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Effects of different doses of glucocorticoids on postoperative atrial fibrillation: a meta-analysis

Effects of different doses of glucocorticoids on postoperative atrial fibrillation: a meta-analysis Background Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery, and its occurrence is closely related to inflammation. This paper intends to apply meta-analysis to investigate the effect of glucocorticoids on POAF. Methods PubMed, Embase, Web of Science, and Cochrane Library were searched using the internationally recog- nized systematic evaluation and retrieval strategy. Two review authors independently selected relevant studies and extracted data based on the Cochrane handbook for systematic reviews of interventions approach. Stata 17 was used for data analysis. In the subgroup analysis, we grouped the participant data according to differences in glucocorti- coids dose and type of surgery. At the same time, we also conducted a meta-analysis on the possible infection and gastrointestinal injury caused by glucocorticoids use. Results 27 studies and 14,442 patients were finally included. Results from the random-effects model indicated that the incidence of POAF was lower in glucocorticoid group (RR 0.80, 95% CI 0.71–0.92, P = 0.001). According to the subgroup analysis result, low doses of glucocorticoids reduced the incidence of POAF (RR 0.81, 95% CI 0.71–0.92, P = 0.001). The effect of high doses glucocorticoids on the POAF was not statistically significant (RR 0.81, 95% CI 0.56– 1.19, P = 0.286). In the coronary artery bypass grafting (CABG) subgroup, the glucocorticoids reduced the incidence of POAF (RR 0.71, 95% CI 0.58–0.87, P = 0.001). In the CABG OR Valvular Surgery group, the effect of glucocorticoids on POAF was not statistically significant (RR 0.88, 95% CI 0.75–1.03, P = 0.108). 15 studies documented postopera- tive complications of infection, two studies were excluded from the system because the end point event was 0, and meta-analysis showed no increased risk of infection from glucocorticoid use (RR 0.85, 95% CI 0.68–1.06, P = 0.158). Eight studies documented the effects of glucocorticoids on gastrointestinal diseases, and meta-analysis showed no differences between the two groups (RR 1.12, 95% CI 0.83–1.50, P = 0.450). Conclusion The use of glucocorticoids can reduce the incidence of POAF. The subgroup analysis result showed that low-dose glucocorticoids were more effective than high-dose glucocorticoids in inhibiting POAF. The use of gluco - corticoids in CABG alone can better inhibit the occurrence of POAF. The effects of glucocorticoids on infection and gastrointestinal injury were not statistically significant. Review registration: PROSPERO, CRD42022304521. Keywords Glucocorticoids, Postoperative atrial fibrillation, Inflammatory, Cardiac surgery, Meta- analysis *Correspondence: Yi Long 619036254@qq.com Department of Cardiology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400025, China © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Zhou et al. BMC Cardiovascular Disorders (2023) 23:16 Page 2 of 14 Exclusion criteria: (1) age less than 18 years; (2) cardio- Introduction vascular risk factors were not considered as primary or POAF is the most common arrhythmia after CABG and secondary endpoints; (3) the full text of the study is not valve surgery, with an overall incidence of 20% to 40% available. and a higher incidence of approximately 30% to 50% in valve surgery [1]. POAF is closely relevant to stroke, hospital stay time, and the cost of treatment [2, 3]. The Quality assessment and data extraction pathological mechanism of POAF is very complex, This meta-analysis was reported per the Preferred and it is related to many factors. At present, the study reporting items for systematic reviews and Meta-Analy- about POAF is increasing rapidly, but no clear conclu- ses (PRISMA) guidelines. sion has been reached. Relevant research found that the The data collected in this study were screened and main influencing factors are structure and electrical extracted by 2 researchers (Zhongzheng Zhou and reconstruction. Furthermore, an increased adrenergic Xin He) in strict accordance with the exclusion crite- tone and changes in metabolic milieus are also possible ria according to the established retrieval strategy. The mechanisms of POAF [4]. Cochrane risk-of-bias assessment tool (RoB 2) was used Data suggests that inflammation might lead to the to evaluate literature bias [12]. Figure  1 shows the flow - POAF [5]. Trauma, ischemia/reperfusion, and cardio- chart of the literature retrieval (Additional file 1). pulmonary bypass during cardiac surgery can induce systemic inflammation; this inflammatory response is Statistical treatment closely related to the occurrence of POAF [6–9]. Glu- In this study, the correlation of glucocorticoids and cocorticoids can inhibit inflammation and, as a result, POAF risk was evaluated by indexes of relative risk (RR) may decrease the POAF risk. The effects of glucocor - and 95% confidence interval (CI). The RR was used to ticoids on POAF have been researched widely in many evaluated glucocorticoids group and placebo group, the countries. According to previous study result, gluco- glucocorticoids group refers to the use of glucocorticoids corticoids reduce postoperative C-reactive protein before or after surgery, while placebo group refers to the (CRP) levels, leukocytes, and other inflammatory mark - use of an equal dose of saline as placebo. Both Cochran’s ers; but the conclusions of these studies are controver- Q test and I index were applied to measure the hetero- sial [10, 11]. Thus, we conducted this meta-analysis to geneity, where heterogeneity was quantified by I , the investigate the effect of glucocorticoids on POAF. range of which is 0 to 100% (judge criteria I = 0–25%, no; 2 2 2 I = 25–50%, low; I = 50–75%, moderate; I = 75–100%, high heterogeneity). In the comprehensive effect study, Methods the random effect model was selected, and subgroup Literature search strategy and criteria analysis was conducted according to different doses. On PubMed, Embase, and Cochrane Library were searched this basis, the possible sources of heterogeneity were dis- based on internationally recognized systematic evalua- cussed. The possibility of publication bias was evaluated tion and retrieval strategy. Retrieval of data began from by Egger test method [13]. The sensitivity is determined the establishment of the database through December by excluding one study at a time, and then the impact of 2021.  