Effect of stellate ganglion block on postoperative nausea and vomiting after general anesthesia: A meta-analysis

Abstract

Objective

To identify the effect of stellate ganglion block on the incidence of postoperative nausea and vomiting.

Methods

We systematically searched electronic databases for published randomized controlled trials comparing stellate ganglion block with placebo for reducing postoperative nausea and vomiting. The primary outcome was the incidence of postoperative nausea and vomiting after general anesthesia. Meta-regression analysis was performed to investigate potential sources of heterogeneity. Trial sequential analysis was also carried out to calculate the required information size.

Results

In total, 16 randomized controlled trials including 1385 patients were included in the study. Stellate ganglion block significantly reduced the incidence of postoperative nausea and vomiting (relative risk, 0.59; 95% confidence interval, 0.49–0.70; P < 0.0001). Our meta-regression analysis confirmed that the significant correlation between stellate ganglion block and reduced postoperative nausea and vomiting risk remained robust and was not significantly influenced by study-level characteristics, including prophylactic antiemetic use, surgical technique, postoperative analgesia, female proportion, age, opioid administration, and inhalation anesthesia. In addition, trial sequential analysis indicated that the Z curve for stellate ganglion block not only crossed the conventional boundary but also the trial sequential analysis boundary for benefit.

Conclusion

This meta-analysis suggested an association of stellate ganglion block with a decreased incidence of postoperative nausea and vomiting after general anesthesia. Trial sequential analysis showed that further studies are unlikely to alter the conclusions regarding the incidence of postoperative nausea and vomiting.

PROSPERO registration number: CRD42024504829.

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 proven efficient in reducing PONV, such as dexmedetomidine, ⁵ dexamethasone, ⁶ and ondansetron. ⁷ In addition, several studies used regional anesthetic technique to prevent PONV.^8–11 A study by Ma et al. ⁹ found that intermittent thoracic paravertebral block with intravenous analgesia could reduce PONV after video-assisted thoracic surgery. In addition, a study by Hung et al. 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 are used. Therefore, some investigators tried to determine other methods to manage PONV, including 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 regulate gastrointestinal function by regulating the autonomic and immune systems.^15,16 However, the contribution of SGB in reducing PONV has bene 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 Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines ¹⁷ and the Assessing the Methodological Quality of Systematic Reviews guidelines ¹⁸ (Supplemental Digital Content 1). The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database under number CRD42024504829.

Search strategy

The PubMed, Embase, Cochrane, Web of Science, and China National Knowledge Infrastructure databases were searched to identify randomized controlled trials (RCTs) that had investigated the effectiveness of SGB versus placebo or no SGB for treating PONV in adult patients after general anesthesia from inception to 1 July 2024. We used both subject words and free-texted terms to search potentially relevant RCTs as follows: ((Topic: PONV) 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: (a) population—adult patients aged >18 years who were administered general anesthesia; (b) intervention—SGB administration before or after general anesthesia; (c) comparison—SGB vs. placebo or no SGB; (d) outcomes—incidence of PONV; and (e) study type—RCTs. The exclusion criteria were (a) case reports, reviews, or observational studies; (b) duplicated data; (c) absence of an English abstract; (d) unavailable in full-text format; and (e) lack of PONV outcomes. Conflicts were resolved by consulting with the corresponding author.

Outcomes and definition

The primary outcome was the incidence of PONV. The following grading established by the World Health Organization ¹⁹ was used: grade 0, no nausea and vomiting; grade 1, nausea but no vomiting; grade 2, mild vomiting (1–2/day); grade 3, moderate vomiting (3–5/day); and grade 4, severe vomiting (>6/day).

Data extraction

We extracted the relevant data and summarized it 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 in cases in which the data of interest were missing or incomplete in the published materials.

