Adding nefopam to oxycodone-based patient-controlled analgesia provides noninferior analgesia with opioid sparing after laparoscopic surgery

To evaluate the analgesic efficacy and opioid-sparing effect of two different doses of nefopam combined with oxycodone in intravenous patient-controlled analgesia (IV PCA) compared with oxycodone alone after laparoscopic abdominal surgery. In this single-center, randomized, single-blind, non-inferiority trial, 246 patients undergoing elective laparoscopic gastrointestinal or colorectal surgery were randomly assigned (1:1:1) to Group A (oxycodone 160 mg + nefopam 120 mg), Group B (oxycodone 130 mg + nefopam 200 mg), or Group C (oxycodone 200 mg, control), each in a 200 mL PCA bag. The primary endpoint was visual analogue scale (VAS) pain score at rest at 24 h postoperatively, with a non-inferiority margin of 1.0. Secondary endpoints included cumulative oxycodone consumption, rescue medication use, quality of recovery, and adverse events. A total of 230 patients were included in the intention-to-treat analysis. Both nefopam-oxycodone combinations were non-inferior to oxycodone monotherapy for the primary endpoint (mean difference, Group A vs. C: -0.33, 95% CI - 0.81 to 0.15; Group B vs. C: 0.00, 95% CI - 0.50 to 0.51). Cumulative oxycodone consumption at 96 h was reduced by 26.2% in Group A and 46.7% in Group B compared with the control group (both P < 0.001). The incidences of any adverse event, sedation, and respiratory depression did not differ among the three groups. In this single-blind trial, adding nefopam to oxycodone-based IV PCA provided non-inferior analgesia while substantially reducing opioid consumption after laparoscopic abdominal surgery. These results require confirmation in a double-blind trial with a fixed-opioid-dose design.Trial Registration: This study was registered at the Clinical Research Information Service of the Korean National Institute of Health (CRIS, http//cris.nih.go.kr), with registration number KCT0003896.