Review

formerly Biology of the Neonate

Neonatology 2008;94:197202 DOI: 10.1159/000143722

Published online: October 2, 2008

Weaning Preterm Infants from Mechanical Ventilation

Eduardo Bancalari Nelson Claure
Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Fla., USA

Key Words Weaning preterm infants Mechanical ventilation Weaning strategies Modes of ventilation and adjunctive methods High-frequency ventilation Synchronized/ patient-triggered ventilation Pressure support ventilation

Abstract Mechanical ventilatory support is required by a large number of neonates in respiratory failure. However, its use in preterm infants is frequently associated with acute complications and long-term respiratory sequelae. Therefore, it is recommended to avoid or limit the exposure to ventilatory support. This is a review of existing practices and novel strategies to achieve weaning of ventilatory support in this population. Copyright 2008 S. Karger AG, Basel

Introduction

the duration of invasive ventilatory support in preterm infants. However, this is difficult in the very immature infant because of inconsistent respiratory drive, a weak respiratory pump and immature and frequently injured lungs. This combination of factors makes them extremely prone to become ventilator-dependent for long periods of time and fall into a negative cycle where the longer they remain ventilator-dependent the more difficult it becomes to achieve adequate gas exchange without mechanical support. For many years most infants were ventilated by controlling their respiration and providing most of the minute ventilation with the ventilator. In recent years the trend is to use ventilators as an assist or support while preserving the patients respiratory effort, and this has been an important step in reducing the duration of mechanical ventilation and its complications. This was made possible by the introduction of ventilators that can synchronize the positive pressure cycle with the infants inspiratory effort.

Mechanical ventilatory support is required by a large proportion of critically ill neonates and is necessary for survival of most extremely premature infants. However, mechanical ventilation is associated with serious acute complications and long-term sequelae. For this reason most clinicians try to avoid or limit as much as possible
2008 S. Karger AG, Basel 16617800/08/09430197$24.50/0 Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Accessible online at: www.karger.com/neo

Weaning Strategies What to Wean First?

The first question is when should weaning be started and what ventilator settings should be lowered first? Because of the high rate of complications associated with
Prof. Eduardo Bancalari Division of Neonatology, Department of Pediatrics University of Miami Miller School of Medicine PO Box 016960 R-131, Miami, FL 33101 (USA) Tel. +1 305 585 6408, Fax +1 305 545 6581, E-Mail EBancalari@miami.edu

mechanical ventilation, weaning should begin as soon as ventilation is started and respiratory function is stabilized. This effort should not cease until the infant is extubated and breathing spontaneously with no mechanical support. The order in which the different ventilator settings are decreased is determined by the relative risk associated with each of them and the cause of respiratory failure. In an infant with severe pulmonary interstitial emphysema the first step should be to reduce the pressures and tidal volume (VT) to avoid more damage. In an infant with poor hemodynamic function, a reduction in positive endexpiratory pressure (PEEP) and mean airway pressure (MAP) may be the most appropriate first step. With the possibility of measuring VT, it has become much simpler to find the appropriate peak inspiratory pressure (PIP) that is required to generate an adequate VT of 35 ml per kg body weight. As lung compliance improves, PIP is reduced to keep VT within normal range. PEEP is usually kept between 4 and 8 cm H2O depending on the type of underlying lung disease and the requirement for supplemental oxygen. PEEP can be decreased gradually as oxygenation improves until a level of 45 cm H2O is reached and this level is maintained until extubation. Inspired oxygen concentration is lowered according to arterial oxygen tension or saturation measured by pulse oximetry. The optimal ranges of oxygenation have not been defined, but until better data become available most clinicians target saturations between 88 and 93% in very preterm infants and somewhat higher in more mature infants where the risk of hyperoxic retinal and lung damage is lower. When VT measurement is not available, reduction in PIP is based on observed chest movement, degree of aeration on chest radiograph and PaCO2 levels. The adjustment of ventilator rate depends on the type of ventilation strategy being used. In intermittent mandatory ventilation (IMV) or synchronized IMV (SIMV) the rate is gradually weaned as spontaneous breathing becomes more consistent and PaCO2 remains within an acceptable range. When the infant is ventilated with synchronized modes such as assist control (A/C) or pressure support (PS), the cycling rate of the ventilator is determined by the infant and the rate set in the ventilator becomes a backup frequency at which the ventilator will cycle when the infants own rate falls below that level. Therefore it is only relevant when the infant becomes apneic or hypoventilates. When the infant is controlled, the ventilator rate is adjusted by the clinician and this is generally based on PaCO2.
198
Neonatology 2008;94:197202

