INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Rhabdomyolysis was first described in the victims of crush injury during the 1940-1941 London, England, bombing raids of World War II. It has many etiologies.

Pathophysiology

Rhabdomyolysis is the breakdown of muscle fibers with leakage of potentially toxic cellular contents into the systemic circulation. The final common pathway of rhabdomyolysis may be a disturbance in myocyte calcium homeostasis.

Clinical sequelae of rhabdomyolysis include the following:

• Hypovolemia (sequestration of plasma water within injured myocytes)
• Hyperkalemia (release of cellular potassium into the systemic circulation)
• Metabolic acidosis (release of cellular phosphate and sulfate)
• Acute renal failure (nephrotoxic effects of liberated myocyte components)
• Disseminated intravascular coagulation (DIC)

Frequency

United States

Rhabdomyolysis accounts for an estimated 8-15% of cases of acute renal failure.

Mortality/Morbidity

The overall mortality rate for patients with rhabdomyolysis is approximately 5%; however, the mortality rate of any single patient is dependent upon the underlying etiology and any existing comorbidities.

Sex

Incidence is higher in males than in females, especially in the subgroups of trauma and inherited enzyme deficiencies.

Age

Rhabdomyolysis may occur in infants, toddlers, and adolescents who have inherited enzyme deficiencies of carbohydrate or lipid metabolism or who have inherited myopathies, such as Duchenne muscular dystrophy and malignant hyperthermia.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

The clinical presentation is often subtle, underscoring the need for a high index of suspicion.

• In a 1982 study of 87 episodes of rhabdomyolysis in adults, Gabow found that only 50% of patients initially complained of muscle pain. A minority of patients reported dark discoloration of the urine.
• In Gabow's series, 97% of patients reported at least 1 risk factor for rhabdomyolysis. Fifty-nine percent reported multiple risk factors.
• • Common risk factors included alcohol abuse (67%), recent soft tissue compression (39%), and seizure activity (24%).
  • Other causative factors included trauma (17%), drug abuse (15%), metabolic derangements (8%), hypothermia (4%), flulike illness (3%), sepsis (2%), and gangrene (1%).
• Ward's 1988 review of 157 patients found the following predisposing factors:
• • Trauma (38%)
  • Ischemia (14%)
  • Polymyositis (8%)
  • Drug overdose (7%)
  • Exertion (6%)
  • Seizures (5%)
  • Burns (5%)
  • Sepsis (3%)
  • Hereditary disorders (3%)
  • Viral illness (1%)
• In a review of 191 pediatric patients with rhabdomyolysis, Mannix et al studied presenting symptoms, causative factors, and incidence of acute renal failure. The average age was 11 years.
• • The most common documented symptoms were muscle pain (45%), fever (40%), and symptoms of viral infection (39%).
  • The most common causes of rhabdomyolysis in this pediatric population were viral myositis (38%), trauma (26%), and connective tissue disease (5%). CK levels greater than 6000 IU/L were more likely to be associated with undiagnosed dermatomyositis or hereditary muscle disease than levels less than 6000 IU/L.
  • Acute renal failure occurred in 4.7% of patients, all of whom had urinary heme dipstick results of at least 2+.

Physical

• Focal or diffuse skeletal muscle swelling is rare. In Gabow's series, only 5% of the patients presented with muscle edema.
• Tense and tender muscle compartments suggest compartment syndrome; peripheral pulses that are within reference range do not rule out compartment syndrome because loss of distal pulses is a very late sign.

Causes

The etiologies may be subdivided into traumatic, exercise induced, toxicologic, environmental, metabolic, infectious, immunologic, and inherited classifications.

