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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"Conversely, opioids have been associated with prolonged ventilation . 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 . Most institutions recommend against routine use of opioids for sedation during mechanical ventilation. "
[Show abstract][Hide abstract] ABSTRACT: Background:
Extremely low birth weight (ELBW) infants are exposed to many painful procedures while in the neonatal intensive care unit (NICU), such as catheter insertion and endotracheal intubation. Exposure of ELBW infants to repetitive pain and stress in the NICU can lead to cardiovascular instability and may alter neuronal and synaptic organization. Opioid analgesics are administered to reduce pain, stress and to potentially reduce poor neurologic outcomes. They may also be utilized as sedation for mechanically ventilated ELBW infants. There is limited data in regards to neurodevelopmental outcomes of preterm infants exposed to opioids, and available studies have conflicting results.
To examine the relationship between cumulative opioid dose in ELBW infants in the NICU and neurodevelopmental outcomes at 20months corrected age (CA).
100 ELBW infants who had complete neurodevelopmental assessments at 20months CA were categorized by cumulative opioid exposure during the NICU stay (high vs. low/no opioid). Outcome measures included cognitive, motor and language scores from the Bayley Scales of Infant and Toddler Development-III (BSITD-III). Multiple regression analyses adjusted for the impact of social and neonatal risk factors on outcome.
There were 60 patients with high and 40 with low/no opioid exposure. Infants in the high dose group had a higher number of median ventilator days (53.5 vs. 45.6days, p=0.046) and a higher incidence of necrotizing enterocolitis (5% vs. 21.7%, p=0.022). There were no significant differences in BSITD-III scores between the two opiate groups. In multivariate analysis cumulative opioid dose was associated with lower cognitive scores on the BSITD-III even after adjusting for social and neonatal risk factors (β=-0.247, p=0.012).
Cumulative opioid dose is associated with worse cognitive scores at 20months CA even after adjusting for social and neonatal risk factors.
Full-text · Article · Jan 2016 · Early human development
"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. "
[Show abstract][Hide abstract] ABSTRACT: Use of preemptive analgesia in Neonatal Intensive Care Units is recommended for severe and/or invasive procedures. However, the potential long-term consequences of such analgesia, which may be prolonged, are only beginning to be studied. In this pilot study, a subset of subjects previously enrolled in the Neurological Outcomes and Preemptive Analgesia in Neonates (NEOPAIN) trial was assessed at early childhood. These ex-preterm infants (born at 23-32 weeks of gestational age) required intubation within 72 h postpartum and were randomized to receive either preemptive morphine analgesia (maximum of 14 days) or placebo within 8h post-intubation. At 5-7 years of age, neuropsychological outcomes, morphometrics, adaptive behavior, parent-rated behavior, motivation, and short-term memory were measured. Although overall IQ and academic achievement did not differ between the morphine treated (n=14) and placebo (n=5) groups, preemptive morphine analgesia was associated with distinct differences in other outcome variables. Head circumference of morphine treated children was approximately 7% smaller (Cohen'sd: 2.83, effect size large) and body weight was approximately 4% less (Cohen'sd: 0.81, effect size large); however, height did not differ. In the short-term memory task (delayed matching to sample), morphine treated children exhibited significantly longer choice response latencies than placebo children (3.86±0.33 and 2.71±0.24 s, respectively) (p<0.03) and completed approximately 27% less of the task than placebo children (Cohen'sd: 0.96, effect size large). Parents described morphine treated children as having more social problems, an effect specific to creating and maintaining friendships (Cohen'sd: -0.83, effect size large). Despite the small sample size and the preliminary nature of this study, these results are strongly suggestive of long-lasting effects of preemptive morphine analgesia. A larger investigation with more comprehensive assessments of some of these key features will enable a more complete understanding of the relationship between preemptive morphine treatment and long-term neurocognitive, behavioral, and adaptive outcomes.
Full-text · Article · Nov 2011 · Neurotoxicology and Teratology
[Show abstract][Hide abstract] ABSTRACT: Drexel University took steps to adopt financial safeguards that are modeled after the Sarbanes-Oxley Act, the tough financial-reporting law imposed on publicly traded companies in 2002. Sarbanes-Oxley is among the most sweeping changes in securities regulations since the reforms that followed the stock-market crash of 1929. Among its provisions, the law strengthens conflict-of-interest rules for company officials and the independence of corporate audit committees, imposes greater accountability on chief executive officers and chief financial officers, and calls for more-rigorous financial disclosures.
No preview · Article · Dec 2002 · The Chronicle of higher education