What is the appropriate diagnostic workup and initial management for a patient with suspected rhabdomyolysis presenting with muscle pain, weakness, swelling, dark urine, and recent trauma, strenuous exercise, prolonged immobilisation, seizures, or statin use?

Rhabdomyolysis: Diagnostic Workup and Initial Management

Immediately initiate aggressive intravenous crystalloid resuscitation with isotonic saline (0.9% NaCl) targeting urine output of at least 300 mL/hour, while simultaneously obtaining creatine kinase (CK), comprehensive metabolic panel with electrolytes (especially potassium), urinalysis for myoglobinuria, and ECG to assess for life-threatening hyperkalemia. 1, 2, 3

Diagnostic Workup

Essential Initial Laboratory Tests

Obtain CK level immediately—this is the diagnostic cornerstone. CK >5 times the upper limit of normal (approximately 1,000 IU/L) confirms rhabdomyolysis. 4, 2 Note that CK peaks between 24-120 hours after the inciting event, so a normal or mildly elevated CK at presentation does not exclude the diagnosis if clinical suspicion is high—repeat testing at 24 hours is critical. 1

Order these labs stat:

• Creatine kinase (total CK, not CK-MB): CK-MB lacks sensitivity and specificity for rhabdomyolysis and is inappropriate for this diagnosis. 1
• Comprehensive metabolic panel: Including creatinine, BUN, electrolytes (potassium, calcium, phosphorus, magnesium). 1
• Urinalysis: Look for brown/dark urine that is positive for blood without RBCs on microscopy (indicating myoglobinuria). 1
• Complete blood count: To evaluate for infection or systemic processes. 1
• Liver function tests (AST, ALT, LDH, aldolase): These muscle enzymes are commonly elevated in rhabdomyolysis. 1
• Arterial blood gas: To assess for metabolic acidosis, which commonly occurs in severe cases. 1
• ECG: Essential to identify cardiac arrhythmias from hyperkalemia. 1

Additional Testing Based on Clinical Context

• Coagulation studies (PT, PTT, fibrinogen): If severe rhabdomyolysis to evaluate for disseminated intravascular coagulation. 1
• Serum myoglobin: Peaks earlier than CK (making it more sensitive for early detection), though CK remains the diagnostic standard. 4
• Cardiac troponin: If cardiac involvement is suspected, though muscle injury can cause false elevations. 1

Etiology-Specific Investigations

Conduct a thorough medication review immediately. Document all prescription medications (especially statins, which cause rhabdomyolysis at 1.6 per 100,000 patient-years), over-the-counter medications, herbal supplements (red yeast rice containing lovastatin, creatine monohydrate, wormwood oil, licorice, Hydroxycut), and recreational drugs (cocaine, methamphetamine, MDMA, heroin). 5, 1

For recurrent or unexplained cases, consider:

• Genetic testing: RYR1 and CACNA1S gene sequencing for malignant hyperthermia susceptibility; CPT2, PYGM, ACADM, AMPD1, VLCAD for metabolic myopathies. 1
• Thyroid function tests: Hypothyroidism predisposes to statin-induced rhabdomyolysis. 1
• Autoimmune markers (ANA, ASMA, anti-HMGCR antibodies): If autoimmune myopathy is suspected. 1

Initial Management

Fluid Resuscitation (The Critical Intervention)

Start aggressive IV crystalloid resuscitation immediately—this is the single most important intervention to prevent acute kidney injury. Early initiation is associated with significantly better outcomes. 1, 4

Fluid protocol:

• Use isotonic saline (0.9% NaCl) as first-line fluid. 1
• Target urine output: ≥300 mL/hour. 2, 3
• Volume requirements based on severity:
  • Severe rhabdomyolysis (CK >15,000 IU/L): May require >6L per day. 1, 4
  • Moderate rhabdomyolysis: 3-6L per day typically sufficient. 1, 4
• Continue IV fluids until CK <1,000 IU/L. 3

Avoid Ringer's lactate if head trauma is a concern. 1

Electrolyte Management

Monitor and correct hyperkalemia emergently—this is life-threatening. Hyperkalemia can precipitate fatal cardiac arrhythmias. 1

Electrolyte monitoring protocol:

• Check potassium, calcium, phosphorus, magnesium initially and serially. 1
• Trend CK, creatinine, and electrolytes daily until CK is declining and renal function is stable. 1
• Maintain urine pH at 6.5 if myoglobin >600 ng/mL. 4

Common pitfall: Hypocalcemia is common early but typically does not require treatment unless symptomatic, as calcium can precipitate in damaged muscle. 6

Medication Management

Immediately discontinue any causative agents:

• Statins (especially simvastatin 80 mg, which carries higher risk). 5, 1
• Supplements: Red yeast rice, creatine monohydrate, wormwood oil, licorice, Hydroxycut. 1
• Avoid succinylcholine in perioperative settings. 1

For statin-induced rhabdomyolysis: After resolution, if lipid management is still needed, consider nonstatin therapies (ezetimibe, PCSK9 inhibitors, bempedoic acid) or hydrophilic statins (pravastatin, fluvastatin) with minimal drug interactions. 5, 1

Pain Management

Use acetaminophen (500-1000 mg, maximum 4-6 grams daily) as first-line analgesic. This avoids nephrotoxic NSAIDs, which are absolutely contraindicated in rhabdomyolysis due to increased acute kidney injury risk. 1

For severe pain unresponsive to acetaminophen:

• Oral morphine (20-40 mg for opioid-naive patients) is first-choice opioid. 1
• If acute kidney injury with eGFR <30 mL/min: Use fentanyl or buprenorphine (safest opioids in renal failure). 1

Compartment Syndrome Surveillance

Assess for compartment syndrome urgently—this is both a cause and complication of rhabdomyolysis. Early signs include pain, tension, paresthesia, and paresis; late signs (pulselessness, pallor) indicate irreversible damage. 1

Fasciotomy indications:

• Compartment pressure >30 mmHg. 1
• Differential pressure (diastolic BP - compartment pressure) <30 mmHg. 1

Disposition

Admit all patients with confirmed rhabdomyolysis. Hospitalization is indicated for those with CK >5 times normal, acute kidney injury risk, electrolyte abnormalities, or need for pain management. 1

Renal replacement therapy: Determine on a case-by-case basis for severe acute kidney injury, refractory hyperkalemia, or volume overload. 2

Critical Pitfalls to Avoid

• Do not rely on a single normal CK at presentation. CK peaks 24-120 hours post-event; repeat at 24 hours if clinical suspicion remains. 1
• Do not use CK-MB for diagnosis—it is inappropriate for rhabdomyolysis. 1
• Do not give NSAIDs for pain—they worsen acute kidney injury risk. 1
• Do not delay fluid resuscitation—early aggressive hydration is the only intervention proven to prevent renal failure. 1, 4
• Impact trauma can elevate CK without true rhabdomyolysis, but assume true muscle breakdown until proven otherwise if CK is rising or clinical features are present. 1

Special Considerations for Altered Mental Status

Determine whether altered mental status is: (1) a precipitating cause (seizures, prolonged immobilization, drug intoxication), (2) a consequence of rhabdomyolysis (electrolyte disturbances, uremia from acute kidney injury), or (3) an unrelated complicating condition (neuroleptic malignant syndrome, serotonin syndrome). 1 This distinction guides both diagnostic workup and management priorities.