Risk of bias and certainty of evidence

We assessed the risk of bias (RoB) of the included RCTs using the recent version of Cochrane RoB tool (RoB 2). ²⁰ The following five domains of potential bias were evaluated for each RCT included in the analysis: (a) biases arising from the randomization process, (b) deviations from intended interventions, (c) missing outcome data, (d) measurement of the outcome, and (e) 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. The certainty of evidence for the primary outcome was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. The strength of evidence was categorized into one of the following four levels of certainty: high, moderate, low, or very low quality. ²¹ Two authors independently conducted literature screening, data extraction, and RoB assessment. Any disagreement was resolved via 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, Texas, USA). The incidence of PONV was reported using the risk ratio (RR) and 95% confidence interval (CI). Random-effects model was used for data pooling for clinical heterogeneity. ²² Heterogeneity was assessed with the I² statistic test and was considered significant at I² > 50%. ²³

Subgroup analyses were performed for analyzing the incidence of PONV across different patient subgroups, including those with and without prophylactic antiemetic drug use, those who underwent open versus minimally invasive surgery, and those who did and did not receive postoperative analgesia. In addition, we conducted meta-regression analysis to explore the potential factors of heterogeneity. According to clinical relevance and methodological considerations, the following factors that may modify the effect of SGB on PONV were considered in the heterogeneity exploration: prophylactic antiemetic drugs use, surgical method (open or minimally invasive surgery), postoperative analgesia use, proportion of female patients, patient age, opioid use, and inhalation anesthesia use. Publication bias was assessed using 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).^24,25 We also estimated the required information size (RIS) needed 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 has been reached and 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 using the data obtained from the included RCTs. To calculate the RIS, monitoring boundary, and futility boundary, we used two-sided tests with a type I error of 5%, power of 80%, and an assumed relative risk reduction of 20% in the PONV incidence for the SGB group versus the placebo group.

Results

Study characteristics

In total, 16 RCTs were included in the final analysis (Figure 1); 661 patients received SGB, while 724 received placebo or no intervention (Table 1). While 3 RCTs^26–28 evaluated the effect of SGB on PONV in patients undergoing thyroid surgery, 6 RCTs^29–34 included patients undergoing endoscopic surgery. PONV was the primary outcome in 6 RCTs.^{26–28,30,31,35} SGB was performed before induction of anesthesia in 13 RCTs^26,30–41 and after induction of anesthesia in 3 RCTs.^27–29 Eight studies^{29,30,32,34–36,40,41} used ropivacaine as the local anesthetic, while six studies^{26–28,31,33,38} selected lidocaine. Eight studies^{26–29,33,36,39,41} used prophylactic antiemetic drugs in both groups, and 11 studies^{28–36,38,41} used opioids or non-steroidal anti-inflammatory drugs for postoperative analgesia.

Figure 1.

PRISMA flowchart of the included studies. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Table 1.

Characteristics of the studies included in the meta-analysis.

Author	Year	Country	Sample		Type of surgery	Sex		Age, y (mean)	SGB details	Timing of administration	PONV prophylaxis
			SGB	Control		Male	Female
Hongjin Zhang	2016	China	40	40	Abdominal operation	23	57	60.7	1% lidocaine 8 mL	Before induction	No
Zhehao Jin	2017	China	30	58	Thyroid Surgery	10	78	47.3	0.5% lidocaine 5 mL	After induction	Granisetron 0.3 mg/kg
Xiaomin Wu	2018	China	35	70	Thyroid Surgery	0	70	39.5	0.5% lidocaine 5 mL	After induction	Ondansetron 4 mg
Caineng Wu	2019	China	43	44	Thoracoscopic surgery	51	36	60.5	0.5% ropivacaine 5 mL	Before induction	No
Jingjing Huang	2020	China	30	30	Supratentorial tumor resection	29	31	53.5	0.25% ropivacaine 4 mL	Before induction	No
Jie Wu	2021	China	40	40	Microvascular decompression	33	47	70.5	0.2% ropivacaine 7 mL	Before induction	No
Jiajia Xu	2022	China	58	58	Thoracolaparoscopic radical resection of esophageal carcinoma	80	36	55.6	0.5% ropivacaine 5 mL	Before induction	No
Meijuan Qian	2022	China	43	43	Shoulder arthroscopy	39	47	52.3	0.25% ropivacaine + 1% lidocaine 6 mL	Before induction	Granisetron 3 mg
Yiqun Mao	2022	China	58	58	Thyroid Surgery	29	87	46.0	1% lidocaine 5 mL	Before induction	Tropisetron 5 mg
Huiling Cao	2023	China	32	30	Radical resection of liver cancer	31	31	70.1	0.5% ropivacaine 7 mL	Before induction	Tropisetron 10 mg
Xiaoyan Ge	2023	China	49	49	Laparoscopic total hysterectomy	0	98	50.2	0.2% ropivacaine 5 mL	Before induction	No
Xiaoci Huang	2023	China	60	60	Laparoscopic cholecystectomy	59	61	45.1	1% lidocaine 6 mL	Before induction	No
Ying Qiu	2023	China	25	25	Arthroscopic acromioplasty	34	16	56.6	0.2% ropivacaine 5 mL	Before induction	Ondansetron 8 mg
Ting Yu	2023	China	26	25	Laparoscopic total hysterectomy	0	51	51.9	1% lidocaine 6 mL	Before induction	Metoclopramide 20 mg
Changjian Yang	2023	China	41	41	Carotid endarterectomy	39	43	61.7	0.25% ropivacaine +1% lidocaine 4 mL	Before induction	No
Han Li	2024	China	51	53	Laparoscopic cholecystectomy	32	72	45.8	0.2% ropivacaine 4 mL	After induction	Granisetron 9 mg