• Rhabdomyolysis may occur after traumatic events, including the following:
• • Significant blunt trauma
  • High-voltage electrical injury
  • Extensive burns
  • Near drowning
  • Prolonged immobilization (eg, after excess alcohol or drug consumption, after an unwitnessed incapacitating stroke, following prolonged surgical procedures)
• Rhabdomyolysis may occur after excessive muscular activity, such as the following:
• • Sporadic strenuous exercise (eg, marathons)
  • Status epilepticus
  • Status asthmaticus
  • Severe dystonia
  • Acute psychosis
• Toxin-mediated rhabdomyolysis may result from substance abuse, including abuse of the following:
• • Ethanol
  • Methanol
  • Ethylene glycol
  • Isopropanol
  • Heroin
  • Methadone
  • Barbiturates
  • Cocaine
  • Amphetamine
  • Phencyclidine
  • 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)
  • Lysergic acid diethylamide (LSD)
• Toxic-mediated rhabdomyolysis may result from prescription and nonprescription medications, including the following:
  • Antihistamines
  • Salicylates
  • Caffeine
  • Fibric acid derivatives (eg, bezafibrate, clofibrate, fenofibrate, gemfibrozil)
  • Neuroleptics
  • Anesthetic and paralytic agents (the malignant hyperthermia syndrome)
  • Amphotericin B
  • Quinine
  • Corticosteroids
  • Atorvastatin
  • Fluvastatin
  • Lovastatin
  • Pitavastatin (marketed in Japan, South Korea, India)
  • Pravastatin
  • Rosuvastatin
  • Simvastatin
  • Cerivastatin (recalled from US market)
  • Theophylline
  • Cyclic antidepressants
  • Selective serotonin reuptake inhibitors (the serotonin syndrome)
  • Aminocaproic acid
  • Phenylpropanolamine (recalled from US market)
  • Propofol (Continuous infusion has caused rhabdomyolysis in children.)
• Rhabdomyolysis may be caused by other toxins, including the following:
  • Carbon monoxide
  • Toluene
  • Hemlock herbs from quail (Rhabdomyolysis after the consumption of quail is well known in the Mediterranean region; it occurs as the result of intoxication by hemlock herbs that the quails consume.)
  • Snake, spider (eg, black widow spider), and massive bee envenomations
• Environmental causes of rhabdomyolysis include the following:
  • Hyperthermia
  • Hypothermia
• Metabolic causes of rhabdomyolysis include the following:
  • Hyponatremia or hypernatremia
  • Hypokalemia
  • Hypophosphatemia
  • Hypothyroidism or hyperthyroidism
  • Diabetic ketoacidosis
  • Nonketotic hyperosmolar diabetic coma
• Viral infectious disease agents may cause rhabdomyolysis, including the following:
  • Influenza types A and B (most common)
  • HIV
  • Coxsackievirus
  • Ebstein-Barr virus
  • Echovirus
  • Cytomegalovirus
  • Adenovirus
  • Herpes simplex virus
  • Parainfluenza virus
  • Varicella-zoster virus
• Bacterial infectious agents may cause rhabdomyolysis, including the following:
  • Francisella tularensis
  • Streptococcus pneumoniae
  • Group B streptococci
  • Streptococcus pyogenes
  • Staphylococcus epidermidis
  • Escherichia coli
  • Borrelia burgdorferi
  • Clostridium perfringens
  • Clostridium tetani
  • Viridans streptococci
  • Plasmodium species
  • Rickettsia species
  • Salmonella species
  • Listeria species
  • Legionella species
  • Mycoplasma species
  • Vibrio species
  • Brucella species
  • Bacillus species
  • Leptospira species
• Fungal infectious agents may cause rhabdomyolysis, including the following:
  • Candida species
  • Aspergillus species
• Causative connective tissue diseases that can cause rhabdomyolysis include the following:
  • Polymyositis
  • Dermatomyositis
• Inherited disorders may cause rhabdomyolysis, including the following:
  • Enzyme deficiencies of carbohydrate or lipid metabolism
  • Myopathies
• Rhabdomyolysis also has been reported in patients with sickle cell anemia and has mistakenly been identified as a pain crisis.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Serotonin syndrome

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Preliminary diagnosis of rhabdomyolysis requires a high index of suspicion. Definitive diagnosis is made by laboratory evaluation.
• The most useful measurement is for serum creatine kinase (CK). This assay is widely available and 100% sensitive. Rhabdomyolysis has been variously defined as total CK levels 5-10 times above normal in a patient with typical symptoms and/or risk factors.
• • Total CK elevation is a sensitive but nonspecific marker for rhabdomyolysis. Suspect early rhabdomyolysis in patients with serum CK levels in excess of 2-3 times the reference range and risk factors for rhabdomyolysis; initiate a full laboratory workup. Remember that the total CK may increase from the initial values, and repeat total CK levels should be drawn every 6-12 hours until a peak level is established.
  • Patients with other disorders, such as acute myocardial infarction and acute stroke, may have high CK levels. CK levels have a wide range of distribution among patients with rhabdomyolysis (several hundred to hundreds of thousands of units per liter).
  • Serum CK levels peak within 24 hours and should decrease by approximately 30-40% per day after the initial insult. Persistent elevation suggests continuing muscle injury or development of a compartment syndrome.
• A urine dipstick test for blood has positive results in the presence of hemoglobin or myoglobin.
• • A urine dipstick test for blood that has positive findings in the absence of red blood cells suggests myoglobinuria.
  • Myoglobinuria may be sporadic or resolve early in the course of rhabdomyolysis.
  • Urine dipstick findings are positive in only 50% of patients with rhabdomyolysis; therefore, a normal urine dipstick test result does not rule out this condition.
• Aldolase, lactate dehydrogenase (LDH), and serum glutamic-oxaloacetic transaminase (SGOT) are nonspecific enzyme markers that are elevated in patients with rhabdomyolysis.
• Hyperkalemia, an immediate threat to life in the hours immediately after injury, occurs in 10-40% of cases.
• • Liberated potassium can cause life-threatening dysrhythmias and death.
  • Measure and closely monitor serum potassium levels.
• Acute renal failure develops in 30-40% of patients and is the most serious complication in the days after initial presentation.
• • Measure and closely monitor blood urea nitrogen (BUN) and creatinine levels.
  • The BUN-creatinine ratio can be decreased because of the conversion of liberated muscle creatine to creatinine.
• Hyperphosphatemia does not require specific therapy.
• Hypocalcemia occurs early in the course of rhabdomyolysis. Supplemental calcium is not recommended.
• Increased purine metabolism causes hyperuricemia. Specific therapy with uricosuric agents or allopurinol is not indicated.
• Obtain the prothrombin time, activated partial thromboplastin time, and platelet count in all patients with rhabdomyolysis. Thromboplastin released from injured myocytes can cause DIC.

