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Mahmood A, Dhall E, Primus CP, Gallagher A, Zakeri R, Mohammed SF, Chahal AA, Ricci F, Aung N, Khanji MY. Heart failure with preserved ejection fraction management: a systematic review of clinical practice guidelines and recommendations. EUROPEAN HEART JOURNAL. QUALITY OF CARE & CLINICAL OUTCOMES 2024; 10:571-589. [PMID: 38918060 PMCID: PMC11537231 DOI: 10.1093/ehjqcco/qcae053] [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: 06/19/2024] [Accepted: 06/24/2024] [Indexed: 06/27/2024]
Abstract
Multiple guidelines exist for the diagnosis and management of heart failure with preserved ejection fraction (HFpEF). We systematically reviewed current guidelines and recommendations, developed by national and international medical organizations, on the management of HFpEF in adults to aid clinical decision-making. We searched MEDLINE and EMBASE on 28 February 2024 for publications over the last 10 years as well as websites of organizations relevant to guideline development. Of the 10 guidelines and recommendations retrieved, 7 showed considerable rigour of development and were subsequently retained for analysis. There was consensus on the definition of HFpEF and the diagnostic role of serum natriuretic peptides and resting transthoracic echocardiography. Discrepancies were identified in the thresholds of serum natriuretic peptides and transthoracic echocardiography parameters used to diagnose HFpEF. There was agreement on the general pharmacological and supportive management of acute and chronic HFpEF. However, differences exist in strategies to identify and address specific phenotypes. Contemporary guidelines for HFpEF management agree on measures to avoid its development and the consideration of cardiac transplantation in advanced diseases. There were discrepancies in recommended frequency of surveillance for patients with HFpEF and sparse recommendations on screening for HFpEF in the general population, use of diagnostic scoring systems, and the role of newly emerging therapies.
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Affiliation(s)
- Adil Mahmood
- William Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
- Newham University Hospital, Barts Health NHS Trust, Glen Road, London E13 8SL, UK
| | - Eamon Dhall
- Newham University Hospital, Barts Health NHS Trust, Glen Road, London E13 8SL, UK
| | - Christopher P Primus
- Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK
| | - Angela Gallagher
- Newham University Hospital, Barts Health NHS Trust, Glen Road, London E13 8SL, UK
- Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK
| | - Rosita Zakeri
- School of Cardiovascular Medicine & Sciences, James Black Centre, King's College London, 125 Coldharbour Lane, London SE5 9NU, UK
| | - Selma F Mohammed
- Department of Cardiology, Creighton University School of Medicine, Omaha, NE 68124, USA
| | - Anwar A Chahal
- William Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
- Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First Str, SW Rochester, MN 55905, USA
- Center for Inherited Cardiovascular Diseases, Department of Cardiology, WellSpan Health, 30 Monument Rd, York, PA 17403, USA
| | - Fabrizio Ricci
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti-Pescara, Via dei Vestini 33, 66100 Chieti, Italy
- University Cardiology Division, SS Annunziata Polyclinic University Hospital, Via dei Vestini 5, 66100 Chieti, Italy
- Department of Clinical Sciences, Lund University, Jan Waldenströms Gata 35, 21428 Malmö, Sweden
| | - Nay Aung
- William Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
- Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK
| | - Mohammed Y Khanji
- William Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
- Newham University Hospital, Barts Health NHS Trust, Glen Road, London E13 8SL, UK
- Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK
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Gogikar A, Nanda A, Janga LSN, Sambe HG, Yasir M, Man RK, Mohammed L. Combination Diuretic Therapy With Thiazides: A Systematic Review on the Beneficial Approach to Overcome Refractory Fluid Overload in Heart Failure. Cureus 2023; 15:e44624. [PMID: 37720125 PMCID: PMC10500380 DOI: 10.7759/cureus.44624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 09/03/2023] [Indexed: 09/19/2023] Open
Abstract
Heart failure (HF) is a notable public health issue, and intravenous loop diuretics are frequently employed to address acute decompensated heart failure (ADHF) and alleviate symptoms of congestion. However, prolonged use of loop diuretics can lead to drug resistance, and some patients experience refractory volume overload that does not respond to treatment. Sequential nephron blockade, which involves combining loop and thiazide diuretics, has been proposed as a strategy to overcome diuretic resistance and improve fluid overload management. This systematic review aims to critically evaluate the effectiveness and safety of this combination diuretic therapy. Following the directives detailed in the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was conducted. Eligibility criteria were established to select relevant studies, including the requirement for studies to be conducted on human subjects and published as free full-text papers in English within the last 10 years. Several databases were searched using a combination of Medical Subject Heading (MeSH) phrases and keywords related to heart failure, loop diuretics, and thiazide diuretics. The search yielded 948 references, and after screening titles, abstracts, and full-text papers, eight final studies (five observational studies and three randomized control trials) were included in the review. Based on the findings of this systematic review, there is substantial evidence to endorse the efficacy of combination diuretic therapy of loop and thiazide diuretics in augmenting diuresis and enhancing outcomes for patients who exhibit insufficient responses to single-agent diuretics. Additionally, the review provides valuable insights about the timing and type of diuretics to use, helping clinicians make informed therapeutic decisions. However, to ensure patient safety and well-being, it is imperative to take into account the potential for electrolyte disturbances and impacts on renal function, necessitating diligent and vigilant monitoring as well as effective management strategies. In light of these findings, further research is warranted to optimize the dosing regimens and to delve deeper into the long-term safety and efficacy of combination therapy. Such research endeavors will undoubtedly contribute to refining treatment approaches and advancing patient care in the field of HF management.
