Thoracic epidural analgesia (TEA), once the standard for pain management in major abdominal operations, is associated with postoperative complications, making preperitoneal continuous wound infiltration (CWI) a promising alternative. This study aimed to compare the effectiveness of CWI and TEA in managing postoperative pain after open pancreatoduodenectomy. In a single-centre, randomized, open-label non-inferiority trial, adult patients undergoing elective open pancreatoduodenectomy were assigned to either CWI or TEA for pain management. The primary outcomes were mean pain scores at rest on the first 3 postoperative days (PODs), using an 11-point numeric rating scale, with a non-inferiority margin of 1 point or less. Secondary outcomes included pain scores at rest and during coughing on PODs 1, 2, and 3; total opioid consumption; incidence of postoperative complications; quality of postoperative recovery; and duration of hospital stay. Among the 134 patients analysed (CWI 70, TEA 64), CWI was non-inferior to TEA in terms of mean pain scores at rest (mean difference -0.13, 95% c.i. -0.72 to 0.47). Additionally, CWI demonstrated superior pain relief at rest and higher-quality recovery scores on POD 3. Compared with CWI, TEA was associated with significantly decreased total opioid consumption and shortened time to the first passage of flatus, but a higher incidence of postoperative hypotension. No other outcome measures showed significant differences between the two groups. CWI was non-inferior to TEA during the early postoperative period, and has emerged as a favourable alternative to TEA, offering better pain relief and enhanced recovery on POD 3. Registration number: NCT04375826 (http://www.clinicaltrials.gov).
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