II. Definition

  1. Skeletal muscle breakdown
  2. Rhabdomyolysis is analogous to other multi-system failure conditions
    1. Acute Tubular Necrosis (ATN)
    2. Disseminated Intravascular Congestion (DIC)
    3. Acute Respiratory Distress Syndrome (ARDS)

III. Pathophysiology: Pathway

  1. Myocyte (muscle) injury by direct Trauma or altered energy production
  2. Muscle injury allows calcium influx
  3. Increased intracellular calcium destroys muscle fibers
  4. Release of muscle fiber contents into circulation
    1. Myoglobin
    2. Potassium (risk of Hyperkalemia)
    3. Calcium (risk of Hypercalcemia)
    4. Phosphate
    5. Creatine Phosphokinase
    6. Uric Acid
  5. Myoglobin overloads Haptoglobin binding capacity
  6. Myoglobin concentrates, precipitates (esp. in acidic environ) and blocks renal tubules (and is directly nephrotoxic)
  7. Results in Acute Renal Failure

IV. Risk Factors

  1. Sickle Cell Anemia
  2. Immbolization (e.g. casted joints)
  3. Myopathy
  4. Statin use

V. Causes

  1. See Rhabdomyolysis Causes
  2. See Statin-Induced Myopathy
  3. Exertional Rhabdomyolysis
    1. Examples: Marathon Running, overexertion
  4. Non-exertional Rhabdomyolysis
    1. Altered energy production
      1. Hypoxia, Carbon Monoxide, Cyanide, Compartment Syndrome, vascular compression
    2. Direct myocyte Trauma
      1. Crush injury, Electrocution, Hypothermia, hyperthermia, Neuroleptic Malignant Syndrome
      2. Chemical-induced: Statin Myopathy, Cocaine, Methamphetamine

VI. Signs

  1. Precautions
    1. Have a high index of suspicion for screening in those at high risk of Rhabdomyolysis
    2. Classic triad of Muscle Weakness, myalgias, tea-colored urine is only present in 10% of cases
    3. Less than 50% report muscle pain or weakness
  2. Muscle pain (myalgias)
  3. Muscle Weakness
  4. Localized swelling or Bruising
  5. Constitutional symptoms
    1. Fever
    2. Malaise
    3. Nausea or Vomiting
    4. Confusion, agitation, or Delirium
  6. Urinary tract symptoms
    1. Tea-colored urine (present in only 3-4% of cases)
    2. Anuria

VII. Labs

  1. Urinalysis: Findings suggestive of Myoglobinuria
    1. Dipstick orthotoluidine positive for blood (poor Test Sensitivity)
    2. No Red Blood Cells seen in freshly spun sediment
    3. Differential diagnosis for positive dipstick blood and negative microscopy
      1. Intravascular Hemolysis with circulating free Hemoglobin
      2. Causes include transfusion reaction, DIC, Hemolytic Uremic Syndrome
  2. Creatine Phosphokinase (CPK) increased
    1. CPK increases within first 12 hours, peaks in 3-5 days, returns to baseline within 10 days
    2. Acute Kidney Injury increases at CPK above 5,000, and especially >16,000
    3. Exertional Rhabdomyolysis has lower risk of Kidney injury despite high CPK levels
    4. Initial CPK is not correlated with prognosis (Renal Failure, mortality), unless >40,000 units/L
    5. CPK levels increase with common exertional activities (e.g. >20x normal at 1 day after marathon)
      1. See Creatine Phosphokinase
  3. Myoglobin level increased
    1. Increased in urine or serum, but has lower Test Sensitivity and is rapidly cleared
    2. Results not available for days after sending sample
    3. Not helpful in acute diagnosis, and not typically recommended
  4. Serum Electrolytes
    1. Basic chemistry panel (including Serum Creatinine, Serum Potassium, Serum Calcium)
    2. Serum Phosphorus
    3. Uric Acid

VIII. Management: Intravenous Fluids

  1. Initial: Forced diuresis
    1. Start immediately (especially in first 6 hours)
    2. Protocol: Increase renal tubular flow and clear myoglobin, correct dehydration and acidosis
      1. Urine output goal >250-300 ml/hour
      2. Lactated Ringers 1.5 Liters per hour
        1. Fluid type (i.e. LR vs NS) may not matter for outcomes
        2. Cho (2007) Emerg Med 24(4): 276-80 +PMID: 17384382 [PubMed]
    3. End-points
      1. No Myoglobinuria
      2. Creatine Phosphokinase (CPK) less than 1000
  2. Maintenance: Alkalinize Urine pH > 6.5
    1. Indications: Low Urine pH in Rhabdomyolysis
      1. Theory: Myoglobin less nephrotoxic in a more alkaline environment
    2. Protocol
      1. Saline 0.45% (1/2 NS) with
      2. Sodium Bicarbonate 40 meq (1 to 2 ampules) and
      3. Mannitol 10 grams per liter
    3. Contraindications
      1. Persistent oliguria despite hydration listed above
      2. Hypocalcemia (provoked by Sodium Bicarbonate)
    4. Efficacy
      1. Use is controversial and is based on expert opinion, not studies
      2. Some animal studies have shown benefit, but not found in retrospective studies

