Effects of Fluid Balance Control in Critically Ill Patients

Study Overview
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Brief Summary
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Most ICU patients develop a positive fluid balance, mainly during the two first weeks of their stay. The causes are multifactorial: a reduced urine output subsequent to shock state, positive pressure mechanical ventilation, acute renal failure, post-operative period of major surgical procedures, and simultaneous fluid loading to maintain volemia and acceptable arterial pressure. Additionally, the efficacy of fluid loading is frequently suboptimal, in relation to severe hypoalbuminemia and inflammatory capillary leakage. This results usually in a cumulated positive fluid balance of more than 10 litres at the end of the first week of stay. A high number of studies have showed that such a positive fluid balance was an independent factor of worse prognosis in selected populations of ICU patients: acute renal failure, acute respiratory distress syndrome (ARDS), sepsis, post-operative of high risk surgery. However, little is known about the putative causal role of positive fluid balance by itself on outcome. However, in two randomized controlled studies in patients with ARDS, a strategy of fluid balance control has been demonstrated to reduce time under mechanical ventilation and ICU length of stay with no noticeable adverse effects. Although avoiding fluid overload is now recommended in ARDS management, there is no evidence that this approach would be beneficial in a more general population of ICU patients (i.e. with sepsis, acute renal failure, mechanical ventilation). In addition, fluid restriction -mainly if applied early could be deleterious in reducing both tissue oxygen delivery and perfusion pressure. There is a place for a prospective study comparing a conventional attitude based on liberal fluid management throughout the ICU stay with a restrictive approach aiming at controlling fluid balance, at least as soon as the patient circulatory status is stabilized. The latter approach would use a simple algorithm using fluid restriction and diuretics based on daily weighing, a common procedure in the ICU, probably more reliable than cumulative measurement of fluid movements in patients whose limits have been underlined.

Official Title
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Effects of Fluid Balance Control in Critically Ill Patients: A Multicenter Randomized Study

Conditions
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Fluid Shifts, Critical Care

Intervention / Treatment
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* Drug: diuretics
* Drug: albumin
* Other: fluid restriction
* Device: renal replacement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients under mechanical ventilation, admitted for > 48h and <72h and no discharge planned for the next 24h Exclusion Criteria: Age < 18 years Failure to weigh the patient Multiple trauma Transfer from another ICU with a previous stay > 24h High probability of withdrawing treatment for ethical purposes within 7 days Pregnancy Patient refusal

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Usual care provided according to the ward policy. Patients have to be weighed at least on admission (day 0), day 7 and day 14. | |
| Experimental: Strategy<br>Patients have to be weighed every day. Use of an algorithm based on weight changes from day 2 to day 14 in order to reduce weight gain (fluid overload) using diuretics, fluid restriction,albumin, and ultrafiltration (the latter when ongoing renal replacement) | Drug: diuretics<br>* Used to reduce fluid overload as evidenced by weight gain<br>* Other names: furosemide;Drug: albumin<br>* Used to reduce fluid overload in addition with diuretics in hypoalbuminemic patients<br>Other: fluid restriction<br>* Used to reduce fluid overload<br>Device: renal replacement<br>* Used to reduce fluid overload in patients with renal replacement<br>* Other names: ultrafiltration;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality at 60 days after inclusion | Vital status collected 60 days after admission; if the patient was dead at the time of assessment, date of death was collected | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluid balance control at day 7 | Mean differences of patient body weight between Day 7 and admission (Day 0) | 7 days | 
| Fluid balance control at day 14 | Mean differences of patient body weight between Day 14 and admission (Day 0) | 14 days | 
| All-cause mortality at 28-day after inclusion | Vital status collected 28 days after admission | 28 days | 
| All-cause in-hospital mortality | Death during the hospital stay where the patient was included in the study | Up to 24 weeks | 
| All-cause mortality at 365 days after inclusion | Vital status collected one year after admission | 365 days | 
| Survival time period at Day 60 | Time-related mortality, calculated from admission to the date of death | 60 days | 
| Survival time period at Day 365 | Time-related mortality, calculated from admission to the date of death | 365 days | 
| Global end-organ damage assessment | Time-related changes of Sequential Organ Failure Assessment (SOFA score): SOFA is a score of organ failure with 6 subscales on organ dysfunction: respiratory, neurological, cardiovascular,hepatic,renal and coagulation. Each ranges from 0 to 4 and the total SOFA score is the sum of each subscale ; increasing severity from 0 (normal) to 24(moribund). Values of SOFA score are tightly correlated with mortality. | 28 days | 
| Dependence on vasopressor drugs | Cumulated number of vasopressor-free days alive from day 0 to day 28 | 28 days | 
| Dependence on mechanical ventilation | Cumulated number of ventilator-free days alive from day 0 to day 28 | 28 days | 
| Dependence on renal replacement therapy | Cumulated number of renal replacement-free days alive from day 0 to day 60 | 60 days | 
| Cumulated number of pre-defined adverse events | Pre-defined adverse events include Systolic arterial pressure< 90 mm Hg, kalemia < 2,8 ,mmol/L, natremia >155 mmol/L, injury level of renal dysfunction (RIFLE scale), acute ischemic events (myocardial infarction, mesenteric ischemia) | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fluid overload, Multiple organ failure, Diuretics, Fluid restriction, Body weight