Reverse shock index multiplied by Glasgow Coma Scale score as a predictor of urgent trauma care and mortality in isolated severe traumatic brain injury: a 10-year nationwide validation study

Reverse shock index multiplied by Glasgow Coma Scale score as a predictor of urgent trauma care and mortality in isolated severe traumatic brain injury: a 10-year nationwide validation study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Reverse shock index multiplied by Glasgow Coma Scale score as a predictor of urgent trauma care and mortality in isolated severe traumatic brain injury: a 10-year nationwide validation study Hiroki Kokeguchi, Chiaki Toida, Taichiro Tsunoyama, Masayuki Iwashita, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7470351/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Patients with traumatic brain injuries (TBIs) have high mortality rates and poor outcomes. Predicting the mortality and need for emergency trauma care is important. There are few urgency indicators in patients with severe TBIs. This study aimed to identify and validate the reverse shock index multiplied by the Glasgow Coma Scale score (rSIG) as an assessment tool for emergency trauma care, including urgent interventions, critical care, and mortality in patients with severe TBIs. Methods: This retrospective validation study included patients of all ages with isolated severe TBIs with Abbreviated Injury Scale (AIS) scores ≥ 3 registered in the Japan Trauma Data Bank (JTDB) dataset between January 1, 2012, and December 31, 2021. The patients were divided into a derivation cohort (January 1, 2012, to December 31, 2018) and a validation cohort (January 1, 2019, to December 31, 2021). The primary outcome measure was a composite outcome of blood transfusions within 24 h of hospital arrival, craniotomy, craterization, intra-cranial pressure (ICP) monitoring, tracheal intubation, intensive care unit (ICU) admission, and in-hospital mortality. Results: A total of 42,375 eligible patients were divided into the derivation (n = 32,483) and validation (n = 9892) cohorts. The derivation cohort included male patients (n=21977, 68%); patients who underwent blood transfusions within 24 h of hospital arrival, craniotomies, and craterizations (n=3114, n=3678, and n=1277, respectively; 10%, 11%, and 4% respectively). The median rSIG and actual survival rate of the derivation cohort were 21.8 (interquartile range [IQR], 14.9–28.0) and 88%. The cut-off point of the rSIG was 16.21. Abnormal rSIGs were associated with a greater odds ratio (OR) for blood transfusions within 24 h of arrival (OR, 4.03; 95% confidence interval [CI], 3.59-4.53), craniotomies (2.86 [2.55-3.21]), craterization (2.61 [2.14-3.17]), ICP monitoring (4.91 [3.96-6.10]), tracheal intubation (6.40 [5.71-7.17]), ICU admission (2.10 [1.93-2.29]), and in-hospital mortality (8.49 [7.45-9.63]) than those with normal rSIGs. Conclusions: The rSIG may be a useful predictor of urgent interventions and neurological critical care, and in-hospital mortality in patients with isolated severe TBIs in the emergency hospital settings. traumatic brain injury reverse shock index multiplied by the Glasgow Coma Scale score emergency care critical care Japan Trauma Data Bank Figures Figure 1 Background Globally, 27–69 million people sustain traumatic brain injuries (TBIs) each year, of which 5.48 million sustain severe TBIs [ 1 , 2 ]. TBIs account for approximately 30% of all trauma-related deaths [ 3 ] and have a high mortality rate. A previous Japanese study reported that the in-hospital mortality trends of all patients with severe TBIs significantly decreased from 2009 to 2018; however, the in-hospital mortality trend of patients with a Glasgow Coma Scale (GCS) score between 3 and 8 did not decrease [ 4 ]. As patients with severe TBIs often have high mortality rates and poor outcomes, it is important to predict mortality and the need for urgent trauma care. In Japan, the Trauma and Injury Severity Score (TRISS) and Revised Trauma Score (RTS) are the most commonly used methods for calculating the survival probability and physiological severity in patients with trauma. Several previous studies have shown that the RTS, TRISS, and the reverse shock index multiplied by the Glasgow Coma Scale Score (rSIG) may be useful for predicting mortality in patients with trauma [ 5 – 7 ]. However, despite the need for indicators that can easily determine whether urgent interventions (such as blood transfusions within 24 h of hospital arrival or surgical procedures) and neurological critical care are needed to improve the prognosis of patients with severe trauma [ 4 , 8 ], calculation of the RTS and TRISS requires complex calculations using coefficients, which makes the assessment less rapid. On the other hand, the rSIG consists of the systolic blood pressure (SBP) divided by heart rate (HR) multiplied by the GCS score and can be easily calculated in the emergency setting [ 7 ]. Because of the rapid and simple nature of the rSIG, it is expected to be used in real-time in clinical practice for predicting severity and mortality in patients with trauma. In recent years, several previous studies have reported that the rSIG may be useful in predicting not only mortality but also the need for urgent interventions [ 7 , 9 – 12 ]. However, the validity of the rSIG for predicting urgent interventions for patients with isolated severe TBIs has never been proved. This study aimed to identify and validate the rSIG as an assessment tool for emergency trauma care, including urgent interventions and critical care, as well as mortality in patients with severe TBIs. Methods Study setting and population Trauma care systems in Japan In 2021, the Japanese Association for the Surgery of Trauma (JAST) recommended the establishment of regional trauma care systems to provide trauma care and rehabilitation for patients with severe trauma [13]. However, trauma care systems in Japan have not yet been established, and many injured patients are transported to the nearest tertiary emergency medical centers. To establish and maintain the trauma care systems, validation is essential. The Japan Trauma Data Bank (JTDB) was established by the JAST (Trauma Registry Committee), the Japanese Association for Acute Medicine (Committee for Clinical Care Evaluation), and is also managed by Japan Trauma Care and Research (JTCR) [14]. This retrospective nationwide validation study was conducted based on data obtained from the JTDB, which registers the data of patients with injuries or burns and records prehospitalization and hospital-related information. The JAST recommends defining patients with severe trauma as patients with Abbreviated Injury Scale (AIS) scores of ≥3 based on anatomical severity scores, which are the most common indicators in Japan. Therefore, the criteria for cases to be registered in the JTDB are patients with AIS scores of ≥3, who are defined as having severe trauma. The JTDB includes data on demographic characteristics, comorbidities, injury types, mechanism of injury, means of transportation, vital signs, AIS scores, prehospital or in-hospital procedures, injury diagnosis as indicated by the AIS score, and clinical outcomes. The JTDB underwent a system change in April 2009; therefore, it had been using the AIS 90 coding scale until 2008 and is now using the AIS 2005 updated 2008 coding scale. Participants and study design The JTDB dataset used in this study included 340,544 patients registered between January 1, 2012, and December 31, 2021. The inclusion criteria