Analgesic Equivalence of NSAIDs and a Weak Opioid in Acute Postoperative Pain Following Minimally Invasive Surgery Under Balanced General Anesthesia: A Pilot Randomized Controlled Trial

Abstract Background Non-steroidal anti-inflammatory drugs (NSAIDs) and weak opioids such as tramadol are cornerstones of multimodal analgesia, particu-larly in settings with limited access to potent opioids. However, cross-class equianalgesic data comparing these agents remain scarce. This pilot ran-domised controlled trial aimed to explore the analgesic equivalence of ke-torolac, diclofenac, and tramadol administered as premedication in patients undergoing minimally invasive surgery. Methods In this double-blind, parallel-group pilot trial, 30 patients scheduled for elective minimally invasive surgery (28 laparoscopic cholecys-tectomies, 2 laparoscopic abdominal wall repairs) under balanced general anaesthesia were randomised to receive intravenous tramadol 150 mg, ke-torolac 60 mg, or diclofenac 150 mg 45 minutes before skin incision. The primary outcome was pain intensity measured using the Numerical Rating Scale (NRS, 0–10) at recovery room arrival (T0) and at 30 (T1), 60 (T2), and 90 (T3) minutes thereafter. Secondary outcomes included Verbal Rating Scale (VRS) scores, rescue morphine consumption, and safety. Between-group comparisons were performed using Kruskal–Wallis tests with Dunn post-hoc corrections; within-group trajectories were analysed using Fried-man tests. Effect sizes were estimated with epsilon-squared and Kendall’s W. Results All 30 patients completed the study. At T0 and T1, NRS scores were higher in the ketorolac group (median 1.5 and 3, respectively) compared with tramadol and diclofenac (both median 0 at T0; T1: tramadol 1, diclofenac 2; p < 0.05 for both). However, by T2 and T3, all three groups converged to a median NRS of 2 (p > 0.05 for between-group differences). Rescue analgesia requirements at T1 were 0/10 (tramadol), 3/10 (ketorolac), and 2/10 (diclofenac), with no statistically significant differences (p = 0.19). No hypersensitivity reactions occurred. Within-group analyses showed con-sistent pain trajectories, with Kendall’s W ranging from 0.31 (ketorolac) to 0.64 (tramadol). Conclusions In this pilot study, equianalgesic doses of tramadol, ke-torolac, and diclofenac provided comparable postoperative pain control over 90 minutes following minimally invasive surgery. All agents were well toler-ated. These findings support the feasibility of a larger definitive trial and offer clinically useful guidance for analgesic selection in resource-limited settings. Trial registration ClinicalTrials.gov - NCT07500454 (retrospectively registered). Highlights Double-blind pilot RCT compared equianalgesic doses of tramadol, ke-torolac, and diclofenac. All three groups converged to median NRS 2 by 60 minutes postoper-atively. Early higher pain in the ketorolac group was partly attributed to age imbalance ( ρ =0.49, p=0.006). No hypersensitivity reactions occurred in any group. Definitive trial requires 27 patients per group (90 total with 10% attri-tion).