Treatment Of Heat Stroke Research Articles

A case of successful pediatric heat stroke treatment using normothermic targeted temperature management

This case report describes a successful use of normothermic targeted temperature management (TTM) for the treatment of a 14-year-old girl with exertional heat stroke. Upon hospitalization, she exhibited a 40.5 ℃ core temperature and multiorgan failure. We immediately applied the TTM, targeting a range of 36-37 ℃. Her condition improved rapidly, with vital signs stabilized and consciousness fully regained by day 3. She experienced a bimodal pattern of rhabdomyolysis during recovery, which was managed without further complications. No neurological sequelae were observed, and all laboratory parameters were normalized before discharge on day 10. This case suggests the potential efficacy of normothermic TTM in pediatric heat stroke.

Rifaximin alleviates intestinal barrier disruption and systemic inflammation via the PXR/NFκB/MLCK pathway and modulates intestinal Lachnospiraceae abundance in heat-stroke mice

Heatstroke is a critical condition with a high mortality rate and intestinal barrier dysfunction is a key factor in its progression to sepsis in some patients. This study aimed to explore the protective effects of rifaximin on the intestinal barrier in heat-stroke mice and the underlying mechanisms. A mouse model of heat stroke was established, followed by rifaximin intervention. Rifaximin significantly improved survival rates, reduced core body temperature, and alleviated intestinal tissue damage. Further mechanistic studies revealed that rifaximin restored heat stroke-induced damage to intestinal barrier function by upregulating the expression of the tight junction proteins, ZO-1 and occludin. Additionally, 16S rRNA sequencing showed that rifaximin significantly increased the abundance of Lachnospiraceae in the gut and enhanced short-chain fatty acid butyrate levels. In vitro experiment results revealed that butyrate promotes the expression of the intestinal epithelial cell protein MUC2, thereby strengthening the intestinal barrier. Rifaximin also activated the pregnane X receptor (PXR) signaling pathway and inhibited the NF-κB/MLCK signaling pathway, reducing the permeability of intestinal epithelial cells. This study demonstrated that rifaximin protects the intestinal barrier in mice with heat stroke through multiple pathways by modulating the gut microbiota, increasing butyrate production, and activating the PXR signaling pathway. These findings provide a new theoretical basis for the clinical application of rifaximin in heat stroke treatment.

Voluntary head dunk: cooperative care for irrigating canine noses and eyes and rapid cooling.

To demonstrate the methods to teach dogs to voluntarily immerse (dunk) their head in a container of water, and to identify the 3 indications for voluntary head dunk: to clear a dog's nostrils of dust/debris, flush a dog's eyes, and cool a dog after exercise. Dogs. With the use of cooperative care and positive reinforcement training, the dog is taught to retrieve a toy or treat from a bucket or large container. Clean, room temperature water is added stepwise until the dog is comfortable immersing its nose and blowing bubbles or immersing its head to retrieve the toy or treat. The training may require minutes, weeks, or months, depending on the dog's motivation. Voluntary head dunk can remove dust and debris from the nasal passages and eyes and can facilitate cooling, especially after exercise. Positive reinforcement creates a cooperative environment in which first aid can be effectively administered. Contraindications include treatment of heat stroke, persistent or serious nasal or ocular discharge, or dogs that are uncomfortable or unable to dunk their heads. Pet owners and handlers of working dogs or canine athletes can teach their dogs to head dunk and implement this first aid technique for exercise-related cooling or ocular/nasal flush, even in environments with limited resources. Some dogs may be rapidly trained in the veterinary environment as an initial approach to a nasal or ocular flush. Cooperative care provides an effective intervention that preserves and enhances the human-animal bond.

The significant mechanism and treatments of cell death in heatstroke.

