{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T20:40:50Z","timestamp":1767904850506,"version":"3.49.0"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,10,25]],"date-time":"2020-10-25T00:00:00Z","timestamp":1603584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>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\u2010related 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<jats:sub>B<\/jats:sub> agonist, may thus be able to correct periodic breathing in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Healthy volunteers were exposed to hypoxia during sleep. Participants who developed periodic breathing (<jats:italic>n<\/jats:italic> = 14 [53 screened]) were randomly assigned to double\u2010blind 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\u2013hypopnoea index, sleep fragmentation index and ventilatory complexity (noise limit).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The analysis was conducted in 9 subjects after exclusion of incomplete datasets. CoVar of respiratory cycle total time significantly increased with baclofen during non\u2010rapid eye movement sleep (median with placebo 56.00% [37.63\u201378.95]; baclofen 85.42% [68.37\u201386.40], <jats:italic>P =<\/jats:italic> .020; significant difference during the N1\u2010N2 phases of sleep but not during the N3 phase). CoVar of tidal volume significantly increased during N1\u2010N2 sleep. The apnoea\u2013hypopnoea index, sleep fragmentation index and ventilatory complexity were not significantly different between placebo and baclofen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14569","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T22:24:05Z","timestamp":1601331845000},"page":"1814-1823","source":"Crossref","is-referenced-by-count":9,"title":["Baclofen destabilises breathing during sleep in healthy humans: A randomised, controlled, double\u2010blind crossover trial"],"prefix":"10.1111","volume":"87","author":[{"given":"Christian","family":"Straus","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), UMRS1158 Neurophysiologie Respiratoire Exp\u00e9rimentale et Clinique  Paris France"},{"name":"AP\u2010HP, Groupe Hospitalier APHP\u2010Sorbonne Universit\u00e9, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re, D\u00e9partement R3S, Service des Explorations Fonctionnelles de la Respiration, de l'Exercice et de la Dyspn\u00e9e  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion","family":"Teulier","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), UMRS1158 Neurophysiologie Respiratoire Exp\u00e9rimentale et Clinique  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9bastien","family":"Morel","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), UMRS1158 Neurophysiologie Respiratoire Exp\u00e9rimentale et Clinique  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Wattiez","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), UMRS1158 Neurophysiologie Respiratoire Exp\u00e9rimentale et Clinique  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Hajage","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Institut Pierre Louis d'Epid\u00e9miologie et de Sant\u00e9 Publique, AP\u2010HP. 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