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Osmanska J, Petrie MC, Docherty KF, Lee MMY, McMurray JJV, Campbell RT. Subcutaneous furosemide in heart failure: a systematic review. EUROPEAN HEART JOURNAL. CARDIOVASCULAR PHARMACOTHERAPY 2025; 11:94-104. [PMID: 39520561 PMCID: PMC11805693 DOI: 10.1093/ehjcvp/pvae083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 08/20/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND AND AIM Intravenous loop diuretics are the primary treatment for congestion in patients with decompensated heart failure (HF). Furosemide is the most commonly used loop diuretic and is licensed for administration either orally, intramuscularly or intravenously but not subcutaneously. Recently developed, pH-neutral, concentrated, and 'skin-friendly' preparations of furosemide have been developed which allow subcutaneous administration. In this systematic review, we summarize and critically appraise the current evidence for subcutaneous furosemide in patients with HF. METHODS AND RESULTS The electronic databases MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov registry were searched up to 30 September 2024. Of the 17 studies identified, 5 were randomized controlled trials (RCTs), 2 were non-randomized controlled studies, 3 were prospective observational cohort studies, and 7 were retrospective observational studies.All RCTs utilized novel pH-neutral, subcutaneous preparations of furosemide. Bioavailability of novel subcutaneous preparations were similar to intravenous furosemide 10 mg/mL: 99.7% for an 8 mg/mL preparation and 112% for a 30 mg/mL preparation. Natriuresis and diuresis were also similar with novel subcutaneous and conventional intravenous furosemide. Adverse events related to novel preparations included infusion site pain or discomfort, localized skin erythema and minimal swelling. All studies of subcutaneous conventional furosemide were non-randomized with very few data regarding bioavailability or diuretic and natriuretic effect. Subcutaneous conventional furosemide was associated with substantial skin irritation (affecting 3-23% of patients), and skin infections requiring treatment with antibiotics (3-17%). CONCLUSION Novel, pH-neutral preparations of subcutaneous furosemide achieved similar diuresis, natriuresis, and bioavailability to intravenous furosemide, and were well tolerated. Novel preparations may be a treatment option for patients with HF.
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Affiliation(s)
- Joanna Osmanska
- School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow 126 University Place, Glasgow G12 8TA, UK
| | - Mark C Petrie
- School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow 126 University Place, Glasgow G12 8TA, UK
| | - Kieran F Docherty
- School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow 126 University Place, Glasgow G12 8TA, UK
| | - Matthew M Y Lee
- School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow 126 University Place, Glasgow G12 8TA, UK
| | - John J V McMurray
- School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow 126 University Place, Glasgow G12 8TA, UK
| | - Ross T Campbell
- School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow 126 University Place, Glasgow G12 8TA, UK
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Hashimoto H, Yamada H, Murata M, Watanabe N. Diuretics for preventing and treating acute kidney injury. Cochrane Database Syst Rev 2025; 1:CD014937. [PMID: 39878152 PMCID: PMC11776056 DOI: 10.1002/14651858.cd014937.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2025]
Abstract
BACKGROUND Acute kidney injury (AKI) is a well-known complication of critical illnesses, significantly affecting morbidity and the risk of death. Diuretics are widely used to ameliorate excess fluid accumulation and oliguria associated with AKI. Their popularity stems from their ability to reduce the energy demands of renal tubular cells by inhibiting transporters and flushing out intratubular casts. Numerous studies have assessed the effects of diuretics in the context of AKI prevention and treatment. However, a comprehensive systematic review addressing this topic has yet to be conducted. OBJECTIVES This review aimed to explore the benefits and harms of diuretics for both the prevention and treatment of AKI. SEARCH METHODS The Cochrane Kidney and Transplant Register of Studies was searched up to May 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA We selected randomised controlled trials (RCTs) and quasi-RCTs in which diuretics were used to prevent or treat AKI. DATA COLLECTION AND ANALYSIS Two authors independently extracted data using standardised data extraction forms. Dichotomous outcomes were expressed as risk ratios (RR) with 95% confidence intervals (CI). Where continuous scales of measurement were used to assess the effects of treatment, the standardised mean difference (SMD) was used. The primary review outcomes for AKI prevention studies were the incidence of AKI and any use of kidney replacement therapy (KRT). For treatment studies, the primary outcome was any use of KRT. The certainty of evidence was assessed per outcome using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS We included 64 studies (83 reports, 9871 participants): 53 prevention studies (8078 participants) and 11 treatment studies (1793 participants). Studies were conducted in the following World Health Organization regions: the Americas (15), Eastern Mediterranean (9), Europe (25), South-East Asia (2), and the Western Pacific (13). Thirty-six studies were single-centre studies, 19 were multicentre, and the setting was unclear in nine studies. Diuretics were compared to placebo, no treatment or conventional therapy, saline solutions (isotonic or hypotonic), 5% dextrose, 5% glucose, Hartmann's solution, and Ringer's acetate. Overall, the risk of bias was low in one study, high in 19 studies, and of some concern in 41 studies. Three studies could not be assessed because they did not report any outcomes of interest. For AKI prevention, compared to control, diuretics may reduce the risk of AKI (38 studies, 5540 participants: RR 0.75, 95%, CI 0.61 to 0.92; I2 = 77%; low-certainty evidence) and probably reduce any use of KRT (32 studies, 4658 participants: RR 0.63, 95% CI 0.43 to 0.91; I2 = 0%, moderate-certainty evidence) and death (33 studies, 6447 participants: RR 0.73, 95% CI 0.59 to 0.92; I2 = 0%; moderate-certainty evidence). The use of diuretics may result in little or no difference in the need for permanent dialysis (2 studies, 956 participants: RR 0.52, 95% CI 0.08 to 3.47; I2 = 21%; low-certainty evidence), hypotension (7 studies, 775 participants: RR 1.27, 95% CI 0.87 to 1.86; I2 = 0%; low-certainty evidence) and hypokalaemia (6 studies, 1383 participants: RR 1.20, 95% CI 0.88 to 1.73; I2 = 43%; low-certainty evidence), and had uncertain effects on arrhythmias (13 studies, 3375 participants: RR 0.77, 95% CI 0.57 to 1.04; I2 = 53%; very-low certainty evidence). Diuretics may make little or no difference to changes in SCr within 30 days (8 studies, 646 participants: SMD 0.41, 95% CI -0.01, to 0.83; I2 = 82%; low-certainty evidence) but it was uncertain whether diuretics increased urinary output (8 studies, 1155 participants: SMD 1.87, 95% CI -0.20 to 3.95; I2 = 99%; very low-certainty evidence). For AKI treatment, diuretics may make little or no difference to any use of KRT (8 studies, 1275 participants: RR 0.93, 95% CI 0.83 to 1.04; I2 = 2%; low-certainty evidence) or death (14 studies, 2052 participants: RR 1.08, 95% CI 0.96 to 1.22; I2 = 0%; low-certainty evidence). Diuretics may increase hypotension (2 studies, 720 participants: RR 1.99, 95% CI 1.16 to 3.41; I2 = 90%; low-certainty evidence) and probably increase arrhythmias (6 studies, 1011 participants: RR 1.62, 95% CI 1.12 to 2.33; I2 = 0%; moderate-certainty evidence). Diuretics may result in little or no difference in hypokalaemia (3 studies, 478 participants: RR 1.52, 95% CI 0.70 to 3.31; I2 = 0%; low-certainty evidence). It was uncertain whether diuretics increased urinary output (3 studies, 329 participants: SMD 4.40, 95% CI -0.94 to 9.74; I2 = 99%; very low-certainty evidence). The need for permanent dialysis and changes in serum creatinine were not reported. AUTHORS' CONCLUSIONS When used for the prevention of AKI, diuretics may reduce the risk of AKI. However, our confidence in the effect estimate is limited. Diuretics probably reduce the incidence of KRT use, and we are moderately confident in the effect estimate. When used for the treatment of AKI, diuretics may make little or no difference to any use of KRT, and our confidence in the effect estimate is limited. More RCTs are needed to explore the role of diuretics for treating established AKI.
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Affiliation(s)
| | - Hiroyuki Yamada
- Department of Primary Care and Emergency Medicine, Kyoto University Hospital, Kyoto, Japan
- Department of Nephrology, Kyoto University Hospital, Kyoto, Japan
| | - Maki Murata
- Department of Emergency Medicine and Critical Care, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Norio Watanabe
- Department of Psychiatry, Soseikai General Hospital, Kyoto, Japan
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Bonilla M, Koyner JL, Neyra JA. Acute Kidney Injury and Critical Care Nephrology. ADVANCES IN KIDNEY DISEASE AND HEALTH 2025; 32:12-23. [PMID: 40175025 DOI: 10.1053/j.akdh.2024.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 10/29/2024] [Accepted: 12/12/2024] [Indexed: 04/04/2025]
Abstract
Critical care nephrology is an increasingly vital subspecialty within internal medicine that focuses on the comprehensive management of a spectrum of kidney-related complications that arise in critically ill patients. This field plays a crucial role in heterogeneous intensive care unit settings, where the dynamic and complex nature of critical illnesses and acute kidney injury phenotypes often necessitates specialized renal care, including renal replacement therapy. In this manuscript, we present board-style review questions that illustrate distinct clinical scenarios and interventions in critical care nephrology, with an emphasis on key teaching points.
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Affiliation(s)
- Marco Bonilla
- Section of Nephrology, Department of Medicine, University of Chicago, Chicago, IL.
