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Rhabdomyolysis

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Ovid: 5-Minute Sports Medicine Consult, The


Rhabdomyolysis
Cherise Russo
Basics
Description
  • Syndrome associated with muscle injury and systemic release of intracellular contents, such as creatine phosphokinase (CPK)
  • A combination of myoglobinuria, hypovolemia, and aciduria leads to acute renal failure.
  • Direct release of potassium from damaged muscle tissue may lead to dysrhythmias and sudden death.
Epidemiology
  • Occurs in up to 85% of trauma patients
  • 10–50% of patients with rhabdomyolysis will develop acute renal failure.
  • ∼26,000 people are affected in the U.S. each year.
  • Exact incidence of exertional rhabdomyolysis is unknown, but is likely comparable to military reports of 0.3–3%
Risk Factors
  • Heritable muscle enzyme deficiencies
  • Electrolyte abnormalities
  • Infections
  • Drugs
  • Toxins
  • Endocrinopathies
  • Exercise in high heat
  • Exercise in high humidity
  • Sudden increase in physically demanding exercise
  • Exercise in dehydrated state
Genetics
Metabolic myopathies:
  • Small percentage of total cases
  • Inherited disorders:
    • Disorder of glycogenolysis
    • Disorder of glycolysis
    • Disorder of lipid metabolism
    • Disorder of purine metabolism
    • Mitochondrial myopathies
  • Increased suspicion when patients have recurrent episodes of rhabdomyolysis associated with exercise
Etiology
Muscle damage and/or necrosis that results in elevation in CPK levels, electrolyte disturbances, and renal compromise:
  • Trauma/crush injuries (motor vehicle accidents, fall from seizure or stroke, struggle against restraints, abuse, prolonged tourniquet)
  • Exercise
  • Hyperthermia (heat stroke, malignant hyperthermia, and neuroleptic malignant syndrome)
  • Hypothermia
  • Prolonged immobile state
  • Drugs/toxins (alcohols, cocaine, amphetamines, opiates, antihistamines, barbiturates, phencyclidine, caffeine, carbon monoxide, cholesterol-lowering agents, succinylcholine, snake venom, bee/hornet venom, etc.)
  • Chronic electrolyte disturbances (hypokalemia, hypophosphatemia, hypoxia)
  • Infections (viral, bacterial, parasitic, protozoan, rickettsial)
  • Endocrinopathies (hyperthyroid state, diabetic ketoacidosis, hyperosmolar)
  • Burn or electrical injury
  • Genetic disorders/metabolic myopathies (McArdle's disease, Tarui's disease)
  • Hematologic disorder (sickle cell trait)
  • Immunological disorders (dermatomyositis, polymyositis)
  • Idiopathic
Diagnosis
  • General symptoms include: Malaise, fever, tachycardia, nausea/emesis along with myalgia
  • Typically, the patient demonstrates decreased flexibility and decreased strength secondary to pain.
  • Muscle pain, reduced flexibility, decreased/painful strength
  • History and physical are insensitive in making the diagnosis.
  • Serum CPK level is criterion standard and must be sent if any clinical suspicion exists.
  • Serum electrolytes, BUN, creatinine, calcium, and liver enzyme levels should be obtained.
