What is the role of urinary alkalization and enhanced excretion in the treatment of salicylate toxicity?

Updated: Jun 06, 2020
  • Author: Muhammad Waseem, MBBS, MS, FAAP, FACEP, FAHA; Chief Editor: Timothy E Corden, MD  more...
  • Print

Provide treatment for correction of fluid deficits and enhancement of excretion and elimination. Administer lactated Ringer or isotonic sodium chloride solution for volume expansion at 10-20 mL/kg/h until a 1- to 1.5-mL/kg/h urine flow is established. Provide maintenance fluids to maintain urinary alkalization. Forced diuresis is not recommended. The greater the urine flow, the more difficult it is to alkalinize the urine. Be cautious of excessive fluid volumes in cases of salicylate-induced pulmonary edema.

Renal excretion of salicylic acid depends on urinary pH. Increasing the urine pH to 7.5 prevents reabsorption of salicylic acid from the urine. [27] Because acidosis facilitates transfer of salicylate into tissues, especially in the brain, it must be aggressively treated by raising blood pH higher than brain pH, thereby shifting the equilibrium from the tissues to the plasma.

Concomitant alkalization of blood and urine keeps salicylates away from brain tissue and in the blood, in addition to enhancing urinary excretion. When the urine pH increases to 8 from 5, renal clearance of salicylate increases 10-20 times. Raising the urinary pH level from 6.1 to 8.1 results in a more than 18-fold increase in renal clearance by preventing nonionic tubular back-diffusion, which decreases the half-life of salicylates from 20-24 hours to less than 8 hours. Because aspirin is a weak acid, it ionizes when exposed to a basic environment, such as alkaline urine. Ions are poorly reabsorbed in the tubules and are excreted more readily. This phenomenon is called ion trapping and also works well for overdoses of other weak acids, such as phenobarbital.

Most experts alkalinize the urine by giving an initial intravenous bolus of 1 mEq/kg of sodium bicarbonate and then start a sodium bicarbonate intravenous infusion. The continuous intravenous infusion is made by adding 3 ampules of sodium bicarbonate (each ampule containing 44 mEq of sodium bicarbonate) to a liter of D5W. The infusion is initially run at 2 times the maintenance rate and then titrated to keep the urinary pH greater than 7.5. Once the patient is putting out good amounts of urine, and it has been established that the patient is not in renal failure and is not hyperkalemic, then 40 mEq of potassium can be added to each liter of this solution. A simple regimen for the use of bicarbonate in pediatric salicylate poisoning has been described by Ong. [28]

Hypokalemia and dehydration limit the effectiveness of urine alkalization. Hypokalemia prevents excretion of alkaline urine by promoting distal tubular potassium reabsorption in exchange for hydrogen ions. Symptomatic patients typically have low or borderline-low serum potassium concentration. Treatment with sodium bicarbonate alone may produce further intracellular shift of potassium ions, which further impairs the ability to excrete alkaline urine. Repletion of potassium is often necessary, even when serum potassium levels are in the low reference range (eg, < 4.5 mEq/L).

Urinary alkalization should be continued at least until serum salicylate levels decrease into the therapeutic range (< 30 mg/dL). Although acetazolamide results in the formation of a bicarbonate-rich alkaline urine, it unfortunately also causes metabolic acidosis that can worsen toxicity and, therefore, should not be used.

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!