Exertional Heat Stroke Patients Research Articles

Monocyte HLA-DR level on admission predicting in-hospital mortality rate in exertional heatstroke: A 12-year retrospective study.

Exertional heatstroke (EHS), a fatal illness, pronounces multiple organ dysfunction syndrome (MODS) and high mortality rate. Currently, no ideal factor prognoses EHS. Decreased monocytehuman leukocyte-DR antigen(mHLA-DR) has been observed in critically ill individuals, particularly in those with sepsis. While most research focus on the pro-inflammatory response exploration in EHS, there are few studies related to immunosuppression, and no report targeted on mHLA-DR in EHS. The present study tried to explore the prognostic value of mHLA-DR levels in EHS patients. This was a single-center retrospective study. Clinical data of EHS patients admitted to the intensive care unitof the General Hospital of Southern Theatre Command between January 1, 2008, and December 31, 2020, were recorded and analyzed. Seventy patients with 54 survivors and 16 nonsurvivors were ultimately enrolled. Levels of mHLA-DR in the nonsurvivors (41.8% [38.1-68.1]%) were significantly lower than those in the survivors (83.1% [67.6-89.4]%, p < 0.001). Multivariate logistic regression indicated that mHLA-DR (odds ratio [OR] = 0.939; 95% confidence interval [CI]: 0.892-0.988; p = 0.016) and Glasgow coma scale (GCS) scores (OR = 0.726; 95% CI: 0.591-0.892; p = 0.002) were independent risk factors related with in-hospital mortality rate in EHS. A nomogram incorporated mHLA-DR with GCS demonstrated excellent discrimination and calibration abilities. Compared to the traditional scoring systems, the prediction model incorporated mHLA-DR with GCS had the highest area under the curve(0.947, 95%CI:[0.865-0.986]) and Youden index (0.8333), with sensitivity of 100% and specificity of 83.33%, and a greater clinical net benefit. Patients with EHS were at a risk of early experiencing decreased mHLA-DR early. A nomogram based on mHLA-DR with GCS was developed to facilitate early identification and timely treatment of individuals with potentially poor prognosis.

Return to Duty Following Exertional Heat Stroke: A Review.

Exertional heat stroke (EHS), which presents with extreme hyperthermia and alteration to the central nervous system, disproportionately affects the military, where warfighters are expected to perform in all types of environmental conditions. Because of an incomplete understanding of individualized recovery from EHS, there are several shortcomings with the current guidance on return to duty (RTD) following an EHS. The purpose of this manuscript is to provide an updated literature review of best practices for return to duty following EHS to guide decision making regarding EHS and explore areas of future research for medical staff who work with warfighters. A literature review related to EHS in both athlete and military populations, as well as any existing guidelines for RTD, was conducted using PubMed and Covidence. Twenty-one articles were identified for this updated review on EHS and RTD, with recommendations focused during and after an EHS event, as well as the role of heat tolerance testing (HTT). EHS has a high morbidity and mortality rate if not treated rapidly. Because the extent of end-organ damage is dependent on the amount of time that the individual is hyperthermic, rapid diagnosis via rectal thermometry, and efficient cooling methods are imperative to the wellbeing of EHS patients. Following EHS, gradual RTD recommendations within the limits of operational demand should be implemented to reduce the risk for a subsequent heat injury event. While many versions of HTT, most notably the Israeli Defense Force (IDF) protocol, have been created to guide RTD recommendations, a universal assessment for heat tolerance has yet to be adopted. As such, medical personnel should apply a multifactorial approach to ensure safe RTD.

Multiparametric cardiac magnetic resonance reveals persistent myocardial inflammation in patients with exertional heat illness.

To explore the clinical potential of multiparametric cardiac magnetic resonance (CMR) in evaluating myocardial inflammation in patients with exertional heat illness (EHI). This prospective study enrolled 28 males with EHI (18 patients with exertional heat exhaustion (EHE) and 10 with exertional heat stroke (EHS)) and 18 age-matched male healthy controls (HC). All subjects underwent multiparametric CMR, and 9 patients had follow-up CMR measurements 3months after recovery from EHI. CMR-derived left ventricular geometry, function, strain, native T1, extracellular volume (ECV), T2, T2*, and late gadolinium enhancement (LGE) were obtained and compared among different groups. Compared with HC, EHI patients showed increased global ECV, T2, and T2* values (22.6% ± 4.1 vs. 19.7% ± 1.7; 46.8ms ± 3.4 vs. 45.1ms ± 1.2; 25.5ms ± 2.2 vs. 23.8ms ± 1.7; all p < 0.05). Subgroup analysis showed that ECV was higher in the EHS patients than those in EHE and HC groups (24.7% ± 4.9 vs. 21.4% ± 3.2, 24.7% ± 4.9 vs. 19.7% ± 1.7; both p < 0.05). Repeated CMR measurements at 3months after baseline CMR showed persistently higher ECV than HC (p = 0.042). With multiparametric CMR, EHI patients demonstrated increased global ECV, T2, and persistent myocardial inflammation at 3-month follow-up after EHI episode. Therefore, multiparametric CMR might be an effective method in evaluating myocardial inflammation in patients with EHI. This study showed persistent myocardial inflammation after an exertional heat illness (EHI) episode demonstrated by multiparametric CMR, which is a potential promising method to evaluate the severity of myocardial inflammation and guide return to work, play, or duty in EHI patients. • EHI patients showed an increased global extracellular volume (ECV), late gadolinium enhancement, and T2 value, indicating myocardial edema and fibrosis. • ECV was higher in the exertional heat stroke patients than exertional heat exhaustion and healthy control groups (24.7% ± 4.9 vs. 21.4% ± 3.2, 24.7% ± 4.9 vs. 19.7% ± 1.7; both p < 0.05). • EHI patients showed persistent myocardial inflammation with higher ECV than healthy controls 3months after index CMR (22.3% ± 2.4 vs. 19.7% ± 1.7, p = 0.042).