The search terms were as follows: “Postoperative a single study on the overall research results is analyzed. atrial fibrillation”, “POAF”, “Cardiac surgery”, “CABG”, The judgment basis of statistical difference was set as “Cardiac valve surgery”, “atrial fibrillation”, “AF”, “Gluco - P < 0.05. Stata 17 software was used for data analysis. corticoids”, “Glucocorticoid”, “Steroid”, “Corticosteroid” In addition, two subgroup analyses were conducted, the and other individual drug names. Articles were also first subgroup research was conducted based on the dose identified by referring to the references of each study to of glucocorticoids. Patients who were administered dexa- supplement the data. methasone doses lower or equal to 100  mg were placed in the low-dose group, and patients who were adminis- tered dexamethasone doses higher than 100  mg were Inclusion and exclusion criteria classified into high-dose group (where different types Inclusion criteria: (1) randomized controlled trial of glucocorticoids are converted to equivalent doses of (RCT) with glucocorticoids treatment and placebo con- dexamethasone). Previous studies indicated that 100  mg trol; (2) all patients required surgical treatment and had dexamethasone might achieve a balance between efficacy no atrial fibrillation before surgery, where the types of and safety, so we used the 100  mg dose as the standard procedures included were CABG, cardiac valve surgery, for subgroup analysis [39]. Second, we divided them into and CABG combined with valve surgery; (3) published CABG group and CABG OR Valvular surgery group for literature. subgroup analysis according to different surgical types, Zhou  et al. BMC Cardiovascular Disorders (2023) 23:16 Page 3 of 14 Fig. 1 Flowchart of literature retrieval Zhou et al. BMC Cardiovascular Disorders (2023) 23:16 Page 4 of 14 Publication bias evaluation and sensitivity analysis where the CABG group refers to patients who underwent In the research process, publication bias were evaluated CABG alone, and the CABG OR Valvular surgery group based on Egger’s test, and the relevant result is shown in refers to patients who had valve surgery or CABG com- Fig.  6. The results of Egger’s test were close to the criti - bined with valve surgery. cal value, suggesting that there might be publication bias in the analysis results (P = 0.050). Sensitivity analysis was Results conducted on the three study endpoints. We used the Literature search leave-one-out analysis method for sensitivity analysis. The literature search process is depicted in Fig.  1. 3743 The vertical axis represents the study type, and the hori - studies were identified by searching each database zontal axis represents the combined results after exclud- according to the search keywords. The titles, abstracts, ing a certain study. Sensitivity analysis results showed and full texts of the initially detected literature were read, that excluding any study, the combined results of the and 27 studies were included based on above criteria remaining studies would not affect the end point out - [14–40]. come, proving that the conclusion was stable (see Fig. 7). Study characteristics Discussion Across the included studies, 14,442 patients were Meta-analysis was used to judge the effect of glucocor - enrolled. Table  1 shows the basic feature and quality ticoids use on POAF. The results showed a lower POAF assessment results of the selected studies. The regions risk in glucocorticoids group, while subgroup analysis involved in these studies mainly include the EU, Asia and showed that low-dose glucocorticoids decreased the inci- USA Interventions in the trial group included dexameth- dence of POAF compared to high-dose glucocorticoids. asone, methylprednisolone, and hydrocortisone. Figure 2 Previous studies on the influence of glucocorticoids on summarizes the results of quality assessment of each POAF were controversial; some previous studies have study according to the Cochrane risk-of-bias assessment yielded positive results, while others have been nega- tool (RoB 2). tive. Past studies included small sample sizes, Van Osch’s study was a single-center substudy of the DECS study [38], and the SIRS study [39] was a large controlled trial. Correlation between glucocorticoids and POAF Their results suggest that glucocorticoids have no cor - A total of 27 studies evaluated the influence of gluco - relation with the incidence of POAF. But the controlled corticoids on POAF; in total, there were 7260 cases in experiment conducted by Al-Shawabkeh in 2016 sug- glucocorticoids group and 7182 cases in control group. gested that glucocorticoids reduced the incidence of that According to the result of Fig.  3, incidence of POAF in [40]. Therefore, we included patients with all types of sur - glucocorticoid group is lower (RR 0.80, 95% CI 0.71–0.92, gery for this meta-analysis. P = 0.001). In certain range, low doses glucocorticoids POAF usually occurs during the initial 4 days after car- can reduce the POAF risk (RR 0.81, 95% CI 0.71–0.92, diac surgery; it is closely related to the type of surgery, P = 0.001). The risk of POAF was not significantly dif - with an incidence about (20–30%) in CABG surgery, (30– ferent between the high-dose glucocorticoids group and 50%) in valvular surgery and a higher incidence in valvu- the placebo group (RR 0.81, 95% CI 0.56–1.19, P = 0.286). lar combined coronary artery bypass surgery (60–80%) In the CABG subgroup, the glucocorticoids reduced the [41, 42]. Some school found that the occurrence of POAF POAF risk (RR 0.71, 95% CI 0.58–0.87, P = 0.001). In the is closely related to the prolongation of postoperative CABG OR Valvular Surgery group, the effect of glucocor - hospital stay and the increases in treatment cost [43, 44]. ticoids on POAF was not statistically significant (RR 0.88, POAF is usually self-limited, and most of cases return to 95% CI 0.75–1.03, P = 0.108) (see Table 2). normal on their own within 24 h of onset [45]; although A total of 15 studies documented postoperative compli- some patients will relapse within 2 days of the first attack cations of infection. However, two studies were excluded [46]. The pathogenesis of POAF is mainly related to local from the system because the end point event was 0, and inflammatory reaction [47, 48], adrenergic activation meta-analysis showed no increased risk of infection from [49], electrolyte disturbances [50], atrial stimulation [51] glucocorticoid use (RR 0.85, 95% CI 0.68–1.06, P = 0.158) and prolonged mechanical ventilation [42]. Among them, (see Fig.  4). And 8 studies documented the effects of the inflammatory