal cord edema
33 Dysphagia in Post-extubation Respiratory Failure
261
Fig. 33.2 Arytenoid

subluxation
body (translaryngeal tube) and the absence of correct stimulation of the laryngeal
and hypopharyngeal mechanoreceptors cause a decrease in sensitivity to the presence of secretions, altering the complex swallowing mechanism, which in turn can
facilitate laryngeal penetration or tracheal aspiration. The length of time intubated
is the most deleterious condition for the development of PED because of muscle
atrophy, and impairment of the nerve endings in the glottic and subglottic region,
interruption of air passage through the glottis, and the loss of pressure in the subglottic region directly affect the cough reflex, laryngeal adduction, and glottis closing capacity. The glottic and subglottic muscles are affected not only by
polyneuropathy in the critical patient but also largely by a lack of use. In fact, restoring air passage through the glottis after extubation or using fenestrated cannulas
and/or speaking valves facilitates rehabilitation and posterior recovery from such
alterations, in addition to correction of the swallowing and speech mechanisms.
The studies conducted to date in relation to laryngeal PED comprise a limited
number of heterogeneous patients [4]. In such studies, it is important to note that,
hours after intubation, patients may develop laryngeal alterations that can persist
for prolonged periods of time. A recent series has reported that in the first 24 h after
extubation, 44 % of the patients suffered aspirations not accompanied by cough
reflex. In one of the largest series the incidence of PED was 84 %, 17 % of them
were classified as severe dysphagia, and moderate 23 %; mild an severe PED was
associated independently with the composite outcome of pneumonia, reintubation
and death agreeing with other series [3, 4]. The use of simple screening methods or
protocolization of the study of such disorders has been shown to be useful, allowing the identification of patients at high risk, with a view to adopting appropriate
management measures.
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33.2
A.F. Carmona et al.
Several studies have proposed the incorporation of noninvasive ventilation (NIV) in

weaning protocols, including prophylactic intervention in chronic obstructive pulmonary disease patients who failed s spontaneous breathing trial (SBT), patients
with repeated SBT failure, and post-surgical patients. This is because NIV may allow
extubation while mechanical ventilation is continued in the form of NIV weaning in
progress. Most of these studies show that NIV reduces weaning time, shortens time
of stay in the intensive care unit (ICU), and, in some studies, decreases the incidence
of nosocomial pneumonia and improves survival rates [5, 6]. Nevertheless, the effectiveness of NIV remains to be determined, the last Cochrane review supports this
weaning strategy [3, 4].
Length of time of mechanical ventilation implies the appearance of PED (nonneurological origin) because of the mere presence of the orotracheal tube as well as
the time that it remains at the larynx. In critical patients with difficulty in mechanical ventilation weaning (the majority will need prolonged ventilation), the presence
of dysphagia not only should be investigated but should be assumed, especially if
neurological injury has been implied. In this sense, although it has not yet been
studied, NIV support can play a determinant role during the weaning phase because
it restores air passage through the natural airway, improving the airway protection
reflex by stimulating nervous endings and rehabilitating laryngeal muscles. Also,
NIV may decrease dyspnea, improve swallowing by increasing the tidal volume and
thus the subglottic pressure during swallowing at the expiratory phase, and improve
breathing-swallowing coordination for the reasons discussed above and by reducing
hypercapnia.
In the past, oral feeding was avoided during NIV therapies because of the
increased risk of aspiration due to swallowing-induced ventilator triggering and the
widespread use of nasobuccal or facial interfaces for the treatment of critical
patients. However, recent investigations on the use of devices that allow patients on
NIV therapy to switch off inspiratory support before swallowing are promising.
They show no bronchial aspiration, ventilator/patient asynchrony, or swallowinginduced ventilator triggering, with a better Borg scale score and a clear preference
on the part of the patient continuing NIV. Other alternatives include intermittent use
of high nasal flow oxygen while the patient eats [10].
No studies in extubated patients have demonstrated the best time to reintroduce
oral nutrition, despite evidence of a high frequency of bronchial aspirations not
accompanied by cough reflex. Traditionally, in many ICUs, these patients have been
subjected to 1224 h of avoid any kind of oral intake to avoid possible complications associated with bronchoaspiration during reintubation in case of extubation
failure, but not in all the units. In general terms, late reintroduction of oral feeding
(probably after more than 48 h of extubation) and exercises of the neck, laryngeal,
and pharyngeal muscles in the form of deep exhalations, forced coughing, Valsalva
maneuver, clearing of the throat, contained slow inspirations, pronunciation of
33 Dysphagia in Post-extubation Respiratory Failure
263
vocals, and so on could be beneficial in extubated patients with a high probability of

suffering some degree of artificial airway oropharyngeal dysphagia.
Once patients are diagnosed with PED, frequent evaluation is required and absolute oral diet is recommended (in addition to the measures previously discussed). If
the dysphagia persists despite the above-mentioned rehabilitation therapy, the possible existence of underlying structural damage should be evaluated, with adoption
of the opportune management measures. Fibroscopy should be performed, with
possible functional evaluation and laryngeal tests to assess vocal cord adduction and
cough reflexes.
A negative result of the presence of dysphagia and NIV might be the development
of secretion encumbrance, which can be a determinant of NIVs failure. The correct
use of medications and postural therapies that minimize esophagic reflux and
enclosed oral secretions production, as well as rapid improvement of the swallowing
impairment, are fundamental to avoiding this complication. The role of impaired
airway secretion clearance in the outcome of post-extubation respiratory failure in
critically ill ventilator-dependent patients is still not clear, but medical evidence indicates a poor prognosis in cases of abnormal cough mechanics, altered mucus rheology, and altered mucociliary clearance (frequent situations in patients needing
prolonged mechanical ventilation). In recent years, mechanical insufflationexsufflation (MI-E) has been shown to be efficient in improving the efficacy of NIV
and to prevent respiratory failure after extubation in a randomized controlled trial [7].
It is advisable to know this technology and to include it in the weaning protocol for
specific subgroups at risk of being reintubated for extubation and NIV failure.
Correct hydration and a rapid beginning (if possible) of oral liquid ingestion will
avoid secretion dehydration that might be deleterious.
The presence of an orotracheal tube is not the only element that can affect swallowing, and other factors also should be considered, such as the background disease
leading to the need for mechanical ventilation, and the patient evolutive stage.
Conclusion
PED is a high-prevalence pathology in the ICU and should be suspected and

treated in all patients needing prolonged mechanical ventilation. Although it
often is an underestimated pathology, it has serious implications and carries
higher morbidity and mortality rates.
NIVs incorporation in weaning protocols does not avoid the appearance of
PED, although it probably improves its recovery by shortening invasive mechanical ventilation time and decreasing the reintubation rate, as well as restoring
anatomical airway flow and rehabilitation. New applications or designs of this
technology might allow better dysphagia rehabilitation and a precocious beginning of safe oral nutrition during the critical care weaning process.
The development of secretion encumbrance can be a determinant of NIV failure. It should be monitored and correctly treated, including in protocols the use
of technologies such as MI-E in case of impaired airway secretion clearance.
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A.F. Carmona et al.
We recommend weaning protocols include NIV because it reduces time of

mechanical ventilation, which is crucial to minimizing PED (although it
does not avoid it), and simultaneously initiates laryngeal rehabilitation.
PED must be suspected and treated in all patients who need prolonged
mechanical ventilation. The best treatment is to restore anatomical air flow.
Beginning oral nutrition must be individually evaluated for every patient.
The accomplishment of a functional test or specific team evaluation is
advisable.
Patients needing NIV during the weaning phase must be closely monitored. In general, in patients diagnosed with PED, an important way to
avoid NIV failure is to guarantee effective cough and respiratory secretion
management.
Specific studies are needed clarify the implications of NIV in PED
treatment.
References
1. Macht M, Wimbish T, Clark BJ, et al. Postextubation dysphagia is persistent and associated
with poor outcomes in survivors of critical illness. Crit Care. 2011;15:R231.
2. Kwok AM, Davis JW, Cagle KM, et al. Post-extubation dysphagia in trauma patients: its hard
to swallow. Am J Surg. 2013;206:9247.
3. Moraes DP, Sassi FC, Mangilli LD, et al. Clinical prognostic indicators of dysphagia following
prolonged orotracheal intubation in ICU patients. Crit Care. 2013;17:R234.
4. Fernndez-Carmona A, Peas-Maldonado L, Yuste-Osorio E, et al. Exploration and approach
to artificial airway dysphagia. Med Intensiva. 2012;36:42333.
2007;29:103356.
6. Burns KE, Meade MO, Premji A, et al. Noninvasive ventilation as a weaning strategy for
mechanical ventilation in adults with respiratory failure: a Cochrane systematic review. CMAJ.
2014;186:E11222.
7. Gonalves MR, Honrado T, Winck JC, et al. Effects of mechanical insufflations-exsufflation in
2012;16:R48.
8. Smith Hammond CA, Goldstein LB. Cough and aspiration of food and liquids due to oralpharyngeal dysphagia: ACCP evidence-based clinical practice guidelines. Chest. 2006;129:
154S68S.
9. Trapl M, Enderle P, Nowotny M, Teuschl Y, Matz K, Dachenhausen A, et al. Dysphagia
Bedside Screening for Acute-Stroke Patients: The Gugging Swallowing Screen. Stroke.
2007;38:294852.
10. Terzi N1, Normand H, Dumanowski E, Ramakers M, Seguin A, Daubin C, Valette X, Masson R,
Sauneuf B, Charbonneau P, du Cheyron D, Lofaso F. Noninvasive ventilation and breathing-swallowing interplay in chronic obstructive pulmonary disease. Crit Care Med. 2014;42(3):56573.
doi: 10.1097/CCM.0b013e3182a66b4a.
Agitation During Prolonged Mechanical

Ventilation and Influence on Weaning
Outcomes
34
Eduardo Tobar and Dimitri Gusmao-Flores
34.1
Introduction
There has been growing recognition of the importance of adequately managing

pain, sedation, delirium, and agitation in patients on mechanical ventilation (MV) to
improve the chances of better outcomes. Agitation is common in the intensive care
unit (ICU). It is important to implement a systematic process for preventing, diagnosing, and managing this condition, to decrease the risk of worsened outcomes
including weaning failure, post-extubation acute respiratory failure, and others.
This chapter reviews the information available regarding agitation in mechanically
ventilated patients as related to the process of removing the ventilator and the strategies recommended for improving management of pain, agitation, and delirium during weaning.
34.2
Definitions and Diagnostic Tools
Agitation is a psychomotor disorder of multifactorial etiology, characterized by

increased motor and psychological activity. From the earliest history of intensive
care, there have been reports of patients with intractable agitation as a result of
altered cerebral function. Managing this condition is a complex challenge for the
attending team.
E. Tobar (*)
Internal Medicine Department North, University of Chile Clinical Hospital,
University of Chile School of Medicine, Santiago, Chile
e-mail: eduardotobar@med.uchile.cl
D. Gusmao-Flores
Universidade Federal da Bahia, Instituto de Ciencias da Saude,
Edgar Santos University Hospital, Salvador, Bahia, Brazil
DOI 10.1007/978-3-319-04259-6_34
265
266
E. Tobar and D. Gusmao-Flores
Over the past 15 years, awareness of the importance of managing delirium in the
ICU has increased. The condition is acute, fluctuating, and multifactorial in origin
and is characterized by disturbances in attention and other brain functions. Delirium
is common, with an incidence of 5085 % in MV patients. Although hypoactive
symptoms are the most typical, mixed or hyperactive forms of delirium occur in
540 % of cases, making delirium the main cause of agitation in the ICU [13].
However, it should be noted that agitation is sometimes attributable to causes
other than delirium; therefore, it is important to systematically monitor for these
other factors. Other causes include pain and withdrawal from illicit drugs or prescription medications. We revisit this point below.
Diagnosis of agitation is simple, based on clinical observation of the patient. The
nurse is typically the first professional to recognize agitation. It is important to use
a valid scale to rate the severity of agitation and to evaluate the need for urgent measures according to severity. Current guidelines for managing pain, sedation, agitation, and delirium recommend the use of the following scales to monitor sedation
level and agitation: Sedation-Agitation Scale (SAS) and the Richmond AgitationSedation Scale (RASS) [47].
34.3
Epidemiology, Risk Factors, and Impact of Agitation
The incidence of agitation among mechanically ventilated patients is 1070 %. In

one of the earliest studies of the condition, Fraser et al. [8] reported that 70 % of MV
patients developed agitation. In 2005, Jaber et al. [9] reported an incidence 52 % in
a French population, with an average onset 4.4 days after ICU admission and an
average duration of about 4 days. Our group found that 32.9 % of patients suffered
at least one episode of agitation; most of the events recorded were mild episodes
(SAS 5, 72 %) [10]. In terms of severe agitation, one report indicates an incidence
of about 16 % in MV patients [11].
The most recent clinical studies comparing various sedatives and/or strategies
for sedative schedules document a lower incidence of agitation between 8 and 15 %
[12, 13]. In view of that data, it is possible that the incidence of agitation is decreasing, but there are no studies regarding this issue.
One issue relevant to the interaction of agitation and the weaning process is the
timing of the onset of agitation, which is often parallel to the timing of the weaning
process. Often, cardiorespiratory and neurological functions are stabilized by days
47 of MV. At this point, weaning from MV and managing problems related to
delirium and/or agitation are frequently priorities.
History of alcohol abuse, illicit drug use, and use of psychoactive medications
are the most consistent risk factors for agitation. Other factors include low pH,
PaO2/FiO2 <200, fever, abnormal sodium levels, and use of sedatives [8, 9, 11, 14].
The relationship between age and agitation is controversial. Some reports indicate
no correlation, whereas others have found higher agitation levels in younger patients.
Given the relationship between delirium and agitation, it is important to consider
the risk factors for delirium in the ICU. According to the Society of Critical Care
34 Agitation During Prolonged Mechanical Ventilation
267
Medicine guidelines, risk factors include history of dementia, hypertension, and/or

alcoholism, and severity of illness upon admission. As with agitation, the effect of
age on the incidence of delirium in the ICU is controversial [6].
Another cause of agitation in the ICU is withdrawal associated with drug and/or
alcohol use. It is important to monitor for this factor, as the presence of withdrawal
changes the recommended therapeutic management of agitation. The various withdrawal syndromes include the following:
(a) Withdrawal associated with illicit or prescription drugs: Similar symptoms have
been reported for withdrawal from recreational and therapeutic drugs. These
cases are typically recognized in the emergency room, where the most severe
cases are labeled excited delirium syndrome (EXDS), characterized by severe
agitation, hyperthermia, and acidosis [15].
(b) Withdrawal associated with sedatives or opioids used in the ICU: An incidence
of 32 % has been reported for patients on MV for more than 1 week, but there
are few studies in this topic. This condition is associated with higher doses of
sedatives, the use of neuromuscular blockers, and the presence of acute respiratory distress syndrome [16]. These cases are particularly complex, given the
difficulty in differential diagnosis of hyperactive delirium without withdrawal
and the theoretically different management of the two situations (standard by
protocol administration of sedatives versus minimizing benzodiazepines).
(c) Withdrawal associated with chronic alcohol abuse: Alcohol-use disorders
(AUD) are common in the ICU. In these patients, the use of sedatives is important. Agitation develops as part of the withdrawal syndrome in 18 % of patients
with AUD [17, 18]
(d) Withdrawal associated with chronic tobacco abuse: Recent studies have reported
an association between nicotine withdrawal and agitation in the ICU [19].
The presence of any of these four withdrawal syndromes should always cue the
team to monitor for agitation in the ICU. If possible, withdrawal symptoms should be
addressed before the onset of agitation in the ICU. If there is no documented history
of alcohol, tobacco, or drug use, it may be advisable to re-interview the family and
document any newly reported history if severe, difficult-to-control agitation occurs.
Adverse events related to agitation are numerous: First, deleterious physiological
consequences of agitation include elevated oxygen consumption, increase in intracranial pressure, hemodynamic instability secondary to both the agitation itself and
the pharmacological interventions used to manage its symptoms, increase in the
work of breathing, and patient ventilator asynchrony. Agitation can develop or
worsen during a spontaneous breathing trial (SBT) and is a common contraindication for SBT and/or cause of SBT failure.
From the point of view of relevant outcomes, agitation is associated with longer
duration of MV, prolonged ICU stay, higher risk of nosocomial infection, higher
rate of unplanned extubation (UE), and unplanned removal of central venous line
[911]. UE is the most-documented adverse event associated with agitation.
Incidence of UE is related to the sedation strategy and the monitoring level used by
268
the nursing team [2022]. Approximately two-thirds of UE cases occur during

weaning, and the main risk factor is agitation.
34.4
Delirium, Agitation, and Weaning
Despite the obvious relationship between the occurrence of delirium, agitation

development and success of the process of weaning, there are few studies exploring
this association and how a better control of agitation or delirium can contribute to a
better outcome of weaning. The relation between agitation and weaning can start at
different times, as shown in Fig. 34.1.
According to the new classification of weaning given at the Consensus
Conference, there are three different groups of patients [23, 24]. In the group of
patients with simple weaning, the role of agitation is minor. Agitation and delirium
play a relevant role as cause or contributors for patients with difficult and prolonged
weaning, but studies of this association are scarce compared with more-studied
mechanisms such as the respiratory pump or cardiovascular dysfunction as etiologies of weaning failure. In patients with prolonged weaning, most times there are
two or three different associated factors. Delirium is frequent in that group of
patients, and sometimes a severe agitation requires restarting sedatives while neuroleptics are started. This obviously means a delay in doing a SBT (weaning test)
because adequate mental status is a criteria for a SBT. In addition, an adequate
mental status is a bit ambiguous and clinically there are a gradients from a hypoactive delirium to severe agitation. To prevent the impact of a new deep sedation on
the capacity to do the next SBT, the election of sedative and/or antipsychotic to treat
delirium and agitation at this time is relevant, as will be discussed below.
Start of
MV
Exitous
extubation
Delirium /
Agitation
MV controlled
(if needed)
Acute phase of MV
Is the SBT
feasible ?
Can I
extubate to
my patient ?
Succesfull
Extubation
Weaning
Fig. 34.1 A temporal view of agitation and weaning of mechanical ventilation
269
Agitation is one of the subjective criteria for failure of a SBT; however, agitation
is a continuum, with mild and severe types, and sometimes isolated mild agitation
can be controlled with nonpharmacological measures and medication. However, in
other cases a new agitation during a SBT is a symptom of cardiovascular or respiratory failure and the patient must be reconnected to MV This difference is not always
easy to detect and it requires a global evaluation of whether mental symptoms of
failure are alone or with other objective or subjective failure criteria. There are no
studies to help to make this decision and a good clinician is needed.
Sometimes agitation begins following extubation. Extubation failure happens in
618 % of patients and is associated with increased ICU mortality, so it is important
to detect it and to quickly determine whether the patient needs to be reintubated.
Similar to agitation during SBT, the new agitation after extubation is a bad sign and,
after a global evaluation for other criteria of failure, the decision must be made
whether to offer noninvasive ventilation (NIV) or a fast reintubation. In our opinion,
significant agitation is in this setting a contraindication for NIV. Only in mild agitation without other signs of failure can we offer NIV with close observation.
The incapacity to follow orders has been studied in neurocritical patients as a risk
factor for extubation failure [25], but another more recent study did not show an
association between delirium and extubation failure [26]. This research area looks
controversial and more studies are needed looking for the association of delirium
and/or agitation with extubation failure.
34.5
Preventing and Managing Agitation
The following measures are recommended to prevent agitation (Table 34.1):

(a) Complete history of risk factors for agitation, including medication list and history of illicit drug, alcohol, or tobacco use.
(b) Serial evaluation or pain, using instruments validated for mechanically ventilated patients such as the behavioral pain scale [27] or the Critical-Care Pain
Observation Tool (CPOT) [28].
(c) Serial monitoring of sedation level and agitation using the SAS or RASS, mentioned above. Chanques et al. [29] reported that systematic monitoring for pain
and agitation alone reduced the incidence of agitation.
Table 34.1 Key elements for the prevention of agitation in MV patients

(a)
(b)
(c)
(d)
(e)
Make a proper anamnesis, with emphasis on assessing risk factors

To implement serial monitoring the presence of pain, sedation, and agitation levels
Monitoring of delirium at least twice a day
A protocolized pharmacological and nonpharmacological management of pain and
delirium
To consider the use of dexmedetomidine as sedative of choice, or as coadjuvant if
agitation during weaning
270
(d) Daily monitoring of delirium. As with pain, sedation, and agitation, valid instruments should be used to monitor delirium, such as the Confusion Assessment
method for the ICU (CAM-ICU) or Intensive Care Delirium Screening Checklist
(ICDSC) scales.
(e) Adherence to recommendations for pain and delirium management. Severe
pain is also recognized as a causal factor in agitation; therefore, optimal analgesia is important. To manage hypoactive delirium, early intervention with nonpharmacological therapy should be deployed, including occupational therapy
and multimodal management.
(f) Use of dexmedetomidine as a sedative in MV patients. There is evidence from
clinical trials as well as level IIB evidence suggesting that dexmedetomidine
reduces the risk of delirium compared with benzodiazepines. Given that delirium is the main cause of agitation, it is reasonable to assume that reducing the
incidence of delirium may reduce the incidence of agitation, although this idea
has not been systematically evaluated.
34.6
Treating Agitation
At onset of agitation, the first priority is to minimize risk to the patients physical
integrity (falls, accidental removal of breathing tube, catheters, drains, or other
equipment), and, in parallel, to protect the hospital staff from physical injury. Severe
agitation in a young patient may require the strength of three or four team members
to apply physical restraints.
It is crucial to evaluate the severity of the condition, as appropriate management
of mild cases can often prevent the onset of severe agitation. Mild cases will respond
to verbal direction, allowing time for appropriate diagnostic and pharmacological
intervention. The diagnostic process should also include evaluation of pain, delirium, and withdrawal syndromes, as previously noted. If these scales suggest the
presence of pain, an opiate bolus is recommended; in our center, we use 25100 g
of fentanyl, depending on body weight, titrating according to clinical response. If
CAM-ICU or ICDSC scores indicate delirium, the use of neuroleptic agents is recommended. Worldwide, the most commonly used drug of this type is haloperidol.
The recommendation is to begin with 0.51.0 mg administered enterally, keeping in
mind that the onset of action is about 20 min. Intravenous administration is discouraged, due to the higher risk of prolonged QT interval and arrhythmias. If no other
administration route or drug is available, we suggest using 0.51 mg of intravenous
haloperidol in 50100 of saline over 30 min, performing an electrocardiogram as
soon as possible to evaluate for QT. It is important to consider that neuroleptics have
potential adverse cardiac and neurological effects (such as extrapyramidal symptoms), and the level of evidence supporting their use is low.
Given their more favorable safety profile, recent studies have evaluated atypical
neuroleptic agents such as risperidone, quetiapine, and olanzapine. One small-scale
study of the use quetiapine in critical care patients suggested a reduced duration of
delirium as compared with a control group [30].
271
For more severe cases, a bolus of sedative may be necessary during the acute
phase to control agitation.
Dexmedetomidine should be considered the sedative of choice for managing agitation during weaning. The goal is not only to control agitation but also to avoid
returning to profound levels of sedation that would delay or limit the application of
the SBT. Dexmedetomidine is a promising candidate for this application due to its
characteristics, although, again, evidence for its use is limited to clinical series and
extrapolations from clinical trials comparing this drug to benzodiazepines as the
sedative of choice during weaning [3133].
Other therapeutic strategies that have been studied at the level of clinical series
or small clinical trials include music therapy and electroconvulsive therapy in
refractory cases.
Conclusion
Agitation is common among mechanically ventilated patients, typically occurring during the weaning period. Agitation limits both the application and the
likelihood for success of the SBT and increases the chance of weaning failure. In
addition to accurately diagnosing agitation, it is important to measure the severity of the condition and monitor for etiologies other than delirium. Using best
practices for managing pain, sedation, and delirium improves outcome and
reduces the impact of agitation during the weaning process.
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BiPAP for Preoxygenation During

Reintubation in Acute Postoperative
Respiratory Failure
35
Farouk-Mike ElKhatib, Anis S. Baraka,

and Mohamad Khatib
35.1
Introduction
Preoxygenation during induction of general anesthesia and tracheal intubation, or

during reintubation in postoperative acute respiratory failure, has become a widely
accepted safety maneuver designed to counterbalance the effect of apnea with general anesthesia as well as the effect of shunt with postoperative acute respiratory
distress [14]. The goal of preoxygenation is to increase oxygen reserve and thereby
delay the onset of arterial oxyhemoglobin desaturation to achieve a safe tracheal
intubation for initiation of mechanical ventilation. In an updated report of the
American Society of Anesthesiologists Task Force on Management of the Difficult
Airway (2013), routine preoxygenation was endorsed as a new minimum standard of care not only during induction of anesthesia and tracheal intubation but also
during emergence from anesthesia and tracheal extubation [4].
Conventional preoxygenation techniques consisted of using a 100 % oxygen
gas source and focused on using different breathing techniques (e.g., tidal volume
breathing for 3 min, four deep breaths technique, eight deep breaths in 60 s) and
devices to achieve the highest fraction of inspired oxygen (FiO2) that will allow
fast and efficient washout of nitrogen gas and its replacement in the functional
residual capacity (FRC) with the inhaled oxygen gas [1]. Inhalation of 100 % oxygen results in an initial very rapid increase of arterial oxyhemoglobin saturation to
between 98 and 99 %, but the attainment of the last 12 % is a much slower
F.-M. ElKhatib, BS A.S. Baraka, MD
School of Medicine, American University of Beirut, Beirut, Lebanon
e-mail: fme21@aub.edu.lb; anisbaraka@live.com
M. Khatib, PhD, MD (*)
Department of Anesthesiology, American University of Beirut Medical Center,
P.O. Box: 11-0236, Beirut 1107-2020, Lebanon
e-mail: mk05@aub.edu.lb
DOI 10.1007/978-3-319-04259-6_35
275
276
F.-M. ElKhatib et al.
process. However, in a subset of patients, the conventional techniques might not

achieve adequate preoxygenation and fail to prevent desaturation. Such conflicting
responses are mainly because of the pathophysiology of hypoxemia, which includes
inadequate alveolar oxygenation, severe ventilation-to-perfusion (V/Q) mismatch,
shunt, low venous blood saturation and low cardiac output, and diffusion abnormalities [5]. Most of these causes have inconsequential effects on oxygenation
when a FiO2 greater than 40 % is used, except with shunt, impaired V/Q, and low
venous blood saturation [5].
35.2
Acute Postoperative Respiratory Failure
Acute postoperative respiratory failure may be attributed to residual effect of

anesthetics or neuromuscular blockers. However, anesthesiologists are usually
vigilant in preventing these causes by the continuous intraoperative management and control of inhaled anesthetics and the use of reversal drugs to counteract the effect of neuromuscular blockers. However, other reasons for acute
postoperative respiratory failure that can go unnoticed include atelectasis, pneumonia, and pulmonary edema. In such conditions, poor oxygenation and respiratory failure can ensue postoperatively after extubation and resuming
spontaneous breathing. Using conventional techniques may lead to inadequate
preoxygenation and fail to prevent oxygen desaturation and alleviate the signs
and symptoms of respiratory failure. No matter how high the FiO2 is, the patient
will never have improved oxygenation, and the only way to improve oxygenation is to fix and reverse the physiologic shunt resulting from atelectasis, pneumonia, and pulmonary edema through the use of efficient and adequate positive
end-expiratory pressure (PEEP) [6].
35.3
Bi-level Positive Airway Pressure
Bi-level positive airway pressure (BiPAP) allows the application of two levels of
positive airway pressures: expiratory positive airway pressure (EPAP) and inspiratory positive airway pressure (IPAP) [7]. EPAP has similar physiological effects to
continuous positive airway pressure (CPAP)/PEEP, whereas IPAP acts as pressure
support ventilation (PSV) on top of EPAP (Fig. 35.1). The toggling between these
two pressure levels is controlled by the patients spontaneous pattern of breathing.
BiPAP therapy can improve oxygenation and relieve respiratory distress by one of
the following mechanisms [7]. First, the use of positive airway pressure during the
expiratory phase of BiPAP (i.e., EPAP) serves as a CPAP/PEEP. The beneficial
effect of CPAP/PEEP contributes to the recruitment of collapsed alveoli, and hence
can increase the FRC and decrease the degree of shunt with a consequent improvement of oxygenation. Also, EPAP can stabilize recruited alveoli and prevent derecruitment. Second, the implementation of positive airway pressure during the
inspiratory phase of the BiPAP therapy (i.e., IPAP) functions as PSV. This not only
35
277
BiPAP for Preoxygenation in Acute Postoperative Respiratory Failure

E
+3
0
3
Spont
E
I
E
I
E
I
5
CPAP
10
IPAP
BiPAP
5
EPAP
Fig. 35.1 Airway pressure versus time with spontaneous breathing, continuous positive airway
pressure (CPAP), and bi-level positive airway pressure (BiPAP)
can contribute to resolving atelectasis, but can improve alveolar oxygenation by the
increase in alveolar ventilation resulting in increase of tidal volume with the use of
IPAP, and will lead to a decrease in the work and oxygen cost of breathing [7].
35.4
BiPAP and Preoxygenation in Acute Postoperative

Respiratory Failure
BiPAP is being more frequently used for acute postoperative respiratory failure as it
provides several advantages over traditional invasive mechanical ventilation. BiPAP is
a form of noninvasive ventilatory support that minimizes the risks of ventilatorinduced lung injuries, reduces the need for excessive sedation, and preserves the upper
airways reflexes and functions for better protection against aspiration and for better
humidification of inspired gas. Two separately adjusted pressure levels, EPAP and
IPAP, allow the clinician to independently maintain upper-airway patency and prevent airway/alveolar collapse/derecruitment during exhalation, thereby preventing
atelectasis and increasing the FRC that is the main oxygen store as well as augmenting
tidal volume and alveolar ventilation and subsequently alveolar oxygenation [7].
BiPAP as a preoxygenation method has been shown to be more effective at reducing
arterial oxyhemoglobin desaturation than conventional preoxygenation techniques
during intubation in hypoxemic patients [8]. Furthermore, the levels of oxygenation
achieved with BiPAP are usually sustained for longer duration after intubation than
conventional preoxygenation techniques with a non-rebreather bag-valve mask [8].
This reflects the possible significant linear correlation between oxyhemoglobin saturation at the end of the preoxygenation period with BiPAP and the minimal oxyhemoglobin saturation during endotracheal intubation.
278
In a prospective randomized study, Delay et al. [9] showed, in morbidly obese

patients, that a larger proportion of patients achieved a 95 % end-tidal oxygen concentration (ETO2) at 5 min with BiPAP than in spontaneously breathing patients. Several
reports confirmed that oxygen administration via BiPAP is safe, feasible, and efficient
in morbidly obese patients in the operating room and provides a faster preoxygenation
than normal spontaneous breathing of high fraction of inspired oxygen [9, 10].
The tonic increase in the baseline pressure that is usually achieved with EPAP
during BiPAP tends to reverse atelectasis and reduce the shunt that could have
developed during the administration of anesthesia and subsequently led to the acute
postoperative respiratory failure. This can significantly increase the non-hypoxic
apnea duration by more than 2 min compared with when no EPAP or BiPAP therapy
is applied during acute postoperative respiratory failure [11].
Following anesthesia, patients with obstructive sleep apnea should be extubated
in a semirecumbent position after they are fully awake and confirmation of airway
patency and after verification of complete reversal of neuromuscular blockade.
Otherwise, there will be a high risk of post-extubation airway obstruction and severe
postoperative oxyhemoglobin desaturation. BiPAP should be applied as soon as
possible after surgery to patients with obstructive sleep apnea who exhibit mild to
severe postoperative oxygen desaturation. Its immediate use after tracheal extubation may prevent oxygen desaturation and eliminate the need for reintubation [11].
BiPAP has also been used for management of hypoxemia associated with unilateral phrenic nerve palsy following surgery for thoracic outlet syndrome. The unilateral phrenic nerve palsy that may mimic one-lung ventilation that creates an obligatory
right-to-left transpulmonary shunt flow through the nonventilated lung and resulting
in severe hypoxemia might not be reversed with simple face mask oxygenation. The
use of BiPAP and supplemental oxygen can significantly improve oxygenation and
reverse signs and symptoms of respiratory distress in these patients [12]. Under these
clinical circumstances, BiPAP with adequate adjustments of EPAP and IPAP can
improve V/Q mismatch, decrease the shunt, and improve alveolar ventilation.
Noninvasive BiPAP is usually provided using a standard pressure-cycled positive
pressure ventilator (whether a stand-alone ICU or an anesthesia-machine incorporated
ventilator) or a specialized BiPAP machine [13]. The therapy can be delivered to the
patient using either a full face mask or a nasal mask. Despite the several clinical benefits, reported adverse effects related to BiPAP have been relatively mild and most
commonly include skin breakdown over the bridge of the nose due to pressure from
the mask (Table 35.1). The use of a bio-occlusive dressing, soft mask cushions, and
intermittent repositioning of the mask can significantly limit these problems.
Additional concerns of BiPAP therapy, particularly with full face masks, are the risk
of gastric insufflation, distention, and aspiration [7]. Gastric distention has been noted
previously with the application of BiPAP, however, to date, no reports document the
occurrence of aspiration. In the event of excessive gastric dilation, it may be necessary
to decompress the stomach with a naso/orogastric tube or decrease the level of IPAP.
In conclusion, BiPAP can be valuable and helpful in the resolution of atelectasis,
improvement of chest wall excursion, reducing of shunt, augmentation of oxygenation, and prevention of need for tracheal intubation. Despite all of the potential
benefits, there is still limited information concerning the use of BiPAP in the
35
BiPAP for Preoxygenation in Acute Postoperative Respiratory Failure
279
Table 35.1 Benefits and risks of BiPAP

Benefits
1. Need for less sedation
2. More effective cough
3. Decreased rate of nosocomial infection
4. Mask can be removed as tolerated
5. Enhanced communication by the patient during therapy resulting in decreased patient
anxiety
Risks
1. Skin breakdown where the mask is in contact with the face
2. Gastric insufflation
3. Air leak around the mask
4. Increased risk of aspiration
immediate postoperative period. Nevertheless, preoxygenation is recommended to

avoid the rapid oxyhemoglobin desaturation secondary to apnea or respiratory
depression during induction of anesthesia and tracheal intubation, or during recovery from anesthesia and following postoperative tracheal extubation. The implementation of BiPAP for preoxygenation might provide several advantages over the
conventional and more traditional techniques of preoxygenation in the preoperative
and immediate postoperative periods.
1. Preoxygenation with BiPAP is safe, feasible, and efficient in the postoperative period.
2. Preoxygenation with BiPAP should be considered over traditional preoxygenation techniques whenever atelectasis and/or pulmonary edema are
expected and causing postoperative oxyhemoglobin desaturation and acute
respiratory failure.
3. Anesthesiologists should be well versed in the initiation and management
of BiPAP therapy.
References
1. Baraka AS, Salem MR. Preoxygenation. In: Benumof J, Hagberg CA, editors. Benumof and
Hagbergs airway management. Philadelphia: Elsevier; 2013. p. 28097.
2. Taha S, Siddik-Sayyid S, El-Khatib M, et al. Nasopharyngeal oxygen insufflation following
pre-oxygenation by the four deep breath technique. Anaesthesia. 2006;61:42730.
3. Taha S, El-Khatib M, Siddik-Sayyed S, et al. Preoxygenation by 8-deep-breaths in 60 seconds
using Mapleson A (Magill) or the circle system versus Mapleson D system. J Clin Anesth.
2009;21(8):5748.
4. Apfelbaum JL, Hagberg CA, Caplan RA, et al. Practice guidelines for management of the difficult airway: an updated report by the American Society of Anesthesiologists Task Force on
Management of the Difficult Airway. Anesthesiology. 2013;118(2):25170.
280
5. Weingart SD. Preoxygenation, reoxygenation, and delayed sequence intubation in the emergency department. J Emerg Med. 2011;40:6617.
6. Imberger G, McIlroy D, Pace NL, et al Positive end-expiratory pressure (PEEP) during anaesthesia for the prevention of mortality and postoperative pulmonary complications. Cochrane
7. Hess DR. Noninvasive ventilation for acute respiratory failure. Respir Care.
2013;58(6):95072.
8. Baillard C, Fosse JP, Sebbane M, et al. Noninvasive ventilation improves preoxygenation
before intubation of hypoxic patients. Am J Respir Crit Care Med. 2006;174:1717.
9. Jean-Marc Delay JM, Sebbane M, Jung B, et al. The effectiveness of noninvasive positive pressure ventilation to enhance preoxygenation in morbidly obese patients: a randomized controlled study. Anesth Analg. 2008;107:170713.
10. El-Khatib M, Kanazi G, Baraka A. Noninvasive bilevel positive airway pressure for preoxygenation of the critically ill morbidly obese patient. Can J Anesth. 2007;54(9):7447.
11. Herriger A, Frascarolo P, Spahn DR, et al. The effect of positive airway pressure during preoxygenation and induction of anaesthesia upon duration of non-hypoxic apnoea. Anaesthesia.
2004;59:2437.
12. Baraka A, Mariane Aouad M, Maalouli J, et al. BiPAP. Management of hypoxemia associated
with unilateral phrenic nerve palsy following surgery for thoracic outlet syndrome. Middle
East J Anesth. 2002;16(5):53542.
13. Hillberg RE, Johnson DC. Noninvasive ventilation. N Engl J Med. 1997;337:174652.
Determinant Factors of Failed

Extubation and the Use of Noninvasive
Ventilation in Trauma Patients
36
Eric Bui, Jayson Aydelotte, Ben Coopwood,

and Carlos V.R. Brown
Abbreviations
CPAP
GCS
ICU
NIV
RCT

Glasgow Coma Scale
Intensive care unit
36.1
Introduction
Trauma patients are frequently admitted to the intensive care unit (ICU) requiring
intubation and prolonged ventilator support. These interventions are necessary and
life-saving but also carry with them potential complications that include but are not
limited to laryngeal and pulmonary trauma, hemodynamic compromise, and pneumonia. For these reasons, patients should be liberated from a ventilator as soon as
feasibly possible. This can be accomplished either by extubation or tracheostomy.
Balancing the need for early liberation from a ventilator is the risk of failed extubation or prolonged ventilator dependence. Patients who require reintubation often
require it in emergent, less than ideal conditions. These patients have higher rates of
E. Bui, MD (*)
Division of Acute Care Surgery, Los Angeles County + USC Medical Center, Los Angeles,
CA, USA
e-mail: ehbui81@gmail.com
J. Aydelotte, MD B. Coopwood, MD C.V.R. Brown, MD
Department of Surgery, Dell Medical School, University of Texas at Austin, Austin, TX, USA
DOI 10.1007/978-3-319-04259-6_36
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E. Bui et al.
adverse outcomes as well, including pneumonia, increased ICU and hospital days,
increased rate of tracheostomy, and increased mortality.
36.2
Risk Factors for Failed Extubation in Trauma
In the general population of ICU patients, risk factors for failed extubation include
duration of ventilation, advanced age, severity of illness at the time of extubation,
anemia, semirecumbent position, intravenous sedation, and unexplained extubation.
The reported rate of failed extubation in the literature ranges from 2 to 25 % across
variable patient populations [1]. However, little is published about risk factors and
outcomes specific to failed extubation in trauma patients.
In 2011, Daigle et al. [1] looked specifically at trauma patients as a population to
identify risk factors for reintubation. A prospective, observational study was performed of all adult trauma patients who required endotracheal intubation admitted
to the ICU over an 18-month period. Failed extubation was defined as unplanned
reintubation within 24 h. Cause of failure of extubation was determined (airway
obstruction, respiratory failure, secretions, hemodynamic instability, and deterioration of neurologic status). All patients were extubated after a spontaneous breathing
trial per institutional protocol.
The two groups (successful vs failed extubation) had similar demographics with
regards to age, gender, body mass index, injury severity score, or need for operations (craniectomy, laparotomy, thoracotomy).
The statistical analysis identified several independent risk factors for failed extubation (Table 36.1). The presence of spine fractures, initial intubation for airway
issues, delirium tremens, and lower Glasgow Coma Scale (GCS) at the time of
extubation (GCS of 9 vs 10) were all associated with need for reintubation [1].
Patients who failed extubation also, interestingly, have a higher initial GCS on
admission than those that did not.
Patients who failed extubation were found to more often require prolonged ventilation (>48 h). Compared with those who tolerated extubation, those who failed
remain intubated for 4 2 days longer [1].
36.3
Noninvasive Ventilation in Trauma Patients
The use of noninvasive ventilation (NIV) techniques, that is, continuous positive
airway pressure (CPAP) in post-extubation respiratory failure has been described in
the literature. Several randomized controlled trials (RCT) have shown mixed results.
Table 36.1 Independent risk factors for failed extubation
Spine fracture
Intubation for airway problem
GCS at time of extubation
Delirium tremens
36
283
A randomized multinational, multi-institutional trial in 2004 evaluated the effect of

NIV on mortality in patients who were electively extubated after 48 h of mechanical
ventilation and developed respiratory failure in the subsequent 48-h post-intubation
period [2]. Patients were randomized to standard medical therapy (supplemental
oxygen, bronchodilators, other therapy as directed by an attending physician) or to
NIV via full-face mask. The study found that, in an unselected population of ICU
patients, NIV did not prevent the need for reintubation and showed a trend toward
higher mortality when NIV was used [2]. The higher rate of mortality in the NIV
group was felt to be the result of the longer interval to re-intubation compared with
the standard therapy group. An earlier RCT with similar design compared NIV with
supplemental oxygen in patients with a history of cardiac or pulmonary disease who
developed respiratory distress within 48 h of being extubated. The study concluded
that there was no difference in the rate of reintubation, mortality, duration of
mechanical ventilation, or length of ICU stay [3].
Subsequent RCTs identified patients who were deemed to be high risk for extubation where NIV showed a benefit; however, this was in a specific subset of patients
with chronic obstructive pulmonary disease, congestive heart failure, and/or hypercapnia [4]. A meta-analysis in 2007 concluded that NIV should be used judiciously
if at all in patients with post-extubation respiratory failure [5].
The issue with extrapolating these data to trauma patients is that the study groups
in the previously referenced studies were a heterogeneous population. Trauma
patients made up only a small percentage of the total study population, and in some
studies were not included at all [4].
The trauma literature is less robust when looking at the use of NIV. In 2002, the
British Thoracic Society Standards of Care Committee gave only a grade C (low)
recommendation on the use of NIV for patients with chest wall trauma who remain
hypoxic despite the use of high-flow oxygen and adequate regional anesthesia,
because of lack of evidence [6]. However, since then there have been several studies
looking specifically at the use of NIV in patients with chest injuries.
A prospective randomized controlled trial in 2010 looked at the use of NIV in
chest trauma-related hypoxia [7]. Adult patients over a 3-year period who sustained
severe thoracic trauma were not intubated and had persistent hypoxemic respiratory
failure (defined as a PaO2/FiO2 ratio <200 mmHg while on high-flow oxygen).
Patients were randomized to receive either NIV or remain on high-flow oxygen via
mask. The trial was stopped prematurely after 50 patients were enrolled because an
interim analysis revealed that the NIV group showed a significantly reduced intubation rate (10 % in the NIV group vs 40 % in the oxygen only group) [7]. There was
no mortality difference between the two groups. The authors concluded that early
and continuous application of NIV in patients with thoracic trauma helped reduced
the need for intubation in this subset of trauma patients [7].
A meta-analysis in 2013 examined the available data on the use NIV versus standard medical therapy (oxygen therapy and/or mechanical ventilation) in chest
trauma patients [8]. It included four RCTs and six observational studies comprising
a total of 368 patients. It was found that NIV significantly reduced the intubation
rate of patients with chest trauma and showed a mortality benefit and a decreased
rate of complications including pneumonia and development of tension
284
E. Bui et al.
pneumothorax [8]. ICU length of stay was also lower in patients who were treated
with NIV. Interestingly, there was no difference when comparing the different
modalities of NIV (CPAP, bi-level positive airway pressure, or noninvasive pressure
support ventilation) [8].
36.4
Discussion
Up to 20 % of patients with multisystem traumatic injuries present with chest injuries. These injuries account for 2040 % of all trauma deaths. The rate of intubation
in chest trauma patients is reported to be 2375 % [7]. This is a significant number
of patients who may end up with the complications associated with endotracheal
intubation that were previously discussed. Thus, strategies to minimize the length of
time on the ventilator are a potential way to minimize these morbidities.
NIV has emerged as an alternative to modalities such as invasive ventilation
requiring endotracheal intubation. The data in the trauma literature at this point is
still somewhat limited; however, the studies that are available seem to show a benefit to the use of NIV in trauma patients with traumatic chest injury by decreasing
the need for initial intubation. However, the benefit of using of NIV as a rescue
modality for failed extubation in trauma patients has yet to be elucidated.
Failed extubation leads to more patient ventilator days and therefore a higher risk
for ventilator-associated complications. Early liberation from the ventilator is ideal;
however, the decision to extubate must not be made haphazardly. Risk factors have
been identified that can help predict which trauma patients are at risk for failed
extubation. Patients with these risk factors should be monitored closely for postextubation failure and may be candidates for NIV. However, NIV should not delay
or replace reintubation if the clinical scenario necessitates it.
What currently is unclear is the subset of trauma patients who would most benefit from NIV. Many trauma patients have multisystem injuries and confounding
factors, such as a decreased level of consciousness secondary to a head injury or
perhaps severe facial fractures, might not be candidates for NIV. Regardless, NIV
appears to be safe and improves outcomes when used in appropriately selected
patients. More investigation in this arena is needed to better define the role of NIV
in the trauma population.
Key Recommendations
1. Patients who have spine fractures, were intubated for an airway issue, have
a depressed GCS at the time of extubation, or have delirium tremens are at
higher risk for failed extubation. These patients should be closely monitored following extubation.
2. NIV is safe in patients with chest trauma who are appropriate candidates
for it and can potentially prevent the need for initial intubation.
3. NIV should not delay endotracheal intubation if intubation is indicated.
4. The exact subset of trauma patients who will best benefit from NIV is yet
to be defined.
36
285
References
1. Brown CV, Daigle J, Foulkrod K, et al. Risk factors associated with early reintubation in
trauma patients: a prospective observational study. J Trauma. 2011;71(1):3742.
2. Esteban A, Frutos-Vivar F, Ferguson N, et al. Noninvasive positive-pressure ventilation for
3. Keenan S, Powers C, McCormack D, et al. Noninvasive positive-pressure ventilation for
postextubation respiratory distress. JAMA. 2002;287(24):323844.
4. Ferrer M, Valencia M, Nicolas M, et al. Early noninvasive ventilation averts extubation failure
in patients at risk. Am J Respir Crit Care Med. 2006;173:16470.
5. Agarwal R, Aggarwal A, Gupta D, et al. Role of noninvasive positive-pressure ventilation in
postextubation respiratory failure: a meta-analysis. Respir Care. 2007;11:14729.
6. British Thoracic Society Standard of Care Committee. Non-invasive ventilation in acute respiratory failure. Thorax. 2002;57:192211.
7. Hernandez G, Fernandez R, Lopez-Reina P, et al. Noninvasive ventilation reduces intubation in
chest trauma-related hypoxemia. Chest. 2010;137(1):7480.
8. Chiumello D, Coppola S, Froio S, et al. Noninvasive ventilation in chest trauma: systematic
review and meta-analysis. Intensive Care Med. 2013;39:117180.

in Tetraplegia
37
Michael A. Gaytant and Mike J. Kampelmacher
Abbreviations
ABG
BiPAP
BW
CPAP
IPV
MAC
NPPV
PCV
PSV
SCI
SDB
TV
VCV
37.1
Arterial blood gas

