Topic Editor: Grant E. Fraser, M.D., FRACGP, FACRRM, ASTEM

Review Date: 10/1/2012

Definition

Rhabdomyolysis is a potentially life-threatening condition where skeletal muscle fibers breakdown with release of myoglobin into the bloodstream. High serum myoglobin concentrations clog renal tubules which may result in renal failure.

Description

• Results from any disease or condition that causes muscle cell (myocyte) lysis
• Common symptoms include muscular pain, weakness, and dark tea-colored urine
• It is most common that the affected muscle will be extremely sore and is often visibly swollen
• Subjective complaints range from asymptomatic to having mild diffuse muscular discomfort, or having more severe localized muscular pain
• Characterized by elevated serum creatine kinase (CK) levels, with most cases having CK levels >5000 U/L (it is not uncommon to have levels >100,000 U/L)
• Minimum criteria for diagnosis of rhabdomyolysis is a CK >5 times the upper limit of normal

Epidemiology

Incidence/Prevalence

• This condition is rare in children and more common in males, and the elderly (e.g., >80 years)
• Rhabdomyolysis results in approximately 26,000 hospitalizations annually in the U.S.

Age

• Cases peak in the early adult years, with a male predominance. Many cases relate to a combination of dehydration and muscular activity
• Rhabdomyolysis may be caused by medications, such as statins (usually in older patients)
• Rhabdomyolysis can occur in infants and children who have metabolic enzyme deficiencies, carbohydrate metabolism deficiency, or inherited myopathies

Risk factors

• Alcoholism
• Genetic disorders (McArdles disease, Duchenne's muscular dystrophy)
• Heat or cold exposure
• Limb ischemia or necrosis
• Long distance running and professions involving excessive muscular activity
• Medications such as statins
• Seizure disorder
• Sickle cell disease
• Stimulant use (amphetamines, cocaine)
• Trauma/Crush injuries

Etiology

Direct muscle injury

• Crush injuries/trauma
• Electrical and lightning injuries
• Prolonged direct pressure to muscle
• Third degree burns

• Agitation
• Intense physical exercise (marathon running)
• Status epilepticus

• Arterial or venous occlusion (emboli, sickle cell crisis)
• Compartment syndrome
• Hypotension
• Immobilization
• Localized compression (tourniquet)
• Reperfusion injury
• Shock

• Exertional hyperthermia
• Frost bite
• Hypothermia
• Malignant hyperthermia
• Neuroleptic malignant syndrome

• Hyperosmolar states
• Hypokalemia
• Hyponatremia
• Hypophosphatemia

• Addison disease
• Diabetic ketoacidosis
• Hyperaldosteronism
• Pheochromocytoma
• Thyroid storm

• Bacterial (Salmonella, tetanus)
• Viral (HIV, varicella zoster)

• Alcohol
• Pharmaceutical agents (statins, opioids)
• Recreational drugs (heroin, amphetamines, cocaine, LSD)
• Toxic animals (snake venom)
• Toxic plants (mushroom)

History

• Decreased urine production
• Muscular aches, pains and/or weakness
• Prolonged immobilization
• Recent traumatic injury to muscle (overuse or direct trauma)
• Significant weight gain, due to sequestration of fluids in the muscles
• Tea-colored urine
• Use of medications known to cause rhabdomyolysis

Physical findings on examination

In most cases, there will be

• Muscle rigidity
• Muscle swelling and tenderness
• Muscle weakness

• Diminished peripheral pulses
• Prolonged capillary refill
• Severe pain

Blood test findings

• CBC: Reduced hemoglobin and platelet count may be present secondary to hemodilution and increased total body fluid. An increased hemoglobin is concerning, as it often corresponds to inadequate hydration, and has an increased mortality risk
• Coagulation profile: PT, PTT, INR, fibrinogen may be elevated secondary to DIC, which may occur with rhabdomyolysis
• Minimum criteria for rhabdomyolysis requires serum CK levels of >5 times the upper limit of normal (they are usually much higher than this)
• In cases of mild elevation of CK to only a few times the upper limit of normal, serial testing is indicated to establish a peak level (CK is mildly elevated in other conditions)
• Renal function should be monitored due to risk of renal failure from renal tubular damage from myoglobin
• Venous blood gas should be obtained along with potassium and bicarbonate to evaluate for acute renal failure, metabolic acidosis, and other complications
• Urine dipstick will be positive for blood, not due to hemoglobin but due to myoglobin, but Urine microscopy should be negative for RBCs.
• Myoglobin should be elevated in blood and urine
• Liver enzymes (ALT/AST) are usually substantially elevated (typically 5-10% of the value of the CK) in cases of rhabdomyolysis. Unless a specific hepatic diagnosis is suspected, hepatic evaluation/imaging is not indicated, and serial monitoring until levels return to baseline, mirroring a declining CK is adequate

