Journal Article

The additive effect of esketamine and clonidine in patients at high risk for acute postoperative pain undergoing laparoscopic surgery: A randomised controlled trial

Persson, Anna K.M., Undén, Johan, Holgersson, Josefine, Mogianos, Krister

2026

Overview

To evaluate if adding esketamine and clonidine has positive effects on postoperative pain, postoperative nausea and vomiting, and quality of recovery in patients who are at high risk for postoperative pain. Patient- and assessor-blinded, superiority, randomised controlled trial. Single centre between 2022 and 2024. 125 adult patients, ASA I – II, planned for elective laparoscopic surgery and risk-classified as high risk of pain, based on perceived pain associated with venous cannulation. Patients were randomised to either an anaesthesia protocol, including an intravenous bolus of esketamine (0.25 mg.kg−1) after induction and clonidine (1 μg.kg−1) during maintenance phase (EC), or standard of care (SOC) no esketamine or clonidine included. Primary outcome: worst pain intensity in the PACU. Secondary outcomes: worst pain, and proportion having NRS ≥ 4, at 24 h (during rest and movement), worst pain and proportion having NRS ≥ 1, at 3- and 6-months (during rest and movement), postoperative recovery at 24 h, PONV in the PACU and at 24 h. Rescue dose opioids in the PACU was an exploratory outcome. Worst pain scores in the PACU were 5.7 in the EC group and 5.5 in SOC group (P = 0.78). After 24 h, no difference in postoperative pain (rest; 5.8 vs 6.1, P = 0.35, movement; 6.1 vs 6.2, P = 0.68), postoperative recovery (P = 0.92) or PONV (P = 0.80) was found. Proportion of patients with NRS ≥ 4 in the PACU was 50 % vs 48 % (P = 0.55) and at 24 h 73 % vs 81 % at rest (P = 0.27) and 76 % vs 81 % during movement (P = 0.50). Rescue opioids in the PACU were similar (5.9 mg vs 6.6 mg, P = 0.47). There were no differences in persistent pain at 3 or 6 months at rest (P = 0.72, P = 0.12) or movement (P = 0.48, P = 0.18). Adding esketamine and clonidine, as an individualised multimodal anaesthesia strategy, did not influence acute or persistent postoperative pain, early recovery, need of rescue opioids or PONV in patients, who were assessed as high risk for APOP. [Display omitted] •Adding esketamine and clonidine did not improve APOP in patients predicted as high-risk for postoperative pain.•Adding esketamine and clonidine did not improve recovery or PONV in patients predicted as high-risk for postoperative pain.•The pursuit for individualised anaesthesia and analgesia needs further refinement.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Acute Pain - diagnosis / Acute Pain - drug therapy / Acute Pain - etiology / Acute Pain - prevention & control / Adult / Aged / Alpha-2-agonism / Analgesics / Analgesics - administration & dosage / Analgesics, Opioid - administration & dosage / Anestesi och intensivvård / Anesthesia / Anesthesia Recovery Period / Anesthesiology and Intensive Care / Clinical Medicine / Clinical trials / Clonidine - administration & dosage / Clonidine - adverse effects / Clonidine - therapeutic use / Drug Therapy, Combination - adverse effects / Drug Therapy, Combination - methods / Elective Surgical Procedures - adverse effects / Ethics / Female / General anesthesia / Health risks / Humans / Ketamine - administration & dosage / Ketamine - therapeutic use / Klinisk medicin / Laparoscopy / Laparoscopy - adverse effects / Male / Medical and Health Sciences / Medicin och hälsovetenskap / Middle Aged / NMDA-antagonism / Nurses / Pain / Pain Measurement / Pain Medicine / Pain sensitivity / Patients / Postoperative Nausea and Vomiting - epidemiology / Postoperative Nausea and Vomiting - etiology / Postoperative Nausea and Vomiting - prevention & control / Postoperative pain / Postoperative Pain - diagnosis / Postoperative Pain - drug therapy / Postoperative Pain - etiology / Postoperative Pain - prevention & control / Postoperative period / Standard of care / Surgeons / Surgery