| | - Jay L Koyner
- Section of Nephrology, Department of Medicine, University of Chicago, Chicago, IL
| | - Javier A Neyra
- Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
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Rasoul D, Zhang J, Farnell E, Tsangarides AA, Chong SC, Fernando R, Zhou C, Ihsan M, Ahmed S, Lwin TS, Bateman J, Hill RA, Lip GY, Sankaranarayanan R. Continuous infusion versus bolus injection of loop diuretics for acute heart failure. Cochrane Database Syst Rev 2024; 5:CD014811. [PMID: 38775253 PMCID: PMC11110107 DOI: 10.1002/14651858.cd014811.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/25/2024]
Abstract
BACKGROUND Acute heart failure (AHF) is new onset of, or a sudden worsening of, chronic heart failure characterised by congestion in about 95% of cases or end-organ hypoperfusion in 5% of cases. Treatment often requires urgent escalation of diuretic therapy, mainly through hospitalisation. This Cochrane review evaluated the efficacy of intravenous loop diuretics strategies in treating AHF in individuals with New York Heart Association (NYHA) classification III or IV and fluid overload. OBJECTIVES To assess the effects of intravenous continuous infusion versus bolus injection of loop diuretics for the initial treatment of acute heart failure in adults. SEARCH METHODS We identified trials through systematic searches of bibliographic databases and in clinical trials registers including CENTRAL, MEDLINE, Embase, CPCI-S on the Web of Science, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry platform (ICTRP), and the European Union Trials register. We conducted reference checking and citation searching, and contacted study authors to identify additional studies. The latest search was performed on 29 February 2024. SELECTION CRITERIA We included randomised controlled trials (RCTs) involving adults with AHF, NYHA classification III or IV, regardless of aetiology or ejection fraction, where trials compared intravenous continuous infusion of loop diuretics with intermittent bolus injection in AHF. We excluded trials with chronic stable heart failure, cardiogenic shock, renal artery stenosis, or end-stage renal disease. Additionally, we excluded studies combining loop diuretics with hypertonic saline, inotropes, vasoactive medications, or renal replacement therapy and trials where diuretic dosing was protocol-driven to achieve a target urine output, due to confounding factors. DATA COLLECTION AND ANALYSIS Two review authors independently screened papers for inclusion and reviewed full-texts. Outcomes included weight loss, all-cause mortality, length of hospital stay, readmission following discharge, and occurrence of acute kidney injury. We performed risk of bias assessment and meta-analysis where data permitted and assessed certainty of the evidence. MAIN RESULTS The review included seven RCTs, spanning 32 hospitals in seven countries in North America, Europe, and Asia. Data collection ranged from eight months to six years. Following exclusion of participants in subgroups with confounding treatments and different clinical settings, 681 participants were eligible for review. These additional study characteristics, coupled with our strict inclusion and exclusion criteria, improve the applicability of the body of the evidence as they reflect real-world clinical practice. Meta-analysis was feasible for net weight loss, all-cause mortality, length of hospital stay, readmission, and acute kidney injury. Literature review and narrative analysis explored daily fluid balance; cardiovascular mortality; B-type natriuretic peptide (BNP) change; N-terminal-proBNP change; and adverse incidents such as ototoxicity, hypotension, and electrolyte imbalances. Risk of bias assessment revealed two studies with low overall risk, four with some concerns, and one with high risk. All sensitivity analyses excluded trials at high risk of bias. Only narrative analysis was conducted for 'daily fluid balance' due to diverse data presentation methods across two studies (169 participants, the evidence was very uncertain about the effect). Results of narrative analysis varied. For instance, one study reported higher daily fluid balance within the first 24 hours in the continuous infusion group compared to the bolus injection group, whereas there was no difference in fluid balance beyond this time point. Continuous intravenous infusion of loop diuretics may result in mean net weight loss of 0.86 kg more than bolus injection of loop diuretics, but the evidence is very uncertain (mean difference (MD) 0.86 kg, 95% confidence interval (CI) 0.44 to 1.28; 5 trials, 497 participants; P < 0.001, I2 = 21%; very low-certainty evidence). Importantly, sensitivity analysis excluding trials with high risk of bias showed there was insufficient evidence for a difference in bodyweight loss between groups (MD 0.70 kg, 95% CI -0.06 to 1.46; 3 trials, 378 participants; P = 0.07, I2 = 0%). There may be little to no difference in all-cause mortality between continuous infusion and bolus injection (risk ratio (RR) 1.53, 95% CI 0.81 to 2.90; 5 trials, 530 participants; P = 0.19, I2 = 4%; low-certainty evidence). Despite sensitivity analysis, the direction of the evidence remained unchanged. No trials measured cardiovascular mortality. There may be little to no difference in the length of hospital stay between continuous infusion and bolus injection of loop diuretics, but the evidence is very uncertain (MD -1.10 days, 95% CI -4.84 to 2.64; 4 trials, 211 participants; P = 0.57, I2 = 88%; very low-certainty evidence). Sensitivity analysis improved heterogeneity; however, the direction of the evidence remained unchanged. There may be little to no difference in the readmission to hospital between continuous infusion and bolus injection of loop diuretics (RR 0.85, 95% CI 0.63 to 1.16; 3 trials, 400 participants; P = 0.31, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show insufficient evidence for a difference in the readmission to hospital between groups. There may be little to no difference in the occurrence of acute kidney injury as an adverse event between continuous infusion and bolus injection of intravenous loop diuretics (RR 1.02, 95% CI 0.70 to 1.49; 3 trials, 491 participants; P = 0.92, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show that continuous infusion may make little to no difference on the occurrence of acute kidney injury as an adverse events compared to the bolus injection of intravenous loop diuretics. AUTHORS' CONCLUSIONS Analysis of available data comparing two delivery methods of diuretics in acute heart failure found that the current data are insufficient to show superiority of one strategy intervention over the other. Our findings were based on trials meeting stringent inclusion and exclusion criteria to ensure validity. Despite previous reviews suggesting advantages of continuous infusion over bolus injections, our review found insufficient evidence to support or refute this. However, our review, which excluded trials with clinical confounders and RCTs with high risk of bias, offers the most robust conclusion to date.
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Affiliation(s)
- Debar Rasoul
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, UK
- Cardiology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Juqian Zhang
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, UK
| | - Ebony Farnell
- General Medicine, Wrightington, Wigan and Leigh Teaching Hospitals NHS Foundation Trust, Wigan, UK
| | - Andreas A Tsangarides
- Emergency Department, The University of New South Wales, The Prince of Wales Hospital, Sydney, Australia
| | - Shiau Chin Chong
- Pharmacy, Hospital Sultan Ismail, Ministry of Health Malaysia, Johor Bahru, Malaysia
| | - Ranga Fernando
- General Medicine, Salford Royal NHS Foundation Trust, Manchester, UK
| | - Can Zhou
- Cardiology, King's College Hospital, London, UK
| | - Mahnoor Ihsan
- Acute Medicine, Mid-Cheshire Hospital NHS Foundation Trust, Crewe, UK
| | - Sarah Ahmed
- Nephrology, East and North Hertfordshire NHS Trust, Stevenage, UK
| | - Tin S Lwin
- Cardiology, Castle Hill Hospital, Hull, UK
| | | | - Ruaraidh A Hill
- Liverpool Reviews and Implementation Group, Department of Health Data Science, University of Liverpool, Liverpool, UK
| | - Gregory Yh Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, UK
- Liverpool John Moores University, Liverpool, UK
- Cardiology, Liverpool Heart & Chest Hospital, Liverpool, UK
- Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Rajiv Sankaranarayanan
- Cardiology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, UK
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Huang L, Zhao X, Liang L, Tian P, Chen Y, Zhai M, Huang Y, Zhou Q, Zhang Y, Zhang J. Renal function modifies the association between hemoconcentration and outcomes in hospitalized heart failure patients. Intern Emerg Med 2024; 19:399-411. [PMID: 38233579 DOI: 10.1007/s11739-023-03488-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Accepted: 11/13/2023] [Indexed: 01/19/2024]
Abstract
Evidence-based management of decongestion is lacking in hospitalized heart failure (HHF) patients, especially in patients with impaired renal function. Hemoconcentration is an objective measure of decongestion that portends a favorable prognosis and guides management in HHF patients with preserved renal function. We aim to investigate whether it remains a prognosticator in patients with renal impairment, and to refine the identification of subpopulations who will benefit from hemoconcentration-guided therapy. HHF patients admitted to Heart Failure Center of Fuwai Hospital were consecutively included from December 2006 to June 2018. Patient characteristics were depicted. Relationships between in-hospital hemoconcentration, worsening renal function (WRF), and one-year all-cause mortality were investigated in the total population and compared between renal function groups using survival analysis and cubic splines, with a special focus on renal function-based interactions. The association was further validated in sensitivity analyses. Clinically relevant cut-offs and subpopulations were identified by subpopulation treatment effect pattern plots (STEPP) and subgroup analysis. 3661 participants (30.4% with impaired renal function) were included. Hemoconcentration, reflected by an in-hospital increase in hemoglobin, hematocrit, or a relative reduction in estimated plasma volume from baseline to discharge, was predictive of decreased one-year mortality in the total cohort despite its correlation with higher WRF incidence. The prognostic value of hemoconcentration differed in patients with impaired and preserved renal function. Hemoconcentration was related to a favorable prognosis in patients with preserved renal function (HR, 0.69; 95% CI, 0.53-0.90; P = 0.007), especially in young male patients with New York Heart Association functional class III-IV, reduced ejection fraction, and baseline eGFR > 75 mL/min/1.73m2. Contrarily, impaired renal function patients experienced a higher incidence of WRF, and hemoconcentration was no longer related to outcome (HR, 0.90; 95% CI, 0.64-1.26; P = 0.545), with findings consistent in all clinically relevant subgroups. In HHF patients, the prognostic value of hemoconcentration differs by renal function, and the clinical utility of hemoconcentration is contingent on preserved renal function.
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Affiliation(s)
- Liyan Huang
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People's Republic of China
| | - Xuemei Zhao
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People's Republic of China
| | - Lin Liang
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People's Republic of China
| | - Pengchao Tian
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People's Republic of China
| | - Yuyi Chen
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People's Republic of China
| | - Mei Zhai
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People's Republic of China
| | - Yan Huang
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People's Republic of China
| | - Qiong Zhou
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People's Republic of China
| | - Yuhui Zhang
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People's Republic of China.
| | - Jian Zhang
- Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People's Republic of China.
- Key Laboratory of Clinical Research for Cardiovascular Medications, National Health Committee, No.167 Beilishi Road, Beijing, 100037, China.
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Weng H, Li Y, Nie X, He C, Feng P, Zhao F, Chen Q, Sun W, Jiang J, Zhang Y, Huo Y, Li J. Comparative effectiveness and safety of bolus vs. continuous infusion of loop diuretics: Results from the MIMIC-III Database. Am J Med Sci 2023; 365:353-360. [PMID: 36572341 DOI: 10.1016/j.amjms.2022.12.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 07/31/2022] [Accepted: 12/14/2022] [Indexed: 12/25/2022]
Abstract
BACKGROUND It is unclear whether fluid management goals are best achieved by bolus injection or continuous infusion of loop diuretics. In this study, we compared the effectiveness and safety of a continuous infusion with that of a bolus injection when an increased loop diuretic dosage is required in intensive care unit (ICU) patients. METHODS We obtained data from the MIMIC-III database for patients who were first-time ICU admissions and required an increased diuretic dosage. Patients were excluded if they had an estimated glomerular filtration rate <15 ml/min/1.73 m2, were receiving renal replacement therapy, had a baseline systolic blood pressure <80 mmHg, or required a furosemide dose <120 mg. The patients were divided into a continuous group and a bolus group. Propensity score matching was used to balance patients' background characteristics. RESULTS The final dataset included 807 patients (continuous group, n = 409; bolus group, n = 398). After propensity score matching, there were 253 patients in the bolus group and 231 in the continuous group. The 24 h urine output per 40 mg of furosemide was significantly greater in the continuous group than in the bolus group (234.66 ml [95% confidence interval (CI) 152.13-317.18, p < 0.01]). There was no significant between-group difference in the incidence of acute kidney injury (odds ratio 0.96, 95% CI 0.66-1.41, p = 0.85). CONCLUSIONS Our results indicate that a continuous infusion of loop diuretics may be more effective than a bolus injection and does not increase the risk of acute kidney injury in patients who need an increased diuretic dosage in the ICU.
