Fatal exertional heat stroke EHSexertional heat stroke due to extreme training such as marathon exercise is mostly combined with multiple organ failure (MODS). Among the predisposing factors, five factors, namely insufficient physical strength, physical training incompatible with physical fitness, lack of proper medical classification of the injured and sick, improper diagnosis, and improper treatment, were found to be significantly different in the fatal cases. Due to the high temperature and high humidity environment, the body heat production increases rapidly, too little heat dissipation, so that the balance of heat production and heat dissipation is out of balance due to. It becomes pyrexia, and its harmfulness is mainly manifested in the toxic effects of high body temperature on cells, including increased creatine kinase, and even increased blood myoglobin, which triggers multi-organ dysfunction in the human body. From mild to severe, it is categorized into three types: heat cramps, heat exhaustion and pyrexia. Pyrexia is the most serious type of heat stroke, which is mainly characterized by high fever (body temperature over 40°C) and mental abnormalities (e.g., coma), and is divided into two categories: exertional and non-exertional. Exertional-type heat stroke, which mostly occurs in high temperature and strenuous exercise (e.g., workers operating under high temperature, outdoor athletes), is prone to rhabdomyolysis. High heat or exercise can cause rhabdomyolysis, and exercise in a high heat environment is more likely to cause rhabdomyolysis. Rhabdomyolysis due to heat stroke (e.g., exertional pyrexia) and exercise rhabdomyolysis are both related and distinct, the main points of differentiation being that the primary cause of the former is heat stroke and hyperthermia, and the primary cause of the latter is exercise. However, it is now believed that malignant hyperthermia, heat stroke and rhabdomyolysis may belong to the same family of syndromes, and there may be some association in the genetic background. Exercise rhabdomyolysis after hyperthermia EHS-EIR (Exertional Heat Stroke-Exercise Rhabdomyolysis) is a clinical syndrome caused by disintegration and rupture of muscle fibers after exercise resulting in the release of myocyte contents into the bloodstream, which is characterized by myalgia, fatigue, muscle swelling, dark-colored urine, and blood levels of myocyte contents (especially myoglobin and creatine kinase) in the blood. For patients with persistent muscle tension, it has been found in recent years that the administration of the skeletal muscle relaxant DANTROLENE DANTROLENE SODIUM, which inhibits the release of intracellular calcium ions, reduces the intracellular calcium content and the serum CK level with better results. Severe athletic rhabdomyolysis can be complicated with acute renal failure, acute fascial interstitial compartment syndrome, diffuse intravascular coagulation and multiple organ dysfunction syndrome, even life-threatening. Early active intravenous rehydration and timely blood purification treatment can prevent further progression of the disease. Most of the disease has a good prognosis, such as the emergence of serious complications mortality rate is significantly higher, and the long-term neurological symptoms of severe feeing damage. Attention should be paid to prevention and treatment in military training and sports. EIR mostly occurs in marathon running, 5km armed cross-country, skiing, rowing, mountaineering, weight lifting, bodybuilding athletes or ordinary infrequent training and suddenly a large number of people with strenuous physical activity, in the greater intensity of military training in the common soldiers. Studies have shown that 39% of recruits can develop increased blood myoglobin levels during the first week of training.EIR Exercise Rhabdomyolysis Factors contributing to the onset of Rhabdomyolysis include usual exercise, pre-exercise physical condition, type of exercise and environment, medication taken, and the presence of underlying hereditary disorders. The risk of developing Rhabdomyolysis is increased by infrequent exercise, recent illnesses such as colds and fever, medications that increase muscle damage, and strenuous exercise in hot, humid environments or at high altitudes. Intensity of exercise is more important than duration. Common genetic disorders that predispose to EIR include carnitine palmitoyltransferase deficiency and sickle cell anemia. Mechanisms of Onset as Muscle Damage 1) Mechanical Damage: After intense, repetitive, prolonged, and high-intensity mechanical contraction of the muscle, the muscle fibers are overstretched, resulting in damage to the structure of the transverse striated muscle. The speed of muscle stretching is the main factor affecting the onset. 