were patients with severe TBIs with AIS scores of ≥ 3 who were transferred from the scene of injury by ambulance or helicopter. Patients with burns, penetrating injuries, injury region other than the head with AIS scores of ≥ 3, survivors with AIS scores of 6, cardiac arrest upon hospital arrival, and missing key data regarding age, injury mechanism, Injury Severity Score (ISS), vital sign required to calculate the rSIG upon hospital arrival, or survival outcomes, were excluded from this study. Figure 1 shows a flow diagram of the patient selection process used in this study. The eligible patients were divided into a derivation cohort registered in the JTDB from January 1, 2012, to December 31, 2018, and a validation cohort registered in the JTDB from January 1, 2019, to December 31, 2021 (Figure 1). To develop and validate our prediction model, we performed an internal validation [15] with a time-series division of the derivation and validation cohorts. The former consisted of the first seven out of the total ten-year period, and the latter of the last three years. Data collection Data sources All healthcare facilities involved in trauma care are eligible to participate in the JTDB; however, case registration in the JTDB must be authorized by the JTCR. Only facilities authorized by the JTCR can receive the de-identified data from the JTDB. The following variables were collected from the JTDB dataset: demographic characteristics (age [years], sex, and injury mechanism), clinical parameters (AIS of the injured region, the RTS, SBP, HR, and GCS at hospital arrival), urgent interventions provided (blood transfusion within 24 h of hospital arrival, craniotomy, and craterization), neurological intensive care (intracranial pressure [ICP] monitoring, tracheal intubation, and Intensive Care Unit [ICU] admission), and length of treatment (days) (mechanical ventilation, ICU stay, and hospital stay). The rSIG was calculated as follows: Ethics statement The Institutional Ethics Committees of Shinshu University School of Medicine Graduate School of Medicine approved this study (approval number 2024-795 on October 8, 2024). Approval for data access was provided by the JAST (Trauma Registry Committee). Due to the observational study design, the need for consent for study participation was waived by the institutional ethics committees that approved our study. Statistical analyses Measurements, study size, and quantitative variables The primary outcome measure was a composite outcome of blood transfusions within 24 h of hospital arrival, craniotomy, craterization, ICP monitoring, tracheal intubation, ICU admission, and in-hospital mortality. Urgent interventions were defined as variables affecting in-hospital mortality due to severe TBIs with reference to a Japanese cohort study [7]. Optimal rSIG cutoff points that had the best predictability for urgent interventions were calculated to predict urgent interventions using the Youden method in the derivation cohort. Patients were subsequently classified into abnormal or normal rSIG groups in the validation cohort with reference to a previous validation study [16]. The abnormal rSIG group included patients with rSIG values below the cutoff points. Results are expressed as medians and interquartile ranges (IQRs) (25 th –75 th percentile) for continuous variables and as frequencies (%) for categorical variables. Variables were compared using the Kruskal–Wallis tests for continuous variables and Fisher’s exact test for categorical variables. Univariate logistic regression was fit for urgent intervention and in-hospital mortality based on the abnormal rSIG group compared with the normal rSIG group in the validation cohort. The odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality were calculated using a logistic regression model. Additionally, we performed a power analysis due to the retrospective nature of the study design, in which we obtained 1.00 as the power using the total number of patients to detect the difference in two mortality rates of 12 and 14% with 0.05 as an alpha level. All statistical analyses were performed using STATA/SE software (version 17.0; StataCorp, College Station, TX, USA). Statistical significance was defined as a two-tailed p-value of <0.05. Patient and public involvement The patients and the public were not involved in the design, conduct, reporting, or dissemination of the study. We intend not to directly disseminate our findings to the participants but rather to disseminate them through the publication of this study. Results During the 10-year study period, 42,375 patients were eligible for inclusion and were divided into derivation (n = 32,483) and validation (n = 9892) cohorts (Fig. 1 ). The median age of the derivation cohort was 67 years (IQR, 46–79). The derivation cohort included male patients (n = 21977, 68%); patients with AIS scores ≥ 3, 4, 5, and 6 (n = 12060, n = 13360, n = 7030, and n = 33, respectively; 37%, 41%, 22%, and 0.1%, respectively); and patients who underwent blood transfusions within 24 h of hospital arrival craniotomies, and craterizations (n = 3114, n = 3678, and n = 1277, respectively; 10%, 11%, and 4%, respectively). The median rSIG and actual survival rate of the derivation cohort were 21.8 (IQR, 14.9–28.0) and 88% (Table 1). [Insert Table 1 here] The cut-off point of the rSIG, which was calculated using the Youden method to predict the need for urgent interventions in the derivation cohort, was 16.21. The validation cohort included patients with abnormal rSIG results (n = 3129, 32%). Table 2 shows a comparison between the abnormal and normal rSIG groups in the validation cohort. The median ISS and in-hospital mortality rates of patients with abnormal rSIGs were significantly higher (20 vs. 14 and 33% vs. 6%, respectively; p < 0.01), and the median RTS and rSIG were significantly lower than those of patients with normal rSIGs (5.97 vs. 7.84 and 9.8 vs. 25.5, respectively; p < 0.01). A greater number of patients with abnormal rSIGs underwent urgent interventions (blood transfusions within 24 h of arrival, craniotomies, or craterization), neurological critical care (ICP monitoring, tracheal intubation, or ICU admission), and long treatment durations (mechanical ventilation, ICU stay, and hospital stay) than those with normal rSIGs. Univariate logistic regression analysis of abnormal rSIGs for outcome variables in the validation cohort showed that abnormal rSIGs were associated with a greater OR for urgent interventions, ICU admission, and in-hospital mortality. The ORs for abnormal rSIGs in the validation cohort are summarized in Table 3. [Insert Table 2 here] [Insert Table 3 here] Discussion We evaluated the validity of the rSIG in predicting urgent interventions, neurological critical care, and mortality in patients with isolated severe TBIs from the JTDB from 2012 to 2021. This study showed that an abnormal rSIG of < 16.21 might be a predictor of urgent trauma care and mortality in patients with isolated severe TBIs. Patients with severe TBIs and high mortality risks should promptly receive urgent interventions and neurological critical care [ 4 , 5 , 8 ]. Therefore, an accurate assessment tool of not only mortality risk but also the need for urgent trauma care is essential. This study found that the rSIG could predict both of the aforementioned factors. Several factors may be responsible for this predictive ability of the rSIG in patients with severe TBIs. First, the predictive variables of the rSIG contain both the shock index, which has proven