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Affiliation(s)
- Haoyu Weng
- Department of Cardiology, Peking University First Hospital, Beijing, China
| | - Yuxi Li
- Department of Cardiology, Peking University First Hospital, Beijing, China
| | - Xiaolu Nie
- Center for Clinical Epidemiology and Evidence-based Medicine, Beijing Children's Hospital, Beijing, China
| | - Chunhui He
- Department of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, Beijing, China
| | | | | | - Qingjie Chen
- Department of Cardiology, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, China
| | - Wen Sun
- Department of Respiration and Critical Care, Peking University First Hospital, Beijing, China
| | - Jie Jiang
- Department of Cardiology, Peking University First Hospital, Beijing, China
| | - Yan Zhang
- Department of Cardiology, Peking University First Hospital, Beijing, China
| | - Yong Huo
- Department of Cardiology, Peking University First Hospital, Beijing, China.
| | - Jianping Li
- Department of Cardiology, Peking University First Hospital, Beijing, China.
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Karedath J, Asif A, Tentu N, Zahra T, Batool S, Sathish M, Sandhu QI, Khan A. Continuous Infusion Versus Bolus Injection of Loop Diuretics for Patients With Congestive Heart Failure: A Meta-Analysis. Cureus 2023; 15:e34758. [PMID: 36909062 PMCID: PMC10005852 DOI: 10.7759/cureus.34758] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/07/2023] [Indexed: 02/10/2023] Open
Abstract
Loop diuretics continue to be a crucial component of pharmacological treatment, to eliminate extra fluid and enhance symptom control in acute decompensated heart failure (ADHF). Understanding the loop diuretics' more efficient form of administration would be very beneficial in improving the management of people's ADHF, resulting in a quicker resolution of symptoms and a notable decrease in morbidity. To assess the outcomes of intravenous continuous infusion with bolus injection of loop diuretics for patients with ADHF, this meta-analysis was carried out. The current meta-analysis was conducted as per the Cochrane Collaboration guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension (PRISMA) guidelines. A search was carried out on PubMed and EMBASE databases for studies comparing continuous infusion with intermittent bolus injection of furosemide in patients with congestive heart failure without restriction on the language of publication from 1 January 2001 to 31 July 2022. The primary outcome of the meta-analysis was all-cause mortality and loss of body weight (kg). Pre-defined secondary outcomes included length of hospital stay (LOS) in days, brain natriuretic peptide (BNP) reduction (pg/ml), number of patients with hypokalemia, and urine output at 24 hours (ml). A total of nine articles were included in this meta-analysis enrolling 713 patients. No significant difference was reported between patients who received intermittent bolus injections and continuous infusion of furosemide in regards to all-cause mortality, LOS, total urine output, the incidence of hypokalemia, and change in BNP. However, the reduction of body weight was greater in the continuous infusion group compared to bolus administration. In conclusion, in the current meta-analysis of nine randomized controlled trials (RCTs), continuous infusion of furosemide seemed to have a greater reduction of body weight. However, no significant difference was there in 24-hrs urine output. However, we cannot conclude that intravenous continuous infusion has a better diuretic effect compared to bolus administration.
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Affiliation(s)
- Jithin Karedath
- Internal Medicine, James Cook University Hospital, Middlesbrough, GBR
| | - Anim Asif
- Medicine, Fauji Foundation, Rawalpindi, PAK
| | - Niharika Tentu
- Internal Medicine, Liaquat National Hospital, Karachi, PAK
| | - Tafseer Zahra
- Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Saima Batool
- Internal Medicine, Hameed Latif Hospital, Lahore, PAK
| | - Meenakshi Sathish
- Surgery, Caribbean Medical University School of Medicine, Chicago, USA
| | - Qudsia I Sandhu
- Medicine, Dera Ghazi Khan Medical College, Dera Ghazi Khan, PAK
| | - Areeba Khan
- Critical Care Medicine, United Medical and Dental College, Karachi, PAK
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8
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Stille K, Kribben A, Herget-Rosenthal S. Incidence, severity, risk factors and outcomes of acute kidney injury in older adults: systematic review and meta-analysis. J Nephrol 2022; 35:2237-2250. [PMID: 35932418 DOI: 10.1007/s40620-022-01381-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Accepted: 06/10/2022] [Indexed: 11/28/2022]
Abstract
OBJECTIVES Old age was identified as a strong risk factor for acute kidney injury (AKI). Our objectives were to provide estimates of AKI, risk factors and outcomes in patients ≥ 75 years for whom data are scarce. METHODS Observational studies and randomized controlled trials between 2005 and 2021 with patients of mean or median age ≥ 75 years, reporting AKI according to current definitions. Data on AKI incidence, risk factors and mortality were analyzed separately in unselected (UC) and acute heart failure (AHF) cohorts. RESULTS Twenty-six observational studies and 4 randomized controlled trials with 51,111 UC and 25,414 AHF patients were included. Ages averaged 79.4 and 79.8 years, respectively. Pooled risk ratios (RRs) of AKI rates were 26.29% (95% confidence intervals (CI) 13.20-41.97) (UC) and 24.21% (95% CI 20.03-28.65) (AHF). In both cohorts, AKI was associated with decreased estimated glomerular filtration rate at baseline, chronic kidney disease (UC: RR 1.80 (95% CI 1.15-2.80), AHF: RR 1.51 (95% CI 1.26-1.95) and hypertension (UC: RR 1.30 (95% CI 1.09-1.56), AHF: RR 1.07 (95% CI 1.05-1.09). RRs of AKI in patients on renin-angiotensin-inhibitors were 0.87 (95% CI 0.78-0.97) and 0.88 (95% CI 0.78-0.98) in UC and AHF, respectively. AKI was consistently associated with increased risk of in-hospital mortality (UC: RR 3.15 (95% CI 2.28-4.35), AHF: RR 4.28 (95% CI 2.53-7.24). CONCLUSION AKI is frequent in patients ≥ 75 years. While reduced renal function at baseline, CKD and hypertension were associated with AKI development, renin-angiotensin-inhibitors may be protective. Older AKI patients showed higher short-term mortality rates.
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Affiliation(s)
- Kolja Stille
- Department of Medicine, Rotes Kreuz Krankenhaus, St. Pauli Deich 24, 28199, Bremen, Germany
| | - Andreas Kribben
- Department of Nephrology, Universitätsklinikum, Universität Duisburg-Essen, Essen, Germany
| | - Stefan Herget-Rosenthal
- Department of Medicine, Rotes Kreuz Krankenhaus, St. Pauli Deich 24, 28199, Bremen, Germany. .,Department of Nephrology, Universitätsklinikum, Universität Duisburg-Essen, Essen, Germany.
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9
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Şaylık F, Cinar T. Comparison of continuous loop diuretic versus bolus injection regimens in patients with heart failure: a comprehensive meta-analysis of the literature. Rev Assoc Med Bras (1992) 2022; 68:1599-1605. [DOI: 10.1590/1806-9282.20220583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Accepted: 07/08/2022] [Indexed: 11/29/2022] Open
Affiliation(s)
| | - Tufan Cinar
- Sultan II. Abdulhamid Han Training and Research Hospital, Turkey
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10
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Comparison of Different Furosemide Regimens in the Treatment of Acute Heart Failure: A Meta-Analysis. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:4627826. [PMID: 36035285 PMCID: PMC9410848 DOI: 10.1155/2022/4627826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/24/2022] [Accepted: 08/03/2022] [Indexed: 11/18/2022]
Abstract
Background. To compare the effects of different dosing schemes of furosemide on acute heart failure (AHF). Methods. Literature that compared the efficacy of continuous and intermittent administration of furosemide in AHF patients was retrieved from PubMed, Embase, the Cochrane Library, and ISI Web of Science from inception to May 2022. The primary endpoints included overall weight loss, 24-hour urine volume, length of hospital stay, 24-hour brain natriuretic peptide (BNP) level change, and all-cause mortality. The RevmMan5.4 software was used to analyze the extracted data. Results. A total of 10 studies with 775 patients, including 338 receiving continuous furosemide administration and 387 receiving intermittent furosemide administration, were included. The analysis results showed significant differences in weight loss (
, 95% CI (0.75~1.40),
) and 24-hour urine volume (MD =335.23, 95% CI (140.98~529.47),
) between the 2 groups. There was no significant difference in terms of length of hospital stay (
, 95% CI (-2.74~1.31),
) and all-cause mortality (
, 95% CI (0.92~2.75),
). Conclusions. Compared with intermittent administration, continuous infusion of furosemide had a significant effect on the 24-hour urine volume and total weight loss in patients with AHF.
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11
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Moreau LA, Holloway I, Fylan B, Hartley S, Cundill B, Fergusson A, Alderson S, Alldred DP, Bojke C, Breen L, Ismail H, Gardner P, Mason E, Powell C, Silcock J, Taylor A, Farrin A, Gale C. Using routine healthcare data to evaluate the impact of the Medicines at Transitions Intervention (MaTI) on clinical outcomes of patients hospitalised with heart failure: protocol for the Improving the Safety and Continuity Of Medicines management at Transitions of care (ISCOMAT) cluster randomised controlled trial with embedded process evaluation, health economics evaluation and internal pilot. BMJ Open 2022; 12:e054274. [PMID: 35487708 PMCID: PMC9058770 DOI: 10.1136/bmjopen-2021-054274] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION Heart failure affects 26 million people globally, approximately 900 thousand people in the UK, and is increasing in incidence. Appropriate management of medicines for heart failure at the time of hospital discharge reduces readmissions, improves quality of life and increases survival. The Improving the Safety and Continuity Of Medicines management at Transitions (ISCOMAT) trial tests the effectiveness of the Medicines at Transition Intervention (MaTI), which aims to enhance self-care and increase community pharmacy involvement in the medicines management of heart failure patients. METHODS AND ANALYSIS ISCOMAT is a parallel-group cluster randomised controlled trial, randomising 42 National Health Service trusts with cardiology wards in England on a 1:1 basis to implement the MaTI or treatment as usual. Around 2100 patients over the age of 18 admitted to hospital with heart failure with at least moderate left ventricular systolic dysfunction within the last 5 years, and planned discharge to the geographical area of the cluster will be recruited. The MaTI consists of training for staff, a toolkit for participants, transfer of discharge information to community pharmacies and a medicines reconciliation/review. Treatment as usual is determined by local policy and practices. The primary outcome is a composite of all-cause mortality and heart failure-related hospitalisation at 12 months postregistration obtained from national electronic health records. The key secondary outcome is continued prescription of guideline-indicated therapies at 12 months measured via patient-reported data and Hospital Episode Statistics. The trial contains a parallel mixed-methods process evaluation and an embedded health economics study. ETHICS AND DISSEMINATION The study obtained approval from the Yorkshire and the Humber-Bradford Leeds Research Ethics Committee; REC reference 18/YH/0017. Findings will be disseminated via academic and policy conferences, peer-reviewed publications and social media. Amendments to the protocol are disseminated to all relevant parties as required. TRIAL REGISTRATION NUMBER ISRCTN66212970; Pre-results.
