Technologies designed to help improve patients outcome

Cyrus M. Calud, DVM, RN

Key challenges in ESRD patients‘ management

Patient outcome

Systemic Inflammation

Response

Cardiovascular Remodelling

Malnourishment /Malnutrition

Patient outcome and dialysis dose

The main aims of dialysis treatment are to prolong patient survival, reduce morbidity and improve quality of life. However, despite many technical advances made over the last few years, morbidity and mortality of dialysis patients remain unacceptably high and their quality of life is often poor. . National Institute of Diabetes, Digestive, Kidney Diseases. (USRDS 2002 annual data report:

atlas of end-stage renal disease in the United States. Bethesda, MD, USA, 2002)

The delivered dose of dialysis can affect morbidity and mortality of dialysis patients . (Port FK, Ashby VB, Dhingra RK, Roys EC, Wolfe RA. Dialysis

dose and body mass index are strongly associated with survival in hemodialysis patients. J Am Soc Nephrol 2002; 13: 1061–1066)

Patient outcome and dialysis dose

Relative risk of death (patients’ survival) improved with higher dialysis dose (Kt/V)

Improved EPO dose response with higher Kt/V

Morbidity, number of days in the hospital and cost of hospitalization are reduced with higher Kt/V

Shinzato et al Kidney Int 1999; 55: 700-712

E. Movilli, R. Maiorca et.al ,NDT:2001(16):111-114

F.K. Port et al. JASN 13:1061-1066, 2002

A. Sehgal et al. AJKD Vol 37, No 6 2001:pp 1223-1231

Dialysis Outcome Initiative, Practical Guidelines, Am J Kidney Dis, 37 (Suppl 1), 2001

Today´s recommendations for dialysis dose:

Adult non-diabetics:

minimal delivered dose spKt/V = 1.2 (Single Pool Variable Volume)

minimal prescribed dose spKt/Vurea = 1.3 (SPVV)

Adult diabetics:

minimal required dose spKt/Vurea = 1.4 - in discussion, but not officially recommended

Guideline II.1.3

Based on the available evidence the minimum prescribed HD dose per

session for a thrice-weekly schedule should be:

• urea eKt/V 1.20

• (sp Kt/V 1.4)

EBPG Expert Group,NDT, Vol 17 (2002) Suppl. 7

European Best Practice Guidelines

Guideline 2 - Regular Measurement of the Delivered

Dose of Hemodialysis (Evidence)

• The dialysis care team should routinely measure and

monitor the delivered dose of hemodialysis

• The delivered dose of HD should be measured at

regular intervals no less than monthly.

• The dose can be measured more frequently by using

on-line methods (conductivity or ionic)

Frequency of Measurement

Measure of dialysis dose in practice URR

- not all patients are able to afford blood tests on a monthly basis; not all computes regularly for URR

URR=100 ×(1 - Ct/C0) (2) in which Ct is the postdialysis BUN and C0 is the predialysis BUN.

Kt/V

- not all RNs are interested to calculate the Kt/Vurea of patients

Kt/V = -Ln(R - 0.008 × t)+(4 - 3.5 ×R) ×UF/W (1)

in which Ln is the natural logarithm; R is the postdialysis BUN ¸ predialysis BUN; t is the dialysis session length in hours; UF is the ultrafiltration volume

in liters; and W is the patient’s postdialysis weight in kilograms

There is a readily available technology for us…

The use of OCM has been validated and approved by CPGs

400

Electrolyte Clearance versus Urea

Clearance electrolyte clearance [ml/min] aqueous solutions

urea clearance [ml/min] Steil H, et.al. ASAIO Trans 1993;39:M348-52

Urea Clearance from blood samples [mL/min]

Electrolyte- Clearance [mL/min]

Kuhlmann U, Goldau R, Samadi N, Graf T, Orlandini G, Lange H: Accuracy and

safety of online clearance monitoring based on conductivity variation. Abstr. EDTA

1999, 249

Blood samples (expensive) Kt/V > 1.2 ...1.8

Dialysate; K and t, (no additional costs)

Monthly / quarterly Frequency In every session

Retrospective Quality Control Continuous, online

Staff, syringes, lab time cost and energy Effort None

Inconvenient Handling Automatic

The conventional procedure today Aspects With OCM option

Accuracy of K 6-8% 5%

Impractical and uncommon

Quality assurance Standard!

Comparison of two techniques

• No additional disposables or reagent (no additional cost)

• Non invasive, One touch operation: extremely easy to use

• Continuous and real time monitoring of k, kt (and calculated kt/v)

• Continuous and real time estimate of plasma sodium concentration

• Effective quality assurance tool verifying delivered dialysis dose each and all

dialysis sessions

• Intradialytic adjustment of treatment allows delivery of individualized dialysis

Online Clearance Monitor (OCM®)

Online Clearance Monitor (OCM ®)

•At effectively no additional work or cost we have a useful Quality Monitoring (QM) measure (Kt/V) for every (100%) of dialysis sessions.

