Feasibility of Prospectively Comparing Opioid Analgesia With Opioid-Free Analgesia After Outpatient General Surgery: A Pilot Randomized Clinical Trial

Abstract

Importance: The overprescription of opioids to surgical patients is recognized as an important factor contributing to the opioid crisis. However, the value of prescribing opioid analgesia (OA) vs opioid-free analgesia (OFA) after postoperative discharge remains uncertain.

Objective: To investigate the feasibility of conducting a full-scale randomized clinical trial (RCT) to assess the comparative effectiveness of OA vs OFA after outpatient general surgery.

Design, setting, and participants: This parallel, 2-group, assessor-blind, pragmatic pilot RCT was conducted from January 29 to September 3, 2020 (last follow-up on October 2, 2020). at 2 university-affiliated hospitals in Montreal, Quebec, Canada. Participants were adult patients (aged ≥18 years) undergoing outpatient abdominal (ie, cholecystectomy, appendectomy, or hernia repair) or breast (ie, partial or total mastectomy) general surgical procedures. Exclusion criteria were contraindications to drugs used in the trial, preoperative opioid use, conditions that could affect assessment of outcomes, and intraoperative or early complications requiring hospitalization.

Interventions: Patients were randomized 1:1 to receive OA (around-the-clock nonopioids and opioids for breakthrough pain) or OFA (around-the-clock nonopioids with increasing doses and/or addition of nonopioid medications for breakthrough pain) after postoperative discharge.

Main outcomes and measures: Main outcomes were a priori RCT feasibility criteria (ie, rates of surgeon agreement, patient eligibility, patient consent, treatment adherence, loss to follow-up, and missing follow-up data). Secondary outcomes included pain intensity and interference, analgesic intake, 30-day unplanned health care use, and adverse events. Between-group comparison of outcomes followed the intention-to-treat principle.

Results: A total of 15 surgeons were approached; all (100%; 95% CI, 78%-100%) agreed to have patients recruited and adhered to the study procedures. Rates of patient eligibility and consent were 73% (95% CI, 66%-78%) and 57% (95% CI, 49%-65%), respectively. Seventy-six patients were randomized (39 [51%] to OA and 37 [49%] to OFA) and included in the intention-to-treat analysis (mean [SD] age, 55.5 [14.5] years; 50 [66%] female); 40 (53%) underwent abdominal surgery, and 36 (47%) underwent breast surgery. Seventy-five patients (99%; 95% CI, 93%-100%) adhered to the allocated treatment; 1 patient randomly assigned to OFA received an opioid prescription. Seventeen patients (44%) randomly assigned to OA consumed opioids after discharge. Seventy-three patients (96%; 95% CI, 89%-99%) completed the 30-day follow-up. The rate of missing questionnaires was 37 of 3724 (1%; 95% CI, 0.7%-1.4%). All the a priori RCT feasibility criteria were fulfilled.

Conclusions and relevance: The findings of this pilot RCT support the feasibility of conducting a robust, full-scale RCT to inform evidence-based prescribing of analgesia after outpatient general surgery.

Trial registration: ClinicalTrials.gov Identifier: NCT04254679.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Balvardi reported receiving governmental student grants from Fonds de Recherche du Québec–Santé and the Canadian Institutes of Health Research and a merit-based operational grant from the Society of University Surgeons outside the submitted work. Dr Lee reported receiving grants from Johnson & Johnson and personal fees from Stryker outside the submitted work. Dr Fiore reported receiving grants from SAGES during the conduct of the study and from Merck Canada outside the submitted work. Dr Chaudhury reported receiving personal fees from AstraZeneca, Ipsen, Merck, Novartis, and Advanced Accelerator Applications outside the submitted work. Dr Di Lena reported receiving personal fees from Ortho Regenerative Technologies Inc outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram

NSAIDs indicates nonsteroidal anti-inflammatory drugs; SDA, same-day admission.

Figure 2.. Between-Group Differences in Postoperative Pain Intensity and Interference

A, The Brief Pain Inventory Severity Scale is a composite of 4 items with a score range of 0 to 10 (higher scores indicate greater pain severity). B, The Interference Scale is a composite of 7 items with a score range of 0 to 10 (higher scores indicate a greater degree of pain-related interference with functioning). Follow-up data were missing for 2 patients in postoperative week (POW) 3 and for 3 patients in POW 4. Squares indicate mean differences, with horizontal lines indicating 95% CIs. Vertical lines represent minimal clinically important differences., POD indicates postoperative day.