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Rhabdomyolysis

Rhabdomyolysis is the breakdown of skeletal muscle due to injury, either mechanical, physical or chemical. The principal result of this process is acute renal failure due to accumulation of muscle breakdown products in the bloodstream, several of which are injurous to the kidney. more...

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Treatment is with intravenous fluids, and dialysis if necessary.

Causes

The injury that leads to rhabdomyolysis can be due to mechanical, physical and chemical causes:

  • mechanical: crush trauma, excessive exertion, intractable convulsions, choreoathetosis, surgery, compression by a tourniquet left for too long, local muscle compression due to comatose states, compartment syndrome, rigidity due to neuroleptic malignant syndrome
  • physical: high fever or hyperthermia, electric current
  • chemical: metabolic disorders, anoxia of the muscle (e.g. Bywaters' syndrome, toxin- and drug-related; various animal toxins, some antibiotics, methylenedioxymethamphetamine (MDMA) better known as ecstasy, statins, alcohol

Drug-induced rhabdomyolysis appears to be increasing in incidencepossibly due to the introduction of increasingly potent drugs into clinical practice. Any drug which directly or indirectly impairs the production or use of adenosine triphosphate (ATP) by skeletal muscle, or increases energy requirements so as to exceed ATP production, can cause rhabdomyolysis (Larbi 1998).

Pathophysiology

Severe cases of rhabdomyolysis often result in myoglobinuria, a condition where the myoglobin from muscle breakdown spills into the urine, making it dark, or "tea colored" (myoglobin contains heme, like hemoglobin, giving muscle tissue its characteristic red color). This condition can cause serious kidney damage in severe cases. The injured muscle also leaks potassium, leading to hyperkalemia, which may cause fatal disruptions in heart rhythm. In addition, myoglobin is metabolically degraded into potentially toxic substances for the kidneys. Massive skeletal muscle necrosis may further aggravate the situation, by reducing plasma volumes and leading to shock and reduced bloodflow to the kidneys.

Diagnosis

The diagnosis is typically made when an abnormal renal function and elevated creatine kinase and potassium levels are observed in a patient. To distinguish the causes, a careful medication history is considered useful. Testing for myoglobin levels in blood and urine is rarely performed due to its cost.

Clinical sequelae

  • Hypovolemia (sequestration of plasma water within injured myocytes)
  • Hyperkalemia (release of cellular potassium into circulation)
  • Metabolic acidosis (release of cellular phosphate and sulfate)
  • Acute renal failure (nephrotoxic effects of liberated myocyte components)
  • Disseminated intravascular coagulation (DIC)
  • Hypocalcemia (low calcium levels due to precipitation with phosphate), followed by hypercalcemia (as renal function recovers)

Read more at Wikipedia.org


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Rhabdomyolysis In Three Lung Transplant Patients Due To The Drug Combination: Cyclosporin, Lovastatin, And Itraconazole
From CHEST, 10/1/99 by Lisa L Allenspach

Purpose: Lung transplant patients frequently are colonized with aspergillus and are subsequently treated with itraconazole. Many such patients also have elevated cholesterol levels due to cyclosporin and are on HMG-CoA reductase inhibitors. Lovastatin combined with cyclosporin has been rarely reported to cause rhabdomyolysis. We describe three lung transplant patients with rhabdomyolysis due to a combination of cyclosporin, lovastatin, and itraconazole.

Methods: From chart review we describe three lung transplant recipients taking cyclosporin and lovastatin for hypercholesterolemia that became colonized with as. pergillus. The addition of itraconazole to their stable medication regimen resulted in the development of rhabdomyolysis.

Results: One individual developed acute renal failure following rhabdomyolysis requiring hospitalization. All 3 patients experienced muscle weakness, pain and fatigue associated with elevated creatine phosphokinase levels and all recovered with discontinuation of lovastatin and/or itraconazole.

Conclusion: The drug interaction as described is preventable and should be kept in mind when patients on cyclosporin and lovastatin are placed on itraconazole. The mechanism of this interaction appears to be the result of itraconazole's ability to inhibit the degradation of lovastatin leading to a marked rise in lovastatin levels.

Clinical Implications: We advocate discontinuation of lovastatin when itraconazole is administered to lung transplant patients on cyclosporin A.

Lisa L Allenspach, MD(*); K G Klosterman, RN, BSN, CCTC; L Thomson, RN; K M Chan, MD and R SD Higgins, MD. Divisions of Pulmonary and Critical Care, and Cardiothoracic Surgery, Henry Ford Hospital, Detroit, MI.

COPYRIGHT 1999 American College of Chest Physicians
COPYRIGHT 2000 Gale Group

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