Safety and Efficacy of Esketamine Weak Opioid Anesthesia in Laparoscopic Gallbladder Surgery
Authors: Zhao Lu , Li Zhengyu , Jin Bi , Hou Nina , Yang Heng 
Published: November 2023

Abstract
Background: Esketamine, a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, plays significance in multimodal analgesia due to its potent analgesic, sedative, and anti-inflammatory properties. Recent studies, however, contradict the belief that laparoscopic surgery notably reduces postoperative pain compared to traditional surgeries. The potential opioid-sparing effects of intravenous esketamine, along with its impact on oxidative stress, inflammatory responses, and cognitive function during laparoscopic surgery, remain unexplored.
Methods: In this study, ninety patients scheduled for laparoscopic cholecystectomy were randomized into three groups, each comprising thirty patients: a normal saline control group (NS), a low-dose esketamine group (LS), and a high-dose esketamine group (HS). The LS and HS groups were administered a 0.5 mg/kg esketamine injection before the initial skin incision, followed by esketamine infusions at 2 µg/kg·min and 4 µg/kg·min respectively. Conversely, the NS control group received an intravenous dose of 0.5 mg/kg saline before the first skin incision, followed by a continuous saline infusion at a rate of 2 µg/kg·min. Subsequently, we monitored several parameters: the hemodynamic responses, levels of stress and inflammatory responses, intraoperative doses of sufentanil, remifentanil, and propofol, as well as sufentanil dosage administered in the 24 hours postoperative. We also evaluated alterations in cognitive function, perioperative indicators, and potential adverse reactions among the three groups.
Results: Compared to their levels five minutes prior to anesthesia (T₀) and thirty minutes post-operation (T₄), the NS group exhibited a more significant decrease in Mean Arterial Pressure (MAP) and Heart Rate (HR) at the various time intervals: five minutes after the skin incision (T₁), thirty minutes post-incision (T₂), and at the conclusion of the operation (T₃), when compared to both the LS and HS groups (P < 0.05). Additionally, the LS and HS groups required lower doses of propofol, remifentanil, and sufentanil compared to the NS group during the operation (P < 0.05). At T₁, T₂, and T₃, the NS group exhibited elevated levels of adrenaline (AD), noradrenaline (NE), and endothelin (ET) compared to T₀ and T₄. However, the LS and HS groups had lower AD, NE, and ET levels at T₁, T₂, and T₃ compared to the NS group (P< 0.05).
In all groups (NS, LS, and HS), serum levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were elevated at T₁, T₂, and T₃ in comparison to levels at T₀ and T₄. Yet, the LS and HS groups had lower CRP, TNF-α, and IL-6 levels at T₁, T₂, and T₃ compared to the NS group (P < 0.05). The Montreal Cognitive Assessment (MoCA) scores of all three groups decreased 24 hours after the operation, however, they were notably higher in the LS and HS groups compared to the NS group (P < 0.05). Furthermore, the recovery time was shorter, and the incidence of nausea, vomiting, and respiratory depression was lower in the LS and HS groups compared to the NS group (P< 0.05).
Conclusion: The administration of low-dose esketamine has been shown to be safe, effective, and dependable in the context of laparoscopic gallbladder surgery. It has the capacity to stabilize hemodynamic responses, ameliorate both stress and inflammatory reactions induced by surgical procedures, and expedite the recovery period from anesthesia. Furthermore, it fosters the restoration of postoperative cognitive function. Notably, when used in conjunction with nalbuphine, low-dose esketamine exhibits opioid-sparing properties, thereby reducing the incidence of postoperative adverse effects.
Trial registration: The trial is registered with the China Clinical Trials Registry Registration Number: ChiCTR2300067596. Retrospectively registered (date of registration: 12/01/2023).