Baclofen destabilises breathing during sleep in healthy humans: A randomised, controlled, double-blind crossover trial.
control of breathing
hypoxia
periodic breathing
sleep-disordered breathing
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
31
08
2020
received:
28
05
2020
accepted:
13
09
2020
pubmed:
29
9
2020
medline:
27
7
2021
entrez:
28
9
2020
Statut:
ppublish
Résumé
Periodic breathing is frequent in patients with severe heart failure. Apart from being an indicator of severity, periodic breathing has its own deleterious consequences (sleep-related oxygen desaturations, sleep fragmentation), which justifies attempts to correct it irrespective of the underlying disease. Animal models and human data suggest that baclofen can reconfigure respiratory central pattern generators. We hypothesised that baclofen, a GABA Healthy volunteers were exposed to hypoxia during sleep. Participants who developed periodic breathing (n = 14 [53 screened]) were randomly assigned to double-blind oral baclofen (progressively increased to 60 mg/d) or placebo. The primary outcome was the coefficient of variation (CoVar) of respiratory cycle total time considered as an indicator of breathing irregularity. Secondary outcomes included the CoVar of tidal volume, apnoea-hypopnoea index, sleep fragmentation index and ventilatory complexity (noise limit). The analysis was conducted in 9 subjects after exclusion of incomplete datasets. CoVar of respiratory cycle total time significantly increased with baclofen during non-rapid eye movement sleep (median with placebo 56.00% [37.63-78.95]; baclofen 85.42% [68.37-86.40], P = .020; significant difference during the N1-N2 phases of sleep but not during the N3 phase). CoVar of tidal volume significantly increased during N1-N2 sleep. The apnoea-hypopnoea index, sleep fragmentation index and ventilatory complexity were not significantly different between placebo and baclofen. Baclofen did not stabilise breathing in our model. On the contrary, it increased respiratory variability. Baclofen should probably not be used in patients with or at risk of periodic breathing.
Substances chimiques
Baclofen
H789N3FKE8
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
1814-1823Subventions
Organisme : Centre d'Assistance Respiratoire à Domicile d'Ile-de-France", Fontenay-aux-Roses, France
Organisme : Département de la Recherche Clinique et du Développement" Assistance Publique - Hôpitaux de Paris, Paris, France
Organisme : Legs Poix - Etablissement Public Chancellerie des Universités de Paris", Paris, France
Organisme : Société de Pneumologie de Langue Française", Paris, France
Informations de copyright
© 2020 British Pharmacological Society.
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