• It is however recommended that the OCM® Kt/V be checked from time to time using standard laboratory methods.

Issues in Clinical Practice – Nutrition

Malnutrition is a common among ESRD.

Around 10% are severely malnourished, and another 33% are moderately malnourished (Maroni BJ. Nutrition and renal disease. In: Greenberg A, ed. Primer on

kidney diseases. San Diego, CA: Academic Presss; 1998:443.)

Moderate to severe malnutrition leads to weight loss and changes in body composition, (reduced fat and muscle mass and an increase in total body fluids (TBW), specifically extracellular water (ECW).

Causes may include inadequate dialysis, decreased protein and caloric intake due to loss of appetite, loss of amino acids in the dialysate, inflammation, catabolic factors and comorbid conditions (Kamyar Kalantar-Zadeh et.

alAmerican Journal of Kidney Diseases, Vol 42, No 5 (November), 2003: pp 864-881)

Malnutrition leads to increased mortality and morbidity

Assessment of nutritional status Combination of science and an art

Procedure Advantage Disadvantage

Subjective Global Assessment

Simple in principle and to

perform

Requires time, expertise, and experience Inter-observer variance

Anthropometric measurement

Laboratory tests (Biochemistry)

Accurate

Confounders in lab results Requires scheduling Costly

Dual Energy X-Ray Absorptiometry (DEXA)

Subjective Global assessment

Issues in Clinical Practice – Fluids

One of the fundamental, yet most problematic, components of the dialysis prescription is the patient’s estimated dry weight (EDW) “The dry weight of each patient must be determined on trial-and error

basis” (Daugirdas, Blake, and Ing 2001) and is ideally evaluated every 2 weeks

Sodium and volume excess is the predominant factor in the pathogenesis of hypertension in dialysis patients leading to structural changes of the heart muscles and blood vessels – called cardiovascular remodeling

LVH is a strong and independent risk factor for cardiovascular morbidity and

mortality, is seen in more than 60% of end-stage renal disease patients.

The Mortality Risk of OH in HD Patient

Survival was retrospectively assessed in 269 prevalent HD patient from 3 European centers (Germany and Polland) after a follow-up at least 3.5 years

The study indicate that HS is an important and independent predictor of mortality in Chronic HD patients

OH<2.5 L ECW of ≤14%

20 40 60 Months

1

0.8

0.6

0.4

Surv

ival

OH>2.5 L ECW of ≥15%

p=0.023

• Hyperhydrated (n=58) • nomohydrated (n=211)

V Wizeman et al. Nephrol Dial Transplant 2009: 24; 1574-1579

Assessment of fluid status

Combination of science and art

Procedure Advantage Disadvantage

Physical assessment

Cheap Immediate Universally available

Requires, expertise, experience, and prone to variation between observers

Chest X - ray Accurate Scheduling time Requires expertise Radiation exposure cost

Ultrasound

Fluid Status Assessment

Road blocks in achieving normovolemia Defining “dry weight” (normovolemia)

Clinical assessment is insensitive and inadequate

We need “tools” to improve diagnostic sensitivity

Achieving “dry weight” (normovolemia) Ultrafiltration (UF) intolerance is increasingly a problem

We need “tools” to improve UF tolerance Reduce UF requirement (a salt-intake issue)

Improve hemodynamic stability (address issues such as thermal homeostasis)

Understanding capillary refilling capacity of the patient

Limitations of current assessment approaches

Nutrition

- Cannot differentiate fats from muscles

- Difficult to assess if weight gain is due to fat, muscles, or fluid

Fluid

- Cannot identify ECF/ICF

- Cannot determine accurate overhydration volume

Risk factors confronting dialysis patients

Risk Factors

Inflammation

intake of nutrient

Loss of appetite

protein catabolism

Hyperparathyroidism

Insulin resistance

etc………

Salt intake

Sodium overload

Fluid intake

Failure diagnose hypervolemia

Failure achieve normovolemia

Antihypertensive medications

etc………….