response is considered to be the most glucocorticoids on gastrointestinal diseases, and meta- important pathogenesis of POAF [52]. The concentra - analysis showed no differences between the glucocorti - tions of CRP [53], number of white blood cells in POAF coid and the control group (RR 1.12, 95% CI 0.83–1.50, patients are higher than those in patients with sinus P = 0.450) (see Fig. 5). Zhou  et al. BMC Cardiovascular Disorders (2023) 23:16 Page 5 of 14 Table 1 Basic information of the studies Author Year Country Sample size Age Type of Cardiopulmonary Type and Placebo Main outcome surgery bypass dose of control evaluation glucocorticoid time Chaney 1998 The United 60 66.5 CABG Yes Methylpredni- Isodose nor- Not mention States solone 30 mg/ mal saline kg IV before surgery Yared 2000 The United 216 63.2 CABG OR Val- Yes Dexamethasone Isodose nor- The first 72 h States vular Surgery 0.6 mg/kg IV mal saline after surgery before surgery Schurr 2001 Swiss 50 62.4 CABG Yes Methylpredni- Isodose nor- The first 72 h solone 10 mg/ mal saline after surgery kg IV before surgery Fillinger 2002 The United 20 65.2 CABG Yes Methylpredni- Isodose nor- The first 72 h States solone 15 mg/ mal saline after surgery kg IV before surgery,0.3 mg every 6 h during the next 24 h Halvorsen 2003 Norway 294 64 CABG Yes Dexamethasone Isodose nor- The first 72 h 4 mg IV before mal saline after surgery surgery,4 mg IV after surgery Oliver 2004 The United 121 61.2 CABG OR Val- Yes Methylpredni- Isodose nor- The first 72 h States vular Surgery solone 1 g IV mal saline after surgery before surgery and of dexa- meth asone 4 mg every 6 h for 1 day after surgery Prasongsu- 2005 Canada 86 64.4 CABG Yes Methylpredni- Isodose nor- The first 7 days karn solone 1 g IV mal saline after surgery before surgery and of dexa- meth asone 4 mg every 6 h for 1 day after surgery Sano 2006 Japan 60 62.5 CABG Yes Hydrocortisone Isodose nor- The first 72 h 50 mg/kg IV mal saline after surgery before surgery Enc Y 2006 Turkey 40 58.3 CABG Yes Methylpredni- Isodose nor- The first 5 days solone 25 mg/ mal saline after surgery kg IV before surgery Whitlock 2006 Canada 51 66.5 CABG Yes Methylpredniso- Isodose nor- The first 4 days lone 250 mg IV mal saline after surgery before surgery Halonen 2007 Finland 241 65 CABG OR Val- Yes Hydrocortisone Isodose nor- The first 84 h vular Surgery 100 mg IV mal saline after surgery before surgery, 1 dose every 8 h during the next 3 days Yared 2007 The United 71 71.5 CABG OR Val- Yes Dexamethasone Isodose nor- The first 3 days States vular Surgery 0.6 mg/kg IV mal saline after surgery before surgery Sobieski 2008 The United 28 63.2 CABG Yes Dexametha- Isodose nor- Not mention States sone 100 mg IV mal saline before surgery Zhou et al. BMC Cardiovascular Disorders (2023) 23:16 Page 6 of 14 Table 1 (continued) Author Year Country Sample size Age Type of Cardiopulmonary Type and Placebo Main outcome surgery bypass dose of control evaluation glucocorticoid time Yasser 2009 Egypt 100 67.5 CABG OR Val- Yes Dexametha- Isodose nor- Not mention vular Surgery sone 1 mg/ mal saline kg IV before surgery,0.5 mg/ kg IV every 8 h Weis 2009 Germany 26 68 CABG Yes Hydrocortisone Isodose nor- Not mention 100 mg IV mal saline before surgery, 10 mg/kg per hour after sur- gery for 24 h Mauermann 2010 The United 121 62.8 CABG OR Val- Yes Methylpredni- Isodose nor- Not mention States vular Surgery solone 1 g IV mal saline before surgery, dexamethasone 4 mg IV every 6 h during the next 24 h Vukovic 2010 Serbia 57 61 CABG Yes Methylpredni- Isodose nor- The first 3 days solone 10 mg/ mal saline after surgery kg IV before surgery Murphy 2011 The United 98 63.1 CABG Yes Dexamethasone Isodose nor- The first 3 days States 4 mg IV before mal saline after surgery surgery Mirhosseini 2011 Iran 120 62 CABG No Methylpredniso- Isodose nor- Not mention lone 5 mg/kg IV mal saline before surgery Kilger 2011 Germany 305 68.5 CABG No Hydrocortisone Isodose nor- Not mention 100 mg IV mal saline before surgery, 10 mg/kg per hour after sur- gery for 24 h Dieleman 2012 Netherlands 4482 66.2 CABG OR Val- Yes Dexamethasone Isodose nor- The first 30 days vular Surgery 1 mg/kg IV mal saline after surgery before surgery Abbaszadeh 2012 Iran 184 60.1 CABG Yes Dexamethasone Isodose nor- The first 7 days 12 mg IV before mal saline after surgery surgery Suezawa 2013 Japan 30 68.5 CABG No Methylpredni- Isodose nor- Not mention solone 1 g IV mal saline before surgery Jacob 2014 Netherlands 62 69.6 CABG OR Val- Yes Dexamethasone Isodose nor- The first 7 days vular Surgery 1 mg/kg IV mal saline after surgery before surgery Van Osch 2015 Netherlands 1316 66.1 CABG OR Val- Yes Dexamethasone Isodose nor- The first 30 days vular Surgery 1 mg/kg IV mal saline after surgery before surgery Whitlock 2015 Canada 7507 67.4 CABG OR Val- Yes Methylpredni- Isodose nor- The first 4 days vular Surgery solone 500 IV mal saline after surgery before surgery Al-Shawabkeh 2016 Saudi Arabia 340 64.9 CABG Yes Methylpredni- Isodose nor- The first 7 days Z solone 1 g IV mal saline after surgery before surgery, dexamethasone 4 mg IV every 8 h during the next 3 day Zhou  et al. BMC Cardiovascular Disorders (2023) 23:16 Page 7 of 14 Fig. 2 Quality assessment of each included study. A Risk bias plot, B Summary of risk of bias Zhou et al. BMC Cardiovascular Disorders (2023) 23:16 Page 8 of 14 Fig. 3 A Meta-analysis of the correlation of the first subgroup. B Meta-analysis of the correlation of the second subgroup Table 2 Subgroup analysis of the of the primary outcome 2 2 Number RR (95%CI) P value I P for I Glucocorticoids dose High doses 12 0.81 (0.56–1.19) 0.286 69.8% < 0.001 Dexamethasone ≥ 100 mg Low doses 15 0.81 (0.71–0.92) 0.001 59.3% 0.002 Dexamethasone < 100 mg Type of surgery CABG 17 0.71 (0.58–0.87) 0.001 26.3% 0.153 CABG OR Valvular Surgery 10 0.88 (0.75–1.03) 0.108 77.4% < 0.001 rhythm [54, 55]; the increase of these inflammatory indi - be as follows: improving the expression of voltage-gated cators is closely related to the occurrence of POAF [56, L-type calcium channel (LTCC), sarcoplasmic/endo- 57]. Glucocorticoids can effectively reduce inflammatory plasmic reticulum calcium adenosine triphosphatase 2 reactions [58], thus reducing the incidence of POAF. (SERCA2), sodium/calcium exchanger 1 (NCX1) and The anti-inflammatory mechanism of glucocorticoids RyR2 genes, this result has important reference value is mainly through inhibiting the activity of immunomod- for the pathological study of POAF [60, 61]; this abnor- ulatory transcription factors such as NF-KB,AP-1, which mal expression may contribute to the development of is dose-dependent. The higher the dose, the stronger arrhythmias. Second, glucocorticoids can activate the the inhibition effect [59]. But in our study, it was found renin–angiotensin–aldosterone system (RASS) system, that compared to the high-dose glucocorticoids, low- leading to increased blood pressure, rapid heart rate [62, dose glucocorticoids were more effective in inhibiting 63]. High doses of glucocorticoids over-activate the RASS the occurrence of POAF. There are a few possible causes system and the sympathetic nervous system, increasing for this observation. First, high doses of glucocorticoids the risk of arrhythmias. Third, intravenous methylpred - cause high expression of calcium regulator mRNA, which nisolone alters myocardial cell stimulation thresholds can shorten the action potential refractory period and and sodium metabolism.  