When weaning the ventilator it is recommended that gradual changes be made reducing one setting at a time to evaluate the response of the infant to each change. Today, with the availability of continuous oxygen and carbon dioxide monitoring devices, it is not necessary to wait for results of arterial blood gas measurements to change ventilator settings and weaning can proceed faster.

Modes of Ventilation and Adjunctive Methods

Synchronized or Patient-Triggered Ventilation The use of synchronized or patient-triggered ventilation (PTV) has become common practice in preterm infants. Most randomized trials comparing PTV with nonsynchronized ventilation have shown a reduction in duration of mechanical ventilation in infants treated with synchronized modes [1]. It is not entirely clear how PTV can lead to a shorter duration of mechanical ventilation but it is probably due to the infant retaining more control on ventilation, and the effectiveness of the mechanical and spontaneous breaths is increased by the synchronization of the positive pressure and the negative pressure generated by the infant. A/C and SIMV are the most common modes of synchronized ventilation used in neonates. Studies indicate faster weaning in A/C than in SIMV [2, 3]. Assisting each spontaneous inspiration avoids what some consider a disadvantage when only some spontaneous breaths are assisted in SIMV. However, SIMV is the preferred mode of weaning in many centers. This may be due to a relatively simpler weaning process where the clinician increases the contribution of spontaneous breathing to minute ventilation by simply reducing the ventilator rate. Pressure Support Ventilation The only randomized trial comparing pressure support ventilation (PSV) with SIMV in preterm infants revealed faster weaning and shorter duration of ventilation in infants who were ventilated with SIMV+PSV when compared with SIMV alone [4]. The addition of PSV allowed faster weaning of larger SIMV breaths and by doing this, it may reduce volume damage to the lung and increase spontaneous respiratory drive accelerating weaning. As shown in figure 1, the proportion of ventilator-dependent infants during the first 28 days was lower in infants ventilated by SIMV+PS and they were weaned from mechanical ventilation earlier than infants supported by SIMV alone.
Bancalari/Claure

Nasal Continuous Positive Airway Pressure after Extubation After extubation the infant is exposed to a number of impediments that explain the frequent need for reintubation in the smaller preterm infants. These include upper airway damage and retained secretions leading to obstruction and atelectasis, loss of lung volume due to poor respiratory effort and a highly compliant chest wall. For these reasons the use of continuous positive airway pressure (CPAP) applied through the nose can significantly reduce the deterioration that frequently occurs in smaller infants after extubation. It is intriguing that despite this improvement in respiratory function produced by nasal CPAP the need for reintubation has not been shown to be reduced by the post-extubation use of nasal CPAP [5]. Nasal Ventilation after Extubation In contrast with nasal CPAP, the use of nasal ventilation after extubation has been shown to significantly reduce extubation failure [6]. Although these studies have included small numbers of infants, the effects have been consistent despite the fact that the techniques used for nasal ventilation have varied considerably. This is a promising alternative that needs further evaluation and the development of suitable equipment to provide synchronized non-invasive support. Respiratory Stimulants Respiratory stimulants including aminophylline and caffeine are effective in increasing respiratory central activity in preterm infants and decreasing severe apneic episodes. These drugs also facilitate successful weaning from mechanical ventilation and decrease the need for reintubation. For this reason most preterm infants receive a loading dose of caffeine or aminophylline before extubation and they are maintained on one of these stimulants for at least the first few days after extubation while they are also maintained on nasal CPAP or nasal ventilation [7]. Permissive Hypercapnia Tolerance of higher carbon dioxide levels has been proposed as a way of reducing mechanical support and ventilator-induced lung damage and BPD. The results of several clinical trials have been inconsistent and have not shown a clear reduction in lung damage. However, some initial trials suggested faster weaning from mechanical ventilation in the group with higher CO2 levels [8]. A more recent study showed no benefit in terms of duration of ventilation with hypercapnia and a possible increase in
Weaning Preterm Infants from Mechanical Ventilation