A nomogram based on lymphocyte percentage for predicting hospital mortality in exertional heatstroke patients: a 13-year retrospective study

A nomogram based on lymphocyte percentage for predicting hospital mortality in exertional heatstroke patients: a 13-year retrospective study

Rectal Temperature Cooling Using 2 Cold-Water Immersion Preparation Strategies.

Cold-water immersion (CWI) is essential to treat patients with exertional heatstroke (EHS). Experts recommend that patients with EHS be immersed in water between 1.7°C and 15°C within 30 minutes of collapse. Some clinicians fill cooling tubs several hours before exercise, keep the tub in hot conditions, and then add ice in the event of an EHS emergency. No data exist on whether adding ice to water at the time of treatment is as effective as keeping water in the recommended range. To (1) compare the cooling rates of individuals immersed in a water bath kept at 10°C (CON) or 17°C water with 75.7 L (20 gal) of ice added to it immediately upon immersion (ICE) and (2) examine perceptual responses before, during, and after cooling. Crossover study. Laboratory. Twelve individuals (7 men, 5 women; age = 22 ± 2 years, height = 176.0 ± 12.8 cm, mass = 74.5 ± 10.6 kg). Participants exercised in the heat until rectal temperature was 39.5°C. They then immersed themselves in CON (initial water volume = 681 ± 7.6 L, 10.0°C ± 0.03°C) or ICE (initial water volume = 605.7 ± 7.6 L water at 17.0°C ± 0.03°C with 75.7 L ice) until rectal temperature was 38°C. Thermal sensation and environmental symptoms questionnaire (ESQ) responses were recorded before, during, and after exercise and cooling. Rectal temperature cooling rates, thermal sensation, ESQ responses. Participants exercised for similar durations (CON = 39.6 ± 18.2 minutes, ICE = 38.8 ± 14.3 minutes, Z11 = 0.94, P = .38) and had similar thermal sensation and ESQ scores immediately postexercise each day (P values > .05). They cooled quickly and at similar rates in both conditions (CON = 0.20°C ± 0.06°C/min, ICE = 0.21°C ± 0.12°C/min, t12 = 0.72, P = .49). Perception data were similar between conditions during and after cooling (P < .05). Clinicians can cool patients with EHS quickly by adding ice to water that has warmed to above expert recommendations. Adding ice to a water bath at the time of EHS emergencies could save time, energy, and resources instead of always maintaining water bath temperatures within expert-recommended ranges.

Immune Cells Characteristics and Their Prognostic Effects in Exertional Heatstroke Patients: A Retrospective Cohort Study.

BackgroundExertional heatstroke (EHS) remains a major problem for those who take strenuous physical activity. Inflammation and immune dysfunction were thought to be crucial to the pathophysiological process of heatstroke. The present study was aimed to investigate the dynamic changes of the immune cells in patients with EHS and determine their prognostic effects to provide the clinical evidence of the above process.MethodsThis single-center retrospective cohort study collected all patients with EHS admitted to the intensive care unit (ICU) of the General Hospital of Southern Theater Command of PLA from October 2008 to May 2019. The dynamic changes of the main immune cell count and ratio were collected, including white blood cell (WBC), neutrophil, monocyte, and lymphocyte. The neutrophil-to-lymphocyte ratios (NLR) were calculated by the neutrophil count/lymphocyte count × 100%. The main outcome was 90-day mortality.ResultsA total of 189 patients were enrolled. For survivors, after 24 h, the WBC and neutrophil counts began to decrease, and they were back to normal in 72 h. In addition, the lymphocyte counts were within normal limits all the time. For non-survivors, the WBC and neutrophil counts were continuous over the normal range, while the lymphocyte count and the ratio began to decrease after 24 h and were continuously low in the following days. Receiver operating characteristic (ROC) curves analysis showed that increased neutrophils and decreased lymphocytes were associated with the poor prognosis of the patients. A prediction model based on immune cell counts and ratios was constructed, and the lymphocyte count was accounted for the maximum weight.ConclusionsIn patients with EHS, increased neutrophils and decreased lymphocytes were associated with the poor prognosis. The lymphocyte count at 72 h after admission was the most important prognostic factor.

