Rhabdomyolysis

A syndrome characterised by muscle necrosis and the release of intracellular muscle constituents into the circulation.

• Similar conceptually to 'reperfusion injury'

Risk factors:

• Trauma
• Medications - myotoxic
• Alcohol/substances
• Prolonged immobilisation
• Heat exposure
• Burns
• Sepsis
• Myopathy
• Electrocution
• Seizure
• Toxins
• Endocrine disease

Pathophysiology

• Reperfusion injury
  • Restoration of blood flow and oxygen
    • Increased production of reactive oxygen species - damages microvasculature and cell membranes
    • ROS activate neutrophils, increasing local inflammatory response
  • Successful reperfusion also increases venous drainage which liberates the byproducts of muscle ischaemia and cell necrosis into the circulation
    • Potassium
    • Phosphate
    • Organic acids
    • Myoglobin
    • Creatine kinase
    • Thromboplastin
  • Results in:
    • Hyperkalaemia
    • Hyperphosphataemia
    • Metabolic acidosis from lactate
    • Myoglobinuria - myoglobin has a greater affinity for oxygen than haemoglobin
    • SIRS
• Complications:
  • AKI - multiple mechanisms
    • Reduction in intravascular volume due to third-spacing
    • Activated RAAS, further reducing renal perfusion
    • Vasopressin released by SNS, further reducing renal perfusion
    • Kidneys overwhelmed by myoglobin, leading to deposits/casts in renal tubules, causing renal toxicity
  • Compartment syndrome
    • Muscle oedema and third-spacing, especially crush injuries
  • DIC
    • Released heme protein which is extremely pro-inflammatory and thrombogenic
    • Thromboplastin released during muscle injury, activating extrinsic pathway
  • Cardiac arrhythmia
    • Due to electrolyte abnormalities

Presentation

• Classic triad:
  • Muscle pain - mostly proximal groups
  • Weakness
  • Dark urine
• Also:
  • Muscle swelling, after fluid repletion
  • Malaise
  • Fever
  • Tachycardia
  • Hypovolaemia
  • Hyperkalaemia, hyperphosphataemia, hypocalcaemia, hyperuricaemia, metabolic acidosis
  • AKI
  • Compartment syndrome
  • DIC
  • Arrhythmias (from electrolyte abnormalities)

Investigation

• Serum creatine kinase
  • Usually >5x ULN is diagnostic, but typically >5000 with non-exertional rhabdo and >10,000 with exertional
  • Transient CK >2000 can occur with physiologic vigorous exercise
  • Begins to rise 2-12 hours following onset of muscle injury and peaks within 24-72 hours
  • CK has a half-life of 1.5 days, and declines at a relatively fixed rate of 40-50% of the previous day's value - if it's not declining as expected, consider ongoing injury
• Urinalysis - check for myoglobinuria to confirm, and differentiate from haematuria
• FBE/UEC/CMP/LFTs/coags/VBG/troponin
• ECG
• Tox screen if indicated

Management approach

• Recognition and management of fluid and electrolyte abnormalities
• Identify specific cause
• Prompt recognition and treatment of compartment syndrome