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Hypertonic saline solution for renal failure prevention in patients with decompensated heart failure
Abstract
Hyponatremia and congestive phenomena indicate a bad prognosis in decompensated heart failure. The occurrence of renal failure is associated to an increased death risk.
To evaluate the safety and efficacy of the hypertonic saline solution in patients with decompensated heart failure for renal failure prevention.
Patients with decompensated heart failure, congestion and hyponatremia participated in the study. In addition to the standard treatment, the patients received hypertonic saline solution and were submitted to clinical as well as laboratory assessment.
Nine patients were enrolled in the study. Mean age was 55 + 14.2 years, being 5 male (55.5%) and 4 (44.5%) female patients. All of them presented functional class III-IV of the New York Heart Association (NYHA), and 5 (55.5%) received dobutamine. All of them presented initial creatinine > 1.4 mg/dl. The mean tonicity of the solution was 4.39% + 0.018% (2.5% to 7.5%) and the duration of treatment was 4.9 days + 4.1 days (1-15 days). There were no severe adverse effects; none of the patients presented clinical worsening or neurologic disorders; hypokalemia occurred in 4 cases (44.5%). The comparison of the variables before and after treatment showed a decrease in urea (105 mg/dl + 74.8 mg/dl vs. 88 mg/dl + 79.4 mg/dl; p = 0.03) and increase in the urinary volume (1,183 ml/day vs. 1,778 ml/day; p = 0.03); there was no tendency to creatinine decrease (2.0 mg/dl + 0.8 mg/dl vs. 1.7 mg/dl + 1.0 mg/dl; p = 0.08). Despite the elevation in sodium levels (131 mEq/l + 2.8 mEq/l vs. 134 mEq/l + 4.9 mEq/l) and weight decrease (69.5 kg + 18.6 kg vs. 68.2 kg + 17.1 kg), there was no statistically significant difference.
The use of hypertonic saline solution in patients with decompensated heart failure can be a safe therapeutic method and potentially related to clinical improvement and renal failure prevention.
... Indeed, both diuretics and vasodilators have the potential for inducing hypotension and relative arterial underfilling, thus eliciting further AVP release. Particularly, hyponatremia is likely to be mostly favored or provoked by erroneous and/or overzealous diuretic therapy [5,6]. Therefore, further impairment in effective arterial circulating volume has frequently been blamed on overly drastic or inappropriate diuretic therapy, resulting in the worsening of renal perfusion and fall in glomerular filtration rate (GFR) [7]. ...
... However, the pathogenesis of hyponatremia in edematous patients is much-debated and has not been completely elucidated yet. Particularly, some authors argue in favor of a causative role of particular biohumoral patterns (poorly controlled RAAS overactivation [8][9][10], excess of BNP release [11,12], relative adrenal insufficiency [13,14]), and controversial therapeutic approaches (intensive intravenous diuretic therapy [4,6], and thiazides [15,16]), regarding both the pathogenesis and persistence over time of this electrolyte trouble. ...
In the congestive heart failure (CHF) setting, chronic hyponatremia is very common. The present review aims at addressing topics relevant to the pathophysiology of hyponatremia in the course of CHF as well as its optimal treatment, including the main advantages and the limitations resulting from the use of the available dietary and pharmacological measures approved for the treatment of this electrolytic trouble. A narrative review is carried out in order to represent the main modalities of therapy for chronic hyponatremia that frequently complicates CHF. The limits of usual therapies implemented for CHF-related chronic hyponatremia are outlined, while an original analysis of the main advancements achieved with the use of vasopressin receptor antagonists (VRAs) is also executed. The European regulatory restrictions that currently limit the use of VRAs in the management of CHF are substantially caused by financial concerns, i.e., the high costs of VRA therapy. A thoughtful reworking of current restrictions would be warranted in order to enable VRAs to be usefully associated to loop diuretics for decongestive treatment of CHF patients with hyponatremia.
... Es decir que, un gran porcentaje de pacientes que ingresan a los servicios de urgencias con disnea, sin ser diagnosticados previamente, tienen como origen de este síntoma a la insuficiencia cardíaca. La hipertensión arterial (HTA) se convierte en un factor importante en la presentación de eventos cerebrovasculares, renales y cardíacos en pacientes con insuficiencia cardíaca (12). La enfermedad arterial coronaria y cerebrovascular son las causantes del 30% de muertes al año (13). ...
... En el presente estudio tuvo mayor relevancia la enfermedad pulmonar obstructiva crónica y la hipertensión arterial en un 31.4% y 21.1% respectivamente. Cabe anotar que la HTA tiene un papel impor-tante en la presentación de eventoscerebrovasculares, renales y cardíacos en pacientes con insuficiencia cardíaca (12). ...
Background: Heart failure is a public health problem in industrialized countries, it is impor-tant to know it for its high morbidity and mortality range. Its incidence increases with the age, being it a great cause of cardiovascular death, 70 % of deaths in Colombia are due to cardiac pa-thologies. Materials and methods: 370 patients with diagnosed heart failure between the year 2005 and 2008 (ASSBASALUD ESE, Manizales-Colombia) were chosen as a sample. Some variables as age, classification (States I, II, III, and IV), base pathology (chronic obstruc-tive pulmonary disease, diabetes mellitus, hypertension) and treatment were used. Results: High male frequency (55.4%) was found. In relation to age, the frequency is higher in the popula-tion between 75 and 80 years old. Higher Prevalence (31.4%) of base pathologies (pathologies of base) was found in chronic obstructive pulmonary disease with high medical appointments to internal medicine (53, 7 %) and a higher heart failure incidence on base of pathologies type 2.The most used therapy scheme was Phurosemide and Captopril (13, 8 %), the first one with a greater use (93.2%). Conclusion: The heart failure is a medical and social problem of first order in public health, because of its great morbidity and mortality rate. You can say that it is very impor-tant to spare no effort in prevention, given that good and healthy habits decrease in a high degree its prevalence and complications. Lately the diagnosis and treatment advances have been really important, but in practice, these have not been applied yet.
... Salino hipertónico: ha sido propuesto por largo tiempo como una terapia conjunta a los diuréticos para el manejo de la congestión en falla cardíaca, basado en el efecto osmótico que permite el transporte de agua desde el intersticio hacia la luz vascular, una vez allí puede ser excretado gracias al uso conjunto de diuréticos, a la par que puede impactar en los efectos hemodinámicos a nivel renal causados por los diuréticos 37 . En un metaanálisis de estudios, comparando salino hipertónico versus furosemida endovenosa, en el cual se incluyeron nueve trabajos 38 , se encontró que el uso de salino hipertónico impacta en la mortalidad por cualquier causa, estancia hospitalaria, pérdida de peso y variación de la creatinina de manera favorable, teniendo un per l de costo efectividad conveniente, incluso puede prevenir desenlaces como necesidad de ultra ltración. ...
... In the SSH group, only 2 (10%) patients showed an increase in serum creatinine, while in the placebo group, 6 (50%) showed this change (p=0.01). 28 Other studies have also demonstrated the power of this solution in promoting an increase in diuresis/natriuresis and weight loss. A meta-analysis with 5 randomized clinical trials and 1,032 patients treated with SSH plus IV furosemide versus 1,032 patients treated with IV furosemide alone demonstrated a decrease in allcause mortality in the SSH group (p = 0.0003), in addition to a reduction in hospitalizations (p = 0.001). ...
... Moreover, several studies in patients with chronic HF (CHF) have reported that IV infusion of hypertonic saline solution (HSS) plus high-dose furosemide is more effective than furosemide alone [8][9][10][11][12], resulting in increased urine output. These findings have allowed for greater weight loss, a shorter length of hospitalization [13][14][15][16], a greater reduction in neurohormonal activation [17], and a significant improvement in renal function [18][19][20][21]. ...
Introduction: Diuretic responsiveness in
patients with chronic heart failure (CHF) is
better assessed by urine production per unit
diuretic dose than by the absolute urine output
or diuretic dose. Diuretic resistance arises over
time when the plateau rate of sodium and water
excretion is reached prior to optimal fluid
elimination and may be overcome when
hypertonic saline solution (HSS) is added to
high doses of furosemide.