PONV: postoperative nausea and vomiting; SGB: stellate ganglion block.

RoB and certainty of evidence

As shown in Figure 2, 7 studies^{27,30,33,36–38,40} had a high RoB, mostly due to biases in outcome evaluation. Four additional studies^29,31,32,39 involved some concerns due to biases in two or fewer domains. All other studies^{26,28,34,35,41} were categorized as having a low RoB. Given the RoB, the quality of evidence for the primary outcome was clarified as moderate, and it retains importance in the pooled estimate (Supplemental Digital Content 2).

Figure 2.

Risk of bias in the included studies.

Primary outcome and TSA

The overall risk of PONV was analyzed from the data of 1385 patients. The risk of PONV was 22.2% in patients receiving SGB versus 38.6% in those receiving placebo. Meta-analysis revealed that SGB significantly decreased the risk of PONV compared with placebo (RR, 0.59 (95% CI, 0.49–0.70); P < 0.0001; I² = 14%; Figure 3). Sensitivity analysis was performed by removing one study at a time and confirmed the robustness of the evidence. The result of Egger’s linear regression test confirmed no evidence of publication bias (P = 0.945).

Figure 3.

Forest plot for the incidence of PONV with and without SGB. PONV: postoperative nausea and vomiting; SGB: stellate ganglion block.

Figure 4 shows the result of the TSA using a 20% RR reduction 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 may not negate the conclusion that SGB reduces PONV.

Figure 4.

Trial sequential analysis for the incidence of PONV with and without SGB. PONV: postoperative nausea and vomiting; SGB: stellate ganglion block.

Subgroup analyses for primary outcome

As mentioned in the Materials and methods section, we conducted subgroup analyses to compare the pooled effect sizes for PONV based on the use of prophylactic antiemetic drugs, surgical method (open or minimally invasive surgery), and use of postoperative analgesia.

A lower risk of PONV was observed in the prophylactic antiemetic group (RR, 0.57; 95% CI, 0.44–0.74, I² = 7%) and the non-prophylactic antiemetic group (RR, 0.60; 95% CI, 0.46–0.79, I² = 30%; Figure 5), and the inter-group difference was not significant (P = 0.76).

Figure 5.

Subgroup analysis for the incidence of PONV with and without SGB. PONV: postoperative nausea and vomiting; SGB: stellate ganglion block.

The subgroup analyses showed that a trend of lower risk of PONV was noted in the endoscope group (RR, 0.55; 95% CI, 0.44–0.68; I² = 4%) and the non-endoscopic group (RR, 0.64; 95% CI, 0.48–0.84; I² = 21%; Figure 5), and the inter-group difference was not significant (P = 0.40). In addition, a lower risk of PONV was observed in the postoperative analgesia group (RR, 0.57; 95% CI, 0.45–0.71, I² = 21%) and the non-postoperative analgesia group (RR, 0.62; 95% CI, 0.45–0.86, I² = 14%；Figure 5), and the group difference was not significant (P = 0.68).

Meta-regression analysis

Sixteen studies were included in the meta-regression analyses assessing the effectiveness of SGB versus placebo in PONV prevention. Meta-regression analyses showed that prophylactic antiemetic drugs use, surgical method (open or minimally invasive surgery), postoperative analgesia use, proportion of female participants, patient age, opioid use, and inhalation anesthesia use were not specific factors affecting the combined results (Supplemental Digital Content 3), indicating that the impact of SGB on reducing PONV was not related to these factors.

