Acute Heart Failure
Conditions
Keywords
acute heart failure, diuretics, BNP, Renal function, acute decompensated Heart Failure,, volume overload
Brief summary
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
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
Interventions
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
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Renal Function in Terms of GFR Values at Discharge | 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 Mean Urine Output Volume During the Infusion Period | time period ranging from 72 h to 120 h. | 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 |
| 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 | participants were followed for the duration of hospital stay, an average of 13 days | evaluation of renal function in terms of changes in creatinine levels during hospitalization in the two arms. |
| Evaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatment | from admission to discharge, an average of 12 days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dopamine Infusion During Hospitalization | in-hospital | — |
| Length of Hospitalization in the Two Groups | in-hospital | percentage of participants with hospital stay \> 10 days |
Countries
Italy
Participant flow
Recruitment details
Department of Internal Medicine, Cardiology Section Centre into a Para-Intensive Unit (Siena, Italy) from April 2011 to December 2012.
Pre-assignment details
22 were excluded because of normal renal function at baseline, 11 for receiving different dosages of intravenous furosemide, 4 for isolated diastolic HF
Participants by arm
| Arm | Count |
|---|---|
| cIV Group The group that received the continuous infusion of furosemide (cIV), consisted of 30 patients. | 30 |
| iIV Group The group that received the intermittent infusion of furosemide (iIV), consisted of 27 patients. | 27 |
| Total | 57 |
Baseline characteristics
| Characteristic | iIV Group | cIV Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 25 Participants | 46 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 5 Participants | 11 Participants |
| Age, Continuous | 73 years STANDARD_DEVIATION 8 | 71 years STANDARD_DEVIATION 7 | 72 years STANDARD_DEVIATION 8 |
| Region of Enrollment Italy | 27 participants | 30 participants | 57 participants |
| Sex: Female, Male Female | 13 Participants | 14 Participants | 27 Participants |
| Sex: Female, Male Male | 14 Participants | 16 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 27 |
| serious Total, serious adverse events | 14 / 30 | 9 / 27 |
Outcome results
Change in Brain Natriuretic Peptide (BNP) Levels From Admission to the Discharge
Time frame: participants were followed for the duration of hospital stay, an average of 13 days
Population: Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values \<0.05 were considered significant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Urine Output in cIV | Change in Brain Natriuretic Peptide (BNP) Levels From Admission to the Discharge | -525 pg/mL | Standard Deviation 615 |
| Urine Output in iIV | Change in Brain Natriuretic Peptide (BNP) Levels From Admission to the Discharge | -148 pg/mL | Standard Deviation 463 |
Evaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatment
Time frame: from admission to discharge, an average of 12 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Urine Output in cIV | Evaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatment | 679 pg/ml | Standard Deviation 397 |
| Urine Output in iIV | Evaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatment | 949 pg/ml | Standard Deviation 548 |
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 frame: time period ranging from 72 h to 120 h.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Urine Output in cIV | Evaluation of Mean Urine Output Volume During the Infusion Period | 2505 mL | Standard Deviation 796 |
| Urine Output in iIV | Evaluation of Mean Urine Output Volume During the Infusion Period | 2140 mL | Standard Deviation 468 |
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.
Time frame: participants were followed for the duration of hospital stay, an average of 13 days
Population: All data were analyzed with intention-to-treat. Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values \<0.05 were considered significant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Urine Output in cIV | Evaluation of Renal Function in Terms of Changes in Creatinine Levels | -0.10 mg/dL | Standard Deviation 0.3 |
| Urine Output in iIV | Evaluation of Renal Function in Terms of Changes in Creatinine Levels | -0.50 mg/dL | Standard Deviation 0.34 |
Evaluation of Renal Function in Terms of Changes in GFR
Time frame: from admission to discharge, an average of 12 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Urine Output in cIV | Evaluation of Renal Function in Terms of Changes in GFR | -3.18 (ml/min·1.73 m2) | Standard Deviation 2.45 |
| Urine Output in iIV | Evaluation of Renal Function in Terms of Changes in GFR | -1.93 (ml/min·1.73 m2) | Standard Deviation 2.9 |
Evaluation of Renal Function in Terms of Creatinine Levels at Discharge
Time frame: from admission to discharge, an average of 12 days
Population: All data were analyzed with intention-to-treat. Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values \<0.05 were considered significant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Urine Output in cIV | Evaluation of Renal Function in Terms of Creatinine Levels at Discharge | 1.78 mg/dL | Standard Deviation 0.5 |
| Urine Output in iIV | Evaluation of Renal Function in Terms of Creatinine Levels at Discharge | 1.51 mg/dL | Standard Deviation 0.3 |
Evaluation of Renal Function in Terms of GFR Values at Discharge
Time frame: from admission to discharge, an average of 12 days
Population: Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values \<0.05 were considered significant
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Urine Output in cIV | Evaluation of Renal Function in Terms of GFR Values at Discharge | 44.8 (ml/min·1.73 m2) | Standard Deviation 6.1 |
| Urine Output in iIV | Evaluation of Renal Function in Terms of GFR Values at Discharge | 46.7 (ml/min·1.73 m2) | Standard Deviation 6.1 |
Dopamine Infusion During Hospitalization
Time frame: in-hospital
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Urine Output in cIV | Dopamine Infusion During Hospitalization | 50 percentage of partecipants |
| Urine Output in iIV | Dopamine Infusion During Hospitalization | 26 percentage of partecipants |
Length of Hospitalization in the Two Groups
percentage of participants with hospital stay \> 10 days
Time frame: in-hospital
Population: Qualitative variables are expressed as percentage and compared with chi-square test . p values \<0.05 were considered significant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Urine Output in cIV | Length of Hospitalization in the Two Groups | 80 percentage of partecipants |
| Urine Output in iIV | Length of Hospitalization in the Two Groups | 44 percentage of partecipants |