Other diagnostic test findings

• In general, if there is a clear underlying cause of rhabdomyolysis, no muscular biopsy is indicated. In pediatric cases or where there is no clear cause, muscle biopsy and other specific testing is often indicated

Myalgia due to other causes

• Critical illness myopathy
• Dermatomyositis
• Fibrositis
• Guillain-Barre syndrome
• Localized infection
• Medications (steroids, diuretics)
• Periodic paralysis
• Polymyalgia rheumatic
• Polymyositis
• Rheumatoid arthritis
• Tendonitis

• Consumption of beets
• Hematuria
• Hemolysis (hemoglobinuria)
• Medications (Rifampin, nitrofurantoin, metronidazole, etc.)
• Porphyria

General treatment items

• IV fluids to achieve urinary output of 1-2 mL/kg/hr
• Although commonly recommended, the addition of sodium bicarbonate, mannitol, or furosemide to IV fluids is not of demonstrated benefit
• If compartment syndrome is present, surgical treatment is urgently required
• In the event of renal failure, urgent dialysis and cautious electrolyte management is required

Note: Despite some practitioners utilizing sodium bicarbonate, mannitol and/or furosemide; no therapy over simply maintaining adequate urinary output has sufficient evidence to recommend.

• Intravenous fluids primarily with normal saline, usually alternated with lactated ringers (Hartman's solution) to avoid hypernatremia/hyperchloremia in adequate quantity to maintain urinary output at 1-2 mL/kg/hr
• Sodium bicarbonate 50 mEq/L added to the first 1-2 liters of IV fluids to alkalinize the urine and theoretically increase renal excretion of myogloblin may be used by some practitioners
• Mannitol (up to 200 g/day) added to IV fluids to induce osmotic diurersis
• IV furosemide (40-120 mg/day) to increase urinary output, along with careful monitoring of potassium levels

Dietary or Activity restrictions

• Protein intake should be restricted in order to lower urea nitrogen (BUN)
• Potassium intake should be limited
• Volume intake should be restricted in cases of anuria; no restrictions are required upon resolution

Disposition

Admission criteria

• In cases of substantial CK rise (at least >5 times the upper limit of normal); admission with serial testing of CK, electrolytes, and renal function is recommended
• Cases with acute renal injury, hyperkalemia, and/or acidosis require admission

Discharge criteria

• In cases of minimal CK increase; outpatient monitoring with serial daily CK, electrolytes and renal function, along with oral rehydration is reasonable

Monitoring

• CK, electrolytes and renal function must be evaluated regularly
• Any continuing renal insufficiency should be monitored
• Myotoxic drugs should be discontinued or monitored

Complications

Early

• Acute renal failure
• Cardiac arrest (usually due to hyperkalemia)
• Cardiac arrhythmias
• Hepatic inflammation
• Hyperkalemia
• Hypocalcemia

• Chronic renal failure
• Disseminated intravascular coagulation (DIC)
• Hypercalcemia

• Compartment syndrome

Prevention

• Avoid overexertion, especially during hot and humid weather
• Increase fluid intake to keep urine dilute
• Avoid drugs that can cause rhabdomyolysis

Prognosis

• Renal failure is rare in cases where adequate hydration (with maintenance of urine output) is started early
• Patients with late presentation with significant acute renal failure, acidosis, and/or hyperkalemia have a significant risk of chronic renal failure, with some needing long term dialysis
• Patients with mild rhabdomyolysis usually return to a normal CK and renal function within a few weeks with adequate hydration
• An occasional patient will exhibit low energy and muscular discomfort for a prolonged duration even after normalization of CK levels and renal function

ICD-9-CM

• 728.88 Rhabdomyolysis

ICD-10-CM

• M62.82 Rhabdomyolysis

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