Rhabdomyolysis is a clinical syndrome involving the breakdown of skeletal muscle tissue. Symptoms and signs include muscle weakness, myalgias, and reddish-brown urine, although this triad is present in less than 10% of patients. Diagnosis of rhabdomyolysis is by history and laboratory confirmation of elevated creatine kinase (CK) of typically greater than 5 times the upper limit of normal. Treatment is supportive with IV fluids as well as treatment of the inciting cause and any ensuing complications.
Prompt recognition and treatment of rhabdomyolysis are vital because severe disease can be associated with life-threatening acute kidney injury (AKI) and electrolyte imbalances.
Pathophysiology of Rhabdomyolysis
Normal skeletal muscle function is dependent on appropriate electrolyte exchange, adequate metabolism of adenosine triphosphate (ATP), and intact plasma membrane of the myocytes. In rhabdomyolysis, these processes are disrupted, resulting in the breakdown of skeletal muscle. Destruction of skeletal muscle tissue leads to release of the intracellular components of myocytes into the plasma, including creatine kinase (CK), myoglobin, and various electrolytes. Myoglobinuria and electrolyte abnormalities cause end-organ complications, including acute kidney injury.
Etiology of Rhabdomyolysis
Any form of muscle damage can theoretically result in rhabdomyolysis. The most common etiologies include
Mechanical trauma or muscle ischemia (eg, crush injuries, electric shocks, seizures, or compartment syndrome)
Medications, illicit drugs, and toxins (eg, statins, antibiotics, anxiolytics, antipsychotics, , amphetamines, alcohol)
Infection (eg, influenza A and B, coxsackievirus, Staphylococcus aureus)
Less common etiologies include
Electrolyte disorders (eg, hypokalemia, hypophosphatemia)
Endocrine disorders (eg, diabetic ketoacidosis and nonketotic hyperglycemia)
Genetic disorders (eg, Duchenne muscular dystrophy, Becker muscular dystrophy)
Extreme exercise or prolonged immobilization
Extremes in body temperature (eg, hypothermia, hyperthermia in neuroleptic malignant syndrome or malignant hyperthermia, and heatstroke)
Symptoms and Signs of Rhabdomyolysis
The classic triad of symptoms in rhabdomyolysis is muscle pain, weakness, and reddish-brown urine. However, this trio of symptoms is present in fewer than 10% of all patients with rhabdomyolysis.
Clinical presentation is variable, and many patients have no muscle complaints at all. When present, muscle pain affects proximal muscle groups, such as shoulders, thighs, lower back, and calves. At a high concentration, myoglobin excreted into the urine changes its color to red or brown and can be assessed with a dipstick analysis positive for blood (caused by myoglobinuria). However, due to rapid excretion of myoglobin, rhabdomyolysis cannot be excluded in the absence of myoglobinuria or urine discoloration.
Other signs and symptoms vary based on the inciting event and complications (eg, fever is present in patients with infection and altered mental status in cases of intoxication).
Acute kidney injury is reported in 15 to 50% of rhabdomyolysis complications (1), and is higher in patients with concurrent dehydration, sepsis, and creatine kinase level over 15,000 IU/L (250 mckat/L).
Symptoms and signs reference
1. Chavez LO, Leon M, Einav S, et al: Beyond muscle destruction: A systematic review of rhabdomyolysis for clinical practice. Crit Care 20(1):135, 2016. doi: 10.1186/s13054-016-1314-5
Diagnosis of Rhabdomyolysis
Serum levels of creatine kinase (CK) > 5 times the upper limit of normal
Rhabdomyolysis is suspected based on history, clinical signs, and symptoms. Confirmation is by laboratory testing of elevated CK. Although a cutoff threshold has not been established, a CK level of > 5 times the upper limit of normal is typically required for diagnosis.
Other corroborating laboratory testing includes the presence of myoglobin in urine, particularly if microscopic urine examination shows no red blood cells. Myoglobinuria is detected when urinary myoglobin exceeds 250 mcg/mL. Other laboratory features include rapidly rising serum creatinine, hyperkalemia, hyperuricemia, hypocalcemia, or hypercalcemia, hyperphosphatemia, lactic acidosis, and thrombocytopenia.
Treatment of Rhabdomyolysis
Supportive therapy
Treatment of underlying cause
Treatment of complications
In general, treatment is supportive along with treatment of cause and of any resulting complications.
Supportive treatment includes intravascular expansion with IV fluids to prevent acute kidney injury as well as other supportive treatments (eg, mechanical ventilation in cases of acute respiratory failurealkalosis or hypocalcemia.
If the inciting event is due to a compartment syndrome, early fasciotomy is done in addition to supportive therapy. Infections are treated with appropriate antimicrobial agents. Any potential inciting medications (eg, statins) are discontinued. Electrolyte disturbances are corrected.
Complications such as acute kidney injury are treated with IV fluids and sometimes hemodialysis. Disseminated intravascular coagulation is treated with fresh frozen plasma.
Key Points
The classic triad of symptoms (myalgias, muscle weakness, and tea-colored urine) is present in < 10% of cases.
A CK level of > 5 times the upper limit of normal is typically required for diagnosis.
Treatment is supportive with IV hydration as well as concurrent treatment of the inciting cause and any resulting complications.
