Causes of Rhabdomyolysis
Rhabdomyolysis is caused by multiple factors including trauma, excessive muscular activity, medications/toxins, metabolic disorders, infections, and temperature alterations, with the common pathophysiological pathway being skeletal muscle breakdown and release of intracellular contents into circulation. 1
Major Categories of Causes
1. Trauma and Direct Injury
- Crush injuries
- Compartment syndrome
- Severe burns
- Prolonged immobilization (especially after falls or substance overdose)
- Surgical procedures (particularly with prolonged positioning)
2. Excessive Muscle Activity
- Intense exercise (particularly in untrained individuals)
- Seizures
- Status epilepticus
- Delirium tremens
- Electrical shock
3. Medications and Toxins
- Statins: Most common drug-related cause
- Risk increases with higher doses and when combined with certain medications 2
- Particularly high risk with:
- Cyclosporine, tacrolimus
- Macrolide antibiotics (azithromycin, clarithromycin, erythromycin)
- Azole antifungals (itraconazole, ketoconazole, fluconazole)
- Calcium antagonists (mibefradil, diltiazem, verapamil)
- HIV protease inhibitors
- Fibrates (particularly gemfibrozil) 2
- Alcohol and illicit drugs
- Cocaine, amphetamines, MDMA ("ecstasy")
- Alcohol (both acute intoxication and withdrawal)
- Other medications
- Red yeast rice supplements (contain lovastatin) 2
- Colchicine
- Neuroleptics
- Zidovudine
- Selective serotonin reuptake inhibitors
4. Metabolic and Endocrine Disorders
- Electrolyte abnormalities
- Hypokalemia
- Hypophosphatemia
- Hyponatremia or hypernatremia
- Diabetic ketoacidosis or hyperosmolar states
- Hypothyroidism
- Hyperthyroidism
5. Infections
- Viral (influenza, HIV, Epstein-Barr virus)
- Bacterial (Legionella, Streptococcus)
- Fungal infections
- Malaria
6. Temperature-Related Causes
- Hyperthermia/heat stroke
- Malignant hyperthermia
- Neuroleptic malignant syndrome
- Hypothermia
7. Hereditary Disorders
- Metabolic myopathies
- Enzyme deficiencies affecting muscle metabolism
- Mitochondrial disorders
8. Autoimmune Conditions
- Statin-associated autoimmune myopathy (characterized by muscle weakness, marked CK elevation, HMGCR antibodies, and necrotizing myopathy) 2
- Polymyositis
- Dermatomyositis
Risk Factors and Prevention
Certain populations are at higher risk for developing rhabdomyolysis:
- Athletes during transition periods (first 4 days of new training cycles) 2
- Patients on multiple medications with potential interactions
- Individuals with underlying metabolic disorders
- Trauma patients with crush injuries
Prevention strategies include:
- Appropriate hydration during exercise
- Gradual progression of exercise intensity
- Careful medication management to avoid interactions
- Proper training protocols for athletes, especially during transition periods 2
- Early recognition of compartment syndrome 2
Clinical Presentation
The classic triad of symptoms includes:
- Muscle pain and weakness
- Dark urine (myoglobinuria)
- Elevated creatine kinase levels (typically >5 times normal, approximately >1000 IU/L) 2
In severe cases, CPK levels above 75,000 IU/L are associated with high incidence of acute kidney injury 2.
Complications
Major complications include:
- Acute kidney injury
- Electrolyte abnormalities (particularly hyperkalemia)
- Compartment syndrome
- Disseminated intravascular coagulation
- Cardiac arrhythmias
Understanding these diverse causes is essential for prompt diagnosis and management of rhabdomyolysis, which can be life-threatening if not recognized and treated appropriately.