BACKGROUND: Renal dysfunction is associated with increased mortality in patients with decompensated heart failure. However, interventions targeted to prevention in this setting have been disappointing. We investigated the effects of hypertonic saline solution (HSS) for prevention of renal dysfunction in decompensated heart failure.
METHODS: In a double-blind randomized trial, patients with decompensated heart failure were assigned to receive three-day course of 100mL HSS (NaCl 7.5%) twice daily or placebo. Primary end point was an increase in serum creatinine of 0.3mg/dL or more. Main secondary end point was change in biomarkers of renal function, including serum levels of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin-NGAL and the urinary excretion of aquaporin 2 (AQP2), urea transporter (UT-A1), and sodium/hydrogen exchanger 3 (NHE3).
RESULTS: Twenty-two patients were assigned to HSS and 12 to placebo. Primary end point occurred in two (10%) patients in HSS group and six (50%) in placebo group (relative risk 0.3; 95% CI 0.09-0.98; P=0.01). Relative to baseline, serum creatinine and cystatin C levels were lower in HSS as compared to placebo (P=0.004 and 0.03, respectively). NGAL level was not statistically different between groups, however the urinary expression of AQP2, UT-A1 and NHE3 was significantly higher in HSS than in placebo.
CONCLUSIONS: HSS administration attenuated heart failure-induced kidney dysfunction as indicated by improvement in both glomerular and tubular defects, a finding with important clinical implications. HSS modulated the expression of tubular proteins involved in regulation of water and electrolyte homeostasis.
BACKGROUND: High values of cardiac troponin in acute decompensated congestive heart failure (ADHF) identify patients at higher risk and worsened prognosis. A cardiac troponin increase during therapy indicates the need for more appropriate intervention, aimed at compensating cardiac disease and effectively minimizing myocardial wall stress and subsequent cytolysis. This study evaluated the effects of an intravenous high dose of furosemide with (group A) or without small volume hypertonic saline solution (HSS) (group B) on myocardial cytolysis in patients with ADHF.
METHODS: A total of 248 consecutive patients with ADHF (148 men, mean age 74.9 ± 10.9 years) were randomly assigned to group A or B. Plasma levels of cardiac troponin-I, brain natriuretic peptide, glomerular filtration rate by Modification of Diet in Renal Disease formula, bioelectrical impedance analysis measurements, and delta pressure/delta time (dP/dt) rate were observed on admission and discharge for all patients.
RESULTS: We observed a significant reduction of cardiac troponin in both groups and a significant improvement in renal function, hydration state, pulmonary capillary wedge pressure (P < .0001), end diastolic volume (P < .01), ejection fraction (P < .01), and dP/dt (P < .004) in group A. We also observed a significant reduction in body weight (64.4 vs 75.8 kg) (P < .001), cardiac troponin I (0.02 vs 0.31 ng/mL) (P < .0001) and brain natriuretic peptide (542 vs 1,284 pg/mL) (P < .0001), and hospitalization time (6.25 vs 10.2 days) (P < .0001) in the HSS group.
CONCLUSIONS: These data demonstrate that intravenous high doses of furosemide do not increase myocardial injury and, in addition, when associated to HSS, significantly reduce cardiac troponin I release. This behavior is mirrored by the achievement of improved hemodynamic compensation at echocardiography and body hydration normalization.
Background: Randomized trials have suggested a benefit of high dose furosemide-hypertonic saline infusion (F-HSS) compared to furosemide IV bolus infusion (F-IVB) in acute decompensated heart failure (ADHF) with preserved renal function. Creatinine (CR) >2mg/dL or BUN >60mg/dL led to exclusion from published trials. Our experience of 72 ADHF patients (pts) treated with F-HSS identified 15 with advanced renal disease, who diuresed with renal improvement. Methods: A double-blind, double-dummy randomized trial was designed testing F-HSS vs F-IVB in ADHF pts with advanced renal disease, for diuretic effect and renal response. From November 2009 to April 2011 after informed consent, 50 ADHF pts, with estimated glomerular filtration rates (eGFR) of <60mL/min were randomly assigned to a 30 minute infusion of 150mL 0.9% saline with 80mg furosemide IV bolus (control) or 150mL 2.4% saline with 250mg furosemide (treatment) and 0.9% saline IV bolus. Sixteen (64%) pts in the control group had the second or subsequent doses doubled versus 6 (24%) pts in the treatment group. The average doses administered was 5 in the control and 4 in the treatment groups. Baseline characteristics between control and treatment groups were similar, with the average age 79.6 ± 6.9 years and left ventricular ejection fraction <45% in 50% of pts. Results: (Table presented) Conclusion: F-HSS led to a non-significant, better diuresis but also BUN elevation from baseline when compared to F-IVB in pts with ADHF with advanced renal disease.
