Exertional Rhabdomyolysis

Other Names

• Rhabdomyolysis
• Rhabdo
• Exertional Rhabdomyolysis (ER)

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Background

• This page refers to Rhabdomyolysis, a phenomenon of muscle necrosis and release of intracellular contents into circulation
  • Although there are many causes of rhabdomyolysis, this page focuses on exertional rhabdomyolysis (ER) seen in athletes

Epidemiology

• Incidence
  • Among military personal, 29.9 per 100,000 person years
• There is an estimated 12,000 cases annually in the United States

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Pathophysiology

• General
  • Muscle necrosis and release of intracellular contents following exertional activity
  • Clinical syndrome: muscle weakness, swelling, pain +/- myoglobinuria
  • Symptoms and Creatinine Kinase (CK) 5 times upper limit of normal is required for diagnosis
  • Most cases are self limited and resolve with hydration, however end organ dysfunction can occur
• Definition of Exertional Rhabdomyolysis (ER):
  • Presence of muscle related symptoms preceded by exercise
  • Elevation of CK greater than 5x the upper limit of normal (ULN)

Etiology

• Exertional
  • Exercise with hyperthermia
  • Exercise with Sickle Cell Trait
  • Exercise with hypokalemia
  • Hyperkinetic states (seizure, stimulant or sympathomimetic use)
• Non-exertional
  • Trauma (crush syndrome, immobilization, compartment syndrome, electrical injuries)
  • Drugs/Tox (sedatives, alcohol, statins, colchicine, carbon monoxide poisoning, mushroom ingestion)
  • Infection (viral, bacterial, toxic shock syndrome)
  • Endocrine (hypothyroidism)
  • Inflammatory myopathies
  • Other (status asthmaticus)

Mechanism

• General
  • Characterized by breakdown and necrosis of skeletal muscle after engaging in physical activity
  • Common final pathway: increased intracellular calcium much higher than normal
  • Trauma: caused by direct injury, rupture of cell membrane
• Exertional Rhabdo (ER)
  • Overproduction of heat, results in increased intracellular calcium via depletion of ATP
  • Loss of ATP, dysfunction of Na/K–ATPase and Ca2+ATPase pumps, increase of intracellular calcium
  • Intracellular calcium leads to activation of proteases, reaction oxygen species, culminating in cell death
  • Cell death leads to release of intracellular contents, causing pain, swelling and potentially end organ damage
  • Intracellular contents includes potassium, myoglobin, creatine kinase, and LDH
  • Release of myoglobin leads to the commonly noted "coca cola" colored urine (psuedo-hematuria)

Associated Conditions

• Acute Compartment Syndrome
  • In one American football camp, 43 players had ER and 3 were also diagnosed with compartment syndrome
• Delayed Onset Muscle Soreness (DOMS)
  • Considered by some to be the extreme end of DOMS
  • Affected individuals typically complain of pain, tenderness, weakness and swelling in the muscles utilized during the activity

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Risk Factors

• Demographic
  • Males under 20
  • Black, non-Hispanic males
• Training related
  • Dehydration
  • Repetitive eccentric loads
  • Alteration in training regimen
  • Poor conditioning
• Environmental
  • Hyperthermia, Heat Related Illness
  • Hypothermia
  • High temperatures and humidity
• Genetic
  • Sickle Cell Trait
• Pharmacology/ Toxicology
  • Phentermine
  • Stimulants
  • NSAIDS
• Sports
  • American Football
  • Swimming
  • Bodybuilding
  • Running
  • Crossfit
• Occupation
  • Military service

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Differential Diagnosis

• Muscle Strain
• Muscle Contusion
• Delayed Onset Muscle Soreness
• Acute Compartment Syndrome
• Acute Lumbar Paraspinal Myonecrosis
• Polymyositis
• Dermatomyositis
• Guillain Barre Syndrome

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Clinical Features

• History
  • There should be a clear history of exertion preceding symptoms
  • Symptoms tend to occur in the muscle group(s) that were overworked
  • Mild cases may be asymptomatic
  • Moderate-to-severe cases may include myalgias, stiffness, weakness, malaise
  • Severe cases can include nausea, vomiting, abdominal pain, hemodynamic instability, mental status changes
  • Fever, typically mild
  • Self reported dark colored urine
• Physical Exam
  • Swelling or tenderness to the associated muscle grups
  • Patients urine may be dark or red colored

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Evaluation

Laboratory

• General
  • Workup will depend on degree of illness and clinical picture
• Total CK
  • Diagnosis based on 5x the upper limit of normal (~2000)
  • Begins to rise around 2-12 hours from injury, peaks at 24-72 hours
  • Quantitative value correlates with muscle injury but not renal failure
• Urinalysis
  • Classically myoglobinuria
  • The presence of myoglobinuria does not correlate with severity of ER
  • May see hematuria without RBC (80% sensitive) (need citation)
• Serum Myoglobin
  • Elevated
  • Levels due not accurately predict risk or degree of renal injury
• CK-MB
  • May be normal or slightly elevated
• Metabolic Panel/ Electrolytes
  • Renal: renal failure can occur, BUN/Creatinine will increase
  • Hyperkalemia
  • Hyperphosphatemia
  • Hypocalcemia
  • Hyperuricemia
• Consider depending on severity of illness
  • CBC
  • Uric Acid
  • Liver function Tests (intramuscular AST/ALT can rise, AST>ALT)
  • Blood gas
  • DIC panel (coags, fibrinogen, dimer)

