Presentation on theme: "Beth Davidson DNP, ACNP, CCRN Kristi Hayes MSN, FNP St"— Presentation transcript:
1Ultrafiltration as a Therapy Option for Diuretic Resistance: Inpatient & Outpatient Case Studies Beth Davidson DNP, ACNP, CCRN Kristi Hayes MSN, FNP St. Thomas Hospital Nashville, TN
2ObjectivesReview the epidemiology and pathophysiology of diuretic-resistant, acute heart failureIdentify volume overload treatment optionsReview/discuss case studies of diuretic-resistance and use of ultrafiltration for volume removal
3Epidemiology of Heart Failure (HF) Section 1: Epidemiology and DemographicsEpidemiology of Heart Failure (HF)Population GroupPrevalenceIncidenceMortalityHospital DischargesCostTotal population5,000,000550,00057,2181,093,000$29.6 billionHeart failure is a major public health problem resulting in substantial morbidity and mortalityMajor cost-driver of HF is high incidence of hospitalizationsJCAHO has initiated quality care indicators for hospitalized HF patientsCMS reimbursement for readmission < 30 days = $ 0Since the 1980s there has been a staggering increase in hospital discharges for heart failure (HF), and it is now the most common reason for hospitalization in the elderly.1HF is a progressive disease associated with high rates of morbidity and mortality—indeed,the natural history is for this disease to progress over time. Even patients with entirelyasymptomatic left ventricular dysfunction have an annual mortality rate that is notinsignificant. As patients’ symptoms progress and left ventricular dysfunction worsens, theannual mortality rate becomes even higher. Additionally, HF patients face both progressiveHF and sudden death. By understanding the mechanisms behind the progression of HF, the therapeutic approach for this disease can be better delineated.Some facts:Most frequent cause of hospitalization over the age of 65, with a prevalence of 5 million people in the United States.21 million patients hospitalized every year with HF as a primary diagnosis, and 2 million hospitalized every year with HF as a secondary diagnosis.2It is the single largest expense for Medicare—at about 28 billion dollars—with the major cost-driver of HF being high incidence of hospitalizations.2In 1996, there were 4.8 million cases, with 400,000 new cases each year. There are million cases in the US alone by the yearThe Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has initiatedHF quality care indicators for hospitalized HF patients.References:Topol E, Califf RM, Isner J, et al. Textbook of Cardiovascular Medicine. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2006;American Heart Association 2005.
4Fluid Overload Symptoms DecompensatedHeart FailureSection 2: Pathophysiology of Acute Decompensated Heart FailureInsultCardiac DysfunctionLV RemodelingNeurohormonalActivation RAAS/SNS Catecholamine EndothelinHemodynamicDecompensation Preload Afterload↓ Cardiac OutputREVISEDI CHANGED THIS ONE. MAKE SURE IT LOOKS OK BEFORE DELETING THE OTHER ONE, SLIDE 4Colucci WS, Braunwald E. Heart Disease: A Textbook of Cardiovascular Medicine. 5th ed. 1997:394.This diagram shows the relationship between the primary myocardial insult and subsequent events that contribute to the clinical syndrome of CHF.1 The pathophysiology of HF involves hemodynamic abnormalities, neurohumoral abnormalities, and myocardial cellular alterations. Left ventricular (LV) dysfunction results from myocardial injury. Neurohumoral activation, which includes activation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS), occurs in response to acute hemodynamic alterations and myocardial injury. This neurohumoral activation is counterproductive in patients with HF. Changes occur in cardiac function and peripheral circulation that contribute to the symptoms and drive the progression of HF.Neurohumoral activation results in an excess of vasoconstrictors—those in the SNS and the RAAS, as well as endothelin—which increase afterload and preload by retention of salt and water. Vasodilators—hormones in the endogenous natriuretic peptide system (NPS)—work to unload the left ventricle and promote natriuretic actions, but they are overwhelmed by the excess of vasoconstricting neurohomones. Vasodilators are ultimately beneficial counterregulatory hormones.2-4Neurohumoral activation results in progressive dilation and dysfunction of the left ventricle (remodeling). There are also fundamental abnormalities at the cellular level, including myocyte dysfunction, programmed cell death (apoptosis), fetal gene expression, hypertrophy, and myocardial fibrosis.5 Other circulating proinflammatory cytokines, such as interleukin-6 and TNF-alpha, can lead to a progressive wasting of lean tissue, fat, and bone mass.4 Based on this model, hemodynamic decompensation and neurohormonal activation may give rise to either acute impairment of LV function or chronic progression of disease, or both, in a vicious cycle.References:Colucci WS, Braunwald E. In: Braunwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine. 5th ed. Philadelphia: Saunders; 1997:Stevenson W. J Am Coll Cardiol. 2005;45:Weber. J Am Coll Cardiol. 2004:44(6):Anker et al. Am J Cardiol. 1999;83:Shah M et al. Rev Cardiovasc Med. 2001;2(suppl 2):S2-S6.Fluid Overload SymptomsMorbidityDeathRenal Vasoconstriction/Fluid Retention