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Affiliation(s)
- Lauren A Moreau
- Leeds Institute for Clinical Trials Research, Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Ivana Holloway
- Leeds Institute for Clinical Trials Research, Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Beth Fylan
- School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford, UK
- NIHR Yorkshire and Humber Patient Safety Translational Research Centre, Bradford Institute for Health Research, Bradford, UK
- Wolfson Centre for Applied Health Research, University of Bradford, Bradford, UK
| | - Suzanne Hartley
- Leeds Institute for Clinical Trials Research, Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Bonnie Cundill
- Leeds Institute for Clinical Trials Research, Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Alison Fergusson
- Leeds Institute for Clinical Trials Research, Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Sarah Alderson
- Academic Unit of Primary Care, University of Leeds, Leeds, UK
| | - David Phillip Alldred
- NIHR Yorkshire and Humber Patient Safety Translational Research Centre, Bradford Institute for Health Research, Bradford, UK
- School of Healthcare, University of Leeds, Leeds, UK
| | - Chris Bojke
- Academic Unit of Health Economics, University of Leeds, Leeds, UK
| | - Liz Breen
- School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford, UK
- NIHR Yorkshire and Humber Patient Safety Translational Research Centre, Bradford Institute for Health Research, Bradford, UK
- Wolfson Centre for Applied Health Research, University of Bradford, Bradford, UK
| | - Hanif Ismail
- School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford, UK
- Wolfson Centre for Applied Health Research, University of Bradford, Bradford, UK
| | - Peter Gardner
- School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford, UK
- Wolfson Centre for Applied Health Research, University of Bradford, Bradford, UK
| | - Ellen Mason
- Leeds Institute for Clinical Trials Research, Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Catherine Powell
- School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford, UK
- Wolfson Centre for Applied Health Research, University of Bradford, Bradford, UK
| | - Jonathan Silcock
- School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford, UK
- Wolfson Centre for Applied Health Research, University of Bradford, Bradford, UK
| | | | - Amanda Farrin
- Leeds Institute for Clinical Trials Research, Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Chris Gale
- University of Leeds Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, UK
- Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
- Leeds Institute for Data Analytics, University of Leeds, Leeds, UK
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12
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Fu K, Hu Y, Zhang H, Wang C, Lin Z, Lu H, Ji X. Insights of Worsening Renal Function in Type 1 Cardiorenal Syndrome: From the Pathogenesis, Biomarkers to Treatment. Front Cardiovasc Med 2022; 8:760152. [PMID: 34970606 PMCID: PMC8712491 DOI: 10.3389/fcvm.2021.760152] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 11/11/2021] [Indexed: 12/16/2022] Open
Abstract
Type-1 cardiorenal syndrome refers to acute kidney injury induced by acute worsening cardiac function. Worsening renal function is a strong and independent predictive factor for poor prognosis. Currently, several problems of the type-1 cardiorenal syndrome have not been fully elucidated. The pathogenesis mechanism of renal dysfunction is unclear. Besides, the diagnostic efficiency, sensitivity, and specificity of the existing biomarkers are doubtful. Furthermore, the renal safety of the therapeutic strategies for acute heart failure (AHF) is still ambiguous. Based on these issues, we systematically summarized and depicted the research actualities and predicaments of the pathogenesis, diagnostic markers, and therapeutic strategies of worsening renal function in type-1 cardiorenal syndrome.
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Affiliation(s)
- Kang Fu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Yue Hu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Hui Zhang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Chen Wang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Zongwei Lin
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Huixia Lu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Xiaoping Ji
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China
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13
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Inpatient Diuretic Management of Acute Heart Failure: A Practical Review. Am J Cardiovasc Drugs 2021; 21:595-608. [PMID: 33709346 DOI: 10.1007/s40256-020-00463-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/10/2020] [Indexed: 02/08/2023]
Abstract
The inpatient treatment of acute heart failure (AHF) is aimed at achieving euvolemia, relieving symptoms, and reducing rehospitalization. Adequate treatment of AHF is rooted in understanding the pharmacokinetics and pharmacodynamics of select diuretic agents used to achieve decongestion. While loop diuretics remain the primary treatment of AHF, the dosing strategies of loop diuretics and the use of adjunct diuretic classes to augment clinical response can be complex. This review examines the latest strategies for diuretic management in patients with AHF, including dosing and monitoring strategies, interaction of diuretics with other medication classes, use adjunctive therapies, and assessing endpoints for diuretic. The goal of the review is to guide the reader through commonly encountered clinical scenarios and pitfalls in the diuretic management of patients with AHF.
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14
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Ong LT. Evidence based review of management of cardiorenal syndrome type 1. World J Methodol 2021; 11:187-198. [PMID: 34322368 PMCID: PMC8299910 DOI: 10.5662/wjm.v11.i4.187] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 05/09/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
Cardiorenal syndrome (CRS) type 1 is the development of acute kidney injury in patients with acute decompensated heart failure. CRS often results in prolonged hospitalization, a higher rate of rehospitalization, high morbidity, and high mortality. The pathophysiology of CRS is complex and involves hemodynamic changes, neurohormonal activation, hypothalamic-pituitary stress reaction, inflammation, and infection. However, there is limited evidence or guideline in managing CRS type 1, and the established therapeutic strategies mainly target the symptomatic relief of heart failure. This review will discuss the strategies in the management of CRS type 1. Six clinical studies have been included in this review that include different treatment strategies such as nesiritide, dopamine, levosimendan, tolvaptan, dobutamine, and ultrafiltration. Treatment strategies for CRS type 1 are derived based on the current literature. Early recognition and treatment of CRS can improve the outcomes of the patients significantly.
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Affiliation(s)
- Leong Tung Ong
- Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Wilayah Persekutuan Kuala Lumpur, Malaysia
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15
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Chrysant SG, Chrysant GS. The pathophysiology and management of diuretic resistance in patients with heart failure. Hosp Pract (1995) 2021; 50:93-101. [PMID: 33596757 DOI: 10.1080/21548331.2021.1893065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
OBJECTIVES The objectives of the study are to investigate the causes of diuretic resistance in patients with advanced congestive heart failure (CHF), since diuretics are the cornerstone of treatment of these patients. Several studies have shown that diuretic resistance in patients with advanced CHF is common, ranging from 25% to 50% in hospitalized patients. METHODS In order to get a current perspective as to the magnitude of diuretic resistance in such patients, a focused Medline search of the English language literature was conducted between 2015 and 2020 using the search terms, CHF, diuretics, treatment, resistance, frequency, and 30 papers with pertinent information were selected. RESULTS The analysis of data from the selected papers demonstrated that diuretic resistance is common in hospitalized patients with advanced CHF and frequently associated with renal failure, which is secondary to CHF. CONCLUSIONS Diuretic resistance appears to be common in patients with advanced CHF and it is mostly due to decreased cardiac output, low blood pressure, decreased glomerular filtration rate, decreased filtration of sodium, and increased tubular reabsorption of sodium. Diuretic resistance in such patients can be overcome with the combination of loop diuretics with thiazide and thiazide-like diuretics, aldosterone antagonists, as well as other agents. The data from these studies in combination with collateral literature will be discussed in this review.
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Affiliation(s)
- Steven G Chrysant
- Department of cardiology, University of Oklahoma Health Sciences Center, Oklahoma, United States.,Department of cardiology, INTEGRIS Baptist Medical Center, Oklahoma, United States
| | - George S Chrysant
- Department of cardiology, University of Oklahoma Health Sciences Center, Oklahoma, United States.,Department of cardiology, INTEGRIS Baptist Medical Center, Oklahoma, United States
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16
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Safe Use of Loop Diuretics in the Management of Acute Decompensated Heart Failure in the Setting of Worsening Renal Function. Am J Ther 2021; 28:e708-e721. [PMID: 33443869 DOI: 10.1097/mjt.0000000000001328] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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17
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Increased mortality in elderly heart failure patients receiving infusion of furosemide compared to elderly heart failure patients receiving bolus injection. J Geriatr Cardiol 2020; 17:359-364. [PMID: 32670365 PMCID: PMC7338932 DOI: 10.11909/j.issn.1671-5411.2020.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
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18
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Continuous versus intermittent administration of furosemide in acute decompensated heart failure: a systematic review and meta-analysis. Heart Fail Rev 2020; 24:31-39. [PMID: 30054781 DOI: 10.1007/s10741-018-9727-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Diuretic therapy is important in critically ill patients because fluid overload impairs organ function and increases mortality. Compared to intermittent administration, continuous infusion of loop diuretics is theoretically superior in terms of diuresis and electrolyte balance. However, the available evidence is susceptible to carryover diuretic effects and resistance in earlier crossover trials. Consequently, we conducted a systematic review and meta-analysis of parallel-group randomized controlled trials to compare these two strategies in adults with acute decompensated heart failure. We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from their inceptions to May 26, 2018. We pooled the data using a random effects model. Our primary outcomes were all-cause mortality, length of hospital stay, and body weight reduction. We analyzed 12 parallel-group randomized controlled trials involving 923 patients. Compared with intermittent administration, continuous infusion of furosemide was not associated with an improvement in all-cause mortality (risk ratio 1.19; 95% confidence interval [CI], 0.65 to 2.16), length of hospital stay (weighted mean difference [WMD] - 0.88 days; 95% CI, - 2.76 to 1.01), or 24-h urine output (WMD 489.17 mL; 95% CI, - 183.18 to 1161.51), but was significantly associated with a greater body weight reduction (WMD 0.63 kg; 95% CI, 0.23 to 1.02). No differences in hypokalemia, hyponatremia, increased serum creatinine level, and hypotension were noted. Continuous infusion of furosemide, compared to intermittent administration, is associated with a greater body weight reduction and potential increase in 24-h urine output. The limited available evidence suggests no difference in adverse events between both strategies. Trial registration: PROSPERO (CRD42017083878).
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19
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Abstract
Cardiorenal syndrome is a complex interplay of dysregulated heart and kidney interaction that leads to multiorgan system dysfunction, which is not an uncommon occurrence in the setting of right heart failure. The traditional concept of impaired perfusion and forward flow recently has been modified to include the recognition of systemic venous congestion as a contributor, with direct and indirect mechanisms, including elevated renal venous pressure, reduced renal perfusion pressure, increased renal interstitial pressure, tubular dysfunction, splanchnic congestion, and neurohormonal and inflammatory activation. Treatment options beyond diuretics and vasoactive drugs remain limited and lack supportive evidence.
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Affiliation(s)
- Thida Tabucanon
- Kaufman Center for Heart Failure Treatment and Recovery, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk J3-4, Cleveland, OH 44195, USA
| | - Wai Hong Wilson Tang
- Kaufman Center for Heart Failure Treatment and Recovery, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk J3-4, Cleveland, OH 44195, USA; Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue, Desk J3-4, Cleveland, OH 44195, USA.
