Methadone + ketamine: 2+2 = 8

Myron Yaster

Murphy GS, Avram MJ, Greenberg SB, Benson J, Bilimoria S, Maher CE, Teister K, Szokol JW:  Perioperative Methadone and Ketamine for Postoperative Pain Control in Spinal Surgical Patients: A Randomized, Double-blind, Placebo-controlled Trial. Anesthesiology 2021; 134:697–70 PMID: 33730151

Editorial

Evan D Kharasch, J David Clark.  Methadone and Ketamine: Boosting Benefits and Still More to Learn. Anesthesiology 2021 May 1;134(5):676-679. PMID: 33740051

Methadone is the only mu-agonist opioid that is also an NMDA receptor antagonist making it a fabulous analgesic for acute pain, cancer pain, sickle cell disease, and opioid use disorder, in both adults and children. Indeed, “multiple clinical studies have demonstrated the clinical benefits and therapeutic advantages of perioperative long-duration methadone compared with shorter-duration opioids, for both inpatient and outpatient surgery. Patients receiving a single intraoperative dose of methadone, compared with shorter-duration opioids, report less pain, use less opioid, and have greater satisfaction with pain relief”.  In our pediatric practices, it is particularly useful for bone and neuropathic pain (think pectus, scoliosis, trauma and major cancer surgery).  In fact, I think Chuck Berde summed this up best in 1991 (!) when he called it the poor man’s PCA (PMID 2066846).  Finally, it has terrific bio-availability, that is, the oral dose is the same as the IV dose, and in most institutions is extremely inexpensive (pennies/dose).  Its biggest disadvantage is its name…it has terrible connotations; many people including families, surgeons, pediatricians, and even some of us equate this drug with its use in opioid abuse disorders and are therefore loathe to prescribe and use it.  

Because of the recent trend to decrease or even completely omit opioids, perioperative ketamine use has exploded as an alternative analgesic, even though its efficacy as a substitute for opioids is highly suspect.  Nevertheless, I’ve often wondered: “is there any need to use ketamine IF one is using methadone because they are essentially working at the same receptor”?  This fantastic paper says emphatically YES!  The 2 drugs together (intraoperative methadone 0.2 mg/kg ideal body weight and ketamine 0.3 mg/kg/hr intraoperatively, then 0.1 mg/kg/hr for the next 48 h) are turbocharged and potentiate each other.  They not only produced longer lasting and dramatically better analgesia, they also had fewer side effects.

Both the article and editorial are worth reading not only for the results AND clinical research design but because they offer many explanations that explain why how and why this combination is so effective.  Finally, although this prospective, randomized controlled study was performed in adult spine patients I don’t think there really is any need to duplicate it in pediatric patients.  In my opinion, this should be the go-to method for spine, pectus, and other major surgeries in children. What do you think? 

Myron Yaster MD 

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