Cardiovascular Risk Factors Nutritional Risk Factors

Volume Overload

Hypertension LVH CVD

Malnutrition

( fat/muscle mass ECV)

Mortality Risk of CKD patients

Available technologies that may help improve patients outcome

Selected Factors Selected Technology

Nutritional Status

Volume and Salt overload &

Hypertension

Intradialytic Hypotension

Body composition assessment

- Body composition Monitor

Biofeedback Control

- Blood Volume Monitor (BVM)

- Blood Temperature Monitor (BTM)

Fluid Assessment

- Body Composition Monitor (BCM)

Body Composition Monitor (BCM)®

The BCM measures and calculates

Overhydration pre-dialysis

Overhydration post-dialysis

Body Mass Index (BMI)

Lean Tissue Index

Fat Tissue Index

Lean Tissue Mass

Relative Tissue Mass

Body Cell Mass

Adipose Tissue Mass

Fat Mass

Relative Fat Mass

Extracellular:Intracelluar Ratio

Extracelluar water

Intracellular water

Total Body Water

BCM and patient management

http://www.bcm-fresenius.com/20.htm

The Body Composition Plot displays the development of the three compartments adipose tissue mass (ATM), lean tissue mass (LTM) and overhydration (OH) over time. In addition, the systolic blood pressure (BP sys) can be displayed, which allows the influence of overhydration on blood pressure to be identified. It is also easy to observe changes in LTM, ATM and the subsequent influence on overhydration. For a more detailed analysis of overhydration, please refer to the Overhydration Plot. The body composition can be viewed in more detail in the LTI FTI Plot.









The patient´s fluid status can be examined in more detail using the Overhydration Plot. The plot also provides

post treatment overhydration which can be used to monitor changes in weight gain. Data can be easily

compared against the green region representing the reference range of a healthy population.









It is well known that overhydration can lead to hypertension. However, underlying comorbidities can radically influence this

relationship in individual patients.

The Hydration Reference Plot combines overhydration and systolic blood pressure in one graph.

It helps to assign patients to different regions regarding blood pressure and overhydration, which partly require different

therapy approaches.





The BP pre Plot depicts the systolic and diastolic blood pressure before dialysis. The green area identifies the systolic reference

area for a healthy population according to WHO standards. The green line at 70 mmHg marks the critical lower limit for the

diastolic blood pressure.






This plot combines information about overhydration together with the patient's nutritional status. The green area

indicates the reference area of a normal population with healthy kidneys (10th and 90th percentile).





Caveat The BCM - Body Composition Monitor performs whole body measurements

between hand and foot and therefore cannot assess regional differences in body composition and fluid status. The device only detects interstitial fluid - a volume of fluid with a large cross-sectional area has little influence on the whole body impedance.

Body Composition Monitor has no approval for ICUs (electrical safety, conformity), but this will be realized in the future.

Body Composition Monitor cannot be used in patients with stents or pacemakers (defibrillators) for safety reasons. Performance can be affected by artificial joints, pins or amputations.

Use the BCM in conjunction with your physical assessments and laboratory values!





Physiological Modules

Biofeedback

mechanism that

responds to

patient’s

tolerance to

ultrafiltration

Blood Volume Monitor

Ultrafiltration and Hemodialysis

Blood volume reduction induced by ultrafiltration

Critical vascular refilling during ultrafiltration

BV = UFR - VRR

Interstitial Fluid Space Vascular Space

Critical!!!

Vascular Refilling Rate

UF Rate > VR Rate HYPOVOLEMIA

The Blood Volume Monitor (BVM®)

The BVM monitors the changes of the relative blood volume during the dialysis treatment.

The goal is to prevent excessive fluid removal, resulting drop in blood pressure (hypotension)

The BVM® control is performed in three zones:

Green zone (Non-critical Zone) • No control performed by the BVM.

Yellow zone (Control Performed) • The BVM prevents the blood volume from decreasing into the crit. RBV zone.

• If the RBV increases - the UFR will be raised again.

• If the RBV reaches the dashed line, the message "Achieving the UF goal is

uncertain“ will be displayed during the first half of the volume.

Red zone (Critical Zone) • The UFR is reduced up to 0ml/min. If the RBV increases the UFR will be raised again.

Blood Volume Monitor (BVM®)

Reduced intradialytic complications

Hypotensive episodes and the need for nursing interventions were significantly reduced when BVM-controlled Uf was compared to standard UF.

Improved Ultrafiltration tolerance, Less Hypotensive Episodes with Blood Volume Control

Ronco C et al Kidney Int 2000; 58: 800-808

Boer et al. Nieren und Hochdruckkrankh 31: 435, 2002

Added value (beyond hemodynamics)

Estimates of blood hemoglobin and hematocrit

Estimates! But as a tracking method reliable for direction and rate of change where validated at certain frequency against lab values

“calibrate” for each patient

In the era of EPO treatment and requirement for frequent monitoring

Frequent “nonlab” noninvasive estimates of Hb and/or HCT

Cost-offset?

Assists in the estimation/determination of EDW

Blood Temperature Monitor

Diurnal Variation in Body Temperature Healthy Individuals versus HD Patients

*P<0.001 vs. 3:30-4:30 group

34

34.5

35

35.5

36

36.5

37

37.5

38

6 am 12 am 4 pm 6:30-

7:30

am

10:30-

11:30

am

3:30-

4:30

pm

* *

Ave

rag

e T

em

pe

ratu

re º

C

Healthy individuals HD pts.

