Clinical trial NCT05214729: A Net Ultrafiltration Challenge to Predict Preload-dependence (UF CHALLENGE)
Official title: Diagnostic Performance of a Net Ultrafiltration Challenge to Predict Preload Dependence in Critically Ill Patients Under Continuous Renal Replacement Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Kidney Injury
Keywords: acute kidney injury
renal replacement therapy
hemodynamics
preload dependence
net ultrafiltration
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2022-01-31
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief summary: Hemodynamic instability episodes are a frequent complication of renal replacement therapies in critically ill patients, and their incidence is associated with worse survival. Hypovolemia, identified by the existence of biventricular preload dependence, is responsible for one episode out of two, and may justify a decrease in or cessation of fluid removal by net ultrafiltration (UF). To date, preload dependence is most frequently identified by evaluating the effects on cardiac output of postural changes (passive leg raising), impact of cardio-pulmonary interactions in ventilated patients, or fluid challenge. However, none of these tests may help identify a patient whose cardiac output is at risk of becoming preload dependent, that is situated at the inflexion point of the Frank Starling curve.

Our study aims to evaluate the effects on cardiac output (measured by a transpulmonary thermodilution technique) of 2 net ultrafiltration challenges, consisting fast removal of 250 ml of ultrafiltrate over 15 and 30 minutes respectively, and compare their diagnostic performance to the reference technique of preload dependence assessed by postural changes (passive leg raising) performed after the UF challenge.

Enrolled participants will undergo both UF challenges, following a randomized crossover design, in which the order of UF challenge duration (15 or 30 minutes) is randomized, separated by a washout period of 24 hours.


Eligibility criteria: Inclusion Criteria:

* adult patient, aged 18 year or older
* under mechanical ventilation and continuous general anesthesia, with a positive end-expiratory pressure of 5 cmH2O or more
* with stage 3 KDIGO acute kidney injury
* treated with continuous renal replacement therapy for less than 14 days
* ongoing continuous cardiac output monitoring
* with a predicted intensive care length of stay of 24 hours or more at time of screening

Exclusion Criteria:

* High arterial lactate concentration, \> 4.0 mmol/L at time of screening
* Calibrated cardiac index \< 2.0 L/min/m2 or \> 4.0 L/min/m2 at time of screening
* Positive postural change maneuver in the last 2 hours preceding screening
* Patient under extracorporeal membrane oxygenation
* Patient with active bleeding requiring emergent transfusion
* Patient under chronic maintenance dialysis or renal transplant recipient
* Acute ischemic or hemorrhagic stroke complicated with coma and requiring mechanical ventilation
* Fulminant hepatitis (acute liver injury, hepatic encephalopathy, icterus and a drop in prothrombin \< 50% in less that 15 days
* Impossible postural change maneuver
* Pregnant or lactating patient
* Imminent death
* Patient under legal protection measures as by French regulation
* Patient already enrolled in the present study
* Patient already participates in a study with protocolized net ultrafiltration, ongoing at time of screening

Primary outcomes:
measure: UF challenge diagnostic performance to identify preload dependence risk, evaluated by the area under the curve of the receiver-operating characteristic curve (ROC) of the relative cardiac output variation
timeFrame: The relative variation in cardiac output induced by UF challenges is quantified immediately at the end of UF challenges. The postural maneuver is performed immediately after the end of UF challenges.
Secondary outcomes:
measure: Respective diagnostic performances of slow and fast UF challenges to identify preload dependence risk, evaluated by their respective ROC of the relative cardiac output variation.
timeFrame: The relative variation in cardiac output induced by UF challenges is quantified immediately at the end of UF challenges. The postural maneuver is performed immediately after the end of UF challenges.
measure: Optimal threshold value of the relative cardiac output variation (in %) following a UF challenge
timeFrame: The relative variation in cardiac output induced by UF challenges is quantified immediately at the end of UF challenges.
measure: UF challenge diagnostic performance to identify pre-existing preload dependence, evaluated by the ROC of the relative cardiac output variation.
timeFrame: The relative variation in cardiac output induced by UF challenges is quantified immediately at the end of UF challenges. The postural maneuver is performed immediately before UF challenges.
measure: Comparison of slow and fast UF challenge diagnostic performance, using their respective ROC of relative cardiac output variation.
timeFrame: The relative variation in cardiac output induced by UF challenges is quantified immediately at the end of UF challenges.
measure: Impact of UF challenges on hemodynamics: central venous pressure (mmHg), heart rate (bpm), mean and pulse arterial pressures (mmHg), extravascular lung water (ml/kg), vascular permeability, and global end diastolic volume (ml/kg).
timeFrame: The variation in hemodynamic parameters induced by UF challenges is quantified immediately at the end of UF challenges.
measure: Association of UF challenges with hemodynamic instability, quantified by the elapsed time between the UF challenge and the occurrence of first hemodynamic instability episode, censored at 8 hours.
timeFrame: Censor time at 8 hours after the end of the UF challenge. This evaluation and time frame is applied twice, after each UF challenge in all enrolled patients.
Other outcomes:
Locations:
city: Lyon
country: France
facility: Department of Intensive Care, Croix Rousse hospital, Hospices Civils de Lyon
Study officials:
affiliation: Hospices Civils de Lyon
name: Laurent BITKER, MD
role: PRINCIPAL_INVESTIGATOR
References: