Effect of stellate ganglion block on postoperative nausea and vomiting after general anesthesia: A meta-analysis, meta-regression and trial sequential analysis of randomized controlled trials

Effect of stellate ganglion block on postoperative nausea and vomiting after general anesthesia: A meta-analysis, meta-regression and trial sequential analysis of randomized controlled trials | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of stellate ganglion block on postoperative nausea and vomiting after general anesthesia: A meta-analysis, meta-regression and trial sequential analysis of randomized controlled trials Shuai Miao, Shixiao Tang, Jingjing Xu, Guodong Song, Shuhan Gu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5333613/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective Stellate ganglion block (SGB) accelerates the return of gastrointestinal transit and improves gastrointestinal function after surgery. However, it is unclear whether such benefits translate into less postoperative nausea and vomiting (PONV). The aim of this meta-analysis was to identify the effect of SGB on the incidence of PONV after general anesthesia. Methods We systematically searched electronic databases for published randomized controlled trials (RCTs) comparing SGB with placebo or no SGB for reducing PONV after general anesthesia. The primary outcome was the incidence of PONV after general anesthesia. The effect size was estimated by calculating the risk ratio (RR), with 95% confidence interval (CI). Trial sequential analysis (TSA) was also carried out to calculate the required information size. Results 16 RCTs including 1385 patients were included in the study. SGB significantly reduced the incidence of PONV (RR, 0.59, 95% CI, 0.49–0.70, P < 0.0001). In addition, TSA indicated that the Z curve for SGB not only crossed the conventional boundary, but also the TSA boundary for benefit. Meta-regression analyses found no significant impact of age, female proportion, type of surgery, type of anesthesia, sample size and prophylactic administration of antiemetic on the correlation between SGB and the risk of PONV. Conclusion This meta-analysis suggested an association of SGB with a decreased incidence of PONV after general anesthesia. TSA suggested that further studies are unlikely to alter the conclusions regarding the incidence of PONV. stellate ganglion block postoperative nausea and vomiting trial sequential analysis meta-regression Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Appropriate postoperative nausea and vomiting (PONV) management is an important part of enhanced recovery after surgery [ 1 ] . However, the cause of PONV is multifactorial [ 2 ] and definite PONV control methods have not yet been established. The incidence of PONV can be up to 80% in some high risk patients [ 3 ] resulting in aspiration pneumonia and postoperative wound dehiscence [ 4 ] . Multiple drugs have been proved efficiency to reduce PONV, such as dexmedetomidine [ 5 ] , dexamethasone [ 6 ] and ondansetron [ 7 ] . In addition, several studies used regional anesthetic technique to prevent PONV [ 8 – 11 ] . Study by Ma [ 9 ] found that intermittent thoracic paravertebral block with intravenous analgesia could reduce PONV after video-assisted thoracic surgery as well as study by Hung [ 8 ] determined that erector spinae plane block could reduce PONV after liver surgery. However, there are some limitations related to the type of surgery in which regional blocks conducted. Therefore, some investigators tried to determine other methods to manage PONV, among of which is stellate ganglion block (SGB). SGB, formed by the inferior cervical sympathetic ganglia (C7-C8) and the superior thoracic sympathetic ganglia (T1) [ 12 ] has been used since the mid-1930s in a variety of medical conditions, such as the sympathetically maintained pain of the face and upper extremity [ 13 , 14 ] . In recent years, SGB was reported to regulates gastrointestinal function by regulating the autonomic and immune systems [ 15 , 16 ] . However, the contribution of SGB in reducing PONV is unclear. This meta-analysis aimed to identify the benefits of SGB, focusing on its PONV-reducing effect in patients after general anesthesia. Materials and methods The current meta-analysis was performed in accordance with the Preferred Items for Systematic Reviews and Meta-analysis statement guidelines [ 17 ] and AMSTAR [ 18 ] (Assessing the methodological quality of systematic reviews) guidelines (Supplemental Digital Content 1). The protocol had been registered in the PROSPERO international database under number CRD42024504829. Search Strategy Pubmed, Embase, Cochrane, Web of Science and CNKI were searched to identify randomized controlled trials (RCTs) investigating the effectiveness of SGB versus placebo or no SGB for PONV in adult patients after general anesthesia from inception to July 1st, 2024. We used both subject words and free-texted terms to search potentially relevant RCTs as following:(( Topic:postoperative nausea and vomiting) OR (Title/Keywords/Abstract: postoperative nausea and vomiting (fuzzy)) AND ((Topic: stellate ganglion) OR (Title/Keywords/Abstract: stellate ganglion (fuzzy))). We applied no language restrictions. The reference lists of eligible trials were also manually searched to identify additional trials. Inclusion and exclusion criteria Studies meeting the following criteria were included: (1) population: adult patients aged > 18 years who underwent general anesthesia; (2) intervention: SGB before or after general anesthesia; (3) comparison: placebo or no SGB; (4) outcomes: incidence of postoperative nausea and vomiting; (5) study type: only RCTs were included. The exclusion criteria were (1) case reports, reviews, or observational studies; (2) duplicated data; (3) no English abstract; (4) not available in full-text format; and (5) lack of PONV outcomes. Conflicts were resolved by consulting with the corresponding author. Outcomes and definition The primary outcome was the incidence of PONV, which was defined as postoperative nausea and vomiting. The grading was established by WHO [ 19 ] : grade 0 with no nausea and vomiting, grade 1 with nausea but no vomiting, grade 2 with mild vomiting (1–2/day), grade 3 with moderate vomiting (3–5/day), and grade 4 with severe vomiting (> 6/day). Data extraction We extracted the relevant data and summarized the data into standard