Bodyweight
Intrapulmonary Percussive Ventilation
Mechanically assisted coughing
Pressure controlled ventilation
Pressure support ventilation
Spinal cord injury
Sleep disordered breathing
Tidal volume
Volume-controlled ventilation
Introduction
Spinal cord injury (SCI) is prevalent worldwide, with an estimated 1540 cases per
million population [1]. Injury to the cervical and upper thoracic cord may disrupt
the function of the diaphragm, intercostal muscles, accessory respiratory muscles,
and abdominal muscles. This causes reduction in spirometric parameters and static
mouth pressures and results in ineffective cough and difficulty in clearing secretions
M.A. Gaytant, MD, PhD (*) M.J. Kampelmacher, MD, PhD
Department of Home Mechanical Ventilation, University Medical Centre Utrecht,
P.O. Box 85500, Utrecht, GA 3508, The Netherlands
e-mail: m.a.gaytant@umcutrecht.nl; m.j.kampelmacher@umcutrecht.nl
DOI 10.1007/978-3-319-04259-6_37
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M.A. Gaytant and M.J. Kampelmacher
[2]. As a result, there is a predisposition to mucus retention, atelectasis, and pulmonary infections. These respiratory complications are the most common cause of
morbidity and mortality in patients with SCI, particularly in patients with cervical
SCI. In acute SCI, 80 % of deaths among hospitalized patients with cervical SCI are
secondary to pulmonary dysfunction, with pneumonia being the cause in 50 % of
the cases [3].
Prevention of respiratory complications is of major importance and needs to
commence immediately after injury [3, 4]. Despite improvement in the first months
of the initially low vital capacity and maximum inspiratory and expiratory flow
rates, patients with SCI still may face problems such as impaired cough or sleepdisordered breathing. These problems, in the acute phase or later, can lead to ventilatory failure requiring ventilatory support. This can either be invasive or
noninvasive.
37.2
Pathophysiology
In the case of an intact central nervous system, respiration occurs via two systems
[3, 5]:
(a) A coordinated activity of the somatic nervous system, which controls the inspiratory and expiratory muscles
(b) The autonomic nervous system, which controls the bronchial tone and
secretion
The diaphragm is the main inspiratory muscle and is innervated by the phrenic
nerve. It receives primary innervation at the C4 level, often with contribution from
C3 and C5. The diaphragm provides 65 % of the tidal volume during normal breathing. Other inspiratory muscles are the external intercostal muscles and the accessory
muscles (scalene, sternocleidomastoid, trapezius, and pectoralis). The intercostal
muscles are innervated by segmental spinal nerves (T111) and assist inspiration by
elevating the ribs, which expands the chest wall. The scalene muscles receive innervation by segmental nerves C48, the trapezius and sternocleidomastoid by C14
and the accessory nerves.
Expiratory muscles are the abdominal muscles and the lateral internal intercostals (T112) and are important for the expulsive force needed for an effective cough
and to clear secretions.
37.3
Respiratory Complications
The development of respiratory complications is directly correlated with the level of

injury as diagnosed by the American Spinal Injury Association Impairment Scale
[6]. Cervical SCI above the C3 level results in complete paralysis of all muscles
involved in respiration and therefore requires immediate mechanical ventilation to
37
Noninvasive Mechanical Ventilation in Tetraplegia
289
sustain life [5]. Respiratory complications occurred in 84 % of patients with C1 to C4

injuries and in 60 % of patients with C5 to C8 injuries [6]. In patients with T1 to T12
lesions, respiratory complications occurred in 65 % of patients and were often related
to direct chest trauma. The main respiratory complications are atelectasis, pneumonia, and ventilatory failure, but the incidence varies with the level of injury: atelectasis 40 % (C14), 34 % (C58), and 65 % (T112); ventilatory failure 40 % (C14),
23 % (C58), and 10 % (T112); and pneumonia 63 % (C14) and 28 % (C58) [3].
Other factors associated with pulmonary complications are age, preexisting (pulmonary) illness, and associated major traumatic injuries. Patients with these premorbid and comorbid conditions are at the highest risk to deteriorate rapidly over
the first 5 days.
Pulmonary complications after acute tetraplegia progressively increase over the
first 5 days following injury [2, 3, 6]. Several respiratory dysfunctions can lead to
respiratory failure:
Vital capacity impairment resulting from (a) a decreased respiratory muscle
strength and fatigue, (b) a reduction in inspiratory capacity, and (c) atelectasis.
Reduced expiratory pressures with ineffective cough will lead to mucus plugging
and atelectasis.
Autonomic nervous system dysfunction will lead to increased secretions, bronchospasms, and pulmonary edema.
37.4
Respiratory Management in the Acute Phase of SCI
Although pulmonary complications are a common problem in patients with SCI,

there is little evidence about their management. Current practice is mainly based on
clinical experience and expert opinion [7].
In patients with acute SCI, it is important to determine the level of injury as
accurately and as soon as possible because it will assist in the assessment and judgment of the patients likely ventilatory dysfunction. Examination must include an
evaluation of the breathing pattern, effectiveness of cough, vital capacity, and respiratory rate. The relevant medical history must include review of prior lung disease,
medication, substance abuse, and smoking history [35].
Because cervical SCI above the C3 level results in complete paralysis of all muscles involved in respiration, immediate and 24-h mechanical ventilation is required
to sustain life. Usually, this will lead to tracheostomal ventilation.
In case of cervical injury at C35, respiratory insufficiency results as a consequence of significant respiratory muscular dysfunction. At the first sign of respiratory distress, semi-elective intubation in these patients is recommended [8]. Criteria
for intubation are vital capacity deteriorating toward less than 10 ml/kg ideal body
weight, increasing oxygen requirements, and increasing respiratory rate with shallow breathing or hypoventilation (PCO2 > 45 mmHg). As the diaphragm receives
primary innervation at the C4 level with contribution commonly seen from C3,
290
there is a high degree of variability of the ability to wean in the C3 and C4 population [9]. In patients with SCI C56 or below, there is a probability to recover sufficient spontaneous ventilation.
As atelectasis, pneumonia, and ventilatory failure are the most common respiratory complications in the acute hospitalization phase of cervical SCI patients, monitoring and early treatment of these patients is of significant importance.
Consortium guidelines on respiratory management recommend that initial
assessment should include investigations like an arterial blood gas (ABG) and chest
X-ray [10]. ABG can show respiratory dysfunction: PaCO2 is used to evaluate ventilation abnormalities and PaO2 is a sensitive tool for evaluation of atelectasis. In the
first few days after injury, one can monitor respiratory function by serial ABG (e.g.,
4 times per 24 h) or by end-tidal CO2 measurements and continuous pulse oximetry.
Serial chest X-rays assess for atelectasis, pulmonary edema, and aspiration. In addition to these investigations, tachypnea, progressive desaturation, and rapid decline
of vital capacity are important signs of impending respiratory failure.
For secretion management and optimal ventilation, suctioning is essential.
However, possible complications like hypoxia, hypotension, infection, tracheal
mucosa damage, and increased bronchial mucous production can occur [3, 11].
In cases of impaired cough, peak cough flow may be augmented by means of
performing an abdominal thrust and/or squeeze over the chest wall in coordination
with either the patients spontaneous breath, an assisted breath, or by airstacking
(insufflation of air in the lungs after maximal inspiration with the use of a manual
resuscitation bag) combined with an abdominal thrust [4, 12].
In cases of chest trauma, internal abdominal trauma, or unstable spine traction,
this is, however, contraindicated. In these circumstances a mechanical insufflationexsufflation device or cough-assist machine might be used for mechanically assisted
coughing (MAC). This is a therapy that simulates the cough cycle through mobilizing secretions by gradually applying a positive pressure to the airways and then
rapidly shifting to negative pressure, generating a high expiratory flow simulating a
natural cough. It may also clear the left airways (which are often not cleared well by
invasive suctioning) and can be used in intubated, tracheotomized, and nonventilated patients [11, 13].
To clear the airways, MAC may be combined with Intrapulmonary Percussive
Ventilation (IPV, Percussionaire Corp., Sandpoint, ID, USA). This is a combination of high-frequency ventilation and intrapulmonary chest percussion. It is used to
mobilize and clear retained secretions and to assist in the resolution of atelectasis by
means of high-frequency ventilations (up to 300 breaths per minute), which loosen
retained secretions and deliver aerosol to hydrate viscous mucous plugs [3, 11].
37.5
Noninvasive Positive-Pressure Ventilation
Noninvasive positive-pressure ventilation (NPPV) may be delivered by a nasal or

oral-nasal interface or by a lip seal [4]. These systems are open and thus require lower
brain reflexes to prevent excessive insufflation leakage, especially during sleep.
37
291
37.5.1 Ventilators
Although any ventilator can be used for NPPV, increasingly ventilators are used that
are designed specifically for NPPV. There are two types that are specifically used:
bi-level positive airway pressure (BiPAP) and intermediate ventilators.
BiPAP ventilators are designed specifically for NPPV and use a single-limb circuit. A leak port, which serves as a passive exhalation port for the patient, is incorporated into the circuit near the patient or into the interface to prevent rebreathing.
Intermediate ventilators use a single-limb circuit with an exhalation valve near the
patient. Some of the intermediate ventilators can also be used with a leak system
like the BiPAP ventilators.
A number of modes can be used with NPPV, and there are advantages and disadvantages of each. The BiPAP ventilators typically provide pressure support or
pressure-controlled ventilation. The newer generations of the intermediate ventilators provide volume-controlled ventilation (VCV), pressure-controlled ventilation
(PCV), and pressure support ventilation (PSV).
PSV This mode is used most commonly for NPPV. With bi-level ventilators, the
difference between inspiratory positive airway pressure and expiratory positive airway pressure is the level of pressure support (PS). With a critical care ventilator, the
level of PS is applied as a pressure above the baseline positive end-expiratory pressure (PEEP).
PCV This is similar to PSV in that the ventilator applies a fixed level of support
with each breath, but there are two differences: there is a back-up rate and the inspiratory time is fixed.
VCV With VCV, the ventilator delivers a fixed tidal volume (TV) and inspiratory
flow with each breath. VCV has been used during NPPV for home mechanical ventilation (HMV) with intermediate ventilators and requires a non-vented interface. It
can also be used to provide mouthpiece ventilation and for breath-stacking
maneuvers.
PCV or PSV will compensate for leaks better than VCV. With VCV, flow and
volume delivery from the ventilator are fixed, so any leak will reduce the TV. To
compensate for a leak, the set TV may be increased but this will usually increase the
leak as well. In case of PSV or PCV, the ventilator targets a constant inspiratory
pressure. Thus, if a leak occurs, there will be a drop in pressure, at which point the
ventilator increases the flow to restore the pressure.
37.5.2 Interfaces
The choice of interface is a major determinant of NPPV success or failure, mainly
because the interface strongly affects patient comfort. This comfort may be affected
292
by air leaks, claustrophobia, facial skin erythema, rash, irritation of the eyes, and
skin breakdown (especially of the nose bridge).
The following masks are used:
Nasal mask: covers the nose but not the mouth

Nasal pillows: plugs inserted into the nostrils
Oronasal mask: covers the nose and mouth
Full face mask: covers the mouth, nose, and eyes
Oral interface: One particular form of NPPV is mouthpiece ventilation, via
15-mm angled or straight mouthpiece that can be kept between the teeth intermittently during the day.
Air leaks may reduce patient tolerance and the effectiveness of NPPV, increase
patient-ventilator asynchrony (loss of triggering sensitivity), and cause discomfort
during sleep.
Nasal masks/pillows have less interference with speech and eating, and allow
coughing and vomiting. Nasal pillows have less dead space than face masks, are less
likely to produce claustrophobia, and allow for wearing glasses. Pillows can be
alternated with oronasal and nasal masks to minimize friction and pressure on the
skin, which could improve tolerance of NPPV and therefore allow for more hours
of ventilation per day. Contraindications are leaks from the mouth during sleep, for
example, due to bulbar pathology.
Oral interfaces are used by patients who have severe chronic respiratory failure
and have to be ventilated during daytime for many hours. During the night they use
a nasal or oronasal mask.
Oronasal masks: The advantages compared with nasal masks are that they cause
less air leaks. They are, however, contraindicated in patients with claustrophobia
and in patients with impairment in arm movement who cannot remove their mask in
case of vomiting.
Full face masks are often used in acute NPPV but not often in long-term NPPV. In
case of severe skin problems of the nose bridge, a full face mask can be used temporarily to let the skin heal.
37.6
NPPV in SCI Patients
For patients with motor complete SCI at the C5 level and below, spontaneous respiratory effort may initially be supported by BiPAP [14]. Positive airway pressure
improves ventilation because of a better gas exchange and improves resting lung
ventilation by increasing the TV. It is also useful in preventing and treating atelectasis. Applying PEEP will generate resistance on exhalation, which may increase
oxygenation and treat atelectasis [3].
If the patient is able to grab a mouthpiece that is fixed near the mouth by a
flexible metal support arm attached to the wheelchair and keep it between his or
her teeth all day, ventilation during daytime is available whenever needed by the
37
293
patient. Alternatively, nasal pillows or a nasal mask may be used for daytime
ventilation [4].
The standard ventilator settings of 68 ml/kg of ideal bodyweight (BW) do not
apply for patients with SCI. In patients with complete tetraplegia, high TVs up to
20 ml/kg of ideal BW have been beneficial in stabilizing their ventilation [11]. Low
TVs delivered to patients with acute tetraplegia can lead to atelectasis, mucous
plugging, and decreased production of surfactant [11]. High TV ventilation recruits
distal airways, stimulates surfactant production, and improves oxygenation. Peak
airway pressures with these higher TVs rarely exceed 30 cm H2O because of flaccid
muscle tone in patients with complete tetraplegia, thus taking away the fear of barotrauma [11].
In a retrospective review of 28 patients with acute SCI, BiPAP was successfully
used in 10 of 17 patients to prevent the need for full-time ventilation [14]. In these
10 patients, vital capacity (VC) on admission measured 1.1 l (range 0.71.8 l) and
decreased to a mean of 0.9 l immediately before starting BiPAP. In the seven patients
in which BiPAP did not prevent ventilatory failure, the mean vital capacity fell to
0.6 l before beginning BiPAP. Bach [3] recommends the use of NPPV, either nasally
or by mouthpiece ventilation, in case of dyspnea or if the VC falls below 1500 ml
over a relative short time, or less than 1200 ml at any time. Reasons to initiate treatment with BiPAP, according to Tromans et al. [14], included respiratory fatigue and
exhaustion with falling oxygen saturation and decreasing vital capacity. Both studies are retrospective and had a limited number of cases.
37.7
Sleep-Disordered Breathing and SCI
In SCI patients, sleep disordered breathing (SDB) is highly prevalent, ranging

between 27 and 62 % [1]. SDB is defined as an apnea/hypopnea index of 15
events/h of sleep. The underlying pathophysiology in relation to SCI is unknown,
and there are insufficient and conflicting data on the type of SDB (central or obstructive) and the relationship between the type of SDB and the level of SCI. Several
studies show evidence, however, that the frequency of SDB in SCI patients is high,
especially for obstructive sleep apnea (OSA), and there seems to be a correlation
with the level of SCI, age, body mass index, neck circumference, abdominal girth,
and the use of sedating medication [5]. In case of OSA without central apneas or
nocturnal hypoventilation, continuous positive airway pressure (CPAP) may be an
effective therapy. However, in case of significant central sleep apneic episodes with
hypercapnia notwithstanding CPAP therapy, BiPAP seems to be more appropriate.
37.8
Discussion
Respiratory complications are still the leading cause of morbidity and mortality in
patients with SCI. In patients with cervical SCI above the C3 level, immediate and
24-h mechanical ventilation is required to sustain life. In practice, this almost always
294
will lead to tracheostomal ventilation. There are, however, experiences with immediate NPPV after extubation [4] and transition to NPPV after a period of tracheostomal ventilation in patients with very high SCI injuries [15].
In case of cervical injury at C35, respiratory insufficiency results as a consequence of significant respiratory muscular dysfunction, which will lead to inadequate VC and inadequate cough. In these patients, there may be a role for NPPV
over the long term instead of invasive ventilation. The success of the transition to
NPPV will depend on knowledge of NPPV techniques and familiarity with techniques like airstacking, MAC and IPV. Without adequate experience of these techniques, failure of NPPV is likely to happen.
In patients with SCI at C56 or below, there is a probability to recover sufficient
spontaneous ventilation. However, they remain at risk for the development of respiratory failure and SDB. Consequently, regular follow-up is recommended with
assessment of respiratory function, nocturnal gas exchange, and symptoms that
would indicate respiratory insufficiency. Noninvasive techniques like airstacking
and MAC may prevent respiratory insufficiency. When respiratory insufficiency
will occur, despite all efforts, NPPV can be initiated.
In recent years, the use of NPPV has been proposed for patients with SCI as respiratory support both in acute conditions, in respiratory weaning, and as long-term nocturnal support for patients with hypoventilation [7]. Most publications, however, are
case reports or retrospective studies with low numbers of patients. According to Bach
[4], the only indication for tracheotomy in SCI patients is when saliva aspiration
occurs to the degree that the oxyhemoglobin saturation (SpO2) decreases and remains
below 95 % irrespective of optimal use of MAC or NPPV. Thus, NPPV in combination with MAC, airstacking, and close monitoring could become the therapy of choice
in SCI patients, either following intubation or instead of intubation but also for SCI
patients who stay ventilator dependent. There remains, however, a need for prospective randomized controlled trials to support the use of NPPV as a substitute for invasive mechanical ventilation, both in the acute setting and over the long term.
References
1. Sankari A, Bascom AT, Chowdhuri S, et al. Tetraplegia is a risk factor for central sleep apnea.
J Appl Physiol (1985). 2014;116(3):34553.
2. Schilero GJ, Spungen AM, Bauman WA, et al. Pulmonary function and spinal cord injury.
Respir Physiol Neurobiol. 2009;166(3):12941. Review.
3. Berlly M, Shem K. Respiratory management during the first five days after spinal cord injury.
J Spinal Cord Med. 2007;30:30918. Review.
4. Bach J. Noninvasive respiratory management of high level spinal cord injury. J Spinal Cord
Med. 2012;35:7280.
5. Biering-Sorensen F, Jennum P, Laub M. Sleep disordered breathing following spinal cord
injury. Respir Physiol Neurobiol. 2009;169:16570.
6. Jackson AB, Groomes TE. Incidence of respiratory complications following spinal cord injury.
Arch Phys Med Rehabil. 1994;75:2705.
7. Galeiras Vasquez R, Rascado Sedes P, Mourelo Farina M, et al. Respiratory management in the
patient with spinal cord injury. Biomed Res Int. 2013;2013:168757.
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8. Como JJ, Sutton ER, McCunn M, et al. Characterizing the need for mechanical ventilation
following cervical spinal cord injury with neurological deficit. J Trauma. 2005;59:9126.
9. Chiodo AE, Scelza W, Forchheimer M, et al. Predictors of ventilator weaning in individuals
with high cervical spinal cord injury. J Spinal Cord Med. 2008;31:727.
10. Consortium for Spinal Cord Medicine. Respiratory management following spinal cord injury:
a clinical practice guideline for health-care professionals. J Spinal Cord Med.
2005;28:25993.
11. Wong SL, Shem K, Crew J. Specialized respiratory management for acute cervical spinal cord
injury: a retrospective analysis. Top Spinal Cord Inj Rehabil. 2012;18(4):28390.
12. Torres-Castro R, Vilar J, Vera-Uribe R, et al. Use of air stacking and abdominal compression
for cough assistance in people with complete tetraplegia. Spinal Cord. 2014;52(5):3547.
13. Winck JC, Goncalves MR, Lourenco C, et al. Effects of mechanical insufflation-exsufflation
on respiratory parameters for patients with chronic airway secretion encumbrance. Chest.
2004;126:77480.
14. Tromans AM, Mecci M, Barrett FH, et al. The use of BiPAP system in acute spinal cord injury.
Spinal Cord. 1998;36:4814.
15. Toki A, Tamura R, Sumida M. Long-term ventilation for high-level tetraplegia: a report of 2
cases of noninvasive positive-pressure ventilation. Arch Phys Med Rehabil. 2008;89:77983.

in Sleep-Related Breathing Disorders
38
Stefanie Keymel, Volker Schulze, and Stephan Steiner
Abbreviations
AHI
APAP
ASV
AVAPS
COPD
CPAP
CSA
CSR
NIV
OSA
PAP
SRBD
Apnea Hypopnea Index

Auto Positive Airway Pressure
Adaptive Servo Ventilation
Average volume-assured pressure support ventilation
Chronic obstructive lung disease
continuous positive airway pressure
Central sleep apnea
Cheyne Stokes Respiration
Non invasive ventilation
Obstructive sleep apnea
Positive airway pressure
sleep related breathing disorders
S. Keymel, MD V. Schulze, MD
Medical Faculty, Division of Cardiology (Prof. Dr. M. Kelm), Pneumology and Angiology,
Department of Medicine, University Hospital Duesseldorf, Duesseldorf, Germany
S. Steiner, MD (*)
Division of Cardiology, Pneumology and Intensive Care Medicine, Department of Medicine,
St. Vincenz Hospital, Auf dem Schafsberg, Limburg/Lahn 65549, Germany
e-mail: s.steiner@st-vincenz.de
DOI 10.1007/978-3-319-04259-6_38
297
298
38.1
S. Keymel et al.
Introduction
Sleep-related breathing disorders (SRBDs) are common in the general public and
can be differentiated by miscellaneous diseases, for example, neuromuscular disorders, obesity-hypoventilation, or sleep apnea syndromes. The latter comprise
obstructive, central, and mixed forms according to different pathomechanisms. As a
result of increasing pathophysiological insights, further definitions, including the
so-called complex sleep apnea or the overlap syndrome, were established. In
addition to improvement of symptoms such as daytime sleepiness and depression,
effective treatment enhances the prognosis, presumably as a result of a reduction in
cardiovascular complications [1]. There are different therapeutic approaches, most
of which include application of positive airway pressure (PAP).
This chapter discusses the different types of PAP (for definitions, see
Table 38.1) and their use is summarized with respect to sleep apnea syndromes.
Although there is a challenging evolution of devices, it should be kept in mind
that the proper choice of ventilation mode depends on an adequate diagnosis and
pressure titration [2].
38.2
Definition of Sleep Apnea
SRBDs refer to an abnormal respiratory pattern or an abnormal reduction in gas

exchange during sleep. An apnea in adults is scored when there is a drop in the
peak signal excursion by 90 % of pre-event baseline for 10 s. Hypopnea in
adults is scored when the peak signal excursions drop by 30 % of pre-event
baseline for 10 s in association with either 3 % arterial oxygen desaturation or
an arousal [3]. Apneas plus hypopneas per hour of sleep define the apnea hypopnea index (AHI). Roughly, SRBDs are divided into three groups: obstructive
sleep apnea (OSA), central sleep apnea (CSA), and sleep-related hypoventilation/hypoxemia syndromes.
OSA is clinically defined by the occurrence of daytime sleepiness, loud snoring,
witnessed breathing interruptions, or awakenings caused by gasping or choking in
the presence of at least five obstructive respiratory events per hour of sleep. The
presence of 15 or more obstructive respiratory events per hour of sleep in the
absence of sleep-related symptoms is also sufficient for the diagnosis of OSA
Table 38.1 Different types

of positive airway pressure
CPAP
APAP
BPAP
ASV
AVAPS

Automatic adjustment continuous positive
airway pressure
Adaptive servo-ventilation
Average volume-assured pressure support
ventilation
38
Noninvasive Mechanical Ventilation in Sleep-Related Breathing Disorders
299
because of the greater association of this severity of obstruction with important

consequences such as increased cardiovascular risk [4].
The CSA syndromes are characterized by sleep-disordered breathing associated
with diminished or absent respiratory effort, coupled with the presence of symptoms including excessive daytime sleepiness, frequent nocturnal awakenings, or
both. CSA may be related to Cheyne-Stokes respiration (CSR), which is characterized by an absence of air flow and respiratory effort followed by hyperventilation
in a crescendo-decrescendo pattern [4]. CSR most often occurs in patients with
congestive heart failure but can also occur in patients with stroke or renal failure.
CSA may also be related to high altitude or to medications such as opioids.
Sleep-related hypoventilation/hypoxemia syndromes are characterized by
reduced alveolar ventilation. In addition to rare idiopathic or congenital forms,
hypoventilation syndromes occur in lung diseases, neuromuscular diseases, or obesity. For adults, sleep hypoventilation is scored when the arterial pCO2 (or surrogate) is >55 mmHg for 10 min or there is an increase in the arterial pCO2 (or
surrogate) 10 mmHg (in comparison to an awake supine value) to a value exceeding 50 mmHg for 10 min [3].
38.3
Indications for PAP Devices
Most evidence concerning indications for ventilation therapy and outcome exists for
patients with OSA. Patients with an AHI 15/h or symptomatic patients with an
AHI 5/h should be considered for treatment of OSA [4]. OSA should be approached
as a chronic disease requiring long-term multidisciplinary management [4]. PAP is
the treatment of choice for mild, moderate, and severe OSA and should be offered
as an option to all patients. Continuous PAP (CPAP) is the first choice of treatment
and is recommended as standard for patients with moderate to severe disease and as
an option for patients with mild disease [4, 5]. Other modalities such as bi-level PAP
(BPAP), autotitrating PAP, or pressure relief may be considered in patients with
CPAP failure [4].
For nonobstructive sleep apnea, the evidence of treatment and outcome is rather
limited. In patients with CSA, CPAP therapy targeted to normalize AHI is indicated
for the initial treatment of CSA related to congestive heart failure. If suppression of
AHI is not sufficient by CPAP, adaptive servo-ventilation (ASV) or BPAP therapy
in a spontaneous timed mode may be applied [6]. In case of hypoventilation/hypoxemia syndrome with proven hypercapnia, BPAP therapy as noninvasive positive
pressure ventilation with true ventilatory support should be considered.
38.4
Continuous Positive Airway Pressure (CPAP)
In a strict sense, CPAP is not a form of ventilation but an application of a constant

pressure during spontaneous breathing. At first sight, effectiveness is quite simple:
PAP acts as a pneumatic splint and, therefore, prevents partial or full occlusion of
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S. Keymel et al.
the upper airway during sleep in OSA syndrome. Thus, the pathophysiologic cascade, which includes hypoxemia, intrathoracic pressure swings, repetitive arousals,
and adrenergic stimulation, is avoided. However, there are other, mostly positive
hemodynamic effects, especially in heart failure patients, and an unloading of the
respiratory system. Because end expiratory lung volume rises, there are beneficial
effects on gas exchange. Beyond these acute effects, it should be kept in mind that
CPAP is known to reduce cardiovascular risk [1] and has positive effects on clinical
course of coronary artery disease [7], restenosis after coronary stent implantation
[8], and ventricular remodeling after myocardial infarction [9].
Auto CPAP (APAP) is a particular form of CPAP. Specific algorithms were
evolved to detect variations of airway obstruction and adjust pressure level. In
clinical practice, areas of application developed: APAP could be used to titrate
CPAP pressure to save costs. Moreover, it could be used in patients with sleep
apnea only during rapid eye movement sleep or respiratory events related to
position [10]. Because APAP allows adaption of pressure to current requirement, median nocturnal pressure is lower compared with conventional CPAP
[11]. This might contribute to better acceptance and, therefore, higher adherence to therapy. If exhalation against positive pressure is associated with patient
discomfort, some devices allow an expiratory pressure contour modification
[12]. APAP should not be used in patients with severe comorbidities such as
heart failure, chronic obstructive pulmonary disease (COPD), or hypoventilation syndromes [12].
38.5
Beyond CPAP: Role of Noninvasive Ventilation

in Therapy of Nocturnal Breathing Disorders
Although OSA can be treated effectively by CPAP in most patients, problems can
occur under some conditions. In this context, it should be considered that sleep
apnea is associated generally with increased work of breathing, especially in hypercapnic patients [13]. There are three main reasons to step up CPAP to noninvasive
ventilation (NIV) in patients with SRBDs:
1. Patients require high pressure, 1015 cmH2O, to eliminate collapse of the upper
airways. Exhalation against high pressures can be uncomfortable, furthering
problems with the interface such as leaks. The need for high pressures is associated with a reduced adherence to therapy [4].
2. Predominantly central apnea, Cheyne-Stokes ventilation, or change from
obstructive to central apnea under CPAP application. As has been emphasized,
OSA syndrome is a matter of upper airway collapse but not a problem of respiratory drive. In contrast, central apnea is characterized by a cessation of central
respiratory drive, often associated with stroke or congestive heart failure.
Therefore, it is not surprising that CPAP attenuates central apnea only for about
50 % of patients [14, 15]. A post hoc analysis of the Canadian Continuous
38
301
Positive Airway Pressure (CANPAP) study showed that, to improve survival, it

is essential to reduce sleep disorders [16]. This implicates the need for additional
ventilator support.
3. Coexistent diseases (overlap syndromes)
It has been recognized for more than 30 years that several respiratory diseases
(e.g., COPD, lung fibrosis, and sleep apnea) can occur in the same patient [17].
Beyond coexistence, diseases might influence each other, mostly negatively. The
common combination of OSA syndrome and COPD (overlap syndrome),
which occurs in about 1 % of the general adult population [18], has been shown
to be associated with a more severe nocturnal hypoxemia and greater risk of
morbidity and mortality [19]. In these patients, CPAP is still a therapeutic option,
with the additional application of nocturnal oxygen if necessary. Nevertheless, to
optimize oxygenation and minimize respiratory workload, NIV might be helpful.
In a review, McNicholas [18] proposed a pragmatic approach: in cases where
OSA syndrome predominates, CPAP might be appropriate; whereas in patients
with significant nocturnal hypoventilation and sustained hypoxemia, NIV may be
advantageous.
38.6
Modes of NIV
In contrast to CPAP, NIV is characterized by administered pressure between inspiratory and expiratory cycles in varying degrees [12]. The major advantages of NIV
with respect to CPAP are listed in Table 38.2. With continuous advancements in
ventilators, several ventilators are now available. The more complex the SRBDs are
(e.g., mixed apnea or changing from obstructive to central apnea), the more sophisticated are the device settings needed.
NIV is characterized by augmentation of inspiratory as well as expiratory flow
and an unloading of respiratory muscles [20]; the latter is associated with a reduction in respiratory work. Further on, enhancement of tidal volumes and minute
ventilation improves hypoventilation. A simple approach to NIV is the use of
BPAP. The difference between inspiratory pressure and positive end-expiratory
pressure inspiration is augmented by an increased pressure support that can be
initiated by an inspiratory trigger. In this case, breathing frequency is regulated by
the patient. In this setting, inspiratory trigger consumes meaningful work of
breathing (up to 3350 % of the work of passive inflation [21]), which might
restrict benefit in patients with coexistent lung disease or neuromuscular disorders
Table 38.2 Major

advantages of NIV
compared with
CPAP/APAP in
sleep apnea
Alveolar ventilation resulting from inspiratory pressure change

Unloading of respiratory muscles
Decrease work of breathing
Mandatory support in case of central apnea
302
S. Keymel et al.
or who are overweight. To minimize work of breathing, the use of a timed mode
might be beneficial.
In cases of central apnea, Cheyne-Stokes respiration, or hypoventilation, BPAP
use is reasonable. In this setting, it is recommended to use the backup rate option.
Other forms of NIV include ASV, which adapts pressure to maintain more consistency of respiration over time. In addition to suppression of hypopnea/apnea, ASV
is designed to promote uniform ventilation and a reduction of arousal [22]. Average
volume-assured pressure support ventilation (AVAPS) combines gains of pressure
support ventilation and volume-controlled ventilation. Because this mode ensures a
delivered tidal volume, it might be utilized in hypoventilation syndromes or in CSA.
Sleep apnea is associated with an increased work of breathing.

CPAP remains the cornerstone of treatment of OSA syndrome.
There are several forms of NIV (e.g., BPAP, ASV, and AVAPS), and therapy can therefore be adapted to individual requirements and pathophysiological needs
NIV should be considered in central apnea, hypoventilation resulting from
overlap syndromes, or when high PAP is needed for patient comfort.
References
1. Marin JM, Carrizo SJ, Vicente E, et al. Long-term cardiovascular outcomes in men with
obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005;365:104653.
2. Force PAPTT, American Academy of Sleep Medicine. Clinical guidelines for the manual titration of positive airway pressure in patients with obstructive sleep apnea. J Clin Sleep Med.
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3. Berry RB, Budhiraja R, Gottlieb DJ, et al. Rules for scoring respiratory events in sleep: update
of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. J Clin Sleep Med.
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4. Force AOSAT, American Academy of Sleep Medicine. Clinical guideline for the evaluation,
management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med.
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5. Kushida CA, Littner MR, Hirshkowitz M. Practice parameters for the use of continuous and
bilevel positive airway pressure devices to treat adult patients with sleep related breathing
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6. Aurora RN, Chowdhuri S, Ramar K, et al. The treatment of central sleep apnea syndromes in
adults: practice parameters with an evidence-based literature review and meta-analyses. Sleep.
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7. Milleron O, Pilliere R, Foucher A, et al. Benefits of obstructive sleep apnoea treatment in coronary artery disease: a long-term follow-up study. Eur Heart J. 2004;25:72834.
8. Steiner S, Schueller P, Hennersdorf M, et al. Impact of obstructive sleep apnea on the occurrence of restenosis after elective percutaneous coronary intervention in ischemic heart disease.
Respir Res. 2008;9:50.
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9. Buchner S, Satzl A, Debl K, et al. Impact of sleep-disordered breathing on myocardial salvage

and infarct size in patients with acute myocardial infarction. Eur Heart J. 2013;35:1929.
10. Fischer J, Dogas Z, Bassetti CL, et al. Standard procedures for adults in accredited sleep medicine centres in Europe. J Sleep Res. 2012;21:35768.
11. Grueger H. CPAP versus APAP-ein Titrationsvergleich im Schlaflabor sowie ein Vergleich mit
der huslichen Therapieeffektivitt. Universitts- und Landesbibliothek der Heinrich-HeineUniversitt Dsseldorf; 2013
12. Antonescu-Turcu A, Parthasarathy S. CPAP and bi-level PAP therapy: news and established
roles. Respir Care. 2010;55:121628.
13. Lee MY, Lin CC, Shen SY, et al. Work of breathing in eucapnic and hypercapnic sleep apnea
syndrome. Respiration. 2009;77:14653.
14. Arzt M, Wensel R, Montalvan S, et al. Effects of dynamic bilevel positive airway pressure
support on central sleep apnea in men with heart failure. Chest. 2008;134:616.
15. Bradley TD, Logan AG, Kimoff RJ, et al. Continuous positive airway pressure for central sleep
apnea and heart failure. N Engl J Med. 2005;353:202533.
16. Arzt M, Floras JS, Logan AG, et al. Suppression of central sleep apnea by continuous positive
airway pressure and transplant-free survival in heart failure: a post hoc analysis of the Canadian
Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure
Trial (CANPAP). Circulation. 2007;115:317380.
17. Fenley D. Sleep in chronic obstructive lung disease. Clin Chest Med. 1985;6:65161.
18. McNicholas WT, Verbraecken J, Marin JM. Sleep disorders in COPD: the forgotten dimension. Eur Respir Rev. 2013;22:36575.
19. Owens RL, Malhotra A. Sleep-disordered breathing and COPD: the overlap syndrome. Respir
Care. 2010;55:133346.
20. Pankow W, Hijjeh N, Schuttler F, et al. Influence of noninvasive positive pressure ventilation
on inspiratory muscle activity in obese subjects. Eur Respir J. 1997;10:284752.
21. Marini JJ, Capps JS, Culver BH. The inspiratory work of breathing during assisted mechanical
22. Caples S, Somers V. Central sleep apnea, hypoventilation syndromes and periodic breathing disorders. In: Randerath W, Sanner B, Somers V, editors. Sleep apnea. Basel: Karger; 2006. p. 18091.
Impact of Noninvasive Positive-Pressure

Ventilation in Unplanned Extubation
39
Emel Eryksel and Turgay elikel
Abbreviations
ICU
NPPV
UE
Intensive care unit

Unplanned extubation
Intubations are among the most common invasive interventions performed in the
intensive care unit (ICU), and most ICU patients who require mechanical ventilation are intubated. Unplanned extubation (UE), an intubation-associated complication, is defined as the removal of an endotracheal tube by a patient or its accidental
removal. The reported frequency of UE ranges between 3 and 16 % among patients
on mechanical ventilatory support [13]. A previous study in our center showed a
similar rate of extubation (11 %) [4]. Among its main causes are inadequate sedation and insufficient nursing care during positioning. Nevertheless, UE may occur
even under optimal conditions where sedation is adequate and all necessary precautions are taken. Successful management of UE may result in shortened duration of
intubation and reduced rate of complications associated with mechanical ventilation. On the other hand, failure to do so may lead to the need for reintubation, leading to an increased risk of complications.
In a case-control study by Epstein et al. [5], a total of 75 patients with UE were
compared with 150 controls. In their center, the incidence of UE was 11 %. Patients
E. Eryksel, MD (*) T. elikel

Pulmonary and Critical Care, Marmara University Hospital,
Mimar Sinan Caddesi No: 41 st Kaynarca, Fevzi akmak Mahallesi Pendik,
Istanbul, Turkey
e-mail: emeleryuksel@yahoo.com
DOI 10.1007/978-3-319-04259-6_39
305
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E. Eryksel and T. elikel
with UE had a longer duration of stay in the ICU as well as prolonged hospitalization. However, patients with UE who did not require reintubation had similar mortality, ICU and hospital stay, and mechanical ventilation duration as controls. In that
study, controls and patients with UE did not significantly differ in terms of inhospital mortality. Furthermore, patients who did or did not require reintubation
after UE had similar rates of in-hospital mortality. Thus, UE emerged as a risk factor
associated with prolonged duration of intensive care and hospitalization.
In another study, by Atkin et al. [6], the clinical outcomes in 50 patients with UE
and 100 controls were compared, whereby the frequency of nosocomial infections
before the occurrence of UE was higher among patients with UE than among controls. However, these authors did not report on the infection incidence following the
occurrence of UE. Similar to the previously mentioned study, patients with UE had
longer hospital and ICU stay, despite the absence of a significant difference in inhospital mortality rates from controls (38 % vs 25 %; p = 0.14).
Krinsley and Barone [7] compared 100 patients with UE and 200 control subjects and observed an increased duration of hospital and ICU stay, in addition to a
prolonged requirement for mechanical ventilation in UE cases. However, there was
a significantly higher mortality rate in controls. As compared with patients with UE
who did not require reintubation, those who required reintubation had an increase in
hospital and ICU stay, requirement for mechanical ventilation, frequency of infections acquired during intensive care, costs associated with intensive care, laboratory
work-up, and diagnostic imaging studies, and, most importantly, they had increased
mortality. In the same study, a multiple logistic regression analysis showed that age
was the single most important determinant of the need for reintubation, while reintubation was the most important determinant of mortality after UE. In that study,
reintubation was not only associated with an increased occurrence of intensive careacquired infections but also with increased mortality.
Between 22 and 74 % of patients require reintubation after UE and most studies
reported increased mortality in patients requiring reintubation after UE. The
reported rate of reintubation was 56 % in the study by Epstein et al. [5]. Risk factors
for UE and factors associated with the need for reintubation were explored by
Chevron et al. [8], who found that a Glasgow Coma Scale score below 11 and a
PaO2/FiO2 ratio below 200 correlated with a higher frequency of the need for reintubation in patients in whom UE occurred during weaning.
Despite the clear association between UE and life-threatening complications,
most institutions still lack standard procedures to be implemented in the case of
UE. While the need for reintubation is immediately evident in a certain proportion
of patients (e.g., inability to maintain an airway, significant oxygen requirement,
unconsciousness) who require prompt reintubation after UE, others may not be in
the need of reintubation despite the continued need for mechanical ventilation at the
time of the occurrence of UE. The need for intubation is not synonymous with the
need for mechanical ventilation, and in a certain group of patients noninvasive
mechanical ventilation may be considered as an alternative to re-intubation.
Invasive mechanical ventilation is a safe method in ICU patients when noninvasive positive-pressure ventilation (NPPV) is contraindicated or not applicable.
39
Impact of Noninvasive Positive-Pressure Ventilation in Unplanned Extubation
307
However, complications like nosocomial pneumonia and intubation-related complications may occur.
Prevalence of nosocomial pneumonia rises significantly with recurrent intubations [9]. In a study examining the role of reintubation in the development of nosocomial pneumonia, 40 patients who underwent reintubation were compared with
controls. A significant proportion (47 %) of patients who underwent reintubation
had pneumonia compared with only 10 % of controls, a statistically significant difference. A logistic regression analysis in the same study showed that reintubation
was the most important factor for the development of pneumonia. Reintubated
patients had a significantly longer total duration of stay in the ICU as well as
increased mortality. Therefore, early administration of NPPV before the development of respiratory failure may decrease the frequency of reintubations, which was
demonstrated in previous studies, along with a decrease in ICU mortality.
Nava et al. [10] examined the effect of early noninvasive mechanical ventilation
versus medical treatment alone on the frequency of reintubation. A total of 97
patients were randomly allocated into two groups to receive either noninvasive
mechanical ventilation for 8 h/day for 2 days after extubation, or to receive standard
medical treatment. Compared with standard medical treatment alone, a significantly
lower need for reintubation was found in the noninvasive mechanical ventilation
group (4 of 48 vs 12 of 49; p = .027). Whereas the need for reintubation was associated with increased mortality (p < 0.01), the use of noninvasive mechanical ventilation resulted in a lower rate of intensive care mortality (10 %, p < 0.01).
In the study by Ferrer et al. [11] involving 162 patients with a high risk of reintubation after extubation, the effect of early noninvasive mechanical ventilation in
the prevention of respiratory failure after extubation was explored in conjunction
with effects on 90-day survival. Although noninvasive ventilation did not result in
an improvement in 90-day survival rates, a subgroup analysis comparing patients
with or without hypercapnia showed both a significantly better intensive care mortality rate and better survival at 90 days with noninvasive ventilation compared with
standard medical management in the former group of subjects.
NPPV is able to improve respiratory failure and decrease mortality and duration
of hospitalization without intubation in eligible patients. Several studies investigated the use of NPPV in the failure of planned extubation or in case of UE. NPPV
is the first treatment of choice in acute respiratory failure secondary to chronic
obstructive pulmonary disease and in cardiogenic acute pulmonary edema. However,
these effects do not result in improved rates of survival, and a higher number of
adverse events occur with NPPV treatment. NPPV is recommended particularly in
immunosuppressed patients with acute respiratory failure because it decreases
infectious complications caused by intubation. Data regarding the successful use of
NPPV in patients with hypoxemic respiratory failure are growing.
To evaluate the effectiveness of NPPV in preventing the need for intubation, Jiang
et al. [12] initiated NPPV following extubation before the development of respiratory
distress and found that NPPV did not result in any survival benefit when compared
with standard medical treatment. They randomized 93 patients in whom UE occurred
or who failed to be extubated into oxygen treatment or NPPV. Of these patients,
308
E. Eryksel and T. elikel
extubation was performed electively in 56, whereas self-extubation occurred in 37.

These patients received either bi-level positive airway pressure or oxygen, and of the
overall group of 93 patients, 20 (21.5 %) required reintubation. A comparison
between patients with and without reintubation did not show any age, gender, or
blood gas concentration (before extubation) differences. No significant difference
between the two groups in terms of reintubation frequency was found. Elective extubation was associated with a significantly better survival compared with UE.
Most of the studies exploring the effect of NPPV on the frequency of reintubation
have been conducted in patients with a failed extubation attempt. Keenan et al. [13]
were not able to demonstrate the superiority of NPPV over standard treatment in their
study involving patients who developed respiratory stress within the 48 h following
extubation. A comparison between a noninvasive treatment group and a standard
medical treatment group did not show any differences in reintubation rates, hospital
mortality, duration of mechanical ventilation, or duration of ICU or hospital stay.
Esteban et al. [14] conducted a study in 221 patients comparing NPPV and standard
treatment and found that NPPV did not reduce the need for reintubation. Most importantly, the study showed that delaying intubation in cases of acute respiratory failure
occurring after extubation was associated with increased mortality. Thus, when UE
occurs, patients must be carefully followed-up, NPPV contraindications should be rapidly reviewed, and patients not eligible for NPPV should be reintubated without delay.
To evaluate the effectiveness of NPPV in preventing the need for intubation,
Eryksel et al. [4] initiated NPPV following self-extubation. Their study differs
from other studies in that patients had an UE without a schedule. Although most of
them were at a point when weaning was being considered, their evaluation within
the previous 24 h did not permit extubation, that is, weaning criteria were not completely met. Of the 11 patients at the weaning period, 10 responded satisfactorily to
NPPV treatment. Indication for intubation had been pneumonia in four of the
patients with successful response. However, evaluation performed just after UE
revealed minimum amounts of secretions. Among the main factors affecting NPPV
success are copious amounts of secretions at the airways and difficulty in expectorating these secretions because of muscular weakness. The good cooperation and
compliance of the patient group to NPPV treatment might have contributed to this
success. In the successful group, two patients were initially intubated for epilepsy
and one for the protection of airways during hemodynamic shock and unconsciousness secondary to gastrointestinal bleeding. By chance, mechanical ventilation had
not been complicated by infection in these patients and NPPV was administered
after UE following more than 72 h of mechanical ventilation.
Conclusion
Based on previous studies, the reported rate of UE in most ICUs is approximately 710 %. Approximately half of all patients with UE will require reintubation. NPPV may be an option in patients with UE during the weaning period.
However, when the UE occurs before weaning criteria are met, NPPV contraindications should be rapidly reviewed and patients not eligible for NPPV should
be reintubated without delay.
39
Impact of Noninvasive Positive-Pressure Ventilation in Unplanned Extubation
309
References
1. Coppolo DP, May JJ. Self-extubations: a 12-month experience. Chest. 1990;98:1659.
2. Jayamanne D, Nandipati R, Patel D. Self-extubation: a prospective study. Chest. 1988;94:3S.
3. Tindol Jr GA, DiBenedetto RJ, Kosciuk L. Unplanned extubations. Chest. 1994;105(6):
18047.
4. Eryksel E, Karakurt S, Celikel T. Noninvasive positive pressure ventilation in unplanned
extubation. Ann Thorac Med. 2009;4:1720.
5. Epstein SK, Nevins ML, Chung J. Effect of unplanned extubation on outcome of mechanical
ventilation. Am J Respir Crit Care Med. 2000;161:19126.
6. Mion LC, Atkins PM, Mendelson W, et al. Characteristics and outcomes of patients who selfextubate from ventilatory support: a case-control study. Chest. 1997;112:131723.
7. Krinsley JS, Barone JE. The drive to survive: unplanned extubation in the ICU. Chest.
2005;128:5606.
8. Chevron V, Mnard JF, Richard JC, et al. Unplanned extubation: risk factors of development
and predictive criteria for reintubation. Crit Care Med. 1998;26:104953.
9. Torres A, Gatell JM, Aznar E, et al. Re-intubation increases the risk of nosocomial pneumonia
in patients needing mechanical ventilation. Am J Respir Crit Care Med. 1995;152:13741.
after extubation in high risk patients. Crit Care Med. 2005;33:246570.
11. Ferrer M, Valencia M, Nicolas JM, et al. Early non-invasive ventilation averts extubation failure in patients at risk: a randomized trial. Am J Respir Crit Care Med. 2006;173:16470.
13. Keenan SP, Powers C, McCormack DG, et al. Noninvasive positive-pressure ventilation for
postextubation respiratory distress: a randomized controlled trial. JAMA. 2002;287:323844.
Part IV
and Decannulation in Tracheostomized
Patients
Tracheostomy Decannulation:
Key Practical Aspects
40
Antonello Nicolini, Ines Maria Grazia Piroddi,

Sofia Karamichali, Paolo Banfi, and Antonio M. Esquinas
Tracheostomy is one of the most frequently performed procedures in the intensive

care unit (ICU) [1], especially after the introduction of percutaneous techniques [2].
It is performed in critically ill patients to protect the airway, remove secretions, or
provide ventilatory support [3]. The indications for placement of a tracheostomy
tube include failure to wean from invasive mechanical ventilation, impaired neurologic status, an inability to handle excessive secretions, and the need to bypass an
upper-airway obstruction [4]. In addition, the placement of a tracheostomy tube
facilitates the transfer of the patient from the ICU to a weaning facility such as a
step-down unit or a long-term care hospital [5].
Tracheostomized patients represent today approximately 20 % of patients who are
mechanically ventilated [6]. The increased prevalence of tracheostomy is associated with
earlier admissions to respiratory ICUs, but the indications and timing of decannulation
are still under discussion [2, 7]. In these patients, there are multiple variables that can
affect clinical outcome and complications. Moreover, in patients with invasive home
mechanical ventilation (HMV) via tracheostomy, long-term mortality and readmission
rate are high [8]. The presence of a tracheotomy may reduce the work of breathing and
therefore may facilitate weaning from a respirator. No statistical differences were found
between patients who received a surgical or percutaneous tracheotomy [2].
A. Nicolini, MD (*) I.M.G. Piroddi, MD

Respiratory Diseases Unit, Hospital of Sestri Levante, Sestri Levante, Italy
e-mail: antonellonicolini@gmail.com
S. Karamichali, MD
Allergy and Respiratory Diseases Department, IRCSS AOU San Martino-IST, Genoa, Italy
P. Banfi, MD
Don Gnocchi Foundation, IRCSS, Milan, Italy
A.M. Esquinas, MD, PhD, FCCP
Intensive Care Unit Hospital Morales Meseguer, Murcia, Spain
DOI 10.1007/978-3-319-04259-6_40
313
314
A. Nicolini et al.
The frequency of tracheostomy in the management of patients receiving mechanical ventilation contrasts with the lack of evidence as to when a tracheostomy tube
should be removed. It seems that the majority of critically ill tracheostomized
patients who survive to ICU discharge can eventually be successfully decannulated
[9]. For percutaneously tracheostomized patients with prolonged weaning and persisting respiratory failure, the adequate time point for safe decannulation and switch
to noninvasive ventilation is an important clinical issue. A systematic review compared patients with a tracheostomy tube in situ who were discharged from an ICU
with patients on a general ward who received care from a dedicated multidisciplinary team or standard care and showed reductions in time to decannulation,
length of stay, and adverse events [10].
Chronic comorbidities and the lack of evidence-based weaning and decannulation guidelines make it difficult to predict weaning outcomes of individual patients.
Clinically stable patients undergoing prolonged mechanical ventilation usually
begin the weaning process by spending increasing amounts of time on a spontaneous breathing trial via humidified tracheostomy mask. Therapist-driven weaning
protocols, such as those involving spontaneous breathing trials or decreasing levels
of pressure support, have been implemented in the postacute care setting and have
been shown to shorten the time required to wean patients from prolonged mechanical ventilation [11, 12].
40.1
Determinants of Tracheostomy Decannulation
Removing a tracheotomy is a fundamental step in the rehabilitation of a patient

recovering from an ICU stay, not only because of the negative repercussions that the
tracheotomy may have on social life activities but also because of the risk of complications: infections, bleeding, stenosis, and fistulas [2]. The prolonged presence of
a tracheostomy may be detrimental to functional recovery in terms of delayed rehabilitation and higher morbidity but can also be associated with longer hospitalization and higher staffing and consumable costs [13].
Clinical judgment by experienced clinicians is an appropriate approach for making decannulation decisions and favors timely decannulation [3]. The decision process prompting decannulation for management of an acute upper-airway obstruction
is very different than assessment for removal of a tracheostomy tube that was placed
for long-term management of complex airway abnormalities or for prolonged
mechanical ventilation (PMV) [7]. Decannulation of patients with prolonged tracheostomy is not as straightforward as tube removal following a resolved acute upperairway obstruction. Patients recently weaned from PMV have prolonged critical
illness, multiple medical comorbidities, and a marginal respiratory status [7].
Five criteria for tube removal most often cited by interviewed centers were stability of respiratory conditions, effective cough, slowly progressive underlying disease, effective swallowing, and no or mild hypercapnia in stable patients. The other
criteria were scored differently among centers, which can be explained by the fact
that there are no exact guidelines for closing tracheostomy [14].
40 Tracheostomy Decannulation: Key Practical Aspects
315
Heffner [15] proposed the following checklist to determine whether the patient
might be decannulated: (1) Is MV no longer required? (2) Are airway secretions
controlled? (3) Is aspiration nonexistent or minimal and well tolerated? (4) Does the
patient have an effective cough? An important point is the absence in Heffners
checklist of judgment about severity of disease (PaCO2, prognosis, and stability).
Studies are needed to evaluate accepted criteria for safely closing tracheostomy.
The common opinion is that tracheostomy decannulation is a multidisciplinary
team decision, made either in the ICU or in step-down units following patient discharge from the ICU [3]. The four most important determinants are clinician-rated
level of consciousness, ability to tolerate tracheostomy tube capping, cough effectiveness, and secretions. Patient comorbidities, etiology of respiratory failure, swallowing function, respiratory rate, adequate nutritional state, absence of delirium or
psychiatric disorders, patent upper airway, and oxygenation were judged to be of
moderate importance [16].
Although the ability to tolerate tracheostomy capping was judged to be an important determinant of tracheostomy decannulation for patients with paralytic conditions, peak cough flow (PCF) can be significantly increased by providing maximal
insufflations. Flows can be further increased by appropriately timing an abdominal
thrust to glottic opening (manually assisted coughing) [17]. All patients for whom
greater than 160 l/min of PCF could be achieved were successfully extubated or
decannulated, whereas no patients with PCFs under 160 l/min were successfully
extubated or decannulated [17].
Though decannulation is not risk free, there are clear-cut benefits to tracheostomy tube removal. The tracheostomy tube is a foreign body that may cause bronchorrhea or excessive cough. The tracheostomy tube impairs normal tracheal
elevation during swallowing. Diverting breathing away from the upper airway and
through the tracheostomy lumen has substantial deleterious effects. The physiologic
benefit of pursed-lips breathing is eliminated. The vocal cords are bypassed, and
there is no laryngeal blast to facilitate effective cough. Partial closure of the vocal
cords maintains a subglottic pressure referred to as physiologic PEEP (positive
end-expiratory pressure). Most importantly, patients are unable to speak when the
tracheostomy tube bypasses the larynx. There are profound consequences of inability to speak. Care is further compromised when the patient is unable to express
symptoms that would normally prompt further investigation or intervention. Clinical
assessment is compromised when mental status cannot be appropriately assessed
because of the lack of verbal communication. For patients with long-term tracheostomy, it is common practice to take an intermediate step prior to completely removing the tracheostomy tube, using a speaking valve [7].
During the post-mechanical ventilation period, patients are predisposed to respiratory muscle fatigue, abnormal ventilatory drive, and another episode of respiratory failure. Individuals with a long-term tracheostomy are at risk for upper-airway
obstruction due to complications of tracheostomy. Additionally, there may be
upper-airway abnormalities that were initially unappreciated or unrecognized at the
time of decannulation. Patients may subsequently experience life-threatening airway compromise requiring emergency reinsertion of the tracheostomy tube [7].
316
40.2
A. Nicolini et al.
Decannulation Failure
Fundamental to reporting decannulation failure rates is the need to define failed

decannulation [3]. In the literature, failed decannulation has been variously defined
as the need to reinsert an artificial airway within 24 h [3], 48 h [18], 4872 h [15],
or within 3 days [17]. Others authors report a 1-week timeframe or the requirement
for a second tracheostomy during hospital admission. However, there is currently
not an accepted definition for decannulation failure [16]. Bach and Saporito [17]
defined successful decannulation as extubation or decannulation and site closure
with no consequent respiratory symptoms or blood gas deterioration for at least 2
weeks. Ceriana et al. [2], in evaluating the feasibility of a decisional flow-chart for
weaning from tracheostomy, defined failure as the need to reopen the tracheotomy
because of an acute episode or progressive worsening of arterial blood gases not
corrected by the application of noninvasive mechanical ventilation. Data suggest
that most clinicians would consider reinsertion of an artificial airway within 4896 h
following planned tracheostomy removal to constitute a decannulation failure.
Furthermore, clinicians appeared to consider a decannulation failure rate of 25 %
to be acceptable [16].
As noted, all anatomical and nearly all stridor problems emerged within the first
4 h after decannulation. Thus, clinicians must assess airway patency, work of breathing, and oxygenation attentively in the first 4 h to detect, and respond to, potential
respiratory problems. Over the first 24 h, sputum retention was the primary cause of
decannulation failure, suggesting clinical vigilance for an inability to independently
expectorate secretions is paramount, and that chest physiotherapy must be maintained to prevent associated adverse events. These findings can be used to provide
guidance to inexperienced nurses managing patients who have been recently
decannulated.
For patients who are neurologically intact, independent expectoration of pulmonary secretions and early mobilization tends to result in successful decannulation.
Patients with significant neurological injury who make very slow or little progress
in their neurological recovery and have prolonged ICU lengths of stay are often
prone to deconditioning [3]. The duration of unsupported breathing, oxygenation,
and age can be predictors of decannulation failure [19].
The assisted PCF but not age, ventilator-free breathing time (VFBT), duration or
extent of ventilator need, or vital capacity significantly predict the ability to safely
extubate or decannulate patients with neuromuscular conditions irrespective of
extent of ventilatory insufficiency. Preliminary data suggest that this parameter may
also be useful for predicting successful extubation or decannulation of patients with
chronic obstructive pulmonary disease (COPD) [17].
A mechanical insufflator-exsufflator (MI-E) can provide 600 l/min of expiratory
flow directly to the airway. We found MI-E to be important for eliminating airway
secretions and permitting safe extubation for all but the COPD patients [17].
In patients with prolonged mechanical ventilation, weaning failure is associated
with poor survival [9]. Moreover, in patients with invasive home mechanical ventilation via tracheostomy, long-term mortality and readmission rate are high [8].
317
Therefore, it appears important to liberate patients from a tracheostoma whenever

possible and to keep the time with a tracheostoma as short as possible. In the decision of decannulation, the duration of spontaneous breathing and oxygenation as
well as a patients age should be considered [19].
40.3
Tracheostomy Tube Changes and Decannulation
Decannulation of long-term tracheostomy patients can be divided into two basic

categories: planned decannulation and accidental decannulation. Accidental decannulation is an unplanned removal of the tracheostomy tube. Such unplanned decannulation can be uneventful or produce a life-threatening situation. There are no
published data on the frequency at which this occurs at home, but common practice
is to provide all long-term tracheostomy patients back-up tubes, including tubes that
are 12 sizes smaller, to be used in the event the primary tube cannot be quickly
reinserted. Many emergency decannulations are unreported, as patients and caregivers are often successful at replacing the primary tube [20].
Planned decannulation is a goal for many tracheostomy patients when the medical need for the tracheostomy no longer exists. A common decannulation process
involves the sequential downsizing of the tube, often in conjunction with plugging
periods leading to eventual decannulation. This process can take several days or
weeks and is often dependent on the patients stability and tolerance of the downsizing and plugging procedures. Another planned decannulation is referred to as
the one-step method. This method is more comprehensive and includes endoscopic evaluation of the airway and, if clinically indicated, the subsequent removal
of the tube. The one-step procedure is considered more intensive and is often
performed in the acute-care setting, followed by 2448 h of decannulation monitoring [20].
All patients undergoing weaning from mechanical ventilation should be carefully monitored using continuous pulse oximetry and cardiac telemetry [5]. Various
weaning methods to decannulation include downsizing the tracheostomy tube
(which sometimes includes capping/corking), insertion of fenestrated tubes, use of
a tracheal button, cuff deflation for sustained periods of time, and rapid removal of
the tube as the patients condition improves [3].
Once a patient demonstrates the ability to tolerate a tracheostomy mask, it is
important to establish that the upper airway (i.e., glottis, vocal cords, and subglottic
space) is patent. The presence of a tracheostomy tube can cause complications that
may result in upper-airway obstruction. The upper airway can be checked noninvasively by fully deflating the cuff on the tracheostomy tube and placing a gloved
finger over the tracheostomy tube opening to deflect air through the upper airway
and vocal cords, allowing phonation. Alternatively, tracheostomy tube manometry
may be used to obtain objective measurements of airway pressures during the use of
a speaking valve or cap. This technique helps identify patients who can tolerate
occlusion of the tracheostomy tube and also those who may benefit from having a
tracheostomy tube with a smaller external diameter.
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A. Nicolini et al.
If the patient is unable to phonate, has stridor or labored breathing, or manifests

any respiratory distress, a thorough endoscopic examination of the airway, including the vocal cords and subglottic space, is recommended [21]. If the airway patency
is compromised by stenosis, granulation tissue, or abnormal vocal cord movement,
otolaryngology should be consulted for further evaluation and treatment. The initial
tracheostomy tube placed can be up to 8 mm inner diameter to facilitate fiberoptic
bronchoscopy. If no pathology is found on endoscopy, the tube may be downsized
and changed to a tight-to-shaft (fully deflated) cuff to enhance air flow around the
occluded tube [5].
40.3.1 Neuromuscular Disease

