What are the diagnostic criteria and treatment options for rhabdomyolysis?

Rhabdomyolysis Diagnosis

Rhabdomyolysis is diagnosed by a creatine kinase (CK) level at least 10 times the upper limit of normal, combined with clinical symptoms of muscle injury and evidence of myoglobinuria. 1, 2

Diagnostic Criteria

Laboratory Thresholds

• CK elevation ≥10 times the upper limit of normal is the primary diagnostic criterion, with levels typically ranging from 1,000 to >100,000 IU/L 1, 2
• Myoglobinuria presents as red-to-brown urine that is positive for blood on urinalysis without red blood cells present, indicating myoglobin release 3, 4
• Plasma myoglobin, CK, and potassium should be measured repeatedly to track disease progression and guide treatment 3

Clinical Presentation

The classic triad of myalgia, weakness, and pigmenturia occurs in less than 10% of patients, making laboratory confirmation essential 1. More commonly:

• Muscle pain, tension, and swelling are present but may be subtle 3, 1
• Severe fatigue, muscle stiffness, and cramping can accompany the syndrome 3
• Asymptomatic CK elevation may be the only finding in mild cases 2

Severity Stratification

CK levels >15,000-16,000 IU/L indicate severe rhabdomyolysis with significantly increased risk of acute kidney injury, requiring aggressive fluid resuscitation 3, 1. The mortality rate is approximately 10% overall but substantially higher when acute renal failure develops 1.

Essential Laboratory Workup

Initial Testing

• Complete electrolyte panel including potassium, calcium, phosphorus, and magnesium is crucial, as hyperkalemia can cause life-threatening cardiac arrhythmias 3
• Serum creatinine and blood urea nitrogen to assess renal function 3
• Liver function tests (AST, ALT, alkaline phosphatase) commonly show transaminitis due to muscle enzyme release 3
• Complete blood count with differential to evaluate for infection or systemic processes 3
• Urinalysis for myoglobinuria showing brown, cloudy urine positive for blood without RBCs 3
• Arterial blood gas to assess for metabolic acidosis in severe cases 3
• Coagulation studies to evaluate for disseminated intravascular coagulation 3

Monitoring During Treatment

• Electrolytes should be monitored every 6-12 hours, with particular attention to potassium 3, 5
• Serial CK measurements to track response to treatment 3
• Cardiac assessment including ECG and troponin in severe cases to rule out cardiac involvement 3

Etiology-Specific Considerations

When to Investigate for Underlying Disease

Most patients experience only one episode of rhabdomyolysis due to identifiable causes (trauma, medications, substance abuse, seizures) and do not require extensive investigation 1. However, further workup is indicated when:

• Recurrent episodes of rhabdomyolysis occur 1, 6
• History of exercise intolerance or family history of neuromuscular disorders is present 1
• Exertional rhabdomyolysis occurs with minimal or routine exercise rather than novel overexertion 7
• Persistently elevated CK (idiopathic hyperCKemia) after full neurological evaluation 8

Genetic and Metabolic Testing

When underlying disease is suspected:

• RYR1 and CACNA1S gene sequencing for malignant hyperthermia susceptibility, particularly in patients with exertional rhabdomyolysis or heat illness 8
• CPT2, PYGM, ACADM, AMPD1, and VLCAD gene testing for metabolic myopathies causing recurrent rhabdomyolysis 8
• SLCO1B1 gene mutations increase risk of statin-induced rhabdomyolysis 3
• Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and 25-hydroxy-vitamin D if metabolic disorder suspected 3
• Viral studies and autoimmune markers (ANA, ASMA, ANCA) if viral or autoimmune myositis suspected 3

Medication Review

Immediately identify and discontinue causative agents, particularly:

• Statins (most common drug cause, incidence 1.6 per 100,000 patient-years) 3
• Dietary supplements: red yeast rice containing lovastatin, creatine monohydrate, wormwood oil, licorice, and Hydroxycut 3, 5
• Succinylcholine in susceptible patients 3

Common Pitfalls

Timing of CK Measurement

CK levels peak 24-120 hours after the inciting event, particularly in traumatic rhabdomyolysis 3. The large CK molecule (82 kDa) requires lymphatic clearance before entering the bloodstream, causing this delay. If initial CK is normal but clinical suspicion remains high, repeat measurement at 24 hours post-event 3.

Distinguishing Contusion from True Rhabdomyolysis

Impact trauma from falls can drastically increase CK levels without reflecting true muscle breakdown, and simple contusion may not carry the same acute kidney injury risk as true rhabdomyolysis 3. Clinical context and serial monitoring are essential.

Compartment Syndrome Recognition

Pain, tension, paresthesia, and paresis are early signs of compartment syndrome, which can both cause and complicate rhabdomyolysis 3. Late signs (pulselessness and pallor) indicate irreversible damage 3. Fasciotomy is indicated when compartment pressure exceeds 30 mmHg or differential pressure (diastolic BP minus compartment pressure) is <30 mmHg 3, 5.