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Affiliation(s)
- Amaresh Gogikar
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ankita Nanda
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | | | - Hembashima G Sambe
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Mohamed Yasir
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ruzhual K Man
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Lubna Mohammed
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Au HY, Chan KY, Yap DYH, Yip T, Wong CY. Letter to the Editor: Effects of Add-On Metolazone to High-Dose Oral Frusemide on Refractory Fluid Overload in Patients with End-Stage Kidney Disease Opting for Conservative Management. J Palliat Med 2023; 26:163-164. [PMID: 36724315 DOI: 10.1089/jpm.2022.0532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Affiliation(s)
- Ho Yan Au
- Palliative Medical Unit, Grantham Hospital, Hong Kong
| | | | - Desmond Y H Yap
- Division of Nephrology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong
| | - Terence Yip
- Department of Medicine, Renal Unit, Tung Wah Hospital, Hong Kong
| | - Chi Yan Wong
- Palliative Medical Unit, Grantham Hospital, Hong Kong
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Côté JM, Goulamhoussen N, McMahon BA, Murray PT. Diuretic combinations in critically ill patients with respiratory failure: A systematic review and meta-analysis. World J Crit Care Med 2022; 11:178-191. [PMID: 36331969 PMCID: PMC9136719 DOI: 10.5492/wjccm.v11.i3.178] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/11/2022] [Accepted: 04/24/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In patients with respiratory failure, loop diuretics remain the cornerstone of the treatment to maintain fluid balance, but resistance is common.
AIM To determine the efficacy and safety of common diuretic combinations in critically ill patients with respiratory failure.
METHODS We searched MEDLINE, Embase, Cochrane Library and PROSPERO for studies reporting the effects of a combination of a loop diuretic with another class of diuretic. A meta-analysis using mean differences (MD) with 95% confidence interval (CI) was performed for the 24-h fluid balance (primary outcome) and the 24-h urine output, while descriptive statistics were used for safety events.
RESULTS Nine studies totalling 440 patients from a total of 6510 citations were included. When compared to loop diuretics alone, the addition of a second diuretic is associated with an improved negative fluid balance at 24 h [MD: -1.06 L (95%CI: -1.46; -0.65)], driven by the combination of a thiazide plus furosemide [MD: -1.25 L (95%CI: -1.68; -0.82)], while no difference was observed with the combination of a loop-diuretic plus acetazolamide [MD: -0.40 L (95%CI: -0.96; 0.16)] or spironolactone [MD: -0.65 L (95%CI: -1.66; 0.36)]. Heterogeneity was high and the report of clinical and safety endpoints varied across studies.
CONCLUSION Based on limited evidence, the addition of a second diuretic to a loop diuretic may promote diuresis and negative fluid balance in patients with respiratory failure, but only when using a thiazide. Further larger trials to evaluate the safety and efficacy of such interventions in patients with respiratory failure are required.
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Affiliation(s)
- Jean Maxime Côté
- Division of Nephrology, Department of Medicine, Centre Hospitalier de l'Université de Montréal, Montréal H2X0C1, Québec, Canada
| | - Nadir Goulamhoussen
- Division of Nephrology, Department of Medicine, Centre Hospitalier de l'Université de Montréal, Montréal H2X0C1, Québec, Canada
| | - Blaithin A McMahon
- Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States
| | - Patrick T Murray
- Department of Medicine, School of Medicine, University College Dublin, Dublin D078NN, Ireland
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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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Hou Y, Yuan P, Fu Y, Zhang Q, Gao L, Wei Y, Zheng X, Feng W. Geniposide from Gardenia jasminoides var. radicans Makino Attenuates Myocardial Injury in Spontaneously Hypertensive Rats via Regulating Apoptotic and Energy Metabolism Signalling Pathway. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:949-962. [PMID: 33688169 PMCID: PMC7937395 DOI: 10.2147/dddt.s292107] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 02/10/2021] [Indexed: 12/15/2022]
Abstract
Introduction Hypertension is closely related to myocardial injury. Long-term hypertension can cause myocardial injury. Therefore, it is very important to find drugs to treat myocardial injury caused by hypertension. The aim of present study is to investigate the effects and mechanisms of geniposide on myocardial injuries in spontaneously hypertensive rats (SHR) and H9c2 cells induced by NaCl solution. Materials and Methods Male Wistar-Kyoto (WKY) and SHR rats were given different doses of geniposide (25 mg/kg/d or 50 mg/kg/d) or distilled water for three consecutive weeks. Meanwhile, an H9c2 cell line-injury model was established using a solution of 150 µmol/L NaCl for 8 h. The cardiac function and related indexes of rats were detected. Results The results showed that geniposide decreased the levels of COI and COIII, which promoted the phosphorylation of AMPK (p-AMPK) and enhanced the energy metabolism pathway. Geniposide improved myocardial apoptosis by regulating apoptotic proteins (p38, BAX and Bcl-2). Finally, heart function was regulated, and the markers of myocardial injury were decreased. Geniposide increased the viability of H9c2 cells treated with the NaCl solution and decreased the rate of apoptosis by regulating the levels of apoptotic proteins. Geniposide could activate energy metabolism signalling pathway (AMPK/SirT1/FOXO1) and reduce H9c2 cell apoptosis. Conclusion Our results showed that the mechanisms by which geniposide improves myocardial injury in SHR may be through regulating the energy metabolism signalling pathway (AMPK/SirT1/FOXO1) and improving myocardial apoptosis by regulating apoptotic proteins.
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Affiliation(s)
- Ying Hou
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China
| | - Peipei Yuan
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China
| | - Yang Fu
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China
| | - Qi Zhang
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China
| | - Liyuan Gao
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China
| | - Yaxin Wei
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China
| | - Xiaoke Zheng
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China.,Engineering and Technology Center for Chinese Medicine Development of Henan Province, Henan Science and Technology Department, Zhengzhou, 450046, People's Republic of China
| | - Weisheng Feng
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China.,Engineering and Technology Center for Chinese Medicine Development of Henan Province, Henan Science and Technology Department, Zhengzhou, 450046, People's Republic of China
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Hansrivijit P, Techorueangwiwat C, Khanal R, Dimech CT, Thongprayoon C, Cheungpasitporn W. Treatment outcomes of bumetanide continuous infusion: A systematic review and meta-analysis. Nephrology (Carlton) 2020; 25:744-748. [PMID: 32725702 DOI: 10.1111/nep.13739] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 04/20/2020] [Accepted: 06/01/2020] [Indexed: 12/01/2022]
Abstract
The clinical use of continuous bumetanide infusion for acute heart failure and volume overload is common. However, there is not enough supporting evidence for the use of continuous bumetanide infusion. Thus, we conducted this systematic review and meta-analysis aiming to describe the treatment outcomes of continuous bumetanide infusion. We searched Ovid MEDLINE, EMBASE and the Cochrane Library for eligible publications. Inclusion criteria were patients age ≥18 years with bumetanide infusion for heart failure, acute kidney injury (AKI) or volume overload. From 1564 citations, three studies (n = 94 patients) were included in the systematic review and meta-analysis. The mean dose of bumetanide was 1.08 ± 0.43 mg/hour with a mean treatment duration of 45.09 ± 10.12 hours. Mean urine output in response to continuous bumetanide infusion was 1.88 mL/kg/hour (95% confidence interval [CI], 1.72-2.05). The incidence of AKI with continuous bumetanide infusion was 24.7% (95% CI, 8.2-54.6). By using Pearson's correlation coefficient, increasing doses of bumetanide were correlated with increased urine output (P = .026) and increased incidence of AKI (P < .01). There was no correlation between increasing urine output and the incidence of AKI (P = .739). In conclusion, with available evidence, continuous bumetanide infusion may be used in the treatment of acute heart failure or volume overload with close monitoring for new-onset or worsening AKI.
