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

Alastair JW Brown, Salvatore L. Cutuli, Glenn M. Eastwood, Laurent Bitker, Philip Marsh, Rinaldo Bellomo

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Abstract

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] v 23.3 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.

Original languageEnglish
Pages (from-to)258-264
Number of pages7
JournalCritical Care and Resuscitation
Volume21
Issue number4
Publication statusPublished - Dec 2019

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