<b>BACKGROUND: </b>The aim of the study was to verify the effects of hypertonic saline solution (HSS) plus a high furosemide dose and light restriction of sodium intake compared with a high-dose infusion of furosemide alone on pulmonary capillary wedge pressure (PCWP), as determined by Doppler echocardiography and tissue Doppler imaging in patients suffering from decompensated heart failure. <b>METHODS AND RESULTS: </b>Consecutive patients in New York Heart Association functional class IV, unresponsive to oral high doses of furosemide up to 250-500 mg/d and/or combinations of diuretics, with ejection fraction <40%, serum creatinine <2 mg/dL, blood urea nitrogen ≤60 mg/dL, reduced urinary volume (<500 mL/24 h), and low natriuresis (<60 mEq/24 h) were randomized into 2 groups (double blind). The first group received a furosemide infusion (250 mg) plus HSS (150 mL 3.0% Na) bid and light Na restriction (120 mmol), and the second group received furosemide infusion (250 mg) twice daily, and low Na diet (80 mmol). The fluid intake of both groups was restricted (1 L/d). Body weight, whole-body bioelectrical impedance analysis (BIA), 24-hour urinary volume, and serum and urinary laboratory parameters were measured daily. Estimations of echocardiographic PCWP (Echo-PCWP) were detected on entry, 1 hour after concluding the initial treatment, and 6 days thereafter. A total of 133 patients (47 women and 86 men), aged 65-82 years, met the entry criteria.The HSS group revealed a significant increase in daily diuresis, natriuresis, and serum sodium compared with the furosemide group. Six days after treatment, renal function was significantly improved in the HSS group. Both groups showed a significant reduction in Echo-PCWP, but the HHS group revealed a faster reduction and significant lower values at 6 days compared with the group taking furosemide alone. We observed a positive correlation between values of Echo-PCWP and BNP and an inverse correlation between BIA parameters and Echo-PCWP. <b>CONCLUSIONS: </b>Our data show that the combination of high diuretic dose and HSS infusion plus light restriction in dietary sodium intake determine a more rapid and significant hemodynamic stabilization through the improvement of echo-PCWP, BNP levels, and BIA parameters than the group treated without HSS.
INTRODUCTION: Hypertonic saline solution (HSS) and a moderate Na restriction plus high furosemide dose showed beneficial effects in compensated heart failure (HF), in short and long terms. The study was aimed to verify the effects of this combination on hospitalization time, readmissions and mortality in patients in New York Heart Association (NYHA) class III.
METHOD: Chronic ischemic or nonischemic cardiomyopathy uncompensated patients with HF in NYHA III functional class with ejection fraction <40%, serum creatinine <2.5 mg/dL, blood urea nitrogen <60 mg/dL and reduced urinary volume were single-blind randomized in 2 groups: the first group received a 30-minute intravenous infusion of furosemide (250 mg) plus HSS (150 mL) twice daily and a moderate Na restriction (120 mmol); the second group received furosemide intravenous bolus (250 mg) twice a day, without HSS and a low Na diet (80 mmol); both groups received a fluid intake of 1000 mL/d. After discharge, the HSS group continued with 120 mmol Na/d; the second group continued with 80 mmol Na/d.
RESULTS: A total of 1771 patients (881 HSS group and 890 without HSS group) met inclusion criteria: the first group (881 patients), compared with the second (890 patients), showed an increase in diuresis and serum Na levels, a reduction in hospitalization time (3.5 + 1 versus 5.5 + 1 days, P < 0.0001) and, during follow-up (57 + 15 months), a lower rate in readmissions (18.5% versus 34.2%, P < 0.0001) and mortality (12.9% versus 23.8%, P < 0.0001); the second group also showed a significant increase in blood urea nitrogen and serum creatinine.
