What is the recommended workup and initial management for a patient with suspected rhabdomyolysis?

Rhabdomyolysis Workup and Initial Management

Immediately obtain creatine kinase (CK), comprehensive metabolic panel with electrolytes (especially potassium), urinalysis for myoglobinuria, and ECG, while simultaneously initiating aggressive IV crystalloid resuscitation targeting urine output ≥300 mL/hour. 1

Essential Initial Laboratory Tests

Core diagnostic panel:

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

Critical electrolyte monitoring:

• Potassium levels immediately: Hyperkalemia can precipitate life-threatening cardiac arrhythmias and cardiac arrest 1, 3
• Calcium and phosphorus: Assess for hypocalcemia and hyperphosphatemia, which are common complications 1, 4
• Arterial blood gas: To assess for metabolic acidosis, which commonly occurs in severe rhabdomyolysis 1, 4

Cardiac assessment:

• ECG immediately: To assess for arrhythmias related to hyperkalemia 1
• Cardiac troponin: Check in patients with severe rhabdomyolysis to rule out cardiac involvement 1, 4

Additional Muscle Enzymes

• LDH, AST (SGOT), ALT (SGPT), and aldolase: These are commonly elevated in rhabdomyolysis and should be measured 1
• Serum myoglobin: Can be detected earlier than CK but has a shorter half-life 4

Etiology-Specific Testing

Medication and substance review:

• Document all prescription medications (especially statins), over-the-counter medications, herbal supplements, and performance-enhancing products 5
• Ask about recreational drug use including cocaine, methamphetamine, ecstasy (MDMA), ketamine, and heroin 5
• Discontinue causative agents immediately, particularly statins, red yeast rice containing lovastatin, creatine monohydrate, wormwood oil, licorice, and Hydroxycut 5

Autoimmune workup (if clinically indicated):

• ANA, anti-CCP, rheumatoid factor, and myositis-specific antibodies if autoimmune myositis is suspected 1
• ESR and CRP to evaluate for inflammatory processes 1

Infectious workup:

• Viral studies if viral myositis is clinically suspected 1, 4

Endocrine evaluation:

• Thyroid function tests to evaluate for hypothyroidism, which predisposes to statin-induced rhabdomyolysis 1

Genetic and metabolic testing (for recurrent or unexplained cases):

• RYR1 and CACNA1S gene sequencing for malignant hyperthermia susceptibility, particularly in patients with exertional rhabdomyolysis or heat illness 5
• CPT2, PYGM, ACADM, AMPD1, and VLCAD gene testing for metabolic myopathies causing recurrent rhabdomyolysis 5

Severity Stratification

Mild rhabdomyolysis:

• CK elevation 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, acute kidney injury, requires >6L fluid resuscitation per day, high risk for complications 1

Monitoring Frequency During Treatment

For severe rhabdomyolysis (CK >5,000 IU/L):

• Monitor CK, electrolytes (especially potassium), and renal function every 6-12 hours initially 4
• Once CK levels begin to decrease, reduce monitoring to daily 4
• Continue IV fluids typically until CK <1,000 U/L 1, 2

For all cases:

• Trend CK levels daily until declining 1
• Monitor renal function (creatinine and BUN) daily until stable 1
• Monitor urine output hourly with target ≥300 mL/hour 1, 2

Critical Complications to Monitor

Acute kidney injury:

• Myoglobin-induced renal tubular obstruction and toxicity is the most serious systemic complication 5, 3
• Monitor creatinine and BUN closely 1

Electrolyte abnormalities:

• Hyperkalemia (can cause cardiac arrhythmias and arrest) 1, 3
• Hypocalcemia and hyperphosphatemia 1, 3
• Metabolic acidosis 1, 3

Compartment syndrome:

• Early signs include pain, tension, paresthesia, and paresis 5
• Late signs include pulselessness and pallor, which often indicate irreversible damage 5
• Consider fasciotomy when compartment pressure exceeds 30 mmHg or when differential pressure (diastolic blood pressure – compartment pressure) is <30 mmHg 5

Disseminated intravascular coagulation:

• Perform coagulation studies to evaluate for DIC 1, 4

Immediate Management

Fluid resuscitation:

• Initiate aggressive IV crystalloid resuscitation immediately with isotonic saline (0.9% NaCl) 5
• Target urine output ≥300 mL/hour 1, 2
• For severe rhabdomyolysis (CK >15,000 IU/L), volumes greater than 6L may be required 5
• Early initiation is critical—delayed treatment is associated with higher risk of acute kidney injury 5

Discontinue causative agents:

• Immediately stop any offending medications, particularly statins 5
• Avoid medications that can exacerbate rhabdomyolysis, particularly succinylcholine 5

Correct electrolyte abnormalities:

• Monitor and correct hyperkalemia emergently 5, 1

Common Pitfalls to Avoid

Timing of CK measurement:

• CK levels peak 24-120 hours after the inciting event, not immediately 5
• At 9 hours post-exercise, CK levels are typically still rising and have not reached their maximum 5
• If clinical suspicion remains high, repeat CK measurement at 24 hours post-event 5

Impact trauma consideration:

• Impact trauma from a fall can drastically increase CK levels without reflecting true muscle breakdown 5
• However, given a doubling trend in CK, assume true muscle breakdown until proven otherwise 5

Altered mental status evaluation:

• Evaluate whether altered mental status is a precipitating cause of rhabdomyolysis (e.g., seizures, prolonged immobilization, drug intoxication), a consequence of rhabdomyolysis (e.g., electrolyte disturbances, uremia), or an unrelated but complicating condition (e.g., neuroleptic malignant syndrome, serotonin syndrome) 5

Pain management:

• Use acetaminophen (500-1000 mg, maximum 4-6 grams daily) as the preferred initial analgesic 5
• Avoid all NSAIDs (ibuprofen, ketoprofen, diclofenac, naproxen, mefenamic acid) due to nephrotoxic effects 5
• Reserve opioids for severe pain unresponsive to acetaminophen; use fentanyl or buprenorphine if eGFR <30 mL/min 5