data tables. The data included the first author’s name, publication year, sample size in each group, gender, age, type of operation, timing of SGB administration, type and dose of SGB administration, outcomes; and intervention details. To ensure the completeness and accuracy of the data, we electronically contacted the corresponding authors to request the necessary data if the data of interest were missing or incomplete in the published materials. Quality evaluation We assessed the risk of bias of the included RCTs using the recent version of Cochrane risk of bias tool (RoB 2) [ 20 ] . The following five domains of potential bias were evaluated for each RCT included in the analysis: (1) biases arising from the randomization process; (2) deviations from intended interventions; (3) missing outcome data; (4) measurement of the outcome and (5) selection of the reported results. The bias risk in each area was determined to be low risk,”some concerns,”or high risk.”The study was considered as high risk if one or more areas were identified as high risk. Two authors independently conducted literature screening, data extraction, and risk of bias assessment. Any disagreement was resolved by discussion between the two authors, and conflicts were resolved by consulting with the corresponding author. Statistical analysis The meta-analysis was conducted using the RevMan software (version 5.4, Cochrane Collaboration, Copenhagen, Denmark) and the STATA software (version 14.0, Stata Corp, College Station, TX, USA). The incidence of PONV was reported by the risk ratio (RR) and 95% confidence intervals (CI). Random-effects model was used for data pooling for clinical heterogeneity [ 21 ] . Heterogeneity was assessed with the I 2 statistic test and was considered to be significant if I 2 > 50% [ 22 ] . Subgroup analyses were conducted for analyzing PONV based on the prophylactic antiemetic drugs (use or not ), surgical method (open or minimally invasive surgery) and postoperative analgesia (use or not). Meta-regression analysis was also conducted for the PONV with the following moderators: prophylactic antiemetic drugs (use or not ), surgical method (open or minimally invasive surgery), postoperative analgesia (use or not), female proportion, age, the timing of SGB (before or after anesthesia), use of opioids and inhalation anesthesia. Publication bias was assessed with the Egger’s linear regression test. Significance was set at P < 0.05. We preformed trial sequential analysis (TSA) to assess the reliability of the primary outcome ( the incidence of PONV) using the TSA viewer software version 0.9.5.5 beta (Copenhagen Trial Unit, Copenhagen, Denmark) [ 23 , 24 ] . We also estimated the required information size (RIS) expected for a stable conclusion. In a TSA diagram, if a Z curve crosses the TSA monitoring boundary or the futility boundary, a sufficient level of evidence have been reached and that further studies are unlikely to change the inference. However, if a Z curve dose not cross the TSA monitoring boundary or the futility boundary and the RIS is not reached, evidence to reach a conclusion is insufficient. The variance was calculated from the data obtained from the included RCTs. To calculate the RIS, monitoring boundary and the futility boundary, we used two-sided tests with a type I error of 5%, a power of 80%, and a relative risk reduction of 20% in the incidence of PONV for the SGB group versus the placebo group. Results Study Characteristics 16 RCTs were included in the final analysis (Fig. 1 ), and a total of 661 patients received SGB while 724 received placebo or no intervention (Table 1). While 3 RCTs [ 25 – 27 ] evaluated the effect of SGB on PONV in patients undergoing thyroid surgery, 6 RCTs [ 28 – 33 ] were in patients undergoing endoscopic surgery. PONV was the primary outcome in 6 RCTs [ 25 – 27 , 29 , 30 , 34 ] . SGB was performed before induction of anesthesia in 13 RCTs [ 25 , 29 – 40 ] , and after induction of anesthesia in 3 RCTs [ 26 – 28 ] . Eight studies [ 28 , 29 , 31 , 33 – 35 , 39 , 40 ] use ropivacaine as local anesthetic, while seven studies [ 25 – 27 , 30 , 32 , 36 , 37 ] selected lidocaine. 9 studies [ 25 – 28 , 30 , 32 , 35 , 38 , 40 ] used prophylactic antiemetic drugs, and 10 studies [ 25 – 30 , 32 , 33 , 35 , 38 ] used opioids or non-steroidal anti-inflammatory drugs for postoperative analgesia. 8 studies [ 25 – 28 , 30 , 34 , 38 , 40 ] had placebo-controlled groups, whereas 10 studies [ 26 , 27 , 29 , 31 , 32 , 35 – 39 ] had no intervention control group [ 23 , 24 , 29 ] . Risk of Bias As shown in Fig. 2 , 7 studies [ 26 , 29 , 32 , 35 – 37 , 39 ] had a high RoB, mostly due to biases in outcome evaluation. Four additional studies [ 28 , 30 , 31 , 38 ] had some concerns due to biases in 2 or fewer domains. All other studies [ 25 , 27 , 33 , 34 , 40 ] were categorized as having low risk”RoB. Primary outcome and TSA The overall risk of PONV was analyzed from 1385 patients. The risk of PONV was 22.2% in patients receiving SGB versus 38.6% in placebo. Meta-analysis revealed that SGB significantly decreased the risk of PONV compared to placebo (RR, 0.59 [95% CI, 0.49–0.70]; P < 0.0001; I 2 = 14%; Fig. 3 ). Sensitivity analysis by removing one study at a time confirmed the robustness of evidence. The result of Egger’s linear regression test confirmed no evidence of publication bias ( P = 0.945). Figure 4 shown the result of the TSA using a 20% RRR threshold. TSA showed that the z curve not only crossed the conventional boundary, but also the TSA boundary despite not reaching the required information sample, indicating that further research not likely to change the conclusion that SGB reduces PONV. Subgroup analyses for primary outcome As mentioned in the methods, we conducted subgroup analyses based on the use of antiemetic drugs, the type of surgery, and postoperative analgesia. A lower risk of PONV was observed in both the prophylactic antiemetic group (RR,0.51; 95% CI,0.39–0.67, I 2 = 21%) and the non-prophylactic antiemetic group (RR,0.65; 95% CI,0.52–0.81, I 2 = 7%;Fig. 5 ), and the group difference was not significant ( P = 0.19). The subgroup analyses showed that a trend of lower risk of PONV were noted in both endoscope group (RR,0.55;95% CI,0.44–0.68; I 2 = 4%) and non-endoscopic group (RR, 0.64;95% CI, 0.48–0.84; I2 = 21%; Fig. 5 ), and the group difference was not significant ( P = 0.40). In addition, a