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

Bin Cao, Zheng Qi, Ying-Ying Zhao, Qiong Xue, Juan-Juan Ren, Wei-Wei Xu, Yu-Ning Fan, Zhen-Hua Nan, Pei-Pei Sun, Hui-Juan Li, Jie Zhang, Jian-Jun YangDepartment of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian-Jun Yang; Jie Zhang, Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel/Fax +86-371-66271657, Email jianjunyangzzu@hotmail.com; joannyzh@163.comObjective: 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.Keywords: electroencephalography, laparoscopic surgery, nociception monitoring, pain threshold index, postoperative analgesia, remifentanil