1 aquapheresis and the aquadex flexflow l0058 rev. b 11/05

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AquapheresisAquapheresis™™ and and the Aquadex the Aquadex FlexFlowFlexFlow™™

L0058 Rev. B 11/05

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ContentsContents

• Key Points• What is Aquapheresis?• How does it work?• What is the Aquadex FlexFlow?• Who are candidates for aquapheresis?• Why use aquapheresis and the Aquadex FlexFlow?• How to use aquapheresis and the Aquadex FlexFlow?• Ultrafiltration/Aquapheresis clinical evidence and background

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Key PointsKey Points

The Aquadex System is indicated for: • Temporary (up to 8 hours) ultrafiltration treatment of patients with fluid overload who have failed diuretic therapy,

and

• Extended (longer than 8 hours) ultrafiltration treatment of patients with fluid overload who have failed diuretic therapy and require hospitalization.

All treatments must be administered by a healthcare provider, under physician prescription, both of whom having received training in extracorporeal therapies.

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Aquapheresis™ is the trademarked name of CHF Solutions’ advanced and simplified form of ultrafiltration (UF) performed by the Aquadex FlexFlow™ and designed for fluid removal.

Aquapheresis is used to describe the clinical treatment that offers safe, convenient, and predictable salt and water removal for patients with fluid overload.

The Aquadex FlexFlow is the system that enables the delivery of that treatment.

To minimize the chances of hypovolemic and hypotensive complications, the rate of fluid removal should not exceed the rate of a patient’s intravascular fluid refilling. Periodic monitoring of a patient’s systolic blood pressure can be used to determine how well these rates are currently matched.

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Key PointsKey PointsIn clinical trials, aquapheresis using the Aquadex FlexFlow:

allowed rapid removal of extracellular and intravascular fluid volume excess, can be safely achieved via peripherally inserted ultrafiltration without the need for central venous catheter placement 1

And is associated with:

• no clinically significant impact on electrolyte balance, heart rate, blood pressure 1

• greater fluid removal, weight loss and symptom relief compared to medical therapy alone 2

• reductions in patient hospital length of stay and hospital readmissions 3

• significant and sustainable reductions in patient weight, cardiac filling pressures and left atrial volume index as well as marked improvements in stroke volume and mitral regurgitant severity 41. Jaski, Journal of Cardiac Failure 2003 9(3);227-231. 2. Costanzo, J Am Coll Cardiol 2005;46:2047-51.

3. Bart, J Am Coll Cardiol 2005;46:2043-46. 4. Saltzberg, J Heart Lung Transpl, Feb 2005, Vol. 24, Issue 2 (Suppl.) S130 270.

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The best sources of the latest information on aquapheresis and the Aquadex FlexFlow can be found in the following:

• Product label and instructions for use documents (e.g. Aquadex FlexFlow User’s Guide, UF-500 blood set)

• Applicable and specific hospital Policy & Procedures and Standing Orders

• Aquadex FlexFlow onscreen help and alarm/alert information

• CHF Solutions’ website, www.chfsolutions.com

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What is Aquapheresis?What is Aquapheresis?

Aquapheresis™

safe, convenient, and predictable salt and water removal from patients with fluid overload as delivered by the Aquadex FlexFlow™ system.

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How does Aquapheresis work?How does Aquapheresis work?

Aquapheresis with the Aquadex FlexFlow works by pulling a small amount of venous blood from the body (10-40 mL/min in increments of 5 mL/min), filtering out the excess salt and water (10-500 mL/hour in increments of 10 mL/hour), and returning the filtered blood back to the patient.

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What is the Aquadex FlexFlow?What is the Aquadex FlexFlow?

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Aquapheresis with the Aquadex Aquapheresis with the Aquadex FlexFlowFlexFlow

• Advanced form of ultrafiltration

• Inpatient or outpatient settings • ICU, CCU, MICU, telemetry, stepdown, observation, ED, outpatient clinics

• Peripheral or central venous access• Flexible access sites and catheters

• 1 to 1 monitoring not required

• No clinically significant impact on electrolyte balance, blood pressure or heart rate

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What is the Aquadex What is the Aquadex FlexFlowFlexFlow™™??

Aquadex FlexFlow console

UF 500 blood circuit set

Console cart

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• Low blood flow: 10-40 mL/min

• Low blood volume: 33 mL

• Precise fluid removal rates: 10-500 mL/hour

• Quick and easy device setup (less than 10 minutes)

• Highly automated operation, nursing oversight is minimized

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On/Off key

Power lights

Alarm Mute key

Alarm/Alert lights

RUN key

Accept key

Clear key

Help key

UF Rate key

Blood Flow key

Contrast key

MANUAL key

STOP key

Menu key

mmHg key

Screen

Arrow Up/Down key

Datakey receptacle

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What is the Aquadex What is the Aquadex FlexFlowFlexFlow™™??

Blood pump cartridge

UF pump cartridge

UF collection bag

UF bag drain

Data key

Withdrawal line

Access ports

Infusion line

Pressure sensors

Blood filter

Priming adaptor

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Who are candidates for Who are candidates for Aquapheresis?Aquapheresis?

