rhabdomyolysis

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, certain mushrooms like Tricholoma equestre, some antibiotics, statins, alcohol

Rhabdomyolysis can occur in acute hepatic porphyrias. Drug induced rhabdomyolysis should be investigated for acute hepatic porphyrias.

Drugs such as lovastatin, a hydroxymethylglutaryl-coenzyme A reductase inhibitor, have been associated with rhabdomyolysis. Drug-induced rhabdomyolysis appears to be increasing in incidence possibly 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. Often the diagnosis is suspected when a urine dipstick test is positive for blood, but no cells are seen on microscopic analysis. This suggests myoglobinuria, and usually prompts a measurement of the serum creatine kinase, which confirms the diagnosis.

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)

Therapy

The main therapeutic measure is hyperhydration (by administering intravenous fluids), and if necessary the use of diuretics (to prevent fluid overload). Alkalinisation of the urine with bicarbonate reduces the amount of myoglobin accumulating in the kidney.

As the electrolytes are frequently deranged, these may require correction, especially hyperkalemia (elevated potassium levels in the blood). Calcium levels are initially low (hypocalcemia), as circulating calcium precipitates in the damaged muscle tissue, presumably with phosphate released from intracellular stores. When the acute renal failure resolves, vitamin D levels rise rapidly, causing hypercalcemia (elevated calcium). Although this resolves eventually, high calcium levels may require treatment with bisphosphonates (e.g. pamidronate).

See also

• Cerivastatin

References

• Cecil Textbook of Medicine
• The Oxford Textbook of Medicine
• Intensive Care Medicine by Irwin and Rippe
• The ICU Book by Marino
• Procedures and Techniques in Intensive Care Medicine by Irwin and Rippe
• Pathogenesis and treatment of renal dysfunction in rhabdomyolysis, S. Holt, K. Moore, Intensive Care Medicine, Volume 27, Number 5, 803 - 811.
• Pathogenesis and treatment of renal dysfunction in rhabdomyolysis, (reply) Panagiotis Korantzopoulos, Dimitrios Galaris, Dimitrios Papaioannides, Intensive Care Medicine, Volume 28, Number 8, 1185 - 1185.
• The pathophysiology of altered calcium metabolism in rhabdomyolysis-induced acute renal failure. Interactions of parathyroid hormone, 25-hydroxycholecalciferol, and 1,25-dihydroxycholecalciferol, Llach F., Felsenfeld A. J., Haussler M. R. ,New Engl J Med 1981; 305:117-123, Jul 16, 1981.
• Serum creatine kinase as predictor of clinical course in rhabdomyolysis: a 5-year intensive care survey, Arthur R. de Meijer, Bernard G. Fikkers, Marinus H. de Keijzer, Baziel G. M. van Engelen, Joost P. H. Drenth, Intensive Care Medicine, Volume 29, Number 7, 1121 - 1125.

External links

• Baggaley, P.: Rhabdomyolysis.
• Rhabdomyolysis. Medline Plus.
• Craig, S.: Rhabdomyolysis. eMedicine.
• Larbi, E.B. Drug-induced rhabdomyolysis