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      Loop diuretics in acute heart failure: beyond the decongestive relief for the kidney

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      Critical Care
      BioMed Central

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          Abstract

          Current goals in the acute treatment of heart failure are focused on pulmonary and systemic decongestion with loop diuretics as the cornerstone of therapy. Despite rapid relief of symptoms in patients with acute decompensated heart failure, after intravenous use of loop diuretics, the use of these agents has been consistently associated with adverse events, including hypokalemia, azotemia, hypotension, and increased mortality. Two recent randomized trials have shown that continuous infusions of loop diuretics did not offer benefit but were associated with adverse events, including hyponatremia, prolonged hospital stay, and increased rate of readmissions. This is probably due to the limitations of congestion evaluation as well as to the deleterious effects linked to drug administration, particularly at higher dosage. The impaired renal function often associated with this treatment is not extensively explored and could deserve more specific studies. Several questions remain to be answered about the best diuretic modality administration, global clinical impact during acute and post-discharge period, and the role of renal function deterioration during treatment. Thus, if loop diuretics are a necessary part of the treatment for acute heart failure, then there must be an approach that allows personalization of therapy for optimal benefit and avoidance of adverse events.

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          Most cited references43

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          Diuretic strategies in patients with acute decompensated heart failure.

          Loop diuretics are an essential component of therapy for patients with acute decompensated heart failure, but there are few prospective data to guide their use. In a prospective, double-blind, randomized trial, we assigned 308 patients with acute decompensated heart failure to receive furosemide administered intravenously by means of either a bolus every 12 hours or continuous infusion and at either a low dose (equivalent to the patient's previous oral dose) or a high dose (2.5 times the previous oral dose). The protocol allowed specified dose adjustments after 48 hours. The coprimary end points were patients' global assessment of symptoms, quantified as the area under the curve (AUC) of the score on a visual-analogue scale over the course of 72 hours, and the change in the serum creatinine level from baseline to 72 hours. In the comparison of bolus with continuous infusion, there was no significant difference in patients' global assessment of symptoms (mean AUC, 4236±1440 and 4373±1404, respectively; P=0.47) or in the mean change in the creatinine level (0.05±0.3 mg per deciliter [4.4±26.5 μmol per liter] and 0.07±0.3 mg per deciliter [6.2±26.5 μmol per liter], respectively; P=0.45). In the comparison of the high-dose strategy with the low-dose strategy, there was a nonsignificant trend toward greater improvement in patients' global assessment of symptoms in the high-dose group (mean AUC, 4430±1401 vs. 4171±1436; P=0.06). There was no significant difference between these groups in the mean change in the creatinine level (0.08±0.3 mg per deciliter [7.1±26.5 μmol per liter] with the high-dose strategy and 0.04±0.3 mg per deciliter [3.5±26.5 μmol per liter] with the low-dose strategy, P=0.21). The high-dose strategy was associated with greater diuresis and more favorable outcomes in some secondary measures but also with transient worsening of renal function. Among patients with acute decompensated heart failure, there were no significant differences in patients' global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose as compared with a low dose. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00577135.).
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            Renal impairment and outcomes in heart failure: systematic review and meta-analysis.

            We estimated the prevalence of renal impairment in heart failure (HF) patients and the magnitude of associated mortality risk using a systematic review of published studies. Renal impairment in HF patients is associated with excess mortality, although precise risk estimates are unclear. A systematic search of MEDLINE (through May 2005) identified 16 studies characterizing the association between renal impairment and mortality in 80,098 hospitalized and non-hospitalized HF patients. All-cause mortality risks associated with any renal impairment (creatinine >1.0 mg/dl, creatinine clearance [CrCl] or estimated glomerular filtration rate [eGFR] 1.03 mg/dl) and moderate to severe impairment (creatinine > or =1.5, CrCl or eGFR or =1.56) were estimated using fixed-effects meta-analysis. A total of 63% of patients had any renal impairment, and 29% had moderate to severe impairment. After follow-up > or =1 year, 38% of patients with any renal impairment and 51% with moderate to severe impairment died versus 24% without impairment. Adjusted all-cause mortality was increased for patients with any impairment (hazard ratio [HR] = 1.56; 95% confidence interval [CI] 1.53 to 1.60, p < 0.001) and moderate to severe impairment (HR = 2.31; 95% CI 2.18 to 2.44, p < 0.001). Mortality worsened incrementally across the range of renal function, with 15% (95% CI 14% to 17%) increased risk for every 0.5 mg/dl increase in creatinine and 7% (95% CI 4% to 10%) increased risk for every 10 ml/min decrease in eGFR. Renal impairment is common among HF patients and confers excess mortality. Renal function should be considered in risk stratification and evaluation of therapeutic strategies for HF patients.
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              High prevalence of renal dysfunction and its impact on outcome in 118,465 patients hospitalized with acute decompensated heart failure: a report from the ADHERE database.

              The prevalence of renal dysfunction in patients hospitalized with acute decompensated heart failure remains poorly characterized. Data from 118,465 hospitalization episodes were evaluated. Glomerular filtration rate (GFR) was estimated using the abbreviated Modification of Diet in Renal Disease formula. At admission, 10,660 patients (9.0%) had normal renal function (GFR > or = 90 mL x min x 1.73 m2), 32,423 patients (27.4%) had mild renal dysfunction (GFR 60-89 mL x min x 1.73 m2), 51,553 patients (43.5%) had moderate renal dysfunction (GFR 30-59 mL.min.1.73 m2), 15,553 patients (13.1%) had severe renal dysfunction (GFR 15-29 mL x min x 1.73 m2), and 8276 patients (7.0%) had kidney failure (GFR < 15 mL x min x 1.73 m2 or chronic dialysis). Despite this, only 33.4% of men and 27.3% of women were diagnosed with renal insufficiency. Diuretic dose, inotrope use, and nesiritide use increased, whereas angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use decreased, with increasing renal dysfunction (all P < .0001 across stages). In-hospital mortality increased from 1.9% for patients with normal renal function to 7.6% and 6.5% for patients with severe dysfunction and kidney failure, respectively (P < .0001). The majority of patients admitted with acute decompensated heart failure have significant renal impairment, which influences treatment and outcomes.
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                Author and article information

                Contributors
                palazzuoli2@unisi.it
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                3 September 2015
                3 September 2015
                2015
                : 19
                : 1
                : 296
                Affiliations
                [ ]Department of Internal and Surgical Medicine, Cardiovascular Diseases Unit, Le Scotte Hospital, University of Siena Viale Bracci, 53100 Siena, Italy
                [ ]Nephrology Dialysis & Transplantation International Renal Research Institute (IRRIV) St. Bortolo Hospital, Viale Rodolfi 37, IT-36100 Vicenza, Italy
                [ ]Baylor University Medical Center, Baylor Heart and Vascular Institute, Baylor Jack and Jane Hamilton Heart and Vascular Hospital, 621 North Hall Street, H030, Dallas, Texas 75226 USA
                Article
                1017
                10.1186/s13054-015-1017-3
                4559070
                26335137
                c66f02f9-347f-4643-b672-e1172fe55d98
                © Palazzuoli et al. 2015

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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                Emergency medicine & Trauma
                Emergency medicine & Trauma

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