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Pharmacoepidemiology of opiate use in the neonatal ICU: Increasing cumulative doses and iatrogenic opiate withdrawal

Tamorah Lewis, MD, Betty Luan Erfe, BS, Tarrah Ezell, BS, Estelle Gauda, MD


Objective: Neonatal intensive care unit (ICU) care involves use of opiates to treat postoperative, ventilated, or chronically ill infants. Opiates provide necessary analgesia and sedation, but the morbidities include prolonged neonatal abstinence syndrome (NAS) and extended length of stay for dose tapering. Our objective was to quantify trends in opiate exposure in a tertiary care NICU. The authors hypothesize that medical opiate exposure and resultant ICU-acquired NAS would increase over time.

Design: Retrospective cross-sectional cohort study.

Setting: Tertiary care NICU.

Patients: High-risk inborn infants admitted in fiscal years 2003-2004, 2007-2008, and 2010-2011.

Main outcome measure: Average cumulative morphine exposure (all opiate doses converted to morphine equivalents) per time epoch was compared in cohorts of clinically similar infants. Linear regression was used to assess the primary outcome, assessing changes in opiate exposure over time.

Results: Sixty-three infants were included in the final analysis. The primary analysis assessing cumulative opiate exposure per infant showed an increase of 134 mg per time epoch (95% CI –12, 279 mg, p-value 0.071). There was a statistically significant increase in the percent of infants with a diagnosis of iatrogenic NAS, increasing from 9 to 35 to 50 percent (p-value 0.012).


neonate, opiate, neonatal abstinence syndrome, iatrogenic exposure, pharmacoepidemiology, withdrawal

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