Author:
VishnuParthasarathy
GabrielWardi
Description
Literally “dissolution of skeletal contents.” Defined as pathologic release of muscle contents - creatine phosphokinase (CPK), myoglobin, potassium, phosphate, urate - with systemic complications. Caused by trauma, direct compression of muscle, poisoning, infection, primary muscle disorders, and many other disease states. Complications include:
- Myoglobinuric renal failure in 15-50% adults, only 5% in children
- Hyperkalemia may lead to sudden death
- Hypocalcemia and acidosis
- Intravascular hypovolemia - fluid sequestration in injured muscle or result of underlying illness
- Hepatic dysfunction in 25%
- Disseminated intravascular coagulation (DIC)
Epidemiology
Incidence
- 26,000 per year in the U.S.
- Disaster situations lead to 100s of cases of renal failure
Risk Factors
- Trauma, particularly crush injuries
- Sepsis
- Prolonged immobilization
- Inherited myopathy
- Alcohol or drug use
- Medications as listed below
- Overexertion with or without risk factors
Pathophysiology
- Ion pumps in sarcolemma normally keep intracellular Ca, Na low, and K high via ATP-dependent processes
- Myocyte damage reduces ATP availability which disrupts ion channel activity
- Prolonged intracellular Ca causes sustained myofibrillar contraction and further ATP depletion leads to ischemia
- Ca-dependent proteases cause cell membrane lysis
- Escape of cell contents: Myoglobin, potassium, phosphate, CPK, lactate, AST, ALT
- Myoglobin causes direct renal toxicity and 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
Adults: Trauma, drug toxicity, seizure, infection
Children: Viral myositis, trauma
- Muscle injury - due to trauma/crush, burn, electrical shock - most 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 (NMS, MH)
- Prolonged immobilization without trauma
- Drugs/toxins: Alcohols, cocaine, amphetamines, and analogs (methamphetamine and ecstasy), toluene, opiates, LSD, phencyclidine (PCP), carbon monoxide, snake venom, bee/hornet venom, hemlock, buffalo fish, tetanus toxin, mushroom poisoning (Tricholoma equestre)
- Medications: Most common - haloperidol, phenothiazines, HMG-CoA reductase inhibitors (statins) especially in combination with fibrates (gemfibrozil)
- Sports supplements including ephedra, caffeine, and rogenic steroids, creatine, diuretics
- Neuroleptic malignant syndrome (idiosyncratic and not dose-related)
- Metabolic disorders: Hypokalemia, hypophosphatemia, hypocalcemia, hyper- and hyponatremia, metabolic acidosis, hyperosmolar state, hypoxia, hyperthyroid state (rare), pheochromocytoma (rare)
- Infections:
- Viral: Coxsackievirus, herpesviruses, HIV, influenza B, cytomegalovirus, Epstein-Barr virus, adeno/echovirus
- Bacterial: Legionnaires disease, pyomyositis, sepsis
- 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)
Signs and Symptoms
History
- Can vary dramatically, reflecting underlying disease process
- Trauma, crush, exertional - usually obvious
- Consider nonaccidental trauma with unclear details of history
- If no trauma, consider 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 40-50%)
- Neurovascular status of involved muscle groups if compartment syndrome is suspected
- Hypovolemic state, dry mucous membranes, poor skin turgor, tachycardia, hypotension
- Decreased urine output
- Tea-colored urine is early sign (although present in a minority of cases)
- Children more often have absent physical findings
Diagnostic Tests & Interpretation
Lab
Initial Lab
- Serum CPK level >1,000 IU/L or 5 times lab limit is most commonly agreed on cut-off for diagnosis although there is no absolute cut-off and CPK levels should be interpreted in the appropriate clinical scenario
- Serum and urine myoglobin levels often normal due to rapid metabolism and excretion
- Risk factors for progression to acute tubular necrosis include level of CPK, electrolyte abnormalities, acidosis, delays in initiation of therapy
- Urine dipstick test positive for heme but absent for RBCs suggests rhabdomyolysis
- Microscopic urinalysis to look for pigmented tubular casts
- 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)
- Urinary pH if considering alkalinization
- 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-stand ing renal failure (small, shrunken kidneys) or renal obstruction (hydronephrosis). Other imaging as indicated to evaluate traumatic injuries, infectious evaluation
Diagnostic Procedures/Surgery
- Early ECG: Hyperkalemia or hypocalcemia before serum levels available
- Placement of Foley catheter if needed in cases of severe rhabdomyolysis to monitor urine output
- Measure compartment pressure if compartment syndrome is suspected
Differential Diagnosis
Conditions that may present with elevated serum CPK but are not rhabdomyolysis:
- Nontraumatic myopathies including muscular dystrophies and inherited myopathies
- Chronic renal failure
- IM injections
- Myocardial injury
- Stroke
Prehospital
- Rapid extrication in case of crush injury
- Early crystalloid administration, even prior to completion of extrication, to prevent complications of restored blood flow to injured limb (hypovolemia, hyperkalemia, etc.)
