What is rhabdomyolysis?

Rhabdomyolysis: Definition, Pathophysiology, and Clinical Implications

Rhabdomyolysis is a potentially life-threatening condition characterized by the breakdown of skeletal muscle tissue with release of intracellular contents including myoglobin, creatine kinase, electrolytes, and other cellular proteins into the circulation, which can lead to acute kidney injury, electrolyte abnormalities, and other serious complications. 1

Pathophysiology

Rhabdomyolysis occurs when skeletal muscle cells are damaged, leading to:

• Release of toxic intracellular contents into the bloodstream
• Increased intracellular calcium, which:
  • Activates proteolytic enzymes
  • Increases muscle cell contractility
  • Causes mitochondrial dysfunction
  • Increases production of reactive oxygen species 2

The fundamental mechanism involves a breakdown in calcium homeostasis within muscle cells, resulting in cell death and release of cellular contents.

Causes

Rhabdomyolysis can be caused by numerous factors, which can be categorized as:

1. Trauma or direct muscle injury:

   • Crush injuries
   • Severe burns
   • Prolonged immobilization

2. Excessive muscle activity:

   • Intense exercise
   • Seizures
   • Delirium tremens

3. Hereditary muscle enzyme defects:

   • Metabolic myopathies
   • Connective tissue disorders

4. Medical causes:

   • Drugs and toxins: Statins (extremely rare at 1.6 per 100,000 patient-years) 1, alcohol, cocaine
   • Metabolic disorders: Electrolyte abnormalities, diabetic ketoacidosis
   • Infections: Viral, bacterial
   • Temperature alterations: Hyperthermia, malignant hyperthermia
   • Ischemia: Compartment syndrome, vascular occlusion 3

Clinical Presentation

The clinical presentation of rhabdomyolysis varies widely:

• Muscle symptoms: Pain, weakness, tenderness, and swelling
• Systemic symptoms: Fever, malaise, nausea, vomiting
• Urine changes: Red to brown-colored urine (myoglobinuria)
• Asymptomatic: Some patients may only present with laboratory abnormalities 4

Diagnosis

The diagnosis of rhabdomyolysis is based on:

• Laboratory findings:

  • Creatine kinase (CK) elevation at least 10 times the upper limit of normal
  • Myoglobinuria
  • Elevated serum potassium, phosphate, and uric acid
  • Decreased serum calcium (early phase)

• Clinical assessment:

  • History of exposure to risk factors
  • Muscle pain and weakness
  • Red to brown urine 5

Complications

Major complications of rhabdomyolysis include:

1. Acute kidney injury (AKI): The most significant complication, caused by:

   • Renal vasoconstriction
   • Direct tubular toxicity from myoglobin
   • Tubular obstruction

2. Electrolyte abnormalities:

   • Hyperkalemia (can cause cardiac arrhythmias)
   • Hyperphosphatemia
   • Hypocalcemia (early)
   • Hypercalcemia (late)

3. Compartment syndrome: Increased pressure within muscle compartments leading to further tissue damage

4. Disseminated intravascular coagulation (DIC): In severe cases 6

Management

The cornerstone of treatment is:

1. Aggressive fluid resuscitation:

   • Immediate IV fluid administration (normal saline)
   • Target urine output of at least 300 mL/hour
   • Continue until CK levels decrease to <1,000 U/L 4

2. Management of electrolyte abnormalities:

   • Close monitoring of potassium, calcium, and phosphate
   • Prompt correction of hyperkalemia to prevent cardiac arrhythmias

3. Urine alkalinization:

   • Sodium bicarbonate may be used in acidotic patients
   • Helps prevent myoglobin precipitation in renal tubules

4. Monitoring for and treating compartment syndrome:

   • Regular assessment of affected limbs
   • Decompressive fasciotomy if necessary 1

Prognosis

The prognosis of rhabdomyolysis depends on:

• Underlying cause
• Severity of muscle damage
• Presence of complications
• Timeliness of treatment

With prompt recognition and appropriate management, most patients recover completely. However, severe cases with AKI may require temporary or permanent renal replacement therapy.

Prevention

For patients at risk (e.g., those on statins), preventive measures include:

• Avoiding drug combinations that increase risk (e.g., statins with fibrates)
• Monitoring for early signs of muscle damage
• Proper hydration during intense physical activity
• Careful monitoring of high-risk patients 1

Early recognition and aggressive treatment remain the most important factors in preventing serious complications of rhabdomyolysis.