Basics
Description
Abnormal systemic release of muscle contents " öcreatine phosphokinase (CPK), myoglobin, potassium, phosphate, urate " öcaused by trauma, poisoning, infection, primary muscle disorders, and many other disease states. Complications include: é á
- Myoglobin-induced renal failure in 15 " ô50% adults, only 5% in children
- Hyperkalemia may lead to sudden death
- Hypocalcemia and acidosis
- Volume loss " öfluid sequestration in injured muscle or result of underlying illness
- Compartment syndrome of muscles in crush, worsened by IV fluid sequestration in damaged tissue
- Hepatic dysfunction in 25%
- DIC (Disseminated intravascular coagulation)
Epidemiology
Incidence
- 26,000 per year in US
- Disaster situations lead to 100s of cases of renal failure.
Risk Factors
- Inherited myopathy
- Alcohol or drug use
- Medications as listed below
- Overexertion with or without risk factors
Pathophysiology
- Sarcolemma keeps intracellular calcium low.
- Etiologies disrupt cell membrane and lead to following cascade.
- Breakdown of sarcolemma Na " ôCa pumps allows calcium to enter cell.
- Calcium-dependent proteases cause destruction.
- Ischemia and neutrophils cause damage.
- Escape of cell contents: Myoglobin, potassium, phosphate, CPK, lactate, etc.
- Myoglobin causes renal damage by direct toxicity in acidic urine.
- Myoglobin precipitates with other proteins to obstruct renal tubular flow.
- Volume depletion also leads to renal vasoconstriction and failure.
- Hyperkalemia can lead to arrhythmias.
- Calcium precipitates with phosphate, leading to systemic hypocalcemia.
Etiology
Cause usually obvious, but not always. é á
Adults: Trauma, toxicity, infection é á
Children: Viral myositis, trauma é á
- Muscle injury " ödue to trauma/crush, burn, electrical shock " ömost common cause overall.
- Muscle exertion: Strenuous exercise; marathon running; exercise in hot, humid conditions; exercise in individuals with an inherited myopathy or with poor physical training; status epilepticus; delirium tremens; tetanus; psychotic agitation
- Muscle ischemia: Extensive thrombosis, multiple embolism, generalized shock, sickle cell crisis
- Surgery: Immobilization, hypotension, ischemia due to vessel clamping
- Massive blood transfusion
- Hypothermia, hyperthermia
- Prolonged immobile state without trauma
- Drugs/toxins: Alcohols, cocaine, amphetamines, and analogs (methamphetamine and ecstasy), toluene, opiates, LSD, phencyclidine (PCP), caffeine, carbon monoxide, snake venom, bee/hornet venom, hemlock, buffalo fish, tetanus toxin, mushroom poisoning (Tricholoma equestre)
- Medications: Most common " öhaloperidol, phenothiazines, HMG " ôCoA reductase inhibitors (statins) and other cholesterol-lowering agents, antihistamines, selective serotonin receptor inhibitors (SSRIs).
- Sports supplements including ephedra, caffeine, androgenic steroids, creatine, diuretics
- Neuroleptic malignant syndrome (idiosyncratic and not dose-related)
- Metabolic disorders: Hypokalemia, hypophosphatemia, hypocalcemia, hyper- and hyponatremia, diabetic ketoacidosis, hyperosmolar state, hypoxia, hyperthyroid state (rare), pheochromocytoma (rare)
- Infections:
- Viral: Coxsackievirus, herpesviruses, HIV, influenza B, cytomegalovirus, Epstein " ôBarr virus, adeno/echovirus
- Bacterial: Legionnaires ' disease, pyomyositis, salmonellosis, shigellosis, Staphylococcus, Streptococcus, Listeria, tetanus, toxic shock syndrome, tularemia, gas gangrene, Bacillus cereus
- Parasitic (Plasmodium falciparum), protozoan (leptospirosis), rickettsial
- Inherited myopathic disorders: McArdle disease, Tarui disease, CPT deficiency.