to be a more sensitive marker of shock than traditional vital signs alone in trauma patients, and the GCS score, which has proven to be an accurate assessment tool for neurological status. Several previous studies showed that patients with severe TBIs with GCS scores of ≤ 8 had a higher mortality risk and requirement for urgent interventions [ 4 , 5 , 11 ]. This suggests that the GCS score may have a predictive capacity for assessing the mortality risk and the need for urgent trauma care in patients with severe TBIs. Second, we calculated the cutoff points of the rSIG in patients with isolated severe TBIs who had a mortality risk and needed urgent trauma care. A previous study showed that the rSIG was less accurate than the RTS for predicting mortality in adult patients with isolated TBIs [ 10 ]. The difference in predictive accuracy may be due to the different injury severities of the eligible cohort with AIS scores of ≥ 2 compared to our study’s cohort with AIS scores of ≥ 3. Predictive accuracy may differ depending on the target group. The rSIG is a predictive tool for easily and promptly calculating numerical objective indicators using predictive variables that can be measured without complicated equipment; therefore, it can be applied in clinical practice. Furthermore, the RTS, the most commonly used physiological severity scoring tool in Japan, is calculated using coefficients and code values based on the GCS score, SBP, and respiratory rate (RR). Therefore, predictive tools such as the RTS, which require complicated calculations, are not practical for promptly determining whether urgent trauma care in critically injured patients with raised mortality risks is necessary in the emergency setting. However, the rSIG has a strong advantage in clinical settings because the assessment of predictive variables for the rSIG and the calculation of the rSIG variables is extremely simple and fast. The obvious place for the rSIG in the pre-hospital setting when deciding regarding transfer to trauma centers, and the limitation of the rSIG in the in-hospital setting is that, on its own, it might not help direct treatment. In the prehospital setting, the rSIG could be used as an advantageous tool to triage cases that are prioritized for transport to a trauma center rather than to a nearby tertiary emergency medical center. However, as this study was limited to isolated severe TBIs with AISs of ≥ 3, the appropriateness of applying the rSIG score was limited to selecting a transport destination for injured patients suspected of TBIs only from the injury mechanism and physical signs in the prehospital setting. In the in-hospital setting, anatomical diagnosis by head CT is essential to determine the treatment strategy, and it is not easy to determine the treatment strategy only from the rSIG score. However, this study included patients with isolated severe TBIs of AIS ≥ 3, who have the potential to have severe intracranial lesions detected on head CT, it may be possible to calculate the risk of requiring urgent interventions and neurological critical care. It may be possible to calculate the risk of a potential indication for urgent interventions or neurological critical care in patients already diagnosed with severe TBIs. Moreover, when considering the clinical application of the rSIG, cutoff points need to be considered. This study identified the rSIG cutoff points for predicting the need for urgent interventions in patients with isolated severe TBIs as 16.21. In several previous studies, different rSIG cutoff points for predicting the need for urgent interventions were established according to the study area, age, severity, and injury region of the eligible cohort [ 9 , 11 , 12 ]. Moreover, using the rSIG independently to predict the need for urgent trauma care may result in over- and under-triage. Therefore, when setting the cutoff points of the rSIG to assess the need for urgent trauma care in patients with severe trauma, the available medical resources in the region should be considered. This study had several limitations. First, the retrospective study design and certain missing data in the JTDB impaired the precision of this analysis, and there was selection bias because not all Japanese hospitals participated in the registration of the JTDB. Second, although different mortality rates have been observed among patients with TBIs across various age groups − particularly with higher mortality rates in younger children and older adults compared to other age groups [ 15 ] – this study did not evaluate the optimal cutoff points of the rSIG for predicting the need for urgent interventions in patients with TBIs based on age. Third, this study also lacks external validation and comparison with other scoring systems. In the future, we aim to determine the optimal cutoff points according to TBI severity within each age group and external and comparative validation with other predicting systems, including the rSIG, in several regions to improve trauma care. Conclusions The rSIG may be a useful predictor of urgent interventions and neurological critical care, including blood transfusions within 24 h of hospital arrival, craniotomy, craterization, ICP monitoring, tracheal intubation, ICU admission, and in-hospital mortality, in patients with isolated severe TBIs in the emergency hospital settings. In the future, the rSIG may assist both emergency medical service providers in prehospital settings and emergency physicians in hospital settings, for early intervention and better outcomes in patients with severe TBIs. Abbreviations AIS Abbreviated Injury Scale CI confidence interval GCS Glasgow Coma Scale HR heart rate ICP intracranial pressure ICU intensive care unit IQR interquartile range ISS Injury Severity Score JAST Japanese Association for the Surgery of Trauma JTCR Japan Trauma Care and Research JTDB Japan Trauma Data Bank OR odds ratio RR respiratory rate rSIG reverse shock index multiplied by the Glasgow Coma Scale score RTS Revised Trauma Score SBP systolic blood pressure TBI traumatic brain injury TRISS Trauma and Injury Severity Score Declarations Ethical approval and consent to participate: The study was approved by the institutional Ethics Committee of Shinshu University School of Medicine Graduate School of Medicine (approval no. 2024-795, October 8, 2024). The need for consent was waived by the Institutional Ethics Committee that approved our study, owing to the observational nature of the study design, as per the Personal Information Protection Law and National Research Ethics Guidelines in Japan. Consent for publication: Not applicable. Availability of data and materials: The dataset and/or analysis results of this study have not been made publicly available because their dissemination was not approved by the Ethics Committee. Competing interest: The authors declare that they have no competing interest. Funding: None. Author contributions: Conceptualization, C.T. and H.K.; methodology, C.T.; validation, H.K., C.T., T.T., M.I., and M.M.; formal analysis, C.T.; investigation, C.T.; resources, C.T. and H.K.; data curation, C.T.; writing, original draft preparation, H.K.; writing, review and editing, H.K., C.T., T.T., M.I., and M.M.; visualization, H.K. and C.T.; supervision, T.T., M.I., and M.M.; project administration and funding acquisition, C.T. All authors have read and agreed to the final version of the manuscript. Acknowledgments: Takeru Abe (Integrated Science Education and Research Center, Fukushima Medical University), who provided purely technical help with the statistical analysis and writing assistance. References GBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. 