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Affiliation(s)
- Panupong Hansrivijit
- Department of Internal Medicine, University of Pittsburgh Medical Center Pinnacle, Harrisburg, Pennsylvania, USA
| | - Chol Techorueangwiwat
- Department of Internal Medicine, University of Hawaii Internal Medicine Residency Program, Honolulu, Hawaii, USA
| | - Resha Khanal
- Department of Internal Medicine, University of Pittsburgh Medical Center Pinnacle, Harrisburg, Pennsylvania, USA
| | - Christina T Dimech
- Department of Internal Medicine, University of Pittsburgh Medical Center Pinnacle, Harrisburg, Pennsylvania, USA
| | - Charat Thongprayoon
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA
| | - Wisit Cheungpasitporn
- Division of Nephrology, University of Mississippi Medical Center, Jackson, Mississippi, USA
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Congestion in heart failure: a contemporary look at physiology, diagnosis and treatment. Nat Rev Cardiol 2020; 17:641-655. [DOI: 10.1038/s41569-020-0379-7] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/02/2020] [Indexed: 12/14/2022]
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Brisco-Bacik MA, Ter Maaten JM, Houser SR, Vedage NA, Rao V, Ahmad T, Wilson FP, Testani JM. Outcomes Associated With a Strategy of Adjuvant Metolazone or High-Dose Loop Diuretics in Acute Decompensated Heart Failure: A Propensity Analysis. J Am Heart Assoc 2019; 7:e009149. [PMID: 30371181 PMCID: PMC6222930 DOI: 10.1161/jaha.118.009149] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Background In acute decompensated heart failure, guidelines recommend increasing loop diuretic dose or adding a thiazide diuretic when diuresis is inadequate. We set out to determine the adverse events associated with a diuretic strategy relying on metolazone or high‐dose loop diuretics. Methods and Results Patients admitted to 3 hospitals using a common electronic medical record with a heart failure discharge diagnosis who received intravenous loop diuretics were studied in a propensity‐adjusted analysis of all‐cause mortality. Secondary outcomes included hyponatremia (sodium <135 mEq/L), hypokalemia (potassium <3.5 mEq/L) and worsening renal function (a ≥20% decrease in estimated glomerular filtration rate). Of 13 898 admissions, 1048 (7.5%) used adjuvant metolazone. Metolazone was strongly associated with hyponatremia, hypokalemia, and worsening renal function (P<0.0001 for all) with minimal effect attenuation following covariate and propensity adjustment. Metolazone remained associated with increased mortality after multivariate and propensity adjustment (hazard ratio=1.20, 95% confidence interval 1.04–1.39, P=0.01). High‐dose loop diuretics were associated with hypokalemia and hyponatremia (P<0.002) but only worsening renal function retained significance (P<0.001) after propensity adjustment. High‐dose loop diuretics were not associated with reduced survival after multivariate and propensity adjustment (hazard ratio=0.97 per 100 mg of IV furosemide, 95% confidence interval 0.90–1.06, P=0.52). Conclusions During acute decompensated heart failure, metolazone was independently associated with hypokalemia, hyponatremia, worsening renal function and increased mortality after controlling for the propensity to receive metolazone and baseline characteristics. However, under the same experimental conditions, high‐dose loop diuretics were not associated with hypokalemia, hyponatremia, or reduced survival. The current findings suggest that until randomized control trial data prove otherwise, uptitration of loop diuretics may be a preferred strategy over routine early addition of thiazide type diuretics when diuresis is inadequate.
