Effect of Esketamine Added to Propofol Sedation on Desaturation and Hypotension in Bidirectional Endoscopy

Abstract

ImportancePropofol sedation is widely used for endoscopic procedures, but it poses risks of hemodynamic and respiratory depression. The addition of esketamine as an adjuvant may reduce propofol requirements and associated adverse events.ObjectiveTo evaluate the effects of low-dose esketamine added to propofol-based sedation on desaturation and hypotension during same-visit bidirectional endoscopy.Design, Setting, and ParticipantsThis multicenter, double-blind, placebo-controlled randomized clinical trial assessed patients from 3 teaching hospitals in China who were scheduled for same-visit bidirectional endoscopy between February 8 and November 30, 2022, and randomly assigned to receive esketamine or normal saline (placebo).InterventionsAfter induction of sedation with 0.1 μg/kg of sufentanil and 0.5 mg/kg of propofol, patients in the esketamine group received 0.15 mg/kg of intravenous esketamine, whereas patients in the placebo group received an equivalent volume of saline. Sedation was achieved through propofol titration.Main Outcomes and MeasuresThe primary outcome was the composite of desaturation and hypotension during the procedures. Secondary outcomes included desaturation, hypotension, propofol requirements, postprocedure pain and fatigue, nausea or vomiting, dizziness or headache, hallucination or nightmare, endoscopist satisfaction, and patient satisfaction.ResultsAmong the 663 initially enrolled patients, 660 completed the study (median [IQR] age, 48 [36-57] years; 355 [53.8%] female), with 331 randomized to the esketamine group and 329 to the placebo group. The administration of esketamine compared with placebo significantly reduced the incidence of the composite outcome of desaturation and hypotension (8.2% vs 21.0%; difference, −12.8 percentage points; odds ratio [OR], 0.34; 95% CI, 0.21-0.54; P < .001). Additionally, esketamine led to significantly lower incidences of desaturation (OR, 0.36; 95% CI, 0.18-0.72; false discovery rate q = .01) and hypotension (OR, 0.33; 95% CI, 0.18-0.60; q < .001) and reduced propofol requirements (difference, −58.9 mg; 95% CI, −65.7 to −52.2 mg; q < .001), without significant effects on other secondary outcomes.Conclusions and RelevanceIn this randomized clinical trial of patients undergoing same-visit bidirectional endoscopy, the administration of low-dose esketamine resulted in an approximately 61% reduction in the incidence of desaturation and hypotension, accompanied by decreased propofol requirements. These findings support the use of esketamine as an adjuvant to propofol-based sedation in endoscopic procedures.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2200055938

Intravenous esketamine as an adjuvant for sedation/analgesia outside the operating room: a systematic review and meta-analysis

“…Six studies involved 698 pediatric participants (age range: 2 days to 12 years) ( Pees et al, 2003 ; Wang et al, 2022 ; Xu (b) et al, 2022; Zheng (b) et al, 2023; Zheng et al, 2022 ; Zhong et al, 2023 ), and the 19 remaining studies involved 2,757 adult participants (18–89 years) ( Chen et al, 2022 ; Chen et al, 2023 ; Cui et al, 2023 ; Eberl et al, 2020 ; Feng (a) et al, 2022; Feng (b) et al, 2022; Lin et al, 2023 ; Liu et al, 2023 ; Lu et al, 2022 ; Ma et al, 2024 ; Nie et al, 2023 ; Si et al, 2024 ; Song et al, 2023 ; Wang et al, 2019 ; Xin et al, 2024 ; Xu (a) et al, 2022; Yang et al, 2022 ; Zhan et al, 2022 ; Zheng (a) et al, 2023). Fifteen studies carried out diagnostic and therapeutic gastrointestinal endoscopy ( Chen et al, 2023 ; Eberl et al, 2020 ; Feng (a) et al, 2022; Liu et al, 2023 ; Lu et al, 2022 ; Ma et al, 2024 ; Song et al, 2023 ; Wang et al, 2022 ; Wang et al, 2019 ; Xu (a) et al, 2022; Yang et al, 2022 ; Zhan et al, 2022 ; Zheng (a) et al, 2023; Zheng (b) et al, 2023; Zheng et al, 2022 ); four conducted fiberoptic bronchoscopy ( Cui et al, 2023 ; Feng (b) et al, 2022; Nie et al, 2023 ; Zhong et al, 2023 ); and six studies involved abortions ( Chen et al, 2022 ), cervical conization ( Si et al, 2024 ), MRI (Xu (b) et al, 2022), cardiac catheterization ( Pees et al, 2003 ), dental extraction ( Xin et al, 2024 ), and percutaneous radiofrequency ablation of lung tumor ( Lin et al, 2023 ), respectively. Twenty-two studies used a combination of esketamine and propofol ( Chen et al, 2022 ; Chen et al, 2023 ; Cui et al, 2023 ; Eberl et al, 2020 ; Feng (a) et al, 2022; Feng (b) et al, 2022; Liu et al, 2023 ; Ma et al, 2024 ; Nie et al, 2023 ; Si et al, 2024 ; Song et al, 2023...…”

