Rhabdomyolysis

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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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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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