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Affiliation(s)
- Meredith A Brisco-Bacik
- 1 Divisions of Cardiology and Cardiovascular Research Lewis Katz School of Medicine at Temple University Philadelphia PA
| | - Jozine M Ter Maaten
- 2 Department of Cardiology University Medical Center Groningen Groningen The Netherlands
| | - Steven R Houser
- 1 Divisions of Cardiology and Cardiovascular Research Lewis Katz School of Medicine at Temple University Philadelphia PA
| | - Natasha A Vedage
- 1 Divisions of Cardiology and Cardiovascular Research Lewis Katz School of Medicine at Temple University Philadelphia PA
| | - Veena Rao
- 3 Department of Internal Medicine Yale University School of Medicine New Haven CT
| | - Tariq Ahmad
- 4 Section of Cardiovascular Medicine Yale University School of Medicine New Haven CT
| | - F Perry Wilson
- 3 Department of Internal Medicine Yale University School of Medicine New Haven CT.,5 Clinical Epidemiology Research Center Veterans Affairs Medical Center New Haven CT
| | - Jeffrey M Testani
- 4 Section of Cardiovascular Medicine Yale University School of Medicine New Haven CT
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Hasan O, Fisher M. Metolazone. PRACTICAL DIABETES 2019. [DOI: 10.1002/pdi.2242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Omar Hasan
- Locum Consultant Cardiologist, Inverclyde Royal Hospital Greenock UK
| | - Miles Fisher
- Consultant Physician, Glasgow Royal Infirmary Glasgow UK
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Frea S, Pidello S, Volpe A, Canavosio FG, Galluzzo A, Bovolo V, Camarda A, Golzio PG, D'Ascenzo F, Bergerone S, Rinaldi M, Gaita F. Diuretic treatment in high-risk acute decompensation of advanced chronic heart failure-bolus intermittent vs. continuous infusion of furosemide: a randomized controlled trial. Clin Res Cardiol 2019; 109:417-425. [PMID: 31256261 DOI: 10.1007/s00392-019-01521-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 06/26/2019] [Indexed: 12/29/2022]
Abstract
BACKGROUND Diuretic resistance is a common issue in patients with acute decompensation of advanced chronic heart failure (ACHF). The aim of this trial was to compare boluses and continuous infusion of furosemide in a selected population of patients with ACHF and high risk for diuretic resistance. METHODS In this single-centre, double-blind, double-dummy, randomized trial, we enrolled 80 patients admitted for acute decompensation of ACHF (NYHA IV, EF ≤ 30%) with criteria of high risk for diuretic resistance (SBP ≤ 110 mmHg, wet score ≥ 12/18, and sodium ≤ 135 mMol/L). Patients were assigned in a 1:1 ratio to receive furosemide by bolus every 12 h or by continuous infusion. Diuretic treatment and dummy treatment were prepared by a nurse unassigned to patients' care. The study treatment was continued for up to 72 h. Coprimary endpoints were total urinary output and freedom from congestion at 72 h. RESULTS 80 patients were enrolled with 40 patients in each treatment arm. Mean daily furosemide was 216 mg in continuous-infusion arm and 195 mg in the bolus intermittent arm. Freedom from congestion (defined as jugular venous pressure of < 8 cm, with no orthopnea and with trace peripheral edema or no edema) occurred more in the continuous infusion than in the bolus arm (48% vs. 25%, p = 0.04), while total urinary output after 72 h was 8612 ± 2984 ml in the bolus arm and 10,020 ± 3032 ml in the continuous arm (p = 0.04). Treatment failure occurred less in the continuous-infusion group (15% vs. 38%, p = 0.02), while there was no significant difference between groups in the incidence of worsening of renal function. CONCLUSION Among patients with acute decompensation of ACHF and high risk of diuretic resistance, continuous infusion of intravenous furosemide was associated with better decongestion. DRAIN TRIAL ClinicalTrials.gov number NCT03592836.
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Affiliation(s)
- Simone Frea
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza University Hospital of Turin, Corso Bramante 88, 10126, Turin, Italy.
| | - Stefano Pidello
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza University Hospital of Turin, Corso Bramante 88, 10126, Turin, Italy
| | - Alessandra Volpe
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza University Hospital of Turin, Corso Bramante 88, 10126, Turin, Italy
| | - Federico Giovanni Canavosio
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza University Hospital of Turin, Corso Bramante 88, 10126, Turin, Italy
| | - Alessandro Galluzzo
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza University Hospital of Turin, Corso Bramante 88, 10126, Turin, Italy
| | - Virginia Bovolo
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza University Hospital of Turin, Corso Bramante 88, 10126, Turin, Italy
| | - Antonio Camarda
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza University Hospital of Turin, Corso Bramante 88, 10126, Turin, Italy
| | - Pier Giorgio Golzio
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza University Hospital of Turin, Corso Bramante 88, 10126, Turin, Italy
| | - Fabrizio D'Ascenzo
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza University Hospital of Turin, Corso Bramante 88, 10126, Turin, Italy
| | - Serena Bergerone
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza University Hospital of Turin, Corso Bramante 88, 10126, Turin, Italy
| | - Mauro Rinaldi
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza University Hospital of Turin, Corso Bramante 88, 10126, Turin, Italy
| | - Fiorenzo Gaita
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza University Hospital of Turin, Corso Bramante 88, 10126, Turin, Italy
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Dos Reis D, Fraticelli L, Bassand A, Manzo-Silberman S, Peschanski N, Charpentier S, Elbaz M, Savary D, Bonnefoy-Cudraz E, Laribi S, Henry P, Guerraoui A, Tazarourte K, Chouihed T, El Khoury C. Impact of renal dysfunction on the management and outcome of acute heart failure: results from the French prospective, multicentre, DeFSSICA survey. BMJ Open 2019; 9:e022776. [PMID: 30782685 PMCID: PMC6340446 DOI: 10.1136/bmjopen-2018-022776] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVES Cardiorenal syndrome (CRS) is the combination of acute heart failure syndrome (AHF) and renal dysfunction (creatinine clearance (CrCl) ≤60 mL/min). Real-life data were used to compare the management and outcome of AHF with and without renal dysfunction. DESIGN Prospective, multicentre. SETTING Twenty-six academic, community and regional hospitals in France. PARTICIPANTS 507 patients with AHF were assessed in two groups according to renal function: group 1 (patients with CRS (CrCl ≤60 mL/min): n=335) and group 2 (patients with AHF with normal renal function (CrCl >60 mL/min): n=172). RESULTS Differences were observed (group 1 vs group 2) at admission for the incidence of chronic heart failure (56.42% vs 47.67%), use of furosemide (60.9% vs 52.91%), insulin (15.52% vs 9.3%) and amiodarone (14.33% vs 4.65%); additionally, more patients in group 1 carried a defibrillator (4.78% vs 0%), had ≥2 hospitalisations in the last year (15.52% vs 5.81%) and were under the care of a cardiologist (72.24% vs 61.63%). Clinical signs were broadly similar in each group. Brain-type natriuretic peptide (BNP) and BNP prohormone were higher in group 1 than group 2 (1157.5 vs 534 ng/L and 5120 vs 2513 ng/mL), and more patients in group 1 were positive for troponin (58.2% vs 44.19%), had cardiomegaly (51.04% vs 37.21%) and interstitial opacities (60.3% vs 47.67%). The only difference in emergency treatment was the use of nitrates, (higher in group 1 (21.9% vs 12.21%)). In-hospital mortality and the percentage of patients still hospitalised after 30 days were similar between groups, but the median stay was longer in group 1 (8 days vs 6 days). CONCLUSIONS Renal impairment in AHF should not limit the use of loop diuretics and/or vasodilators, but early assessment of pulmonary congestion and close monitoring of the efficacy of conventional therapies is encouraged to allow rapid and appropriate implementation of alternative therapies if necessary.