“…Fifteen studies carried out diagnostic and therapeutic gastrointestinal endoscopy ( Chen et al, 2023 ; Eberl et al, 2020 ; Feng (a) et al, 2022; Liu et al, 2023 ; Lu et al, 2022 ; Ma et al, 2024 ; Song et al, 2023 ; Wang et al, 2022 ; Wang et al, 2019 ; Xu (a) et al, 2022; Yang et al, 2022 ; Zhan et al, 2022 ; Zheng (a) et al, 2023; Zheng (b) et al, 2023; Zheng et al, 2022 ); four conducted fiberoptic bronchoscopy ( Cui et al, 2023 ; Feng (b) et al, 2022; Nie et al, 2023 ; Zhong et al, 2023 ); and six studies involved abortions ( Chen et al, 2022 ), cervical conization ( Si et al, 2024 ), MRI (Xu (b) et al, 2022), cardiac catheterization ( Pees et al, 2003 ), dental extraction ( Xin et al, 2024 ), and percutaneous radiofrequency ablation of lung tumor ( Lin et al, 2023 ), respectively. Twenty-two studies used a combination of esketamine and propofol ( Chen et al, 2022 ; Chen et al, 2023 ; Cui et al, 2023 ; Eberl et al, 2020 ; Feng (a) et al, 2022; Feng (b) et al, 2022; Liu et al, 2023 ; Ma et al, 2024 ; Nie et al, 2023 ; Si et al, 2024 ; Song et al, 2023 ; Wang et al, 2022 ; Wang et al, 2019 ; Xin et al, 2024 ; Xu (a) et al, 2022; Xu (b) et al, 2022; Yang et al, 2022 ; Zhan et al, 2022 ; Zheng (a) et al, 2023; Zheng (b) et al, 2023; Zheng et al, 2022 ; Zhong et al, 2023 ), two studies used esketamine plus benzodiazepines ( Pees et al, 2003 ; Lu et al, 2022 ), and one study used esketamine combined with dexmedetomidine ( Lin et al, 2023 ). Eighteen studies involved one esketamine group with doses ranging from 0.15 to 1.0 μg/kg ( Cui et al, 2023 ; Eberl et al, 2020 ; Feng (b) et al, 2022; Lin et al, 2023 ; Liu et al, 2023 ; Lu et al, 2022 ; Ma et al, 2024 ; Nie et al, 2023 ; Pees et al, 2003 ; ...…”