CONCLUSION: This study suggests that in-hospital HSS administration, combined with moderate Na restriction, reduces hospitalization time and that a moderate sodium diet restriction determines long-term benefit in patients with NYHA class III HF.
BACKGROUND AND AIMS: Neurohormonal activation and inflammation characterizes heart failure, relates to outcome, and is a therapeutic target. The aim of this study was to evaluate the effects of high-dose furosemide plus small-volume hypertonic saline solutions (HSS) on natriuretic peptides and immuno-inflammatory marker levels and to analyze, after treatment, the response to acute saline loading.
METHODS AND RESULTS: 120 patients with heart failure treated with high-dose furosemide+HSS (Furosemide/HSS group) were matched with: 30 subjects with heart failure treated with high-dose furosemide (furosemide group), 30 controls with asymptomatic left-ventricular dysfunction (ALVD) (asymptomatic group) and 30 controls without heart failure or ALVD (Healthy group). We evaluated plasma levels of natriuretic peptides and cytokine levels in baseline, after treatment and after acute saline load. After treatment with high-dose furosemide+HSS compared to treatment with furosemide alone we observed a significant lowering of ANP [96 (46.5-159.5) pg/ml vs 64 (21-150) pg/ml], BNP [215.5 (80.5-487) pg/ml vs 87 (66-141.5) pg/ml], TNF-α [389.5 (265-615.5) pg/ml vs 231.5 (156-373.5) pg/ml], IL-1β [8 (7-9) pg/ml vs 4 (3-7) pg/ml], IL-6 [5 (3-7.5) pg/ml vs 3 (2-4) pg/ml], plasma values and after an acute saline load, a lower percentage change of ANP (+18.6% vs +28.03% vs +25% vs +29%), BNP (+14.5% vs +29.2% vs +30% vs +29.6%) TNF-α (+10.8% vs +15.8% vs +17.8% vs +11.3%), IL-1β (+20% vs 34.4% vs 40% vs 34.4%) compared to control groups.
CONCLUSIONS: Treatment with HSS could be responsible for a stretching relief that could influence natriuretic and immuno-inflammatory markers.
OBJECTIVES: The aim of this study was to evaluate the effect of a new treatment for refractory congestive heart failure (CHF) on brain natriuretic peptide (BNP) plasma levels and hydration station.
BACKGROUND: The study was aimed at evaluating the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) in refractory CHF patients.
METHODS: A total of 94 patients (34 women/60 men) with refractory CHF (age 55 to 80 years) were enrolled. They had to have an ejection fraction <35%, serum creatinine <2 mg/dl, blood urea nitrogen <60 mg/dl, a reduced urinary volume, and a low natriuresis (<500 ml/24 h and <60 mEq/24 h, respectively). Patients were divided (double-blind) into two groups: group 1 (18 women/30 men) received an intravenous furosemide (500 to 1,000 mg) plus HSS twice a day in 30 min. Group 2 (16 women/30 men) received an intravenous bolus of furosemide (500 to 1,000 mg/twice a day) alone, for four to six days. At entry, body weight, blood pressure, heart rate, and laboratory parameters were checked during hospitalization; BNP levels were measured on admission, 6 and 30 days after discharge, while on admission and 6 days after, impedance plethysmography was performed. The HSS group received 120 mmol of Na intake versus 80 mmol in non-HSS group. Fluid intake of 1,000 was given to both groups.
RESULTS: The groups were similar for clinical characteristics. A significant increase in daily diuresis and natriuresis was observed in HSS group, p < 0.05. The BNP values showed significant intragroup and intergroup differences, 6 and 30 days after treatment. The patients from the HSS group reached a better hydration state than the non-HSS group after six days. In addition, the HSS group showed a significant reduction in hospitalization time and readmission rate.
CONCLUSIONS: Our data show that the HSS group reached dry weight more rapidly, a significantly faster reduction in BNP levels, shorter hospitalization stay, and lower incidence in readmissions in the 30-day study period.
