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

1. Trauma or muscle compression
   • Crush Syndrome
   • Immobilization
   • Compartment Syndrome
2. Nontraumatic Exertional
   • Exercise + hot weather
   • Exercise + sickle cell
   • Exercise + Hypokalemia
   • Hyperkinetic states
     • Seizure
     • DTs
     • Stimulant / Sympathomimetic overdose
     • Malignant Hyperthermia
     • Neuroleptic malignant syndrome
3. 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 (rhabdomyolysis only described in case reports)
   • Miscellaneous
     • Status Asthmaticus
     • TSS
     • Mushroom ingestion

Clinical Features

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

Differential Diagnosis

Extremity trauma

• Peripheral nerve injury
• Vascular injury
• Tendon injury
• Laceration
• Fracture
  • Open fracture
• Open joint injury
• Crush syndrome
• Compartment syndrome
• Rhabdomyolysis
• Contusion
• Myositis ossificans

Red Urine

• Hematuria
• Hemoglobinuria
• Porphyria
• Myoglobinuria (rhabdomyolysis)
• Foods
  • Blackberries
  • Beets
  • Blackberries
  • Rhubarb
  • Food coloring
  • Fava beans
• Drugs
  • Laxatives
  • Phenophthalein
  • Rifampin
  • Doxorubicin
  • Deferoxamine
  • Ibuprofen
  • Chloroquine
  • Hydroxocobalamin

Evaluation

Work-up

• Obtain immediate ECG (electrolyte abnormalities)
• Total CK
• Urinalysis
• CBC
• Chemistry, including Mag, Phos
• Uric acid
• LFTs
• DIC panel
  • Coags, FSP, fibrinogen

Evaluation

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

Management

Trend:

• Volume status
• Urine pH
• Chemistry
• CK
• Calcium, phosphorus

IV Fluids

• Start with NS 1-2 L/hr
• Once urination occurs maintain urine output of 200-300 mL/hr
• Frequently need ~10 L/day

Urinary alkalinization

• Admistered as bicarbonate drip
  • Mix 150 mL [3 amps] of 8.4% sodium bicarbonate with 1 L D5W
  • Infuse at 200 mL/hour; rate is adjusted to achieve urine pH of >6.5
• 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
  • Arterial pH and serum calcium should be monitored q2hr
• Discontinue alkalinization:
  • Urine pH does not rise above 6.5 after 3-4hr
  • Patient develops symptomatic hypocalcemia
  • Arterial pH > 7.5
  • Serum bicarbonate >30 meq/L

Mannitol

• Mannitol administration can worsen dehydration and oliguria and although used in the past should generally be avoided
• No RCT to date has demonstrated benefit

Intubation/RSI

• Use Rocuronium due to the potential elevations in potassium that result from the rhabdomyolysis

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 rhabdomyolysis with out 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 within several days
• Compartment Syndrome
• Peripheral nerve injury
  • Usually resolves within few days-weeks

See Also

• Crush Syndrome
• Sympathomimetic Toxicity

References

Authors

Ross Donaldson