Opioids for neonates receiving mechanical ventilation: A systematic review and meta-analysis

Neonatal Intensive Care Unit, Alessandro Manzoni Hospital, Lecco, Italy.
Archives of Disease in Childhood - Fetal and Neonatal Edition (Impact Factor: 3.12). 07/2009; 95(4):F241-51. DOI: 10.1136/adc.2008.150318
Source: PubMed


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.
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.
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.
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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Available from: Roberto Bellu, Feb 12, 2015
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    • "Conversely, opioids have been associated with prolonged ventilation [9]. A meta-analysis showed no differences in duration of mechanical ventilation but increased time to reach full enteral feeding in infants receiving opioids for sedation [10]. Most institutions recommend against routine use of opioids for sedation during mechanical ventilation. "
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    • "For example , the pharmacokinetics/pharmacodynamics of repeated analgesic treatment in the neonate are only beginning to be described (Anand et al., 2008). Less known, however, are the long-term global effects of neonatal analgesia (see American Academy of Pediatrics (Committee on Fetus and Newborn et al., 2000; Anand et al., 2006; Bellu et al., 2010; Fitzgerald and Walker, 2009; Hall et al., 2007) for the need for followup studies). Given the long-term neurological impact of untreated neonatal pain (Fitzgerald and Walker, 2009), it is essential to determine the long-term effects of preemptive analgesia. "
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