eMedicine Specialties > Emergency Medicine > Trauma & Orthopedics

Rhabdomyolysis

Author: Sandy Craig, MD, Adjunct Associate Professor, Department of Emergency Medicine, University of North Carolina at Chapel Hill, Carolinas Medical Center
Contributor Information and Disclosures

Updated: Oct 1, 2009

Introduction

Background

Rhabdomyolysis was first described in the victims of crush injury during the 1940-1941 London, England, blitzkrieg  bombing raids of World War II.1 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.2

Clinical sequelae of rhabdomyolysis include the following:

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 is more common in adults, though it 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

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%).3
  • 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%)4
  • More recently, Fernandez et al reviewed 97 adult patients who presented to a university emergency department with rhabdomyolysis and found that the most common risk factors were cocaine use (30), exercise (29), and immobilization (18). Direct trauma, seizures, and alcohol withdrawal each accounted for 4 cases.5
  • Melli et al reviewed 475 patients with rhabdomyolysis hospitalized at Johns Hopkins Hospital and found that the most common risk factors were exogenous toxins, with illicit drugs, alcohol, and prescription medications responsible in 46% of patients. A linear correlation was found between serum CPK and between multiple risk factors and acute renal failure.6
  • 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+.7
  • Patients with statin-induced rhabdomyolysis typically present with flulike symptoms, fatigue, or progressive low back pain and proximal muscle weakness. The average duration of statin therapy is approximately 1 year.8

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 or crush injury9
    • 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, squats, push-ups, sit-ups)10
    • Status epilepticus
    • Status asthmaticus11
    • Severe dystonia
    • Acute psychosis
    • Excessive computer keyboard use/gaming12
  • 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
    • Caffeine13
    • Fibric acid derivatives (eg, bezafibrate, clofibrate, fenofibrate, gemfibrozil)14
    • Neuroleptics/antipsychotics15
    • Anesthetic and paralytic agents (the malignant hyperthermia syndrome)
    • Amphotericin B
    • Quinine
    • Corticosteroids
    • Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors)8
    • Theophylline
    • Cyclic antidepressants
    • Selective serotonin reuptake inhibitors (the serotonin syndrome)
    • Aminocaproic acid
    • Phenylpropanolamine (recalled from US market)
    • Propofol (continuous infusion)16
    • Protease inhibitors
  • Rhabdomyolysis may be caused by other toxins, including the following:
    • Carbon monoxide17
    • 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 envenomations of Africanized honey bees
  • Environmental causes of rhabdomyolysis include the following:
    • Hyperthermia
    • Hypothermia18
  • Metabolic causes of rhabdomyolysis include the following:
    • Hyponatremia19 or hypernatremia
    • Hypokalemia20
    • Hypophosphatemia
    • Hypothyroidism or hyperthyroidism21
    • Diabetic ketoacidosis
    • Nonketotic hyperosmolar diabetic coma
  • Viral infectious disease agents may cause rhabdomyolysis, including the following:22
    • Influenza types A and B (most common)
    • HIV23
    • Coxsackievirus24
    • Ebstein-Barr virus
    • Echovirus
    • Cytomegalovirus
    • Adenovirus
    • Herpes simplex virus
    • Parainfluenza virus
    • Varicella-zoster virus25
    • West Nile virus26
  • Bacterial infectious agents may cause rhabdomyolysis, including the following:27
    • Francisella tularensis28
    • 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 species29
    • Mycoplasma species30
    • Vibrio species
    • Brucella species
    • Bacillus species
    • Leptospira species31
  • Fungal infectious agents may cause rhabdomyolysis, including the following:27
    • 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, lipid, or amino acid metabolism32,33
    • Myopathies34
  • Rhabdomyolysis also has been reported in patients with sickle cell anemia and has mistakenly been identified as a pain crisis.

More on Rhabdomyolysis

Overview: Rhabdomyolysis
Differential Diagnoses & Workup: Rhabdomyolysis
Treatment & Medication: Rhabdomyolysis
Follow-up: Rhabdomyolysis
References
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References

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  3. Gabow PA, Kaehny WD, Kelleher SP. The spectrum of rhabdomyolysis. Medicine (Baltimore). May 1982;61(3):141-52. [Medline].

  4. Ward MM. Factors predictive of acute renal failure in rhabdomyolysis. Arch Intern Med. Jul 1988;148(7):1553-7. [Medline].

  5. Fernandez WG, Hung O, Bruno GR, Galea S, Chiang WK. Factors predictive of acute renal failure and need for hemodialysis among ED patients with rhabdomyolysis. Am J Emerg Med. Jan 2005;23(1):1-7. [Medline].