100

SIMV SIMV + PS

80

Ventilator dependency (%)

60

40

20

0 0 5 10 15 Time (days) 20 25 28

Fig. 1. Proportion of ventilator-dependent infants during the first

28 days. Infants in the SIMV+PS group were weaned from mechanical ventilation earlier than infants supported by SIMV alone. From Reyes et al. [4], with permission.

mortality and neurological impairment in infants in the minimal ventilation group [9, 10]. While these results should caution against tolerating high CO2 levels in premature infants during the acute stages of their course, in infants with chronic lung damage it is very difficult to achieve weaning of ventilator settings unless some degree of hypercapnia is tolerated. In fact, in infants with severe BPD it is common to observe high levels of PaCO2 that are usually compensated by metabolic alkalosis that persists for long periods of time after weaning from mechanical ventilation. Dead Space Reduction Tracheal Ventilation The anatomical dead space in preterm infants is relatively large [11]. In these infants the instrumental dead space reduces alveolar ventilation [12] and can contribute to delay in weaning of ventilator settings. In continuous tracheal gas insufflation (CTGI), gas is pumped through small capillaries to the distal end of the endotracheal tube to produce a continuous washout of the tube. CTGI was first shown to reduce arterial CO2 with the same ventilator settings or maintain similar CO2 levels with less support [13]. In a randomized trial, CTGI shortened the weaning process [14]. This method is limNeonatology 2008;94:197202

199

ited by the need for additional equipment and a specialized endotracheal tube. Proximal flow sensors used for synchronization and volume measurement have small dead spaces; however, they can induce CO2 rebreathing in smaller infants who need to increase their spontaneous ventilation to compensate for the increased dead space. A simple method consisting of a continuous side stream gas leak washes out the flow sensor and reduces rebreathing in preterm infants recovering from RDS [15]. Extubation from Intermittent Mandatory Ventilation or Continuous Positive Airway Pressure For many years, infants on mechanical ventilation were extubated only after they had tolerated several hours on CPAP applied through the endotracheal tube maintaining reasonable levels of arterial blood gases. This strategy was changed by a simple and small trial where it was demonstrated that infants extubated from a low IMV rate had better success rates than those kept on CPAP for 6 h before extubation [16]. This probably avoids extubating an already exhausted infant and thus saves the infants breathing effort for the crucial period following extubation. Monitoring Tidal Volume Improvements in respiratory system mechanics and enhanced contribution of spontaneous inspiratory effort lead to an increase in VT. Continuous monitoring of VT in newer mechanical ventilators can therefore be used to wean PIP. Although the effects of VT monitoring on weaning have not been fully evaluated, it can facilitate detection of lung overdistension and consequently lead to weaning of PIP [17]. Retrospective data suggest less air leaks and intraventricular hemorrhage among infants in whom VT was kept within normal limits compared to those not monitored [18].

The pressure amplitude is gradually reduced following the levels of PaCO2. A possible problem during weaning from HFV is that when MAP is weaned to low levels before the infant has spontaneous respiratory effort, there can be rapid loss of lung volume and atelectasis. For this reason it is advisable to lower the pressure amplitude to allow the CO2 to increase and stimulate spontaneous breathing before MAP is lowered below 10 or 8 cm H2O.
Prediction of Successful Extubation

Weaning from High Frequency Ventilation

While infants ventilated with high frequency ventilation (HFV) are commonly switched to conventional ventilation prior to extubation, this is not always necessary. Infants can be extubated from HFV and the steps prior to accomplishing this are not substantially different from those used with conventional ventilation. Reduction in MAP is done according to oxygenation and lung expansion estimated by chest radiographs while inspired oxygen concentration (FiO2) is adjusted to maintain the desired oxygenation levels.
200
Neonatology 2008;94:197202