Volume Overloaded:

As evidenced by two or more of the following

- Peripheral edema (e.g.>2+) 1,2,3

- Ascites 2,3

- Pulmonary rales, paroxysmal nocturnal dyspnea PND), or orthopnea 2,3

- Jugular venous distention (e.g.>7 cm ) 2,3

- Significantly above dry weight (e.g. 10+ lbs ) 8

AND

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Inadequate Diuretic and/or Natriuretic Response (as a subset of patients with volume overload):

As evidenced by two or more of the following:

- High daily diuretic doses (e.g. furosemide > 80 mg, torsemide > 40 mg, and bumetamide > 2 mg ) 2

- Low urine volume (e.g. < 1,000 ml in 24 hours ) 4

- Elevated serum creatinine 2,5

- Increasing serum creatinine on standard therapy 6,7

AND


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Special Considerations Should Be Given IfAny Of The Following Are Present:

- Need for renal replacement therapy 2

- Unstable hemodynamic condition 1,2,3

- Documented hypercoagulable state 2

- Hemoconcentrated (e.g. Hct > 53% ) 1,2,3


1. Jaski, Journal of Cardiac Failure 2003 9(3);227-231. 2. Costanzo, J Am Coll Cardiol 2005;46:2047-51. 3. Bart, J Am Coll Cardiol 2005;46:2043-46.

4. Gottlieb, JACC 2000;35(1):56-59. 5. Gottlieb, JCF 2002;8 (3):136-41. 6. Butler, Am Heart J 2004; 147:331-338.

7. Akhter, Am J Cardiol 2004; 94:957-960.8. 74% of admitted patients lose less than 10 lbs over course of standard therapy, Q3 2004 ADHERE™ Registry National Benchmark Report, Scios Inc. 2005.

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Why should Aquapheresis be Why should Aquapheresis be used?used?

• Current options not performing as Current options not performing as they NEED tothey NEED to

• Current options are not achieving the Current options are not achieving the standard of carestandard of care

• Current options have undesirable Current options have undesirable clinical impactsclinical impacts

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•89% of patients present with difficulty breathing (dypsnea, i.e. fluid in lungs)

•Average duration of IV loop diuretic treatment = 2.9 days

• IV heart failure medications include …

ADHERE Registry Quarter Benchmark Report (AD001444)

Not performing as they NEED Not performing as they NEED toto

2121

88

6 73

10 9

0

10

20

30

40

50

60

70

80

90

100

IV Heart Failure Medications

% o

f P

ati

en

ts

ADHERE:ADHERE: Inpatient IV Medications Inpatient IV Medications Acute Heart FailureAcute Heart Failure

All Enrolled Discharges over 12 monthsAll Enrolled Discharges over 12 monthsn=52,047n=52,047


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43% of patients are “improved but still symptomatic at time of discharge”

This number has been increasing each quarter by 1% since Q1 2003.


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75% of patients are discharged with 10 lbs or less change in weight from admission.

This number is unchanged for over 2 years.


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Current options are not achieving Current options are not achieving the standard of carethe standard of care

• ““In general, patients should not be discharged from In general, patients should not be discharged from the hospital until a stable and effective diuretic the hospital until a stable and effective diuretic regimen is established, and ideally, not until regimen is established, and ideally, not until euvolemia is achieved. Patients who are sent home euvolemia is achieved. Patients who are sent home before these goals are reached are at high risk of before these goals are reached are at high risk of recurrence of fluid retention and early readmission recurrence of fluid retention and early readmission because unresolved edema may itself attenuate the because unresolved edema may itself attenuate the response to diuretics.”response to diuretics.”

-- Hunt et. al. Management of Fluid Status, -- Hunt et. al. Management of Fluid Status, ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the AdultACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult , © 2001 by the American , © 2001 by the American College of Cardiology and the American Heart Association, Inc. (College of Cardiology and the American Heart Association, Inc. (http://http://www.acc.org/clinical/guidelines/failure/hf_index.htmwww.acc.org/clinical/guidelines/failure/hf_index.htm, , http://http://www.americanheart.org/presenter.jhtml?identifierwww.americanheart.org/presenter.jhtml?identifier=11841=11841

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Current options are not Current options are not achieving the standard of careachieving the standard of care• ““Appropriate use of diuretics is a key element in the success of Appropriate use of diuretics is a key element in the success of

other drugs used for the treatment of HF. The use of other drugs used for the treatment of HF. The use of inappropriately low doses of diuretics will cause fluid retention, inappropriately low doses of diuretics will cause fluid retention, which can diminish the response to ACE inhibitors and increase which can diminish the response to ACE inhibitors and increase the risk of treatment with beta-blockers. Conversely, the use of the risk of treatment with beta-blockers. Conversely, the use of inappropriately high doses of diuretics will lead to volume inappropriately high doses of diuretics will lead to volume contraction, which can increase the risk of hypotension with contraction, which can increase the risk of hypotension with ACE inhibitors and vasodilators and the risk of renal ACE inhibitors and vasodilators and the risk of renal insufficiency with ACE inhibitors and angiotensin II receptor insufficiency with ACE inhibitors and angiotensin II receptor antagonists. Optimal use of diuretics is the cornerstone of any antagonists. Optimal use of diuretics is the cornerstone of any successful approach to the treatment of HF.”successful approach to the treatment of HF.”