With global warming, extreme environmental heat is becoming a social issue of concern, which can cause adverse health results including heatstroke (HS). Severe heat stress is characterized by cell death of direct heat damage, excessive inflammatory responses, and coagulation disorders that can lead to multiple organ dysfunction (MODS) and even death. However, the significant pathophysiological mechanism and treatment of HS are still not fully clear. Various modes of cell death, including apoptosis, pyroptosis, ferroptosis, necroptosis and PANoptosis are involved in MODS induced by heatstroke. In this review, we summarized molecular mechanism, key transcriptional regulation as for HSF1, NRF2, NF-κB and PARP-1, and potential therapies of cell death resulting in CNS, liver, intestine, reproductive system and kidney injury induced by heat stress. Understanding the mechanism of cell death provides new targets to protect multi-organ function in HS.

Study on the Ideas and Methods of Bloodletting Therapy in the Treatment of Heat Stroke

Study on the Ideas and Methods of Bloodletting Therapy in the Treatment of Heat Stroke

A novel indicator for temperature control in heat stroke treatment

AbstractBackgroundTemperature control plays a pivotal role in patients with heat stroke (HS), but little work has been done sufficiently on the use of temperature control to reflect disease progression. Here, we defined and analyzed the concrete role of controlling time for core temperature to physiological level (CTTP), in order to explore a potential index to guide the treatment of HS.MethodThis is a retrospective cohort study. From three hospitals located in Sichuan province, China, we collected a total of 179 HS cases with clinical diagnosis and treatment records. We defined CTTP as the time interval of HS onset to stabilization of core temperature (rectal temperature) below 37.7°C and analyzed the correlation between CTTP and inpatient death of HS patients.ResultsOf all the cases, 64.80% were male and 53.07% were exertional heat stroke (EHS). The median (IQR) age was 59 (23.5–73) years old, and the median (IQR) onset temperature was 42 (40.4–42)°C. Multivariable analysis demonstrated significantly high inpatient death in the highest CTTP tertile (>18 h) (hazard ratio: 18.75; 99% confidence interval: 4.06–86.59; p = .0002). In addition, compared with patients in lowest CTTP tertile, patients in highest CTTP tertile were at significantly higher risk of organ damage: 3.48‐fold for respiratory failure (95% CI: 1.41–8.59, p = .0069); 3.18‐fold for shock (95% CI: 1.37–7.39, p = .0071); 4.09‐fold for rhabdomyolysis (95% CI: 1.73–9.64, p = .0013); 4.64‐fold for renal damage (95% CI: 2.12–10.14, p = .0001).ConclusionLong of CTTP predicts inpatient death of HS patients with a CTTP tertile >18 h associated with the highest rate of inpatient death.

Tarp-Assisted Cooling for Exertional Heat Stroke Treatment in Wildland Firefighting

Exertional heat stroke is a life-threatening emergency necessitating immediate treatment with rapid body cooling. A field-expedient alternative may be tarp-assisted cooling, requiring only water and a tarp. The objective of this study was to compare core temperature (Tc) cooling rates of tarp-assisted cooling using the limited resources available to a wildland firefighter and the current standard care provided in wilderness settings. This cross-over, randomized control trial of 17 healthy individuals consisted of exercise in a 42±1°C, 32±4% relative humidity environment while wearing wildland firefighter attire, followed by cooling. Body cooling consisted of either pouring 11 L of 25±1°C water over the torso while lying supine on a tarp configured to hold water close to the individual (Tarp) or dousing the water on the participant followed by lying supine with a light breeze, current standard care in the wilderness (Current Care). Cooling occurred until Tc reached 38°C. Participants walked until a similar Tc was achieved in Tarp (39.59±0.04°C) and Current Care (39.55±0.22°C; P=0.36). Core temperature cooling rate was not different between Tarp (0.076±0.042°C·min-1) and Current Care (0.088±0.046°C·min-1; P=0.41). In hyperthermic individuals, Tarp did not provide a faster cooling rate compared to the current exertional heat stroke care provided in the wilderness, and both provided a slower cooling rate than that provided by the traditional method of cold water immersion (>0.20°C·min-1) to treat exertional heat stroke patients.

