TY - JOUR
T1 - Methadone Destabilizes Cardiac Repolarization During Sleep
AU - Solhjoo, Soroosh
AU - Punjabi, Naresh M.
AU - Ivanescu, Andrada E.
AU - Crainiceanu, Ciprian
AU - Gaynanova, Irina
AU - Wicken, Cassie
AU - Buckenmaier, Chester
AU - Haigney, Mark C.
N1 - Publisher Copyright:
© 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics
PY - 2021/10
Y1 - 2021/10
N2 - Methadone, 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.
AB - Methadone, 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.
UR - http://www.scopus.com/inward/record.url?scp=85112043275&partnerID=8YFLogxK
U2 - 10.1002/cpt.2368
DO - 10.1002/cpt.2368
M3 - Article
C2 - 34287835
AN - SCOPUS:85112043275
SN - 0009-9236
VL - 110
SP - 1066
EP - 1074
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 4
ER -