Archives of Academic Emergency Medicine. 2023; 11(1): e55 REV I EW ART I C L E Prevalence of Compartment Syndrome and Disseminated Intravascular Coagulation following Rhabdomyolysis; a Systematic Review and Meta-Analysis Bardia Danaei1, Ali Sharifi2∗, Hamid Mazloom3, Iraj Najafi4, Mehri Farhang Ranjbar5, Saeed Safari5,1 † 1. Men’s Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Assistant Professor of Hepatopancreaticobiliary & Organ Transplantation Surgery, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Emergency Department, Shohadaye Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4. Nephrology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. 5. Research Center for Trauma in Police Operations, Directorate of Health, Rescue & Treatment, Police Headquarter, Tehran, Iran. Received: June 2023; Accepted: July 2023; Published online: 1 August 2023 Abstract: Introduction: Rhabdomyolysis (RM) may cause some complications such as compartment syndrome and dissemi- nated intravascular coagulation (DIC), which can affect its prognosis. This systematic review and meta-analysis aimed to investigate the prevalence of the mentioned complications following RM. Methods: Medline, Embase, and Scopus databases were searched using keywords related to compartment syndrome, DIC, and rhabdomyolysis with appropriate combination. Cohort and cross-sectional studies that conducted research on the prevalence of compartment syndrome and DIC in patients with RM were included in the present study. The desired data were extracted from the included stud- ies and meta-analysis was conducted on them to calculate pooled prevalence of these complications. Results: Twenty articles were included in our systematic review. The rate of compartment syndrome reported in these studies ranged from 0 to 30.7%. Our meta-analysis revealed the pooled prevalence of 4% (95% confidence interval (CI): 2.20 to 7.40) for compartment syndrome in these studies. The pooled prevalence of this complication was 7.1% (95% CI: 2.90 to 16.00) among patients with severe RM and 4.4% (95% CI: 1.80 to 10.00) in traumatic RM. The rate of DIC reported in the in- cluded studies ranged from 0 to 40.47%. Our meta-analysis showed the pooled prevalence of 8.3% (95% CI: 03.90 to 16.50) for this complication among RM patients. Conclusion: We reported the rates of compartment syndrome and DIC in RM patients based on rhabdomyolysis etiologies through an epidemiologic systematic review and meta-analysis. The rate of compartment syndrome was slightly higher in patients with severe RM and its rate in patients with traumatic RM was close to the overall rate of compartment syndrome. Keywords: Rhabdomyolysis; Compartment syndromes; Disseminated intravascular coagulation; Systematic review Cite this article as: Danaei B, Sharifi A, Mazloom H, Fazli F, Najafi I, Farhang Ranjbar M, Safari S. Prevalence of Compartment Syndrome and Disseminated Intravascular Coagulation following Rhabdomyolysis; a Systematic Review and Meta-Analysis. Arch Acad Emerg Med. 2023; 11(1): e55. https://doi.org/10.22037/aaem.v11i1.2083. ∗Corresponding Author: Ali Sharifi; Hepatopancreaticobiliary & Organ Trans- plantation Surgery, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Email: sharifi331@yahoo.com, ORCID: https://orcid.org/000- 0002-4179-202X. † Corresponding Author: Saeed Safari; Men’s Health and Reproduc- tive Health Research Center, Shohadaye Tajrish Hospital, Tajrish Square, Tehran, Iran. Email: safari266@gmail.com, Tel: 009822721155, ORCID: https://orcid.org/0000-0002-7407-1739. 1. Introduction Rhabdomyolysis (RM) is a clinical condition characterized by a loss of muscle strength, muscle pain, and swelling. This condition is associated with a creatine kinase (CK) level ex- ceeding 1000 IU/L or CK being more than five times the upper limit of normal (ULN) for a mild form of RM as per standard definition. If myoglobinuria and acute kidney in- jury (AKI) are present, it indicates a severe form of RM (1). The development of rhabdomyolysis is caused by an eleva- tion of ionized calcium levels within the cytoplasm, which contributes to its pathogenesis. In theory, rhabdomyolysis This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index B. Danaei et al. 2 can be triggered by various forms of muscle damage and any factors that result in or contribute to muscle damage (2). Among adults, the existing data indicate that the most fre- quent causes of rhabdomyolysis are drug