Intraoperative Methadone

A single methadone bolus of 0.2 mg/kg was given before incision. Compared with a sufentanil infusion it halved opioid requirement at 48 and 72 hours and halved pain scores at 48 hours.

One 0.2 mg/kg dose before incision is the regimen behind the halved opioid requirement at 48 and 72 hours in this multilevel spine trial.

Pooled across ten studies, methadone reduced 24-hour opioid consumption by only about 15 mg oral morphine equivalents and improved analgesia satisfaction. There was no difference in nausea, sedation or respiratory depression, so the feared side effects did not appear in the pooled data — but the analgesic effect size is modest, about 15 mg of oral morphine equivalents over 24 hours.

The pooled signal is a modest 15 mg oral morphine equivalent reduction with better satisfaction and no excess nausea, sedation or respiratory depression.

A single induction dose of intravenous methadone did not prolong the QTc. A new QTcF above 500 ms occurred in 2.5% of patients who received methadone versus 8.3% of those who did not, and there was no correlation between dose and QTcF. Because this is a prospective observational cohort, it shows no observed QTc prolongation rather than proving methadone is safe in any given patient.

In this observational cohort a single induction dose did not prolong the QTc, and new QTcF above 500 ms was actually less frequent with methadone than without it — 2.5% versus 8.3%.

The meta-analysis reported that across 13 trials intraoperative methadone lowered pain at rest and on movement at 24, 48 and 72 hours and cut opioid consumption. The sequential analysis indicated no further trials are needed only for pain at rest out to 48 hours. That closure statement does not extend to pain on movement, to the 72-hour time point, or to opioid consumption.

The sequential analysis closes exactly one cell of that table — pain at rest to 48 hours — and says nothing about pain on movement, 72 hours, or opioid consumption.