Diuretic Resistance in Heart Failure[利尿性心力衰竭](54)课件.ppt
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- 利尿性心力衰竭 Diuretic Resistance in Heart Failure利尿性心力衰竭54课件 Failure 利尿 心力衰竭 54 课件
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1、Diuretic Resistance in Heart FailureRobert J.DiDomenico,PharmDClinical Associate ProfessorAffiliate Faculty,Center for Phamacoeconomic ResearchUniversity of Illinois at ChicagoColleges of Pharmacy&MedicineCardiovascular Clinical PharmacistUniversity of Illinois Medical Center at ChicagoTo Pee or Not
2、 to PeeDisclosures Scios,Inc.Honoraria,consulting,research support Sanofi-Aventis/Bristol Myers Squibb Honoraria(c/o STRIVE network)The Medicines Company Honoraria(c/o University Pharmacotherapy Associates)Case54yo MPMH:CHF HTN CAD s/p CABG DL DM OSA(morbid obesity)Meds Furosemide 160mg bid Spironol
3、actone 25mg bid Enalapril 20mg bid Valsartan 80mg bid Digoxin 0.25mg daily ECASA 325mg daily Lovastatin 80mg qhs Insulin Advair TheoplyllineBP 113/73,HR 118,RR 4095%on 2L O2Phys exam Wt 117kg JVD 10cm B crackles at bases w/wheezing 2+LEE to kneesLabs 138 101 41(baseline 20)4.1 19 1.7(baseline 1.2)BN
4、P 414Initial Treatment(Med C)80mg IV furosemide in ED,then 80mg IV q12hResponse Urine output(18 hours)=980ml Increasing dyspneaTypical ADHF Treatment CourseADHERE Q1 2006 Final Cumulative Benchmark Report.Scios,Inc.:Sunnyvale,2006.Hauptman PJ,et al.JAMA 2006;296:1877-84.DiDomenico RJ,et al.April,200
5、7.Typical ADHF Treatment CourseADHERE Q1 2006 Final Cumulative Benchmark Report.Scios,Inc.:Sunnyvale,2006.Hauptman PJ,et al.JAMA 2006;296:1877-84.DiDomenico RJ,et al.April,2007.Typical ADHF Treatment CourseADHERE Q1 2006 Final Cumulative Benchmark Report.Scios,Inc.:Sunnyvale,2006.Hauptman PJ,et al.J
6、AMA 2006;296:1877-84.DiDomenico RJ,et al.April,2007.Diuretic Resistance Commonly referred to as Cardiorenal Syndrome Often associated with renal insufficiency(acute and/or chronic)Definitions vary Persistent edema despite adequate diuretic doses Diminished natriuretic response to repeated doses Dail
7、y furosemide doses 80mg1 Prevalence Chronic:35%1 Acute:unknown1Neuberg GW,et al.Am Heart J 2002;144:31-8.Diuretic Resistance&Mortality Eshaghian S,et al.Am J Cardiol 2006;97:1759-64.Diuretic ResistanceWhat About in ADHF?Greenhalgh E,DiDomenico RJ Retrospective analysis of ADHF admissions to UIMCC in
8、 2006 Inclusion 18yo,ADHF with volume overload,Tx with IV diuretic Exclusion Initial Tx doesnt include IV diuretic Use of IV vasoactives in 1st 24 hours N=264 Definition Urine output 500ml within 2 hours of IV furosemide Urine output 1000ml within 4 hours of IV furosemide Goals Characterize diuretic
9、 resistance in the acute setting Investigate if there are any reliable risk factors for diuretic resistance in ADHF Clinical characteristics Demographics,clinical presentation,NYHA FC LV Fxn,renal Fxn BP Dose of diuretic Home&inpatient Concomitant medsDiuretic ResistanceDiuretic Mechanism of Action&
10、Mechanisms of Diuretic ResistanceDiuretic Mechanism/Site of ActionDe Bruyne LKM.Postgrad Med J 2003;79:268-71.Mechanisms of Diuretic Resistance Diminished effect in heart failure&renal failure Stimulation of neurohormonal axes Hypertrophy of distal tubules impairs natriuretic response Post-diuretic
11、NaCl retention Venous congestion impairs renal tubular function?Normal patients Furosemide 40mg IVP 200 250mEq Na 3 4 L over 3 4 hrs CHF patients natriuretic response Absorption&peak effect delayed 1/3 1/4 that of normal patients Renal insufficiency(RI)1/5 1/10 furosemide secreted into renal tubules
12、 Free concentrations of diuretic may be in nephrotic syndrome due to protein bindingDiuretic PharmacodynamicsSodium&Water ExcretionBrater DC.New Engl J Med 1998;339:387-95.Diuretics Pharmacodynamics Sodium&Water ExcretionEllison DH.Cardiology 2001;96:132-43.Diuretics&NeurohormonesDiuretic Resistance
13、&Renal FunctionProximal TubuleAT2 increases sodium reabsorbtionCollecting DuctHypertrophy of distal tubules.Aldosterone increases sodium reabsorbtionGlomerulusNorepinephrine,endothelin,AT2 decrease renal blood flow and GFRWeber KT.NEJM.2001;345:1689-1697.Francis GS et al.Ann Intern Med.1984;101:370-
14、377.Dzau VJ.Kidney Int.1987;31:1402-1415.Diuretic ResistanceNeurohormonal StimulationFrancis GS,et al.Ann Intern Med 1985;103:1-6.Baseline20 minutes*p0.01*Francis GS,et al.Ann Intern Med 1985;103:1-6.Baseline20 minutes3.5 hours2085+1035ml urine*p0.01*Diuretic ResistanceHemodynamic EffectsDoes Venous
15、 Congestion Impair Renal Function?Doty JM et al.J Trauma 1999;47:1000-3.Doty JM et al.J Trauma 1999;47:1000-3.Does Venous Congestion Impair Renal Function?Does Venous Congestion Impair Renal Function?Patel KP,Carmines PK.Am J Physiol Regulatory Integrative Comp Physiol 2001;281:R239-45.Treatment Opt
16、ions for Diuretic Resistance Change diuretics?Continuous infusion Combination of Loop diuretic+thiazide IV vasoactive drugs Combination hypertonic saline+Loop diuretic?Investigational therapies Vasopressin antagonists Adenosine antagonistsTreatment of Diuretic ResistanceAre All Diuretics Created Equ
17、al?More frequent dosing of furosemide&bumetanide may be necessary to overcome postdiuretic NaCl retentionBrater DC.New Engl J Med 1998;339:387-95.Treatment of Diuretic ResistanceContinuous Infusion of Diureticvs.Intermittent Bolus DosingTreatment of Diuretic ResistanceIV Bolus vs Continuous Infusion
18、Urine output(48hrs)IV bolus:3790mlCont inf:4490mlP0.01Lahav M,et al.Chest 1992;102:725-31.Treatment of Diuretic ResistanceIV Bolus vs Continuous InfusionDormans TPJ,et al.J Am Coll Cardiol 1996;28:376-82.Cumulative doses(area under the curve)of furosemide not significantly different 39 patients with
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