Protective and immunomodulatory effects of mesenchymal stem cells on multiorgan injury in male rats with heatstroke

Heatstroke (HS) causes multiple organ dysfunction syndrome (MODS) with a mortality rate of 60% after hospitalization. Currently, there is no effective and targeted approach for the treatment of HS. Despite growing evidence that mesenchymal stem cells (MSCs) may reduce multiorgan damage and improve survival through immunomodulatory effects in several diseases, no one has tested whether MSCs have immunomodulatory effects in heatstroke. The present study focused on pathological changes and levels of the cytokines and immunoglobulins to investigate the mechanisms underlying the protective effect and the anti-inflammatory effects of MSCs. We found that MSCs treatment significantly reduced the 28-day mortality rate (P < 0.05), the levels of hepatic and renal function markers on day 1 (P < 0.01) and the pathological lesion scores of multiple organs in HS rats. The levels of IgG1, IgM, and IgA of the HS + MSC group was significantly higher than that in HS group on days 3 and 28(P < 0.05). In conclusion, MSCs contribute to protecting against multiorgan injury, reducing pro-inflammatory cytokines, stabilizing immunoglobulins, and reducing the mortality rate of HS rats.

Xuebijing Injection Attenuates Heat Stroke-Induced Brain Injury through Oxidative Stress Blockage and Parthanatos Modulation via PARP-1/AIF Signaling.

Heat stroke (HS) is a potentially fatal acute condition caused by an interplay of complex events including inflammation, endothelial injury, and coagulation abnormalities that make its pharmacological treatment a challenging problem. The traditional Chinese medicine Xuebijing injection (XBJ) has been shown to reduce inflammatory responses and prevent organ injuries in HS-induced mice. However, the underlying mechanism of XBJ in HS-induced brain injury remains unclear. In this study, HS-induced rat models and cell models were established to elucidate the effects and underlying mechanisms of XBJ injection on HS-induced brain injury in vivo and in vitro. The results revealed that XBJ injection improved the survival outcome of HS rats and attenuated HS-induced brain injury in a concentration-dependent manner. Subsequently, the reduction in viability and proliferation of neurons induced by HS were reversed by XBJ treatment, while the HS-induced increased ROS levels and neuron death were also inhibited by XBJ injection. Mechanistically, HS activated PARP-1/AIF signaling in vitro and in vivo, inducing the translocation of AIF from the cytoplasm to the nucleus, leading to PARP-1-dependent cell death of neurons. Additionally, we compared XBJ injection effects in young and old age rats. Results showed that XBJ also provided protective effects in HS-induced brain injury in aging rats; however, the treatment efficacy of XBJ injection at the same concentration was more significant in the young age rats. In conclusion, XBJ injection attenuates HS-induced brain injury by inhibiting oxidative stress and Parthanatos via the PARP-1/AIF signaling, which might provide a novel therapeutic strategy for HS treatment.

Expert consensus on the prevention and treatment of heatstroke in children (2023)

Due to the immature development of temperature regulation in the central nervous system, children have a weakened ability to regulate heat and are susceptible to heatstroke, which can lead to organ damage. Based on the evidence evaluation criteria of the Oxford Centre for Evidence-Based Medicine, this expert consensus group evaluated the current evidence on heatstroke in children, and formed this consensus through thorough discussion with the aim of providing reference for the prevention and treatment of heatstroke in children. This consensus includes classifications, pathogenesis, prevention measures, as well as pre-hospital and in-hospital treatment plans for heatstroke in children.

Monitoring heat stroke with a HClO-activatable near-infrared fluorescent probe

Heat stroke is devastating pathology associated with a high morbidity and mortality rate. If heat cytotoxicity mechanisms are understood early, stroke-related diseases can be prevented or treated. Unfortunately, the details of lysosome's role in heat stroke remain poorly understood due to a lack of adequate tools. Recent studies indicate a correlation between lysosome HClO and the development of heat stroke. For better interpretation and treatment of heat stroke, the urgent and reliable real-time tools for tracking the correlation between HClO level and heat stroke is necessary. Herein, we present MB-HClO, a near-infrared (NIR) probe for rapidly detecting lysosome HClO. In addition to being an easy chemical to synthesize, MB-HClO shows remarkable selectivity and sensitivity to HClO. By applying MB-HClO to living cells, we have successfully monitored levels of both exogenous and endogenous HClO. Furthermore, this probe can distinguish inflammation from a normal brain state in LPS-induced neuroinflammation. Additionally, HClO can be measured non-invasively and visually for the first time in response to heat shock by imaging lysosome HClO increase. Therefore, MB-HClO is a promising candidate for research on heat stroke's complex biological mechanism.

