What is the management of Rhabdomyolysis (muscle breakdown disease)?

Management of Rhabdomyolysis

Immediately initiate aggressive intravenous fluid resuscitation with isotonic saline targeting urine output of at least 300 mL/hour, while simultaneously discontinuing any causative agents and monitoring for life-threatening hyperkalemia. 1, 2, 3

Immediate Actions and Initial Assessment

Discontinue Causative Agents

• Stop all potentially offending medications immediately, including statins, fibrates, red yeast rice containing lovastatin, creatine monohydrate, wormwood oil, licorice, and Hydroxycut 1, 4
• Avoid succinylcholine in any patient with suspected or confirmed rhabdomyolysis due to risk of severe hyperkalemia and cardiac arrest 5, 1
• Review all over-the-counter medications, herbal supplements, performance-enhancing products, and recreational drugs (cocaine, methamphetamine, MDMA, ketamine, heroin) 1

Obtain Immediate Laboratory Testing

• Creatine kinase (CK) is diagnostic when ≥5-10 times upper limit of normal (typically >1,000 U/L, with severe disease >50,000 U/L) 2, 3, 6
• Comprehensive metabolic panel including creatinine, BUN, electrolytes (especially potassium), glucose, calcium, and phosphorus 2
• Potassium level must be checked immediately as hyperkalemia can precipitate life-threatening cardiac arrhythmias and arrest 1, 2, 6
• Urinalysis for myoglobinuria (brown/dark urine positive for blood without RBCs present) 2, 3
• Arterial blood gas to assess for metabolic acidosis 1, 2
• ECG immediately to assess for arrhythmias related to hyperkalemia 2
• Cardiac troponin in severe cases to rule out cardiac involvement 2

Fluid Resuscitation Protocol

Volume and Rate

• For severe rhabdomyolysis (CK >50,000 IU/L or >15,000 IU/L with renal dysfunction): administer >6L of isotonic saline per day 1, 2, 4
• For moderate rhabdomyolysis (CK 15,000-50,000 IU/L): administer 3-6L of isotonic saline per day 1, 2
• Target urine output of ≥300 mL/hour to prevent myoglobin-induced acute kidney injury 1, 4, 3, 6
• Use isotonic saline (0.9% NaCl) as the initial fluid of choice; avoid hypotonic solutions like Ringer's lactate if head trauma is present 1

Duration of Therapy

• Continue IV fluids until CK decreases to <1,000 U/L 2, 6
• Early initiation of fluid resuscitation is critical, as delayed treatment significantly increases risk of acute kidney injury 1

Common Pitfall

• Do not wait for creatinine elevation to 1.5 mg/dL before initiating aggressive fluid therapy—this threshold is specific to cirrhotic patients and does not apply to rhabdomyolysis 1

Electrolyte Management

Hyperkalemia (Life-Threatening Priority)

• Monitor potassium every 6-12 hours in severe cases and correct emergently if elevated 1, 2
• Hyperkalemia can precipitate cardiac arrhythmias and cardiac arrest, requiring immediate treatment 1, 2, 4

Other Electrolyte Abnormalities

• Monitor and correct hypocalcemia, hyperphosphatemia, and hypomagnesemia 2
• Assess for metabolic acidosis and treat accordingly 2, 3

Monitoring During Treatment

Serial Laboratory Assessment

• Trend CK, creatinine, and electrolytes daily until CK is declining and renal function is stable 1, 2
• Check electrolytes (particularly potassium) every 6-12 hours in severe cases 2
• Monitor renal function (creatinine and BUN) daily until stable 2
• Monitor urine output hourly with target ≥300 mL/hour 2

Compartment Syndrome Surveillance

• Early signs include pain, tension, paresthesia, and paresis; late signs include pulselessness and pallor (often indicating irreversible damage) 1, 4
• Consider fasciotomy when compartment pressure exceeds 30 mmHg or when differential pressure (diastolic BP minus compartment pressure) is <30 mmHg 1
• Early fasciotomy is indicated for established compartment syndrome 1

Pain Management

First-Line Approach

• Acetaminophen 500-1000 mg is the preferred initial analgesic (onset 15-30 minutes, maximum 4-6 grams daily) as it avoids nephrotoxic effects 1

Agents to Avoid

• All NSAIDs (ibuprofen, ketoprofen, diclofenac, naproxen, mefenamic acid) must be avoided due to gastrointestinal and renal toxicity in patients already at high risk for acute kidney injury 1

Severe Pain Management

• Reserve opioids for severe muscle pain unresponsive to acetaminophen 1
• Oral morphine 20-40 mg is first-line for opioid-naive patients with severe pain 1
• In patients with established AKI (eGFR <30 mL/min), use fentanyl or buprenorphine as the safest opioid choices 1

Severity Stratification

Mild Rhabdomyolysis

• CK elevation <15,000 IU/L with normal renal function and no significant electrolyte abnormalities 2

Moderate Rhabdomyolysis

• CK 15,000-50,000 IU/L with mild renal dysfunction, requiring 3-6L fluid resuscitation per day 2

Severe Rhabdomyolysis

• CK >50,000 IU/L with acute kidney injury, requiring >6L fluid resuscitation per day and carrying high risk for complications including renal failure, severe electrolyte derangements, compartment syndrome, and disseminated intravascular coagulation 2, 3, 7

Etiology-Specific Considerations

Drug-Induced Rhabdomyolysis

• For statin-induced cases, discontinue statin immediately and evaluate CK, creatinine, and urinalysis for myoglobinuria 1
• Consider alternative lipid-lowering strategies: pravastatin or fluvastatin (minimal CYP450 metabolism), ezetimibe, PCSK9 inhibitors, or bempedoic acid 1, 4
• Never combine gemfibrozil with any statin due to 10-fold higher rhabdomyolysis risk compared to fenofibrate 1
• SLCO1B1 gene mutations increase risk of statin-induced rhabdomyolysis 1

Exertional Rhabdomyolysis

• Properly calibrate training and conditioning sessions, especially during transition periods (returning after injury) 1, 4
• Maintain adequate hydration throughout exercise and perioperative periods 1, 4

Trauma-Related Rhabdomyolysis

• Crush injuries and severe limb trauma are major risk factors 1
• Note that simple contusion from falls can elevate CK without true muscle breakdown; CK peaks 24-120 hours post-trauma, so repeat measurement at 24 hours if clinical suspicion remains high 1

Recurrent or Unexplained Cases

• Consider genetic testing including RYR1 and CACNA1S gene sequencing for malignant hyperthermia susceptibility 1
• Test CPT2, PYGM, ACADM, AMPD1, and VLCAD genes for metabolic myopathies causing recurrent rhabdomyolysis 1
• Persistently elevated CK (idiopathic hyperCKemia) after full neurological evaluation requires further investigation 1

Renal Replacement Therapy

• Determine need for renal replacement therapy on a case-by-case basis for severe acute kidney injury, refractory hyperkalemia, severe metabolic acidosis, or volume overload 3, 8, 6

Disposition

• Most patients require hospital admission for aggressive fluid resuscitation and monitoring 3, 6
• Admission is mandatory for patients with CK >15,000 IU/L, any degree of renal dysfunction, significant electrolyte abnormalities, or inability to maintain adequate oral hydration 2, 6