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The Japanese Association for the Surgery of Trauma Inclusive Trauma Care System Investigation Committee Report: Chiiki ni okeru houkatsuteki gaishou shinryou taisei ni tsuite no teigen Recommendations on Inclusive Trauma Care System in the Community. J. Jpn. Assoc. Surg. Trauma in press. http://www.jasthp.org/pdf/ JAST_inclusive_trauma_care_system_statement.pdf. Accessed 25 March 2021. Japan Trauma Data Bank report 2022. https://www.jtcr-jatec.org/traumabank/dataroom/data/JTDB2022.pdf/ Accessed 1 Febr 2025. Steyerberg EW. Clinical Prediction Models: a practical approach to development, validation, and updating. 2 nd ed. New Yortk: Springer; 2019. Reppuci ML, Cooper E, Nolan MM, Lyttle BD, Gallagher LT, Jujare S, et al. Use of prehospital reverse shock index times Glasgow Coma Scale to identify children who require the most immediate trauma care. J Trauma Acute Care Surg. 2023;95:347-53. doi:10.1097/ta.0000000000003903. Chuang JF, Rau CS, Wu SC, Liu HT, Hsu SY, Hsieh HY, et al. Use of the reverse shock index for identifying high-risk patients in a five-level triage system. Scand J Trauma Resusc Emerg Med. 2016;24:12. doi:10.1186/s13049-016-0208-5. Tables Tables 1 to 3 are available in the Supplementary Files section Additional Declarations No competing interests reported. Supplementary Files Table1.xlsx Table2.xlsx Table3.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7470351","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":506305922,"identity":"48408c1a-786a-4eef-9fc1-0ed9ba5eaa71","order_by":0,"name":"Hiroki Kokeguchi","email":"","orcid":"","institution":"Teikyo University School of Medicine Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hiroki","middleName":"","lastName":"Kokeguchi","suffix":""},{"id":506305923,"identity":"bb5390ac-f534-4001-ba52-94d3fcb0258a","order_by":1,"name":"Chiaki Toida","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYFACxgYJMM3ewMCQABFKwKuBB66F5wDRWhgYIFok8CtEAHv25sYbPxgO2/XPfGO64eEOBnn+BoZnD/DawnOw2bKH4XDyjNs5ZjcSzzAYzjjAkG6AV4tEYpsE77/DyQbSIC1tDIwbGBjSJAhpkfwDtMVA8gxYiz1RWqR5gH4xkOABa0kkrOXMwWZrGYb0BIkzaWVALRLJMw4T8At7e/vDm28YrO352w9vu/mzzca2v70n7QE+LVDQnNgAYQCdxMyTRoQOhjp7ZJuPEaNlFIyCUTAKRg4AAAECRuVX5Z8XAAAAAElFTkSuQmCC","orcid":"","institution":"Shinshu University School of Medicine Graduate School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Chiaki","middleName":"","lastName":"Toida","suffix":""},{"id":506305924,"identity":"1dd94350-ef8b-4993-bdd2-bfc60d56ca37","order_by":2,"name":"Taichiro Tsunoyama","email":"","orcid":"","institution":"Teikyo University School of Medicine Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Taichiro","middleName":"","lastName":"Tsunoyama","suffix":""},{"id":506305925,"identity":"fdd1b2f4-bfb4-4b08-b57b-c1ad5d74130d","order_by":3,"name":"Masayuki Iwashita","email":"","orcid":"","institution":"Teikyo University School of Medicine Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Masayuki","middleName":"","lastName":"Iwashita","suffix":""},{"id":506305927,"identity":"53689f76-b0d3-462a-9d75-de7c0d7e4fcb","order_by":4,"name":"Yasufumi Miyake","email":"","orcid":"","institution":"Teikyo University School of Medicine Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yasufumi","middleName":"","lastName":"Miyake","suffix":""}],"badges":[],"createdAt":"2025-08-27 09:53:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7470351/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7470351/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90318051,"identity":"1c40b6fe-36b2-4f9c-a4d0-41b17e6c88cf","added_by":"auto","created_at":"2025-09-01 10:30:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":52957,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow diagram of the patient selection and inclusion process.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJTDB, Japanese Trauma Data Bank; AIS, Abbreviated Injury Scale; rSIG, reverse shock index multiplied by the Glasgow Coma Scale score\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7470351/v1/661c0542ffcd423385359f8e.png"},{"id":90321634,"identity":"c95e8e77-5204-4623-b1f6-2b398506f0c8","added_by":"auto","created_at":"2025-09-01 10:54:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":571359,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7470351/v1/b417a5c5-d41b-452f-be87-b6a18a2689f3.pdf"},{"id":90318058,"identity":"23fdab84-ebf5-4f68-aee1-a580401c11b5","added_by":"auto","created_at":"2025-09-01 10:30:10","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":12559,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7470351/v1/d6142cd944df95d067ebe145.xlsx"},{"id":90318056,"identity":"70af469c-2b39-4f13-8069-e4f3d83c2d9a","added_by":"auto","created_at":"2025-09-01 10:30:10","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":13012,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7470351/v1/8f4a443cc7a8f4609fd18e22.xlsx"},{"id":90318874,"identity":"26655a62-a7e6-462a-b047-acbf43af0132","added_by":"auto","created_at":"2025-09-01 10:38:10","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":11511,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7470351/v1/e0317e2fb0e8f855a85a9326.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Reverse shock index multiplied by Glasgow Coma Scale score as a predictor of urgent trauma care and mortality in isolated severe traumatic brain injury: a 10-year nationwide validation study","fulltext":[{"header":"Background","content":"\u003cp\u003eGlobally, 27\u0026ndash;69\u0026nbsp;million people sustain traumatic brain injuries (TBIs) each year, of which 5.48\u0026nbsp;million sustain severe TBIs [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. TBIs account for approximately 30% of all trauma-related deaths [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] and have a high mortality rate. A previous Japanese study reported that the in-hospital mortality trends of all patients with severe TBIs significantly decreased from 2009 to 2018; however, the in-hospital mortality trend of patients with a Glasgow Coma Scale (GCS) score between 3 and 8 did not decrease [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAs patients with severe TBIs often have high mortality rates and poor outcomes, it is important to predict mortality and the need for urgent trauma care. In Japan, the Trauma and Injury Severity Score (TRISS) and Revised Trauma Score (RTS) are the most commonly used methods for calculating the survival probability and physiological severity in patients with trauma. Several previous studies have shown that the RTS, TRISS, and the reverse shock index multiplied by the Glasgow Coma Scale Score (rSIG) may be useful for predicting mortality in patients with trauma [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, despite the need for indicators that can easily determine whether urgent interventions (such as blood transfusions within 24 h of hospital arrival or surgical procedures) and neurological critical care are needed to improve the prognosis of patients with severe trauma [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], calculation of the RTS and TRISS requires complex calculations using coefficients, which makes the assessment less rapid. On the other hand, the rSIG consists of the systolic blood pressure (SBP) divided by heart rate (HR) multiplied by the GCS score and can be easily calculated in the emergency setting [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Because of the rapid and simple nature of the rSIG, it is expected to be used in real-time in clinical practice for predicting severity and mortality in patients with trauma. In recent years, several previous studies have reported that the rSIG may be useful in predicting not only mortality but also the need for urgent interventions [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, the validity of the rSIG for predicting urgent interventions for patients with isolated severe TBIs has never been proved.