These changes may lead to the induce arrhythmia. Oakley analyzed the signal pathways variation of electrolyte shifts in the membranes of the related to dysregulated genes, and the results showed heart muscle, result in arrhythmias [64, 65]. Fourth, the that the mechanism of glucocorticoids on POAF might use of high doses of glucocorticoids can induce insulin Zhou  et al. BMC Cardiovascular Disorders (2023) 23:16 Page 9 of 14 Fig. 4 Meta-analysis of the correlation of glucocorticoids and postoperative infection resistance, which may prevent glucose from entering patients were enrolled in 8 studies to assess the effect cardiac muscle cells, aggravate an ischemic injury, and of glucocorticoids on gastrointestinal injury, includ- induce arrhythmias [49].Low-doses of glucocorticoids ing postoperative gastrointestinal bleeding, vomiting, are less likely to cause these adverse reactions and may gastrointestinal ulceration, or gastrointestinal dysfunc- have a better control effect on POAF. We investigated tion, meta-analysis results suggested that the effect of the influence of glucocorticoids on AF after different glucocorticoids on gastrointestinal injury was not sig- types of surgery, glucocorticoids reduced the incidence of nificant. The present results seem to be at variance with POAF in CABG group, but the effect of glucocorticoids our past consensus, and we speculate that this may be in combined group was not statistically significant. We due to the shorter duration of glucocorticoid use in all hypothesized that this may be due to the lower incidence studies and the smaller single dose, which needs to be of POAF and the lower inflammatory response in CABG confirmed in more and larger controlled trials. In addi - alone. tion to increased risk of infection and gastrointestinal The main side effects of glucocorticoids are gastro - damage, the use of glucocorticoids may cause abnormal intestinal bleeding and an high risk of infection, which glucose tolerance, electrolyte disorder, abnormal fat limits the application of glucocorticoids in heart sur- metabolism, osteoporosis, slow wound healing, nerv- gery. We also conducted a meta-analysis of these risks, ous system abnormalities, and even lead to thrombo- 12,126 cases were enrolled in 15 studies to assess the embolism. When the drug is stopped for a long time, effects of glucocorticoids on infections including medi - it can also lead to withdrawal reaction, adrenal cortical astinal, pulmonary, digestive and urinary tract infec- dysfunction, hypotension, and even shock. These side tions, suggesting that glucocorticoids use did not lead effects also limit the further use of glucocorticoids. to an higher risk of infection. Besides, a total of 11,155 Zhou et al. BMC Cardiovascular Disorders (2023) 23:16 Page 10 of 14 Fig. 5 Meta-analysis of correlation of glucocorticoids and gastrointestinal injury Fig. 6 Egger’s publication bias plot of glucocorticoids and POAF Zhou  et al. BMC Cardiovascular Disorders (2023) 23:16 Page 11 of 14 Fig. 7 A Sensitivity analysis of glucocorticoid to POAF; B Sensitivity analysis of glucocorticoid to infection; C Sensitivity analysis of glucocorticoid to gastrointestinal injury Zhou et al. BMC Cardiovascular Disorders (2023) 23:16 Page 12 of 14 Acknowledgements Limitations None. Firstly, the heterogeneity of the primary end points was too high. Subgroup analysis was conducted, but Author contributions ZZ and YL designed the methods and carried out the statistical analyses. ZZ, our grouping criteria were established in advance. In XH and YL made substantial contributions to the acquisition and analysis the second subgroup analysis, we found a significant of the data and to the interpretation of data. All the authors contributed to reduction in heterogeneity in the CABG group, in the the data extraction, drafted the article, and approved the final version of the manuscript. CABG OR Valvular Surgery group, the heterogeneity was significantly higher than that in the CABG group Funding due to the inclusion of patients undergoing combined This work was supported by The Scientific Research Institution Performance Incentive and Guidance Special Project of Chongqing (cstc2019jxj1130010). surgery. And in valve surgery, different valve lesions have different effects on cardiac function. Therefore, Availability of data and materials we believe that the differences in surgical methods are We declare that the data supporting the conclusions of this article are fully described within the article. the main reason for the heterogeneity. In future trials, we plan to conduct more rigorous surgical classifica - Declarations tion to reduce heterogeneity. Due to the differences in drug sensitivity among the included population and the Ethics approval and consent to participate large differences in the dose of glucocorticoids used in This article does not contain any studies with human participants or animals performed by any of the authors. each subgroup, this may be another factor leading to the generation of heterogeneity. We analyzed and dis- Consent for publication cussed the source of heterogeneity in Limitations and Not applicable. finally choose to use random effect model to synthesize Competing interests heterogeneity, and we cautiously recommend the final The authors declare that they have no competing interests. conclusion. Secondly, there was a lack of recent large clinical studies. Received: 7 July 2022 Accepted: 9 December 2022 Conclusions The results of this study showed that glucocorticoids References were beneficial in reducing the effect of POAF, and low- 1. 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Effects of different doses of glucocorticoids on postoperative atrial fibrillation: a meta-analysis

