Treatment of respiratory distress syndrome in premature infants with continuous positive airway pressure (CPAP) preserves surfactant and keeps the lung open but is insufficient in severe surfactant deficiency. Traditional surfactant administration is related to short periods of positive pressure ventilation and implies the risk of lung injury. CPAP with surfactant but without any positive pressure ventilation may work synergistically. This randomized trial investigated a less invasive surfactant application protocol (LISA).OBJECTIVE To test the hypothesis that LISA increases survival without bronchopulmonary dysplasia (BPD) at 36 weeks' gestational age in extremely preterm infants. DESIGN, SETTING, AND PARTICIPANTSThe Nonintubated Surfactant Application trial was a multicenter, randomized, clinical, parallel-group study conducted between April 15, 2009, and March 25, 2012, in 13 level III neonatal intensive care units in Germany. The final follow-up date was June 21, 2012. Participants included 211 of 558 eligible (37.8%) spontaneously breathing preterm infants born between 23.0 and 26.8 weeks' gestational age with signs of respiratory distress syndrome. In an intention-to-treat design, infants were randomly assigned to receive surfactant either via a thin endotracheal catheter during CPAP-assisted spontaneous breathing (intervention group) or after conventional endotracheal intubation during mechanical ventilation (control group). Analysis was conducted from September 6, 2012, to June 20, 2013.INTERVENTION LISA via a thin catheter. MAIN OUTCOMES AND MEASURESSurvival without BPD at 36 weeks' gestational age. RESULTSOf 211 infants who were randomized, 104 were randomized to the control group and 107 to the LISA group. Of the infants who received LISA, 72 (67.3%) survived without BPD compared with 61 (58.7%) of those in the control group. The reduction in absolute risk was 8.6% (95% CI, −5.0% to 21.9%; P = .20). Intervention group infants were less frequently intubated (80 infants [74.8%] vs 103 [99.0%]; P < .001) and required fewer days of mechanical ventilation. Significant reductions were seen in pneumothorax (5 of 105 intervention group infants [4.8%] vs 13 of 103 12.6%]; P = .04) and severe intraventricular hemorrhage (11 infants [10.3%] vs 23 [22.1%]; P = .02), and the combined survival without severe adverse events was increased in the intervention group (54 infants [50.5%] vs 37 [35.6%]; P = .02; absolute risk reduction, 14.9; 95% CI, 1.4 to 28.2).CONCLUSIONS AND RELEVANCE LISA did not increase survival without BPD but was associated with increased survival without major complications. Because major complications are related to lifelong disabilities, LISA may be a promising therapy for extremely preterm infants.

Results: There were 13 inborn neonates enrolled for INSURE, mean gestational age was 30 weeks + 3 days and mean birth weight was 1428 g (range 1170-1780 g). We stopped our observational study ahead of time due to significant cardiovascular side effects. Propofol generally offered good intubating conditions, but we encountered severe problems with arterial hypotension. A low propofol bolus of 1 mg/kg caused a distinctive decline of mean arterial blood pressure from 38 mmHg (range 29-42 mmHg) prior premedication to 24 mmHg (22-40 mmHg) 10 minutes after propofol application.Conclusions: Our experience with propofol as induction agent for endotracheal intubation in preterm neonates reveals distinctive cardiovascular effects which represent an important risk factor for serious complications of prematurity like intraventricular haemorrhage or periventricular leucomalacia. Propofol should be used with caution in very preterm neonates with respiratory distress during the first hours of life.

The success of nCPAP increased with increasing use of nCPAP with surfactant. Simultaneously, mortality decreased without deterioration of other outcomes indicating that the use of surfactant in spontaneous breathing with nCPAP could be beneficial.

In this pilot study, INSURE with remifentanil was associated with good intubating conditions and early extubation resulting in an excellent neonatal outcome.