Rhabdomyolysis

Rhabdomyolysis
Specialty	Emergency medicine

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 creatine kinase (CK) 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.

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)
• 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.

Any drug that 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.

Pathophysiology

Severe cases of rhabdomyolysis often result in myoglobinuria, a condition wherein 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

In general, the diagnosis is 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. This procedure 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 sodium bicarbonate's action in this role is unknown. However, sodium bicarbonate's beneficial effect on kidney function is known to be via the effects of alkalinisation both increasing the urinary solubility of myoglobin leading to its increased excretion and stabilizing ferryl myoglobin complex so preventing myoglobin-induced lipid peroxidation.

References

• Dennis Ausiello; Goldman, Lee. Cecil Textbook of Medicine Single Volume e-dition -- Text with Continually Updated Online Reference. Philadelphia, PA: W.B. Saunders Company. ISBN 0721639011.{{cite book}}: CS1 maint: multiple names: authors list (link)
• Edward Benz; David Weatherall; David Warrell; Cox, Timothy J.; Firth, John B. Oxford Textbook of Medicine. Oxford [Oxfordshire]: Oxford University Press. ISBN 0198569785.{{cite book}}: CS1 maint: multiple names: authors list (link)
• Holt SG, Moore KP (2001). "Pathogenesis and treatment of renal dysfunction in rhabdomyolysis". Intensive care medicine. 27 (5): 803–11. PMID 11430535.
  Subsequent reply:
  * Korantzopoulos P, Galaris D, Papaioannides D (2002). "Pathogenesis and treatment of renal dysfunction in rhabdomyolysis". Intensive care medicine. 28 (8): 1185, author reply 1186. PMID 12400515.{{cite journal}}: CS1 maint: multiple names: authors list (link)* Llach F, Felsenfeld AJ, Haussler MR (1981). "The pathophysiology of altered calcium metabolism in rhabdomyolysis-induced acute renal failure. Interactions of parathyroid hormone, 25-hydroxycholecalciferol, and 1,25-dihydroxycholecalciferol". N. Engl. J. Med. 305 (3): 117–23. PMID 6894630.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• de Meijer AR, Fikkers BG, de Keijzer MH, van Engelen BG, Drenth JP (2003). "Serum creatine kinase as predictor of clinical course in rhabdomyolysis: a 5-year intensive care survey". Intensive care medicine. 29 (7): 1121–5. doi:10.1007/s00134-003-1800-5. PMID 12768237.{{cite journal}}: CS1 maint: multiple names: authors list (link)

External links

• Baggaley, P. (1997). "Rhabdomyolysis". Retrieved 2007-10-14.