Heatstroke is a severe form of heat-related illness characterized by a rapid elevation of core body temperature exceeding 40°C, accompanied by central nervous system dysfunction (1, 2). Heatstroke can be classified into two main types: classical heatstroke and exertional heatstroke (1, 3). Classical heatstroke is typically associated with passive exposure to high temperature and humidity and often manifests in epidemic outbreaks. It primarily affects older people with pre-existing medical conditions. On the other hand, exertional heatstroke predominantly occurs in young, otherwise healthy individuals engaged in vigorous physical activities in hot or mildly hot environments (4). Within the intensive care unit (ICU) setting, the mortality rates for patients with exertional and classical heatstroke are reported as 26.5 and 63.2%, respectively (5).

Heatstroke can result in varying degrees of organ dysfunction (6). When the body’s core temperature surpasses 40°C and the compensatory mechanisms fail, cellular damage occurs (7). This, in turn, can trigger ischemia–reperfusion injury, excessive inflammatory response, and disseminated intravascular coagulation, leading to further impairment of organ function (8–10). The primary manifestations of heatstroke-induced organ dysfunction encompass central nervous system disorders, coagulation abnormalities (11), liver dysfunction (12, 13), circulatory failure, respiratory failure, and renal failure (14), among others (5, 15).

Considering the limited availability of multicenter descriptive data regarding intensive care unit (ICU) patients, this multicenter study was designed with the aim of describing and analyzing the characteristics of such patients. This effort aims to offer assistance in standardizing the diagnosis and treatment of Heatstroke, with the ultimate goal of enhancing the prognosis for Heatstroke patients.

“Heatstroke” represents the most critical stage in the progression of heat-related illnesses. It occurs when there is an excessive buildup of heat in the body, surpassing its capacity to dissipate heat, typically following intense physical exertion or exposure to extreme thermal conditions (16). Clinical manifestations of heatstroke include central nervous system (CNS) dysfunction, multiple organ failure, and a significant rise in body temperature, often exceeding 40.0°C (5, 17). In our dataset, the median of the initial temperature measurement among heatstroke patients was recorded as 40.8 (40, 41.4) °C. Heatstroke can be further classified into classical and exertional types based on its underlying causes (1, 2). Among our study participants, 565 (73.57%) patients were identified as having classical heatstroke. Classical heatstroke primarily occurs when individuals are exposed to high ambient temperatures and experience impaired heat dissipation mechanisms. This type of heatstroke is commonly observed in older adults, children, and individuals with underlying health conditions (18). In line with this observation, the median age of patients with classical heatstroke in our dataset was 75 (66, 82) in Supplementary Table S1, reinforcing the aforementioned conclusion.

Cardiovascular disease, respiratory disease, and diabetes are known to impair the body’s ability to adapt to environmental changes (16). Among the 474 Heatstroke patients in our study, 200 (42.2%) had hypertension, 127 (26.8%) had chronic obstructive pulmonary disease, and 92 (19.4%) had diabetes. Hypertension is characterized by increased peripheral vascular resistance and various alterations in peripheral circulation, including vascular smooth muscle hypertrophy and vascular remodeling. These changes can impair the regulation of skin blood flow, thus compromising the body’s ability to regulate core temperature (19–21). Epidemiological evidence suggests that individuals with respiratory conditions such as asthma, chronic obstructive pulmonary disease, lung cancer, influenza, pneumonia, bronchitis, tuberculosis, and cystic fibrosis may be more susceptible to the effects of heat exposure (22, 23). A meta-analysis has reported that people with respiratory diseases have a higher risk of mortality during heat waves (odds ratio 1.61, 95% confidence interval 1.2 to 2.1) (24). Additionally, studies have shown that poor glycemic control and the presence of neuropathy in individuals with type 2 diabetes can affect the sweating response, further impacting heat regulation (25, 26). However, the specific mechanisms underlying the relationship between these factors and heatstroke are not yet fully understood, and further research is needed to elucidate their interplay (27, 28).