In regard to neuromuscular disease (NMD) patients, there are no extubation studies
on continuously noninvasive ventilation-dependent patients. Goncalves et al. [22]
defined extubation criteria for unweanable ventilator-dependent patients without:
vital capacity less than 20 % of normal, PaCO2 40 mmHg or less, peak inspiratory
pressures less than 35 cm H2O on full setting assist/control mode at a rate of 1013/
min, frequent and aggressive manually assisted cough to expel secretions and maintain or return SpO2 over 95 %, fully alert and cooperative, receiving no sedative
medications, chest radiograph abnormalities cleared or clearing and absent phlogosis signs, and air leakage via upper airway sufficient for vocalization upon cuff
deflation. In addition to hypoventilation, ineffective PCF has been associated with
extubation failure [22].
40.4
Post-decannulation Monitoring
After decannulation, continuous telemetry and oximetry are important for at least
24 h to monitor for unexpected airway compromise.
A patient may exhibit reduced voice quality due to air-flow diversion through
the healing stoma on exhalation. Vocalization may be enhanced by gently placing
two fingers over the gauze-covered stoma during speech to minimize leak and
maximize air flow to the vocal cords. Vocalization will usually return to normal
once the stoma has closed completely. The tracheostomy stoma heals by secondary
intention within 57 days in the majority of patients. However, tracheostomy stoma
closure rates are variable and closure may occur in a single day or may take weeks.
A persistent tracheocutaneous fistula may remain in some patients and may require
surgical closure [5].
Conclusion
A review by Santus et al. [23] provides a hypothetical score for practical use
with objective quantitative parameters, major criteria, and semiquantitative or
subjective parameters, minor criteria, to help clinicians in choosing decannulation timing. If all main criteria are satisfied, regardless of minor criteria,
decannulation with high probability of positive outcome can be assumed, but
319
Table 40.1 Protocol criteria for tracheostomy decannulation from prolonged mechanical
ventilation
Absence of distress and stable ABG values on prolonged mechanical ventilation for 5 days
Stable clinical conditions (hemodynamic stability, absence of fever or active infection)
PaCO2 < 60 mmHg
Normal endoscopic examination or revealing stenotic lesions occupying <30 % of the airways
Adequate swallowing evaluated by gag reflex, blue dye, and video fluoroscopy
MEP >40 cmH2O or PCF > 160 l/min (NMD patients)
Tube capping >24 h
ABG arterial blood gases, PaCO2 partial pressure of carbon dioxide, MEP maximum expiratory
pressure, PCF peak cough flow
this requires discussion and a prospective validation study. Table 40.1 provides
our proposed practical protocol criteria for tracheostomy decannulation from
PMV.
In conclusion, decannulation is usually well tolerated by the patient, but a
systematic approach to patient evaluation is needed. Following decannulation,
patients require close monitoring to identify signs of airway compromise.
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12. Vitacca M, Vianello A, Colombo D, Clini E, Porta R, Bianchi L, et al. Comparison of two
methods for weaning patients with chronic obstructive pulmonary disease requiring mechanical ventilation for more than 15 days. Am J Respir Crit Care Med. 2001;164(2):22530.
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Transfer to Noninvasive Ventilation

as an Alternative to Tracheostomy
in Obstructive Pulmonary Disease:
Key Practical Topics
41
Gerhard Laier-Groeneveld
Abbreviations
COPD
CPAP
ICU
pCO2
PEEP
pO2
RICU
T-tube

Intensive Care Unit
Arterial partial pressure of carbon dioxide
Arterial partial pressure of oxygen
Respiratory intensive care unit
Endotracheal tube attached with a device to add oxygen to the inspiratory air
Noninvasive ventilation has widened both the indications and use of mechanical
ventilation to outside the intensive care unit (ICU), to early and preventive use, to
therapy to improve ventilator function [1], and as an alternative to invasive ventilation. Noninvasive ventilation can replace invasive ventilation at almost any stage of
disease. This extends weaning, which originally meant termination of (invasive)
mechanical ventilation, to also include avoidance of intubation by noninvasive ventilation, to transfer from intubation to continuing mechanical ventilation by noninvasive means, to arrange home mechanical ventilation for those who require
continuous intermittent ventilator support, and, if life quality cannot be restored, to
terminal weaning to noninvasive ventilation, retaining the option of reintubation in
G. Laier-Groeneveld
Medical Clinic II, Pneumology, Thoracic Oncology, Ventilatory Support and Sleep,
Klinikum Niederrhein, Steinbrinkstrasse, D44160 Oberhausen, Germany
e-mail: laier-groeneveld@t-online.de
DOI 10.1007/978-3-319-04259-6_41
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G. Laier-Groeneveld
case of failure. With noninvasive ventilation, additional techniques are required in

intensive care to handle secretions, to best fit tracheal cannulas and masks, and to
cope with aspirations and phonation while ventilated either via tracheostomy or via
masks. Air stacking, assisted cough, bronchoscopy, made-to-measure tracheal cannulas, and a set of nasal, naso-oral, total face, and mouth masks are available to
meet almost any need. To fulfill all these purposes, special units are warranted,
respiratory ICUs (RICUs) or weaning units. Weaning in respiratory intensive care
not only aims for survival of the patient but more broadly for his or her discharge in
a better condition than when admitted and with all the prerequisites for a good quality of life: equipment, technique, care, and knowledge.
Two important aspects have been recognized with the introduction of noninvasive ventilation into intensive care treatment. First, mechanical ventilation can be
used early before overt ventilatory failure develops and before only immediate intubation is life saving. This requires the intensivist to explore the risk for intubation
early, mainly upon admission to the hospital. Noninvasive ventilation can be started
outside the ICU. Discharge from the ICU is possible while mechanical ventilation
is still in place. Second, mechanical ventilation is not only life-saving but also therapeutic. It improves the patients breathing capacity. Improvement of spontaneous
breathing capacity with lower or normal pCO2 [1], relief of symptoms, increase in
quality of life, and prolonged survival occur as a result of proper mechanical ventilation [2]. All these effects have been clearly shown as a therapeutic effect of
mechanical ventilation alone [2]. This requires an unloading ventilator strategy, a
proper setting of the ventilator, and a good adaptation of the patient to the ventilator
during passive mechanical ventilation.
Both aspects render noninvasive mechanical ventilation ideal as a weaning tool,
replacing invasive ventilation to avoid the inherent risks and improving breathing
capacity without the need for continuous ventilatory support. Although a large randomized trial is lacking, a meta-analysis shows a consistent positive effect of noninvasive ventilation use in weaning from intubation [2].
41.1
How to Recognize Difficult Weaning
Mechanical ventilation may be started during surgery and continued thereafter for
complications following the surgical procedure. Patients may wean completely with
the techniques available after they have stabilized. Awareness and withholding sedatives helps allow extubation as early as possible. If patients have been intubated for
a minor reason but the underlying disorder is considerably severe, they do not wean
completely with the strategies available, and they are considered difficult to wean.
The patients history should be extensively explored, first, for the severity of the
acute condition under which intubation has been performed and, second, for a
chronic impairment present before the deterioration occurred. Chronic obstructive
pulmonary disease (COPD) with severe airflow obstruction, emphysematous lung
destruction, hypoxemia, or hypercapnia is the most common underlying disorder. In
addition, neuromuscular disorders, scoliosis, severe heart failure, and severe sleep
41
Transfer to Noninvasive Ventilation as an Alternative to Tracheostomy
323
apnea predispose for weaning difficulties. Minor complications at the time of intubation together with a severe underlying chronic disorder should immediately call
alternative weaning procedures into place.
If an underlying chronic disease is less severe or absent, alternative weaning
strategies should be sought as soon as the patient does not readily wean for any of
the possible reasons. The problem may become evident when the patient is extubated, awake, and breathing spontaneously. We see patients being weaned within a
few days but requiring months to recover from sequelae of long-term mechanical
ventilation. Immobility, muscular weakness, and mental disorders contribute. Time
is a critical factor in invasively ventilated patients.
One alternative weaning strategy is the transfer from intubation directly to noninvasive ventilation. Mechanical ventilation is continued but the airway access is
changed from the endotracheal tube to a well-fitting mask. This separates mechanical ventilation from intensive care treatment. Invasive ventilation and transfer to
noninvasive ventilation requires the resources of an ICU. However, once noninvasive ventilation is performed safely, the patient can be discharged from the ward to
regular care, rehabilitation, or even home, despite being on mechanical ventilation.
An early decision can first be made regarding how to ventilate and where. Then, the
decision regarding whether the patient needs to be ventilated at all can be postponed
until physical recovery is complete.
During invasive mechanical ventilation, if there is no clear history, tests to
explore for a chronic disease and for breathing capacity are limited and leave considerable uncertainty. We therefore prepare any patient for transfer and are happy if
noninvasive ventilation after extubation is not needed.
41.2
When to Start Weaning
Invasive mechanical ventilation is not safe. Numerous comparisons between intubation and noninvasive ventilation in various conditions have shown the hazards of
intubation and invasive mechanical ventilation in COPD [4]. Mortality is increased,
complications frequently occur, intensive care stay and hospital stay are prolonged,
nosocomial infections and sepsis are increased, and ventilator-induced diaphragmatic dysfunction and critical care polyneuropathy almost inevitably occur with
prolonged invasive mechanical ventilation. In patients with neuromuscular disease,
even a short time of inactivity can impair their abilities to a degree that is difficult to
recover from. Noninvasive ventilation shows no or at least a much lower rate of
complications. Once stable noninvasive ventilation is in place, the outcome is usually more favorable [5]. As a consequence, weaning from endotracheal ventilation
should begin as soon as possible. We propose starting immediately after intubation
or as soon as the patient is transferred to the weaning unit.
After intubation or after transfer, the strategy of mechanical ventilation must first
be questioned. There are two strategies: (a) the lung-protecting strategy with high
positive end-expiratory pressure (PEEP) and low tidal volume, which sometimes
requires deep sedation for tolerance; and (b) the ventilator support or unloading
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G. Laier-Groeneveld
strategy, which requires sufficient volume to unload the patients ventilatory pump
to sufficient hyperventilation to suppress respiratory drive and, thus, rest the muscles and relieve dyspnea. These strategies have not been compared in studies.
During weaning, the unloading strategy is more advantageous and is the strategy of
choice. In COPD, the lung-protective strategy has not been shown to have a place.
Patients with COPD are excluded because, in COPD, there is airway over-distention
and a positive alveolar end-expiratory pressure called intrinsic PEEP. Airway collapse is not present and lung protection, therefore, is not needed.
With the unloading strategy, sedative requirements should be questioned immediately after intubation or after transfer. Most patients are exhausted at the time of
intubation or after struggling with the ventilator. They do not need sedatives for a
considerable period thereafter, especially if dyspnea is absent as a consequence of
the unloading strategy. Removal of sedatives under these conditions is safe. Only
rarely are bolus applications required. It has been shown that tube mechanical ventilation can be performed without any sedatives and, once the tube is in place, is well
tolerated, similar to tracheostomal ventilation [5, 6]. Considerable time usually
elapses after intubation or removal of sedation until the patient experiences discomfort and the decision either to extubate or to sedate is inevitable, providing sufficient
time to explore the patients cooperation and ability for spontaneous breathing to
allow extubation.
Simultaneously with the introduction of the unloading strategy and the withdrawal of all sedatives, other conditions should be addressed. Excessive fluid should
be removed as it impairs spontaneous breathing capacity. Underlying diseases
should be treated. Airway obstruction is frequently involved. If airway obstruction
is present or cannot be clearly ruled out, appropriate treatment is necessary.
Corticosteroids and agonists may be necessary, first intravenously and then by
inhalation. Secretions should be removed. In COPD, secretions may accumulate in
the peripheral airways, as suctioning only clears the central airways in sedated
patients. The secretions may be viscous or purulent and contribute to hypoxemia
and difficulties in spontaneous breathing. Bronchoscopic lavage is often helpful in
successful weaning. If no pulmonary disease is present, hypoxemia or atelectasis
require clearance of secretions, especially in patients with neuromuscular disease.
In patients with COPD, in contrast, hypoxemia is a consequence of their disease. A
decrease in oxygen saturation can be caused by several pulmonary complications,
such as airway obstruction, fluid overload, pleural effusions, pulmonary embolism,
hypersecretions, purulent bronchitis, or pulmonary infiltrations or may be persistent
as a result of advanced disease. Such complications should be actively investigated
during the weaning process (Table 41.1).
41.3
Discontinuous Versus Continuous Weaning
There is no evidence that spontaneous breathing trials train the patient and his or her
muscles. In fact, it is unlikely that spontaneous breathing trials result in increasing
the strength of respiratory muscles. It has been clearly shown that, if intensity of
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325
Table 41.1 Transfer to noninvasive ventilation should be performed early

Check for underlying disease and explore severity
Define condition requiring intubation and determine
severity
Observe weaning progress
If underlying disease is severe
If condition requiring intubation is minor
If weaning does not readily progress
Choose transfer to noninvasive ventilation
load is not monitored and guaranteed, no training effect can be expected [6].
Spontaneous breathing trials do not improve the patients condition but provided
information about how to continue. Spontaneous breathing capacity reflects the
impact of the disease and the necessity of mechanical ventilation. Frequently, the
spontaneous breathing capacity displayed is much better than anticipated before the
trial is performed. This allows more rapid weaning to proceed. Impacts on pCO2 and
dyspnea reveal whether spontaneous breathing is safe or risks resulting in muscular
fatigue if unduly prolonged. The evolution of oxygen saturation during spontaneous
breathing reveals whether hypoxemia can be managed without intubation. In addition, physical and behavioral ability to cooperate and tolerate an unpleasant respiratory load without panic or anxiety can be tested during a spontaneous breathing
trial. Some patients who have experienced life-threatening episodes during their
intensive care stay may become anxious about any change that is made. Explaining
the process to the patient and staying him or her, asking about discomfort, and terminating the trial as soon as adverse events occur may be prerequisites for success.
There are two approaches to spontaneous breathing trials: (a) breathing spontaneously while on the ventilator, with minimum support by continuous positive airway pressure (CPAP) and pressure support, and (b) T-tube breathing, with the tube
in place but not connected to the ventilator and with an oxygen adaptor inserted to
apply additional oxygen as required.
Supporters of the CPAP trial argue that the patient is still monitored by the ventilator. However, as previously mentioned, the spontaneous breathing trial should be
monitored by an experienced therapist to recognize and avoid any adverse event and
to motivate the patient. Thirty minutes of spontaneous breathing have been shown
to be sufficient, with no additional information gained if the trial is prolonged
beyond that point [7]. A well-supervised T-piece trial does not require any monitoring by the ventilator. Perfect interaction with the ventilator during CPAP and pressure support can be difficult to accomplish in a spontaneous breathing, swallowing,
and coughing subject, and we worry that breathing against the machine may impair
the patient. Additionally, ventilator support, although minimal, may mask some
consequences of spontaneous breathing [9, 10] because of muscle overload or noncompensable hypoxemia and, as a consequence, the risk for reintubation. In severe
COPD, CPAP must be kept low, at least below the intrinsic PEEP, if increased
hyperinflation might further aggravate. Because intrinsic PEEP is variable with time
and not homogenously distributed in the lung, we prefer the T-tube trial [11].
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41.4
G. Laier-Groeneveld
Ready to Extubate
As soon as the patient is extubated and the endotracheal tube is replaced by a nasal
or naso-oral interface, mechanical ventilation can be performed intermittently
according to the patients spontaneous breathing capacity. Until complete stabilization is reached, spontaneous breathing periods may be kept short to avoid exhaustion and rapid shallow breathing followed by difficulties to readapt to noninvasive
ventilation. Thereafter, prolongation of spontaneous breathing and reduction of the
time on the ventilator may follow the overall improvement. Noninvasive ventilation,
in contrast to endotracheal ventilation, allows the patient to be transferred to the
normal ward, to a rehabilitation center, or to home even if the patient is not completely weaned. Sufficient care and cooperation to continue with intermittent ventilation and stability are the only requirements (Table 41.2).
Noninvasive ventilation can be successfully performed in the totally ventilator
dependent patient. However, the more spontaneous breathing is preserved, the lower
the risk for reintubation. Thirty minutes of a stable T-piece trial with stable pCO2
and oxygen saturation should be achieved prior to extubation and transfer to noninvasive ventilation. However, with sufficient expertise and the support of well-trained
specialists, most of our patients are extubated after a shorter T-piece trial [5]. Full
cooperation and perfect adaptation are the major determinants of failure or success
[12]. If the patient is fully cooperative and adapts well to invasive tube ventilation
without the need of sedatives, mask ventilation can be expected to work equally
effectively. Uncooperativeness or the necessity to apply sedatives considerably
increase the risk of failure.
The best patient for extubation can cooperate in closing his or her mouth and follow
the commands of the therapist. The patient should be able to breathe spontaneously for
up to 30 min. The best parameters of success are the patients tolerance, comfort, and
progressive improvement. In patients with healthy lungs, which is the case in those
Table 41.2 Pathway transfer to noninvasive ventilation

Adapt the patient to passive normocapnic ventilation, pco2 < 40 mmHg, low or no PEEP,
oxygen as required
Treat the underlying conditions, fluid overload, COPD, heart failure, secretions
Withdraw all sedatives
If the patient is cooperative, perform a > 30 min T-tube breathing trial
Ideal target: full cooperation and >20 min spontaneous breathing with minor hypercapnia and
hypoxemia (with supplemental oxygen as required)
Extubate after a period of passive ventilation, suctioning all secretions
Immediately start passive noninvasive ventilation, pCO2 < 40 mmHg, low or no PEEP, oxygen
as required
Monitor secretions and remove properly
Start with periods of spontaneous breathing when the patient is stable
Monitor pCO2, saturation, and performance and resume noninvasive ventilation before
deterioration occurs
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327
with neuromuscular disease, a decrease in oxygen saturation may warrant immediate

intervention to remove secretions. To early detect accumulation, patients should, whenever possible, be treated without additional oxygen. In lung disease, hypoxemia is a
common occurrence, especially in COPD. Such patients readily tolerate periods of
hypoxemia, especially if they occur for a limited period of time. They do not require
oxygen saturations above 92 %. If subjectively tolerated, they should not be prevented
from spontaneous breathing by hypoxemia, but such periods may be kept short.
41.5
Which Ventilatory Setting to Choose
We support the high intensity or better physiological strategy in the setting of the
ventilator [1]. This means that mechanical ventilation should restore the pCO2 to the
normal healthy range below 40 mmHg and, in addition, unload the ventilator pump
completely. We could add evidence to this strategy with a randomized controlled study
in chronic hypercapnic COPD patients [2]. The physiological strategy showed a significant improvement in survival and quality of life, together with a decrease in pCO2
on spontaneous breathing compared with the control group. Several controlled studies
did not improve pCO2 by the ventilator setting and, during spontaneous breathing, did
not show any substantial benefit [15]. Achieving the goal of a pCO2 below 40 mmHg
and of unloading the ventilator pump is usually feasible in patients with neuromuscular
disease because they require lower tidal volumes and pressures. In COPD, many more
options must be used. In some cases, the goal can only achieved with time.
During spontaneous breathing, COPD patients develop an intrinsic PEEP. This is
variable from breath to breath with the tidal volume, the expiratory time, and breathing frequency. Respiratory muscles have to enlarge the thorax until the intrinsic
PEEP has been reached and positive alveolar pressure becomes negative. It is not
until then that inflow of air starts and the trigger of the ventilator is activated. Most
work of breathing may be done to overcome intrinsic PEEP and only minor work is
added to inflate the lung [10]. In this case, an elevated pressure at end expiration
(PEEP) will prevent the thorax from settling below and relieve the respiratory muscles from the initial part of work.
If the patient is passively ventilated and all breaths are totally ventilator initiated,
setting a PEEP on the ventilator is not necessary. The ventilator can easily provide
the additional work required to overcome intrinsic PEEP. The alveoli never collapse
in COPD because the alveolar pressure always remains positive because of the
intrinsic PEEP in this disorder. We therefore use little or no PEEP in mechanically
ventilated patients with COPD, whether ventilated invasively and noninvasively.
As the driving pressure is required to reach the tidal volume necessary, the introduction of PEEP increases the peak inspiratory pressure. Higher pressures increase
the risk of leaks during noninvasive ventilation. The air flow from the ventilator
during expiration may interfere with speaking and swallowing in noninvasively ventilated patients, further reasons not to use PEEP.
During pressure preset ventilation, the inspiratory time can be used to increase
tidal volume. The longer the pressure is applied during inspiration, the more the
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G. Laier-Groeneveld
lungs are inflated. In patients with COPD, care should be taken that expiration is
fully completed before the following inspiration starts, but an inspiratory-expiratory
ratio of 1:1.4 can be reached in most of patients without any air trapping. During
volume preset ventilation, a prolonged inspiratory time will help to decrease peak
inspiratory pressure and can equally be used to provide more comfort to the patient.
Despite these additional measures to increase tidal volume, the major determinant is the inspiratory pressure in pressure preset ventilation and the adjusted tidal
volume in the volume preset setting. As much as 30 or 40 mbar may be needed to
normalize the arterial pCO2 [1, 3]. During invasive ventilation, normocapnia can
usually be instantly achieved with this setting, whereas during noninvasive ventilation, as a consequence of leaks, several days may be needed and different masks and
settings tried until the adaptation is free from leaks and complete. The study of
Khnlein et al. [3] and other work, however, show that an improvement in pCO2 can
be reached in patients with COPD once a goal is set.
COPD is a broad spectrum of disease, from the least to the most severe, from the less
affected lung to the completely emphysematous lung, from severe bronchospasm to
irreversible airflow limitation, from hypersecretion to severe obstruction by secretions,
from occasional to total ventilator dependency, from severe hypoxemia to extreme
hypercapnia. Any of these may cause failure of noninvasive or invasive ventilation. One
after the other should be evaluated and treated once the normocapnic goal is not readily
achieved. Different intensities of mechanical ventilation in volume or pressure, in time,
and in the acceptable leakage may be sufficient depending on the patient. Nevertheless,
the best unloading should be chosen during transfer from intubation to noninvasive ventilation because reintubation has been shown to be a major determinant of adverse outcome and complications and, by any preventive measures, should be avoided [1, 4].
Key Recommendations
Weaning should start immediately after intubation or after admission to the

weaning unit.
Intubated patients can be prepared for transfer to noninvasive ventilation,
although some do not require noninvasive ventilation after extubation.
The more minor the complication prior to intubation and the more severe
the chronic underlying disease, the more transfer to noninvasive ventilation is needed to avoid the hazards of tracheotomy.
An unloading strategy of mechanical ventilation, a setting to normalize
pCO2, and ventilation that is comfortable and passive for the patient while
intubated and while ventilated noninvasively is recommended.
Full patient cooperation during a spontaneous T-tube breathing trial with a
tolerable increase in pCO2 and stable oxygen saturation of up to 30 min
may prove that noninvasive ventilation will succeed after extubation.
All possible complications should be ruled out, corrected, and treated to
rapidly reach a stable situation after transfer from intubation to noninvasive ventilation.
41
329
References
1. Laier-Groeneveld G, Schucher B, Crie CP. Die Ursache der chronischen Hyperkapnie. Med
Klin. 1997;92:339.
liberation from mechanical ventilation. Can J Anaesth. 2006;53:30515.
3. Khnlein T, Windisch W, Khler D, Drabik A, et al. Non invasive positive pressure ventilation
for the treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre, randomized, controlled clinical trial. Lancet Respir Med. 2014;9:698705.
4. Keenan SP, Kerneman PD, Cook DJ, Martin CM, et al. Effect of noninvasive positive pressure
ventilation on mortality in patients admitted with acute respiratory failure: a meta-analysis.
Crit Care Med. 1997;25:168592.
5. Laier-Groeneveld G, Abazed Y, Bauer JU. Noninvasive ventilation during weaning. J Physiol
Pharmacol. 2007;58:3358.
6. Strom T, Martunissen T, Toft P. A protocol of no sedation for critically ill patients receiving
mechanical ventilation: a randomized trial. Lancet. 2010;375:47580.
7. Hill K, Jenkins SC, Philippe DL, Cecins N, et al. High intensity inspiratory muscle training in
COPD. Eur Respir J. 2006;27:111928.
8. Esteban A, Alia I, Gordo F, Fernandez R, et al. Extubation outcome after spontaneous breathing trials with T-tube or pressure support ventilation. The Spanish Lung Failure Collaborative
Group. Am J Respir Crit Care Med. 1997;156:45965.
9. Rasche K, Laier-Groeneveld G, Weyland W, Braun U, et al. Sauerstoffverbrauch der
Atemmuskulatur unter kontrollierter bzw. assistierter Beatmung bei Patienten mit chronischer
Ateminsuffizienz. Med Klein. 1994;89:436.
10. Weyland W, Schuhmann M, Rathgeber J, Weyland A, et al. Oxygen cost of breathing for
assisted spontaneous breathing modes: investigation into three states of pulmonary function.
11. Marini JJ. Dynamic hyperinflation and auto-positive end-expiratory pressure: lessons learned
over 30 years. Am J Respir Crit Care Med. 2011;184:75662.
12. Laier-Groeneveld G, Crie CP. Weaning by transfer to nasal ventilation. Eur Respir
J. 1997;10:268S.
13. Alberts CH, Hanau S, Laier-Groeneveld G. Properatives weaning versus postoperatives prolongiertes weaning. Pneumologie. 2012;67:P474.
14. Cabrini L, Landoni G, Oriani A, Plumari VP, et al. Noninvasive ventilation and survival in
acute care setting: a comprehensive systematic review and metaanalysis of randomized controlled trials. Crit Care Med. 2015;43:8808.
15. Clini E, Sturani C, Rossi A, Vioggi S, et al. The Italian multicentre study on noninvasive ventilation in chronic obstructive pulmonary patients. Eur Respir J. 2002:52938.
Extubation and Decannulation

of Unweanable Patients
with Neuromuscular Weakness
42
John Robert Bach
Abbreviations
ALS
CPF
CNVS
DMD
ICU
IPPV
MIE
NMD
NVS
O2 sat
PAP
SCI
SMA1
TMV
URI
VC

Cough peak flows
Continuous noninvasive ventilatory support
Duchenne muscular dystrophy
Intensive care unit
Intermittent positive pressure ventilation
Mechanical insufflation-exsufflation
Neuromuscular weakness/disease and/or inspiratory muscle dysfunction
resulting in inability to sustain alveolar ventilation
Noninvasive ventilatory support (noninvasive intermittent positive pressure ventilation)
Pulse oxyhemoglobin saturation
Positive airway pressure
Spinal cord injury
Spinal muscular atrophy (type 1)
Tracheostomy mechanical ventilation
Upper respiratory tract infection
Vital capacity
J.R. Bach, MD
Department of Physical Medicine and Rehabilitation, Rutgers University
New Jersey Medical School, Newark, NJ, USA
Department of Physical Medicine and Rehabilitation, University Hospital B-403,
150 Bergen Street, Newark, NJ 07103, USA
e-mail: bachjr@njms.rutgers.edu
DOI 10.1007/978-3-319-04259-6_42
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42.1
J.R. Bach
Introduction
42.1.1 Respiratory Muscle Aids

The three respiratory muscle groups include the inspiratory muscles, expiratory muscles, and bulbar-innervated muscles. The inspiratory and expiratory muscles can be
assisted or supported indefinitely by applying pressure to the body or airways such
that no extent of dysfunction should result in respiratory failure or require resorting to
tracheotomy [1]. Inspiratory and expiratory muscle aids are devices and techniques
that involve the manual or mechanical application of forces to the body or pressure
changes to the airway to assist or substitute for inspiratory or expiratory muscle function. Negative pressure applied to the airway during expiration assists the expiratory
muscles during coughing, just as positive pressure applied to the airway during inhalation (noninvasive intermittent positive-pressure ventilation (IPPV)) assists inspiratory
function [1]. A manual thrust applied to the abdomen during expiration or exsufflation, especially when combined with mild chest compression, assists expiratory muscle function to increase cough flows. Patients with little or no measurable vital capacity
(VC) or any ability to autonomously sustain alveolar ventilation or cough can be managed without invasive tubes using these methods. However, even when inspiratory and
expiratory muscles are functional, patients with bulbar-innervated muscle dysfunction
and spasticity or other irreversible airway obstruction, for whom continuous aspiration of airway secretions results in decrease in an O2 sat baseline below 95 %, need to
undergo tracheotomy to survive [2]. When this occurs, the patient has usually already
lost the ability to speak and swallow food. This usually occurs only in patients with
advanced bulbar amyotrophic lateral sclerosis (ALS) and some patients with spinal
muscular atrophy type 1 (SMA1).
42.2
Acute Respiratory Decompensation and Conventional

Management
Inspiratory and expiratory muscle aids can be used at home or in the hospital to
prevent episodes of pneumonia and respiratory failure that would otherwise occur
during intercurrent upper respiratory tract infections (URIs) and episodes of bronchitis due to ineffective coughing. Both mechanical insufflation-exsufflation (MIE)
and continuous noninvasive ventilatory support (CNVS) are often needed during
these episodes when, quite possibly, they are not required at other times [26]. The
feedback obtained by using an oximeter during acute URIs to guide in the use of
noninvasive ventilatory support (NVS) and, especially MIE, is important in keeping
the O2 sat over 94 % or returning it to over 94 % quickly if it should decrease below
95 %. This is because O2 sat is only normal when it is 95 % or greater. It is impossible to develop respiratory failure with O2 sat greater than 94 % in ambient air. Any
O2 sat below 95 % must indicate some combination of hypoventilation, airway
secretion congestion, and intrinsic lung disease such as atelectasis or pneumonia.
When the O2 sat cannot be kept above 94 %, patients usually require hospitalization
for pneumonia and possible acute respiratory failure [3].
42
Extubation and Decannulation of Unweanable Patients
333
Typically, the dyspneic patient arrives at the emergency room of a local hospital
and immediately receives supplemental oxygen. The patients already-elevated CO2
further increases and CO2 narcosis results in ventilatory arrest, intubation, and then
failure to wean from invasive ventilatory support via a translaryngeal tube. A tracheotomy is performed and the patient is left with a lifetime of invasive ventilatory
support. Once a tracheostomy tube is placed, the patient often loses all ventilatorfree breathing ability. This occurs most often because the tracheostomy tube causes
airway secretions that block the respiratory exchange membrane, ventilation via the
tube causes inspiratory muscle deconditioning [7], and chronically and invasively
ventilated patients tend to be hypocapnic and therefore tolerate less ventilator-free
breathing [8]. Their demand for increased ventilator volumes or pressures may be
related to bypassing the upper airway sensory input.
Supplemental oxygen should not be given until attempts have been made to normalize O2 sat (>94 %) by using full-setting NVS to normalize ventilation (PaCO2)
and MIE to clear the airways of secretions. Intubation becomes appropriate when
optimal use of NVS and MIE fail to maintain normal O2 sat and the patient develops
respiratory distress, most often as a result of pneumonia.
42.2.1 Conventional Outcomes of Acute Respiratory Failure

Intubated patients who fail spontaneous breathing trials are usually told that tracheostomy is their only option. Conventionally, unweanable intubated patients are only
extubated following tracheotomy. Once a tracheostomy is placed, the majority of
patients will eventually die from complications directly attributable to the tube,
including hemorrhage, tracheoesophageal fistulae, respiratory infection, trachectasis, pneumonia, accidental disconnection from the ventilator, and ventilator failure.
In a review of four papers discussing outcomes of tracheostomy ventilation for
Duchenne muscular dystrophy (DMD), 17 patients survived more than 2 years,
including 1 for 18 years; 3 died from complications of the tube in less than 2 years;
and 2 died after 2 years of use [912]. In a relatively large study, Bach et al. [13]
reported mean survival for 17 DMD tracheostomy IPPV users of 7.3 8 years
(range, 7 days to 12 years). At least 4 of the patients died from complications associated with the tube. Likewise, 32 of our 40 ALS patients using tracheostomy mechanical ventilation (TMV) died as a result of complications caused by the tracheostomy
tube after about 5 years of continuous TMV [14].
42.3
Extubation of Unweanable Patients to NVS

or Manually Assisted Coughing
Many successfully extubated unweanable patients have been continuously NVS

dependent with no ventilator-free breathing ability for decades before being hospitalized and intubated, whether for general anesthesia or an intercurrent pneumonia. These
patients typically do not want to switch from CNVS to continuous TMV [15]. In 1996,
a different approach to extubation and decannulation was described. Instead of
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J.R. Bach
Fig. 42.1 Ten-year-old girl with neurofibromatosis status post spinal cord tumor resection, extubated with a vital capacity of 180 ml and no ventilator-free breathing ability, using a 15-mm angled
mouthpiece (Malincrodt-Puritan-Bennett, Pleasanton, CA, USA) for ventilatory support
ventilator weaning with oxygen supplementation then extubation to supplemental oxygen and continuous or bi-level positive airway pressure (PAP), the invasive tube was
removed and the patient set-up with via a 15 mm angled mouthpiece or nasal interface
(Fig. 42.1) to wean himself or herself in ambient air by taking fewer and fewer IPPVs
[16]. All patients with assisted cough peak flows (CPF) 160 l/m were successfully
extubated to NVS and MIE [16]. Subsequently, we successfully extubated more than
250 unweanable neuromuscular disease (NMD) patients with ALS, myopathies and
muscular dystrophies, critical care myopathy, post-polio, myasthenia gravis, spinal
muscular atrophy, and spinal cord high tetraplegia [17, 18]. Once the extubation criteria
noted in Table 42.1 were satisfied, 100 % of the patients with CPF greater than 160 l/m
and 85 % with CPF less than 160 l/m succeeded with extubation, despite most having
failed extubation and/or spontaneous breathing trials in other institutions. These
patients had been told that they could only survive by undergoing tracheotomy.
Successful extubation of continuously ventilator-dependent patients with no ventilator-free breathing ability was achieved using the following protocol. Normal alveolar ventilation was maintained and MIE used (pressures 40 to 70 cm H2O to 40 to
70 cm H2O with exsufflation-timed abdominal thrust) via the translaryngeal tube as
needed until O2 sat remained 95 % in ambient air for 12 h or more. Once spontaneous breathing trials were failed but extubation criteria were met, the nasogastric tube
was removed if present to facilitate immediate postextubation NVS. The VC was
measured. The patient was then extubated directly to NVS on pressure control
1820 cm H2O or assist/control mode 8001500 ml delivered volumes and backup
rate of 1012/min. The NVS was provided via mouthpiece [19], nasal, or oronasal
interface. The patients using mouthpiece NVS kept 15 or 22 mm angled mouthpieces
accessible to their mouths (Fig. 42.1). Patients weaned themselves, when possible, by
taking fewer and fewer mouthpiece IPPVs as tolerated. Diurnal nasal IPPV was used
for children and for those who could not grab or retain a mouthpiece because of oral
42
335
Table 42.1 Extubation criteria for continuously ventilator-dependent patients

Diagnosis of neuromuscular weakness (including critical care ventilatory failure) with
inability to pass spontaneous breathing trials or autonomously breathe
Afebrile
Normal white blood cell count
Absence of fixed airway obstruction due to upper motor neuron disease
Oxyhemoglobin saturation 95 % for 12 h or more in ambient air
All oxyhemoglobin desaturations <95 % reversed by mechanical insufflation-exsufflation via
translaryngeal tube
Fully alert and cooperative, receiving no sedative medications
Chest radiograph abnormalities cleared or clearing
Sufficient air leakage via upper airway for verbalization upon tube cuff deflation
Normal PaCO2 at peak inspiratory pressures <35 cm H2O with the cuff deflated
muscle weakness, inadequate jaw opening, or insufficient neck movement. Being

open systems, the patients took as much of the delivered volumes as needed for comfortable alveolar ventilation. No supplemental oxygen was used. For episodes of
SpO2 < 95 %, the following were evaluated: ventilator positive inspiratory pressure
(PIP), interface air leak, CO2, and ventilator settings.
The success in extubating patients with little or no measurable CPF was the result
of a variety of factors, but the experience of our respiratory therapists and the patients
families with NVS and MIE was the most important factor. We relied on family
members to provide MIE every 2030 min as needed post extubation until the O2 sat
no longer dipped below 95 %. Such a regimen simulates normal coughing frequency
during episodes of bronchitis and pneumonia. The aggressive use of MIE via the
endotracheal tube was the main intervention that resulted in normalization of SpO2
in ambient air, the most important criterion for extubation, and increasing VC [18].
Generally, pressures of 40 to 60 cm H2O to 40 to 60 cm H2O were also used
with an exsufflation-timed abdominal thrust post extubation. Thus, the hospital staff
and patients care providers used oximetry as feedback to maintain O2 sat 95 % by
MIE and NVS. Extubation was only considered successful if the patient was discharged home without requiring reintubation.
Ventilator-dependent patients with NMD can only achieve successful extubation
by using full NVS and MIE. Because of our extubation success rates for unweanable NMD patients, we no longer consider tracheotomy for ventilator-dependent
patients with NMD who can be made to satisfy Table 42.1 criteria and now offer
extubation and decannulation even to those with CPF < 160 l/m.
42.4
Decannulation of Unweanable Patients
Any patient with an indwelling tracheostomy tube who has understandable speech
when the tube cuff is deflated is evaluated for decannulation. Patients without severe
speech and swallowing impairment are usually good candidates. The ability to
effect glottic closure and maintain airway patency during a cough is critical for successful decannulation. Unweanable patients for whom CPF can approach 160 l/m
336
J.R. Bach
Fig. 42.2 Twenty-six-year old man with Duchenne muscular dystrophy transferred for extubation
after failing three extubations over a 26-day period. He used a 15-mm angled mouthpiece, as in
Fig. 42.1, for daytime ventilatory support and a lip seal phalange with nasal prongs (Hybrid,
Teleflex Medical, Research Triangle Park, NC, USA) for nocturnal ventilatory support
by manually assisted coughing (air stacking then a cough-timed abdominal thrust)

[20] or by using MIE via the upper airway with the tracheostomy tube capped and
those with experience in using NVS are strong candidates for decannulation, even if
inspiratory and expiratory muscles are completely paralyzed.
If CPF via the upper airways with a capped fenestrated tracheostomy tube present is much lower than 160 l/m, the tube is removed, at least temporarily, and the
ostomy covered. This decreases obstruction to upper airway airflows, permits
greater assisted CPF, and facilitates the use of NVS as well as autonomous breathing. If, despite air stacking and coordinated abdominal thrusts, CPF levels still fail
to approach 160 l/m, vocal cord paralysis, hypopharyngeal collapse, tracheal stenosis, or other reasons for airway obstruction are considered and the patient is referred
for fiberoptic evaluation of the upper airway to eliminate possible reversible causes
of upper airway obstruction.
Any nasogastric tube that is present is removed before decannulation. The
patient is decannulated directly to full NVS and a pressure dressing is placed
over the ostomy until the skin is closed (Fig. 42.2) (Tegaderm, 3M Company, St.
Paul, MN, USA) [2125]. Upon decannulation, most patients with VCs greater
than 250 ml wean to nocturnal-only NVS [9, 21]. All patients transferred from
continuous TMV to NVS prefer NVS overall and for safety, convenience, swallowing, speech, appearance, and comfort [15]. Noninvasive management also
minimizes cost and facilitates return to the community rather than long-term
institutionalization [26]. Whereas tracheostomized ventilator users will always
be afraid of asphyxia from ventilator failure and accidental disconnection, twothirds of NVS users with no inspiratory or expiratory muscle function and little
or no measurable VC can be taught glossopharyngeal breathing for security in
42
337
the event of ventilator malfunction or loss of access to the NVS interface [22, 23,
27]. The need to decannulate TMV users to NVS can be avoided, however, if
unweanable patients are extubated without resort to tracheotomy. We have decannulated more than 200 continuously ventilator-dependent patients without a single failure [3, 16, 20, 22, 23]. In some cases, our decannulated and extubated
continuously ventilator-supported cases have depended on NVS for more than 60
years for prolonged survival [28]. Unfortunately, few centers decannulate continuously ventilator-dependent patients [2325].
Finally, after years of debate and consensus conferences of experts whose
knowledge of noninvasive ventilation is limited to CPAP and the use of low-span
bi-level PAP for patients with sleep-disordered breathing, a Centers for Disease
Control panel of respiratory experts and other consensus groups have recommended
that NVS be used long term for up to 24 h per day ventilator dependence [29, 30].
Despite the fact that our center has managed more than 100 CNVS dependent DMD
patients and has not needed to resort to tracheotomy to prevent respiratory mortality
for DMD patients in more than 30 years, it has taken this long for recognition of the
fact that, even in the absence of inspiratory or expiratory function, these patients can
be managed noninvasively. No informed NMD patient, trained in NVS and MIE,
prefers to undergo tracheotomy [15]. However, family and caregiver involvement in
providing NVS and MIE is important for long-term success. The only appropriate
indications for tracheotomy are failure of NVS and MIE to maintain normal O2 sat
because of continuous saliva aspiration and irreversible upper airway obstruction
resulting from upper motor neuron lesions. In our experience, this only occurs in
patients with advanced bulbar ALS or severe central nervous system disease.
Patients with neuromuscular disease do not require tracheostomies for

continuous ventilatory support or for failing extubation other than those
with advanced bulbar amyotrophic lateral sclerosis.
A noninvasive ventilatory support, oximetry feedback protocol, can prevent episodes of pneumonia and acute respiratory failure.
Ventilator unweanable patients can be extubated or decanulated of tracheostomy tubes to continuous noninvasive ventilatory support and use
mechanical insufflation-exsufflation to expulse airway secretions.
References
1. Bach JR. Update and perspectives on noninvasive respiratory muscle aids: part 1 the inspiratory muscle aids. Chest. 1994;105:123040.
2. Bach JR, Bianchi C, Aufiero E. Oximetry and indications for tracheotomy for amyotrophic
lateral sclerosis. Chest. 2004;126:15027.
3. Gomez-Merino E, Bach JR. Duchenne muscular dystrophy: prolongation of life by noninvasive respiratory muscle aids. Am J Phys Med Rehabil. 2002;81:4115.
338
J.R. Bach
4. Bach JR, Saltstein K, Sinque D, Weaver B, Komaroff E. Long term survival in WerdnigHoffmann Disease. Am J Phys Med Rehabil. 2007;86:33945.
5. Bach JR, Baird JS, Plosky D, Nevado J, Weaver B. Spinal muscular atrophy type 1: management and outcomes. Pediatr Pulmonol. 2002;34:1622.
6. Bach JR. Amyotrophic lateral sclerosis: prolongation of life by noninvasive respiratory aids.
Chest. 2002;122:928.
7. Levine S, Nguyen T, Taylor N, Friscia ME, Budak MT, Rothenberg P, Zhu J, Sachdeva R,
Sonnad S, Kaiser LR, et al. Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med. 2008;358:132735.
8. Haber II, Bach JR. Normalization of blood carbon dioxide levels by transition from conventional
ventilatory support to noninvasive inspiratory aids. Arch Phys Med Rehabil. 1994;75:114550.
9. Gatin G. Inret de la ventilation assise dans les dystrophies musculaires. Ann Readapt Med
Phys. 1983;26:11128.
10. Splaingard ML, Frates RC, Harrison GM, Carter RE, Jefferson LS. Home positive pressure
ventilation: twenty years experience. Chest. 1984;4:37682.
11. Baydur A, Gilgoff I, Prentice W, Carlson M, Fischer DA. Decline in respiratory function and
experience with long term assisted ventilation in advanced Duchennes muscular dystrophy.
Chest. 1990;97:8849.
12. Fukunaga H, Okubo R, Moritoyo T, Kawashima N, Osame M. Long term follow up of patients
with Duchenne muscular dystrophy receiving ventilatory support. Muscle Nerve. 1993;16:
5548.
13. Bach JR, OBrien J, Krotenberg R, Alba A. Management of end stage respiratory failure in
Duchenne muscular dystrophy. Muscle Nerve. 1987;10:17782.
14. Bach JR. Amyotrophic lateral sclerosis: communication status and survival with ventilatory
support. Am J Phys Med Rehabil. 1993;72(6):3439.
15. Bach JR. A comparison of long term ventilatory support alternatives from the perspective of
the patient and care giver. Chest. 1993;104:17026.
17. Bach JR, Gonalves MR, Hamdani I, Winck JC. Extubation of unweanable patients with neuromuscular weakness: a new management paradigm. Chest. 2010;137(5):10339.
18. Bach JR, Sinquee D, Saporito LR, Botticello AL. Efficacy of mechanical insufflationexsufflation in extubating unweanable subjects with restrictive pulmonary disorders. Respir
Care. 2015;60:47783.
19. Bach JR, Alba AS, Saporito LR. Intermittent positive pressure ventilation via the mouth as an
alternative to tracheostomy for 257 ventilator users. Chest. 1993;103:17482.
20. Bach JR, Saporito LR, Shah HR, Sinquee D. Decanulation of patients with severe respiratory muscle
insufficiency: efficacy of mechanical insufflation-exsufflation. J Rehabil Med. 2014;46:103741.
21. Bach JR, Goncalves M. Ventilator weaning by lung expansion and decanulation. Am J Phys
Med Rehabil. 2004;83:5608.
22. Bach JR, Alba AS. Noninvasive options for ventilatory support of the traumatic high level
quadriplegic. Chest. 1990;98:6139.
23. Bach JR. New approaches in the rehabilitation of the traumatic high level quadriplegic. Am
J Phys Med Rehabil. 1991;70:1320.
24. Viroslav J, Sortor S, Rosenblatt R. Alternatives to tracheostomy ventilation in high level SCI
[abstract]. J Am Paraplegia Soc. 1991;14:87.
25. Viroslav J, Rosenblatt R, Tomazevic SM. Respiratory management, survival, and quality of
life for high level traumatic tetraplegics. Respir Care Clin N Am. 1996;3:31322.
26. Bach JR, Intintola P, Alba AS, Holland I. The ventilator-assisted individual: cost analysis of
institutionalization versus rehabilitation and in-home management. Chest. 1992;101:2630.
27. Bach JR, Bianchi C, Vidigal-Lopes M, Turi S, Felisari G. Lung inflation by glossopharyngeal
breathing and air stacking in Duchenne muscular dystrophy. Am J Phys Med Rehabil.
2007;86:295300.
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28. Bach JR, Mehta AD. Respiratory muscle aids to avert respiratory failure and tracheostomy: a
new patient management paradigm. J Neurorestoratal. 2014;2:2535.
29. Birnkrant DJ, Bushby KM, Amin RF, Bach JR, Benditt JO, Eagle M, Finder JD, Kalra MS,
Kissel JT, Koumbourlis AC, Kravitz RM. The respiratory management of patients with
Duchenne muscular dystrophy: a DMD care considerations working group specialty article.
Pediatr Pulmonol. 2010;45(8):73948.
30. Bach JR, Gonalves MR, Hon AJ, Ishikawa Y, De Vito EL, Prado F, Dominguez ME. Changing
trends in the management of end-stage respiratory muscle failure in neuromuscular disease:
current recommendations of an international consensus. Am J Phys Med Rehabil.
2013;92(3):26777.
Tracheostomy Decannulation
After Cervical Spinal Cord Injury
43
Erik J.A. Westermann and Mike J. Kampelmacher
Abbreviations
CPFi
CPF
ENT
FiO2
FVC
GPB
ICU
LVR
MIC
MI-E
MPPV
NPPV
PaCO2
PDT
SBT
SCI
SpO2
Involuntary cough peak flow

