RHABDOMYOLYSIS

Differential Diagnosis

This disorder results from skeletal muscle injury leading to the release of the damaged cellular constituents into the extracellular fluid. Rhabdomyolysis is a potentially fatal disorder and is an etiology of acute renal failure . Common causes of rhabdomyolysis include physical overexertion, especially in hot and humid climates, muscle crush injuries, alcohol and heroin abuse, hypokalemia, and hypophosphatemia. Exercise induced rhabdomyolysis is seen almost exclusively in men even though women commonly participate in strenuous activity.

Symptoms of rhabdomyolysis include an acute illness shortly after the precipitating event characterized by fever, weakness, and muscles that are painful, swollen, and tender. Nausea and vomiting are commonly associated with the acute event.

Darkening of the urine is a commonly associated abnormality. Dark urine may be secondary to one of four etiologies: myoglobinuria, hemoglobinuria, porphyria, or hematuria. The urine of porphyria, unlike the other etiologies, will not yield a positive hematest on dipstick. Also, patients with acute intermittent porphyria and porphyria cutanea tarda will give a history of urine that went from colorless to red or brown after exposure to light. Patients with erythropoietic uroporphyria will have red or pink urine but will also develop vesicular skin lesions on exposure to light, and this will occur at an early age. Myoglobin, unlike hemoglobin, does not bind to haptoglobin when released into the plasma; therefore, myoglobinuria, which occurs secondary to myoglobinemia (the result of muscular damage), is not associated with a decreased serum haptoglobin level as is hemoglobinuria. Hemoglobinuria means free hemoglobin is present in the urine. This uncommon lab abnormality is usually the result of intravascular hemolysis. A quick and effective method to differentiate hemoglobinuria from myoglobinuria is to examine the patients plasma, which will be red with hemoglobinuria but will appear normal with myoglobinuria. Myoglobinuria and hemoglobinuria may be differentiated from hematuria in that all will have a dipstick positive hematest, but only hematuria will have red blood cells present on microscopic examination of the urine.

Rhabdomyolysis is characterized by an elevated CK level usually into the thousands (this is characteristic of rhabdomyolysis). Laboratory abnormalities often associated with rhabdomyolysis include hyperkalemia, hyperuricemia, hypocalcemia (this is a finding early in the disease course), metabolic acidosis with an elevated anion gap, hyperphosphatemia, hypermagnesemia, and hypercalcemia (this occurs later in the disease course). If myoglobin induced nephrotoxicity occurs, acute renal failure (ARF) may be present. With rhabdomyolysis induced acute renal failure, the rise in serum creatinine is often rapid with daily increases of 1 mg/dL or more. Acute renal failure associated with rhabdomyolysis is different from other causes of acute tubular necrosis (ATN) in that the fractional excretion of sodium (FENa) is low (<1%) whereas other causes of ATN have an elevated FENa (>3%).

Therapy for rhabdomyolysis includes aggressive intravenous normal saline resuscitation. If oliguria is still present after adequate intravenous fluids, intravenous furosemide (40-120 mg) and/or a single dose of mannitol (100 ml of 25% solution IV over 15 minutes) is prudent. The plasma osmolality and osmolal gap (measured osmolality minus calculated osmolality) should be followed serially during mannitol therapy and treatment should be discontinued if there is a lack of diuretic response or if the osmolal gap rises above 55 mOsm/kg. An adequate volume status with good urine output are important goals of therapy acutely and diuretics should be withheld until this is acheived. Some physicians favor alkalinization of the urine with intravenous sodium bicarbonate therapy. This is controversial because even though acidic urine promotes myoglobin nephrotoxicity, the administration of bicarbonate to rhabdomyolysis patients may also promote enhanced deposition of calcium salts in the injured muscles. The serum levels of bicarbonate, calcium and potassium along with the urine pH should be monitored during sodium bicarbonate therapy and treatment should be discontinued if there is a lack of diuretic response or if the urine pH does not rise after 4 to 6 hours. Supportive measures include managing electrolyte abnormalities. Hyperkalemia, which is potentially fatal when associated with oliguria or anuria, may be treated with Kayexalate (15-60 gm PO or 30-50 gm via retention enema). Hyperphosphatemia usually does not require treatment, but if it is severe, therapy may be offered in the form of aluminum hydroxide (600 mg or 5 ml PO Q 4 hours). Hypocalcemia results secondary to the deposition of calcium salts in the damaged muscles. Therapy for hypocalcemia should be withheld as the calcium salts deposited in the damaged muscles are mobilized during the diuretic phase of the associated acute renal failure and result in hypercalcemia, which may be fatal. If the initially low calcium was treated with calcium supplements, this will exacerbate the later occurring hypercalcemia and may even promote fatal levels of hypercalcemia.