Rhabdomyolysis

See Also

Definitions

Rhabdomyolysis
1. Skeletal Muscle breakdown or necrosis
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)

Pathophysiology
Pathway

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

Risk Factors

Sickle Cell Anemia
Immbolization (e.g. casted joints)
Myopathy
Statin use

Causes

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

Signs

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
4. Consider in comatose or altered patients who are found "down"
Muscle pain, soreness or stiffness (myalgias)
1. Shoulders
2. Thighs
3. Low Back
Muscle Weakness
Localized swelling or Bruising
Constitutional symptoms
1. Fever
2. Malaise
3. Nausea or Vomiting
4. Confusion, Agitation, or Delirium
Urinary tract symptoms
1. Tea-colored, dark red or brown, urine (present in only 3-4% of cases)
2. Anuria
Observe for signs of prolonged immobility
1. Pressure Sores
2. Skin Discoloration

Labs

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
Creatine Phosphokinase (CPK) increased
1. Consistent with Rhabdomyolysis if Creatine Phosphokinase (CPK) >5 times normal (or>1000 U/L)
2. CPK increases within first 12 hours, peaks in 2-3 days (up to 3-5 days), and returns to baseline within 10 days
3. Acute Kidney Injury increases at CPK above 5,000, and especially >16,000
4. Exertional Rhabdomyolysis has lower risk of Kidney injury despite high CPK levels
5. Initial CPK is not correlated with prognosis (Renal Failure, mortality), unless >40,000 units/L
6. CPK levels increase with common exertional activities (e.g. >20x normal at 1 day after marathon)
  1. See Creatine Phosphokinase
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
Serum Electrolytes
1. Basic chemistry panel (including Serum Creatinine, Serum Potassium, Serum Calcium)
2. Serum Creatinine rise rapidly in Rhabdomyolysis related Renal Failure
  1. Contrast with other Renal Failure causes, in which Serum Creatinine rise is more gradual
3. Serum Phosphorus
4. Uric Acid
Other labs
1. Consider Liver Function Test
2. Consider Venous Blood Gas

Diagnostics

Electrocardiogram (EKG)
1. See Hyperkalemia Related EKG Changes

Management
Intravenous Fluids

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. Normal Saline 1.5 Liters per hour
    1. Decrease rate of fluid Resuscitation in elderly or CHF (500 ml boluses, followed by IVC Ultrasound)
    2. Some guidelines recommend avoiding fluids containing lactate (in addition to Potassium)
    3. However, fluid type (i.e. LR vs NS) may not matter for outcomes
      1. Cho (2007) Emerg Med 24(4): 276-80 +PMID: 17384382 [PubMed]
3. End-points
  1. No Myoglobinuria
  2. Creatine Phosphokinase (CPK) less than 1000
Maintenance: Alkalinize Urine pH > 6.5 (not generally recommended)
1. Indications: Low Urine pH in Rhabdomyolysis
  1. Theory: Myoglobin is less nephrotoxic in a more alkaline environment
2. Protocol: Option 1
  1. Sodium Bicarbonate (3 ampules)
  2. Dextrose 5% Solution
  3. Infuse at 100 ml/hour
3. Protocol: Option 2
  1. Saline 0.45% (1/2 NS) with
  2. Sodium Bicarbonate 40 meq (1 to 2 ampules) and
  3. Mannitol 10 grams per liter
4. Contraindications
  1. Persistent Oliguria despite hydration listed above
  2. Hypocalcemia (provoked by Sodium Bicarbonate)
5. Efficacy
  1. No significant evidence for benefit
  2. Use is controversial and is based on expert opinion, not studies
  3. Some animal studies have shown benefit, but not found in retrospective studies

Management
Specific Complication Protocols

Hyperkalemia
1. See Hyperkalemia 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

Management
Disposition

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
Monitoring of elderly with comorbid conditions
1. Intensive Care unit admission
2. Hourly Vital Signs including input and output
3. Consider invasive monitoring
Home Restrictions
1. Avoid exertion until CPK normalizes (typically as much as 10-14 days)
2. On restarting activity, start slowly

Precautions

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

Complications

Electrolyte disturbance
1. Early findings
2. Late findings
  1. Hypercalcemia
  2. Hypophosphatemia
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 Creatine Kinase over 16,000 units/L (esp.>40,000 units/L)
Miscellaneous complications
1. Liver inflammation
2. Cardiac Arrhythmia or Cardiac Arrest
3. Disseminated Intravascular Coagulation
4. Compartment Syndrome

Prognosis

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]
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]
Predictors of worse outcomes
1. McMahon Rhabdomyolysis Score >=6
2. Nonexertional Rhabdomyolysis
3. Acute Renal Failure

References

DeLaney in Herbert (2018) EM:Rap 18(3): 9-12
Marx in Rosen (2002) Emergency Medicine 1762-70
Rendon and Opfer (2019) Crit Dec Emerg Med 33(10): 3-8
Sauret (2002) Am Fam Physician 65(5):907-12 [PubMed]