Rhabdomyolysis

Basics

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, androgenic 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)

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