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Relative Blood Volume
Monitoring and
Applications in Dialysis
Christos Argyropoulos MD, PhD FASN
Division of Nephrology, University of New Mexico
Disclosures
• Nothing to disclose
Learning Objectives
• Understand the physiologic principles of R(elative)
B(lood) V(olume) monitoring
• Describe compartmental fluid shifts and RBV
profiles in relationship to the Guyton Curve
• Evidence supporting the use of RBV for
• BP management in ESRD
• Setting the target EDW in dialysis patients
• RBV in acute dialysis settings
Physiologic Principles of
Real Time RBV
monitoring
Non Invasive Vascular Monitoring:
the “critline”
• Continuous Hct
• Continuous BV change
• Continuous O2 saturation
• Recirculation
• Access Blood Flow
• (Overload) Remove more fluid without Intradialytic
Morbidity
• (Dehydration of Intravascular space)
Remove fluid without Intradialytic Morbidity
• (Hypoxemia) Ability to Determine and Treat
Hypoxemia in HD patients
• (ABF) Access Blood Flow measurements (not going to
be discussed)
Potential Applications of Crit-Lines
Emitter
Blood Flow
Blood
Chamber
Detector
Crit-Line Monitor Technology
Crit-Line vs Coulter Counter
5 10 15 20 25 30 35 40 45 50 55 60 65
5
10
15
20
25
30
35
40
45
50
55
60
65
Coulter Counter Hct
Crit-LineHct
R = .998
SD = ± 1.04
n = 52
O2 Saturation Accuracy
IL-482 Co-Oximeter
Crit-LineO2
Total Blood
Volume (BV)
Red Cell
Volume
(RCV)
Test tube represents
circulating blood volume
Hct =
RCV
BV
Plasma
Volume
Fundamental Parameter: Hematocrit (Hct)
0 1 2 3 4
0
-5
-10
-15
-20
-25
27
29
31
33
35
%BV(Loss)
Hct
Hct =
RCV
BV
X 100
Hematocrit and Blood Volume
∆𝑅𝐵𝑉 =
𝐶0
𝐶 𝑡
−1 × 100%
HCT Thresholds, RBV
profiles and non-invasive
monitoring of
compartmental fluid shifts
2
Intra-
cellular
Space Extra-
cellular
Space
Intra-
Vascular
Space
Circulating
Blood Volume
Toxins
Fluid
Toxins
Fluid
Toxins
Fluid
Dialyzer
Three Compartment Model
23 Liters 17 Liters 5 Liters
BVM Profile Screen
Fluid Removal Profiles
0
1
2
3
4
5
6
7
8
5 10 15 20 25 30 35 400
Adapted from Guyton, AC:
Textbook of Medical Physiology, 1991, pg.324
Normal
Death
Hypovolemia
C
B
AEdema
BloodVolume(liters)
Extracellular Fluid Volume (liters)
Shift
Due
to:
Low O2
Meds
UFR
Na+
Temp
Posture
TIME 03:37 HCT 30.7 BV - 0.0 SAT 94
-20
0
-10
5
BV
BV Profile A
TIME 03:20 HCT 34.7 BV -12.6 SAT 94
-20
0
-10
5
BV
BV Profile C
TIME 3:08 HCT 37.4 BV -18.4 SAT 91
-20
0
-10
5
BV
BV Profile B
0
1
2
3
4
5
6
7
8
5 10 15 20 25 30 35 400
Adapted from Guyton, AC:
Textbook of Medical Physiology, 1991,
pg.324
Normal
Death
A
Edema
BloodVolume(liters)
Extracellular Fluid Volume (liters)
TIME 03:25 HCT 31.2 BV 0.2 SAT 98
-20
0
-10
5
BV
PROFILE A: < 3% RBV/hour
0
1
2
3
4
5
6
7
8
5 10 15 20 25 30 35 400
Adapted from Guyton, AC:
Textbook of Medical Physiology, 1991, pg.324
Normal
Death
BBloodVolume(liters)
Extracellular Fluid Volume (liters)
TIME 03:25 HCT 34.7 BV -17.3 SAT 94
-20
0
-10
5
BV
PROFILE B: < 3 to 8% RBV/hour
%BV
1 2 3 4
-20
-10
0
5
A -3 to -8% slope in BV per hour (a “B” profile) is generally safe for patients who
have a urinary output of less than 1000 mls per day – unless they reach their
HCT Threshold
Exceptions to the 3-8% RBV profile
Minimal changes in HCT (a flat line) are also
acceptable when the patient is:
• Near HCT threshold
• UFR at minimum (<300-400 ml. per hour)
• Polyuric renal failure (why?)
• Diarrhea (why?)
• Little or no wt gain (assuming their EDW has been
correctly set)
• Double Amputee (why?) or Poor Ejection Fx (why?)
Intradialytic Hypotension and the “C”
profile
Time (hours)
%BV
SystolicBloodPressure


