Restrictive fluid management versus usual care in acute kidney injury (REVERSE-AKI): a pilot randomized controlled feasibility trial

Abstract

Purpose: We compared a restrictive fluid management strategy to usual care among critically ill patients with acute kidney injury (AKI) who had received initial fluid resuscitation.

Methods: This multicenter feasibility trial randomized 100 AKI patients 1:1 in seven ICUs in Europe and Australia. Restrictive fluid management included targeting negative or neutral daily fluid balance by minimizing fluid input and/or enhancing urine output with diuretics administered at the discretion of the clinician. Fluid boluses were administered as clinically indicated. The primary endpoint was cumulative fluid balance 72 h from randomization.

Results: Mean (SD) cumulative fluid balance at 72 h from randomization was - 1080 mL (2003 mL) in the restrictive fluid management arm and 61 mL (3131 mL) in the usual care arm, mean difference (95% CI) - 1148 mL (- 2200 to - 96) mL, P = 0.033. Median [IQR] duration of AKI was 2 [1-3] and 3 [2-7] days, respectively (median difference - 1.0 [- 3.0 to 0.0], P = 0.071). Altogether, 6 out of 46 (13%) patients in the restrictive fluid management arm and 15 out of 50 (30%) in the usual care arm received renal replacement therapy (RR 0.42; 95% CI 0.16-0.91), P = 0.043. Cumulative fluid balance at 24 h and 7 days was lower in the restrictive fluid management arm. The dose of diuretics was not different between the groups. Adverse events occurred more frequently in the usual care arm.

Conclusions: In critically ill patients with AKI, a restrictive fluid management regimen resulted in lower cumulative fluid balance and less adverse events compared to usual care. Larger trials of this intervention are justified.

Keywords: Acute kidney injury; Critically ill; Fluid balance; Restrictive fluid management.

Fig. 1

Flowchart of trial patients. ICU intensive care unit, RRT renal replacement therapy. ^a Diabetic ketoacidosis, non-ketotic coma, severe burns or other clinical reason determined by the medical staff. ^b Glomerulonephritis, vasculitis, acute interstitial nephritis, or post-renal obstruction. ^c Including two exclusion criteria that were removed in a protocol amendment in April 2018 (1) Metformin-induced lactic acidosis or acute liver failure (n = 8) (2) AKI stage 2 or greater is known to have been present for > 48 h (n = 14). These criteria were amended to clarify the exclusion criteria

Fig. 2

Daily fluid input, fluid output and daily fluid balance from randomization in restrictive versus usual care. Boxplots represent median with IQR and range in mL. Bars present the daily balance (not cumulative) in mL. RFM restrictive fluid management