Critical illness aspects of heatstroke: A hot topic.

Heatstroke represents the most severe end of the heat illness spectrum, and is increasingly seen in those undergoing exercise or exertion ('exertional heatstroke') and those exposed to high ambient temperatures, for example in heatwaves ('classical heatstroke'). Both forms may be associated with significant thermal injury, leading to organ dysfunction and the need for admission to an intensive care unit. The process may be exacerbated by translocation of bacteria or endotoxin through an intestinal wall rendered more permeable by the hyperthermia. This narrative review highlights the importance of early diagnosis, rapid cooling and effective management of complications. It discusses the incidence, clinical features and treatment of heatstroke, and discusses the possible role of intestinal permeability and advances in follow-up and recovery of this condition. Optimum treatment involves an integrated input from prehospital, emergency department and critical care teams, along with follow-up by rehabilitation teams and, if appropriate, sports or clinical physiologists.

Heat stroke management during the COVID-19 pandemic: Recommendations from the experts in Japan (2nd edition).

Both coronavirus disease 2019 (COVID-19) and heat stroke have symptoms of fever or hyperthermia and the difficulty in distinguishing them could lead to a strain on emergency medical care. To mitigate the potential confusion that could arise from actions for preventing both COVID-19 spread and heat stroke, particularly in the context of record-breaking summer season temperatures, this work offers new knowledge and evidence that address concerns regarding indoor ventilation and indoor temperatures, mask wearing and heat stroke risk, and the isolation of older adults. Specifically, the current work is the second edition to the previously published guidance for handling heat stroke during the COVID-19 pandemic, prepared by the "Working group on heat stroke medical care during the COVID-19 epidemic," composed of members from four organizations in different medical and related fields. The group was established by the Japanese Association for Acute Medicine Heatstroke and Hypothermia Surveillance Committee. This second edition includes new knowledge, and conventional evidence gleaned from a primary selection of 60 articles from MEDLINE, one article from Cochrane, 13 articles from Ichushi, and a secondary/final selection of 56 articles. This work summarizes the contents that have been clarified in the prevention and treatment of infectious diseases and heat stroke to provide guidance for the prevention, diagnosis, and treatment of heat stroke during the COVID-19 pandemic.

Treating exertional heat stroke: Limited understanding of the female response to cold water immersion.

According to an expansive body of research and best practice statements, whole-body cold water immersion is the gold standard treatment for exertional heat stroke. However, as this founding evidence was predominantly drawn from males, the current guidelines for treatment are being applied to women without validation. Given the recognised differences in thermal responses experienced by men and women, all-encompassing exertional heat stroke treatment advice may not effectively protect both sexes. In fact, recent evidence suggests that hyperthermic women cool faster than hyperthermic men during cold water immersion. This raises the question of whether overcooling is risked if the present guidelines are followed. The current mini-review examined the literature on women's response to cold water immersion as a treatment for exertional heat stroke and aimed to clarify whether the current guidelines have appropriately considered research investigating women. The potential implications of applying these guidelines to women were also discussed.

Outer membrane vesicles derived from heatstroke-associated intestinal microbiota promote multiple organ injury in mice.

