Intraoperative Methadone Reduces Pain and Opioid Consumption in Acute Postoperative Pain: A Systematic Review and Meta-analysis

Abstract

BACKGROUND: Methadone is a potent opioid exerting an analgesic effect through N-methyl-d-aspartate receptor antagonism and the inhibition of serotonin and noradrenaline reuptake. It has also been used in several procedures to reduce postoperative pain and opioid use. This meta-analysis aimed to determine whether the intraoperative use of methadone lowers postoperative pain scores and opioid consumption in comparison to other opioids. METHODS: Double-blinded, controlled trials without language restrictions were included from MEDLINE, Embase, LILACS, The Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL via EBSCOhost. The included studies tracked total opioid consumption, postoperative pain scores, opioid-related side effects, and patient satisfaction until 72 hours postoperatively. Mean difference (MD) was used for effect size. RESULTS: In total, 476 articles were identified and 13 were considered eligible for inclusion in the meta-analysis. In 486 patients (7 trials), pain at rest (MD, 1.09; 95% confidence interval (CI), 1.47–0.72; P < .00001) and at movement (MD, 2.48; 95% CI, 3.04–1.92; P = .00001) favored methadone 24 hours after surgery. In 374 patients (6 trials), pain at rest (MD, 1.47; 95% CI, 3.04–1.02; P < .00001) and at movement (MD, 2.03; 95% CI, 3.04–1.02; P < .00001) favored methadone 48 hours after surgery. In 320 patients (4 trials), pain at rest (MD, 1.02; 95% CI, 1.65–0.39; P = .001) and at movement (MD, 1.34; 95% CI, 1.82–0.87; P < .00001) favored methadone 72 hours after surgery. A Trial Sequential Analysis was performed and the Z-cumulative curve for methadone crossed the monitoring boundary at all evaluations, additionally crossing Required Information Size at 24 and 48 hours at rest. Methadone group also showed lower postoperative opioid consumption in morphine equivalent dosage (mg) at 24 hours (MD, 8.42; 95% CI, 12.99–3.84 lower; P < .00001), 24–48 hours (MD, 14.33; 95% CI, 26.96–1.91 lower; P < .00001), 48–72 hours (MD, 3.59; 95% CI, 6.18–1.0 lower; P = .007) postoperatively. CONCLUSIONS: Intraoperative use of methadone reduced postoperative pain scores compared to other opioids, and Trial Sequential Analysis suggested that no more trials are required to confirm pain reduction at rest until 48 hours after surgery. Methadone also reduced postoperative opioid consumption and led to better patient satisfaction scores through 72 hours postoperatively compared to other opioids.

Intra‐operative methadone effect on quality of recovery compared with morphine following laparoscopic gastroplasty: a randomised controlled trial

“…In our study, the methadone group had a lower incidence of both events in PACU and a lower incidence of nausea during the whole stay on the surgical ward. These findings are comparable with results observed after open bariatric surgery [14], but contradict those of a recent metaanalysis that did not detect this benefit [27]. It is likely this finding was not observed by Machado et al [27] because they included operations with a low incidence of PONV in their meta-analysis, which would require a larger sample size to detect the effect of methadone in reducing these events compared with control groups.…”

The Effect of Intraoperative Methadone Compared to Morphine on Postsurgical Pain: A Meta-Analysis of Randomized Controlled Trials

“…First, in order to minimize clinical heterogeneity, we compared methadone to morphine only. It is possible that the use of intraoperative methadone can have greater postoperative analgesic effects when compared to other commonly used intraoperative opioids (e.g., fentanyl) [37,38]. Secondly, we limited our comparison to the intraoperative phase.…”

Minimally Invasive Cardiac Surgery—Identifying Opportunities for Further Improvement in the Quality of Postoperative Patient Recovery

“…9 The beneficial analgesic effects of methadone have been noted in adult and pediatric cardiac surgery. [10][11][12] Murphy et al have demonstrated, in a prospective randomized trial (n = 156: adult cardiac surgery with cardiopulmonary bypass), that intraoperative methadone significantly reduced postoperative pain and rescue opioid requirements, with enhanced patient-perceived quality of pain management. 10 A recent meta-analysis confirmed the superior analgesic and opioid-sparing properties of methadone for acute postoperative pain due to its potent analgesic effects, including N-methyl-Daspartate receptor antagonism, as well as inhibition of serotonin and noradrenaline uptake.…”

“…10 A recent meta-analysis confirmed the superior analgesic and opioid-sparing properties of methadone for acute postoperative pain due to its potent analgesic effects, including N-methyl-Daspartate receptor antagonism, as well as inhibition of serotonin and noradrenaline uptake. 12 The cumulative literature, together with the findings from Burtoft et al, suggested that methadone could be considered more often for enhanced recovery after cardiac surgery, including minimally invasive cardiac surgery. [8][9][10][11][12] Beyond methadone, what are further options to reduce the high incidence of severe postoperative pain and improve the quality of recovery in this setting?…”

“…12 The cumulative literature, together with the findings from Burtoft et al, suggested that methadone could be considered more often for enhanced recovery after cardiac surgery, including minimally invasive cardiac surgery. [8][9][10][11][12] Beyond methadone, what are further options to reduce the high incidence of severe postoperative pain and improve the quality of recovery in this setting? A clear message from the literature is to consider multimodal perioperative protocols that include regional analgesic techniques.…”