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Rhabdomyolysis

By

Anna Malkina

, MD, University of California, San Francisco

Last full review/revision Dec 2020| Content last modified Dec 2020
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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.

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 Acute Kidney Injury (AKI) Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more .

Etiology of Rhabdomyolysis

Any form of muscle damage can theoretically result in rhabdomyolysis. The most common etiologies include

Less common etiologies include

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 about 50% of patients have no muscle complaints at all (1 Symptoms and signs references 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... read more ). 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. 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 (1–3 Symptoms and signs references 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... read more ), and is higher in patients with concurrent dehydration, sepsis, and creatine kinase level over 15,000 IU/L (250 mckat/L).

Symptoms and signs references

  • Gabow P, Kaehny W, Kelleher S: The spectrum of rhabdomyolysis. Medicine 62:141-152, 1982. doi: 10.1097/00005792-198205000-00002

  • Melli G, Chaudhry V, Cornblath DR: Rhabdomyolysis: An evaluation of 475 hospitalized patients. Medicine (Baltimore) 84(6):377, 2005. doi: 10.1097/01.md.0000188565.48918.41

  • Veenstra J, Smit WM, Krediet RT, et al: Relationship between elevated creatine phosphokinase and the clinical spectrum of rhabdomyolysis. Nephrol Dial Transplant 9(6):637, 1994. doi: 10.1093/ndt/9.6.637

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. Myoglobinuria is detected when urinary myoglobin exceeds 250 mcg/mL. Other laboratory features include rapidly rising serum creatinine, hyperkalemia Hyperkalemia Hyperkalemia is a serum potassium concentration > 5.5 mEq/L (> 5.5 mmol/L), usually resulting from decreased renal potassium excretion or abnormal movement of potassium out of cells. There are... read more , hyperuricemia, hypocalcemia Hypocalcemia Hypocalcemia is a total serum calcium concentration 8.8 mg/dL ( 2.20 mmol/L) in the presence of normal plasma protein concentrations or a serum ionized calcium concentration 4.7 mg/dL ( 1.17... read more , or hypercalcemia Hypercalcemia Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism, vitamin... read more , hyperphosphatemia Hyperphosphatemia Hyperphosphatemia is a serum phosphate concentration > 4.5 mg/dL (> 1.46 mmol/L). Causes include chronic kidney disease, hypoparathyroidism, and metabolic or respiratory acidosis. Clinical features... read more , lactic acidosis Lactic Acidosis Lactic acidosis is a high anion gap metabolic acidosis due to elevated blood lactate. Lactic acidosis results from overproduction of lactate, decreased metabolism of lactate, or both. (See also... read more , and thrombocytopenia Overview of Platelet Disorders Platelets are cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes,... read more Overview of Platelet Disorders .

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.

If the inciting event is due to a compartment syndrome Compartment Syndrome Compartment syndrome is increased tissue pressure within a closed fascial space, resulting in tissue ischemia. The earliest symptom is pain out of proportion to the severity of injury. Diagnosis... read more , early fasciotomy is done in addition to supportive therapy. Infections are treated with appropriate antimicrobial agents. Any potential inciting drugs (eg, statins) are discontinued. Electrolyte disturbances are corrected.

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.

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