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Randomized Controlled Trial
. 2022 Dec 1;5(12):e2244514.
doi: 10.1001/jamanetworkopen.2022.44514.

Effect of Intraoperative Esketamine Infusion on Postoperative Sleep Disturbance After Gynecological Laparoscopy: A Randomized Clinical Trial

Di Qiu  1 , Xing-Ming Wang  1   2 , Jin-Jin Yang  1 , Sai Chen  1 , Cai-Bao Yue  1 , Kenji Hashimoto  2 , Jian-Jun Yang  1
Affiliations
Randomized Controlled Trial

Effect of Intraoperative Esketamine Infusion on Postoperative Sleep Disturbance After Gynecological Laparoscopy: A Randomized Clinical Trial

Di Qiu et al. JAMA Netw Open. .

Abstract

Importance: Postoperative sleep disturbance (PSD) is common in patients after surgery.

Objective: To examine the effect of intraoperative esketamine infusion on the incidence of PSD in patients who underwent gynecological laparoscopic surgery.

Design, setting, and participants: This single-center, double-blind, placebo-controlled randomized clinical trial was conducted from August 2021 to April 2022 in the First Affiliated Hospital of Zhengzhou University in China. Participants included patients aged 18 to 65 years with an American Society of Anesthesiologist Physical Status classification of I to III (with I indicating a healthy patient, II a patient with mild systemic disease, and III a patient with severe systemic disease) who underwent gynecological laparoscopic surgery. Patients were randomly assigned to either the esketamine group or control group. Data were analyzed using the per protocol principle.

Interventions: Patients in the esketamine group received a continuous infusion of esketamine, 0.3 mg/kg/h, intraoperatively. Patients in the control group received an equivalent volume of saline.

Main outcomes and measures: The primary outcome was the incidence of PSD on postoperative days (PODs) 1 and 3. Postoperative sleep disturbance was defined as a numeric rating scale score of 6 or higher or an Athens Insomnia Scale score of 6 points or higher. The secondary outcomes included postoperative anxiety and depression scores using the Hospital Anxiety and Depression Scale, postoperative pain using the visual analog scale, postoperative hydromorphone consumption, and risk factors associated with PSD.

Results: A total of 183 female patients were randomized to the control group (n = 91; median [IQR] age, 45 [35-49] years) and the esketamine group (n = 92; median [IQR] age, 43 [32-49] years). The incidence of PSD in the esketamine group was significantly lower than in the control group on POD 1 (22.8% vs 44.0%; odds ratio [OR], 0.38 [95% CI, 0.20-0.72]; P = .002) and POD 3 (7.6% vs 19.8%; OR, 0.33 [95% CI, 0.13-0.84]; P = .02). There were no differences in postoperative depression and anxiety scores between the 2 groups. Postoperative hydromorphone consumption in the first 24 hours (3.0 [range, 2.8-3.3] mg vs 3.2 [range, 2.9-3.4] mg; P = .04) and pain scores on movement (3 [3-4] vs 4 [3-5] points; P < .001) were significantly lower in the esketamine group than in the control group. On multivariable logistic regression, preoperative depression (OR, 1.31; 95% CI, 1.01-1.70) and anxiety (OR, 1.67; 95% CI, 1.04-1.80) scores, duration of anesthesia (OR, 1.04; 95% CI, 1.00-1.08), and postoperative pain score (OR, 1.92; 95% CI, 1.24-2.96) were identified as risk factors associated with PSD.

Conclusions and relevance: Results of this trial showed the prophylactic effect of intraoperative esketamine infusion on the incidence of PSD in patients who underwent gynecological laparoscopic surgery. Further studies are needed to confirm these results.

Trial registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100048587.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Hashimoto reported receiving personal fees from Abbott, Meiji Seika Pharma, and Seikagaku Corporation; receiving grants from Sumitomo Pharma, Taisho, Otsuka, Murakami Farm, and Perception Neuroscience; and being the inventor with filed patent applications for “The use of R-ketamine in the treatment of psychiatric diseases,” “(S)-norketamine and salt thereof as pharmaceutical,” “R-ketamine and derivative thereof as prophylactic or therapeutic agent for neurodegeneration disease or recognition function disorder,” “Preventive or therapeutic agent and pharmaceutical composition for inflammatory diseases or bone diseases,” “R-ketamine and its derivatives as a preventive or therapeutic agent for a neurodevelopmental disorder,” and “TGF-β1 in the treatment of depression” by Chiba University outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Participant Flowchart
Figure 2.
Figure 2.. Incidence of Postoperative Sleep Disturbance (PSD) on Preoperative Day 1, Postoperative Day 1, and Postoperative Day 3
aP < .01 esketamine vs control groups. bP < .001 esketamine vs control groups.
Figure 3.
Figure 3.. Forest Plot of Factors Analyzed for Association With Incidence of Postoperative Sleep Disturbance in Multivariable Logistic Regression
HADS-A indicates Hospital Anxiety and Depression Scale-Anxiety; HADS-D, Hospital Anxiety and Depression Scale-Depression; OR, odds ratio.
See this image and copyright information in PMC

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