PURPOSE: Furosemide is the most commonly used diuretic in intensive care units (ICU). We aimed to evaluate the physiological effects of adjunctive acetazolamide with furosemide on diuresis and the prevention of potential furosemide-induced metabolic alkalosis. MATERIALS AND METHODS: We performed a two-center, pilot, open-label, randomized trial. Where the treating physicians planned intravenous diuretic therapy, we randomized ICU patients to a bolus of furosemide (40 mg) plus acetazolamide (500 mg) (n = 15) or furosemide alone (40 mg) (n = 15). Urine output, additional furosemide use, acid-base parameters, and electrolytes were compared following a Bayesian framework. RESULTS: Adjunctive acetazolamide didn't increase urine output in the first six hours (mean difference: -112 ml, credible interval: [-742, 514]). However, compared with furosemide alone, it maintained a greater urine output response to furosemide over 24 h, with 100 % probability. Acetazolamide also acidified plasma (pH difference: -0.045, [-0.081, -0.008]) while alkalinizing urine (1.10, [0.04, 2.11]) at six hours, compared to furosemide alone with >
95 % probability. Finally, we didn't observe severe acidosis or electrolyte disturbances over 24 h. CONCLUSIONS: Adjunctive acetazolamide may increase diuretic efficacy and counterbalance furosemide-induced metabolic alkalosis without safety concerns. Larger trials are warranted to verify these findings and assess their impacts on clinical outcomes. REGISTRATION NUMBER: ACTRN12623000624684. REGISTRATION TITLE: A pilot trial of single versus dual diuretic therapy in the intensive care unit.