Acute exertional rhabdomyolysis

Author: Robin L. Line, George S. Rust
Date: August, 1995

Acute exertional rhabdomyolysis is a potentially serious clinical illness caused by an injury to skeletal muscle that results in the release of myoglobin and other cellular contents, including creatine kinase (CK-MM fraction) and aldolase, into the circulatory system. Mild to moderate cases of acute exertional rhabdomyolysis can cause metabolic disorders such as hypernatremia, hyperkalemia, hyperphosphatemia, hypocalcemia, lactic acidosis and hyperuricemia. Severe cases may result in disseminated intravascular coagulation, renal failure and death.(1) Most commonly, acute exertional rhabdomyolysis occurs after severe physical exertion; pain and swelling of affected muscles is the chief complaint. Myoglobinuria is revealed by urinalysis and is characterized by dark color of urine, heme-positive dipstick and the absence of red blood cells under microscopic examination. Levels of CK-MM isoenzyme are often markedly elevated (600 U per L or greater).(2)

Beause acute exertional rhabdomyolysis is a common and underdiagnosed condition, a knowledge of early clinical manifestations and the potential for serious complications is essential so that appropriate therapy may be instituted early in the course of the illness. The family physician plays a critical preventive role in counseling patients who have environmental, recreational, occupational or medical risk factors for this potentially life-threatening illness.(3)

Historical and Epidemiologic Perspectives

Until 1960, acute exertional rhabdomyolysis was thought to be a rare phenomenon. A review of the literature conducted in 1960 revealed only 36 cases of "primary myoglobinuria" that were reported during the first half of the century. Another report in 1960 cited 60 marine recruits who sought medical attention during a period of one year because of pigmenturia and muscle pain associated with exertion.(4) Awareness of this syndrome among military personnel increased in 1971 when 40 men in the Marine Corps were admitted to the hospital for treatment of pigmenturia, muscle pain, swelling and weakness.(4)

Numerous cases of acute exertional rhabdomyolysis have been reported in association with physical training programs for law enforcement and fire departments. In 1988, for example, all 50 participants in a law enforcement training class demonstrated laboratory evidence of rhabdomyolysis (CK level greater than 10 times normal), and 13 patients were admitted to the hospital with clinical complaints of dark urine, abdominal pain, nausea and back pain.(2) Nine patients (69 percent) had evidence of renal insufficiency (serum creatinine level of 2.0 mg per dL [180 [micro]mol per L] or greater), and six patients required hemodialysis. One patient died of complications of rhabdomyolysis and heat stroke, which included renal and hepatic failure.

Populations at Risk

Acute exertional rhabdomyolysis is a problem in athletes as well as workers whose jobs require extreme physical labor. Rhabdomyolysis has been reported in long-distance runners, weight lifters, football players(5) and other athletes. Poorly conditioned "weekend warriors" may be at increased risk, although rigorous studies are lacking. Risk factors include high ambient temperatures and humidity levels, poor physical conditioning and inadequate fluid intake.(6) Certain individuals may be at especially high risk for medical reasons. Sickle cell trait significantly increases the risk of acute exertional rhabdomyolysis.(7)(8) Other risk factors include the use of certain medications (aspirin, phenothiazines, anticholinergic agents and others), cocaine or alcohol abuse, renal insufficiency, previous history of heat exhaustion and recent viral illness.(9) Occupational, recreational, environmental and medical risk factors are listed in Table 1.

TABLE 1 Risk Factors for Acute Exertional Rhabdomyolysis

EnvironmentalHigh ambient temperatureHigh humidity levelInadequate consumption of drinking waterHigh altitudeOccupationalMilitary trainingLaw enforcement and firefighter trainingConstruction and roofing tradesFarm labor and other outdoor physical laborPhysical labor associated with high temperature or restrictive clothing/equipmentRecreationalLong-distance runningFootballWeight liftingOther high-intensity exercisePoor physical conditioningSporadic exercise ("weekend warriors")MedicalSickle cell traitRenal insufficiencyDehydrationFatiguePrior history of heat exhaustionRecent viral illnessUse of medications (aspirin and anticholinergic agents)Cocaine or alcohol use

Early Recognition of Acute Exertional Rhabdomyolysis

Early recognition of acute exertional rhabdomyolysis is important so that severe complications, such as renal failure, disseminated intravascular coagulation and compartment compression syndrome, can be prevented. The following case report demonstrates the subtle presentation this disease may have.