... En el ámbito renal, la administración de la SSH se ha asociado con una mejoría en la función tubular con disminución de los marcadores de daño renal temprano y un probable efecto que evita el deterioro en la función renal durante la terapia diurética intensiva, asociado al incremento de la perfusión renal durante la FCD (20,25,26) . El aumento de sodio a nivel tubular distal, contrarresta la retención de sodio posterior al túbulo proximal, evitando el fenómeno de «frenado» (27) . ...
RESUMEN
La presencia de una descompensación en falla cardiaca continúa siendo una condición con altas tasas de hospitalización, impacto en el sistema de salud y calidad de vida de quienes la padecen. El eje principal del tratamiento en estos casos son los diuréticos; sin embargo, en ocasiones se puede presentar resistencia a este grupo farmacológico, lo que genera un inadecuado balance negativo de líquidos y persistencia de la congestión con desenlaces clínicos negativos. La solución salina hipertónica junto con dosis altas de diurético surge como una opción terapéutica para este grupo de pacientes, con probables beneficios fisiológicos, clínicos e impacto en tasas de hospitalización y reingreso por descompensación de falla cardiaca. A continuación, se realiza una revisión de los aspectos más relevantes y beneficios de esta combinación.
... The proposed mechanism is that salt restriction leads to a reduction in chloride sensing by the macula densa in the distal nephron, which leads to a sodium-avid state in the kidney [105]. Beyond the initial reports from Italy [106], several groups have also demonstrated the potential benefits of concomitant saline infusion during aggressive diuresis during acute HF admissions [107][108][109][110]. However, a small single-center, pilot randomized trial in patients with underlying advanced chronic kidney disease failed to demonstrate incremental benefits of hypertonic saline use [111]. ...
Purpose of review:
This review aims to summarize our current understanding and management strategies of acute cardiorenal syndrome (CRS).
Recent findings:
The definition of acute CRS remains debated, in part due to the lack of reliable insights into salt and water handling of the kidneys beyond impairment in glomerular filtration. Protocolized use of loop diuretics to ensure adequate delivery to their target of action, as well as segmental tubular blockade with adjunctive use of thiazide diuretics, acetazolamide, amiloride, or sodium-glucose transporter 2 (SGLT2) inhibitors, may result in more effective natriuresis in patients with acute CRS who exhibit diuretic resistance. Other strategies, such as modulating renal sodium avidity with the use of hypertonic saline, reduction of intra-abdominal pressure, or device-based salt and volume removal, are promising and warrant further investigation. Acute CRS remains a significant contributor of morbidity and mortality for the acute heart failure population. New strategies have challenged current dogmas in our understanding of its pathophysiology, which may lead to potential new treatment approaches.
... Thus, patients with pre-existing hyponatremia were excluded from this study. While our and several other investigations [14,15,22,26,45,46] on hypertonic saline in the critically ill did not reveal sodium-related adverse events caused by HSinduced acute and transient hypernatremia, it should be noted that the quality of evidence regarding adverse outcomes of hypertonic saline infusions is low [22]. Thus, it seems important that a degree of uncertainty remains as to whether infusion of hypertonic saline is safe in the critically ill, warranting further large-scale investigations. ...
PurposeRecent evidence questions a liberal approach to fluid resuscitation in intensive care unit (ICU) patients. Here, we assess whether use of hypertonic saline applied as single infusion at ICU admission after cardiac surgery can reduce cumulative perioperative fluid volume.Methods
Prospective randomized double-blind single-center clinical trial investigates effects of a single infusion of hypertonic saline (HS) versus normal saline (comparator). Primary endpoint was the cumulative amount of fluid administered in patients in the hypertonic saline versus the 0.9% saline groups (during ICU stay). Upon ICU admission, patients received a single infusion of 5 ml/kg body weight of 7.3% NaCl (or 0.9% NaCl) over 60 min. Patients undergoing cardiac surgery for elective valvular and/or coronary heart disease were included. Patients with advanced organ dysfunction, infection, and/or patients on chronic steroid medication were excluded.ResultsA total of 101 patients were randomized to receive the study intervention (HS n = 53, NS n = 48). Cumulative fluid intake on the ICU (primary endpoint) did not differ between the HS and the NS groups [median 3193 ml (IQR 2052–4333 ml) vs. 3345 ml (IQR 2332–5043 ml)]. Postoperative urinary output until ICU discharge was increased in HS-treated patients [median 2250 ml (IQR 1640–2690 ml) vs. 1545 ml (IQR 1087–1976 ml)], and ICU fluid balance was lower in the HS group when compared to the NS group [296 ml (IQR − 441 to 1412 ml) vs. 1137 ml (IQR 322–2660 ml)].Conclusion
In a monocentric prospective double-blind randomized clinical trial, we observed that hypertonic saline did not reduce the total fluid volume administered on the ICU in critically ill cardiac surgery patients. Hypertonic saline infusion was associated with timely increase in urinary output. Variations in electrolyte and acid–base homeostasis were transient, but substantial in all patients.
... Se usa de forma irregular desde hace aproximadamente quince años, en concentraciones desde 1,4 hasta 4,6%. Se ha encontrado pérdida ponderal adicional de 3 kg, reducción del tiempo de hospitalización en un promedio de 3,5 días, disminución del riesgo de descompensación del 35% y aumento de diuresis en 600 ml por día vs. pacientes con falla cardiaca manejados únicamente con diuréticos; no muestra cambios en la concentración de ácido úrico, pero sí reducción del riesgo de lesión renal aguda en comparación con dosis alta de furosemida intravenosa 69,70 . ...
Resumen
La definición más actualizada de falla cardiaca avanzada incluye síntomas refractarios al tratamiento convencional, independiente de la fracción de eyección del ventrículo izquierdo, acompañados de elevación de péptidos natriuréticos. En esta nueva definición se destacan condiciones específicas como son la necesidad usual de diurético intravenoso, hospitalizaciones o consultas frecuentes por falla cardíaca, medicación inotrópica intermitente y arritmias malignas recurrentes.
Esta condición está presente en aproximadamente 4 a 6% de los pacientes con falla cardiaca y se asocia a más síntomas, más comorbilidades y mayor mortalidad (hasta 75% a un año). En este punto, las terapias convencionales han fallado o son refractarias y se requiere la toma de decisiones para instaurar tratamientos más avanzados (p. ej.: inotrópicos, asistencia ventricular, trasplante cardiaco, cuidado paliativo, entre otras).
El tratamiento representa un reto para los sistemas de salud de Colombia por la necesidad de optimizar y racionalizar el uso de estos recursos; por esto se debe considerar que estos pacientes, en algún momento de su evolución, que sean remitidos para valoración en las Clínicas de Falla Cardíaca ya que estos servicios cuentan con personal altamente calificado y una estructura administrativa, logística y tecnológica que garantizan el acceso a un tratamiento integral y multidisciplinario con estándares de calidad internacionales que es lo que finalmente se requiere en estas condiciones.
En el “Consenso colombiano de falla cardiaca avanzada” se presentan diferentes opciones de tratamiento a considerar y un modelo de atención integral que inicia desde el momento del diagnóstico hasta etapas refractarias y avanzadas.
... Patients admitted to the hospital with a primary diagnosis of ADHF according to the Framingham criteria [15,21] were investigated prospectively as long as they could be included in the study within a maximum period of 24 h after admission to the hospital. Exclusion criteria were: patients with estimated creatinine clearance <30 mL/min/1.73 ...
Background:
We tested the hypothesis that a normal sodium diet could be associated with preservation of serum sodium during treatment of acute decompensated heart failure (ADHF).
