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Intensive Care Med

DOI 10.1007/s00134-015-3945-4 WHATS NEW IN INTENSIVE CA RE

Pieter O. Depuydt
John P. Kress
The ten diseases that are not true diseases
Jorge I. F. Salluh

complexities of biological phenomena with the use of


Received: 11 January 2015
Accepted: 23 June 2015 concepts such as diseases and syndromes (Fig. 1). Identi-
fying causes may lead to prevention or etiological therapy,
Springer-Verlag Berlin Heidelberg and ESICM 2015 and unravelling courses may lead to strategies for reversal
or mitigation. However, reality is often much more com-
P. O. Depuydt plex and unpredictable than our concepts. As such, some
Department of Intensive Care, Ghent University Hospital and diseases may be rather mental constructs or oversimplifi-
Heymans Institute of Pharmacology, Ghent University, cations, and syndromes may be ragbags: in both cases, they
De Pintelaan 185, 9000 Ghent, Belgium are poor or even misleading guides for therapy.
J. P. Kress
Section of Pulmonary and Critical Care, University of Chicago,
5841 South Maryland Ave., 60637, MC 6026 Chicago, IL, USA
1. ARDS
J. I. F. Salluh
DOr Institute for Reasearch and Education, Rio de Janeiro, Brazil Despite recent refinement and stratification of the ARDS
definition [2], a clinical diagnosis of ARDS is poorly
J. I. F. Salluh
Programa de Pos-Graduacao em Oncologia, Instituto Nacional de
correlated with the histopathological substrate. Diagnos-
Cancer, Rio de Janeiro, Brazil ing ARDS is important in selecting patients for
interventions that limit iatrogenic pulmonary damage
J. I. F. Salluh ()) such as muscle relaxation or prone ventilation, but lacks
Rua Diniz Cordeiro, 30. Botafogo, 22281-100 Rio De Janeiro, accuracy in predicting a response to pharmacological
Brazil treatment of the disease process. Indeed, a diverse spec-
e-mail: jorgesalluh@gmail.com trum of pathologies may hide under the moniker of
Tel.: ?55 21 2538 3541
nonresolving ARDS [3]: some of these can be charac-
terized by specific histological patterns (such as
bronchiolitis obliterans organizing pneumonia or forms of
subacute hypersensitivity pneumonitis) and are likely to
respond to corticosteroid therapy, while others, especially
Introduction those with predominant fibrosis, are much more refractory
to corticosteroids.
Intensive care medicine is a young medical speciality. As
tremendous advances in life-supporting therapies have
allowed patients to be kept alive for a prolonged time
despite essential organs or biological systems failing [1], 2. VAP and VAT
we have entered new medical territory with its own
pathologies and disorders. Our way to chart this unknown In the absence of a gold standard diagnosis, defining
domain recapitulates how we have developed medicine in ventilator-associated pneumonia (VAP) remains elu-
general. First of all, we try to add some order to the sive [4]. A clinical/radiological diagnosis of VAP is
Fig. 1 What makes a disease a
true disease? Framework for a
causal, clinical, biologic, and
pathologic definition of diseases

inaccurate, includes many non-infectious conditions, and 4. Sick euthyroid illness


leads to antibiotic overtreatment; requiring more stringent
microbiological criteria for diagnosis increases specificity In the absence of true understanding of how critical ill-
at the cost of reduced sensitivity and missed opportunities ness profoundly affects or alters homeostasis, we project
for timely antibiotic therapy. Rather than considering VAP definitions and concepts from non-critically ill to criti-
as a clear-cut disease, it should be approached as the more cally ill patients. This results in the introduction of
relative concept of a probability tool guiding antibiotic diagnoses that are essentially defined by numbers and not
decisions. The inaccuracy of VAP diagnosis and the by actual pathophysiological derangements. Aiming to
continuum between colonization and tissue invasion by correct the below normal hormone levels in patients
pathogens inevitably lead to intermediate clinical pictures. diagnosed with sick euthyroid illness has no consistent
Ventilator-associated tracheobronchitis (VAT) is VAP effect and may be associated with increased harm [9].
minus the presence of new infiltrates on chest X-ray.
Given the suboptimal sensitivity of portable X-ray and the
interobserver variability for alveolar infiltrates, it is likely
that VAT has a significant overlap with VAP. Currently 5. Relative adrenal insufficiency
we are not sure how to approach VAT. The impact of early
systemic or aerosolized antibiotic therapy on the outcome While there is no doubt that adrenocortical function may
of VAT remains unclear [5] and a recent study using a pre- be impaired by critical illness and that corticoid substi-
emptive approach in a cardiovascular surgery population tution may help to overcome the adverse metabolic and
reduced the incidence of VAP and VAT but did not change hemodynamic effects of cortisol deficiency, the syndrome
major clinical outcomes and had the potential to induce of relative adrenal insufficiency (RAI) continues to be an
antimicrobial resistance [6]. area of great uncertainty. There exists no uniformly
accepted diagnostic test for RAI, the relationships
between plasma cortisol levels and patient outcome are
complex, and cortisol substitution has not consistently
3. VAE been shown to improve outcome in RAI [10].