A 24-year-old man presented to the clinic with a history of pain and bilateral swelling of the arms and chest. Two days before his visit, he had completed an intense two-hour weight-lifting session with heavy weights. Physical examination revealed bilateral swelling, tenderness and tenseness of the pectoralis biceps and triceps muscles.

Even though the patient did not appear to be in great distress, a urinalysis was ordered. The urinalysis revealed normal results, with the exception of 3+ positive heme, and results were negative for red blood cells under microscopic examination. The CK level was 13,758 IU per L with an almost 100 percent CK-MM fraction. The patient was hospitalized and vigorously hydrated. His CK level peaked at 50,200 IU per L before slowly returning to normal over the next six days. He had no overt bleeding and renal function remained normal.


In this case, the patient was ambulatory and was not in acute distress at the time of the examination, which illustrates the need for suspicion when patients who do not train regularly present with overexertion injuries. In this patient, casual treatment with nonsteroidal anti-inflammatory medications and rest without vigorous hydration could have resulted in acute oliguric renal failure and/or disseminated intravascular coagulation.

In another case,(1) massive rhabdomyolysis developed in a 32-year-old physician who was accustomed to running 30 miles per week but had performed exhaustive exercise in hot weather. He ran in a marathon on a warm day (85[degrees]F [29[degrees]C]), and after nine miles he collapsed, experiencing severe pain in his calves and thighs. His CK level peaked at 108,000 IU per L, and he required dialysis therapy as well as treatment for "compartment compression syndrome" in his thighs and calves. He had a full recovery after six months.


Rhabdomyolysis occurs when the integrity of the skeletal muscle membrane is violated, causing CK-MM, aldolase and myoglobin to leak into the circulation at the time of injury. The CK level is the most reliable clinical indicator and can be 60 times higher than normal. However, early in the course of the illness, the CK level may be only modestly elevated. Filtration and excretion of myoglobin in the kidney results in myoglobinuria.(10) In the clinical setting, such a patient would present with a positive urine dipstick test for heme pigment but with no red blood cells on microscopic examination of the urine.(6) Also, CK level would be abnormally elevated and a 1+ or 2+ reaction for protein would be noted on urinary dipstick testing. Serum myoglobin levels are not an accurate indicator of clinical disease.

Additional early findings may include hypernatremia, hyperkalemia, hyperuricemia and lactic acidosis. Hypernatremia is the result of dehydration, and hypovolemia is due to third spacing of intravascular fluids. Potassium is released from contracting muscles into the interstitial fluid, which diffuses into the circulation, resulting in so-called "exercise hyperkalemia." Purine precursors, including adenosine triphosphate, adenosine diphosphate and adenosine monophosphate are released from the injured muscle and result in marked overproduction of uric acid. Glycogen depletion in the muscle, often combined with hypoxia, increases anaerobic metabolism and lactate production, and may result in lactic acidosis.(2)

Later in the course of illness (within 12 to 24 hours), hypocalcemia, hyperphosphatemia, hypoalbuminemia, frank oliguric acute renal failure and disseminated intravascular coagulation may occur. Hypocalcemia in these patients is the result of deposition of calcium phosphate and calcium carbonate in injured skeletal muscle. Hyperphosphatemia is the result of leakage from the injured muscle, which then precipitates as calcium phosphate in soft tissue, blood vessels and the eyes. Hypoalbuminemia is the result of massive capillary destruction with consequent leakage of albumin into the interstitial fluid of skeletal muscle and other organs. Renal failure appears to result from a combination of hypovolemia, hypoxia, lactic acidosis and sludging of myoglobin in the renal tubule.

Some degree of disseminated intravascular coagulation will occur in virtually every patient with acute rhabdomyolysis, with thrombocytopenia being the most prominent finding. Hypofibroginemia and prolongation of the prothrombin time may also occur. Disseminated intravascular coagulation is usually worse on the third to fifth day, with spontaneous improvement occurring by the 10th to 14th day.

Special attention should be given to patients who have had massive skeletal muscle necrosis involving the legs. Usually, on the second day, the extremities become more swollen and painful; paresthesias, decreased sensation and decreased peripheral pulses also may occur. The tight fascial compartment of the tibialis anterior is particularly vulnerable to this complication. In such cases, early fasciotomy may be necessary to prevent further necrosis and gangrene.(1)


Early fluid replacement is the key to managing acute exertional rhabdomyolysis. Patients may require as much as 4 to 10 L of normal saline in the first 24 hours to maintain circulation and stabilize blood pressure. At the same time, the clinician should be alert for the development of compartmental compression syndrome. Maintaining a good urine output, particularly during the first two to three days, may avert acute tubular necrosis and the need for dialysis.