-- Hunt et. al. Management of Fluid Status, -- Hunt et. al. Management of Fluid Status, ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the AdultACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, © 2001 by the American College of Cardiology and the , © 2001 by the American College of Cardiology and the American Heart Association, Inc. (American Heart Association, Inc. (http://http://www.acc.org/clinical/guidelines/failure/hf_index.htmwww.acc.org/clinical/guidelines/failure/hf_index.htm, , http://http://www.americanheart.org/presenter.jhtml?identifierwww.americanheart.org/presenter.jhtml?identifier=11841=11841

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Current options are not Current options are not achieving the standard of careachieving the standard of care

• “… “… ultrafiltration or hemofiltration may be needed to ultrafiltration or hemofiltration may be needed to achieve adequate control of fluid retention. The use achieve adequate control of fluid retention. The use of such mechanical methods of fluid removal can of such mechanical methods of fluid removal can produce meaningful clinical benefits in patients with produce meaningful clinical benefits in patients with diuretic-resistant HF and may restore responsiveness diuretic-resistant HF and may restore responsiveness to conventional doses of loop diuretics.”to conventional doses of loop diuretics.”

-- Hunt et. al. Management of Fluid Status, -- Hunt et. al. Management of Fluid Status, ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the AdultACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult , © 2001 by the American , © 2001 by the American College of Cardiology and the American Heart Association, Inc. (College of Cardiology and the American Heart Association, Inc. (http://http://www.acc.org/clinical/guidelines/failure/hf_index.htmwww.acc.org/clinical/guidelines/failure/hf_index.htm, , http://http://www.americanheart.org/presenter.jhtml?identifierwww.americanheart.org/presenter.jhtml?identifier=11841=11841

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• The “Good” about diuretics– Induce hypotonic urine, reduce total body volume in majority of

patients 8

• The “Bad” about diuretics– Direct Activation of renin-aldosterone (RAA) system 7,14

– Enhanced Myocardial Aldosterone uptake 16

– Loss of K, Mg, Ca, secondary myocyte Ca loading 16

– Indirect Reduction of Cardiac Output 14,15

– Increased Total Systemic Vascular Resistance 15

– Reduced Natriuresis 12

– Reduction of GFR 11,13

• The “Ugly” about diuretics– Associated with enhanced morbidity 6

– Associated with increased mortality 6,9,10

• Diuretics are inefficient in reduction of edema and effective in reduction of symptomatic congestion 5

5. Q3 2004 National Benchmark Report, Scios Inc. 6. Emerman, JCF 2004;10(4):S116:368. 7. Bayliss, Br Heart J 1987;57:17-22.8. Faris, Int J Cardiol. 2002;82(2): 149-58. 9. Mehta, JAMA 2002;288(20):2547-53. 10. Butler, Am Heart J 2004; 147:331-338.

11. Gottlieb, JACC, 2000;35(1):56-59. 12. Brater DC. N Engl J Med. 1998;339:387. 13. Firth et al Lancet 5/7/88.14. Francis AIM 1985;103:1-6. 15. Ribboli Am J Physiol. 1994 Sep;267(3 Pt 2):H1054-61. 16. McCurley, JACC 2004;44(6):1301-1307.

Current options have undesirable Current options have undesirable clinical impactsclinical impacts

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• ““Braking Braking Phenomenon”Phenomenon”– A decrease in response

to a diuretic after the first dose has been administered

• Long-term ToleranceLong-term Tolerance– Tubular hypertrophy to

compensate for salt loss

Brater DC. N Engl J Med. 1998;339:387

Current options have undesirable Current options have undesirable clinical impactsclinical impacts

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Diuretics Worsen CHF by Diuretics Worsen CHF by Reducing GFR and Activating Reducing GFR and Activating NeurohormonesNeurohormones

Gottlieb SS et al. Circulation. 2002;105:1348–1353 (n=63)

•Gottlieb showed that loop diuretics diminish GFR In patients with heart failure

•Bayliss showed that the significant increase in renin and aldosterone occurred as a response to diuretic treatment rather than as a result of the disease process itself

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The High Morbidity and Mortality in The High Morbidity and Mortality in CHF Is Strongly Related to Renal CHF Is Strongly Related to Renal FunctionFunction

• Total of 1906 patients

• NYHA ClassIII (n = 1138)III/IV (n = 607)IV (n =161)

• GFRc = Uses Cockroft- Gault Eqn

• Impaired renal function is a strong predictor of mortality

Relationship of GFRc with Mortality in 1,906 Pts. With CHF

Hillege HL et al. Circulation 2000; 102: 203-10

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Diuretic Dose Predicts Mortality in Diuretic Dose Predicts Mortality in Pts. With Advanced HFPts. With Advanced HF

• Neuberg did sub-analysis of PRAISE study (n=1153)• High diuretic, low ACE-I dose

High mortality

• Philbin studied 1,150 patients with decompensated CHF treated in community setting• High mortality in patient

having less rapid clearance of volume excess despite greater use of IV diuretics.