    • Urine dipstick that is positive for heme but absent for RBCs suggests rhabdomyolysis (myoglobinuria):
      • Because of rapid urinary excretion of myoglobin, up to 26% of patients with rhabdomyolysis have negative urine dipstick.
History
  • Wide range of severity of symptoms
  • Classic features: Myalgia, weakness, and dark urine (seen in <10% of patients)
  • General symptoms include: Malaise, fever, tachycardia, nausea/emesis
Physical Exam
  • Signs and symptoms can vary dramatically, reflecting underlying disease process.
  • Obvious crushing injury
  • Hypothermia/hyperthermia
  • Patient may be either alert or obtunded
  • Muscle tenderness, swelling (calves and lower back most commonly involved)
  • Change in urine color; orange to cola-colored to black
  • Hypovolemic state, dry mucous membrane, poor skin turgor, tachycardia, hypotension
  • Decreased urine output
Diagnostic Tests & Interpretation
Lab
  • CPK levels are the most sensitive; CK-MM isoenzyme is most elevated
  • CPK levels rise within 12 hr, peak in 1–3 days, and reduce 3–5 days after underlying cause of muscle injury is addressed.
  • CPK levels >5,000 U/L relate to renal failure.
  • Serum and urine myoglobin levels useful in acute phase; has short half-life and may return to normal within 6–8 hr
  • Perform urine dipstick to evaluate for myoglobinuria and urine analysis to detect casts, protein, and uric acid crystals.
  • Arterial blood gas
  • Carbonic anhydrase III more specific for skeletal muscle
  • Metabolic profile (hyperkalemia, hypocalcemia, hyperphosphatemia, hyperuricemia)
  • Blood urea nitrogen level to creatinine ratio decreases to 6:1 or less
  • Serum glucose, lactate dehydrogenase, serum glutamic oxaloacetic transaminase, albumin
  • Toxicology screen in absence of physical injury
  • Prothrombin time/partial thromboplastin time, platelet count, fibrinogen, fibrin-split products if disseminated intravascular coagulopathy is suspected
Imaging
  • MRI is 90–95% sensitive in visualizing muscle injury.
  • MRI is not typically ordered because the imaged muscle damage does not change initial treatment.
Diagnostic Procedures/Surgery
Forearm ischemic test:
  • To differentiate genetic causes of rhabdomyolysis
  • Performed after rhabdomyolysis is resolved
  • Obtain baseline ammonia and lactic acid levels.
  • Inflate sphygmomanometer to >200 mm Hg.
  • Patient performs hand-grip exercises to fatigue.
  • Cuff is removed and serial blood tests are drawn.
  • Minimal or no rise in lactic acid suggests carbohydrate metabolism disorder or McArdle's disease.
  • Delayed rise or no rise in the ammonia level suggests myoadenylate deaminase deficiency.
  • Normal rise in ammonia and lactic acid levels suggests the presence of a disorder of lipid metabolism.
Differential Diagnosis
The following conditions may present with elevated serum CPK but may not lead to complications of rhabdomyolysis:
  • Nontraumatic myopathies
  • Renal failure
  • IM injections
  • Myocardial injury
  • Hypothyroidism
  • Hyperthyroidism
  • Stroke
  • Surgery