The Relationship Between 24-Hour Indicators and Mortality in Patients with Exertional Heat Stroke.

Exertional heat stroke (EHS) is a life-threatening illness that can lead to multiple organ damage in the early stage. This study aimed to investigate the relationship between 24-hour indicators and mortality in patients with EHS. The records of EHS patients hospitalized were collected and divided into the death group and the survival group. We then analyzed the demographic characteristics and APACHE II scores and laboratory results of the participants in the blood within the first 24 h after hospitalization, and assessed whether these candidate indicators differed between the death group and the survival group. Cox regression analysis of the survival data was performed to explore the relationship between early indicators and prognosis. The levels of plasma PT, APTT, TT, and INR were significantly higher in the death group than in the survival group. The blood PLT count and the levels of PTA and Fb were significantly lower in the death group than in the survival group, while the levels of BU, SCr, ALT, AST, TBil, and DBil were significantly higher in the death group than in the survival group. Furthermore, the levels of Mb, LDH, TNI, and NT-proBNP were significantly higher in the death group than in the survival group, while there was no significant difference in CK levels between the two groups. Patients with EHS often had multiple organ injuries in the early stage (within 24 h), while those cases in the death group were more severe.

The value of the exertional heat stroke score for the prognosis of patients with exertional heat stroke.

This study aims to evaluate the exertional heat stroke score (EHSS) system for the prognosis of exertional heat stroke (EHS) patients. Forty-two EHS patients who had been treated in our hospital between January 2017 and December 2019 were divided into two groups according to their prognosis, a survival group and a non-survival group. All the patients had received comprehensive EHS treatment after admission, and their EHSS parameters were collected within 24h of admission, including body temperature, hepatorenal function, and coagulation function. A retrospective comparative evaluation was made of the effectiveness of the EHSS, the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) in making an EHS prognosis. Among 42 patients, 28 patients were treated successfully and discharged from the hospital, 5 were given a poor prognosis, and 9 died, amounting to a fatality rate of 21.42%. Univariate analysis showed that within 24h of admission, the differences were statistically significant (p<0.05) in the comparison of the following factors: lactate concentration, platelets, prothrombin time, fibrinogen, troponin, aspartate aminotransferase, total bilirubin, urinary creatinine, acute gastrointestinal injury, temperature, and Glasgow coma score. However, no statistically significant difference in blood pH was observed between the two groups of patients (p=0.117). The EHSS, APACHE II, and SOFA scores of the survival group were significantly lower than those of the non-survival group (p<0.001). The area under the receiver operating characteristic curve of the EHSS, APACHE II and SOFA scores were the area under the curve (AUC) EHSS=0.96 (0.901, 0.990), AUC Apache II = 0.895 (0.802, 0.950), and AUC SOFA = 0.884 (0.837, 0.964), respectively. Thus, the EHSS diagnostic efficacy of the survival group was significantly higher than that of the other two scores. In addition, the sensitivity and specificity of EHSS were higher than those of the APACHE II and SOFA scores. The EHSS has a good diagnostic efficacy for the prognosis of EHS patients and is significantly higher than that of the APACHE II and SOFA scores. This finding provides a theoretical basis for further increasing the rescue success rate of EHS patients and improving their prognostic quality of life.

Status of US Emergency Medical Service Protocols Regarding Pre-Transfer Cooling for Exertional Heat Stroke

Objective: Exertional heat stroke (EHS) is a significant cause of morbidity and mortality in athletes and active individuals. In the field, initial management of exertional heat illness is based on rapid whole-body cooling. Cold-water immersion (CWI) is considered the superior cooling modality for EHS treatment. However, there often is a disconnect between the sports medicine community and the emergency medical service (EMS) community. Well-written emergency action plans may fail if EMS protocols do not allow for CWI in initial management. This is the first study to look at the current national EMS protocols regarding prehospital management of EHS. The purpose of our study was to assess the status of heat illness protocols regarding CWI for EHS in all 50 states plus Washington, DC. Methods: An internet search was performed to find EHS protocols. Statewide protocols were preferred. Several parameters were recorded for each protocol including whether: 1) CWI was the recommended cooling treatment for EHS and 2) CWI was explicitly permitted to be completed prior to transportation.Results: We found nine of the 51 protocols, or 17.6%, explicitly recommended CWI and 11 of the 51, or 21.6%, specifically instructed EMS personnel to complete CWI or cooling methods prior to transport. However, six protocols, or 11.8%, provided the recommendation instructing some variation of the phrase “do not delay transport to cool the patient.”Conclusion: Despite the medical literature endorsing CWI as the most effective treatment modality in a prehospital setting for exertional heat illness, EMS protocols largely fail to reflect this which leads to mismanagement and inadequate care of EHS patients. While CWI is not always available, all EMS protocols should include a systematic practical guideline for a heat illness patient when employing cooling treatment with an emphasis on CWI when available as the preferred treatment technique for EHS and the concept of “cool first, transport second.”

