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Opioids for neonates receiving mechanical ventilation: a systematic review and meta-analysis
  1. R Bellù1,
  2. Koert de Waal2,
  3. R Zanini1
  1. 1Neonatal Intensive Care Unit, Alessandro Manzoni Hospital, Lecco, Italy
  2. 2Department of Neonatology, John Hunter Hospital, New Lambton, New South Wales, Australia
  1. Correspondence to Roberto Bellù, Neonatal Intensive Care Unit, Alessandro Manzoni Hospital, Via dell'Eremo 9, I-23900 Lecco, Italy; r.bellu{at}


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.

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  • Ethics approval Not required.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

    This paper is based on a Cochrane review published in The Cochrane Library 2008, Issue 1. Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback and The Cochrane Library should be consulted for the most recent version of the review.