Single versus multiple doses of acetazolamide for metabolic alkalosis in critically ill medical patients: A randomized, double-blind trial

Objective: To compare two dosing regimens of acetazolamide for the reversal of metabolic alkalosis in mechanically ventilated patients with asthma or chronic obstructive pulmonary disease. Design:A randomized, double-blind, placebo-controlled trial. Setting: A 35-bed medical intensive care unit in a tertiary care teaching h ospital. Patients: Forty mechanically ventilated patients with a metabolic alkalosis (arterial pH greater than or equal to 7.48 and serum bicarbonate concentra tion greater than or equal to 26 mEq/L) resistant to fluid or potassium the rapy (serum potassium concentration, greater than or equal to 4 mEq/L) not receiving acetazolamide or sodium bicarbonate in the previous 72 hrs. Interventions: Stratified by previous diuretic use and randomized to receiv e intravenous administration of acetazolamide, one dose of 500 mg or 250 mo every 6 hrs for a total of four doses. Measurements and Main Results: Serum bicarbonate and potassium concentratio ns were drawn every 6 hrs for 72 hrs, arterial blood gases were drawn every 12 hrs for 72 hrs, and both urine chloride and pH were drawn at hours 0, 6 , 12, 18, 24, 48, and 72. By using generalized estimating equation techniqu es, no difference was found between the two dosing regimens at any point ov er the study period for serum bicarbonate, serum potassium, or urine chlori de end points. Results did not differ between diuretic- and nondiuretic-tre ated patients. Serum bicarbonate concentrations remained significantly decr eased in both treatment groups 72 hrs after administration of the first ace tazolamide dose (31.8 +/- 4.9-25.3 +/- 3.8 mEq/L, p < .0001 [250 mg x 4]; 3 1.9 +/- 25.4-25.4 +/- 3.6 mEq/L, p < .0001 [500 mg x 1]). Conclusions: We conclude that a single 500-mg dose of acetazolamide reverse s nonchloride responsive metabolic alkaloses in medical intensive care unit patients as effectively as multiple doses of 250 mg. Studies to examine th e prolonged duration of action of acetazolamide observed in this study as w ell as the effect of acetazolamide on clinical end points, such as duration of mechanical ventilation, are warranted.