Allied Professionals (Non-physician submissions only) -> Clinical Research D-PO02 - Poster Session II (ID 47) Poster

D-PO02-043 - Sleep Destabilizes Cardiac Repolarization In Methadone Users (ID 174)


Background: Opioid use was associated with over 70,000 deaths in the USA in 2017. Among opioids, methadone has the highest risk of death; however, it is still widely prescribed for the management of chronic pain and opioid addiction. While methadone is associated with respiratory depression (like all opioids), it also prolongs the QT interval. Most methadone deaths occur during sleep, potentially implicating central sleep apnea as a cause; however, methadone may directly affect the interaction between sleep disordered breathing and cardiac repolarization.
Objective: To determine whether sleep alters the stability of cardiac repolarization in methadone users.
Methods: The study sample consisted of 24 patients on chronic methadone therapy referred for overnight polysomnography to a tertiary care sleep clinic. Two comparator samples were included: one consisted of patients referred to the sleep clinic but not on methadone, and the other was a cohort of community-based volunteers. Both groups were matched to the patients on methadone therapy on age, sex, body-mass index, and apnea-hypopnea index. Each group consisted of 12 men and 12 women between the ages of 31 and 81 (55.5 ± 13.7) years. None of the study subjects had any history of congestive heart failure or arrhythmias.
Results: For each of the 72 subjects, the first 7 hours of sleep were used to calculate mean heart rate, QT, QTc and QT variability index (QTVI), a measure of repolarization stability that has been shown to predict ventricular arrhythmias and cardiovascular death in heart failure. No differences in HR, QT, QTc or QTVI were noted during wakefulness across the three groups. During sleep, no significant differences were found between heart rate, QT or QTc. QTVI, however, was significantly greater in methadone users versus either of the comparator groups: -0.84 ± 0.76 (methadone users), -1.31 ± 0.56 (clinic, p < 0.023), and -1.49 ± 0.37 (community, p < 0.004).
Conclusion: The current study shows that despite similar values for QT and QTVI when awake, methadone users have a significantly higher QT variability during sleep compared to matched control subjects. These data suggest that sleep increases the pro-arrhythmic impact of methadone and may in part explain the increased mortality associated with this opioid.