Philbin, et al. AJC 1997; 80: 519-22.

Neuberg GW et al. AHJ 2002; 144: 31-8.

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Why Aquapheresis instead of Why Aquapheresis instead of CVVH?CVVH?

CVVH devices designed to offer several modes of Continuous Renal Replacement Therapy (CRRT) in ICU settings to patients with acute renal failure.

Aquadex FlexFlow device designed to offer solely fluid removal by aquapheresis in many settings to patients with fluid overload.

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CRRT (Continuous Renal Replacement Therapy) is an umbrella term that incorporates several common modes of therapy.

All modes remove plasma water, but most remove other solutes as well.

All modes use the technique of convection, diffusion or a combination of both.


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Convection - can be thought of as water as it passes over a waterfall. A slow gentle waterfall will not pull many “solutes” with it as compared to a rushing waterfall that will drag large amounts of “solutes” as it flows over the waterfall

Diffusion - solutes move from an area of high concentration to an area of low solute concentration


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Common modes of CRRTCommon modes of CRRT

Slow Continuous Ultrafiltration (SCUF)Used to remove fluid: not able to remove many solutes and/or urea.Utilizes convection

Continuous Venovenous Hemofiltration (CVVH)Removes fluids, small to medium solutes and some ureaUtilizes convection

Continuous Venovenous Hemodialysis (CVVHD)Continuous slow dialysis, medium and large solutes removedUtilizes diffusion

Continuous Venovenous Hemodiafiltration (CVVHDF)

Removes small and medium solutes, clears ureaUtilizes both convection and diffusion

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AquapheresisAquapheresis CVVHCVVH

PatientPatient Fluid overloadFluid overload Renal complicationsRenal complications

Primary Primary PhysicianPhysician

Cardiologist, Nephrologist, Cardiologist, Nephrologist, Surgeon, etc.Surgeon, etc.

NephrologistNephrologist

Treatment Treatment VenueVenue

Inpatient/OutpatientInpatient/Outpatient ICUICU

Blood Blood Withdrawal Withdrawal RatesRates

10 – 40 mL/min.10 – 40 mL/min. 100 – 300 mL/min.100 – 300 mL/min.

Extracorporeal Extracorporeal VolumesVolumes

33 mL33 mL 100 – 300 mL100 – 300 mL

AccessAccess Peripheral or CentralPeripheral or Central Central onlyCentral only

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“We do a lot of CVVH. But if we just need to take some fluid off, aquapheresis with the Aquadex FlexFlow is simply easier and cheaper.”

“That’s why we prefer it in those patients with fluid overload.”

-- Todd Y., MS, CNS, CNP, Clinical Nurse Specialist, Cardiology


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How to Use How to Use Aquapheresis and Aquapheresis and

the Aquadex the Aquadex FlexFlow FlexFlow

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ResponsibilitiesResponsibilities

Physician

• Identifies appropriate patient(s) according to accepted criteria (refer to Patient Selection / Identification)

• Completes Standing Orders for Ultrafiltration / Aquapheresis

Establishes / coordinates venous access site, catheter, and insertion (refer to Choosing Venous Access)

Defines quantity of total fluid to be removed (in liters) and/or total duration of treatment (in hours)

Defines initial fluid removal rateDefines / details / clarifies criteria for adjusting fluid

removal rate and/or blood flow Prescribes and communicates anticoagulation plan Establishes fluid restriction

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ResponsibilitiesResponsibilities

Nurse

• Treatment Set Up• Begin per physicians orders• Basic Monitoring

Enforce and record intake and output (I & O’s).Monitor patient as appropriate.If necessary, adjust the fluid removal rate as prescribed. Listen for possible alarms and respond as necessary.Perform basic troubleshooting to assure proper functioning.Assess venous access sites periodically.If required, titrate anticoagulation as ordered.

• Confirm patient at physician prescribed amount of fluid removed or duration of therapy.

• Disconnect patient from the device.• Care or dispose of blood set and catheters according to

institutional policy.• Routine console cleaning.

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Loading and setupLoading and setup

Prior to use, the UF-500 blood set must be properly installed and connected to the Aquadex FlexFlow console. This can be achieved by the several different methods listed below:

• Aquadex FlexFlow User’s Guide instructions (Chapter 2)

• One page Aquadex FlexFlow Instructions for Setup and Priming document

• Interactive, step by step onscreen instructions (e.g. press PRIME then Help key)

• Graphic step by step instructions on UF-500 blood set label

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PrimingPriming

Before starting PRIME, ensure that…

• both of the UF-500 blood set pump cartridges are fully and properly inserted• all three of the pressure sensors are inserted• tubing is properly inserted into the air and blood leak sensors• new datakey provided with the new UF-500 blood set is inserted• withdrawal line is spiked into priming solution bag and is hanging from the cart hook• clear infusion line is connected to the collection bag and its hanging from the weight scale hook• all clamps are open

Press PRIME then ACCEPT key to begin.

