Fluid Overload, Critical Illness, Sepsis, ARDS, Trauma
Conditions
Keywords
sepsis, acute respiratory distress syndrome, multiple trauma, critical illness
Brief summary
The RADAR-Canada trial is a pilot RCT undertaken to assess the acceptability of, compliance with, and biologic consequences of a deresuscitation protocol designed to expedite the removal of excess interstitial fluid in patients who remain in a positive fluid balance following admission to an intensive care unit (ICU).
Detailed description
Background: Over the course of an acute illness, critically ill patients typically receive substantial volumes of intravenous fluids, administered for resuscitation, maintenance, and as diluents for medications. A positive fluid balance is associated with adverse clinical outcomes. Whether active reversal of a positive fluid balance through fluid restriction and diuresis will improve outcomes is uncertain. Methods: The Role of Active Deresuscitation After Resuscitation (RADAR) trial is a pilot study to determine the feasibility of a larger trial powered for clinically important outcomes, the acceptability of a deresuscitation protocol, and the impact of a trial on stability of practice patterns. RADAR is an open label pilot trial that will recruit 120 patients from 10 to 12 active sites in Canada. Eligible patients will be 18 years or older, mechanically ventilated \>48 hours but in the ICU for less than five days, and in a calculated positive fluid balance of \> three liters. Patients will be randomized to either usual care or a deresuscitation protocol incorporating a fluid minimization strategy and diuresis. Results and Discussion: Evidence that recruited patients will be managed according to the trial protocol, with a withdrawal rate of less than 5%, a compliance rate of \>75% and a crossover rate of \<10% will establish the acceptability of the protocol. A mean difference in fluid balance between groups of more than three liters 72 hours after enrolment will establish the feasibility of the protocol. Analyses of clinical effects will be secondary analyses. Survival to day 90 following randomization will be measured, and other clinical measures will provide estimates of rates of key outcomes to inform the design of a definitive, adequately powered trial.
Interventions
o.5 mg/kg bid or tid IV
Diuretic as needed
Sponsors
Canadian Institutes of Health Research (CIHR)
Unity Health Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Masking of the health care team will not be feasible as they must administer the intervention
Intervention model description
RADAR-Canada is a parallel group CT in which study participants are randomized in a 1:1 ratio to protocolized deresuscitation or usual care
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or older 2. Mechanically ventilated for \> 48 hours 3. Calculated volume accumulation \> 3 liters since ICU admission or pitting edema in at least two sites (arms, legs, or trunk) 4. Admitted to ICU for ≤ five days 5. Informed consent obtained from patient or alternate decision-maker
Exclusion criteria
1\. Lack of consent from patient or substitute decision maker or from responsible physician 2. Active bleeding (defined as \> 2 units transfused RBC in past 24 hours) 3. Hemodynamic instability (defined as use of vasopressors \>0.1 µg/kg/minute norepinephrine or equivalent, or increase in vasopressor dose over past 6 hours) 4. Currently receiving dialysis, or plans to initiate dialysis imminently 5. P/F ratio \< 75 6. Subarachnoid hemorrhage 7. Severe traumatic brain injury with admission GCS \<8 8. Diabetic ketoacidosis or hyperosmolar state 9. Acute cardiac failure or cardiogenic shock 10. Suspected or established diabetes insipidus 11. Allergy to furosemide 12. High probability of death within 24 hours \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acceptability of protocol | Day 1 | Percentage of eligible patients who consent to randomization |
| Efficacy: Mean cumulative fluid balance | 72 hours following randomization | Total fluid input (mL) - output (mL) in each group |
| Compliance with deresuscitation protocol | Each 24 hours over first week | Daily fluid balance in mL \>10 liters, target \>2.0 liters/24 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Organ support-free days | 28 days following randomization | Days alive and free from respiratory or hemodynamic support |
| All cause mortality | 90 days following randomization | Deaths |
| New onset organ dysfunction | 7 days following randomization | Change in aggregate Multiple Organ Dysfunction (MOD) score from baseline, where the range is 0 - 25, and higher values indicate more severe organ dysfunction |
Other
| Measure | Time frame | Description |
|---|---|---|
| Inflammatory and renal biomarkers - change from baseline values | 3 days following randomization | including, but not limited to IL-6, sTNFr1, ICAM, HCO3-, protein C, CRP) or markers of AKI (including, but not limited to N-GAL, KIM-1, TIMP2-IGFBP-7, cystatin C |
Countries
Canada
Contacts
Primary ContactLaura Romero, RN
Backup ContactMichael Sklar, MD
Outcome results
None listed