5ACC/AHA Guidelines: Management of Fluid Status Patients should not be discharged from the hospital until a stable and effective diuretic regimen is established, and ideally, not until euvolemia is achievedPatients who are sent home before these goals are reached are at high risk of recurrence of fluid retention and early readmission because unresolved edema may itself attenuate the response to diuretics
6Diuretics Current “Standard of Care” Diuretics… Still more diuretics…
7Change in Weight During Hospitalization Outcomes with Standard Care Evidence of Incomplete Relief From CongestionNearly 50% of ADHF patients discharged with weight gain or losing less than 5 lbs27%302526%20Enrolled Discharges (%)1513%16%7%6%10Adhere National Benchmark Report Data, January 2001 to April 2006Despite the use of diuretics in 90% of patients, 20% gain weight on dischargeNote: n represents the number of patients who have both baseline and discharge weight, and the percentage is calculated based on the total patients in the corresponding population. Patients without baseline or discharge weight are omitted from the histogram calculations.3%2%5(<-20)(–20 to –15)(-15 to –10)(–10 to –5)(–5 to 0)(0 to 5)(5 to 10)(>10)Change in Weight (lbs)
8Outcomes with Standard Care Hospital ReadmissionsMortality50%50%33%37%20%12%Fonarow, GC. Rev Cardiovasc Med. 2002;3(suppl 4):S Jong P et al. Arch Intern Med. 2002;162:1689Rudiger et. al. Eur J Heart Fail 7:662– O’Connor CM. JCF 2005;11:3:Setoguchi S et.al. Am Heart J 2007;154:“To shorten lengths of stay, patients are discharged too early while they still have evidence of volume overload.” (O’Connor, n=908)Setoguchi: “A potential explanation was due to the treatment a patient received during hospitalization. With each subsequent HF hospitalization, there is additional exposure to diuretics.”O’Connor: A possible explanation… the patients’ heart failure symptoms were incompletely treated before hospital discharge.Despite advances in care – medical Rx and devices – mortality remains high30Days3Months6Months30Days12Months5YearsPatients have persistently high event rates despite use of evidence-based therapies…
9Effect of Loop Diuretics on RAAS in Cardiac Failure Section 3: Diuretic Therapy in Acute Decompensated Heart FailureLoop Diuretic Inhibition of Macula DensaIncreased Renin-AngiotensinIncreasedAldosteroneCardiac Remodeling and FibrosisLeft Ventricular DysfunctionCARDIAC FAILURESchrier. J Am Coll Cardiol. 2006;47:1-8.The renin-angiotensin system is known to be activated in the ADHF patient.1 The activation of this system is due to a variety of factors, including poor renal perfusion related to cardiac pump failure and/or loop diuretic inhibition of the macula densa. The resulting upregulation may cause progression of the cardiac dysfunction by: (1) direct myocardial effects of angiotensin and aldosterone causing cardiac remodeling and fibrosis; (2) increasing proximal sodium reabsorption and impairing aldosterone escape, thereby perpetuating volume overload with the potential for cardiac dilation, left ventricular hypertrophy, and blunting beneficial atrial-renal reflexes; and (3) moreover, the resultant volume overload in chronic HF patients is most frequently treated with loop diuretics. The loop diuretics in turn block sodium chloride transport at the macula densa, with resultant further activation of renin-angiotensin-aldosterone system.2References:Schrier R. J Am Coll Cardiol. 2006;47:1-8.He X-R et al. Effects of furosemide and verapamil on the NaCl dependency of macula densa-mediated secretion. Hypertension. 1995;26:
10Current Options May Have Undesirable Clinical Impacts Section 3: Diuretic Therapy in Acute Decompensated Heart FailureFavorable aspects of diuretic therapyIncreases urine output; reduces total body volumeAdverse aspects of diuretic therapyDirect activation of renin-angiotensin-aldosterone systemEnhanced myocardial aldosterone uptakeLoss of K, Mg, Ca, secondary myocyte Ca loadingIndirect reduction of cardiac outputIncreased total systemic vascular resistanceReduced natriuresis and GFRAssociated with increased morbidity and mortalityReferences:1. ADHERE® Registry. 3rd Quarter National Benchmark Report.2. Emerman. J Card Fail. 2004;10:S116:368.3. Bayliss. Br Heart J. 1987;57:17-22.4. Faris. Int J Cardiol. 2002;82:5. Mehta. JAMA. 2002;288:6. Butler. Am Heart J. 2004;147:7. Gottlieb. J Am Coll Cardiol. 2000;35:56-59.8. Brater DC. N Engl J Med. 1998;339:387.9. Firth et al. Lancet. 5/7/1988.10. Francis. Ann Intern Med. 1985;103:1-6.11. Ribboli. Am J Physiol Sep;267(3 pt 2):H1054-H1061.12. McCurley. J Am Coll Cardiol. 2004;44:
11Diuretics and ADHF No consensus dosing guidelines Section 3: Diuretic Therapy in Acute Decompensated Heart FailureDiuretics and ADHFNo consensus dosing guidelinesNo common definition of diuretic resistantNo long-term studies of diuretic therapy for the treatment of heart failureNo outcomes data regarding morbidity and mortalityAlthough diuretics are widely used in the treatment of ADHF, there have been few controlled studies to assess the relative safety and efficacy of these agents, especially compared with more recent additions to therapeutic options for ADHF.1,2References:Ravnan SL et al. Congest Heart Fail. 2002;8:80.Kramer et al. Nephrol Dial Transplantation. 1999;14(suppl 4):39-42.14):39-42.