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Displaying the pressuresDisplaying the pressures

The pressures in the Aquadex FlexFlow blood circuit set (UF-500 blood set) may be displayed on the Aquadex FlexFlow screen by pressing the Graph or mmHg keys.

The numbers displayed are in units of millimeters of mercury (mmHg) and represent the 3 individual pressures that are monitoring during treatment – withdrawal (Pw), infusion, (Pi) and ultrafiltrate (Pu).

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Displaying the pressuresDisplaying the pressuresPw: measures the withdrawal pressure and is typically negative (-) and depending upon the chosen access, usually between -50 to -200 mmHg. Obtaining the lowest pressure is best (i.e. the smallest negative number), but Pw should also be below 0 mmHg to prevent a withdrawal disconnect alarm from occurring. Below -300 mmHg, the pumps may slow and a withdrawal occlusion alert may occur.

Pi: the infusion pressure range is of the same order as the withdrawal pressure but positive (+), that is, usually between +50 to +200 mmHg. Below 0 mmHg, an infusion disconnect alarm may occur. Above +300 mmHg, the pumps may slow and an infusion occlusion alert may occur.

Pu: can range from nearly Pi’s current value to -300 mmHg. Pu is limited to -300 mmHg by the Aquadex FlexFlow. A more negative Pu indicates that the resistance of the filter is higher than expected (e.g. if the filter is clotted/fouled).

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Expected pressure rangesExpected pressure ranges

The pressures generated during operation is a function of blood flow rate, blood viscosity, and patient and catheter resistance.

The Aquadex FlexFlow blood flow rate is adjustable by the user, but always between 10-40 mL/min.

Blood viscosity is a function of blood temperature and hematocrit (Hct).

Patient resistance is a function of where the catheter is placed, a patient’s venous vasculature, and the patient’s body positioning.

Catheter resistance is a function of the diameter and length of the selected catheter.

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Understanding the pressuresUnderstanding the pressures

One way to think of this is using a “straw in a milkshake analogy”.

How much milkshake you actually get out (blood flow rate) is dependent upon how thick the milkshake is (viscosity), where exactly is the straw in the glass (patient resistance), and what kind of straw you’re using (catheter resistance).

The thicker the milkshake or the longer and thinner the straw is, the more you will have to suck on the straw (withdrawal) to get the same amount of milkshake out, the higher the resistance is, the more negative the pressure will be in the straw. If you were blowing into the same straw to make bubbles (infusion), the higher resistance will make the pressure more positive.

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How much? How fast?How much? How fast?

As with any mechanical method of extracorporeal fluid removal, the rate of fluid removed per hour from the intravascular space must not exceed the rate of fluid entering the intravascular space from the interstitial and intracellular spaces.

Setting the appropriate fluid removal rate to not exceed this intravascular refilling is crucial to minimizing risk of

• hypovolemia, • hypotension, • transient renal malperfusion, • increases in creatinine,• arrhythmias

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rate of fluid removed from the intravascular space = UF rate (UFR)

rate of fluid entering the intravascular space = Plasma Refill Rate (PRR)

Therefore,

UFR < PRR

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This can be most easily achieved with a periodic monitoring of the systolic blood pressure and setting specific limits that would warrant a reduction in the fluid removal rate (refer to the hospital’s Aquapheresis Standing Orders)

For example, Vital signs Q 15 minutes x 1 hour, Q 30-60 for the remainder of treatment. If SBP < 90 mmHg or HR > 130 bpm after 2 consecutive 5 minute observation periods, decrease the fluid removal rate (UF Rate) by 100 mL/hr or place at 0 mL/hr for 30 minutes or until patient is stable. Then, resume UF rate 100 mL/hr lower than the level at which the patient became unstable.

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Setting the Fluid Removal Rate (UF Rate)Setting the Fluid Removal Rate (UF Rate)

Using the UF Rate key, , users can set the fluid removal rate from 10 to 500 mL/hour in increments of 10 mL/hour. Default is 0 mL/min.

• Press the UF RATE key• Press Arrow UP or DOWN keys to set a desired value.• Press ACCEPT.

With this feature, our users can set the fluid removal rate that is best for the chosen patient.

F

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How long?How long?

Most physicians prescribe a treatment length based on any of the following:

• Indication For Use• Desired fluid goal being achieved• Desired weight reduction goal being achieved• Desired symptom relief goal being achieved• Desired time goal being achieved• Filter clotting• Shifts in BP, sCr, etc.

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AnticoagulationAnticoagulation

For maximal UF-500 blood set life, it is recommended that during treatment the patient have a therapeutic range of anticoagulation, that is, twice normal (e.g. an ACT of 180 - 220 seconds).

Refer to the appropriate institutional policy (i.e. weight based protocol) for recommended bolus and drip requirements and make sure that all parties involved understand what is expected and required.

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Common anticoagulants used with the Aquadex FlexFlow are heparin, lovenox, argatroban and coumadin.

Many hospitals periodically take a blood sample and test what level of anticoagulation is being achieved in the patient during treatment (e.g. every 4 hours).

Intravenous anticoagulation can be administered through either the withdrawal or infusion access ports on the UF-500 blood circuit set, but the withdrawal line access port is most common.