  


  
 
0 1 2 3 4
0
10
-10
-20
-30
0
25
50
75
100
125
150
UFR = 1428 ml/hr



UF Off
BP cuff: post- facto measurement RBV : predictive measurement
HCT Threshold
• Definition: The HCT at which the patient experiences
symptoms of morbidity.
• Maximum degree of hemoconcentration ( UFR) a patient may
tolerate before symptoms occur
• Rule of thumb…. Until you establish a Threshold
set the HCT Limit at 15% of the starting HCT.
• Review it every 3 weeks: it can change as the RBC mass
changes with EPO titration.
Just because a patient “Crashes”
It does NOT Mean they are “DRY”!!!
Time (hr)
%BV
1 2 3 4
-20
-10
0
5
8.0 L
Removed
7.0 L
Goal
0 1 2 3 4
Time (hours)
0
10
-10
-20
-30
BVChange(%)
1
2
Refill: An Indicator of Over-hydration
Dynamic crit line monitoring : try to investigate after a crash or when challenging
DRY
WET
Causes of Intradialytic Hypotension
• Posture
• Low O2 saturation
• Medications / Antihypertensives
• Incorrect Ultrafiltration rate
• Hypotonic environment / Hypoalbumemia
• Dialysate at body temperature or warmer: core body heating
• Splanchnic vasodilatation secondary to food ingestion
• Electrolyte / Acid-Base Imbalances
• Severe anemia / Occult hemorrhage
• Unstable cardiovascular status / Arrhythmias / Pericardial
tamponade / MI
• Septicemia
• Dialyzer reaction, Hemolysis and Air embolism
6 reasons for a “wet crash”
• O2 below 90% for Graft
or fistula and below
60% for a CVC
• Position
• UFR higher than plasma
refill
• Medications that cause
vasodilatation
• Temperature
• Hypotonic internal
environment: i.e.: low
Na+
Effects of Intradialytic Hypotension
• Tissue Hypoxia
• Adenosine release causing decrease in PVR
• Changes in Mental status / Seizures / Stroke
• Vision changes
• Silent cardiac ischemia / MI
• Ischemia / Infarct to the gut
• Decrease in Residual Renal Function
• Ischemia = decrease in URR
02 Delivery 20+ % of HD patients have intradialytic
Hypoxemia; up to70% are sleep apneics.
0 1 2 3 4
Time (hours)
80
85
90
95
OxygenSaturation
Sleep Apnea Profile
Sleep
Complimentary Oxygen Delivery Issues
• Oxygen saturation: The percent to which the
hemoglobin is filled with oxygen.
• Must interpret in relationship to HGB / HCT
• 90 to 100% is considered normal for arterial sats:
thru access needles
• > 60 % for mixed venous sats: CVC lines
Oxygen Saturation
Intradialytic Oxygen Therapy
Increasing Oxygen:
• Increases Vascular tone / Vasoconstriction
• Increases Peripheral Vascular Resistance
• Increases Plasma Refill
One of the measures suggested for preventing/treating IDH
Application of RBV for
Fluid, EDW and BP
management in ESRD
Water : The Most Important Uremic Toxin ?
• A patient at their EDW should be:
- asymptomatic and
- normotensive
- on minimum blood pressure medications
- while preserving organ perfusion and
- maintaining existing residual renal
function
Volume Overload Indices In Stable
Hemodialysis Patients
Blood Purif 2013;35:202–208
𝑆𝑙𝑜𝑝𝑒4ℎ =
∆𝐵𝑉 (%/ℎ)
𝑈𝐹(𝐿) 𝑆𝑒𝑠𝑠𝑖𝑜𝑛 𝐷𝑢𝑟𝑎𝑡𝑖𝑜𝑛 (ℎ𝑜𝑢𝑟𝑠)
Curves A,B,C or 1—6 ?
Blood Purif 2013;35:202–208
Curves A,B,C or 1—6?
Blood Purif 2013;35:202–208
Take home points:
• Slope4h : highest dynamic range
• A flat curve is truly a sign of FO
• Only 11% of the variability of the BVM marker can be explained by FO.
Crit-Line Intradialytic
Monitoring Benefit
(CLIMB) Study
J Am Soc Nephrol 16: 2162–2169, 200
Can Crit-Line monitoring
improve fluid removal and
reduce morbidity in ESRD?
CLIMB Study Flowchart and Study
Characteristics
J Am Soc Nephrol 16: 2162–2169, 200
Implementation of the intervention in
CLIMB was variable and inconsistent
J Am Soc Nephrol 16: 2162–2169, 200
