Acetazolamide in Salicylate poisoning

We discussed about a case of salicylate poisoning in noon conference today.

We had some interesting discussion about the role of Acetazolamide in salicylate poisoning.

Acetazolamide is a non bacteriostatic sulfonamide which acts as a carbonic anhydrase inhibitor and thereby causes bicarbonate , sodium and potassium loss in urine. It causes urine alkalization and this is favourable for salicylate excretion in its ionic form. However , acetazolamide has a tendency to decrease systemic Ph because of bicarbonate loss in urine and can potentially increase the neurotoxicity of salicylate. In the clinical setting where we are constantly infusing sodium bicarbonate to achieve alkalemia, the systemic acidosis caused by acetazolamide may not have clinical implication, especially since it is a long acting drug which needs several hours to cause systemic acidosis. If we are aggressively infusing sodium bicarbonate(after a bolus of 2-3 mEq/kg) to prevent systemic acidosis, starting acetazolamide appears reasonable.

There are several case reports of using acetazolamide successfully in older literature(1950-1980)

I do not see any evidence for its use or contra-indication in recent literature.

Many of the salicylate poisoning patients have concomitant hypokalemia and volume contraction.

Hypokalemia leads to increased ammoniageneis and subsequent increased net acid excretion. Volume contraction leads to  secondary hyperaldosteronism and subsequent hypokalemia and alkalemia(by increasing net acid excretion). Both hypokalemia and volume contraction do not favor the excretion of salicylate !

The focus should be on aggressively managing hypokalemia(even if not manifested at the time of presentation, we notice hypokalemia while treating with sodium bicarbonate) , alkalinizing the blood and urine. It is not now considered a standard of care to give acetazolamide for salicylate poisoning since it aggravates hypokalemia, volume contraction and systemic acidosis (although theoretically it can help alkalinize urine -which may not occur in the setting of volume contraction and hypokalemia-both factors resist urine alkalinization)and potentially worsens neurotoxicity of salicylate!

Can we consider acetazolamide to sustain high urine pH after aggressively correcting the volume, hypokalemia and achieving systemic alkalosis? The answer is anybody’s guess!

 

Yuvaraj