\u003c/p\u003e\u003cp\u003eThis study aimed to identify and validate the rSIG as an assessment tool for emergency trauma care, including urgent interventions and critical care, as well as mortality in patients with severe TBIs.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy setting and population\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eTrauma care systems in Japan\u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn 2021, the Japanese Association for the Surgery of Trauma (JAST) recommended the establishment of regional trauma care systems to provide trauma care and rehabilitation for patients with severe trauma [13]. However, trauma care systems in Japan have not yet been established, and many injured patients are transported to the nearest tertiary emergency medical centers. To establish and maintain the trauma care systems, validation is essential. The Japan Trauma Data Bank (JTDB) was established by the JAST (Trauma Registry Committee), the Japanese Association for Acute Medicine (Committee for Clinical Care Evaluation), and is\u0026nbsp;also managed by Japan Trauma Care and Research (JTCR) [14]. This retrospective nationwide validation study was conducted based on data obtained from the JTDB, which registers the data of patients with injuries or burns and records prehospitalization and hospital-related information. The JAST recommends defining patients with severe trauma as patients with Abbreviated Injury Scale (AIS) scores of \u0026ge;3 based on anatomical severity scores, which are the most common indicators in Japan. Therefore, the criteria for cases to be registered in the JTDB are patients with AIS scores of \u0026ge;3, who are defined as having severe trauma. The JTDB includes data on demographic characteristics, comorbidities, injury types, mechanism of injury, means of transportation, vital signs, AIS scores, prehospital or in-hospital procedures, injury diagnosis as indicated by the AIS score, and clinical outcomes. The JTDB underwent a system change in April 2009; therefore, it had been using the AIS 90 coding scale until 2008 and is now using the AIS 2005 updated 2008 coding scale.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eParticipants and study design\u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe JTDB dataset used in this study included 340,544 patients registered between January 1, 2012, and December 31, 2021. The inclusion criteria were patients with severe TBIs with AIS scores of \u0026ge; 3 who were transferred from the scene of injury by ambulance or helicopter. Patients with burns, penetrating injuries, injury region other than the head with AIS scores of \u0026ge; 3, survivors with AIS scores of 6, cardiac arrest upon hospital arrival, and missing key data regarding age, injury mechanism, Injury Severity Score (ISS), vital sign required to calculate the rSIG upon hospital arrival, or survival outcomes, were excluded from this study. Figure 1 shows a flow diagram of the patient selection process used in this study. The eligible patients were divided into a derivation cohort registered in the JTDB from January 1, 2012, to December 31, 2018, and a validation cohort registered in the JTDB from January 1, 2019, to December 31, 2021 (Figure 1). To develop and validate our prediction model, we performed an internal validation [15] with a time-series division of the derivation and validation cohorts. The former consisted of the first seven out of the total ten-year period, and the latter of the last three years.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData collection\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eData sources\u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll healthcare facilities involved in trauma care are eligible to participate in the JTDB; however, case registration in the JTDB must be authorized by the JTCR. Only facilities authorized by the JTCR can receive the de-identified data from the JTDB. The following variables were collected from the JTDB dataset: demographic characteristics (age [years], sex, and injury mechanism), clinical parameters (AIS of the injured region, the RTS, SBP, HR, and GCS at hospital arrival), urgent interventions provided (blood transfusion within 24 h of hospital arrival, craniotomy, and craterization), neurological intensive care (intracranial pressure [ICP] monitoring, tracheal intubation, and Intensive Care Unit [ICU] admission), and length of treatment (days) (mechanical ventilation, ICU stay, and hospital stay). The rSIG was calculated as follows:\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"data:image/png;base64,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\"\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics statement\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Institutional Ethics Committees of Shinshu University School of Medicine Graduate School of Medicine approved this study (approval number 2024-795 on October 8, 2024). Approval for data access was provided by the JAST (Trauma Registry Committee). Due to the observational study design, the need for consent for study participation was waived by the institutional ethics committees that approved our study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical analyses\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eMeasurements, study size, and quantitative variables\u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome measure was a composite outcome of blood transfusions within 24 h of hospital arrival, craniotomy, craterization, ICP monitoring, tracheal intubation, ICU admission, and in-hospital mortality. Urgent interventions were defined as variables affecting in-hospital mortality due to severe TBIs with reference to a Japanese cohort study [7].\u003c/p\u003e\n\u003cp\u003eOptimal rSIG cutoff points that had the best predictability for urgent interventions were calculated to predict urgent interventions using the Youden method in the derivation cohort. Patients were subsequently classified into abnormal or normal rSIG groups in the validation cohort with reference to a previous validation study [16]. The abnormal rSIG group included patients with rSIG values below the cutoff points.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResults are expressed as medians and interquartile ranges (IQRs) (25\u003csup\u003eth\u003c/sup\u003e\u0026ndash;75\u003csup\u003eth\u003c/sup\u003e percentile) for continuous variables and as frequencies (%) for categorical variables. Variables were compared using the Kruskal\u0026ndash;Wallis tests for continuous variables and Fisher\u0026rsquo;s exact test for categorical variables. Univariate logistic regression was fit for urgent intervention and in-hospital mortality based on the abnormal rSIG group compared with the normal rSIG group in the validation cohort. The odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality were calculated using a logistic regression model. Additionally, we performed a power analysis due to the retrospective nature of the study design, in which we obtained 1.00 as the power using the total number of patients to detect the difference in two mortality rates of 12 and 14% with 0.05 as an alpha level. All statistical analyses were performed using STATA/SE software (version 17.0; StataCorp, College Station, TX, USA). Statistical significance was defined as a two-tailed p-value of \u0026lt;0.05.