Opioids for neonates receiving mechanical ventilation

Mechanical ventilation is a potentially painful intervention widely used in neonatal intensive care units. Since newborn babies (neonates) demonstrate increased sensitivity to pain, which may affect clinical and neurodevelopmental outcomes, the use of drugs which reduce pain might be very important.

To determine the effect of opioid analgesics (pain-killing drugs derived from opium e.g. morphine), compared to placebo, no drug, or other non-opioid analgesics or sedatives, on pain, duration of mechanical ventilation, mortality, growth and neurodevelopmental outcomes in newborn infants on mechanical ventilation.

Electronic searches included: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2004); MEDLINE (1966 to June 2004); EMBASE (1974 to June 2004); and CINAHL (1982 to 2003). Previous reviews and lists of relevant articles were cross-referenced.

Randomised controlled trials or quasi-randomised controlled trials comparing opioids to a control, or to other analgesics or sedatives in newborn infants on mechanical ventilation.

Data were extracted by two reviewers independently. Categorical outcomes were analysed using relative risk and risk difference; and continuous outcomes with weighted mean difference or standardised mean difference. A fixed effect model was used for meta-analysis except where heterogeneity existed, when a random effects model was used.

Thirteen studies on 1505 infants were included. Infants given opioids showed reduced premature infant pain profile (PIPP) scores compared to the control group (weighted mean difference -1.71; 95% confidence interval -3.18 to -0.24). Differences in execution and reporting of trials mean that this meta-analysis should be interpreted with caution. Heterogeneity was significantly high in all analyses of pain, even when lower quality studies were excluded and analysis limited to very preterm newborns. Meta-analyses of mortality, duration of mechanical ventilation, and long and short term neurodevelopmental outcomes showed no statistically significant differences. Very preterm infants given morphine took significantly longer to reach full enteral feeding than those in control groups (weighted mean difference 2.10 days; 95% confidence interval 0.35 to 3.85). One study compared morphine with a sedative: the treatments showed similar pain scores, but morphine had fewer adverse effects.

There is insufficient evidence to recommend routine use of opioids in mechanically ventilated newborns. Opioids should be used selectively, when indicated by clinical judgment and evaluation of pain indicators. If sedation is required, morphine is safer than midazolam. Further research is needed.