Exploratory Analysis of Analgesic Equivalence of NSAIDs vs. a Weak Opioid in Acute Postoperative Pain: a Pilot Randomized Controlled Trial
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Background
Non-steroidal anti-inflammatory drugs (NSAIDs) and weak opioids such as tramadol are cornerstones of multimodal analgesia, particularly in settings with limited access to potent opioids. However, cross-class equianalgesic data are scarce, and the feasibility of a definitive trial com-paring these agents in minimally invasive surgery is unknown. This pilot randomized controlled trial assessed feasibility and generated exploratory, hypothesis-generating data on analgesic outcomes.
Methods
In this double-blind, parallel-group pilot trial, 30 patients undergoing elective minimally invasive surgery under balanced general anesthesia were randomised to intravenous tramadol 150 mg, ketorolac 60 mg, or diclofenac 150 mg 45 minutes before skin incision. Feasibility out-comes included recruitment rate (patients/month), retention at 90 min, protocol adherence, and variance of Numeric Rating Scale (NRS, 0–10) pain scores to inform future sample size. Exploratory outcomes were NRS and Verbal Rating Scale (VRS) scores, rescue morphine consumption, and safety. Between-group comparisons used Kruskal–Wallis tests; p-values are hypothesis-generating only.
Results
Over 1 month, 30 patients were enrolled ( ≈ 7.5 patients/week); retention and adherence were 100%. The pooled standard deviation of NRS at 60 min was 2.1. Exploratory analyses showed that at T0 and T1, NRS scores were higher in the ketorolac group (median 1.5 and 3) compared with tramadol and diclofenac (both median 0 at T0; T1: tramadol 1, diclofenac 2; p < 0.05). By T2 (60 min) and T3 (90 min), all three groups had median NRS 2 (p > 0.05). Rescue morphine was required in 0/10 (tramadol), 3/10 (ketorolac), and 2/10 (diclofenac) (p = 0.19). No hypersensitivity reactions occurred.
Conclusions
A definitive RCT comparing NSAIDs and tramadol in minimally invasive surgery is feasible. Exploratory hypothesis-generating data suggest that all three agents provide similar pain control after 60 minutes. Variance estimates (SD = 2.1) indicate that 27 patients per group would be required for a non-inferiority trial. These findings warrant confirmation in a larger study.
Trial registration
ClinicalTrials.gov - NCT07500454 (retrospectively registered).
Highlights
Pilot RCT (n=30) assessing feasibility of comparing NSAIDs vs tramadol in minimally invasive surgery.
Recruitment rate 7.5 patients/month; 100% retention and protocol adherence.
Exploratory analysis: all three groups had median NRS 2 by 60 minutes postoperatively.
Early higher pain in ketorolac group partly attributed to age imbalance ( ρ = 0.49, p = 0.006).
Variance estimate (SD = 2.1) suggests 27 patients/group needed for a definitive non-inferiority trial.
No hypersensitivity reactions occurred; all agents were well tolerated.