Methods and results:
Forty-four patients hospitalized for ADHF were blindly randomized by using block method to a low sodium diet (LS: 3 g/day of dietary sodium chloride; n = 22, 59.5 ± 11.9 y.o., 50% males. LVEF = 30.0 ± 13.6%); and a normal sodium diet (NS: 7 g/day; n = 22, 56.4 ± 10.3 y.o., 68% males; LVEF = 27.8 ± 11.7%), and both groups were submitted to fluid restriction of 1.000 mL/day. At the 7th day of intervention 16 patients of LS group and 15 patients of NS group were assessed for difference in serum sodium. Both groups had equivalent decongestion, reflected by similar percent reduction of body weight (LS: -5.0 ± 4.7% vs NS: -4.5 ± 5.2%. p = 0.41). Reduction of the N terminal fragment of type B natriuretic peptide (NT-proBNP) was significant only in the NS (-1497.0 [-18843.0 - 1191.0]. p = 0.04). The LS group showed lower levels of serum sodium (135.4 ± 3.5 mmol/L) compared to the NS group (137.5 ± 1.9 mmol/L; p = 0.04). Four cases of hyponatremia were observed only in the LS group (22%). The NS group exhibited higher mean blood pressure values (79.4 ± 2.4 mmHg vs 75.5 ± 3.0 mmHg. p = 0.03), and lower heart rate (73.2 ± 1.6 bpm vs 75.5 ± 2.1 bpm. p = 0.02).
Conclusions:
These results suggest that a normal sodium diet, when compared to a low sodium diet, is associated with similar degrees of decongestion, but with higher levels of natremia, blood pressure and lower neurohormonal activation during ADHF treatment.
Trial registration:
clinicaltrials.gov Identifier no. NCT03722069.
... Among the proposed mechanisms to explain the benefits of HSS, it has been reported that it would prevent intravascular depletion due to diuretics [15,16] and thus would maintain renal flow and the glomerular filtration rate (GFR) during intensive treatment of intravenous furosemide [17] . Compared to the administration of high doses of intravenous furosemide alone, concomitant use of HSS (HSS + F) has shown, in patients with ADHF, a more rapid and complete resolution of the signs and symptoms of congestion by increasing urine volume and by potentiating weight loss [16,18,19] , the potential to protect against deterioration of renal function during intensive diuretic therapy [15,20] , an improvement of cardiac biomarkers and echocardiographic parameters [19,21,22] , a reduced length of hospital stay and frequency of re-hospitalizations [23] and a good safety profile [24] . Therefore, the aim of the present report was to test the safety and effectiveness of HSS + F as a strategy for weight loss and prevention of further deterioration of renal function compared to the usual intensive treatment with intravenous furosemide alone. ...
AIM
To test the safety and effectiveness of hypertonic saline solution (HSS + F) as a strategy for weight loss and prevention of further deterioration of renal function.
METHODS
Patients admitted with acute decompensated heart failure (ADHF) who received HSS + F were included in the study. After a period of a standard ADHF treatment, our patients received an intravenous infusion of furosemide (250 mg) combined with HSS (150 mL of 3% NaCl) twice a day for a mean duration of 2.3 d. Our primary outcomes were weight loss and a change in serum creatinine per day of treatment. The parameters of the period prior to treatment with HSS + F were compared with those of the period with HSS + F.
RESULTS
A total of 47 patients were included. The mean creatinine on admission was 155 μmol/L ± 65 μmol/L, the ejection fraction was 40% ± 17%. The experimental treatment (HSS + F) resulted in greater weight loss per day of treatment than the standard treatment (-1.4 kg/d ± 1.4 kg/d vs -0.4 kg/d ± 1.0 kg/d, P = 0.0168). Importantly, the change in creatinine was not significantly different.
CONCLUSION
This study supports the effectiveness of HSS + F on weight loss in patients with ADHF. The safety profile, particularly with regard to renal function, leads us to believe that HSS + F may be a valuable option for those patients presenting with ADHF who do not respond to conventional treatment with intravenous furosemide alone.
... In addition to greater decongestive efficacy, HSS use may also preserve renal function during diuresis. Previous cohorts have suggested a lower incidence of worsening renal function during treatment for AHF [39][40][41]. Further, a meta-analysis of nine studies of patients receiving HSS as an adjunct to loop diuretic therapy in AHD revealed a consistent trend in the renoprotective effects of HSS use [42]. ...
Electrolyte abnormalities are common in heart failure and can arise from a variety of etiologies. Neurohormonal activation from ventricular dysfunction, renal dysfunction, and heart failure medications can perturb electrolyte homeostasis which impact both heart failure-related morbidity and mortality. These include disturbances in serum sodium, chloride, acid-base, and potassium homeostasis. Pharmacological treatments differ for each electrolyte abnormality and vary from older, established treatments like the vaptans or acetazolamide, to experimental or theoretical treatments like hypertonic saline or urea, or to newer, novel agents like the potassium binders: patiromer and zirconium cyclosilicate. Pharmacologic approaches range from limiting electrolyte intake or directly repleting the electrolyte, to blocking or promoting their resorption, and to neurohormonal antagonism. Because of the prevalence and clinical impact of electrolyte abnormalities, understanding both the older and newer therapeutic options is and will continue to be necessity for the management of heart failure.
... Moreover, several studies in patients with chronic HF (CHF) have reported that IV infusion of hypertonic saline solution (HSS) plus high-dose furosemide is more effective than furosemide alone [8][9][10][11][12], resulting in increased urine output. These findings have allowed for greater weight loss, a shorter length of hospitalization [13][14][15][16], a greater reduction in neurohormonal activation [17], and a significant improvement in renal function [18][19][20][21]. ...
Introduction:
Diuretic responsiveness in patients with chronic heart failure (CHF) is better assessed by urine production per unit diuretic dose than by the absolute urine output or diuretic dose. Diuretic resistance arises over time when the plateau rate of sodium and water excretion is reached prior to optimal fluid elimination and may be overcome when hypertonic saline solution (HSS) is added to high doses of furosemide.
Methods:
Forty-two consecutively hospitalized patients with refractory CHF were randomized in a 1:1:1 ratio to furosemide doses (125 mg, 250 mg, 500 mg) so that all patients received intravenous furosemide diluted in 150 ml of normal saline (0.9%) in the first step (0-24 h) and the same furosemide dose diluted in 150 ml of HSS (1.4%) in the next step (24-48 h) as to obtain 3 groups as follows: Fourteen patients receiving 125 mg (group 1), fourteen patients receiving 250 mg (group 2), and fourteen patients receiving 500 mg (group 3) of furosemide. Urine samples of all patients were collected at 30, 60, and 90 min, and 3, 4, 5, 6, 8, and 24 h after infusion. Diuresis, sodium excretion, osmolality, and furosemide concentration were evaluated for each urine sample.
Results:
After randomization, 40 patients completed the study. Two patients, one in group 2 and one in group 3 dropped out. Patients in group 1 (125 mg furosemide) had a mean age of 77 ± 17 years, 43% were male, 6 (43%) had heart failure with a preserved ejection fraction (HFpEF), and 64% were in New York Heart Association (NYHA) class IV; the mean age of patients in group 2 (250 mg furosemide) was 80 ± 8.1 years, 15% were male, 5 (38%) had HFpEF, and 84% were in NYHA class IV; and the mean age of patients in group 3 (500 mg furosemide) was 73 ± 12 years, 54% were male, 6 (46%) had HFpEF, and 69% were in NYHA class IV. HSS added to furosemide increased total urine output, sodium excretion, urinary osmolality, and furosemide urine delivery in all patients and at all time points. The percentage increase was 18,14, and 14% for urine output; 29, 24, and 16% for total sodium excretion; 45, 34, and 20% for urinary osmolarity; and 27, 36, and 32% for total furosemide excretion in groups 1, 2, and 3, respectively. These findings were translated in an improvement in the furosemide dose-response curves in these patients.
Conclusion:
These results may serve as new pathophysiological basis for HSS use in the treatment of refractory CHF.
... The efficacy of various concentrations of HSS has been evaluated in patients with heart failure [26,29,30]. It was reported that infusion of 7.5 % NaCl solution resulted in vasodilatation and increased coronary and renal blood flow in experimental shock models [31,32]. ...
BACKGROUND: There are few prospective data available for establishing a standard diuretic administration regimen for patients with acute decompensated heart failure (ADHF). We aimed to assess the safety and efficacy of three regimens of furosemide administration in patients with ADHF with regard to diuresis, renal functions, and in-hospital outcomes.
