Early nasal CPAP or intubation for very preterm infants

Assisted ventilation and surfactant have been the standard treatment for very preterm infants for two decades. However, since ventilation may damage the lungs, it has been hypothesized that the avoidance of ventilation might lead to less bronchopulmonary dysplasia (BPD). Results of some observational studies have suggested that treating very preterm infants with nasal continuous positive airway pressure (CPAP) during resuscitation may reduce the intubation rate and incidence of BPD without increasing morbidity. They have also suggested that CPAP may be started at birth for most infants of more than 25 weeks’ gestation. However, observational studies alone are not sufficient to justify changing clinical practice and the need for a randomized, controlled trial comparing CPAP with intubation and ventilation has been raised.
On these bases, an Australian group have recently published in the New England Journal of Medicine results of Continuous Positive Airway Pressure or Intubation at Birth (COIN) trial. This international randomized trial investigated whether nasal CPAP, rather than intubation and ventilation, shortly after birth would reduce the rate of death or BPD in very preterm infants.
In total, 610 infants at 25-to-28-weeks’ gestational age (GA) were randomized to CPAP (n=307) or intubation and ventilation (n=303) at 5 minutes after birth. The primary outcome was death or occurrence of BPD. Secondary outcomes included the incidence of intubation, the need for oxygen treatment at 28 days, the fraction of inspired oxygen (O2) at 36 weeks’ GA, and the dose of surfactant.
Results show that at 36 weeks’ GA, 33.9% of infants in CPAP group had died or had BPD, as compared with 38.9% in intubation group (P=not significant). At 28 days of age, the unadjusted OR for death or need for oxygen treatment was 0.63 in favor of the CPAP group (P=0.006). There was no significant difference in overall mortality. In the CPAP group, 46% of infants were intubated during the first 5 days, and the use of surfactant was halved. At 36 weeks’ gestational age, an O2 concentration ≥30% was received by 8.8% of the intubation group and 9.4% of the CPAP group (P=0.80). The incidence of pneumothorax was 9% in the CPAP group, as compared with 3% in the intubation group (P<0.001).
In conclusion, these findings show no statistical advantage in terms of death or BPD incidence at 36 weeks’ GA between infants receiving early nasal CPAP and those assigned to intubation. The benefits of CPAP included a lower risk of the combined outcome of death or the need for oxygen therapy at 28 days and fewer days of assisted ventilation. It should be noticed that, at 36 weeks’ GA, only 9% of infants in each group of survivors were receiving an oxygen concentration ≥ 30%. However, early nasal CPAP was associated to an increase in the number of pneumothoraxes. Overall, starting early nasal CPAP treatment in very preterm infants was not detrimental. It should be finally mentioned that in general the results of this trial do not encourage intubation specifically for the use of surfactant for stable infants treated with CPAP, although the authors express the need of randomized trials to compare this technique with CPAP.

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