12Diuretic ResistanceCan be described as a clinical state in which the diuretic response is diminished or lost before the therapeutic goal of relief from edema has been reachedAffects 20%–30% of patients with HF
13Diuretic Resistance: Two Types “Braking” phenomenonA decrease in response to a diuretic after the first dose has been administeredLong-term toleranceTubular hypertrophy to compensate for salt lossCauses of diuretic resistance: renal insuff, variable diuretic absorption, RAAS/SNS, increased Na intake, noncompliance, infrequent dosing
14Diuretic Therapeutic Dilemma Diminished renal function and concurrent sodium and water retention in ADHF presents a therapeutic dilemma with regard to sub-maximal diuretic therapyFluid removal by ultrafiltration may be recommended in this clinical settingSchrier. J Am Coll Cardiol. 2006;47:1-8.
15What is Aquapheresis? Method to safely achieve euvolemia Section 7: AQUADEX™ FlexFlow™ Device OverviewWhat is Aquapheresis?Method to safely achieve euvolemiaSimplified form of ultrafiltrationInpatient or outpatient settingsICU, CCU, MICU, telemetry, step-down, observation, ED, outpatient clinicsPeripheral or central venous accessFlexible access sites and cathetersDiverse physician prescriptionHighly automated operationNo clinically significant impact on electrolyte balance, blood pressure, or heart rateor heart rate*If an appropriate rate of ultrafiltration is selected and where vascular refill rate is not exceeded. The specific clinical circumstances at the time of device use may also have an impact on patient hemodynamics.
16Fluid Removal by Ultrafiltration Section 4: Ultrafiltration History and PhysiologyUltrafiltration can remove fluid from the blood at the same rate that fluid can be naturally recruited from the tissueThe transient removal of blood illicits compensatory mechanisms, termed plasma or intravascular refill (PR), aimed at minimizing this reductionInterstitialSpace (edema)NaPH2ONaKUFKPRThe plasma refill (PR) response is a compensatory response by the circulation in response to volume loss.1 The rate of plasma refill is important, for if the ultrafiltration rate is too aggressive intravascular volume may decrease because the rate of refill from the interstitial to the intravascular space is exceeded. This in turn may lead to hemodynamic instability and renal dysfunction. There have been studies that document an increase in creatinine and hemodynamic instability when ultrafiltration rates are too aggressive in a high-risk, advanced HF subset of patients,2 and thus the clinician should be aware of this risk.“Balanced diuresis”References:1. Marenzi et al. J Am Coll Cardiol. 2001;38:4.2. Liang KV et al. J Card Fail. 2006;12:PNaVascularSpaceVascularSpaceNa
17The EUPHORIA Study Single center, prospective study, 20 patients Initial UF within 12 hours of hospitalization and before any significant administration of IV diuretics and/or vasoactive drugsResultsRemoved an average of 8.6 liters of fluid60% of patients were discharged in ≤ 3 daysAverage hospitalization was 3.7 daysBaseline Cre 2.1Average volume removal = 9LSustained decrease in weight, BNP, and Cre over time (90 days)7/20 normalized their hyponatremia
18The EUPHORIA Study Rehospitalization In the three months preceding ultrafiltration:10 hospitalizations in 9 patientsAfter ultrafiltration:1 readmission for ADHF within 30 days
19The UNLOAD Study200 patients (100 each arm) randomized, multi- center study comparing ultrafiltration versus standard care for acutely decompensated patientsSuperior salt & water removal/weight lossAt 48 hours, ultrafiltration demonstrated38% greater weight loss28% greater net fluid lossAt 90 days, reduced readmissions50% reduction in re-hospitalization episodes63% reduction in total re-hospitalized days52% reduction in emergency department or clinic visitsCostanzo, ACC.06 Smaller Trial Late-Breaking Clinical Trials II, American College of Cardiology 2006 Scientific Sessions;March 12, 2006; Atlanta, GA. Publication in JACC expected Feb 13, 2007.Standard care – IV lasix (bolus or continuous 2X oral dose)No statistical diff in serum Cre b/w groupsEqual dyspnea score b/w groupsDecreased rehospitalization/unscheduled visits in UF arm