or alcohol abuse, use of certain medications, traumatic injuries, neuroleptic malignant syndrome (NMS), and prolonged periods of im- mobility (3). RM may cause some complications, which can affect its prognosis (4). The most important one is AKI, for which re- search indicated a wide range prevalence of 15% to over 50% in RM patients (3, 5, 6). However, besides AKI there are other complications that need to be noticed by clinicians; includ- ing compartment syndrome, disseminated intravascular co- agulation (DIC), and electrolyte imbalance (7). The release of muscle cells’ content can cause local edema, which remains trapped within fascia and can lead to com- partment syndrome (8). Compartment syndrome occurs when elevated pressure within a closed anatomical space poses a threat to the viability of muscles and nerves in that compartment. This condition arises due to compromised blood flow and localized ischemia (9). Although, there has not been sufficient evidence regarding its incidence rate in RM, it’s not considered to be a rare complication (4). Hence, it is crucial to closely monitor clinical signs and compartment pressures with respect to compartment syndrome, as it has the potential to progress into a surgical emergency. Disseminated intravascular coagulation is drastic activation of the coagulation system, leading to microvascular throm- bosis and potentially life-threatening hemorrhage due to consumption of coagulation factors and platelets (10). The release of thromboplastin and other substances with pro- thrombotic properties from the injured muscle tissue in RM, especially severe forms of it, can cause DIC (4). Due to the fact that DIC mostly occurs as a complication of severe medical conditions, its prevalence remains higher in more severe settings (11). In this article our primary goal is to conduct an epidemio- logic systematic review on published literature to report the prevalence of compartment syndrome and DIC in patients with RM based on the RM’s etiology. Our secondary goal is to conduct a meta-analysis, if adequate data is available, to determine the pooled prevalence of these complications fol- lowing RM. 2. Methods 2.1. Study design and setting The present study is a systematic review of observational studies conducted with the aim of investigating the preva- lence of compartment syndrome and DIC in patients with RM. Since this systematic review is dedicated to just report- ing the prevalence of an event in observational studies there is no comparison of data in this research. This systematic re- view conforms to the “Preferred Reporting Items for System- atic Reviews and Meta-Analyses” (PRISMA) statement (12). This study follows the guidelines for Meta-Analyses and Sys- tematic Reviews of Observational Studies in Epidemiology (MOOSE) (13). 2.2. Search strategy To find an answer to the question of the present study, Medline, Embase, and Scopus databases were searched. Keywords related to compartment syndrome, DIC, and rhabdomyolysis were selected and then searched in each database with the appropriate combination. The keywords of search strategy for this study are reported in supplemen- tary table 1. The search was conducted on April 30, 2023 and included every record till then. In addition to the systematic search, a manual search was also performed in gray litera- ture. The search strategy is presented in the appendix. 2.3. Selection criteria Two reviewers, I.N. and M.F.R independently screened the records by title/abstract and full text to exclude records un- related to the topic. A third reviewer, B.D., would decide if the two reviews couldn’t agree on a particular article. Co- hort studies and cross-sectional studies in English, which conducted research on the prevalence of compartment syn- drome and DIC in patients with RM were included in the present study. Exclusion criteria were failure to report com- partment syndrome or DIC as an outcome, not identify- ing RM’s etiologies, clinical trials, case-control studies, case reports, review studies, repeated studies, retracted studies, conference abstracts, editorials, and letters to editors. 2.4. Quality assessment Assessment of the quality of included articles was done by two reviewers, B.D. and M.F.R., using the National Heart, Lung, and Blood Institute (NHLBI) quality assessment tools for observational cohort and cross-sectional studies (14). This tool is a 14-question checklist, based on which the qual- ity of articles is assessed in terms of methodology, report of findings, and possible distortions. A third reviewer, A.S., would decide if the two reviews couldn’t agree on a particular assessment. 