2) Ischemia-reperfusion injury: excessive muscle contraction leads to muscle ischemia, and when the ischemic muscle is reperfused, ATP depletion in the tissues and reduction of glycogen storage lead to further muscle damage.3) Thermal injury: excessive contraction of the muscle can cause an increase in muscle temperature, which is more pronounced in hot and humid environments in which heat dissipation is difficult. High heat not only increases the rate of energy metabolism and ATP consumption, but also improves the activity of degradation enzymes (for every 1℃ rise in body temperature, the enzyme activity is increased by 10%), which makes myocytes more susceptible to damage and affects the integrity of myocyte membranes, leading to rhabdomyolysis and necrosis.4) Lipid peroxidation injury: excessive contraction of muscles and ischemia and hypoxia, which can produce inflammatory mediators, disrupting the osmotic balance of cell membranes, increasing the permeability and increasing the fluid permeability, and decreasing the body fluid permeability and the body fluid permeability, which leads to further damage. permeability increases, and body fluids accumulate in the tissue interstitial space resulting in local edema and a decrease in effective circulating blood volume.5) Sodium and calcium ion overload in myocytes: sodium ion in-flow will be followed by water in-flow, resulting in cell swelling and even cell death. Mechanisms of concomitant renal injury 1) Myoglobin tubular obstruction of renal tubules: after destruction of a large number of skeletal muscle cells, myoglobin enters the bloodstream and is filtered through the glomerulus, the concentration of myoglobin in the renal tubules rises above the threshold of renal excretion, and a tubular obstruction of renal tubules is formed, which causes an increase in tubular luminal pressure and thus hinders glomerular filtration. 2) Direct nephrotoxicity of myoglobin: in an acidic environment of the urine, myoglobin is decomposed into Myoglobin is decomposed into pearl protein and ferrous hemoglobin in the acidic environment of urine, and the latter induces the formation of oxygen free radicals and lipid peroxidation damage to the epithelial cells of the renal tubules. Ferrous hemoglobin is also a scavenger of the vasodilatory factor nitric oxide (NO), which can cause ischemic injury to the renal tubules .3) Renal ischemia: a large amount of sweating during strenuous activities, the blood volume decreases markedly; due to the large amount of blood supply to the muscles, the blood is redistributed, the renal blood supply is reduced by about 50%, and the glomerular filtration rate decreases by 30% to 60%. Hypovolemia or dehydration and aciduria are important prerequisites for myoglobinuria-induced ARF. In the absence of hypovolemia and aciduria, myoglobin is only minimally nephrotoxic, but when both of these conditions are present it can lead to renal injury through the mechanisms described above. The clinical manifestations of EHS-EIR vary in severity and include those primary to rhabdomyolysis and those secondary to electrolyte disturbances, ARF, diffuse intravascular coagulation (DIC), acute fascial compartment syndrome, and other complications. The typical “triad” of symptoms that originate from rhabdomyolysis includes myalgia, fatigue and dark urine. The symptoms of myalgia, fatigue, muscle tenderness, and muscle contracture can be localized or generalized. In some patients, the symptoms are found in the thigh, gastrocnemius, and lumbar muscles. Abnormal urine color is often the first symptom of EIR. Depending on the amount of myoglobin in the urine, the urine may be washed water color, strong tea color, soy sauce color, with varying shades. Some patients may have transient loss of consciousness, profuse sweating, headache, nausea, vomiting, high fever and other systemic symptoms. Physical examination reveals swelling and tenderness of the affected muscles, increased tension, limited subcutaneous bruising, petechiae, decreased muscle strength, decreased active and passive range of motion, and weakened or even absent tendon reflexes. However, only a small number of patients may present the above typical manifestations, and most of them only present muscle pain, weakness and other symptoms similar to viral infections. EIR may also present with clinical manifestations of electrolyte disorders. Hypocalcemia can cause limb numbness, laryngeal stridor, painful muscle spasms, hand and foot twitching, and transient generalized tonic and clonic seizures; while hyperkalemia can lead to slow heart rate, arrhythmia, and in severe cases, ventricular fibrillation and cardiac arrest, resulting in death. ARF and DIC often appear 12-72 h after acute onset of the disease. ARF and DIC usually appear 12 to 72 hours after the acute onset of the disease. Patients with ARF may have oliguria or even anuria, while DIC is characterized by extensive cutaneous, mucosal, and visceral hemorrhage, drop in blood pressure, and symptoms of shock and embolism. Acute fascial compartment syndrome usually occurs in the anterior tibial region of the lower leg and is characterized by severe pain, swelling, sensory abnormalities, inability to dorsiflex the foot, and diminished or absent dorsalis pedis arterial pulsation, and can also occur in the thighs and buttocks. If not treated in time, muscle necrosis may occur, resulting in amputation or even life-threatening. In a few patients, multiple