Morphine, Hypotension, and Intraventricular Hemorrhage in the Ventilated Premature Infant

Abstract

The article in this issue of Pediatrics entitled “Morphine, Hypotension, and Adverse Outcomes Among Preterm Neonates: Who’s to Blame?” is a reanalysis of a data set recently published.1,2 Before attributing blame and passing judgment, it is important to briefly review the data. Thus, the genesis of the study was based on pilot observations that suggest that morphine infusions decrease the frequency of early neurologic injury in ventilated infants.3 The authors extended these initial observations and conducted a multicenter, blinded, randomized trial to test the hypothesis that preemptive morphine, compared with a placebo group, would significantly reduce the frequency of early neurologic injury in ventilated preterm neonates. The primary outcome was neonatal death, severe intraventricular hemorrhage (IVH) (grade III/IV), or periventricular leukomalacia (PVL) defined as cystic echolucency adjacent to the lateral ventricles on cranial sonography obtained at 4 to 7 days and at 28 to 35 days of postnatal life. Ventilated infants were stratified by gestational age (GA) at birth as follows: 23 to 26, 27 to 29, and 30 to 32 weeks. The principal findings were that both groups had similar rates of composite outcome, severe IVH, and PVL. Because open-labeled morphine was an option for both groups, when the data were reanalyzed the morphine as well as the placebo group of infants, who received open-labeled morphine, had significantly worse rates of severe IVH or composite outcome, respectively.2 Regarding adverse effects, infants in the group receiving morphine had an increased incidence of hypotension (defined as the need for vasopressor support or intravenous fluid boluses ≥20 mL/kg), particularly during the … Address correspondence to Jeffrey M. Perlman, MB, ChB, Department of Pediatrics, Weill Cornell Medical Center, New York, NY 10021. E-mail: jmp2007{at}med.cornell.edu