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Abstract

Background Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery, and its occurrence is closely related to inflammation. This paper intends to apply meta-analysis to investigate the effect of glucocorticoids on POAF. Methods PubMed, Embase, Web of Science, and Cochrane Library were searched using the internationally recog- nized systematic evaluation and retrieval strategy. Two review authors independently selected relevant studies and extracted data based on the Cochrane handbook for systematic reviews of interventions approach. Stata 17 was used for data analysis. In the subgroup analysis, we grouped the participant data according to differences in glucocorti- coids dose and type of surgery. At the same time, we also conducted a meta-analysis on the possible infection and gastrointestinal injury caused by glucocorticoids use. Results 27 studies and 14,442 patients were finally included. Results from the random-effects model indicated that the incidence of POAF was lower in glucocorticoid group (RR 0.80, 95% CI 0.71–0.92, P = 0.001). According to the subgroup analysis result, low doses of glucocorticoids reduced the incidence of POAF (RR 0.81, 95% CI 0.71–0.92, P = 0.001). The effect of high doses glucocorticoids on the POAF was not statistically significant (RR 0.81, 95% CI 0.56– 1.19, P = 0.286). In the coronary artery bypass grafting (CABG) subgroup, the glucocorticoids reduced the incidence of POAF (RR 0.71, 95% CI 0.58–0.87, P = 0.001). In the CABG OR Valvular Surgery group, the effect of glucocorticoids on POAF was not statistically significant (RR 0.88, 95% CI 0.75–1.03, P = 0.108). 15 studies documented postopera- tive complications of infection, two studies were excluded from the system because the end point event was 0, and meta-analysis showed no increased risk of infection from glucocorticoid use (RR 0.85, 95% CI 0.68–1.06, P = 0.158). Eight studies documented the effects of glucocorticoids on gastrointestinal diseases, and meta-analysis showed no differences between the two groups (RR 1.12, 95% CI 0.83–1.50, P = 0.450). Conclusion The use of glucocorticoids can reduce the incidence of POAF. The subgroup analysis result showed that low-dose glucocorticoids were more effective than high-dose glucocorticoids in inhibiting POAF. The use of gluco - corticoids in CABG alone can better inhibit the occurrence of POAF. The effects of glucocorticoids on infection and gastrointestinal injury were not statistically significant. Review registration: PROSPERO, CRD42022304521. Keywords Glucocorticoids, Postoperative atrial fibrillation, Inflammatory, Cardiac surgery, Meta- analysis *Correspondence: Yi Long 619036254@qq.com Department of Cardiology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400025, China © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Zhou et al. BMC Cardiovascular Disorders (2023) 23:16 Page 2 of 14 Exclusion criteria: (1) age less than 18 years; (2) cardio- Introduction vascular risk factors were not considered as primary or POAF is the most common arrhythmia after CABG and secondary endpoints; (3) the full text of the study is not valve surgery, with an overall incidence of 20% to 40% available. and a higher incidence of approximately 30% to 50% in valve surgery [1]. POAF is closely relevant to stroke, hospital stay time, and the cost of treatment [2, 3]. The Quality assessment and data extraction pathological mechanism of POAF is very complex, This meta-analysis was reported per the Preferred and it is related to many factors. At present, the study reporting items for systematic reviews and Meta-Analy- about POAF is increasing rapidly, but no clear conclu- ses (PRISMA) guidelines. sion has been reached. Relevant research found that the The data collected in this study were screened and main influencing factors are structure and electrical extracted by 2 researchers (Zhongzheng Zhou and reconstruction. Furthermore, an increased adrenergic Xin He) in strict accordance with the exclusion crite- tone and changes in metabolic milieus are also possible ria according to the established retrieval strategy. The mechanisms of POAF [4]. Cochrane risk-of-bias assessment tool (RoB 2) was used Data suggests that inflammation might lead to the to evaluate literature bias [12]. Figure  1 shows the flow - POAF [5]. Trauma, ischemia/reperfusion, and cardio- chart of the literature retrieval (Additional file 1). pulmonary bypass during cardiac surgery can induce systemic inflammation; this inflammatory response is Statistical treatment closely related to the occurrence of POAF [6–9]. Glu- In this study, the correlation of glucocorticoids and cocorticoids can inhibit inflammation and, as a result, POAF risk was evaluated by indexes of relative risk (RR) may decrease the POAF risk. The effects of glucocor - and 95% confidence interval (CI). The RR was used to ticoids on POAF have been researched widely in many evaluated glucocorticoids group and placebo group, the countries. According to previous study result, gluco- glucocorticoids group refers to the use of glucocorticoids corticoids reduce postoperative C-reactive protein before or after surgery, while placebo group refers to the (CRP) levels, leukocytes, and other inflammatory mark - use of an equal dose of saline as placebo. Both Cochran’s ers; but the conclusions of these studies are controver- Q test and I index were applied to measure the hetero- sial [10, 11]. Thus, we conducted this meta-analysis to geneity, where heterogeneity was quantified by I , the investigate the effect of glucocorticoids on POAF. range of which is 0 to 100% (judge criteria I = 0–25%, no; 2 2 2 I = 25–50%, low; I = 50–75%, moderate; I = 75–100%, high heterogeneity). In the comprehensive effect study, Methods the random effect model was selected, and subgroup Literature search strategy and criteria analysis was conducted according to different doses. On PubMed, Embase, and Cochrane Library were searched this basis, the possible sources of heterogeneity were dis- based on internationally recognized systematic evalua- cussed. The possibility of publication bias was evaluated tion and retrieval strategy. Retrieval of data began from by Egger test method [13]. The sensitivity is determined the establishment of the database through December by excluding one study at a time, and then the impact of 2021.  