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

Abstract

Background and Aims: Exertional 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. Methods: This 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. Results: In 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. Conclusions: In 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.

Biomarkers of heatstroke‐induced organ injury and repair

“…Notably, these pathological findings also identified that the extent of liver damage was greater when survival following heatstroke exceeded 30 h (Malamud et al., 1946b), suggesting that the aetiology of liver damage initiated by heat cytotoxicity is likely amplified (or worsened) by ischaemia–reperfusion injury and an exacerbated systemic inflammatory response. This interpretation is supported by the timing of changes in ALT and AST following heatstroke, with peak concentrations being observed 2–3 days post‐heatstroke (Ji et al., 2021; Ward et al., 2020). There are no formally identified biomarkers, as defined herein, quantifying the extent of liver damage or recovery post‐heatstroke.…”

“…There are no formally identified biomarkers, as defined herein, quantifying the extent of liver damage or recovery post‐heatstroke. Nevertheless, it is important to recognize that recent evidence supports that increased circulating clinical markers of hepatic dysfunction, including ALT and AST, are associated with an increased likelihood of EHS mortality (Ji et al., 2021; Li et al., 2022). However, it is unknown whether this is due to hepatic causes per se or simply reflects the more severe clinical condition of these patients (Ji et al., 2021).…”

“…Nevertheless, it is important to recognize that recent evidence supports that increased circulating clinical markers of hepatic dysfunction, including ALT and AST, are associated with an increased likelihood of EHS mortality (Ji et al., 2021; Li et al., 2022). However, it is unknown whether this is due to hepatic causes per se or simply reflects the more severe clinical condition of these patients (Ji et al., 2021). This conclusion is supported by evidence that heatstroke elicits liver injury via IL‐1β mechanisms (Geng et al., 2015) and that pretreatment with specific antibodies that inhibit circulating HMGB1 protein, which is at least partially implicated in the inflammatory response during EHS (Tong et al., 2011a), alleviates CHS‐provoked liver pathology (Tong et al., 2013).…”

Sequential Organ Failure Assessment Score for Prediction of Mortality of Patients With Rhabdomyolysis Following Exertional Heatstroke: A Longitudinal Cohort Study in Southern China

“…Acute liver injury (ALI) ( 15 ): Plasma TBIL ≥ 34.2 μmol/L and INR ≥ 1.5, or with any grade of hepatic encephalopathy.…”

Characteristics and Outcome of Exertional Heatstroke Patients Complicated by Acute Hepatic Injury

“…We have read the article titled "Characteristics and Outcome of Exertional Heatstroke Patients Complicated by Acute Hepatic Injury: A Cohort Study" by Ji et al 1 We congratulate the authors for this insightful article. In this letter, we would like to raise several issues about the article to provide constructive criticisms.…”