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatient and public involvement\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patients and the public were not involved in the design, conduct, reporting, or dissemination of the study. We intend not to directly disseminate our findings to the participants but rather to disseminate them through the publication of this study.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the 10-year study period, 42,375 patients were eligible for inclusion and were divided into derivation (n\u0026thinsp;=\u0026thinsp;32,483) and validation (n\u0026thinsp;=\u0026thinsp;9892) cohorts (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe median age of the derivation cohort was 67 years (IQR, 46\u0026ndash;79). The derivation cohort included male patients (n\u0026thinsp;=\u0026thinsp;21977, 68%); patients with AIS scores\u0026thinsp;\u0026ge;\u0026thinsp;3, 4, 5, and 6 (n\u0026thinsp;=\u0026thinsp;12060, n\u0026thinsp;=\u0026thinsp;13360, n\u0026thinsp;=\u0026thinsp;7030, and n\u0026thinsp;=\u0026thinsp;33, respectively; 37%, 41%, 22%, and 0.1%, respectively); and patients who underwent blood transfusions within 24 h of hospital arrival craniotomies, and craterizations (n\u0026thinsp;=\u0026thinsp;3114, n\u0026thinsp;=\u0026thinsp;3678, and n\u0026thinsp;=\u0026thinsp;1277, respectively; 10%, 11%, and 4%, respectively). The median rSIG and actual survival rate of the derivation cohort were 21.8 (IQR, 14.9\u0026ndash;28.0) and 88% (Table\u0026nbsp;1).\u003c/p\u003e\u003cp\u003e[Insert Table\u0026nbsp;1 here]\u003c/p\u003e\u003cp\u003eThe cut-off point of the rSIG, which was calculated using the Youden method to predict the need for urgent interventions in the derivation cohort, was 16.21. The validation cohort included patients with abnormal rSIG results (n\u0026thinsp;=\u0026thinsp;3129, 32%). Table\u0026nbsp;2 shows a comparison between the abnormal and normal rSIG groups in the validation cohort. The median ISS and in-hospital mortality rates of patients with abnormal rSIGs were significantly higher (20 vs. 14 and 33% vs. 6%, respectively; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), and the median RTS and rSIG were significantly lower than those of patients with normal rSIGs (5.97 vs. 7.84 and 9.8 vs. 25.5, respectively; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). A greater number of patients with abnormal rSIGs underwent urgent interventions (blood transfusions within 24 h of arrival, craniotomies, or craterization), neurological critical care (ICP monitoring, tracheal intubation, or ICU admission), and long treatment durations (mechanical ventilation, ICU stay, and hospital stay) than those with normal rSIGs.\u003c/p\u003e\u003cp\u003eUnivariate logistic regression analysis of abnormal rSIGs for outcome variables in the validation cohort showed that abnormal rSIGs were associated with a greater OR for urgent interventions, ICU admission, and in-hospital mortality. The ORs for abnormal rSIGs in the validation cohort are summarized in Table\u0026nbsp;3.\u003c/p\u003e\u003cp\u003e[Insert Table\u0026nbsp;2 here]\u003c/p\u003e\u003cp\u003e[Insert Table\u0026nbsp;3 here]\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe evaluated the validity of the rSIG in predicting urgent interventions, neurological critical care, and mortality in patients with isolated severe TBIs from the JTDB from 2012 to 2021. This study showed that an abnormal rSIG of \u0026lt;\u0026thinsp;16.21 might be a predictor of urgent trauma care and mortality in patients with isolated severe TBIs.\u003c/p\u003e\u003cp\u003ePatients with severe TBIs and high mortality risks should promptly receive urgent interventions and neurological critical care [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Therefore, an accurate assessment tool of not only mortality risk but also the need for urgent trauma care is essential. This study found that the rSIG could predict both of the aforementioned factors. Several factors may be responsible for this predictive ability of the rSIG in patients with severe TBIs. First, the predictive variables of the rSIG contain both the shock index, which has proven to be a more sensitive marker of shock than traditional vital signs alone in trauma patients, and the GCS score, which has proven to be an accurate assessment tool for neurological status. Several previous studies showed that patients with severe TBIs with GCS scores of \u0026le;\u0026thinsp;8 had a higher mortality risk and requirement for urgent interventions [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This suggests that the GCS score may have a predictive capacity for assessing the mortality risk and the need for urgent trauma care in patients with severe TBIs. Second, we calculated the cutoff points of the rSIG in patients with isolated severe TBIs who had a mortality risk and needed urgent trauma care. A previous study showed that the rSIG was less accurate than the RTS for predicting mortality in adult patients with isolated TBIs [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The difference in predictive accuracy may be due to the different injury severities of the eligible cohort with AIS scores of \u0026ge;\u0026thinsp;2 compared to our study\u0026rsquo;s cohort with AIS scores of \u0026ge;\u0026thinsp;3. Predictive accuracy may differ depending on the target group.\u003c/p\u003e\u003cp\u003eThe rSIG is a predictive tool for easily and promptly calculating numerical objective indicators using predictive variables that can be measured without complicated equipment; therefore, it can be applied in clinical practice. Furthermore, the RTS, the most commonly used physiological severity scoring tool in Japan, is calculated using coefficients and code values based on the GCS score, SBP, and respiratory rate (RR).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eTherefore, predictive tools such as the RTS, which require complicated calculations, are not practical for promptly determining whether urgent trauma care in critically injured patients with raised mortality risks is necessary in the emergency setting. However, the rSIG has a strong advantage in clinical settings because the assessment of predictive variables for the rSIG and the calculation of the rSIG variables is extremely simple and fast. The obvious place for the rSIG in the pre-hospital setting when deciding regarding transfer to trauma centers, and the limitation of the rSIG in the in-hospital setting is that, on its own, it might not help direct treatment. In the prehospital setting, the rSIG could be used as an advantageous tool to triage cases that are prioritized for transport to a trauma center rather than to a nearby tertiary emergency medical center. However, as this study was limited to isolated severe TBIs with AISs of \u0026ge;\u0026thinsp;3, the appropriateness of applying the rSIG score was limited to selecting a transport destination for injured patients suspected of TBIs only from the injury mechanism and physical signs in the prehospital setting. In the in-hospital setting, anatomical diagnosis by head CT is essential to determine the treatment strategy, and it is not easy to determine the treatment strategy only from the rSIG score. However, this study included patients with isolated severe TBIs of AIS\u0026thinsp;\u0026ge;\u0026thinsp;3, who have the potential to have severe intracranial lesions detected on head CT, it may be possible to calculate the risk of requiring urgent interventions and neurological critical care. It may be possible to calculate the risk of a potential indication for urgent interventions or neurological critical care in patients already diagnosed with severe TBIs.