- Pediatric recommendation: 10-15 mL/kg/hr saline initially, then switch to hypotonic (0.45%) saline upon arrival to hospital. Add 50 mEq bicarbonate to each second or third liter to alkalinize urine
Initial Stabilization/Therapy
- Manage ABCs
- Immobilization of trauma/crush injuries
- Adult crush injury treatment literature extrapolated to children
- Cornerstone of management is aggressive fluid resuscitation with crystalloid to reverse hypovolemia and prevent myoglobinuric renal failure
ED Treatment/Procedures
- Goal is to ensure urine output of at least 200-300 cc/hr, starting rate of 2.5 cc/kg/hr of crystalloid is appropriate for most patients without obvious fluid overload
- Urinary alkalinization with bicarbonate (prevents dissociation of myoglobin into hematin and globin at urinary pH <5.6, both of which are nephrotoxic agents) has lost favor in recent years due to lack of meaningful human data it improves outcomes but can be considered in case by case scenarios (e.g., profound acidosis with hyperkalemia)
- Mannitol 20%: 50 mL (10 g added to each liter up to 120-200 g/d (1-2 g/kg/d): Diuretic, free radical scavenger. May help compartment syndrome (controversial as this therapy has never been shown to improve outcomes when compared to crystalloid approaches alone)
- Furosemide and other loop diuretics second-line therapy in management of oliguric (<500 mL/d) renal failure after aggressive crystalloid resuscitation; controversial
- 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 phosphate crystallization may occur and worsen renal failure
- Discontinue offending drug
- Renal replacement therapy is indicated in situations of life-threatening electrolyte abnormalities (e.g., hyperkalemia), profound acidosis, or significant volume overload
Surgery/Other Procedures
- Hemodialysis for refractory hyperkalemia, fluid overload, anuria, acidosis
- Consider central venous monitoring of volume
- Fasciotomy for compartment syndrome
Disposition
Admission Criteria
- Rise or minimal decrease in CPK despite fluid resuscitation (there is no CPK cutoff for admission)
- Acute renal failure with minimal improvement after fluid resuscitation or requiring hemodialysis
- Significant electrolyte derangements (hyperkalemia, hypocalcemia)
- Hemodynamic instability
- Compartment syndrome
- Underlying severe illness/comorbidities or profound inciting event (e.g., massive crush injury, septic shock, DIC)
Discharge Criteria
Decreasing CPK levels with normal renal function, inciting etiology of rhabdomyolysis identified, reversed and no other indication for admission
Complications
- Myoglobinuric renal failure
- Hyperkalemia
- Compartment syndrome
- Hypocalcemia
- Acidosis
- Death
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- ChavezLO, LeonM, EinavS, et al. Beyond muscle destruction: A systematic review of rhabdomyolysis for clinical practice . Critical Care. 2016;20(1):135.
- GenthonA, WilcoxSR. Crush syndrome: A case report and review of the literature . J Emerg Med. 2014;46(2):313-319.
- LuckRP, VerbinS. Rhabdomyolysis: A review of clinical presentation, etiology, diagnosis, and management . Pediatr Emerg Care. 2008;24:262-268.
- McMahonGM, ZengX, WaikarSS. A risk prediction score for kidney failure or mortality in rhabdomyolysis . JAMA Intern Med. 2013;173(19):1821-1827.
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- TorresPA, HelmstetterJA, KayeAM, et al. Rhabdomyolysis: Pathogenesis, diagnosis, and treatment . Ochsner J. 2015;15(1):58-69.
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