Cough peak flow
Ear, nose, and throat
Fraction of oxygen in inspired air
Forced vital capacity
Glossopharyngeal breathing
Intensive care unit
Lung volume recruitment
Maximum insufflation capacity
Mechanical insufflation-exsufflation
Mouthpiece positive pressure ventilation
Partial pressure of arterial carbon dioxide
Percutaneous dilatational tracheostomy
Spinal cord injury
Pulse oximetry saturation
E.J.A. Westermann, MD (*) M.J. Kampelmacher, MD, PhD

Centre for Home Mechanical Ventilation Utrecht, University Medical Center Utrecht,
Utrecht, The Netherlands
e-mail: e.westermann@umcutrecht.nl; m.j.kampelmacher@umcutrecht.nl
DOI 10.1007/978-3-319-04259-6_43
341
342
43.1
E.J.A. Westermann and M.J. Kampelmacher
Introduction
Decannulation, or tracheostomy tube removal, is the final procedure of the threestep process of liberating a patient who is clinically improving from invasive
mechanical ventilation. In the intensive care unit, this process first involves a spontaneous breathing trial (SBT) to determine the patients readiness for discontinuing
mechanical ventilation. After passing this test, discontinuing mechanical ventilation
may follow as a second step. Third, the subsequent removal of the tracheostomy
tube may be considered. This chapter discusses the decannulation of patients with a
cervical spinal cord injury (SCI).
Among patients with cervical SCI, we can distinguish those who regain spontaneous respiration and for whom invasive mechanical ventilation can be discontinued, leaving them breathing sufficiently, from those who remain completely or
partially ventilatory insufficient, for example, only during the night. The former
patients are obvious candidates for tracheostomy tube removal. However, depending on the level of their SCI, respiratory reserve may still be absent or marginal at
best. Consequently, they remain at risk for future ventilatory failure if their respiratory reserve is overwhelmed by an increasing respiratory load, for example, as in
airway secretion retention, pneumonia, or weight gain. The latter group of patients,
who are left without the ability to breathe or can breathe only for several hours a
day, remain dependent on mechanical ventilatory support. In general, they have
been tracheostomized and invasively ventilated earlier or later during their clinical
course. Mostly because of their inability to pass an SBT, discontinuation of invasive
mechanical ventilation is considered impossible and is thus not attempted during
their intensive care unit (ICU) stay. Subsequently, patients are discharged to a
chronic care facility while they remain invasively ventilated. Therefore, it seems
straightforward that these patients keep their tracheostomy tubes to allow for chronic
invasive mechanical ventilation and invasive removal of airway secretions.
Although a tracheotomy probably is the most frequent surgical procedure performed in critically ill patients, it is not known when and how to safely remove the
tracheostomy tube. Intensivists usually consider decannulation if the reasons for
which the artificial airway was necessary have been resolved, mechanical ventilation is no longer needed, and the patient can manage his or her airway secretions
with a vigorous spontaneous cough. In an international survey of 309 physicians
and respiratory therapists with expertise in managing tracheostomized patients, the
level of consciousness, the ability to tolerate capping of the tracheostomy tube,
cough effectiveness, the ability to manage secretions, and oxygenation were rated as
the most important factors in deciding to decannulate patients [1].
On the other hand, to avoid a difficult decision to decannulate, intensivists can
choose not to tracheostomize their patients and keep them translaryngeally intubated
on mechanical ventilation for prolonged periods of time. However, for these patients,
there is still debate about how to proceed if prolonged mechanical ventilation is anticipated. Generally, a tracheostomy is performed earlier or later in the course of recovery
because of pulmonary complications, to facilitate bronchial suctioning procedures
and oropharyngeal hygiene, or to prevent laryngeal and tracheal damage caused by
swallowing and head movement. To date, there are no randomized controlled trials
43
Tracheostomy Decannulation After Cervical Spinal Cord Injury
343
comparing early (i.e., within 7 days after intubation) with late tracheostomy, which is
performed 21 days after intubation. A retrospective study suggested a policy favoring
early tracheostomy over a later procedure because of earlier discontinuation of
mechanical ventilation, shorter ICU stay, and less frequent complications of prolonged intubation (tracheal stenosis and granulomas) in patients who were operated
on within 7 days [2]. Because of the length of time already spent in the ICU, the
removal of the tracheostomy tube may be left to be performed outside the safe and
monitored environment of the ICU, which may carry additional risks for the patient
within the first 1236 h after decannulation [3]. Caution is advised to avoid inappropriate discontinuation of mechanical ventilation in patients with severely restrictive
respiratory syndromes and their discharge with artificial airways to the nursing ward
while breathing spontaneously but insufficiently and in a hypercapnic state [4]. These
patients are at high risk of erroneously being treated with oxygen to resolve desaturations, resulting in respiratory arrest during the night and subsequent cardiopulmonary
resuscitation or even death.
For most SCI patients who have adequate ventilator-free breathing ability to pass
an SBT, the removal of the tracheostomy tube may not be as straightforward as in the
general ICU population. These patients usually have marginal or even absent ventilatory reserves and swallowing dysfunction from long-term tracheostomy tube cannulation. Their ventilatory reserve may just enable them to sustain or prohibit them from
handling an increased respiratory load by increasing respiratory rate or tidal volume,
maintaining eucapnia or causing hypercapnia, respectively. If followed by aspiration,
impaired swallowing may, in fact, be the cause of such an increased respiratory load,
possibly or definitely rendering these patients hypercapnic. Periodic hypercapnia,
whatever its cause, is especially treacherous if it occurs only during sleep, which may
be regarded as a stress test for a depleted ventilatory reserve. Ventilatory reserve may
be further compromised by neuromuscular abnormalities associated with critical illness in addition to the multiple medical comorbidities also present in the general
medico-surgical ICU population. Therefore, monitoring of ventilatory sufficiency
during sleep after discontinuing mechanical ventilation should be routinely performed
in the ICU, especially before the patient is transferred to the nursing ward. During an
European Respiratory Society online lecture series on neuromuscular diseases in
November 2012, with topics on noninvasive and invasive mechanical ventilation,
44 % of attending international colleagues would discontinue mechanical ventilation
even if patients could not maintain eucapnia. In practice, such a policy may put
patients at risk for recurring episodes of ventilatory failure, which obviously should be
prevented.
43.2
SCI Patients Who Can Breathe and for Whom

Mechanical Ventilation Has Been Discontinued
The patient should be assessed for a patent upper airway, cough effectiveness, and
the ability to protect the airway from aspiration of saliva. Patency of the upper airway may be checked by temporarily blocking the artificial airway after deflation of
the cuff. The patient then should be able to breathe alongside the endotracheal tube
344
Table 43.1 Decannulation criteria for patients who can breathe (conventional)
Prerequisites
Alert and cooperative
Clinical hemodynamic stability
Normal gas exchange on room air
Ventilator-free breathing ability
Preferably, absence of aspiration
Exclusion of upper airway

abnormalities caused by
endotracheal intubation or
tracheostomy
Ability to tolerate deflation of
tracheostomy tube cuff
Ability to tolerate capping of the
tracheostomy tube
Ability to maintain airway patency
Recommendation
No sedative medications to improve sleep
No vasoactive medications
PaCO2 < 45 mmHg (6.0 kPa), PaO2 > 94 %
Perform an SBT; if successful, discontinue mechanical
ventilation
ENT swallow evaluation assessment by speech
pathologist
Perform Evans blue dye test
ENT endoscopic evaluation of larynx and upper trachea
Perform endotracheal suctioning during cuff deflation

Perform a capping trial [7]. Subsequently, monitor for
respiratory distress caused by increased airway
resistance for 1224 h
Evaluate voice quality during temporary occlusion of
tube with cuff deflated
Measure involuntary CPF while intubated (should
exceed 58.5 l/min [5]); measure voluntary CPF with
capped tracheostomy tube (should exceed 130 l/min [8])
Decannulate
PaCO2 partial pressure of arterial carbon dioxide, SBT spontaneous breathing trial, ENT ear, nose,
and throat, CPF cough peak flow
or tracheostomy tube without discomfort or respiratory distress, maintaining normal

gas exchange.
For intubated patients, involuntary cough peak flow (CPFi) can be measured
using a hand-held respiratory mechanics monitor after instilling 2 ml of normal
saline solution down the tube at the end of inspiration. Extubation success can be
quite reliably predicted if CPFi can exceed 58.5 l/min [5].
Aspiration can be obvious, for example, when symptoms of asphyxiation follow
deflation of the cuff of the tracheostomy tube in case of pooling of laryngeal and
tracheal secretions above the cuff, but also chronic and subtle. Aspiration is very
common, occurring in approximately 77 % of patients with artificial airways. It
occurs even more often in tracheostomized patients, despite an inflated cuff [6].
Aspiration can lead to hypoxemia, bronchospasm, airway obstruction, atelectasis,
and pulmonary infection.
Patients with cervical SCIs often do not comply with all of the suggested prerequisites for decannulation and thus may remain cannulated for prolonged periods of
time. Therefore, some necessary recommendations (Table 43.1) are made and executed before a trial decannulation is performed. Among these, a capping trial should
43
345
be performed as a screening tool for decannulation [7]. This test showed a high
sensitivity (90 %) and positive predictive value (100 %) for successful decannulation among 57 patients screened over a 12-month period. Patients were enrolled
from eight different clinical services and included four neurological patients and
only one patient from the ICU. One patient failed the capping trial and was decannulated but reintubated to manage secretions. Unfortunately, this study did not mention how secretions were routinely managed other than by conventional invasive
methods or spontaneous coughing.
In the study of Pandian et al. [7], the following criteria for eligibility for capping
were defined:
The patient should have a small tracheostomy tube, preferably size four cuffless.
While occluding the tube with a finger for 1 min, the breathing pattern should
remain comfortable without release of positive pressure from the tracheostomy
tube upon removal of the finger as a sign of air trapping.
The patient should be able to tolerate a speaking valve without respiratory distress.
Coughing should be adequate to mobilize airway secretions.
Airway suctioning should be required less frequently than every 4 h.
Capping of the tracheostomy tube should be tolerated without respiratory distress.
The patient should maintain stable oxygen saturation at all times.
The patient should be alert and sufficiently dexterous to remove the cap from the
tracheostomy tube within 30 s without assistance from healthcare personnel.
During capping, sedation must be avoided. Those patients already known to have a
difficult airway according to their medical history or anesthesiology assessment upon prior intubation were evaluated by a ear, nose, and throat (ENT) specialist, who then could advise whether to proceed with or withhold a capping
trial. SCI patients will not be able to satisfy a number of the above-mentioned
criteria because of their tetraplegia. Therefore, nursing attendance should be
continuous and an adequate call bell should be provided and its effective operation by the patient should be ascertained.
Next, because of the increased risk of dysphagia in SCI patients, an ENT investigation evaluating swallowing is recommended. Tracheostomy tubes should be
removed early in the morning, preferably at the beginning of the week, to allow for
close monitoring by as many knowledgeable professionals as possible over the following 2448 h.
During this period patients should be continuously monitored by pulse oximetry
and checked every 30 min for the need for suctioning or assisted coughing. Forced
vital capacity should be assessed every 4 h to identify respiratory deterioration or
signs of exhaustion. Respiratory rate should also be monitored, counting for 30 s
once every 15 min for the first 4 h and consecutively every 30 min for the next 20 h
and once hourly for the following 24 h. A spare tracheostomy tube of the same size
and one size smaller should be kept in readiness to recannulate the patient if the
need should arise [9].
346
43.3
SCI Patients for Whom Mechanical Ventilation Cannot

Yet Be Discontinued
Patients with high-level cervical SCIs for whom mechanical ventilation cannot yet
be discontinued either will or will not pass an SBT, depending on the recurrence of
some ventilator-free breathing ability. They usually remain cannulated for prolonged periods of time, often indefinitely. They remain at increased risk of airway
damage from suctioning procedures, complications associated with the tracheostomy, airway microbial colonization, pulmonary infection, and recurrent ICU
admission. Because they cannot breathe, a capping trial may seem inappropriate or
even dangerous for the simple reason of interrupting invasive mechanical ventilation. Often, the presumed permanent dependence on the artificial airway is accepted
by physicians because of the continuous necessity for removal of bronchial secretions. It is rarely appreciated that these artificial airways cause and increase secretions and impair the ability to cough. Many tracheostomized patients, however,
choose to be decannulated or to forgo tracheostomy if noninvasive techniques are
available [10].
The question then arises regarding whether and how to remove the tracheostomy
tube for these patients. In the 1990s, Bach and coworkers [11, 12] showed that
patients with high-level cervical SCIs without ventilator-free breathing ability could
be extubated and decannulated by converting them from invasive to noninvasive
ventilation using facial interfaces during the night and mouthpiece ventilation during the day. It was extremely important that patients were able to manage their
bronchial secretions, which were the main reason for oxygen desaturation, atelectasis, retention pneumonia, and hospitalization. When using assisted coughing techniques following aggressive lung volume recruitment (LVR), a cough peak flow
(CPF) of > 160 l/min could usually be achieved, and this proved enough to safely
permit the removal of the tracheostomy tube. Bach et al. proposed continuing LVR
techniques following decannulation every day to prevent airway secretion encumbrance. Patients could use air (or breath) stacking or glossopharyngeal breathing
(GPB) to augment lung volume, improve voice volume, improve respiratory compliance, facilitate noninvasive mechanical ventilation, and improve CPFs. In addition, they could regain ventilator-free breathing ability by using GPB as a breathing
method. McKim and coworkers [8] demonstrated that, using LVR and assisted
coughing techniques, CPFs measured after decannulation were some 3040 l/min
greater than during coughing with the capped cannula in place using these techniques, probably because of the surplus airway resistance of the endotracheal part
of the tube. They suggested that, in cannulated patients, these findings might lower
the CPF threshold of 160 l/min with this flow difference as an indication for safe
decannulation.
For the high cervical SCI patient who cannot pass an SBT, discontinuing invasive
mechanical ventilation often seems impossible. In the ICU it may go unnoticed that
one of the main reasons for failure to discontinue invasive ventilation is airway
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347
secretion encumbrance. During their training, intensivists have been taught to rely
on artificial airways to invasively remove airway secretions and they have seldom
been trained in using LVR techniques, which are necessary to effectively resolve
retention of bronchial secretions. Hence, they may be reluctant to remove the tracheostomy tube because they think the patients depend on them for mucus removal.
Of note, contrary to what is seldom considered, these patients often can be successfully liberated from their artificial airways [13]. In these patients, the aims are to
discontinue invasive ventilation, proceed with mechanical ventilation noninvasively,
and remove the artificial airway. The latter goal cannot be achieved without effective airway clearance techniques [13, 14].
For SCI patients in the ICU, early treatment with LVR techniques is recommended. For an effective tution of air stacking or GPB, the patient should be awake,
alert, cooperative, and highly motivated to achieve the maximum insufflation capacities necessary to enhance CPFs for mucus removal. Training in these techniques is
time consuming and requires a dedicated and patient teacher. In the early postinjury phase it is more prudent to use mechanical insufflation-exsufflation (MI-E)
with a cough-assist device, which can also be operated on a cuffed tracheostomy
tube for unresponsive patients. Only after lungs and airways have been completely
cleared of secretions, which in our experience can never be achieved with invasive
suctioning procedures only, training in noninvasive mechanical ventilation may be
initiated. Starting invasive LVR techniques early in the course of recovery may prevent pulmonary complications and can shorten ICU stay and length of hospital
admission [14].
In clinical practice, patients in the ICU grow accustomed to regular bagging
procedures with a manual resuscitator prior to cuffed artificial airway suctioning.
They should again be acquainted with airflow through the upper airways to tolerate capping of the tracheostomy tube and to be safely converted to noninvasive
(mouthpiece) ventilation during the day. The difference between closed-circuit
mechanical ventilation via a cuffed tracheostomy tube and the air leakage customary to noninvasive ventilation should be thoroughly explained to the patient.
While still on the ventilator, which should be able to perform in noninvasive
mode, the cuff is deflated and the patient is given mechanical ventilation by hand
with a manual resuscitator connected by a length of corrugated tubing to a
mouthpiece, which is presented to the patient. While being ventilated by hand
through the mouthpiece in sync with the ventilator equipment, its minute volume
is gradually dialed down until the patient is ventilated completely by hand. At
this point, the ventilator can be disconnected from the tracheostomy tube, which
subsequently can be capped. The patient is then adjusted to a mechanical ventilator in volume-controlled mode using the mouthpiece. The same procedure applies
when adjusting the patient to noninvasive ventilation by nasal or oronasal interfaces. Table 43.2 lists prerequisites and recommendations as a stepwise approach
for tracheostomy tube removal in patients with high-level SCIs who have limited
or no ventilator-free breathing ability.
Decannulate. Apply pressure dressing

Monitor gas exchange, triggering frequency, VC and CPF, MIC, and CPF after MIC
Discontinue noninvasive MI-E; continue air stacking with abdominal thrusts thrice daily
Consult home mechanical ventilation service
Recommendation
Avoid sedative medications
No vasoactive medications
Decrease FiO2; use pulse oximetry as biofeedback
Use invasive MI-E with exsufflation timed abdominal thrusts
Check blood gas analysis regularly, PaCO2 < 45 mmHg (6.0 kPa)
If SpO2 < 95 %, continue MI-E until SpO2 > 94 %
Normal white blood cell count and absent serum variables of infection; normal chest X-ray
Tight-fitting tracheostomy tube by PDT or Lipkin tracheostomy surgical technique
Deflate tracheostomy tube cuff; rule out aspiration
Train patient in using mouthpiece noninvasive ventilation, teach to get used to
oropharygeal and laryngeal airflow; increase airflow to at least 90 l/min
Use mouthpiece ventilation only; cap tracheostomy tube. Check blood gas analysis and
adjust ventilation accordingly. Teach to master air stacking as LVR technique
Discontinue invasive MI-E
Perform capping trial and monitor for respiratory distress during either spontaneous or
mouthpiece ventilation, check gas exchange, apply LVR as necessary to maintain SpO2
> 94 % on room air
Check blood gas analysis or monitor nocturnal PCO2 transcutaneously or by
oxicapnometry
Exclude anxiety related to NPPV; fear of going to sleep with NPPV
SpO2 pulse oximetry saturation, FiO2 fraction of oxygen in inspired air, PaCO2 partial pressure of arterial carbon dioxide, MI-E mechanical insufflation-exsufflation, PDT percutaneous dilatational tracheostomy, LVR lung volume recruitment, NPPV noninvasive positive pressure ventilation, MPPV mouthpiece positive pressure ventilation, VC vital capacity, CPF cough peak flow, MIC maximum insufflation capacity, ICU intensive care unit
Prepare for ICU discharge
Tolerance of noninvasive mask ventilation during the night with

capped tracheostomy tube
Ability to sustain noninvasive positive pressure ventilation day
and night
Ability to sustain noninvasive MI-E by oronasal mask
Maintain normal gas exchange for 2448 h using NPPV, MPPV,
and LVR
Tolerance of tracheostomy tube being capped
Prerequisites
Awake, alert, and cooperative
Clinical hemodynamic stability
Maintain SpO2 > 94 % on an FiO2 = 0.21
Complete clearance of airway secretions
Normal gas exchange
Any desaturations < 95 % resolved by MI-E or other LVR technique
Absence of infectious (pulmonary) disease
Prevent stomal air leakage alongside tube
Ability to tolerate cuff deflation
Tolerance of mouthpiece noninvasive ventilation while on
tracheostomy mechanical ventilation
Discontinue tracheostomy tube ventilation during the day
Table 43.2 Decannulation criteria for patients with limited or without ventilator-free breathing ability
348
43
43.4
349
Failure to Decannulate
Decannulation failure is defined as the need to reinsert an artificial airway within

4896 h of planned tracheostomy tube removal. Clinicians are prepared to accept a
decannulation failure rate of 25 % [1]. Although failing a capping trial may predict
failure to remove the artificial airway in some patients [7], it is not a criterion to
exclude most patients with SCIs from decannulation attempts. The most common
reasons for failure to decannulate are inability to resolve airway mucus encumbrance, persistent pulmonary infection with need for oxygen administration, continuous aspiration, but also lassitude in teaching LVR techniques by health-care
providers. However, because most patients with cervical SCIs maintain normal glottic function and therefore can learn to air stack, they usually can achieve CPFs
>160 l/min and may be decannulated, regardless of whether or not they regain any
ventilator-free breathing ability [1113]. It should be noted, however, that these
reported successes are highly dependent on the presence of an experienced, driven,
dedicated, and able team of physicians and respiratory therapists. If prolonged
mechanical ventilation is anticipated, tracheotomy usually is unavoidable, and without experience in LVR, decannulation may not be feasible.
In a retrospective review of 164 patients with cervical SCIs, risk factors for postinjury tracheostomy were high-level cervical SCI (especially C2C4 injuries), age
(> 45 years), concomitant pulmonary disease, smoking history, premorbid comorbidity, severity of impaired consciousness, high-level injury severity score, and
active pneumonia [15]. A risk factor for failure to decannulate was a high cervical
complete SCI without the ability to shrug the shoulders within 3 weeks post-injury,
with shoulder shrug indicating some preservation of diaphragmatic function. Of
note, this study did not mention the application of LVR techniques.
43.5
Summary
In high-level SCI patients for whom airway management has resulted in tracheostomy tube placement during their ICU course, decannulation can be achieved for
most of them by using a stepwise approach (Tables 43.1 and 43.2), and if executed
by an experienced and dedicated health-care team. Also, the selected patient with an
aspiration hazard may be liberated from an artificial airway. With the aggressive use
of different LVR techniques accompanied by timed abdominal thrusts it has been
clearly shown that decannulation is feasible, even if not initially considered because
of complete ventilator dependency or prolonged airway secretion encumbrance. By
gaining experience in the application of LVR techniques and mechanical-assisted
coughing, intensivists can liberate SCI patients from invasive mechanical ventilation and from their tracheostomy tubes during their ICU stay. Thus, they can shorten
admission times, reduce health-care costs, and generally improve the quality of life
of their patients, who now can be managed at home using noninvasive ventilation
and noninvasive LVR techniques for ventilatory support and airway clearance,
respectively.
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References
1. Stelfox HT, Crimi C, Berra L, Noto A, et al. Determinants of tracheostomy decannulation: an
international survey. Crit Care. 2008;12:R26.
2. Romero J, Vari A, Gambarrutta C, et al. Tracheostomy timing in traumatic spinal cord injury.
Eur Spine J. 2009;18:14527. doi:10.1007/s00586-009-1097-3.
3. Reibel JF. Decannulation: how and where. Respir Care. 1999;44(7):8569.
4. Bach JR. Inappropriate weaning and late onset ventilatory failure of individuals with traumatic
spinal cord injury. Paraplegia. 1993;31:4308.
5. Su W-L, Chen Y-H, Chen C-W, et al. Involuntary cough strength and extubation outcomes for
patients in an ICU. Chest. 2010;137(4):77782.
6. Elpern EH, Jacobs ER, Bone RC. Incidence of aspiration in tracheally intubated patients.
Heart Lung. 1987;16:52731.
7. Pandian V, Miller CR, Schiavi AJ, et al. Utilization of a standardized tracheostomy capping
and decannulation protocol to improve patient safety. Laryngoscope. 2014;124(8):1794800.
doi:10.1002/lary.24625.
8. McKim DA, Hendin A, LeBlanc C, et al. Tracheostomy decannulation and cough peak flows
in patients with neuromuscular weakness. Am J Phys Med Rehabil. 2012;91:66670.
9. Ross J, White M. Removal of the tracheostomy tube in the aspirating spinal cord-injured
patient. Spinal Cord. 2003;41:63642.
10. Bach JR. A comparison of long-term ventilatory support alternatives from the perspective of
the patient and the care giver. Chest. 1993;104:17026.
11. Bach JR, Alba AS. Noninvasive options for ventilatory support of the traumatic high level
quadriplegic. Chest. 1990;98:6139.
12. Bach JR. New approaches in the rehabilitation of the traumatic high level quadriplegic. Am
J Phys Med Rehabil. 1991;70:1320.
13. Bach JR, Gonalves MR, Hamdani I, et al. Extubation of patients with neuromuscular weakness. A new management paradigm. Chest. 2010;137(5):10339.
14. Gonalves MR, Honrado T, Winck JC, et al. Effects of mechanical insufflation-exsufflation in
2012;16:R48. http://ccforum.com/content/16/2/R48.
15. Nakashima H, Yukawa Y, Imagama S, et al. Characterizing the need for tracheostomy placement and decannulation after cervical spinal cord injury. Eur Spine J. 2013;22:152632.
Part V
Discharge Ventilator Depend Patients
Criteria for Discharging Patients

with Prolonged and Difficult Weaning
from Intensive Care Unit to Weaning
Center
44
Gatan Beduneau, Christophe Girault,

Dorothe Carpentier, and Fabienne Tamion
Abbreviations
COPD
ICU
MV
SBT
SWU
44.1

Intensive care unit
Specialized weaning unit
Introduction
During the past two decades, an abundant literature on weaning from mechanical
ventilation (MV) has permitted a better understanding of this process, which may
account for about 40 % of the total time spent on MV [1]. The majority of patients
G. Beduneau, MD (*) C. Girault, MD

Department of Medical Intensive Care, Charles Nicolle University Hospital,
Rouen University, Rouen, France
UPRES EA 3830-IRIB, Institute for Biomedical Research, Rouen University, Rouen, France
e-mail: gaetan.beduneau@chu-rouen.fr
D. Carpentier, MD
F. Tamion, MD, PhD
INSERM UMR 1096-IRIB, Institute for Biomedical Research, Rouen University,
Rouen, France
DOI 10.1007/978-3-319-04259-6_44
353
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G. Beduneau et al.
can be weaned easily, as soon as the first trial [13], provided that clinicians
promptly detect the ability to be weaned, avoid excess sedation, and perform a spontaneous breathing trial (SBT) [1]. For some patients, weaning is difficult and they
require a potentially complex pathophysiological analysis to diagnose and treat the
etiology of failure before resuming an SBT. Finally, a smaller proportion of patients
recovering from catastrophic illness and/or having severe underlying comorbidities
require a long time before being separated from the ventilator. They constitute the
prolonged weaning group, with a usually poor outcome [1]. For these patients,
weaning from MV could depend on specific measures; among them, transfer to a
specialized weaning unit could be discussed [4]. In this chapter, we consider criteria
for discharging these particular patients in such a structure.
44.2
Discussion
44.2.1 Extended Stay and Consequences

Length of intensive care unit (ICU) stay is a classical and important tool to evaluate
quality of care and activity of the ICU. For clinicians, ensuring optimal care with a
short length of stay is important because of the association between prolongation of
ICU stay and complications, with an effect in terms of morbidity and mortality [5].
To our knowledge, no consensus exists that defines when a stay is considered to be
prolonged; moreover, these settings might be different, depending on the characteristics of the ICU (surgical or not, and type of surgical ICU) [6]. However, an ICU
stay of 14 days seems to be relatively consensual for a nonspecific ICU [7]. Over the
years, probably related to patient evolution (with increasing comorbidities) and
progress in intensive care, a new category of patients has appeared and is expected
to increase: They experience a catastrophic illness and survive after a long ICU stay
and aggressive therapy, but they remain dependent on a ventilator. Moreover, these
patients suffer from consequences of multiple organ failure, including renal insufficiency, acquired weakness, malnutrition, and colonization with multidrug-resistant
bacteria. We can designate them as chronic critically ill patients [8, 9].
44.2.2 Ventilator-Dependent Patient or Prolonged

Weaning Patient
We can find many definitions for prolonged weaning. Thus, in the United States,
when a patient is ventilated more than 21 days, he or she can be systematically considered as a prolonged ventilated patient, regardless of the weaning process issue.
This definition is directly related to economic considerations [10]. Indeed, some
patients may not benefit from weaning attempts, because of the severity and persistence of the underlying disease that lead to prolonged invasive MV. Thereby, in
2007, an international consensus conference [1] proposed a classification of the
weaning process according of the number of spontaneous breathing trials performed
44
Criteria for Discharging Patients with Prolonged and Difficult Weaning
355
and the success of extubation. The third group in this new classification is referred
to as prolonged weaning, defined as requiring more than three weaning attempts
or 7 days to be separated from the ventilator. Although these prolonged weaning
patients represent fewer than 10 % of the whole population of ICU patients, they
paradoxically require a prolonged ICU stay, accounting for up to 40 % of ICU
expenditures [11, 12].
44.2.3 Objective and Organization of a Specialized Weaning Unit

The concept of a specialized weaning unit (SWU) was developed in the United
States [13], based on epidemiologic (an increase of patients with difficult and prolonged ventilation) and economic (lower operating costs of these units and preservation of ICU bed availability) arguments. The notion of a SWU was also introduced
by the international consensus conference on weaning, and discharge of these
patients in specific units should now be encouraged [1]. Several modalities of organization have been described [4]. Schematically, a SWU could be supported by an
ICU or located in a specific long-term care hospital.
The concept of chronic critically ill patients emerged in the last decade from
cohort studies and can be applied to many ICU patients [14]. Recent studies confirm
that prolonged weaning is associated with a higher mortality, longer ICU stay, and
longer duration of MV [3]. This finding has led to the development of the SWU
because of the high cost of conventional ICU wards and because ICUs may lack the
necessary organization and specialized staff to manage prolonged weaning patients
[15]. These specific units also facilitate more efficient use of critical care resources
by increasing the availability of acute ICU beds. Thus, in their retrospective study,
Lone et al. [16] showed that an SWU could decrease by 810 % the number of ICU
day-beds occupied and permit a savings of nearly $500,000/year.
SWUs also offer expertise in prolonged weaning and specialized multidisciplinary teams composed of clinicians, physiotherapists, nurses, nutritionists, and
psychotherapists. Moreover, these units are characterized by a suitable environment, with less noise and less activity, especially at night, both of which are sleep
promoting. Thus, they can provide more specifically adapted care with reference to
the patients needs, together with cost savings related to the reduced nurse-to-patient
ratio, specific monitoring, and technical equipment.
44.2.4 Criteria for Discharge to an SWU

To our knowledge, no study has compared different ICU criteria to define those used
for discharging patients to an SWU. In relation to the purpose of such a unit, patients
must be classified in the prolonged weaning category, provided that a wellconducted weaning from MV has been initiated but resulted in weaning failure.
Consequently, a real weaning project should exist and be planned. Therefore, patients
with persistent coma, spinal cord injury with diaphragmatic impairment, or terminal
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G. Beduneau et al.
chronic respiratory failure do not appear to be good candidates for SWU admission.
At the stage of prolonged weaning from MV, eligible patients for an SWU should
have already been tracheostomized to facilitate their global and ventilatory management [15]. Recent studies have demonstrated that performing a tracheostomy does
not alter outcome in terms of mortality or duration of MV [17]. It is generally
acknowledged, however, that performing a tracheostomy in these ventilatordependent patients permits reduction of the work of breathing and sedation level and
more easily restores mobilization, nursing, swallowing, oral nutrition, and speech
[18, 19]. In addition, no other vital organ failure than ventilatory dependence should
persist, even though patients may present some consequences of multiple-organ failure (e.g., denutrition, renal failure). Thus, there are benefits from a transfer to an
SWU for such patients: the patients benefit by the different conduct of their specific
management, and the community benefits as it frees up some ICU beds.
In sum, we must carefully select patients for admission into an SWU, but, of
course, results and outcome will depend on the severity of the criteria used. To our
knowledge, criteria used for SWU admission have been poorly reported, excepted in
the study of Rose et al. [20]. Their admission criteria were as follows: MV for more
than 21 days, clinical stability, tracheostomy performed, appropriate nutritional
intake, ability to decide, and advance directives collected. Exclusion criteria were as
follows: fatal disease, dementia, and progressive neurological disease. We also developed a six-bed SWU in our French teaching hospital, linked to our medical ICU. Our
specific admission criteria are as follows: prolonged weaning defined as group III
(prolonged weaning) of the international consensus conference classification [1], tracheostomy being performed, clinical stability (specifically no catecholamine drugs),
no central neurological or cognitive disorders making weaning out-of-hand hopeless,
and good functional autonomy prior to ICU hospitalization [21].
44.2.5 Management and Results in an SWU

These units should be characterized by a standardized therapist-driven weaning
protocol, a specific program to restore autonomy and functional independence,
and an adapted area with resources for rehabilitation techniques while focusing
specifically on sleep quality [22]. Scheinhorn et al. [8, 15] report data on 1,419
consecutive ventilator-dependent patients enrolled in a 1-year period in 23 SWUs
in the United States. These two descriptive studies provide important information on the characteristics of these patients, their premorbid diagnoses, and the
procedures performed during SWU hospitalization. In these reports, the median
patient age was 72 years, median duration of MV in ICU prior to admission was
25 days, and median length of stay in an SWU was 40 days. The number of premorbid diagnoses averaged 2.6 per patient (hypertension in 47 %, chronic
obstructive pulmonary disease (COPD) in 42 %), and a medical illness led to
ventilator dependency in 61 % of patients. Overall, these patients require considerable medical interventions and treatments. In the above-mentioned study, the
44
357
median time to be weaned was 15 days, and 54 % had weaning success, 21 % had
persistence of ventilator dependence, and 25 % of patients died. One year after
discharge, 30 % of patients were still alive [8, 15]. Finally, these cohort studies
clearly illustrate the need for prolonged weaning of chronic critically ill patients
in terms of human and technical resources.
Although ventilatory management remains essential, no specific protocol has
been demonstrated to outperform other strategies in this difficult-to-wean patient
group [23]. Interestingly, much attention must be paid to the decannulation protocol. For instance, decannulation can greatly interfere with the patients work of
breathing [24] and it seems to us important to wait until the appropriate time before
removing the cannula. To our knowledge, only one study has reported and outlined
the need for a step-by-step clinical protocol for weaning these patients from the
tracheostomy [25].
Conclusion
Characteristics of patients with prolonged weaning from MV illustrate the concept of chronic critically ill patients. They need very specific care, with the main
objectives of MV weaning and ICU discharge but also rehabilitation and return
to functional autonomy for hospital discharge. The management of these patients,
dependent on MV and also on ICU resources, represents, therefore, a true challenge for the clinician. Specific units, such as an SWU, dedicated to weaning
from MV and global rehabilitation, must provide sufficient human resources and
technical skills to achieve these different objectives. Patients discharged to these
units must have initiated but failed the weaning process. Finally, there is still a
need for scientific research in this field, focusing particularly on criteria for SWU
admission, modalities of management and outcome, and populations that are
more susceptible to benefit.
The concept of chronic critically ill patients is emerging and growing

and requires multidisciplinary consideration for specific care.
Prolonged weaning from MV, frequently related to chronic critically ill
patients, requires a specific approach for the weaning process, often
through the use of a tracheostomy, especially to alternate mechanical and
spontaneous ventilation.
In transferring a patient to an SWU, the existence of real hope of discharge
for this patient must be considered, without any other life-threatening
organ failure than mechanical dependence.
The aim of an SWU is to provide specific care in an adapted environment
with a lower cost than in the ICU. The objectives in this unit are MV weaning, decannulation, and physical and mental rehabilitation.
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References
1. Boles J-M, Bion J, Connors A, Herridge M, Marsh B, Melot C, et al. Weaning from mechanical
ventilation. Eur Respir J. 2007;29(5):103356.
2. Funk G-C, Anders S, Breyer M-K, Burghuber OC, Edelmann G, Heindl W, et al. Incidence and
outcome of weaning from mechanical ventilation according to new categories. Eur Respir
J. 2010;35(1):8894.
3. Peuelas O, Frutos-Vivar F, Fernndez C, Anzueto A, Epstein SK, Apeztegua C, et al.
Characteristics and outcomes of ventilated patients according to time to liberation from
mechanical ventilation. Am J Respir Crit Care Med. 2011;184(4):4307.
4. Kahn JM. The evolving role of dedicated weaning facilities in critical care. Intensive Care
Med. 2010;36(1):810.
5. Rimachi R, Vincent JL, Brimioulle S. Survival and quality of life after prolonged intensive care
unit stay. Anaesth Intensive Care. 2007;35(1):627.
6. Mahesh B, Choong CK, Goldsmith K, Gerrard C, Nashef SAM, Vuylsteke A. Prolonged stay
in intensive care unit is a powerful predictor of adverse outcomes after cardiac operations. Ann
Thorac Surg. 2012;94(1):10916.
7. Zampieri FG, Ladeira JP, Park M, Haib D, Pastore CL, Santoro CM, et al. Admission factors
associated with prolonged (>14 days) intensive care unit stay. J Crit Care. 2014;29(1):605.
8. Scheinhorn DJ, Hassenpflug MS, Votto JJ, Chao DC, Epstein SK, Doig GS, et al. Ventilatordependent survivors of catastrophic illness transferred to 23 long-term care hospitals for weaning from prolonged mechanical ventilation. Chest. 2007;131(1):7684.
9. Polverino E, Nava S, Ferrer M, Ceriana P, Clini E, Spada E, et al. Patients characterization,
hospital course and clinical outcomes in five Italian respiratory intensive care units. Intensive
Care Med. 2010;36(1):13742.
10. MacIntyre NR, Epstein SK, Carson S, Scheinhorn D, Christopher K, Muldoon S, et al.
Management of patients requiring prolonged mechanical ventilation: report of a NAMDRC
consensus conference. Chest. 2005;128(6):393754.
11. White AC. Long-term mechanical ventilation: management strategies. Respir Care.
2012;57(6):88997; discussion 8989.
12. Arabi Y, Venkatesh S, Haddad S, Al Shimemeri A, Al Malik S. A prospective study of prolonged stay in the intensive care unit: predictors and impact on resource utilization. Int J Qual
Health Care. 2002;14(5):40310.
13. Scheinhorn DJ, Chao DC, Stearn-Hassenpflug M, Wallace WA. Outcomes in post-ICU
mechanical ventilation: a therapist-implemented weaning protocol. Chest. 2001;119(1):
23642.
14. Nelson JE, Cox CE, Hope AA, Carson SS. Chronic critical illness. Am J Respir Crit Care Med.
2010;182(4):44654.
15. Scheinhorn DJ, Hassenpflug MS, Votto JJ, Chao DC, Epstein SK, Doig GS, et al. Post-ICU
mechanical ventilation at 23 long-term care hospitals: a multicenter outcomes study. Chest.
2007;131(1):8593.
16. Lone NI, Walsh TS. Prolonged mechanical ventilation in critically ill patients: epidemiology,
outcomes and modelling the potential cost consequences of establishing a regional weaning
unit. Crit Care Lond Engl. 2011;15(2):R102.
17. Terragni PP, Antonelli M, Fumagalli R, Faggiano C, Berardino M, Pallavicini FB. Early vs late
tracheotomy for prevention of pneumonia in mechanically ventilated adult ICU patients: a
randomized controlled trial. JAMA. 2010;303(15):14839.
18. Diehl JL, El Atrous S, Touchard D, Lemaire F, Brochard L. Changes in the work of breathing
induced by tracheotomy in ventilator-dependent patients. Am J Respir Crit Care Med.
1999;159(2):3838.
19. Nieszkowska A, Combes A, Luyt C-E, Ksibi H, Trouillet J-L, Gibert C, et al. Impact of tracheotomy on sedative administration, sedation level, and comfort of mechanically ventilated
intensive care unit patients. Crit Care Med. 2005;33(11):252733.
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20. Rose L, Fraser IM. Patient characteristics and outcomes of a provincial prolonged-ventilation
weaning centre: a retrospective cohort study. Can Respir J. 2012;19(3):21620.
21. Beduneau G, Ardanuy C, Clabault K, Richard JCM. Prolonged weaning from mechanical ventilation: impact of a specialised weaning unit. Intensive Care Med. 2008;34 Suppl 1:S80.
22. Ambrosino N, Venturelli E, Vagheggini G, Clini E. Rehabilitation, weaning and physical therapy strategies in chronic critically ill patients. Eur Respir J. 2012;39(2):48792.
23. Vitacca M, Vianello A, Colombo D, Clini E, Porta R, Bianchi L, et al. Comparison of two
methods for weaning patients with chronic obstructive pulmonary disease requiring mechanical ventilation for more than 15 days. Am J Respir Crit Care Med. 2001;164(2):22530.
24. Chadda K, Louis B, Benassa L, Annane D, Gajdos P, Raphal JC, et al. Physiological effects
of decannulation in tracheostomized patients. Intensive Care Med. 2002;28(12):17617.
25. Ceriana P, Carlucci A, Navalesi P, Rampulla C, Delmastro M, Piaggi G, et al. Weaning from
tracheotomy in long-term mechanically ventilated patients: feasibility of a decisional flowchart and clinical outcome. Intensive Care Med. 2003;29(5):8458.
Discharge Planning of Neuromuscular

Patients with Noninvasive Mechanical
Ventilation After Difficult Weaning
from Invasive Mechanical Ventilation:
From ICU to Home Care
45
E. Barrot-Corts, L. Jara-Palomares, and C. Caballero-Eraso
45.1
Introduction
About 5 % of patients under mechanical ventilation longer than 7 days are difficult
to wean after 4 weeks and have been classified as chronic ventilator-dependent
patients (VDPs) [1]. The presence of a neuromuscular disease is one of the most
important reasons for this weaning failure.
After the resolution of an acute episode in a neuromuscular patient (NMP), it is
important to consider such questions as, How and when can noninvasive mechanical ventilation (NIV) be implemented? Will NIV avoid invasive mechanical ventilation forms such as tracheostomy? What is the most appropriate site for optimal
long-term care that will allow greatest independence, function, and quality of life?
When and how can the patient be transferred from the intensive care unit (ICU) to
home?
Today, it is recognized that NIV has an important impact on the care of
VDPs, particularly in those with neuromuscular disorders and thoracic skeletal
disorders. The purpose of this chapter is to provide principles and guidelines
for the selection and treatment of VDPs with neuromuscular diseases in nonICU sites.
Recommendations are provided regarding the continued care of VDPs at available sites, the criteria for discharge to a general ward from an ICU, and steps for
making decisions on the most appropriate site for an individual patient until it is
possible to consider their transfer to home. At this point, it is relevant to explore
planning for discharge, care, and rehabilitation of ventilator-assisted patients needed
after discharge and the necessary equipment and resources.
E. Barrot-Corts, PhD (*) L. Jara-Palomares, PhD C. Caballero-Eraso, MD

Pneumology Service, Universitary Hospital Virgen Roco, Seville, Spain
e-mail: emilia.barrot.sspa@juntadeandalucia.es
DOI 10.1007/978-3-319-04259-6_45
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45.2
E. Barrot-Corts et al.
Advances in medical care and the acute application of invasive mechanical ventilation have resulted in increased survival of critically ill patients, some of whom may
become dependent on long-term mechanical ventilation. In a study by Bach et al.
[2], most long-term ventilator-assisted patients (62 %) were in acute care hospitals,
22 % were in chronic care hospitals, and only 20 % were at home. Other studies [3]
have demonstrated that most long-term ventilator-assisted patients continue to be
located in acute care hospitals, consuming most of the available resources [4].
45.2.1 Objectives and Goals for VDPs

Determining objectives and goals for the management of VDPs not only contributes
to the best possible care but also enables decisions on sites and resources that will
best enhance the patients lives and make care more cost effective. Three objectives
guide the management of VDPs: (1) treat the patients acute illness, (2) wean the
patient from mechanical ventilation when possible, and (3) enhance the patients
quality of life.
A 1986 American College of Chest Physicians Consensus Conference included
the following goals for the management of VDPs: provide an environment that
enhances the individuals potential, improve physical and physiologic function,
reduce morbidity, extend life, and provide cost-effective care [5]. These goals may
be applied equally to each of the objectives for treatment. For example, improvement of physical and physiologic function is an appropriate goal for acutely ill
patients (to reverse the pathophysiologic aspects of the presenting disease), and also
for long-term VDPs with limited physical function (such as NMPs or patients with
spinal cord injury).
45.2.1.1 Criteria for Long-Term Mechanical Ventilation Beyond

the ICU
Mechanical ventilation is required when spontaneous efforts are unable to sustain
adequate alveolar ventilation. The most obvious group of patients to identify as
candidates for long-term ventilation are those with absent or severely impaired
spontaneous breathing efforts. These patients include those with central hypoventilation secondary to an inadequate central respiratory drive (e.g., central alveolar
hypoventilation) or severe respiratory muscle failure (e.g., neuromuscular diseases
or high spinal cord injury). This group of patients is unable to sustain spontaneous
breathing effort and is dependent on mechanical ventilation for life support.
Some may be successfully treated with NIV, but patients who require continuous
mechanical ventilation usually require more support personnel and respiratory
equipment (Table 45.1). Usually, these patients breathe spontaneously for several
hours, but when longer periods are required, deterioration of respiratory function
occurs, provoking a respiratory failure, and reinstitution of mechanical ventilation
is needed. NIV is preferred over invasive ventilation because of ease of
45
Discharge Planning of Neuromuscular Patients with NIV
363
Table 45.1 Indications for mechanical ventilation beyond the ICU

Indications for NIV
Patient has chronic stable or slowly progressive respiratory failure:
Significant daytime CO2 retention (>50 mmHg) with appropriately compensated pH or
Mild daytime or nocturnal CO2 retention (4550 mmHg) with symptoms attributable to
hypoventilation (morning headaches, restless sleep, nightmares, enuresis, daytime
hypersomnolence)
Significant nocturnal hypoventilation or oxygen desaturation
The following conditions have been met:
Patient has had optimal medical therapy for underlying respiratory disorders
Patient is able to protect airway and clear secretions adequately
Patients reversible contributing factors have been treated (obstructive sleep apnea,
hypothyroidism, congestive heart failure, severe electrolyte disturbance).
The diagnosis is appropriate and may include neuromuscular disorders and other pathologies
such as chest wall deformity, central hypoventilation syndrome or obesity hypoventilation,
obstructive sleep apnea, etc.
Indications for invasive ventilation
Patient meets indications for NIV and has the following:
Uncontrollable airway secretions despite use of noninvasive expiratory aids or
Impaired swallowing leading to chronic aspiration and repeated pneumonias
Patient has persistent symptomatic respiratory insufficiency and fails to tolerate or improve
with NIV
Patient needs round-the-clock (>20 h) ventilatory support because of severely weakened or
paralyzed respiratory muscles (e.g., quadriplegia due to high spinal cord lesions or end-stage
neuromuscular disease) and patient or provider prefers invasive ventilation
Modified from Make et al. [6]
administration, preservation of upper airway function, enhanced quality of life, and

lower cost.
A second mechanical ventilator and alternate power source should be available
for emergency use in the home and at all care sites for patients who cannot sustain
independent, spontaneous ventilation for >4 h [6, 7].
45.2.2 Criteria for Discharge to Non-ICU Facilities

New information suggests that the ICU environment is not needed for long-term
ventilator care and may even interfere with optimization of functional potential.
Patients requiring long-term ventilation may reach a state of relative clinical stability and not require ICU nursing or invasive monitoring. Furthermore, most, if not
all, long-term ventilator-assisted patients require significant rehabilitation, and a
multidisciplinary treatment plan focusing on rehabilitation is difficult to implement
in an ICU.
Decisions on the most appropriate non-ICU setting for long-term mechanical
ventilation must be individualized, but regardless of the site chosen, several
364
essential criteria for patient stability must be met to ensure that discharge to an
alternative site is safe, logistically possible, and cost saving. Clinical criteria for
stability of a VDP transferred to a more intensely supervised site (such as a specialized respiratory care unit in an acute care facility) are less rigid than for patients
discharged to an intermediate care facility (such as a rehabilitation hospital) or to a
long-term facility or home.
Patients should also meet the criteria for respiratory stability. They should have
a secure airway or be stabilized on a regimen of NIV. They should not have episodic severe dyspnea or desaturations, and oxygenation needs should be met easily
without requiring high supplementary oxygen concentrations or high levels of
positive end-expiratory pressure. Respiratory secretions should be manageable
outside of the ICU environment, and variations in airway resistance should be minimal. In addition, the patient should not be undergoing frequent ventilator setting
changes, other than for weaning, and should not require sophisticated ventilator
modes.
For VDPs who are being considered for transfer home, additional psychological
and social stability criteria should also be met to ensure that the patient presents a
successful psychological adaptation to home and will have sufficient human and
financial resources to sustain that success. It is also advantageous to have a family
that fully comprehends the situation, is capable and desirous of participating in the
patients care, and has sufficient support from an experienced multidisciplinary
team of health-care professionals.
All members of the health-care team should evaluate these factors as they relate
to the individual requiring assisted ventilation. Should the current level of care be
continued? Or is an alternate site now appropriate? The patient and the patients
family should be asked to provide input. The physician, as the individual responsible for ordering services and care, has a key role in this process and should determine the amount of medical care, monitoring, and intervention required by listing
the needs and goals of the VDP.
45.2.3 Discharge Planning

The discharge planning process should ensure a smooth transition and safety in
addition to an optimal outcome in the new site both when planning the patients
discharge from the hospital to home and when transferring the patient from an ICU
to non-ICU acute care. The patients goals and a list of patient needs, including
personnel requirements and specific equipment, should be clearly defined.
Guidelines for the discharge planning process have been written by the American
Medical Association [8], the American Association of Respiratory Care [9], and a
group of health-care professionals at a university medical center [10].
Successful transition of a VDP from the ICU to an intermediate or long-term
care site outside the traditional hospital setting, particularly to the home, requires
the collaborative efforts of a discharge team [11]. The team identifies all patient care
issues that must be resolved prior to discharge and develops a plan to facilitate the
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transfer. The team, which includes the patient and his or her family, should be comprised of key hospital and community-based personnel, many of whom will play an
ongoing role in the patients care once he or she is discharged. Discharge planning
team members should include the following:
Patient and family: The most essential members of the discharge team, mainly
transferring to home, are the patient and his or her family.
Physicians: Those responsible for the VDPs transition and care are the pulmonary or rehabilitation medicine specialist and the primary care physician, who
should have experience in the management of long-term mechanical ventilation.
Because a VDP at home imposes a significant burden on the family, the physician
should inform the patient and family of the burdens as well as the benefits of home
mechanical ventilation.
Discharge coordinator: One team member should be designated as the coordinator who will serve as a liaison among the multiple disciplines involved. This person
is usually a nurse, preferably specialized in pulmonary care, who will collaborate
with a respiratory care practitioner.
The patient and their family need to learn skills about care, and on this way
the role of doctors and nurses is crucial. The coordinator usually selects the specific types of home respiratory care equipment and ensures that the patient, family, and other caregivers have a detailed understanding of the equipment. When
patients are discharged to long-term care sites, including the home, the home
care company should be responsible for equipment maintenance and should also
provide personal trained in NIV management when necessary. A social worker
can also provide an evaluation of the alternate site as well as of community and
home resources and support available for long-term care. In addition, beds,
wheelchairs, and other general medical equipment must be provided or their
acquisition facilitated (see the checklist in Table 45.2 for equipment and supplies
required).
Occupational therapist: Occupational therapists should be consulted if the
patient must learn new skills to facilitate discharge or rehabilitation. This specialist
may participate in home assessment, especially if the patient is wheelchair bound,
evaluate the need for assistive devices that increase patient function and enhance
performance of daily activities, and train the patient in work simplification and
energy conservation.
Physical therapist: Many patients require consultation by a physical therapist.
Rehabilitation prior to discharge and as an intermediate step before home discharge
is frequently needed to increase the patients strength, endurance, and function. The
physical therapist also assists the patient in choosing the appropriate wheelchair,
especially when a motorized chair is needed.
The discharge plan should contain three components: assessment, education and
training, and a plan of care. The assessment should include three different aspects:
(1) patient stability (Table 45.1); (2) resources available where long-term care will
be performed; and (3) caregiver skills, education, and training. The discharge plan
tries to provide the patient and family the tools necessary for the VDP management
at home.
366
Table 45.2 Checklist of equipment and supplies that should be considered for ventilator-dependent
patients (<4 h with spontaneous ventilation and/or tracheostomy) planning to discharge to home
Mechanical ventilator
Primary
Secondary or backup system (portability)
Battery and connecting cable for emergency (power source)
Ventilator circuit
Exhalation valve
Noninvasive patient interfaces (face mask, nasal mask or nasal pillows, mouthpiece)
Humidifier and heater
Head gear, chin straps
Tracheostomy supplies
Tracheostomy tube adapter/connector, T-tube adapter
Tracheostomy tube (including next smaller size)
10-ml syringe, used only to inflate or deflate cuff
Heat and moisture exchanger
Disinfectant solution
Tracheostomy dressings or Velcro tracheostomy tube strap
Manual resuscitator
Oxygen supply system (stationary and portable), nasal cannulas
Suction machine (stationary and portable), suction catheters
Manual and mechanical secretion clearance aids such as cough in-exsufflator
Compressor for aerosolized medications
Monitors and alarms for ventilator and patient (when needed)
Others supplies:
Patient communication system
Wheelchair
Hospital bed and mattress
Commode, bedpan, urinal, or elevated toilet seat
Patient lifter
Safety bars in bathroom
Hand-held shower
Shower chair
Modified from ODonohue et al. [5]
The physician plays an essential role in the non-ICU acute care sites, including
home. He or she should be in contact with those responsible for the patients. Based
on the information the physician receives, the physician should be able to adjust the
patients treatment when an acute problem occurs, aiming to avoid unnecessary
hospital visits.
The identified caregivers should be able and willing to undergo the extensive
training required to perform all the patient care procedures and must be able to
dedicate the time required to learn these procedures while the patient is still in an
acute or intermediate care facility. Not all caregivers are willing to learn
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procedures they find particularly distasteful, such as suctioning, bladder catheter

care, or even bathing. Some caregivers are intimidated by the ventilator and other
medical equipment and may be reluctant to learn how to use it. Education and
training should cover all aspects of ventilator care, including the care and function
of the ventilator, use of accessory equipment, airway care, oxygen therapy, and
emergency measures.
Emergency measures need particular attention and the patient and family require
step-by-step training. At the hospital, NIV should be performed with the ventilator
that the patient will use at home. Placing the patient on the portable ventilator allows
the hospital staff sufficient time to fine-tune the ventilator settings and ensure that
the ventilator can meet the patients needs. During this period, caregivers should be
trained in ventilator management and they should know which alarms are the most
important and how to respond to the alarms.
Plan of care: A written, comprehensive management plan, covering both respiratory and other medical care, should be developed for the alternate site. The management plan should accomplish the following: identify primary and consulting
physicians; identify the local hospital emergency department; specify the appropriate medical center for care reevaluation; designate the roles of health-care providers; and designate the role of the patient and others in daily care. A checklist for the
respiratory care plan is provided in Table 45.2. This plan should outline how the
ventilator should be used (continuous, nocturnal, with free periods) and the ventilator settings. In patients using invasive ventilation, a sterile technique for suctioning
should be explained, along with how often tracheostomy care should be done and
how often the tracheostomy tube should be changed, and whether the tube change
will take place in the alternate site or at the hospital. It should also include any procedures necessary to assist the patient with communication, either with speaking
valve, cuff deflation, or tube plugging.
The plan for other medical care should describe nursing care procedures such as
gastrostomy tube maintenance and activities of daily living. It should specify ways
of addressing needs for physical, occupational, and speech therapy. In addition, the
comprehensive plan should contain guidelines for caregivers on medical conditions
that might require treatment, and on psychosocial developments that might necessitate evaluation, to help the caregivers to understand not only what should be
reported but also when to contact the physician, nurse, or respiratory care practitioner for assistance.
Home care provider companies are an essential resource and should be implicated on the basis of their ability to provide and maintain the necessary equipment
as well as their ability to assist in patient follow-up. A 24-h equipment maintenance
service and an adequate equipment inventory to meet equipment failures in longterm settings such as the home are mandatory. Close liaison with the discharge
planning team and with other care personnel must be established. Providers who
make home visits must be knowledgeable and experienced in patient education and
should review and reinforce patient education during each visit to the home or other
long-term setting. The use of respiratory care practitioners, who are skilled at both
patient and equipment assessment and education, is essential.
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Conclusion
A patient-specific discharge plan should be developed and implemented by a discharge planning team. Discharging a VDP from an ICU requires a coordinated
team of health-care providers, including the individual and his or her family, a
physician, nurse/discharge planner, social worker, respiratory therapist, and home
care company. It should contain three components: assessment, education and
training, and a plan of care.
1. Additional data are needed to document the costs of care for VDPs in
intermediate and long-term care facilities, including the home. Data are
also needed on survival, complications, physiologic consequences of care,
and quality of life.
2. Patients with chronic hypercapnia (PaCO2 >50 mmHg) in the daytime,
particularly when secondary to neuromuscular disorders, are candidates
for long-term ventilator assistance. Patients who develop symptomatic
nocturnal hypercapnia, even in the absence of daytime hypercapnia, are
also candidates for long-term ventilatory assistance.
3. Use of NIV in such patients may be associated with fewer adverse effects
than invasive ventilation. In general, patients who can maintain spontaneous ventilation for significant periods of time (>4 h/day) are easier to monitor and require less support personnel and respiratory equipment (such as
monitoring equipment and backup ventilators).
4. Manually assisted coughing is recommended for patients with weakened
expiratory muscles who have excessive secretions. Techniques such as
mechanical insufflation-exsufflation are usually reserved for use when
manually assisted coughing is inadequate.
5. Resources should be available to provide the respiratory and other needs of
VDPs outside the ICU. These resources include respiratory-care-trained
personnel, equipment, and equipment maintenance in the home and other
alternate sites.
References
1. Knaus WA. Prognosis with mechanical ventilation: the influence of disease, severity of disease, age, and chronic health status on survival from an acute illness. Am Rev Respir Dis.
1989;140(suppl):S813.
2. Bach JR, Intintola P, Alba AS, et al. The ventilator-assisted individual: cost analysis of institutionalization vs rehabilitation and in-home management. Chest. 1992;101:2630.
3. Milligan S. AARC and Gallup estimate numbers and costs of caring for chronic ventilator
patients. AARC Times. 1991;15:306.
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4. Wagner DP. Economics of prolonged mechanical ventilation. Am Rev Respir Dis.

