Effect of Intraoperative Esketamine Infusion on Postoperative Sleep Disturbance After Gynecological Laparoscopy

Abstract

ImportancePostoperative sleep disturbance (PSD) is common in patients after surgery.ObjectiveTo examine the effect of intraoperative esketamine infusion on the incidence of PSD in patients who underwent gynecological laparoscopic surgery.Design, Setting, and ParticipantsThis 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.InterventionsPatients 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 MeasuresThe 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.ResultsA 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 RelevanceResults 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 RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2100048587

Effect of esketamine on postoperative depressive symptoms in patients undergoing thoracoscopic lung cancer surgery: A randomized controlled trial

“…The demographic and baseline characteristics were comparable between the two groups ( Table 1 ). The mean (SD) age was 54 ( 12 ) years for both groups. 69.2% of patients in the esketamine group and 76.9% in the normal saline group were female sex.…”

“…Furthermore, several studies also suggested that the use of esketamine prevented postpartum depressive symptoms after cesarean section ( 31 , 32 ). A recent study showed that intraoperative esketamine infusion improved postoperative sleep disturbance, but not depression symptoms, after gynecological laparoscopy ( 12 ). However, there is lack of evidence regarding the effects of esketamine on depression after cancer surgery.…”

“…Studies have suggested that perioperative use of esketamine was associated with reduced pain intensity and opioid requirements after surgery ( 12 , 15 , 20 ). However, our study did not show such a relationship.…”

“…Preclinical studies suggested that those side effects of ketamine may be attributed to S-ketamine, but not R-ketamine ( 7 , 13 ). However, recent clinical evidence showed that perioperative use of ketamine increased the risk of psychotomimetic adverse events ( 14 ), while esketamine did not significantly increase the risk ( 12 , 15 ).…”

“…A recent meta-analysis showed that intravenous ketamine was associated with reduced postoperative depressive symptoms within 3 days after surgery ( 10 ). Esketamine has been shown to reduce postoperative depression scores from 3 days to 1 month postoperatively in patients with breast cancer ( 11 ), while a recent study found that continuous intraoperative esketamine infusion did not reduce depression scores at 3 days after gynecological laparoscopy ( 12 ). Therefore, further investigations are still required to ascertain the effects of ketamine or esketamine on depressive symptoms in surgical patients.…”