The slow ultrafiltration challenge will be performed once in all enrolled participants, in the order defined by randomization. The slow ultrafiltration challenge consists of the net removal of 250 ml of ultrafiltrate by setting net ultrafiltration rate to 500 ml/h, applied for 30 minutes. The cardiac output will be measured before and after the UF challenge, by mean of the transpulmonary thermodilution technique, and its relative variation from baseline will be quantified to evaluate the impact of the UF challenge on cardiac preload.

The UF challenge will be preceded and immediately followed by a postural change maneuver to assess the presence or absence of preload dependence. The postural change maneuver is positive in case of a +10% variation in continuous cardiac index over 1 minute, and is considered as the reference diagnostic test to which UF challenge diagnostic performance will be compared.

The rate (in %) of UF NET challenges after which a preload-dependence status was identified using the reference diagnostic method, consisting of a postural maneuver (passive leg raising or Trendelenburg maneuver) during which the relative variation in pulse-contour continuous cardiac index was assessed over 1 minute. The test was positive if the relative variation in pulse-contour continuous cardiac index increased by more than 10% during the maneuver, and negative otherwise.

The Slow to Fast Group corresponds to enrolled patients randomized, following the sequential crossover design, to first perform the slow UF challenge immediately after inclusion, followed by the fast UF challenge after a washout period of 24 hours.

Fast ultrafiltration challenge consists of the net removal of 250 ml of ultrafiltrate by setting net ultrafiltration rate to 1000 ml/h, applied for 15 minutes.

Slow ultrafiltration challenge consists of the net removal of 250 ml of ultrafiltrate by setting net ultrafiltration rate to 500 ml/h, applied for 30 minutes.

Total of all reporting groups

Race and Ethnicity were not collected from any participant.

Total SOFA score, ranging from 0 (lowest possible value) to 24 (highest possible value), constructed on the addition of the sub-scores related to 6 organ-failure domains (hemodynamic, respiratory, neurological, renal, liver and coagulation), each with a value between 0 and 4. Higher score values indicate greater clinical severity.

The respective diagnostic performance of fast and slow challenges was assessed using the area under the receiver-operating curve (AUROC) of the relative variation in calibrated cardiac index, measured at baseline and at the end of fast and slow challenges, and compared to the reference standard consisting in the result of a postural maneuver (passive leg raising or Trendelenburg) evaluating preload dependence using pulse-contour continuous cardiac index variation (positive if > 10% or negative if ≤ 10%) performed at the end of the challenge.

All enrolled patients underwent two UF NET challenges, one fast and one slow, consisting in the removal of 250 ml of ultrafiltrate in randomized order and in a cross-over design (with a 24h wash-out period between challenged). 4 patients did not perform the second challenge (1 fast and 3 slow) due to the presence of predefined exit criteria during the wash-out period.

The rate (in %) of UF NET challenges after which a preload-dependence status was identified using the reference diagnostic method, consisting of a postural maneuver (passive leg raising or Trendelenburg maneuver) during which the relative variation in pulse-contour continuous cardiac index was assessed over 1 minute. The test was positive if the relative variation in pulse-contour continuous cardiac index increased by more than 10% during the maneuver, and negative otherwise.

Five challenges (4 fast, 1 slow, all related to the first visit) were a posteriori identified as being preload-dependent prior to challenge start, leaving 31 challenges (in 17 patients) out of a total of 36 challenges (in 20 patients).

This analysis was a priori planned to be performed on all UF NET challenges (irrespective of their duration, slow or fast), and each study groups (slow and fast, respectively).

Slow ultrafiltration challenge consists of the net removal of 250 ml of ultrafiltrate by setting net ultrafiltration rate to 500 ml/h, applied for 30 minutes.

Hemodynamic instability was defined as the occurence of tachycardia (>120 bpm), hypotension (MAP < 65 mmHg with a therapeutic intervention), drop in cardiac index > 15%, new onset mottles. Multiple episodes could be reported in the same patient.