1989;140(suppl):S148.
5. ODonohue WJ, Giovannoni RR, Goldberg AI, et al. Long-term mechanical ventilation: guidelines for management in the home and at alternate community sites: report of the Ad Hoc
Committee, Respiratory Care Section, American College of Chest Physicians. Chest.
1986;90(suppl):1S37.
6. Make BJ, Hill NS, Goldberg AI. Mechanical ventilation beyond the intensive care unit. Chest.
1998;113(5 suppl):289344.
7. Crescimanno G, Greco F, Marrone O. Monitoring noninvasive ventilation in neuromuscular
patients: feasibility of unattended home polysomnography and reliability of sleep diaries.
Sleep Med. 2014;15(3):33641.
8. American Medical Association Home Care Advisory Panel. Physicians and home care: guidelines for the medical management of the home care patient. Chicago: American Medical
Association; 1992.
9. American Association of Respiratory Care. Clinical practice guideline: discharge planning for
the respiratory care patients with respiratory disease. Respir Care. 1995;40:130812.
10. Baldwin-Meyers A, Geiger-Broncky M, Chacona A, et al. Standards of care for the ventilatorassisted individual: a comprehensive management plan from hospital to home. Loma Linda:
Loma Linda University Medical Center; 1992.
11. Gilmartin M. Transition from the intensive care unit to home: patient selection and discharge
planning. Respir Care. 1994;39:45680.
Part VI
Weaning Units. Organization
Organization of a Weaning Unit
46
Enrico M. Clini, Gloria Montanari, Laura Ciobanu,

and Michele Vitacca
Abbreviations
CINMA
CVFs
ICU
MV
NIV
PMV
SWUs
SBT
46.1
Critical illness neuromuscular abnormalities

Chronic ventilator facilities
Intensive care units
Prolonged mechanical ventilation
Specialized weaning units
Background: The Clinical Context
Weaning from mechanical ventilation (MV) is an essential and universal element in

the care of critically ill patients receiving MV for a prolonged time to restore unassisted breathing. There is much evidence that weaning tends to be delayed, exposing
the patient to unnecessary discomfort, increased risk of complications, and increased
cost of care. In the past 15 years, availability of beds in intensive care units (ICUs)
E.M. Clini (*) G. Montanari
Department of Medical and Surgical Sciences, AOU Policlinico,
University of Modena Reggio Emilia, Modena, Italy
e-mail: enrico.clini@unimore.it
L. Ciobanu
Clinical Hospital of Rehabilitation, University of Medicine and Pharmacy Gr T Popa,
Iasi, Romania
M. Vitacca
Fondazione Maugeri IRCCS, Rehabilitation Centre, Pneumology Unit,
Lumezzane (BS), Italy
DOI 10.1007/978-3-319-04259-6_46
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and new technologies, such as noninvasive mechanical ventilation, coupled with

improved levels of care, have highlighted a new population of patients labeled as
survivors of a catastrophic illness. Although this group of patients represents less
than 10 % of all ICU admissions, they account for a disproportionate burden on
health-care financial resources. In most studies, weaning failure occurs when a
spontaneous breathing trial (SBT) fails and reintubation is needed [1]. Failure of an
SBT is defined by (1) objective indices of failure, such as tachypnea, tachycardia,
hypertension, hypotension, hypoxemia or acidosis, and arrhythmia, and (2) subjective indices, such as agitation or distress, depressed mental status, diaphoresis, and
evidence of increasing effort. Several studies have proposed the use of noninvasive
ventilation (NIV) for extubated patients in different clinical situations, including
prophylactic intervention in patients with chronic obstructive pulmonary disease
who failed SBT [2], patients with repeated SBT failure [3], and postsurgical patients.
Weaning success is defined as extubation and the absence of ventilatory support
48 h following the extubation. Weaning failure is defined as one of the following:
(1) failed SBT, (2) reintubation and/or resumption of ventilator support following
successful extubation, or (3) death within 48 h following extubation. The increased
use of NIV raises the question of how to define weaning success or failure. Because
NIV may allow extubation while MV is continuing through a mask or other external
interfaces, an intermediate category called weaning in progress is recommended
for patients who are extubated but remain supported by NIV.
A classification of patients entering the weaning process has been proposed during the International Consensus Conference, according to the difficulty and length
of the weaning process [4]. The simple weaning group called group 1 includes
patients who successfully pass the initial SBT and are successfully extubated on the
first attempt. Group 2, difficult weaning, includes patients who require up to three
SBTs or as long as 7 days from the first SBT to achieve successful weaning. Group
3, prolonged weaning, includes patients who require more than three SBTs or 7
days of weaning after the first SBT. Other authors have defined prolonged mechanical ventilation (PMV) as more than 21 days of MV for at least 6 h per day [5].
Weaning from MV categorized as either difficult or prolonged is associated with a
longer hospital stay, higher in-hospital mortality [6], and increased and sustained
loss of functions in the individual patient [7]. A thorough and systematic search for
potentially reversible pathologies should be conducted in all patients who do not
fulfill simple weaning as previously defined. As suggested by Brochard [4], this
places the patient in group 2 or 3, and reversible etiologies for weaning failure may
be categorized as follows: respiratory load, cardiac load, neuromuscular competence, critical illness neuromuscular abnormalities (CINMA), neuropsychological
factors, and metabolic and endocrine disorders [8].
46.2
The Weaning Unit (History, Types, and Organization)
Once the precipitating cause of their acute episode of respiratory failure has been
solved, these chronically ill patients are often discharged from the ICU but still
require MV. Post-discharge care for PMV requires transfer to a long-term care or
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rehabilitation facilities [9]. These protected environments for the treatment of

patients requiring PMV are generically defined as chronic ventilator facilities
(CVFs). Acute-care units probably lack the necessary focus, personnel, and organizational structure to care for patients with prolonged weaning failure. In contrast,
specialized weaning units (SWUs) offer skilled teams (e.g., nurses, physiologists,
respiratory therapists, nutritionists, etc.) and an appropriate bridge to home environment for such patients and their families (e.g., privacy, daytime activity, longer
visiting hours, and undisturbed sleep). In Italy and most European countries, the
story of specific SWUs parallels the development of the so-called respiratory ICUs,
step-down environments where close cardiopulmonary monitoring and weaning
from MV have been so far provided to patients referred from the general ICUs. The
increasing use of NIV was one of the factors that promoted the opening of such
units since the 1990s in several European countries. Observational studies indicate
that 3460 % of patients in SWUs can be weaned successfully from ventilator support. These studies also suggest that successful weaning can occur up to 3 months
after admission to these units. More importantly, the long-term mortality rate is not
adversely affected by the transfer to a SWU [10].
These units can be of two types: (1) step-down units or respiratory ICUs within
acute-care hospitals and (2) regional weaning centers that serve several acute-care
hospitals within the region. The type of unit of preference will depend on the healthcare structure and financing system of each individual region or country. There is no
agreement about the classification of facilities for patients needing PMV because of
geographic differences, lack of consensus regarding the appropriate timing of transfer from the ICU, and different criteria for admission. The most logical classification of CVFs is one based on the location of the different facilities, specifically
whether the facility is inside or outside a so-called acute-care hospital.
46.2.1 Facilities Within Acute-Care Hospitals

In the late 1980s, CVFs started to emerge in acute-care hospitals as an attempt to
provide an alternative therapeutic environment for ICU patients requiring
PMV. These units were devoted mainly to patients requiring PMV. The organization
and staffing of CVFs inside acute-care hospitals appear to be homogeneous and
more similar to that of an ICU than to that of a CVF located outside an acute-care
hospital. Most of these CVFs provide noninvasive monitoring, the nurse-patient
ratio is usually 1:2 to 1:4, and a lead respiratory therapist is assigned permanently
and present in the unit. General medical care is provided around the clock by medical house staff under the direction of an attending physician in either critical care or
pulmonology. The nursing staff usually is specially trained through orientation and
in-service programs to address the needs of this particular patient population. There
is a multidisciplinary patient approach involving dieticians, psychologists, physical
therapists, speech therapists, social workers, and clergy as needed. Because these
CVFs are located within an acute-care hospital, all the diagnostic (e.g., computed
tomographic scans, nuclear magnetic resonance imaging) and therapeutic (e.g.,
major surgery) options are readily available.
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46.2.2 Facilities Outside Acute-Care Hospitals

These consists of several CVFs going under names such as regional weaning centers, prolonged respiratory-care units, long-term acute-care units, and respiratory
ICUs inside rehabilitation hospitals. These units were established either as freestanding hospitals, as in the case of most regional weaning centers, or within an
acute-care hospital but operating with total independence. As such, their governance is independent of the host hospital, and reimbursement is not based on a
diagnosis-related group system. Unlike CVFs located within acute-care hospitals,
CVFs located outside appear to have a rather heterogeneous organization and staffing. This heterogeneity occurs despite the facilities espousing a program based on
the common ideal of providing comprehensive medical, nursing, and respiratory
care to ventilator-dependent patients.
In Europe, CVFs outside acute-care hospitals are run mainly by full-time attending physicians who are specialists in respiratory and/or critical-care medicine.
These physicians are in charge of the admission and discharge of patients and the
weaning protocols. They are on duty 24 h a day. The doctor-patient ratio is at least
1:8. The nurse-patient ratio is usually similar to that of North American centers (the
nurse-patient ratio is about 1:4 during the day and 1:8 at night and on weekends).
Respiratory therapists in Europe are involved mainly in specific rehabilitation programs, for about 8 h a day (excluding Sundays and holidays), rather than in the
weaning process. Indeed, they provide physical and pulmonary rehabilitation,
which has been shown to help in freeing patients from MV and restoring them to an
acceptable level of autonomy. CVFs located outside acute-care hospitals are
intended to provide privacy, rest, and longer visiting hours for relatives and friends.
46.2.3 Nursing Homes

A small percentage of ventilator-dependent patients are discharged from an ICU
directly to a nursing home. Nursing homes, however, are more likely to receive such
patients once they have left a CVF. About 20 % of patients cared for in a ventilatordependent unit are transferred to a nursing home simply because they are not ready
to go home. Apparently, there is no standardization of admission criteria, staffing,
or organization of these units apart from the person needing 24-h of nursing care
for a cognitive or physical impairment. Nurses working in this specialized area
should be trained to perform specific procedures such as suctioning, tracheotomy
care, and monitoring of ventilator parameters [11].
46.3
Activities in the Weaning Unit
Despite a lack of strong scientific evidence, specific facilities for ventilatordependent patients do provide some clinical and financial advantages over ICU care
in terms of good prognostic outcome, tracheostomy tube removal, full rehabilitation
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Fig. 46.1 Bedside attended session of muscular active training involving the upper limbs
program with better physical function recovery, better control of emotional status,
low rate of readmission, and lower costs. Weaning from PMV is a complex and
time-consuming process that involves not only the selection of the best ventilation
method for a particular patient, but also comprehensive procedures such as protocoldriven weaning, including management of the ventilator and tapering sedation.
Severe disability following acute illness onset, psychiatric symptoms, frequent
sleep disturbances and disruptions, and swallowing problems are common problems in these patients with prolonged weaning. Therefore, several activities and
facilities in these units aim to restore maximal functions for each individual patient.
Given the nature of critical illness and the modalities used to manage it, prolonged bed rest, with well-known adverse physiological effects, is a common feature of the ICU. Physiotherapy has the important potential to restore the lost
peripheral muscle function. Moreover, it traditionally does not start until ICU discharge. Critically ill patients are often viewed as too sick to tolerate physical
activity in the early phase of their illness and, therefore, immobilization is frequently
prolonged. Physiotherapy is the process of restoring health or normal life by training and therapy after illness, but it would be preferable to do it proactively by optimizing and preserving physiological reserve in earlier stages of acute disease, as
well as trying to restore it in the later phases of chronic critical illness. Figure 46.1
shows bedside active muscular training involving the arms in the very early phase
of stay. Sometimes, recovery of muscular function can succeed earlier than weaning; patients are thus encouraged to move actively while still needing ventilatory
assistance (see an example in Fig. 46.2).
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E.M. Clini et al.
Fig. 46.2 An advanced recovery phase: patients flat walking using a rollator but still needing the
ventilatory assistance
Patients who survive the acute phase of critical illness experience has a wide
range of physical disabilities, including: neuromyopathies with muscle wasting,
weakness, and fatigability; joint deformities and contractures; and additional residual disease-related damage to specific organ systems. Patients who remain ventilatordependent in ICUs may suffer from additional burdens of continuing systemic
inflammation and catabolism combined with limited mobility and suboptimal nutrition, and this particularly affects the neuromuscular system. In addition to neuromuscular disorders, patients experience other physical and psychosocial effects,
like changes to skin and hair, endocrine impairment, sleep, mood and libido disorders, and chronic pain.
Open visiting hours for family members and comfort among patients and caregivers may be enhanced by return to a more physiologic circadian rhythm as
opposed to that found in a typical ICU. Sleep deprivation can have significant consequences and has been shown to impair cognitive function, increase protein catabolism, decrease immune function, and alter respiratory mechanics that might
eventually impact weaning from MV. A more natural environment like a CVF
may minimize the number and intensity of some critical factors involved in the
genesis of poor sleep, such as noise and light intensity.
Aspiration is common in patients with tracheostomies receiving prolonged
ventilation, and with advanced age the risk of aspiration increases. Swallowing
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problems are seldom assessed with the appropriate technique (i.e., video fluoroscopy) in the ICU, and the most important specific rehabilitative therapy is rarely
started. A less stressed environment than of ICUs, combining less sedative drugs
and more comprehensive teamwork by nurses, respiratory therapists, psychologists, and clergy, typical for a CVF, may improve the patient-clinician relationship. In this view, the expectations and outcomes may be better defined and
discussed.
Therefore, organization of a weaning unit requires interaction among different
health professionals with specific competence [11]. A medical doctor is generally referred as the most prominent managing figure of the team, often involved
in the difficult patient care decision algorithm and in communication with the
relatives. Overall, the optimal physician-to-patient ratio in these units is about
1:6. Nurses should assist each patient more than 135 min/day and physiotherapists for 60 min/day or 360 min per week. Other professional figures such as the
psychologist and the nutritionist should be involved for at least 10 and 3 h per
week, respectively.
46.4
Patient Characteristics in the Weaning Unit
Although advances in intensive care have enabled more patients to survive an acute
critical illness, they also have created a large and growing population of chronically
critically ill patients with prolonged dependence on MV and other intensive care
therapies. The American College of Critical Care Medicine states in its guidelines
for admission to and discharge from adult intermediate-care units that medically
stable ventilator patients for weaning and chronic care are the ideal candidates for
these environments. The hallmark of chronic critical illness is respiratory failure
requiring prolonged dependence on MV. Besides prolonged ventilator dependence,
evidences point out that chronic critical illness is a syndrome comprising additional
characteristic features. These include profound weakness attributed to myopathy,
neuropathy, and alterations of body composition including loss of lean body mass,
increased adiposity, and anasarca; distinctive neuroendocrine changes including
loss of pulsatile secretion of anterior pituitary hormones, contributing to low target
organ hormone levels and impaired anabolism; increased vulnerability to infection,
often with multiresistant microbial organisms; brain dysfunction manifesting as
coma or delirium that is protracted or permanent; skin lesions and breakdown; all
associated with nutritional deficiencies, edema, urinary incontinence, and prolonged
immobility. Patients report significant distress from symptoms like pain, thirst, dyspnea, depression, and anxiety, and from inability to communicate during endotracheal intubation [12]. Chronic critical illness is uniquely characterized by the
presence of these features as a clinical constellation in association with prolonged
dependence on MV. Between 5 and 10 % of patients who require MV for acute
conditions develop chronic critical illness. Between 30 and 53 % of chronically
critically ill patients are liberated from MV in the acute-care hospital. Better outcomes are reported by some SWUs, but they often select patients with higher
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potential for ventilator liberation and rehabilitation. Reimbursement incentives discourage some weaning facilities from admitting patients who have severe irreversible pulmonary processes, require hemodialysis, or have profound neurologic
injuries with invariably high mortality rate over 3 months [13]; however, there are
more outcomes for the best candidates with such facilities.
Overall, ideal patients are those with respiratory, cardiologic, and neuromuscular
diseases referred from general ICUs after failing weaning attempts (see above) and
prolonged stay. They are usually tracheostomized and need time to recover their
vital functions. Patients with multiorgan failure, extracorporeal supporting devices
other than ventilators (i.e., dialysis), or with life expectancy below 15 days are not
likely to be successfully managed in the SWUs.
46.5
Conclusion
Over the past 15 years, the availability of ICU beds, new technology, and improved
levels of care have produced a new population of patients called survivors of catastrophic illness. These patients often require prolonged weaning. The rate of achieving complete ventilator independence in specific and dedicated weaning units is
generally high. It has been demonstrated that these units are cost-saving alternatives
to an ICU for carefully selected patients and survivors have an acceptable long-term
quality of life. The different international medical systems need to adopt new organizational innovations and highlight the need for a diverse program of comparative
effectiveness research to determine the optimal organization of care for patients
recovering from critical illness, including the best way to maximize survival and
control costs for this high-risk patient group [14]. Chronic critical illness is a devastating condition: mortality exceeds that for most malignancies, and functional
dependence persists for most survivors. Most chronically critically ill patients are
older adults who have underlying comorbid conditions and develop sepsis and other
acute comorbidities with treatment for acute medical, surgical, neurologic, or cardiac critical illness. Beyond prolonged ventilator dependence, which is its hallmark,
increasing evidence indicates that chronic critical illness is a syndrome encompassing other characteristic clinical features and affecting multiple systems and organs.
Long-term acute-care hospitals play an increasingly important role in patients with
chronic critical illness.
With increased efforts to reduce health-care costs, patients will be shifted away
from ICUs toward other clinical settings, such as dedicated weaning facilities, to
care for more and increasingly complex patients. The main benefits of chronic ventilator facilities are the possibility of relieving congestion of ICU beds, maintaining
a high level of nursing assistance, responding to sudden changes in a patients clinical condition, allowing enough time for a multidisciplinary rehabilitation approach,
and acting as a bridge to home-care programs or other forms of continuous chronic
assistance.
Notwithstanding, few data exist to guide decision making about transfer or
discharge to these facilities [15], and more research is needed to assess the
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impact of weaning facilities on costs and outcomes. In particular, the following

questions should be assessed: whether weaning facilities best operate as units
within hospitals or as stand-alone hospitals; the optimum nurse, physician, and
ancillary staff of weaning facilities, and the true effects of weaning facilities
on critical care [16].
Specialized weaning units offer an appropriate bridge to home environment for patients under prolonged weaning and their families, with a
potential favorable cost/benefit ratio.
Comprehensive care for the chronically critically ill includes multiple components, with five key goals: ventilator liberation, physiotherapy, nutritional
support, cognitive and functional recovery, and attention to palliative needs.
Given the unique and complex challenges, a dedicated interdisciplinary
team of professionals may be the best team to provide this care.
The growing population of chronically critically ill patients with prolonged
dependence on MV and other intensive care therapies specifically requires
long-term acute units for care.
References
1. Esteban A, Frutos F, Tobin MJ, et al. A comparison of four methods of weaning patients from
mechanical ventilation. Spanish Lung Failure Collaborative Group. N Engl J Med.
1995;332:34550.
2. Vitacca M, Vianello A, Colombo D, et al. Comparison of two methods for weaning patients
with chronic obstructive pulmonary disease requiring mechanical ventilation for more than 15
days. Am J Respir Crit Care Med. 2001;164:22530.
3. Ferrer M, Esqinas A, Arancibia F, et al. Noninvasive ventilation during persistent weaning
failure. Am J Respir Crit Care Med. 2003;168:706.
4. Brochard L (2005) Pressure support is the preferred weaning method. As presented at the 5th
international consensus conference in intensive care medicine: weaning from mechanical ventilation. Hosted by ERS, ATS, ESICM, SCCMand SRLF, Budapest, 2829 Apr 2005.
5. Boles JM, Bion J, Connors A, et al. Weaning from mechanical ventilation Statement of the
Sixth International Consensus Conference on Intensive Care Medicine. Eur Respir J.
2007;29:103356.
6. Funk GC, Anders S, Breyer MK, et al. Incidence and outcome of weaning from mechanical
ventilation according to new categories. Eur Respir J. 2010;35(1):8894.
7. Burtin C, Clerckx B, Robbeets C, et al. Early exercise in critically ill patients enhances shortterm functional recovery. Crit Care Med. 2009;37:2499505.
8. Nava S, Vitacca M. Chronic ventilator facilities. In: JTobin M, editor. Principles and practice
of mechanical ventilation. 3rd ed. New York: McGraw-Hill; 2013. p. 77792.
ventilation. Chest. 1997;112(1):18692.
10. Seneff MG, Wagner D, Thompson D, et al. The impact of long-term acute-care facilities on the
outcome and cost of care for patients undergoing prolonged mechanical ventilation. Crit Care
Med. 2000;28:34250.
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E.M. Clini et al.
11. Vitacca M, Clini E, Nava S, et al. High complexity rehabilitation in prolonged weaning patient:
role of pneumologist. Rass Patol App Respir. 2013;28:17987.
12. Nelson JE, Cox CE, Hope AA, et al. Chronic critical illness. Am J Respir Care Med.
2010;182:44654.
13. Nelson JE, Meier DE, Litke A, et al. The symptom burden of chronic critical illness. Crit Care
Med. 2004;32:152734.
14. Kahn JM, Benson NM, Appleby D, et al. Long-term acute care hospital utilization after critical
illness. JAMA. 2010;303(22):22539.
15. Vitacca M, Nava S. Incomplete network for survivors of catastrophic illness after release from
ICUs. Respir Care. 2013;58(2):3845.
16. Kahn JM. The evolving role of dedicated weaning facilities in critical care. Intensive Care
Med. 2010;36:810.
Difficult and Prolonged Weaning:

The Italian Experience
47
Raffaele Scala
47.1
Introduction
In Italy, the implementation of pulmonologist centers working as step-down units

for the management of patients discharged from intensive care units (ICUs) as a
result of difficult or prolonged weaning from invasive mechanical ventilation (IMV)
largely coincides with the birth and growth of respiratory ICUs (RICUs) [17].
In the past 15 years, a crucial role has been played by the educational and
political activities of the Italian Hospital Pulmonologist Association (AIPO) that
has captured the interest of intensive care and rehabilitation pulmonologists in
respiratory critical medicine and has achieved at the institutional level the recognition of RICUs as specialized units for the management of respiratory system
failure. Among the main catalysts that stimulated the dissemination of Italian
RICUs, in addition to the popularity of noninvasive ventilation (NIV) for the
treatment of acute respiratory failure (ARF) and acute-on-chronic respiratory failure (ACRF), we should consider the increasing need for specialized areas devoted
to weaning [17]. According to the AIPO definition [1, 2], an RICU is a specialized setting where monitoring and mechanical ventilation, preferentially but not
exclusively performed in a noninvasive manner, could be provided to treat ARF/
ACRF, or where patients with prolonged or difficult weaning from IMV, or candidates for decannulation, may be admitted. Like the Task Force of the European
Respiratory Society [8], the AIPO document [2] identifies three different levels of
care for RICUs (intensive, intermediate, monitoring) depending on the amount of
structural and human resources available and on the complexity of the interventions provided.
R. Scala, MD, FCCP
Pulmonology and Respiratory Intensive Care Unit, AUSL 8, S. Donato Hospital, Via Pietro
Nenni, 20, 52100 Arezzo, Italy
e-mail: raffaele_scala@hotmail.com
DOI 10.1007/978-3-319-04259-6_47
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384
47.2
R. Scala
Mission
The mission of RICUs that function as weaning centers [9] is crucial in the context
of clinical governance of ARF/ACRF because they work as a strategic node for (1)
the quick discharge of critically ill patients from the ICU, where they failed repeated
attempts of disconnections from the ventilator, to these units dedicated to weaning
with an optimization of the limited health resources; (2) the achievement of a greater
rate of success in totally or partially liberating ventilator-dependents patients from
IMV through protocol-driven, multidisciplinary, intensive rehabilitative interventions; and (3) the delicate transitional process at home of chronically critical patients
(e.g., with chronic obstructive pulmonary disease (COPD), end-stage heart failure,
advanced neuromyopathy, pluri-comorbidities, postsurgical sequelae), thanks to the
activation of integrated pathways between hospital and territory.
47.3
Second AIPO Census of the RICU
The latest data depicting an Italian snapshot of pulmonologists activity on

difficult/prolonged weaning may be extrapolated from the last national survey
on the RICUs conducted by the AIPO at the end of 2007 [5, 6]. Compared with
the first census performed in 1997, the second survey showed that, over the past
10 years, there has been an increase not only in the number of RICUs but also
in their efficiency, as the admissions for monitoring have been reduced only in
favor of those for active interventions (i.e., mechanical ventilation, weaning and
decannulation). The weaning activity of the Italian RICU has more than doubled
in the past decade as the admissions for problems of weaning have increased
from 8 to 19 % [5, 6] (Fig. 46.1a). These data refer to patients who were transferred from ICUs after failing one or more attempts at disconnection from the
ventilator for at least 7 days; these patients belong to the categories of difficult and prolonged weaning, which are correlated with greater rate of mortality and higher health costs compared with those belonging to the simple
weaning category [10].
The 2007 AIPO survey has clearly shown that the different attitude of the Italian
RICUs in performing weaning activities depends essentially on two factors: (1) the
level of respiratory care available (intensive, intermediate, monitoring) and (2) the
type of location (acute care hospital , rehabilitative Institute). Concerning the first
aspect, weaning-correlated problems have been the cause of admission in 25 % of
cases in RICUs providing higher levels of assistance (intensive and intermediate)
versus 10 % of the admissions observed in the monitoring units (Fig. 46.1b). As
regards the second aspect, the survey has shown that the RICUs located in the acute
care hospitals (80 % of the total surveyed units) work largely as step-up units for
supporting NIV patients with ARF/ACRF transferred from emergency departments
and general wards, whereas they function less frequently as step-down units for
difficult-to wean patients coming from ICUs. Conversely, the RICUs set up within
rehabilitative centers (20 % of the total surveyed units) work primarily as step-down
units of intermediate level in favor of the ICUs belonging to the surrounding acute
46
385
Difficult and Prolonged Weaning: The Italian Experience
a
2007 (n.44)
1997 (n.26)
Decannulation
Weaning
IMV
NIV
Monitoring
0
10
20
30
40
50
60
%
60
RMU (n = 13)
RIICU (n = 24)
RICU (n = 7)
Percent of patients
50
40
30
20
10
0
Monitoring
NIV
Invasive
ventilation
Weaning Decannulation
Fig. 47.1 (a) Interventions performed in the Italian RICU according to the two national surveys
in 1997 and 2007. Differences for each intervention were statistically significant (p <0,05) between
1997 and 2007 (Modified from [14]). (b) Distribution of interventions in the surveyed RICUs in
2007 according to the level of care (modified from [5]). Differences between the three levels of
RICU care were statistically significant for all interventions (p <0.05) except weaning in RIICUs
vs RICUs. RMU respiratory monitoring unit, RIICU respiratory intermediate intensive care unit,
RICU respiratory intensive care unit
care hospitals. These RICUs act as weaning and rehabilitative centers for prolonged
invasively ventilated patients, most of them having a tracheostomy tube [5, 6]. In
accordance with these data is the 1-year experience of one expert RICU showing a
rehabilitative vocation that analyzed the interventions performed on 96 patients:
65 % of them came from ICUs and 42 % of them were admitted for prolonged
R. Scala
386
weaning [11]. Likewise, according to a retrospective study [12] including more than
3,000 patients in the period 19902005 in five Italian RICUs working as step-down
units, the management of prolonged weaning was the cause of the admission in
66 % of cases.
47.4
Models
In Italy, there are two main organizational patterns for the management of patients
with prolonged weaning within the pulmonologists rehabilitative critical area
(Fig. 46.2).
The first clinical pathway involves the transfer of ventilator-dependents patients
into the eight RICUs with rehabilitative attitude where long-term (>30 days)
multidisciplinary interventions may be applied. The role played by these units is
oriented first to recovering as much as possible of the patients functional autonomy, from ventilation to neuromotor activities, and, then, to activate home-care
programs for patients who remain partly or totally dependent on mechanical ventilation [1214]. The weakness of this model is due to the small number of these
rehabilitative RICUs scattered throughout the national territory and their location
in institutions lacking ICU facilities. The latter may have negative implications
for safety in case of multiorgan deterioration of the patient during the weaning
process.
The second clinical option is based on the transfer of patients with difficult/
prolonged weaning into the 36 RICUs located inside acute care hospitals, where
the strategy followed to achieve the maximum ventilatory autonomy could be
applied for a shorter period of time (<30 days) [5, 14]. In case of failure of further weaning attempts in these acute RICUs, patients could be transferred, if one
is available in their regional area, to a rehabilitative RICU. Otherwise, the length
of stay in the acute RICU is likely to be extended with the consequence of a
reduced turnover of beds available for the admission of new ARF/ACRF patients.
The integrated sequential activity of a RICU located in an acute care hospital
with that of a weaning center implemented in a close rehabilitative center was the
ICU
RICU/RIICU
DW
PW
Hospitals for
acute
Home
nursing-home
RIICU
PW
Rehabilitative
centers
Fig. 47.2 Different clinical models for the care of patients with weaning problems in Italy. ICU
intensive care unit, RIICU respiratory intermediate intensive care unit, RICU respiratory intensive
care unit, DW difficult weaning, PW prolonged weaning
46
387
subject of a pilot experience in Tuscany. In a sample of 49 tracheostomized ventilator-dependent patients who were transferred from the ICU to the acute RICU
of the same hospital, the passage from the second to the third step of care
improved the success rate of weaning from 67.3 to 79.6 % with a positive economic impact [13].
The number of RICUs surveyed nationwide being, unfortunately, still insufficient, a third clinical option involves a prolonged stay of yet unweaned patients in
the ICU with negative consequences in terms of efficiency of the resource management system.
47.5
Resources
The importance of allocating enough human resources in a weaning center is

highlighted by the finding of a very high nursing workload required to manage
patients with weaning problems during the first 2 days of admission into an Italian
rehabilitative RICU [15]. Unfortunately, the snapshot of the Italian RICUs has
clearly pointed out that, in the last decade, there has been a contraction in the
amount of human resources, in terms of doctor- and nurse-to-patient ratio, albeit
without a significant variation in the instrumental resources for monitoring and
mechanical ventilation [5, 6] (Fig. 46.3). Moreover, despite the important role of
respiratory physiotherapy in critically ill patients, surprisingly, the physiotherapist-to-patient ratio in the RICUs surveyed in 2007 was less than 1:11 for all levels of care units, a value that is lower than the ratio of 1:6 recommended by the
AIPO document [2]. Similar results emerged from a retrospective multicenter
study conducted in five rehabilitative RICUs [12]. According to this analysis, the
reduced doctor-to-patient ratio observed from 1990 to 2005 was associated with a
prolonged length of stay, a lower rate of weaning success, and fewer patients dischargeable to home.
Ratio between MD/N and patients

average
11.6
1997
2007
12
10
8
6
*
4.5
*
3.2
4.4
4
2
0
Doctors(MD)
Nurse(N)
Fig. 47.3 Changes in the average ratio between medical doctors (MD) and nurses (N) to patients
in RICUs according to the two national surveys in 1997 and 2007 (Modified from [6]) (* p <0.005
1997 vs 2007)
388
47.6
R. Scala
Diseases
The AIPO survey highlighted that the pattern of diseases treated in the Italian
RICUs changed from 1997 to 2007, with a contraction of the admissions for acute
exacerbation of COPD, largely treated with NIV, in favor of an increase in patients
with ventilatory decompensation in neuromuscular diseases and severe hypoxemia
de novo, who are more likely to require IMV and tracheostomy [5, 6]. Similarly, the
experience of some rehabilitative RICUs showed an increase in admissions for neuromuscular diseases, mainly due to problems of weaning, and a significant increase
in the impact of comorbidity [12]. Another type of patient referred more often to
Italian RICUs for difficult/prolonged weaning is one with postoperative ARF, often
complicating cardiac surgery, which represents a quarter of the total number of
admissions of a typical step-down unit [11].
47.7
Training
Training and expertise of the team working in an RICU are the crucial ingredients for achieving the success of the treatments, with the inclusion of weaning
from IMV. A recent survey of the respiratory intensive care unit study group of
AIPO [16] showed that the professional education pathway of the pulmonologist
in terms of RICU procedures is disappointing during the postgraduate course.
According to the data from this survey, the training for most of the procedures
required in the RICU (NIV, intubation, bronchoscopy, chest drainage, etc.) coincides with the employment of the pulmonologist in the hospital. These are the
same procedures pulmonologist use to deal with difficult/prolonged weaning.
The same survey [16] showed that about 20 % of the nurse staff working in the
RICUs had never received any training course and more than 20 % of them had
never attended a course of retraining. Other worrying concerns are the limited
use (in less than 20 % of cases) of weaning protocols in more than 40 % of the
sample interviewed [16].
Conclusions
The Italian snapshot of the current role of the pulmonologist in the clinical care
of patients with prolonged/difficult weaning brings forth the following points:
1. The the growth of RICUs has stimulated the interest of Italian pulmonologists
in critical respiratory medicine and, hence, weaning strategies.
2. There is insufficient training of medical and nursing staff in RICU procedures
resulting from a still-inadequate university educational program.
3. The heterogeneous mission of the Italian RICUs results from the prevalent
rehabilitative or acute vocations, location, human resources, organizational and structural models, and integration with the territory.
4. Regional networks need to be set up according to the logic of hubs and spokes
that are able to create sequential links between the various existing structures
46
389
to optimize the limited health-care resources and direct them toward the
common goal of giving the best response in terms of expertise and rapid solutions to patients with weaning problems.
References
1. Corrado A, Ambrosino N, Rossi A, et al. Gruppo di Studio AIPO Riabilitazione e Terapia
Intensiva Respiratoria. Unit di Terapia Intensiva Respiratoria. Rass Patol App Respir.
1994;9:11523.
2. Corrado A, Ambrosino N, Cavalli A, et al. Unit di Terapia Intensiva Respiratoria: update.
Rass Patol App Respir. 2004;19:1834.
3. Confalonieri M, Mollica C, Nava S, et al. Censimento delle Unit di Terapia Intensiva
Respiratoria in Italia. Rass Patol App Respir. 1998;13:18692.
4. Confalonieri M, Gorini M, Mollica C, et al. Scientific Group on Respiratory Intensive Care of
the Italian Association of Hospital Pneumonologists (AIPO). Respiratory intensive care units
in Italy: a national census and prospective cohort study. Thorax. 2001;56:3738.
5. Scala R, Corrado A, Confalonieri M, et al. Gruppo di Studio AIPO Terapia Intensiva
Respiratoria. Increased number and expertise of Italian Respiratory High-Dependency Care
Units: the second national survey. Respir Care. 2011;56:11007.
6. Scala R, Confalonieri M, Corrado A, et al. Il secondo censimento AIPO delle UTIR in Italia
tra certezze scientifiche e criticit organizzative. Rass Pat App Respir. 2011;26:2429.
7. Marchese S, Corrado A, Scala R, et al. Tracheostomy in patients with long-term mechanical
ventilation. Respir Med. 2010;104:74953.
8. Corrado A, Roussos C, Ambrosino N, et al. European Respiratory Society Task Force on epidemiology of respiratory intermediate care in Europe. Respiratory intermediate care units: a
European survey. Eur Respir J. 2002;20:134350.
9. MacIntyre NR, Epstein SK, Carson S, et al. National Association for Medical Direction of
Respiratory Care. Management of patients requiring prolonged mechanical ventilation: report
of a NAMDRC consensus conference. Chest. 2005;128(6):393754.
2007;29(5):103356.
11. Ceriana P, Delmastro M, Rampulla C, et al. Demographics and clinical outcomes of patients
admitted to a respiratory intensive care unit located in a rehabilitation center. Respir Care.
2003;48(7):6706.
12. Polverino E, Nava S, Ferrer M, et al. Patients characterization, hospital course and clinical
outcomes in five Italian respiratory intensive care units. Intensive Care Med.
2010;36(1):13742.
13. Carpen N, Vagheggini G, Panait E, et al. A proposal of a new model for long-term weaning:
respiratory intensive care unit and weaning center. Respir Med. 2010;104(10):150511.
14. Scala R. Respiratory High-Dependency Care Units for the burden of acute respiratory failure.
Eur J Intern Med. 2012;23(4):3028.
15. Vitacca M, Clini E, Porta R, et al. Preliminary results on nursing workload in a dedicated
weaning center. Intensive Care Med. 2000;26(6):7969.
16. Facciolongo N, Scala R, Garuti G, et al. Gds AIPO di Terapia Intensiva Respiratoria. Survey
nazionale su formazione e pratica clinica dello Pneumologo in Terapia Intensiva Respiratoria.
Rass Patol App Respir. 2010;25:3643.
Part VII
Non Invasive Mechanical Ventilatio
in Neonatology and Pediatric
Noninvasive Ventilation Interfaces

and Equipment in Neonatology
48
Daniele De Luca, Anne Claire Servel, and Alan de Klerk
48.1
Introduction
Noninvasive respiratory support of the neonate, in the broadest sense, may include,
from least invasive up, ambient oxygen (such as via an oxyhood), low-flow nasal cannula, high-flow nasal cannula (delivered as heated, humidified, high-flow nasal cannula), continuous positive airway pressure (CPAP), phasic noninvasive ventilation,
and, more recently, nasal high-frequency ventilation (nHFV). The focus of this chapter is on positive-pressure noninvasive ventilation (NIV) in neonates. Therefore, this
discussion focuses on drivers of CPAP, phasic NIV, and nHFV, and of the impact of
those drivers and modalities on the efficacy of the delivered noninvasive support.
48.2
NIV Drivers and Equipment
48.2.1 Continuous Positive Airway Pressure

CPAP can be generated by either constant-flow or variable-flow devices. The most
common constant-flow (also referred to as continuous-flow) methods of CPAP delivery
are generated by bubble CPAP or by conventional ventilators. In the case of bubble
CPAP, heated, humidified, blended gas flows are delivered to the infant, typically by
nasal prongs or a mask, with the distal end of the expiratory tubing submerged in sterile
D. De Luca (*) A.C. Servel

Division of Pediatrics and Neonatal Critical Care, South Paris University Hospitals,
Medical Center A. Bclre APHP, Paris, France
A. de Klerk, MBChB, MHCM
Department of Pediatrics, Division of Neonatology, Nemours Childrens Hospital,
13535 Nemours Parkway, Orlando, FL 32827, USA
e-mail: adeklerk@nemours.org
DOI 10.1007/978-3-319-04259-6_48
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D. De Luca et al.
water (or in some centers, 0.25 % acetic acid) to the depth required to generate the
desired airway pressure (e.g., 6 cm below the surface to generate 6 cmH2O pressure).
Most, if not all, modern conventional neonatal ventilators are able to provide CPAP via
a continuous gas flow source directed against a controlled resistance in the expiratory
limb of the circuit. Although some conventional ventilators are also able to provide
variable-flow CPAP, modulating the expiratory resistance valve and the circuit flow to
maintain the pressure, this technology is different from what is generally considered
true variable-flow CPAP, as described below. In addition to bubble and ventilator CPAP,
the Benveniste gas-jet valve (Dameca, Copenhagen, Denmark) has been used (predominantly in Scandinavia) as a constant-flow CPAP device that works via the Venturi
principle using two coaxially positioned tubes connected by a ring.
Variable-flow CPAP became increasingly popular in the 1990s and beyond.
A number of devices and name changes have occurred over the past two decades,
with the Infant Flow CPAP/SiPAP system (CareFusion, Yorba Linda, CA, USA)
being the dominant current device. Applying several fluidic principles of operation
(including the Bernoulli, Coanda, and fluidic flip effects), gas delivered via dual
injector jets at high velocity generates CPAP at the airway by the gas flow into the
device and the leak around the nasal prongs.
Bubble CPAP produces measurable pressure oscillations around the baseline
CPAP level. In preterm lambs, bubble CPAP may be associated with a higher pH,
better oxygenation and ventilation, and less ventilation inhomogeneity, suggesting
that the stochastic recruitment effect system may result in the need for a lower mean
airway pressure to achieve the same level of volume recruitment, with potential
reduced risk of adverse effects of higher CPAP pressures [1]. However, studies in
human neonates are conflicting as to possible beneficial effects on gas exchange
[2, 3]. Comparing the various CPAP devices in terms of efficacy, studies have shown
improved lung compliance and decreased inspiratory work of breathing (WOBI) and
its component resistive work of breathing (RWOB) with variable-flow versus constant-flow CPAP via a ventilator [4]. Variable flow CPAP was also shown to reduce
RWOB (but not WOBI) and respiratory asynchrony when compared with bubble
CPAP [5]. Despite these observed differences, studies to date comparing the different
devices have not reported consistent improvements in clinically important outcomes.
Stefanescu et al. [6] showed fewer days on supplemental oxygen and shorter hospital
stay post-extubation using either Infant Flow CPAP or ventilator CPAP, but no differences in extubation failure. Comparing similar devices, Mazzella [7] demonstrated a
lower oxygen requirement and decreased respiratory rate on Infant Flow CPAP, but
no differences in successful weaning, need for mechanical ventilation, or duration of
treatment. In a study comparing variable-flow and bubble CPAP in preterm infants,
extubation failure was lower and the duration of support was shorter in infants ventilated less than 14 days when supported with bubble CPAP following extubation [8].
In the face of incomplete and often conflicting evidence, it seems prudent to use
bubble or variable-flow CPAP (rather than ventilator CPAP) for their potential benefits on pulmonary mechanical parameters and some clinical outcomes. When
deciding between these two options, the stochastic recruitment benefits of bubble
CPAP may offer advantage in acute atelectasis-prone patients with respiratory
48 Noninvasive Ventilation Interfaces and Equipment in Neonatology
395
distress syndrome. In contrast, the lower RWOB associated with variable-flow

CPAP may benefit infants with chronic respiratory disease, impaired respiratory
muscle contractility, and susceptibility to fatigue [9]. However, selection of an optimal patient interface and attention to detail in CPAP delivery (such as optimal prong
size, minimizing leaks around the prongs and via the mouth, and appropriate airway
care and positioning) may be at least as important as the CPAP device chosen. In all
cases, adequately heated and humidified gas should be delivered at appropriate
flows to avoid airway mucosal injury and condensation.
48.2.2 Phasic NIV

Phasic NIV consists of continuous positive pressure augmented with additional
breaths delivered by periods of increased airway pressure, potentially facilitating
ventilation and oxygenation. These breaths may be regular and nonsynchronized
(nasal intermittent positive pressure ventilation NIPPV) or synchronized with the
infants respiratory efforts (synchronized nasal intermittent positive pressure ventilation SNIPPV). NIPPV/SNIPPV is typically delivered by conventional mechanical ventilators, in some cases with adaptations for these specific modalities, although
the ventilator used in studies of SNIPPV is no longer commercially available.
SNIPPV has been shown to reduce respiratory asynchrony, improve tidal and minute volumes, decrease respiratory rate, and augment respiratory drive when compared with CPAP [10]. No strong evidence exists for benefits of SNIPPV over
NIPPV. Something of a hybrid form of phasic ventilation is that of bi-level CPAP
(commonly using the Infant Flow SiPAP system), in which intermittent modest
increases in airway pressure are superimposed on a baseline CPAP. Evidence is
lacking to support either safety or efficacy of bi-level CPAP versus NIPPV/SNIPPV.
When compared with CPAP in neonates, NIPPV has been shown to further
reduce the frequency of apnea [11], the need for intubation when used as primary
respiratory support [12], and extubation failure (need for reintubation after extubation) [13]. However, NIPPV has not been shown to be superior to CPAP in preventing bronchopulmonary dysplasia (BPD) [14] or preventing death or BPD. [15]
These data suggest that a significant subpopulation of neonates may enjoy shortterm benefits from NIPPV as opposed to CPAP when avoiding or weaning from
invasive ventilatory support. Because many infants can be successfully managed on
CPAP alone for apnea, primary respiratory support, and following extubation, the
difficulty is identifying those infants who may require the additional benefits of
NIPPV and instituting this support modality in a timely manner. Evidence-based
guidelines to aid in this important task are lacking.
48.2.3 Nasal HFV