  6. Melli G, Chaudhry V, Cornblath DR. Rhabdomyolysis: an evaluation of 475 hospitalized patients. Medicine (Baltimore). Nov 2005;84(6):377-85. [Medline].

  7. Mannix R, Tan ML, Wright R, Baskin M. Acute pediatric rhabdomyolysis: causes and rates of renal failure. Pediatrics. Nov 2006;118(5):2119-25. [Medline].

  8. Ahn SC. Neuromuscular complications of statins. Phys Med Rehabil Clin N Am. Feb 2008;19(1):47-59, vi. [Medline].

  9. Malinoski DJ, Slater MS, Mullins RJ. Crush injury and rhabdomyolysis. Crit Care Clin. Jan 2004;20(1):171-92. [Medline].

  10. Lin AC, Lin CM, Wang TL, Leu JG. Rhabdomyolysis in 119 students after repetitive exercise. Br J Sports Med. Jan 2005;39(1):e3. [Medline].

  11. Chen YJ, Chang SH, Yuan A, Huang CH, Lee CC. Rhabdomyolysis after successful resuscitation of a patient with near-fatal asthma. Am J Emerg Med. Jul 2007;25(6):736.e3-4. [Medline].

  12. Song SH, Lee DW, Lee SB, Kwak IS. Rhabdomyolysis caused by strenuous computer gaming. Nephrol Dial Transplant. Apr 2007;22(4):1263-4. [Medline].

  13. Wrenn KD, Oschner I. Rhabdomyolysis induced by a caffeine overdose. Ann Emerg Med. Jan 1989;18(1):94-7. [Medline].

  14. Holoshitz N, Alsheikh-Ali AA, Karas RH. Relative safety of gemfibrozil and fenofibrate in the absence of concomitant cerivastatin use. Am J Cardiol. Jan 1 2008;101(1):95-7. [Medline].

  15. Hung CF, Huang TY, Lin PY. Hypothermia and rhabdomyolysis following olanzapine injection in an adolescent with schizophreniform disorder. Gen Hosp Psychiatry. Jul-Aug 2009;31(4):376-8. [Medline].

  16. Wysowski DK, Pollock ML. Reports of death with use of propofol (Diprivan) for nonprocedural (long-term) sedation and literature review. Anesthesiology. Nov 2006;105(5):1047-51. [Medline].

  17. Kao LW, Nañagas KA. Toxicity associated with carbon monoxide. Clin Lab Med. Mar 2006;26(1):99-125. [Medline].

  18. Aslam AF, Aslam AK, Vasavada BC, Khan IA. Hypothermia: evaluation, electrocardiographic manifestations, and management. Am J Med. Apr 2006;119(4):297-301. [Medline].

  19. Strachan P, Prisco D, Multz AS. Recurrent rhabdomyolysis associated with polydipsia-induced hyponatremia - a case report and review of the literature. Gen Hosp Psychiatry. Mar-Apr 2007;29(2):172-4. [Medline].

  20. Agrawal S, Agrawal V, Taneja A. Hypokalemia causing rhabdomyolysis resulting in life-threatening hyperkalemia. Pediatr Nephrol. Feb 2006;21(2):289-91. [Medline].

  21. Lichtstein DM, Arteaga RB. Rhabdomyolysis associated with hyperthyroidism. Am J Med Sci. Aug 2006;332(2):103-5. [Medline].

  22. Nauss MD, Schmidt EL, Pancioli AM. Viral myositis leading to rhabdomyolysis: a case report and literature review. Am J Emerg Med. Mar 2009;27(3):372.e5-372.e6. [Medline].

  23. Patel N, Patel N, Espinoza LR. HIV infection and rheumatic diseases: the changing spectrum of clinical enigma. Rheum Dis Clin North Am. Feb 2009;35(1):139-61. [Medline].

  24. Wang YM, Zhang Y, Ye ZB. Rhabdomyolysis following recent severe coxsackie virus infection in patient with chronic renal failure: one case report and a review of the literature. Ren Fail. 2006;28(1):89-93. [Medline].

  25. Pirounaki M, Liatsos G, Elefsiniotis I, Skounakis M, Moulakakis A. Unusual onset of varicella zoster reactivation with meningoencephalitis, followed by rhabdomyolysis and renal failure in a young, immunocompetent patient. Scand J Infect Dis. 2007;39(1):90-3. [Medline].

