Loop Diuretics Administration and Acute Heart Failure

Study Overview
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Brief Summary
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Intravenous loop diuretics is the therapy most commonly used to treat pulmonary congestion and systemic fluid overload. In theory, continuous infusion should allow for a more consistent diuresis, avoiding the sodium reabsorption in the distal tubule as well as the neurohormonal activation. This should lead to renal function improvement and BNP decrease.

Detailed Description
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Patients were eligible if they were admitted with a primary diagnosis of ADHF, randomized within 12 h after hospital presentation, and with evidence of volume overload (pulmonary congestion) on a chest X-ray study and had BNP levels >100 pg/ml. Patients also displayed mild to moderate renal dysfunction with creatinine values up to 1.4 mg/dl. Some patients were supported with non invasive ventilation before randomization. Once the initial 12 h dose was determined, patients were randomized using a 1:1 ratio using a computer-generated scheme to receive the furosemide dose either divided into a twice-daily bolus injection or in a continuous infusion (mixed as a 1:1 ratio in 5 % dextrose in water) for a time period ranging from 72 to 120 h. The randomization was casual, and the physicians did not previously know the assigned arm. The dose escalation and subsequent titration of furosemide was guided by clinical response in terms of urine output volume and body weight reduction .Before randomization, renal function parameters and BNP levels were measured in all patients. Subsequent titration of the furosemide dosage was at the discretion of the attending physician, but was guided by a dose-escalation algorithm based on the treatment response (weight loss and urine output volume), symptom improvement, changes in renal function, electrolyte balance, and chest radiography. The specific doses of furosemide and the use of additional agents to manage ADHF (dopamine, IV vasodilators, hypertonic saline infusion) were decided based upon blood pressure measurements, renal function evaluation and diuresis response. Supplementary treatment was left to the discretion of the treating physician. The duration of infusion was continued for up to 72 h, at 48 h the physicians had the possibility to adjust diuretic dose administration on the basis of the clinical response. After 72 h the treatment could be stopped or continued for an additional 36-48 h depending on the patient's condition and diuresis response. Acute kidney injury (AKI) was defined following the RIFLE criteria. Abbreviations: (AKI) Acute kidney injury (ADHF) Acute decompensated heart failure (BNP) B-type natriuretic peptide (CHD) Coronary heart disease (cIV) Continuous infusion (iIV) Intermittent infusione (eGFR)Estimated glomerular filtration rate (Hb) Hemoglobin (HF) Heart failure (Hct) Hematocrit (LVEF) Left ventricular ejection fraction (RBC) Red blood cells

Official Title
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Continuous Versus Intermittent Loop Diuretics Infusion Dosing in Acute Heart Failure: Effects on Renal Function, Outcome and BNP Levels

Conditions
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Acute Heart Failure

Intervention / Treatment
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* Drug: furosemide infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients took part in the random sample selection if they met the diagnostic criteria for acute decompensated HF. Patients with primary diagnosis of ADHF, volume overload with cardia dilation and LVEF <50%, and had BNP levels >100 pg/ml. Exclusion Criteria: Patients were excluded if they had received more than 2 IV doses of furosemide or any continuous infusion of furosemide 1 month before randomization If they had end-stage renal disease or the need for renal replacement therapy, isolated diastolic dysfunction. Recent myocardial infarction

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Continuous furosemide infusion<br>The group that received the continuous infusion of furosemide (cIV), consisted of 30 patients; | Drug: furosemide infusion<br>* Patients were randomized in a 1:1 ratio to receive furosemide dose divided into twice-daily bolus injection (group 0) or continuous infusion (group 1)(mixed as a 1:1 ratio in 5% dextrose in water) for a time period ranging from 72 to 120 hours. The mean daily diuretic dosage was similar in the two groups. The median time from presentation to randomization was 16 hours, and the median duration of study-drug administration was 112± 24 hours<br>* Other names: Continuous vs intermittent intravenous furosemide infusion;|
| Experimental: Intermittent furosemide infusion<br>The group that received the bolus infusion of furosemide (iIV), consisted of 27 patients | Drug: furosemide infusion<br>* Patients were randomized in a 1:1 ratio to receive furosemide dose divided into twice-daily bolus injection (group 0) or continuous infusion (group 1)(mixed as a 1:1 ratio in 5% dextrose in water) for a time period ranging from 72 to 120 hours. The mean daily diuretic dosage was similar in the two groups. The median time from presentation to randomization was 16 hours, and the median duration of study-drug administration was 112± 24 hours<br>* Other names: Continuous vs intermittent intravenous furosemide infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Mean Urine Output Volume During the Infusion Period | this study aimed to evaluate the effects of continuous infusion of furosemide in comparison to twice daily regimens at similar doses with respect to changes in renal function in terms of creatinine levels and GFR, urine output and BNP levels from admission to discharge | time period ranging from 72 h to 120 h. | 
| Evaluation of Renal Function in Terms of Creatinine Levels at Discharge |  | from admission to discharge, an average of 12 days | 
| Evaluation of Renal Function in Terms of Changes in Creatinine Levels | evaluation of renal function in terms of changes in creatinine levels during hospitalization in the two arms. | participants were followed for the duration of hospital stay, an average of 13 days | 
| Evaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatment |  | from admission to discharge, an average of 12 days | 
| Change in Brain Natriuretic Peptide (BNP) Levels From Admission to the Discharge |  | participants were followed for the duration of hospital stay, an average of 13 days | 
| Evaluation of Renal Function in Terms of Changes in GFR |  | from admission to discharge, an average of 12 days | 
| Evaluation of Renal Function in Terms of GFR Values at Discharge |  | from admission to discharge, an average of 12 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of Hospitalization in the Two Groups | percentage of participants with hospital stay > 10 days | in-hospital | 
| Dopamine Infusion During Hospitalization |  | in-hospital | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BNP, acute heart failure, diuretics, Renal function, acute decompensated Heart Failure,, volume overload