Characteristics and Outcome of Exertional Heatstroke Patients Complicated by Acute Hepatic Injury: A Cohort Study.

Background and AimsExertional heatstroke (EHS) is associated with strenuous physical activity in hot environments. The present study aimed to investigate dynamic changes of hepatic function indices in EHS patients and determine risk factors for death.MethodsThis single-center retrospective cohort study considered all patients with EHS admitted to the intensive care unit at the General Hospital of Southern Theater Command of PLA from October 2008 to May 2019. Data on general characteristics, organ function parameters, and the 90-day outcome of enrolled patients were collected. Hepatic indices were collected dynamically, and patients with acute hepatic injury (AHI) were identified by plasma total bilirubin (TBIL) ≥34.2 µmol/L and an international normalized ratio ≥1.5, or with any grade of hepatic encephalopathy.ResultsIn patients who survived, TBIL, alanine aminotransferase and aspartate aminotransferase were increased at 24 h, peaked at 2–3 days, and began to decrease at 5 days. In non-survivors, TBIL continuously increased post-admission. The area under the receiver operating characteristic curve for the prediction of mortality based on sequential organ failure assessment (SOFA) scores was 89.8%, and the optimal cutoff value was 7.5. Myocardial injury and infection were identified as independent risk factors for death in EHS patients with AHI.ConclusionsIn EHS patients, hepatic dysfunction usually occurred within 24 h. Patients with AHI had more severe clinical conditions, and significantly increased 90-day mortality rates. SOFA scores over 7.5, complicated with myocardial injury or infection, were found to be risk factors for death in EHS patients with AHI.

Incidence of Recurrent Exertional Heat Stroke in a Warm-Weather Road Race

Background and Objectives: Exertional heat stroke (EHS) survivors may be more susceptible to subsequent EHS; however, the occurrence of survivors with subsequent EHS episodes is limited. Therefore, the purpose of this study was to evaluate the incidence of participants with repeated EHS (EHS-2+) cases in a warm-weather road race across participation years compared to those who experienced 1 EHS (EHS-1). Materials and Methods: A retrospective observational case series design was utilized. Medical record data from 17-years at the Falmouth Road Race between 2003–2019 were examined for EHS cases. Incidence of EHS-2+ cases per race and average EHS cases per EHS-2+ participant were calculated (mean ± SD) and descriptive factors (rectal temperature (TRE), finish time (FT), Wet Bulb Globe Temperature (WBGT), age, race year) for each EHS was collected. Results: A total of 333 EHS patients from 174,853 finishers were identified. Sixteen EHS-2+ participants (11 males, 5 females, age = 39 ± 16 year) accounted for 11% of the total EHS cases (n = 37/333). EHS-2+ participants had an average of 2.3 EHS cases per person (range = 2–4) and had an incidence rate of 2.6 EHS per 10 races. EHS-2+ participants finished 93 races following initial EHS, with 72 of the races (77%) completed without EHS incident. Initial EHS TRE was not statistically different than subsequent EHS initial TRE (+0.3 ± 0.9 °C, p > 0.050). Initial EHS-2+ participant FT was not statistically different than subsequent EHS FT (−4.2 ± 7.0 min, p > 0.050). The years between first and second EHS was 3.6 ± 3.5 year (Mode: 1, Range: 1–12). Relative risk ratios revealed that EHS patients were at a significantly elevated risk for subsequent EHS episodes 2 years following their initial EHS (relative risk ratio = 3.32, p = 0.050); however, the risk from 3–5 years post initial EHS was not statistically elevated, though the relative risk ratio values remained above 1.26. Conclusions: These results demonstrate that 11% of all EHS cases at the Falmouth Road Race are EHS-2+ cases and that future risk for a second EHS episode at this race is most likely to occur within the first 2 years following the initial EHS incident. After this initial 2-year period, risk for another EHS episode is not significantly elevated. Future research should examine factors to explain individuals who are susceptible to multiple EHS cases, incidence at other races and corresponding prevention strategies both before and after initial EHS.

Roundtable on Preseason Heat Safety in Secondary School Athletics: Prehospital Care of Patients With Exertional Heat Stroke.