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Affiliation(s)
| | | | - Adrien Bassand
- SAMU-SMUR-SAU Nancy, Hôpital Central, Nancy, Lorraine, France
| | | | | | - Sandrine Charpentier
- Emergency Department, Rangueil University Hospital, Toulouse, France
- INSERM, U1027, Toulouse, France
- Medical Department, Université Toulouse III – Paul Sabatier, Toulouse, France
| | - Meyer Elbaz
- Department of Cardiology, Rangueil Hospital, Toulouse, France
| | - Dominique Savary
- Emergency Department and Intensive Care Unit, Metz-Tessy, France
| | | | - Said Laribi
- Emergency Medicine Department, University Hospital of Tours, Tours, France
- INSERM UMR-S 942, Université Paris-Diderot, Paris, France
| | - Patrick Henry
- Lariboisière Hospital, Department of Cardiology, Université Paris-Diderot, Paris, France
| | | | - Karim Tazarourte
- Emergency Department, Edouard Herriot Hospital, Rhône-Alpes, France
| | - Tahar Chouihed
- SAMU-SMUR-SAU Nancy, Hôpital Central, Nancy, Lorraine, France
- Centre d’Investigation Clinique Plurithématique 1433, Institut Lorrain du Cœur et des Vaisseaux, Vandoeuvre-lès-Nancy, France
- INSERM U1116, Université de Lorraine, Nancy, France
| | - Carlos El Khoury
- Emergency Department and RESCUe Network, Lucien Hussel Hospital, Vienne, France
- University Lyon, Claude Bernard Lyon 1 University, HESPER EA, Lyon, France
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13
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Harjola VP, Mullens W, Banaszewski M, Bauersachs J, Brunner-La Rocca HP, Chioncel O, Collins SP, Doehner W, Filippatos GS, Flammer AJ, Fuhrmann V, Lainscak M, Lassus J, Legrand M, Masip J, Mueller C, Papp Z, Parissis J, Platz E, Rudiger A, Ruschitzka F, Schäfer A, Seferovic PM, Skouri H, Yilmaz MB, Mebazaa A. Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur J Heart Fail 2017; 19:821-836. [PMID: 28560717 DOI: 10.1002/ejhf.872] [Citation(s) in RCA: 260] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 03/20/2017] [Accepted: 04/04/2017] [Indexed: 12/18/2022] Open
Abstract
Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field.
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Affiliation(s)
- Veli-Pekka Harjola
- Emergency Medicine, University of Helsinki, Helsinki University Hospital, Helsinki, Finland
| | - Wilfried Mullens
- Department of Cardiology, Ziekenhuis Oost Limburg, Genk, Belgium.,Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium
| | - Marek Banaszewski
- Intensive Cardiac Therapy Clinic, Institute of Cardiology, Warsaw, Poland
| | - Johann Bauersachs
- Department of Cardiology and Angiology, Medical School Hannover, Hannover, Germany
| | | | - Ovidiu Chioncel
- Institute of Emergency in Cardiovascular Disease, University of Medicine Carol Davila, Bucharest, Romania
| | - Sean P Collins
- Department of Emergency Medicine, Vanderbilt University Medical Centre, Nashville, TN, USA
| | - Wolfram Doehner
- Centre for Stroke Research, Berlin, Germany.,Department of Cardiology, Charité Medical University, Berlin, Germany
| | - Gerasimos S Filippatos
- National and Kapodistrian University of Athens, School of Medicine, Athens University Hospital Attikon, Athens, Greece
| | - Andreas J Flammer
- University Heart Centre, University Hospital Zurich, Zurich, Switzerland
| | - Valentin Fuhrmann
- Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.,Department of Intensive Care Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Mitja Lainscak
- Department of Internal Medicine, General Hospital Murska Sobota, Murska Sobota, Slovenia.,Department of Research and Education, General Hospital Murska Sobota, Murska Sobota, Slovenia.,Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Johan Lassus
- Cardiology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland
| | - Matthieu Legrand
- U942 Inserm, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.,Investigation Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT), Nancy, France.,Department of Anaesthesiology, Critical Care and Burn Unit, St Louis Hospital, University Paris Denis Diderot, Paris, France
| | - Josep Masip
- Consorci Sanitari Integral (Public Health Consortium), University of Barcelona, Barcelona, Spain.,Department of Cardiology, Hospital Sanitas CIMA, Barcelona, Spain
| | - Christian Mueller
- Department of Cardiology, University Hospital Basel, Basel, Switzerland.,Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland
| | - Zoltán Papp
- Division of Clinical Physiology, Department of Cardiology, Research Centre for Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - John Parissis
- National and Kapodistrian University of Athens, School of Medicine, Athens University Hospital Attikon, Athens, Greece
| | - Elke Platz
- Department of Emergency Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Alain Rudiger
- Cardio-Surgical Intensive Care Unit, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Frank Ruschitzka
- University Heart Centre, University Hospital Zurich, Zurich, Switzerland
| | - Andreas Schäfer
- Department of Cardiology and Angiology, Medical School Hannover, Hannover, Germany
| | - Petar M Seferovic
- Department of Internal Medicine, Belgrade University School of Medicine, Belgrade, Serbia.,Heart Failure Centre, Belgrade University Medical Centre, Belgrade, Serbia
| | - Hadi Skouri
- Division of Cardiology, Department of Internal Medicine, American University of Beirut Medical Centre, Beirut, Lebanon
| | - Mehmet Birhan Yilmaz
- Department of Cardiology, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey
| | - Alexandre Mebazaa
- U942 Inserm, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.,Investigation Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT), Nancy, France.,University Paris Diderot, Paris, France.,Department of Anaesthesia and Critical Care, University Hospitals Saint Louis-Lariboisière, Paris, France
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14
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Shulenberger CE, Jiang A, Devabhakthuni S, Ivaturi V, Liu T, Reed BN. Efficacy and Safety of Intravenous Chlorothiazide versus Oral Metolazone in Patients with Acute Decompensated Heart Failure and Loop Diuretic Resistance. Pharmacotherapy 2016; 36:852-60. [PMID: 27393709 DOI: 10.1002/phar.1798] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