Multiple organ injury is a common issue in heatstroke (HS); however, the underlying pathogenesis remains unclear. As an early event in HS, intestinal injury is an active participant that drives organ injury. Outer membrane vesicles (OMVs), a group of vesicles shed by unbalanced intestinal microbiota as "danger signals," mediate different functional cargo transport in cells and modulate varying biological events in distant target cells. However, the role of OMVs in HS-mediated organ damage remains unclear. Therefore, this study examined OMV production in HS and explored the effect of regulating multiple organ injury. To construct a mouse model, animals were exposed to hyperthermia. OMVs from the intestinal microbiota of HS and control mice were extracted by standardized differential ultracentrifugation. Thereafter, OMVs were characterized and infused into recipient mice via the tail vein. Cl-amidine (a pan-peptidylarginine deiminase inhibitor and OMV production inhibitor) was injected intraperitoneally (2mg/kg) 2h before HS treatment, and the absorption of HS OMVs by different organs was tracked. The effect of OMVs on inducing organ pathological changes, inflammatory infiltration, inflammatory cytokine expression, and serum organ injury biomarkers was demonstrated. HS increased OMV production by intestinal microbiota; OMVs were absorbed by different organs in vivo, and were especially enriched in the liver and lung. Compared to control OMVs, infusion with HS OMVs induced significant organ pathological changes, elevated inflammatory cell (macrophages and neutrophil) infiltration, inflammatory cytokine (TNF-ɑ, IL-1β, IL-6) expression, as well as serum biomarkers of organ injury. Similarly, inhibition of endogenous OMVs alleviated these organ injury indicators induced by HS. To our knowledge, the present study is the first to illustrate that OMVs induce acute organ impairment during severe HS, offering a foundation for subsequent studies and providing novel therapeutic targets.

Chinese foreign medical aid work should pay attention to heat stroke as a preventable disease under global warming context

Within the global warming context, heat stroke heavily threatens human health as the most severe type of heat-related illnesses. Despite the urgent onset, severe condition and poor prognosis, heat stroke is entirely preventable and treatable. Most of the recipient countries of Chinese foreign medical aid work are concentrated in the tropical and subtropical regions. It is necessary to popularize the knowledge of heat stroke and improve the ability of diagnose and treatment among foreign medical aid members, which is critical to enhance the quality of medical service and provide better medical care for recipient countries and workers in Chinese-funded institutions. This article reviews the latest research progress in the epidemiology, pathophysiology, diagnosis, and treatment of heat stroke to provide scientific reference for actively implementing interventions and reducing morbidity and mortality.

HMGB1-activatied NLRP3 inflammasome induces thrombocytopenia in heatstroke rat.

BackgroundThrombocytopenia, an early common complication in heatstroke (HS), has been widely considered as a mortality predictor of HS. The mechanism underlying thrombocytopenia in HS remains unknown. It is not known whether NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is activated in HS platelet, which, in turn, induces platelet activation and thrombocytopenia. This study tried to clarify the activation of the NOD-like receptor signaling pathway under HS conditions and investigate its roles in mediating HS-induced thrombocytopenia.MethodsRat HS models were established in a certain ambient temperature and humidity. Platelets, isolated from blood, were counted and CD62P, an index of platelet activation, was measured by flow cytometry in all rats. The colocalization of NLRP3 inflammasome in platelet was detected by confocal fluorescence microscopy. Mitochondrial-derived reactive oxygen species (ROS) was detected using the molecular probes. Plasma HMGB1 and IL-1β levels were measured by ELISA.ResultsPlatelet activation, showed by upregulated CD62P, and thrombocytopenia were observed in HS rats. HS activated the NLRP3 inflammasome, which was induced by elevated levels of ROS, while the upregulated CD62P and thrombocytopenia triggered by NLRP3 inflammasome were attributed to the high mobility group box protein 1 (HMGB1) inplasma. Moreover, inhibition of the NOD-like receptor signaling pathway in rats with HS suppressed platelet activation and the decline of platelet count. Similar results were obtained when the receptor toll-like receptor 4 (TLR4)/advanced glycation end product (RAGE) was blocked.ConclusionsThe NOD-like receptor signaling pathway induces platelet activation and thrombocytopenia in HS rats. These findings suggested that the NLRP3 inflammasome might be the potential target for HS treatment.