One of the most difficult decisions in ventilated infants is to decide the best time for extubation. Many infants remain intubated for longer than they really need. This is supported by the finding that many infants who accidentally extubate are able to breathe spontaneously without need for further respiratory support. Many studies have evaluated different tools to predict successful extubation. These include measurement of lung mechanics, inspiratory strength, ability to cope with mechanical loads, lung volume levels before and after extubation, and the efficacy of spontaneous minute ventilation to maintain gas exchange during a period when ventilator cycling is stopped [1921]. Although some of these tools predict successful extubation with some accuracy, none have been widely accepted in clinical practice. The decision to extubate is usually based on the level of inspired oxygen and ventilator support that the infant needs to maintain acceptable arterial blood gas levels. In general terms, when an infant is receiving less than 30 or 40% oxygen, a ventilator rate of less than 15 per minute and peak pressures below 15 cm H2O and keeps acceptable blood gases, most clinicians attempt extubation. The lower the gestational age, the more likely that infants will fail weaning from the ventilator and will require reintubation. In most cases this failure is because of poor respiratory effort or severe apneic episodes while in others it is due to loss of lung volume with increasing distress and oxygen requirement following extubation. Upper airway damage and obstruction as well as retained secretions can also produce respiratory failure after extubation.

Automatic Weaning

Volume-Targeted Ventilation Automatic weaning of PIP can be achieved as the mechanical conditions of the lung improve or the contribution of spontaneous breathing effort increases. This is
Bancalari/Claure

achieved by automatic decreases of PIP as VT increases using volume-targeted ventilation where the ventilator continuously adjusts PIP to achieve a preset VT [22]. Volumetargeted ventilation achieves automatic weaning independent of the clinician who only decides what VT is delivered by the ventilator. There is some evidence from randomized trials that volume-targeting strategies can achieve faster weaning from mechanical ventilation although the results have not been entirely consistent [23, 24]. Targeted Minute Ventilation Mechanically ventilated preterm infants often show fluctuations in spontaneous ventilation during weaning due to inconsistent respiratory drive and acute changes in respiratory mechanics. These fluctuations often lead clinicians to set higher ventilator rates or PIP to provide sufficient ventilation at all times which delays the weaning process. Targeted minute ventilation is an experimental mode where the ventilator rate is adjusted automatically. During periods of consistent spontaneous breathing and improved respiratory mechanics with minute ventilation above the target level, the ventilator rate is automatically reduced or vice versa. In preterm infants recovering from RDS, targeted minute ventilation reduced the ventilator rate by half in comparison to SIMV. The lower ventilator rate was compensated by greater spontaneous minute ventilation, while arterial blood gases remained unchanged [25]. Targeted minute ventilation and volume-targeted ventilation can be combined to achieve automated adjustments of rate and PIP simultaneously. The application of this combined mode in an animal model resulted in weaning of the support during periods of stable breathing while it maintained stability of ventilation and gas exchange during periods of apnea or impaired lung mechanics [26]. Mandatory minute ventilation is an adult weaning mode now also available for infants, where the ventilator rate is turned off if minute ventilation exceeds a set level or otherwise delivers volume-controlled breaths at a set rate. This mode also achieved faster weaning in a group of near term infants without lung disease [27].

nized and consistent ventilatory strategies. One of these algorithms was evaluated in infants with RDS [28]. Based on the input from blood gas status and ventilator settings, management assisted by the algorithm led to improvements in gas exchange and avoided unnecessary increases in ventilator settings. Routine care corrected hypoxemia and hypercapnia more effectively than hyperoxia and hypocapnia, whereas computer-assisted weaning was effective in both situations. This suggests potential benefits of computer-assisted weaning, but this kind of strategy has not been fully explored.

