Early Opioid Infusion and Neonatal Outcomes in Preterm Neonates ≤28 Weeks' Gestation

ABSTRACT

We sought to assess risk-adjusted neonatal outcomes of extremely preterm infants who received opioid infusion during early postnatal period. A retrospective analysis of preterm infants ≤28 weeks' gestational age (GA) admitted to neonatal intensive care units in the Canadian Neonatal Network was conducted comparing infants on the basis of receipt of opioid infusion during day 1 and day 3 after birth. Rates of mortality, severe neurological injury, severe retinopathy of prematurity, and chronic lung disease were compared. A total 362 infants received opioid infusion on day 1 and day 3, whereas 4419 infants did not receive opioid infusion. Baseline comparison revealed higher number of males, infants of GA <26 weeks, low Apgar score, and higher Score for Neonatal Acute Physiology scores among those who received opioid infusion. Neonates who received opioid infusion had higher risk for mortality (adjusted odds ratio [AOR] 1.57, 95% confidence interval [CI] 1.13, 2.18), severe neurological injury (AOR 1.63, 95% CI 1.30, 2.04), severe retinopathy of prematurity (AOR 1. 39, 95% CI 1.08, 1.79), and bronchopulmonary dysplasia (AOR 1.36, 95% CI 1.03, 1.79). Early exposure to opioid infusion in the first 3 days was associated with higher risk of adverse outcomes in extremely preterm infants.

KEYWORDS

Chronic lung disease - infant - premature - intraventricular hemorrhage - mortality - retinopathy of prematurity - sedation - analgesic

REFERENCES

• 1 Anand K J, Barton B A, McIntosh N et al.. Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates.  Arch Pediatr Adolesc Med. 1999;  153 331-338
• 2 Simons S H, van Dijk M, van Lingen R A et al.. Routine morphine infusion in preterm newborns who received ventilatory support: a randomized controlled trial.  JAMA. 2003;  290 2419-2427
• 3 Anand K J, Hall R W, Desai N NEOPAIN Trial Investigators Group et al. Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial.  Lancet. 2004;  363 1673-1682
• 4 Carbajal R, Lenclen R, Jugie M, Paupe A, Barton B A, Anand K J. Morphine does not provide adequate analgesia for acute procedural pain among preterm neonates.  Pediatrics. 2005;  115 1494-1500
• 5 Rao R, Sampers J S, Kronsberg S S, Brown J V, Desai N S, Anand K J. Neurobehavior of preterm infants at 36 weeks postconception as a function of morphine analgesia.  Am J Perinatol. 2007;  24 511-517
• 6 Bellù R, de Waal K, Zanini R. Opioids for neonates receiving mechanical ventilation: a systematic review and meta-analysis.  Arch Dis Child Fetal Neonatal Ed. 2010;  95 F241-F251
• 7 Shah P S, Deyne C, Zhang K, Lee S K. on behalf of Database and Annual Report Committee .Canadian Neonatal Network: Annual report. Edmonton: Canadian Neonatal Network; 2008
• 8 Lee S K, McMillan D D, Ohlsson A et al.. Variations in practice and outcomes in the Canadian NICU network: 1996–1997.  Pediatrics. 2000;  106 1070-1079
• 9 Gray J E, Richardson D K, McCormick M C, Workman-Daniels K, Goldmann D A. Neonatal therapeutic intervention scoring system: a therapy-based severity-of-illness index.  Pediatrics. 1992;  90 561-567
• 10 Richardson D K, Corcoran J D, Escobar G J, Lee S K. SNAP-II and SNAPPE-II: Simplified newborn illness severity and mortality risk scores.  J Pediatr. 2001;  138 92-100
• 11 Shennan A T, Dunn M S, Ohlsson A, Lennox K, Hoskins E M. Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period.  Pediatrics. 1988;  82 527-532
• 12 Papile L A, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm.  J Pediatr. 1978;  92 529-534
• 13 International Committee for the Classification of Retinopathy of Prematurity . The International Classification of Retinopathy of Prematurity revisited.  Arch Ophthalmol. 2005;  123 991-999
• 14 Laprairie J L, Johns M E, Murphy A Z. Preemptive morphine analgesia attenuates the long-term consequences of neonatal inflammation in male and female rats.  Pediatr Res. 2008;  64 625-630
• 15 Boasen J F, McPherson R J, Hays S L, Juul S E, Gleason C A. Neonatal stress or morphine treatment alters adult mouse conditioned place preference.  Neonatology. 2009;  95 230-239
• 16 Bhandari V, Bergqvist L L, Kronsberg S S, Barton B A, Anand K J. NEOPAIN Trial Investigators Group . Morphine administration and short-term pulmonary outcomes among ventilated preterm infants.  Pediatrics. 2005;  116 352-359
• 17 Menon G, Boyle E M, Bergqvist L L, McIntosh N, Barton B A, Anand K J. Morphine analgesia and gastrointestinal morbidity in preterm infants: secondary results from the NEOPAIN trial.  Arch Dis Child Fetal Neonatal Ed. 2008;  93 F362-F367
• 18 Enders J, Gebauer C, Pulzer F, Robel-Tillig E, Knüpfer M. Analgosedation with low-dose morphine for preterm infants with CPAP: risks and benefits.  Acta Paediatr. 2008;  97 880-883
• 19 da Silva O, Alexandrou D, Knoppert D, Young G B. Seizure and electroencephalographic changes in the newborn period induced by opiates and corrected by naloxone infusion.  J Perinatol. 1999;  19 120-123
• 20 Young G B, da Silva O P. Effects of morphine on the electroencephalograms of neonates: a prospective, observational study.  Clin Neurophysiol. 2000;  111 1955-1960
• 21 Anand K J, Anderson B J, Holford N H NEOPAIN Trial Investigators Group et al. Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial.  Br J Anaesth. 2008;  101 680-689