First, we will update recommendations for the prehospital management and care of patients with exertional heat stroke (EHS) in the secondary school setting. Second, we provide action items to aid clinicians in developing best-practice documents and policies for EHS. Third, we supply practical strategies clinicians can use to implement best practice for EHS in the secondary school setting. An interdisciplinary working group of scientists, physicians, and athletic trainers evaluated the current literature regarding the prehospital care of EHS patients in secondary schools and developed this narrative review. When published research was nonexistent, expert opinion and experience guided the development of recommendations for implementing life-saving strategies. The group evaluated and further refined the action-oriented recommendations using the Delphi method. Exertional heat stroke continues to be a leading cause of sudden death in young athletes and the physically active. This may be partly due to the numerous barriers and misconceptions about the best practice for diagnosing and treating patients with EHS. Exertional heat stroke is survivable if it is recognized early and appropriate measures are taken before patients are transported to hospitals for advanced medical care. Specifically, best practice for EHS evaluation and treatment includes early recognition of athletes with potential EHS, a rectal temperature measurement to confirm EHS, and cold-water immersion before transport to a hospital. With planning, communication, and persistence, clinicians can adopt these best-practice recommendations to aid in the recognition and treatment of patients with EHS in the secondary school setting.

Experience of treating batches of exertional heat stroke patients in military training

To explore the process and segments of intense treatment of patients suffered from exertional heat stroke (EHS), and to provide the experience and guidance for treating batches of EHS patients. A retrospective study of the curing process of eight EHS patients admitted to the Eighth Medical Center of Chinese PLA General Hospital on May 18th, 2019 was conducted, including onsite treatment and subsequent transshipment to hospital for treatment. Based on the medical history with high-intensity exercise and the clinical manifestation of central nervous system dysfunction, the eight patients were quickly diagnosed as EHS on the site, and were immediately rehydrated and attained the systematic cooling. An emergency plan for the treatment of batches of patients was initiated instantly for quick medical evacuation and care, and the patients were quickly transferred to the Eighth Medical Center of Chinese PLA General Hospital. A therapeutic principle was strictly followed, concerning the transshipment accompanied by systematic cooling while the medical evacuation and care, therapeutic preparation and immediate opening of the green channel were started up in the hospital. Sticking to the plan of allocating patients vs. nurses vs. doctor by 1:3:1, enough persons were dispatched. Ventilators, hemofiltration machines and ice blanket machines were prepared. Through the professional diagnosis and treatment in the emergency department, the patients were transferred to the ICU department. The relevant medical departments were coordinated with the centralization of the ICU department. The vital signs of patients were monitored closely. The titration and precise treatment were implemented, based on the changes in blood routine examination, blood biochemical indexes, blood clotting function, and blood gas analysis. The continuous renal replacement therapy (CRRT) was performed for four patients, the ice blanket machine cooling therapy for two patients, and the tracheal intubation and mechanical ventilation for one patient. Low molecular weight heparin sodium anticoagulant treatment was used in one patient with the diffuse intravascular coagulation (DIC) on the basis of coagulation factors such as plasmas and fibrinogens supplementation. The function of the damaged organs was significantly improved in 5-11 days. Eight patients were finally transferred out from ICU department. All patients were recovered and discharged after 11-20 days. A normative treatment process (rapid recognition on the site, rapid cooling, rapid and safe medical evacuation, in-hospital multidisciplinary collaboration) combined bundles of therapeutic strategy such as systematic cooling and rehydration, CRRT, and supplying the coagulation factors while anticoagulation treatment can provide a strong guarantee for rescuing batches of EHS patients and achieve satisfactory treatment outcomes.

Exertional Heat Stroke, Modality Cooling Rate, and Survival Outcomes: A Systematic Review.

Background and Objectives: The purpose of this systematic review is to synthesize the influence cooling modality has on survival with and without medical complications from exertional heat stroke (EHS) in sport and military populations. Methods and Materials: All peer-reviewed case reports or series involving EHS patients were searched in the following online databases: PubMed, Scopus, SPORTDiscus, Medline, CINAHL, Academic Search Premier, and the Cochrane Library: Central Registry of Clinical Trials. Cooling methods were subdivided into “adequate” (>0.15 °C/min) versus “insufficient” (<0.15 °C/min) based on previously published literature on EHS cooling rates. Results: 613 articles were assessed for quality and inclusion in the review. Thirty-two case reports representing 521 EHS patients met the inclusion criteria. Four hundred ninety-eight (498) patients survived EHS (95.58%) and 23 (4.41%) patients succumbed to complications. Fischer’s Exact test on 2 × 2 contingency tables and relative risk ratios were calculated to determine if modality cooling rate was associated with patient outcomes. EHS patients that survived who were cooled with an insufficient cooling rate had a 4.57 times risk of medical complications compared to patients who were treated by adequate cooling methods, regardless of setting (RR = 4.57 (95%CI: 3.42, 6.28)). Conclusions: This is the largest EHS dataset yet compiled that analyzes the influence of cooling rate on patient outcomes. Zero patients died (0/521, 0.00%) when treatment included a modality with an adequate cooling rate. Conversely, 23 patients died (23/521, 4.41%) with insufficient cooling. One hundred seventeen patients (117/521, 22.46%) survived with medical complications when treatment involved an insufficient cooling rate, whereas, only four patients had complications (4/521, 0.77%) despite adequate cooling. Cooling rates >0.15 °C/min for EHS patients were significantly associated with surviving EHS without medical complications. In order to provide the best standard of care for EHS patients, an aggressive cooling rate >0.15 °C/min can maximize survival without medical complications after exercise-induced hyperthermia.