Imaging Studies

• Imaging studies generally play no role in the initial diagnosis of rhabdomyolysis.
• Magnetic resonance imaging (MRI) may be useful in distinguishing various etiologies of rhabdomyolysis.
• • One study suggests that bacterial myositis, focal myositis, and idiopathic rhabdomyolysis show a characteristic gadolinium enhancement on MRI (Beese, 1996). Abscesses were found only in bacterial myositis.
  • Polymyositis and dermatomyositis have a characteristic uniform distribution pattern with emphasis on the quadriceps muscles.

Other Tests

• Obtain an electrocardiogram (ECG) early in the course of ED evaluation.
• ECG may reveal changes of acute hyperkalemia, including peaked T waves, prolongation of the PR and QRS intervals, and loss of the P wave or the sine wave.

Procedures

• Measure the compartment pressures in any patient with severe focal muscle tenderness and a firm muscle compartment.
• Perform a fasciotomy if compartment pressures are sustained in excess of 25-30 mm Hg.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

Vigorous hydration with isotonic crystalloid is the cornerstone of therapy for rhabdomyolysis. Retrospective studies of patients with severe crush injuries resulting in rhabdomyolysis suggest that the prognosis is better when prehospital personnel provide fluid resuscitation. Support of the intravascular volume increases the glomerular filtration rate (GFR) and oxygen delivery and dilutes myoglobin and other renal tubular toxins.

• Immediately obtain intravenous access with a large-bore catheter.
• Administer isotonic crystalloid 500 mL/h and then titrate to maintain a urine output of 200-300 mL/h.
• Because injured myocytes can sequester large volumes of extracellular fluid, crystalloid requirements may be surprisingly large.

Emergency Department Care

Assess ABCs and support as needed. Treat any underlying conditions, such as trauma, infection, or toxins. General recommendations for the treatment of rhabdomyolysis include fluid resuscitation and prevention of end-organ complications.

• Patients with CK elevation in excess of 2-3 times the reference range, appropriate clinical history, and risk factors should be suspected of having rhabdomyolysis. Administer isotonic crystalloid 500 mL/h and titrate to maintain a urine output of 200-300 mL/h. (Consider central venous pressures or Swan-Ganz catheterization in patients with cardiac or renal disease. These invasive studies can assist in the assessment of the intravascular volume.) Repeat CK assay every 6-12 hours in order to determine peak CK level.
• Acute renal failure develops in 30-40% of patients with rhabdomyolysis. Suggested mechanisms include precipitation of myoglobin and uric acid crystals within renal tubules, decreased glomerular perfusion, and the nephrotoxic effect of ferrihemate (formed upon dissociation of myoglobin in the acidic environment of the renal parenchyma). In a 1988 review, Ward suggested that predictors for the development of renal failure include peak CK level more than 6000 IU/L, dehydration (hematocrit >50, serum sodium level >150 mEq/L, orthostasis, pulmonary wedge pressure <5 mm Hg, urinary fractional excretion of sodium <1%), sepsis, hyperkalemia or hyperphosphatemia on admission, and the presence of hypoalbuminemia. Acute renal failure has occasionally developed in severely dehydrated patients with peak CK level as low as 2000 IU/L. To prevent renal failure, many authorities advocate urine alkalinization, mannitol, and loop diuretics.
• • Urinary alkalinization to prevent the development of acute renal failure in patients with rhabdomyolysis has been supported by animal studies and retrospective human studies, although prospective randomized human studies are lacking.
  • Urinary alkalinization is recommended for patients with rhabdomyolysis and CK levels in excess of 6000 IU/L. Alkalinization should be considered earlier in patients with acidemia, dehydration, or underlying renal disease. A suggested regimen is 0.5 isotonic sodium chloride solution with one ampule of sodium bicarbonate administered at 100 mL/h and titrated to a urine pH higher than 7.
  • After establishing an adequate intravascular volume, mannitol may be administered to enhance renal perfusion.
  • Loop diuretics may be used to enhance urinary output in oliguric patients, despite adequate intravascular volume.
• Treatment of hyperkalemia consists of intravenous sodium bicarbonate, glucose, and insulin; oral or rectal sodium polystyrene sulfonate (Kayexalate); and hemodialysis. Administer intravenous calcium chloride for patients who are hemodynamically compromised and hyperkalemic.
• Hypocalcemia is noted early in the course of rhabdomyolysis and generally is not of clinical significance. Calcium supplementation is not recommended.
• Compartment syndrome requires immediate orthopedic consultation for fasciotomy.
• DIC should be treated with fresh frozen plasma, cryoprecipitate, and platelet transfusions.
• Hyperuricemia and hyperphosphatemia rarely are of clinical significance and rarely require treatment.

