What is the appropriate workup and management for a patient suspected of having rhabdomyolysis (muscle breakdown)?

Rhabdomyolysis Workup

The workup for suspected rhabdomyolysis requires immediate measurement of creatine kinase (CK), comprehensive metabolic panel with electrolytes (particularly potassium), urinalysis for myoglobinuria, and serial monitoring of renal function, with CK ≥5-10 times the upper limit of normal being diagnostic. 1, 2, 3

Initial Diagnostic Laboratory Tests

Essential Core Labs (Obtain Immediately)

• Creatine kinase (CK): The primary diagnostic test, with levels ≥5-10 times the upper limit of normal considered diagnostic for rhabdomyolysis 2, 3, 4
• Comprehensive metabolic panel: Including creatinine, BUN, electrolytes (sodium, potassium, chloride, bicarbonate), glucose, calcium, and phosphorus 1
• Urinalysis: Look specifically for brown/dark urine that is positive for blood without red blood cells present, indicating myoglobinuria 1
• Complete blood count with differential: To evaluate for infection or other systemic processes 1

Critical Electrolyte Monitoring

• Potassium levels: Must be checked immediately and monitored closely, as hyperkalemia can precipitate life-threatening cardiac arrhythmias and cardiac arrest 1, 5
• Calcium, phosphorus, and magnesium: Essential to assess for hypocalcemia and hyperphosphatemia, which are common complications 1
• Arterial blood gas: To assess for metabolic acidosis, which commonly occurs in severe rhabdomyolysis 1

Additional Muscle Enzymes

• AST (SGOT), ALT (SGPT), LDH, and aldolase: These are commonly elevated in rhabdomyolysis due to muscle enzyme release 1
• Plasma myoglobin: Should be included in repeated bioassessment along with CK and potassium 1

Etiology-Specific Testing

Medication and Toxin Screening

• Comprehensive medication review: Document all prescription medications (especially statins), over-the-counter medications, herbal supplements, and performance-enhancing products 1
• Recreational drug screening: Ask specifically about cocaine, methamphetamine, ecstasy (MDMA), ketamine, and heroin use 1
• High-risk supplements: Identify use of red yeast rice (containing lovastatin), creatine monohydrate, wormwood oil, licorice, and Hydroxycut 1

Autoimmune and Inflammatory Workup (When Indicated)

• Autoimmune markers: If autoimmune myositis is suspected, check ANA, anti-CCP, rheumatoid factor, and myositis-specific antibodies (anti-TIF1γ, anti-NXP2) 6, 1
• Inflammatory markers: ESR and CRP to assess for inflammatory processes 6
• Viral studies: Consider testing for viral myositis if clinically indicated 1

Genetic and Metabolic Testing (For Recurrent or Unexplained Cases)

• Malignant hyperthermia susceptibility: RYR1 and CACNA1S gene sequencing, particularly in patients with exertional rhabdomyolysis or heat illness 1
• Metabolic myopathies: CPT2, PYGM, ACADM, AMPD1, and VLCAD gene testing for recurrent rhabdomyolysis 1
• SLCO1B1 gene mutations: Increases risk of statin-induced rhabdomyolysis 1
• Metabolic disorder screening: Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and 25-hydroxy-vitamin D if hereditary disorder suspected 1

Cardiac Assessment

• ECG: Perform immediately to assess for arrhythmias related to hyperkalemia 1
• Cardiac troponin: Check in patients with severe rhabdomyolysis to rule out cardiac involvement 1

Monitoring During Treatment

Serial Laboratory Monitoring

• CK levels: Trend daily until declining; continue IV fluids typically until CK <1,000 U/L 4
• Electrolytes: Check every 6-12 hours in severe cases, with particular attention to potassium 1
• Renal function: Monitor creatinine and BUN daily until stable 1
• Urine output: Hourly monitoring with bladder catheterization; target ≥300 mL/hour 5, 2, 4

Compartment Syndrome Surveillance

• Clinical assessment: Monitor for pain, tension, paresthesia, and paresis (early signs); pulselessness and pallor indicate irreversible damage (late signs) 1
• Compartment pressure measurement: Consider fasciotomy when pressure exceeds 30 mmHg or when differential pressure (diastolic BP – compartment pressure) is <30 mmHg 1
• EMG and MRI: Consider when diagnosis is uncertain or overlap with neurologic syndromes is suspected 6

Severity Stratification

Mild Rhabdomyolysis

• CK elevated but <15,000 IU/L
• Normal renal function
• No significant electrolyte abnormalities 1

Moderate Rhabdomyolysis

• CK 15,000-50,000 IU/L
• Mild renal dysfunction
• Requires 3-6L fluid resuscitation per day 1

Severe Rhabdomyolysis

• CK >50,000 IU/L (can reach 100,000 IU/L)
• Acute kidney injury present
• Requires >6L fluid resuscitation per day
• High risk for complications including acute renal failure, severe electrolyte abnormalities, compartment syndrome, and disseminated intravascular coagulation 1, 3

Common Pitfalls to Avoid

• Delayed CK measurement: CK peaks 24-120 hours after the inciting event, not immediately; if initial CK at 9 hours is only mildly elevated but clinical suspicion remains high, repeat measurement at 24 hours 1
• Missing myoglobinuria: The classic triad of myalgia, weakness, and pigmenturia is seen in <10% of patients; absence of symptoms does not exclude rhabdomyolysis 3
• Underestimating trauma-related CK elevation: Simple contusion from falls can drastically increase CK without true rhabdomyolysis; the large CK molecule (82 kDa) clears via lymphatics, explaining the delayed peak 1
• Ignoring recurrent episodes: Patients with recurrent rhabdomyolysis, exercise intolerance, or family history of neuromuscular disorders require genetic and metabolic testing 1, 3
• Failing to monitor coagulation: Check coagulation studies to evaluate for disseminated intravascular coagulation in severe cases 1