Laboratory Workup for Rhabdomyolysis
The essential initial laboratory tests for diagnosing rhabdomyolysis include creatine kinase (CK), comprehensive metabolic panel with electrolytes, urinalysis for myoglobinuria, and complete blood count, with CK ≥5-10 times the upper limit of normal (>975-1000 IU/L) being diagnostic. 1, 2
Core Diagnostic Tests
Creatine Kinase (CK) is the biochemical gold standard for diagnosis of rhabdomyolysis. 3 Order total CK, not CK-MB, as CK-MB lacks sensitivity and specificity for rhabdomyolysis assessment and is primarily useful for cardiac injury. 4 CK levels should be measured immediately and trended daily until declining, typically until <1,000 U/L. 1
Serum Myoglobin serves as the gold standard for prognostication, particularly in non-traumatic rhabdomyolysis, as it is released earlier than CK but has a shorter half-life. 3, 5 However, note that urine myoglobin detected by dipstick is positive in only 19% of cases, so its absence does not exclude rhabdomyolysis. 2
Comprehensive Metabolic Panel must include:
- Creatinine and BUN to monitor for acute kidney injury, which occurs in 13-50% of rhabdomyolysis cases 3, 1
- Electrolytes (sodium, potassium, chloride, bicarbonate) 1
- Glucose, calcium, and phosphorus 1
- Liver function tests (AST, ALT, alkaline phosphatase) to assess for transaminitis from muscle enzyme release 4, 5
Additional muscle enzymes including LDH, AST (SGOT), ALT (SGPT), and aldolase should be measured as they are commonly elevated. 6, 4
Critical Electrolyte Monitoring
Potassium levels require immediate assessment and close monitoring as hyperkalemia can precipitate life-threatening cardiac arrhythmias and cardiac arrest. 1, 4 In severe cases, check potassium every 6-12 hours. 1
Complete electrolyte panel is essential to assess for:
- Hyperkalemia (most dangerous complication) 5, 1
- Hypocalcemia 5, 1
- Hyperphosphatemia 5, 1
- Hypomagnesemia 1
Repeated bioassessment should include plasma myoglobin, CK, and potassium measurements throughout treatment. 4
Urinalysis and Renal Assessment
Urinalysis should be performed immediately to look for myoglobinuria, indicated by brown or dark urine that is positive for blood without red blood cells present. 1 This is a key diagnostic finding but remember that qualitative assays may be falsely negative in 81% of cases. 2
Renal function monitoring includes daily creatinine and BUN until stable, with hourly urine output monitoring targeting ≥300 mL/hour. 1
Additional Essential Tests
Complete Blood Count with Differential to evaluate for infection or other systemic processes. 1, 4
Arterial Blood Gas to assess for metabolic acidosis, which commonly occurs in severe rhabdomyolysis. 5, 1
Coagulation Studies to evaluate for disseminated intravascular coagulation, a potential complication of severe rhabdomyolysis. 5, 4
ECG should be performed immediately to assess for arrhythmias related to hyperkalemia. 1, 5
Cardiac Troponin should be checked in patients with severe rhabdomyolysis to rule out cardiac involvement. 1, 5
Etiology-Specific Testing
When the cause is unclear or recurrent episodes occur, consider:
Autoimmune markers (ANA, ASMA, ANCA, anti-CCP, rheumatoid factor, myositis-specific antibodies) if autoimmune myositis is suspected. 5, 1, 4
Inflammatory markers including ESR and CRP to evaluate for inflammatory processes. 1, 6
Viral studies if viral myositis is clinically suspected. 5, 1
Genetic and metabolic testing for recurrent rhabdomyolysis, including:
- RYR1 and CACNA1S gene sequencing for malignant hyperthermia susceptibility 4, 5
- CPT2, PYGM, ACADM, AMPD1, and VLCAD gene testing for metabolic myopathies 4
- Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and 25-hydroxy-vitamin D if metabolic disorder suspected 4
Thyroid function tests to evaluate for hypothyroidism, which predisposes to statin-induced rhabdomyolysis. 4, 6
Monitoring Frequency Based on Severity
For severe rhabdomyolysis (CK >50,000 IU/L or >15,000 IU/L with complications):
- Monitor CK, electrolytes, and renal function every 6-12 hours initially 5, 1
- Once CK begins to decrease, reduce to daily monitoring 5
- Continue IV fluids until CK <1,000 U/L 1
For moderate rhabdomyolysis (CK 15,000-50,000 IU/L):
- Daily monitoring of CK, electrolytes, and renal function 1
For mild rhabdomyolysis (CK <15,000 IU/L with normal renal function):
- Daily CK and basic metabolic panel until trending downward 1
Common Pitfalls to Avoid
Do not rely on urine myoglobin alone for diagnosis, as qualitative dipstick testing is positive in only 19% of cases despite true rhabdomyolysis. 2
Do not order CK-MB instead of total CK for rhabdomyolysis diagnosis, as CK-MB is specific for cardiac injury and lacks sensitivity for skeletal muscle breakdown. 4
Remember that CK levels peak 24-120 hours after the inciting event, so initial levels may not represent the peak and serial measurements are essential. 4
In trauma cases, impact trauma can elevate CK without true rhabdomyolysis, but given clinical suspicion, assume true muscle breakdown until proven otherwise and repeat CK at 24 hours if initial levels are equivocal. 4