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dc.contributor.authorSolhjoo, Soroosh
dc.contributor.authorPunjabi, Naresh M
dc.contributor.authorIvanescu, Andrada E
dc.contributor.authorCrainiceanu, Ciprian
dc.contributor.authorGaynanova, Irina
dc.contributor.authorWicken, Cassie
dc.contributor.authorBuckenmaier, Chester
dc.contributor.authorHaigney, Mark C
dc.date.accessioned2021-08-18T13:09:26Z
dc.date.available2021-08-18T13:09:26Z
dc.date.issued2021-07-19
dc.identifier.urihttp://hdl.handle.net/10713/16410
dc.description.abstractMethadone, a widely prescribed medication for chronic pain and opioid addiction, is associated with respiratory depression and increased predisposition for torsades de pointes, a potentially fatal arrhythmia. Most methadone-related deaths occur during sleep. The objective of this study was to determine whether methadone's arrhythmogenic effects increase during sleep, with a focus on cardiac repolarization instability using QT variability index (QTVI), a measure shown to predict arrhythmias and mortality. Sleep study data of 24 patients on chronic methadone therapy referred to a tertiary clinic for overnight polysomnography were compared with two matched groups not on methadone: 24 patients referred for overnight polysomnography to the same clinic (clinic group), and 24 volunteers who had overnight polysomnography at home (community group). Despite similar values for heart rate, heart rate variability, corrected QT interval, QTVI, and oxygen saturation (SpO2 ) when awake, patients on methadone had larger QTVI (P = 0.015 vs. clinic, P < 0.001 vs. community) and lower SpO2 (P = 0.008 vs. clinic, P = 0.013 vs. community) during sleep, and the increase in their QTVI during sleep vs. wakefulness correlated with the decrease in SpO2 (r = -0.54, P = 0.013). QTVI positively correlated with methadone dose during sleep (r = 0.51, P = 0.012) and wakefulness (r = 0.73, P < 0.001). High-density ectopy (> 1,000 premature beats per median sleep period), a precursor for torsades de pointes, was uncommon but more frequent in patients on methadone (P = 0.039). This study demonstrates that chronic methadone use is associated with increased cardiac repolarization instability. Methadone's pro-arrhythmic impact may be mediated by sleep-related hypoxemia, which could explain the increased nocturnal mortality associated with this opioid.en_US
dc.description.urihttps://doi.org/10.1002/cpt.2368en_US
dc.language.isoenen_US
dc.publisherWiley-Blackwellen_US
dc.relation.ispartofClinical Pharmacology and Therapeuticsen_US
dc.rights© 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.en_US
dc.subjectcardiac repolarization instabilityen_US
dc.subject.meshMethadone--adverse effectsen_US
dc.subject.meshSleepen_US
dc.titleMethadone Destabilizes Cardiac Repolarization During Sleepen_US
dc.typeArticleen_US
dc.identifier.doi10.1002/cpt.2368
dc.identifier.pmid34287835
dc.source.journaltitleClinical pharmacology and therapeutics
dc.source.countryUnited States


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