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20
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Lunney M, Ruospo M, Natale P, Quinn RR, Ronksley PE, Konstantinidis I, Palmer SC, Tonelli M, Strippoli GF, Ravani P. Pharmacological interventions for heart failure in people with chronic kidney disease. Cochrane Database Syst Rev 2020; 2:CD012466. [PMID: 32103487 PMCID: PMC7044419 DOI: 10.1002/14651858.cd012466.pub2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Approximately half of people with heart failure have chronic kidney disease (CKD). Pharmacological interventions for heart failure in people with CKD have the potential to reduce death (any cause) or hospitalisations for decompensated heart failure. However, these interventions are of uncertain benefit and may increase the risk of harm, such as hypotension and electrolyte abnormalities, in those with CKD. OBJECTIVES This review aims to look at the benefits and harms of pharmacological interventions for HF (i.e., antihypertensive agents, inotropes, and agents that may improve the heart performance indirectly) in people with HF and CKD. SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies through 12 September 2019 in consultation with an Information Specialist and using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA We included randomised controlled trials of any pharmacological intervention for acute or chronic heart failure, among people of any age with chronic kidney disease of at least three months duration. DATA COLLECTION AND ANALYSIS Two authors independently screened the records to identify eligible studies and extracted data on the following dichotomous outcomes: death, hospitalisations, worsening heart failure, worsening kidney function, hyperkalaemia, and hypotension. We used random effects meta-analysis to estimate treatment effects, which we expressed as a risk ratio (RR) with 95% confidence intervals (CI). We assessed the risk of bias using the Cochrane tool. We applied the GRADE methodology to rate the certainty of evidence. MAIN RESULTS One hundred and twelve studies met our selection criteria: 15 were studies of adults with CKD; 16 studies were conducted in the general population but provided subgroup data for people with CKD; and 81 studies included individuals with CKD, however, data for this subgroup were not provided. The risk of bias in all 112 studies was frequently high or unclear. Of the 31 studies (23,762 participants) with data on CKD patients, follow-up ranged from three months to five years, and study size ranged from 16 to 2916 participants. In total, 26 studies (19,612 participants) reported disaggregated and extractable data on at least one outcome of interest for our review and were included in our meta-analyses. In acute heart failure, the effects of adenosine A1-receptor antagonists, dopamine, nesiritide, or serelaxin on death, hospitalisations, worsening heart failure or kidney function, hyperkalaemia, hypotension or quality of life were uncertain due to sparse data or were not reported. In chronic heart failure, the effects of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) (4 studies, 5003 participants: RR 0.85, 95% CI 0.70 to 1.02; I2 = 78%; low certainty evidence), aldosterone antagonists (2 studies, 34 participants: RR 0.61 95% CI 0.06 to 6.59; very low certainty evidence), and vasopressin receptor antagonists (RR 1.26, 95% CI 0.55 to 2.89; 2 studies, 1840 participants; low certainty evidence) on death (any cause) were uncertain. Treatment with beta-blockers may reduce the risk of death (any cause) (4 studies, 3136 participants: RR 0.69, 95% CI 0.60 to 0.79; I2 = 0%; moderate certainty evidence). Treatment with ACEi or ARB (2 studies, 1368 participants: RR 0.90, 95% CI 0.43 to 1.90; I2 = 97%; very low certainty evidence) had uncertain effects on hospitalisation for heart failure, as treatment estimates were consistent with either benefit or harm. Treatment with beta-blockers may decrease hospitalisation for heart failure (3 studies, 2287 participants: RR 0.67, 95% CI 0.43 to 1.05; I2 = 87%; low certainty evidence). Aldosterone antagonists may increase the risk of hyperkalaemia compared to placebo or no treatment (3 studies, 826 participants: RR 2.91, 95% CI 2.03 to 4.17; I2 = 0%; low certainty evidence). Renin inhibitors had uncertain risks of hyperkalaemia (2 studies, 142 participants: RR 0.86, 95% CI 0.49 to 1.49; I2 = 0%; very low certainty). We were unable to estimate whether treatment with sinus node inhibitors affects the risk of hyperkalaemia, as there were few studies and meta-analysis was not possible. Hyperkalaemia was not reported for the CKD subgroup in studies investigating other therapies. The effects of ACEi or ARB, or aldosterone antagonists on worsening heart failure or kidney function, hypotension, or quality of life were uncertain due to sparse data or were not reported. Effects of anti-arrhythmic agents, digoxin, phosphodiesterase inhibitors, renin inhibitors, sinus node inhibitors, vasodilators, and vasopressin receptor antagonists were very uncertain due to the paucity of studies. AUTHORS' CONCLUSIONS The effects of pharmacological interventions for heart failure in people with CKD are uncertain and there is insufficient evidence to inform clinical practice. Study data for treatment outcomes in patients with heart failure and CKD are sparse despite the potential impact of kidney impairment on the benefits and harms of treatment. Future research aimed at analysing existing data in general population HF studies to explore the effect in subgroups of patients with CKD, considering stage of disease, may yield valuable insights for the management of people with HF and CKD.
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Affiliation(s)
- Meaghan Lunney
- University of Calgary, Department of Community Health Sciences, 3330 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4N1
| | - Marinella Ruospo
- The University of Sydney, Sydney School of Public Health, Sydney, Australia
- University of Bari, Department of Emergency and Organ Transplantation, Bari, Italy
| | - Patrizia Natale
- The University of Sydney, Sydney School of Public Health, Sydney, Australia
- University of Bari, Department of Emergency and Organ Transplantation, Bari, Italy
| | - Robert R Quinn
- University of Calgary, Department of Community Health Sciences, 3330 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4N1
- Cumming School of Medicine, University of Calgary, Department of Medicine, Calgary, Canada
| | - Paul E Ronksley
- University of Calgary, Department of Community Health Sciences, 3330 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4N1
| | - Ioannis Konstantinidis
- University of Pittsburgh Medical Center, Department of Medicine, 3459 Fifth Avenue, Pittsburgh, PA, USA, 15213
| | - Suetonia C Palmer
- Christchurch Hospital, University of Otago, Department of Medicine, Nephrologist, Christchurch, New Zealand
| | - Marcello Tonelli
- Cumming School of Medicine, University of Calgary, Department of Medicine, Calgary, Canada
| | - Giovanni Fm Strippoli
- The University of Sydney, Sydney School of Public Health, Sydney, Australia
- University of Bari, Department of Emergency and Organ Transplantation, Bari, Italy
- The Children's Hospital at Westmead, Cochrane Kidney and Transplant, Centre for Kidney Research, Westmead, NSW, Australia, 2145
| | - Pietro Ravani
- University of Calgary, Department of Community Health Sciences, 3330 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4N1
- Cumming School of Medicine, University of Calgary, Department of Medicine, Calgary, Canada
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Rangaswami J, Bhalla V, Blair JEA, Chang TI, Costa S, Lentine KL, Lerma EV, Mezue K, Molitch M, Mullens W, Ronco C, Tang WHW, McCullough PA. Cardiorenal Syndrome: Classification, Pathophysiology, Diagnosis, and Treatment Strategies: A Scientific Statement From the American Heart Association. Circulation 2020; 139:e840-e878. [PMID: 30852913 DOI: 10.1161/cir.0000000000000664] [Citation(s) in RCA: 731] [Impact Index Per Article: 146.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Cardiorenal syndrome encompasses a spectrum of disorders involving both the heart and kidneys in which acute or chronic dysfunction in 1 organ may induce acute or chronic dysfunction in the other organ. It represents the confluence of heart-kidney interactions across several interfaces. These include the hemodynamic cross-talk between the failing heart and the response of the kidneys and vice versa, as well as alterations in neurohormonal markers and inflammatory molecular signatures characteristic of its clinical phenotypes. The mission of this scientific statement is to describe the epidemiology and pathogenesis of cardiorenal syndrome in the context of the continuously evolving nature of its clinicopathological description over the past decade. It also describes diagnostic and therapeutic strategies applicable to cardiorenal syndrome, summarizes cardiac-kidney interactions in special populations such as patients with diabetes mellitus and kidney transplant recipients, and emphasizes the role of palliative care in patients with cardiorenal syndrome. Finally, it outlines the need for a cardiorenal education track that will guide future cardiorenal trials and integrate the clinical and research needs of this important field in the future.
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Okamura T, Hashimoto Y, Miki A, Kaji A, Sakai R, Iwai K, Osaka T, Kitagawa N, Ushigome E, Hamaguchi M, Asano M, Yamazaki M, Fukui M. High brain natriuretic peptide is associated with sarcopenia in patients with type 2 diabetes: a cross-sectional study of KAMOGAWA-DM cohort study. Endocr J 2019; 66:369-377. [PMID: 31019148 DOI: 10.1507/endocrj.ej19-0024] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Association between heart failure and sarcopenia has been reported, however, the association between sarcopenia and brain natriuretic peptide (BNP) is unclear. Thus, we investigated the association between sarcopenia and BNP in type 2 diabetic patients without heart failure. In this cross-sectional study, skeletal muscle mass index (SMI, kg/m2) was calculated as appendicular muscle mass, measured by bioimpedance analyzer, by the square of the height. Sarcopenia was defined as having both handgrip strength of <26 kg for men and <18 kg for women, and SMI of <7.0 kg/m2 for men and <5.7 kg/m2 for women. To investigate the impact of BNP levels on the presence of sarcopenia, propensity-score matching analysis was used to remove the bias of confounding variables, including age, sex, duration of diabetes, body mass index, exercise, systolic blood pressure, smoking status, hemoglobin A1c, creatinine, energy and protein intake. The area under the curve (AUC) of BNP levels for the presence of sarcopenia was calculated by the receiver operating characteristic curve (ROC). Among 433 patients (236 men and 65.4 (11.1) years), 32 patients (7.4%) were diagnosed as sarcopenia. In the propensity-matched 58 patients, BNP levels (Δ10 pg/mL incremental) were associated with the presence of sarcopenia by logistic regression analysis, (odds ratio: 1.56, 95% confidence interval: 1.14-2.13, p = 0.002). The optimal cut-off point of BNP levels for sarcopenia is 27.3 pg/mL (AUC 0.777, 95%CI, 0.691-0.863, sensitivity = 0.813, specificity = 0.736, p < 0.001). In conclusion, BNP levels were associated with sarcopenia in type 2 diabetic patients without heart failure.
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Affiliation(s)
- Takuro Okamura
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Akane Miki
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Ayumi Kaji
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Ryosuke Sakai
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Keiko Iwai
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Takafumi Osaka
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Noriyuki Kitagawa
- Department of Diabetology, Kameoka Municipal Hospital, Kameoka, Japan
| | - Emi Ushigome
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
- Department of Diabetology, Kameoka Municipal Hospital, Kameoka, Japan
| | - Mai Asano
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Masahiro Yamazaki
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
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Abstract
PURPOSE OF REVIEW We provide a concise review of recent studies focusing on the management of patients with acute heart failure (AHF). RECENT FINDINGS In well designed randomized trials, no mortality benefit has been observed with the use of diuretics, ultrafiltration, inotropes and vasodilators in AHF. Recent trials examining the role of novel inotropes and vasodilators as well as the role of mineralocorticoid receptor antagonists in the AHF population, is reviewed. SUMMARY The focus of therapy in AHF should be directed towards symptom management. No mortality benefit has been observed despite good quality studies.
