Methadone

Dose-dependent duration — doses ≤10 mg produce 3–4 hours of analgesia (redistribution-limited); doses ≥20 mg leverage the long elimination half-life for ~35-hour effect.

Opioid use disorder patients — patients on chronic methadone maintenance should continue their baseline dose throughout the perioperative period; perioperative supplemental methadone or additional opioid analgesia should be provided as needed, distinct from maintenance dosing.

QT prolongation — risk of this is meaningful primarily at high chronic doses (e.g., opioid use disorder treatment); single perioperative IV doses carry minimal risk.

ERAS friendly - single-dose methadone reduces postoperative opioid requirements, supporting ERAS goals

Respiratory depression risk — comparable to other opioids at equivalent analgesic doses

High-risk populations — obese patients, the elderly, and those with OSA require cautious dosing and enhanced monitoring; specific dosing guidelines for these groups are not yet established.

Serotonin syndrome risk — methadone inhibits the serotonin transporter; perioperative IV use has not been directly linked to serotonin syndrome, but caution is warranted in patients on serotonergic antidepressants (SSRIs, SNRIs, TCAs).

Ketamine synergy — methadone + ketamine infusion (intra- and postoperative) provides additive/synergistic analgesia with reduced opioid consumption; consider this combination for high-pain-burden cases.

Dialysis Patients — Not significantly removed by hemodialysis due to high protein binding and large volume of distribution

Similar to conventional opioids — PONV and sedation risk

Drug interactions — Methadone inhibits the serotonin transporter; perioperative IV use has not been directly linked to serotonin syndrome, but vigilance is warranted in patients on serotonergic antidepressants (SSRIs, SNRIs, TCAs). Combining methadone with gabapentinoids increases respiratory depression risk. Drugs that induce CYP2B6 (e.g., phenobarbital, phenytoin) lower methadone plasma levels; inhibitors (e.g., fluoxetine, sertraline, ticlopidine) raise methadone plasma levels.

Pediatric use - evidence supports efficacy in children aged 3–18 for major surgical procedures; adolescents undergoing spine surgery have been studied most extensively;

OB considerations — methadone crosses the placenta; neonates born to methadone-maintained mothers require monitoring for neonatal opioid withdrawal syndrome (NOWS). Single-dose perioperative IV methadone has not been systematically studied in obstetric surgery; use with caution

Absolute — respiratory depression in an unmonitored setting without resuscitative equipment

Relative — Concurrent use of MAO inhibitors (within 14 days); severe hepatic impairment

Caution — Elderly patients (age-related increase in half-life); obstructive sleep apnea; morbid obesity; co-administration of serotonergic agents; concurrent QT-prolonging drugs; patients receiving chronic methadone therapy (dose overlap risk)

Base on ideal body weight; reduce in elderly/high-risk patients

Adult — 20mg for inpatients, 15mg for those expected to be discharged the following day, and 10mg for patients undergoing same-day discharge procedures.

Pediatric — 0.1–0.3 mg/kg IV; 0.25 mg/kg commonly used for adolescents;

Not used for perioperative management; Bolus strategy preferred

Hepatic

Fecal (primary), Renal (minor)

Naloxone (Narcan); Lasts 30–45 minutes (significantly shorter than methadone's duration) — repeat dosing or infusion may be required.