We present a case of heat stroke (HS) and acute kidney injury (AKI) due to severe rhabdomyolysis in a 14-year-old previously healthy female patient. When she was practicing strenuous exercise she suffered acute seizures and high fever. These symptoms were followed by coma and multiple organ failure (MOF), which included AKI, encephalopathy, fulminant hepatic failure (FHF), and disseminated intravascular coagulation (DIC). The patient was managed in the ICU with renal replacement therapy, ventilatory support, and other vital supporting measures. After three weeks of ICU treatment she made a full recovery.
Rhabdomyolysis is a syndrome characterized by the leakage of muscle-cell contents into the circulation. Strenuous exercise and HS are the most common causes of rhabdomyolysis. The severity of illness ranges from asymptomatic elevations of the serum levels of muscle enzymes to life-threatening cases associated with extreme elevations of creatine kinase (CK) and liver enzymes (ALT, AST), electrolyte imbalances, and AKI. There are two forms of rhabdomyolysis: traumatic, often resulting from crush injuries and extensive trauma sustained in natural disasters and wars and nontraumatic, which include, among other causes, excessive physical exertion, HS, exogenous toxins, usage of illicit drugs, malignant hyperthermia, alcohol, and prescription medications. The risk of AKI in rhabdomyolisis is usually low when CK levels on admission are less than 20000 U/L. Nevertheless, AKI is still at risk with values of CK as low as 5000 U/L when other coexisting conditions occurs such as sepsis, severe dehydration, and acidosis [
The classic presentation of rhabdomyolysis includes myalgias, limb weakness, and pigmenturia due to myoglobinuria without hematuria. AKI is a potential complication of severe rhabdomyolysis independently of its etiology, which accounts for 8–15% of all cases of AKI in the US. The mortality rate of HS can be as high as 70%, especially when treatment is delayed, and the presence of MOF [
On admission to the ICU her physical examination revealed a temperature of 38°C, blood pressure of 160/90 mmHg, pulse rate of 150/min, and respiratory rate of 35/min. Oxygen saturation was 90%. Except for dry mucous membranes, the rest of her physical examination was unremarkable. Soon after admission to the ICU she became unconscious, requiring tracheal intubation and ventilatory support. A chest X-ray and EKG were normal. A cerebral CT scan revealed mild cerebral edema in both hemispheres.
Laboratory testing revealed serum creatinine 2.4 mg/dL, blood urea nitrogen (BUN) 104 mg/dL, potassium 3 mEq/L, sodium 150 mEq/L, CPK level 24,385 U/L, serum myoglobin >3000 ng/mL, total bilirubin 3.12 mg/dL (d/i: 1.49/1.71), ALAT 382 U/L and AST of 282 U/L, and LDH of 1,376 U/L; serum ammonium 16 mmol/L (reference values 10–80 mmol/L); INR 2.73, and serum fibrinogen of 203 mg/dL. The urinalysis revealed reddish brown urine highly positive for myoglobin. The diagnosis of severe exertional HS and rhabdomyolysis with ensuing AKI was established. The patient received IV hydration, ventilatory support, sodium bicarbonate, corticosteroids, and enteral nutrition. During the next 3 days, her CPK level increased to 36,423 U/L, the serum myoglobin >3000 ng/mL, ALAT 9,942 U/L, AST 5,910 U/L, and LDH to 4,623 U/L. Serum ammonium 117 mmol/L, INR 4.7, and the total bilirubin 11.9 mg/dL (d/i: 9.6/2.3). These last laboratory findings and the onset of encephalopathy and coagulopathy in a patient with not known previous liver disease were consistent with the diagnosis of FHF.
The platelet count decreased to 18,000/mm3, the plasma fibrinogen to 104 mg/dL, and the fibrinogen split products were 20
Two forms of HS have been described: the classic or nonexertional HS, which occurs frequently during environmental heat waves, and exertional HS, which usually occurs in healthy, young, and physically active people who engage in strenuous exercise. Renal dysfunction is a well-documented feature in HS that occurs in 30% of cases approximately. The etiology is multifactorial, and this includes direct thermal injury, rhabdomyolysis, DIC, and renal hypoperfusion due to volume depletion and arterial hypotension [
In spite of early volume replacement and correction of transient arterial hypotension, AKI was an early feature in the present case, suggesting that rhabdomyolysis played a central role in the pathophysiology of this complication. Massive rhabdomyolysis may follow strenuous physical exertion, particularly when associated with other risk factors such as extremely hot and humid conditions, poor physical fitness, and hypokalemia [
Differential diagnosis of pigmenturia.
Hematuria | Hemoglobinuria | Myoglobinuria | Bile pigments | Porphyria | Alkaptonuria | |
Pigment | RBC* | Hemoglobin | Myoglobin | Bilirubin/Urobilin | Porphobilinogen | Homogentisinic acid |
Urine color | Red | Pink | Red to brown | Brown | Turns brown, red, purple or black on standing at sunlight. Fluoresces with UV light | Turns dark in alkaline solutions. Darkens on standing at sunlight. |
Urine Sedi-ment*** | RBC and RBC casts | Normal** | Normal | Normal | Normal | Normal |
Supernatant urine color | Yellow | Red to brown | Red to brown | Brown | Red. (Watson-Schwartz test positive) | Normal (Ferric chloride test positive) |
Urine dipstick test**** | 1 to 4 + | 1 to 4 + | 1 to 4 + | Normal | Normal | Normal |
Serum | Normal | Pink (low haptoglobin) | Normal (increase ofmyoglobin,creatinine kinase, and liverenzymes inrhabdomyolysis) | Icteric | Normal | Normal |
Muscle symptoms | No | No | Myalgias | No | Abdominal cramps. | No (ochronosis and arthritis) |
*RBC red blood cells.
**Normal refers to white or yellow in color.
***The sediment and supernatant urine examined after centrifugation.
****Semiquantitative test (orthotolidine or peroxidase) detects heme peroxidase activity in RBC, hemoglobin or myoglobin with reported sensitivity of 91–100%. (1 + = 5–10 RBC/
One of the first steps in managing patients with HS in addition to rapid body cooling is prompt IV repletion of fluids. However, once renal damage supervenes, as occurred with our patient, renal replacement therapy is required to control hyperkalemia, fluid overload, and uremia. The outcome of rhabdomyolysis is usually good provided there is no renal failure. Mortality data vary widely according to severity and coexisting conditions. In cases of rhabdomyolysis secondary to limb ischemia (crush injury) mortality can be as high as 32% [
Liver dysfunction and increased serum levels of liver enzymes are commonly observed in HS, whereas FHF is a rare event FHF, defined as ‘‘the onset of encephalopathy and coagulopathy in patients with no known previous liver disease,’’ is very uncommon in HS, and only three reports of such cases have been previously published. Two of them recovered completely with conservative ICU treatment [
The severity and complications of exertional HS correlate with the temperature duration curve, suggesting that a rapid reduction in the core temperature by any cooling method (immersion in iced water, iced peritoneal, or gastric lavage) as early as possible should have a positive effect on prognosis. In fact, this single measure seems to be the most effective way of preventing MOF in HS patients. Unfortunately, the ‘‘golden hour’’ for our patient had probably passed by the time she arrived at the ICU [
Although rapid reduction of body temperature and repletion of body fluids remain the vital first priority in the treatment of HS, this together with vigorous intensive care management and vital supporting measures may result in patient survival and complete recovery. Nevertheless, to date little is known about the prognosis of patients with HS, and more data are needed to determine the most appropriate and effective management strategies for these cases.
The authors are indebted to Mr. Michael Bench for his assistance in the preparation of the paper.