Consultations

• Nephrologist: Indications for hemodialysis include hyperkalemia that is persistent despite therapy, severe acid-base disturbances, refractory pulmonary edema, and progressive renal failure.
• Orthopedist: Consult an orthopedist in cases of suspected compartment syndrome.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical therapy focuses on restoring adequate intravascular volume using isotonic crystalloid. Adjunctive measures that may decrease the incidence of acute myoglobinuric renal failure include urinary alkalinization and osmotic and loop diuresis.

Drug Category: Alkalinizing agents

Sodium bicarbonate is administered IV to alkalinize urine in patients with rhabdomyolysis. This may prevent toxicity caused by the presence of myoglobin in acidic urine and crystallization of uric acid.

Drug Category: Osmotic diuretics

These agents increase osmolarity of glomerular filtrate and induce diuresis. They hinder tubular reabsorption of water, causing sodium and chloride excretion to increase.

Drug Category: Loop diuretics

These agents elicit a loss of free water, increasing diuresis.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Admit patients with rhabdomyolysis for continued volume support and urinary alkalinization. Obtain serial CK measurements to verify that values have peaked and are returning to reference range.
• Serial physical examinations and laboratory studies are indicated to monitor for compartment syndrome, hyperkalemia, acute oliguric or nonoliguric renal failure, and DIC.
• In patients with no apparent precipitating factors for rhabdomyolysis, consider inherited disorders of carbohydrate or lipid metabolism and myopathies.

Transfer

• Patients may be transferred to another facility after establishing intravenous access and addressing life- and limb-threatening conditions. Follow guidelines of the Consolidated Omnibus Budget Reconciliation Act (COBRA) and the Emergency Medical Treatment and Labor Act (EMTALA).

Complications

• Death from hyperkalemia or renal failure
• Compartment syndrome
• DIC
• Hepatic insufficiency
• Acute renal failure

Prognosis

• The prognosis is dependent upon the underlying etiology and any existing comorbidities.

Patient Education

• Advise patients with rhabdomyolysis caused by hyperthermia and/or inordinate exertion to exercise in moderation with careful attention to hydration and external methods of cooling.
• Advise patients with rhabdomyolysis related to ethanol, recreational drugs, or prescription medications to discontinue use of the offending agent and refer them to a rehabilitation program.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to recognize rhabdomyolysis on initial presentation
• Failure to institute early and aggressive volume replacement
• Insufficient monitoring for serious complications, such as compartment syndrome and severe hyperkalemia

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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• Sinert R, Kohl L, Rainone T, Scalea T. Exercise-induced rhabdomyolysis. Ann Emerg Med. Jun 1994;23(6):1301-6. [Medline].
• Singh U, Scheld WM. Infectious etiologies of rhabdomyolysis: three case reports and review. Clin Infect Dis. Apr 1996;22(4):642-9. [Medline].
• Visweswaran P, Guntupalli J. Rhabdomyolysis. Crit Care Clin. Apr 1999;15(2):415-28, ix-x. [Medline].
• Ward MM. Factors predictive of acute renal failure in rhabdomyolysis. Arch Intern Med. Jul 1988;148(7):1553-7. [Medline].
• Will MJ, Hecker RB, Wathen PI. Primary varicella-zoster-induced rhabdomyolysis. South Med J. Sep 1996;89(9):915-20. [Medline].
• Wrenn KD, Oschner I. Rhabdomyolysis induced by a caffeine overdose. Ann Emerg Med. Jan 1989;18(1):94-7. [Medline].
• Zager RA. Rhabdomyolysis and myohemoglobinuric acute renal failure. Kidney Int. Feb 1996;49(2):314-26. [Medline].

Article Last Updated: Nov 30, 2006