Methadone (Dolophine) is a narcotic best known for providing a safe albeit slow recovery from opioid addiction (even in pregnancy) by replacing more traditional opioids like oxycodone, fentanyl, hydromorphone, and even heroin as part of methadone maintenance therapy.

Methadone’s high lipid solubility and slow metabolism translate to an elimination half-life of ~24 hours on average, but this varies tremendously and can be well over 100 hours in some patients (somewhat dependent on P450 enzyme activity). Because of this extended duration, it’s often dosed once a day.

Since it works on the same receptor as the aforementioned medications, cross-tolerance can develop; however, it’s much slower with methadone. Patients enrolled in the maintenance programs experience reduced withdrawal symptoms and euphoria due to more stable plasma levels of this opioid compared to others. In that sense, it’s a “safer” opioid compared to others.

In the ICU, I most often administer intravenous or enteral methadone for burn victim patients who have tremendously high analgesic requirements especially with dressing changes and debridements. New initiation of methadone can lead to hypoventilation and arrhythmias (watch for QTc prolongation), so these patients must be carefully monitored. Similar to ketamine, methadone also has NMDA receptor antagonistic properties which confers a second mechanism of analgesia on top of mu opioid receptor activation.

In the OR, I’ll administer ~ 0.1 – 0.2 mg/kg of methadone prior to long cases (thoracoabdominal aortic aneurysm repairs, extensive scoliosis surgery, etc.) to provide a stable-ish plasma opioid concentration with the benefits of NMDA antagonism.

Drop me a comment below with questions! 🙂

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  1. Hi Rishi,

    In a patient on methadone could we also use ketamine for induction or would its efficacy be reduced due to the methdone acting on the NMDA receptors.

    • I don’t think there’s anything saying that methadone would completely negate additional NMBA-based effects conferred by ketamine. Maybe there’s some synergy at play, and when one factors in pharmacokinetics, perhaps the NMDA antagonism peaks at different time points.


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