Preventive Versus Curative Treatment of Fluid Overload

Effect of a Systematic Preventive Versus Curative Strategy of Fluid Removal on the Weaning of Mechanical Ventilation

Sponsors

Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Source Assistance Publique - Hôpitaux de Paris
Brief Summary

Fluid overload is associated with a poor prognosis in critically ill patients, especially during weaning from mechanical ventilation as it may promote weaning induced pulmonary edema. Previous data suggest that early administration of diuretics ("preventive depletion") could shorten the duration of mechanical ventilation. However, this strategy may expose patients to a risk of metabolic complications. On the other hand, initiating fluid removal only in case of weaning induced pulmonary edema (curative depletion) may reduce the risk of metabolic complications, but prolong the duration of mechanical ventilation. Currently, there is no recommendation for a preventive or curative use of diuretics during weaning. There is therefore an equipoise on the timing of initiation of diuretics during weaning from mechanical ventilation.

Detailed Description

Mechanical ventilation is a cornerstone treatment for critically ill patients that is however associated with complications that may alter the prognosis. A major objective is therefore to separate patients from the ventilator as quickly as possible, but without exposing them to the risk of extubation failure. Pulmonary edema is a frequent cause of extubation failure (up to 60% in recent series) and a positive fluid balance has been identified as an important risk factor for extubation failure. Studies have tested the effect of a conservative strategy regarding the administration of fluids in patients with acute respiratory distress syndrome. This strategy is associated with an improvement in hemodynamic parameters despite an increase in urine output with a negative fluid balance and a significant weight loss as compared to a liberal strategy. The conservative approach also shows a significant improvement in oxygenation with a nonsignificant trend towards a shorter duration of artificial ventilation and ICU stay. During the specific phase of weaning from mechanical ventilation, a randomized trial (BMW trial) demonstrated that a strategy of fluid removal guided by measurement of the plasmatic B-type natriuretic peptide significantly reduced the duration of weaning. Likewise, the interest of obtaining a negative fluid balance through the administration of diuretics in weaning induced pulmonary edema has been established for decades ("curative depletion"). In this context, the hypothesis of the present study is that a preventive and systematic strategy of fluid removal through the use of diuretics initiated just before the weaning phase, as soon as the patients is stabilized would shorten the duration of weaning from mechanical ventilation as compared to a curative strategy of fluid removal, only initiated after a failure of the spontaneous breathing trial associated with weaning induced pulmonary edema. The design of the study will be a randomized (1:1) controlled trial, open label, with 2 arms, to evaluate the superiority of the preventive strategy. The weaning process will be protocolized and similar for the two groups.

Overall Status Recruiting
Start Date 2020-02-01
Completion Date 2022-12-01
Primary Completion Date 2022-03-01
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Duration of weaning from mechanical ventilation 28 days
Secondary Outcome
Measure Time Frame
Percentage of patients with metabolic complications 28 days
Percentage of patients with hemodynamic complications 28 days
Daily and cumulated fluid balance 28 days
Rate of patients who failed the first spontaneous breathing trial 28 days
Rate of reintubation 7 days
Rate of tracheotomy 28 days
Percentage of patients with use of unplanned non invasive ventilation (NIV) and high flow nasal cannula (HFNC) oxygen 7 days
Ventilator free days At 14 days and 28 days
Total number of days of mechanical ventilation 28 days
Percentage of patients with ventilator associated pneumonia 28 days
Duration of stay in the ICU 28 days
Duration of stay in the hospital 28 days
Percentage of deaths in the ICU among patients 28 days
Enrollment 410
Condition
Intervention

Intervention Type: Other

Intervention Name: Preventive initiation of fluid removal

Description: Preventive initiation of fluid removal will be started right after the randomization with intravenous diuretics according to a predefined algorithm based on the urine output every three hours. The weaning process and post extubation preventive strategy will be protocolized based on the last international guidelines

Arm Group Label: 1

Intervention Type: Other

Intervention Name: Curative initiation of fluid removal

Description: The initiation of fluid removal will be considered by the attending physician only in case of failure to the spontaneous breathing trial with a clinical suspicion of weaning induced pulmonary edema. The weaning process and post extubation preventive strategy will be protocolized based on the last international guidelines

Arm Group Label: 2

Eligibility

Criteria:

Inclusion Criteria: 1. age>18 2. intubation and mechanical ventilation >= 24 hours 3. positive cumulated fluid balance or increase in body weight since admission 4. clinical stability as defined by: 4.1. stable oxygenation (SpO2 ≥ 90 % with FiO2 ≤ 50 % and positive end-expiratory pressure (PEEP) ≤ 8 cm H2O) 4.2. stable hemodynamics (no pressors, no fluid expansion within the last 12 hours) 4.3. stopped or decreased sedation within the last 48 hours and stable neurologic state. 4.4. temperature >36,0 ◦C and < 39◦C 5. consent signed by the patient or next of kin or emergency procedure Exclusion Criteria: 1. extracorporal membrane oxygenation 2. pregnancy or breastfeeding 3. allergy to furosemide, sulfamides or spironolactone 4. tracheotomy 5. hydrocephaly 6. acute right ventricle failure 7. cardiac arrest with estimated poor prognosis 8. already enrolled in an interventional study on weaning from mechanical ventilation 9. Guillain Barre, myasthenia crisis 10. planned extubation on the day 11. criteria of clinical stability (as described above) present since more than 24 hours 12. natremia > 150 mEq/L, kaliemia < 3.5 mEq/L, metabolic alkalosis with pH>7.5 13. administration of iodinated contrast within the last 6 hours 14. ongoing or planned use of artificial kidney within the next 48 hours 15. no affiliation to the health insurance system 16. patient under curatorship 17. imprisoned patient

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Contact

Last Name: Martin DRES

Phone: +33142167888

Email: [email protected]

Location
Facility: Status: Contact: Investigator: GH Pitié Salpêtrière - Charles Foix Martin DRES Martin DRES, Dr Principal Investigator
Location Countries

France

Verification Date

2021-05-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: 1

Type: Experimental

Description: Preventive initiation of fluid removal

Label: 2

Type: Other

Description: Curative initiation of fluid removal

Acronym PCT-Fluid
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Health Services Research

Masking: None (Open Label)

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