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Neurodevelopmental outcomes in the early CPAP and pulse oximetry trial
Seminars in Fetal & Neonatal Medicine 18 (2013) 116
Contents lists available at SciVerse ScienceDirect
Seminars in Fetal & Neonatal Medicine journal homepage: www.elsevier.com/locate/siny
Lessons from the current literature
Neurodevelopmental outcomes in the early CPAP and pulse oximetry trial Luc Cornette Department of Neonatology, AZ St Jan Bruges Ostend AV, Ruddershove 10, B-8000 Bruges, Belgium
YE Vaucher et al. N Engl J Med 2012;367(26):2495e2504
Abstract This study follows up on results reported in 2010 (Neonatal Research Network Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial e ‘SUPPORT’), in which the authors randomly assigned 1316 infants born between 24 and 28 weeks of gestation to: either early continuous positive airway pressure (CPAP) with a limited ventilation strategy, or intubation and early surfactant administration; and to either lower (85e89%) or higher (91e95%) target ranges of oxygen saturation (pulse oximeters blinded). Their main findings were: no significant difference in the outcome of death or bronchopulmonary dysplasia (i.e. persistent oxygen requirement at 36 weeks) when comparing early CPAP vs early surfactant; and a lower rate of severe retinopathy but a higher mortality rate in the lower (vs higher) target range of oxygen saturation. In the current paper, the authors report longer-term results within the same group of infants. The primary composite outcome was death before assessment at 18e22 months, or neurodevelopmental impairment at 18e22 months of corrected age. This outcome was determined for 1234 of 1316 enrolled infants (93.8%); 990 of the 1058 surviving infants (93.6%) were evaluated at 18e22 months of corrected age. The main findings reinforce the conclusions of the original paper: no significant differences in the composite outcome of death or neurodevelopmental impairment; this composite outcome was present in 27.9% of the CPAP group (173/621 infants) vs 29.9% of the surfactant group (183/613) [relative risk (RR): 0.93; 95% confidence interval (CI): 0.78e1.10; P ¼ 0.38], and in 30.2% of the lower-oxygen-saturation group (185/612) vs 27.5% of the E-mail address: [email protected]. 1744-165X/$ e see front matter http://dx.doi.org/10.1016/j.siny.2013.01.003
higher-oxygen-saturation group (171/622) (RR: 1.12; 95% CI: 0.94e1.32; P ¼ 0.21); mortality was 22.1% in the lower-oxygen-saturation group, but lower (18.2%) in the higher-oxygen-saturation group (RR: 1.25; 95% CI: 1.00e1.55; P ¼ 0.046). Comments This report adds to the evidence that stabilising the preterm infant using CPAP may be a better option than immediate intubation after birth. Early stabilisation of (extremely) premature infants in the delivery room using CPAP lowers the risk of death or neurological impairment just as effectively as surfactant treatment. In other words, delaying intubation until it is needed does not increase the risk of developmental disability (blindness, hearing impairment, or cerebral palsy) or death either. By contrast with the Continuous Positive Airway Pressure or Intubation at Birth (COIN) trial, there was no significant difference in the number of infants developing a pneumothorax (6.8% vs 7.4%), which may be related to the fact that infants randomised to CPAP in the COIN trial received a positive end-expiratory pressure (PEEP) of 8 cm H2O and were intubated at FiO2 >0.60, whereas PEEP was 5 cmH2O in the SUPPORT trial and infants were intubated at FiO2 >0.50. Thus, in clinical practice, it remains important to choose liberal CPAP failure criteria, to allow for surfactant administration when needed and to reduce the risk of pneumothorax. Although there are no data yet on the longer term safety of CPAP as the primary mode of respiratory support in extremely premature neonates, the current body of evidence suggests that an INSURE policy (selective INtubation, SURfactant, Extubation to CPAP) may result in even better outcomes. This report also concludes that lower oxygen-saturation targets cannot be recommended in extremely preterm infants, as this results in a higher mortality as well as in visual and neurodevelopmental problems at follow-up, compared with a higheroxygen-saturation group. In accordance, the Benefits Of Oxygen Saturation Targeting (BOOST) II trials stopped patient recruitment after a significantly higher mortality risk was detected in infants within the low oxygen group. It is likely that, when tolerating low SpO2 target ranges, episodes of hypoxia may occur and hence may worsen the overall prognosis. The data currently available make it difficult to continue recommending SpO2 target ranges <90% in extremely premature infants, although currently we do not know the optimum target range for SpO2.