The search terms were as follows: “Postoperative a single study on the overall research results is analyzed. atrial fibrillation”, “POAF”, “Cardiac surgery”, “CABG”, The judgment basis of statistical difference was set as “Cardiac valve surgery”, “atrial fibrillation”, “AF”, “Gluco - P < 0.05. Stata 17 software was used for data analysis. corticoids”, “Glucocorticoid”, “Steroid”, “Corticosteroid” In addition, two subgroup analyses were conducted, the and other individual drug names. Articles were also first subgroup research was conducted based on the dose identified by referring to the references of each study to of glucocorticoids. Patients who were administered dexa- supplement the data. methasone doses lower or equal to 100  mg were placed in the low-dose group, and patients who were adminis- tered dexamethasone doses higher than 100  mg were Inclusion and exclusion criteria classified into high-dose group (where different types Inclusion criteria: (1) randomized controlled trial of glucocorticoids are converted to equivalent doses of (RCT) with glucocorticoids treatment and placebo con- dexamethasone). Previous studies indicated that 100  mg trol; (2) all patients required surgical treatment and had dexamethasone might achieve a balance between efficacy no atrial fibrillation before surgery, where the types of and safety, so we used the 100  mg dose as the standard procedures included were CABG, cardiac valve surgery, for subgroup analysis [39]. Second, we divided them into and CABG combined with valve surgery; (3) published CABG group and CABG OR Valvular surgery group for literature. subgroup analysis according to different surgical types, Zhou  et al. BMC Cardiovascular Disorders (2023) 23:16 Page 3 of 14 Fig. 1 Flowchart of literature retrieval Zhou et al. BMC Cardiovascular Disorders (2023) 23:16 Page 4 of 14 Publication bias evaluation and sensitivity analysis where the CABG group refers to patients who underwent In the research process, publication bias were evaluated CABG alone, and the CABG OR Valvular surgery group based on Egger’s test, and the relevant result is shown in refers to patients who had valve surgery or CABG com- Fig.  6. The results of Egger’s test were close to the criti - bined with valve surgery. cal value, suggesting that there might be publication bias in the analysis results (P = 0.050). Sensitivity analysis was Results conducted on the three study endpoints. We used the Literature search leave-one-out analysis method for sensitivity analysis. The literature search process is depicted in Fig.  1. 3743 The vertical axis represents the study type, and the hori - studies were identified by searching each database zontal axis represents the combined results after exclud- according to the search keywords. The titles, abstracts, ing a certain study. Sensitivity analysis results showed and full texts of the initially detected literature were read, that excluding any study, the combined results of the and 27 studies were included based on above criteria remaining studies would not affect the end point out - [14–40]. come, proving that the conclusion was stable (see Fig. 7). Study characteristics Discussion Across the included studies, 14,442 patients were Meta-analysis was used to judge the effect of glucocor - enrolled. Table  1 shows the basic feature and quality ticoids use on POAF. The results showed a lower POAF assessment results of the selected studies. The regions risk in glucocorticoids group, while subgroup analysis involved in these studies mainly include the EU, Asia and showed that low-dose glucocorticoids decreased the inci- USA Interventions in the trial group included dexameth- dence of POAF compared to high-dose glucocorticoids. asone, methylprednisolone, and hydrocortisone. Figure 2 Previous studies on the influence of glucocorticoids on summarizes the results of quality assessment of each POAF were controversial; some previous studies have study according to the Cochrane risk-of-bias assessment yielded positive results, while others have been nega- tool (RoB 2). tive. Past studies included small sample sizes, Van Osch’s study was a single-center substudy of the DECS study [38], and the SIRS study [39] was a large controlled trial. Correlation between glucocorticoids and POAF Their results suggest that glucocorticoids have no cor - A total of 27 studies evaluated the influence of gluco - relation with the incidence of POAF. But the controlled corticoids on POAF; in total, there were 7260 cases in experiment conducted by Al-Shawabkeh in 2016 sug- glucocorticoids group and 7182 cases in control group. gested that glucocorticoids reduced the incidence of that According to the result of Fig.  3, incidence of POAF in [40]. Therefore, we included patients with all types of sur - glucocorticoid group is lower (RR 0.80, 95% CI 0.71–0.92, gery for this meta-analysis. P = 0.001). In certain range, low doses glucocorticoids POAF usually occurs during the initial 4 days after car- can reduce the POAF risk (RR 0.81, 95% CI 0.71–0.92, diac surgery; it is closely related to the type of surgery, P = 0.001). The risk of POAF was not significantly dif - with an incidence about (20–30%) in CABG surgery, (30– ferent between the high-dose glucocorticoids group and 50%) in valvular surgery and a higher incidence in valvu- the placebo group (RR 0.81, 95% CI 0.56–1.19, P = 0.286). lar combined coronary artery bypass surgery (60–80%) In the CABG subgroup, the glucocorticoids reduced the [41, 42]. Some school found that the occurrence of POAF POAF risk (RR 0.71, 95% CI 0.58–0.87, P = 0.001). In the is closely related to the prolongation of postoperative CABG OR Valvular Surgery group, the effect of glucocor - hospital stay and the increases in treatment cost [43, 44]. ticoids on POAF was not statistically significant (RR 0.88, POAF is usually self-limited, and most of cases return to 95% CI 0.75–1.03, P = 0.108) (see Table 2). normal on their own within 24 h of onset [45]; although A total of 15 studies documented postoperative compli- some patients will relapse within 2 days of the first attack cations of infection. However, two studies were excluded [46]. The pathogenesis of POAF is mainly related to local from the system because the end point event was 0, and inflammatory reaction [47, 48], adrenergic activation meta-analysis showed no increased risk of infection from [49], electrolyte disturbances [50], atrial stimulation [51] glucocorticoid use (RR 0.85, 95% CI 0.68–1.06, P = 0.158) and prolonged mechanical ventilation [42]. Among them, (see Fig.  4). And 8 studies documented the effects of the inflammatory response is considered to be the most glucocorticoids on gastrointestinal diseases, and meta- important pathogenesis of POAF [52]. The concentra - analysis showed no