Intraoperative Methadone in Next-day Discharge Outpatient Surgery: A Randomized, Double- blinded, Dose-finding Pilot Study
Summary by Spencer Willette, DO 11.05.23
https://pubmed.ncbi.nlm.nih.gov/37350677/
Clinical Hypothesis:
Single-dose intraoperative methadone for next-day discharge would result in less postoperative opioid use compared with conventional short-duration opioids.
The authors decided against a formal hypothesis for the following reason:
Formal hypothesis testing for clinical efficacy or effectiveness outcomes is not recommended for pilot studies, because they are underpowered to do so and lack statistical power to detect significant differences. Therefore, formal hypothesis testing was not the aim of the investigation.
Main Takeaways:
Anesthesia with single-dose intraoperative methadone was both feasible and effective for next-day discharge outpatient surgery.
The intraoperative methadone dose that best combined opioid-sparing analgesia, minimal adverse events, and advantages compared with shorter-acting opioids was 0.25mg/kg ideal body weight (median, 14mg).
Compared with short-duration opioids, methadone was associated with less pain postoperatively and was not associated with more adverse effects (nausea, emesis, respiratory depression) or delayed PACU discharge.
Summary:
Background:
This study aimed to evaluate the efficacy of single-dose intraoperative methadone feasibility for next-day discharge outpatient surgery, determine an optimally analgesic and well-tolerated dose, and explore whether methadone would result in less postoperative opioid use compared with conventional short-duration opioids.
Study Design:
This study was a double-blind, randomized, dose-escalation feasibility and pilot study in next-day discharge surgery compared intraoperative single-dose IV methadone (0.1 then 0.2, 0.25, and 0.3mg/kg ideal body weight) versus as-needed short-duration opioid (fentanyl, hydromorphone) controls.
Methods:
Patients were randomized by blocks of three, in a 2:1 ratio (methadone: control), with 129 receiving the allocated intervention.
Inclusion criteria:
Patients aged 18 to 65 yr and undergoing elective next-day discharge outpatient surgery (intended hospital stay lasting one but less than two midnights) under general anesthesia.
Exclusion criteria:
A history of liver or kidney disease, pregnant or nursing females, and potentially opioid-tolerant patients (i.e., daily methadone, more than 20 mg/day oxycodone or hydrocodone, or fentanyl transdermal patch).
Primary outcome:
The primary pilot outcomes were methadone dose and in-hospital (intraoperative and postoperative) opioid utilization.
Secondary outcome:
Secondary outcomes were in-hospital postoperative pain scores, postoperative 30-day opioid consumption, and pain scores, in-hospital and post-discharge opioid side effects, leftover unused take-home opioids, and pain interference after surgery.
Results:
Exploratory statistical analysis found significantly less total in-hospital opioid use in patients receiving higher doses of methadone compared to controls (short-duration opioid; P < 0.001 in all methadone groups).
Also, there was a significantly different fraction of take-home opioids used in patients receiving methadone compared to short-duration opioids (P < 0.01 in all groups).
Across each opioid group, the fraction of unused post-discharge opioids was 74% in controls, and 81%, 80%, and 90% with 0.2, 0.25, and 0.3mg/kg ideal body weight methadone,
Discussion/conclusion:
The most effective and well-tolerated single intraoperative induction dose of methadone for next-day discharge surgery was 0.25mg/ kg ideal body weight (median, 14 mg). Single-dose intraoperative methadone was analgesic and opioid-sparing in next-day discharge outpatient surgery.
Compared with short-duration opioids, methadone was associated with less pain postoperatively and was not associated with more adverse effects (nausea, emesis, respiratory depression) or delayed PACU discharge.
If intraoperative methadone decreases postoperative pain and opioid use, then post-discharge opioid prescriptions can be diminished, along with the potential for leftover opioids.
Limitations of this investigation include small numbers of patients with low follow-up compliance, and a predominance of women was enrolled, reflecting the surgical population. A larger comparative effectiveness trial would be needed to fully evaluate all of the primary and secondary outcomes, adverse events, and enhance generalizability.