Morphine Administration and Short-term Pulmonary Outcomes Among Ventilated Preterm Infants

Abstract

Background. The use of opioid therapy for sedation and analgesia among ventilated infants varies among care providers. The impact of opioid therapy early in the neonatal course of respiratory distress syndrome (RDS) on pulmonary outcomes is not known. Objective. We tested the hypothesis that preterm neonates randomized to the morphine infusion group would have improved ventilatory outcomes, measured as shorter durations of ventilator or oxygen therapy, fewer air leaks, and lower incidence of bronchopulmonary dysplasia. Methods. All 898 subjects (gestational age [GA] of ≥23 to ≤32 weeks) who were enrolled in the Neurologic Outcomes and Preemptive Analgesia in Neonates (NEOPAIN) trial formed the study cohort (morphine: 449 patients; placebo: 449 patients). Subjects received the masked study drug until they were weaned from the ventilator or for 14 days, whichever occurred earlier. Outcome measures included air leaks, duration of ventilation or oxygen therapy, hospitalization, bronchopulmonary dysplasia, and death. Results. Subjects in the 2 groups had similar baseline characteristics (mean ± SD, morphine versus placebo: GA: 27.3 ± 2.3 vs 27.4 ± 2.3 weeks; birth weight: 1037 ± 340 vs 1054 ± 354 g). Infants in the morphine group required ventilator therapy significantly longer, compared with the placebo group (median [interquartile range]: 7 days [4–20 days] vs 6 days [3–19 days]). This difference in ventilation duration was significant for infants with GA of 27 to 29 weeks (6 days [4–12 days] vs 5 days [2–9 days]) and 30 to 32 weeks (4 days [3–6 days] vs 3 days [2–5 days]). Infants who received additional analgesia with intermittent morphine doses in both groups were sicker than those who were not given open-label morphine. After adjustment for birth weight, Clinical Risk Index for Babies scores, maternal chorioamnionitis, RDS requiring surfactant, and patent ductus arteriosus in a logistic regression model, the use of additional analgesia with morphine was associated independently with increased air leaks and longer durations of high-frequency ventilation, nasal continuous positive airway pressure, and oxygen therapy. Conclusions. Morphine infusions do not improve short-term pulmonary outcomes among ventilated preterm neonates. Additional morphine doses were associated with worsening respiratory outcomes among preterm neonates with RDS.