117 Update: Dantrolene Sodium Suspension (250 Mg/5mL) in Patients with Exertional Heat Stroke

Exertional heat stroke (EHS) is a rare, sudden and unpredictable hyperthermic, hypermetabolic crisis that may affect anyone performing intense physical activity. EHS is one of the most severe forms of heat illness and a leading cause of death and disability in athletes, outdoor workers and military personnel. EHS is marked by severe hyperthermia (core body temp. ≥40°C) and CNS dysfunction (eg, seizures, coma, abnormal behavior). The sporadic, unpredictable and life-threatening nature of EHS limits the ability to conduct prospective controlled clinical trials. Current treatment is limited to efficient body cooling which is infrequently available and inconsistently administered. Up to 1/3 of survivors may have long-term neurologic sequelae despite rapid body cooling. The objective was to evaluate the efficacy and safety of dantrolene sodium for injectable suspension (Ryanodex®) (DSS) for the treatment of EHS, administered as an adjunct to body cooling (BC). We conducted two comparable clinical studies evaluating DSS+BC compared to BC alone in patients with EHS. Study 1 (ITT N=34, mITT N=24) and Study 2 (ITT N=17) were randomized, controlled, 2-arm parallel studies. Patients had a core temp. ≥40°C, impaired level of consciousness (LOC)(GCS score <13) and tachycardia. The primary efficacy endpoint in both studies was the cumulative incidence of recovery of LOC defined as a GCS score ≥13 at or prior to 90 minutes post-randomization. Safety and tolerability were assessed. As reported at the 2017 ACEP Research Forum, the mITT population in Study 1 excluded patients who were intubated at baseline (precluding full assessment of GCS). Study 2 ran from August 2018 to August 2019. These multicenter studies were conducted in a real-world emergency medicine setting in the same hospitals. Due to the limitations enrolling EHS patients and given the comparability of the studies, an integrated analysis of efficacy was warranted. Study 1 and Study 2 demonstrated consistent, clinically meaningful results. Demographics and baseline characteristics in the integrated analysis were balanced between the DSS+BC (n=19) and BC only (n=22) groups regarding age (median 45 vs 43.5 yrs.), baseline GCS (mean 7.1 vs 6.2) and baseline rectal temp. (mean 41.6 vs 41.3°C). 51% were male. A statistically significant number of patients in the DSS+BC group met the primary endpoint vs BC alone (47.4% vs 18.2%, p=0.0452). Safety and tolerability findings were comparable in both groups and consistent with the known safety profile in the approved indication. Conducting clinical studies for EHS is challenging due to its rare, unpredictable and life-threatening nature. We conducted two comparable studies showing consistent and clinically meaningful benefit from the addition of DSS to BC. Approximately twice as many DSS treated subjects in each study achieved the primary endpoint. The integrated analysis of efficacy demonstrates that DSS added to BC results in a clinically meaningful and statistically significant improvement of neurologic impairment in subjects with EHS within 90 minutes of administration.

Establishment and effectiveness evaluation of a scoring system for exertional heat stroke by retrospective analysis

BackgroundHeat stroke (HS) is a serious, life-threatening disease. However, there is no scoring system for HS so far. This research is to establish a scoring system that can quantitatively assess the severity of exertional heat stroke (EHS).MethodsData were collected from a total of 170 exertional heat stroke (EHS) patients between 2005 and 2016 from 52 hospitals in China. Univariate statistical methods and comparison of the area under the receiver operating characteristic (ROC) curve (AUC) were used to screen exertional heat stroke score (EHSS) parameters, including but not limited body temperature (T), Glasgow Coma Scale (GCS) and others. By comparing the sizes of the AUCs of the APACHE II, SOFA and EHSS assessments, the effectiveness of EHSS in evaluating the prognosis of EHS patients was verified.ResultsThrough screening with a series of methods, as described above, the present study determined 12 parameters – body temperature (T), GCS, pH, lactate (Lac), platelet count (PLT), prothrombin time (PT), fibrinogen (Fib), troponin I (TnI), aspartate aminotransferase (AST), total bilirubin (TBIL), creatinine (Cr) and acute gastrointestinal injury (AGI) classification – as EHSS parameters. It is a 0–47 point system designed to reflect increasing severity of heat stroke. Low (EHSS< 20) and high scores (EHSS> 35) showed 100% survival and 100% mortality, respectively. We found that AUCEHSS > AUCSOFA > AUCAPACHE II.ConclusionA total of 12 parameters – T, GCS, pH, Lac, PLT, PT, Fib, TnI, AST, TBIL, Cr and gastrointestinal AGI classification – are the EHSS parameters with the best effectiveness in evaluating the prognosis of EHS patients. As EHSS score increases, the mortality rate of EHS patients gradually increases.

