EMmedonline

Definition

• Rhabdomyolysis is a clinical and biochemical syndrome that results from acute necrosis of skeletal muscle fibres and leakage of cellular contents into circulation.

Pathophysiology

• Damage to myocyte causes an influx of sodium into cell and an accumulation of cytosolic calcium due to a combination of direct injury to the cell and to increased activity of the sodium-calcium exchange mechanism that attempts to extrude sodium from the cell in exchange for calcium.

• The high intracytoplasmic calcium concentration has a number of deleterious effect, including activation of phospholipase A2, which results in the production of toxic metabolite and cell death.

ETIOLOGY

DIAGNOSIS

• Total CK

  • Total Creatine Kinase is the most sensitive test.

  • A five fold or greater increase in serum CK in the absence of cardiac or brain injury is diagnostic of rhabdomyolysis

• Myoglobin

  • Myoglobin is an oxygen binding protein found in skeletal and cardiac muscle and is involved in oxidative metabolism.

  • Myoglobin elevates even before CK elevates. Myoglobin enters urine when the plasma concentration is >1.5 mg/dl .

  • Urine Myoglobin causes typical reddish brown discolouration of the urine.

  • Myoglobin is rapidly and unpredictably eliminated by hepatic metabolism.Myoglobin reaches normal value within 1 -6 hrs. Therefore test for myoglobin in plasma or urine are not a sensitive diagnostic procedure.

  • Red discoluration of the urine when erythrocyte cannot be detected by microscope must be hemoglobinuria or myoglobinuria unless the colour of urine is due to drugs or metabolite.

  • Dip stick test : Since myoglobin contains heme qualitative test such as dip stick donot differentiate among hemoglobin, myoglobin and red blood cells

• Serum electrolytes including phosphorus and calcium should be determined.

• Uric acid level

• CBC, PT, aPPT, Fibrinogen levels has to checked.

• ABG : Wide anion gap acidosis

Complication

• Acute renal failure :

  • It is due to renal vasconstriction, intraluminal cast formation and direct heme induced cytotoxicity

  • Myoglobin is usually bound to plasma, when large amount of myoglobin exceeding the capacity to bind is released, it gets filtered by glomeruli and reaches tubules, where it may cause obstruction and renal dysfunction.

• Metabolic disarrangement

  • Hyperkalemia

  • Hyperphosphatemia : Due to release of phosphorus from the damaged cells.

  • Hyperuricemia : Nucleosides are released from disintegrating cell nuclei into blood and metabolized in the liver to purines such as xanthine, hypoxanthine and uric acid which causes tubular obstruction.

  • Hypocalcemia : Occurs early in rhabdomyolysis. It is due to deposition of calcium salts in necrotic muscles, due to the hyperphosphatemia and decreased levels of 1,25 dihydroxycholecalciferol.

  • Hypercalcemia : Occurs during recovery period due to secondary hyperparathyroidism and extrusion of calcium from recovering muscle cells.

  • Hypophosphatemia

• Albumin

  • Initially patient may have hyperalbuminemia but once the patient is hydrated plasma volume expands and there will be leak of albumin due to capillary leak leading to hypoalbuminemia.

• DIC

• Mechanical complication

  • Compartment syndrome

  • Peripheral neuropathy

Treatment

• Hydration

  • Aggressive IV rehydration for first 24 -72 hrs.

  • Rapid infusion of IV crystalloids at a rate of 2.5 ml/kg/h with a goal of maintaining urine output of 2ml/kg/h.

  • Potassium or lactate containing fluid must be avoided.

• Correction of electrolytes

• Alkalinisation of urine

  • Alkalination of urine may inhibit myoglobin induced lipid peroxidation.

  • It is achieved by continuous IV Infusion of sodium bicarbonate aiming for a urinary Ph >7.

  • Suggested regimen is 0.9% NaCl with 1 amp of sodium bicarbonate at 100ml/hr

  • OR Each litre of NS alternate with 1L of 5% Dextrose with 100 mmol of bicarbonate.

  • Disadvantage : Hypocalcemia

• Mannitol :

  • Mannitol is controversial. Efficacy is not proven. Currently not recommended

  • 10 ml/hr if urine output >20ml/hr

Advantages of using mannitol

• Mannitol increases renal blood flow and GFR

• It is an osmotic agent that attracts fluid from interstitial compartment

• Mannitol is an osmotic diuretic that increases urinary flow and prevents obstructive myoglobin cast.

• Myoglobin scavenges free radicals.

• Diuretics

  • Loop diuretics increases tubular flow and decrease the risk of precipitation of myoglobin, while simultaneously acidifying urine and calcium losses.

Reference

• Tintinalli

• Rhadomyolysis, By John D hunter ;Oxford journal 2006