Increasing interest has been paid in recent years to the potential role of nHFV, in
particular noninvasive high-frequency oscillatory ventilation and nasal
396
D. De Luca et al.
high-frequency percussive ventilation via nasal prongs. A limited number of laboratory and small clinical trials have demonstrated the feasibility of providing nHFV
and addressed some of the technical aspects of this modality [16, 17], as well as
suggested that nHFV may be associated with superior CO2 elimination [1820],
shorter duration of supplemental oxygen support and respiratory distress [21], and
sustained extubation success [22, 23]. However, additional large trials of safety and
efficacy are needed before nHFV can be recommended for routine use in neonates.
48.3
Interfaces Evolution
In the study of Roberts et al., the use of CPAP without mechanical ventilation for
neonates increased from 2001 to 2008, with a particularly notable rise among infants
of >32 weeks of gestation and at non-tertiary hospitals following the publication of
a randomized trial showing CPAP decreased the need for neonatal transfer [24, 25].
CPAP has been applied to preterm infants using an array of devices. Its first
application to the preterm neonate with respiratory distress was via an endotracheal
tube or by enclosure of the head in a plastic pressure chamber. Subsequent CPAP
devices included a pressurized plastic bag fitted over the infants head, face chambers, and face masks. The use of tight-fitting facial masks and devices requiring a
neck seal declined as a consequence of serious complications associated with their
application, including an increased incidence of cerebellar hemorrhage and posthemorrhagic hydrocephalus [26].
Nasal devices remained popular, as they facilitated better access to the infants:
nasal masks, nasal cannulae, and single and binasal tubes/prongs of varying lengths
[26].
The initial mode of delivery through an endotracheal tube or head chamber was
superseded by the use of nasal prongs which could deliver CPAP in a simpler and
less invasive manner.
Randomized trials have shown a reduced rate of extubation failure with the use
of double nasal prong devices compared with single nasal prongs [13]. Double nasal
prongs with sealing both nostrils certainly result in better transmission of pressure
to the upper airways and the lungs.
For preterm infants primarily treated with NCPAP soon after birth, Mazzella
found a significantly lower oxygen requirement and respiratory rate in those randomized to short binasal prongs when compared with CPAP delivered via the nasopharyngeal prong [7]. It suggests that short binasal prongs are more effective than
nasopharyngeal CPAP in the treatment of early respiratory distress syndrome.
There is now a broad range of prongs used to deliver NCPAP.
One important characteristic of a NCPAP device is its resistance to airflow. This
determines the fall in pressure from that measured in the delivery circuit to that
transmitted to the respiratory tract. The study of De Paoli et al. [27] has measured
the pressure drop across a variety of NCPAP devices used in current neonatal practice. Devices with short double prongs had the lowest resistance to flow. In the
Cochrane Review of De Paoli in 2008, although the Infant Flow Driver appears
397
more effective than Medicorp prongs (in one study), the most effective short binasal
prong device remains to be determined. Indeed, the Infant Flow interface is engineered to allow sufficient flow to the infant on inspiration while minimizing expiratory resistance and then reduced work of breathing when compared with conventional
devices [26].
Another way to deliver NCPAP is nasal mask. With the first masks developed in
the 1970s, it was difficult to obtain an adequate seal and there was a tendency to
cause nasal airway obstruction [26]. With the new generation of nasal masks, this
kind of problems is totally minimized.
In a cohort of 120 children <31 weeks of gestation, NCPAP was more effective
to prevent intubation and ventilation within 72 h of starting therapy when given via
nasal masks compared with nasal prongs [28]. Nasal trauma occurred in a small
proportion of infants, with equal frequency with each interface (prongs/mask) and
after several weeks of therapy. Trauma related to nasal prongs tends to be maximum
around the medial aspect of the nasal septum and the columella, whereas trauma
related to nasal masks is more often seen at the junction of the nasal septum and
philtrum and at the glabella. As masks and prongs cause nasal trauma in different
distribution, the interface used is alternated in many units. Kieran et al. recommend
to start CPAP on nasal mask and to alternate the interface only after 72 h.
Short binasal prongs are the most widespread, although well-known disadvantages are nasal trauma and unstable pressure delivered to the airway because of
mouth opening. Insufficiently applied pressure and the babys open mouth result in
lowering of the pharyngeal pressure and may lead to failure of nCPAP.
Good tolerability has been demonstrated with hood CPAP in adults and more
recently in newborns. The potential advantage of this system is the absence of air
leakage caused by the babys open mouth, producing more stable pressure in the
airways. The study of Colnaghi in 2008 compared set CPAP values and pharyngeal pressure readings in premature infants with mild respiratory distress syndrome treated with either hood CPAP or the conventional nCPAP system [29].
This is a small study (20 patients) but the preliminary results show more effective
pressure transmission during hood CPAP compared with nCPAP, because of the
absence of the effect of the babys open mouth. The hood CPAP system may represent a potential improvement, as it allows good transmission of the applied pressure without the possible dislodgement of nasal prongs thereby avoiding nasal
trauma. The risk of infection and obstructive apnea due to excessive production of
nasal secretion is also potentially reduced. This suggests high tolerability of the
hood CPAP system.
Zaramella et al. [30] assessed cerebral blood flow and relative changes in cerebral blood volume in infants treated with hood CPAP and nCPAP and found no
differences in relative blood volume, although cerebral blood flow was lower during
hood CPAP. No difference in the occurrence of brain lesions was observed, but further larger randomized trials are needed to investigate potential limitations and
unknown risks. Another problem suggested by the study of Trevisanuto et al. [31] is
noise intensities generated by the neonatal helmet CPAP. The neonatal helmet CPAP
is noisier than a conventional nCPAP system. In the helmet, the noise intensity
398
D. De Luca et al.
depends on the gas flow rate and the presence of a humidifier and a filter in the
system.
Nasal cannulae are most often used in neonates to deliver supplemental oxygen
at low flows with no intention of generating significant airway pressure. Despite
their relative small caliber, nasal cannulae with an outer diameter of 3 mm and flows
up to 2 L/min were reported to increase intra-esophageal pressure and reduce thoracoabdominal motion asynchrony [32]. But optimal flows setting, appropriate cannulae size, and the effect on important outcomes with this nasal interface require
further research.
Bubble or variable-flow continuous positive airway pressure (CPAP)

devices have potential benefits over continuous-flow devices on pulmonary
mechanical parameters.
Selection of an optimal patient interface and attention to detail in CPAP
delivery may be at least as important as the CPAP device chosen.
The optimal interface may not be the same for each neonate and for each
moment during their disease. Each interface has different mechanical
properties that must be taken into account for the choice. Alternating interfaces may be useful for long term ventilated neonates.
A significant subpopulation of neonates may enjoy short-term benefits
from nasal intermittent positive pressure ventilation (NIPPV) as opposed
to CPAP when avoiding or weaning from invasive ventilatory support or to
treat apnea of prematurity.
Limited evidence supports the feasibility of nasal high-frequency ventilation (nHFV) in neonates, and that it may result in some improved clinical
outcomes in select patients.
References
1. Lee KS, Dunn MS, Fenwick M, et al. A comparison of underwater bubble continuous positive
airway pressure with ventilator-derived continuous positive airway pressure in premature neonates ready for extubation. Biol Neonate. 1998;73:6975.
2. Pillow JJ, Hillman N, Moss TJ, et al. Bubble continuous positive airway pressure enhances
lung volume and gas exchange in preterm lambs. Am J Respir Crit Care Med.
2007;176:639.
3. Morley CJ, Lau R, De Paoli A, et al. Does underwater bubbling improve gas exchange of
babies on nasal continuous positive airway pressure: a randomized crossover trial. Pediatr Res.
2003;53:360A.
4. Pandit PB, Courtney SE, Pyon KH, et al. Work of breathing during constant- and variable-flow
nasal continuous positive airway pressure in preterm neonates. Pediatrics.
2001;108(3):6825.
5. Liptsen E, Aghai ZH, Pyon KH, et al. Work of breathing during nasal continuous positive
airway pressure in preterm infants: a comparison of bubble vs. variable-flow devices. J
Perinatol. 2005;25(7):4538.
399
6. Stefanescu BM, Murphy WP, Hansell BJ, et al. A randomized, controlled trial comparing two
different continuous positive airway pressure systems for the successful extubation of
extremely low birth weight infants. Pediatrics. 2003;112(5):10318.
7. Mazzella M, Bellini C, Calevo MG, et al. A randomised control study comparing the Infant
Flow Driver with nasal continuous positive airway pressure in preterm infants. Arch Dis Child
Fetal Neonatal Ed. 2001;85(2):8690.
8. Gupta S, Sinha SK, Tin W, et al. A randomized controlled trial of post-extubation bubble continuous positive airway pressure versus Infant Flow Driver continuous positive airway pressure
in preterm infants with respiratory distress syndrome. J Pediatr. 2009;154(5):64550.
9. Pillow J. Which continuous positive airway pressure system is best for the preterm infant with
respiratory distress syndrome? Clin Perinatol. 2012;39(3):48396.
10. DeMauro SB, Millar D, Kirpalani H. Noninvasive respiratory support for neonates. Curr Opin
Pediatr. 2014;26(2):15762.
11. Lemyre B, Davis PG, de Paoli AG. Nasal intermittent positive pressure ventilation (NIPPV)
versus nasal continuous positive airway pressure (NCPAP) for apnea of prematurity. Cochrane
12. Meneses J, Bhandari V, Alves JG. Nasal intermittent positive-pressure ventilation vs. nasal
continuous positive airway pressure for preterm infants with respiratory distress syndrome: a
systematic review and meta-analysis. Arch Pediatr Adolesc Med. 2012;166:3726.
13. Davis PG, Lemyre B, De Paoli AG. Nasal intermittent positive pressure ventilation (NIPPV)
versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation. Cochrane Database of Syst Rev. 2001;(3):CD003212.
14. Kirpalani H, Millar D, Lemyre B, et al. A trial comparing noninvasive ventilation strategies in
preterm infants. N Engl J Med. 2013;369:61120.
15. Lemyre B, Millar KH, Roberts D, et al. Nasal intermittent positive pressure ventilation vs.
nasal continuous positive airway pressure for preterm neonates after extubation. Washington:
Pediatric Academic Societies; 2013.
16. De Luca D, Carnielli VP, Conti G, Piastra M. Noninvasive high frequency oscillatory ventilation through nasal prongs: bench evaluation of efficacy and mechanics. Intensive Care Med.
2010;36(12):2094100.
17. De Luca D, Piastra M, Pietrini D, et al. Effect of amplitude and inspiratory time in a bench
model of non-invasive HFOV through nasal prongs. Pediatr Pulmonol. 2012;47(10):10128.
18. Colaizy TT, Younis UM, Bell EF. Nasal high-frequency ventilation for premature infants. Acta
Paediatr. 2008;97(11):151822.
19. van der Hoeven M, Brouwer E, Blanco CE. Nasal high frequency ventilation in neonates with
moderate respiratory insufficiency. Arch Dis Child Fetal Neonatal Ed. 1998;79(1):F613.
20. Mukerji A, Finelli M, Belik J. Nasal high-frequency oscillation for lung carbon dioxide clearance in the newborn. Neonatology. 2013;103:1604.
21. De La Roque ED, Bertrand C, Tandonnet O, et al. Nasal high frequency percussive ventilation
versus nasal continuous positive airway pressure in transient tachypnea of the newborn. Pediatr
Pulmonol. 2011;46:21822.
22. Czernik C, Schmalisch G, Bhrer C, et al. Weaning of neonates from mechanical ventilation
by use of nasopharyngeal high frequency oscillatory ventilation: a preliminary study. J Matern
Fetal Neonatal Med. 2012;25(4):3748.
23. Mukerji A, Singh B, Helou SE, Fusch C, Dunn M, Belik J, Shah V, et al. Use of noninvasive
high-frequency ventilation in the neonatal intensive care unit: a retrospective review. Am J
Perinatol. 2015;30(2):1716.
24. Roberts CL, Badgery-Parker T, Algert CS, et al. Trends in use of neonatal CPAP: a populationbased study. BMC Pediatr. 2011;11:89.
25. Buckmaster AG, Arnolda GR, Wright IM, Henderson-Smart DJ. CPAP use in babies with
respiratory distress in Australian special care nurseries. J Paediatr Child Health.
2007;43(5):37682.
26. De Paoli AG, Davis PG, Faber B, Morley CJ. Devices and pressure sources for administration
of nasal continuous positive airway pressure (NCPAP) in preterm neonates. Cochrane Database
Syst Rev. 2008;(1):CD002977. doi:10.1002/14651858.CD002977.pub2.
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27. De Paoli AG, Davis PG, Faber B, Morley CJ. Devices and pressure sources for administration
of nasal continuous positive airway pressure (NCPAP) in preterm neonates. Cochrane Database
Syst Rev. 2002;(4):CD002977.
28. Kieran EA, Twomey AR, Molloy EJ, et al. Randomized trial of prongs or mask for nasal continuous positive airway pressure in preterm infants. Pediatrics. 2012;130(5):e11706.
29. Colnaghi M, Matassa PG, Fumagalli M, Messina D, Mosca F. Pharyngeal pressure value using
two continuous positive airway pressure devices. Arch Dis Child Fetal Neonatal Ed.
2008;93(4):F3024.
30. Zaramella P, Freato F, Grazzina N, et al. Does helmet CPAP reduce cerebral blood flow and
volume by comparison with Infant Flow driver CPAP in preterm neonates? Intensive Care
Med. 2006;32(10):16139.
31. Trevisanuto D, Camiletti L, Doglioni N, Cavallin F, et al. Noise exposure is increased with
neonatal helmet CPAP in comparison with conventional nasal CPAP. Acta Anaesthesiol Scand.
2011;55(1):358.
32. de Jongh BE, Locke R, Mackley A, et al. Work of breathing indices in infants with respiratory
insufficiency receiving high-flow nasal cannula and nasal continuous positive airway pressure.
J Perinatol. 2014;34(1):2732.
Noninvasive Ventilation Strategies

to Prevent Post-extubation Failure:
Neonatology Perspective
49
Erik A. Jensen and Georg M. Schmlzer
Abbreviations
BPD
BW
CPAP
FRC
HFNC
MV
NAVA
NICU
NIPPV
RCT
Bronchopulmonary dysplasia
Birth weight
Functional residual capacity
Neurally adjusted ventilator assist
Neonatal intensive care unit
Funding Support Georg M. Schmlzer is a recipient and a Heart and Stroke Foundation Canada
Scholarship/University of Alberta Professorship of Neonatal Resuscitation.
E.A. Jensen, MD (*)
Department of Pediatrics, Division of Neonatology, The Childrens Hospital of Philadelphia,
The University of Pennsylvania, 34th & Civic Center Boulevard, 2nd Floor Main
Neonatology, Philadelphia, PA, 19104, USA
e-mail: jensene@email.chop.edu
G.M. Schmlzer, MD, PhD
Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit,
Royal Alexandra Hospital, Edmonton, AB, Canada
Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
Division of Neonatology, Department of Pediatrics, Medical University, Graz, Austria
DOI 10.1007/978-3-319-04259-6_49
401
402
49.1
E.A. Jensen and G.M. Schmlzer
Introduction
Respiratory failure is the most common problem encountered in the neonatal intensive care unit (NICU) [1]. Nearly two-thirds of infants born less than 29 weeks
gestation require endotracheal intubation and mechanical ventilation (MV) while
admitted to the NICU [1]. Although MV is often lifesaving, it is associated with
multiple short- and long-term sequelae, including subglottic injury, infection, bronchopulmonary dysplasia (BPD), and neurocognitive impairment [2]. As a consequence, clinicians try to avoid or minimize the duration of MV and extubate infants
as early as possible. Following extubation, application of a continuous distending
pressure to the airways helps prevent alveolar collapse and maintain gas exchange [3].
Although noninvasive respiratory support has become routine for post-extubation
management in preterm infants, optimal strategies to prevent extubation failure
have not been clearly defined. This chapter aims to review the definitions of postextubation failure and describe the available equipment and techniques for noninvasive post-extubation respiratory support in preterm infants.
49.2
Definitions of Post-extubation Failure
There are currently no uniform criteria to define extubation failure in preterm

infants. As a consequence, there is considerable heterogeneity between studies for
this outcome. Common definitions include post-extubation apnea, respiratory acidosis, increased supplemental oxygen requirement, or reintubation and MV [4, 5].
Among these criteria, the threshold used to define failure also varies [4]. Moreover,
extubation failure rates depend on the window of observation following extubation.
In a systematic review of the topic, Giaccone et al. [4] found that the average reintubation rate in studies primarily enrolling infants with birth weights (BWs) 1000 g
increased without apparent plateau from 13 % at 24 h to 35 % a week after
extubation.
49.3
Noninvasive Respiratory Therapies Following

Extubation
49.3.1 Continuous Positive Airway Pressure

Noninvasive continuous positive airway pressure (CPAP) is typically generated in
the NICU either by a ventilator or from a compressed gas source bubbled under a
desired depth of water. It can be administered via short single or binasal prongs,
longer nasopharyngeal prong(s), or by nasal mask. Compared with oxygen therapy
alone, CPAP results in lower rates of extubation failure in preterm infants [5].
However, which CPAP pressure level, source, and interface are most effective to
prevent extubation failure has not been established.
49 Noninvasive Ventilation Strategies to Prevent Extubation Failure in Infants
403
CPAP is typically initiated at 48 cm H2O, although pressures as high as 15 cm

H2O have been used historically [3]. A minimum CPAP level of 5 cm H2O is likely
necessary to provide adequate post-extubation support, although higher pressures
may be more effective [5, 6]. Buzzella et al. [6] compared two CPAP ranges (46 vs
79 cm H2O) and reported lower extubation failure and reintubation rates within
96 h in extremely low birth weight infants (BW <1000 g) treated with the higher
level. Gupta et al. [7] compared bubble CPAP to a variable flow CPAP device (both
at 6 cm H2O) in 140 preterm infants. The overall incidence of extubation failure was
similar between the groups, however, among infants mechanically ventilated for
14 days, fewer infants supported on bubble CPAP required reintubation (14 % vs
29 %, p = 0.046).
A 2008 Cochrane Review concluded that short binasal prongs are superior to
single-prong interfaces for prevention of extubation failure [8]. More recently,
Kieran et al. [9] reported lower reintubation rates within 72 h in preterm infants
treated with a nasal mask compared with short binasal prongs (28 % vs 52 %,
p = 0.007). However, a small paired crossover study found fewer apnea, bradycardia, and desaturation events with nasal prongs compared with mask [10]. Nasal
trauma, the most common complication of nasal CPAP, occurs equally often with
prongs and mask [11].
Although there are concerns for pneumothoraces with CPAP, the risk is likely
overestimated [12]. With provider education, the risk of pneumothorax is decreased
and, when present, need for urgent treatment of pneumothoraces is rare [12].
49.3.2 Noninvasive Positive Pressure Ventilation

Noninvasive positive pressure ventilation (NIPPV), also referred to as noninvasive
mandatory ventilation, provides a continuous distending pressure with the addition
of an intermittent higher peak inspiratory pressure. In contrast to CPAP, which primarily facilitates lung recruitment and maintenance of functional residual capacity,
NIPPV may improve CO2 exchange as well as oxygenation [13]. Most published
studies utilized a conventional ventilator to deliver peak NIPPV pressures similar to
pre-extubation levels (1424 cm H2O) [13]. NIPPV can be synchronized with the
infants own respiratory effort or delivered unsynchronized at regular intervals.
A 2014 Cochrane Review including 8 randomized controlled trials (RCT) compared NIPPV to CPAP for prevention of endotracheal reintubation in preterm infants
(total n = 1301) [14]. Five of the RCTs used synchronized NIPPV (SNIPPV), two
used un-synchronized NIPPV, and the largest by Kirpalani et al (n = 845) [15] used
both methods. NIPPV, irrespective of synchronization, reduced the need for reintubation up to one week after extubation (RR 0.76; 95% CI 0.65-0.88) [14]. In an
analysis subdivided by synchronization status of the RCT, the variably defined outcome of extubation failure was only reduced in the 5 trials (total n = 272) that
compared SNIPPV to CPAP (RR 0.25; 95% CI 0.150.41). The outcome of endotracheal reintubation was not reported by trial subtype. Importantly, three of the
404
RCTs that studied SNIPPV used abdominal pneumatic capsules for synchronization
and the ventilators that utilize these capsules are no longer commercially available.
In a small RCT (n = 63), Moretti et al. [16] reported greater extubation success
with nasal-flow (pneumotachograph) synchronized NIPPV compared with CPAP.
However, this device is less effective if there is leak at the mouth or nose, and difficulty with its use has been reported [13]. Neurally adjusted ventilator assist
(NAVA) provides reliable synchronization for intubated infants and may be beneficial in conjunction with NIPPV, although reports of its noninvasive use are limited
to adults and animal models [17].
49.3.3 High-Flow Nasal Cannula

Heated, humidified high-flow nasal cannula (HFNC) has gained considerable popularity as a mode of noninvasive respiratory support in preterm infants [17]. HFNC
utilizes short, tapered binasal prongs that do not occlude the nares (in contrast to
CPAP prongs or mask that typically have minimal air leak at the nares) to provide
oxygen or blended oxygen and air at flow rates greater than 12 l/min. The higher
flow rates compared with low-flow nasal cannula are intended to provide continuous distending pressure similar to CPAP. Proponents of HFNC cite reduced nasal
trauma, improved infant comfort, greater ability to maintain the nasal prongs within
the nares, and facilitation of parent bonding and developmental care as the benefits
of HFNC over standard CPAP [17]. However, a formal assessment of patient comfort and ease of care demonstrated no difference between HFNC and CPAP and
there are concerns about the safety and efficacy of HFNC, particularly in the most
premature infants [1719].
Several RCTs compared HFNC with CPAP for post-extubation respiratory support in preterm infants [1721]. Campbell et al. [21] reported, in a single-center
RCT (n = 40), lower reintubation rates within the first 7 days among infants treated
with CPAP of 56 cm H2O compared with HFNC of 1.41.7 l/min (RR 2.1; 95 %
CI 1.33.0). Three more recent RCTs compared CPAP with HFNC flows ranging
from 3 to 8 l/min [1820]. Manley et al. [19] used a non-inferiority trial design
(n = 303) and concluded that HFNC was non-inferior to CPAP with the treatment
effect nonsignificantly favoring extubation to CPAP (risk difference 8.4 percentage
points; 95 % CI 1.918.7). However, the upper bound of the 95 % CI approached
the arbitrarily selected 20 percentage point non-inferiority margin. Moreover, nearly
half of the infants who failed HFNC were successfully rescued with CPAP and did
not require reintubation. In the subgroup of infants with gestational ages <26 weeks
(n = 63), the risk difference was 20 percentage points, in favor of CPAP. The remaining two trials reported nonsignificant differences with the opposite direction of
effect, favoring extubation to HFNC [18, 20]. A meta-analysis of these RCTs concluded that there was no difference in extubation failure risk between the two therapies (RR 1.05; 95 % CI 0.791.39) [17].
The primary safety concern with HFNC is the potential for high, unmeasured
distending pressures [17]. In an in vitro model, Sivieri et al. [22] recorded pressures
49 Noninvasive Ventilation Strategies to Prevent Extubation Failure in Infants
405
up 2030 cm H2O with flow rates >2 l/min. However, data compiled from the recent
HFNC trials indicated a low risk of pneumothorax (incidence <1 %) with a nonsignificantly higher rate in the CPAP group [17].
Nasal CPAP or other form of a continuous distending airway pressure

should be used to maintain lung recruitment and reduce extubation failure
risk in preterm infants.
Synchronized NIPPV may be more effective than CPAP at preventing
extubation failure, but this therapy requires investigation in a large RCT to
quantify the benefit and to determine the optimal synchronization device.
Until further safety and efficacy data are available, HFNC should be
avoided in infants with gestational age <26 weeks.
References
1. Stoll BJ, Hansen NI, Bell EF, et al. Neonatal outcomes of extremely preterm infants from the
NICHD neonatal research network. Pediatrics. 2010;126:44356.
2. Bancalari E, Sinclair JC. Mechanical Ventilation. In: Sinclair JC, Bracken MB, Eds. Effective
care of the newborn infant. New York, Oxford: Oxford University Press; 1992. pp 200220.
3. Berger T, Fontana M, Stocker M. The journey towards lung protective respiratory support in
preterm neonates. Neonatology. 2013;104:26574.
4. Giaccone A, Jensen E, Davis P, et al. Definitions of extubation success in very premature
infants: a systematic review. Arch Dis Child Fetal Neonatal Ed. 2014;99:F1247.
5. Davis PG, Henderson-Smart DJ. Nasal continuous positive airways pressure immediately after
extubation for preventing morbidity in preterm infants. Cochrane Database Syst Rev.
2003;(2):CD000143.
6. Buzzella B, Claure N, DUgard C, et al. A randomized controlled trial of two nasal continuous
positive airway pressure levels after extubation in preterm infants. J Pediatr. 2014;164:4651.
7. Gupta S, Sinha SK, Tin W, et al. A randomized controlled trial of post-extubation bubble continuous positive airway pressure versus infant flow driver continuous positive airway pressure
in preterm infants with respiratory distress syndrome. J Pediatr. 2009;154:64550.
8. De Paoli AG, Davis PG, Faber B, et al. Devices and pressure sources for administration of
nasal continuous positive airway pressure (NCPAP) in preterm neonates. Cochrane Database
Syst Rev. 2008;(1):CD002977.
9. Kieran EA, Twomey AR, Molloy EJ, et al. Randomized trial of prongs or mask for nasal continuous positive airway pressure in preterm infants. Pediatrics. 2012;130:e11706.
10. Jackson H, Lim K, Gale T, et al. Mask versus prongs for CPAP delivery: incidence of bradycardia, apnea and desaturation (BAD) events [abstract]. J Paediatr Child Health. 2013;49 suppl
2:A072.
11. Yong S, Chen S, Boo N. Incidence of nasal trauma associated with nasal prong versus nasal
mask during continuous positive airway pressure treatment in very low birthweight infants: a
randomised control study. Arch Dis Child Fetal Neonatal Ed. 2005;90:F4803.
12. Buckmaster A. Nasal continuous positive airway pressure for respiratory distress in nontertiary care centres: what is needed and where to from here? J Paediatr Child Health.
2012;48:74752.
406
13. Roberts C, Davis P, Owen L. Neonatal non-invasive respiratory support: synchronised NIPPV,
non-synchronised NIPPV or bi-level CPAP: what is the evidence in 2013? Neonatology.
2013;104:2039.
14. Lemyre B, Davis PG, De Paoli AG, Kirpalani H. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates
after extubation. Cochrane Database Syst Rev. 2014;9:CD003212.
15. Kirpalani H, Millar D, Lemyre B, et al. A trial comparing noninvasive ventilation strategies in
preterm infants. N Engl J Med. 2013;369:61120.
16. Moretti C, Giannini L, Fassi C, et al. Nasal flow-synchronized intermittent positive pressure
ventilation to facilitate weaning in very low-birthweight infants: unmasked randomized controlled trial. Pediatr Int. 2008;50:8591.
17. DeMauro SB, Millar D, Kirpalani H. Noninvasive respiratory support for neonates. Curr Opin
Pediatr. 2014;26:15762.
18. Yoder BA, Stoddard RA, Li M, et al. Heated, humidified high-flow nasal cannula versus nasal
CPAP for respiratory support in neonates. Pediatrics. 2013;131:e148290.
19. Manley BJ, Owen LS, Doyle LW, et al. High-flow nasal cannulae in very preterm infants after
extubation. N Engl J Med. 2013;369:142533.
20. Collins CL, Holberton JR, Barfield C, et al. A randomized controlled trial to compare heated
humidified high-flow nasal cannulae with nasal continuous positive airway pressure postextubation in premature infants. J Pediatr. 2013;162:94954. e941.
21. Campbell D, Shah P, Shah V, et al. Nasal continuous positive airway pressure from high flow
nasal cannula versus infant flow for preterm infants. J Perinatol. 2006;26:5469.
22. Sivieri EM, Gerdes JS, Abbasi S. Effect of HFNC flow rate, cannula size, and nares diameter
on generated airway pressures: an in vitro study. Pediatr Pulmonol. 2013;48:50614.
Application of Noninvasive Ventilation

in Preventing Extubation Failure
in Children with Heart Disease:
Key Topics and Clinical Implications
50
Yolanda Lpez-Fernndez and F. Javier Pilar-Orive
Abbreviations
BPAP
CHD
CPAP
CPB
EPAP
FRC
FT
ICU
IPAP
LOS
NAVA
NIV
P/F
PC
PEEP
PIP
PS
Qp
Qs

Congenital heart disease
Cardiopulmonary bypass
Expiratory positive airway pressure
Functional residual capacity
Fast track (fast-tracking)
Intensive care unit
Inspiratory positive airway pressure
Length of stay
Neurally adjusted ventilation assist
Arterial oxygen pressure/fraction of inspired oxygen ratio
Pressure controlled
Positive inspiratory pressure
Pressure support
Pulmonary circulation
Systemic circulation
Y. Lpez-Fernndez, MD (*) F.J. Pilar-Orive, MD

PICU, Cruces University Hospital, Barakaldo, Spain
e-mail: yolandamarg.lopezfernandez@osakidetza.eus; fco.javier.pilarorive@osakidetza.eus
DOI 10.1007/978-3-319-04259-6_50
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408
50.1
Y. Lpez-Fernndez and F.J. Pilar-Orive
Introduction
Surgery for congenital heart disease (CHD) using cardiopulmonary bypass (CPB)
usually requires postoperative mechanical ventilation [1]. However, advances in
anesthesia and surgical procedures have changed the expectations for mechanical
ventilation following cardiac surgery [2]. Some centers attempt early endotracheal
extubation as part of a fast-tracking approach, whereas others prefer extubation
from mechanical ventilation in the intensive care unit (ICU) as their standard patient
management.
Extubation failure after mechanical ventilation is relatively common. It occurs in
approximately 10 % of children after cardiac surgery (22 % in children after a
Norwood procedure). When urgent reintubation is required, this may produce substantial hemodynamic instability, excessive airway trauma, increased risk for nosocomial infections, and prolonged mechanical ventilation and ICU length of stay
(LOS) [3].
Either by fast-tracking or by a more conservative approach, there is no doubt
that noninvasive ventilation (NIV) can play an important role as a rescue therapy. In
addition, NIV can be used as an elective or prophylactic therapy when the patient is
at high risk for extubation failure [3].
50.2
Fast Track Versus Standard Management
In general, the concept of fast-tracking (FT) is applied when the endotracheal

tube is removed within 68 h after the surgery; the term has also been used when
extubation is performed in the operating room [1, 2]. This early extubation pattern has become widely adopted in adult cardiac practice surgery, where the literature clearly demonstrates reductions in ICU and hospital LOS and costs,
without increased incidence of mortality or morbidity. A number of studies have
suggested that this practice can be performed safely in simple and complex surgical cases for all age groups.
The experience with early extubation in pediatric cardiac surgery has not yet
been proven, and extrapolation from the adult practice may be inappropriate.
There are substantial differences in anesthesia practices and heterogeneity in
patient age, physiology, and anatomic complexity. Compared with adults, children often have fewer comorbidities, making them at least just as good candidates for FT. A pediatric meta-analysis recently concluded that the application of
this practice could be performed in appropriately selected patients, even including those with pulmonary hypertension, those who required hypothermic circulatory arrest, and neonates [2, 4]. Reintubation rates in a large case series ranged
from 0 to 13 % of extubated patients.
Patients with single-ventricle physiology and, more precisely, children after
palliative bidirectional Glenn and Fontan surgeries, have been proven to be particularly good candidates for early extubation, with improvements in hemodynamics compared with pre-extubation values. In patients undergoing a Fontan
50
Application of Noninvasive Ventilation in Preventing Extubation Failure
409
procedure, mean pulmonary artery pressure was lower and mean arterial pressure was higher in the early extubation group compared with the nonearly extubation group. In addition, these patients require less inotropic support and shorter
duration of thoracic drainage [4, 5].
Other institutions prefer to control mechanical ventilation in the ICU as their
standard patient management in the postoperative period [1]. Earlier studies
established that infants and young children with CHD are at risk for prolonged
mechanical ventilation and failed extubation after cardiac surgery [6]. It makes
sense to transfer the patient to the ICU, where the choice of when to extubate can
be determined in a controlled setting using objective criteria to consider hemodynamic stability, coagulation status, pulmonary gas exchange, systemic oxygen
delivery, or fever. Moreover, systemic inflammatory response induced by surgery
with CPB contributes to the presence of several components that may influence
or intensify an extubation failure in the postoperative period [7].
Patients who had longer CPB times, longer aortic cross-clamp times, and
higher preoperative mean pulmonary vascular resistance and systemic ventricular end-diastolic pressure seem to be good candidates for delayed extubation in
the ICU using an organized evaluative process with continuous assessment of
patients recovery [7].
50.3
Extubation Failure
The incidence of failed extubation after pediatric cardiac surgery is greater compared with that in the general pediatric population. These patients are particularly
vulnerable to the increased metabolic demands imposed by spontaneous breathing,
and cardiac output may be compromised by altered respiratory mechanics [8].
Common causes in children with heart disease that contribute to extubation failure
include lung disease, cardiac dysfunction, diaphragmatic paralysis, airway edema,
and vocal cord paralysis [3]. Cardiac dysfunction has been found to be the etiology
of extubation failure in 2765 % of children with CHD [9].
Not surprisingly, extubation is challenging in pediatric patients undergoing cardiac procedures. Preoperative factors that may contribute to an extubation failure
are low body weight, chromosomal abnormalities, poor nutritional status, and, consequently, limited body reserves and functional immaturity of organ systems [8,
10]. Intraoperative factors also should be considered as possible reasons for extubation failure, such as complex operative procedures, prolonged CPB time, balancing
pulmonary (Qp) and systemic circulation (Qs), and delayed sternal closure [10].
Once the patient is admitted to the ICU, making the decision to extubate not only
should be based on the above-described factors, but others also have to be considered, such as altered respiratory mechanics or increased multiorgan dysfunction.
Residual effects from sedative agents and neuromuscular blockade, and diaphragmatic paresis or paralysis, presumably from nerve injury, may affect pulmonary
mechanics [10]. Furthermore, due to complex cardiopulmonary interactions, low
cardiac output syndrome is a determining factor in extubation not being a success.
410
Vasoactive medication dependence is associated with extubation failure, and children who fail extubation frequently required increased vasoactive support and
develop metabolic acidosis [9].
Accurate prediction of extubation success requires assessment of not only respiratory function but also cardiac performance. Prior to an extubation attempt, the patient
should be closely assessed using clinical, laboratory, and monitoring parameters:
Vital signs and physical examination: postoperative weight should return to
1020 % of preoperative values
Acid-base balance, serum lactate levels
Disorders such as hypokalemia and hypophosphatemia that can impair strength
and endurance [10]
Invasive monitoring of arterial blood and central venous pressures
Regional oxygen saturation (as measured by near-infrared spectroscopy) [11].
50.4
Role of NIV in Preventing Extubation Failure
NIV has been used as a preventive measure in patients with high risk for extubation
failure and can be effectively applied as an alternative means of respiratory support
in patients with hypoxemic or hypercarbic failure with signs of respiratory distress
who were considered likely to require reintubation after cardiac surgery. Improving
ventilation by NIV in these patients is associated mostly with reduced work of
breathing and has alleviated respiratory muscle fatigue [8].
Decreased functional residual capacity (FRC) that is repeatedly present in
patients after cardiac surgery can be improved with continuous positive airway pressure (CPAP). The use of positive end-expiratory pressure (PEEP, EPAP) improves
FRC, allowing better gas exchange [12]. This improvement can be increased by
additional pressure support (PS) and/or pressure-controlled (PC) breaths, which can
help preserve good lung volume and reduce the load of the inspiratory muscles and
the work of breathing [8].
Common causes of respiratory failure after cardiac surgery were pulmonary
edema, pneumonia, and atelectasis [13]. To prevent extubation failure, NIV may be
a useful therapy in certain scenarios, such as those involving lung disease, diaphragmatic paralysis, and airway edema. In other scenarios, such as those related to vocal
cord paralysis, NIV may be dangerous because these patients are at high risk for
aspiration [3].
NIV can be started:
As elective or prophylactic therapy, when started directly after extubation
As rescue therapy, taking place after signs and symptoms of acute respiratory
failure develop [3]
Few studies on the use of NIV in children after pediatric cardiac surgery have
been published to date, therefore, the reported clinical experience is too small to
50
411
draw clear and valid conclusions [12]. There are no published studies that show an
advantage of elective NIV over rescue NIV in postoperative cardiac patients.
Accordingly, elective NIV cannot yet be recommended as a routine approach [14].
50.5
Clinical Intervention
50.5.1 Indications
NIV should be considered as treatment when the patient, within 2448 h after extubation, presents with:
Acute hypercapnia (pCO2 >55 mmHg) or hypoxemia (increased oxygen requirements) or both
Clear signs of increased work of breathing, such as high respiratory rate, use of
accessory muscles, and intercostal retractions [12]
The patient prepared for NIV should be conscious and cooperative, stable hemodynamically, and at no risk for asphyxia (aspiration, gastrointestinal hemorrhage, or
abundant airway secretions) [13]. Major indications and contraindications of NIV
after cardiac surgical procedures are shown in Table 50.1.
50.5.2 Devices
Any standard ventilator with an NIV option can be used. However, there could be
limitations in the smallest children due to their inaccurate trigger systems and insufficient leak compensation. NIV-specific ventilators allow reaching programmed
pressures despite high levels of leakage, resulting in a more accurate setting of
activation and cycling-off trigger. Furthermore, newer generations of ventilators
offer more sophisticated systems to overcome some of these limitations as well as
Table 50.1 Indications and contraindications of NIV after pediatric cardiac surgical procedures
Indications
Atelectasis
Acute pulmonary edema
Pneumonia
Diaphragmatic paralysis
Airway edema: post-extubation laryngitis
Weaning in patient with polyneuromyopathy
Alternative to reintubation if unplanned
extubation
Support procedures with sedoanalgesia
Contraindications
Unconscious/noncooperative
Hemodynamic instability
Abundant and thick secretions
Severe respiratory failure (P/F <150; S/F
<200)
Vomiting/gastrointestinal hemorrhage
Vocal cord paralysis
Facial trauma or cranial malformations
Pneumothorax (not drained)
412
Table 50.2 Selection of adequate NIV interface

Age
Newborn
First choice
Infant
Full-face mask
Child
Oronasal mask
Full-face mask
Bi-nasal prongs
Second choice
Nasopharyngeal tube
Nasal mask
Full-face mask
Bi-nasal prongs
Nasopharyngeal tube
Nasal mask
Nasal mask
alternative trigger systems, such as triggering based on diaphragmatic activity signal (neurally adjusted ventilation assist, NAVA) [13, 14]. Table 50.2 offers different
options when selecting an NIV interface according to the patients age.
50.5.3 Modes
CPAP: may improve oxygenation, increasing lung volume derived from alveoli
recruitment and fluid redistribution. Myocardial function may be improved
through a decrease in left ventricular afterload. Low CPAP levels (56 cm H2O)
are recommended to start ventilation, increasing gradually 12 cm H2O up to
10 cm H2O according to respiratory requirements. Levels above 12 cm H2O are
usually not well tolerated [8, 14].
Bi-level positive airway pressure (BPAP): additional PS and/or PC breaths. Its
use is reserved for more distressed patients. These modes combine inspiratory
positive airway pressure (IPAP, PPI) and expiratory positive airway pressure
(EPAP, PEEP). A backup respiratory rate is added when the inspiratory effort
generated by young children is often too small to be detected by the ventilator.
To enhance comfort and compliance, ventilation settings start with PEEP (or
EPAP) at 45 cm H2O and increase as necessary, up to a maximum of 10 cm
H2O. Inspiratory positive airway pressure (PPI or IPAP) is started at 68 cm H20
and gradually increased to 1820 cm H2O. The parameters are increased gradually to appropriate clinical setting within 30120 min [8, 13].
50.5.4 Interfaces
The choice of the right interface may be challenging in young children. NIV can
be delivered by way of nasal, oronasal, and full-face masks; nasal prongs and
oropharyngeal tubes are commonly used in for infants. Full-face and oronasal
masks are best suited for hypoxemic patients and advanced hypercapnic respiratory failure, in particular for more dyspneic patients. Nasal-type masks are usually indicated for hypercapnic patients, but only in those who are not very
50
413
dyspneic and can keep their mouth closed. The main disadvantage of most of the
interfaces is the difficulty of preserving a good seal and achieving adequate pressure [8, 14].
50.5.5 Ancillary Treatments

Heated humidifiers should be used to deliver adequate humidity close to body
temperature
Colloid ulcer dressings are used to prevent skin breakdown
A nasogastric tube may be inserted to deflate the stomach and to provide enteral
feeding
Low-dose sedation is applied to allow better tolerance in some selected patients
[12]
50.5.6 Monitoring
Patients should be closely monitored in terms of
Vital signs and physical examination

Respiratory rate, dyspnea, breath effort, retractions, use of accessory muscles
Exhaled tidal volume, patient-ventilator synchrony, leakage
Oxygen saturation and blood gas
Complications: gastric distension, exacerbation of gastroesophageal reflux disease, aspiration, pneumothorax, irritative conjunctivitis [13]
Oxygenation is evaluated by the effect of NIV on the decrease of heart rate,

respiratory rate, FiO2 requirement, and the increase of oxygen saturation, arterial
oxygen pressure/fraction of inspired oxygen ratio (P/F), or transcutaneous oxygen
saturation/fraction of inspired oxygen ratio (S/F) [15]. Ventilation is judged by
decreased concentrations of pCO2 and bicarbonate. PCO2 can be continuously monitored through the measurement of transcutaneous CO2. These measurements suggest that ventilation is effective and can be continued. Otherwise, ventilator
parameters should be readjusted or NIV removed, considering reintubation and
invasive mechanical ventilation [13].
Conclusions
NIV can be used as a preventive measure in patients with high risk for extubation
failure and can be effectively applied as an alternative means of respiratory support in patients with hypoxemic or hypercarbic failure with signs of respiratory
distress who are considered likely to require reintubation after cardiac surgery.
Improving ventilation by NIV in these patients is associated mostly with reduced
work of breathing and has alleviated respiratory muscle fatigue.
414
Early extubation has become widely adopted in cardiac practice surgery,

showing reductions in ICU and hospital LOS without increased incidence
of mortality. It can be performed safely in simple and complex surgical
cases for all age groups.
Infants and young children with CHD are at risk for prolonged mechanical
ventilation after cardiac surgery. The time choice of extubation can be
determined using an organized evaluative process with continuous assessment of hemodynamic stability, coagulation status, and pulmonary gas
exchange.
To prevent extubation failure, NIV may be a useful therapy in certain scenarios, such as those involving lung disease, diaphragmatic paralysis, and
airway edema. Common causes of respiratory failure after cardiac surgery
are pulmonary edema, pneumonia, and atelectasis.
The patient prepared for NIV should be conscious and cooperative, stable
hemodynamically, and at no risk for asphyxia (without aspiration, gastrointestinal hemorrhage, or abundant airway secretions).
CPAP may improve oxygenation, increasing lung volume derived from
alveoli recruitment and fluid redistribution. Myocardial function may be
improved through a decrease in left ventricular afterload. BPAP adds additional PS and/or PC breaths
References
1. Kin N, Weismann C, Srivastava S, et al. Factors affecting the decision to defer endotracheal
extubation after surgery for congenital heart disease: a prospective observational study. Anesth
Analg. 2011;113:32935.
2. Alghamdi AA, Singh SK, Hamilton BCS, et al. Early extubation after pediatric cardiac surgery: systematic review, meta-analysis, and evidence-based recommendations. J Card Surg.
2010;25:58695.
3. Gupta P, Kuperstock JE, Hashmi S, et al. Efficacy and predictors of success of non invasive
ventilation for prevention of extubation in critically ill children with heart disease. Pediatr
Cardiol. 2013;34:96477.
4. Mittnacht AJC. Pro: early extubation following surgery for congenital heart disease.
J Cardiothorac Vasc Anesth. 2011;25:8746.
5. Mittnacht AJ, Hollinger I. Fast-tracking in pediatric cardiac surgery the current standing.
Ann Card Anaesth. 2010;13:92101.
6. Shi S, Zhao Z, Liu X, et al. Perioperative risks factors for prolonged mechanical ventilation
following cardiac surgery in neonates and young infants. Chest. 2008;134:76874.
7. DiNardo JA. Con: extubation in the operating room following pediatric cardiac surgery.
J Cardiothorac Vasc Anesth. 2011;25:8779.
8. Kovacikova L, Skrak P, Dobos D, et al. Noninvasive positive pressure ventilation in critically
ill children with cardiac disease. Pediatr Cardiol. 2014;35:67683.
9. Harkel AD, van der Vorst MM, Hazekamp MZ, et al. High mortality rate after extubation
failure after pediatric cardiac surgery. Pediatr Cardiol. 2005;26:75661.
50
415
10. Gupta P, McDonald R, Gossett JM, et al. A single-center experience of extubation failure in
infants undergoing the Norwood operation. Ann Thorac Surg. 2012;94:12628.
11. Foster CB, Spaeder MC, McCarter RJ, et al. The use of near-infrared spectroscopy during an
extubation readiness trial as a predictor of extubation outcome. Pediatr Crit Care Med.
2013;14:58792.
12. Dohna-Schwake C, Stehling F, Tschiedel E, et al. Non-invasive ventilation on a pediatric
intensive care unit: feasibility, efficacy and predictors of success. Pediatr Pulmonol.
2011;46:111420.
13. Zhang C, Tan L, Shi S, et al. Noninvasive ventilation via bilevel positive airway pressure support in pediatric patients after cardiac surgery. World J Pediatr. 2006;4:297302.
14. Rimensberger P, Heulitt MJ, Meliones J, et al. Mechanical ventilation in the pediatric cardiac
intensive care unit: the essentials. World J Pediatr Congenital Heart Surg. 2011;2:60919.
15. Mayordomo-Colunga J, Pons M, Lpez Y, et al. Predicting non-invasive ventilation failure in
children from the SpO2/FiO2 (SF) ratio. Intensive Care Med. 2013;39:1095103.
Noninvasive Ventilation After

Extubation in Pediatric Patients:
Determinants of Response
and Key Topics
51
Juan Mayordomo-Colunga, Alberto Medina,

Mart Pons-dena, Teresa Gili, and Mara Gonzlez
Abbreviations
ARF
BLPAP
CPAP
e-NIV
NAVA
NIV
PICU
r-NIV
SF

Post-extubation elective NIV
Neurally adjusted ventilatory assist
Pediatric intensive care unit
Post-extubation rescue NIV
Transcutaneous oxygen saturation/fraction of inspired oxygen
J. Mayordomo-Colunga, PhD (*)

