Association between sedation-analgesia and neurodevelopment outcomes in neonatal hypoxic-ischemic encephalopathy

J Perinatol. 2018 Aug;38(8):1060-1067. doi: 10.1038/s41372-018-0126-7. Epub 2018 May 24.

Abstract

Objective: To evaluate the association between sedation-analgesia (SA) during initial 72 h and death/disability at 18 months of age in neonatal hypoxic-ischemic encephalopathy (HIE).

Design: This was a secondary analysis of the NICHD therapeutic hypothermia (TH) randomized controlled trial in moderate or severe HIE. Receipt of SA and anticonvulsant medications at five time points were considered: prior to and at baseline, 24, 48, and 72 h of TH or normothermia. Disability was defined as mental developmental index <85, cerebral palsy, blindness, hearing impairment, or Gross Motor Function Classification System 2-5.

Results: Of the 208 RCT participants, 38 (18%) infants had no exposure to SA or anticonvulsants at any of the five time points, 20 (10%) received SA agents only, 81 (39%) received anticonvulsants only, and 69 (33%) received both SA and anticonvulsants. SA category drugs were not administered in 57% of infants while 18% received SA at ≥3 time points; 72% infants received anticonvulsants during 72 h of intervention. At 18 months of age, disability among survivors and death/disability was more frequent in the groups receiving anticonvulsants, with (48 and 65%) or without (37 and 58%) SA, compared to groups with no exposure (14 and 34%) or SA (13 and 32%) alone. Severe HIE (aOR 3.60; 1.59-8.13), anticonvulsant receipt (aOR 2.48; 1.05-5.88), and mechanical ventilation (aOR 7.36; 3.15-17.20) were independently associated with 18-month death/disability, whereas TH (aOR 0.28; 0.13-0.60) was protective. SA exposure showed no association with outcome.

Conclusions: The risk benefits of SA in HIE need further investigation.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Analgesics / adverse effects
  • Analgesics / therapeutic use*
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Developmental Disabilities / epidemiology*
  • Female
  • Humans
  • Hypnotics and Sedatives / adverse effects
  • Hypnotics and Sedatives / therapeutic use*
  • Hypothermia, Induced
  • Hypoxia-Ischemia, Brain / mortality*
  • Hypoxia-Ischemia, Brain / therapy*
  • Infant
  • Infant, Newborn
  • Logistic Models
  • Male
  • Pain Management
  • Severity of Illness Index
  • United States / epidemiology

Substances

  • Analgesics
  • Anticonvulsants
  • Hypnotics and Sedatives