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Rhabdomyolysis

Definition

Rhabdomyolysis is a clinical syndrome resulting from acute skeletal muscle breakdown (injury) → release of intracellular component (including creatine kinase, myoglobin, electrolytes) into the circulation

Aetiology

Key causes of rhabdomyolysis (non-exhaustive): [Ref1][Ref2]

Traumatic
  • Crush injury
  • Prolonged immobilisation
  • Limb compression
  • Major artery occlusion
  • Burns
  • Electrical shock
Non-traumatic Exertional
  • Strenuous exercise (e.g. from marathon) – common benign cause
  • Seizures
  • Neuroleptic malignant syndrome
  • Hyperthermia, heatstroke
Drugs / toxins
  • Lipid lowering drugs: statins (most important), fibrates
  • Fibrates
  • Alcohol
  • Antipsychotics
  • Recreational drugs: cocaine, heroin

Note that corticosteroids can cause a non-inflammatory myopathy, BUT it is NOT associated with rhabdomyolysis or ↑ creatine kinase.

Autoimmune / inflammatory
  • Polymyositis
  • Dermatomyositis
Metabolic / genetic
  • Glycogen storage disease
  • Fatty acid oxidation defects
  • Mitochondrial myopathies
Infectious
  • Viral infections (e.g. influenza, COVID-19, HIV)
  • Bacterial infections (e.g. pyomyositis, streptococcus pyogenes)

Clinical Features

Classic triad of: [Ref]

  • Myalgia
  • Weakness
  • Dark-coloured urine (from myoglobinuria)

 

Other features:

  • Patients may present only with complications (e.g. AKI or electrolyte disturbances)
  • Systemic features (e.g. fever, nausea, vomiting, malaise, tachycardia) may also occur

Complications

Key acute complications: [Ref]

  • AKI – most common and important (due to myoglobin-induced tubular toxicity)
  • Electrolyte disturbances
    • Hyperkalaemia (may cause arrhythmia)
    • Hyperphosphatemia
    • Hypocalcaemia – calcium enters injured muscle tissue and form calcium-phosphate complexes within necrotic muscle fibres → ↓ serum calcium
  • Metabolic acidosis
  • Compartment syndrome (from muscle swelling and ↑ intracompartmental pressure)

DIC is a rare but serious complication, which happens when prothrombotic substances are released from necrotic muscle.

Investigation and Diagnosis

Test of choice: serum creatine kinase [Ref]

  • ↑ Creatine kinase + >5 times above the upper limit of normal is diagnostic
  • For instance, if the provided reference range for creatine kinase is 25-200 IU/L. A creatine kinase of >1,000 (200 x 5 = 1,000) is diagnostic.

 

Additional findings (supportive but not diagnostic): [Ref]

Electrolyte disturbances
  • ↑ Potassium
  • ↑ Phosphate
  • ↓ Calcium (ionised calcium) – calcium enters injured muscle tissue and form calcium-phosphate complexes within necrotic muscle fibres → ↓ serum calcium
Metabolic panel
  • ↑ LDH
  • ↑ Uric acid
  • ↑ AST, ALT
  • ↑ Creatinine
Blood gas
  • ↑ Anion gap metabolic acidosis
Urinalysis
  • Blood +ve (technically a false +ve)
  • No red blood cells under microscopy

Do NOT mix up the following terms:

  • Creatine kinase: intracellular enzyme found predominantly in skeletal muscle. It is the most sensitive and specific diagnostic marker for rhabdomyolysis
  • Creatinine: the breakdown product of creatine and phosphocreatine from muscle metabolism. It is used as a marker of renal function (and to calculate eGFR), but is NOT a marker of muscle injury. Serum creatinine may be elevated in rhabdomyolysis, due to increased muscle breakdown and/or AKI, but is NOT diagnostic of rhabdomyolysis itself
  • Creatine: a nitrogenous organic acid stored in muscle as phosphocreatine, provides energy for ATP regeneration during muscle contraction. Routine laboratory tests do not measure creatine levels, it is more commonly recognised as a component of fitness and bodybuilding supplements.

Management

Immediate management: aggressive IV fluid resuscitation [Ref1][Ref2]

  • 0.9% NaCl is most commonly used
  • Aim for urine output at least 200-300 mL/hr

 

Other aspects of management: [Ref1][Ref2]

  • Treat any reversible causes of rhabdomyolysis + consider stopping medications associated with rhabdomyolysis
  • Correct any electrolyte disturbances (esp. hyperkalaemia – see the Hyperkalaemia article for more information)

There is NO strong evidence supporting routine use of urinary alkalinisation (with sodium bicarbonate), mannitol, or loop diuretics for prevention of AKI in rhabdomyolysis.

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