IX. Management: Acute Renal Failure

  1. Results from Acute Tubular Necrosis
  2. Daily Hemodialysis may be indicated
  3. Many patients show partial or complete renal recovery

X. Management: Disposition

  1. Indications for hospitalization
    1. Severe symptoms (myalgias, Muscle Weakness)
    2. Acute Kidney Injury
    3. Atypical trigger
    4. Recurrent Rhabdomyolysis with low level Mechanism (may suggest genetic predisposition, underlying Myopathy)
    5. Nonexertional Rhabdomyolysis, esp. if CPK >5000 (nonexertional cases have worse outcomes)
    6. Electrolyte abnormalities
    7. Compartment Syndrome risk
    8. Hyperthermia or Hypothermia
  2. Monitoring of elderly with comorbid conditions
    1. Intensive care unit admission
    2. Hourly Vital Signs including input and output
    3. Consider invasive monitoring
  3. Home Restrictions
    1. Avoid exertion until CPK normalizes (typically as much as 10-14 days)
    2. On restarting activity, start slowly

XI. Precautions

  1. Aggressive hydration is critical
  2. Avoid Diuretics (may provoke Renal Failure)
  3. Do not correct Hypocalcemia unless symptomatic
    1. Anticipate Serum Calcium increase in recovery phase
    2. Calcium re-mobilized from injured muscles

XII. Complications

  1. Electrolyte disturbance
    1. Early findings
      1. Hyperkalemia
      2. Hypocalcemia
      3. Hyperphosphatemia
      4. Hyperuricemia
    2. Late findings
      1. Hypercalcemia
      2. Hypophosphatemia
  2. Acute Renal Failure (Acute Tubular Necrosis)
    1. Occurs in almost half of Rhabdomyolysis cases (responsible for 10-15% of Acute Kidney Injury in U.S.)
    2. Mechanism: Myoglobin overload, hypovolemia, acidosis
    3. Associated with Creatinine kinase over 16,000 units/L (esp.>40,000 units/L)
  3. Miscellaneous complications
    1. Liver inflammation
    2. Cardiac arrhythmia or Cardiac Arrest
    3. Disseminated Intravascular Coagulation
    4. Compartment Syndrome

XIII. Prognosis

  1. Initial CPK are not correlated with prognosis or Acute Renal Failure, unless CPK >40,000 units/L
    1. Baeza-Trinidad (2015) Intern Med J 45(11): 1173-8 +PMID:26010490 [PubMed]
    2. McMahon (2013) JAMA Intern Med 173(19):1821-8 +PMID:24000014 [PubMed]
  2. Exertional Rhabdomyolysis is typically associated with benign course regardless of initial CPK level
    1. Oh (2015) Mil Med 180(2): 201-7 +PMID: 25643388 [PubMed]
  3. Predictors of worse outcomes
    1. Nonexertional Rhabdomyolysis
    2. Acute Renal Failure

XIV. References

  1. DeLaney in Herbert (2018) EM:Rap 18(3): 9-12
  2. Marx in Rosen (2002) Emergency Medicine 1762-70
  3. Sauret (2002) Am Fam Physician 65(5):907-12 [PubMed]

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Ontology: Rhabdomyolysis (C0035410)

Definition (CHV) a potentially fatal disease that destroys skeletal muscle
Definition (MSH) Necrosis or disintegration of skeletal muscle often followed by myoglobinuria.
Concepts Pathologic Function (T046)
MSH D012206
ICD9 728.88
ICD10 M62.82
SnomedCT 268106003, 156729009, 311511000009102, 240131006, 89010004
English Rhabdomyolyses, Rhabdomyolysis, RHABDOMYOLYSIS, rhabdomyolysis, rhabdomyolysis (diagnosis), Rhabdomyolysis [Disease/Finding], Necrosis of skeletal muscle, Skeletal muscle necrosis, Necrosis of skeletal muscle (finding), Rhabdomyolysis (disorder), Rhabdomyolysis (morphologic abnormality)
French RHABDOMYOLYSE, Rhabdomyolyse
Portuguese RABDOMIOLISE, Rabdomiólise
Spanish RABDOMIOLISIS, rabdomiólisis (anomalía morfológica), rabdomiólisis, Rabdomiolisis, rabdomiólisis (trastorno), Rabdomiólisis
German RHABDOMYOLYSE, Rhabdomyolyse
Swedish Rabdomyolys
Czech rabdomyolýza, rhabdomyolýza, Rabdomyolýza
Finnish Rabdomyolyysi
Croatian Not Translated[Rhabdomyolysis]
Polish Liza mięśni prążkowanych, Rabdomioliza
Japanese 横紋筋融解症, オウモンキンユウカイショウ
Hungarian Rhabdomyolysis
Norwegian Rabdomyolyse
Dutch rabdomyolyse, Myolyse, rabdo-, Rabdomyolyse
Italian Rabdomiolisi