\u003c/p\u003e\u003cp\u003eMoreover, when considering the clinical application of the rSIG, cutoff points need to be considered. This study identified the rSIG cutoff points for predicting the need for urgent interventions in patients with isolated severe TBIs as 16.21. In several previous studies, different rSIG cutoff points for predicting the need for urgent interventions were established according to the study area, age, severity, and injury region of the eligible cohort [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Moreover, using the rSIG independently to predict the need for urgent trauma care may result in over- and under-triage. Therefore, when setting the cutoff points of the rSIG to assess the need for urgent trauma care in patients with severe trauma, the available medical resources in the region should be considered.\u003c/p\u003e\u003cp\u003eThis study had several limitations. First, the retrospective study design and certain missing data in the JTDB impaired the precision of this analysis, and there was selection bias because not all Japanese hospitals participated in the registration of the JTDB. Second, although different mortality rates have been observed among patients with TBIs across various age groups\u0026thinsp;\u0026minus;\u0026thinsp;particularly with higher mortality rates in younger children and older adults compared to other age groups [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] \u0026ndash; this study did not evaluate the optimal cutoff points of the rSIG for predicting the need for urgent interventions in patients with TBIs based on age. Third, this study also lacks external validation and comparison with other scoring systems. In the future, we aim to determine the optimal cutoff points according to TBI severity within each age group and external and comparative validation with other predicting systems, including the rSIG, in several regions to improve trauma care.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe rSIG may be a useful predictor of urgent interventions and neurological critical care, including blood transfusions within 24 h of hospital arrival, craniotomy, craterization, ICP monitoring, tracheal intubation, ICU admission, and in-hospital mortality, in patients with isolated severe TBIs in the emergency hospital settings. In the future, the rSIG may assist both emergency medical service providers in prehospital settings and emergency physicians in hospital settings, for early intervention and better outcomes in patients with severe TBIs.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAIS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAbbreviated Injury Scale\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003econfidence interval\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGCS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eGlasgow Coma Scale\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eheart rate\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eICP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eintracranial pressure\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eintensive care unit\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003einterquartile range\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eISS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eInjury Severity Score\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eJAST\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eJapanese Association for the Surgery of Trauma\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eJTCR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eJapan Trauma Care and Research\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eJTDB\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eJapan Trauma Data Bank\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eodds ratio\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003erespiratory rate\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003erSIG\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ereverse shock index multiplied by the Glasgow Coma Scale score\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRTS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eRevised Trauma Score\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSBP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003esystolic blood pressure\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTBI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003etraumatic brain injury\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTRISS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTrauma and Injury Severity Score\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate:\u003c/strong\u003e The study was approved by the institutional Ethics Committee of Shinshu University School of Medicine Graduate School of Medicine (approval no. 2024-795, October 8, 2024). The need for consent was waived by the Institutional Ethics Committee that approved our study, owing to the observational nature of the study design, as per the Personal Information Protection Law and National Research Ethics Guidelines in Japan.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e The dataset and/or analysis results of this study have not been made publicly available because their dissemination was not approved by the Ethics Committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest:\u003c/strong\u003e The authors declare that they have no competing interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e None.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e Conceptualization, C.T. and H.K.; methodology, C.T.; validation, H.K., C.T., T.T., M.I., and M.M.; formal analysis, C.T.; investigation, C.T.; resources, C.T. and H.K.; data curation, C.T.; writing, original draft preparation, H.K.; writing, review and editing, H.K., C.T., T.T., M.I., and M.M.; visualization, H.K. and C.T.; supervision, T.T., M.I., and M.M.; project administration and funding acquisition, C.T. All authors have read and agreed to the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e Takeru Abe (Integrated Science Education and Research Center, Fukushima Medical University), who provided purely technical help with the statistical analysis and writing assistance.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eGBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990\u0026ndash;2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18:56-87. doi:10.1016/S1474-4422(18)30415-0.\u003c/li\u003e\n \u003cli\u003eDewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC, Punchak M, et al. Estimating the global incidence of traumatic brain injury. J Neurol Surg. 2018;130:1080-97. doi:10.3171/2017.10.JNS17352.\u003c/li\u003e\n \u003cli\u003eIaccarino C, Carretta A, Nicolosi F,Morselli C. Epidemiology of severe traumatic brain injury. J Neurosurg Sci. 2018;62:535-41. doi:10.23736/S0390-5616.18.04532-0.