Rhabdomyolysis is a syndrome characterized by striated muscle lysis with resulting muscle damage and leakage of intracellular contents into the circulation. The presentation may range from an asymptomatic elevation of creatine kinase (CK) to severe muscle injury with irreversible kidney failure. In general, a 5- to 10-fold elevation of CK levels, muscle pain, and myoglobinuria in an appropriate clinical setting (see below) are sufficient criteria for the diagnosis of rhabdomyolysis. Acute kidney injury (AKI), which is not a diagnostic criterion of rhabdomyolysis, typically results from multiple factors, including volume depletion, tubular obstruction, direct heme pigment-induced proximal tubular cell injury, and renal vasoconstriction.

• Classic triad of muscle pain, weakness, and dark urine from myoglobinuria
• Muscle tenderness is present in half of cases
• Muscle swelling occurs after intravenous fluid repletion
• Muscular rigidity
• Fever
• In rhabdomyolysis secondary to long-term statin administration, fatigue (74%) is nearly as common as muscle pain (88%)
• Oliguria or anuria with AKI

Causes can be divided into three categories:

• Traumatic or muscle compression
  1. High-current electrical injury
  2. Crush injury and compartment syndrome
  3. Tourniquet and limb ischemia
  4. Reperfusion after revascularization procedures for ischemia
  5. Extensive surgical (spinal) dissection, bariatric surgery
• Nontraumatic exertional
  1. Exercise: More than 10 genetically predisposing gene sequence variants are associated with exertional rhabdomyolysis
  2. Sickle cell trait, rarely: Usually additional predisposing factors are involved (e.g., body mass index [BMI] >30 kg/m², tobacco use, statin use, antipsychotic use, high altitude)
  3. Heat stroke
  4. Metabolic myopathies
  5. Malignant hyperthermia and neuroleptic malignant syndrome
  6. Seizure activity
• Nontraumatic, nonexertional
  1. Drug-induced (statins alone, combinations of statins with fibrates or erythromycin, simvastatin and amiodarone, amphetamines, haloperidol, levofloxacin, macrolide antibiotics)
  2. Chronic ethanol ingestion
  3. Hypothyroidism
  4. Infectious and inflammatory myositis

Table 1 summarizes various causes of rhabdomyolysis.

“Creatine Kinase Elevation” in Section IV describes a clinical algorithm for the evaluation of CK elevation.

• Creatine kinase: Usually CK is 5 to 10 times the upper limit of the normal range and typically peaks 24 to 72 hr after the initial insult (Fig. 1). Levels >15,000 IU/L are more likely associated with AKI. However, in patients with concomitant risk factors such as hypokalemia or volume depletion, CK levels as low as 5000 U/L may be associated with AKI.
• Myoglobin: Filtration into urine produces a “port wine” color at concentrations of 100 to 300 mg/dl. Myoglobinuria can be suspected by a positive urine dipstick test for blood within urine or by light microscopy detection of red blood cells. Due to its rapid hepatic metabolism, myoglobin lacks sensitivity for detection and diagnosis of rhabdomyolysis. Therefore serum and/or urine myoglobin measurement is not recommended to establish the diagnosis of rhabdomyolysis. Blood urea nitrogen and plasma creatinine concentrations are used to monitor severity of AKI.
• Potassium, calcium, phosphorus, and uric acid are released from damaged muscle, and levels should be monitored. Hyperkalemia is less common in nontraumatic rhabdomyolysis.
• Calcium: Hypocalcemia from deposition of calcium phosphate complexes in damaged muscle tissue. Hypercalcemia may follow resolution of rhabdomyolysis from liberation of calcium from damaged muscle into the circulation and increased gut calcium absorption from enhanced vitamin D production.
• Anion gap metabolic acidosis may occur from release of organic acids and phosphates from damaged muscle. Metabolic acidosis is less common in nontraumatic rhabdomyolysis.
• Urinalysis: Myoglobin is detected as blood on dipstick, but red blood cells are absent on microscopy. Microscopic identification of pigmented tubular casts establishes acute tubular necrosis.
• Rhabdomyolysis-induced acute tubular necrosis may occur with a low fractional excretion of sodium (FE_Na <1%).
• Box 1 summarizes laboratory abnormalities observed with rhabdomyolysis.

• Identify precipitating factor(s) and discontinue potentially contributory drugs or toxins.
• Early, aggressive, high-volume intravenous fluid replacement with normal saline. Extracellular fluid volume-loading and diuresis reduce the risk for renal damage by elimination of urate and phosphate that can precipitate in the kidneys. Fig. 2 describes a treatment algorithm for rhabdomyolysis.
• Fasciotomy is indicated in compartment syndrome for preservation of muscle and nerve function.
• Initiate volume repletion with normal saline at a rate of 200 to 1000 ml/hr, depending on clinical circumstances and severity of muscle damage. Titrate the infusion rate to maintain a urine output of at least 200 ml/hr. Consider treatment with mannitol (up to 200 g per day with cumulative dose up to 800 g) to enhance urine flow rate. Typically, a 20% mannitol infusion at a dose of 0.5 g/kg is given over a 15-min interval followed by an infusion at 0.1 gram/kg per hr. Discontinue mannitol and volume resuscitation if a diuresis threshold of >20 ml/hr is not established. Maintain volume repletion until myoglobinuria stops (negative urine dipstick blood test) or plasma CK levels decrease to <5000 U/L.
• Correct hypocalcemia if symptomatic or hyperkalemia that produces electrocardiographic changes.
• Treatment of all electrolyte imbalances.
• Urine alkalinization: Maintain urine pH at 6 to 7 and plasma pH at ∼7.50. This recommendation is controversial. Early volume resuscitation and expansion are the most important treatments.
• Initiation of renal replacement therapy is determined by severity of kidney injury and/or electrolyte imbalances. Continuous renal replacement therapy and specialized hemodialysis membranes to enhance myoglobin clearance have not been systematically studied or proven superior to intermittent hemodialysis.

Figure 2 Early goal-directed therapy for rhabdomyolysis.

CK, Creatine kinase; CVP, central venous pressure; D5NL bicarb, 5% dextrose in normal sodium bicarbonate solution; EGDT, early goal-directed therapy; IV, intravenous; IVF, intravenous fluid; NS, normal saline; RRT, renal replacement therapy; UOP, urinary output.

From Adams JG et al: Emergency medicine, clinical essentials, ed 2, Philadelphia, 2013, Elsevier.

Early diagnosis and management are required to prevent AKI.

Renal consultation and surgical consultation if compartment syndrome develops

• Statin-induced rhabdomyolysis occurs 12 times more frequently when statins are combined with fibrates than when used alone.
• Short-term, high-dose glucocorticoid steroid administration (500 to 1000 mg methylprednisolone) has been used for treatment of alcohol-induced rhabdomyolysis that is refractory to volume repletion. This treatment may be efficacious in cases of severe rhabdomyolysis by reducing secondary leukocyte inflammatory muscle injury.

Rhabdomyolysis (Patient Information)

Statin-Induced Muscle Syndrome (Related Key Topic)