METHODS: A total of 43 patients who presented with ADHF were randomized into three groups: (a) continuous infusion (cIV) of 160 mg furosemide for 16 h/day (n = 15); (b) bolus injections (bI) of 80 mg furosemide twice a day (n = 14); (c) and administration of 160 mg furosemide plus hypertonic saline solution (HSS) as an infusion for 30 min once a day (n = 14). All regimens were continued for 48 h. Study endpoints were negative fluid balance assessed by loss of body weight, change in the serum creatinine (baseline to 48 h and baseline to compensated state), and length of hospitalization.
RESULTS: There was no significant difference in the mean change in serum creatinine level at the end of 48 h between groups (p = 0.08). There was also no significant difference among groups regarding loss of body weight (p = 0.66). A significantly shorter hospitalization was observed in patients treated with HSS compared with the other groups (cIV group 6.6 ± 3.4 days vs. bI group 7.9 ± 4.1 days vs. HSS group 3.7 ± 1.3 days; p < 0.01).
CONCLUSION: All three furosemide regimens have similar renal safety and efficacy measures. However, administration of furosemide plus HSS may be the preferred diuretic strategy because of its shorter hospital stay.
... El uso de salino hipertónico no supuso la aparición de congestión pulmonar ni el empeoramiento de la clase funcional y, por el contrario, redujo significativamente el porcentaje de reingresos y la mortalidad a largo plazo. Resultados similares se han observado en otros estudios más modestos 19 . Estos resultados han propiciado que las Guías Canadienses ...
Mujer de 66 años con valvulopatía mitral reumática evoluciona-da (ecocardiograma: ventrículo izquierdo no dilatado ni hiper-trófico con función sistólica conservada, dilatación moderada de aurícula izquierda, dilatación aneurismática de cavidades dere-chas y movimiento anómalo del septo con aplanamiento tanto sistólico como diastólico indicativo de sobrecarga de presión y volumen). Insuficiencia mitral de grado 2/4, insuficiencia tricus-pídea grave que permite estimar una hipertensión pulmonar gra-ve (PSAP 82 mmHg). Fibrilación auricular crónica anticoagulada. En el último año presenta cinco ingresos por insuficiencia car-díaca de predominio derecho con distintos desencadenantes: infección respiratoria en dos ocasiones, bradicardia por hiper-potasemia, vómitos por intoxicación digitálica y descompen-sación hiperglucémica. En todos ellos presenta deterioro de función renal con recupe-ración parcial y en los tres últimos, hiponatremia. La analítica al alta del último ingreso muestra urea/cr 67/1,3 mg/dl y Na 135 mEq/l, mientras que hace un año tenía urea/cr 36/0,7 mg/dl y Na 142 mEq/l. La paciente ingresa de nuevo a las tres semanas del alta por clínica de insuficiencia cardíaca de predo-minio derecho. En la analítica de sangre destacan urea/cr 143/2,7 mg/dl, Na/K 128/5 mEq/l, osmolalidad plasmática 275 mOsm/kg y en orina de micción espontánea Na/K 23/33 mEq/l, cr 106 mg/dl y osmolalidad urinaria 280 mOsm/kg.
... Não existe prevenção ou tratamento especifico para insuficiência renal a não ser evitar a hipovolemia e hipoperfusão renal. Em pacientes hospitalizados investiga-se o papel de antagonistas da adenosina e solução hipertônica 376 . ...
... Small volumes of saline solutions have also been tested in patients with heart failure, [21,22] and most studies focused on safety and effectiveness aspects. A randomized trial reported as a secondary finding in a selective population of patients highly resistant to diuretics, that the infusion of saline solution with different tonicities was associated with lower creatinine levels [23]. ...
Abstract
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.
... In patients, the infusion of 7.5% NaCl has been successfully used in cardiogenic shock arising from right ventricular infarction (74). Small volumes of saline solutions have also been tested in patients with heart failure (75,76), and most studies have focused on the aspects of safety and effectiveness. A randomized trial reported, as a secondary finding in a selective population of patients highly resistant to diuretics, that the infusion of saline solutions with different tonicities was associated with lower creatinine levels (77). ...
Renal dysfunction is common during episodes of acute decompensated heart failure, and historical data indicate that the mean creatinine level at admission has risen in recent decades. Different mechanisms underlying this change over time have been proposed, such as demographic changes, hemodynamic and neurohumoral derangements and medical interventions. In this setting, various strategies have been proposed for the prevention of renal dysfunction with heterogeneous results. In the present article, we review and discuss the main aspects of renal dysfunction prevention according to the different stages of heart failure.
... Moreover, several studies in patients with chronic HF (CHF) have reported that IV infusion of hypertonic saline solution (HSS) plus high-dose furosemide is more effective than furosemide alone [8][9][10][11][12], resulting in increased urine output. These findings have allowed for greater weight loss, a shorter length of hospitalization [13][14][15][16], a greater reduction in neurohormonal activation [17], and a significant improvement in renal function [18][19][20][21]. ...
... Small volumes of saline solutions have also been tested in patients with heart failure, [21,22] and most studies focused on safety and effectiveness aspects. A randomized trial reported as a secondary finding in a selective population of patients highly resistant to diuretics, that the infusion of saline solution with different tonicities was associated with lower creatinine levels [23]. ...
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.
... Additionally, these data were generally from patients with cardiogenic shock resulting from right ventricular infarction. 2 Another report also evaluated the use of hypertonic saline as an adjunct therapy in uncompensated heart failure patients and indicated that hypertonic saline had positive effects on renal function. 3 In experimental models, hypertonic saline improved myocardial contractility, 4 but its immediate impact on the hemodynamic profile during acute UHF has not been studied or reported to date. In the present case study, hypertonic saline was the only available non-invasive option for the treatment of the patient. ...
Uncompensated heart failure (UHF) is a leading cause of hospitalization. The available drugs to treat acute UHF include inotropes, diuretics and vasodilators. In recent years, hypertonic saline (HTS) has emerged as a new potential therapy for refractory heart failure, usually in association with high doses of diuretics. However, there have been no reports describing the use of HTS as a first-line treatment for UHF. Here, we report a case in which a 10% NaCl solution was used as the primary therapy for a patient with UHF. Almost immediately, hypertonic saline was able to restore the patient's hemodynamic profile and to eliminate Cheyne-Stokes respiration (CSR), which is associated with a low cardiac output state.
... Não existe prevenção ou tratamento especifico para insuficiência renal a não ser evitar a hipovolemia e hipoperfusão renal. Em pacientes hospitalizados investiga-se o papel de antagonistas da adenosina e solução hipertônica 376 . ...
... In a study on 9 patients with ADHF and hyponatremia (mean serum Na level 131 mEq/L), Issa et al did not report any worsening in pulmonary congestion with use of hypertonic saline, and found an increase in urine output and reduction in serum blood urea nitrogen (BUN) with no significant change in weight. 17 In a randomized single-blind study on 107 patients with refractory HF, Licata et al used intravenous (IV) furosemide combined with small volumes of hypertonic saline, and compared the results with those of patients who received only IV furosemide. 18 While the first group showed significant improvement in their hyponatremia (increase in serum Na from 135.8 to 142.3 mEq/L, P < 0.001), serum Na levels decreased in those patients who received furosemide alone (134.8 to 130.2 mEq/L, P < 0.007). ...
Hyponatremia is frequently encountered in patients with heart failure (HF), and its association with adverse outcomes is well-established in this population. While hyponatremia is an independent marker for severity of HF, it is not certain whether it has a causal impact on the progression of the disease. There are no universally accepted consensus guidelines regarding therapeutic strategies for HF-associated hyponatremia and volume overload; current societal guidelines do not address management of this complication. Whereas thiazide diuretics are known to induce or worsen hyponatremia in this setting through a number of mechanisms, loop diuretics can be considered a readily available first-line pharmacologic therapy. Consistent with pathophysiology of the disease and mechanisms of action of loop diuretics, available clinical evidence supports such an approach provided that patients can be closely monitored. Use of vasopressin receptor antagonists is an emerging therapeutic strategy in this setting, and the efficacy of these agents has so far been shown in a number of clinical studies. These agents can be reserved for patients with HF in whom initial appropriate loop diuretic therapy fails to improve serum sodium levels.