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If the withdrawal line access port is used with an infusion pump, occlusion alarms may occur if the infusion pump’s occlusion pressure limits are not set appropriately.

It is recommended that the occlusion limit for the infusion pump be set to at least 400 mmHg.

Refer to the infusion pump’s operator’s manual for instructions on setting its occlusion pressure limits.

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Choosing Venous AccessChoosing Venous Access

For optimal performance and minimal inconvenience, the Aquadex FlexFlow requires adequately sized catheter lumens and a steady flow of venous blood.

If the required blood flow cannot be achieved without causing higher than normal pressures, the Aquadex FlexFlow may alert and interrupt treatment more often than desired.

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Antecubital Vein

Basilic Vein

External Jugular Vein

Internal Jugular Vein

Femoral Vein

Subclavian Vein

Hand Vein

Lower Arm Vein

Possible Aquapheresis Venous Access SitesPossible Aquapheresis Venous Access Sites

Central Peripheral

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Choosing Venous AccessChoosing Venous Access

It is imperative that the required blood flow set on the machine matches that which can be delivered using the chosen catheter / catheter lumen (i.e. catheter flow rating).

For more information on choosing a catheter and setting the blood flow, press HELP from STOP mode and select the appropriate menu item.

For a complete view of the most appropriate catheter and blood flow selection, refer to the latest version of the Aquadex Catheter Compatibility Guide.

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Setting the Blood FlowSetting the Blood Flow

Using the BLOOD FLOW key, , users can set the blood flow from 10 to 40 mL/min in increments of 5 mL/min. Default is 40 mL/min.

Therefore, if users do not set blood flow to something, the console will operate just as it did before. That’s why it’s considered optional.

• Pressing the BLOOD FLOW key• Press Arrow UP or DOWN key to set a desired value• Press ACCEPT

With this feature, our users can set the blood flow that is best for the chosen patient and the chosen venous access catheter.

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Setting the Blood FlowSetting the Blood Flow

Getting good venous access FIRST is still ESSENTIAL to successful therapy but, users can adjust blood flow to possibly reduce blood flow alarms and possibly use venous access sites and catheters not available before.

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TroubleshootingTroubleshooting

The Aquadex FlexFlow displays helpful information and suggests remedies to correct alarms/alerts that it may experience during treatment.

The usual troubleshooting procedure is:

1.Press the alarm mute key (mutes for 2 minutes).

2.Read and follow the instructions displayed.3.When corrected, press the Clear key to clear

screen and alarm to continue.4.If further information is needed, refer to the

Aquadex FlexFlow User’s Guide and/or call customer service (1-866-709-4030)

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Ultrafiltration/Ultrafiltration/Aquapheresis Aquapheresis

Clinical Evidence and Clinical Evidence and Background Background

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Clinical trials of Ultrafiltration in HF Clinical trials of Ultrafiltration in HF Study NameStudy Name

Study Type & Study Type & Inclusion CriteriaInclusion Criteria

PtsPts Conclusion(s)Conclusion(s)

UNLOADUNLOAD 20062006

Randomized, Randomized, multicenter, multiple multicenter, multiple substudies, aquapheresis substudies, aquapheresis vs. standard therapy vs. standard therapy (diuretics)(diuretics)

100 / 100 / 100100

Enrollment complete, publications expected early 2006Enrollment complete, publications expected early 2006

Costanzo, J Am Coll Costanzo, J Am Coll Cardiol Cardiol 2005;46:2047-51.2005;46:2047-51.

Prospective, case series, Prospective, case series, Early UF in Diuretic Early UF in Diuretic Resistant + CRSResistant + CRS

1919 EEarly treatment strategy with aquapheresis effectively and safely arly treatment strategy with aquapheresis effectively and safely decreases length of stay and readmissions. Clinical benefits persist at 3 decreases length of stay and readmissions. Clinical benefits persist at 3 months after treatment.months after treatment.

Bart, J Am Coll Bart, J Am Coll Cardiol Cardiol 2005;46:2043-46.2005;46:2043-46.

Randomized, Early UF Randomized, Early UF vs. Diuretics vs. Diuretics

4040 Aquapheresis is effective, safe and can be applied in a variety of Aquapheresis is effective, safe and can be applied in a variety of community-based hospitals. Cumulative fluid removal after is greater community-based hospitals. Cumulative fluid removal after is greater than that achieved by aggressive use of diuretics and is not associated than that achieved by aggressive use of diuretics and is not associated with adverse hemodynamic or laboratory sequelae.with adverse hemodynamic or laboratory sequelae.

Jaski B Current Heart Jaski B Current Heart Failure Reports Failure Reports 2005, 2005, 2:2:148–154.148–154.

Review, summary of Review, summary of recent clinical work.recent clinical work.

---- Compared with diuretics, ultrafiltration provides a more predictable Compared with diuretics, ultrafiltration provides a more predictable and safer way to achieve euvolemia with minimal electrolyte and safer way to achieve euvolemia with minimal electrolyte abnormalities and neurohormonal activation. The emerging familiarity abnormalities and neurohormonal activation. The emerging familiarity and ease of use of ultrafiltration suggests that in the future this will be and ease of use of ultrafiltration suggests that in the future this will be an important therapy for the treatment of acute and chronic volume an important therapy for the treatment of acute and chronic volume overload associated with decompensated heart failure.overload associated with decompensated heart failure.