\u003c/li\u003e\n \u003cli\u003eToida C, Muguruma T, Gakumazawa M, Shinohara M, Abe T, Takeuchi I, et al. Age- and Severity-Related In-Hospital Mortality Trends and Risks of Severe Traumatic Brain Injury in Japan: A Nationwide 10-Year Retrospective Study. J Clin Med. 2021;10:1072. doi:10.3390/jcm10051072.\u003c/li\u003e\n \u003cli\u003eJiang D, Chen T, Yuan X, Shen Y, Huang Z. Predictive value of the Trauma Rating Index in Age, Glasgow Coma Scale, Respiratory rate and Systolic blood pressure score (TRIAGES) and Revised Trauma Score (RTS) for the short-term mortality of patients with isolated traumatic brain injury. Am J Emerg Med. 2023;71:175-81. doi:10.1016/j.ajem.2023.06.030.\u003c/li\u003e\n \u003cli\u003eJeong TS, Choi DH, Kim WK; Korea Neuro-Trauma Data Bank (KNTDB) Investigators2. The Relationship Between Trauma Scoring Systems and Outcomes in Patients With Severe Traumatic Brain Injury. Korean J Neurotrauma. 2022;18:169-77. doi:10.13004/kjnt.2022.18.e54.\u003c/li\u003e\n \u003cli\u003eKimura A, Tanaka N. Reverse shock index multiplied by Glasgow Coma Scale score (rSIG) is a simple measure with high discriminant ability for mortality risk in trauma patients: an analysis of the Japan Trauma Data Bank. Crit Care. 2018;22:87. doi:10.1186/s13054-018-2014-0.\u003c/li\u003e\n \u003cli\u003eKramer AH, Zygun DA. Do neurocritical care units save lives? Measuring the impact of specialized ICUs. Neurocrit Care. 2011;14:329-33. doi:10.1007/s12028-011-9530-y.\u003c/li\u003e\n \u003cli\u003eLee YT, Bae BK, Cho YM, Park SC, Jeon CH, Huh U, et al. Reverse shock index multiplied by Glasgow coma scale as a predictor of massive transfusion in trauma. Am J Emerg Med. 2021;46:404-9. doi:10.1016/j.ajem.2020.10.027.\u003c/li\u003e\n \u003cli\u003eWu SC, Rau CS, Kuo SCH, Chien PC, Hsieh HY, Hsieh CH. The Reverse Shock Index Multiplied by Glasgow Coma Scale Score (rSIG) and Prediction of Mortality Outcome in Adult Trauma Patients: A Cross-Sectional Analysis Based on Registered Trauma Data. Int J Environ Res Public Health. 2018;15:2346. doi:10.3390/ijerph15112346.\u003c/li\u003e\n \u003cli\u003eReppucci ML, Acker SN, Cooper E, Meier M, Stevens J, Phillips R, et al. Improved identification of severely injured pediatric trauma patients using reverse shock index multiplied by Glasgow Coma Scale. J Trauma Acute Care Surg. 2022;92:69-73. doi:10.1097/ta.0000000000003432.\u003c/li\u003e\n \u003cli\u003eUemura T, Kimura A, Matsuda W, Yamamoto H, Sasaki R. Reverse Shock Index Multiplied by Glasgow Coma Scale score as a point-of-care severity assessment for initial trauma management: A nationwide cohort study. Injury. 2024;55:111267. doi:10.1016/j.injury.2023.111267.\u003c/li\u003e\n \u003cli\u003eThe Japanese Association for the Surgery of Trauma Inclusive Trauma Care System Investigation Committee Report: Chiiki ni okeru houkatsuteki gaishou shinryou taisei ni tsuite no teigen Recommendations on Inclusive Trauma Care System in the Community. J. Jpn. Assoc. Surg. Trauma in press. http://www.jasthp.org/pdf/ JAST_inclusive_trauma_care_system_statement.pdf. Accessed 25 March 2021.\u003c/li\u003e\n \u003cli\u003eJapan Trauma Data Bank report 2022. https://www.jtcr-jatec.org/traumabank/dataroom/data/JTDB2022.pdf/ Accessed 1 Febr 2025.\u003c/li\u003e\n \u003cli\u003eSteyerberg EW. Clinical Prediction Models: a practical approach to development, validation, and updating. 2\u003csup\u003end\u003c/sup\u003e ed. New Yortk: Springer; 2019.\u003c/li\u003e\n \u003cli\u003eReppuci ML, Cooper E, Nolan MM, Lyttle BD, Gallagher LT, Jujare S, et al. Use of prehospital reverse shock index times Glasgow Coma Scale to identify children who require the most immediate trauma care. J Trauma Acute Care Surg. 2023;95:347-53. doi:10.1097/ta.0000000000003903.\u003c/li\u003e\n \u003cli\u003eChuang JF, Rau CS, Wu SC, Liu HT, Hsu SY, Hsieh HY, et al. Use of the reverse shock index for identifying high-risk patients in a five-level triage system. Scand J Trauma Resusc Emerg Med. 2016;24:12. doi:10.1186/s13049-016-0208-5.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"traumatic brain injury, reverse shock index multiplied by the Glasgow Coma Scale score, emergency care, critical care, Japan Trauma Data Bank","lastPublishedDoi":"10.21203/rs.3.rs-7470351/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7470351/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Patients with traumatic brain injuries (TBIs) have high mortality rates and poor outcomes. Predicting the mortality and need for emergency trauma care is important. There are few urgency indicators in patients with severe TBIs. This study aimed to identify and validate the reverse shock index multiplied by the Glasgow Coma Scale score (rSIG) as an assessment tool for emergency trauma care, including urgent interventions, critical care, and mortality in patients with severe TBIs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This retrospective validation study included patients of all ages with isolated severe TBIs with Abbreviated Injury Scale (AIS) scores ≥ 3 registered in the Japan Trauma Data Bank (JTDB) dataset between January 1, 2012, and December 31, 2021. The patients were divided into a derivation cohort (January 1, 2012, to December 31, 2018) and a validation cohort (January 1, 2019, to December 31, 2021). The primary outcome measure was a composite outcome of blood transfusions within 24 h of hospital arrival, craniotomy, craterization, intra-cranial pressure (ICP) monitoring, tracheal intubation, intensive care unit (ICU) admission, and in-hospital mortality.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e A total of 42,375 eligible patients were divided into the derivation (n = 32,483) and validation (n = 9892) cohorts. The derivation cohort included male patients (n=21977, 68%); patients who underwent blood transfusions within 24 h of hospital arrival, craniotomies, and craterizations (n=3114, n=3678, and n=1277, respectively; 10%, 11%, and 4% respectively). The median rSIG and actual survival rate of the derivation cohort were 21.8 (interquartile range [IQR], 14.9–28.0) and 88%. The cut-off point of the rSIG was 16.21. Abnormal rSIGs were associated with a greater odds ratio (OR) for blood transfusions within 24 h of arrival (OR, 4.03; 95% confidence interval [CI], 3.59-4.53), craniotomies (2.86 [2.55-3.21]), craterization (2.61 [2.14-3.17]), ICP monitoring (4.91 [3.96-6.10]), tracheal intubation (6.40 [5.71-7.17]), ICU admission (2.10 [1.93-2.29]), and in-hospital mortality (8.49 [7.45-9.63]) than those with normal rSIGs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e The rSIG may be a useful predictor of urgent interventions and neurological critical care, and in-hospital mortality in patients with isolated severe TBIs in the emergency hospital settings.\u003c/p\u003e","manuscriptTitle":"Reverse shock index multiplied by Glasgow Coma Scale score as a predictor of urgent trauma care and mortality in isolated severe traumatic brain injury: a 10-year nationwide validation study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-01 10:30:06","doi":"10.21203/rs.3.rs-7470351/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e04a2e50-f0cd-479a-8798-7fb0c4c28ae7","owner":[],"postedDate":"September 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-01T10:30:08+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-01 10:30:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7470351","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7470351","identity":"rs-7470351","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}