Fluid balance neutralization secured by hemodynamic monitoring versus protocolized standard of care in patients with acute circulatory failure requiring continuous renal replacement therapy: results of the GO NEUTRAL randomized controlled trial

Abstract

Purpose: Net ultrafiltration (UF_NET) during continuous renal replacement therapy (CRRT) can control fluid balance (FB), but is usually 0 ml·h^-1 in patients with vasopressors due to the risk of hemodynamic instability associated with CRRT (HIRRT). We evaluated a UF_NET strategy adjusted by functional hemodynamics to control the FB of patients with vasopressors, compared to the standard of care.

Methods: In this randomized, controlled, open-label, parallel-group, multicenter, proof-of-concept trial, adults receiving vasopressors, CRRT since ≤ 24 h and cardiac output monitoring were randomized (ratio 1:1) to receive during 72 h a UF_NET ≥ 100 ml·h^-1, adjusted using a functional hemodynamic protocol (intervention), or a UF_NET ≤ 25 ml·h^-1 (control). The primary outcome was the cumulative FB at 72 h and was analyzed in patients alive at 72 h and in whom monitoring and CRRT were continuously provided (modified intention-to-treat population [mITT]). Secondary outcomes were analyzed in the intention-to-treat (ITT) population.

Results: Between June 2021 and April 2023, 55 patients (age 69 [interquartile range, IQR: 62; 74], 35% female, Sequential Organ Failure Assessment (SOFA) 13 [11; 15]) were randomized (25 interventions, 30 controls). In the mITT population, (21 interventions, 24 controls), the 72 h FB was -2650 [-4574; -309] ml in the intervention arm, and 1841 [821; 5327] ml in controls (difference: 4942 [95% confidence interval: 2736-6902] ml, P < 0.01). Hemodynamics, oxygenation and the number of HIRRT at 72 h, and day-90 mortality did not statistically differ between arms.

Conclusion: In patients with vasopressors, a UF_NET fluid removal strategy secured by a hemodynamic protocol allowed active fluid balance control, compared to the standard of care.

Keywords: Acute circulatory failure; Continuous renal replacement therapy; Fluid balance; Functional hemodynamics; Pulse contour; Transpulmonary thermodilution.

Fig. 1

Hemodynamic protocol applied 4-hourly in the intervention arm. The protocol was applied by the nursing staff every 4 h between inclusion (H0) and 72 h, and relied on the evaluation of cardiac indices measured by transpulmonary thermodilution, arterial lactate concentrations measured at least every 8 h, central venous pressure, and the result of a postural maneuver (either passive leg raising or Trendelenburg maneuver, represented in the diagram by the silhouettes) evaluating preload dependence. Based on a 3-steps approach, the staff categorized the hemodynamic profile of the patient using the 9 letters and the 3 profile colors, which subsequently led to the adjustment of the UF_NET on the CRRT monitor. Of note, a CVP < 4 mmHg led to a decrease in UF_NET whatever the value of the other parameters. The evaluation took into account the results of the previous evaluation performed 4 h earlier. CVP central venous pressure, PLD-FBT preload dependence evaluated by a fluid bolus challenge, UF_NET net ultrafiltration

Fig. 2

Study flowchart. The total number of patients who met eligibility criteria was estimated using the medical information system of participating ICUs to identify patients receiving vasopressors and CRRT, as exact and continuous screening was rendered difficult due to the coronavirus disease 2019 (COVID-19) pandemic. Hence, reason for non-inclusion could not be prospectively collected and reported. AKI acute kidney injury, CRRT continuous renal replacement therapy, ITT intention-to-treat, mITT modified intention-to-treat, RRT renal replacement therapy

Fig. 3

Cumulative fluid balance measured between H0 and H72 in each study group of the mITT population. The figure shows the cumulative fluid balance in the two groups (controls in red, intervention in blue) over time, between inclusion (H0) up to H72 in the modified ITT population (N = 45). Data is presented using the median value (large dots) of the cumulative fluid balance at each time point, with its interquartile range (vertical bars). At H72, the primary outcome measure of the trial is identified with the large dots circled in black. Individual values of the H72 fluid balance in each study group are also shown (small dots). The “v” symbol at H72 in the intervention arm indicates an outlier value not represented in the figure (H72 fluid balance in this patient = −23,636 ml). The P value evaluates the difference in the cumulative fluid balance at H72 (identified with large data points circled in black) using the Wilcoxon–Mann–Whitney rank-sum test. mITT modified intention-to-treat