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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 |
URI: | http://hdl.handle.net/10044/1/67323 |
DOI: | https://dx.doi.org/10.1089/ther.2018.0052 |
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: https://www.liebertpub.com/doi/full/10.1089/ther.2018.0052 |
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 NIHR/CS/010/022 n/a RDD10 MR/R001375/1 PG08117 |
Publication Status: | Published online |
Embargo Date: | 2020-02-26 |
Online Publication Date: | 2019-02-26 |
Appears in Collections: | Department of Medicine Faculty of Medicine |