A prehospital risk assessment tool predicts clinical outcomes in hospitalized patients with heat-related illness: a Japanese nationwide prospective observational study
Study design and settings
This analysis was conducted using a registered database of a prospective, multicenter, observational study (the Heatstroke Study) in Japan from July 1st to September 30th in 2019, 2020, and 2021. Briefly, the Japanese Association for Acute Medicine (JAAM; Heatstroke and Hypothermia Surveillance Committee) established the Heatstroke Study in 2006. It involved a survey of patients with presumed heat-related illnesses who were transferred to emergency hospitals by EMS personnel11,19,20,21,22,23. Since 2017, this registry has been used to gather information regarding only patients admitted to the hospital owing to a diagnosis of heat-related illness. Approximately 142 emergency hospitals from all over Japan took part in the registry during the study period12. Data were manually recorded by the staff at each participating hospital by using standardized record sheets. The study protocol was approved by the Teikyo University Ethical Review Board for Medical and Health Research (approval number; 17-021-5, board name; “Heatstroke STUDY”, approval date; May 21st, 2020), which waived the requirement for informed patient consent owing to participant anonymity. The procedures followed were in accordance with the ethical standards of the institution’s responsible committee on human experimentation and with the Helsinki Declaration of 1975, as most recently amended.
Definition of heat-related illnesses
Heat-related illnesses were defined as conditions in the spectrum of illnesses progressing from heat exhaustion to heatstroke during exercise or exposure to environmental heat stress. Heat-related illness was diagnosed by the attending physician in the emergency department where the patient was admitted.
Selection of participants
This study included adult patients (aged ≥ 18 years) with a diagnosis of heat-related illness who were admitted to the hospital. The heat-related illness was diagnosed by the modified definition of heatstroke (mJAAM) criteria19. Briefly, the mJAAM criteria consist of factors such as CNS manifestations, hepatic/renal dysfunction, and DIC, but not body temperature. Patients who were not directly transferred from the occurrent site to the participant’s hospital, for whom transportation data were missing, or who suffered cardiopulmonary arrest on arrival were excluded from this study. In addition, patients for whom data on the primary outcome, J-ERATO score, event location, and/or the circumstances of the occurrence were missing were excluded from the analyses.
Patient demographics, prehospital information collected by the EMS personnel, and in-hospital information were prospectively recorded (i.e., event location, circumstances of the occurrence, transportation, pre-existing functional dependency, age, sex, prehospital vital signs [Glasgow Coma Scale score, pulse rate, non-invasive blood pressure, respiratory rate, body temperature, and peripheral pulse oximetry], medical history [liver disease, cerebrovascular disease, respiratory disease, chronic kidney disease, immunocompromised disease, psychological disorder, diabetes mellitus with organ dysfunction, and previous heat-related illness], physical findings assessed by the EMS at the scene (seizure, dry skin, skin redness, and skin hotness to touch), in-hospital information [the location of admission, i.e., the ICU or a non-ICU general ward), and survival to hospital discharge. In addition, we gathered information about the patients’ Sequential Organ Failure Assessment (SOFA) score24 on the first day after admission (day 1) and the presence of DIC on day 1. Owing to the lack of a specific mortality prediction tool for heat-related illnesses, the SOFA score, which is a general scoring system for critically ill patients, is commonly used to estimate the severity of heat-related illnesses25. DIC was diagnosed according to the JAAM DIC diagnostic criteria26,27, with a total score ≥ 4 establishing a diagnosis of DIC. Scoring is based on peripheral blood platelet counts, prothrombin time, fibrinogen/fibrin degradation products or D-dimer levels, and the presence of systemic inflammatory response syndrome.
The primary outcome was survival to hospital discharge. The secondary outcomes were occurrences of DIC and SOFA score on day 1.
Baseline characteristics were summarized using medians and interquartile ranges for continuous variables and frequencies (%) for categorical variables. The differences between groups were tested using the Mann–Whitney U test. The chi-square or Fisher’s exact test was used to compare binary variables. We evaluated the relationship between the J-ERATO and SOFA scores using Spearman’s rank correlation test.
Multivariable logistic regression was used to adjust for the selected covariates to determine whether the J-ERATO is related to the prognosis of patients hospitalized for heat-related illnesses. The following independent variables were selected for the model: the J-ERATO score, event location, circumstances of the occurrence, medical history of psychiatric disorder, and age. A set of selected covariates was chosen a priori based on biological plausibility and a priori knowledge28,29,30,31,32.
We calculated the areas under the receiver operating characteristic curve (AUCs) and their 95% confidence intervals (CIs) to evaluate the predictive ability of J-ERATO score to differentiate between survival and non-survival at hospital discharge, and between patients with and those without DIC on day 1. The best cut-off point for the J-ERATO score to determine the highest mortality risk was based on Youden’s index. We also performed multivariable analyses in the subgroup of ICU-admitted patients, adjusting for the same variables as in the overall analyses.
All statistical analyses were carried out with a two-sided significance level of 5% via JMP PRO 16.0.0 (http://www.jmp.com).