What is rhabdomyolysis?

Rhabdomyolysis: Definition, Diagnosis, and Management

Rhabdomyolysis is a potentially life-threatening syndrome characterized by the breakdown of skeletal muscle tissue with release of intracellular contents into circulation, which can lead to acute kidney injury, electrolyte abnormalities, and in severe cases, death. 1

Pathophysiology

Rhabdomyolysis occurs when skeletal muscle cells are damaged, resulting in:

• Release of muscle cell contents into the bloodstream, including:

  • Myoglobin
  • Creatine kinase (CK)
  • Electrolytes (potassium, phosphate)
  • Purines

• The pathophysiological hallmark is an increase in intracellular free ionized calcium due to:

  • Cellular energy depletion
  • Direct plasma membrane rupture 2

• Increased intracellular calcium leads to:

  • Activation of proteases
  • Increased muscle cell contractility
  • Mitochondrial dysfunction
  • Increased production of reactive oxygen species
  • Ultimate skeletal muscle cell death 2

Causes

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

1. Trauma or direct injury
2. Excessive muscle activity
3. Hereditary muscle enzyme defects
4. Medical causes:
   • Drugs and toxins (including statins)
   • Muscle hypoxia
   • Metabolic and endocrine disorders
   • Infections
   • Temperature extremes 3

Specific high-risk scenarios include:

• Statin therapy (extremely rare at 1.6 per 100,000 patient-years) 1
• Crush injuries and limb trauma 1
• Malignant hyperthermia reactions during anesthesia 1

Clinical Presentation

The classic triad of symptoms includes:

• Muscle pain
• Muscle weakness
• Dark urine (myoglobinuria) 4

Additional clinical features may include:

• Swelling of affected muscles
• Fever
• Malaise
• Nausea and vomiting
• Confusion (in severe cases)

Diagnosis

Diagnosis is based on:

1. Laboratory findings:

   • Elevated CK levels (typically at least 10 times the upper limit of normal)
   • Myoglobinuria
   • Elevated serum creatinine and BUN (in cases of kidney involvement)
   • Electrolyte abnormalities (hyperkalemia, hyperphosphatemia, hypocalcemia) 5

2. Clinical presentation:

   • Muscle pain and weakness
   • History of red-to-brown urine 3

Complications

Major complications include:

1. Acute kidney injury (AKI) - Most significant complication due to:

   • Myoglobin toxicity to renal tubules
   • Renal vasoconstriction
   • Tubular obstruction 1

2. Electrolyte abnormalities:

   • Hyperkalemia (can lead to cardiac arrhythmias)
   • Hypocalcemia
   • Hyperphosphatemia
   • Hyperuricemia 5

3. Compartment syndrome - Can develop as early or late finding 5

4. Disseminated intravascular coagulation (DIC) 6

5. Acidosis 6

Management

The cornerstone of treatment is:

1. Aggressive fluid resuscitation:

   • Rapidly initiate intravenous saline
   • Maintain urine output of at least 300 mL/hour
   • Continue IV fluids until CK levels decrease to <1,000 U/L 5

2. Electrolyte management:

   • Monitor and correct electrolyte abnormalities
   • Pay particular attention to potassium levels to prevent cardiac arrhythmias 5

3. Additional therapies:

   • Sodium bicarbonate for acidotic patients
   • Mannitol if urine output goals are not met 5
   • Decompressive fasciotomy for compartment syndrome 5

4. Monitoring:

   • Serial CK levels
   • Renal function tests
   • Electrolyte levels
   • Urine output 7

5. Nephrology referral:

   • For significantly elevated CK levels
   • Signs of developing acute kidney injury
   • Need for potential renal replacement therapy 7

Prevention

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

• Avoid concurrent use of medications that increase risk (e.g., gemfibrozil with statins) 1
• Consider genetic testing for SLCO1B1 gene mutations in patients with risk factors 1
• Monitor for early signs of muscle pain or weakness 1

Special Considerations

• In patients with statin-associated autoimmune myopathy, chronic immunosuppressive therapy may be required and statins should not be reintroduced 1
• Patients with severe statin-associated muscle symptoms or rhabdomyolysis who require lipid-lowering therapy should be considered for non-statin therapies 1
• Patients undergoing surgery should avoid medications like succinylcholine that can cause rhabdomyolysis 1

Early recognition and aggressive treatment are essential to prevent serious complications, particularly acute kidney injury, which is the most significant cause of morbidity and mortality in rhabdomyolysis.