Heatstroke can result in various degrees of organ dysfunction (29). The inflammatory response observed in heatstroke bears similarities to systemic inflammatory response syndrome (SIRS), which can rapidly deteriorate clinical status and lead to disseminated intravascular coagulation, multiple organ failure syndrome, and ultimately, death (17). Among heatstroke patients in the ICU, there are diverse complications, including disturbances in water and electrolyte balance (n = 454), liver function impairment (n = 331), renal function impairment (n = 316), myocardial damage (n = 306), central nervous system damage (n = 289), respiratory failure (n = 272), coagulation dysfunction (n = 235), rhabdomyolysis (n = 130), gastrointestinal bleeding (n = 89), and others. Retrospective studies have identified metabolic acidosis as a prominent acid–base alteration (30). In heatstroke-induced multiple organ dysfunction syndrome (MODS), the liver is recognized as one of the organs most susceptible to early damage (31). The mechanism underlying liver injury in heatstroke involves not only systemic factors such as systemic inflammatory reactions and coagulation dysfunction but also pathological mechanisms like aberrant hepatocyte death and impaired function of Kupffer cells (32).

Neurological alterations are significant features observed in both classical heatstroke and exertional heatstroke (5). These changes typically manifest suddenly in approximately two-thirds of patients and can present as mental disorders, including confusion, delirium, or drowsiness (33–35). The patient cohort was categorized into two groups: those with neurological symptoms as the initial episode (n = 715) and those without neurological symptoms as the initial episode (n = 104). It was determined that patients with neurological symptoms as the first episode had a higher risk of ICU mortality, with a hazard ratio of 2.382 (95% CI 1.665, 4.870) (p = 0.017). The susceptibility of the central nervous system to hyperthermia leads to increased metabolic rate in the brain, reduced blood flow, enhanced permeability of the blood–brain barrier, and greater infiltration of inflammatory factors and pathogens into the brain (36). Consequently, the central nervous system represents a primary target organ in severe heatstroke (37). Previous clinical investigations have demonstrated that neurological disabilities exert an adverse impact on long-term ICU mortality in heat-related diseases (38–40).

Currently, treatment for heat radiation disease remains supportive, lacking a specific therapy (5). This condition arises when the body’s heat accumulation surpasses its capacity to dissipate heat, either due to inadequate thermoregulation in an uncompensated thermal environment or a breakdown of thermoregulation caused by dehydration (41, 42). Given the era of global warming, adopting effective preventive measures against heat radiation disease appears crucial.

This study has several limitations that should be acknowledged. Firstly, the geographical scope of the study was predominantly limited to the southwest region of China. To enhance the generalizability of the findings, it is imperative to include more diverse regions in future research. Secondly, being a retrospective multicenter cohort study, inherent biases in data collection are inevitable. For example, information bias may occur, including systematic errors in the collection and collation of relevant disease data. It is important to recognize that the study findings may be influenced by these biases. Thirdly, the relatively small sample size of patients with Exertional Heatstroke (EHS) in our study might diminish the statistical power and precision of the analysis. Nevertheless, no comprehensive investigation has been conducted to determine the potential neuroprotective effects of induced hypothermia on patients with Heatstroke, nor its impact on prognosis. Consequently, our research team intends to initiate a multicenter prospective study in 2023, aimed at addressing this knowledge gap and resolving this issue.

Heatstroke can result in varying degrees of organ dysfunction. Furthermore, the intensive care unit (ICU) outcomes for patients with heatstroke presenting with initial symptoms related to the nervous system are poorer compared to those without such symptoms. In 2022, most of the patients with Heatstroke in southwest China are patients with classical Heatstroke. Most of the patients were infected when they were admitted to ICU. In addition, Heatstroke can lead to different types of complications. Due to the large geographical span of China, the occurrence of Heatstroke is different in different regions. In the future, we plan to include as many centers and more cases as possible in different regions, so as to provide more abundant evidence for Heatstroke.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving humans were approved by Ethical approval was obtained from the ethics committee of the West China Hospital of Sichuan University (NO: 2022-1542). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

LS: Writing – original draft. BW: Writing – original draft. QW: Writing – review & editing. JY: Methodology, Writing – original draft. LW: Writing – original draft. DW: Writing – original draft. YW: Writing – original draft. ZF: Writing – review & editing. WZ: Writing – review & editing. LL: Writing – review & editing. WW: Writing – review & editing. JC: Writing – review & editing. XA: Writing – review & editing. JZ: Writing – review & editing. ZZ: Supervision, Writing – review & editing. MH: Writing – review & editing.