Objectives:
To evaluate the efficacy of the simultaneous hypertonic saline solution and IV furosemide (HSS+Fx) for patients with fluid overload compared with IV furosemide alone (Fx).
Data sources:
Electronic databases (MEDLINE, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, PsycINFO, Scopus, and WOS) were searched from inception to March 2020.
Study selection:
Randomized controlled trials on the use of HSS+Fx in adult patients with fluid overload versus Fx were included.
Data extraction:
Data were collected on all-cause mortality, hospital length of stay, heart failure-related readmission, along with inpatient weight loss, change of daily diuresis, serum creatinine, and 24-hour urine sodium excretion from prior to post intervention. Pooled analysis with random effects models yielded relative risk or mean difference with 95% CIs.
Data synthesis:
Eleven randomized controlled trials comprising 2,987 acute decompensated heart failure patients were included. Meta-analysis demonstrated that HSS+Fx was associated with lower all-cause mortality (relative risk, 0.55; 95% CI, 0.46-0.67; p < 0.05; I2 = 12%) and heart failure-related readmissions (relative risk, 0.50; 95% CI, 0.33-0.76; p < 0.05; I2 = 61%), shorter hospital length of stay (mean difference, -3.28 d; 95% CI, -4.14 to -2.43; p < 0.05; I2 = 93%), increased daily diuresis (mean difference, 583.87 mL; 95% CI, 504.92-662.81; p < 0.05; I2 = 76%), weight loss (mean difference, -1.76 kg; 95% CI, -2.52 to -1.00; p < 0.05; I2 = 57%), serum sodium change (mean difference, 6.89 mEq/L; 95% CI, 4.98-8.79; p < 0.05; I2 = 95%), and higher 24-hour urine sodium excretion (mean difference, 61.10 mEq; 95% CI, 51.47-70.73; p < 0.05; I2 = 95%), along with decreased serum creatinine (mean difference, -0.46 mg/dL; 95% CI, -0.51 to -0.41; p < 0.05; I2 = 89%) when compared with Fx. The Grading of Recommendation, Assessment, Development, and Evaluation certainty of evidence ranged from low to moderate.
Conclusions:
Benefits of the HSS+Fx over Fx were observed across all examined outcomes in acute decompensated heart failure patients with fluid overload. There is at least moderate certainty that HSS+Fx is associated with a reduction in mortality in patients with acute decompensated heart failure. Factors associated with a successful HSS+Fx utilization are still unknown. Current evidence cannot be extrapolated to other than fluid overload states in acute decompensated heart failure.
Recently, we and other group have reported that furosemide administration along with hypertonic saline solution enhanced diuretic efficiency of furosemide. However, little is known about factors which associated with high diuretic efficiency by hypertonic saline solution with furosemide therapy. To identify predictors of diuretic efficiency in the hypertonic saline solution with furosemide therapy, we recruited 30 consecutive hospitalized heart failure (HF) patients with volume overload (77 ± 10 years, systolic blood pressure > 90 mmHg, and estimated glomerular filtration rate > 15 ml/min/1.73 m²). Hypertonic saline with furosemide solution, consisting of 500 ml of 1.7% hypertonic saline solution with 40 mg of furosemide, was administered continuously over 24 h. The patients were divided into two groups on the basis of 24-h urine volume (UV) after initiation of diuretic treatment ≥ 2000 ml (high urine volume: HUV) and < 2000 ml (low urine volume: LUV). The basal clinical characteristics of both groups were analyzed and the predictors of HUV after receiving the treatment were identified. There were not significant differences between two groups in baseline clinical characteristics and medication. Univariate logistic analysis revealed that blood urea nitrogen/creatinine ratio, urine urea nitrogen/creatinine ratio (UUN/UCre), fractional excretion of sodium, and tricuspid annular plane systolic excursion positively associated with HUV. Multivariate logistic regression analysis revealed that UUN/UCre at baseline was independently associated with HUV, and UUN/UCre best predicts HUV by the therapy with a cut-off value of 6.16 g/dl/g Cre (AUC 0.910, 95% CI 0.696–0.999, sensitivity 80%, specificity 87%). The Kaplan–Meier curves revealed significant difference for HF rehospitalization and death rate at 180 days between patients with UUN/UCre ≥ 6.16 g/dl/g Cre and those with UUN/UCre < 6.16 g/dl/g Cre (log-rank P = 0.0489). UUN/UCre at baseline strongly predicted of diuretic efficiency in the hypertonic saline solution with furosemide therapy, and was associated with HF prognosis.
Introduction:
Diuretic failure is a potential life-ending event but is unpredictable and poorly understood. The objectives of this study were to evaluate pharmacodynamic markers of furosemide-induced diuresis and to investigate mechanisms of diuretic braking in dogs receiving constant rate infusion (CRI) of furosemide.
Animals:
Six healthy male dogs.
Methods:
Raw data and stored samples from one arm of a previously published study were further analyzed to mechanistically investigate causes of diuretic braking in these dogs. Urine volume was recorded hourly during a 5-h furosemide CRI. Urine and blood samples were collected hourly to measure serum and urine electrolytes, urine aldosterone, and plasma and urine furosemide. Serum electrolyte fractional excretion was calculated. Urine sodium concentration was indexed to urine potassium (uNa:uK) and urine furosemide (uNa:uFur) concentrations, plasma furosemide concentration was indexed to urine furosemide concentration (pFur:uFur), and urine aldosterone was indexed to urine creatinine (UAldo:C). Temporal change and the relationship to urine volume were evaluated for these measured and calculated variables.
Results:
Urine volume was significantly correlated with urine electrolyte amounts and with uNa:uK. The ratio of pFur:uFur decreased during the infusion, whereas furosemide excretion was unchanged.
Conclusions:
There was a strong relationship between urine volume and absolute urine electrolyte excretion. Urine volume was strongly correlated to uNa:uK, giving it potential as a spot indicator of urine production during diuresis. The decrease in uNa:uK over time during the infusion is consistent with mineralocorticoid modification of urinary electrolyte excretion, supporting renin-angiotensin-aldosterone activation as a cause of diuretic braking in this model.
Introduction
The optimal approach to fluid management in critically ill patients is highly debated. Fluid resuscitation using hypertonic saline was used in the past for more than thirty years, but has recently disappeared from clinical practice. Here we provide an overview on the currently available literature on effects of hypertonic saline infusion for fluid resuscitation in the critically ill.
Methods
Systematic analysis of reports of clinical trials comparing effects of hypertonic saline as resuscitation fluid to other available crystalloid solutions.
A literature search of MEDLINE and the Cochrane Controlled Clinical trials register (CENTRAL) was conducted to identify suitable studies.
Results
The applied search strategy produced 2284 potential publications. After eliminating doubles, 855 titles and abstracts were screened and 40 references retrieved for full text analysis. At total of 25 scientific studies meet the prespecified inclusion criteria for this study.
Conclusion
Fluid resuscitation using hypertonic saline results in volume expansion and less total infusion volume. This may be of interest in oedematous patients with intravascular volume depletion. When such strategies are employed, renal effects may differ markedly according to prior intravascular volume status. Hypertonic saline induced changes in serum osmolality and electrolytes return to baseline within a limited period in time. Sparse evidence indicates that resuscitation with hypertonic saline results in less perioperative complications, ICU days and mortality in selected patients. In conclusion, the use of hypertonic saline may have beneficial features in selected critically ill patients when carefully chosen. Further clinical studies assessing relevant clinical outcomes are warranted.
Objective:
The goal of this study was to investigate the short-term safety and diuretic efficacy of furosemide constant rate infusion (CRI) diluted with 5% dextrose in water (D5W) compared to dilution with 2.4% hypertonic saline in healthy dogs.
Animals:
Six healthy dogs.