2.5. Data extraction Compartment syndrome and DIC prevalence were extracted from included articles, along with the etiology of rhabdomy- olysis, age group of patients, and studies’ demographic infor- mation such as data collection period, country, study design, and sampling method. We also collected data on definitions of these conditions in the included articles, when available. Collected data were summarized using a checklist designed This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index 3 Archives of Academic Emergency Medicine. 2023; 11(1): e55 based on the MOOSE statement guidelines (13). 2.6. Statistical analysis The prevalence of compartment syndrome and DIC in RM patients was investigated using the Comprehensive Meta- Analysis software, version 2.0 (Biostat Inc., Englewood, NJ, USA). we reported pooled prevalence with a 95% confidence interval (CI). Random effect model was used for groups of studies with significant heterogeneity between their research methodologies; and for groups of studies without significant heterogeneity, fixed effect model was used. In addition, if possible, subgroup analysis was performed based on the eti- ology and severity of RM. Finally, funnel plot and Egger’s test were used to identify publication bias. 3. Results At the last stage of our screenings there were 20 articles, which were included in our systematic review via selection process (figure 1). Six of them were conducted in USA (15- 20), two in Australia (21, 22), two in Norway (23, 24), and 10 in other countries, which can be seen in table 1. All stud- ies were retrospective cohorts except one, which was cross- sectional (25). The sampling method in all of the included studies were consecutive. 17 studies consisted only of adult patients (18 years old or above) and the three remaining stud- ies consisted of children as well as adults. The total number of RM patients in these studies were 1310 patients, approxi- mately 55% of which were male. Quality of included articles was assessed based on NHLBI quality assessment tool (supplementary table 2). Included articles were rated as poor quality (0 to 4 out of 14 questions), fair quality (5 to 10 out of 14 questions), or good quality (11 to 14 out of 14 questions). All included studies had fair quality. 3.1. Compartment syndrome prevalence in in- cluded studies Sixteen of the included studies reported compartment syn- drome prevalence in RM patients. There were 928 adults with RM in these studies, approximately 54% of which were male. RM definitions were different in these studies. One study defined RM patients as having International Classifica- tion of Diseases (ICD) version 9 code related to RM diagno- sis (17). Other studies defined RM disease by the level of the creatine kinase (CK) enzyme in blood of the patients. Most authors diagnosed rhabdomyolysis based on CK levels five times the upper limit of normal levels (>1000 U/L) (16, 19, 20, 22, 23, 25-28). This diagnostic cut-off was lower than 1000 in one study (15), and four studies exclusively included patients with CK levels more than 5000 (15, 21, 24, 29, 30). CK level more than 5000 is considered to indicate severe RM (31). The criteria for RM definition were not available in one study (32). The primary etiologies in these patients comprise exercise, earthquake-related trauma, snake venom, drug toxicity, pro- longed immobilization, and surgery (table 2). The compart- ment syndrome definition was not reported in most of the in- cluded articles. One study mentioned clinical diagnosis by a surgeon (24) and another one mentioned requirement of fas- ciotomy (22) as compartment syndrome diagnosis method. The rate of compartment syndrome in the included studies ranged from 0% to 30.7%. The pooled prevalence of compart- ment syndrome was 4% (95% CI: 2.20 to 7.40; p < 0.001) in these studies (figure 2). Due to the high levels of heterogene- ity between these studies we tried to conduct a sub-group analysis based on RM severity, and RM etiology dividing RM causes between traumatic and non-traumatic etiologies. Traumatic causes included exercise, earthquake trauma, pro- longed immobilization, and surgery. The pooled prevalence of compartment syndrome in severe RM cases was 7.1% (95% CI: 2.90 to 16.00; p < 0.001; supplementary figure 1). The pooled prevalence of this complication in trauma-induced RM was 4.4% (95% CI: 1.80 to 10.00, p < 0.001; supplemen- tary figure 2). Finally, the publication bias was investigated via funnel plot and Egger’s test, which showed no significant publication bias (supplementary figure 3). 