Journal Article

A double-blinded, placebo-controlled, randomized study to evaluate the efficacy of perioperative dextromethorphan compared to placebo for the treatment of postoperative pain: a study protocol

Heckmann, Nathanael D., Lieberman, Jay R., Ratto, Christina E., Longjohn, Donald B., Oakes, Daniel A., Piple, Amit S., Christ, Alexander B., Gucev, Gligor V., Jones, Ian A., Yan, Pui Yuk, Gilbert, Paul K.

2023

Overview

Background Pain management is a critical component of comprehensive postsurgical care, as it influences patient safety and outcomes, and inadequate control has been associated with the development of chronic pain syndromes. Despite recent improvements, the management of postoperative pain following total knee arthroplasty (TKA) remains a challenge. The use of opioid-sparing, multimodal analgesic regimens has broad support, but there is a paucity of high-quality evidence regarding optimal postoperative protocols and novel approaches are needed. Dextromethorphan stands out among both well-studied and emerging pharmacological adjuncts for postoperative pain due its robust safety profile and unique pharmacology. The purpose of this study is to evaluate the efficacy of multi-dose dextromethorphan for postoperative pain control following TKA. Methods This is a single-center, multi-dose, randomized, double-blinded, placebo-controlled trial. A total of 160 participants will be randomized 1:1 to receive either 60 mg oral dextromethorphan hydrobromide preoperatively, as well as 30 mg 8 h and 16 h postoperatively, or matching placebo. Outcome data will be obtained at baseline, during the first 48 h, and the first two follow-up visits. The primary outcome measure will be total opioid consumption at 24 h postoperatively. Secondary outcomes related to pain, function, and quality of life will be evaluated using standard pain scales, the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR) questionnaire, the Patient-Reported Outcomes Measurement Information System (PROMIS-29) questionnaire, and clinical anchors. Discussion This study has a number of strengths including adequate power, a randomized controlled design, and an evidence-based dosing schedule. As such, it will provide the most robust evidence to date on dextromethorphan utilization for postoperative pain control following TKA. Limitations include not obtaining serum samples for pharmacokinetic analysis and the single-center study design. Trial registration This trial has been registered on the National Institute of Health’s ClinicalTrials.gov (NCT number: NCT05278494). Registered on March 14, 2022.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analgesics - adverse effects / Analgesics, Opioid - adverse effects / Anesthesia / Arthritis / Biomedicine / Care and treatment / Clinical outcomes / Clinical trials / Dextromethorphan / Dextromethorphan - adverse effects / Drug dosages / Drug therapy / Health Sciences / Humans / Information systems / Joint replacement surgery / Knee / Medicine / Medicine & Public Health / Morphine / Narcotics / Opioids / Osteoarthritis / Pain / Pain control / Pain management / Pain, Postoperative / Pain, Postoperative - diagnosis / Pain, Postoperative - drug therapy / Pain, Postoperative - etiology / Patient safety / Postoperative pain control / Postoperative period / Quality of Life / Questionnaires / Randomized Controlled Trials as Topic / Statistics for Life Sciences / Study Protocol / Testing / Total knee arthroplasty / Treatment Outcome