Methods:
Dogs were studied in a randomized, blinded, crossover manner. Furosemide 3.3mg/kg was diluted to 2.2mg/mL with either 1.5mL/kg D5W for the DEX method or with 1.0mL/kg D5W and 0.5mL/kg of 7.2% hypertonic saline for the H-SAL method. After a 0.66mg/kg furosemide IV bolus, the infusion rate was 0.3 mL/kg/hr for 5 h such that both methods delivered 0.66 mg/kg/hr (total 3.3mg/kg) furosemide in equal volume for the study duration. Urine output, water intake, central venous pressure (CVP), physical parameters, furosemide concentrations, blood and urine electrolytes, and urine aldosterone to creatinine ratio (UAldo:C) were evaluated.
Results:
Measured variables were not different between methods but showed changes over time consistent with diuresis. Mean CVP decreased over time similarly for both methods. Plasma furosemide and urine concentrations were stable and not different between methods. Both furosemide CRI methods showed an increase in the UAldo:C, however, the rise was greater for DEX than for H-SAL.
Conclusions:
Diuresis was similar for both furosemide CRI methods; however, the H-SAL method induced less renin-angiotensin-aldosterone system activation than the DEX method. The absence of intravascular volume expansion based on CVP suggests that dilution of a furosemide CRI with 2.4% hypertonic saline may be well tolerated in heart failure.
In this brief review, the pathophysiology of hyponatremia and its clinical significance in the course of chronic heart failure (CHF) are illustrated. Moreover, issues concerning the optimal treatment for hyponatremia during CHF are addressed and discussed. In addition, advantages and limitations resulting from the use of vasopressin receptor antagonists, drugs that have recently emerged as the best available resource against hyponatremia, are highlighted.
In advanced congestive heart failure (CHF), intravenous (i.v.) inotropic agents, i.v. diuretics, ultrafiltration, and hemodialysis have been shown to not yield better clinical outcomes. In this scenario, the simultaneous administration of hypertonic saline solution (HSS) and furosemide may offer a more effective therapeutic option with a good safety profile.
Therefore, a meta-analysis was performed to compare combined therapy, consisting of i.v. furosemide plus concomitant administration of HSS, with i.v. furosemide alone for acute decompensated heart failure (ADHF). The outcomes we chose were all-cause mortality, risk of re-hospitalization for ADHF, length of hospital stay, weight loss, and variation of serum creatinine.
Based on five randomized controlled trials (RCTs) involving 1,032 patients treated with i.v. HSS plus furosemide vs. 1,032 patients treated with i.v. furosemide alone, a decrease in all-cause mortality in patients treated with HSS plus furosemide was proven [RR = 0.57; 95 % confidence interval (CI) = 0.44-0.74, p = 0.0003]. Likewise, combined therapy with HSS plus furosemide was shown to be associated with a reduced risk of ADHF-related re-hospitalization (RR = 0.51; 95 % CI = 0.35-0.75, p = 0.001). Besides, combined therapy with HSS plus furosemide was found to be associated with a reduced length of hospital stay (p = 0.0002), greater weight loss (p < 0.00001), and better preservation of renal function (p < 0.00001).
HSS as an adjunct to i.v. furosemide for diuretic-resistant CHF patients led to a better renal safety profile and improved clinical endpoints such as mortality and heart failure-related hospitalizations.
Advanced congestive heart failure (CHF) therapies include intravenous inotropic agents, change in class of diuretics, and venous ultrafiltration or hemodialysis. These modalities have not been associated with improved prognosis and are limited by availability and cost. Compared to high-dose furosemide alone, concomitant hypertonic saline solution (HSS) administration has demonstrated improved clinical outcomes with good safety profile.
A literature search was conducted for randomized controlled trials that investigated the use of HSS in patients admitted to hospital with acute CHF.
1032 patients treated with HSS and 1032 controls, demonstrated decreased all-cause mortality in patients treat with HSS with RR of 0.56 (95% CI 0.41-0.76,p=0.0003). 1012 patients treated with HSS and 1020 controls, demonstrated decreased heart failure hospital readmission with RR of 0.50 (95% CI 0.33-0.76,p=0.001). Patients treated with HSS also demonstrated decreased hospital length of stay (p=0.0002), greater weight loss (p<0.00001), and preservation of renal function (p<0.00001).
The results of this meta-analysis demonstrate that in patients with advanced CHF concomitant hypertonic saline administration improved weight loss, preserved renal function, and decreased length of hospitalization, mortality and heart failure rehospitalization. A future adequately powered, multi-centre, placebo controlled, randomized, double dummy, blinded trial is needed to assess the benefit of hypertonic saline in patients with renal dysfunction, in diverse patient populations, as well using a patient population on optimal current heart failure treatment. Pending further validation, there is promise for hypertonic saline as an advanced therapy for the management of acute advanced CHF.
Heart failure is a disease with high incidence and prevalence in the population. The costs with hospitalization for decompensated heart failure reach approximately 60% of the total cost with heart failure treatment, and mortality during hospitalization varies according to the studied population, and could achieve values of 10%. In patients with decompensated heart failure, history and physical examination are of great value for the diagnosis of the syndrome, and also can help the physician to identify the beginning of symptoms, and give information about etiology, causes and prognosis of the disease. The initial objective of decompensated heart failure treatment is the hemodynamic and symptomatic improvement preservation and/or improvement of renal function, prevention of myocardial damage, modulation of the neurohormonal and/or inflammatory activation and control of comorbidities that can cause or contribute to progression of the syndrome. According to the clinical-hemodynamic profile, it is possible to establish a rational for the treatment of decompensated heart failure, individualizing the proceedings to be held, leading to reduction in the period of hospitalization and consequently reducing overall mortality.
Chronic hyponatremia is frequently found in some syndromes characterized by widespread edema coupled to impairment in arterial effective circulating volume, such as congestive chronic heart failure (CHF). In this setting, it is unclear whether the hyponatremia itself makes this condition worse or whether it represents a simply marker of decompensation. The factors responsible for development of hyponatremia in CHF have not exhaustively been elucidated yet. The aim of this paper was to ascertain whether some laboratory, clinical and therapeutical factors are able to predict occurrence of hyponatremia in CHF patients.
A case-control study was carried out by recruiting 57 CHF patients, whose 19 characterized by hyponatremia (serum Na+<135 mEq/L) and 38 controls, matched for age, sex, etiology of CHF, time elapsed since beginning of both symptoms and diuretic therapy. Eligibility criteria included right or biventricular heart failure in NYHA class III, absence of hyponatremia at the first visit and therapy at enrollment with oral dose not less than 175 mg per week of furosemide or equivalent weekly dose of torsemide. Exclusion criteria were electrostimulation therapies (pace-maker or cardiac resynchronization therapy), documented episodes- one or more- of infective gastroenteritis or diarrhea and use of any drug influencing neuroendocrine mechanisms of arginin-vasopressin (AVP) secretion, such as opiates, tetracyclines, phenothiazines, lithium, serotonin selective reuptake inhibitors (SSRIs) etc.
At univariate analysis, intensive intravenous (iv) therapy with furosemide (one or more courses), ascites, mixed regimen with thiazide diuretic plus furosemide, high (>3 ng/mL/h) plasma renin activity, serum creatinine ≥2,2 mg/dl and oligoanuria were shown to be associated with hyponatremia. At multivariate analysis a role of predictor of hyponatremia was maintained by combined therapy with thiazide diuretic plus furosemide (OR=35.68 95%CI: 2.83-449.37 P=0.0057) as well as by intensive iv furosemide therapy (OR=12.44 95%CI: 1.207-128.27 P=0.0342).
Inhibition of free water clearance by thiazides may account for association found between their use and hyponatremia development in congestive CHF setting. Even though loop diuretics are known to promote free water excretion, in our experience hyponatremia might have been favored by iv furosemide high doses, because drop in effective circulating volume and further impairment in arterial underfilling due to overzealous iv loop diuretic administration are able to foster AVP non osmotic release, thereby leading to hemodilution hyponatremia.
Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure.
To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens.
According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50%, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30% from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg.
57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8%) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes.
In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.
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.
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.
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.
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.
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.
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.
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.
Although a low-sodium diet is indicated for heart failure HF, there is no evidence this dietary restriction is beneficial to all patients.
