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Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 8e >
Chapter 89: Rhabdomyolysis
Francis L. Counselman; Bruce M. Lo
INTRODUCTION AND EPIDEMIOLOGY
Rhabdomyolysis is the destruction of skeletal muscle, caused by any mechanism that results in
injury to myocytes and their membranes. Direct muscle injury and genetic and biochemical factors can
predispose to rhabdomyolysis. Acute necrosis of skeletal muscle fibers and the leakage of cellular
contents into the circulation result in myoglobinuria.
Several classification systems have been developed to characterize the numerous causes of
rhabdomyolysis. None of these systems is universally recognized, and each has its limitations,
Table 89-1 lists commonly recognized conditions associated with rhabdomyolysis. In general, the
most common causes of rhabdomyolysis in adults appear to be alcohol and drugs of abuse,
followed by medications, muscle diseases, trauma, neuroleptic malignant syndrome, seizures,
immobility, infection, strenuous physical activity, and heat-related illness.+-? A host of drugs and
toxins have been identified that are associated with or causative of rhabdomyolysis.2 Multiple causes
are present in more than half of patients.1 In children, rhabdomyolysis is less common and is thought
to be more benign.2 In one study of children, the most common causes of nonrecurrent
rhabdomyolysis were trauma, viral myositis, and connective tissue disease. For adults and children,
inherited metabolic disorders should be suspected with recurrent episodes of rhabdomyolysis,
especially if associated with exercise intolerance.
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TABLE 89-1 Common Conditions Associated with Rhabdomyolysis in Adults
Immunologic diseases
Trauma involving muscle Ischemic injury
Crush injury Dermatomyositis Compartment syndrome
Electrical or lightning injury Polymyositis Compression
Drugs of abuse Bacterial infection Medications
Amphetamines [including ecstasy (3,4-
methylenedioxymethamphetamine)] Clostridium Antipsychotics
Group A B-hemolytic
stononeen Barbiturates
Caffeine Legionella Benzodiazepines
Cocaine Salmonella Clofibrate
Ethanol Shigella Colchicine
Heroin Staphylococcus aureus Corticosteroids
Streptococcus
Lysergic acid diethylamide pnapioeoe Diphenhydramine
Methamphetamines Viral infection Isoniazid
Opiates Coxsackievirus Lithium
Monoamine oxidase
Phencyelidine Cytomegalovirus inhibitors
Environment and excessive muscular Epstein-Barr virus Narcotios
Contact sports Enterovirus Neuroleptic agents
Delirium tremens Hepatitis virus Phenothiazines
Dystonia Herpes simplex virus Propofol
Human
Psychosis immunateficiency virus Salloylates
Influenza virus (A and Selective serotonin
Seizures B) reuptake inhibitors
Marathons, military basic training Rotavirus Statins
Heat stroke Mycoplasma Theophyline
Genetic disorders Tricyclic antidepressants
Glycolysis and glycogenolysis disorders Zidovudine
Some novel cancer
Fatty acid oxidation disorders chemotherapeutic agents
Mitochondrial and respiratory chain
metabolism disorders
Patients in coma are at risk for rhabdomyolysis from unrelieved pressure on gravity-dependent body
parts, Alcohol consumption can result in rhabdomyolysis secondary to coma-induced muscle
compression and a direct toxic effect. Nutritional compromise, hypokalemia, hypomagnesemia, and
hypophosphatemia, all common in alcoholics, increase the risk of rhabdomyolysis, Alcohol and drugs
are thought to play a role in most cases of rhabdomyolysis in adults. Drugs of abuse are commonly
implicated in acute rhabdomyolysis, and many commonly prescribed medications have been
associated as well.2 Statin-related myopathies include myalgias with or without elevation of creatine
Kinase level, muscle weakness, and rhabdomyolysis. Statin-related rhabdomyolysis is rare, varies with
the particular statin, and is also dose related. Drug combinations, including combinations with
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cyclosporine, macrolide antibiotics, warfarin, digoxin, and dual statin therapy, carry an increased risk
for rhabdomyolysis.22
‘A number of bacterial and viral infections have been associated with rhabdomyolysis.2 Strenuous
physical activity, as seen in athletes, marathon runners, military recruits, and outdoor laborers, is a
‘common cause. Physical activity that produces high-force eccentric contractions, such as strength
training or heavy lifting, leads to greater breakdown in muscle and higher levels of creatine kinase
than concentric contractions, such as endurance-based exercises. Factors that increase the risk in
this group of patients include poor physical conditioning, inadequate fluid intake, wearing of restrictive
clothing, high ambient temperatures, and high humidity levels.
PATHOPHYSIOLOGY
Rhabdomyolysis is a syndrome characterized by injury to skeletal muscle with subsequent effects
from the release of intracellular contents. These contents include myoglobin, creatine kinase,
aldolase, lactate dehydrogenase, aspartate aminotransferase, and potassium. Although numerous
‘causes of rhabdomyolysis have been described, the common terminal event appears to involve the
disruption of the Na*K*ATPase pump and calcium transport, which results in increased intracellular
calcium and subsequent muscle cell necrosis. In addition, calcium activates phospholipase Az and
various vasoactive molecules and proteases and induces the production of free oxygen radicals.22
CLINICAL FEATURES
The presenting symptoms of rhabdomyolysis are usually acute in onset and include myalgias,
stiffness, weakness, malaise, low-grade fever, and dark (usually brown) urine. Muscle symptoms,
however, may be present in only half of cases.4 Nausea, vomiting, abdominal pain, and tachycardia
can occur in severe rhabdomyolysis. Mental status changes may develop from urea-induced
encephalopathy. Swelling and tenderness of the involved muscle groups and hemorrhagic
discoloration of overlying skin may be observed but are not common. Muscle involvement may be
localized or diffuse, depending on the cause. Commonly, the postural muscles of the thighs, calves,
and lower back are involved. Muscle swelling may not become apparent until after rehydration with IV
fluids. An important point to remember is that acute rhabdomyolysis may be present without any of
these signs or symptoms, and the patient may have normal findings on physical examination. For this
reason, the diagnosis often is made only after soliciting a historical clue (e.g., recent cocaine use) or
finding an elevated serum creatine kinase level or the presence of dark urine on routine laboratory
testing.
DIAGNOSIS
An elevated serum creatine kinase is the most sensitive and reliable indicator of muscle injury. The
degree of elevation correlates with the amount of muscle injury and the severity of illness, but not the
development of renal failure or other morbidity. Most investigators consider a fivefold or greater
increase above the upper threshold of normal in serum creatine kinase level, in the absence of
cardiac or brain injury, as the requirement for the diagnosis of rhabdomyolysis. In general, the
level begins to rise approximately 2 to 12 hours after the onset of muscle injury, peaks within 24 to 72
hours, and then declines at the relatively constant rate of 39% of the previous day's value. Ongoing
muscle necrosis should be suspected in patients with elevated values that fail to decrease in this
manner. The isoenzyme CK-MM (found in skeletal and cardiac muscle) is responsible in large part for
the elevation in serum creatine kinase. The MB fraction of creatine kinase (found primarily in cardiac
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