lower risk of PONV was observed in both the postoperative analgesia group (RR,0.57;95% CI,0.45–0.71, I 2 = 21%) and the non-postoperative analgesia group (RR,0.62;95% CI,0.45–0.86, I 2 = 14%;Fig. 5 ), and the group difference was not significant ( P = 0.68). Meta-regression Analysis Sixteen studies of SGB were included for the meta-regression analysis. Meta-regression analyses showed no influence of covariates on the outcome, such as type of surgery, inhalation anesthesia, prophylactic use of antiemetic, postoperative analgesia, proportion of female, sample size and age (Supplemental Digital Content 2). Discussion This meta-analysis included 16 RCTs with 1385 patients to demonstrate the effect of SGB on PONV after general anesthesia. We found that SGB significantly reduced the incidence of PONV. The TSA results revealed that the current evidence is sufficient for the primary outcome. Furthermore, type of surgery, inhalation anesthesia, prophylactic use of antiemetic, postoperative analgesia, proportion of female, sample size and age had no significant influence on the correlation between SGB and PONV risk according to meta-regression analysis. The prevention of PONV after anesthesia is a clinically relevant medical intervention. Many factors result to PONV [ 41 ] , such as the patient’s preoperative condition, surgical procedures and gender. The prevention of PONV has focused primarily on antiPONV drugs. Commonly used drugs for the prevention of PONV include 5-hydroxytryptamine (5-HT) receptor antagonists [ 7 ] , α-2 receptor agonists (dexmedetomidine) [ 5 ] and steroids (dexamethasone) [ 42 ] . However, when drug administered by intravenous route, potential advance effects could not be ignored, which may limit their use in all patients, such as extrapyramidal symptoms, excessive sedation and osteoporosis [ 43 , 44 ] . To decrease advance effects, some clinicians [ 8 – 11 ] choose other interventions on prevention of PONV. In a recent prospective, randomized, double-blind study, Frelich et al [ 45 ] evaluate the effect of Bispectral Index (BIS)-guided anesthesia in reducing PONV. They found a significant lower incidence of PONV with the use of BIS-guided anesthesia compared to the control group [RR, 0.48; 95% CI, 0.27–0.86) in children undergoing adenoidectomy. Our meta-analysis included the comparison of SGB for the prevention of PONV versus placebo, and a clear benefit was present for SGB. However, the exact pathophysiology of PONV is not well understood but is believed to result from complex interactions between the gastrointestinal system, central nervous system, and autonomic nervous system [ 46 ] . and our meta-analysis summarizes the significant effect of SGB in alleviating PONV. We summarize that the prevention of SGB on PONV are related to regulating multiple systems, including the digestive, immune, and endocrine systems. The mechanisms may be as following: Firstly, SGB stimulates the vagus nerve indirectly [ 47 ] , regulating the secretion of gastrointestinal hormones, which restores gastrointestinal motility and reduces PONV. Secondly, SGB activates the neuroendocrine-immune axis [ 48 ] , stimulates neurons in the central extreme posterior area, promotes the secretion of neurotransmitters such as acetylcholine and serotonin, enhances the proliferative capacity of gastric wall cells, and improves the repair and regeneration ability of gastric mucosa tissues. This strengthens the immune protection of the gastrointestinal tract, promotes postoperative gastrointestinal function recovery, and effectively reduces the occurrence of PONV. Thirdly, SGB can regulate the inflammatory process triggered by tissue injury, inhibit the migration of leukocytes to the inflammation site, and reduce the release of inflammatory factors [ 49 ] . This method can reduce the body's inflammatory response and oxidative stress damage, thus protecting the integrity of tissue cells. Fourth, The extensive distribution of stellate ganglion fibers and the blockade of sympathetic nerve excitation conduction in the posterior part of the laryngeal and tracheal mucosa are related to preventing the sympathetic nervous function from effectively acting on corresponding organs and tissues, thereby weakening the peripheral vomiting reflex and potentially reducing PONV. Additionally, SGB may contribute to postoperative analgesia by increasing the release of endogenous endorphins and other morphine-like substances, raising the pain threshold, and reducing the need for postoperative opioid analgesics, thus reducing PONV [ 50 ] . Our study does face some limitations. Primarily, concerning the implementation of SGB, some researches favored ropivacaine as the primary agent, with others opted for lidocaine. Notably, inconsistencies in volume, doses and concentration among these studies. These disparities could potentially affect the effectiveness of SGB and demonstrate that the clinical use of SGB is not strictly regulated. Future dose-response studies may focus on this aspect. Second, the search strategy could have also affected the results of this study since we only included published literature. Conclusion In this meta-analysis, we analyzed the association of SGB on PONV after general anesthesia. We found that SGB has a positive impact on reducing the incidence of PONV after general anesthesia. Further research is necessary to fully understand SGB’s effect on PONV. Declarations Ethics approval and consent to participate : Ethics approval and consent to participate were not applicable because only published research data were included. Consent for publication : All authors provided feedback and approved the final version. Availability of data and materials : The datasets are available from the corresponding author on reasonable request. Competing interests : None Funding : This study was funded by the National Natural Science Foundation of China (82201378 Y.Q), and Outstanding Young Medical and Health Talents of Wuxi (HB2023005 Y.Q). This study was also funded by the National Natural Science Foundation of China (82271251 X.Z), Jiangsu Distinguished Medical Expert Project (X.Z), and Jiangsu Health Innovation Team Project (X.Z). Authors' contributions : Design of the meta-analysis: SM, XZ,YLQ. Statistical analysis: SM, SXT,JJX. Data extraction: SXT,JJX,GDS, SHG,WKC. Drafting: SM, SXT, JJX, XZ, YLQ. 