organ dysfunction syndrome may occur as a complication. Laboratory and imaging tests.1 Serum enzyme test Creatine kinase (CK) is the most sensitive indicator of myocyte injury. CK begins to rise within 12 h after muscle injury, peaks in 1-3 d, and begins to fall in 3-5 d. CK decreases every 24 h, and then decreases by about 1.5 d after muscle injury. CK decreases by about 40% every 24 h. If the decrease is slow, it indicates that there may be progressive muscle damage. It is generally believed that CK exceeding 5 times or more than the normal peak value has diagnostic significance for rhabdomyolysis. CK shows a significant positive correlation with changes in serum potassium, urea nitrogen, creatinine, and its peak value can be used as a predictor of prognosis, and patients with CK ≥5,000 U?L1 have a higher likelihood of developing ARF. CK has three isoenzymes, CK sings MB mainly in cardiac muscle, CK sings BB mainly in brain tissue and CK sings MM predominantly in skeletal muscle [15], so it is feasible to exclude cardiac muscle and brain tissue injury by isoenzyme detection. Carbonic anhydrase III is only found in skeletal muscle, and its elevated level is more specific than CK, but due to the complexity and cost of the assay, it is not routinely used as a test.2 Lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) are also elevated in EIR but lack specificity.2 Myocardial isotope assay is not recommended for cardiac and cerebral tissue injury. lack of specificity.2 Myoglobin When large amounts of muscle tissue are destroyed, myoglobin is released from the cells into the blood and filtered from the kidneys, resulting in a marked increase in both blood and urinary myoglobin concentrations, and the appearance of dark reddish-brown myoglobinuria. Due to the short plasma half-life of myoglobin, the sensitivity is not high, so the negative blood myoglobin can not exclude EIR, and the positive has the diagnostic value of the disease.4.3 Urine examination The urine can be reddish brown due to the inclusion of myoglobin, and the occult blood test is positive (prescription ～ specimen), but the microscopic examination does not have obvious red blood cells (0 ～ ＜ 5RBC / HPF). Urine sediment examination shows brown pigmented tubular pattern and renal tubular epithelial cells. However, when acute tubular necrosis or other acute kidney injury occurs, urinary erythrocytes and other urinalysis abnormalities, such as abnormally high urinary KIM sing 1, NAG, NAGL. When patients are complicated with ARF, urinary electrolytes can be used to reflect the function of the renal tubules, and the most important index is the fraction of filtered sodium excretion (FNA), which is a sensitive index to identify prerenal azotemia and acute tubular necrosis. When acute tubular necrosis occurs, the urinary sodium concentration is elevated (>20 meq/l) and the FNA is >1%.3 Blood biochemistry tests Blood creatinine and urea nitrogen may be elevated in patients with EIR. The ratio of blood urea nitrogen to creatinine is normally about 10:1, and decreases to 6:1 or less in rhabdomyolysis. However, in the later stages of disease development, the production of urea increases significantly due to the breakdown of large amounts of muscle protein, and the ratio of blood urea nitrogen to creatinine is higher than normal. Patients with EIR may develop marked hyperuricemia because of the release of large amounts of purines from damaged myocytes. Electrolyte disorders such as hyperkalemia, hyperphosphatemia, and hypocalcemia may occur in the acute phase, and hypercalcemia may occur in some patients during the recovery phase.4 Imaging examination Ultrasound suggests that the muscle texture is blurred, and the echoes are not homogeneous, and enhancement of the echoes is predominant, with hypoechoic echoes in the intervals; CT can see the thickening of the fascia, and the damaged muscles are swollen; MRI shows that the muscle signals are increased. MRI shows increased muscle signal. Nuclear medicine technology can also be applied to the diagnosis of EIR, 99m u singing methylenediphosphite bone scintigraphy (Tc singing 99mMDP bonescintigraphy) can be used to localize and quantitatively diagnose the damaged muscles. The following indicators can be used as the main diagnostic basis: 1) onset at the time of or after strenuous exercise or high-intensity military training, especially in high temperature, high humidity environment or after a long period of no exercise after sudden exercise; 2) myalgia, fatigue, and dark urine, accompanied by transient loss of consciousness, profuse sweating, headache, nausea, vomiting, high fever and other systemic symptoms; 3) serum myosin profiles are significantly elevated, especially CK 5 times or more than the normal peak value and dominated by CK sing MM; 4) elevated blood and urine myoglobin concentration; 5) positive urine occult blood test, no obvious red blood cells on microscopic examination, and brown pigmented tubular pattern on sediment examination; 6) elevated blood creatinine, urea nitrogen, uric acid and electrolyte disorders, such as hyperkalemia, hyperphosphatemia, hypocalcemia, etc. 