Furosemide and Albumin for Diuresis of Edema: A Pilot Randomized Controlled Trial

Phase 3

Completed

Brief Summary: Critically ill patients usually require intravenous fluids to correct low blood pressure and improve blood flow to vital organs. However, once the patient's blood pressure has improved, these fluids can leak out into various organs, including the lung, kidneys, and skin. Excess fluid in these tissues, called edema, has been associated with longer ICU stays and higher mortality. Thus removing excess fluid is an important goal. The simplest way to treat edema is to use diuretics, such as furosemide, which increase urine output.

To further improve urine output, patients are sometimes given albumin, a protein which helps to suck fluid out from the tissues, and keep it in the blood vessel, where it can be filtered in the kidney and removed in the urine. Although albumin is often used for this purpose, there is little evidence to support it. A large randomized controlled trial is needed to determine if albumin plus furosemide is truly more effective than furosemide alone in critically ill patients with low levels of blood albumin. We will perform a pilot study to assess the feasibility of such a trial.

Recruitment & Eligibility

Inclusion Criteria

Hemodynamically stable for at least 24 hours (absence of persistent [>1 h] hypotension [systolic blood pressure <90 mmHg), not currently on vasopressors, less than 2 L crystalloid or colloid boluses, or 2 units red blood cells administered, maintenance fluids excluded
Hypoproteinemia (serum albumin <30 mg/L or total protein < 60 mg/L)
Clinical decision to diurese at least 3 L net fluid balance within the next 72 hours for any reason

Exclusion Criteria

known pregnancy
patient or surrogate unable or unwilling to consent to blood product administration, including albumin
history of adverse reactions or allergy to either albumin or furosemide
acute kidney injury (RIFLE criteria "F" or greater) without any improvement in past 24 hours, or otherwise expected to necessitate dialysis within 48 hours in opinion of treating physician
chronic kidney injury requiring dialysis
clinically documented cirrhosis
clinically documented nephrotic syndrome
serum sodium greater than 150 milliequivalent/L or serum potassium less than 2.5 mEq/L that connote be treated prior to administration of study treatment
inability to measure urine output and fluid balance
Receipt of hyperoncotic albumin within preceding 24 hours
previous enrollment in this trial, or any research studies which may interfere with this study
estimated survival or ICU stay less than 72 hours

Arm && Interventions

Group	Intervention	Description
Intravenous albumin	Intravenous albumin	Administration of 25% albumin by intravenous infusion, twice daily for a total of 72 hours (6 treatments)
Normal saline	Normal saline	Administration of 100 mL normal saline by intravenous infusion, twice daily, for 72 hours (6 treatments)

Primary Outcome Measures

Name	Time	Method
Ventilator-free Days	30 days	Ventilator-free days

Secondary Outcome Measures

Name	Time	Method
Oxygenation	Day 1, Day 3, Day 5	Changes in oxygenation (FiO2, P/F ratio, oxygenation index) from baseline at day 3 and day 5
Treatment Interruptions	Day 1, Day 2, Day 3	Number of episodes of interrupting treatment with furosemide (eg. hypotensive episodes, renal failure, contraction alkalosis, etc.)
Length of ICU Stay	Study end
Serum Albumin and Colloid Osmotic Pressure	Day 1, Day 3, Day 5	Changes in serum albumin and serum colloid osmotic pressure measurements from Day 1, Day 3, Day 5
Mortality	30 days	Total ICU mortality and mortality at 30 days.
Duration of Mechanical Ventilation	30 days	Total duration of mechanical ventilation
Fluid Balance and Body Weight	Day 1, Day 3, Day 5	Change in total fluid balance and body weight from baseline at 3 days and 5 days