3.2. DIC prevalence in included studies Ten of the included studies reported the prevalence of DIC syndrome or related hematologic failures in RM patients. There were 797 patients with RM in these studies, approx- imately 53% of which were male. RM definitions were dif- ferent in these studies. The RM definition in one study was based on International Classification of Diseases (ICD) ver- sion 9 code related to RM diagnosis (18). Like in articles related to compartment syndrome, most studies diagnosed rhabdomyolysis based on CK levels five times the upper limit of normal levels (>1000 U/L) (19, 26, 27, 33-35). Two studies exclusively included patients with CK levels more than 5000 (24, 29). Criteria for RM diagnosis were not available in one study (32). The primary etiologies in these patients comprised exercise, salicylate intoxication, snake venom, drug toxicity, mush- room poisoning, and exertional heat stroke, as shown in ta- ble 3. The DIC syndrome definition was not reported in most of the included articles. Korean Society on Thrombosis and Hemostasis (KSTH) DIC scoring system and International Society for Thrombosis and Hemostasis (ISTH) DIC scoring system were used as criteria for DIC syndrome diagnosis in two of the studies (26, 35). One study only mentioned hema- tologic failure as outcome of RM (18). DIC syndrome prevalence in RM patients in the included studies ranged from 0% to 40.47%. Our meta-analysis showed the pooled prevalence of 8.3% (95% CI: 03.90 to 16.50; p < 0.001) in all studies (figure 3). Due to the high levels This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index B. Danaei et al. 4 of heterogeneity between these studies, we tried to conduct a sub-group analysis based on RM severity and etiology. How- ever, because of the insufficient number of studies in these sub-groups it was not possible. Publication bias was inves- tigated using funnel plot and Egger’s test, which revealed no significant publication bias in the included studies (supple- mentary figure 4). 4. Discussion Compartment syndrome and disseminated intravascular co- agulation are two of the serious complications that can arise following rhabdomyolysis (36-38). If these complications oc- cur, they can significantly impact the prognosis of the dis- ease and result in morbidity and mortality for RM patients (39). Compartment syndrome is not a rare finding in rhab- domyolysis (4). It can induce ischemia in the affected area, impeding the healing process and exacerbating RM in a self- perpetuating vicious loop (40, 41). DIC can trigger systemic hematologic and circulatory dysfunction, giving rise to life- threatening events such as severe hemorrhage and organ fail- ure (42). Therefore, it is important to investigate the occurrence rate of these complications among individuals with rhabdomyol- ysis. The overall prevalence of compartment syndrome in our study was calculated to be 4% (95% CI: 2.20 to 7.40). It has been shown that the majority of cases of acute compartment syndrome occur after trauma, with an estimated incidence of 7.3 per 100,000 in males and 0.7 per 100,000 in females (9). As we showed in this systematic review, it can result from rhabdomyolysis with both traumatic and non-traumatic ori- gins. However, the rate of compartment syndrome was much higher in the study that included patients with RM due to the earthquake trauma (25). The pooled prevalence of this com- plication in exclusive trauma-induced RM was 4.4% (95% CI: 1.80 to 10.00) in our study, which is close to overall preva- lence. The pooled prevalence of compartment syndrome calculated from studies exclusively reporting severe RM was 7.1% (95% CI: 2.90 to 16.00) and the etiology of RM in all of them was exercise. We classified severe rhabdomyolysis as having creatine kinase (CK) levels exceeding 5000 IU/L. Other studies also have reported that CK levels higher than 4000 IU/L are associated with compartment syndrome (43, 44). In the present study, pooled prevalence of DIC syndrome was calculated to be 8.3% (95% CI: 03.90 to 16.50). Direct com- parison and analysis of the incidence of DIC across studies is challenging