BACKGROUND: Diuretics have been accepted as first-line treatment in refractory congestive heart failure (CHF), but a lack of response to them is a frequent event. A randomized, single-blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) infusion in the treatment of refractory New York Heart Association (NYHA) class IV CHF and a normosodic diet during follow-up. Materials and Methods One hundred seven patients (39 women and 68 men, age range 65-90 years) with refractory CHF (NYHA class IV) of different etiologies, who were unresponsive to high oral doses of furosemide, angiotensin-converting enzyme inhibitors, digitalis, and nitrates, were enrolled. Inclusion criteria included an ejection fraction (EF) <35%, serum creatinine level <2 mg/dL, blood urea nitrogen level < or =60 mg/dL, reduced urinary volume, and low natriuresis. The patients were randomized in 2 groups (single-blind). Patients in group 1 (20 women and 33 men) received an intravenous (IV) infusion of furosemide (500-1000 mg) plus HSS (150 mL of 1.4%-4.6% NACl) twice a day in 30 minutes. Patients in group 2 (19 women and 35 men) received an IV bolus of furosemide (500-1000 mg) twice a day, without HSS, during a period lasting 6 to 12 days. Both groups received IV KCl (20-40 mEq) to prevent hypokalemia. At study entry, all patients underwent a physical examination and measurement of body weight (BW), blood pressure (BP), and heart rate (HR), an evaluation of signs of CHF, and measurement of control levels of serum Na, K, Cl, bicarbonate, albumin, uric acid, creatinine, urea, and glycemia daily during hospitalization, and measurements of the daily output of urine for Na, K, and Cl. A chest radiograph, electrocardiogram, and echocardiogram were obtained at study entry, during hospitalization, and at the time of discharge from the hospital. During the treatment and after discharge, the daily dietary Na intake was 120 mmol in group 1 versus 80 mmol in group 2, with a fluid intake of 1000 mL daily in both groups. An assessment of BW and 24-hour urinary volume, serum, and urinary laboratory parameters were performed daily until patients reached a compensated state, when IV furosemide was replaced with oral administration (250-500 mg/d). After discharge from the hospital, patients were observed as outpatients weekly for the first 3 months and, subsequently, once a month. RESULTS: The groups were similar in age, sex, EF, risk factors, treatment, and etiology of CHF. All patients showed a clinical improvement. Ten patients in both groups had hyponatremia at entry. A significant increase in daily diuresis and natriuresis was observed in both groups, but it was more significant in the group receiving HSS (P <.05). The serum Na level increased in group 1 and decreased in group 2 (P <.05). The serum K level was decreased in both groups (P <.05). BW was reduced in both groups (P <.05). Group 2 had an increase in serum creatinine level. Serum uric acid levels increased in both groups. BP values decreased and HR was corrected to normal values in both groups. In the follow-up period (31 +/- 14 months), 25 patients from group 1 were readmitted to the hospital for heart failure. In group 2, 43 patients were readmitted to the hospital at a higher class than at discharge. Twenty-four patients in group 1 died during follow-up, versus 47 patients in group 2 (P <.001). CONCLUSION: This treatment is effective and well tolerated, improves the quality of life through the relief of signs and symptoms of congestion, and may delay more aggressive treatments. The effects were also beneficial in a long period for mortality reduction (55% vs 13% survival rate) and for clinical improvement.
