Renal response and acid-base balance alterations during furosemide administration

Introduction

Furosemide is one of the most employed diuretics in the ICU for its ability to induce negative water balance. However, one common side effect is metabolic alkalosis [1]. We aimed to describe the time course of urinary excretion and changes in plasmatic acid-base balance in response to the administration of furosemide.

Methods

We connected the urinary catheter of 39 ICU patients to a quasi-continuous urine analyzer (Kidney INstant monitorinG^®), allowing measurement of pH (pHU), sodium, chloride, potassium and ammonium concentrations (Na+U, Cl-U, K+U, NH4+U) every 10 minutes. The study period lasted 3 hours after a single intravenous bolus of furosemide (time 0). In 13 patients receiving two or more administrations over a longer period (46 (26 to 49) hours), according to clinical needs, we reviewed data on fluid therapy, hemodynamics and acid-base balance from the beginning to the end of the observation.

Results

Ten minutes after furosemide administration, Na+U and Cl-U rose from 65 ± 6 to 140 ± 5 and from 109 ± 6 to 150 ± 5 mEq/l respectively, while K+U fell from 60 ± 5 to 39 ± 4 mEq/l (P 0.001 for all electrolytes vs. time 0) with a consequent increase in urinary anion gap (AGU = Na+U + Cl-U - K+U). Urinary output increased from 10 (5 to 19) to 53 (29 to 71) ml/10 minutes (P 0.05). After the first hour Cl-U remained higher than Na+U, which progressively decreased, leading to a reduction in AGU and pHU over time. In parallel, a progressive increment in NH4+U was observed. In patients receiving more than one administration we observed an increase in arterial base excess (1.8 ± 0.8 vs. 5.0 ± 0.6 mmol/l, P 0.001) and plasmatic strong ion difference (SIDpl) (31 (30 to 33) vs. 35 (34 to 36) mEq/l, P = 0.01) during the study period. These changes were due to a decrease in plasmatic Cl^- concentration (109.0 ± 1.1 vs. 106.6 ± 0.9 mEq/l, P = 0.009). Plasmatic sodium and potassium concentrations did not change. In these patients, considering the total amount of administered fluids and urine, a negative water and chloride balance was observed (-460 ± 403 ml and -48 ± 48 mEq, respectively).

Conclusion

Furosemide acts immediately after administration, causing a rise in urinary output, Na+U and Cl-U concentrations. Loop-diuretic-induced metabolic alkalosis may be due to an increased urinary chloride loss and the associated increase in SIDpl.