What is the treatment for Rhabdomyolysis (muscle breakdown disease)?

Treatment of Rhabdomyolysis

Aggressive intravenous fluid resuscitation is the cornerstone of treatment for rhabdomyolysis and must be initiated immediately upon diagnosis to prevent acute kidney injury, which is the most significant complication. 1, 2

Immediate Fluid Resuscitation

Begin isotonic saline (0.9% NaCl) immediately with the following volume targets based on severity 1, 2:

• Severe rhabdomyolysis (CK >15,000 IU/L): Administer >6L of fluid per day 1, 2
• Moderate rhabdomyolysis: Administer 3-6L per day 1, 2
• Target urine output: 300 mL/hour to facilitate myoglobin clearance and prevent renal tubular obstruction 2, 3, 4

Critical timing consideration: Delayed fluid resuscitation is directly associated with higher risk of acute kidney injury and worse outcomes—do not wait for laboratory confirmation if clinical suspicion is high 1, 2

Electrolyte Monitoring and Correction

Monitor potassium levels closely and correct hyperkalemia emergently, as it can precipitate life-threatening cardiac arrhythmias and pulseless electrical activity 1, 2:

• Check electrolyte panels every 6-12 hours in severe cases 2
• Perform repeated bioassessment including plasma myoglobin, CK, and potassium measurements 1
• Correct significant electrolyte abnormalities promptly, including hypocalcemia and hyperphosphatemia 1, 2
• Assess for metabolic acidosis, which commonly occurs in severe rhabdomyolysis 1, 2

Discontinue Causative Agents

Immediately discontinue all potentially causative medications and supplements 1, 5, 2:

• Statins (most common drug-related cause, with incidence of 1.6 per 100,000 patient-years) 1
• Dietary supplements: Red yeast rice containing lovastatin, creatine monohydrate, wormwood oil, licorice, and Hydroxycut 1, 2
• Cease the physical activity that triggered exertional rhabdomyolysis 2

Laboratory Monitoring

Trend CK, creatinine, and electrolytes daily until CK is declining and renal function is stable 1:

• Complete blood count with differential 1
• Liver function tests (AST, ALT, alkaline phosphatase) to assess for transaminitis 1
• Urinalysis showing brown color, cloudiness, and positive for blood without RBCs indicates myoglobinuria 1
• Monitor renal function through serial creatinine and BUN measurements 2

Compartment Syndrome Surveillance

Maintain high suspicion for compartment syndrome, which can both cause and complicate rhabdomyolysis 1, 5, 2:

• Early signs: Pain, tension, paresthesia, and paresis 1, 5, 2
• Late signs: Pulselessness and pallor (indicating irreversible damage) 1, 5, 2
• Perform early fasciotomy when compartment pressure exceeds 30 mmHg or when differential pressure (diastolic BP – compartment pressure) is <30 mmHg 1, 5, 2

Pain Management

Use acetaminophen as the preferred initial analgesic at 500-1000 mg (maximum 4-6 grams daily), as it avoids nephrotoxic effects that are particularly problematic in rhabdomyolysis patients already at high risk for acute kidney injury 1

Avoid all NSAIDs (ibuprofen, ketoprofen, diclofenac, naproxen, mefenamic acid) due to their gastrointestinal and renal toxicity 1

For severe pain unresponsive to acetaminophen, use opioids 1:

• Oral morphine 20-40 mg for opioid-naive patients (first choice) 1
• If acute kidney injury develops with eGFR <30 ml/min, use fentanyl or buprenorphine as the safest options 1

Renal Replacement Therapy

Initiate RRT if CK remains persistently elevated despite 4 days of adequate hydration, as this indicates severe rhabdomyolysis with significant risk of irreversible kidney damage 2:

• Early initiation of RRT is associated with improved outcomes in severe cases 2
• Consider RRT for refractory hyperkalemia, severe metabolic acidosis, or progressive acute kidney injury 2
• Consider discontinuation when urine output recovers adequately (>100 mL/day) 2

Advanced Interventions

After ensuring adequate volume expansion, a diuretic challenge with furosemide may help assess kidney function in select cases, as response to diuretics may predict successful recovery 2

Maintain urine pH at approximately 6.5 if possible 2

Etiology-Specific Considerations

For statin-associated autoimmune myopathy with rash: Discontinue statin immediately and consider referral to a neurologist specializing in neuromuscular disorders 5

For immune checkpoint inhibitor-induced myositis with rash: High-dose corticosteroids are the cornerstone of initial treatment 5

For infectious causes (e.g., Rocky Mountain Spotted Fever presenting with fever, headache, myalgia, and rash): Appropriate antimicrobial therapy based on suspected pathogen plus supportive care with fluid resuscitation 5

For recurrent rhabdomyolysis: Consider genetic testing including RYR1, CACNA1S (malignant hyperthermia susceptibility), CPT2, PYGM, ACADM, AMPD1, VLCAD (metabolic myopathies), and SLCO1B1 gene mutations (statin sensitivity) 1

Critical Pitfalls to Avoid

Do not delay fluid resuscitation waiting for laboratory confirmation—this is the single most important error associated with worse outcomes 1, 2

Do not use inadequate fluid volumes (<6L/day in severe cases), as this may fail to prevent renal complications 2

Do not miss compartment syndrome, particularly in traumatic or severe exertional cases, as this results in irreversible muscle and nerve damage 2

Do not use the 1.5 mg/dL creatinine threshold as a trigger for intervention in trauma-related rhabdomyolysis, as this threshold is specific to cirrhotic patients with acute kidney injury and is not applicable here 1

For athletes with sickle cell trait experiencing collapse: This represents a medical emergency requiring immediate cessation of activity, supplemental oxygen, IV hydration, and possible cooling, as metabolic insult with lactic acidosis and hyperkalemia can lead to pulseless electrical activity where external defibrillation may be ineffective 2