A pilot randomised controlled trial evaluating the pharmacodynamic effects of furosemide versus acetazolamide in critically ill patients

Objective: To compare the physiological and biochemical effects of a single intravenous dose of furosemide or acetazolamide in critically ill patients. Design: Single centre, pilot randomised controlled trial. Setting: Large tertiary adult intensive care unit (ICU). Participants: Twenty-six adult ICU patients deemed to require diuretic therapy. Intervention: Single dose of intravenous 40 mg furosemide or 500 mg acetazolamide. Main outcome measures: Data were collected on urine output, cumulative fluid balance, and serum and urine biochemistry for 6 hours before and 6 hours after diuretic administration. Results: Study patients had a median age of 55 years (IQR, 50-66) and median APACHE III score of 44 (IQR, 37-52). Furosemide caused a much greater increase in-urine output and much greater median mass chloride excretion (121.7 mmol [IQR, 81.1-144.6] v23.3 mmol [IQR, 20.4-57.3]; P < 0.01) than acetazolamide. Furosemide also resulted in a progressively more negative fluid balance while acetazolamide resulted in greater alkalinisation of the urine (change in median urinary pH, +2 [IQR, 1.75-2.12] v 0 [IQR, 0-0.5]; P = 0.02). In keeping with this effect, furosemide alkalinised and acetazolamide acidified plasma (change in median serum pH, +0.03 [IQR, 0.01-0.04] v -0.01 [IQR, -0.04 to 0]; P = 0.01; change in median serum HCO3-, +1.5 mmol/L [IQR, 0.75-2] v -2 mmol/L [IQR, 3 to 0]; P < 0.01). Conclusions: Furosemide is a more potent diuretic and chloriuretic agent than acetazolamide in critically ill patients, and achieves a threefold greater negative fluid balance. Compared with acetazolamide, furosemide acidifies urine and alkalinises plasma. Our findings imply that combination therapy might be a more physiological approach to diuresis in critically ill patients.