STUDY OBJECTIVE To assess the efficacy and safety of intravenous (IV) chlorothiazide versus oral metolazone when added to loop diuretics in patients with acute decompensated heart failure (ADHF) and loop diuretic resistance. DESIGN Retrospective cohort study. SETTING Large urban academic medical center. PATIENTS Adults admitted with ADHF between 2005 and 2015 who had loop diuretic resistance, defined as administration of IV furosemide at a dose of 160 mg/day or higher (or an equivalent dose of IV bumetanide), during hospitalization, and who then received at least one dose of IV chlorothiazide (88 patients) or oral metolazone (89 patients) to augment diuresis. MEASUREMENTS AND MAIN RESULTS The primary efficacy end point was a change in 24-hour net urine output (UOP) from before to after thiazide-type diuretic administration, and the study was designed to test for the noninferiority of metolazone. Safety end points included changes in renal function and electrolyte concentrations. The mean dose of IV loop diuretic therapy (in IV furosemide equivalents) at baseline (before thiazide-type diuretic administration) was higher in the chlorothiazide group (mean ± SD 318.9 ± 127.7 vs 268.4 ± 97.6 mg/day in the metolazone group, p=0.004), but net UOP was similar (mean ± SD 877.0 ± 1189.0 ml in the chlorothiazide group vs 710.6 ± 1145.9 ml in the metolazone group, p=0.344). Mean doses of chlorothiazide and metolazone were 491 ± 282 mg and 5.8 ± 3.5 mg, respectively. Following thiazide-type diuretic administration, net UOP improved to a similar degree (2274.6 ± 1443.0 ml vs 2030.2 ± 1725.0 ml in the chlorothiazide and metolazone groups, respectively, p=0.308). For the primary efficacy end point, metolazone met the threshold for noninferiority by producing a net UOP of 1319.6 ± 1517.4 ml versus 1397.6 ± 1370.7 ml for chlorothiazide (p=0.026 for noninferiority). No significant differences in renal function were observed between the groups. Although hypokalemia was more frequent in the chlorothiazide group (75% with chlorothiazide vs 60.7% with metolazone, p=0.045), no significant differences in the rates of severe hypokalemia or other electrolyte abnormalities were observed between the groups. CONCLUSION Oral metolazone was noninferior to IV chlorothiazide for enhancing net UOP in patients with ADHF and loop diuretic resistance and was similarly safe with regard to renal function and electrolyte abnormalities. Given the significant cost disparity between the two agents, these findings suggest that oral metolazone may be considered a first-line option in this patient population.
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Affiliation(s)
| | - Anthony Jiang
- University of California Davis Medical Center, Sacramento, CA
| | - Sandeep Devabhakthuni
- University of Maryland School of Pharmacy, Baltimore, MD.,Applied Therapeutics, Research, and Instruction at the University of Maryland (ATRIUM) Cardiology Collaborative, Baltimore, MD
| | - Vijay Ivaturi
- University of Maryland School of Pharmacy, Baltimore, MD
| | - Tao Liu
- University of Maryland School of Pharmacy, Baltimore, MD
| | - Brent N Reed
- University of Maryland School of Pharmacy, Baltimore, MD.,Applied Therapeutics, Research, and Instruction at the University of Maryland (ATRIUM) Cardiology Collaborative, Baltimore, MD
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15
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Abstract
Acute kidney injury is a frequent complication of acute heart failure syndromes, portending an adverse prognosis. Acute cardiorenal syndrome represents a unique form of acute kidney injury specific to acute heart failure syndromes. The pathophysiology of acute cardiorenal syndrome involves renal venous congestion, ineffective forward flow, and impaired renal autoregulation caused by neurohormonal activation. Biomarkers reflecting different aspects of acute cardiorenal syndrome pathophysiology may allow patient phenotyping to inform prognosis and treatment. Adjunctive vasoactive, neurohormonal, and diuretic therapies may relieve congestive symptoms and/or improve renal function, but no single therapy has been proved to reduce mortality in acute cardiorenal syndrome.
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Affiliation(s)
- Jacob C Jentzer
- Department of Critical Care Medicine, UPMC Presbyterian Hospital, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213, USA
| | - Lakhmir S Chawla
- Division of Intensive Care Medicine, Department of Medicine, Washington DC Veterans Affairs Medical Center, 50 Irving Street, Washington, DC 20422, USA; Division of Nephrology, Department of Medicine, Washington DC Veterans Affairs Medical Center, 50 Irving Street, Washington, DC 20422, USA.
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16
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Thomas CA, Morris JL, Sinclair EA, Speicher RH, Ahmed SS, Rotta AT. Implementation of a diuretic stewardship program in a pediatric cardiovascular intensive care unit to reduce medication expenditures. Am J Health Syst Pharm 2016; 72:1047-51. [PMID: 26025996 DOI: 10.2146/ajhp140532] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
PURPOSE The implementation of a diuretic stewardship program in a pediatric cardiovascular intensive care unit (ICU) is described. METHODS This retrospective study compared the use of i.v. chlorothiazide and i.v. ethacrynic acid in pediatric cardiovascular surgery patients before and after implementation of a diuretic stewardship program. All pediatric patients admitted to the pediatric cardiovascular service were included. The cardiovascular surgery service was educated on formal indications for specific diuretic agents, and the diuretic stewardship program was implemented on January 1, 2013. Under the stewardship program, i.v. ethacrynic acid was indicated in patients with a sulfonamide allergy, and i.v. chlorothiazide was considered appropriate in patients receiving maximized i.v. loop diuretic doses. A detailed review of the pharmacy database and medical records was performed for each patient to determine i.v. chlorothiazide and i.v. ethacrynic acid use and expenditures, appropriateness of use, days using a ventilator, and cardiovascular ICU length of stay. RESULTS After implementation of diuretic stewardship, the use of i.v. chlorothiazide decreased by 74% (531 fewer doses) while i.v. ethacrynic acid use decreased by 92% (47 fewer doses), resulting in a total reduction of $91,398 in expenditures on these diuretics over the six-month study period and an estimated annual saving of over $182,000. The median number of days using a ventilator and the length of ICU stay did not differ significantly during the study period. CONCLUSION Implementation of a diuretic stewardship program reduced the use of i.v. chlorothiazide and i.v. ethacrynic acid without adversely affecting clinical outcomes such as ventilator days and length of stay in a pediatric cardiovascular ICU.