Pediatric Intensive Care Unit, Hospital Universitario Central de Asturias, Oviedo, Spain
e-mail: jmcolunga@hotmail.com
A. Medina, PhD
Pediatric Intensive Care Unit, Hospital Universitario Central de Asturias, Oviedo, Spain
e-mail: amedinavillanueva@gmail.com
M. Pons-dena, PhD
Pediatric Intensive Care Unit, Hospital Sant Joan de Du, Barcelona, Spain
e-mail: mpons@hsjdbcn.org
T. Gili, PhD
Pediatric Intensive Care Unit, Hospital Parc Taul, Sabadell, Spain
e-mail: tgili@tauli.cat
M. Gonzlez, PhD
Department of Pediatrics, Hospital Valle del Naln, Langreo, Spain
e-mail: marutxi_5@hotmail.com
DOI 10.1007/978-3-319-04259-6_51
417
418
51.1
J. Mayordomo-Colunga et al.
Introduction
Despite being frequently used in many pediatric intensive care units (PICUs) for
some years, published data regarding noninvasive ventilation (NIV) use after extubation in children are scarce. Many studies have analyzed NIV episodes in patients
with no previous invasive ventilation together with other episodes in children who
received NIV after extubation [1, 2]. Moreover, some authors used continuous positive airway pressure (CPAP) or two levels of pressure (bi-level positive airway pressure, or BLPAP) indistinctly [3, 4]. Because of this, no A or B recommendations can
be provided for this technique.
51.2
Analysis of Postextubation NIV in Pediatric Patients
Most authors agree that NIV episodes with no previous invasive ventilation should
be considered different from postextubation ones. Conditions after extubation place
patients in a completely different situation than that occurring when a child has not
been previously ventilated [4].
Postextubation NIV can be used in three ways: (1) as an adjunct in weaning
patients from conventional mechanical ventilation by early extubation directly to
NIV, (2) as a preventive application for NIV in high-risk patients who are extubated
at the time they fulfill standard extubation criteria, or (3) as a curative or rescue
application of NIV to patients who develop acute respiratory failure (ARF) after
being extubated according to standard criteria. The first two indications have been
suggested by some pediatric studies to be the so-called postextubation elective NIV
(e-NIV) group, which includes high-risk children treated with NIV immediately
after the endotracheal tube is removed. Those patients who develop ARF within
hours after extubation and receive NIV to try to avoid reintubation are considered
the so-called rescue NIV (r-NIV) group [4, 5].
These two groups should be analyzed separately, according to several adult studies [6] and to some pediatric reports [4]. However, there are few studies about
postextubation NIV in children. As has been previously mentioned, some studies
analyzed NIV episodes with or without previous invasive ventilation [1, 2]. In the
case of analyzing postextubation NIV, these studies frequently do not consider
r-NIV and e-NIV separately [3].
Some studies have underlined the usefulness of NIV after some surgeries. Most
of them focus on cardiac surgery, and others describe its utility after liver transplantation or scoliosis surgery [1, 712]. Postoperative NIV is especially useful in pediatric patients, who develop atelectasis quite frequently because of a lack of collateral
pathways for ventilation and low conductance of the central airways.
Children receiving NIV after cardiac surgery are a group of patients that deserve
special consideration. Early extubation is desirable and is associated with a better
outcome, and thus e-NIV is increasingly being used in these cases to shorten the
length of invasive ventilation. As such, NIV is frequently used to prevent
51
Noninvasive Ventilation After Extubation in Pediatric Patients
419
extubation failure. A study by Gupta et al. [7] suggested that NIV can be successfully applied for critically ill children with heart disease to avoid reintubation.
These benefits have been related to NIV improvement of existing or preexisting
lung disease, diaphragmatic paralysis, and airway edema (stenting of the airway).
These authors also included a sample of children with cardiac disease who received
r-NIV. They found an intubation rate similar to that in patients in whom e-NIV was
used. However, this study was retrospective and there were no clear criteria to initiate NIV [7].
It should be highlighted that a randomized controlled trial in infants following
cardiac surgery showed no advantage in using elective CPAP versus rescue CPAP in
all patients after cardiac surgery [8]. Thus, further studies are needed to clarify
which patients would benefit from the use of e-NIV.
A main limitation of NIV in pediatrics is related to the lack of specific interfaces and ventilators featuring adequately sensitive triggers. This limits its use,
mainly in smaller and younger patients, and, importantly, it may affect the efficacy of this technique, especially when BLPAP is applied [1, 4]. Fortunately,
some new interfaces are appearing, such as full-face masks for infants, which may
have an impact on the usefulness and spread of post-extubation NIV in children
(and other types of NIV). Furthermore, neurally adjusted ventilatory assist
(NAVA) has been suggested to help solve some synchrony issues, because leakage
would not be a problem and neural trigger should be superior to flow or pressure
inspiratory triggers.
An important point affecting NIV outcome in pediatric patients is the need for
physiotherapy to improve secretion drainage, especially in the younger patients and
also in children with neuromuscular diseases. Indeed, some studies focusing on
spinal surgery in this type of patient include the use of a mechanical cough-assisted
technique in addition to NIV [10]. It has been suggested that this postoperative
management may be useful in diminishing the occurrence of atelectasis and pneumonia in these patients in whom bronchial secretions accumulate rapidly after surgery due to the inability to clear them effectively.
51.3
Discussion
The different studies on NIV use after extubation in children cannot be adequately
compared regarding success rates and causes of NIV failure because of the different
inclusion criteria. Thus, further studies with clearly defined inclusion criteria are
needed to draw definitive conclusions about post-extubation NIV in children.
However, given that this technique seems to be useful for such patients, as suggested by many observational studies and some physiological ones, a prospective
randomized controlled trial would be difficult to realize because of ethical considerations. Indeed, Stucki et al. [13] showed in a pilot study that NIV in infants developing ARF after extubation were able to unload respiratory muscles by means of a
turbine flow generator with no deleterious effects.
420
We will discuss the available data in literature to date below. It should be noted
that all the studies have a very small number of episodes requiring reintubation.
Thus, these results should be interpreted with caution.
A prospective, preliminary study by Mayordomo-Colunga et al. [4] showed a
higher risk of failure in r-NIV cases than in e-NIV (50 % vs 19 %), similar to the
data shown in adults. They also found that hypoxemia (lower PaO2/FiO2 ratio),
higher oxygen requirements, and respiratory rate evolution were also related to
NIV failure in these patients. An underlying neurologic condition was also associated with NIV failure. In this study, criteria for r-NIV were well defined, but
e-NIV was used if the attending physician thought that the child was at high risk
for extubation failure.
Pons-Odena [5] described in his doctoral thesis, in a larger sample of postextubation patients, that e-NIV failure rate was 23 % (N = 134), and 16 % in
r-NIV (N = 75). This author identified age under 6 months as the only predictive
factor of failure in r-NIV, whereas no figure was independently linked to NIV
success or failure.
Lum et al. [2] reported an 86 % success rate in a 98-patient sample treated with
e-NIV, and an 74.5 % success rate in a total of 51 children who received
r-NIV. Predictors of failure were analyzed in this study together with a large
sample of episodes that had not received previous invasive ventilation.
Essouri et al. [1] published a relevant study that included a sample of 114 NIV
episodes. Among these, 61 patients received NIV due to respiratory failure after
extubation, with a 67 %success rate. They reported that the change in PCO2 and
in respiratory rate, and the respiratory rate and PCO2 recorded after 2 h of NIV,
were all associated with NIV outcome. However, this analysis was performed
considering the whole sample, thus including 53 children with no previous invasive ventilation.
James et al. [3] reported an 81 % success rate in 80 children who received postextubation NIV. These authors do not specify whether or not NIV was applied
immediately after the tracheal tube was removed. The only independent NIV
outcome predictor was the systolic arterial pressure 2 h after extubation.
A doctoral thesis by Gonzlez [14], based on a multicenter study in 12 PICUs
(10 Spanish and 2 Portuguese), included a sample of 100 e-NIV episodes, and 61
r-NIV cases. Again, criteria for r-NIV were well defined, but e-NIV was used if
the attending physician thought that the child was at high risk for extubation
failure. This study has the strength of being based on daily clinical practice, but
it does not allow one to draw definitive conclusions. The failure rates were 16
and 15 % in e-NIV and r-NIV, respectively. Failure was independently associated
with respiratory rate (RR) at 2 h in e-NIV, whereas FiO2 was the only predictive
factor of success or failure in r-NIV (a cutoff value of 55 % was suggested).
As suggested in many adult and pediatric NIV studies with no previous mechanical ventilation, oxygen requirement seems to be related to NIV success or failure.
One pediatric study has described the usefulness of the transcutaneous oxygen
51
Noninvasive Ventilation After Extubation in Pediatric Patients
421
1. Despite the lack of definitive data, NIV after extubation seems to be useful
to avoid reintubation in pediatric patients.
2. Elective NIV should be considered in high-risk patients, especially after
cardiac or spinal surgery.
3. High oxygen needs (FiO2 >5560 %) should be considered as a NIV failure predictor, especially in r-NIV. SF ratio may be useful for monitoring
these patients.
4. NIV should be used in addition to mechanical cough-assisted and other
respiratory therapy techniques in some children, especially in those with
neuromuscular diseases.
saturation/fraction of inspired oxygen (SF) ratio to predict NIV outcome, avoiding

the need for performing repeated arterial blood gas analysis [15]. We believe that SF
ratio would also be useful as an outcome marker for children receiving post-extubation NIV, as long as the transcutaneous oxygen saturation is reliable and maintained
within the range of 9097 %.
References
1. Essouri S, Chevret L, Durand P, et al. Noninvasive positive pressure ventilation: five years of
experience in a pediatric intensive care unit. Pediatr Crit Care Med. 2006;7:32934.
2. Lum LC, Abdel-Latif ME, de Bruyne JA, et al. Noninvasive ventilation in a tertiary pediatric
intensive care unit in a middle-income country. Pediatr Crit Care Med. 2011;12:e713.
3. James CS, Hallewell CP, James DP, et al. Predicting the success of non-invasive ventilation in
preventing intubation and re-intubation in the paediatric intensive care unit. Intensive Care
Med. 2011;37:19942001.
4. Mayordomo-Colunga J, Medina A, Rey C, et al. Non invasive ventilation after extubation in
paediatric patients: a preliminary study. BMC Pediatr. 2010;10:29.
5. Pons-Odena M. Anlisis de la efectividad de la ventilacin no invasiva en el paciente peditrico
con insuficiencia respiratoria aguda. MS thesis, University of Barcelona, Department of
Obstetrics and Gynecology. Pediatrics, Radiology and Medicine Physic, Anatomy, Spain;
2013. http://hdl.handle.net/10803/126115. Web. 21 Apr 2014.
respiratory failure: a meta-analysis. Heart Lung. 2014;43:99104.
7. Gupta P, Kuperstock JE, Hashmi S, et al. Efficacy and predictors of success of noninvasive
ventilation for prevention of extubation failure in critically Ill children with heart disease.
Pediatr Cardiol. 2013;34:96477.
8. Wakeman R. A randomised trial of elective continuous positive airway pressure (CPAP) versus
rescue CPAP after extubation in infants following cardiac surgery. Available at: www.
controlled-trials.com/isrctn/pf/00171143. Accessed 10 June 2014.
9. Cai-Yun Z, Lin-Hua T, Shan-Shan S, et al. Noninvasive ventilation via bilevel positive airway
pressure support in pediatric patients after cardiac surgery. World J Pediatr. 2006;2:
297302.
10. Kovacikova L, Skrak P, Dobos D, et al. Noninvasive positive pressure ventilation in critically
Ill children with cardiac disease. Pediatr Cardiol. 2014;35:67683.
422
11. Khirani S, Bersanini C, Aubertin G, et al. Non-invasive positive pressure ventilation to facilitate the post-operative respiratory outcome of spine surgery in neuromuscular children. Eur
Spine J. 2014;23 Suppl 4:S40611.
12. Murase K, Chihara Y, Takahashi K, et al. Use of noninvasive ventilation for pediatric patients
after liver transplantation: decrease in the need for reintubation. Liver Transpl. 2012;18:
121725.
13. Stucki P, Perez MH, Scalfaro P, et al. Feasibility of non-invasive pressure support ventilation
in infants with respiratory failure after extubation: a pilot study. Intensive Care Med.
2009;35:16237.
14. Gonzlez Snchez M. Saturacin transcutnea/fraccin inspirada de oxgeno es til para predecir el fracaso de la ventilacin no invasiva? MS thesis, Departamento de Medicina, Facultad
de Medicina, Universidad de Oviedo, Spain; 2014.
15. Mayordomo-Colunga J, Pons M, Lpez Y, et al. Predicting non-invasive ventilation failure in
children from the SpO2/FiO2 (SF) ratio. Intensive Care Med. 2013;39:1095103.
High-Flow Nasal Cannula Oxygen

in Acute Respiratory Post-extubation
Failure in Pediatric Patients:
Key Practical Topics and Clinical
Implications
52
F. Javier Pilar and Yolanda M. Lopez Fernandez
Abbreviations
CPAP
HFFM
HFNC
HFNP
HR
ICU
NCPAP
NIV
RR
WOB

High-flow face mask
High-flow nasal prongs
Heart rate
Intensive care unit
Nasal continuous positive airway pressure
Respiratory rate
Work of breathing
Optimal oxygen supply is the cornerstone of treatment of patients in critical condition, especially in patients at high risk of extubation failure. A high-flow nasal cannula is a relatively new device for delivery of heated and humidified medical gas
mixtures at flow rates that exceed a patients inspiratory flow rate [1, 2]. The use of
this device has been associated with improvements in washout of nasopharyngeal
dead space; reduction of the inhalation resistance related to the passage of air
through the nasopharyngeal airway; improvement in pulmonary compliance and
elasticity compared with dry, cold gas; lung mucociliary clearance; and a certain
degree of distending pressure for alveolar recruitment [3]. There are many experiences in the use of this device, mainly in neonatology and adult intensive care,
including weaning from invasive ventilation.
F.J. Pilar, MD, FCO (*) Y.M.L. Fernandez
PICU, Cruces University Hospital, Baracaldo, Spain
e-mail: FCO.JAVIER.PILARORIVE@osakidetza.eus;
YOLANDAMARG.LOPEZFERNANDEZ@osakidetza.net
DOI 10.1007/978-3-319-04259-6_52
423
F.J. Pilar and Y.M.L. Fernandez
424
52.1
Introduction
Delivery of supplementary oxygen represents the first step in supporting patients

who have a respiratory problem, including after endotracheal extubation. The most
usual techniques to administer oxygen are via a face mask, alone or with a bag, or a
nasal cannula. This oxygen is not usually heated, so humidity obtained with these
devices is inadequate. As a rule, low oxygen flows are used, given the poor tolerance
of nonhumidified higher flows. Depending on the age of the patient, low flows are
considered to be 1 l/min in neonates, 2 l/min in children, and <6 l/min in adults.
52.2
Concept
In high-flow oxygen (HFO) therapy, a flow of oxygen, which may or may not be
mixed with air, is delivered through a nasal cannula. This gas is humidified (>99 %
relative humidity) and heated (to body temperature). The heating and humidification in the vapor phase allow comfortable delivery at higher flows [1, 2]. Figure 52.1
shows the mechanism through which the high flow obtains better concentrations of
oxygen compared with low-flow systems. High flow is considered to be between
When
inspiratory peak flow > delivered flow :
Flow
(l/min)
When
inspiratory peak flow < delivered flow :
Flow
21%
(ambiant air)
(l/min)
Delivered flow
Delivered flow
Delivered concentration
Delivered concentration
Delivered gas
dilution with
ambiant air
Inspired FiO2 < Delivered O2

concentration setting
Inspired FiO2 =
Delivered O2 concentration setting
Fig. 52.1 Mechanism by which HFO therapy obtains better oxygen concentrations in relation to
low-flow systems
52 High-Flow Nasal Cannula Oxygen in Acute Respiratory Post-extubation Failure
425
2 and 8 l/min in neonates, 5 and 20 l/min in children, and 6 and 40 l/min in adults.
The HFO therapy concept was first used in neonatal intensive care units as an alternative to nasal continuous positive airway pressure (CPAP) in premature neonates.
52.3
Mechanism of Action [3]
HFO accomplishes washout of nasopharyngeal dead space. The extrathoracic dead

space in children is proportionally two or three times greater than in adults. It may
measure up to 3 ml/kg in newborns; after 6 years of age it becomes similar to the
adult volume. Under normal conditions in children, during breathing, approximately
30 % of the tidal volume inhaled is anatomic dead space. At the beginning of the
inhalation, this dead space is filled with gas from the previous breath remaining at
the end of the exhalation. Therefore, HFO may improve breathing efficiency by
flooding the nasopharyngeal dead space with clean gas, thereby contributing to
improving the minute ventilation. As in the case of any reduction in anatomic or
physiological dead space, this treatment contributes to establishing better alveolar
gas fractions, facilitating oxygenation, and bringing a theoretical improvement in
carbon dioxide (CO2) elimination.
Because HFO provides a flow that is sufficient to equal or exceed the patients
inhalation flow, it is likely to reduce the inhalation resistance related to the passage
of air through the nasopharyngeal airway. This gives rise to a change in the work of
breathing (WOB).
The appropriate heating and humidification of the airways is associated with
improved pulmonary compliance and elasticity compared with dry, cold gas. In
addition, the nasal mucosa receptors respond to cold, dry gas by provoking a protective bronchoconstriction in normal and asthmatic subjects. The heated, humidified
air generates a beneficial effect on the ciliary movement, clearing of secretions, and
prevention of atelectasis. HFO reduces the metabolic work required to heat and
humidify external air, which is drier and colder with respect to body temperature
and humidity.
Despite the different hypotheses postulated in the literature with respect to the
mechanisms of action of HFO, there seems to be agreement about the fact that it
originates a certain positive pressure on the airway. This pressure is variable
(ranging from scant to excessive), is relatively unpredictable, cannot be regulated,
and is related to the flow, size of the patients nasal cannulas, leaks, and whether
the mouth is closed. One of the main differences between HFO and noninvasive
ventilation (NIV) is that the former maintains a fixed flow and generates variable
pressures, whereas NIV systems use variable flows to obtain a fixed pressure.
HFO improves the ventilation pattern, reducing the respiratory frequency, heart
rate, and oxygen needs, but does not normally affect alveolar partial pressure carbon dioxide (PaCO2) or pH. The devices are easy to apply and allow the children
to eat, talk, and move. The tendency to use HFO is partly the result of a perception
of greater ease in using it and improved tolerance by the patient, thereby achieving further benefits.
426
Table 52.1 Advantages and disadvantages of HFO therapy

Advantages
Noninvasive
99 % humidity
High oxygen concentrations
Prevents claustrophobia
Easy to use
Better tolerated than CPAP
Allows patient to eat and talk
52.4
Disadvantages
Rhinorrhea, sialorrhea
Less effective in oral respiration
Prolonged situations: nasal trauma
Pneumothorax, pneumomediastinum
High level of noise correlated with the flow
Advantages and Disadvantages
There are few disadvantages because this system has good tolerance. In some cases,
abdominal distension may be observed due to flatulence. Condensation may occur
in the nasal cannula at low flows. There has been described air leak syndrome
(pneumothorax, pneumomediastinum) [4]. In prolonged situations, nasal trauma
may occur, and another disadvantage is the high level of noise correlated with the
flow (Table 52.1).
52.5
Administration Methods
There are several commercial systems for administering HFO (Fig. 52.2):
Precision Flow (Vapotherm, Exeter, UK), the first system approved for use in
patients by the US Food and Drug Administration in 2004
Optiflow system (Fisher & Paykel, Auckland, New Zealand)
Comfort-flo (Teleflex Medical, Durham, NC, USA).
No studies have demonstrated differences in efficacy between systems. They
may be used in all age groups (neonates, infants, children, and adults). These devices
require a gas source (air and oxygen) to generate the necessary flow, a heated
humidifier, circuit tubing sized for the patient, and a nasal cannula.
The nasal cannula may be of different sizes, depending on the flow used; the
outer diameter of the cannula should be less than the internal diameter of the nose,
to ensure it is not completely high-flow oxygen therapy and continuous positive
airway pressure blocked and to prevent excess pressure and pressure sores. It is
advisable for it to measure at least half the diameter of the nostril. One difference
between the systems is the presence of an (Precision Flow, Optiflow system). This
allows the maximum pressure generated by the device to be controlled, thus reducing the risk of a sudden increase in the pressure in the airways, which suggests they
may be useful in neonatal air leak syndromes.
Precision flow (Vapotherm)
427
Optiflow system (Fisher & Paykel)
Fig. 52.2 Commercial systems for administering HFO
The HFO system can be used to incorporate medicinal gases (e.g., heliox 70/30,
NO) and drugs in aerosol form can also be administered. In vitro studies show that
with this method high dosis of drug are requiered, otherwise we can use heliox as a
vehicle to achive the appropiate levels. Until new studies emerge, the administration
of these drugs using this device is not recommended.
52.6
Indications
No evidence can be found to allow determination of the safety or effectiveness of

the high-flow nasal cannula (HFNC) therapy as a form of respiratory support in
children [5]. Nor are there established guidelines or decision-making pathways to
guide use of the HFNC therapy in adults. In summary, there are no clearly established indications for the use of HFO. They are extrapolated from observational or
physiological studies, mainly in adults and premature infants without evidence
(Table 52.2). It is used for the same indications as the traditional method of CPAP
and may be more effective than standard oxygen supply devices for oxygenation in
the post-extubation period.
428
Table 52.2 Indications for the use of HFNC

HFNC indications
Moderate respiratory failure and/or need for high oxygen intake
Apnea pauses. Obstructive sleep apnea
Upper airway obstruction. Laryngitis after extubation
Airway inflammation (asthma, bronchiolitis)
Heart failure
Withdrawal of mechanical ventilation or noninvasive ventilation
For clinical practice, HFO seems feasible in mild to moderate forms of respiratory distress and hypoxemia, transcutaneous oxygen saturation (SpO2) <90 %,
despite standard flow oxygen. It is useful in hypoxemic, nonhypercapnic patients
who require fraction of inspired oxygen (FiO2) >0.3 using a face mask (type I
respiratory failure). It is not considered useful in type II respiratory failure
because it does not reduce PaCO2 levels and is not indicated in CO2 retainers
because it reduces the respiratory stimulus triggered by hypoxia that is produced
in hypoventilation.
Most pediatric studies published refer to infants with bronchiolitis, proving its
safety and efficacy, however, its efficacy has not been demonstrated in asthma or
pneumonia. The beneficial clinical effects of HFO (increase in SpO2, reduction in
O2, respiratory rate (RR) and heart rate (HR) needs, and improvement in breathing
difficulty symptoms) should be observed during the first 6090 min from initiation;
otherwise, more aggressive ventilation support should be considered.
Schibler et al. [6], who used HFO over a period of 5 years, determined that the
general need for intubation was reduced from 37 to 7 % in infants with bronchiolitis. This was not detected in children with other pathologies. They also showed that
infants using HFO who had a reduction of more than 20 % in RR and HR compared
with the initial rates did not require increased respiratory support.
If no improvement is observed after 90 min of support with HFO, it is essential
to evaluate the need to intensify respiratory assistance.
52.7
Instructions for Use
At present, there are no guidelines and/or decision-taking guides established in

adults or in children that could serve as a guide for applying treatment with
HFO. Some authors start by adjusting the flow to 810 times the minute volume of
the patient from approximately 812 l/min in infants and 2030 l/min in children. It
is advisable to start with low flows:
Start off with: 6 l/min

In infants: 1 l/kg/min up to 2 l/kg/min
In children 1 l/kg/min up to 1.5 l/kg/min (max. 2030 lpm)
In adults: 20 l/min up to 4050 lpm
429
FiO2 is set to achieve target saturation >92 % then gradually increased until the
desired effect is obtained. Some patients improve with low flows and others need to
reach the maximum established limits.
Unfortunately, currently, there is no evidence to suggest that any particular
approach to weaning HFNC is either more effective or efficient. Once the respiratory rate has been normalized and the oxygenation improved, weaning can commence. It usually starts by decreasing the oxygen concentration to FiO2 40 %, then
the flow is reduced 510 l/min every 12 h until it reaches the initial level. It is not
uncommon to use high flow without oxygen trying to keep the pressure of alveolar
distension. At this point, an oxygen mask or nasal cannula is used and the response
is evaluated. Some centers use other approaches to weaning, such as gradually
reducing FiO2 to 0.21 (room air) while maintaining appropriate oxygen saturations.
HFNC therapy is discontinued when the child remains well saturated in air.
In cases in which hypoxemia of the patient does not improve with HFO and he
or she is unable to tolerate continuous CPAP, CPAP used alternately with HFO can
be used.
A study by Milesi et al. [7] on infants under the age of 6 months with bronchiolitis in which the esophageal and pharyngeal pressure was measured showed that
positive pharyngeal pressures were obtained with flows higher than 6 l/min during
inspiration as well as expiration. When using flows of 2 l per kg of weight, the average pharyngeal pressure reached was higher than 4 cm of H2O. The 21 patients
studied by Milesi were 1.5 months old (95 % CI 0.752.19, range 0.56) and
weighed 4.3 kg (95 % CI 3.64.9, range 2.67.3). To prevent leaks, pacifiers and a
cannula with a diameter at least half that of the nostril was used. It was considered
that the basic fundamental of improving WOB in these children was reached at this
positive pressure.
52.8
Weaning of Mechanical Ventilation
In the neonatal population, weaning from invasive ventilation is one of the main
indications for HFO. Nasal CPAP is known to be superior to no positive-pressure
support and is the current standard of care for noninvasive respiratory support of
very preterm infants. The use of HFNC is an alternative means of providing noninvasive respiratory support to very preterm infants.
Manley et al. [8], in a multicenter, randomized, noninferiority trial, studied 303
very preterm infants receiving treatment with either HFNC (56 l per minute) or
nasal CPAP (7 cm of water) after extubation. The primary outcome was treatment
failure within 7 days. They showed that the use of HFNC was noninferior to the use
of nasal CPAP, with treatment failure occurring in 52 of 152 infants (34.2 %) in the
nasal cannula group and in 39 of 151 infants (25.8 %) in the CPAP group (risk difference, 8.4 % points; 95 % CI, 1.9 to 18.7). Almost half the infants in whom
treatment with HFNC failed were successfully treated with CPAP without reintubation. The efficacy of HFNC was similar to that of CPAP as respiratory support for
very preterm infants after extubation
430
Collins et al. [9] studied whether post-extubation respiratory support via heated,
humidified, HFNC resulted in a greater proportion of infants younger than 32 weeks
gestation being successfully extubated after a period of endotracheal positive pressure ventilation compared with conventional nasal continuous positive airway pressure (NCPAP). The authors did not find differences in the rates of extubation failure
between infants randomized to HFNC or NCPAP in the first 7 days after extubation.
HFNC was associated with significantly less nasal trauma compared with NCPAP.
In the Cochrane review on HFO for respiratory support in premature infants,
Wilkinson et al. [10] concluded that here is insufficient evidence to determine the
safety and efficacy of HFO in infants.
No definitive data support that HFO is superior to CPAP in neonatal respiratory
distress.
In infants younger than 18 months, Testa et al. [11], in a randomized controlled
trial with 89 patients, compared HFO to conventional oxygen therapy in extubation
48-h after cardiac surgery. HFNC was not useful in decreasing PaCO2 in postcardiac
surgery infants. Conversely, the use of HFNC in pediatric cardiac surgical patients
can be considered safe and a better option than O2 therapy to improve oxygenation
and to decrease the need for noninvasive post-extubation respiratory support.
In the adult population, a few studies have suggested the advantages of using
HFO for this indication. Parke et al. [12] showed that in adult patients with cardiac
conditions, the use of post-extubation HFNC was not associated with an increase in
postoperative oxygenation compared with the usual therapy, although it may have
been associated with a reduced requirement for escalation of therapy and slightly
lower PaCO2. They concluded that, in the absence of any demonstrable benefit, it
would be hard to justify the routine use of HFNC after extubation in patients undergoing a normal postoperative trajectory after cardiac surgery.
Tiruvoipati et al. [13] compared high-flow face mask (HFFM) with high-flow
nasal prongs (HFNP) in extubated patients. Their study reveals that HFNP are comparable with HFFM in terms of providing adequate gas exchange. HFNPs were
tolerated better than HFFM, and there was a trend toward better patient comfort
with the use of HFNPs that did not reach statistical significance. However, the study
does not address other important issues such as the requirement of reintubation,
noninvasive ventilation, duration of intensive care unit (ICU) and hospital stay, and
survival. This study is the first to evaluate the short-term physiologic benefits of
HFNC compared with non-rebreathing mask in these subjects.
Rittayamai et al. [14], in a randomized crossover study of 17 mechanically ventilated patients after extubation, found that the use of HFO via nasal cannula reduced
dyspnea and resulted in a lower breathing frequency and heart rate compared with
oxygen via non-rebreathing mask.
Finally, Maggiore et al. [15], in a randomized, controlled open-label trial with
105 patients with a PaO2/FiO2 ratio 300 immediately before extubation, compared
the effects of the Venturi mask and nasal high-flow therapy. The latter resulted in
better oxygenation for the same set FiO2 after extubation, better comfort, fewer
desaturations, and a lower reintubation rate.
431
Conclusions
HFO is an interesting method for respiratory support, despite the lack of established benefits in the medical literature. Until this happens, it should be considered a method of respiratory support that is easy to use, well tolerated, and with
few side effects, such as local trauma, but with potential risks (unpredictable
pressure in airways, pneumothorax, etc.).
Based on some reports, HFO may be effectively and safely applied to a
broader spectrum of patient ages and diagnoses. Based on our experience with
this method, we believe that HFO can be included as a therapy in respiratory
care. When initiating support with oxygen using nasal prongs or a mask, the next
step, depending on the patients situation, would be HFO before using other
options such as CPAP, NIV, mechanical conventional ventilation, and high-frequency oscillatory ventilation.
For the moment, application of HFO in weaning is based only on clinical
judgment and initiated with great caution.
1. There are no clearly established indications for the use of HFO therapy.
2. No evidence can be found to allow determination of the safety or effectiveness of HFNC therapy as a form of respiratory support in children.
3. HFO should be considered as a method of respiratory support that is easy to
use, well tolerated, and has few side effects, such as local trauma, but with
potential risks (unpredictable pressure in airways, pneumothorax, etc.).
4. HFO use seems feasible in mild to moderate forms of respiratory distress,
hypoxemia, and transcutaneous oxygen saturation (SpO2) <90% despite
standard flow oxygen.
5. In postoperative use of HFO in adults, studies found a better tolerance with
HFO but the studies do not address other important issues such as the
requirement of reintubation, NIV, duration of ICU and hospital stay, and
survival.
References
1. Pilar J, Lopez Y, Morteruel E. High flow oxygen therapy and continuous positive airway pressure. In: Medina A, editor. Non-invasive ventilation in pediatrics. 2014. p. 5360.
2. Lee JH, Rehder KJ, Williford L, Cheifetz IM, Turner DA. Use of high flow nasal cannula in
critically ill infants, children, and adults: a critical review of the literature. 3rd edition ERGON
Barcelona 2014. Intensive Care Med. 2013;39:24757.
3. Dysart K, Miller TL, Wolfson MR, et al. Research in high flow therapy: mechanism of action.
Respir Med. 2009;103:14005.
4. Hegde S, Prodhan P. Serious air leak syndrome complicating high-flow nasal cannula therapy:
a report of 3 cases. Pediatrics. 2013;131:e16.
432
5. Mayfield S, Jauncey-Cooke J, Hough JL, et al. High flow nasal cannula therapy for respiratory
support in children. Cochrane Database Syst Rev. 2014;3, CD009850.
6. Schibler A, Pham TM, Dunster KR, et al. Reduced intubation rates for infants after introduction of high flow nasal prong oxygen delivery. Intensive Care Med. 2011;37:84752.
7. Milesi C, Baleine J, Matecki S, et al. Is treatment with a high flow nasal cannula effective in
acute viral bronchiolitis? A physiologic study. Intensive Care Med. 2013;39:108894.
8. Manley BJ, Owen LS, Doyle LW, et al. High-flow nasal cannulae in very preterm infants after
extubation. N Engl J Med. 2013;369:142533.
9. Collins CL, Holberton J, Barfield C, et al. A randomized controlled trial to compare heated
humidified high-flow nasal cannulae with nasal continuous positive airway pressure postextubation in premature infants. J Pediatr. 2013;162:94954.
10. Wilkinson D, Andersen C, ODonnell C, et al. High flow nasal cannula for respiratory support
in preterm infants. Cochrane Database Syst Rev. 2011;5, CD006405.
11. Testa G, Iodice F, Ricci Z, et al. Comparative evaluation of high-flow nasal cannula and conventional oxygen therapy in paediatric cardiac surgical patients: a randomized controlled trial.
Interact Cardiovasc Thorac Surg. 2014;19:45661.
12. Parke R, McGuinness S, Dixon R, et al. Open-label, phase II study of routine high-flow nasal
oxygen therapy in cardiac surgical patients. Br J Anaesth. 2013;111:92531.
13. Tiruvoipati R, Lewis D, Haji K, et al. High-flow nasal oxygen vs high-flow face mask: a randomized crossover trial in extubated patients. J Crit Care. 2010;25:4638.
14. Rittayamai N, Tscheikuna J, Rujiwit P. High-flow nasal cannula versus conventional oxygen
therapy after endotracheal extubation: a randomized crossover physiologic study. Respir Care.
2014;59:48590.
15. Maggiore SM, Idone FA, Vaschetto R, et al. Nasal high-flow versus Venturi mask oxygen
therapy after extubation effects on oxygenation, comfort, and clinical outcome. Am J Respir
Crit Care Med. 2014;190:2828.
Noninvasive Positive Pressure

Ventilation by Means of a Nasal Mask
May Avoid Recannulation After
Decannulation in Pediatric Patients: Key
Practical Aspects and Implications
53
Brigitte Fauroux, Alessandro Amaddeo, Marion Blanchard,

and Nicolas Leboulanger
53.1
Introduction
Tracheostomy is an age-old technique that has undergone a remarkable transformation in recent years, both in its indications and in the profile of the tracheostomized
patients. Until some 40 years ago, it was considered a short-term emergency procedure, mainly to resolve acute upper-airway obstruction, mostly for infectious causes,
such as diphtheria, epiglottis, or laryngotracheitis. Despite the decrease of these
pathologies, the incidence of tracheostomy in children has remained stable over the
past decades. This is explained by the increased survival of technology-dependent
children, referring mainly to children on long-term assisted ventilation, or with congenital or acquired upper-airway anomalies [1]. Indeed, congenital or acquired
upper-airway abnormalities are common in children. These abnormalities may concern the nose (i.e., choanal atresia); the mid- and lower face (mid-face hypoplasia,
achondroplasia, Down syndrome, Pierre Robin syndrome, Treacher Collins syndrome); the larynx (laryngomalacia, subglottic stenosis, vocal cord paralysis); and
the trachea (tracheomalacia, tracheal stenosis). All these conditions may be
B. Fauroux, MD, PhD (*)

Pediatric Noninvasive Ventilation and Sleep Unit, AP-HP, Necker University Hospital, Paris
Descartes University, Research Unit Inserm U 955, Team 13, 94000 Creteil, France
e-mail: brigitte.fauroux@nck.aphp.fr
A. Amaddeo, MD
Pediatric Noninvasive Ventilation and Sleep Unit, AP-HP, Necker University Hospital, Paris,
France
e-mail: alessandro.amaddeo@gmail.com
M. Blanchard, MD N. Leboulanger, MD, PhD
Pediatric Head and Neck Surgery Department, AP-HP, Necker University Hospital, Paris,
France
e-mail: marion.blanchard@nck.aphp.fr; nicolas.leboulanger@nck.aphp.fr
DOI 10.1007/978-3-319-04259-6_53
433
434
B. Fauroux et al.
responsible for severe upper-airway obstruction, which may persist despite medical
and surgical treatment. A large (including 249 children) prospective national survey
performed in Spain showed that the main indications for a tracheostomy were prolonged ventilation (63 %), acquired subglottic stenosis (14 %), congenital or
acquired craniofacial anomalies (10 %), and congenital airway anomalies (9.6 %)
[1]. The most frequent underlying disorders were neurological (51 %) and respiratory diseases (39 %).
However, tracheostomy is associated with significant morbidity and discomfort
and may impair normal development, particularly language development. The frequency of complications directly related to the tracheostomy is high, reaching
almost 5080 % in most series. Infections, endotracheal granulation, tracheal hemorrhage, cannula obstruction by mucus plugs, accidental displacement or removal,
pneumothorax, subcutaneous emphysema, or trachea-innominate artery fistula are
rare but life-threatening complications. In addition to medical complications, family
and social problems such as social life and family disruption are common in patients
with a tracheostomy. Although tracheostomized children may be safely discharged
home after careful family education and training, home treatment may be difficult
or even unfeasible for some families.
Thus, whenever possible, a decannulation should be proposed. But decannulation failure is common, and decannulation rates have been shown to be quite low in
some series, ranging between 17 and 24 % [1, 2]. Apart from the medical consequences, the psychological consequence of decannulation failure on the child and
the family are important to consider. Indeed, restlessness, anxiety, and depression
were observed more frequently by nursing staff in children who failed decannulation compared with those who were successfully decannulated.
Noninvasive ventilation (NIV), which consists of the delivery of positive airway
pressure by means of a noninvasive interface, is an effective procedure for the treatment of upper-airway obstruction and alveolar hypoventilation due to lung diseases
such as cystic fibrosis, bronchopulmonary dysplasia, and bronchiolitis obliterans.
There is thus a rationale to use NIV as a tool to improve the rate of successful decannulation in children.
53.2
Decannulation Procedure in Children
For decannulation to be successful, the patient must be able to breathe spontaneously around the tracheostomy tube using the natural airway. This ability is evaluated in clinical practice by occluding or capping the cuffless (or deflated if cuffed)
tracheal cannula and evaluating the patient tolerance to this challenge. Several factors, such as the patients age, level of consciousness, duration of spontaneous
breathing prior to decannulation, cough effectiveness, secretions, and level of oxygenation have been identified as predictors of successful decannulation in adults.
However, decannulation procedures vary among centers, which may explain the
variable and often high rate of decannulation failure. One study showed the efficacy
of a standardized tracheostomy capping and decannulation protocol to improve
53
Noninvasive ventilation to facilitate decanulation
435
patient safety and decannulation success in adult patients [3]. However, pediatric
patients cannot be compared with adult patients because of different underlying
diseases and a smaller diameter of the trachea in relation to the cannula, which may
preclude capping. NIV and, in particular, continuous positive airway pressure
(CPAP) in the case of isolated upper-airway obstruction, may constitute extremely
valuable tools to increase the success of decannulation in borderline situations of
respiratory compromise.
Before a decannulation, the patient should fulfill the following conditions [4]
(Fig. 53.1):
The patient should be in a stable condition for at least 1 month. This delay
depends on the childs age and also on the season (with a greater risk of respiratory infection precluding a decannulation during the winter season).
A flexible laryngoscopy should document a patent airway with at least one
mobile vocal cord.
Any granulation tissue should be excised prior to decannulation.
Stable condition for at least one month

Patent airway on endoscopy
Prior excisation of any granulation tissue
No aspiration event
Ability to breathe spontaneously around the cuffless or deflated cuffed cannula during daytime
YES
NO
Overnight sleep study with a cuffless or deflated cuffed (small) cannula

Normal nocturnal gas exchange + normal breathing
NO
YES
Decannulation without
noninvasive continuous
positive airway pressure
No decannulation
Decannulation with
noninvasive continuous
Normal nocturnal gas exchange +
normal breathing
YES
Decannulation with noninvasive continuous

Long term follow up with repeated clinical, endoscopy and sleep evaluations
Fig. 53.1 Necker hospital decannulation flow chart
NO
436
B. Fauroux et al.
There should be no signs of ongoing aspiration events such as pneumonia or

pooling secretions with the need of multiple suctioning to clear secretions.
Children over the age of 2 years should be able to breathe spontaneously around
the cuffless or deflated cuffed cannula during daytime. If the child tolerates a cap,
options prior to decannulation include but are not limited to a capped overnight
sleep study with at least a careful clinical observation with oximetry and carbon
dioxide monitoring. Prior to this test, the tracheal cannula should be changed for
a smaller model, to favor easier breathing during nocturnal sleep.
In children younger than 2 years of age, capping is not recommended and the
decannulation protocol should be individualized.
Adequate airway patency during sleep should be assessed by the absence of
obstructive symptoms such as stridor, agitation, arousals, night sweats, and the
absence of nocturnal hypoxemia (less than 5 consecutive minutes with a pulse
oximetry (SpO2) <90 %) and/or hypercapnia (transcutaneous carbon dioxide
(PtcCO2) >50 mmHg) while sleeping in room air with a cuffless or deflated
cuffed cannula.
If the patient fulfils these criteria, decannulation can be performed without
CPAP. A short-term (following days and nights), intermediate (following weeks),
and long-term (following months) evaluation should be systematically performed
with clinical examination, endoscopic evaluations when indicated, and regular nocturnal gas exchange recordings.
If the patient presents with persistent airway obstruction during sleep, as reflected
by obstructive symptoms as described above and abnormal nocturnal gas exchange
in room air with at least 5 consecutive minutes with a SpO2 <90 % and/or a PtcCO2
>50 mmHg, CPAP can be proposed prior to decannulation to promote sufficient
airway patency. CPAP can also be proposed after several previous failed decannulation attempts. The CPAP acclimatization may be quite difficult in this group of
patients because of young age and the anxiety associated with breathing without a
cannula. The decannulation procedure with CPAP may take several days, according
to the patient. The first step consists of the acclimatization of the patient to the nasal
mask only, without the CPAP device. This step may take between 2 and 15 days,
depending on the age of the patient, and on his or her medical and psychological
history. Then, when the patient accepts wearing the nasal mask with the headgear,
CPAP without sedation is tried for short periods, lasting 25 min, which are repeated
during the daytime. When daytime tolerance exceeds 15 continuous minutes, CPAP
is tried during the night with a cuffless or deflated cuffed cannula. Because of the
partial airway obstruction due to the presence of the cannula, the CPAP pressure
should be set at least 2 cm H2O above the level that would have been chosen without
the cannula in place. Overnight SpO2 and PtcCO2 recordings should be systematically performed. When the child is acclimatized to CPAP, the tracheal cannula can
be removed with the adjustment of the CPAP settings to obtain a normal breathing
pattern without stridor and normal nocturnal gas exchange.
CPAP devices are continuous positive pressure devices set in a constant pressure
mode, as bi-level pressure has not proved to be superior to constant CPAP. But the
53
Noninvasive ventilation to facilitate decanulation
437
choice of an adequate interface is even more important for the acceptance and tolerance of CPAP [5]. Because of their excellent tolerance, nasal cannula or prongs are
used as a first-line interface but they are only available for children over the age of
68 years [5]. Nasal masks, or facial masks in case of mouth leaks, are proposed as
second-line choice interfaces. The availability of industrial nasal masks for infants
will help to expand the use of CPAP in this setting. Unintentional leaks through the
tracheal stoma, which may compromise the efficacy and tolerance of NIV, can be
managed by occluding the tracheal stoma with a sticking plaster. A surgical closure
of the tracheal stoma should be discussed in case of persistent leaks through the
tracheal stoma.
Discharge at home with CPAP is allowed when the following criteria are fulfilled: (1) ability to sleep at least 5 h with CPAP, (2) absence of nocturnal hypoxemia
or hypercapnia while on CPAP without supplemental oxygen, and (3) parents and
family adequately educated to CPAP.
In our experience, CPAP has been shown to be an effective tool for the decannulation of children who could not tolerate overnight sleep with a cuffless or deflated
cuffed cannula and also to avoid recannulation in case of upper-airway obstruction
recurrence after a successful immediate decannulation [6].
Conclusion
Tracheotomy remains an effective treatment for severe upper-airway obstruction, but this procedure is associated with a significant morbidity and mortality.
CPAP, by maintaining upper-airway patency by means of a noninvasive interface, may increase the rate of success of decannulation and reduce the need for
recannulation. Close collaboration between ear, nose, and throat (ENT) surgeons and pediatric pulmonologists with an expertise in NIV is highly
recommended.
A decannulation should be discussed as soon as possible for every

tracheostomy.
Standardized protocols increase the rate of successful decannulation.
Noninvasive ventilation by means of a constant positive pressure may
improve the rate of successful decannulation in children and may avoid
recannulation in case of upper-airway obstruction recurrence after a successful immediate decannulation.
Optimal decannulation profits from a close collaboration between ENT
surgeons and pediatric pulmonologists with expertise in NIV/CPAP.
438
B. Fauroux et al.
References
1. Prez-Ruiz E, Caro P, Prez-Fras J, et al. Paediatric patients with a tracheostomy: a multicentre epidemiological study. Eur Respir J. 2012;40:15027.
2. Dursun O, Ozel D. Early and long-term outcome after tracheostomy in children. Pediatr Int.
2011;53:2026.
3. Pandian V, Miller CR, Schiavi AJ, et al. Utilization of a standardized tracheostomy capping and
decannulation protocol to improve patient safety. Laryngoscope. 2014;124(8):1794800.
4. Mitchell RB, Hussey HM, Setzen G, et al. Clinical consensus statement: tracheostomy care.
Otolaryngol Head Neck Surg. 2013;148:620.
5. Ramirez A, Delord V, Khirani S, et al. Interfaces for long term noninvasive positive pressure
ventilation in children. Intensive Care Med. 2012;38:65562.
6. Fauroux B, Leboulanger N, Roger G, et al. Noninvasive positive-pressure ventilation avoids
recannulation and facilitates early weaning from tracheotomy in children. Pediatr Crit Care
Med. 2010;11:317.
Home Mechanical Ventilation

in Ventilator-Dependent Children:
Criteria, Outcome, and Health
Organization
54
Noninvasive Ventilation in Ventilator-Dependent

Children with Neuromuscular Disease
Amit Agarwal and Punkaj Gupta
Abbreviations
ARDS
ARF
BIPAP
BiPA
CPAP
FiO2
IPPV
NPPV
NIV
PICU
PaO2
PaCO2
SpO2
54.1
Acute respiratory distress syndrome

Biphasic positive pressure ventilation
Bilevel positive pressure ventilation
Fraction of inspired oxygen
Invasive positive pressure ventilation
Non-invasive positive pressure ventilation
Non-invasive ventilation
Pediatric intensive care unit
Arterial partial pressure of oxygen
Arterial partial pressure of carbon dioxide
Arterial oxygen saturation measured by pulse oximetry
Introduction
The common etiologies of respiratory failure requiring chronic ventilatory support in

children include neuromuscular diseases (NMDs), congenital central hypoventilation
syndrome, spinal cord injury, craniofacial abnormalities, severe tracheobronchomalacia, chronic lung disease, and bronchopulmonary dysplasia. Prevalence of NMD is
A. Agarwal (*) P. Gupta
Department of Pediatrics Divison of Pediatric, Pulmonology and Sleep Medicine,
University Of Arkansas for Medical Sciences, Little Rock Arkansas, USA
DOI 10.1007/978-3-319-04259-6_54
439
440
A. Agarwal and P. Gupta
about 1 in 3,000. Positive-pressure ventilation is often used to provide respiratory support for children with acute respiratory failure (ARF) because it increases the tidal
volume and therefore helps to recruit lung tissue and maximize lung volumes, reversing hypoxemia and hypercapnia. Mechanical ventilation (MV) can be delivered via
positive-pressure breaths or negative-pressure breaths. Additionally, the positive-pressure breaths may be delivered noninvasively or invasively. Noninvasive ventilation
(NIV) is defined as the use of a mask or nasal prongs to provide ventilatory support
through a patients nose and/or mouth. By definition, this technique is distinguished
from those ventilatory techniques that bypass the patients upper airway with an artificial airway (endotracheal tube, laryngeal mask airway, or tracheostomy tube). To
reduce the effect of complications associated with protracted invasive ventilation,
investigators have explored the role of NIV in weaning patients from invasive ventilation. Noninvasive weaning involves extubating patients directly to NIV for the purpose
of weaning to reduce the duration of invasive ventilation and, consequently, complications related to intubation. Use of NIV has seen increasing popularity in pediatric
patients with both chronic respiratory failure and ARF of numerous etiologies [1].
Negative-pressure ventilation is an alternative form of NIV that uses a rigid cuirass that covers the chest and abdomen. Applied negative-pressure leads to diaphragmatic descent and ventilation, provided that the upper airway is stable. Modern
pediatric machines are available, but they are relatively expensive and offer little
clinical advantage over positive-pressure machines and thus are infrequently used
for ARF or chronic respiratory failure.
The benefits of noninvasive positive pressure ventilation (NPPV) for ARF are
being increasingly recognized in patients with chronic respiratory insufficiency. It
has been applied to pediatric patients with a variety of respiratory disorders associated with impending ARF of almost any etiology, including pneumonia, pulmonary
edema, postoperative respiratory decompensation in sleep apnea syndrome, status
asthmaticus, neuromuscular weakness, airway obstruction (including laryngotracheal malacia), postextubation atelectasis, and chronic respiratory failure [27].
The success of this technique depends not only on the diagnosis of respiratory failure and patients characteristics but also on when the ventilation is started and the
setting in which the patient is treated. A study in the state of Massachusetts in the
United States found that the highest percentage of children requiring MV is no longer due to the chronic lung disease associated with premature birth but rather for
reasons related to congenital and neurological disorders and NMDs [8]. This chapter focuses on positive-pressure ventilation via noninvasive interface in pediatric
patients with ARF and chronic neuromuscular weakness.
54.2
Management of ARF in Children with NMD
Respiratory failure is the most common cause of morbidity and mortality in patients
with slowly or rapidly progressive NMD. There are a wide variety of NMDs that
can compromise respiratory functions, as summarized in Table 54.1. Depending on
clinical onset of ARF, NMDs can be also classified as: (1) slowly progressive NMD
with acute exacerbations of chronic respiratory failure, and (2) rapidly progressive
54
Home Mechanical Ventilation in Ventilator-Dependent Children
441
Table 54.1 Neuromuscular diseases affecting respiratory functions

Myopathies
Acquired myopathies
Polymyositis, dermatomyositis
Critical illness myopathy
Toxic myopathy
Hereditary myopathies
Progressive muscular dystrophy
Duchenne muscular dystrophy
Becker muscular dystrophy
Facioscapulohumeral muscular dystrophy
Limb-girdle muscular dystrophy
Myotonic dystrophy
Congenital myopathies
Myofibrillar myopathy, nemaline myopathy, central core diseases, myotubular myopathy
Congenital muscular dystrophy
Ullrich congenital muscular dystrophy, EmeryDreifuss muscular dystrophy, merosindeficient congenital muscular dystrophy, merosin-positive congenital muscular dystrophy,
rigid spine muscular dystrophy
Metabolic myopathies
Mitochondrial myopathy, glycogen storage disease type 2
Neuropathic disease
Motor neuron disease
Poliomyelitis, post-polio syndrome
Spinal muscular atrophy
Paralytic rabies
Peripheral neuropathies
GuillainBarre syndrome, chronic inflammatory demyelinating
Polyneuropathy
Critical illness polyneuropathy
Unilateral or bilateral diaphragm paralysis
CharcotMarieTooth disease
Disorders of the neuromuscular junction
Myasthenia gravis, congenital myasthenic syndrome, LambertEaton myasthenic syndrome
Botulism, poisoning with curare and organophosphate
NMD with acute episodes of respiratory failure. Spinal muscular atrophy (SMA)
and inherited myopathies (e.g., Duchenne muscular dystrophy) are the most frequent slowly progressive NMDs in children.
When these patients develop chronic respiratory failure, long-term MV is the
main therapeutic intervention to support their respiratory muscle function, increasing life expectancy and health-related quality of life. However, these patients are at
high risk of developing acute exacerbations of respiratory failure. The potential
causes of respiratory failure in patients with NMD include upper respiratory tract
442
Inspiratory
Muscle
Weakness
Ventilatory Dysfunction
Hypoventilation
Ventilation perfusion
mismatch
Diurnal
Ventilation
failure
Impaired
Bulbar
Function
Expiratory
Muscle
Weakness
Upper air way

dysfunction
Impaired Cough
Impaired clearance of
tracheal secretions
Atelectasis
Pneumonia
Swallowing Dysfunction
Aspiration
Sleep
Disordered
Breathing
Fig. 54.1 Mechanisms of Respiratory dysfunction in children with neuromuscular disease
infections, pneumonia, atelectasis, cardiac failure secondary to cardiomyopathy

and/or arrhythmia, sedative drugs, aspiration, pneumothorax, pulmonary embolism,
and acute gastric distension associated with use of NIV.
54.3
Mechanisms Underlying ARF in NMD
In patients with slowly progressive NMD, ARF is caused by an imbalance

between the respiratory load and muscle strength, resulting in ineffective alveolar ventilation and hypercapnia. In contrast, in patients with rapidly progressive
NMD, such as myasthenia gravis, Guillain-Barr syndrome, and inflammatory
myopathies, ARF is generally caused only by an acute and severe decrease in
muscle strength, without necessarily the presence of triggers or other respiratory diseases.
Respiratory muscle weakness results in a decline of the functional residual
capacity of the lungs. This increases the work of breathing, and the reduction of
lung volume alters ventilation/perfusion relationships, resulting in less efficient gas
exchange. Weakness of expiratory muscles combined with inadequate lung inflation
prevents effective coughing and airway clearance, altering airway resistance and
54
443
increasing the risk of developing atelectasis and pneumonia [9]. Thus, hypoventilation, upper-airway obstruction, aspiration lung disease, secretion retention and
lower airway infection, and the mechanical effects of progressive scoliosis are seen
as a consequence of neuro muscular weakness (NMW). Bulbar muscle weakness
(facial, oropharyngeal, and laryngeal muscles) can affect the ability to speak, swallow, and clear airway secretions, resulting in an increased likelihood of aspiration
(Fig. 54.1)
Respiratory table infections are the most frequent cause of acute exacerbation of
chronic neuromuscular respiratory failure. During these events, the respiratory load
increases and the strength of the inspiratory muscles further worsens, resulting in
impaired alveolar ventilation. Moreover, weakness of expiratory and bulbar muscles
causes ineffective coughing and airway mucus accumulation, further increasing the
work of breathing and leading to respiratory distress.
54.4
Airway Clearance
Clinical assessment of respiratory health regarding the progression of muscle weakness, the degree of ambulation, and the degree of muscle fatigability is necessary.
Posture, seating, and the development of kyphosis and scoliosis should be regularly
assessed, as should growth and nutritional status. The ability to cope with respiratory infection, aspiration, progression of scoliosis, and sleep-disordered breathing
should be also taken in account [10].
In patients with an acute exacerbation of respiratory failure, techniques to
improve airway clearance and MV should be always considered. During acute illness, assisted coughing techniques should be used in cases of (1) oxygen desaturation, (2) increased dyspnea, (3) sense of retained secretions, (4) presence of rhonchi,
and (5) increased ventilator peak airway pressures.
The most appropriate and effective methods of secretion clearance varies from
child to child. Cough augmentation involves two steps: first, increasing inspiratory
volumes and, second, increasing the expiratory forces applied to the inspired volume.
Two techniques that have been used in children and adults with neuromuscular disease to mobilize secretions from more peripheral to central airways are highfrequency chest-wall oscillation and intrapulmonary percussive ventilation. Both
techniques result in oscillation of the airways and generation of high-velocity but
short-frequency waves of airflow. With high-frequency chest-wall oscillation, energy
is applied to the chest wall and transmitted to the airways. Vibration of the chest wall
produces oscillatory airflow, which in turn promotes mobilization of secretions from
the peripheral airways toward the mouth. With intrapulmonary percussive ventilation, oscillations (100300+ cycles per minute) are applied directly to the airway
opening. This creates an internal vibration (percussion) within the lungs and promotes secretion clearance.
Manual-assisted cough, manual and mechanical insufflation, and mechanical
exsufflation with negative pressure have all been used to augment airway clearance
444
in sick children with NMD [11, 12]. Baseline peak cough expiratory flow rate measurements above 160 l/min, however, do not guarantee adequate airway clearance,
because respiratory muscle function can deteriorate during respiratory infections.
Therefore, a peak cough expiratory flow rate of 270 has been used to identify
patients who would benefit from an assisted cough technique. The common goal of
all of these interventions, used alone or in combination, is to increase the velocity of
expiratory flow during a cough maneuver. Peak cough flow was the single most
important factor in determining whether the artificial airway (endotracheal or tracheostomy tube) could be removed in a group of 37 adults with NMD who required
assistance with secretion removal [13].
54.5
NPPV in NMD
NPPV and assisted coughing techniques have become standard therapy for the treatment of acute-on-chronic neuromuscular respiratory failure in the critical care setting as an alternative to invasive MV, both in the outpatient patient and in the
intensive care unit (ICU). If it fails or is contraindicated (e.g., due to severe bulbar
impairment), patients can be intubated as a short-term measure. MV should be considered in patients with acute exacerbation who have at least one of the following
issues: (1) dyspnea, as referred by the patient; (2) lethargy; or (3) acute respiratory
acidosis (i.e., arterial pH <7.35 with PaCO2 >45 mmHg [14]).
In children with neuromuscular weakness, NIV can be used to reduce the frequency of recurrent chest infections and improve growth of chest wall and/or in the
perioperative period during intercurrent surgery (e.g., correction of scoliosis). NIV
may work by (1) improving ventilator mechanics; (2) resting fatigued respiratory
muscles, thereby improving strength and endurance; and (3) enhancing ventilatory
sensitivity to CO2. In addition, improvement in sleep stage distribution may increase
chemosensitivity and enhance sleep quality [12].
There are two main types of ventilators: pressure-targeted and volume-targeted.
Pressure-targeted ventilation is the most widely used in the noninvasive setting and
delivers bi-level positive airway pressure (BiPAP) at operator-set expiratory and
inspiratory pressures. The major advantage of pressure-targeted ventilation is that
flow will increase until the preset pressure is reached and, as such, it adjusts well for
unintentional leaks around the mask. Continuous positive airway pressure (CPAP)
is continuous pressure delivered to the lower airways through the pharynx by different types of airway interfaces. It helps to unload respiratory muscles and enhance
minute ventilation by relieving upper-airway obstruction. BiPAP provides respiratory support at two levels. The inspiratory positive airway pressure and CPAP or
end-expiratory pressures and back-up rate can be set up by the operator. Volumetargeted ventilation is most often used for invasive ventilationeither via an endotracheal tube or a tracheostomy tubein situations where it is important to be able
to set the desired minute ventilation.
54
445
Interfaces connect the patients airway to the ventilator tubing. Six types of interfaces are commercially available that can be used to apply positive pressure to the
upper airway during an episode of ARF: full-face (or oronasal) mask, total face
mask, nasal mask, mouthpieces, nasal pillows or plugs, and a helmet. For acute
applications, most clinicians use face masks that span from chin to nasal bridge.
These tend to be used when there are problems with nasal masks, either because of
a large mouth leak or pressure effects from the nasal mask. All nasal and full-face
masks are held in place by some form of headgear [10].
With short-term use (up to several days), the most likely complications associated with NIV are skin breakdown and eye irritation from mask leak. Prevention of
skin breakdown requires careful attention to mask fitting, avoidance of overtightened straps, and use of gel pads on at-risk contact points, particularly the bridge of
the nose and the forehead. Full-face masks covering the nose and mouth can be
associated with aerophagia and uncomfortable abdominal distension. They also
carry a risk of asphyxia if the child vomits into the mask and it is not promptly
removed. Long-term use of nasal or face masks in children whose faces are still
growing is associated with underdevelopment of the maxilla, leading to mid-face
flattening and malocclusion of the teeth.
In acute care settings appropriate to handle a child with an endotracheal tube,
NIV is monitored with an electronic cardiorespiratory monitor, pulse oximeter, and
airway-disconnect alarm. Transcutaneous CO2 monitoring is extremely valuable in
children at risk of type II respiratory failure. Monitoring of mask interface pressures
is also helpful, especially in the presence of a large leak around the interface wherein
the mask pressure may be substantially lower than the set pressures on the ventilator. In children using NIV during the day and at night, humidification is helpful in
preventing drying of secretions and may improve tolerability.
The best predictive factors for the NPPV failure in ARF appear to be the level of
FiO2 and PaCO2 on admission or within the first few hours after starting NPPV. NPPV
failure is defined as the inability to reduce dyspnea or lethargy, decrease the respiratory rate, or improve blood gas exchange (i.e., arterial pH <7.30 or below the value
on admission, or failure to maintain a PaO2 >65 mmHg with a FiO2 >0.6) within the
first 612 h of application, despite optimal ventilation. NPPV treatment is not advised
for pediatric-age patients with significant respiratory distress complicated by cardiovascular instability, complete nasopharyngeal obstruction, hemoptysis, obstruction
of the proximal airway with a foreign object, or advanced stages of acute respiratory
distress syndrome. In children with neuromuscular weakness, bulbar dysfunction
and difficulty clearing airway secretions were associated with NIV failure.
Tracheostomy could be considered in patients with severe bulbar dysfunction
resulting in frequent aspiration and if acute exacerbation has led to a period of invasive
ventilation and repeated extubation attempts have failed despite optimal management.
If NIV has failed to correct hypoxemia or hypercapnia or when a child requires ventilation for more than 16 h in each 24-h period, a tracheostomy may provide a more
satisfactory interface between the child and the ventilator than a mask [10].
446
54.6
NIV Outcomes in Patients with Neuromuscular

