Extremely preterm babies –those born between 24 and 27 weeks- are at high risk of morbidity and mortality. Since these infants are usually intubated promptly after birth, they are exposed to the risks of prolonged mechanical ventilation, including the development of bronchopulmonary dysplasia. Administration of supplemental oxygen, resulting in higher hemoglobin oxygen saturation, can contribute to the retinopathy of prematurity. This week we publish two reports from a large randomized trial with a 2-by-2 factorial design aimed at refining treatment to reduce the rate of complications and death for these high-risk neonates.
In a report by Carlo et al., a lower target range of oxygen saturation (85 to 89%) was compared with a higher target range (91 to 95%) in 1316 extremely preterm infants. There was no significant difference between groups in the combined competing outcomes of surviving to develop severe retinopathy or death. When the two components of this outcome were assessed separately, the lower oxygen saturation target resulted in an increase in mortality but a substantial decrease in severe retinopathy among survivors.
The same group of infants was also randomly assigned to receive either intubation and surfactant treatment (within 1 hour after birth) or initiation of continuous positive airway pressure (CPAP) in the delivery room and subsequent use of a protocol-driven limited ventilation strategy. Finer et al. report that the rate of death or bronchopulmonary dysplasia (the primary outcome) did not differ significantly between the two groups. The CPAP group required intubation less frequently and for fewer days than did the surfactant group, with no increase in neonatal adverse events.
“The comparison of the higher vs. lower oxygen saturation strategy presents clinicians and parents with the Hobbesian dilemma of two unsatisfactory choices. One strategy optimizes survival at the expense of increased risk for retinopathy while the other strategy minimizes retinopathy at the expense of increased mortality,” says Mike Greene, M.D., Associate Editor at NEJM. “The other comparison of immediate intubation and surfactant vs. immediate CPAP followed by more invasive ventilatory support, if needed, seems to give providers much less ambiguous guidance in care.”
In an accompanying editorial, CPAP and Very Low Oxygen Saturation for Preterm Babies?, Dr. Colin Morley of Royal Women’s Hospital and University of Melbourne concludes, “Predicting which babies will not have an adequate response to treatment with CPAP and should therefore receive early ventilation and surfactant should be a future goal. Targeting oxygen saturation levels is difficult, and a recommended oxygen saturation range that is effective yet safe remains elusive.”
Should these results affect the levels of oxygen used in extremely preterm infants? Should CPAP be considered as the primary treatment in place of intubation and surfactant?