Perioperative Methadone and Ketamine for Postoperative Pain Control in Spinal Surgical Patients: A Randomized, Double-blind, Placebo-controlled Trial

Abstract

Background Despite application of multimodal pain management strategies, patients undergoing spinal fusion surgery frequently report severe postoperative pain. Methadone and ketamine, which are N-methyl-d-aspartate receptor antagonists, have been documented to facilitate postoperative pain control. This study therefore tested the primary hypothesis that patients recovering from spinal fusion surgery who are given ketamine and methadone use less hydromorphone on the first postoperative day than those give methadone alone. Methods In this randomized, double-blind, placebo-controlled trial, 130 spinal surgery patients were randomized to receive either methadone at 0.2 mg/kg (ideal body weight) intraoperatively and a 5% dextrose in water infusion for 48 h postoperatively (methadone group) or 0.2 mg/kg methadone intraoperatively and a ketamine infusion (0.3 mg · kg−1 · h−1 infusion [no bolus] intraoperatively and then 0.1 mg · kg−1 · h−1 for next 48 h [both medications dosed at ideal body weight]; methadone/ketamine group). Anesthetic care was standardized in all patients. Intravenous hydromorphone use on postoperative day 1 was the primary outcome. Pain scores, intravenous and oral opioid requirements, and patient satisfaction with pain management were assessed for the first 3 postoperative days. Results Median (interquartile range) intravenous hydromorphone requirements were lower in the methadone/ketamine group on postoperative day 1 (2.0 [1.0 to 3.0] vs. 4.6 [3.2 to 6.6] mg in the methadone group, median difference [95% CI] 2.5 [1.8 to 3.3] mg; P < 0.0001) and postoperative day 2. In addition, fewer oral opioid tablets were needed in the methadone/ketamine group on postoperative day 1 (2 [0 to 3] vs. 4 [0 to 8] in the methadone group; P = 0.001) and postoperative day 3. Pain scores at rest, with coughing, and with movement were lower in the methadone/ketamine group at 23 of the 24 assessment times. Patient-reported satisfaction scores were high in both study groups. Conclusions Postoperative analgesia was enhanced by the combination of methadone and ketamine, which act on both N-methyl-d-aspartate and μ-opioid receptors. The combination could be considered in patients having spine surgery. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Transcriptional Activation, Deactivation and Rebound Patterns in Cortex, Hippocampus and Amygdala in Response to Ketamine Infusion in Rats

“…Introduced as a general anesthetic in the 1960s, its use as an analgesic has gained renewed attention, reflecting the need to utilize non-opioid alternatives in the management of acute and chronic pain. Despite strong interest in the use of ketamine in clinical practice, either alone or in combination with other analgesics ( Kharasch and Clark, 2021 ; Murphy et al, 2021 ) many questions remain regarding the molecular and systems-level consequences of ketamine administration. Although ketamine exerts its primary pharmacodynamic effects by acting as an N -methyl- D -aspartate Receptor (NMDAR) antagonist, the ubiquitous nature of the NMDAR throughout the central nervous system and abundant evidence for non-NMDAR ketamine actions ( Roth et al, 2013 ; Maeng et al, 2008 ; Zanos et al, 2016 ; Yao et al, 2018 ) necessitate additional comprehensive molecular evaluations.…”

Role of Ketamine as Part of the Anti-Hyperalgesic Approach in Opioid-Free Anesthesia (OFA) and Postoperative Analgesia (OFAA)

“…Recent publications have recommended the use of methadone (0.15-0.2 mg/ kg bolus) at the start of anesthetic induction in complex spinal surgery [48]. Methadone has been shown to provide a postoperative opioid-sparing effect and improved pain control.…”

21st Panhellenic Congress on Regional Anaesthesia, Pain Management and Palliative Care

“…Perioperative low dose Ketamine treatment has been advocated for chronic pain patients [12,13]. A combination of Methadone and Ketamine showed impressive results in spinal surgery patients [14]. Gabapentinoid treatment should be continued but not initiated for surgery [15,16].…”