Rhabdomyolysis

Clinical syndrome characterised by widespread destruction of skeletal muscle leading to massive release of intracellular contents into the bloodstream, leading to:

Crush syndrome is a related entity which occurs when a crush injury leads to rhabdomyolysis but also prevents venous return from the affected limb, limiting systemic sequelae.

Relief of the crushing force (generally during extraction) results in reperfusion and ischaemic washout, which may precipitate profound haemodynamic instability or hyperkalaemic arrest.

Epidemiology and Risk Factors

At-risk groups include:

  • Males
  • Morbidly obese
  • Statin users
  • Post-operative

Pathophysiology

Common pathway of muscle destruction:

  • Loss of cellular ATP ↓ efficacy of membrane pumps, resulting in intracellular Na+
  • Secondary ↑ in Ca2+ occurs as 2Na+/Ca2+ pumps activate to correct ↑ Na+
  • ↑ Intracellular Ca2+ activates various proteases, which destroy cellular and mitochondrial membranes
  • Muscle cells necrose, releasing cytotoxic intracellular machinery
    • Myoglobin may precipitate, causing renal tubular obstruction
      This occurs due to interaction with the Tamm-Horsfall protein, and is accelerated in acidic conditions.
    • Hydroxyl radicals lead to lipid peroxidation and tubular sloughing
    • Metabolic acidosis promotes myoglobin cast formation in the DCT

Aetiology

  • Neuromuscular
    • Seizures
  • Fluid and electrolyte
    • DKA
    • Hypokalaemia
    • Hypophosphataemia
    • Hypocalcaemia
  • Traumatic
    • Crush injury
    • Compartment syndromes
    • Burns
    • Prolonged lie
  • Infective
    • NSTI
    • Influenza
    • EBV
    • Primary HIV
    • Legionella
  • Environmental
    • Heat injury
    • Exercise
  • Toxic
    • Statins
    • MH
    • Serotonin syndrome
    • Propofol infusion syndrome
    • Alcohol
      • Delirium tremens
  • Congenital
    • Various mitochondrial disorders
    • Lipid metabolic disorders
  • Idiopathic

Clinical Features

  • Muscle pain
  • Weakness
  • Dark-tea coloured urine
    Requires 100mg/dL of myoglobin, therefore not all cases of rhabdomyolysis develop frank myoglobinuria.
  • Oligo-anuria
  • Intravascular volume depletion
    Due to tissue oedema.
Myoglobinuria

Assessment

History

Exam

Investigations

Bedside:

Laboratory:

  • Blood
    • ↑ K+
    • ↑ PO4
    • ↓ Ca2+
    • ↑ AST
    • ↑ LDh
    • CK
      Generally 5-10× ULN (~1000-2000) U/L is diagnostic, through values can rise much higher.
      • Rise during first 12 hours
      • Peak at 3-5 days
      • Return to baseline over following 6-10 days
    • Myoglobin
      Pathognomonic, but rarely measured.
    • ↓ Urea:Creatinine ratio
      Due to ↑↑ creatinine, secondary to muscular destruction.
  • Urine
    • Myoglobin
    • Dipstick
      Also interactions with myoglobin - myoglobinuria can be inferred with a positive (for blood) dipstick with no red cells in the sediment.

Imaging:

Other:

Diagnostic Approach and DDx

Management

  • Early, aggressive volume resuscitation
    • Limit degree of AKI
  • Target urine output >300ml/hr
  • Consider RRT
  • Avoid correcting calcium

Resuscitation:

  • C
    • Volume resuscitation
      Often in the order of litres per day, targeting a urine output of >300mL/hr in adults.
  • F
    • Correct electrolytes
      • Rapid correction of hyperkalaemia
      • Avoid correction of calcium to ↓ risk of calcium-phosphate precipitation

Specific therapy:

Urinary alkalinisation is covered under Urinary Alkalinisation.

  • Pharmacological
    • Mannitol
      Consider if volume resuscitation does not lead to adequate UO. Avoid in anuric patients.
    • Sodium Bicarbonate
      Reasonable to correct systemic acidosis. Urinary alkalinisation:
      • Is sometimes recommended
      • May ↓ myoglobin toxicity by limiting myoglobin cast formation
      • Can be abandoned if urinary pH does not ↑ to >6.5
  • Procedural
    • RRT
      Effectively clears myoglobin.
  • Physical

Supportive care:

  • F
    • Avoid replacing calcium

Disposition:

Preventative:

Marginal and Ineffective Therapies

  • Loop diuretics
    Can be considered if inadequate urine output is not achieved with volume resuscitation and mannitol.

Anaesthetic Considerations

Complications

  • Death
    20-60% among ICU patients with rhabdomyolysis.
  • F
    • AKI
      10-60% of cases.
    • ↑ Ca2+
      May complicate renal recovery, which occurs due to mobilisation of precipitated calcium and normalisation of PO4.
  • I
    • Soft tissue CaPO4 deposition

Prognosis

Key Studies

References

  1. Chavez LO, Leon M, Einav S, Varon J. Beyond muscle destruction: a systematic review of rhabdomyolysis for clinical practice. Critical Care. 2016;20(1):135. doi:10.1186/s13054-016-1314-5
  2. Bosch X, Poch E, Grau JM. Rhabdomyolysis and Acute Kidney Injury. New England Journal of Medicine. 2009;361(1):62-72. doi:10.1056/NEJMra0801327