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Strategies to accelerate weaning from respiratory support
Early Human Development 89S1 (2013) S4–S6
Contents lists available at ScienceDirect
Early Human Development j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / e a r l h u m d ev
Strategies to accelerate weaning from respiratory support Eduardo Bancalari*, Nelson Claure Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida, USA
article info
summary
Keywords: Premature Respiratory failure Extubation
Because mechanical ventilation is associated with severe complications in premature infants, it is important to limit its duration as much as possible. This can be accomplished by using startegies that preserve spontaneous respiration such as patient triggered and volume target ventilation. The use of respiratory stimulants and nasal CPAP or nasal IPPV after extubation are also effective and improve extubation success. A short course of systemic steroids can also expedite weaning and extubation. © 2013 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Mechanical ventilation in premature infants is associated with acute complications and long-term sequelae [1]. For this reason it is important to avoid or limit the duration of invasive respiratory support in these infants. This is difficult in the very immature infants because they have immature lungs, inconsistent respiratory drive and a weak respiratory pump. Because of this, they often become ventilator-dependent for long periods of time and the longer they remain on a ventilator the more likely it is that their lungs will be damaged and the more difficult it becomes to wean them from respiratory support. For years infants were ventilated by controlling their respiration with sedation, hyperventilation and sometimes even muscle relaxation. Today ventilators are preferentially used to assist the patient’s respiratory effort to achieve adequate gas exchange. This has been an important step in reducing the duration of mechanical ventilation and has become possible with the introduction of ventilators that can synchronize the mechanical cycle with the infant’s inspiratory effort. 2. Weaning ventilator settings The longer a premature infant remains on mechanical respiratory support the higher the risk of complications. Therefore the aim should always be to wean the infant as soon as possible. The decision on which parameters to wean, first should take into consideration the mechanism of the respiratory failure and the association of each parameter with complications. In infants with signs of air leak the first step should be reducing the peak inspiratory pressure (PIP) and tidal volume (VT ) while in infants with compromised hemodynamic function a reduction * Corresponding author. Eduardo Bancalari, M.D., Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine, PO Box 016960 R-131, Miami, FL 33101, USA. E-mail address: [email protected] (E. Bancalari). 0378-3782/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved.
in positive end expiratory pressure (PEEP) and mean airway pressure (MAP) may be the more appropriate first step. Monitoring of VT facilitates weaning of PIP. As lung mechanics and spontaneous inspiratory effort improve, PIP is adjusted to achieve adequate VT in the range of 3–6 mL per kg body weight to avoid overdistention. When VT measurement is not available reduction in PIP must be based on chest movement and PaCO2 levels. The level of PEEP is usually kept between 4 and 8 cmH2 O depending on the type and severity of the lung disease and it is guided by the requirement for supplemental oxygen and the radiographic picture. The adjustment of ventilator rate depends on the modality of ventilation being used. In modalities where the infant determines the mechanical rate, such as assist control (A/C) or pressure support (PSV), the set ventilator rate will only provide a backup when the infant becomes apneic. With intermittent mandatory ventilation (IMV) or synchronized IMV (SIMV) the rate is gradually weaned as spontaneous breathing contributes more consistently to the total minute ventilation and as long as PaCO2 remains within an acceptable range. Several clinical trials have explored minimal ventilation by permissive hypercapnia as a strategy to expedite weaning in this population, but the results have been inconsistent. Although some studies showed a reduction in the duration of mechanical ventilation they did not show a clear reduction in lung damage or BPD, and one trial showed a possible increase in mortality and neurological impairment in infants in the minimal ventilation group [2–4]. In infants with chronic respiratory failure, like those with BPD, it is difficult if not impossible to wean from the ventilator unless some degree of hypercapnia is tolerated. These infants frequently have metabolic alkalosis that is aggravated by chronic diuretic therapy and therefore their respiratory acidosis is compensated. The inspired oxygen (FiO2 ) is lowered according to PaO2 or more frequently to oxygen saturation measurements by pulse oximetry (SpO2 ). This is aimed at avoiding hyperoxemia and reducing the exposure of the lung to high FiO2 . The