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Diskin JB, Walker CB, Oberle MD, Diskin CJ. Use of the Fractional Excretion of Urea in an Azotemic Nonoliguric State: Type 1 Cardiorenal Syndrome. Ther Apher Dial 2018; 22:319-324. [DOI: 10.1111/1744-9987.12661] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Revised: 10/22/2017] [Accepted: 11/17/2017] [Indexed: 11/29/2022]
Affiliation(s)
- James B Diskin
- Edward via School of Osteopathic Medicine, Auburn University; Auburn AL USA
| | | | - Michael D Oberle
- Edward via School of Osteopathic Medicine, Auburn University; Auburn AL USA
| | - Charles J Diskin
- Edward via School of Osteopathic Medicine, Auburn University; Auburn AL USA
- Hypertension, Nephrology, Dialysis & Transplantation; Opelika AL USA
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Ohad DG, Segev Y, Kelmer E, Aroch I, Bdolah-Abram T, Segev G, Klainbart S. Constant rate infusion vs. intermittent bolus administration of IV furosemide in 100 pets with acute left-sided congestive heart failure: A retrospective study. Vet J 2018; 238:70-75. [PMID: 30103918 DOI: 10.1016/j.tvjl.2018.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Revised: 05/27/2018] [Accepted: 07/10/2018] [Indexed: 10/28/2022]
Abstract
The aim of this study was to determine whether the addition of constant rate infusion (CRI) to intermittent intravenous bolus (IVB) administration of furosemide resulted in an improvement in medical outcomes in dogs and cats with acute left-sided congestive heart failure (L-CHF). A total of 76 client-owned dogs and 24 client-owned cats admitted with acute L-CHF were retrospectively divided between an IVB group (43 dogs and 16 cats) and a CRI group (33 dogs and 8 cats). The median furosemide dose used in dogs in the CRI group (median 0.99mg/kg/h; range 0.025-3.73mg/kg/h) was lower than the dose used in dogs in the IVB group (median 1.19mg/kg/h; range 0.027-7.14mg/kg/h; P=0.008). Respiratory rates were lower in the IVB group (P=0.005) and the CRI group (P=0.039) compared to pre-treatment values. The overall short-term mortality was 15%. A trend of longer hospitalisation in the IVB group relative to the CRI group (P=0.07) was shown. Creatinine and total plasma protein concentrations increased more in the CRI group than in the IVB group, suggestive of a higher risk of dehydration and azotaemia. There may be safety profile differences between CRI and IVB, warranting a prospective study using a larger sample size.
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Affiliation(s)
- D G Ohad
- Department of Cardiology, Veterinary Teaching Hospital of the Koret School of Veterinary Medicine, Robert H. Smith Faculty of Agriculture, Food, and Environment, Hebrew University of Jerusalem, P.O. Box 12, Rehovot 761001, Israel.
| | - Y Segev
- Department of Small Animal Internal Medicine, Veterinary Teaching Hospital of the Koret School of Veterinary Medicine, Robert H. Smith Faculty of Agriculture, Food, and Environment, Hebrew University of Jerusalem, P.O. Box 12, Rehovot 761001, Israel
| | - E Kelmer
- Department of Small Animal Emergency and Critical Care, Veterinary Teaching Hospital of the Koret School of Veterinary Medicine, Robert H. Smith Faculty of Agriculture, Food, and Environment, Hebrew University of Jerusalem, P.O. Box 12, Rehovot 761001, Israel
| | - I Aroch
- Department of Small Animal Internal Medicine, Veterinary Teaching Hospital of the Koret School of Veterinary Medicine, Robert H. Smith Faculty of Agriculture, Food, and Environment, Hebrew University of Jerusalem, P.O. Box 12, Rehovot 761001, Israel
| | - T Bdolah-Abram
- Department of Small Animal Internal Medicine, Veterinary Teaching Hospital of the Koret School of Veterinary Medicine, Robert H. Smith Faculty of Agriculture, Food, and Environment, Hebrew University of Jerusalem, P.O. Box 12, Rehovot 761001, Israel
| | - G Segev
- Department of Small Animal Internal Medicine, Veterinary Teaching Hospital of the Koret School of Veterinary Medicine, Robert H. Smith Faculty of Agriculture, Food, and Environment, Hebrew University of Jerusalem, P.O. Box 12, Rehovot 761001, Israel
| | - S Klainbart
- Department of Small Animal Emergency and Critical Care, Veterinary Teaching Hospital of the Koret School of Veterinary Medicine, Robert H. Smith Faculty of Agriculture, Food, and Environment, Hebrew University of Jerusalem, P.O. Box 12, Rehovot 761001, Israel
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Abstract
Although much remains unknown regarding the pathophysiology of acute heart failure (AHF), precipitating events are thought to involve a complex set of interactions between the heart, kidneys, and peripheral vasculature. In addition to these interactions, which are considered the primary abnormalities in patients with AHF, several other organ systems may also be affected and contribute to disease progression. Currently available scientific literature suggests that the natural history and pathophysiology of AHF consists of two phases: (1) an "initiation phase" involving a series of triggering events, and (2) an "amplification phase," in which multiple mechanisms contribute to worsening HF and exacerbate end-organ damage. Biomarkers of cardiac, renal, pulmonary, and other organ function have been identified during episodes of AHF, including brain natriuretic peptide, troponin I, and troponin T; biomarkers associated with AHF have proven to be useful tools for studying the pathophysiology of the syndrome, predicting clinical outcomes, and identifying patient management strategies. Despite considerable advances in recent years, AHF continues to be a leading cause of hospitalization and death in patients with chronic HF. Moreover, AHF remains a major healthcare issue exacting a considerable cost burden. Addressing this ongoing unmet need requires prioritizing efforts to better understand the natural history and pathophysiology of AHF; only then can targeted therapies be developed to prevent rehospitalization in patients with AHF, or at least alter the trajectory of disease progression toward improved clinical outcomes.
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Affiliation(s)
- Hani N Sabbah
- Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Health System, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI, 48202, USA.
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Ragab D, Taema KM, Farouk W, Saad M. Continuous infusion of furosemide versus intermittent boluses in acute decompensated heart failure: Effect on thoracic fluid content. Egypt Heart J 2018; 70:65-70. [PMID: 30166884 PMCID: PMC6112354 DOI: 10.1016/j.ehj.2017.12.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Accepted: 12/05/2017] [Indexed: 01/06/2023] Open
Abstract
INTRODUCTION The administration of loop diuretics in the management of acute decompensated heart failure (ADHF) whether IV boluses or continuous infusion is still controversial. We intended to evaluate differences between the two administration routes on the thoracic fluid content (TFC) and the renal functions. METHODS Sixty patients with ADHF admitted to the critical care medicine department (Cairo University, Egypt) were initially enrolled in the study. Twenty patients were excluded due to EF > 40%, myocardial infarction within 30 days, and baseline serum creatinine level > 4.0 mg/dL. Furosemide (120 mg/day) was given to the remaining 40 pts who continued the study after 1:1 randomization to either continuous infusion (group-I, 20 pts) or three equal intermittent daily doses (group-II, 20 pts). Subsequent dose titration was allowed after 24 h, but not earlier, according to patient's response. No other diuretic medications were allowed. All patients were daily evaluated for NYHA class, urine output, TFC, body weight, serum K+, and renal chemistry. RESULTS The median age (Q1-Q3) was 54.5 (43.8-63.8) years old with 24 (60%) males. Apart from TFC which was significantly higher in group-I, the admission demographic, clinical, laboratory and co-morbid conditions were similar in both groups. There was statistically insignificant tendency for increased urine output during the 1st and 2nd days in group-I compared to group-II (p = .08). The body weight was decreased during the 1st day by 2 (1.5-2.5) kg in group-I compared to 1.5 (1-2) kg in group-II, (p = .03). These changes became insignificant during the 2nd day (p = .4). The decrease of TFC was significantly higher in group-I than in group-II [10 (6.3-14.5) vs 7 (3.3-9.8) kΩ-1 during the first day and 8 (6-11) vs 6 (3.3-8.5) kΩ-1 during the second day in groups-I&II respectively, P = .02 for both]. There was similar NYHA class improvement in both groups (p = .7). The serum creatinine was increased by 0.2 (0.1-0.5) vs 0 (-0.1 to 0.2) mg% and the CrCl was decreased by 7.4 (4.5-12.3) vs 3.1 (0.2-8.8) ml/min in groups-I&II respectively (p = .009 and .02 respectively). CONCLUSIONS We concluded that continuous furosemide infusion in ADHF might cause greater weight loss and more decrease in TFC with no symptomatic improvement and possibly with more nephrotoxic effect.
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Miles M, Alvis BD, Hocking K, Baudenbacher F, Guth C, Lindenfeld J, Brophy C, Eagle S. Peripheral Intravenous Volume Analysis (PIVA) for Quantitating Volume Overload in Patients Hospitalized With Acute Decompensated Heart Failure-A Pilot Study. J Card Fail 2018; 24:525-532. [PMID: 29777760 DOI: 10.1016/j.cardfail.2018.05.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Revised: 04/23/2018] [Accepted: 05/11/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND To determine the feasibility of peripheral intravenous volume analysis (PIVA) of venous waveforms for assessing volume overload in patients admitted to the hospital with acute decompensated heart failure (ADHF). METHODS Venous waveforms were captured from a peripheral intravenous catheter in subjects admitted for ADHF and healthy age-matched controls. Admission PIVA signal, brain natriuretic peptide, and chest radiographic measurements were related to the net volume removed during diuresis. RESULTS ADHF patients had a significantly greater PIVA signal on admission compared with the control group (P = .0013, n = 18). At discharge, ADHF patients had a PIVA signal similar to the control group. PIVA signal, not brain natriuretic peptide or chest radiographic measures, accurately predicted the amount of volume removed during diuresis (R2 = 0.781, n = 14). PIVA signal at time of discharge greater than 0.20, demonstrated 83.3% 120-day readmission rate. CONCLUSIONS This study demonstrates the feasibility of PIVA for assessment of volume overload in patients admitted to the hospital with ADHF.
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Affiliation(s)
- Merrick Miles
- Vanderbilt University Medical Center, Department of Anesthesiology, Division of Critical Care, Nashville, Tennessee
| | - Bret D Alvis
- Vanderbilt University Medical Center, Department of Anesthesiology, Division of Critical Care, Nashville, Tennessee.
| | - Kyle Hocking
- Vanderbilt University Medical Center, Department of Surgery, Nashville, Tennessee
| | - Franz Baudenbacher
- Vanderbilt University, Institute for Integrative Biosystems Research and Education (VIIBRE) Department of Engineering, Nashville, Tennessee
| | - Christy Guth
- Vanderbilt University Medical Center, Department of Surgery, Nashville, Tennessee
| | - Joann Lindenfeld
- Vanderbilt University Medical Center, Department of Medicine, Division of Cardiology, Nashville, Tennessee
| | - Colleen Brophy
- Vanderbilt University Medical Center, Department of Surgery, Nashville, Tennessee
| | - Susan Eagle
- Vanderbilt University Medical Center, Department of Anesthesiology, Division of Cardiac & Thoracic Anesthesia, Nashville, Tennessee
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Intermittent furosemide administration in patients with or at risk for acute kidney injury: Meta-analysis of randomized trials. PLoS One 2018; 13:e0196088. [PMID: 29689116 PMCID: PMC5915682 DOI: 10.1371/journal.pone.0196088] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Accepted: 04/05/2018] [Indexed: 12/13/2022] Open
Abstract
Background Furosemide is the most common loop diuretic used worldwide. The off-label administration of furosemide bolus(es) for the prevention or to reverse acute kidney injury (AKI) is widespread but not supported by available evidence. We conducted a meta-analysis of randomized trials (RCTs) to investigate whether bolus furosemide to prevent or treat AKI is detrimental on patients’ survival. Methods Electronic databases were searched through October 2017 for RCTs comparing bolus furosemide administration versus any comparator in patients with or at risk for AKI. The primary endpoint was all-cause longest follow-up mortality. Secondary endpoints included new or worsening AKI, receipt of renal replacement therapy, length of hospital stay, and peak serum creatinine after randomization. Results A total of 28 studies randomizing 3,228 patients were included in the analysis. We found no difference in mortality between the two groups (143/892 [16%] in the furosemide group versus 141/881 [16%] in the control group; odds ratio [OR], 0.84; 95% confidence interval [CI], 0.63 to 1.13; p = 0.25). No significant differences in secondary outcomes were found. A significant improvement in survival was found in the subgroup of patients receiving furosemide bolus(es) as a preventive measure (43/613 [7.0%] versus 67/619 [10.8%], OR 0.62; 95% CI, 0.41 to 0.94; p = 0.03) Conclusions Intermittent furosemide administration is not associated with an increased mortality in patients with or at risk for AKI, although it may reduce mortality when used as a preventive measure. Future high-quality RCTs are needed to define the role of loop diuretics in AKI prevention and management. Trial registration The study protocol was registered on PROSPERO database for systematic reviews (Registration no. CRD42017078607 – http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017078607).
