Opioids for neonates receiving mechanical ventilation: a systematic review and meta-analysis.
OBJECTIVE
To evaluate the effect of opioid analgesics, 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.


METHODS
This was a systematic review and meta-analysis of randomised controlled trials (RCTs). Data sources used were Cochrane, MEDLINE, EMBASE and CINAHL databases, and references from review articles. RCTs or quasi-RCTs comparing opioids to a control, or to other analgesics or sedatives in newborn infants on mechanical ventilation were reviewed.


RESULTS
A total of 13 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 (WMD) -1.71, 95% CI -3.18 to -0.24). Heterogeneity was significantly high in all analyses of pain. Meta-analyses of mortality, duration of mechanical ventilation and long-term 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 (WMD 2.10 days, 95% CI 0.35 to 3.85). One study that compared morphine with midazolam showed similar pain scores, but fewer adverse effects with morphine.


CONCLUSIONS
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.
Bellù
R
R
Neonatal Intensive Care Unit, Alessandro Manzoni Hospital, Lecco, Italy. r.bellu@ospedale.lecco.it
de Waal
Koert
K
Zanini
R
R
D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D015931:Intensive Care, Neonatal / Q000379:methods*; D010146:Pain / Q000517:prevention & control*; D010147:Pain Measurement / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D012121:Respiration, Artificial; D016896:Treatment Outcome
D000701:Analgesics, Opioid