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Supplementary Files Table1.baseline.xlsx SupplementalDigitalContent1.AMSTAR2.pdf Supplemental Digital Content 1.AMSTAR 2 SupplementalDigitalContent2.doc Supplemental Digital Content 2. Multivariable meta-regression analysis for overall incidence of PONV with modelled variables. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5333613","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":373219983,"identity":"88116f22-ff71-4b77-ac15-243062af0b33","order_by":0,"name":"Shuai Miao","email":"","orcid":"","institution":"The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shuai","middleName":"","lastName":"Miao","suffix":""},{"id":373219984,"identity":"447a81f7-c62a-4f39-be24-1d735a255e48","order_by":1,"name":"Shixiao Tang","email":"","orcid":"","institution":"The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shixiao","middleName":"","lastName":"Tang","suffix":""},{"id":373219985,"identity":"e9ed885d-9a71-4080-a8f6-3bad9d48bf23","order_by":2,"name":"Jingjing Xu","email":"","orcid":"","institution":"The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jingjing","middleName":"","lastName":"Xu","suffix":""},{"id":373219986,"identity":"a13334fe-0175-4bfc-83c6-9172eb937b4f","order_by":3,"name":"Guodong Song","email":"","orcid":"","institution":"The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Guodong","middleName":"","lastName":"Song","suffix":""},{"id":373219988,"identity":"68650fb1-062d-4748-8092-c250663a3552","order_by":4,"name":"Shuhan Gu","email":"","orcid":"","institution":"The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shuhan","middleName":"","lastName":"Gu","suffix":""},{"id":373219990,"identity":"f6c8d5f4-5e34-426b-bba1-659defe1611a","order_by":5,"name":"Wankun Chen","email":"","orcid":"","institution":"Zhongshan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wankun","middleName":"","lastName":"Chen","suffix":""},{"id":373219991,"identity":"3ad99091-2e86-4b1e-a920-f32f159b5b51","order_by":6,"name":"Xin Zhang","email":"","orcid":"","institution":"The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Zhang","suffix":""},{"id":373219992,"identity":"edc021cd-b5aa-4a02-ab73-36c5893204b2","order_by":7,"name":"Yiling Qian","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYFAC5oYDHyr+yzEwHADziNHC2HhwxhlmY5K0NB/mbWNObIDaSVgD343EhsM8Z9jStzOeTpNgqLBObGA/ewCvFkmgloNzKnhydzac3SbBcCY9sYEnLwGvFgOglgNvzkjkbjgA1MLYdjixQYLHgLAW3jaDdAOwln9EajnI25aQANHSQIQWyTMPG4CBfMAQ6LDNFgnH0o3beHLwa+E7nnz4w4eKA/IGN85uvPGhxlq2n/0Mfi0MFxKgDIkDDAwgNht+9UBw/gCUwd9AUO0oGAWjYBSMUAAAY4NWcck/UIcAAAAASUVORK5CYII=","orcid":"","institution":"The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University","correspondingAuthor":true,"prefix":"","firstName":"Yiling","middleName":"","lastName":"Qian","suffix":""}],"badges":[],"createdAt":"2024-10-25 16:08:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5333613/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5333613/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":69427980,"identity":"5350fcd1-9cef-4b58-8eb9-f5e7f3226544","added_by":"auto","created_at":"2024-11-20 09:03:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":136144,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flowchart of the included studies.\u003c/p\u003e","description":"","filename":"FIG1.flowchart.png","url":"https://assets-eu.researchsquare.com/files/rs-5333613/v1/c9f7367f347cd43710ab3b06.png"},{"id":69427979,"identity":"46d32bce-fbc3-4a7a-b430-357e99a59b18","added_by":"auto","created_at":"2024-11-20 09:03:50","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":126116,"visible":true,"origin":"","legend":"\u003cp\u003eRisk of bias of the included studies.\u003c/p\u003e","description":"","filename":"FIG2.RISKOFBIAS.png","url":"https://assets-eu.researchsquare.com/files/rs-5333613/v1/ee7e5e34d9951ad0eafed08b.png"},{"id":69429170,"identity":"b5924e63-a948-414f-b7cb-37cd8375decb","added_by":"auto","created_at":"2024-11-20 09:11:50","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":25868,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot for the incidence of PONV with and without SGB.\u003c/p\u003e","description":"","filename":"FIG3.PONV.png","url":"https://assets-eu.researchsquare.com/files/rs-5333613/v1/01e1239f711675eca159b712.png"},{"id":69427983,"identity":"28b3752f-f4d2-4aac-922e-8528ed5e5101","added_by":"auto","created_at":"2024-11-20 09:03:50","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":89825,"visible":true,"origin":"","legend":"\u003cp\u003eTrial Sequential Analysis for the incidence of PONV with and without SGB.\u003c/p\u003e","description":"","filename":"FIG4.TSA.png","url":"https://assets-eu.researchsquare.com/files/rs-5333613/v1/cf6c5cbb3149bc31620cf8fe.png"},{"id":69427984,"identity":"b56d9ba0-ebcd-4cf9-a7a1-8121b30880b2","added_by":"auto","created_at":"2024-11-20 09:03:51","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":784850,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup analysis for the incidence of PONV with and without SGB.\u003c/p\u003e","description":"","filename":"FIG5.subgroup.png","url":"https://assets-eu.researchsquare.com/files/rs-5333613/v1/c58661a1228d40070d590ee1.png"},{"id":87793777,"identity":"94caed2b-cff6-4117-9e36-d8c6a87bbb1a","added_by":"auto","created_at":"2025-07-29 06:32:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1732748,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5333613/v1/8f2f1253-a8b5-4959-92ee-18e76cef036a.pdf"},{"id":69427977,"identity":"3754ba9b-361f-4671-9e16-28bd92c6e239","added_by":"auto","created_at":"2024-11-20 09:03:50","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":12382,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.baseline.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5333613/v1/071c243913e872b6867f7272.xlsx"},{"id":69427982,"identity":"de0caad8-8646-48a5-8b1b-ec8d2c28aff0","added_by":"auto","created_at":"2024-11-20 09:03:50","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":367644,"visible":true,"origin":"","legend":"\u003cp\u003eSupplemental Digital Content 1.AMSTAR 2\u003c/p\u003e","description":"","filename":"SupplementalDigitalContent1.AMSTAR2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5333613/v1/5f0c118f5d4c97f67270846b.pdf"},{"id":69427981,"identity":"c9d2e8c2-df82-478e-96ac-0dbfe229a339","added_by":"auto","created_at":"2024-11-20 09:03:50","extension":"doc","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":18432,"visible":true,"origin":"","legend":"\u003cp\u003eSupplemental Digital Content 2. Multivariable meta-regression analysis for overall incidence of PONV with modelled variables.