To prospectively study the acute effectsof a low-sodium diet in patients (pts) with heart failure (HF).
Fifty stable outpatients with mild to moderate HF who reported previously consuming 6.6 g table salt/day were studied. In Phase 1, all pts were submitted to a diet with 2 g of salt during 7 days, followed by randomization in 2 subgroups (Phase 2): one to receive 6 g of salt (subgroup 1) and the other, 2 g of salt/day for 7 days (subgroup II).
Phase 1: the diet with 2 g of salt reduced the BMI, plasma and urinary sodium, protein consumption, iron, zinc, selenium and vitamin B12; it increased plasma levels of norepinephrine, nitrate, serum aldosterone and improved quality of life. Phase 2: for pts with low BMI, the use of 6 g salt/day acutely decreased the levels of norepinephrine, albumin and cholesterol in plasma. No difference was observed in pts with higher BMI.
The diet with 2 g salt/day for pts with HF increased the neurohormonal activation associated to HF progression. The BMI can influence the response to the neurohormonal activation in a low-sodium diet in pts with HF. Further studies to test salt restriction for longer periods are recommended.
This brand-new series of articles aims at delivering to national and international readers some of the cutting-edge contributions from the Brazilian medical literature. Recently papers published in the main Brazilian medical journals are carefully selected and analyzed by skilled medical editors. In addition we asked editors to choose keywords to be highlighted in order to claim for reader's attention. Articles are organized by area of interest to facilitate reading. To get the most of the limited available editorial space we did not include the names of the authors of the related articles in the text itself but a complete reference guide is provided at the end of the article. The result carries the most important messages from the original paper accompanied by a personal interpretation. Directed to the busy medical doctor we hope that this initiative may help in the successful translation of knowledge from scientific evidence to clinical practice.
A growing body of evidence suggests that the fluid accumulation plays a key role in the pathophysiology of heart failure (HF) and that the inflammatory and neurohormonal activation contribute strongly to the progression of this disorder.
The study evaluated the long-term effects of 2 different sodium diets on cytokines neurohormones, body hydration and clinical outcome in compensated HF outpatients (New York Heart Association Class II). A total of 173 patients (105 males, mean age 72.5+/-7) recently hospitalized for worsening advanced HF and discharged in normal hydration and in clinical compensation were randomized in 2 groups (double blind). In Group 1, 86 patients received a moderate restriction in sodium (120mmol to 2.8g/day) plus oral furosemide (125 to 250mg bid); in Group 2, 87 patients: received a low-sodium diet (80mmol to 1.8g/day) plus oral furosemide (125 to 250mg bid). Both groups were followed for 12 months and the treatment was associated with a drink intake of 1000mL daily. Neurohormonal (brain natriuretic peptide, aldosterone, plasma rennin activity) and cytokines values (tumor necrosis factor-alpha, interleukin-6) were significantly reduced with a significant increase of the anti-inflammatory cytokine interleukin-10 at 12 months in normal, P < .0001) than low-sodium group. The low-sodium diet showed a significant activation of neurohormones and cytokines and worsening the body hydration, whereas moderate sodium restriction maintained dry weigh and improved outcome in the long term.
Our results appear to suggest a surprising efficacy of a new strategy to improve the chronic diuretic response by increasing Na intake and limiting fluid intake. This counterintuitive approach underlines the need for a better understanding of factors that regulate sodium and water handling in chronic congestive HF. A larger sample of patients and further studies are required to evaluate whether this is due to the high dose of diuretic used or the low-sodium diet.
Studies have shown that patients with compensated heart failure (HF) receiving high diuretic doses associated with normal sodium diet and fluid intake restrictions demonstrated significant reductions in readmissions and mortality compared with those who received low-sodium diets, and over a 6-month observation period, a reduction in neurohormonal activation was also observed. The aim of this study was to evaluate the effects of different sodium diets associated with different diuretic doses and different levels of fluid intake on hospital readmissions and neurohormonal changes after 6-month follow-up in patients with compensated HF. Four hundred ten consecutive patients with compensated HF (New York Heart Association class II to IV) aged 53 to 86 years, with ejection fractions <35% and serum creatinine <2 mg/dl, were randomized into 8 groups: group A (n = 52): 1,000 ml/day of fluid intake, 120 mmol/day, and 250 mg furosemide twice daily; group B (n = 51): 1,000 ml/day of fluid intake, 120 mmol/day, and 125 mg furosemide twice daily; group C (n = 51): 1,000 ml/day fluid intake, 80 mmol/day, and 250 mg furosemide twice daily; group D (n = 51): 1,000 ml/day fluid intake, 80 mmol/day, and 125 mg furosemide twice daily; group E (n = 52): 2,000 ml/day fluid intake, 120 mmol/day, and 250 mg furosemide twice daily; group F (n = 50): 2,000 ml/day fluid intake, 120 mmol/day, and 125 mg furosemide twice daily; group G (n = 52): 2,000 ml/day fluid intake, 80 mmol/day, and 250 mg furosemide twice daily; and group H (n = 51): 2,000 ml/day fluid intake, 80 mmol/day, and 125 mg furosemide twice daily. All patients received the treatments >or=30 days after discharge and for 180 days afterward. Signs of HF, body weight, blood pressure, heart rate, laboratory parameters, electrocardiograms, echocardiograms, brain natriuretic peptide, aldosterone, and plasma renin activity were examined at baseline and 180 days later. Group A showed the best results, with a significant reduction (p <0.001) in readmissions, brain natriuretic peptide, aldosterone, and plasma renin activity compared with the other groups during follow-up (p <0.001). In conclusion, these data suggest that the combination of a normal-sodium diet with high diuretic doses and fluid intake restriction, compared with different combinations of sodium diets with more modest fluid intake restrictions and conventional diuretic doses, leads to reductions in readmissions, neurohormonal activation, and renal dysfunction.
OBJETIVO: Estudar a prevalência e o valor prognóstico da anemia em uma população hospitalizada por insuficiência cardíaca descompensada. MÉTODOS: De julho a setembro de 2001, 204 pacientes foram incluídos em um registro hospitalar multicêntrico de insuficiência cardíaca (Estudo EPICANiterói). Os 142 que tinham dados sobre hematócrito e hemoglobina coletados na admissão hospitalar compuseram esta análise retrospectiva. A idade média foi de 69,5±13,3 anos e 72 (50,7%) eram do sexo masculino. Considerou-se como anemia uma hemoglobina < 13,5 g/dL para os homens e < 12 g/dL para as mulheres. Avaliou-se através de análise uni e multivariada por regressão logística a relação da anemia com a mortalidade hospitalar. RESULTADOS: Anemia foi observada em 89 (62,6%) pacientes, sendo 52 (58%) homens e 37 (42%) mulheres. A mortalidade foi de 16,8% nos pacientes anêmicos contra 8% nos não anêmicos (p=0,11). Em ambos os sexos, as taxas de mortalidade nos anêmicos e não anêmicos foram, respectivamente, 19,2% vs 0% (p=0,034) e 13,5% vs 12,2% (p=0,86). Através de análise multivariada, as variáveis que se relacionaram de modo independente com a mortalidade hospitalar foram, hiponatremia (RR=7,0, intervalo de confiança de 95% [IC 95%] 6,1 a 8,7, p=0,0001), anemia (RR=3,1, IC 95%=2,4 a 4,3, p=0,024) e presença de classe funcional IV da NYHA (RR=1,9, IC 95%=1,3 a 2,6, p=0,04). CONCLUSÃO: Na população estudada com insuficiência cardíaca descompensada, a presença de anemia foi um marcador independente de mortalidade hospitalar. A mortalidade no grupo com anemia foi significativamente alta nos homens.
