EEG-Derived Pain Threshold Index-Guided Remifentanil Titration During Laparoscopic Abdominal Surgery: A Randomized Trial

OBJECTIVE: To determine whether remifentanil titration guided by the pain threshold index (PTi), an electroencephalography-derived proxy for nociceptive tolerance rather than subjective pain, reduces intraoperative remifentanil infusion during laparoscopic abdominal surgery. METHODS: In this prospective, single-center, assessor-blinded randomized trial, adults undergoing elective laparoscopic abdominal surgery with propofol-remifentanil target-controlled infusion were assigned 1:1 to PTi-guided or conventional hemodynamic-guided remifentanil titration. The primary endpoint was intraoperative remifentanil infusion rate. The principal analysis used the full-analysis set and covariate-adjusted linear regression with heteroskedasticity-consistent robust standard errors. RESULTS: Among 200 randomized patients, 195 were analyzed (98 PTi-guided; 97 control). The primary endpoint was neutral: mean (SD) remifentanil infusion rate was 7.44 (1.43) versus 7.63 (1.41) µg kg-1 h-1; adjusted mean difference, -0.06 µg kg-1 h-1 (95% CI, -0.44 to 0.32; P=0.758). Per-protocol results were similar. Median (IQR) NRS at post-anesthesia care unit (PACU) admission was 2.0 (2.0-3.0) versus 3.0 (2.0-4.0), and Ramsay score was 2.0 (2.0-2.0) in both groups. In exploratory secondary analyses, rescue opioid was used in the PACU by 18/98 (18.4%) versus 31/97 (32.0%) patients and any rescue opioid through 48 h by 29/98 (29.6%) versus 44/97 (45.4%). Any postoperative nausea and vomiting (PONV) through 48 h occurred in 17/98 (17.3%) versus 29/97 (29.9%) patients. Total postoperative opioid exposure through 48 h was not reduced. CONCLUSION: PTi-guided remifentanil titration did not reduce intraoperative remifentanil infusion. PACU pain and sedation scores were not materially different. Lower early rescue-opioid use and fewer PONV events through 48 h were exploratory secondary findings, were not accompanied by lower postoperative opioid dose, and require prospective confirmation.