Saltzberg, J Heart Lung Saltzberg, J Heart Lung Transpl, 2005, Vol. 24, Transpl, 2005, Vol. 24, Issue 2 Suppl S130 270Issue 2 Suppl S130 270

Prospective, case series, Prospective, case series, Early UF in Diuretic Early UF in Diuretic Resistant + CRSResistant + CRS

1010 Aquapheresis in acutely decompensated HF pts mediates significant Aquapheresis in acutely decompensated HF pts mediates significant and sustainable reductions in pt weight, cardiac filling pressures and and sustainable reductions in pt weight, cardiac filling pressures and LAVI as well as marked improvements in SV and MR severity.LAVI as well as marked improvements in SV and MR severity.

Sheppard, J Card Fail. Sheppard, J Card Fail. 2004 Oct;10(5):380-32004 Oct;10(5):380-3

Retrospective, case Retrospective, case series, FC III-IV, series, FC III-IV, Intermittent outpatient Intermittent outpatient UFUF

1919 Our study suggests that UF is a safe, feasible therapy and has the Our study suggests that UF is a safe, feasible therapy and has the potential for offering another important therapeutic option for patients potential for offering another important therapeutic option for patients with severe and refractory CHFwith severe and refractory CHF

6363

Clinical trials of Ultrafiltration Clinical trials of Ultrafiltration in HF in HF

Study NameStudy NameStudy Type & Study Type &

Inclusion CriteriaInclusion CriteriaPtsPts Conclusion(s)Conclusion(s)

Saltzberg, J Card Failure Saltzberg, J Card Failure Vol. 9 No. 5 Suppl. 2003 Vol. 9 No. 5 Suppl. 2003 S46 163S46 163

Prospective, case series, Prospective, case series, FC III-IV, Diuretic FC III-IV, Diuretic Resistant Resistant

2525 1) Safely and effectively removes large volumes of excess fluid 2) 1) Safely and effectively removes large volumes of excess fluid 2) Produces significant symptomatic and functional improvement 3) Produces significant symptomatic and functional improvement 3) Reduces neurohormonal activation and 4) Reduces LOS by almost 2 Reduces neurohormonal activation and 4) Reduces LOS by almost 2 days compared to that observed nationally in DHF patients receiving days compared to that observed nationally in DHF patients receiving conventional heart failure treatment.conventional heart failure treatment.

Raman, Int J Artif Organs. Raman, Int J Artif Organs. 2003 Aug;26(8):753-72003 Aug;26(8):753-7

Randomized, case series, Randomized, case series, CV Surg CV Surg

61/5761/57 Hemofiltration during CPB attenuates postoperative anemia, Hemofiltration during CPB attenuates postoperative anemia, thrombocytopenia and hypoalbuminemia, may reduce post-operative thrombocytopenia and hypoalbuminemia, may reduce post-operative bleeding and appears to decrease post-operative pulmonary bleeding and appears to decrease post-operative pulmonary complications.complications.

Jaski, Journal of Cardiac Jaski, Journal of Cardiac Failure 2003 9(3);227-231Failure 2003 9(3);227-231

Prospective, case series, Prospective, case series, FC IIIFC III

2121 Rapid removal of extracellular and intravascular fluid volume excess Rapid removal of extracellular and intravascular fluid volume excess can be safely achieved via peripherally inserted ultrafiltration without can be safely achieved via peripherally inserted ultrafiltration without the need for central venous catheter placement.the need for central venous catheter placement.

Marenzi, J Am Coll Cardiol Marenzi, J Am Coll Cardiol 2001;38:4:963-9682001;38:4:963-968

Prospective, case series, Prospective, case series, FC IIIFC III

2424 In patients with rCHF, subtraction of plasma water by UF is associated In patients with rCHF, subtraction of plasma water by UF is associated with hemodynamic improvement. Hypotension does not occur when with hemodynamic improvement. Hypotension does not occur when plasma refilling rate is adequate to prevent hypovolemiaplasma refilling rate is adequate to prevent hypovolemia

Canaud, Nephrol Dial Canaud, Nephrol Dial Transplant 1998 13Transplant 1998 13 [Suppl 4]:51-55[Suppl 4]:51-55

Prospective, Severe Prospective, Severe CHF, class IVCHF, class IV

5252 Veno-venous ultrafiltration has the potential to block the deleterious Veno-venous ultrafiltration has the potential to block the deleterious effects of the cardiac and renal interactions secondary to severe CHF. effects of the cardiac and renal interactions secondary to severe CHF. In a significant proportion of patients, it improves cardiac performance In a significant proportion of patients, it improves cardiac performance and a number of clinical parameters.and a number of clinical parameters.

Blake, Blake, Adv Ren Replace Adv Ren Replace Ther. 1996 Apr;3(2):166-73Ther. 1996 Apr;3(2):166-73

Referenced summary of Referenced summary of clinical work to date.clinical work to date.