7) except for rhabdomyolysis due to other causes. Tests for central impairment are shown in the table below Rehydration is the most important part of the treatment of EIR and the key to preventing EHS-ERF. Once EIR occurs, a large amount of crystalloid should be infused at an early stage, and the volume of rehydration can be up to 10 ～12L/24h, to maintain the effective circulating blood volume, improve renal ischemia, increase the glomerular filtration rate, and maintain the urine output at 200 ～ 300 ml/h, so as to prevent the formation of tubular pattern of myoglobin. If the urine volume decreases with sufficient rehydration, the cause of oliguria should be fully considered and rehydration should be done carefully. Patients mostly have hyperkalemia, so care should be taken to avoid empirical potassium supplementation. Hypocalcemia may resolve on its own, and calcium supplementation is usually not given unless severe symptoms occur, and blind calcium supplementation may aggravate rhabdomyolysis. When the urine is acidic, intravenous application of 5% sodium bicarbonate to alkalinize the urine, so that the urine pH is greater than 6.5 or even greater than 7.5, can reduce the production of ferrous hemoglobin and thus reduce myoglobin nephrotoxicity. Mannitol can effectively promote the release of Fe2+ in myoglobin, reduce its direct toxicity to the renal tubules and tubular formation, and promote the excretion of myoglobin through diuresis, but the use of large amounts of sodium bicarbonate can aggravate hypocalcemia, and excessive use of mannitol can induce and aggravate renal damage. Once a significant decrease in urine output is found, blood purification therapy should be given promptly. If blood creatinine and urea nitrogen gradually increase or severe hyperkalemia occurs, blood purification treatment should be given even if there is no obvious decrease in urine output. If conditions are favorable, continuous renal replacement therapy (CRRT) is appropriate. Nutritional support and the prevention and treatment of complications can be given to patients who can eat, give adequate enteral nutrition; patients who can not eat, intravenous supplementation of sufficient calories, appropriate amount of vitamins and trace elements, can reduce the decomposition of the body’s proteins and promote the repair of damaged cells. In the case of concurrent fascial interstitial syndrome, early conservative treatment with mannitol can be used to reduce interstitial pressure, and fasciotomy can be avoided as much as possible, which can easily lead to large amounts of exudate, bleeding, and infection. If combined with DIC or other organ damage, give appropriate treatment. Prevention should pay attention to the following points: 1) strengthen physical exercise, there should be adaptive training before strenuous activities, and avoid sudden large exercise activities; 2) adjust the physical state before exercise, do not use diuretics or drink a lot of alcohol, and those who are in the midst of the disease or at the beginning of the recovery of the disease should try to avoid participating in strenuous activities, and they should be supplemented with enough water before, during and after the training period; 3) avoid large exercise activities in the direct sunlight and hot humid summer; avoid prolonged, large exercise activities; avoid long time, large exercise activities, and avoid long time, large exercise activities, and avoid long time, large exercise activities. Avoid long time and high intensity exercise or training, and pay attention to the combination of work and rest; 4) If fainting, nausea, vomiting, or discomfort occurs after training, we should pay attention to checking serum CK and blood and urine myoglobin for timely diagnosis and early rehydration treatment. P.S. The heat index is a measure of an individual’s ability to perceive temperature and humidity as well as to self-regulate cooling Heat Index in degrees Fahrenheit The heat index can be calculated as tHI = -42.379 + 2.04901523 t + 10.14333127 φ – 0.22475541 t φ – 0.00683783 t2 – 0.05481717 φ2 + 0.00122874 t2 φ + 0.00085282 t φ2 – 0.00000199 (T φ)2 (1) where tHI = heat index (oF) t = air temperature (oF) (t > 57oF) φ = relative heat index (oF) (t > 0.00000199) 57oF) φ = relative humidity (%) Apparent Temperature Heat Stress Index (oF) Relative Humidity T(oC) = 5/9[T(oF) – 32] Sunstroke and heat exhaustion: 1) Caution – Fatigue is possible with prolonged exposure and/or physical activity 2) Extreme Caution – Sunstroke, heat cramps and heat exhaustion are possible with prolonged exposure and/or physical activity. Sunstroke, heat cramps and heat exhaustion are possible with prolonged exposure and/or physical activity 3) Danger – Sunstroke, heat cramps and heat exhaustion are likely. Heat stroke is possible with prolonged exposure and/or physical activity. Heat stroke is possible with prolonged exposure and/or physical activity 4)Extreme Danger – Heatstroke/sunstroke is highly likely with continued exposure Heat Index in degrees Celsius. degrees Celsius P.S.: New England Journal of Medicine on Heat Shock