Sex Differences In The Clinical Sequelae Of Exertional Heat Stroke In Military Servicemembers

Exertional heat stroke (EHS) represents a significant source of morbidity and mortality for the military and other occupational and athletic populations. EHS patients tend to present with elevated biomarkers of acute liver and kidney injury, rhabdomyolysis, and altered hematological parameters. However, little is know about how men and women may respond differently to EHS, in terms of clinical severity and/or biochemical responses. PURPOSE: The aim of this study was to characterize clinical and biochemical differences between male and female servicemembers immediately following an EHS episode. METHODS: We performed a retrospective analysis of EHS patient records in all US military personnel (41% between 20-24 years old) from 2008-2014 using the Military Health Systems Data Repository. We compared diagnoses of organ failure during the course of treatment and clinical laboratory markers of end organ damage. Sex differences in clinical outcomes are presented with odds ratios, and biomarker differences are presented as the median difference with 95% confidence intervals in brackets. RESULTS: A total of 2,529 EHS cases were recorded with 9.8% [8.7, 11.2] occuring in women. Per patient treatment cost was lower in women by $1110 [620, 1647]. Men were 2.35 [1.6, 3.58] times more likely to experience renal failure (p = < .001). Blood urea nitrogen, (difference = -121.05 mg/dL [41.9, 182.28]), myoglobin (difference = 3 ng/mL [2, 4]), aspartate transaminase (difference = 7 units/L [1, 14]), and alanine transaminase (difference = 13 units/L [8.5, 15.92]) were elevated in men (all p < .01). Platelet count was also lower in men compared to women (difference = -22.14*103 per uL [-39.25, -2.99], p = 0.03). CONCLUSION: Female servicemembers appear to have a slightly less severe response to EHS compared to their male counterparts. In particular, renal failure was more common, and numerous markers of end-organ damage (hepatic, renal, and cardiovascular) were more likely to be elevated immediately following EHS in men. Supported by USAMRDC; author views not official US Army or DoD policy.

Optimization of a Rhabdomyolysis Model in Mice With Exertional Heat Stroke Mouse Model of EHS-Rhabdomyolysis.

Exertional heat stroke (EHS) is a life-threatening disease characterized by high mortality and incidence of rhabdomyolysis (RM). It would therefore be valuable to establish a stable EHS-induced RM model that accurately reflects the clinical characteristics of EHS patients and provides an objective animal model for further study of the pathogenesis of RM. In the current study, 8∼9-week-old, male, wild-type C57BL/6J mice, at the stage of sexual maturity, were randomly divided into four groups: the EHS group, the classical heat stroke (CHS) group, the sham heat exercise group, and sham heat rest group. The survival rate of mice was determined under relatively high levels of temperature and humidity (37.5°C, 65% relative humidity (RH); 37.5°C, 70% RH; 39.5°C, 65% RH; and 39.5°C, 70% RH) as well as a high core temperature (Tc; 42, 42.5, and 43°C). Results showed that the environmental condition of 39.5°C and 65% RH was most suitable for EHS modeling. The end point of EHS evaluation was exhaustion or an individual’s core temperature reaching 43°C. The survival rate of mice in the EHS group within 24 h under these conditions was 37.34%, which is consistent with the high mortality characteristics noted in EHS patients. Severe RM was observed in the EHS group by H&E staining and transmission electron microscopy. Creatine kinase levels in the EHS group mostly exceeded 10,000 U/L, which was approximately 10 times higher than that in the sham heat rest group. Renal tubules of the EHS group exhibited severe necrosis, and calcium overload in the skeletal muscles of this group was also observed using intravital 2-photon microscopy. In conclusion, we made improvements to a stable EHS-induced RM animal model to truly reflect the clinical characteristics of EHS patients. This new model should be helpful in the further study of RM pathogenesis.

