Does Buprenorphine/Naloxone Therapy Prolong Ventricular Repolarization During Sleep?

PURPOSE: The mortality rates associated with opioid use have increased dramatically, especially with methadone. Opioids cause central sleep apnea and may adversely affect myocardial repolarization leading to lethal ventricular arrhythmias. Buprenorphine, a semisynthetic partial mu-opioid agonist in combination with naloxone, has become increasingly prescribed because of its reputed protective ceiling effect regarding respiratory suppression. However, buprenorphine/naloxone has recently been shown to produce serious breathing disturbances during sleep and data concerning electrocardiographic effects during sleep do not exist. We hypothesized that buprenorphine/naloxone could prolong repolarization during sleep. METHOD(S): Single lead (II) ECG previously obtained from overnight polysomnography recordings of 20 consecutive patients receiving buprenorphine/naloxone for detoxification therapy and without other cardiac or medication risk factors for delayed ventricular repolarization were analyzed. Four data points randomly selected for each parameter were blindly obtained during stages Wake, N1, N2 and Rapid Eye-Movement Sleep for the following intervals: RR, PR, QRS, Tp-e, QT, and corrected QTc using Bazett's formula. Data was compared with normal appropriate age, BMI, and gender matched controls that had also previously undergone polysomnography. Independent sample t-tests were used for comparison. RESULT(S): There were no significant differences between the buprenorphine/naloxone and control groups in demographics or parameters that reflect delayed ventricular repolarization. For the buprenorphine/naloxone group, the mean (SD) for QT, QTc and Tp-e measured 392.9 (36.6), 418.30 (24.0) and 81.5 (14.0) msec respectively compared to the control group which measured 388.8 (30.6), 425.8 (26.2), and 79.8 (12.1) msec. CONCLUSION(S): Statistically significant abnormal electrocardiographic markers of delayed ventricular repolarization due to buprenorphine/naloxone were not observed. However, the prevalence of this effect based upon other studies may be small. Therefore, the possibility of adverse cardiac effects due to buprenorphine/naloxone cannot be excluded. Further studies with larger numbers are needed. CLINICAL IMPLICATIONS: Due to the association of opioids with central sleep apnea and increased mortality rates, it is important to further study buprenorphine/naloxone's effect on myocardial repolarization to help provide crucial information to physicians for prescription considerations.