Pre-emptive morphine during therapeutic hypothermia after neonatal encephalopathy: a secondary analysis

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Title: Pre-emptive morphine during therapeutic hypothermia after neonatal encephalopathy: a secondary analysis
Authors: Thayyil, S
Liow, N
Montaldo, P
Lally, P
Teiserskas, J
Bassett, P
Oliveira, V
Mendoza, J
Slater, R
Shankaran, S
Item Type: Journal Article
Abstract: Although therapeutic hypothermia (TH) improves outcomes after neonatal encephalopathy (NE), the safety and efficacy of preemptive opioid sedation during cooling therapy is unclear. We performed a secondary analysis of the data from a large multicountry prospective observational study (Magnetic Resonance Biomarkers in Neonatal Encephalopathy [MARBLE]) to examine the association of preemptive morphine infusion during TH on brain injury and neurodevelopmental outcomes after NE. All recruited infants had 3.0 Tesla magnetic resonance imaging and spectroscopy at 1 week, and neurodevelopmental outcome assessments at 22 months. Of 223 babies recruited to the MARBLE study, the data on sedation were available from 169 babies with moderate (n = 150) or severe NE (n = 19). Although the baseline characteristics and admission status were similar, the babies who received morphine infusion (n = 141) were more hypotensive (49% vs. 25%, p = 0.02) and had a significantly longer hospital stay (12 days vs. 9 days, p = 0.009) than those who did not (n = 28). Basal ganglia/thalamic injury (score ≥1) and cortical injury (score ≥1) was seen in 34/141 (24%) and 37/141 (26%), respectively, of the morphine group and 4/28 (14%) and 3/28 (11%) of the nonmorphine group (p > 0.05). On regression modeling adjusted for potential confounders, preemptive morphine was not associated with mean (standard deviation [SD]) thalamic N-acetylaspartate (NAA) concentration (6.9 ± 0.9 vs. 6.5 ± 1.5; p = 0.97), and median (interquartile range) lactate/NAA peak area ratios (0.16 [0.12–0.21] vs. 0.13 [0.11–0.18]; p = 0.20) at 1 week, and mean (SD) Bayley-III composite motor (92 ± 23 vs. 94 ± 10; p = 0.98), language (89 ± 22 vs. 93 ± 8; p = 0.53), and cognitive scores (95 ± 21 vs. 99 ± 13; p = 0.56) at 22 months. Adverse neurodevelopmental outcome (adjusted for severity of encephalopathy) was seen in 26 (18%) of the morphine group, and none of the nonmorphine group (p = 0.11). Preemptive morphine sedation during TH does not offer any neuroprotective benefits and may be associated with increased hospital stay. Optimal sedation during induced hypothermia requires further evaluation in clinical trials.
Issue Date: 26-Feb-2019
Date of Acceptance: 30-Jan-2019
ISSN: 2153-7658
Publisher: Mary Ann Liebert
Journal / Book Title: Therapeutic Hypothermia and Temperature Management
Copyright Statement: © 2019, Mary Ann Liebert, Inc., publishers. Final publication is available from Mary Ann Liebert, Inc., publishers:
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
National Institute for Health Research
Imperial College Healthcare NHS Trust
Medical Research Council (MRC)
Cerebral Palsy Alliance
Funder's Grant Number: RDD01 79560
Publication Status: Published online
Embargo Date: 2020-02-26
Online Publication Date: 2019-02-26
Appears in Collections:Department of Medicine
Faculty of Medicine

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