E. Bancalari, N. Claure / Early Human Development 89S1 (2013) S4–S6
optimal ranges for oxygenation targets for preterm infants are still not well defined but until more definitive data become available the goal of most clinicians is to maintain SpO2 between 90% and 95%. Automatic modes of respiratory support have been developed for use in preterm infants. These systems automatically adjust the PIP to maintain a target VT , ventilator frequency to maintain a target minute ventilation level or FiO2 to maintain a target range of SpO2 . Further discussion on the efficacy of these automatic systems in weaning is provided in the article on automation of respiratory support in premature infants in this supplement [5]. 3. Respiratory stimulants Aminophylline and caffeine are effective respiratory stimulants that increase central respiratory drive in preterm infants and decrease the incidence of apneic episodes. Because of this, these drugs also increase the chance of successful weaning from mechanical ventilation and decrease the need for reintubation [6]. Caffeine is generally preferred because of a longer half-life, broader therapeutic range and fewer side effects. It is not clear if early initiation of caffeine therapy in mechanically ventilated preterm infants can shorten the duration of ventilation or improve their respiratory outcome. 4. Postnatal steroids Systemic steroids given to ventilator-dependent infants can produce a rapid improvement in lung function and facilitate weaning from the ventilator, reducing the incidence of BPD [7,8]. However systemic steroid administration is associated with complications that include arterial hypertension, hyperglycemia, increased proteolysis, adrenocortical suppression, somatic and lung growth suppression, and hypertrophic myocardiopathy. More concerning is the worse neurologic outcome, including an increased incidence of cerebral palsy associated with prolonged steroid therapy. Because of this the use of systemic steroids should only be considered after the first two weeks of life in infants who show clear evidence of severe pulmonary damage and remain ventilator dependent. The duration of steroid therapy must be limited to 5–7 days and the potential benefits and risks should be discussed with the family before initiating this therapy. Inhaled steroids have also been used but data on effectiveness are not conclusive enough to recommend their routine use. 5. Synchronized or patient-triggered ventilation Most randomized trials comparing patient-triggered ventilation (PTV) with non-synchronized ventilation have shown a
reduction in duration of mechanical ventilation in infants treated with synchronized modes [9]. This advantage is most likely due to the fact that the infant retains spontaneous respiratory activity and continues to “exercise” his respiratory pump during PTV. Studies have not indicated consistent differences in weaning from mechanical ventilation when using A/C compared to SIMV in premature infants. During IMV or SIMV the weaning is accomplished by gradual reduction of the mechanical rate allowing the patient to increase his contribution to minute ventilation. During A/C or PSV the reduction of the ventilator rate does not have any effect except for reducing the backup rate when the infant stops breathing or slows down his/her spontaneous breathing frequency below that set in the ventilator. The only randomized trial comparing SIMV combined with PSV to SIMV alone in preterm infants revealed faster weaning and shorter duration of ventilation in infants who were ventilated with SIMV in combination with PSV [10]. In this trial, infants with birth weights between 700 g and 1000 g who were ventilated with SIMV and PSV also spent less time on supplemental oxygen than those managed with SIMV alone. 6. Nasal continuous positive airway pressure post extubation The use of nasal CPAP reduces the deterioration that frequently occurs in smaller infants after extubation and reduces the need for reintubation in comparison to oxygen administration alone [11]. Still, a good number of infants fail extubation and most particularly the smaller infants with lung disease. Although nasal CPAP has been used for many years, there are no data on the most effective level of pressure to use in these infants. Results from a recent randomized clinical trial indicate that extubation to nasal CPAP in the range of 7–9 cmH2 O reduces extubation failure compared to the traditional range of 4–6 cmH2 O in preterm infants with residual lung disease [12]. 7. Nasal ventilation Nasal ventilation (NIPPV) has been reintroduced as an effective alternative to NCPAP after extubation. NIPPV has been shown to significantly reduce respiratory failure post extubation and the need for reintubation [13]. In general the settings used during NIPPV are similar to those used during the final weaning stages of invasive ventilation. NIPPV is a promising alternative to invasive ventilation but needs further evaluation and the development of suitable equipment to provide noninvasive respiratory support in premature infants. Table 1 lists the possible steps to expedite weaning from mechanical ventilation.