differences between the glucocorti - tions of CRP [53], number of white blood cells in POAF coid and the control group (RR 1.12, 95% CI 0.83–1.50, patients are higher than those in patients with sinus P = 0.450) (see Fig. 5). Zhou  et al. BMC Cardiovascular Disorders (2023) 23:16 Page 5 of 14 Table 1 Basic information of the studies Author Year Country Sample size Age Type of Cardiopulmonary Type and Placebo Main outcome surgery bypass dose of control evaluation glucocorticoid time Chaney 1998 The United 60 66.5 CABG Yes Methylpredni- Isodose nor- Not mention States solone 30 mg/ mal saline kg IV before surgery Yared 2000 The United 216 63.2 CABG OR Val- Yes Dexamethasone Isodose nor- The first 72 h States vular Surgery 0.6 mg/kg IV mal saline after surgery before surgery Schurr 2001 Swiss 50 62.4 CABG Yes Methylpredni- Isodose nor- The first 72 h solone 10 mg/ mal saline after surgery kg IV before surgery Fillinger 2002 The United 20 65.2 CABG Yes Methylpredni- Isodose nor- The first 72 h States solone 15 mg/ mal saline after surgery kg IV before surgery,0.3 mg every 6 h during the next 24 h Halvorsen 2003 Norway 294 64 CABG Yes Dexamethasone Isodose nor- The first 72 h 4 mg IV before mal saline after surgery surgery,4 mg IV after surgery Oliver 2004 The United 121 61.2 CABG OR Val- Yes Methylpredni- Isodose nor- The first 72 h States vular Surgery solone 1 g IV mal saline after surgery before surgery and of dexa- meth asone 4 mg every 6 h for 1 day after surgery Prasongsu- 2005 Canada 86 64.4 CABG Yes Methylpredni- Isodose nor- The first 7 days karn solone 1 g IV mal saline after surgery before surgery and of dexa- meth asone 4 mg every 6 h for 1 day after surgery Sano 2006 Japan 60 62.5 CABG Yes Hydrocortisone Isodose nor- The first 72 h 50 mg/kg IV mal saline after surgery before surgery Enc Y 2006 Turkey 40 58.3 CABG Yes Methylpredni- Isodose nor- The first 5 days solone 25 mg/ mal saline after surgery kg IV before surgery Whitlock 2006 Canada 51 66.5 CABG Yes Methylpredniso- Isodose nor- The first 4 days lone 250 mg IV mal saline after surgery before surgery Halonen 2007 Finland 241 65 CABG OR Val- Yes Hydrocortisone Isodose nor- The first 84 h vular Surgery 100 mg IV mal saline after surgery before surgery, 1 dose every 8 h during the next 3 days Yared 2007 The United 71 71.5 CABG OR Val- Yes Dexamethasone Isodose nor- The first 3 days States vular Surgery 0.6 mg/kg IV mal saline after surgery before surgery Sobieski 2008 The United 28 63.2 CABG Yes Dexametha- Isodose nor- Not mention States sone 100 mg IV mal saline before surgery Zhou et al. BMC Cardiovascular Disorders (2023) 23:16 Page 6 of 14 Table 1 (continued) Author Year Country Sample size Age Type of Cardiopulmonary Type and Placebo Main outcome surgery bypass dose of control evaluation glucocorticoid time Yasser 2009 Egypt 100 67.5 CABG OR Val- Yes Dexametha- Isodose nor- Not mention vular Surgery sone 1 mg/ mal saline kg IV before surgery,0.5 mg/ kg IV every 8 h Weis 2009 Germany 26 68 CABG Yes Hydrocortisone Isodose nor- Not mention 100 mg IV mal saline before surgery, 10 mg/kg per hour after sur- gery for 24 h Mauermann 2010 The United 121 62.8 CABG OR Val- Yes Methylpredni- Isodose nor- Not mention States vular Surgery solone 1 g IV mal saline before surgery, dexamethasone 4 mg IV every 6 h during the next 24 h Vukovic 2010 Serbia 57 61 CABG Yes Methylpredni- Isodose nor- The first 3 days solone 10 mg/ mal saline after surgery kg IV before surgery Murphy 2011 The United 98 63.1 CABG Yes Dexamethasone Isodose nor- The first 3 days States 4 mg IV before mal saline after surgery surgery Mirhosseini 2011 Iran 120 62 CABG No Methylpredniso- Isodose nor- Not mention lone 5 mg/kg IV mal saline before surgery Kilger 2011 Germany 305 68.5 CABG No Hydrocortisone Isodose nor- Not mention 100 mg IV mal saline before surgery, 10 mg/kg per hour after sur- gery for 24 h Dieleman 2012 Netherlands 4482 66.2 CABG OR Val- Yes Dexamethasone Isodose nor- The first 30 days vular Surgery 1 mg/kg IV mal saline after surgery before surgery Abbaszadeh 2012 Iran 184 60.1 CABG Yes Dexamethasone Isodose nor- The first 7 days 12 mg IV before mal saline after surgery surgery Suezawa 2013 Japan 30 68.5 CABG No Methylpredni- Isodose nor- Not mention solone 1 g IV mal saline before surgery Jacob 2014 Netherlands 62 69.6 CABG OR Val- Yes Dexamethasone Isodose nor- The first 7 days vular Surgery 1 mg/kg IV mal saline after surgery before surgery Van Osch 2015 Netherlands 1316 66.1 CABG OR Val- Yes Dexamethasone Isodose nor- The first 30 days vular Surgery 1 mg/kg IV mal saline after surgery before surgery Whitlock 2015 Canada 7507 67.4 CABG OR Val- Yes Methylpredni- Isodose nor- The first 4 days vular Surgery solone 500 IV mal saline after surgery before surgery Al-Shawabkeh 2016 Saudi Arabia 340 64.9 CABG Yes Methylpredni- Isodose nor- The first 7 days Z solone 1 g IV mal saline after surgery before surgery, dexamethasone 4 mg IV every 8 h during the next 3 day Zhou  et al. BMC Cardiovascular Disorders (2023) 23:16 Page 7 of 14 Fig. 2 Quality assessment of each included study. A Risk bias plot, B Summary of risk of bias Zhou et al. BMC Cardiovascular Disorders (2023) 23:16 Page 8 of 14 Fig. 3 A Meta-analysis of the correlation of the first subgroup. B Meta-analysis of the correlation of the second subgroup Table 2 Subgroup analysis of the of the primary outcome 2 2 Number RR (95%CI) P value I P for I Glucocorticoids dose High doses 12 0.81 (0.56–1.19) 0.286 69.8% < 0.001 Dexamethasone ≥ 100 mg Low doses 15 0.81 (0.71–0.92) 0.001 59.3% 0.002 Dexamethasone < 100 mg Type of surgery CABG 17 0.71 (0.58–0.87) 0.001 26.3% 0.153 CABG OR Valvular Surgery 10 0.88 (0.75–1.03) 0.108 77.4% < 0.001 rhythm [54, 55]; the increase of these inflammatory indi - be as follows: improving the expression of voltage-gated cators is closely related to the occurrence of POAF [56, L-type calcium channel (LTCC), sarcoplasmic/endo- 57]. Glucocorticoids can effectively reduce inflammatory plasmic reticulum calcium adenosine triphosphatase 2 reactions [58], thus reducing the incidence of POAF. (SERCA2), sodium/calcium exchanger 1 (NCX1) and The anti-inflammatory mechanism of glucocorticoids RyR2 genes, this result has important reference value is mainly through inhibiting the activity of immunomod- for the pathological study of POAF [60, 61]; this abnor- ulatory transcription factors such as NF-KB,AP-1, which mal expression may contribute to the development of is dose-dependent. The higher the dose, the stronger arrhythmias. Second, glucocorticoids can activate the the inhibition effect [59]. But in our study, it was found renin–angiotensin–aldosterone system (RASS) system, that compared to the high-dose glucocorticoids, low- leading to increased blood pressure, rapid heart rate [62, dose glucocorticoids were more effective in inhibiting 63]. High doses of glucocorticoids over-activate the RASS the occurrence of POAF. There are a few possible causes system and the sympathetic nervous system, increasing for this observation. First, high doses of glucocorticoids the risk of arrhythmias. Third, intravenous methylpred - cause high expression of calcium regulator mRNA, which nisolone alters myocardial cell stimulation thresholds can shorten the action potential refractory period and and sodium metabolism.  