Description

“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

Risk Factors

• Trauma, particularly crush injuries
• 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
• Pathologic release of intra-cellular 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 results in renal vasoconstriction and injury
• Hyperkalemia may lead to arrhythmias
• Calcium precipitates with phosphate, causing systemic hypocalcemia and renal injury

Etiology

Cause usually obvious, but not always

Adults: Trauma and crush injuries, intoxication, seizure, infection

Children: Viral infections, 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 embolisms, 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 3,4-methylenedioxymethamphetamine [MDMA]), 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
• Metabolic disorders: Hypokalemia, hypophosphatemia, hypocalcemia, hyper- and hyponatremia, metabolic acidosis, hyperosmolar state, hypoxia, hyper- and hypothyroid 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 use disorder
• Elderly and acutely immobile (found on floor)