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Affiliation(s)
- Christopher A Thomas
- Christopher A. Thomas, Pharm.D., is Clinical Pharmacy Specialist-Pediatric Cardiovascular Intensive Care Unit (ICU), Department of Pharmacy, Riley Hospital for Children at Indiana University Health (IUH), Indianapolis; at the time of writing he was Clinical Pharmacy Specialist-Pediatric Cardiovascular ICU, Department of Pharmacy Services, Phoenix Children's Hospital, Phoenix, AZ. Jennifer L. Morris, Pharm.D., is Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Texas Children's Hospital, Houston; at the time of writing she was Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Riley Hospital for Children at IUH. Elizabeth A. Sinclair, Pharm.D., is Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Texas Children's Hospital, Houston. Richard H. Speicher, M.D., is Medical Director, Pediatric ICU, Division of Pediatric Critical Care, Rainbow Babies and Children's Hospital, Cleveland, OH, and Assistant Professor, Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland. Sheikh S. Ahmed, M.D., is Assistant Professor of Clinical Pediatrics, Section of Pediatric Pulmonology, Critical Care and Allergy, Riley Hospital for Children at IUH. Alexandre T. Rotta, M.D., is Chief, Division of Pediatric Critical Care, Rainbow Babies and Children's Hospital, and Professor, Department of Pediatrics, School of Medicine, Case Western Reserve University.
| | - Jennifer L Morris
- Christopher A. Thomas, Pharm.D., is Clinical Pharmacy Specialist-Pediatric Cardiovascular Intensive Care Unit (ICU), Department of Pharmacy, Riley Hospital for Children at Indiana University Health (IUH), Indianapolis; at the time of writing he was Clinical Pharmacy Specialist-Pediatric Cardiovascular ICU, Department of Pharmacy Services, Phoenix Children's Hospital, Phoenix, AZ. Jennifer L. Morris, Pharm.D., is Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Texas Children's Hospital, Houston; at the time of writing she was Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Riley Hospital for Children at IUH. Elizabeth A. Sinclair, Pharm.D., is Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Texas Children's Hospital, Houston. Richard H. Speicher, M.D., is Medical Director, Pediatric ICU, Division of Pediatric Critical Care, Rainbow Babies and Children's Hospital, Cleveland, OH, and Assistant Professor, Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland. Sheikh S. Ahmed, M.D., is Assistant Professor of Clinical Pediatrics, Section of Pediatric Pulmonology, Critical Care and Allergy, Riley Hospital for Children at IUH. Alexandre T. Rotta, M.D., is Chief, Division of Pediatric Critical Care, Rainbow Babies and Children's Hospital, and Professor, Department of Pediatrics, School of Medicine, Case Western Reserve University
| | - Elizabeth A Sinclair
- Christopher A. Thomas, Pharm.D., is Clinical Pharmacy Specialist-Pediatric Cardiovascular Intensive Care Unit (ICU), Department of Pharmacy, Riley Hospital for Children at Indiana University Health (IUH), Indianapolis; at the time of writing he was Clinical Pharmacy Specialist-Pediatric Cardiovascular ICU, Department of Pharmacy Services, Phoenix Children's Hospital, Phoenix, AZ. Jennifer L. Morris, Pharm.D., is Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Texas Children's Hospital, Houston; at the time of writing she was Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Riley Hospital for Children at IUH. Elizabeth A. Sinclair, Pharm.D., is Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Texas Children's Hospital, Houston. Richard H. Speicher, M.D., is Medical Director, Pediatric ICU, Division of Pediatric Critical Care, Rainbow Babies and Children's Hospital, Cleveland, OH, and Assistant Professor, Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland. Sheikh S. Ahmed, M.D., is Assistant Professor of Clinical Pediatrics, Section of Pediatric Pulmonology, Critical Care and Allergy, Riley Hospital for Children at IUH. Alexandre T. Rotta, M.D., is Chief, Division of Pediatric Critical Care, Rainbow Babies and Children's Hospital, and Professor, Department of Pediatrics, School of Medicine, Case Western Reserve University
| | - Richard H Speicher
- Christopher A. Thomas, Pharm.D., is Clinical Pharmacy Specialist-Pediatric Cardiovascular Intensive Care Unit (ICU), Department of Pharmacy, Riley Hospital for Children at Indiana University Health (IUH), Indianapolis; at the time of writing he was Clinical Pharmacy Specialist-Pediatric Cardiovascular ICU, Department of Pharmacy Services, Phoenix Children's Hospital, Phoenix, AZ. Jennifer L. Morris, Pharm.D., is Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Texas Children's Hospital, Houston; at the time of writing she was Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Riley Hospital for Children at IUH. Elizabeth A. Sinclair, Pharm.D., is Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Texas Children's Hospital, Houston. Richard H. Speicher, M.D., is Medical Director, Pediatric ICU, Division of Pediatric Critical Care, Rainbow Babies and Children's Hospital, Cleveland, OH, and Assistant Professor, Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland. Sheikh S. Ahmed, M.D., is Assistant Professor of Clinical Pediatrics, Section of Pediatric Pulmonology, Critical Care and Allergy, Riley Hospital for Children at IUH. Alexandre T. Rotta, M.D., is Chief, Division of Pediatric Critical Care, Rainbow Babies and Children's Hospital, and Professor, Department of Pediatrics, School of Medicine, Case Western Reserve University
| | - Sheikh S Ahmed
- Christopher A. Thomas, Pharm.D., is Clinical Pharmacy Specialist-Pediatric Cardiovascular Intensive Care Unit (ICU), Department of Pharmacy, Riley Hospital for Children at Indiana University Health (IUH), Indianapolis; at the time of writing he was Clinical Pharmacy Specialist-Pediatric Cardiovascular ICU, Department of Pharmacy Services, Phoenix Children's Hospital, Phoenix, AZ. Jennifer L. Morris, Pharm.D., is Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Texas Children's Hospital, Houston; at the time of writing she was Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Riley Hospital for Children at IUH. Elizabeth A. Sinclair, Pharm.D., is Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Texas Children's Hospital, Houston. Richard H. Speicher, M.D., is Medical Director, Pediatric ICU, Division of Pediatric Critical Care, Rainbow Babies and Children's Hospital, Cleveland, OH, and Assistant Professor, Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland. Sheikh S. Ahmed, M.D., is Assistant Professor of Clinical Pediatrics, Section of Pediatric Pulmonology, Critical Care and Allergy, Riley Hospital for Children at IUH. Alexandre T. Rotta, M.D., is Chief, Division of Pediatric Critical Care, Rainbow Babies and Children's Hospital, and Professor, Department of Pediatrics, School of Medicine, Case Western Reserve University
