The benefit of urinary alkalinization and mannitol in the treatment of rhabdomyolysis

One discussion this week included the benefits of urinary alkalinization and mannitol in treating rhabdomyolysis (RM).

Reference: Bada A, Smith N, and Surgical Critical Care Guidelines Committee. Rhabdomyolysis: Prevention and Treatment. SurgicalCritical 2018, Jul 24.

Summary: RM is the dissolution muscle and release of potentially toxic intracellular components into the systemic circulation. RM has the potential to cause myoglobinuric ARF in 10-15% of such patients. Overall, 10-15% of ARF in the United States is from RM.

There are various causes of RM: vascular interruption, ischemia-reperfusion, crush injury, improper patient positioning, alcohol ingestion, seizures, extreme exercise, electrical injury, infection, hyperthermia, and steroids and neuromuscular blockade (especially in combination).

Non-traumatic causes are being seen with increasing frequency, including bariatric surgery patients. RM is increasingly being seen in clinical practice as the popularity of bariatric surgery is gaining momentum. Several longitudinal studies have found rates of RM after bariatric surgery ranging from 7-77%. A rare syndrome leading to RM specifically related to these patients is known as gluteal compartment syndrome.

Prompt and aggressive restoration of volume is essential and critical to prevent progression to ARF and the need for renal replacement therapy and its inherent cost, morbidity, and mortality. Volume depletion, hypotension and shock combined with afferent arteriolar vasoconstriction due to circulating catecholamines, vasopressin and thromboxane leads to decreased GFR and deficient oxygen delivery to the renal parenchyma. Volume administration can combat some of these disturbances and also dilutes the MG load and reduces cast formation.

Alkalization of urine: High concentrations of MG in the renal tubules cause precipitation with secretory proteins from the tubule cells (Tamm-Horsfell protein) leading to the formation of tubular casts and resultant tubular obstruction to urinary flow. Acidic urine favors this process hence the theoretic benefit of bicarbonate use. These patients are typically already acidotic and have acidic urine. Bicarbonate use increases MG solubility, induces a solute diuresis and can potentially reduce the amount of trapped MG. Complications of overzealous bicarbonate administration, however, include hyperosmolar states, “overshoot alkalosis” and hypernatremia. The use of Diamox has been used for the development of iatrogenic alkalosis.

Mannitol has several potentially beneficial qualities. It is an osmotic diuretic with a rapid onset of action. In contrast to loop diuretics which inhibit the Na-K+/H+ ATPase in the distal tubule cell leading to aciduria, mannitol does not acidify the urine. It is a volume expander, reduces blood viscosity, and acts as a renal vasodilator increasing renal blood flow and leading to increased GFR. Perhaps more importantly, it has been found to be an oxygen free radical scavenger. Free radicals are molecules with an uneven number of electrons and in excess can lead to damage of critical cellular ultrastructural elements, lipid membranes, hyaluronic acid and even DNA. Free radicals lead to lipid peroxidation resulting in increased permeability, cellular edema, calcium influx, cell lysis and release of MG, further perpetuating the clinical syndrome of RM.

1) In patients with significant rhabdomyolysis (CPK ≥ 5,000 IU/L) AND acute renal failure (Cr ≥ 2.0 mg/dL), maintain a urinary output of at least 100 mL/hour. Invasive hemodynamic monitoring may be necessary to ensure adequate volume resuscitation. If such a diuresis is not possible with saline alone, add sodium bicarbonate and mannitol as outlined below until a steady trend towards normalization of CPK is established or until the CPK level is below 5000 IU/L or urinary output averages > 100 mL/hour for 12 consecutive hours. In addition to the patient’s maintenance IVF (Lactated Ringer’s solution), add:

a. In patients with a serum sodium ≤147 meq/L:
• ½ NS with 100 mEq NaHCO3 / L @ 125 cc / hour
b. In patients with a serum sodium > 147 meq/L:
• D5W with 100 mEq NaHCO3 / L @ 125 cc / hour

2) Administer Mannitol, 12.5 g IV q 6 hours.

3) In patients receiving bicarbonate, check a daily ABG.
a. For a pH of ≤ 7.15 or a serum bicarbonate of ≤ 15 mg/dL bolus with 100 mEq NaHCO3 and recheck ABG in 3 hours and repeat until the pH is > 7.15 AND the serum bicarbonate is > 15.
b. Discontinue bicarbonate infusion if pH ≥ 7.50.

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