Using VAP rates as a marker of quality of ICU care is


hampered by subjectivity of various components of the
diagnosis and by variability of VAP rates using different 6. Delirium
diagnostic criteria [7]. The concept of ventilator-associ-
ated event (VAE) has been proposed as a more objective From what initially was perceived as confusion, ICU
and thus more solid tool for benchmarking. However, psychosis, withdrawal state, or was overlooked alto-
VAE is a very heterogeneous condition, capturing VAP gether, we have recognized a syndrome called delirium,
only partially and including many non-infectious com- and started to gain knowledge of its epidemiology, risk
plications [8]. Before embarking on widespread and/or factors, and impact on outcomes. ICU delirium has been
compulsory VAE monitoring and reporting, it should be identified as an independent predictor of poor outcome,
made more clear to what extent VAE reflects quality of yet it seems likely that ICU delirium is largely a mani-
care and whether it is preventable. festation of underlying vulnerability [11]. The incidence
of ICU delirium varies widely across different studies, associated with increased morbidity and mortality. How
which is attributable to differences in terminology, seda- to define the nutritional needs of critically ill patients and
tion practices, and patient case-mix [1214]. While data how to meet them are less clear. Studies that compared
are accumulating about strategies and interventions to different nutritional strategies have produced conflicting
prevent delirium in the ICU, we are still unsure about how or inconclusive results, and better achievement of prede-
aggressively we should treat it when it is present [15]. fined nutritional goals has not necessarily translated in
better outcome [19]. Whereas in the general population
several diseases have been linked to malnutrition and
nutrient deficiencies and may be prevented or reversed by
7. Acute renal failure/acute kidney injury adequate substitution, malnutrition in the ICU still
behaves as a moving target that escapes our one-menu-
Studies on the epidemiology, impact, and treatment of fits-all approach [20].
acute renal failure (ARF) have been plagued by confusion
through the lack of consensus about its practical defini-
tion. In addition, the concept of ARF as a principal
disease or syndrome of the kidney is probably flawed. On 10. SIRS and sepsis
the one hand, minor changes in serum creatinine of little
immediate clinical importance have a major impact on Although widely embraced by the critical care commu-
overall outcome. On the other hand, mortality remains nity as a condition with undisputable clinical and
excessively high in ICU patients requiring renal replace- epidemiologic relevance, perhaps the Achilles heel of
ment therapy, despite its efficacy in eliminating sepsis is related to its definition. Since it was first
nitrogenous waste products, restoring fluid balances, and defined in 1992 along with the systemic inflammatory
normalizing electrolyte levels. Different modalities, response syndrome (SIRS) criteria, the definitions have
intensity, and timing of renal replacement therapy have evolved in an attempt to capture the growing knowledge
not resulted in better outcomes (e.g., [16]). The concept of of pathophysiology as well as the mechanisms and fea-
ARF has been superseded by that of acute renal injury, tures of organ dysfunctions. The broad definitions, while
which encompasses a much wider spectrum of abnor- important for epidemiologic purposes, have failed to
malities and appreciates the heterogeneous character of provide adequate groups of patients with homogeneous
the concept. etiologies, presentations, and outcomes. This fact is
often ascribed as one of the causes for the failure of
several randomized controlled trials (RCTs) that tested
the efficacy of adjuvant sepsis therapies. A good
8. Catheter-associated urinary tract infection example of how better clinical phenotyping may help
guide therapy comes from the 1980s when patients with
In patients with indwelling urinary catheters, it is recom- Pneumocystis jiroveci pneumonia and acquired immun-
mended to take into account clinical signs and symptoms odeficiency syndrome (AIDS) were stratified to receive
to distinguish catheter-associated urinary tract infection steroids according to a clinical profiling approach. Then,
(CAUTI) from asymptomatic bacteriuria not requiring patients with a specific immunologic profile (T cell type
treatment with antibiotics. However, in critically ill immunodeficiency), with a single pathogen (P. jiroveci),
patients, symptoms such as dysuria, urge, and abdominal presenting with a well-defined organ dysfunction (severe
pain often cannot be reliably assessed, are often absent in hypoxemia and respiratory failure) were considered eli-
CAUTI, or may be elicited by the catheter itself. Bac- gible to receive adjunctive corticosteroids [21].
teremia associated with CAUTI is rare [17]. Despite the For these reasons and also as a result of recent chal-
lack of any reliable diagnosis of CAUTI in the ICU and no lenges to the SIRS definition in light of new
clear benefit associated with the use of antibiotics [18], a epidemiologic data [22], new definitions are being
clinical suspicion of CAUTI remains one of the main developed and should be available in 2015 [23].
drivers of antibiotic consumption in the ICU.
Acknowledgments Dr. Salluh is supported in part by individual
research grant from CNPq and FAPERJ.

Conflicts of interest None.


9. Malnutrition
Energy depletion, nutrient deficiencies, and protein cata-
bolism are common in critically ill patients and have been
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