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Jung YH, Steppan J, Goeddel LA. Continuous Versus Bolus Furosemide in the Critically Ill: More Questions than Answers. J Cardiothorac Vasc Anesth 2018; 32:2311-2312. [PMID: 29678434 DOI: 10.1053/j.jvca.2018.02.029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Indexed: 11/11/2022]
Affiliation(s)
- Youn-Hoa Jung
- Department of Anesthesiology and Critical Care Medicine, Divisions of Cardiac Anesthesia and Adult Critical Care, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Jochen Steppan
- Department of Anesthesiology and Critical Care Medicine, Divisions of Cardiac Anesthesia and Adult Critical Care, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Lee A Goeddel
- Department of Anesthesiology and Critical Care Medicine, Divisions of Cardiac Anesthesia and Adult Critical Care, The Johns Hopkins Medical Institutions, Baltimore, MD
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Affiliation(s)
- David H. Ellison
- Oregon Clinical & Translational Research Institute, Oregon Health & Science University and VA Portland Health Care System, Portland, OR
| | - G. Michael Felker
- Duke University School of Medicine and Duke Clinical Research Institute, Durham, NC
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Palazzuoli A, Ruocco G, Vescovo G, Valle R, Di Somma S, Nuti R. Rationale and study design of intravenous loop diuretic administration in acute heart failure: DIUR-AHF. ESC Heart Fail 2017; 4:479-486. [PMID: 28980452 PMCID: PMC5695186 DOI: 10.1002/ehf2.12226] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Revised: 08/05/2017] [Accepted: 09/01/2017] [Indexed: 11/07/2022] Open
Abstract
AIMS Although loop diuretics are the most commonly used drugs in acute heart failure (AHF) treatment, their short-term and long-term effects are relatively unknown. The significance of worsening renal function occurrence during intravenous treatment is not clear enough. This trial aims to clarify all these features and contemplate whether continuous infusion is better than an intermittent strategy in terms of decongestion efficacy, diuretic efficiency, renal function, and long-term prognosis. METHODS AND RESULTS This is a prospective, multicentre, randomized study that compares continuous infusion to intermittent infusion and a low vs. high diuretic dose of furosemide in patients with a diagnosis of acute heart failure, BNP ≥ 100 pg/mL, and specific chest X-ray signs. Randomization criteria have been established at a 1:1 ratio using a computer-generated scheme of either twice-daily bolus injection or continuous infusion for a time period ranging from 72 to 120 h. The initial dose will be 80 mg/day of intravenous furosemide and, in the case of poor response, will be doubled using an escalation algorithm. A high diuretic dose is defined as a furosemide daily amount >120 mg/day respectively. CONCLUSIONS Continuous and high dose groups could reveal a more intensive diuresis and a greater decongestion with respect to intermittent and low dose groups; high dose and poor loop diuretic efficiency should be related to increased diuretic resistance, renal dysfunction occurrence, and greater congestion status. Poor diuretic response will be associated with less decongestion and an adverse prognosis.
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Affiliation(s)
- Alberto Palazzuoli
- Department of Internal Medicine, Cardiovascular Diseases UnitS. Maria alle Scotte Hospital, University of SienaSienaItaly
| | - Gaetano Ruocco
- Department of Internal Medicine, Cardiovascular Diseases UnitS. Maria alle Scotte Hospital, University of SienaSienaItaly
| | | | | | - Salvatore Di Somma
- Department of Emergency MedicineUniversity of Roma, Sant'Andrea HospitalRomeItaly
| | - Ranuccio Nuti
- Department of Internal Medicine, Cardiovascular Diseases UnitS. Maria alle Scotte Hospital, University of SienaSienaItaly
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Beltrami M, Ruocco G, Ibrahim A, Lucani B, Franci B, Nuti R, Palazzuoli A. Different trajectories and significance of B-type natriuretic peptide, congestion and acute kidney injury in patients with heart failure. Intern Emerg Med 2017; 12:593-603. [PMID: 28181125 DOI: 10.1007/s11739-017-1620-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 01/25/2017] [Indexed: 01/29/2023]
Abstract
The exact relationship existing among congestion status, brain natriuretic peptide (BNP) changes and acute kidney injury (AKI) has not been elucidated in patients with acute heart failure (AHF). The aims of this study are: to investigate the relation and prognostic role of BNP, AKI and clinical congestion after discharge; to define the exact BNP cut off value or a BNP in-hospital reduction to identify patients with higher risk during vulnerable post-discharge phase. We consecutively enrolled 157 patients with a diagnosis of AHF. BNP and creatinine were measured in all patients, and degree of failure was assessed. AKI was defined as a creatinine increase ≥0.3 mg/dL or eGFR reduction ≥20% during hospitalization. All patients were followed for 1 and 3 months. Of 146 included patients, 110 patients (75%) displayed effective decongestion, 116 (79%) showed a BNP decrease ≥30%, and 28 (19%) developed in-hospital AKI. BNP in-hospital decrease ≥30% was found more often in patients who showed good decongestion in comparison to patients in persistent failure (63 vs 22%; p < 0.001). The ROC curve analyses at 3 months show that both BNP reduction of 30% between admission and discharge and decongestion at discharge identifies patients with a reduced incidence of cardiovascular events (AUC = 0.79, confidence interval 0.68-0.90, sensibility 90%, sensitivity 50% p < 0.001). Kaplan-Meier survival plots show a better outcome in patients with a BNP decrease ≥30% and good decongestion at discharge (p = 0.03). BNP reduction in AHF is associated with decongestion. BNP reduction associated with decongestion at discharge is a favorable prognostic indicator at 90-day survival irrespective of the AKI occurrence.
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Affiliation(s)
- Matteo Beltrami
- Cardiovascular Diseases Unit, Department of Internal Medicine, S. Maria alle Scotte Hospital, University of Siena, Siena, Italy
| | - Gaetano Ruocco
- Cardiovascular Diseases Unit, Department of Internal Medicine, S. Maria alle Scotte Hospital, University of Siena, Siena, Italy
| | - Aladino Ibrahim
- Cardiovascular Diseases Unit, Department of Internal Medicine, S. Maria alle Scotte Hospital, University of Siena, Siena, Italy
| | - Barbara Lucani
- Cardiovascular Diseases Unit, Department of Internal Medicine, S. Maria alle Scotte Hospital, University of Siena, Siena, Italy
| | - Beatrice Franci
- Cardiovascular Diseases Unit, Department of Internal Medicine, S. Maria alle Scotte Hospital, University of Siena, Siena, Italy
| | - Ranuccio Nuti
- Cardiovascular Diseases Unit, Department of Internal Medicine, S. Maria alle Scotte Hospital, University of Siena, Siena, Italy
| | - Alberto Palazzuoli
- Cardiovascular Diseases Unit, Department of Internal Medicine, S. Maria alle Scotte Hospital, University of Siena, Siena, Italy.
- Department of Internal Medicine and Metabolic Diseases, Cardiology, Le Scotte Hospital, Viale Bracci, 53100, Siena, Italy.
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Different diuretic dose and response in acute decompensated heart failure: Clinical characteristics and prognostic significance. Int J Cardiol 2016; 224:213-219. [DOI: 10.1016/j.ijcard.2016.09.005] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2016] [Revised: 08/24/2016] [Accepted: 09/08/2016] [Indexed: 11/22/2022]
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Abstract
We present the case of a patient with heart failure and severe congestion who was responding poorly to diuretic therapy. We discuss the key problems concerning the pathophysiology and bedside therapeutic approach to congestion and fluid overload in this clinical setting, and we give practical suggestions to overcome congestion, especially in the setting of diuretic resistance and worsening renal function. We conclude that the application of key pharmacokinetic and pharmacodynamic principles of diuretic therapy, along with in-depth knowledge of the pathophysiology of heart failure, still represent the cornerstones for a correct approach to decongestive therapy in these patients.
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Furosemide continuous rate infusion diluted with 5% dextrose in water or hypertonic saline in normal adult dogs: a pilot study. J Vet Cardiol 2016; 19:44-56. [PMID: 27840084 DOI: 10.1016/j.jvc.2016.09.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Revised: 09/15/2016] [Accepted: 09/20/2016] [Indexed: 11/23/2022]
Abstract
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.