\u003c/p\u003e","description":"","filename":"SupplementalDigitalContent2.doc","url":"https://assets-eu.researchsquare.com/files/rs-5333613/v1/ac139841178473257bcabc25.doc"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of stellate ganglion block on postoperative nausea and vomiting after general anesthesia: A meta-analysis, meta-regression and trial sequential analysis of randomized controlled trials","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAppropriate postoperative nausea and vomiting (PONV) management is an important part of enhanced recovery after surgery\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. However, the cause of PONV is multifactorial\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e and definite PONV control methods have not yet been established. The incidence of PONV can be up to 80% in some high risk patients\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e resulting in aspiration pneumonia and postoperative wound dehiscence\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Multiple drugs have been proved efficiency to reduce PONV, such as dexmedetomidine\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e, dexamethasone\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e and ondansetron\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. In addition, several studies used regional anesthetic technique to prevent PONV\u003csup\u003e[\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Study by Ma\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e found that intermittent thoracic paravertebral block with intravenous analgesia could reduce PONV after video-assisted thoracic surgery as well as study by Hung\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e determined that erector spinae plane block could reduce PONV after liver surgery.\u003c/p\u003e \u003cp\u003eHowever, there are some limitations related to the type of surgery in which regional blocks conducted. Therefore, some investigators tried to determine other methods to manage PONV, among of which is stellate ganglion block (SGB). SGB, formed by the inferior cervical sympathetic ganglia (C7-C8) and the superior thoracic sympathetic ganglia (T1)\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e has been used since the mid-1930s in a variety of medical conditions, such as the sympathetically maintained pain of the face and upper extremity\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. In recent years, SGB was reported to regulates gastrointestinal function by regulating the autonomic and immune systems\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. However, the contribution of SGB in reducing PONV is unclear. This meta-analysis aimed to identify the benefits of SGB, focusing on its PONV-reducing effect in patients after general anesthesia.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eThe current meta-analysis was performed in accordance with the Preferred Items for Systematic Reviews and Meta-analysis statement guidelines\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e and AMSTAR\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e (Assessing the methodological quality of systematic reviews) guidelines (Supplemental Digital Content 1). The protocol had been registered in the PROSPERO international database under number CRD42024504829.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSearch Strategy\u003c/h2\u003e \u003cp\u003ePubmed, Embase, Cochrane, Web of Science and CNKI were searched to identify randomized controlled trials (RCTs) investigating the effectiveness of SGB versus placebo or no SGB for PONV in adult patients after general anesthesia from inception to July 1st, 2024. We used both subject words and free-texted terms to search potentially relevant RCTs as following:(( Topic:postoperative nausea and vomiting) OR (Title/Keywords/Abstract: postoperative nausea and vomiting (fuzzy)) AND ((Topic: stellate ganglion) OR (Title/Keywords/Abstract: stellate ganglion (fuzzy))). We applied no language restrictions. The reference lists of eligible trials were also manually searched to identify additional trials.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInclusion and exclusion criteria\u003c/h3\u003e\n\u003cp\u003eStudies meeting the following criteria were included: (1) population: adult patients aged\u0026thinsp;\u0026gt;\u0026thinsp;18 years who underwent general anesthesia; (2) intervention: SGB before or after general anesthesia; (3) comparison: placebo or no SGB; (4) outcomes: incidence of postoperative nausea and vomiting; (5) study type: only RCTs were included. The exclusion criteria were (1) case reports, reviews, or observational studies; (2) duplicated data; (3) no English abstract; (4) not available in full-text format; and (5) lack of PONV outcomes. Conflicts were resolved by consulting with the corresponding author.\u003c/p\u003e\n\u003ch3\u003eOutcomes and definition\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was the incidence of PONV, which was defined as postoperative nausea and vomiting. The grading was established by WHO\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e: grade 0 with no nausea and vomiting, grade 1 with nausea but no vomiting, grade 2 with mild vomiting (1\u0026ndash;2/day), grade 3 with moderate vomiting (3\u0026ndash;5/day), and grade 4 with severe vomiting (\u0026gt;\u0026thinsp;6/day).\u003c/p\u003e\n\u003ch3\u003eData extraction\u003c/h3\u003e\n\u003cp\u003eWe extracted the relevant data and summarized the data into standard data tables. The data included the first author\u0026#146;s name, publication year, sample size in each group, gender, age, type of operation, timing of SGB administration, type and dose of SGB administration, outcomes; and intervention details. To ensure the completeness and accuracy of the data, we electronically contacted the corresponding authors to request the necessary data if the data of interest were missing or incomplete in the published materials.