- Immunologic disorders: Dermatomyositis, polymyositis
- Idiopathic
Commonly Associated Conditions
- Crush syndrome
- Compartment syndrome
- Alcohol and drug abuse
- Elderly and acutely immobile (found on floor)
Diagnosis
Signs and Symptoms
History
- Can vary dramatically, reflecting underlying disease process.
- Trauma or crush usually obvious.
- Consider nonaccidental trauma with unclear details of history.
- If no trauma, consider in drug toxicity, heat illness, immobilization, or overexertion states.
- Ask about reddish brown urine and decreased urine output
- Most nontraumatic cases in children <9 yr old are due to viral illness with myositis
Physical Exam
- Hypothermia/hyperthermia
- Alert/obtunded
- Muscle pain (only 40 " ô50%)
- Neurovascular status of involved muscle groups if compartment syndrome is suspected.
- Hypovolemic state, dry mucous membranes, poor skin turgor, tachycardia, hypotension
- Decreased urine output
- Urine color (tea-colored) is early sign
- Children more often have absent physical findings
Diagnosis Tests & Interpretation
Lab
Initial lab tests é á
- History and physical exam are insensitive in making the diagnosis
- Serum and urine myoglobin levels often normal due to rapid metabolism and excretion.
- Serum CPK level >1,000 (standard) considered positive
- CPK level not always predictive of renal failure but most often associated with level >15,000
- Urine dipstick test positive for heme but absent for RBCs suggests rhabdomyolysis
- Microscopic urinalysis to look for pigmented tubular casts
- Because of rapid urinary excretion of myoglobin, some patients with rhabdomyolysis have negative urine dipstick test.
- In children, heme <2+ on urine dip correlates with reduced risk of acute renal failure (ARF)
- Serum electrolytes (potassium, calcium, magnesium, phosphorus, BUN, creatinine, uric acid, bicarbonate)
- In addition to above consider:
- Arterial and venous blood gases (ABG/VBG) (baseline pH if considering bicarbonate therapy).
- Urine/serum myoglobin, but may be too transient to be useful
- Serum glucose
- LFTs including GGTP, LDH, albumin
- Toxicology screen in absence of physical injury
- PT/PTT, platelet count, fibrinogen, fibrin split products if DIC is suspected
Imaging
- Renal US to rule out long-standing renal failure (small, shrunken kidneys) or renal obstruction (hydronephrosis)
- MRI is 90 " ô95% sensitive in visualizing muscle injury but does not change initial ED treatment.
- Other imaging as indicated
Diagnostic Procedures/Surgery
- Early ECG: Hyperkalemia or hypocalcemia before serum levels available
- Measure compartment pressure if compartment syndrome is suspected.
Differential Diagnosis
Conditions that may present with elevated serum CPK but are not rhabdomyolysis: é á
- Nontraumatic myopathies including muscular dystrophies and inherited myopathies
- Chronic renal failure
- IM injections
- Myocardial injury
- Stroke
Treatment
Pre-Hospital
- Rapid extrication in case of crush injury
- Early IV saline before extrication to prevent complications of restored blood flow to injured limb (hypovolemia, hyperkalemia, etc.)
- "Crush injury cocktail " Ł during extrication is 1.5 L 0.9% NS per hour; consider adding 1 amp (50 mEq) bicarbonate and 10 g of mannitol to each liter (controversial)
- Pediatric recommendation: 10 " ô15 mL/kg/h saline initially, then switch to hypotonic (0.45%) saline upon arrival to hospital. Add 50 mEq bicarbonate to each 2nd or 3rd liter to alkalinize urine
Initial Stabilization/Therapy
- Manage ABCs
- Immobilization of trauma/crush injuries
- Adult crush injury treatment literature extrapolated to children
- IV saline for hypovolemia at rate of 1 " ô1.5 L/h (10 " ô20 mL/kg/h). Volume restored within 6 hr helps prevent renal failure
Ed Treatment/Procedures
- May need 12 L/d, 4 " ô6 of which should include bicarbonate. Use CVP, urine output
- Diuretics only after patients volume restored to keep urine output 200 " ô300 mL/h (3 " ô5 mL/kg/h)
- Mannitol: Diuretic, free radical scavenger. May help compartment syndrome
- Furosemide and other loop diuretics if indicated in management of oliguric (<500 mL/d) renal failure; controversial
- Bicarbonate: Alkalinize urine (pH >6.5) most studied in crush/trauma. Most authorities recommend its use as long as urine pH and calcium are monitored.