Discussion

This meta-analysis included 16 RCTs with 1385 patients that assessed 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 to confirm the effect of SGB on the primary outcome (PONV incidence). Furthermore, type of surgery, inhalation anesthesia, prophylactic use of antiemetic, postoperative analgesia use, proportion of female participants, sample size, and patient age did not have a significant influence on the correlation between SGB and PONV risk according to meta-regression analysis.

The prevention of PONV after anesthesia is a clinically important medical intervention. Many factors influence the incidence of PONV, ⁴² such as the patient’s preoperative condition, surgical procedures, and gender. The prevention of PONV has focused primarily on anti-PONV drugs. Commonly used drugs for the prevention of PONV include 5-hydroxytryptamine receptor antagonists, ⁷ α-2 receptor agonists (dexmedetomidine), ⁵ and steroids (dexamethasone). ⁴³ However, when drugs are administered via the intravenous route, adverse effects such as extrapyramidal symptoms, excessive sedation, and osteoporosis can occur, and these may limit their use in all patients.^44,45 To reduce the incidence of adverse effects, some clinicians^8–11,46 choose other interventions for PONV prevention. In a recent prospective, randomized, double-blind study, Frelich et al. ⁴⁷ evaluated the effect of bispectral index (BIS)–guided anesthesia in reducing PONV. In pediatric patients undergoing adenoidectomy, those who were administered BIS-guided anesthesia showed a significantly lower incidence of PONV compared with controls (RR, 0.48; 95% CI, 0.27–0.86). Our meta-analysis compared the effectiveness of SGB with that of placebo for PONV prevention, and a clear benefit was observed in favor of SGB. The exact pathophysiology of PONV is not well understood; however, it is believed to result from complex interactions between the gastrointestinal, central nervous, and autonomic nervous systems. ⁴⁸ Moreover, our meta-analysis summarizes the significant effect of SGB in alleviating PONV.

We found that the preventive effect of SGB on PONV is related to the regulation of multiple systems, including the digestive, immune, and endocrine systems. The mechanisms may be as follows. First, SGB stimulates the vagus nerve indirectly, ⁴⁹ regulating the secretion of gastrointestinal hormones; this is followed by the restoration of gastrointestinal motility and reduced PONV. Second, SGB activates the neuroendocrine-immune axis, ⁵⁰ 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 enhances immune protection of the gastrointestinal tract, promotes postoperative gastrointestinal function recovery, and effectively reduces the occurrence of PONV. Third, 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. ⁵¹ 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 the prevention of effective action of sympathetic nervous function on the corresponding organs and tissues, which weakens the peripheral vomiting reflex and potentially reduces 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. ⁵²

Clinical implications

Our findings suggest that SGB may serve as a promising option for the following two key populations: (a) patients with intractable PONV unresponsive to conventional antiemetics ⁵³ and (b) those with a history of severe PONV for whom standard prophylaxis is inadequate. Future studies should focus on validating the efficacy of SGB in these high-risk groups.

Our study has certain limitations. Primarily, concerning the implementation of SGB, some researches favored ropivacaine as the primary agent, while others opted for lidocaine. Notably, there were inconsistencies in the drug volume, dose, and concentration in 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. All included trials were conducted in China, which may limit the extrapolation of our findings to other populations and healthcare systems. Future multinational studies would prove valuable in confirming these results across diverse clinical settings. Third, while our meta-analysis demonstrated the efficacy of SGB in reducing PONV, its safety profile warrants careful consideration. In addition, the included studies provided insufficient data on adverse reactions to SGB; thus, our analysis could not quantitatively assess safety outcomes. This gap highlights the need for future trials to prioritize safety monitoring.

Conclusion

In this meta-analysis, we analyzed the effect of SGB on PONV after general anesthesia. We found that SGB reduces the incidence of PONV after general anesthesia. Further research is necessary to fully understand the effect of SGB on PONV.

Authors’ contributions

Design of the meta-analysis: S.M., X.Z., and Y.L.Q. Statistical analysis: S.M., S.X.T., and J.J.X. Data extraction: S.X.T., J.J.X., G.D.S., S.H.G., and W.K.C. Drafting: S.M., S.X.T., J.J.X., X.Z., and Y.L.Q.

Availability of data and materials

The datasets are available from the corresponding author on reasonable request.

Consent for publication

All authors provided feedback and approved the final version of the manuscript.

Declaration of conflicting interests

None.

Ethics approval and consent to participate

Ethics approval and consent to participate were not applicable because only published research data were included.

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.).

Supplemental material

Supplemental material for this article is available online.