| | - Alexandre T Rotta
- Christopher A. Thomas, Pharm.D., is Clinical Pharmacy Specialist-Pediatric Cardiovascular Intensive Care Unit (ICU), Department of Pharmacy, Riley Hospital for Children at Indiana University Health (IUH), Indianapolis; at the time of writing he was Clinical Pharmacy Specialist-Pediatric Cardiovascular ICU, Department of Pharmacy Services, Phoenix Children's Hospital, Phoenix, AZ. Jennifer L. Morris, Pharm.D., is Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Texas Children's Hospital, Houston; at the time of writing she was Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Riley Hospital for Children at IUH. Elizabeth A. Sinclair, Pharm.D., is Clinical Pharmacy Specialist-Pediatric ICU, Department of Pharmacy Services, Texas Children's Hospital, Houston. Richard H. Speicher, M.D., is Medical Director, Pediatric ICU, Division of Pediatric Critical Care, Rainbow Babies and Children's Hospital, Cleveland, OH, and Assistant Professor, Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland. Sheikh S. Ahmed, M.D., is Assistant Professor of Clinical Pediatrics, Section of Pediatric Pulmonology, Critical Care and Allergy, Riley Hospital for Children at IUH. Alexandre T. Rotta, M.D., is Chief, Division of Pediatric Critical Care, Rainbow Babies and Children's Hospital, and Professor, Department of Pediatrics, School of Medicine, Case Western Reserve University
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17
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Abstract
The administration of loop diuretics to achieve decongestion is the cornerstone of therapy for acute heart failure. Unfortunately, impaired response to diuretics is common in these patients and associated with adverse outcomes. Diuretic resistance is thought to result from a complex interplay between cardiac and renal dysfunction, and specific renal adaptation and escape mechanisms, such as neurohormonal activation and the braking phenomenon. However, our understanding of diuretic response in patients with acute heart failure is still limited and a uniform definition is lacking. Three objective methods to evaluate diuretic response have been introduced, which all suggest that diuretic response should be determined based on the effect of diuretic dose administered. Several strategies have been proposed to overcome diuretic resistance, including combination therapy and ultrafiltration, but prospective studies in patients who are truly unresponsive to diuretics are lacking. An enhanced understanding of diuretic response should ultimately lead to an improved, individualized approach to treating patients with acute heart failure.
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18
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Goldstein S, Bagshaw S, Cecconi M, Okusa M, Wang H, Kellum J, Mythen M, Shaw A. Pharmacological management of fluid overload. Br J Anaesth 2014; 113:756-63. [DOI: 10.1093/bja/aeu299] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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19
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20
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Cheng HWB, Sham MK, Chan KY, Li CW, Au HY, Yip T. Combination therapy with low-dose metolazone and furosemide: a “needleless” approach in managing refractory fluid overload in elderly renal failure patients under palliative care. Int Urol Nephrol 2014; 46:1809-13. [PMID: 24824145 DOI: 10.1007/s11255-014-0724-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Accepted: 04/21/2014] [Indexed: 11/25/2022]
Affiliation(s)
- Hon Wai Benjamin Cheng
- Palliative Medical Unit, Grantham Hospital, 125 Wong Chuk Hang Road, Aberdeen, Hong Kong, China,
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21
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Wittkowski KM, Sonakya V, Bigio B, Tonn MK, Shic F, Ascano M, Nasca C, Gold-Von Simson G. A novel computational biostatistics approach implies impaired dephosphorylation of growth factor receptors as associated with severity of autism. Transl Psychiatry 2014; 4:e354. [PMID: 24473445 PMCID: PMC3905234 DOI: 10.1038/tp.2013.124] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2013] [Revised: 11/16/2013] [Accepted: 11/25/2013] [Indexed: 01/05/2023] Open
Abstract
The prevalence of autism spectrum disorders (ASDs) has increased 20-fold over the past 50 years to >1% of US children. Although twin studies attest to a high degree of heritability, the genetic risk factors are still poorly understood. We analyzed data from two independent populations using u-statistics for genetically structured wide-locus data and added data from unrelated controls to explore epistasis. To account for systematic, but disease-unrelated differences in (non-randomized) genome-wide association studies (GWAS), a correlation between P-values and minor allele frequency with low granularity data and for conducting multiple tests in overlapping genetic regions, we present a novel study-specific criterion for 'genome-wide significance'. From recent results in a comorbid disease, childhood absence epilepsy, we had hypothesized that axonal guidance and calcium signaling are involved in autism as well. Enrichment of the results in both studies with related genes confirms this hypothesis. Additional ASD-specific variations identified in this study suggest protracted growth factor signaling as causing more severe forms of ASD. Another cluster of related genes suggests chloride and potassium ion channels as additional ASD-specific drug targets. The involvement of growth factors suggests the time of accelerated neuronal growth and pruning at 9-24 months of age as the period during which treatment with ion channel modulators would be most effective in preventing progression to more severe forms of autism. By extension, the same computational biostatistics approach could yield profound insights into the etiology of many common diseases from the genetic data collected over the last decade.
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Affiliation(s)
- K M Wittkowski
- The Rockefeller University, Center for Clinical and Translational Science, New York, NY, USA
| | - V Sonakya
- The Rockefeller University, Center for Clinical and Translational Science, New York, NY, USA
| | - B Bigio
- The Rockefeller University, Center for Clinical and Translational Science, New York, NY, USA
| | - M K Tonn
- Hochschule Koblenz, RheinAhrCampus, Joseph-Rovan-Allee 2, Remagen, Germany
| | - F Shic
- Yale School of Medicine, Yale Autism Program, New Haven, CT, USA
| | - M Ascano
- Tuschl Laboratory of RNA Molecular Biology, The Rockefeller University, New York, NY, USA
| | - C Nasca
- McEwen Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA
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