COMPARISON OF 2 STRATEGIES FOR SURFACTANT PROPHYLAXIS IN VERY PREMATURE-INFANTS - A MULTICENTER RANDOMIZED TRIAL

Introduction. Previous trials of surfactant therapy in premature infan ts have demonstrated a survival advantage associated with prophylactic therapy as an immediate bolus, compared with the rescue treatment of established respiratory distress syndrome. The optimal strategy for pr ophylactic therapy, however, remains controversial. When administered as an endotracheal bolus immediately after delivery, surfactant mixes with the absorbing fetal lung fluid and may reach the alveoli before t he onset of lung injury. This approach, however, causes a brief delay in the initiation of standard neonatal resuscitation, including positi ve pressure ventilation, and is associated with a risk for surfactant delivery into the right main stem bronchus or esophagus. As an alterna tive approach, surfactant prophylaxis may be administered in small ali quots soon after resuscitation and confirmation of endotracheal tube p osition. Although this strategy has substantial logistical advantages in clinical practice, its efficacy has not been established. Objective . The purpose of this study was to determine whether the established b enefits of the immediate bolus strategy for surfactant prophylaxis cou ld still be achieved using a postventilatory aliquot strategy after in itial standard resuscitation and stabilization. Design. Multicenter ra ndomized clinical trial with patients randomized before delivery to im mediate bolus or postventilatory aliquot therapy. Participants. inborn premature infants delivered to mothers at an estimated gestational ag e of 24[0/7] to 28[6/7] weeks. Interventions. Those infants who were r andomized to the immediate bolus strategy were intubated as rapidly as possible after birth, and a 3-mL intratracheal bolus of calf lung sur factant extract (Infasurf) was administered before the initiation of p ositive pressure ventilation. Those infants who were randomized to the postventilatory aliquot strategy received standard resuscitation meas ures with intubation by 5 minutes of age, if not required earlier. At 10 minutes after birth, 3 mt of surfactant was administered in 4 divid ed aliquots of 0.75 mt each. Patients in both groups were eligible to receive up to three additional doses of surfactant as rescue therapy i n the neonatal intensive care unit, if needed. Outcome Measures. The p rimary outcome variable was survival to discharge to home. Secondary v ariables included neonatal complications and requirement for oxygen th erapy at 36 weeks' postmenstrual age. Results. Among three centers, 65 1 infants were enrolled and randomized before delivery. Survival to di scharge to home was similar for the two strategies for surfactant ther apy as prophylaxis: 76% for the immediate bolus group and 80% for the postventilatory aliquot group. In a secondary analysis, the rate of su pplemental oxygen administration at 36 weeks' postmenstrual age was 18 % for the immediate bolus group and 13% for the postventilatory aliquo t group. Conclusions. Survival to discharge to home was similar with i mmediate bolus and postventilatory aliquot strategies for surfactant p rophylaxis. Because of its logistical advantages in the delivery room and its beneficial effects on prolonged oxygen requirements, we recomm end the postventilatory aliquot strategy for surfactant prophylaxis of premature infants delivered before 29 weeks' gestation.