\u003c/p\u003e\n\u003ch3\u003eQuality evaluation\u003c/h3\u003e\n\u003cp\u003eWe assessed the risk of bias of the included RCTs using the recent version of Cochrane risk of bias tool (RoB 2)\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. The following five domains of potential bias were evaluated for each RCT included in the analysis: (1) biases arising from the randomization process; (2) deviations from intended interventions; (3) missing outcome data; (4) measurement of the outcome and (5) selection of the reported results. The bias risk in each area was determined to be low risk,\u0026#148;some concerns,\u0026#148;or high risk.\u0026#148;The study was considered as high risk if one or more areas were identified as high risk. Two authors independently conducted literature screening, data extraction, and risk of bias assessment. Any disagreement was resolved by discussion between the two authors, and conflicts were resolved by consulting with the corresponding author.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe meta-analysis was conducted using the RevMan software (version 5.4, Cochrane Collaboration, Copenhagen, Denmark) and the STATA software (version 14.0, Stata Corp, College Station, TX, USA). The incidence of PONV was reported by the risk ratio (RR) and 95% confidence intervals (CI). Random-effects model was used for data pooling for clinical heterogeneity\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. Heterogeneity was assessed with the \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e statistic test and was considered to be significant if \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026gt;\u0026thinsp;50%\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Subgroup analyses were conducted for analyzing PONV based on the prophylactic antiemetic drugs (use or not ), surgical method (open or minimally invasive surgery) and postoperative analgesia (use or not). Meta-regression analysis was also conducted for the PONV with the following moderators: prophylactic antiemetic drugs (use or not ), surgical method (open or minimally invasive surgery), postoperative analgesia (use or not), female proportion, age, the timing of SGB (before or after anesthesia), use of opioids and inhalation anesthesia. Publication bias was assessed with the Egger\u0026rsquo;s linear regression test. Significance was set at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. We preformed trial sequential analysis (TSA) to assess the reliability of the primary outcome ( the incidence of PONV) using the TSA viewer software version 0.9.5.5 beta (Copenhagen Trial Unit, Copenhagen, Denmark)\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. We also estimated the required information size (RIS) expected for a stable conclusion. In a TSA diagram, if a Z curve crosses the TSA monitoring boundary or the futility boundary, a sufficient level of evidence have been reached and that further studies are unlikely to change the inference. However, if a Z curve dose not cross the TSA monitoring boundary or the futility boundary and the RIS is not reached, evidence to reach a conclusion is insufficient. The variance was calculated from the data obtained from the included RCTs. To calculate the RIS, monitoring boundary and the futility boundary, we used two-sided tests with a type I error of 5%, a power of 80%, and a relative risk reduction of 20% in the incidence of PONV for the SGB group versus the placebo group.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStudy Characteristics\u003c/h2\u003e \u003cp\u003e16 RCTs were included in the final analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), and a total of 661 patients received SGB while 724 received placebo or no intervention (Table\u0026nbsp;1). While 3 RCTs\u003csup\u003e[\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e evaluated the effect of SGB on PONV in patients undergoing thyroid surgery, 6 RCTs\u003csup\u003e[\u003cspan additionalcitationids=\"CR29 CR30 CR31 CR32\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e were in patients undergoing endoscopic surgery. PONV was the primary outcome in 6 RCTs\u003csup\u003e[\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e. SGB was performed before induction of anesthesia in 13 RCTs\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan additionalcitationids=\"CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37 CR38 CR39\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/sup\u003e, and after induction of anesthesia in 3 RCTs\u003csup\u003e[\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. Eight studies\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/sup\u003e use ropivacaine as local anesthetic, while seven studies\u003csup\u003e[\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/sup\u003e selected lidocaine. 9 studies\u003csup\u003e[\u003cspan additionalcitationids=\"CR26 CR27\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/sup\u003e used prophylactic antiemetic drugs, and 10 studies\u003csup\u003e[\u003cspan additionalcitationids=\"CR26 CR27 CR28 CR29\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/sup\u003e used opioids or non-steroidal anti-inflammatory drugs for postoperative analgesia. 8 studies\u003csup\u003e[\u003cspan additionalcitationids=\"CR26 CR27\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/sup\u003e had placebo-controlled groups, whereas 10 studies\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan additionalcitationids=\"CR36 CR37 CR38\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/sup\u003e had no intervention control group\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eRisk of Bias\u003c/h2\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, 7 studies\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/sup\u003e had a high RoB, mostly due to biases in outcome evaluation. Four additional studies\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/sup\u003e had some concerns due to biases in 2 or fewer domains. All other studies\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/sup\u003e were categorized as having low risk\u0026#148;RoB.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePrimary outcome and TSA\u003c/h2\u003e \u003cp\u003eThe overall risk of PONV was analyzed from 1385 patients. The risk of PONV was 22.2% in patients receiving SGB versus 38.6% in placebo. Meta-analysis revealed that SGB significantly decreased the risk of PONV compared to placebo (RR, 0.59 [95% CI, 0.49\u0026ndash;0.70]; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;14%; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Sensitivity analysis by removing one study at a time confirmed the robustness of evidence. The result of Egger\u0026rsquo;s linear regression test confirmed no evidence of publication bias (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.945).