Routine morphine infusion in preterm newborns who received ventilatory support: a randomized controlled trial

JAMA. 2003 Nov 12;290(18):2419-27. doi: 10.1001/jama.290.18.2419.


Context: Newborns admitted to neonatal intensive care units (NICUs) undergo a variety of painful procedures and stressful events. Because the effect of continuous morphine infusion in preterm neonates has not been investigated systematically, there is confusion regarding whether morphine should be used routinely in this setting.

Objective: To evaluate the effects of continuous intravenous morphine infusion on pain responses, incidence of intraventricular hemorrhage (IVH), and poor neurologic outcome (severe IVH, periventricular leukomalacia, or death).

Design, setting, and patients: A randomized, double-blind, placebo-controlled trial conducted between December 2000 and October 2002 in 2 level III NICUs in the Netherlands of 150 newborns who had received ventilatory support (inclusion criteria: postnatal age younger than 3 days and ventilation for less than 8 hours; exclusion criteria: severe asphyxia, severe IVH, major congenital malformations, and administration of neuromuscular blockers).

Interventions: Intravenous morphine (100 microg/kg and 10 microg/kg per hour) or placebo infusion was given for 7 days (or less because of clinical necessity in several cases).

Main outcome measures: The analgesic effect of morphine, as assessed using validated scales; the effect of morphine on the incidence of IVH; and poor neurologic outcome.

Results: The analgesic effect did not differ between the morphine and placebo groups, judging from the following median (interquartile range) pain scores: Premature Infant Pain Profile, 10.1 (8.2-11.6) vs 10.0 (8.2-12.0) (P =.94); Neonatal Infant Pain Scale, 4.8 (3.7-6.0) vs 4.8 (3.2-6.0) (P =.58); and visual analog scale, 2.8 (2.0-3.9) vs 2.6 (1.8-4.3) (P =.14), respectively. Routine morphine infusion decreased the incidence of IVH (23% vs 40%, P =.04) but did not influence poor neurologic outcome (10% vs 16%, P =.66). In addition, analyses were adjusted for the use of additional open-label morphine (27% of morphine group vs 40% of placebo group, P =.10).

Conclusions: Lack of a measurable analgesic effect and absence of a beneficial effect on poor neurologic outcome do not support the routine use of morphine infusions as a standard of care in preterm newborns who have received ventilatory support. Follow-up is needed to evaluate the long-term effects of morphine infusions on the neurobehavioral outcomes of prematurity.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / therapeutic use
  • Double-Blind Method
  • Female
  • Humans
  • Infant, Newborn
  • Infant, Premature*
  • Infusions, Intravenous
  • Intracranial Hemorrhages / epidemiology
  • Leukomalacia, Periventricular / epidemiology
  • Male
  • Morphine / administration & dosage*
  • Morphine / therapeutic use
  • Pain / drug therapy
  • Pain / prevention & control*
  • Pain Measurement
  • Respiration, Artificial*
  • Treatment Outcome


  • Analgesics, Opioid
  • Morphine