Acute Kidney Injury
Conditions
Keywords
acute kidney injury, renal replacement therapy, hemodynamics, preload dependence, net ultrafiltration
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.
Interventions
DIAGNOSTIC_TESTFast ultrafiltration challenge
The fast ultrafiltration challenge will be performed once in all enrolled participants, in the order defined by randomization. The 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. 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.
DIAGNOSTIC_TESTSlow ultrafiltration challenge
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.
Sponsors
Hospices Civils de Lyon
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic Performance of the Net Ultrafiltration (UF NET) Challenge to Detect de Novo Preload Dependence | Baseline and immediately at the end ot each UF NET challenge (approximately 15-30 minutes, 1 day apart) | The diagnostic performance 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 the challenge, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Respective Diagnostic Performance of the Fast and Slow Net Ultrafiltration (UF NET) Challenge to Detect de Novo Preload Dependence | Between baseline and end of the UF NET challenge | 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. |
| Preload Dependence Prevalence After a UF NET Challenge | At the end of the UF NET challenge | 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. |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORLaurent BITKER, MD
Hospices Civils de Lyon
Participant flow
Recruitment details
64 patients were screened between june 2022 and december 2024
Pre-assignment details
20 patients were randomized. Of the 44 not randomized, 44 met inclusion criteria and met exclusion criteria.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62 years |
| Norepinephrine dose (tartrate formula) | 0.23 µg/kg/min |
| Race and Ethnicity Not Collected | 0 Participants |
| Region of Enrollment France | 20 participants |
| Sepsis-related Organ Failure Assessment (SOFA) | 12 Units on a scale |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 19 | 0 / 17 |
| serious Total, serious adverse events | 11 / 19 | 13 / 17 |
Outcome results
None listed