Automatic Weaning of Supplemental Oxygen

Ventilated infants often need supplemental oxygen which increases the risk for lung and retinal injury, particularly when exposure to high FiO2 is prolonged. In these infants, hyperoxemia is frequently induced by an excessive FiO2 and it is therefore modifiable by appropriate weaning. However, these infants spend prolonged periods of time with arterial oxygen saturation above recommended levels [29]. Moreover, alarms in pulse oximeters are often ignored or even set above the recommended range [30]. FiO2 weaning is often delayed due to frequent episodes of hypoxemia and basal FiO2 is maintained at higher levels by staff in the belief that it may prevent or ameliorate the episodes of hypoxemia. Automated FiO2 control is more effective in maintaining oxygenation within a desired range than routine care. This is in large part accomplished by avoidance of hyperoxemia resulting from automatic weaning of FiO2 as soon as saturation exceeds the set target range [3134]. In conclusion, there are many strategies that can be used to facilitate weaning of infants from mechanical respiratory support and reduce exposure to invasive ventilation and its complications. Automation of ventilator settings is making this task more consistent and less demanding on staff and may improve outcome.
References
1 Greenough A: Update on patient-triggered ventilation. Clin Perinatol 2001; 28:533546. 2 Chan V, Greenough A: Comparison of weaning by patient-triggered ventilation or synchronous mandatory intermittent ventilation. Acta Paediatr 1994;83:335337. 3 Dimitriou G, Greenough A, Griffin F, Chan V: Synchronous intermittent mandatory ventilation modes versus patient-triggered ventilation during weaning. Arch Dis Child 1995;72:F188F190.

Computer-Assisted Weaning

Ventilator management involves adjustments of several settings that can all affect the infants ventilation and gas exchange. Algorithms for ventilator management have been proposed as a way to achieve efficient, orgaWeaning Preterm Infants from Mechanical Ventilation

Neonatology 2008;94:197202

201

4 Reyes ZC, Claure N, Tauscher MK, DUgard C, Vanbuskirk S, Bancalari E: Randomized, controlled trial comparing synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in preterm infants. Pediatrics 2006;118:14091417. 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;CD000143. 6 De Paoli AG, Davis PG, Lemyre B: Nasal continuous positive airway pressure versus nasal intermittent positive pressure ventilation for preterm neonates: a systematic review and meta-analysis. Acta Paediatr 2003; 92: 70 75. 7 Henderson-Smart DJ, Davis PG: Prophylactic methylxanthines for extubation in preterm infants. Cochrane Database Syst Rev 2003;CD000139. 8 Mariani G, Cifuentes J, Carlo WA: Randomized trial of permissive hypercapnia in preterm infants. Pediatrics 1999; 104: 1082 1088. 9 Carlo WA, Stark AR, Wright LL, Tyson JE, Papile LA, Shankaran S, Donovan EF, Oh W, Bauer CR, Saha S, Poole WK, Stoll B: Minimal ventilation to prevent bronchopulmonary dysplasia in extremely-low-birthweight infants. J Pediatr 2002;141:370374. 10 Thome UH, Carroll W, Wu TJ, Johnson RB, Roane C, Young D, Carlo WA: Outcome of extremely preterm infants randomized at birth to different PaCO2 targets during the first seven days of life. Biol Neonate 2006;90: 218225. 11 Numal AH, Newth CJ: Anatomic dead space in infants and children. J Appl Physiol 1996; 80:14851489. 12 Figueras J, Rodriguez-Migulez JM, Botet F, Thi M, Jimnez R: Changes in TcPCO2 regarding pulmonary mechanics due to pneumotachometer dead space in ventilated newborns. J Perinat Med 1997;25:333339. 13 Danan C, Dassieu G, Janaud JC, Brochard L: Efficacy of dead-space washout in mechanically ventilated premature newborns. Am J Respir Crit Care Med 1996;153:15711576. 14 Dassieu G, Brochard L, Benani M, Avenel S, Danan C: Continuous tracheal gas insufflation in preterm infants with hyaline membrane disease. A prospective randomized trial. Am J Respir Crit Care Med 2000; 162: 826831.