- Monitor for hyperkalemia frequently with serum levels and ECG. Higher potassium correlates with more severe injury
- Treat hyperkalemia as usual but do not use calcium unless it is severe
- Hypocalcemia: Treat only if symptomatic (tetany or seizures) or arrhythmias present. Calcium infusion can lead to hypercalcemia later as precipitated calcium mobilizes
- Bicarbonate can trigger symptoms by increasing free calcium binding to albumin
Follow-Up
Disposition
Admission Criteria
All but the most trivial elevations in CPK (<1,000) should be admitted, since complications can occur at any level and are difficult to predict. Children seem to be less susceptible to renal complications: é á
- Critical care admission criteria:
- Hyperkalemia or CPK levels >15,000 " ô30,000 due to worse prognosis
- Underlying severe illness
Discharge Criteria
Levels decreased to <1,000 after therapy é á
Treatment
Medication
First Line
- Bicarbonate; add 50 mEq bicarbonate to each 2nd or 3rd liter to keep urine pH >6.5. Discontinue if urine pH fails to rise after 6 hr or if symptomatic hypocalcemia develops
- Albuterol, insulin/dextrose, polystyrene resin (kayexalate), for hyperkalemia treatment. Avoid calcium if possible.
Second Line
- Mannitol 20%: 50 mL (10 g added to each liter up to 120 " ô200 g/d (1 " ô2 g/kg/d)
- Discontinue if fail to achieve diuresis and osmolal gap >55
Surgery/Other Procedures
- Hemodialysis for refractory hyperkalemia, fluid overload, anuria, acidosis
- Consider central venous monitoring of volume
- Fasciotomy for compartment syndrome
Follow-Up
Prognosis
- No renal failure " öalmost no mortality
- Renal failure " ö3.4 " ô30% mortality
- ICU " ö59% if renal failure, 22% without
Complications
- ARF
- Hyperkalemia
- Compartment syndrome
- Hypocalcemia
- Acidosis
Pearls and Pitfalls
Suspect in unexplained renal failure. é á
Additional Reading
- Bosch é áX, Poch é áE, Grau é áJM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009;361(1):62 " ô72.
- Huerta-Alard â şn é áAL, Varon é áJ, Marik é áPE. Bench-to-bedside review: Rhabdomyolysis " öan overview for clinicians. Crit Care. 2005;9(2):158 " ô169.
- Luck é áRP, Verbin é áS. Rhabdomyolysis: A review of clinical presentation, etiology, diagnosis, and management. Pediatr Emerg Care. 2008;24:262 " ô268.
- Reinertson é áR. Suspension trauma and rhabdomyolysis. Wilderness Environ Med. 2011;22(3):286 " ô287.
- Sever é áMS, Vanholder é áR, Lameire é áN. Management of crush-related injuries after disasters. N Engl J Med. 2006;354:1052 " ô1063.
See Also (Topic, Algorithm, Electronic Media Element)
- Compartment Syndrome
- Hyperkalemia
Codes
ICD9
- 728.88 Rhabdomyolysis
- 958.90 Compartment syndrome, unspecified
ICD10
- M62.82 Rhabdomyolysis
- T79.6XXA Traumatic ischemia of muscle, initial encounter
SNOMED
- 240131006 Rhabdomyolysis (disorder)
- 111245009 Compartment syndrome (disorder)
- 72960004 Exertional rhabdomyolysis
- 240125008 Muscle crush syndrome (disorder)
- 240132004 Non-traumatic rhabdomyolysis (disorder)