  26. Gupta M, Ghaffari M, Freire AX. Rhabdomyolysis in a patient with West Nile encephalitis and flaccid paralysis. Tenn Med. Apr 2008;101(4):45-7. [Medline].

  27. Singh U, Scheld WM. Infectious etiologies of rhabdomyolysis: three case reports and review. Clin Infect Dis. Apr 1996;22(4):642-9. [Medline].

  28. Eliasson H, Broman T, Forsman M, Bäck E. Tularemia: current epidemiology and disease management. Infect Dis Clin North Am. Jun 2006;20(2):289-311, ix. [Medline].

  29. Antonarakis ES, Wung PK, Durand DJ, Leyngold I, Meyerson DA. An atypical complication of atypical pneumonia. Am J Med. Oct 2006;119(10):824-7. [Medline].

  30. Weng WC, Peng SS, Wang SB, Chou YT, Lee WT. Mycoplasma pneumoniae--associated transverse myelitis and rhabdomyolysis. Pediatr Neurol. Feb 2009;40(2):128-30. [Medline].

  31. Turhan V, Atasoyu EM, Kucukardali Y, Polat E, Cesur T, Cavuslu S. Leptospirosis presenting as severe rhabdomyolysis and pulmonary haemorrhage. J Infect. Jan 2006;52(1):e1-2. [Medline].

  32. Scheuerman O, Wanders RJ, Waterham HR, Dubnov-Raz G, Garty BZ. Mitochondrial trifunctional protein deficiency with recurrent rhabdomyolysis. Pediatr Neurol. Jun 2009;40(6):465-7. [Medline].

  33. Korematsu S, Kosugi Y, Kumamoto T, Yamaguchi S, Izumi T. Novel mutation of early, perinatal-onset, myopathic-type very-long-chain acyl-CoA dehydrogenase deficiency. Pediatr Neurol. Aug 2009;41(2):151-3. [Medline].

  34. Brumback RA, Feeback DL, Leech RW. Rhabdomyolysis in childhood. A primer on normal muscle function and selected metabolic myopathies characterized by disordered energy production. Pediatr Clin North Am. Aug 1992;39(4):821-58. [Medline].

  35. Lappalainen H, Tiula E, Uotila L. Elimination kinetics of myoglobin and creatine kinase in rhabdomyolysis: implications for follow-up. Crit Care Med. Oct 2002;30(10):2212-5. [Medline].

  36. Minnema BJ, Neligan PC, Quraishi NA, Fehlings MG, Prakash S. A case of occult compartment syndrome and nonresolving rhabdomyolysis. J Gen Intern Med. Jun 2008;23(6):871-4. [Medline].

  37. Young SE, Miller MA, Docherty M. Urine dipstick testing to rule out rhabdomyolysis in patients with suspected heat injury. Am J Emerg Med. Sep 2009;27(7):875-7. [Medline].

  38. Li SF, Zapata J, Tillem E. The prevalence of false-positive cardiac troponin I in ED patients with rhabdomyolysis. Am J Emerg Med. Nov 2005;23(7):860-3. [Medline].

  39. Moratalla MB, Braun P, Fornas GM. Importance of MRI in the diagnosis and treatment of rhabdomyolysis. Eur J Radiol. Feb 2008;65(2):311-5. [Medline].

  40. Better OS, Stein JH. Early management of shock and prophylaxis of acute renal failure in traumatic rhabdomyolysis. N Engl J Med. Mar 22 1990;322(12):825-9. [Medline].

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Further Reading

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Contributor Information and Disclosures

Author

Sandy Craig, MD, Adjunct Associate Professor, Department of Emergency Medicine, University of North Carolina at Chapel Hill, Carolinas Medical Center
Sandy Craig, MD is a member of the following medical societies: Alpha Omega Alpha and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Lance W Kreplick, MD, MMM, FAAEM, FACEP, Medical Director of Hyperbaric Medicine, Fawcett Wound Management and Hyperbaric Medicine; Consulting Staff in Occupational Health and Rehabilitation, Company Care Occupational Health Services; President and Chief Executive Officer, QED Medical Solutions, LLC
Lance W Kreplick, MD, MMM, FAAEM, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physician Executives
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Tom Scaletta, MD, President, Emergency Excellence (EmEx) (www.emergencyexcellence.com); Assistant Professor of Emergency Medicine, Rush Medical College, Cook County Hospital; Chairperson, Department of Emergency Medicine, Edward Hospital; Past-President, American Academy of Emergency Medicine
Tom Scaletta, MD is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Rick Kulkarni, MD, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

 
 
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