ObjectiveTo compare two dosing regimens of acetazolamide for the reversal of metabolic alkalosis in mechanically ventilated patients with asthma or chronic obstructive pulmonary disease.DesignA randomized, double-blind, placebo-controlled trial.SettingA 35-bed medical intensive care unit in a tertiary care teaching hospital.Patientsor=to4 mEq/L) not receiving acetazolamide or sodium bicarbonate in the previous 72 hrs.InterventionsStratified by previous diuretic use and randomized to receive intravenous administration of acetazolamide, one dose of 500 mg or 250 mg every 6 hrs for a total of four doses.Measurements and Main ResultsSerum bicarbonate and potassium concentrations 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 techniques, no difference was found between the two dosing regimens at any point over the study period for serum bicarbonate, serum potassium, or urine chloride end points. Results did not differ between diuretic- and nondiuretic-treated patients. Serum bicarbonate concentrations remained significantly decreased in both treatment groups 72 hrs after administration of the first acetazolamide dose (31.8 +/- 4.9-25.3 +/- 3.8 mEq/L, p < .0001 [250 mg x 4]; 31.9 +/- 25.4-25.4 +/- 3.6 mEq/L, p < .0001 [500 mg x 1]).ConclusionsWe conclude that a single 500-mg dose of acetazolamide reverses nonchloride responsive metabolic alkaloses in medical intensive care unit patients as effectively as multiple doses of 250 mg. Studies to examine the prolonged duration of action of acetazolamide observed in this study as well as the effect of acetazolamide on clinical end points, such as duration of mechanical ventilation, are warranted. (Crit Care Med 1999; 27:1257-1261)