due to various factors. For instance, diagnos- tic scoring systems for DIC are not consistently utilized in all hospitals, and different criteria have been employed to diag- nose it (10). The studies in this field may underestimate the actual prevalence of DIC, especially mild, subclinical, and transient episodes, since they might have no clinical mani- festations (4). In one study conducted in Japan the rate of DIC was reported to be 1% in hospitalized patients (45). This rate was reported to be approximately 10 to 30% in intensive care unit (ICU) patients (46-50). Studies also suggested ap- proximate rate of 8 to 33% in patients resuscitated from out- of-hospital cardiac arrest (51, 52) and 36 to 41% in patients with head trauma (53, 54). Our study holds some limitations. The small population size in the included studies and the limited number of these stud- ies were limitations that needed to be noticed. Many articles on DIC and compartment syndrome prevalence pertained to single-center studies, lacked specific definitions of these complications, were published long ago, and did not provide evidence on presence of confounding factors and comorbidi- ties that can play a role in occurrence of these complica- tions. These limitations highlight the need of new researches on the epidemiology of DIC and compartment syndrome in rhabdomyolysis patients with larger population and utilizing standard diagnostic criteria to report their incidence. Furthermore, conduction of meta-analysis on observational studies is challenging due to the inherent limitations of the observational studies. Observational studies cannot ad- dress all potential confounding factors and the heterogeneity among these studies is usually high. Despite efforts to main- tain methodological consistency and control for confound- ing factors, such as sub-group analysis and using random ef- fects model, complete homogeneity cannot be achieved (55). Further studies are needed to investigate prevalence and tolls of these complications in larger populations of RM patients. 5. Conclusion According to our results the pooled prevalence of compart- ment syndrome and DIC in RM patients were 4% (95% CI: 2.20 to 7.40) and 8.3% (95% CI: 03.90 to 16.50) respectively. The rate of compartment syndrome was slightly higher in pa- tients with severe RM and its rate in patients with traumatic RM was close to the overall rate of compartment syndrome in all RM patients. 6. Declarations 6.1. Acknowledgments Not applicable. 6.2. Conflict of interest The authors declare no competing interests. 6.3. Funding and support None. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). 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Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index B. Danaei et al. 8 Table 1: Characteristics of included articles Authors Publication year Study period Country Study design Age group Sampling method Arnautovic et al. (15) 2018 2014-2016 USA R-Cohort Adult Consecutive Bäcker et al. (16) 2019 2012-2017 USA R-Cohort Adult Consecutive Cutler et al. (17) 2015 2010-2014 USA R-Cohort Adult Consecutive Hernández-Contreras et al. (32) 2015 2012-2013 Spain R-Cohort Adult Consecutive Huynh et al. (21) 2016 2013-2014 Australia R-Cohort Adult Consecutive Jabur et al. (29) 2018 2009-2015 UAE R-Cohort Adult Consecutive Kaewput et al. (18) 2021 2003-2014 USA R-Cohort All ages Consecutive Li et al. (25) 2021 2016-2016 Taiwan Cross-sectional Adult Consecutive Luetmer et al. (19) 2020 2003-2015 USA R-Cohort Adult Consecutive Moon et al. (26) 2023 2010-2021 Korea R-Cohort Adult Consecutive Nishimura et al. (33) 2016 2003-2014 Japan R-Cohort Adult Consecutive O’Connor et al. (20) 2014 2010-2013 USA R-Cohort All ages Consecutive Rogliano et al. (27) 2020 2012-2018 France R-Cohort Adult Consecutive Shroff et al. (30) 2022 2018-2019 Singapore R-Cohort Adult Consecutive Tazmini et al. (24) 2017 2011-2015 Norway R-Cohort Adult Consecutive Trakulsrichai et al. (34) 2020 2012-2016 Thailand R-Cohort All ages Consecutive Vangstad et al. (23) 2017 2003-2012 Norway R-Cohort Adult Consecutive Wang et al. (35) 2021 2008-2019 China R-Cohort Adult Consecutive Yim et al. (22) 2019 2013-2017 Australia R-Cohort Adult Consecutive Youssef et al. (28) 2010 2007-2009 Egypt R-Cohort Adult Consecutive R-Cohort: Retrospective Cohort. Table 2: Compartment syndrome prevalence in rhabdomyolysis patients Authors RM definition Male n(%) RM etiology CS definition