P.513


Treatment
Aggressive fluid resuscitation is paramount to reducing renal compromise.
Pre-Hospital
  • Need for rapid extrication in case of crush injury
  • Early IV fluids to prevent complications (hypovolemia, acute renal failure [ARF], hyperkalemia, etc.)
ED Treatment
  • Directed toward treating or reversing the underlying cause of rhabdomyolysis
  • Prevent ARF:
    • Immediate IV isotonic saline (1,2)[B]
    • Mannitol following IV saline promotes diuresis, acts as renal vasodilator, and may act as free-radical scavenger), but clinical effects are unproven (1,2)[C].
    • Furosemide administration is controversial (3).
  • Hyperkalemia: IV fluid, dextrose, insulin, monitor/electrocardiogram
  • Acidosis: Bicarbonate administration is debated, may worsen hypocalcemia (1,2)[C]
  • Overdose: Activated charcoal, lavage, antidote
  • Infection: Broad-spectrum antibiotics
  • Compartment syndrome: Fasciotomy (compartment pressure >35 mm Hg)
  • Neuroleptic malignant syndrome: Dantrolene, bromocriptine
  • Need for hemodialysis: Refractory to treatment, hyperkalemia, hyperphosphatemia, hyperuricemia, volume overload, overdose
Medication
Medication guidelines (1,2):
  • Administer IV isotonic saline at 1,000–1,500 mL/hr initially.
  • Goal: To achieve urine output of 300 mL/hr until myoglobinuria resolves
  • Dextrose may be added after initial resuscitation to 0.45NS
  • Bicarbonate and mannitol have been recommended but have unproven benefit.
  • Furosemide administration is also controversial.
First Line
IV fluids: Isotonic saline
Second Line
  • Bicarbonate and mannitol have been recommended but have unproven benefit.
  • Furosemide administration is also controversial.
In-Patient Considerations
Initial Stabilization
  • ABCs
  • Immobilization of trauma/crush injuries
  • IV fluids for hypotension and hypovolemia
Admission Criteria
  • Because it is impossible to predict which patients will develop complications, all patients with significant elevated CPK or suspicion for rhabdomyolysis must be admitted.
  • Admit to monitored bed for patients with electrolyte abnormalities.
  • Admit to intensive care unit bed for patients who might require hemodialysis or closer fluid and electrolyte monitoring.
IV Fluids
Plasma volume resuscitation with isotonic saline is first-line treatment.
Nursing
  • Frequency of hemodynamic monitoring determined by stability of patient
  • Monitor urinary output closely.
Discharge Criteria
  • No patients suspected of having rhabdomyolysis should be discharged from the emergency department.
  • Patient must be hemodynamically stable before discharge from hospital.
  • Stable electrolytes and adequate renal function before discharge from hospital
  • Patient should follow up within 1 wk after discharge.
Ongoing Care
  • Underlying cause of rhabdomyolysis should be determined if etiology was not discovered during hospital stay.
  • Genetic testing and muscle biopsies should be considered when warranted.
  • Medications, if implicated, should be stopped.
  • Metabolic-modifying supplements and enhancing agents should be stopped.
  • Activity modification if exercise-induced
Follow-Up Recommendations
  • No specific guidelines exist for return to exercise after exertional rhabdomyolysis.
  • Areas to consider:
    • Symptoms should be completely resolved.
    • All bloodwork and urine tests should be within normal limits.
    • Examination should demonstrate clinical resolution.
    • Patient should be able to demonstrate full strength.
    • Gradual return to exercise with acclimatization and adequate hydration
    • Return to exercise should begin with mild to moderate intensity.
Patient Monitoring
  • Initially, patient should be monitored clinically at regular short intervals.
  • For example, the physician may want to re-evaluate the athlete every 48 hr as intensity increases.
Diet
  • Education should be provided about hydration.
  • Specific diet recommendations may be considered for specific myopathies.
Patient Education
Prevention strategies for return to sports after rhabdomyolysis:
  • Appropriate hydration counseling should be provided.
  • Gradual return to exercise may include acclimatization.
  • Return to exercise should begin with mild to moderate intensity.
  • Advise against significant dietary changes initially.
  • Athlete should be advised to stop activity if he or she experiences similar symptoms and physician should be contacted immediately.
Complications
  • Early complications:
    • Hyperkalemia
    • Hypocalcemia
    • Cardiac arrhythmia
    • Cardiac arrest
    • Hepatic inflammation
    • Compartment syndrome
  • Late complications (past 12 hr):
    • Acute life-threatening renal failure
    • Disseminated intravascular coagulation
    • Compartment syndrome
References
1. Bagley WH, Yang H, Shah KH. Rhabdomyolysis. Intern Emerg Med. 2007.
2. Huerta-Alardín AL, Varon J, Marik PE. Bench-to-bedside review: Rhabdomyolysis—an overview for clinicians. Crit Care. 2005;9:158–169.
3. Sauret JM, Marinides G, Wang GK. Rhabdomyo-lysis. Am Fam Physician. 2002;65:907–912.
Additional Reading
Miller, Marc L. Rhabdomyolysis. www.uptodate.com. April 30, 2009.
Codes
ICD9
728.88 Rhabdomyolysis
Clinical Pearls
  • Classic features: Myalgia, weakness, and dark urine
  • Aggressive fluid resuscitation is paramount to treatment.


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