Pharmacokinetics during therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy: a literature review

Background Neonatal hypoxic ischaemic encephalopathy due to perinatal asphyxia, can result in severe neurodevelopmental disability or mortality. Hypothermia is at present the only proven neuroprotective intervention. During hypothermia, the neonate may need a variety of drugs with their specific pha...

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Main Authors: Karel Allegaert, Isabelle Claire Lutz, Jan N de Hoon, Heleen Marynissen
Format: Article
Language:English
Published: BMJ Publishing Group 2020-02-01
Series:BMJ Paediatrics Open
Online Access:https://bmjpaedsopen.bmj.com/content/4/1/e000685.full
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author Karel Allegaert
Isabelle Claire Lutz
Jan N de Hoon
Heleen Marynissen
author_facet Karel Allegaert
Isabelle Claire Lutz
Jan N de Hoon
Heleen Marynissen
author_sort Karel Allegaert
collection DOAJ
description Background Neonatal hypoxic ischaemic encephalopathy due to perinatal asphyxia, can result in severe neurodevelopmental disability or mortality. Hypothermia is at present the only proven neuroprotective intervention. During hypothermia, the neonate may need a variety of drugs with their specific pharmacokinetic profile. The aim of this paper is to determine the effect that hypothermia for neonates suffering from hypoxic ischaemic encephalopathy has on the pharmacokinetics and to what extent dosing regimens need adjustments.Method A systematic search was performed on PubMed, Embase and Cochrane Library of literature (2000–2020) using a combination of the following search terms: therapeutic hypothermia, neonate, hypoxic ischemic encephalopathy and pharmacokinetics. Titles and abstracts were screened, and inclusion/exclusion criteria were applied. Finally, relevant full texts were read, and secondary inclusion was applied on the identified articles.Results A total of 380 articles were retrieved, and 34 articles included after application of inclusion/exclusion criteria and duplicate removal, two additional papers were included as suggested by the reviewers. Twelve out of 36 studies on 15 compounds demonstrated a significant decrease in clearance, be it that the extent differs between routes of elimination and compounds, most pronounced for renal elimination (phenobarbital no difference, midazolam metabolite −21%, lidocaine −24%; morphine −21% to −47%, gentamicin −25% to −35%, amikacin −40%) during hypothermia. The data as retrieved in literature were subsequent compared with the dosing regimen as stated in the Dutch paediatric formulary.Conclusion Depending on the drug-specific disposition characteristics, therapeutic hypothermia in neonates with hypoxic ischaemic encephalopathy affects pharmacokinetics.
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spelling doaj-art-c03f2291488f4e81a3ece6a0a5a10beb2025-08-20T02:51:46ZengBMJ Publishing GroupBMJ Paediatrics Open2399-97722020-02-014110.1136/bmjpo-2020-000685Pharmacokinetics during therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy: a literature reviewKarel Allegaert0Isabelle Claire Lutz1Jan N de Hoon2Heleen Marynissen34 Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, BelgiumFaculty of Medicine, Katholieke Universiteit Leuven, Leuven, BelgiumDepartment of Pharmaceutical and Pharmacological Sciences, Center for Clinical Pharmacology, KU Leuven, Leuven, BelgiumDepartment of Pharmaceutical and Pharmacological Sciences, Center for Clinical Pharmacology, KU Leuven, Leuven, BelgiumBackground Neonatal hypoxic ischaemic encephalopathy due to perinatal asphyxia, can result in severe neurodevelopmental disability or mortality. Hypothermia is at present the only proven neuroprotective intervention. During hypothermia, the neonate may need a variety of drugs with their specific pharmacokinetic profile. The aim of this paper is to determine the effect that hypothermia for neonates suffering from hypoxic ischaemic encephalopathy has on the pharmacokinetics and to what extent dosing regimens need adjustments.Method A systematic search was performed on PubMed, Embase and Cochrane Library of literature (2000–2020) using a combination of the following search terms: therapeutic hypothermia, neonate, hypoxic ischemic encephalopathy and pharmacokinetics. Titles and abstracts were screened, and inclusion/exclusion criteria were applied. Finally, relevant full texts were read, and secondary inclusion was applied on the identified articles.Results A total of 380 articles were retrieved, and 34 articles included after application of inclusion/exclusion criteria and duplicate removal, two additional papers were included as suggested by the reviewers. Twelve out of 36 studies on 15 compounds demonstrated a significant decrease in clearance, be it that the extent differs between routes of elimination and compounds, most pronounced for renal elimination (phenobarbital no difference, midazolam metabolite −21%, lidocaine −24%; morphine −21% to −47%, gentamicin −25% to −35%, amikacin −40%) during hypothermia. The data as retrieved in literature were subsequent compared with the dosing regimen as stated in the Dutch paediatric formulary.Conclusion Depending on the drug-specific disposition characteristics, therapeutic hypothermia in neonates with hypoxic ischaemic encephalopathy affects pharmacokinetics.https://bmjpaedsopen.bmj.com/content/4/1/e000685.full
spellingShingle Karel Allegaert
Isabelle Claire Lutz
Jan N de Hoon
Heleen Marynissen
Pharmacokinetics during therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy: a literature review
BMJ Paediatrics Open
title Pharmacokinetics during therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy: a literature review
title_full Pharmacokinetics during therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy: a literature review
title_fullStr Pharmacokinetics during therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy: a literature review
title_full_unstemmed Pharmacokinetics during therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy: a literature review
title_short Pharmacokinetics during therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy: a literature review
title_sort pharmacokinetics during therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy a literature review
url https://bmjpaedsopen.bmj.com/content/4/1/e000685.full
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AT janndehoon pharmacokineticsduringtherapeutichypothermiaforneonatalhypoxicischaemicencephalopathyaliteraturereview
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