Rhabdomyolysis

Risk factors

• Trauma: crush injuries, compartment syndrome, prolonged immobilization (down for hours), electrical injury, burns
• Exertional: prolonged or unaccustomed exercise (marathon, military training, CrossFit), heatstroke, sickle cell trait
• Medications: statins (atorvastatin, simvastatin, rosuvastatin — especially with fibrates or CYP3A4 inhibitors), colchicine, daptomycin, neuroleptics (NMS), succinylcholine
• Toxins/drugs of abuse: alcohol, cocaine, methamphetamine, opioids (immobilization), heroin, MDMA
• Infections: influenza, Legionella, sepsis, HIV
• Inherited myopathies: McArdle disease, carnitine palmitoyltransferase II deficiency
• Electrolyte derangements: hypokalemia, hypophosphatemia, hypocalcemia
• Endocrine: hypothyroidism, DKA, hyperthermia

Pathophysiology

Direct or indirect muscle injury depletes ATP and impairs Ca2+ regulation, leading to sarcoplasmic Ca2+ overload, activation of proteases and phospholipases, mitochondrial dysfunction, and sarcolemmal rupture. Released myoglobin causes AKI via three mechanisms: renal vasoconstriction (volume depletion, sequestration), direct tubular toxicity (heme-induced oxidative injury), and intratubular obstruction by myoglobin casts (worsened by acidic urine). Hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia complete the metabolic picture.

Clinical presentation

Differential diagnosis

• Myocardial infarction (with mild CK elevation) — Troponin specific to cardiac injury; CK-MB fraction; ECG changes
• Statin myopathy without rhabdomyolysis — Mild CK elevation, myalgias without significant AKI; resolves with drug withdrawal
• Hemoglobinuria from intravascular hemolysis — Pink plasma, normal CK; LDH elevated, haptoglobin low
• Polymyositis / dermatomyositis — Subacute proximal muscle weakness; CK elevated; positive myositis antibodies; rash (dermatomyositis)
• Neuroleptic malignant syndrome — Antipsychotic + fever + rigidity + autonomic instability + altered mental status + elevated CK
• Malignant hyperthermia — Volatile anesthetic + succinylcholine exposure; hyperthermia, rigidity, rapidly rising CO2; treat with dantrolene
• Serotonin syndrome — Serotonergic agents + clonus, hyperreflexia, tremor; CK may be elevated

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Muscle injury<br/>trauma, exertion, drugs, toxins] --> B[Sarcolemma rupture]
  B --> C[Release of CK, myoglobin,<br/>K, PO4, urate]
  C --> D[Myoglobinuria]
  D --> E{Adequate<br/>volume?}
  E -->|Yes| F[Myoglobin cleared,<br/>kidney preserved]
  E -->|No| G[Renal vasoconstriction]
  G --> H[Tubular obstruction<br/>by myoglobin casts]
  H --> I[Direct heme toxicity]
  I --> J[Pigment-induced AKI / ATN]
  C --> K[Hyperkalemia, hyperPO4,<br/>hypocalcemia, AG acidosis]
  K --> L[Cardiac arrhythmia]

Treatment

Complications

• AKI (10-50% of cases; pigment-induced ATN)
• Hyperkalemia → cardiac arrhythmia
• Hyperphosphatemia, hypocalcemia (initial), hypercalcemia (recovery phase)
• Hyperuricemia
• High anion gap metabolic acidosis
• Compartment syndrome (and conversely, compartment syndrome causes rhabdomyolysis — vicious cycle)
• DIC in severe cases
• Death — overall mortality 5-10%, much higher in severe cases or comorbid disease

PANCE pearls

• Dipstick urine 'blood' positive with NO RBCs on microscopy = myoglobinuria (or hemoglobinuria) — myoglobin and hemoglobin both react with the heme test.
• CK peaks 24-72 hours after the inciting event and declines with ~50% half-life; trend rather than single values inform progression and resolution.
• Aggressive IV fluid resuscitation is the single most important intervention. Target urine output ≥200-300 mL/h until CK <5,000.
• Bicarbonate and mannitol have NOT been shown to outperform aggressive saline alone in modern studies; they remain controversial.
• Always check for compartment syndrome — both as a cause (crush, prolonged immobilization) and as a complication (massive limb swelling from rhabdo). Surgical emergency.
• AST > ALT in rhabdomyolysis reflects muscle (not liver) source. CK is more specific to muscle injury.
• Statin-induced rhabdomyolysis: risk highest with simvastatin, increased by CYP3A4 inhibitors (macrolides, azoles, grapefruit, fibrates — especially gemfibrozil).

References

• Bosch 2009 — Rhabdomyolysis and acute kidney injury (Bosch et al., NEJM 2009)
• Chavez 2016 — Beyond muscle destruction: a systematic review of rhabdomyolysis for clinical practice (Chavez et al., Crit Care 2016)
• Petejova 2014 — Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review (Petejova and Martínek, Crit Care 2014)