Single-dose intraoperative methadone and QTc interval: a prospective observational cohort investigation

Methadone is increasingly used for perioperative care. High-dose methadone, for opioid use disorder or chronic pain, can prolong the cardiac QTc interval, which increases the risk of dangerous cardiac arrhythmias. This investigation evaluated single-dose perioperative methadone effects on QTc.

This prospective observational cohort study evaluated adults undergoing elective surgery under general anaesthesia. Patients received methadone i.v. or no methadone (typically fentanyl) at induction of anaesthesia (provider discretion). QTc was determined before and for 1 h after opioid administration and rate-corrected using Fridericia's formula (QTcF). The primary outcome was new-onset QTcF >500 ms. Secondary outcomes were any QTcF>500 ms; QTcF increase (ΔQTcF)>60 ms; QTcF>500 ms for >15 min; QTcF>450 ms (males) or >470 ms (females); maximum QTcF and ΔQTcF; and methadone dose vs QTcF or ΔQTcF.

Patients were 59 (median; range 18-86) yr of age, and received methadone (n=282, median 20 mg, IQR [15-20], range 10-60 mg) or no methadone (n=265, typically fentanyl, 250 μg [100, 350], 0-750 μg). New QTcF>500 ms occurred in 2.5% of patients receiving methadone and 8.3% receiving no methadone (relative risk [RR] 0.34, 95% confidence interval [0.16-0.75] P=0.009). Secondary outcomes with methadone vs no methadone found that any QTcF>500 ms occurred less (3.5% vs 8.3%, RR 0.43); ΔQTcF>60 ms occurred less (4.6% vs 12.1%, RR 0.39); maximum ΔQTcF was less (28 ms vs 37 ms); and sex-specific thresholds were exceeded less (22.3% vs 33.6%) (all P<0.03). There was no correlation between methadone dose and QTcF or ΔQTcF.

A single-dose at induction of methadone i.v. did not prolong QTcF. Methadone had no clinically meaningful QTcF effects, specifically or in comparison with no use of methadone.