Introduction
Methods
Study design
Inclusion criteria
Exclusion criteria
Laboratory analysis
In-hospital outcomes
Late outcomes
Sample size estimation
Statistical analysis
Results
Baseline characteristics
Continuous infusion (n = 43) | Bolus (n = 39) | |
---|---|---|
Age (years) | 80 ± 4 | 79 ± 5 |
Sex | ||
Female | 24 | 18 |
Male | 19 | 21 |
Baseline weight (kg) | 72 ± 7 | 69.7 ± 10 |
Blood pressure (mmHg) | 142/87 | 145/86 |
Heart rate (beats/minute) | 102 ± 12 | 98 ± 16 |
Cardiac disease | ||
Coronary artery disease | 24 | 21 |
Idiopathic cardiomyopathy | 7 | 7 |
Hypertrophic cardiomiopathy | 4 | 6 |
Valvular disease | 8 | 5 |
Baseline creatinine (mg/dl) | 1.62 ± 0.5 | 1.52 ± 0.4 |
BUN | 100.60 ± 60 | 69.2 ± 31 |
eGFR (mL/min/1.73 m2)) | 43.2 ± 7.6 | 45.7 ± 8.7 |
Serum sodium (mEq/L) | 137.2 ± 5 | 138 ± 5 |
Serum potassium (mEq/L) | 4.19 ± 0.4 | 4.26 ± 0.5 |
Left ventricular ejection fraction (%) | 34.3 ± 10 | 35.8 ± 8 |
LV internal diastolic diameter (mm) | 68 ± 8 | 66 ± 9 |
LV internal systolic diameter (mm) | 48 ± 10 | 45 ± 8 |
Estimated Pulmonary Artery (PA) systolic pressure (mmHg) | 50 ± 6 | 48 ± 5 |
Signs of congestion | ||
Elevated jugular venous pressure | 16 | 18 |
Additive heart sound | 11 | 13 |
Peripheral edema | 33 | 30 |
Pulmonary rales | 38 | 35 |
Coronary risk factors (%) | ||
Diabetes mellitus | 55.2 | 61.1 |
Hypertension | 89.4 | 87.9 |
Dyslipidemia | 72.4 | 75 |
Previous Coronary artery disease (CAD) | 46.2 | 49.4 |
Atrial fibrillation (%) | 36.6 | 41.3 |
Baseline BNP (pg/mL) | 1204 ± 693 | 1099 ± 571 |
Previous therapy | ||
ACE-inhibitors | 38 | 33 |
β-Blockers | 22 | 21 |
Nitrates | 25 | 26 |
Diuretics | 39 | 35 |
Angiotensin receptor blockers | 5 | 7 |
Digoxin | 13 | 11 |
Aldosterone antagonist | 15 | 12 |
Laboratory values and urine output
Continuous infusion | Bolus | P-value | |
---|---|---|---|
Urine output/24 h (mL) | 2295 ± 775 | 2090 ± 421 | <0.002 |
Serum creatinine (mg/dl) | 1.78 ± 0.6 | 1.34 ± 0.3 | <0.0001 |
eGFR (mL/min/1.73 m2) | 40.6 ± 10.5 | 50.4 ± 11.4 | <0.01 |
BUN (mg/dl) | 100 ± 60 | 69 ± 31 | <0.02 |
BNP (pg/mL) | 723 ± 497 | 822 ± 548 | <0.05 |
Serum sodium (mEq/L) | 138 ± 4 | 135 ± 16 | NS |
Serum potassium (mEq/L) | 3.6 ± 0.8 | 4.0 ± 0.7 | <0.04 |
Primary endpoints
Confinuous infusion | Bolus | P-value | |
---|---|---|---|
Δ Serum creatinine (mg/dl) | +0.8 ± 0,4 | -0.8 ± 0.3 | <0.01 |
Δ eGFR (mL/min/173 m2) | -9 ± 7 | +5 ± 6 | <0.05 |
Δ BNP (pg/mL) | -576 ± 655 | -181 ± 527 | 0.02 |
Continuous infusion | Bolus | P-value | |
---|---|---|---|
Acute kidney injury | 22% | 15% | 0.30 |
Hypertonic saline solution | 33% | 18% | 0.01 |
Inotropes infusion | 35% | 23% | 0.02 |
Length of hospital stay (days), mean ± SD | 14 ± 5 | 11 ± 5 | <0.03 |
Death or rehospitalization | 58% | 23% | 0.001 |
Weight loss (kg), mean ± SD | -4.1 ± 1,9 | -3.5 ± 2.4 | 0.23 |
Multivariate results and late outcome
Rehospitalization or Death | ||||
---|---|---|---|---|
Univariate | Multivariate | |||
Variable | HR (95% CI of HR) | P-value | HRa(95% CI of HR) | P-value |
BUN | 1.01 (1.00, 1.02) | 0.03 | 1.00 (0.99, 1.01) | NS |
BNP AT* | 1.01 (1.00, 1.02) | 0.03 | 1.01 (1.00, 1.02) | 0.04 |
eGFR AT* | 0.98 (0.94, 1.03) | NS | 1.06 (0.97, 1.15) | NS |
Creatinine AT* | 2.43 (0.94, 6.35) | NS | 6.40 (1.25, 32.62) | 0.02 |
Continuous vs bolus | 2.91 (1.28, 6.63) | 0.01 | 2.57 (1.01, 6.58) | 0.04 |
Discussion
Continuous versus intermittent loop diuretic administration
Pharmacology of loop diuretics
Reduction in renal filtration, B-type natriuretic peptide, and outcomes
Previous management studies
Limitations
Conclusions
Key messages
-
Continuous infusion of loop diuretics is associated with greater urine output and greater reduction in BNP in respect to intermittent infusion during hospitalization in patients with ADHF
-
In this population continuous infusion of loop diuretics is associated with an increased rate of AKI before discharge
-
An increased use of additional therapy has been observed in the continuous infusion arm because of increased rates of hypotension and hyponatremia
-
An increased rate of worsened renal function in the continuous arm appears related to impaired long-term outcome in patients with ADHF
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A larger multicenter study utilizing a more tailored diuretic dose and administration could clarify this bimodal trend