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.
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).
Intravenous morphine (100 µg/kg and 10 µg/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.
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).
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.