Weakness
In children, two noncontrolled trials assessed the efficacy of NPPV in these settings.
The application of NPPV as a means of facilitating ventilation weaning and as
curative treatment for post-extubation respiratory failure was associated with success rates of 8186 and 5075 %, respectively [15, 16]. Another prospective cohort
study evaluating only NMD patients treated with a noninvasive approach (NPPV
and mechanical insufflation-exsufflation) showed a low mortality rate (8.3 %) and a
short hospital stay (12.05 7.04 days) [17]. A meta-analysis by Burns et al. [18]
found that, compared with invasive weaning, NIV was (12.05 7.04) days associated with lower mortality (relative risk 0.41), less ventilator-associated pneumonia
(relative risk 0.28), shorter MV (by 7.33 days), shorter ICU stay (by 6.88 days), and
shorter hospital stay (by 7.33 days). There was no effect on the probability of weaning success.
NIV in Duchenne muscular dystrophy has markedly changed the natural history
of the disorder. From a median age at death of 1820 years, patients using NIV
now live to their late twenties and around a third may live into their thirties or forties [19, 20]. NIV may be used to palliate symptoms and facilitate discharge home
in some children with a very poor prognosis. The study by chatwin et al. [21] highlights the role of NIV to palliate symptoms of respiratory distress in children with
Type 1 SMA. NIV was used to allow transfer from hospital to home so could the
child could spend the last months with their family.
Conclusion
NIV is a useful alternative therapy to MV in many different situations where

patients may be experiencing ARF. Children with restrictive disorders complicated by pneumonia or atelectasis accompanied by a reduction in functional
residual capacity are especially likely to benefit from NPPV therapy.
Noncontrolled trials have shown NPPV was well tolerated with rare major complications and was associated with improved gas exchange, decreased work of
breathing, and decreased need for endotracheal intubation. Both critical care
ventilators and portable ventilators have been used for NPPV. The combination
of inspiratory muscle assistance with NIV and expiratory muscle assistance with
cough insufflation-exsufflation is effective and well tolerated during acute respiratory exacerbations by patients with neuromuscular weakness. In cases of sick
patients who fail to respond to NIV or deteriorate on NIV, intubation and MV
should not be delayed.
References
1. Teague WG. Non-invasive positive pressure ventilation: current status in paediatric patients.
Paediatr Respir Rev. 2005;6(1):5260.
2. Padman R, Lawless ST, Kettrick RG. Noninvasive ventilation via bilevel positive airway pressure support in pediatric practice. Crit Care Med. 1998;26(1):16973.
54
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3. Fortenberry JD, Del Toro J, Jefferson LS, Evey L, Haase D. Management of pediatric acute
hypoxemic respiratory insufficiency with bilevel positive pressure (BiPAP) nasal mask ventilation. Chest. 1995;108(4):105964.
4. Hertzog JH, Siegel LB, Hauser GJ, Dalton HJ. Noninvasive positive-pressure ventilation
facilitates tracheal extubation after laryngotracheal reconstruction in children. Chest.
1999;116(1):2603.
5. Friedman O, Chidekel A, Lawless ST, Cook SP. Postoperative bi-level positive airway pressure
ventilation after tonsillectomy and adenoidectomy in childrena preliminary report. Int J
Pediatr Otorhinolaryngol. 1999;51(3):17780.
6. Serra A, Polese G, Braggion C, Rossi A. Non-invasive proportional assist and pressure support ventilation in patients with cystic fibrosis and chronic respiratory failure. Thorax.
2002;57(1):504.
7. Najaf-Zadeh A, Leclerc F. Noninvasive positive pressure ventilation for acute respiratory failure in children: a concise review. Ann Intensive Care. 2011;1:15.
8. Graham RJ, Fleegler EW, Robinson WM. Chronic ventilator need in the community: a 2005
pediatric census of Massachusetts. Pediatrics. 2007;119(6):e12807.
9. Racca F, Del Sorbo L, Mongini T, et al. Respiratory management of acute respiratory failure
in neuromuscular diseases. Minerva Anestesiol. 2010;76:51e62.
10. Hull J, Aniapravan R, Chan E, Chatwin M, Forton J, et al. Thoracic society guideline for respiratory management of children with neuromuscular weakness. Thorax. 2012;67(1):2012201964.
11. Chatwin M, Ross E, Hart N, Nickol AH, Polkey MI, Simonds AK. Cough augmentation with
mechanical insufflation/exsufflation in patients with neuromuscular weakness. Eur Respir J.
2003;21(3):5028.
12. Panitch HB. Respiratory issues in the management of children with neuromuscular disease.
Respir Care. 2006;51(8):88593.
ventilatory failure: a different approach to weaning. Chest. 1996;110(6):156671.
14. Vianello A, Bevilacqua M, Arcaro G, Gallan F, et al. Non-invasive ventilatory approach to
treatment of acute respiratory failure in neuromuscular disorders. A comparison with endotracheal intubation. Intensive Care Med. 2000;26:38490.
15. Lum LC, Abdel-Latif ME, de Bruyne JA, Nathan AM, et al. Noninvasive ventilation in a tertiary pediatric intensive care unit in a middle-income country. Pediatr Crit Care Med.
2011;12:e713.
16. Mayordomo-Colunga J, Medina A, Rey C, Concha A, Menendez S, et al. Non invasive ventilation after extubation in paediatric patients: a preliminary study. BMC Pediatr. 2010;10:29.
17. Servera E, Sancho J, Zafra MJ, Catal A, Vergara P, Marn J. Alternatives to endotracheal
intubation for patients with neuromuscular diseases. Am J Phys Med Rehabil.
2005;84:8517.
liberation from mechanical ventilation. Can J Anaesth. 2006;53(3):30515.
19. Eagle M, Baudouin SV, Chandler C, et al. Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscul
Disord. 2002;12:9269.
20. Simonds AK, Muntoni F, Heather S, et al. Impact of nasal ventilation on survival in hypercapnic Duchenne muscular dystrophy. Thorax. 1998;53:94952.
21. Chatwin M, Bush A, Simonds AK. Outcome of goal-directed non-invasive ventilation and
mechanical insufflation/exsufflation in spinal muscular atrophy type I. Arch Dis Child.
2011;96:42632.
Part VIII
and Weaning. Outcome
Noninvasive Ventilation and Weaning

Outcome
55
Karen E.A. Burns and Neill K.J. Adhikari
Abbreviations
CI
COPD
CPAP
FEV1
GRADE
I2
ICU
MD
NIV
PS
RR
Confidence interval
Forced expiratory volume in 1 s
Grading of Recommendations Assessment Development and Evaluation
Measure of heterogeneity
Intensive care unit
Mean difference
Pressure support
Relative risk
K.E.A. Burns, MD, FRCPC, MSc (*)

Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada
Division of Critical Care Medicine, St Michaels Hospital, 30 Bond Street, 4-045 Donnelly
Wing, Toronto, ON, M5B 1W8, Canada
Li Ka Shing Knowledge Institute, St. Michaels Hospital, Toronto, ON, Canada
e-mail: burnsk@smh.ca
N.K.J. Adhikari, MDCM, MSc
Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON,
Canada
Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada
e-mail: neill.adhikari@utoronto.ca
DOI 10.1007/978-3-319-04259-6_55
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55.1
K.E.A. Burns and N.K.J. Adhikari
Introduction
Guidelines recommend noninvasive ventilation (NIV) for severe exacerbations of

chronic obstructive pulmonary disease (COPD) and cardiogenic pulmonary edema
to prevent intubation and enhance survival [1, 2]. However, clinicians apply NIV to
a broader array of clinical conditions to provide partial respiratory support and to
limit intubation-related complications, including pneumonia and prolonged
mechanical ventilation. Regardless of the indication, the clinicians goal in using
NIV is to reduce patient morbidity and mortality.
In the weaning and peri-extubation period, NIV has been used to decrease the
duration of invasive weaning, prevent recurrent respiratory failure in at-risk patients
who are extubated, and rescue patients with a failed attempt at extubation [3]
(Fig. 55.1). In the first case, clinicians extubate selected patients who are ready for
weaning, but who have failed a spontaneous breathing trial, directly to NIV. The
objectives are to reduce the duration of invasive ventilation, limit intubation-related
complications, and minimize failed attempts at extubation. In the second case, clinicians prophylactically apply NIV to patients at risk of reintubation, such as in the
intensive care unit (ICU) or postoperative setting, with the goal of reducing extubation
failure. Finally, by applying NIV to rescue patients who fail extubation, clinicians aim
to avoid reintubation and reduce further exposure to invasive ventilation and its
complications.
In 2001, an International Consensus Conference stated that the use of NIV to
shorten weaning time and avoid reintubation represents a promising indication
for NIV but made no recommendation [4]. The authors of this statement also
noted that, although NIV holds potential to improve physiologic outcomes without serious side effects in postoperative patients, the ability of NIV to modify
relevant clinical outcomes in these patients is less clear [4]. In 2002, a British
Thoracic Society guideline stated that NIV has been used successfully to wean
patients from invasive ventilation, and should be used when conventional
Initial
Treatment
Phase of care
Respiratory
failure
Role of
noninvasive
ventilation
Avoidance of
intubation in
COPD, CPE,
other
indications
Weaning from invasive ventilation and and peri-extubation
Intubation (no
ninvasive
ventilation
failed or not
indicated)
Resolution of
primary
process
and/or failed
SBT
Weaning
strategy
(COPD vs.
non-COPD)
Elective
Extubation
Prevention
of respiratory
failure (high
risk vs. all
patients)
Post-extubation
respiratory
failure
Treatment of
recurrent
respiratory failure
Fig. 55.1 Roles for NIV in the weaning and peri-extubation period. COPD chronic obstructive
pulmonary disease, CPE cardiogenic pulmonary edema, SBT spontaneous breathing failure
55
Noninvasive Ventilation and Weaning Outcome
453
weaning strategies fail. The authors assigned a level B evidence grade to this
recommendation and cited support from two randomized controlled trials (RCTs)
[5]. Subsequently, the statement of the Sixth International Consensus Conference
in Intensive Care Medicine on weaning from mechanical ventilation stated that
NIV techniques to shorten the duration of intubation should be considered in
selected patients, especially those with hypercapnic respiratory failure and
should not be routinely used as in the event of extubation failure [6]. A more
recent Canadian Clinical Practice Guideline [7] developed comprehensive recommendations for NIV use in weaning and extubation. First, it suggested that
NIV be used to facilitate early liberation from mechanical ventilation in patients
who have COPD, but only in centers that have expertise. This statement was
designated as a Grading of Recommendations Assessment, Development and
Evaluation (GRADE) 2B recommendation [8, 9]. Because of insufficient evidence, there was no recommendation regarding NIV for weaning in patients
without COPD. Second, the guideline suggested that NIV be used after planned
extubation in patients who are considered to be at high risk of recurrent respiratory failure, but only in centers that have expertise in this type of therapy
(GRADE 2B recommendation) and suggested that NIV not be used after planned
extubation in patients considered to be at low risk of respiratory failure (GRADE
2C recommendation). Finally, in the setting of post-extubation acute respiratory
failure, it suggested that noninvasive positive pressure ventilation not be routinely used in patients who do not have COPD (GRADE 2C recommendation)
and made no recommendation for patients with COPD because of a lack of evidence. In this chapter, we summarize current RCTs and meta-analyses pertaining
to the application of NIV to wean patients from invasive ventilation, prevent
extubation failure in at-risk patients, and to treat post-extubation respiratory
failure.
55.2
Analysis
55.2.1 NIV to Prevent or Treat Post-extubation Respiratory

Failure
In 2007, Agarwal and colleagues [10] published the first meta-analysis to examine
the effect of NIV in patients with post-extubation respiratory failure (Table 55.1).
They identified 4 trials, of which 2 trials evaluated patients at risk for postextubation failure and 2 examined patients with established post-extubation respiratory failure. In 259 patients at high risk of post-extubation respiratory failure, NIV
applied after extubation, compared with standard therapy, significantly decreased
reintubation (relative risk (RR) 0.46, 95 % confidence interval (CI) 0.250.84)
and ICU mortality (RR 0.26, 95 % CI 0.100.66) but not hospital mortality (RR
0.71, 95 % CI 0.421.20). Conversely, in 302 patients with post-extubation respiratory failure, NIV had no effect (RR for reintubation 1.03, 95 % CI 0.841.25; RR
for ICU mortality 1.14, 95 % CI 0.433.00). The authors concluded that NIV
454
appeared promising to prevent reintubation in patients at risk for post-extubation

respiratory failure but should be used judiciously, if at all, in patients with established post-extubation respiratory failure.
In 2014, Lin and colleagues [11] published an updated meta-analysis of NIV
in the prevention or management of post-extubation respiratory failure
(Table 55.1). They identified 10 randomized or quasi-randomized trials enrolling 1,382 patients, including 8 trials in the setting of prevention and the same 2
trials found by Agarwal et al. [10] in the setting of established post-extubation
respiratory failure. Early application of NIV to prevent respiratory failure did
not reduce reintubation (RR 0.75, 95 % CI 0.491.15); however, in the subgroup
of patients extubated after passing a spontaneous breathing trial, NIV reduced
reintubation (RR 0.65, 95 % CI 0.460.93), ICU mortality (RR 0.41, 95 % CI
0.210.82), and hospital mortality (RR 0.59, 95 % CI (0.380.93). Tests of
interaction required for the correct interpretation of subgroup analyses were not
reported. There was no effect of NIV in patients with established post-extubation respiratory failure on reintubation or ICU mortality, similar to the earlier
meta-analysis [10].
In 2013, Olper and colleagues [12] conducted a meta-analysis of randomized
trials of NIV for patients after cardiac, thoracic, and thoracoabdominal vascular
surgery (Table 55.1). They identified 14 randomized trials (n = 1,211) of which
6 used continuous positive airway pressure (CPAP), 7 used noninvasive pressure support (PS), and 1 used both. Two trials used NIV to treat post-extubation
respiratory failure, and 12 used NIV to prevent it. Of the trials of prophylactic
NIV, 1 included patients with impaired preoperative pulmonary function (forced
expiratory volume in 1 s (FEV1) <70 % predicted), 2 evaluated patients after
thoracoabdominal surgery, and 9 trials evaluated low-risk patients. Nine trials
applied NIV during the first operative day only, 2 trials used NIV for less than
1 h, and 1 trial used NIV for 7 days prior to and following surgery. Metaanalyses showed that NIV significantly reduced reintubation (RR 0.29, 95 % CI
0.160.53), hospital length of stay (MD 2.25 days, 95 % CI ( 4.21 to 1.10))
and mortality (RR 0.26 95 % CI (0.110.66)). The authors explored subgroup
effects related to baseline risk of developing postoperative respiratory failure,
but these analyses were underpowered and did not use appropriate tests of
interaction.
55.2.2 NIV in Weaning and After Extubation

In 2012, Glossop et al. [13] summarized RCTs (limited to English) that compared
NIV to standard care in patients weaning from invasive mechanical ventilation (5
trials), extubated in the ICU (6 trials), or extubated immediately after major surgery
(5 trials) (Table 55.1). Among trials of patients extubated in the ICU, 4 enrolled
patients at risk of respiratory failure and 2 enrolled patients who had developed
55
455
Table 55.1 Summary of meta-analytic effects of noninvasive ventilation in weaning

Heterogeneity
Effect
(I 2, %)
Outcome
Prevention or treatment of post-extubation respiratory failure10
ICU mortality
Prevention
RR 0.26 (0.10, 0.66)
0
Treatment
RR 1.14 (0.43, 3.00)
70
Hospital mortality
Prevention
RR 0.71 (0.42, 1.20)
0
Reintubation
Prevention
RR 0.46 (0.25, 0.84)
0
Treatment
RR 1.03 (0.84, 1.25)
0
Prevention or treatment of post-extubation respiratory failure11
ICU mortality
Prevention (all trials)
NR
NR
Prevention (passed SBT)
RR 0.59 (0.38, 0.93)
0
70
Treatment
RR 1.33 (0.83, 2.13)a
Hospital mortality
NR
NR
26
RR 0.41 (0.21, 0.82)a
Treatment
NR
NR
Reintubation
RR 0.75 (0.49, 1.05)
51
47
RR 0.65 (0.43, 0.93)a
0
Treatment
RR 1.02 (0.83, 1.25)a
Cardiac, thoracic, and thoracoabdominal surgery12
Mortality
Preventive low-risk
NA
NA
Preventive high-risk
RR 0.26 (0.03, 2.25)
NA
Curative
RR 0.26 (0.10, 0.73)
0
Reintubation
All trials
RR 0.29 (0.16, 0.53)
0
Preventive low-risk
RR 0.42 (0.12, 0.48)
NR
RR 0.19 (0.04, 0.84)
NR
Curative
RR 0.25 (0.07, 0.89)
NR
Pneumonia
Preventive low-risk
RR 0.48 (0.12, 1.96)
14
RR 0.14 (0.01, 2.63)
NR
Curative
NA
NA
Hospital length of stay
Preventive low-risk
MD 0.08 d (1.09,
94
0.93)
No. of trials,
patients, events
2, 259, 26
2, 302, 59
2, 259, 47
2, 259, 43
2, 302, 163
NR
4, 403, 68
2, 302, 59
NR
4, 771, 38
NR
8, 1080, 180
6, 849, 112
2, 302, 163
NA
1, 70, NR
2, 106, NR
8, 854, 58
NR
NR
NR
6, 734
2, 82
NA
4, 598
(continued)
456

Outcome
Effect
Heterogeneity
(I 2, %)
No. of trials,
patients, events
3, 152
MD 7.40 d (11.90,
91
2.91)
Curative
MD 4.30 d (4.60,
NA
1, 48
13.20)
Weaning from mechanical ventilation, post-extubation in ICU, and postoperative13(b)
ICU mortality
Weaning
OR 1.20 (0.63, 2.27)
76.5
3, 246, 45
Post-ICU extubation
OR 0.81 (0.54, 1.19)
56
5, 750, 178
Postoperative
NA
NA
1, 50, 0
Hospital mortality
Weaning
OR 1.82 (1.02, 3.23)
36
4, 279, 71
Post-ICU extubation
OR 0.81 (0.51, 1.28)
0
4, 479, 89
Postoperative
OR 0.22 (0.065, 0.74)
0
3, 307, 116
Reintubation
Weaning
OR 0.96 (0.50, 1.83)
16
2, 181, 51
Post-ICU extubation
OR 0.72 (0.51, 1.02)
20.5
6, 740, 230
Postoperative
OR 0.24 (0.12, 0.50)
0
5, 979, 48
Pneumonia
Weaning
OR 0.12 (0.05, 0.31)
24
4, 191, 46
Post-ICU extubation
OR 0.72 (0.42, 1.25)
19
3, 349, 70
Postoperative
OR 0.27 (0.09, 0.77)
0
4, 931, 20
ICU length of stay
Weaning
MD 5.12 d (7.91,
62
4, 191
2.32)
Post-ICU extubation
MD 0.05 d (0.86,
31
5, 519
0.96)
95
5, 979
Postoperative
MD 0.04 d (0.05,
0.03)
Weaning
MD 6.45 d (12.41,
33
3, 141
0.48)
Post-ICU extubation
MD 0.67 d (1.88,
0
5, 519
0.54)
Postoperative
MD 1.03 d
96
5, 979
(1.13,0.93)
Weaning from mechanical ventilation14
Mortality
37
16, 994, 173
All patients
RR 0.53 (0.36, 0.80)c
COPD
RR 0.36 (0.24, 0.56)
0
9, 632, 93
Mixed population
RR 0.81 (0.47, 1.40)
35
7, 362, 80
39
8, 605, 178
Weaning failures
RR 0.63 (0.42, 0.96)d
55
457

Outcome
Reintubation
Nosocomial pneumonia
ICU length of stay
Duration of mechanical
ventilation (total)
ventilation (invasive)
ventilation (weaning)
Tracheostomy
Effect
RR 0.65 (0.44, 0.97)e
RR 0.25 (0.15, 0.43)f
MD 5.59 d (7.90,
3.28)g
MD 6.04 d (9.22,
2.87)h
MD 5.64 d (9.50,
1.77)i
MD 7.44 d (10.34,
4.55)j
MD 0.25 d (2.06,
1.56)k
RR 0.19 (0.08, 0.47)l
Heterogeneity
(I 2, %)
41
38
77
No. of trials,
patients, events
10, 789, 202
14, 953, 174
13, 907
78
10, 803
86
7, 385
90
12, 717
87
9, 645
10
7, 572, 52
Refers to a fixed-effects analysis. The remaining analyses used random-effects models except
where noted
b
Glossop et al. did not specify whether fixed-effects or random-effects analyses were used
c
Interaction p = 0.02 between the COPD and mixed population subgroups
d
Interaction p = 0.40 between the COPD and mixed population subgroups (subgroup data not
shown for this or subsequent analyses)
e
f
Interaction p = 0.30 between the COPD and mixed population
g
h
i
j
k
l
respiratory failure (the same trials identified previously [10, 11]). Similarly, among
the surgical trials, 2 enrolled patients with postoperative hypoxemia and 3 studied
NIV to prevent respiratory failure. Amidst moderate to high heterogeneity, the
authors found that NIV reduced ICU stay when used for weaning (MD 5.12 days,
95 % CI 7.91 to 2.32) and after surgery (MD 0.04 days, 95 % CI 0.05 to
0.03), with similar results for length of hospital stay (MD 6.45 days, 95 % CI
12.41 to 0.48 for weaning; MD 1.03 days, 95 % CI 1.13 to 0.93 after surgery). The length of stay meta-analyses in postoperative patients were dominated by
one trial. NIV did not have similar effects in the ICU post-extubation group. NIV
also reduced pneumonia in the weaning (OR 0.12, 95 % CI 0.050.31) and postsurgery (OR 0.27, 95 % CI 0.090.77) groups and the risk of reintubation in the
post-surgery group (OR 0.24, 95 % CI 0.120.50). Notwithstanding these findings,
meta-analyses found that NIV increased hospital mortality in the weaning group
(OR 1.82, 95 % CI 1.02, 3.23), had no effect in the post-ICU extubation group (OR
0.81, 95 % CI 0.51, 1.28), and decreased hospital mortality in the postoperative
group (OR 0.22, 95 % CI 0.065, 0.74).
458
55.2.3 NIV in Weaning from Mechanical Ventilation

In an updated systematic review published in 2014, Burns et al. [14] summarized
the effects of noninvasive weaning in 16 trials enrolling 994 patients, including one
quasi-randomized trial (Table 55.1). Nine trials exclusively involved patients with
COPD and 7 trials included mixed or non-COPD populations. In these 7 trials,
COPD was diagnosed in about 75 % of patients in 3 trials, in about 30 % of patients
in 2 trials, and in more than 20 % of patients in 1 trial; COPD was an exclusion
criterion in the final trial. Among all trials, patients were considered difficult to
wean in 2 trials and had persistent weaning failures in 1 trial. Four trials included
patients with COPD with respiratory failure due to pulmonary infection. Trials varied regarding pre-randomization ventilation management, strategies to identify
weaning candidates, inclusion criteria, and post- randomization ventilation strategies. Overall, the quality of included trials was moderate to good.
The authors found that noninvasive weaning reduced mortality (RR 0.53, 95 % CI
0.360.80) with moderate heterogeneity. This effect differed significantly (interaction p = 0.02) between trials enrolling COPD patients (RR 0.36, 95 % CI 0.240.56)
versus mixed populations (RR 0.81, 95 % CI 0.471.40). In secondary outcomes,
noninvasive weaning significantly reduced weaning failures (RR 0.63, 95 % CI 0.42
0.95) and ventilator-associated pneumonia (RR 0.25, 95 % CI 0.150.43), both with
moderate heterogeneity. Noninvasive weaning significantly reduced ICU (MD 5.59
days, 95 % CI 7.90 to 3.28) and hospital (MD 6.04 days, 95 % CI 9.22 to
2.87) length of stay, the total duration of mechanical ventilation (MD 5.64 days,
95 % CI 9.50 to 1.77) and the duration of invasive ventilation (MD 7.44 days,
95 % CI 10.34 to 4.55), all with considerable heterogeneity. There was no effect
on the duration of mechanical ventilation related to weaning (MD 0.25 days, 95 %
CI 2.06 to 1.56). Noninvasive weaning significantly lowered rates of reintubation
(RR 0.65, 95 % CI (0.440.97) and tracheostomy (RR 0.19, 95 % CI 0.080.47) with
moderate and little heterogeneity, respectively.
Effects on length of stay and pneumonia were similar to previous work [13].
However, by including more trials with more events, effects on other outcomes
became statistically significant, and the increased harm of noninvasive weaning on
hospital mortality detected previously [13] was no longer detected. In addition, a
clinically and statistically subgroup effect for mortality became apparent, with noninvasive weaning saving lives in COPD patients but not in mixed populations.
55.3
Discussion
In the absence of a single large, well-designed RCT of NIV in the weaning and
peri-extubation period for a well-defined patient population, pooled data from
meta-analyses provide the highest level of evidence of its effects on clinical outcomes. As with any form of empirical evidence, meta-analyses have limitations.
First, they implicitly assume that trials are more similar than different with respect
to populations, interventions, and outcome definitions; however, results from large
trials may disagree with meta-analyses in 1023 % of comparisons [15]. Second,
55
459
although differences among trial results that are felt to have sufficient clinical similarity to justify pooling can be handled statistically, limitations of the standard
methods used have recently been highlighted [16]. Third, statistical power is
related to the number of patients and outcome events, and even statistically significant results based on few events can be fragile [17]. Therefore, in the specific case
of NIV for prevention and treatment of post-extubation respiratory failure, the
strength of inferences is limited by relatively few events and clinical and statistical
heterogeneity of trials. While the meta-analysis of noninvasive weaning includes
more trials than other indications, the number of events remains lower than optimal
for clinically important outcomes of mortality and ventilator-associated pneumonia [18]. Despite the emerging evidence base for NIV in weaning from mechanical
ventilation, no single large clinical trial, stratified for the presence of COPD, has
been conducted.
Accordingly, additional large definitive trials are needed to evaluate noninvasive
weaning from mechanical ventilation, especially in non-COPD patients, and prophylactic NIV for patients at high risk of post-extubation respiratory failure in the critical
care and postoperative settings. Finally, we note that no new trials of NIV to treat
post-extubation respiratory failure in the ICU have been published since 2006, when
a prominent trial cited in all the meta-analyses was stopped early for harm [19].
NIV for Weaning

1. We suggest that NIV be used to facilitate early weaning from mechanical
ventilation in patients who have COPD, but only in centers that have
expertise in this type of therapy.
2. We make no recommendation about the use of NIV to facilitate early liberation from mechanical ventilation in patients who do not have COPD,
due to insufficient evidence.
Prophylactic NIV Application After Planned Extubation

1. We suggest that NIV be used after planned extubation in patients who are
considered to be at high risk of recurrent respiratory failure, but only in
centers that have expertise in this type of therapy.
2. We suggest that NIV not be used after planned extubation in patients who
are considered to be at low risk of recurrent respiratory failure.
NIV for Post-extubation Respiratory Failure

1. We make no recommendation about the use of NIV in patients who have
COPD and develop post-extubation respiratory failure, due to insufficient
evidence.
2. We suggest that NIV not be routinely used in patients who do not have
COPD and develop post-extubation respiratory failure.
460
Similar to the Canadian guideline, we synthesize evidence into recommendations using GRADE terminology including recommend, suggest, or no recommendation [7]. For topics with sufficient quality and quantity of supporting
evidence from RCTs, we use the phrase we recommend. For topics with insufficient supporting evidence, we use the phrase we suggest; when evidence is sparse,
we make no recommendation. For weaning, we suggest NIV to facilitate early
weaning in COPD patients in centers with expertise but make no recommendation
regarding its use for non-COPD patients. For NIV to prevent respiratory failure
after planned extubation, we suggest its use in patients considered to be high risk in
centers with expertise and we suggest that it not be used in low-risk patients. We
make no recommendation regarding treatment of COPD patients with postextubation respiratory failure and suggest that NIV not be routinely used in nonCOPD patients with post-extubation respiratory failure.
References
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obstructive pulmonary disease benefit from noninvasive positive-pressure ventilation? A systematic review of the literature. Ann Intern Med. 2003;138(11):86170.
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C. Noninvasive ventilation in acute cardiogenic pulmonary edema: a meta-analysis of randomized controlled trials. J Card Fail. 2011;17(10):8509.
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Sanders K, Dodek P, Canadian Critical Care Trials Group/Canadian Critical Care Society
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of GRADE grid to reach decisions on clinical practice guidelines when consensus is elusive.
BMJ. 2008;337:32730.
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13. Glossop AJ, Shepherd N, Bryden DC, Mills GH. Non-invasive ventilation for weaning, avoiding reintubation after extubation and in the postoperative period: a meta-analysis. Br J Anaesth.
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Index
A
Acute respiratory failure (ARF), 29, 30, 32,
33, 37, 61, 86, 88, 96, 97, 99, 103,
111114, 119, 120, 125, 139145, 147,
150, 165, 166, 168, 169, 175, 183, 186,
187, 191195, 199201, 207, 208, 217,
218, 221, 222, 229, 233, 235239, 247,
249, 250, 253, 255, 265, 275, 279, 307,
308, 332, 333, 337, 383, 385, 386, 388,
410, 417, 418, 439, 440, 453
Anesthesia, 59, 97, 175, 179, 180, 191, 199,
222, 233235, 239, 275, 278, 279,
283, 333, 408
ARF. See Acute respiratory failure (ARF)
Assisted coughing, 51, 54, 121, 247, 250,
252255, 287, 290, 315, 333, 336,
345, 346, 349, 368, 443, 444
Atelectasis, 6, 97, 111, 141, 175, 179, 180,
186, 199, 201, 207, 208, 221, 222,
225229, 235, 236, 242, 248250,
253, 254, 259, 276279, 288290,
292, 293, 324, 332, 344, 346, 394,
410, 411, 414, 418, 419, 425, 440,
442, 443, 446
B
Bilevel positive airway pressure (BIPAP),
88, 122, 123, 132, 155, 156, 160,
161, 236238, 275279, 287,
291293, 439, 444
C
CABG. See Coronary artery bypass graft
(CABG)
Cardiac surgery, 25, 105, 134, 175, 177, 181,

186, 191195, 388, 408410, 413, 414,
418, 419, 421, 430
Cardiogenic pulmonary edema, 159, 165, 166,
174, 183, 221, 452
CHF. See Congestive heart failure (CHF)
Chronic critical illness, 3, 15, 16,
377, 379, 380
(COPD), 6, 15, 17, 30, 32, 58, 64, 77,
78, 86, 91, 96, 111, 143, 148, 152, 159,
165, 174, 180, 183, 193, 199, 200, 208,
213, 221, 227, 235, 262, 283, 300, 307,
316, 322, 356, 374, 384, 452
Clinical prediction rule, 74
Complications, 29, 37, 57, 91, 117, 129136,
151, 159, 166, 175, 179, 183, 192, 198,
207, 213, 221, 225, 233, 249, 262, 281,
298, 305, 313, 322, 333, 354, 373, 413,
434, 440, 452
Congenital heart defects (CHD),
408, 409, 414
Congestive heart failure (CHF), 96, 99,
174175, 177, 180, 181, 208, 283, 299,
300, 363
Continuous positive airway pressure (CPAP),
88, 97, 122, 173, 179181, 183, 193,
201, 217, 227, 236, 276, 282, 293, 298,
325, 393, 402403, 410, 418, 425, 435,
444, 454
COPD. See Chronic obstructive pulmonary
disease (COPD)
Coronary artery bypass graft (CABG),
174176, 198
CPAP. See Continuous positive airway
pressure (CPAP)

DOI 10.1007/978-3-319-04259-6
463
464
D
Decannulation, 61, 118, 120, 122125,
313319, 331337, 341349, 357,
383385, 433437
Diaphragm, 69, 12, 13, 17, 29, 31, 34, 45,
46, 48, 58, 64, 97, 151, 173, 180, 181,
186, 202, 208, 214, 228, 234236,
287289, 323, 349, 355, 409412,
414, 419, 440, 441
Difficult weaning, 7381, 8588, 117125,
147158, 322, 353357, 361368
Dysphagia, 68, 69, 174, 259264, 345
E
Extubation, 6, 22, 32, 5155, 5761, 85,
9193, 95105, 112, 118, 132,
139145, 147, 159, 165, 181, 183, 192,
197205, 209, 222, 237, 241244, 250,
259265, 275, 281284, 294, 305308,
316, 322, 331337, 355, 395, 401405,
407414, 417421, 423431, 452
Extubation failure, 5155, 57, 9193, 95, 123,
150, 154, 165, 185, 192, 197205, 254,
262, 284, 318, 395, 401405, 407414,
419, 423431
G
General surgery, 174
H
High flow nasal cannula, 139145, 202, 404,
423431
Home care, 252, 361368, 380, 386
I
Inspiratory muscle training, 45
Intensive care, 4, 16, 21, 26, 38, 44, 57, 64, 74,
86, 91, 95, 117, 132, 142, 148, 181,
183, 192, 199, 209, 213, 228, 233, 241,
249, 265, 281, 305, 313, 321, 342, 344,
361, 373, 383, 402, 418, 423, 444
Intrapulmonary percussive ventilation, 5859,
290, 443
L
Long term acute care hospital (LTAC),
18, 44, 380
Long term care hospital, 313, 355
Lung transplantation, 198, 201, 213218
Index
M
Malnutrition, 7, 9, 17, 6466, 70, 149,
259, 354
Mechanical insufflation-exsufflation (MI-E),
58, 6061, 263, 316, 332, 335, 337,
347, 348, 368, 446
Mechanically assisted coughing,
247, 250, 290
Mechanical ventilation (MV), 313, 1521,
3741, 4348, 5155, 64, 7381,
8588, 9193, 95105, 112, 117125,
129136, 147159, 165170, 180, 183,
191195, 198200, 208, 213218,
221223, 233239, 262, 265, 297302,
305, 313, 321, 333, 342, 353, 361368,
373, 383, 394, 402, 418, 428, 439446
Mechanical ventilator weaning, 46
N
Nasal high flow oxygen therapy, 140
Neurally adjusted ventilatory assist (NAVA),
29, 31, 32, 419
Neuromuscular, 4, 17, 46, 52, 61, 120, 150,
180, 221, 247255, 259, 276, 316, 323,
331337, 361368, 374, 388, 439446
Neuromuscular disease (NMD), 6, 19, 52, 54,
61, 111, 120, 121, 150, 153, 157, 200,
222, 247255, 299, 318, 323, 324, 327,
334, 337, 343, 361, 362, 380, 388, 419,
421, 439446
(NIPPV), 150, 159162, 173, 202,
253, 395, 403
Noninvasive ventilation (NIV), 17, 2934, 37,
54, 57, 74, 91, 96, 111114, 122, 132,
140, 147, 160, 165170, 181, 183187,
193, 197205, 225231, 233, 242,
259264, 281284, 300301, 383,
393398, 401405, 407414, 430,
434, 439446
Noninvasive weaning, 160, 440, 458, 459
Nutritional status, 103, 122, 409, 443
Nutritional support, 19, 65, 381
O
Obesity, 6, 92, 111, 120, 121, 123, 152, 180,
222, 233235, 241244
Oxygen, 9, 58, 85, 92, 100, 112, 118, 130,
140, 149, 161, 166, 173, 180, 184, 192,
200, 209, 214, 221, 226, 235, 241, 251,
262, 267, 283, 289, 298, 306, 315, 324,
342, 409, 413, 414, 423, 428, 434
Index
P
Patient-ventilator interaction, 29, 30, 33, 87
Peak cough expiratory flow, 5153, 55,
254, 444
Pediatrics, 254, 408411, 417421, 423431,
433437, 440, 445, 446
Physical therapy, 4648, 61, 254
Pneumonia, 17, 32, 39, 80, 86, 87, 95, 103,
119, 129136, 143, 148, 151, 153,
154, 157, 160162, 165, 166, 168,
169, 174, 175, 179181, 183, 186,
192195, 201, 207, 208, 214, 217,
221, 222, 226, 227, 229, 235237,
239, 249253, 261, 262, 276, 281283,
288290, 307, 308, 332, 333, 335,
337, 342, 346, 349, 363, 410, 411,
414, 419, 428, 436, 440, 442, 443,
446, 452, 455459
Positive pressure ventilation, 7, 9, 10, 148,
150, 186, 348, 430, 440
Post-extubation, 6, 32, 33, 54, 61, 86, 91100,
102, 104, 105, 118120, 123, 150,
153155, 157, 176, 185187, 192, 193,
195, 216, 255, 259263, 265, 278, 282,
283, 394, 401405, 411, 419, 421,
423431, 446, 453457, 459, 460
Post-extubation failure, 61, 86, 9193, 97,
150, 154, 185, 192195, 401405,
423431
Post-operative, 25, 88, 9698, 100, 105, 143,
175177, 179181, 183187, 191, 192,
194, 198, 199, 202, 204, 205, 209, 210,
213215
Post-operative pulmonary complications, 97,
175, 179, 186, 192, 221, 222, 225, 229,
230, 289, 324, 342, 347
Pre-oxygenation, 143
Prevention, 38, 99, 117, 120, 123, 124,
129136, 141, 151, 154155, 181, 186,
192, 193, 216, 229, 237, 269, 278, 288,
307, 403, 425, 445, 454, 455, 459
Procedures and techniques-therapeutic, 217
Prolonged mechanical ventilation, 313,
1520, 4348, 5155, 69, 7381, 96,
117125, 129136, 207210, 213218,
263271, 314, 316, 319, 342, 349, 373,
374, 408, 409, 414, 452
Prolonged weaning, 13, 1520, 7981, 85, 86,
147158, 166, 268, 314, 354357,
373381, 383388
Pulmonary, 5, 6, 8, 10, 16, 17, 59, 61, 64, 97,
98, 122, 130, 143, 149151, 166,
174176, 179, 181, 183, 186, 191,
193, 195
465
R
Rehabilitation, 18, 19, 46, 48, 65, 68, 192,
203, 214, 260, 261, 263, 264, 314, 323,
326, 356, 357, 363365, 368, 375, 376,
380, 383
Reintubation, 25, 54, 55, 57, 61, 74, 86, 88, 92, 93,
9599, 118, 123, 125, 132, 143, 147, 148,
150, 151, 154, 158, 165, 166, 168170,
176, 179, 181, 183187, 192195, 209,
215218, 221, 226230, 233, 239, 241,
242, 254, 261263, 269, 275279,
281284, 305308, 321, 325, 326, 328,
335, 374, 395, 402404, 408, 410, 411,
413, 418421, 429431, 452458
Respiratory
failure, 16, 19, 29, 30, 32, 33, 37, 54,
5761, 66, 86, 88, 92, 95105,
111114, 119, 120, 122, 123, 125,
139145, 147, 150158, 165, 166, 168,
169, 174176, 180, 181, 183187,
191195, 199204, 207210, 214,
216218, 221, 222, 228230, 234,
236239, 241, 242, 247249, 251253,
255, 259264, 275279, 282, 283, 289,
290, 294, 314, 333, 337, 352, 363, 374,
383, 402, 410413, 417, 418, 420,
439441, 443
function, 4, 40, 65, 66, 144, 175, 198, 199,
201, 209, 214, 222, 223, 226, 228,
233237, 239, 247249, 294, 362, 410,
440, 441
insufficiency, 64, 66, 68, 117119, 214,
253, 289, 294, 363, 440
muscles, 57, 9, 11, 17, 44, 51, 54, 111,
112, 148, 180, 181, 201, 236, 239,
242, 247249, 287, 301, 324, 327,
363, 419, 444
Restrictive lung disease, 64
S
Saturation, 11, 87, 88, 100, 103, 112, 140,
142, 144, 145, 149, 192, 199, 214, 222,
229, 251, 253, 255, 276, 293, 294,
324328, 335, 345, 348, 410, 413, 421,
428431
SCI. See Spinal cord injury (SCI)
Scoliosis, 123, 222, 223, 248, 322,
418, 443, 444
Sedation, 17, 18, 21, 34, 3741, 46, 87, 117,
120, 121, 131, 136, 137, 145, 152, 157,
167, 169, 183, 192, 193, 199, 265, 266,
269271, 277, 279, 282, 305, 323, 324,
345, 354, 356, 377, 413, 436
466
Shunt, 141, 175, 191, 235, 236, 275, 276, 278
Sleep apnea, 111, 120, 180, 200, 234, 244,
278, 293, 298302, 363, 428, 440
Sleep disordered breathing, 293, 299, 337, 443
Specialized weaning units (SWUs), 18, 120,
354, 355, 375, 381
Spinal cord injury (SCI), 64, 66, 287,
341349, 355, 362, 439
Spinal surgery, 221223, 419, 421
Spontaneous breathing trial, 5, 11, 16, 21, 44,
47, 51, 54, 55, 58, 80, 85, 92, 96, 99,
103, 112, 132, 136, 147, 149, 151153,
156, 160, 165, 184, 242, 243, 254, 262,
267, 282, 314, 324, 325, 334, 335, 342,
344, 354, 374, 452
Surgery, 5, 25, 48, 59, 60, 88, 97, 98, 100,
105, 175177, 179181, 184, 186, 187,
191195, 197205, 208, 209, 214216,
218, 221223, 225231, 235, 236, 238,
251, 278, 322, 375, 388, 408410, 413,
418, 419, 444, 454
SWUs. See Specialized weaning units (SWUs)
Synchrony, 6, 17, 29, 30, 3234, 38, 100, 102,
157, 202, 254, 262, 267, 292, 394, 395,
398, 413, 419
T
Tetraplegia, 287294, 334, 345
Thoracic surgery, 48, 98, 105, 180, 181, 186,
197205, 208210, 214, 216
Tracheostomy, 16, 18, 19, 47, 48, 59, 60, 74,
80, 118, 125, 129, 135, 151153,
160162, 168170, 173, 192, 201, 215,
222, 249, 254, 255, 281, 282, 313319,
321328, 333, 335337, 341349, 356,
357, 361, 366, 367, 385, 388, 433, 434,
437, 440, 444, 445, 457, 458
Tracheotomy, 5, 24, 87, 117, 120, 135, 249,
254, 255, 260, 294, 313, 314, 319, 328,
332335, 337, 342, 349, 376, 437
Index
U
Unplanned extubation, 86, 97, 132, 267,
305308, 411
V
VAP. See Ventilator-associated pneumonia
(VAP)
Ventilator, 3, 8, 16, 2934, 38, 44, 54, 6370,
7381, 86, 91, 95106, 111114,
117, 129136, 147, 159, 165, 173,
176, 183, 192, 200, 207, 213, 223,
236, 241244, 251, 262, 265271,
277, 281284, 287294, 297302,
305308, 313, 321, 332, 342, 354,
361, 374, 384, 393, 402, 411
Ventilator-associated pneumonia (VAP),
95, 129137, 149, 154, 157, 166,
168, 169, 183, 192, 193, 214, 446,
458, 459
Ventilator setting, 17, 47, 103, 251, 255, 293,
327, 335, 364, 367
W
Weaning failure, 4, 5, 8, 1013, 1617,
19, 48, 64, 66, 68, 87, 92, 148, 150,
151, 155, 157, 160, 166168, 209,
265, 268, 271, 316, 355, 361, 374,
375, 456, 458
Weaning from mechanical ventilation, 3741,
51, 53, 118, 119, 122, 125, 160,
165170, 192, 317, 353, 373, 453,
456459
Weaning protocol, 20, 25, 4348, 93, 117,
155, 156, 158, 215, 262264, 314, 356,
376, 388
Work of breathing, 5, 16, 17, 21, 65, 66, 97,
101, 102, 141, 143, 148, 150, 151, 161,
166, 167, 169, 173, 191, 193, 202, 203,
205, 208, 209

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Noninvasive Mechanical Ventilation and Difficult Weaning in Critical Care

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Antonio M.

Key Topics and

Noninvasive Mechanical Ventilation

Library of Congress Control Number: 2015960386

To wife Rosario, my daughters and Rosana

Antonio M. Esquinas, MD, PhD, FCCP

Weaning From Mechanical Ventilation.

Physiologic Determinants of Prolonged Mechanical

Automated Weaning Modes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Neurally Adjusted Ventilatory Assist in Noninvasive

Recommendations of Sedation and Anesthetic

Implications of Manual Chest Physiotherapy

Nutrition in Ventilator-Dependent Patients. . . . . . . . . . . . . . . . . . . . . .

Predictive Models of Prolonged Mechanical

Non Invasive Mechanical Ventilation

Noninvasive Mechanical Ventilation in Difficult

High-Flow Nasal Cannula Oxygen in Acute

Post Extubation Failure and Use

Use of Noninvasive Ventilation to Facilitate Weaning

Predictors of Prolonged Mechanical Ventilation

Noninvasive Ventilation Following Abdominal Surgery. . . . . . . . . . .

Noninvasive Mechanical Ventilation in Postoperative

Noninvasive Ventilation After Extubation in Obese

Noninvasive Mechanical Ventilation in Patients

Dysphagia in Post-extubation Respiratory Failure:

Determinant Factors of Failed Extubation

Noninvasive Mechanical Ventilation

Noninvasive Mechanical Ventilation

Non Invasive Mechanical Ventilation

Tracheostomy Decannulation: Key Practical

Extubation and Decannulation of Unweanable

Discharge Ventilator Depend Patients

Criteria for Discharging Patients with Prolonged

Weaning Units. Organization

Organization of a Weaning Unit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Difficult and Prolonged Weaning: The Italian

Noninvasive Ventilation Interfaces and Equipment

Noninvasive Ventilation Strategies to Prevent

Application of Noninvasive Ventilation in Preventing

Non Invasive Mechanical Ventilatio

Non Invasive Mechanical Ventilation

Noninvasive Ventilation and Weaning Outcome . . . . . . . . . . . . . . . . .

Physiologic Determinants of Prolonged

D. Lagonidis and I. Chouris

Respiratory Physiological Determinants

1.2.1.1 Factors Determining Increased Respiratory Load

1 Physiologic Determinants of Prolonged Mechanical Ventilation and Unweanable Patients 5

on inspiratory muscle capacity. It is worthy of consideration that in patients on PMV,

D. Lagonidis and I. Chouris

1 Physiologic Determinants of Prolonged Mechanical Ventilation and Unweanable Patients 7

1.2.1.2 Factors Determining Reduced Respiratory Capacity

D. Lagonidis and I. Chouris

1 Physiologic Determinants of Prolonged Mechanical Ventilation and Unweanable Patients 9

mechanical load/capacity balance, predominantly because of reduced Pdimax rather

D. Lagonidis and I. Chouris

1 Physiologic Determinants of Prolonged Mechanical Ventilation and Unweanable Patients 11

D. Lagonidis and I. Chouris

Increased motor drive (very

Inspiratory muscle weakness or

1 Physiologic Determinants of Prolonged Mechanical Ventilation and Unweanable Patients 13

D. Lagonidis and I. Chouris

Prolonged Weaning from Mechanical

acute physiology and health evaluation

V. Papaioannou, MD, MSc, PhD (*) I. Pneumatikos, MD, PhD, FCCP

V. Papaioannou and I. Pneumatikos

Pathophysiology of Weaning Failure

Prolonged Weaning from Mechanical Ventilation: Pathophysiology and Weaning