Rhabdomyolysis

Background

• Muscle necrosis and release of intracellular muscle constituents into the circulation
• Recurrent episodes suggests inherited metabolic disorder
• Alcohol and drugs play a role in up to 80% of cases

Etiology

• Trauma or muscle compression
  • Crush Syndrome
  • Immobilization
  • Compartment Syndrome
• Nontraumatic Exertional
  • Exercise + hot weather
  • Exercise + sickle cell
  • Exercise + Hypokalemia
  • Hyperkinetic states
    • Seizure
    • DTs
    • Stimulant overdose
    • Malignant Hyperthermia
    • Neuroleptic malignant syndrome
• Nontraumatic Nonexertional
  • Drugs and toxins
    • Coma induced by sedatives
    • Alcohol
      • Coma-induced muscle compression
      • Direct toxic effect
      • Nutritional compromise increases risk (hypoK, hypoMg, HypoPhos)
    • Statins
    • Colchicine
    • CO Poisoning
  • Infection
    • Viral myositis - Influenza, Coxsackie, EBV, HSV, HIV, CMV
    • Bacterial pyomyositis
    • Septicemia
  • Endocrine
    • Hypothyroidism
  • Inflammatory myopathies
    • Moderate CK elevations only (rhabdo only described in case reports)
  • Miscellaneous
    • Status Asthmaticus
    • TSS
    • Mushroom ingestion

Differential Diagnosis

Red or Purple Urine

• Hematuria
• Hemoglobinuria
• Porphyria
• Myoglobinuria (rhabdomyolysis)
• Foods
  • Blackberries
  • Beets
  • Blackberries
  • Rhubarb
  • Food coloring
  • Fava beans
• Drugs
  • Laxatives
  • Phenophthalein
  • Rifampin
  • Doxorubicin
  • Deferoxamine
  • Ibuprofen
  • Chloroquine
  • Hydroxocobalamin
• Purple urine bag syndrome
• Uric acid crystalluria (neonates)

Clinical Features

• Myalgia, stiffness, weakness, malaise, low-grade fever, dark urine
  • Musculoskeletal symptoms may be present in only half of cases
• N/V, abd pain, tachycardia in severe cases
• Mental status changes secondary to urea-induced encephalopathy

Work-up

• Total CK
• UA
• CBC
• Chemistry, including Mag, Phos
• Uric acid
• LFTs
• DIC panel
  • Coags, FSP, fibrinogen

Diagnosis

• Total CK
  • Most consider rhabdo if 5x or greater increase above upper limit of normal (~2000)
  • Serum CK begins to rise 2-12hr after injury, peaks w/in 24-72hr
  • Degree of CK elevation correlates w/ muscle injury, but NOT renal failure
• CK-MB
  • May be normal or mildly elevated (<5% of total)
• Uric Acid - elevates before CK
• Myoglobinuria
  • UA = +blood, no RBCs (Sn ~80%)
  • Myoglobin is cleared w/in 1-6hr (often see elevated CK with no myoglobinuria)
• Acute renal failure
  • Creatinine increase
• Electrolyte abnormalities
  • Hyperkalemia
  • Hyperphosphatemia
  • Hypocalcemia
  • Hyperuricemia

Management

• Aggressive IVF
  • Start with NS 1-2 L/hr
  • Once diuresis occurs maintain urine output of 200-300 mL/hr
  • Frequently need ~10 L/day
• Trend:
  • Volume status
  • Urine pH
  • Chemistry
  • CK
  • Calcium, phosphorus
• Urinary alkalinization (with bicarbonate)
  • Controversial; no RCT to date have demonstrated benefit
  • Consider if CK >5000, severe muscle injury (crush injury), rising CK AND urine pH <6.5
  • Contraindications:
    • Severe hypocalcemia
    • Arterial pH > 7.50
    • Serum bicarbonate > 30 meq/L
  • Mix 150 mL [3 amps] of 8.4% sodium bicarbonate w/ 1 L D5W
  • Infuse at 200 mL/hour; rate is adjusted to achieve urine pH of >6.5
  • Arterial pH and serum calcium should be monitored q2hr
  • Discontinue if:
    • Urine pH does not rise above 6.5 after 3-4hr
    • Pt develops symptomatic hypocalcemia
    • Arterial pH > 7.5
    • Serum bicarbonate >30 meq/L
• Mannitol
  • Controversial; no RCT to date has demonstrated benefit
  • Mannitol administration can worsen dehydration and oliguria, cause hyperkalemia
  • Consider in pts w/marked elevations in CK (>30K)
  • Contraindicated if urinary flow is inadequate (<20 mL/hr)
  • Add 50 mL of 20% mannitol to each liter of fluid; give at rate of 5g/hr
  • Must check plasma osmolaity and plasma osmolal gap q4-6hr
    • Discontinue if osmolal gap > 55 mosmol/kg
• Intubation/RSI
  • Use Rocuronium

Disposition

• Discharge if:
  • Exertional rhabdo
  • Otherwise healthy
  • No comorbidities (heat stress, dehydration, trauma)
  • Downtrending total CK
    • Consider admission for CK >30,000
• Otherwise admit to monitored bed

Complications

• Acute Renal Failure
  • Neither presence of myoglobinuria nor degree of CK rise is predictive of ARF
  • Rare in exertional rhabdo w/o presence of dehydration, heat stress, trauma
  • Most commonly oliguric
• Hyperkalemia
  • Renal function, not release of K+, is most important determinant
  • Treat aggressively; insulin may be ineffective; may require dialysis
• Hypocalcemia (initial phase)
  • Treat only if symptomatic or severely hyperkalemic (often have rebound hypercalcemia)
• Hypercalcemia (recovery phase)
• Hyperphosphatemia
  • Treat cautiously (treatment may worsen calcium precipitation in muscle)
  • Consider oral phosphate binders when level >7
• DIC
  • Usually resolves spontaneously w/in several days
• Compartment Syndrome
• Peripheral nerve injury
  • Usually resolves w/in few days-weeks

See Also

• Crush Syndrome
• Sympathomimetic Toxicity