20ACC/AHA Guidelines: Class IIa, Level of Evidence B I IIa IIb IIIUltrafiltration is reasonable for patients with refractory congestion not responding to medical therapyAquapheresis is now ranked HIGHER in theLevel of Evidence than:- salt restriction- strict I/Os- higher doses of loop diuretics- addition of a second diuretic- continuous infusion of a loop diuretic- vasodilators – IV nitroglycerin, nesiritide- IV inotropesAll of these are Level of Evidence: CClass IIa: Data derived from a single randomized trial, more studies neededLevel of Evidence B: consensus opinion, standard of care, limited evidence20
21Case Study 68 yo WM Diastolic heart failure Ischemic heart disease CAB 4/06HTNAfibrillation/flutterAnemiaHospitalized every6 months for exacerbation
22Case Study: Inpatient Therapy Inpatient ultrafiltration – January 2010Access issues – extended length catheter (ELC)Creatinine after 48 hrs of treatmentCreatinine 1.6 at dischargeTherapy/ACEI discontinuedDiuresed with IV lasix continuous infusionLOS = 5 daysNet volume loss = 7 kgs
23Case Study: Outpatient Therapy 1st treatment- 2/22/10ELC catheter1850 cc ultrafiltrate over 7 hrsWt loss = 2 lbsSerum Cre = 1.8 pre and at termination of therapyHct 29 – sent home with hemoccult cardsPositive x 3- referred to PCP – no follow-upSPELL OUT ELC – you have room
24Case Study: Outpatient Therapy 2nd treatment – 3/26/10ELC catheter and 18 g peripheral IVAccess issues!2130 ultrafiltrate over 6.5 hrsAlso treated with Lasix 240mg IV due to loss of time waiting for accessSerum Cre = 1.7 pre and post termination of therapyHct 26 - referred to HematologyEP f/u 3/29- was found to be in aflutter- TEE 3/31. Started on coumadinHematologist appt 4/15- Hgb- 19! Admitted for transfusion of blood products, which in turn, caused decompensated HF
25Saint Thomas Hospital: Inpatient Outcomes 54 UF treatments from 5/1/08 – 6/1/10Average treatment time = 37 hours, 28 minutesAverage fluid removal = 6.15 liters/circuitMinimal adverse events9 episodes of worsening renal insufficiencyNo significant electrolyte disturbancesNo significant hypotension1 asymptomatic, small apical pneumothorax6 minor bleeding episodes – epistaxis, line insertion site, generalized “oozing”54 treatments – 39 different patientsAverage treatment time - national average = 24 hoursAverage fluid removal - national average = 4.0 litersMost issues with renal insuff occurred early after implementation – too dry, too quicklyIncreased bleeding when on coumadin at baseline – standardized heparin protocol with target PTT25
26Saint Thomas Hospital: Inpatient Outcomes Readmissions < 30 days1 re-admitted with LOC changes2 discharged to hospiceultrafiltration for palliation1 patient, 5 re-admissionsnow on dialysis for volume controlno readmits since dialysis except for recent hip fracture1 expired within 90 days of readmission1 patient, 2 re-admissionssuspect non-compliance – eating Whopper at discharge!Several readmissions, but only with a few patients
27Saint Thomas Hospital: Outpatient Outcomes 1st outpatient treatment – January 19, 201013 treatments – 7 ptsavg treatment time 5.79 hrsavg volume removal 1.49 L1 repeated hospitalizationnow on peritoneal dialysis1 deceased1 ARFpatient did not followmedication dischargeinstructionsEffective in keeping pts out of hospital > 30 daysNeed more dataPt satisfaction and QOL are most important!I DID NOT CHANGE-NOT SURE OF LAYOUT, BUT LOOKS FUNNY WITH SPACE AFTER 1ST ITEM
28Advanced Heart Failure Clinic Saint Thomas Hospital
30Challenges and Opportunities for Improvement Early identification of patients that could benefit from outpatient therapy to decrease readmission within 30 daysProcess improvement – timely, efficient IV access to allow faster initiation of therapyPatient education – medications, line care, follow-up appointments, etc…Anticoagulation – preserve integrity of circuit