What are the causes of rhabdomyolysis?

Causes of Rhabdomyolysis

Rhabdomyolysis is caused by multiple factors including medications, exertional activities, toxins, metabolic disorders, and trauma, with toxins being the most frequent cause in approximately 46% of cases. 1

Common Causes of Rhabdomyolysis

Medications and Toxins

• Statins, particularly when combined with other medications that affect their metabolism, can cause myopathy progressing to rhabdomyolysis 2
• Macrolide antibiotics (azithromycin, clarithromycin, erythromycin) when combined with statins increase the risk of rhabdomyolysis 3
• Fibrates, especially gemfibrozil, particularly when combined with statins, significantly increase the risk of severe myopathy and rhabdomyolysis 4
• Other medications including cyclosporine, antifungal drugs, and niacin can contribute to rhabdomyolysis, especially when combined with statins 2
• Alcohol and illicit drugs are among the most common toxin-related causes 1
• Red yeast rice supplements containing lovastatin can cause drug-induced rhabdomyolysis 2

Physical Factors

• Excessive muscle activity, especially novel overexertion or unaccustomed volume/intensity of exercise 2
• Trauma or direct muscle injury 5
• Prolonged muscle compression during surgery or immobilization 2
• Extreme temperatures (hyperthermia or hypothermia) 5

Metabolic and Genetic Causes

• Hereditary muscle enzyme defects account for approximately 10% of cases, with a high percentage of recurrence 1
• Metabolic disorders including electrolyte abnormalities (particularly hypokalemia, hypophosphatemia) 5
• Endocrine disorders such as hypothyroidism or hyperthyroidism 5
• Glycogen storage diseases, particularly type III, can predispose to rhabdomyolysis 2

Infections

• Various bacterial, viral, and fungal infections can trigger rhabdomyolysis, particularly in the pediatric population where infections are among the most common causes 6

Other Causes

• Hypoxic conditions affecting muscle tissue 5
• Sickle cell trait, particularly during intense physical exertion 2
• In approximately 7% of cases, no specific cause is identified 1

Risk Factors for Developing Rhabdomyolysis

• Advanced age, especially over 80 years 3
• Female sex and small body frame 3
• Chronic renal insufficiency 3
• Polypharmacy (use of multiple medications) 3
• Complex medical problems 2
• Transition periods in athletic training (first 4 days of new training regimens) 2

Clinical Manifestations

• Classic triad of symptoms (present in approximately 50% of patients): muscle pain, weakness, and dark urine 6
• Severity ranges from asymptomatic elevation of muscle enzymes to life-threatening complications 7
• Complications include acute renal failure (occurring in 15-33% of cases), electrolyte abnormalities, acidosis, compartment syndrome, and disseminated intravascular coagulation 8

Prevention Strategies

• Careful monitoring when using combinations of medications known to increase rhabdomyolysis risk, particularly statins with fibrates or macrolides 2, 3
• Appropriate calibration and limitation of training volume and intensity during transition periods for athletes 2
• Proper documentation of training sessions for athletes 2
• Discontinuation of supplements associated with rhabdomyolysis risk prior to surgery 2
• Development and rehearsal of emergency action plans for managing exertional rhabdomyolysis in athletic settings 2

Diagnostic Considerations

• Elevated creatine kinase (CK) levels, typically more than 5 times the upper limit of normal 1
• Myoglobinuria may be present but its absence does not exclude rhabdomyolysis (positive in only 19% of cases by qualitative assay) 1
• Muscle biopsy and genetic testing should be considered in cases of recurrent rhabdomyolysis or suspected metabolic myopathy 6

Early recognition and aggressive hydration are crucial for preventing complications, particularly acute kidney injury, which occurs in approximately 46% of hospitalized patients with rhabdomyolysis 1.