What are the diagnostic criteria and treatment options for a patient with suspected rhabdomyolysis, particularly one with a history of strenuous physical activity or medication use that increases the risk of muscle injury?

Diagnosis of Rhabdomyolysis

Rhabdomyolysis is diagnosed when creatine kinase (CK) levels are elevated ≥5-10 times the upper limit of normal (typically >1,000 IU/L, with severe cases >50,000 IU/L), accompanied by clinical symptoms of muscle injury and evidence of myoglobin release. 1

Diagnostic Criteria

The diagnosis requires both laboratory and clinical components:

Laboratory confirmation:

• CK elevation ≥5-10 times upper limit of normal is the primary diagnostic criterion 1
• A reasonable consensus definition includes CK elevation of at least 10 times the upper limit of normal followed by a rapid decrease toward normal values 2
• Severe rhabdomyolysis is characterized by CK >50,000 IU/L with high risk for acute kidney injury 1

Clinical presentation:

• The classic triad of myalgia, muscle weakness, and dark/pigmented urine (myoglobinuria) is seen in less than 10% of patients 2
• Muscle pain, stiffness, cramping, and severe fatigue are common symptoms 3
• Urinalysis showing brown or dark urine that is positive for blood without red blood cells indicates myoglobinuria 3, 1

Essential Initial Laboratory Workup

Immediate testing upon suspicion:

• CK levels - the primary diagnostic test 1
• Comprehensive metabolic panel including creatinine, BUN, electrolytes (especially potassium), glucose, calcium, and phosphorus 1
• Urinalysis for myoglobinuria 1
• Complete blood count with differential to evaluate for infection or systemic processes 1
• Arterial blood gas to assess for metabolic acidosis in severe cases 3, 1

Critical electrolyte monitoring:

• Potassium levels must be checked immediately as hyperkalemia can precipitate life-threatening cardiac arrhythmias and cardiac arrest 1, 4
• Calcium, phosphorus, and magnesium to identify hypocalcemia and hyperphosphatemia 1

Cardiac assessment:

• ECG immediately to assess for arrhythmias related to hyperkalemia 1
• Cardiac troponin in severe cases to rule out cardiac involvement 1

Additional muscle enzymes:

• LDH, AST, ALT, and aldolase are commonly elevated and support the diagnosis 3

Severity Stratification

Mild rhabdomyolysis:

• CK <15,000 IU/L with normal renal function and no significant electrolyte abnormalities 1

Moderate rhabdomyolysis:

• CK 15,000-50,000 IU/L with mild renal dysfunction, requiring 3-6L fluid resuscitation per day 1

Severe rhabdomyolysis:

• CK >50,000 IU/L with acute kidney injury, requiring >6L fluid resuscitation per day and high risk for complications 1
• Risk of acute renal failure is particularly high when CK >16,000 IU/L, which may reach as high as 100,000 IU/L 2

Etiology-Specific Testing

For suspected drug-induced rhabdomyolysis:

• Immediately discontinue statins or other causative medications including red yeast rice, creatine monohydrate, wormwood oil, licorice, and Hydroxycut 3, 4
• Document all over-the-counter medications, herbal supplements, and performance-enhancing products 3
• Screen for recreational drug use including cocaine, methamphetamine, ecstasy (MDMA), ketamine, and heroin 3

For recurrent or unexplained rhabdomyolysis:

• Autoimmune markers (ANA, anti-CCP, rheumatoid factor, myositis-specific antibodies) if autoimmune myositis suspected 1
• Genetic testing for RYR1 and CACNA1S genes for malignant hyperthermia susceptibility 3
• Metabolic myopathy testing including CPT2, PYGM, ACADM, AMPD1, and VLCAD genes 3
• Consider testing for SLCO1B1 gene mutations in statin-induced cases 3

Monitoring During Treatment

Serial laboratory monitoring:

• CK levels daily until declining, with IV fluids continued typically until CK <1,000 U/L 1
• Electrolytes (especially potassium) every 6-12 hours in severe cases 1
• Renal function (creatinine, BUN) monitored daily until stable 1
• Urine output monitored hourly with target ≥300 mL/hour 1, 4

Critical Timing Considerations

CK kinetics:

• CK levels peak 24-120 hours after the inciting event, not immediately 3
• At 9 hours post-exercise, CK levels are typically still rising and have not reached maximum 3
• Repeat CK measurement at 24 hours post-event if clinical suspicion remains high despite initial normal values 3

Common Diagnostic Pitfalls

Impact trauma can drastically increase CK levels without reflecting true muscle breakdown - CK elevation from simple contusion may not carry the same risk of acute kidney injury as true rhabdomyolysis 3

The classic triad is rare - do not wait for myalgia, weakness, and pigmenturia to all be present before diagnosing, as this occurs in <10% of cases 2

Early signs of compartment syndrome (pain, tension, paresthesia, paresis) must be recognized, as late signs (pulselessness, pallor) indicate irreversible damage 3, 4

Life-Threatening Complications Requiring Immediate Recognition

• Acute kidney injury with myoglobin-induced renal tubular obstruction 3
• Severe hyperkalemia causing cardiac arrhythmias 1, 4
• Compartment syndrome requiring early fasciotomy when pressure >30 mmHg 3, 4
• Metabolic acidosis 1
• Disseminated intravascular coagulation 3

Mortality rate is approximately 10% and significantly higher in patients with acute renal failure 2