Electrocardiogram

• Strongly consider if suspicious of electrolyte abnormalities

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Classification

• No widely accepted classification system exists
  • ER can be loosely divided into physiologic and clinically significant categories.
• Physiologic ER:
  • CK level is less than 50x the upper limit of normal (CK elevation deemed a physiologic response to the exercise)
  • Patient lacks muscle weakness/swelling
  • No noted myoglobinuria or signs of ARF
• Clinically significant ER:
  • Muscle symptoms more than simple myalgia
  • Significant comorbidities
  • Myoglobinuria
  • CK level greater than 50x the upper limit of normal
  • Prior episodes of rhabdomyolysis
  • Concomitant heat stroke

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Management

• Mild cases (physiologic ER)
  • Often go undiagnosed
  • Can be treated on an outpatient basis with oral hydration and rest
  • Recheck CK and Urinalysis at 72 hours
• Moderate/ Severe cases
  • Athletes with CK > 5 times upper limit of normal, hospital admission should be considered
  • It is important to demonstrate CK is trending down, electrolytes are normalizing
• Trend
  • Volume/ fluid status
  • Follow urine pH, chemistry, CK, electrolytes, LFTs
• PO/IV Fluids
  • Mild cases can orally hydrate
  • 1-2 liters per hour of IV fluid if needed
  • Goal urinate output is 200-300 ml/HR
• Urinary alkalinization
  • Controversial, no clear benefit in the literature
  • Consider bicarbonate
  • Contraindications (severe hypocalcemia, pH > 7.50, bicarb > 30 meq/L)
  • Discontinue when (urine pH does not rise about 6.5 at 3-4 hours, symptomatic hypocalcemia, pH > 7.50, bicarb > 30 meq/L)
• Hemodialysis
  • Indicated if patient cant maintain appropriate volume or electrolyte balance
• Drugs to avoid
  • Mannitol or other diuretics can worsen dehydration, oliguria

Disposition

• Discharge if
  • Clearly exertional
  • Otherwise healthy
  • No comorbidities (heat stress, dehydration, other risk factors)
  • Downtrending CK
• Admit if they do not meet the above criteria

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Rehab and Return to Play

High- and Low-risk athletes (click to enlarge)

Rehabilitation

• No specific rehabilitation guidelines exist

Return to Play/ Work

• General
  • There are no evidence based guidelines for return to play after ER
  • Athletes should be characterized as high risk or low risk (see table)
  • High risk athletes should under go testing
    • Consider electromyogram, genetic, muscle biopsy, exercise challenge, caffeine halothane test
  • Low risk athletes can begin a gradual return when:
    • Afebrile, symptom free, well hydrated, CK levels normal, resolution of myoglobinuria

CHAMP Guidelines

• Phase 1
  • Rest for 72 hours, encourage oral hydration
  • 8 hours of sleep nightly
  • Remain in a thermally controlled environment if the episode of ER was in relation to heat illness
  • Follow-up after 72 hours with a repeat serum CK level and UA
  • If the CK has dropped to below 5 times the upper limit of normal and the UA is negative, the athlete can progress to phase 2; if not, reassessment in 72 additional hours is warranted
  • Should the UA remain abnormal or the CK remain elevated for 2 weeks, expert consultation is recommended
• Phase 2
  • Begin light activities, no strenuous activity
  • Physical activity at own pace/distance
  • Follow-up with a care provider in 1 week
  • If there is no return of clinical symptoms, the athlete can progress to phase 3; if not, the athlete should remain in phase 2 checking with the health care professional every week for reassessment; if muscle pain persists beyond the fourth week, consider expert evaluation to include psychiatry
• Phase 3
  • Gradual return to regular sport/physical training
  • Follow-up with care provider as needed

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Complications and Prognosis

Prognosis

• Self limited disease in most cases
  • Recurrent cases will require workup

Complications

• Acute Renal failure
  • Difficult to predict; neither myoglobinuria or total CK reliably predict ARF
  • Rare in exertional rhabdo without presence of dehydration or heat illness
  • Oliguria is common
• Cardiac Dysrhythmias
• Hyperkalemia
  • Related to kidney injury more than intra-cellular potassium release
  • Treat aggressively, may require ICU/ dialysis
• Hypocalcemia (early)
  • Treat if symptomatic or if severe hyperkalemia (2/2 rebound hypercalcemia)
• Hypercalcemia (recovery phase)
• Hyperphosphatemia
  • Treat cauctiously
  • Consider phosphate binders if level >7
• Disseminated intravascular coagulation (DIC)
  • Usually self limited
• Compartment syndrome
• Peripheral nerve injury
  • Usually resolves within days to weeks

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See Also

• Muscle Pathology (Main)

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