OBJETIVO: Analisar a sobrevida e fatores prognósticos associados à mortalidade em pacientes com insuficiência cardíaca sistólica acompanhados desde o início de seus sintomas. MÉTODOS: Coorte de 204 pacientes consecutivos com insuficiência cardíaca sistólica, identificada com início dos sintomas até seis semanas do primeiro atendimento e seguida por 46 meses. As variáveis prognósticas analisadas foram coletadas à inclusão e correlacionadas com a mortalidade cardiovascular. A Fração de Ejeção (FE) < 40% ao ecocardiograma caracterizava a disfunção sistólica ventricular. RESULTADOS: A taxa geral de sobrevida pela técnica de Kaplan-Meier foi de 98,0%, 90,6% e de 70,2% aos três, 12 e 48 meses de seguimento, respectivamente. A análise multivariada identificou o efeito independente de seis variáveis sobre o risco de morte cardiovascular. As classes funcionais III e IV aumentou em 2,7 vezes o risco em relação à classe II; incrementos de 10 mmHg na pressão arterial sistólica reduziram em 25% o risco de morte; cada aumento de 10 bpm na freqüência cardíaca elevava o risco de morte em 1,6 vezes e cada incremento de 0,25 mg/dL na creatinina sérica acarretava um aumento de risco de 60%. A presença de 3ª bulha aumentou em 3,0 vezes o risco de morte e a etiologia chagásica também se associou à mortalidade cardiovascular (P<0,0001). CONCLUSÃO: Estas evidências mostram que a mortalidade na fase inicial não é elevada e que a etiologia, classe funcional avançada, hipotensão arterial, taquicardia, presença de 3ª bulha e creatinina sérica elevada, conferem um pior prognóstico.
To study the prevalence and prognostic value of anemia in a population hospitalized due to decompensated heart failure.
From July to September, 2001, 204 patients were included in a multicenter hospital registry of heart failure (EPICA Study--Niterói). This retrospective analysis comprised 142 patients with data about hematocrit and hemoglobin levels collected on hospital admission. The mean age was 69.5+/-13.3 years, and 72 (50.7%) patients were men. Hemoglobin levels < 13.5 g/dL for men and < 12 g/dL for women were considered anemia. The relation between anemia and in-hospital mortality was assessed through univariate and multivariate analysis with logistic regression.
Anemia was observed in 89 (62.6%) patients, 52 (58%) men and 37 (42%) women. Mortality in anemic patients was 16.8% and, in nonanemic, it was 8% (P=0.11). In both sexes, the mortality rates in anemic and nonanemic patients were, respectively, 19.2% vs 0% (P=0.034) and 13.5% vs 12.2% (P=0.86). Through multivariate analysis, the following variables were found to be independently related to in-hospital mortality: hyponatremia [RR=7.0; 95% confidence interval (95% CI)=6.1 to 8.7; P=0.0001], anemia (RR=3.1, 95% CI=2.4 to 4.3; P=0.024), and presence of NYHA functional class IV (RR=1.9; 95% CI=1.3 to 2.6; P=0.04).
In the population studied with decompensated heart failure, the presence of anemia was an independent marker of in-hospital mortality. Mortality in the group with anemia was significantly high among men.
To study survival and prognostic factors associated with mortality in patients with systolic heart failure followed up since symptom onset.
We carried out a study with a cohort of 204 consecutive patients with systolic heart failure, whose symptom onset occurred within the 6 weeks preceding the first medical visit. They were followed up for 46 months. The prognostic variables analyzed were collected when the patients were included in the study and were correlated with cardiovascular mortality. An EF < or =40% on echocardiography characterized systolic ventricular dysfunction.
The overall survival rates according to the Kaplan-Meier technique were 98.0%, 90.6%, and 70.2% at 3, 12, and 48 months of follow-up, respectively. The multivariate analysis identified the independent effect of 6 variables on the risk of cardiovascular death. Functional classes III and IV increased risk 2.7 times as compared with class II; 10-mmHg increments in systolic blood pressure reduced the risk of death by 25%; each 10-bpm increase in heart rate increased the risk of death 1.6 times; and each 0.25-mg/dL increment in serum creatinine caused a 60% increase in risk. The presence of the third cardiac sound caused a 3-fold increase in the risk of death, and chagasic etiology was also associated with cardiovascular mortality (P<0.0001).
Evidence shows that mortality in the initial phase is not elevated, and that etiology, advanced functional class, arterial hypotension, tachycardia, presence of the third cardiac sound, and elevated serum creatinine lead to a worse prognosis.
Small volumes (4-6 mL/kg) of 7.5% hypertonic saline solution (HTS) are reported to be effective for resuscitation from circulatory shock. When infused rapidly into either hypovolemic or normovolemic subjects, HTS can cause an immediate and severe hypotension before cardiovascular improvement. In the present study, we examined the hypothesis that the early hypotension produced by HTS was mediated by an acute and transient depression of cardiac contractility. left ventricular pressure and wall motions were measured simultaneously in 10 anesthetized dogs for the assessment of cardiac contractility. Infusion of HTS at 3 mL/kg in 1 min significantly decreased mean arterial blood pressure by 49%, from 95 +/- 4 to 51 +/- 5 mm Hg (P less than 0.05, mean +/- SEM) at 45 s after the onset of infusion. This initial decrease in arterial blood pressure was abrupt and transient (106 +/- 9 s). Concomitantly, cardiac output and coronary blood flow increased significantly from 2.8 +/- 1.0 to 3.9 +/- 1.1 L/min and from 23.7 +/- 5.3 to 49.8 +/- 4.7 mL/min, respectively. Although heart rate remained constant, systolic shortenings of left ventricular diameter and wall thickness increased from 5.6% +/- 0.5% to 7.8% +/- 0.5% and from 13.9% +/- 0.6% to 15.1% +/- 1.2%, respectively, indicating an improvement in cardiac contractility. This was confirmed by subsequent analysis of the left ventricular end-systolic pressure-diameter relationship. Systemic and pulmonary vascular resistance decreased by 60% and 27%, respectively. Despite an initial period of hypotension after rapid infusion of HTS, mean arterial blood pressure, cardiac output, and contractility were all significantly increased at 5 min after HTS infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Infusion of small volumes of hypertonic saline solution (HS) seems to be of benefit in patients with impaired perfusion. The cardiorespiratory response to a 7.2% NaCl solution prepared in hydroxyethylstarch (HES) solution was investigated prospectively in patients undergoing prolonged cardiopulmonary bypass (CPB) (HS-HES group; n = 15); 6% HES 200/0.5 solution was infused in a control group (HES group; n = 15). Volume was given preoperatively to double low pulmonary artery occlusion pressure (less than 4 mm Hg) within 20 minutes. Hemodynamics, oxygen transport variables, and pulmonary gas exchange were studied before and after infusion as well as before and after CPB. Significantly less HS-HES solution (3.06 +/- 0.2 mL/kg) than 6% HES 200/0.5 solution (10.3 +/- 0.9 mL/kg) was necessary to double baseline pulmonary artery occlusion pressure. Fluid balance during CPB was negative in the HS-HES patients (-0.05 mL/kg.min CPB) and was lowest in this group even 5 hours after CPB. Mean arterial pressure, pulmonary arterial pressure, and heart rate were without differences between the groups. Changes in cardiac index (+40%) and total systemic resistance (-25%) were significantly most pronounced in the HS-HES patients, continuing even until the end of operation. Pulmonary gas exchange (arterial oxygen tension, intrapulmonary right-to-left shunting) was least compromised in these patients, particularly after bypass. Oxygen consumption was without difference between the groups; oxygen delivery increased significantly more in the HS-HES patients due to the larger increase in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertonic saline-dextran (HSD) solutions have been used for hemorrhagic shock, aortic aneurysm, and cardiopulmonary bypass surgery (CPB). Jehovah's Witness patients refuse blood and derivatives even under life-threatening conditions. A negative fluid balance for Jehovah's Witnesses would avoid further hemodilution. In this study we compared clinical, hemodynamic, laboratory evolution, and fluid balance of 20 Jehovah's Witnesses over the first 72 h following CPB. Ten received HSD immediately prior to CPB. All patients survived and were maintained in stable hemodynamic and metabolic condition throughout the study period. HSD induced high cardiac output, low vascular resistance immediately after administration. Vascular resistance remained low until the end of CPB. HSD patients ran a slightly negative fluid balance, while control patients ran a large positive fluid balance. HSD pretreatment is now used routinely for Jehovah's Witnesses undergoing CPB in our facility.