Effect of Multimodal Pre-emptive Analgesia with Pregabalin Versus Naproxen on Post-Thoracotomy Pain and Opioid Consumption: A Randomized Clinical Trial.

OBJECTIVE: Thoracotomy produces severe postoperative pain that limits deep breathing and coughing and may worsen recovery. Opioid-centred regimens can cause adverse effects; pre-emptive multimodal analgesia may reduce central sensitisation and opioid use. METHODS: In this randomized, active-controlled, assessor-blinded trial (CTRI/2022/07/043800), adults aged 18-70 years (American Society of Anesthesiologists I-II) undergoing thoracotomy were randomized (39 per group) to receive oral pregabalin 2.5 mg kg-1 or oral naproxen 7 mg kg-1 (maximum 500 mg) 2 hours preoperatively. All patients received standardized general anaesthesia combined with thoracic epidural analgesia. Numerical rating scale (NRS) pain at rest and during deep breathing and coughing were assessed at 2, 6, 12, and 24 hours. A rescue opioid was administered when NRS exceeded 3. Time to first rescue, total 24-hour opioid consumption, number of rescue doses, sleep interference, and adverse events were recorded. RESULTS: Baseline demographics and perioperative haemodynamics were comparable. Resting pain scores and sleep interference were similar between groups. Pregabalin reduced opioid requirement: fewer patients required rescue analgesia (46.2% vs. 69.2%; P=0.042), time to first rescue was longer (7.6±3.1 vs. 5.4±2.8 h; P=0.001), and 24-hour opioid consumption was lower (6.2±3.0 vs. 8.6±3.4 mg morphine equivalents; P=0.001). Dynamic pain during deep breathing and coughing was lower with pregabalin at early time points; sedation was slightly higher at 2 hours, without significant adverse neurocognitive events. CONCLUSION: Pre-emptive pregabalin improved functional analgesia and produced an opioid-sparing effect compared with naproxen after thoracotomy, with acceptable short-term safety, thereby supporting enhanced recovery pathways.