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'Rhabdomyolysis' is the rapid breakdown of skeletal muscle tissue due to traumatic injury, either mechanical, physical or chemical. The principal result is a large release of the CPK enzymes and other cell byproducts into the blood system and acute renal failure due to accumulation of muscle breakdown products, several of which are injurious to the kidney. Treatment is with intravenous fluids, and dialysis if necessary.

Contents

Causes

Pathophysiology

Diagnosis

Therapy

References

External links

Causes

Injury leading to rhabdomyolysis can be due to mechanical, physical and chemical causes:

★ mechanical: crush trauma, burns, 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, extreme physical exertion (although most heavy exercise does not cause kidney damage)^[1]

★ 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, first-generation H1-receptor antagonists (e.g. diphenhydramine), alcohol, heritable muscle enzyme deficiencies, electrolyte abnormalities, infections, or endocrinopathies. Skeletal muscle relaxants that are consumed in overdose are rarely associated with this condition.[1]
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 CPK 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, but may be useful.
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 CPK, which confirms the diagnosis.

Therapy

The main therapeutic measure is hyperhydration (by administering intravenous fluids), and if necessary the use of osmotic 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).
If the exacerbating cause includes overdose of skeletal muscle relaxants and/or tricyclic antidepressants the treatment protocols include Gastric decontamination since it is fairly effective because the Anticholinergic effects of tricyclics and cyclobenzaprine delay gastric emptying and therefore it becomes possible to obtain tablet residues even after significant time elapse. Ventricular arrhythmias QRS widening, or intraventricular conduction abnormalities should be treated with sodium bicarbonate 1 meq/kg IV bolus and repeated if arrhythmias persist this should be followed by IV infusion of sodium bicarbonate to produce an arterial pH of 7.5. The mechanism of action of sodium bicarbonate is unknown.[2]

References

1. Serum creatine kinase levels and renal function measures in exertional muscle damage, Clarkson P, Kearns A, Rouzier P, Rubin R, Thompson P, , , Med Sci Sports Exerc, 2006


★ Cecil Textbook of Medicine

★ The Oxford Textbook of Medicine

★ 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, July 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.

★ Larbi, E.B. Drug-induced rhabdomyolysis

★ Chabria, S.B Cyclobenzaprine induced rhabdomyolysis