---- UF relieves pulmonary edema, reduces ascites and peripheral edema, UF relieves pulmonary edema, reduces ascites and peripheral edema, enhances the response to subsequent diuretic therapy, improves overall enhances the response to subsequent diuretic therapy, improves overall volume status, normalizes filling pressures, and reduces clinical volume status, normalizes filling pressures, and reduces clinical symptoms, and offers an improvement in overall quality of life.symptoms, and offers an improvement in overall quality of life.

Agostoni, Am J Med. 1994 Agostoni, Am J Med. 1994 Mar;96(3):191-9Mar;96(3):191-9

Randomized, UF vs. IV Randomized, UF vs. IV bolus Lasixbolus Lasix

8/88/8 After ultrafiltration, the favorable circulatory and ventilatory After ultrafiltration, the favorable circulatory and ventilatory adjustments consequent to the reabsorption of lung water improved the adjustments consequent to the reabsorption of lung water improved the functional capacity of these patients. The improvement continued 3 functional capacity of these patients. The improvement continued 3 months after the proceduremonths after the procedure

6464

Clinical trials of Ultrafiltration Clinical trials of Ultrafiltration in HF in HF

Study NameStudy NameStudy Type & Study Type &

Inclusion CriteriaInclusion CriteriaPtsPts Conclusion(s)Conclusion(s)

Pepi, Br Heart J. 1993 Pepi, Br Heart J. 1993 Aug;70(2):135-40.Aug;70(2):135-40.

Randomized, controlled Randomized, controlled FC II-IIIFC II-III

12/1212/12 In the ultrafiltration group, variations in the ventricular filling pattern, In the ultrafiltration group, variations in the ventricular filling pattern, lung water content, and functional performance persisted for three lung water content, and functional performance persisted for three months in all cases. None of these changes was detected in the control months in all cases. None of these changes was detected in the control group.group.

Agostoni, J Am Coll Agostoni, J Am Coll Cardiol. 1993 Feb; Cardiol. 1993 Feb; 21(2):424-3121(2):424-31

Randomized, Randomized, controlled, FC II-IIIcontrolled, FC II-III

18/1818/18 In patients with moderate congestive heart failure, ultrafiltration In patients with moderate congestive heart failure, ultrafiltration reduces the severity of the syndrome.reduces the severity of the syndrome.

Marenzi,, Am J Med. 1993 Marenzi,, Am J Med. 1993 Jan;94 (1):49-56Jan;94 (1):49-56

Prospective, class II - Prospective, class II - IVIV

3232 Refractory CHF requires the interruption of the humoral-hemodynamic Refractory CHF requires the interruption of the humoral-hemodynamic vicious circle, and ultrafiltration is able to accomplish that.vicious circle, and ultrafiltration is able to accomplish that.

Susuni, Crit Care Med Susuni, Crit Care Med 1990; 18:14-181990; 18:14-18

Prospective, FC IV, Prospective, FC IV, diuretic resistantdiuretic resistant

2020 UF may be considered an effective tool for the treatment of acute UF may be considered an effective tool for the treatment of acute pulmonary edema refractory to drug therapy, as an alternative to pulmonary edema refractory to drug therapy, as an alternative to mechanical ventilation, and as a remedy for excessive extravascular mechanical ventilation, and as a remedy for excessive extravascular lung water.lung water.

Rimondini, Am J Med. Rimondini, Am J Med. 1987 Jul;83(1):43-81987 Jul;83(1):43-8

Prospective, case series, Prospective, case series, FC IV, diuretic resistantFC IV, diuretic resistant

1111 Hemofiltration promoted relief of dyspnea and of clinical and Hemofiltration promoted relief of dyspnea and of clinical and radiographic evidence of lung congestion and pleural effusion, and radiographic evidence of lung congestion and pleural effusion, and substantially reduced the dependent edema and abdominal girthsubstantially reduced the dependent edema and abdominal girth

Fauchald, Acta Med Fauchald, Acta Med Scand. 1986;219(1):47-52Scand. 1986;219(1):47-52

Prospective, case series, Prospective, case series, FC III-IV, diuretic FC III-IV, diuretic resistantresistant

66 Ultrafiltration is a safe method of fluid removal in patients with Ultrafiltration is a safe method of fluid removal in patients with therapy-resistant cardiac edema and can be used as preparation for therapy-resistant cardiac edema and can be used as preparation for cardiac catheterization or surgery.cardiac catheterization or surgery.

6565

Clear, Beneficial Hemodynamic Clear, Beneficial Hemodynamic Effects of UF In CHFEffects of UF In CHF

Marenzi et.al. 2001

6666

Changes in Plasma Volume and Changes in Plasma Volume and Refilling Rate During UFRefilling Rate During UF

Marenzi GC et al. JACC 2001; 38: 963-968

6767

Aquapheresis and Aquapheresis and Aquadex FlexFlow Aquadex FlexFlow

Certification ProgramCertification Program

Certificate of Completionis hereby granted to:

for completing the Aquapheresis and Aquadex FlexFlow Certification

Program

CHF Solutions, Inc. Date

Paul A. Sobotka, MD, Chief Medical Officer CHF Solutions,

Inc.

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