Pharmacokinetics and toxicity of high-dose baclofen in ICU patients.
Agitation-related adverse events
Alcohol use disorders
Alcohol withdrawal syndrome
Baclofen
Intensive care unit
Pharmacokinetics
Journal
Progress in neuro-psychopharmacology & biological psychiatry
ISSN: 1878-4216
Titre abrégé: Prog Neuropsychopharmacol Biol Psychiatry
Pays: England
ID NLM: 8211617
Informations de publication
Date de publication:
08 06 2019
08 06 2019
Historique:
received:
29
10
2018
revised:
20
01
2019
accepted:
27
02
2019
pubmed:
4
3
2019
medline:
26
9
2019
entrez:
4
3
2019
Statut:
ppublish
Résumé
High-dose baclofen could prove beneficial in patients with unhealthy alcohol use in intensive care units (ICU). However, the pharmacokinetic properties of baclofen are unknown in this population. Our objectives were to investigate the pharmacokinetics of baclofen and the relationship between baclofen exposure and its toxicity in the ICU. As part of a healthcare quality improvement project, we conducted a prospective, single-center study in a surgical intensive care unit at Nantes University Hospital in order to assess our local protocol of sedation in patients with consumption of alcohol above the recommended limits by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Baclofen pharmacokinetics were investigated by a non-compartment analysis and a population approach in 20 patients under mechanical ventilation. After a baclofen loading dose on day 1, daily doses were divided into 3 intakes adapted to glomerular filtration rate (GFR) and blood samples were withdrawn on day 3 for pharmacokinetic analysis. Baclofen was administered until extubation or tracheostomy and agitation-related events as well as the potential side effects of baclofen were noted. In this population, pharmacokinetic parameters [absorption latency time = 0.37 h, absorption constant rate = 2.2 h The a priori planned algorithm for dose adaptation according to renal clearance appeared to be suitable in our population. Daily administration of 150 mg of baclofen in ICU patients with preserved renal function did not lead to toxic concentrations in the plasma. A dose reduction of approximately 40%, 60% and 70% in patients with mild, moderate and severe renal failure could be suggested.
Sections du résumé
BACKGROUND
High-dose baclofen could prove beneficial in patients with unhealthy alcohol use in intensive care units (ICU). However, the pharmacokinetic properties of baclofen are unknown in this population. Our objectives were to investigate the pharmacokinetics of baclofen and the relationship between baclofen exposure and its toxicity in the ICU.
MATERIALS AND METHODS
As part of a healthcare quality improvement project, we conducted a prospective, single-center study in a surgical intensive care unit at Nantes University Hospital in order to assess our local protocol of sedation in patients with consumption of alcohol above the recommended limits by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Baclofen pharmacokinetics were investigated by a non-compartment analysis and a population approach in 20 patients under mechanical ventilation. After a baclofen loading dose on day 1, daily doses were divided into 3 intakes adapted to glomerular filtration rate (GFR) and blood samples were withdrawn on day 3 for pharmacokinetic analysis. Baclofen was administered until extubation or tracheostomy and agitation-related events as well as the potential side effects of baclofen were noted.
RESULTS
In this population, pharmacokinetic parameters [absorption latency time = 0.37 h, absorption constant rate = 2.2 h
CONCLUSIONS
The a priori planned algorithm for dose adaptation according to renal clearance appeared to be suitable in our population. Daily administration of 150 mg of baclofen in ICU patients with preserved renal function did not lead to toxic concentrations in the plasma. A dose reduction of approximately 40%, 60% and 70% in patients with mild, moderate and severe renal failure could be suggested.
Identifiants
pubmed: 30826461
pii: S0278-5846(18)30854-6
doi: 10.1016/j.pnpbp.2019.02.016
pii:
doi:
Substances chimiques
Baclofen
H789N3FKE8
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
450-456Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.