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Ruocco G, Pellegrini M, De Gori C, Franci B, Nuti R, Palazzuoli A. The prognostic combined role of B-type natriuretic peptide, blood urea nitrogen and congestion signs persistence in patients with acute heart failure. J Cardiovasc Med (Hagerstown) 2016; 17:818-27. [DOI: 10.2459/jcm.0000000000000350] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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Palazzuoli A, Lombardi C, Ruocco G, Padeletti M, Nuti R, Metra M, Ronco C. Chronic kidney disease and worsening renal function in acute heart failure: different phenotypes with similar prognostic impact? EUROPEAN HEART JOURNAL-ACUTE CARDIOVASCULAR CARE 2016; 5:534-548. [DOI: 10.1177/2048872615589511] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Accepted: 05/10/2015] [Indexed: 12/28/2022]
Affiliation(s)
- Alberto Palazzuoli
- Department of Internal and Surgical Medicine, Cardiology Unit, University of Siena, Italy
| | - Carlo Lombardi
- Department of Experimental and Applied Medicine, University and Civil Hospital of Brescia, Italy
| | - Gaetano Ruocco
- Department of Internal and Surgical Medicine, Cardiology Unit, University of Siena, Italy
| | | | - Ranuccio Nuti
- Department of Internal and Surgical Medicine, Cardiology Unit, University of Siena, Italy
| | - Marco Metra
- Department of Experimental and Applied Medicine, University and Civil Hospital of Brescia, Italy
| | - Claudio Ronco
- Nephrology Dialysis and Transplantation International Renal Research Institute (IRRIV), St Bortolo Hospital, Italy
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Prognostic Significance of Hyperuricemia in Patients With Acute Heart Failure. Am J Cardiol 2016; 117:1616-1621. [PMID: 27040576 DOI: 10.1016/j.amjcard.2016.02.039] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2016] [Revised: 02/16/2016] [Accepted: 02/16/2016] [Indexed: 02/07/2023]
Abstract
Serum uric acid (UA) is associated with death and hospitalization in chronic heart failure (HF). However, UA in acute HF has not been well studied with respect to its relation to renal dysfunction and vascular congestion. We measured admission serum UA along with baseline variables in 281 patients with acute HF screened from the Loop Diuretics Administration and Acute Heart Failure (Diur-HF) trial. Hyperuricemia was defined as serum UA >7 mg/dl in men and >6 mg/dl in women. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m(2) before hospital admission. Death or HF hospitalization at 6 months was the primary outcome. The mean UA concentration was 6.4 ± 2.5 mg/dl, and 121 patients (43.1%) were classified as hyperuricemic. UA values were significantly increased in patients with CKD compared to patients without CKD (6.8 ± 2.7 vs 6.1 ± 2.1 mg/dl; p = 0.02); however, UA was not associated with the development of acute kidney injury. Patients with hyperuricemia had greater degrees of pulmonary and systemic congestion than normouricemic patients (congestion score 3.5 vs 2.1, p <0.01). Hyperuricemia was associated with higher risk of death or HF rehospitalization (univariate hazard ratio 1.46 [1.02 to 2.10]; p = 0.04, multivariate hazard ratio 1.69 [1.16 to 2.45]; p = 0.005). In conclusion, hospitalized patients with acute HF, elevated UA levels were associated with both CKD and pulmonary congestion. After controlling for potential confounders, hyperuricemia was associated with rehospitalization and death at 6 months.
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Abstract
Acute kidney injury (AKI) is one of the most relevant complications after major surgery and is a predictor of mortality. In Western countries, patients at risk of developing AKI are mainly those undergoing cardiovascular surgical procedures. In this category of patients, AKI depends on a multifactorial etiology, including low ejection fraction, use of contrast media, hemodynamic instability, cardiopulmonary bypass, and bleeding. Despite a growing body of literature, the treatment of renal failure remains mainly supportive (e.g. hemodynamic stability, fluid management, and avoidance of further damage); therefore, the management of patients at risk of AKI should aim at prevention of renal damage. Thus, the present narrative review analyzes the pathophysiology underlying AKI (specifically in high-risk patients), the preoperative risk factors that predispose to renal damage, early biomarkers related to AKI, and the strategies employed for perioperative renal protection. The most recent scientific evidence has been considered, and whenever conflicting data were encountered possible suggestions are provided.
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Affiliation(s)
- Nora Di Tomasso
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Fabrizio Monaco
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giovanni Landoni
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
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Obi Y, Kim T, Kovesdy CP, Amin AN, Kalantar-Zadeh K. Current and Potential Therapeutic Strategies for Hemodynamic Cardiorenal Syndrome. Cardiorenal Med 2016; 6:83-98. [PMID: 26989394 PMCID: PMC4790039 DOI: 10.1159/000441283] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Cardiorenal syndrome (CRS) encompasses conditions in which cardiac and renal disorders co-exist and are pathophysiologically related. The newest classification of CRS into seven etiologically and clinically distinct types for direct patient management purposes includes hemodynamic, uremic, vascular, neurohumoral, anemia- and/or iron metabolism-related, mineral metabolism-related and protein-energy wasting-related CRS. This classification also emphasizes the pathophysiologic pathways. The leading CRS category remains hemodynamic CRS, which is the most commonly encountered type in patient care settings and in which acute or chronic heart failure leads to renal impairment. SUMMARY This review focuses on selected therapeutic strategies for the clinical management of hemodynamic CRS. This is often characterized by an exceptionally high ratio of serum urea to creatinine concentrations. Loop diuretics, positive inotropic agents including dopamine and dobutamine, vasopressin antagonists including vasopressin receptor antagonists such as tolvaptan, nesiritide and angiotensin-neprilysin inhibitors are among the pharmacologic agents used. Additional therapies include ultrafiltration (UF) via hemofiltration or dialysis. The beneficial versus unfavorable effects of these therapies on cardiac decongestion versus renal blood flow may act in opposite directions. Some of the most interesting options for the outpatient setting that deserve revisiting include portable continuous dobutamine infusion, peritoneal dialysis and outpatient UF via hemodialysis or hemofiltration. KEY MESSAGES The new clinically oriented CRS classification system is helpful in identifying therapeutic targets and offers a systematic approach to an optimal management algorithm with better understanding of etiologies. Most interventions including UF have not shown a favorable impact on outcomes. Outpatient portable dobutamine infusion is underutilized and not well studied. Revisiting traditional and novel strategies for outpatient management of CRS warrants clinical trials.
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Affiliation(s)
- Yoshitsugu Obi
- Division of Nephrology and Hypertension, Orange, Calif., USA
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Orange, Calif., USA
| | - Taehee Kim
- Division of Nephrology and Hypertension, Orange, Calif., USA
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Orange, Calif., USA
- Department of Medicine, Inje University, Busan, South Korea
| | - Csaba P. Kovesdy
- Division of Nephrology, University of Tennessee Health Sciences Center, Memphis, Tenn., USA
| | - Alpesh N. Amin
- Department of Medicine, University of California Irvine, Orange, Calif., USA
| | - Kamyar Kalantar-Zadeh
- Division of Nephrology and Hypertension, Orange, Calif., USA
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Orange, Calif., USA
- Department of Medicine, VA Long Beach Health Care System, Long Beach, Calif., USA
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Senni M, D'Elia E, Emdin M, Vergaro G. Biomarkers of Heart Failure with Preserved and Reduced Ejection Fraction. Handb Exp Pharmacol 2016; 243:79-108. [PMID: 28181009 DOI: 10.1007/164_2016_86] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Biomarkers are increaingly being used in the management of heart failure not only for the purpose of screening, diagnosis, and risk stratification, but also as a guide to evaluate the response to treatment in the individual patient and as an entry criterion and/or a surrogate marker of efficacy in clinical trials testing novel drugs. In this chapter, we review the role of established biomarkers for heart failure management, according to the main classification of HF phenotypes, based on the measurement of left ventricular ejection fraction, including heart failure with reduced (<40%), preserved (≥50%), and, as recently proposed, mid-range (40-49%) ejection fraction.
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Affiliation(s)
- Michele Senni
- Department of Cardiology, Heart Failure and Heart Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
- CardioVascular Department, Ospedale Papa Giovanni XXIII Hospital, Bergamo, Italy.
| | - Emilia D'Elia
- CardioVascular Department, Ospedale Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Michele Emdin
- Life Science Institute, Scuola Superiore Sant'Anna, Pisa, Italy
- Fondazione Toscana G. Monasterio, Pisa, Italy
| | - Giuseppe Vergaro
- Life Science Institute, Scuola Superiore Sant'Anna, Pisa, Italy
- Fondazione Toscana G. Monasterio, Pisa, Italy
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Palazzuoli A, Ruocco G, Ronco C, McCullough PA. Loop diuretics in acute heart failure: beyond the decongestive relief for the kidney. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2015; 19:296. [PMID: 26335137 PMCID: PMC4559070 DOI: 10.1186/s13054-015-1017-3] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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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Affiliation(s)
- Alberto Palazzuoli
- Department of Internal and Surgical Medicine, Cardiovascular Diseases Unit, Le Scotte Hospital, University of Siena Viale Bracci, 53100, Siena, Italy.
| | - Gaetano Ruocco
- Department of Internal and Surgical Medicine, Cardiovascular Diseases Unit, Le Scotte Hospital, University of Siena Viale Bracci, 53100, Siena, Italy
| | - Claudio Ronco
- Nephrology Dialysis & Transplantation International Renal Research Institute (IRRIV) St. Bortolo Hospital, Viale Rodolfi 37, IT-36100, Vicenza, Italy
| | - Peter A McCullough
- 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
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Schartum-Hansen H, Løland KH, Svingen GFT, Seifert R, Pedersen ER, Nordrehaug JE, Bleie Ø, Ebbing M, Berge C, Nilsen DWT, Nygård O. Use of Loop Diuretics is Associated with Increased Mortality in Patients with Suspected Coronary Artery Disease, but without Systolic Heart Failure or Renal Impairment: An Observational Study Using Propensity Score Matching. PLoS One 2015; 10:e0124611. [PMID: 26030195 PMCID: PMC4452510 DOI: 10.1371/journal.pone.0124611] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2014] [Accepted: 03/03/2015] [Indexed: 11/18/2022] Open
Abstract
Background Loop diuretics are widely used in patients with heart and renal failure, as well as to treat hypertension and peripheral edema. However, there are no randomized, controlled trials (RCT) evaluating their long term safety, and several observational reports have indicated adverse effects. We sought to evaluate the impact of loop diuretics on long term survival in patients with suspected coronary artery disease, but without clinical heart failure, reduced left ventricular ejection fraction or impaired renal function. Method and Findings From 3101 patients undergoing coronary angiography for suspected stable angina pectoris, subjects taking loop diuretics (n=109) were matched with controls (n=198) in an attempted 1:2 ratio, using propensity scores based on 59 baseline variables. During median follow-up of 10.1 years, 37.6% in the loop diuretics group and 23.7% in the control group died (log-rank p-value 0.005). Treatment with loop diuretics was associated with a hazard ratio (95% confidence interval) of 1.82 (1.20, 2.76), and the number needed to harm was 7.2 (4.1, 30.3). Inclusion of all 3101 patients using propensity score weighting and adjustment for numerous covariates provided similar estimates. The main limitation is the potential of confounding from unmeasured patient characteristics. Conclusions The use of loop diuretics in patients with suspected coronary artery disease, but without systolic heart failure or renal impairment, is associated with increased risk of all-cause mortality. Considering the lack of randomized controlled trials to evaluate long term safety of loop diuretics, our data suggest caution when prescribing these drugs to patients without a clear indication.
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Affiliation(s)
- Hall Schartum-Hansen
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
- * E-mail:
| | - Kjetil H. Løland
- Section for Cardiology, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Gard F. T. Svingen
- Section for Cardiology, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Reinhard Seifert
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
| | - Eva R. Pedersen
- Section for Cardiology, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Jan E. Nordrehaug
- Section for Cardiology, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Øyvind Bleie
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
| | - Marta Ebbing
- Norwegian Institute of Public Health, Bergen, Norway
| | - Christ Berge
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
| | - Dennis W. T. Nilsen
- Section for Cardiology, Department of Clinical Science, University of Bergen, Bergen, Norway
- Stavanger University Hospital, Stavanger, Norway
| | - Ottar Nygård
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
- Section for Cardiology, Department of Clinical Science, University of Bergen, Bergen, Norway
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de Grooth HJS, Girbes AR, Tuinman PR. Intravenous furosemide in decompensated heart failure: do not protocolize dosing but the desired effect! Crit Care 2014; 18:709. [PMID: 25672666 PMCID: PMC4273483 DOI: 10.1186/s13054-014-0709-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
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