What is rhabdomyolysis?

Definition of Rhabdomyolysis

Rhabdomyolysis is a potentially life-threatening condition characterized by the rapid breakdown of skeletal muscle tissue, resulting in the release of muscle cell contents including myoglobin, creatine kinase, and electrolytes into the bloodstream, which can lead to acute kidney injury and other serious complications.

Pathophysiology

Rhabdomyolysis occurs when skeletal muscle cells are damaged and their contents leak into the circulation. The key pathophysiological processes include:

• Muscle cell membrane disruption
• Release of intracellular components (myoglobin, creatine kinase, electrolytes)
• Myoglobin filtration by kidneys, potentially causing renal tubular obstruction
• Development of acute kidney injury through multiple mechanisms:
  • Direct myoglobin toxicity to renal tubules
  • Tubular obstruction from myoglobin precipitation
  • Renal vasoconstriction

Clinical Features

The classic clinical presentation includes:

• Muscle pain (myalgia)
• Muscle weakness
• Dark, tea-colored urine (due to myoglobinuria)

However, this classic triad is present in only about half of all cases 1. Other common manifestations include:

• Swelling of affected muscles
• Malaise and fatigue
• Fever
• Nausea and vomiting
• Altered mental status (in severe cases)

Diagnostic Criteria

The diagnosis of rhabdomyolysis is primarily based on laboratory findings:

• Creatine kinase (CK) elevation: A CK level at least 10 times the upper limit of normal is typically considered diagnostic 2
• Myoglobinuria: Presence of myoglobin in urine, causing dark or tea-colored urine
• Other laboratory abnormalities:
  • Elevated serum myoglobin
  • Hyperkalemia
  • Hypocalcemia (early)
  • Hyperphosphatemia
  • Elevated liver enzymes
  • Elevated blood urea nitrogen (BUN) and creatinine (in cases with kidney involvement)

Causes

Rhabdomyolysis can result from numerous causes, which can be categorized as:

1. Traumatic:

   • Crush injuries
   • Prolonged immobilization
   • Electrical injuries
   • Severe burns

2. Non-traumatic:

   • Exertional: Extreme physical activity, especially in untrained individuals
   • Medications/toxins: Statins (extremely rare at 1.6 per 100,000 patient-years) 3, alcohol, illicit drugs
   • Infections: Viral, bacterial
   • Metabolic disorders: Electrolyte abnormalities, diabetic ketoacidosis
   • Temperature extremes: Hyperthermia, malignant hyperthermia
   • Genetic/inherited disorders: Especially important in pediatric populations 1

Complications

Major complications of rhabdomyolysis include:

• Acute kidney injury (AKI): Occurs in 13-50% of cases 4
• Electrolyte abnormalities: Hyperkalemia (potentially life-threatening), hypocalcemia
• Compartment syndrome: Requiring urgent fasciotomy
• Disseminated intravascular coagulation (DIC)
• Acidosis: Both metabolic and respiratory

Management

The cornerstone of management is:

1. Aggressive fluid resuscitation:

   • Immediate intravenous saline to maintain urine output of at least 300 mL/hour 2
   • For severe rhabdomyolysis (CPK >15,000 IU/L), volumes greater than 6L may be required 3
   • For moderate rhabdomyolysis, 3-6L per day is typically sufficient 3

2. Monitoring and management of complications:

   • Regular monitoring of CK levels, electrolytes, and renal function
   • Correction of electrolyte abnormalities, particularly hyperkalemia
   • Monitoring for and treating compartment syndrome
   • Consideration of sodium bicarbonate for acidosis

3. Specific interventions:

   • Maintaining urine pH >6.5 to prevent myoglobin precipitation in renal tubules 3
   • Consideration of mannitol in patients not achieving target urine output
   • Renal replacement therapy for severe AKI or refractory hyperkalemia

4. Continued monitoring:

   • Continue intravenous fluids until CK levels decrease to <1,000 U/L 2
   • Regular assessment of renal function and electrolyte status

Prevention

For patients at risk of rhabdomyolysis:

• Avoid known triggers (excessive exercise, certain medications)
• Maintain adequate hydration, especially during exercise
• Monitor for drug interactions that increase risk (e.g., statins with gemfibrozil) 3
• Consider genetic testing in cases of recurrent rhabdomyolysis 1

Prognosis

The prognosis for rhabdomyolysis is generally good with prompt recognition and treatment, but depends significantly on:

• The underlying cause
• Presence and severity of complications, especially AKI
• Timeliness of diagnosis and treatment
• Patient's baseline health status

Early recognition and aggressive fluid resuscitation are the most important factors in preventing the development of AKI and improving outcomes.