15 Claure N, DUgard C, Bancalari E: Elimination of ventilator dead space during synchronized ventilation in premature infants. J Pediatr 2003;143:315320. 16 Kim EH, Boutwell WC: Successful direct extubation of very low birth weight infants from low intermittent mandatory ventilation rate. Pediatrics 1987;80:409414. 17 Fisher JB, Mammel MC, Coleman JM, Bing DR, Boros SJ: Identifying lung overdistention during mechanical ventilation by using volume-pressure loops. Pediatr Pulmonol 1988;5:1014. 18 Rosen WC, Mammel MC, Fisher JB, Coleman JM, Bing DR, Holloman KK, Boros SJ: The effects of bedside pulmonary mechanics testing during infant mechanical ventilation: a retrospective analysis. Pediatr Pulmonol 1993;16:147152. 19 Vento G, Tortorolo L, Zecca E, Rosano A, Matassa PG, Papacci P, Romagnoli C: Spontaneous minute ventilation is a predictor of extubation failure in extremely-low-birthweight infants. J Matern Fetal Neonatal Med 2004;15:147154. 20 Gillespie LM, White SD, Sinha SK, Donn SM: Usefulness of the minute ventilation test in predicting successful extubation in newborn infants: a randomized controlled trial. J Perinatol 2003;23:205207. 21 Kamlin CO, Davis PG, Morley CJ: Predicting successful extubation of very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2006;91:F180F183. 22 Herrera CM, Gerhardt T, Claure N, Everett R, Musante G, Thomas C, Bancalari E: Effects of volume-guaranteed synchronized intermittent mandatory ventilation in preterm infants recovering from respiratory failure. Pediatrics 2002;110:529533. 23 Sinha SK, Donn SM, Gavey J, McCarty M: Randomised trial of volume controlled versus time cycled, pressure limited ventilation in preterm infants with respiratory distress syndrome. Arch Dis Child Fetal Neonatal Ed 1997;77:F202F205. 24 Singh J, Sinha SK, Clarke P, Byrne S, Donn SM: Mechanical ventilation of very low birth weight infants: is volume or pressure a better target variable? J Pediatr 2006;149:308313.

25 Claure N, Gerhardt T, Hummler H, Everett R, Bancalari E: Computer-controlled minute ventilation in preterm infants undergoing mechanical ventilation. J Pediatr 1997; 131: 910913. 26 Claure N, Suguihara C, Peng J, Hehre D, DUgard C, Bancalari E: Targeted minute ventilation and tidal volume in an animal model of acute changes in lung mechanics and episodes of hypoxemia. Neonatology 2008, in press. 27 Guthrie SO, Lynn C, Lafleur BJ, Donn SM, Walsh WF: A crossover analysis of mandatory minute ventilation compared to synchronized intermittent mandatory ventilation in neonates. J Perinatol 2005; 25: 643646. 28 Carlo WA, Pacifico L, Chatburn RL, Fanaroff AA: Efficacy of computer-assisted management of respiratory failure in neonates. Pediatrics 1986;78:139143. 29 Hagadorn JI, Furey AM, Nghiem TH, Schmid CH, Phelps DL, Pillers DA, Cole CH; AVIOx Study Group: Achieved versus intended pulse oximeter saturation in infants born less than 28 weeks gestation: the AVIOx study. Pediatrics 2006;118:15741582. 30 Clucas L, Doyle LW, Dawson J, Donath S, Davis PG: Compliance with alarm limits for pulse oximetry in very preterm infants. Pediatrics 2007;119:10561060. 31 Beddis JR, Collins P, Levy NM, Godfrey S, Silverman M: New technique for servo-control of arterial oxygen tension in preterm infants. Arch Dis Child 1979;54:278280. 32 Dugdale RE, Cameron RG, Lealman GT: Closed-loop control of the partial pressure of arterial oxygen in neonates. Clin Physics Physiol Meas 1988;9:291305. 33 Claure N, Gerhardt T, Everett R, Musante G, Herrera C, Bancalari E: Closed-loop controlled inspired oxygen concentration for mechanically ventilated very low birth weight infants with frequent episodes of hypoxemia. Pediatrics 2001;107:11201124. 34 Urschitz MS, Horn W, Seyfang A, Hallenberger A, Herberts T, Miksch S, Popow C, Mller-Hansen I, Poets CF: Automatic control of the inspired oxygen fraction in preterm infants: a randomized crossover trial. Am J Respir Crit Care Med 2004; 170: 1095 1100.

202

Neonatology 2008;94:197202

Bancalari/Claure

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.