The hemodynamic effects of esketamine-based opioid-free anesthesia in laparoscopic hepatectomy: a randomized clinical trial

Background: Controlled low central venous pressure is recommended for laparoscopic hepatectomy. This study aimed to evaluate the effects of esketamine-based opioid-free anesthesia on hemodynamic stability and perioperative safety during this procedure, particularly under CLCVP conditions. Materials and Methods: This prospective, randomized, double-blind, controlled trial was conducted from June 2024 to February 2025 at a university hospital in Nanjing. Participants scheduled for laparoscopic hepatectomy were randomly allocated to receive either esketamine-based opioid-free anesthesia (esketamine, lidocaine, dexmedetomidine) or opioid-inclusive anesthesia (sufentanil and remifentanil). All patients underwent surgery with controlled low central venous pressure management, including restrictive fluid therapy and intermittent Pringle maneuvers. The primary outcome was the change in mean arterial pressure within 1 minute after the first Pringle maneuver release. Secondary outcomes included mean arterial pressure variation after the final release and intraoperative vasopressor requirements. Results: A total of 146 patients (median [IQR] age, 59.0 [54.0-65.0] years) were included in the intention-to-treat analysis. Compared with the opioid-inclusive group, patients in the opioid-free group experienced significantly smaller mean arterial pressure reductions within 1 minute following the first Pringle maneuver release (mean [SD], 0.8 [6.4] mmHg vs 12.5 [7.5] mmHg; mean difference, 11.64 mmHg; 95% CI: 9.37-13.92, P < 0.001), as well as milder blood pressure fluctuations after the final release. Intraoperative vasoactive drug consumption was also significantly lower in the opioid-free group. Conclusions: In patients undergoing laparoscopic hepatectomy with controlled low central venous pressure, esketamine-based opioid-free anesthesia significantly improved intraoperative hemodynamic stability and reduced vasopressor requirements. These findings support the use of OFA as a viable alternative to opioid-inclusive strategies in enhanced recovery protocols for hepatobiliary surgery.