Pergola PE, Habiba NM, Johnson JM, Am J Kidney Dis. 2004 Jul;44(1):155-165 Mackowiak PA, Wasserman SS, Levine MM, JAMA. 1992 Sep 23-30;268(12):1578-1580

Ora

l te

mp

era

ture

be

fore

dia

lysis

(ºC

)

Observations Pergola PE, Habiba NM, Johnson JM, Am J Kidney Dis. 2004 Jul;44(1):155-165

Oral Predialysis Temperatures of 75 Patients

N = 75 patients

3 measurement same week

Fixed Dialysate

Tº36.5 ºC

High Dialysate Temperatures Cause Haemodynamic Instability (e.g. Dialysate 37.5ºC vs. 35.5ºC )

Literatures: Ayoub A, Finlayson M, Nephrol Dial Transplant. 2004; 19(1):190-4

Fine A, Penner B, Am J Kidney Dis. 1996; 28(2): 262-5

Maggiore Q et al, Int J Artif Organs. 1995; 18(9): 518-25. Review.

Jost CM et al, Kidney Int. 1993 Sep; 44(3): 606-12

Kerr PG, van Bakel C, Dawborn JK., Nephron. 1989; 52(2): 166-9

Marcen R et al, Nephron. 1988; 49(1): 29-32

Bazzato G et al, Kidney Int Suppl. 1985; 17: S161-5

Sherman RA et al, Am J Kidney Dis. 1985; 5(2): 124-7

Pizzarelli F et al, Int J Artif Organs. 1983; 6(1): 37-41

Coli U, et al, Trans Am Soc Artif Intern Organs. 1983; 29: 71-5

Maggiore Q et al, Trans Am Soc Artif Intern Organs. 1982; 28: 523-7

Maggiore Q et al, Proc Eur Dial Transplant Assoc. 1981; 18: 597-602

Prepared by: Khoji Lugasan

Conflicting physiological control mechanism in hemodialysis patients’

Ultrafiltration Symptomatic

Hypotension

Blood volume

Total peripheral resistance

VASOCONSTRICTION

Blood flow to skin

Retain heat

Surface heat loss

Surface heat loss

Blood flow to skin

VASODILATION

Total peripheral resistance

Core temperature

+ body heating by

Dialysate temperature

CONFLICT

Gotch et al ASAIO Trans 35:622-24, 1989

Biofeedback Control

Patient

responds to

changes in

treatment Temperature

Arterial

Temperature

Venous

Heater

control

Patient

BTM

Hydraulic system

Dialyzer

Drain

CHANGE DIAL T IN DIRECTION TO

DESIRED EFFECT

READ DIAL T READ VEN T

READ ART T

READ ART T SET DESIRED

EFFECT


Study done on the use of BTM The BTM monitors and regulates changes in core body temperature to

prevent temperature-induced changes in vascular tone.

It provides the active control necessary to stabilise body temperature, and reduces the frequency of haemodialysis sessions with hypotensive episodes.

Maggiore Q et al, Am J Kidney Dis. 2002 Aug;40(2):280-290

Studies with BTM demonstrate evidence for the maintenance of body temperature and BP during HD

Barendregt JN, et al, Kidney Int. 1999 Jun;55(6):2598-608

Kaufman AM, et al, .J Am Soc Nephrol. 1998 May;9(5):877-883

Maggiore Q et al, Am J Kidney Dis. 2002 Aug; 40(2):280-290

Van der Sande FM, et al, Am J Kidney Dis. 1999 Jun;33(6):1115-1121

Tart begin of dialysis

Tart end of dialysis

Tart begin of dialysis

Tart end of dialysis

Isothermic/cold

dialysis

Conventional

dialysis

Hemodynamic

stability Maggiore 2002 v.d. Sande 1999 Barendregt 1999 Kaufmann 1998

Temp. (ºC)

n=95 n=12 n=9

n=15

37.5

37.0

36.5

36.0

35.5

35.0


Additional function of BTM

Thermodilution Methods for Access

& Cardiopulmonary Recirculation

measurement


Existing technologies for better patient outcome

On-line Hemodiafiltration

– maximizes diffusive and convective therapy for wider range of solute

removal

- reduction of pro-inflammatory cytokines

Ultrafilter and modern Water Treatment System, for utrapure water and ultrapure dialysate

- reduce treatment bioincompatibility thus reduction of inflammatory

response

Polysulfone dialyzer

- for biocompatible treatment, reduction of inflammatory response

Putting it all together

Online Clearance Monitor

(OCM)

Body Composition Monitor

(BCM)

Blood Volume Monitor

(BVM)

Blood Temperature Monitor

(BTM)

Positive patient outcome

Thank you!

“Will entertain queries now”...

Documents

Technologies designed to help improve patients outcome