Which enzymes are elevated in rhabdomyolysis, what levels indicate severity, and how should they be monitored?

Elevated Enzymes in Rhabdomyolysis

Creatine kinase (CK) is the primary and most important enzyme elevated in rhabdomyolysis, with diagnostic levels ≥5-10 times the upper limit of normal, and severity stratified by CK >15,000 IU/L for moderate disease and >50,000 IU/L for severe disease. 1

Primary Diagnostic Enzyme

Creatine Kinase (CK) is the gold standard for diagnosis and monitoring:

• Total CK (not CK-MB) should always be measured for rhabdomyolysis assessment, as CK-MB lacks the sensitivity and specificity needed and is inappropriate for this diagnosis 2
• Diagnostic threshold: CK ≥5-10 times the upper limit of normal is required to establish the diagnosis 1
• CK levels typically peak 24-120 hours after the inciting event, meaning initial levels may not represent the true severity and repeat testing is essential 2
• Monitor CK daily until levels are declining and continue IV fluids typically until CK falls below 1,000 U/L 1

Severity Stratification by CK Level

The CK level directly correlates with complications and guides management intensity:

• Mild rhabdomyolysis: CK <15,000 IU/L with normal renal function and no significant electrolyte abnormalities 1
• Moderate rhabdomyolysis: CK 15,000-50,000 IU/L with mild renal dysfunction, requiring 3-6L fluid resuscitation per day 2, 1
• Severe rhabdomyolysis: CK >50,000 IU/L with acute kidney injury, requiring >6L fluid resuscitation per day and carrying high risk for life-threatening complications 2, 1
• Acute kidney injury risk is particularly elevated when CK >16,000 IU/L, with levels potentially reaching 100,000 IU/L in severe cases 3

Additional Muscle Enzymes Commonly Elevated

While CK is diagnostic, other muscle enzymes are frequently elevated and can support the diagnosis:

• AST (aspartate aminotransferase) is elevated in 93% of rhabdomyolysis cases and decreases in parallel with CK, suggesting skeletal muscle as the source 4
• ALT (alanine aminotransferase) is elevated in 75% of cases but is less sensitive than AST 4
• LDH (lactate dehydrogenase) and aldolase are commonly elevated and should be measured as additional muscle enzymes 2, 1

Important Caveat on Transaminases

AST elevation in rhabdomyolysis does not indicate liver injury—it reflects skeletal muscle breakdown 4. The AST falls in parallel with CK during recovery, confirming its muscle origin rather than hepatic source 4. This is a common pitfall: clinicians may mistakenly pursue hepatic workup when elevated transaminases are simply reflecting muscle injury.

Critical Monitoring Parameters Beyond Enzymes

Myoglobin should be measured in plasma, though urinalysis for myoglobinuria (brown/dark urine positive for blood without RBCs) is more practical 2, 1

Electrolytes require intensive monitoring as they determine mortality risk:

• Potassium must be checked immediately and every 6-12 hours in severe cases, as hyperkalemia causes life-threatening cardiac arrhythmias and is the most urgent complication 1
• Calcium, phosphorus, and magnesium should be assessed for hypocalcemia and hyperphosphatemia 1
• Arterial blood gas is essential to assess for metabolic acidosis in severe cases 2, 1

Renal function monitoring is critical:

• Check creatinine and BUN daily until stable 1
• Monitor urine output hourly with target ≥300 mL/hour 1
• Comprehensive metabolic panel should include glucose, calcium, and phosphorus 1

Monitoring Algorithm

For all suspected rhabdomyolysis cases:

1. Immediate labs: Total CK, comprehensive metabolic panel with electrolytes (especially potassium), urinalysis for myoglobinuria, ECG 1
2. Additional muscle enzymes: AST, ALT, LDH, aldolase 2, 1
3. Cardiac assessment: Troponin in severe cases to rule out cardiac involvement 1
4. Repeat CK at 24 hours if initial level is borderline or clinical suspicion remains high, as levels may still be rising 2

During treatment:

• CK, creatinine, and electrolytes daily until CK is declining and renal function is stable 2
• Potassium every 6-12 hours in severe cases 1
• Urine output hourly 1

Common Pitfalls to Avoid

• Do not use CK-MB for rhabdomyolysis diagnosis—it is inappropriate and lacks sensitivity; always order total CK 2
• Do not assume initial CK represents peak severity—levels continue rising for 24-120 hours and require repeat measurement 2
• Do not mistake elevated AST/ALT for primary liver disease—in rhabdomyolysis, these reflect muscle breakdown, not hepatotoxicity 4
• Do not delay treatment waiting for peak CK—early aggressive fluid resuscitation is critical to prevent acute kidney injury 2
• Impact trauma alone can elevate CK without true rhabdomyolysis, but if CK is trending upward, assume true muscle breakdown until proven otherwise 2