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e shown the result of the TSA using a 20% RRR threshold. TSA showed that the z curve not only crossed the conventional boundary, but also the TSA boundary despite not reaching the required information sample, indicating that further research not likely to change the conclusion that SGB reduces PONV.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup analyses for primary outcome\u003c/h2\u003e \u003cp\u003eAs mentioned in the methods, we conducted subgroup analyses based on the use of antiemetic drugs, the type of surgery, and postoperative analgesia. A lower risk of PONV was observed in both the prophylactic antiemetic group (RR,0.51; 95% CI,0.39\u0026ndash;0.67, \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;21%) and the non-prophylactic antiemetic group (RR,0.65; 95% CI,0.52\u0026ndash;0.81, \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;7%;Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e), and the group difference was not significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.19).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe subgroup analyses showed that a trend of lower risk of PONV were noted in both endoscope group (RR,0.55;95% CI,0.44\u0026ndash;0.68; \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;4%) and non-endoscopic group (RR, 0.64;95% CI, 0.48\u0026ndash;0.84; I2\u0026thinsp;=\u0026thinsp;21%; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e), and the group difference was not significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.40). In addition, a lower risk of PONV was observed in both the postoperative analgesia group (RR,0.57;95% CI,0.45\u0026ndash;0.71, \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;21%) and the non-postoperative analgesia group (RR,0.62;95% CI,0.45\u0026ndash;0.86, \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;14%;Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e), and the group difference was not significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.68).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eMeta-regression Analysis\u003c/h2\u003e \u003cp\u003eSixteen studies of SGB were included for the meta-regression analysis. Meta-regression analyses showed no influence of covariates on the outcome, such as type of surgery, inhalation anesthesia, prophylactic use of antiemetic, postoperative analgesia, proportion of female, sample size and age (Supplemental Digital Content 2).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis meta-analysis included 16 RCTs with 1385 patients to demonstrate the effect of SGB on PONV after general anesthesia. We found that SGB significantly reduced the incidence of PONV. The TSA results revealed that the current evidence is sufficient for the primary outcome. Furthermore, type of surgery, inhalation anesthesia, prophylactic use of antiemetic, postoperative analgesia, proportion of female, sample size and age had no significant influence on the correlation between SGB and PONV risk according to meta-regression analysis.\u003c/p\u003e \u003cp\u003eThe prevention of PONV after anesthesia is a clinically relevant medical intervention. Many factors result to PONV\u003csup\u003e[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/sup\u003e, such as the patient\u0026#146;s preoperative condition, surgical procedures and gender. The prevention of PONV has focused primarily on antiPONV drugs. Commonly used drugs for the prevention of PONV include 5-hydroxytryptamine (5-HT) receptor antagonists\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e, α-2 receptor agonists (dexmedetomidine)\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e and steroids (dexamethasone)\u003csup\u003e[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/sup\u003e. However, when drug administered by intravenous route, potential advance effects could not be ignored, which may limit their use in all patients, such as extrapyramidal symptoms, excessive sedation and osteoporosis\u003csup\u003e[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/sup\u003e. To decrease advance effects, some clinicians\u003csup\u003e[\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e choose other interventions on prevention of PONV. In a recent prospective, randomized, double-blind study, Frelich et al\u003csup\u003e[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]\u003c/sup\u003e evaluate the effect of Bispectral Index (BIS)-guided anesthesia in reducing PONV. They found a significant lower incidence of PONV with the use of BIS-guided anesthesia compared to the control group [RR, 0.48; 95% CI, 0.27\u0026ndash;0.86) in children undergoing adenoidectomy. Our meta-analysis included the comparison of SGB for the prevention of PONV versus placebo, and a clear benefit was present for SGB. However, the exact pathophysiology of PONV is not well understood but is believed to result from complex interactions between the gastrointestinal system, central nervous system, and autonomic nervous system\u003csup\u003e[\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]\u003c/sup\u003e. and our meta-analysis summarizes the significant effect of SGB in alleviating PONV.\u003c/p\u003e \u003cp\u003eWe summarize that the prevention of SGB on PONV are related to regulating multiple systems, including the digestive, immune, and endocrine systems. The mechanisms may be as following: Firstly, SGB stimulates the vagus nerve indirectly\u003csup\u003e[\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]\u003c/sup\u003e, regulating the secretion of gastrointestinal hormones, which restores gastrointestinal motility and reduces PONV. Secondly, SGB activates the neuroendocrine-immune axis\u003csup\u003e[\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]\u003c/sup\u003e, stimulates neurons in the central extreme posterior area, promotes the secretion of neurotransmitters such as acetylcholine and serotonin, enhances the proliferative capacity of gastric wall cells, and improves the repair and regeneration ability of gastric mucosa tissues. This strengthens the immune protection of the gastrointestinal tract, promotes postoperative gastrointestinal function recovery, and