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Opioids for Neonates Receiving Mechanical Ventilation. A Systematic Review and Meta-Analysis
  1. Roberto Bellu' (r.bellu{at}
  1. NICU - Manzoni Hospital, Italy
    1. Koert deWaal (k.a.dewaal{at}
    1. Neonatology, Academic Medical Centre, Netherlands
      1. Rinaldo Zanini (r.zanini{at}
      1. NICU - Manzoni Hospital, Italy


        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.

        Design: Sistematic review and meta-analysis of randomized controlled trials.

        Data sources: Cochrane, Medline, Embase, and Cinhal databases, references from review articles.

        Review methods: 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.

        Results: 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). Heterogeneity was significantly high in all analyses of pain. 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 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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