BACKGROUND: Diuretics, have been accepted as first-line treatment in refractory heart failure, but a lack of response is a frequent event. A randomised single blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) infusion in the treatment of refractory NYHA class IV congestive heart failure (CHF). MATERIALS AND METHODS: Sixty patients (21 F/39 M) with refractory CHF (NYHA class IV) of different etiologies, unresponsive to high oral doses of furosemide, ACE-inhibitors, digitalis, and nitrates, aged 65-90 years, were enrolled. They had to have an ejection fraction (EF) <35%, serum creatinine <2 mg/dl, BUN </=60 mg/dl, a reduced urinary volume and a low natriuresis. The patients were randomised in two groups (single blind): group 1 (11 F/19 M) received an i.v. infusion of furosemide (500-1000 mg) plus HSS (150 ml of 1.4-4.6% NaCl) b.i.d. in 30 min. Group 2 (10 F/20 M) received an i.v. bolus of furosemide (500-1000 mg) b.i.d., without HSS, during a period lasting 6-12 days. Both groups received KCl (20-40 mEq.) i.v. to prevent hypokalemia. All patients underwent at entry a physical examination, measurement of body weight (BW), blood pressure (BP), heart rate (HR), evaluation of signs of CHF, and controls of serum Na, K, Cl, bicarbonate, albumin, uric acid, creatinine, urea and glycemia and daily during hospitalization, as well as the daily output of urine for, Na, K and Cl measurements. Chest X-ray, ECG and echocardiogram were obtained at entry during and at the discharge. During the treatment and after discharge the daily dietary Na intake was 120 mmol with a drink fluid intake of 1000 ml daily. An assessment of BW and 24-h urinary volume, serum and urinary laboratory parameters, until reaching a compensated state, were performed daily, when i.v. furosemide was replaced with oral administration (250-500 mg/day). After discharge, patients were followed as outpatients weekly for the first 3 months and subsequently once per month. RESULTS: The groups were similar for age, sex, EF, risk factors, treatment and etiology of CHF. All patients showed a clinical improvement. Six patients in both groups had hyponatremia (from 120 to 128 mEq./l) at entry. A significant increase in daily diuresis in both groups was observed (from 390+/-155 to 2100+/-626, and from 433+/-141 to 1650+/-537 ml/24 h, P<0.05). Natriuresis (from 49+/-15 to 198+/-28 mEq./24 h) was higher in group 1 vs. group 2 (from 53.83+/-12 to 129+/-39 mEq./24 h, P<0.05). Serum Na (from 135.9+/-6.8 to 142.2+/-3. 8 mEq./l, P<0.05) increased in the group 1 and decreased in the group 2 (from 134.7+/-7.9 to 130.1+/-4.3 mEq./l). Serum K was decreased (from 4.4+/-0.6 to 3.9+/-0.6, and 4.6+/-9 to 3.6+/-0.5 mEq. /l, P<0. 05) in both groups. BW was reduced (from 73.8+/-9.1 to 63. 8+/-8.8, and from 72.9+/-10.2 to 64.5+/-7.5 kg, P<0. 05) in both groups. Group 2 showed more patients in NYHA class III than group 1 (18 vs. 2 patients, P<0.05). Group 2 showed an increase of serum creatinine. Serum uric acid increased in both groups. BP values decreased, and HR was corrected to normal values in both groups. Group 2 showed a longer hospitalization time than group receiving HHS infusion (11.67+/-1.8 vs. 8.57+/-2.3 days, P<0.001). In the follow-up (6-12 months), none of the patients from group 1 were readmitted to the hospital and they maintained the NYHA class achieved at the discharge. Group 2 showed 12 patients readmitted to hospital and a higher class than at discharge. CONCLUSION: Our data suggest that the combination of furosemide with HSS is feasible and it appears that this combination produces an improvement of hemodynamic and clinical parameters, reduces the hospitalization time and maintains the obtained results over time in comparison with those receiving high-dose furosemide as bolus.
Renal dysfunction is associated with increased mortality in patients with decompensated heart failure. However, interventions targeted to prevention in this setting have been disappointing. We investigated the effects of hypertonic saline solution (HSS) for prevention of renal dysfunction in decompensated heart failure.
METHODS:
In a double-blind randomized trial, patients with decompensated heart failure were assigned to receive three-day course of 100mL HSS (NaCl 7.5%) twice daily or placebo. Primary end point was an increase in serum creatinine of 0.3mg/dL or more. Main secondary end point was change in biomarkers of renal function, including serum levels of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin-NGAL and the urinary excretion of aquaporin 2 (AQP2), urea transporter (UT-A1), and sodium/hydrogen exchanger 3 (NHE3).
RESULTS:
Twenty-two patients were assigned to HSS and 12 to placebo. Primary end point occurred in two (10%) patients in HSS group and six (50%) in placebo group (relative risk 0.3; 95% CI 0.09-0.98; P=0.01). Relative to baseline, serum creatinine and cystatin C levels were lower in HSS as compared to placebo (P=0.004 and 0.03, respectively). NGAL level was not statistically different between groups, however the urinary expression of AQP2, UT-A1 and NHE3 was significantly higher in HSS than in placebo.
CONCLUSIONS:
HSS administration attenuated heart failure-induced kidney dysfunction as indicated by improvement in both glomerular and tubular defects, a finding with important clinical implications. HSS modulated the expression of tubular proteins involved in regulation of water and electrolyte homeostasis.
