Tapentadol vs Pregabalin for Postoperative Pain in Lower Limb Surgery

Acute postoperative pain affects over 80% of surgical patients, with orthopaedic lower limb procedures causing particularly severe pain. Preemptive analgesia may attenuate central sensitisation before surgical incision. Tapentadol (μ-opioid agonist + norepinephrine reuptake inhibitor) and pregabalin (voltage-gated calcium channel modulator) are pharmacologically distinct options, but direct comparative data are lacking.

This single-centre, double-blind, parallel-group pilot randomised controlled trial was conducted at Hospital Regional "General Ignacio Zaragoza," ISSSTE, Mexico City. Forty-six patients (ASA I-II, age 18-50 years, BMI 18-35 kg/m²) scheduled for elective lower limb surgery under neuraxial anaesthesia were randomised 1:1 to receive either tapentadol 50 mg orally every 12 hours (n=23) or pregabalin 75 mg orally every 24 hours (n=23), both initiated 72 hours before surgical incision.

The primary outcome was postoperative pain intensity assessed using the Numeric Rating Scale (NRS 0-10) at PACU arrival (T0) and at 30 (T1), 60 (T2), 90 (T3), and 120 (T4) minutes thereafter. Secondary outcomes included Verbal Rating Scale (VRS) scores, rescue morphine consumption (4 mg IV on request), and incidence of nausea/vomiting and hypersensitivity reactions. The primary longitudinal analysis used a linear mixed model with Group, Time, and Group×Time interaction as fixed effects and a random intercept per patient. Between-group contrasts at each timepoint were derived from estimated marginal means with Holm correction. Effect sizes are reported as Cohen's d.

The trial was approved by the institutional ethics and research committee (RPI #386-2024) and registered with the ISSSTE institutional research registry prior to enrolment. Due to institutional policy restrictions at the time of study initiation, registration on ClinicalTrials.gov was completed after data collection; this is disclosed transparently in accordance with CONSORT 2025 guidance on retrospective registration disclosure.

Inclusion criteria

• Age 18-50 years
• ASA physical status I or II
• Body mass index between 18 and 35 kg/m²
• Scheduled for elective lower limb surgery under neuraxial anaesthesia
• Willing to provide written informed consent

Exclusion criteria

• Chronic use of analgesics or gabapentinoids
• Known hypersensitivity to tapentadol or pregabalin
• Pre-existing chronic pain

Elimination Criteria:

• Hypersensitivity reaction to any study drug during administration
• Hemodynamic shock of any etiology
• Requirement for advanced airway management or postoperative mechanical ventilation
• Surgical duration exceeding 120 minutes
• Requirement of an epidural catheter dose within the first two postoperative hours
• Voluntary withdrawal of consent at any point