Methadone: perioperative pain use

Methadone for perioperative pain #methadone #pain #ERAS

There’s a lot of great data that methadone use decreases postoperative narcotics use in cardiac surgery patients, and I believe it would really be a beneficial drug in an ERAS pathway for early extubation, decreased LOS in ICU and hospital, and better patient satisfaction.  Please see the articles below/attached for references.

Methadone for cardiac surgery: 0.2-0.3 mg/kg prior to incision – perhaps different metabolism on CPB so consider split dosing pre-pump and post-pump. Dose adjustment with age and other co-morbidities. At induction, one half of the study opioid (either 0.15 mg/kg of methadone or 6 μg/kg of fentanyl) was administered via an infusion pump over 5 min. The remainder of the study opioid (0.15 mg/kg of methadone or 6 μg/kg of fentanyl) was infused over the next 2 h. Either 0.3 mg/kg of methadone (maximum dose of 30 mg) or 12 μg/kg of fentanyl (maximum dose of 1200 μg) was added to 100-ml bags of normal saline (total volume 100 ml).

Methadone for non-cardiac surgery: 0.2mg/kg prior to incision. REVIEW: Intraoperative Methadone in Surgical Patients: A Review of Clinical Investigations. Anesthesiology 9 2019, Vol.131, 678-692.

Methadone for obesity: 0.15 mg/kg IBW+20% at induction. J Pain Res. 2018; 11: 2123–2129. Intraoperative use of methadone improves control of postoperative pain in morbidly obese patients: a randomized controlled study.

Methadone for outpatient surgery: 0.15 mg/kg ideal body weight. Anesth Analg. 2019 Apr; 128(4): 802–810. Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study.

OVERALL: A variety of doses have been used in clinical trials, ranging from 0.1 to 0.3 mg/kg, with the majority of studies using a dose of either 0.2 mg/kg or a fixed dose of 20 mg.

Methadone has a long elimination half-life (1–2 days). It is cleared predominantly by hepatic metabolism, primarily via N-demethylation to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), which is pharmacologically inactive, and thence secondarily to 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP).

Together these investigations established that a) CYP3A has no influence on single-dose intravenous or oral methadone plasma concentrations, b) CYP3A plays a minimal (if any) role clinically in single-dose methadone N-demethylation and clearance, c) methadone is not a clinical CYP3A substrate, and d) clinical guidelines stating that methadone is a CYP3A4 substrate and warning about CYP3A4 drug interactions needed revision. In addition, CYPs 2C9, 2C19, and 2D6 do not appear to contribute materially to clinical methadone N-demethylation and clearance.

In summary, it is now obvious that CYP2B6 a) is a predominant catalyst of methadone metabolism in vitro; b) mediates clinical methadone metabolism, clearance, stereoselective disposition, and drug-drug interactions; and c) genetic polymorphisms influence methadone disposition. Thus, both constitutive variability due to CYP2B6 genetics, and CYP2B6-mediated drug interactions, can alter methadone disposition, clinical effect, and drug safety. Rewritten clinical guidelines stating that methadone is a CYP2B6 substrate and warning about CYP2B6 drug interactions may improve methadone use, treatment of pain and substance abuse, and patient safety.

FDA Drug Datasheet

From Anesthesiology 5 2015, Vol.122, 1112-1122.
From Anesth Analg. 2019 Apr; 128(4): 802–810.

What I’m doing these days:

  • July 2020

Adult Cardiothoracic

Adult Non-Cardiac

Adult Outpatient

Pediatric Surgery

Methadone Pharmacology & Effects

Updated July 2020

Prescription of Controlled Substances: Benefits and Risks. [Updated 2020 Jun 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from:

The role of methadone in opioid rotation-a Polish experience. Support Care Cancer. 2009 May;17(5):607-12.

Methylene Blue

Case: 65 yo male with septic endocarditis and septic emboli with + valve vegetations.  Severe MR, mod AI, mod TR, no PFO, EF 60-70%. Mild pericardial effusion. Large bilateral pleural effusions.


Vasoplegic syndrome—the role of methylene blue. European Journal of Cardio-Thoracic Surgery, Volume 28, Issue 5, 1 November 2005, Pages 705–710.

OpenAnesthesia: Methylene Blue

2 mg/kg bolus –> 0.5 mg/kg/hr x 12 hours
Worked wonderfully for vasoplegia unresponsive to levophed or vasopressin.

Intraoperative cystoscopy and ureteral visualization

Over the years, I’ve been asked to inject various dyes to help light up the urine for visualization of the ureters.  Now, we’ve moved to fluorescein because it “lights up” quicker than other previous dyes.  Why are we always switching?  Drug shortages.

Dosing: 0.25 – 1.0 ml of 10% preparation of sodium fluorescein

Dose: 5 ml. bolus of 10% fluorescein intravenously.