These changes may lead to the induce arrhythmia. Oakley analyzed the signal pathways variation of electrolyte shifts in the membranes of the related to dysregulated genes, and the results showed heart muscle, result in arrhythmias [64, 65]. Fourth, the that the mechanism of glucocorticoids on POAF might use of high doses of glucocorticoids can induce insulin Zhou  et al. BMC Cardiovascular Disorders (2023) 23:16 Page 9 of 14 Fig. 4 Meta-analysis of the correlation of glucocorticoids and postoperative infection resistance, which may prevent glucose from entering patients were enrolled in 8 studies to assess the effect cardiac muscle cells, aggravate an ischemic injury, and of glucocorticoids on gastrointestinal injury, includ- induce arrhythmias [49].Low-doses of glucocorticoids ing postoperative gastrointestinal bleeding, vomiting, are less likely to cause these adverse reactions and may gastrointestinal ulceration, or gastrointestinal dysfunc- have a better control effect on POAF. We investigated tion, meta-analysis results suggested that the effect of the influence of glucocorticoids on AF after different glucocorticoids on gastrointestinal injury was not sig- types of surgery, glucocorticoids reduced the incidence of nificant. The present results seem to be at variance with POAF in CABG group, but the effect of glucocorticoids our past consensus, and we speculate that this may be in combined group was not statistically significant. We due to the shorter duration of glucocorticoid use in all hypothesized that this may be due to the lower incidence studies and the smaller single dose, which needs to be of POAF and the lower inflammatory response in CABG confirmed in more and larger controlled trials. In addi - alone. tion to increased risk of infection and gastrointestinal The main side effects of glucocorticoids are gastro - damage, the use of glucocorticoids may cause abnormal intestinal bleeding and an high risk of infection, which glucose tolerance, electrolyte disorder, abnormal fat limits the application of glucocorticoids in heart sur- metabolism, osteoporosis, slow wound healing, nerv- gery. We also conducted a meta-analysis of these risks, ous system abnormalities, and even lead to thrombo- 12,126 cases were enrolled in 15 studies to assess the embolism. When the drug is stopped for a long time, effects of glucocorticoids on infections including medi - it can also lead to withdrawal reaction, adrenal cortical astinal, pulmonary, digestive and urinary tract infec- dysfunction, hypotension, and even shock. These side tions, suggesting that glucocorticoids use did not lead effects also limit the further use of glucocorticoids. to an higher risk of infection. Besides, a total of 11,155 Zhou et al. BMC Cardiovascular Disorders (2023) 23:16 Page 10 of 14 Fig. 5 Meta-analysis of correlation of glucocorticoids and gastrointestinal injury Fig. 6 Egger’s publication bias plot of glucocorticoids and POAF Zhou  et al. BMC Cardiovascular Disorders (2023) 23:16 Page 11 of 14 Fig. 7 A Sensitivity analysis of glucocorticoid to POAF; B Sensitivity analysis of glucocorticoid to infection; C Sensitivity analysis of glucocorticoid to gastrointestinal injury Zhou et al. BMC Cardiovascular Disorders (2023) 23:16 Page 12 of 14 Acknowledgements Limitations None. Firstly, the heterogeneity of the primary end points was too high. Subgroup analysis was conducted, but Author contributions ZZ and YL designed the methods and carried out the statistical analyses. ZZ, our grouping criteria were established in advance. In XH and YL made substantial contributions to the acquisition and analysis the second subgroup analysis, we found a significant of the data and to the interpretation of data. All the authors contributed to reduction in heterogeneity in the CABG group, in the the data extraction, drafted the article, and approved the final version of the manuscript. CABG OR Valvular Surgery group, the heterogeneity was significantly higher than that in the CABG group Funding due to the inclusion of patients undergoing combined This work was supported by The Scientific Research Institution Performance Incentive and Guidance Special Project of Chongqing (cstc2019jxj1130010). surgery. And in valve surgery, different valve lesions have different effects on cardiac function. Therefore, Availability of data and materials we believe that the differences in surgical methods are We declare that the data supporting the conclusions of this article are fully described within the article. the main reason for the heterogeneity. In future trials, we plan to conduct more rigorous surgical classifica - Declarations tion to reduce heterogeneity. Due to the differences in drug sensitivity among the included population and the Ethics approval and consent to participate large differences in the dose of glucocorticoids used in This article does not contain any studies with human participants or animals performed by any of the authors. each subgroup, this may be another factor leading to the generation of heterogeneity. We analyzed and dis- Consent for publication cussed the source of heterogeneity in Limitations and Not applicable. finally choose to use random effect model to synthesize Competing interests heterogeneity, and we cautiously recommend the final The authors declare that they have no competing interests. conclusion. Secondly, there was a lack of recent large clinical studies. Received: 7 July 2022 Accepted: 9 December 2022 Conclusions The results of this study showed that glucocorticoids References were beneficial in reducing the effect of POAF, and low- 1. 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Journal

BMC Cardiovascular DisordersSpringer Journals

Published: Jan 12, 2023

Keywords: Glucocorticoids; Postoperative atrial fibrillation; Inflammatory; Cardiac surgery; Meta- analysis

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