Table 1 Strategies to minimize duration of mechanical ventilation • Optimize lung function: Maintenance of lung volume and airway patency, reduce fluid overload and closure of symptomatic PDA • Avoid conditions leading to respiratory depression (e.g. hypoxia, metabolic alkalosis, drugs, infections) • Patient triggered ventilation – Preserve spontaneous breathing • Volume targeted ventilation – Manual or ventilator adjusted • Permissive hypercapnia in infants with chronic ventilator dependency • Avoid routine re-intubation after self-extubation • Respiratory stimulants • Post extubation NCPAP or NIPPV • Adherence to pre-established extubation criteria
S5
S6
E. Bancalari, N. Claure / Early Human Development 89S1 (2013) S4–S6
8. Prediction of successful extubation The decision on the timing to wean an infant from the ventilator is difficult and because of this many infants remain intubated for longer periods than needed. Various tools to predict successful extubation have been developed but none has been widely accepted in clinical practice. A simple test is the so-called “spontaneous breathing test” where the ventilator cycling is turned off and the infant is observed for three minutes while on CPAP. If no hypoxia or bradycardia is observed during this period the infant has an excellent chance of tolerating extubation [14]. The decision to remove an infant from respiratory support is usually based on the FiO2 and ventilator support that the infant is requiring to maintain acceptable arterial blood gas levels. Most clinicians will attempt extubation when FiO2 is less than 0.3 or 0.4, the ventilator rate is less than 15 or 20 breaths per minute, PIP is below 14 or 16 cmH2 O and the infant has acceptable blood gases. Because there is frequently some inertia to wean infants from mechanical ventilation it is useful to have written criteria to guide weaning from the ventilator and extubation.
2. 3.
4.
5. 6. 7.
8.
9. 10.
11.
Acknowledgements We are grateful to the University of Miami Project: NewBorn for their continuous support.
12.
13.
Conflict of interest statement The authors have no conflict of interest to report. References 1. Walsh MC, Morris BH, Wrage LA, Vohr BR, Poole WK, Tyson JE, et al.; National Institutes of Child Health and Human Development Neonatal Research Network.
14.
Extremely low birthweight neonates with protracted ventilation: mortality and 18-month neurodevelopmental outcomes. J Pediatr 2005;146:798–804. Mariani G, Cifuentes J, Carlo WA. Randomized trial of permissive hypercapnia in preterm infants. Pediatrics 1999;104:1082–8. Carlo WA, Stark AR, Wright LL, Tyson JE, Papile LA, Shankaran S, et al. Minimal ventilation to prevent bronchopulmonary dysplasia in extremely-low-birthweight infants. J Pediatr 2002;141:370–4. Thome UH, Carroll W, Wu TJ, Johnson RB, Roane C, Young D, et al. Outcome of extremely preterm infants randomized at birth to different PaCO2 targets during the first seven days of life. Biol Neonate 2006;90:218–25. Claure N, Bancalari E. Automation of respiratory support in premature infants. Early Hum Dev 2013;89(Suppl 1):S28–30. Henderson-Smart DJ, Davis PG. Prophylactic methylxanthines for endotracheal extubation in preterm infants. Cochrane Database Syst Rev 2010;12:CD000139. Halliday HL, Ehrenkranz RA, Doyle LW. Late (>7 days) postnatal corticosteroids for chronic lung disease in preterm infants. Cochrane Database Syst Rev 2009; 1:CD001145. Doyle LW, Ehrenkranz RA, Halliday HL. Dexamethasone treatment after the first week of life for bronchopulmonary dysplasia in preterm infants: a systematic review. Neonatology 2010;98:289–96. Greenough A. Update on patient-triggered ventilation. Clin Perinatol 2001;28: 533–46. Reyes ZC, Claure N, Tauscher MK, D’Ugard 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;118:1409–17. 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. Buzzella B, Claure N, D’Ugard C, Bancalari E. A randomized controlled trial of two nasal CPAP ranges for extubation in preterm infants with residual lung disease. Pediatric Academic Societies 2013 meeting. 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;92:70–5. Kamlin CO, Davis PG, Morley CJ. Predicting successful extubation of very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2006;91:F180–3.