Predictive value of myoglobin and D-dimer on severe heat stroke: a clinical analysis of 38 patients with severe heat stroke

To explore the clinical characteristics and early sensitive indicators of severe heat stroke patients in order to predict the development of severe heat stroke in the early stage. Thirty-eight patients with severe heat stroke admitted to emergency department of Beijing Daxing District People's Hospital from July 30th to August 5th in 2018 were enrolled. There were 18 patients suffered from exertional heat stroke (EHS), and 12 patients suffered from classical heat stroke (CHS), and 8 patients with heat spasm and heat exhaustion were selected as control group. The gender, age, onset time, body temperature, heart rate (HR), lactic acid (Lac), platelet (PLT), alanine aminotransferase (ALT), alanine aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (SCr), serum sodium at admission of hospital, as well as positive rate of myoglobin (MYO) and D-dimer (the positive threshold of MYO and D-dimer was 107 μg/L and 600 μg/L respectively) were recorded and compared among the groups. Receiver operating characteristic (ROC) curve was plotted to analyze the prognostic value of MYO and D-dimer on heat stroke. The outcome of all patients was followed up, and the 28-day mortality between EHS and CHS patients was compared. The patient's body temperature was measured again after 4 hours of active cooling treatment (T4 h), and the relationship between T4 h and 28-day mortality was discussed. The majority of severe heat stroke patients were male, especially in EHS patients. EHS patients were younger than CHS ones, and had shorter onset time, with significant differences among the groups. The body temperature and HR at admission in the EHS group and the CHS group were significantly higher than those in the control group [body temperature (centigrade): 41.34±0.67, 40.39±0.58 vs. 37.80±1.39; HR (bpm): 139.78±15.63, 113.08±17.70 vs. 92.00±15.89, all P < 0.05], PLT was significantly lowered (×109/L: 164.94±73.80, 165.78±53.49 vs. 249.50±84.22, both P < 0.05), and the positive rates of MYO and D-dimer were also significantly increased [MYO positive rate: 100.0% (18/18), 100.0% (12/12) vs. 50.0% (4/8); D-dimer positive rate: 77.8% (14/18), 100.0% (12/12) vs. 12.5% (1/8), all P < 0.05]. ROC curve analysis showed that positive MYO and D-dimer at admission had certain diagnostic value for heat stroke, the area under ROC curve (AUC) was 0.750 and 0.871, the sensitivity was 50.0% and 87.5%, and the specificity was 100% and 86.7%, respectively. The 28-day mortality of the EHS group was significantly higher than that of the CHS group [44.4% (8/18) vs. 8.3% (1/12), P < 0.05]. Furthermore, the 28-day mortality of the patients with T4 h ≥ 38 centigrade in the EHS group was significantly higher than those with T4 h < 38 centigrade [70.0% (7/10) vs. 12.5% (1/8), P < 0.05]. The decreased PLT and the increased D-dimer in the early stage of heat stroke indicate that the damage of coagulation mechanism is prominent in patients with heat stroke. EHS patients have the characteristics of acute onset, severe condition, rapid progression and poor prognosis, and the 28-day mortality is significantly higher than that of CHS patients. MYO and D-dimer are sensitive indicators in early stage of heat stroke patients, which can be used as reference for early diagnosis of heat stroke.

Heart rate variability dynamics during treatment for exertional heat strain when immediate response is not possible.

What is the central question of this study? Does a delay in cold water immersion treatment affect the cardiac autonomic control of exertionally heat-strained individuals? What is the main finding and its importance? Cold water immersion is effective for treating exertionally heat-strained individuals even when treatment is commenced with a significant delay. However, that treatment delay leads to only partial/transient restoration of cardiac autonomic control. Therefore, we recommend that exertional heatstroke patients are continuously monitored for several hours even after core temperature has returned to normal values. Immediate cold water immersion (CWI) is the gold-standard treatment for exertional heatstroke. In the field, however, treatment is often delayed, primarily owing to a delayed paramedic response and/or inaccurate diagnosis. We examined the effect of treatment (reduction of rectal temperature to 37.5°C) delays of 5 (short), 20 (moderate) and 40 (prolonged) min on cardiac autonomic control [as assessed via heart rate variability (HRV)] in eight exertionally heat-strained (40.0°C rectal temperature) individuals. Eleven HRV indices were computed that have been described commonly in the literature and characterize almost all known domains of the variability and complexity of the cardiopulmonary system. We found that the cardiac autonomic control (as assessed via HRV) of exertionally heat-strained individuals was significantly affected by the amount of time it took for the CWI treatment to be applied. Six out of 11 HRV indices studied, from all variability domains, displayed strong (P≤0.005) time×delay interaction effects. Moreover, the number of significantly (P≤0.005) abnormal (i.e. different from the short delay) HRV indices more than doubled (sevenversus 15) from the moderate delay to the prolonged delay. Finally, our results demonstrated that a CWI treatment applied with delays of 20 and, primarily, 40min did not lead to a full restoration of cardiac autonomic control of exertionally heat-strained individuals. In conclusion, this study supports CWI for treating exertionally heat-strained individuals even when applied with prolonged delay, but it highlights the importance of continued cardiac monitoring of patients who have suffered exertional heatstroke for several hours after restoration of core temperature to normal.