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

Background

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

Methods

We prospectively recorded 24 h holters 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.

Results

There were 58 patients (methadone[19], buprenorphine[20], control[19]); median age 35y (20-56y); 33 males. Baseline characteristics were similar. Median dose of methadone was 110 mg/d (70-170 mg/d) and buprenorphine was 16 mg/d (12-32 mg/d). Seven participants had abnormal QT intervals. There was a significant difference in the proportion prescribed methadone with abnormal QT intervals, 7/19 (37%;95%CI:17-61%), compared to controls 0/19 (0%;95%CI:0-21%;p = 0.008), but no difference between buprenorphine and controls (0/20). QT versus 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.

Conclusions

Methadone is associated with prolonged QT intervals, but there was no association with dose. Buprenorphine did not prolong the QT interval. 24 h holter recordings using the QT nomogram is a feasible method to assess the QT interval in patients prescribed methadone.

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