In the presence of acute renal failure, treatment may include furosemide (Lasix), 40 to 120 mg over 10 minutes, and/or mannitol, in a single 100-mL dose of 25 percent solution intravenously over 15 minutes. Both mannitol and furosemide dilute the concentration of myoglobin and have clinically been shown to reduce nephrotoxicity.(2) Continued monitoring of laboratory values (i.e., blood urea nitrogen, creatinine, electrolytes, [Ca.sup.++], phosphate and CK) is critical.

Alkalinization of the urine is controversial. Alkalinization lowers the elevated potassium level and protects the kidney from the nephrotoxic effects of myoglobin and uric acid.(11) However, hypocalcemia is likely to be aggravated by the large amounts of bicarbonate needed.

It is important to monitor prothrombin time, partial thromboplastin time, and platelet counts with fibrinogen and fibrin split products if disseminated intravascular coagulation is suspected. Disseminated intravascular coagulation may be associated with severe hemorrhage and, if this occurs, frozen plasma is the replacement fluid of choice. Use of heparin in this situation is controversial and should be avoided unless absolutely necessary since disseminated intravascular coagulation usually resolves spontaneously after several days.

Hyperkalemia can be life-threatening and is best treated with glucose and insulin, which have a rapid onset but short duration of action, and an exchange resin such as sodium polystyrene sulfonate (Kayexalate), which has a delayed but long-term effect. Hypocalcemia and hyperphosphatemia usually normalize after a few days of adequate hydration. Albumin is rarely indicated for the treatment of hypoalbuminemia since it may leak into the interstitial space and cause muscle swelling to worsen. In the presence of uremic pericarditis or encephalopathy, severe hyperkalemia or refractory fluid overload, dialysis is recommended.(2)


As family physicians become increasingly more involved in sports medicine, they will likely encounter athletes who are seeking training advice. Data from the military suggest that prolonged lower intensity training reduces the risk for acute exertional rhabdomyolysis, compared with more intense exercise over a shorter period of time. Much higher levels of postexercise serum enzyme activity have been noted in persons who are untrained or who are performing high-intensity exercise.

Three features that should be present in all athletic training programs have been suggested: (1) emphasis on prolonged submaximal exercise rather than repetitive exhaustive exercise; (2) a high intake of carbohydrates and rest periods spaced to enhance glycogen repletion, and (3) adequate hydration to promote renal clearance of myoglobin.(4) Also, patients should be encouraged to limit activity during periods of higher-than-average ambient temperature and humidity.(4) In New York City, the fire department training program implemented such preventive measures, and only 32 of 16,506 candidates were hospitalized with rhabdomyolysis and/or renal impairment over a 19-month monitoring period.(2)


(1.)Knochel JP. Rhabdomyolysis and myoglobinuria. Semin Nephrol 1981; 1:75-85.

(2.)Exertional rhabdomyolysis and acute renal impairment--New York City and Massachussetts, 1988. MMWR Morb Mortal Wkly Rep 1990; 39:751-6.

(3.)Knochel JP. Rhabdomyolysis and myoglobinuria. Annu Rev Med 1982; 33:435-43.

(4.)Olerud JE, Homer LD, Carroll HW. Incidence of acute exertional rhabdomyolysis. Serum myoglobin and enzyme levels as indicators of muscle injury. Arch Intern Med 1976; 136:692-7.

(5.)Rosenthal MA, Parker DJ. Collapse of a young athlete. Ann Emerg Med 1992; 21:1493-8.

(6.)Knochel JP. Catastrophic medical events with exhaustive exercise: "white collar rhabdomyolysis." Kidney Int 1990; 38:709-19.

(7.)Kark JA, Posey DM, Schumacher HR, Ruehle CJ. Sickle-cell trait as a risk factor for sudden death in physical training. N Engl J Med 1987; 317:781-7.

(8.)Sherry P. Sickle cell trait and rhabdomyolysis: case report and review of the literature. Mil Med 1990; 155:59-61.

(9.)Gabow PA, Kaehny WD, Kelleher SP. The spectrum of rhabdomyolysis. Medicine 1982; 61:141-52.

(10.)Milne CJ. Rhabdomyolysis, myoglobinuria and exercise. Sports Med 1988; 6:93-106.

(11.)Better OS, Stein JH. Early management of shock and prophylaxis of acute renal failure in traumatic rhabdomyolysis. N Engl J Med 1990; 322:825-9.

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