“…Twenty-two studies used a combination of esketamine and propofol ( Chen et al, 2022 ; Chen et al, 2023 ; Cui et al, 2023 ; Eberl et al, 2020 ; Feng (a) et al, 2022; Feng (b) et al, 2022; Liu et al, 2023 ; Ma et al, 2024 ; Nie et al, 2023 ; Si et al, 2024 ; Song et al, 2023 ; Wang et al, 2022 ; Wang et al, 2019 ; Xin et al, 2024 ; Xu (a) et al, 2022; Xu (b) et al, 2022; Yang et al, 2022 ; Zhan et al, 2022 ; Zheng (a) et al, 2023; Zheng (b) et al, 2023; Zheng et al, 2022 ; Zhong et al, 2023 ), two studies used esketamine plus benzodiazepines ( Pees et al, 2003 ; Lu et al, 2022 ), and one study used esketamine combined with dexmedetomidine ( Lin et al, 2023 ). Eighteen studies involved one esketamine group with doses ranging from 0.15 to 1.0 μg/kg ( Cui et al, 2023 ; Eberl et al, 2020 ; Feng (b) et al, 2022; Lin et al, 2023 ; Liu et al, 2023 ; Lu et al, 2022 ; Ma et al, 2024 ; Nie et al, 2023 ; Pees et al, 2003 ; Si et al, 2024 ; Song et al, 2023 ; Wang et al, 2019 ; Xin et al, 2024 ; Xu (a) et al, 2022; Xu (b) et al, 2022; Zheng (a) et al, 2023; Zheng (b) et al, 2023; Zhong et al, 2023 ), and seven studies involved more than one esketamine group with doses ranging from 0.05 to 1.0 μg/kg ( Chen et al, 2022 ; Chen et al, 2023 ; Feng (a) et al, 2022; Wang et al, 2022 ; Yang et al, 2022 ; Zhan et al, 2022 ; Zheng et al, 2022 ). With respect to drug regimens in the control groups, 10 studies used propofol alone ( Cui et al, 2023 ; Feng (a) et al, 2022; Liu et al, 2023 ; Nie et al, 2023 ; Wang et al, 2022 ; Yang et al, 2022 ; Zhan et al, 2022 ; Zheng (a) et al, 2023; Zheng (b) et al, 2023; Zheng et al, 2022 ); 13 studies used propofol in combination with opioids ( Chen et al, 2022 ; Chen et al, 202...…”

“…Eighteen studies involved one esketamine group with doses ranging from 0.15 to 1.0 μg/kg ( Cui et al, 2023 ; Eberl et al, 2020 ; Feng (b) et al, 2022; Lin et al, 2023 ; Liu et al, 2023 ; Lu et al, 2022 ; Ma et al, 2024 ; Nie et al, 2023 ; Pees et al, 2003 ; Si et al, 2024 ; Song et al, 2023 ; Wang et al, 2019 ; Xin et al, 2024 ; Xu (a) et al, 2022; Xu (b) et al, 2022; Zheng (a) et al, 2023; Zheng (b) et al, 2023; Zhong et al, 2023 ), and seven studies involved more than one esketamine group with doses ranging from 0.05 to 1.0 μg/kg ( Chen et al, 2022 ; Chen et al, 2023 ; Feng (a) et al, 2022; Wang et al, 2022 ; Yang et al, 2022 ; Zhan et al, 2022 ; Zheng et al, 2022 ). With respect to drug regimens in the control groups, 10 studies used propofol alone ( Cui et al, 2023 ; Feng (a) et al, 2022; Liu et al, 2023 ; Nie et al, 2023 ; Wang et al, 2022 ; Yang et al, 2022 ; Zhan et al, 2022 ; Zheng (a) et al, 2023; Zheng (b) et al, 2023; Zheng et al, 2022 ); 13 studies used propofol in combination with opioids ( Chen et al, 2022 ; Chen et al, 2023 ; Eberl et al, 2020 ; Feng (b) et al, 2022; Lu et al, 2022 ; Ma et al, 2024 ; Si et al, 2024 ; Song et al, 2023 ; Xu (a) et al, 2022; Zhong et al, 2023 ), ketamine ( Wang et al, 2019 ), or dexmedetomidine ( Xin et al, 2024 ; Xu (b) et al, 2022); one study used ketamine and midazolam ( Pees et al, 2003 ); and one study used sufentanil in combination with dexmedetomidine ( Lin et al, 2023 ). The characteristics of the included studies are shown in Table 1 .…”

“…(ii) Twenty-three of the 25 included studies (92%) were performed in China, which may have led to bias in the results. (iii) Some continuous variables (such as propofol consumption, awakening time, recovery time, and orientation recovery time) of the included studies were reported as medium or with different measurement units, making them unsuitable for direct data merging ( Cui et al, 2023 ; Eberl et al, 2020 ; Feng (b) et al, 2022; Ma et al, 2024 ; Si et al, 2024 ; Song et al, 2023 ; Wang et al, 2022 ; Wang et al, 2019 ; Xu (a) et al, 2022; Xu (b) et al, 2022; Yang et al, 2022 ; Zhan et al, 2022 ; Zheng et al, 2022 ; Zhong et al, 2023 ). In our study, these data were excluded from the meta-analysis because we failed to obtain raw data from the authors.…”