effectively reduces the occurrence of PONV. Thirdly, SGB can regulate the inflammatory process triggered by tissue injury, inhibit the migration of leukocytes to the inflammation site, and reduce the release of inflammatory factors\u003csup\u003e[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]\u003c/sup\u003e. This method can reduce the body's inflammatory response and oxidative stress damage, thus protecting the integrity of tissue cells. Fourth, The extensive distribution of stellate ganglion fibers and the blockade of sympathetic nerve excitation conduction in the posterior part of the laryngeal and tracheal mucosa are related to preventing the sympathetic nervous function from effectively acting on corresponding organs and tissues, thereby weakening the peripheral vomiting reflex and potentially reducing PONV. Additionally, SGB may contribute to postoperative analgesia by increasing the release of endogenous endorphins and other morphine-like substances, raising the pain threshold, and reducing the need for postoperative opioid analgesics, thus reducing PONV\u003csup\u003e[\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur study does face some limitations. Primarily, concerning the implementation of SGB, some researches favored ropivacaine as the primary agent, with others opted for lidocaine. Notably, inconsistencies in volume, doses and concentration among these studies. These disparities could potentially affect the effectiveness of SGB and demonstrate that the clinical use of SGB is not strictly regulated. Future dose-response studies may focus on this aspect. Second, the search strategy could have also affected the results of this study since we only included published literature.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this meta-analysis, we analyzed the association of SGB on PONV after general anesthesia. We found that SGB has a positive impact on reducing the incidence of PONV after general anesthesia. Further research is necessary to fully understand SGB\u0026#146;s effect on PONV.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eEthics approval and consent to participate were not applicable because only published research data were included.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eAll authors provided feedback and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003eThe datasets are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eThis study was funded by the National Natural Science Foundation of China (82201378 Y.Q), and Outstanding Young Medical and Health Talents of Wuxi (HB2023005 Y.Q). This study was also funded by the National Natural Science Foundation of China (82271251 X.Z), Jiangsu Distinguished Medical Expert Project (X.Z), and Jiangsu Health Innovation Team Project (X.Z).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e Design of the meta-analysis: SM, XZ,YLQ. Statistical analysis: SM, SXT,JJX. Data extraction: SXT,JJX,GDS, SHG,WKC. Drafting: SM, SXT, JJX, XZ, YLQ.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eNone\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLiu YZ, Luhrs A, Tindal E, et al. Initial experience with enhanced recovery after surgery (ERAS) and early discharge protocols after robotic extended totally extraperitoneal (eTEP) hernia surgery. 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Ultrasound-guided stellate ganglion block benefits the postoperative recovery of patients undergoing laparoscopic colorectal surgery: a single-center, double-blinded, randomized controlled clinical trial. BMC Anesthesiol. 2024;24(1):137.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"stellate ganglion block, postoperative nausea and vomiting, trial sequential analysis, meta-regression","lastPublishedDoi":"10.21203/rs.3.rs-5333613/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5333613/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eStellate ganglion block (SGB) accelerates the return of gastrointestinal transit and improves gastrointestinal function after surgery. However, it is unclear whether such benefits translate into less postoperative nausea and vomiting (PONV). The aim of this meta-analysis was to identify the effect of SGB on the incidence of PONV after general anesthesia.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe systematically searched electronic databases for published randomized controlled trials (RCTs) comparing SGB with placebo or no SGB for reducing PONV after general anesthesia. The primary outcome was the incidence of PONV after general anesthesia. The effect size was estimated by calculating the risk ratio (RR), with 95% confidence interval (CI). Trial sequential analysis (TSA) was also carried out to calculate the required information size.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e16 RCTs including 1385 patients were included in the study. SGB significantly reduced the incidence of PONV (RR, 0.59, 95% CI, 0.49\u0026ndash;0.70, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). In addition, TSA indicated that the Z curve for SGB not only crossed the conventional boundary, but also the TSA boundary for benefit. Meta-regression analyses found no significant impact of age, female proportion, type of surgery, type of anesthesia, sample size and prophylactic administration of antiemetic on the correlation between SGB and the risk of PONV.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis meta-analysis suggested an association of SGB with a decreased incidence of PONV after general anesthesia. TSA suggested that further studies are unlikely to alter the conclusions regarding the incidence of PONV.\u003c/p\u003e","manuscriptTitle":"Effect of stellate ganglion block on postoperative nausea and vomiting after general anesthesia: A meta-analysis, meta-regression and trial sequential analysis of randomized controlled trials","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-20 09:03:45","doi":"10.21203/rs.3.rs-5333613/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4d96c0e7-10d8-45f8-b602-99ebe0677b86","owner":[],"postedDate":"November 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-29T06:24:13+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-20 09:03:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5333613","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5333613","identity":"rs-5333613","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}