Persistent Knowledge Gaps Regarding Exertional Heat Stroke Treatment.

Individualized patient care is ideal for treating and rehabilitating patients with athletic illnesses and injuries. Exertional heat stroke (EHS) treatment best-practice recommendations state that all patients should undergo identical cold-water immersion (CWI) treatment for ideal outcomes. It is unknown, however, whether CWI can be optimized with individualized treatment plans, encouraging personalized medicine. To accomplish this task, clinicians and researchers need to better understand the factors affecting CWI effectiveness. In this short report, we will provide an update to the American College of Sports Medicine Roundtable on Exertional Heat Stroke, review research regarding EHS treatment, and identify knowledge gaps in EHS treatment.

Design and application of a cooling device based on the phase-change material for heat stroke

Heat stroke is a critical and health-threatening disease, triggered by thermal stimulus and progressing rapidly. It can give rise to multiple organ dysfunction syndrome (MODS), resulting in a high mortality rate. Nearly 30% of survivors will suffer with different sequelae, for instance, the neurological sequelae. Currently, the early rapid cooling is the focus of therapy for heat stroke. Therefore, it is imperative to design a cooling module suitable for the treatment of heat stroke in the field and in the hospital to realize the goal of early rapid cooling and the effective targeted temperature management (TTM). The cooling device is composed of a cooling blanket and a cooling cap. The blanket and cap are made by temperature changeable fabric. The cooling blanket comprises a backing layer, a buffer layer, a flexible heat conduction capsule body, a temperature changing component, a fixed part and a temperature sensor. The cooling cap includes a main body and two side ears, in which the main body is worn on the top of the patient's head, and the front is equipped with a flexible display screen, which is convenient for real-time monitoring the temperature of the temperature change component of the cooling blanket. The lateral ear can wrap the patient's ears and neck, and the tympanic membrane thermometer is designed to monitor the tympanic membrane temperature in real time. The tympanic membrane thermometer is also designed at the ear to monitor the tympanic auditory canal temperatures in real time.Continuous dynamic temperature monitoring can guide the duration of cooling treatment and stop cooling in time. The cooling component is portable, easy to operate, real-time temperature monitoring, excellent cooling effect and reusable. It is used for on-site first aid, transportation and continuous cooling for patients with heat stroke in the ward.

Mesenchymal stem cells regulate activation of microglia cells to improve hippocampal injury of heat stroke rats.

Heat stroke is a severe systemic inflammatory response disease caused by high fever, mainly with nervous system damage. Mesenchymal stem cells (MSCs) are currently believed to have anti-inflammation and immunomodulatory effects. Therefore, we aimed to explore the protective effect and mechanism of MSCs on heat stroke-induced excessive inflammation and neurological dysfunction. We established a heat stroke model in rats under conditions of continuous high temperature and high humidity. After modeling, rats were randomly divided into heat stroke model group, MSCs treatment group and normal temperature control group without any treatment. We performed survival analysis, neurological deficit score, histological staining of hippocampus and cerebellum, immunofluorescence staining of microglia, detection of inflammatory and chemokine levels in the hippocampus and cerebellum in each group. We found that MSCs treatment not only significantly reduced early (day 3) and late (day 28) mortality, but also prominently reduced nerve injury in heat stroke rats, and improved pathology and neuronal cell damage in the hippocampus and cerebellum. In addition, MSCs treatment can significantly inhibit the over-activation of hippocampal microglia in heat stroke rats and the levels of pro-inflammatory factors and chemokines in the hippocampus. Early treatment of MSCs can greatly promote the activation of cerebellar microglia in heat stroke rats. Meanwhile, MSCs treatment has an inhibitory effect on the level of chemokine in the cerebellum of rats in the early stage of heat stroke. In conclusion, the application of MSCs in the treatment of heat stroke in rats can significantly reduce mortality and neurological deficits and improve hippocampal damage, possibly by inhibiting the excessive activation of hippocampal microglia in heat stroke rats.