Contents lists available at ScienceDirect
Early Human Development j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / e a r l h u m d ev
Strategies to accelerate weaning from respiratory support Eduardo Bancalari*, Nelson Claure Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida, USA
article info
summary
Keywords: Premature Respiratory failure Extubation
Because mechanical ventilation is associated with severe complications in premature infants, it is important to limit its duration as much as possible. This can be accomplished by using startegies that preserve spontaneous respiration such as patient triggered and volume target ventilation. The use of respiratory stimulants and nasal CPAP or nasal IPPV after extubation are also effective and improve extubation success. A short course of systemic steroids can also expedite weaning and extubation. © 2013 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Mechanical ventilation in premature infants is associated with acute complications and long-term sequelae [1]. For this reason it is important to avoid or limit the duration of invasive respiratory support in these infants. This is difficult in the very immature infants because they have immature lungs, inconsistent respiratory drive and a weak respiratory pump. Because of this, they often become ventilator-dependent for long periods of time and the longer they remain on a ventilator the more likely it is that their lungs will be damaged and the more difficult it becomes to wean them from respiratory support. For years infants were ventilated by controlling their respiration with sedation, hyperventilation and sometimes even muscle relaxation. Today ventilators are preferentially used to assist the patient’s respiratory effort to achieve adequate gas exchange. This has been an important step in reducing the duration of mechanical ventilation and has become possible with the introduction of ventilators that can synchronize the mechanical cycle with the infant’s inspiratory effort. 2. Weaning ventilator settings The longer a premature infant remains on mechanical respiratory support the higher the risk of complications. Therefore the aim should always be to wean the infant as soon as possible. The decision on which parameters to wean, first should take into consideration the mechanism of the respiratory failure and the association of each parameter with complications. In infants with signs of air leak the first step should be reducing the peak inspiratory pressure (PIP) and tidal volume (VT ) while in infants with compromised hemodynamic function a reduction * Corresponding author. Eduardo Bancalari, M.D., Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine, PO Box 016960 R-131, Miami, FL 33101, USA. E-mail address: [email protected] (E. Bancalari). 0378-3782/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved.
in positive end expiratory pressure (PEEP) and mean airway pressure (MAP) may be the more appropriate first step. Monitoring of VT facilitates weaning of PIP. As lung mechanics and spontaneous inspiratory effort improve, PIP is adjusted to achieve adequate VT in the range of 3–6 mL per kg body weight to avoid overdistention. When VT measurement is not available reduction in PIP must be based on chest movement and PaCO2 levels. The level of PEEP is usually kept between 4 and 8 cmH2 O depending on the type and severity of the lung disease and it is guided by the requirement for supplemental oxygen and the radiographic picture. The adjustment of ventilator rate depends on the modality of ventilation being used. In modalities where the infant determines the mechanical rate, such as assist control (A/C) or pressure support (PSV), the set ventilator rate will only provide a backup when the infant becomes apneic. With intermittent mandatory ventilation (IMV) or synchronized IMV (SIMV) the rate is gradually weaned as spontaneous breathing contributes more consistently to the total minute ventilation and as long as PaCO2 remains within an acceptable range. Several clinical trials have explored minimal ventilation by permissive hypercapnia as a strategy to expedite weaning in this population, but the results have been inconsistent. Although some studies showed a reduction in the duration of mechanical ventilation they did not show a clear reduction in lung damage or BPD, and one trial showed a possible increase in mortality and neurological impairment in infants in the minimal ventilation group [2–4]. In infants with chronic respiratory failure, like those with BPD, it is difficult if not impossible to wean from the ventilator unless some degree of hypercapnia is tolerated. These infants frequently have metabolic alkalosis that is aggravated by chronic diuretic therapy and therefore their respiratory acidosis is compensated. The inspired oxygen (FiO2 ) is lowered according to PaO2 or more frequently to oxygen saturation measurements by pulse oximetry (SpO2 ). This is aimed at avoiding hyperoxemia and reducing the exposure of the lung to high FiO2 . The
E. Bancalari, N. Claure / Early Human Development 89S1 (2013) S4–S6
