Preventive Versus Curative Treatment of Fluid Overload

Not Applicable

Recruiting

• Conditions: Respiratory Insufficiency
• Interventions: Other: Preventive initiation of fluid removal; Other: Curative initiation of fluid removal

• Registration Number: NCT04050007
• Lead Sponsor: 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.

Study Timeline

• Study First Submitted: 2019-08-06
• Study First Submitted QC: 2019-08-06
• Study First Posted: 2019-08-08
• Study Start: 2020-02-01
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-16
• Last Update Posted: 2024-01-17
• Primary Completion: 2024-03-01
• Study Completion: 2024-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 410

Inclusion Criteria

1. age>18

2. intubation and mechanical ventilation >= 24 hours

3. cumulative fluid balance judged positive 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Preventive initiation of fluid removal	Preventive initiation of fluid removal
2	Curative initiation of fluid removal	Curative initiation of fluid removal

Primary Outcome Measures

Name	Time	Method
Duration of weaning from mechanical ventilation	28 days	Time elapsed between the day of randomization and the day of successful extubation (patient alive without reintubation 7 days after extubation)

Secondary Outcome Measures

Name	Time	Method
Percentage of patients with use of unplanned non invasive ventilation (NIV) and high flow nasal cannula (HFNC) oxygen	7 days	Decision of use of NIV and HFNC by the attending physician, based on the international guidelines
Total number of days of mechanical ventilation	28 days	Number of days from intubation to successful extubation (patient alive without reintubation within 7 days after extubation)
Percentage of deaths in the ICU among patients	28 days
Rate of patients who failed the first spontaneous breathing trial	28 days	Failure of the first spontaneous breathing trial defined according to international guidelines
Ventilator free days	At 14 days and 28 days	Number of ventilator free days
Rate of tracheotomy	28 days	Decision of tracheotomy by the attending physician
Duration of stay in the ICU	28 days	Time elapse from ICU admission to ICU discharge
Percentage of patients with metabolic complications	28 days	At least one among hypernatremia (\>150 mEq/L), hypokaliemia (\<2.5 mEq/L) or kidney injury (KDIGO classification stades 2 et 3)
Percentage of patients with hemodynamic complications	28 days	At least one among hypotension with systolic blood pressure \<90 mmHg, introduction or increase in vasopressors dose, use of fluid expansion, atrial fibrillation, ventricular fibrillation
Daily and cumulated fluid balance	28 days	Difference between fluids intake and output (mL)
Rate of reintubation	7 days	Rate of patients who have been reintubated on the basis of predefined criteria (coma, cardiac or respiratory arrest, shock, post extubation acute respiratory distress)
Duration of stay in the hospital	28 days	Time elapse from hospital admission to hospital discharge
Percentage of patients with ventilator associated pneumonia	28 days	as per consensus definition: presence of the 3 criteria: * Clinical suspicion (temperature\> 38.3 ° C, leukocytosis (\> 12000 / mm3) or leukopenia (\<4000 / mm3), hypoxemia, auscultatory signs, or septic shock without obvious focus; * New radiological infiltrate; * Positive respiratory sampling in culture (quantitative or non-quantitative)

Trial Locations

Locations (1)

GH Pitié Salpêtrière - Charles Foix; 🇫🇷 Paris, France