CS prevalence n(%) Arnautovic et al. (15) CK > 342 41 (33) Exercise NR 0 (0) Bäcker et al. (16) CK ≥ 1000 42 (36) Exercise NR 0 (0) Cutler et al. (17) ICD-9 code 728.88 29 (18) Exercise NR 2 (6.89) Hernández-Contreras et al. (32) NR 11 (5) Exercise NR 0 (0) Huynh et al. (21) CK ≥ 25000 12 (11) Exercise NR 1 (8.33) Jabur et al. (29) CK > 5000 25 (25) Exercise NR 3 (12) Li et al. (25) CK more than 5 times the ULN value 13 (NR) Earthquake trauma NR 4 (30.76) Luetmer et al. (19) CK > 1000 21 (18) Exercise NR 0 (0) Moon et al. (26) CK ≥ 1000 90 (NR) Snake venom NR 1 (1.11) O’Connor et al. (20) CK > 1000 43 (NR) Stimulant drugs toxicity NR 3 (6.97) Rogliano et al. (27) CK ≥ 1000 237 (138) Drug poisoning NR 5 (2.11) Shroff et al. (30) CK > 20000 43 (21) Exercise NR 0 (0) Tazmini et al. (24) CK > 5000 31 (15) Exercise Clinical diagnosis by a surgeon 0 (0) Vangstad et al. (23) Male (18-49 years): CK > 2000 Male (age > 49 years): CK > 1400 Female: CK > 1050 204 (130) Prolonged immobilization NR 1 (0.49) Yim et al. (22) CK > 1000 79 (54) Illicit drug use Requirement of fasciotomy due to CS 3 (3.79) Youssef et al. (28) CK > 1000 7 (4) Roux-en-Y gastric bypass bariatric surgery NR 0 (0) RM: Rhabdomyolysis; CK: Creatine Kinase; ULN: Upper Limit of Normal; CS: Compartment Syndrome; NR: Not Reported; ICD-9: International Classification of Diseases version 9. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index 9 Archives of Academic Emergency Medicine. 2023; 11(1): e55 Table 3: Disseminated intravascular coagulation (DIC) prevalence in rhabdomyolysis patients Authors RM definition Male n(%) RM etiology DIC definition DIC prevalence n(%) Hernández-Contreras et al. (32) NR 11 (5) Exercise NR 0 (0) Jabur et al. (29) CK > 5000 25 (25) Exercise NR 0 (0) Kaewput et al. (18) identified by the ICD-9 diagnosis 728.88 258 (136) Salicylate intoxication Hematological failure 30 (11.62) Luetmer et al. (19) CK > 1000 21 (18) Exercise NR 1 (4.76) Moon et al. (26) CK ≥ 1000 90 (NR) Snake venom KSTH DIC scoring system 1 (1.11) Nishimura et al. (33) CK more than 5 times the ULN value 7 (NR) Snake venom NR 1 (14.28) Rogliano et al. (27) CK ≥ 1000 237 (138) Drug poisoning NR 29 (12.23) Tazmini et al. (24) CK > 5000 31 (15) Exercise NR 0 (0) Trakulsrichai et al. (34) CK > 1000 33 (NR) Mushroom poisoning NR 1 (3.03) Wang et al. (35) CK > 1000 84 (84) Exertional heatstroke ISTH DIC scoring system 34 (40.47) RM: Rhabdomyolysis; CK: Creatine Kinase; ULN: Upper Limit of Normal; NR: Not Reported; ICD-9: International Classification of Diseases version 9; KSTH: Korean Society on Thrombosis and Hemostasis; ISTH: International Society for Thrombosis and Hemostasis. Supplementary figure 1: Meta-analysis on rate of compartment syndrome in studies including patients with severe rhabdomyolysis. Overall Heterogeneity: I2 = 23.12%, P-value = 0.27. CI: confidence interval. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index B. Danaei et al. 10 Figure 1: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart of the studies identified and included in the systematic review. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index 11 Archives of Academic Emergency Medicine. 2023; 11(1): e55 Figure 2: Results of meta-analysis of compartment syndrome prevalence in rhabdomyolysis patients. CI: confidence interval. Figure 3: Results of meta-analysis of disseminated intravascular coagulation (DIC) syndrome prevalence in rhabdomyolysis patients. CI: confidence interval. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index B. Danaei et al. 12 Supplementary figure 2: Meta-analysis on rate of compartment syndrome in studies including patients with traumatic rhabdomyolysis. Overall Heterogeneity: I2 = 54.54%, P-value = 0.01. CI: confidence interval. Supplementary figure 3: Publication bias assessment of included studies reporting compartment syndrome prevalence. Egger’s regression test: Intercept = -1.18, Standard error = 0.90, P-value (2-tailed) = 0.21. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index 13 Archives of Academic Emergency Medicine. 2023; 11(1): e55 Supplementary figure 4: Publication bias assessment of included studies reporting disseminated intravascular coagulation (DIC) syndrome prevalence. Egger’s regression test: Intercept = -1.69, Standard error = 1.28, P-value (2-tailed) = 0.23. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index Introduction Methods Results Discussion Conclusion Declarations References