optimal ranges for oxygenation targets for preterm infants are still not well defined but until more definitive data become available the goal of most clinicians is to maintain SpO2 between 90% and 95%. Automatic modes of respiratory support have been developed for use in preterm infants. These systems automatically adjust the PIP to maintain a target VT , ventilator frequency to maintain a target minute ventilation level or FiO2 to maintain a target range of SpO2 . Further discussion on the efficacy of these automatic systems in weaning is provided in the article on automation of respiratory support in premature infants in this supplement [5]. 3. Respiratory stimulants Aminophylline and caffeine are effective respiratory stimulants that increase central respiratory drive in preterm infants and decrease the incidence of apneic episodes. Because of this, these drugs also increase the chance of successful weaning from mechanical ventilation and decrease the need for reintubation [6]. Caffeine is generally preferred because of a longer half-life, broader therapeutic range and fewer side effects. It is not clear if early initiation of caffeine therapy in mechanically ventilated preterm infants can shorten the duration of ventilation or improve their respiratory outcome. 4. Postnatal steroids Systemic steroids given to ventilator-dependent infants can produce a rapid improvement in lung function and facilitate weaning from the ventilator, reducing the incidence of BPD [7,8]. However systemic steroid administration is associated with complications that include arterial hypertension, hyperglycemia, increased proteolysis, adrenocortical suppression, somatic and lung growth suppression, and hypertrophic myocardiopathy. More concerning is the worse neurologic outcome, including an increased incidence of cerebral palsy associated with prolonged steroid therapy. Because of this the use of systemic steroids should only be considered after the first two weeks of life in infants who show clear evidence of severe pulmonary damage and remain ventilator dependent. The duration of steroid therapy must be limited to 5–7 days and the potential benefits and risks should be discussed with the family before initiating this therapy. Inhaled steroids have also been used but data on effectiveness are not conclusive enough to recommend their routine use. 5. Synchronized or patient-triggered ventilation Most randomized trials comparing patient-triggered ventilation (PTV) with non-synchronized ventilation have shown a
reduction in duration of mechanical ventilation in infants treated with synchronized modes [9]. This advantage is most likely due to the fact that the infant retains spontaneous respiratory activity and continues to “exercise” his respiratory pump during PTV. Studies have not indicated consistent differences in weaning from mechanical ventilation when using A/C compared to SIMV in premature infants. During IMV or SIMV the weaning is accomplished by gradual reduction of the mechanical rate allowing the patient to increase his contribution to minute ventilation. During A/C or PSV the reduction of the ventilator rate does not have any effect except for reducing the backup rate when the infant stops breathing or slows down his/her spontaneous breathing frequency below that set in the ventilator. The only randomized trial comparing SIMV combined with PSV to SIMV alone in preterm infants revealed faster weaning and shorter duration of ventilation in infants who were ventilated with SIMV in combination with PSV [10]. In this trial, infants with birth weights between 700 g and 1000 g who were ventilated with SIMV and PSV also spent less time on supplemental oxygen than those managed with SIMV alone. 6. Nasal continuous positive airway pressure post extubation The use of nasal CPAP reduces the deterioration that frequently occurs in smaller infants after extubation and reduces the need for reintubation in comparison to oxygen administration alone [11]. Still, a good number of infants fail extubation and most particularly the smaller infants with lung disease. Although nasal CPAP has been used for many years, there are no data on the most effective level of pressure to use in these infants. Results from a recent randomized clinical trial indicate that extubation to nasal CPAP in the range of 7–9 cmH2 O reduces extubation failure compared to the traditional range of 4–6 cmH2 O in preterm infants with residual lung disease [12]. 7. Nasal ventilation Nasal ventilation (NIPPV) has been reintroduced as an effective alternative to NCPAP after extubation. NIPPV has been shown to significantly reduce respiratory failure post extubation and the need for reintubation [13]. In general the settings used during NIPPV are similar to those used during the final weaning stages of invasive ventilation. NIPPV is a promising alternative to invasive ventilation but needs further evaluation and the development of suitable equipment to provide noninvasive respiratory support in premature infants. Table 1 lists the possible steps to expedite weaning from mechanical ventilation.