Contents lists available at SciVerse ScienceDirect
Seminars in Fetal & Neonatal Medicine journal homepage: www.elsevier.com/locate/siny
Lessons from the current literature
Neurodevelopmental outcomes in the early CPAP and pulse oximetry trial Luc Cornette Department of Neonatology, AZ St Jan Bruges Ostend AV, Ruddershove 10, B-8000 Bruges, Belgium
YE Vaucher et al. N Engl J Med 2012;367(26):2495e2504
Abstract This study follows up on results reported in 2010 (Neonatal Research Network Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial e ‘SUPPORT’), in which the authors randomly assigned 1316 infants born between 24 and 28 weeks of gestation to: either early continuous positive airway pressure (CPAP) with a limited ventilation strategy, or intubation and early surfactant administration; and to either lower (85e89%) or higher (91e95%) target ranges of oxygen saturation (pulse oximeters blinded). Their main findings were: no significant difference in the outcome of death or bronchopulmonary dysplasia (i.e. persistent oxygen requirement at 36 weeks) when comparing early CPAP vs early surfactant; and a lower rate of severe retinopathy but a higher mortality rate in the lower (vs higher) target range of oxygen saturation. In the current paper, the authors report longer-term results within the same group of infants. The primary composite outcome was death before assessment at 18e22 months, or neurodevelopmental impairment at 18e22 months of corrected age. This outcome was determined for 1234 of 1316 enrolled infants (93.8%); 990 of the 1058 surviving infants (93.6%) were evaluated at 18e22 months of corrected age. The main findings reinforce the conclusions of the original paper: no significant differences in the composite outcome of death or neurodevelopmental impairment; this composite outcome was present in 27.9% of the CPAP group (173/621 infants) vs 29.9% of the surfactant group (183/613) [relative risk (RR): 0.93; 95% confidence interval (CI): 0.78e1.10; P ¼ 0.38], and in 30.2% of the lower-oxygen-saturation group (185/612) vs 27.5% of the E-mail address: [email protected]. 1744-165X/$ e see front matter http://dx.doi.org/10.1016/j.siny.2013.01.003
higher-oxygen-saturation group (171/622) (RR: 1.12; 95% CI: 0.94e1.32; P ¼ 0.21); mortality was 22.1% in the lower-oxygen-saturation group, but lower (18.2%) in the higher-oxygen-saturation group (RR: 1.25; 95% CI: 1.00e1.55; P ¼ 0.046). Comments This report adds to the evidence that stabilising the preterm infant using CPAP may be a better option than immediate intubation after birth. Early stabilisation of (extremely) premature infants in the delivery room using CPAP lowers the risk of death or neurological impairment just as effectively as surfactant treatment. In other words, delaying intubation until it is needed does not increase the risk of developmental disability (blindness, hearing impairment, or cerebral palsy) or death either. By contrast with the Continuous Positive Airway Pressure or Intubation at Birth (COIN) trial, there was no significant difference in the number of infants developing a pneumothorax (6.8% vs 7.4%), which may be related to the fact that infants randomised to CPAP in the COIN trial received a positive end-expiratory pressure (PEEP) of 8 cm H2O and were intubated at FiO2 >0.60, whereas PEEP was 5 cmH2O in the SUPPORT trial and infants were intubated at FiO2 >0.50. Thus, in clinical practice, it remains important to choose liberal CPAP failure criteria, to allow for surfactant administration when needed and to reduce the risk of pneumothorax. Although there are no data yet on the longer term safety of CPAP as the primary mode of respiratory support in extremely premature neonates, the current body of evidence suggests that an INSURE policy (selective INtubation, SURfactant, Extubation to CPAP) may result in even better outcomes. This report also concludes that lower oxygen-saturation targets cannot be recommended in extremely preterm infants, as this results in a higher mortality as well as in visual and neurodevelopmental problems at follow-up, compared with a higheroxygen-saturation group. In accordance, the Benefits Of Oxygen Saturation Targeting (BOOST) II trials stopped patient recruitment after a significantly higher mortality risk was detected in infants within the low oxygen group. It is likely that, when tolerating low SpO2 target ranges, episodes of hypoxia may occur and hence may worsen the overall prognosis. The data currently available make it difficult to continue recommending SpO2 target ranges <90% in extremely premature infants, although currently we do not know the optimum target range for SpO2.