- Design
- Prospective observational cohort study with treatment allocated at provider discretion
- Population
- 547 adults having elective surgery under general anaesthesia; 282 received intravenous methadone (median 20 mg) and 265 did not, typically receiving fentanyl; median age 59
- Primary outcome
- New-onset QTcF above 500 ms within one hour of opioid administration
- Effect
- 2.5% with methadone vs 8.3% without (relative risk 0.34, 95% CI 0.16-0.75, p=0.009); rise above 60 ms 4.6% vs 12.1%; no correlation between methadone dose and QTc
The QT warning attached to methadone comes from high-dose maintenance treatment for opioid use disorder and chronic pain, and it has been carried across to perioperative single-dose use without evidence. That caution keeps a useful long-acting opioid off many anaesthetic charts. This prospective observational cohort measured what actually happens.
547 adults having elective surgery under general anaesthesia received either intravenous methadone at induction (n=282, median 20 mg, range 10-60) or no methadone (n=265, typically fentanyl). QTc was measured before and for an hour after, corrected by Fridericia's formula.
New-onset QTcF above 500 ms occurred in 2.5% of the methadone group and 8.3% of those who did not receive it (relative risk 0.34, 95% CI 0.16-0.75, p=0.009). Every secondary measure went the same way: any QTcF above 500 ms 3.5% versus 8.3%; a rise of more than 60 ms in 4.6% versus 12.1%; smaller maximum increase (28 ms versus 37 ms). There was no correlation between methadone dose and QTc.
Read this carefully: it is observational, and anaesthetists chose who received methadone, so patients with known QT risk were probably steered away from it - which could produce exactly this result. The comparison group is not a placebo group but patients who mostly received fentanyl, along with everything else that accompanies an anaesthetic.
The defensible conclusion is the narrow one the authors draw: a single induction dose of methadone did not prolong QTc in this cohort, and the labelled concern derived from chronic high-dose use should not by itself rule out perioperative single-dose use. It does not license methadone in a patient with congenital long QT or on multiple QT-prolonging drugs, where a preoperative ECG remains the sensible step.
- Do not withhold single-dose perioperative methadone solely because of the chronic-dosing QT warning
- Still get a preoperative ECG in patients on other QT-prolonging drugs or with a family history of sudden death
- Note the selection: prescribers chose who received methadone, and probably avoided high-risk patients
- Correct QT with Fridericia's formula rather than Bazett's under anaesthesia - heart rates vary widely
- Methadone's long half-life still requires postoperative respiratory monitoring appropriate to the dose
The statistics, in plain English
A relative risk of 0.34 appears to show methadone protecting against QT prolongation, which is not biologically plausible and is the clearest signal that this is a selection effect rather than a drug effect - clinicians decided who received methadone. The honest interpretation is the absence of harm rather than the presence of benefit. That there was no correlation between methadone dose and QTc across a 10 to 60 mg range strengthens the no-harm reading, since a true QT effect would ordinarily be dose-dependent.
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