Table 1 Strategies to minimize duration of mechanical ventilation • Optimize lung function: Maintenance of lung volume and airway patency, reduce fluid overload and closure of symptomatic PDA • Avoid conditions leading to respiratory depression (e.g. hypoxia, metabolic alkalosis, drugs, infections) • Patient triggered ventilation – Preserve spontaneous breathing • Volume targeted ventilation – Manual or ventilator adjusted • Permissive hypercapnia in infants with chronic ventilator dependency • Avoid routine re-intubation after self-extubation • Respiratory stimulants • Post extubation NCPAP or NIPPV • Adherence to pre-established extubation criteria
S5
S6
E. Bancalari, N. Claure / Early Human Development 89S1 (2013) S4–S6
8. Prediction of successful extubation The decision on the timing to wean an infant from the ventilator is difficult and because of this many infants remain intubated for longer periods than needed. Various tools to predict successful extubation have been developed but none has been widely accepted in clinical practice. A simple test is the so-called “spontaneous breathing test” where the ventilator cycling is turned off and the infant is observed for three minutes while on CPAP. If no hypoxia or bradycardia is observed during this period the infant has an excellent chance of tolerating extubation [14]. The decision to remove an infant from respiratory support is usually based on the FiO2 and ventilator support that the infant is requiring to maintain acceptable arterial blood gas levels. Most clinicians will attempt extubation when FiO2 is less than 0.3 or 0.4, the ventilator rate is less than 15 or 20 breaths per minute, PIP is below 14 or 16 cmH2 O and the infant has acceptable blood gases. Because there is frequently some inertia to wean infants from mechanical ventilation it is useful to have written criteria to guide weaning from the ventilator and extubation.
2. 3.
4.
5. 6. 7.
8.
9. 10.
11.
Acknowledgements We are grateful to the University of Miami Project: NewBorn for their continuous support.
12.
13.
Conflict of interest statement The authors have no conflict of interest to report. References 1. Walsh MC, Morris BH, Wrage LA, Vohr BR, Poole WK, Tyson JE, et al.; National Institutes of Child Health and Human Development Neonatal Research Network.
14.
Extremely low birthweight neonates with protracted ventilation: mortality and 18-month neurodevelopmental outcomes. J Pediatr 2005;146:798–804. Mariani G, Cifuentes J, Carlo WA. Randomized trial of permissive hypercapnia in preterm infants. Pediatrics 1999;104:1082–8. Carlo WA, Stark AR, Wright LL, Tyson JE, Papile LA, Shankaran S, et al. Minimal ventilation to prevent bronchopulmonary dysplasia in extremely-low-birthweight infants. J Pediatr 2002;141:370–4. Thome UH, Carroll W, Wu TJ, Johnson RB, Roane C, Young D, et al. Outcome of extremely preterm infants randomized at birth to different PaCO2 targets during the first seven days of life. Biol Neonate 2006;90:218–25. Claure N, Bancalari E. Automation of respiratory support in premature infants. Early Hum Dev 2013;89(Suppl 1):S28–30. Henderson-Smart DJ, Davis PG. Prophylactic methylxanthines for endotracheal extubation in preterm infants. Cochrane Database Syst Rev 2010;12:CD000139. Halliday HL, Ehrenkranz RA, Doyle LW. Late (>7 days) postnatal corticosteroids for chronic lung disease in preterm infants. Cochrane Database Syst Rev 2009; 1:CD001145. Doyle LW, Ehrenkranz RA, Halliday HL. Dexamethasone treatment after the first week of life for bronchopulmonary dysplasia in preterm infants: a systematic review. Neonatology 2010;98:289–96. Greenough A. Update on patient-triggered ventilation. Clin Perinatol 2001;28: 533–46. Reyes ZC, Claure N, Tauscher MK, D’Ugard 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;118:1409–17. 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. Buzzella B, Claure N, D’Ugard C, Bancalari E. A randomized controlled trial of two nasal CPAP ranges for extubation in preterm infants with residual lung disease. Pediatric Academic Societies 2013 meeting. 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;92:70–5. Kamlin CO, Davis PG, Morley CJ. Predicting successful extubation of very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2006;91:F180–3.