Oral Premedication with Tapentadol versus Pregabalin for Acute Postoperative Pain in Lower Limb Surgery Under Neuraxial Anesthesia: A Pilot Randomized Controlled Trial

Background

Acute postoperative pain affects more than 80% of surgical patients, with orthopedic lower limb procedures consistently associated with severe pain intensity and high opioid requirements. Preemptive analgesia with oral agents has been proposed to attenuate central and peripheral sensitization prior to surgical incision. Tapentadol, a dual-mechanism µ -opioid receptor agonist and norepinephrine reuptake inhibitor, and pregabalin, a voltage-gated calcium channel modulator, represent pharmacologically distinct premedication options; however, direct comparative data in this surgical context are lacking. This pilot randomized controlled trial assessed feasibility and generated exploratory, hypothesis-generating data on the comparison of analgesic efficacy and safety of 72-hour oral premedication with tapentadol versus pregabalin in patients undergoing elective lower limb surgery under neuraxial anesthesia.

Methods

In this double-blind, parallel-group pilot trial, 46 patients undergoing elective lower limb surgery under neuraxial anaesthesia were randomized to tapentadol 50 mg q12h or pregabalin 75 mg q24h for 72 h preoperatively. Feasibility outcomes included recruitment rate, retention, 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 a linear mixed model; p-values are reported as hypothesis-generating.

Results

Over 1 month , 46 patients were enrolled (9.2 patients/week); retention and adherence were 100%. The pooled standard deviation of NRS at 60 min was 1.2. Exploratory analyses showed that pain scores diverged from 30 min onward, with a large observed difference at 90 min (mean NRS difference –0.91, p = 0.006, Cohen’s d = –0.96). Rescue morphine was required in 4.3% (tapentadol) vs. 21.7% (pregabalin). Nausea/vomiting occurred in 17.4% of both groups; no hypersensitivity reactions.

Conclusions

A definitive RCT comparing tapentadol and pregabalin in lower limb surgery is feasible. Exploratory hypothesis-generating data suggest a clinically relevant difference in pain scores and rescue analgesia, favouring tapentadol. Variance estimates (SD = 1.2) indicate that 40 patients per group would be required for a non-inferiority trial. These findings warrant confirmation in a larger study.

Trial registration

ClinicalTrials.gov - NCT07587645 (retrospectively registered).

Highlights