QT interval prolongation in opioid agonist treatment: analysis of continuous 12-lead electrocardiogram recordings

Methadone is a widely used opioid agonist treatment associated with QT prolongation and torsades de pointes. We investigated the QT interval in patients treated with methadone or buprenorphine using continuous 12-lead Holter recordings.

We prospectively made 24-h Holter recordings in patients prescribed methadone or buprenorphine, compared to controls. After their normal dose a continuous 12-lead Holter recorder was attached for 24 h. Digital electrocardiograms were extracted hourly from the Holter recordings. The QT interval was measured automatically (H-scribe software, Mortara Pty Ltd) and checked manually. The QT interval was plotted against heart rate (HR) on the QT nomogram to determine abnormality. Demographics, dosing, medical history and laboratory investigations were recorded.

There were 58 patients (19 methadone, 20 buprenorphine and 19 control); median age 35 years (20-56 years); 33 males. Baseline characteristics were similar. Median dose of methadone was 110 mg day^-1 (70-170 mg day^-1 ) and buprenorphine was 16 mg day^-1 (12-32 mg day^-1 ). Seven participants had abnormal QT intervals. There was a significant difference in the proportion of prescribed methadone with abnormal QT intervals, 7/19 (37%; 95% confidence interval: 17-61%), compared to controls 0/19 (0%; 95% confidence interval: 0-21%; P = 0.008), but no difference between buprenorphine and controls (0/20). QT vs. HR plots showed patients prescribed methadone had higher QT-HR pairs over 24 h compared to controls. There was no difference in dose for patients prescribed methadone with abnormal QT intervals and those without.

Methadone is associated with prolonged QT intervals, but there was no association with dose. Buprenorphine did not prolong the QT interval. Twenty four-hour Holter recordings using the QT nomogram is a feasible method to assess the QT interval in patients prescribed methadone.