Application of RBV did not modify BP in CLIMB
J Am Soc Nephrol 16: 2162–2169, 200
Application of RBV increased mortality
and hospitalizations
J Am Soc Nephrol 16: 2162–2169, 200
Mortality at 6 mo was greater in the Crit-Line than the
conventional monitoring group (8.7 and 3.3%, respectively; P
0.021 by log-rank test).
Using RBV to manage BP & estimated
EDW in stable chronic dialysis patients
Hypertension. 2010;55:305-311
Hypertension. 2009;53: 500–507
Prevalent HD patients (>3 mos on HD) with
interdialytic ambulatory BP > 135/85
Intervention
probed pts EDW
by decreasing
until symptoms
occurred
Using RBV to manage BP & estimated
EDW in stable chronic dialysis patients
Hypertension. 2010;55:305-311
Hypertension. 2009;53: 500–507
When EDW is not probed, pts
w/o change in slope had no
change in BP
When EDW is probed, pts who
go from flap to steep had the
largest, most robust BP changes
“Flat” < 1.33%/hr
Prespecified analysis of a trial in
which change in EDW => affects
slope
Does not establish that tracking of
slope is useful in adjusting dry
weight
Problems with the measurement of RBV
Blood Purif 2012;33:177–182
RBV ≠ Absolute Blood Volume
Fahraeus effect (F-cell) = hematocrit
mixed blood / central hematocrit varies
during HD
• Postural changes in the first 30 mins
• Observed decrease in RBV under-
estimates changes in total blood
volume
? Not as good in preventing
hypotension
? Better at managing overload
RBV and ScvO2 in Acute
Dialysis Settings
RBV Monitoring in Acute Dialysis In the ICU
Kidney International, Vol. 62 (2002), pp. 1075–1080
Only prospective study to date included 20 patients dialyzing in the ICU for a total of
57 treatments (less than 2 weeks worth of data in our service)
?? Any takers for a quality project
RBV Monitoring of Acute Dialysis In the ICU
Kidney International, Vol. 62 (2002), pp. 1075–1080
Access: Catheter
Normal 60-80 %
SvO2
Venous Blood
Lower O2 Saturation
ScvO2
ScvO2
Venous Blood
Lower O2 Saturation
Cardiac Output (L/min) = Oxygen
consumption (ml/minute) Art O2
content - Ven O2 Content
 ScvO2 = CO = BP (BP = CO X PVR)
Continuous monitoring of SvO2 is a
sensitive parameter of cardiac output
C. O. = Heart Rate x Stroke Volume
Nephrol Dial Transplant (2017) 1–
doi: 10.1093/ndt/gfx271
Unanswered questions:
1. could changes in acute patients (dialyzing with CVCs) be inferred to
stand for myocardial stunning?
2. Could we trend SvO2 to prevent IDH in acute dialysis patients?
Conclusions
• The value of RBV monitoring remains highly uncertain
• Inconsistent application of RBV monitoring may even
be associated with worse clinical outcomes
• At present the device seems more able to identify
volume overloaded patients than prevent hypotension
• Standardization of measurements are important given
postural changes around the start of dialysis
• Further studies are needed to probe the utility of other
device channels (e.g. SvO2) in acute and chronic
settings
• Modifications of the standard critline readout to
estimate the absolute blood volume may be useful in
future applications

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Relative Blood Volume Monitoring and Applications in Dialysis

  • 1. Relative Blood Volume Monitoring and Applications in Dialysis Christos Argyropoulos MD, PhD FASN Division of Nephrology, University of New Mexico
  • 3. Learning Objectives • Understand the physiologic principles of R(elative) B(lood) V(olume) monitoring • Describe compartmental fluid shifts and RBV profiles in relationship to the Guyton Curve • Evidence supporting the use of RBV for • BP management in ESRD • Setting the target EDW in dialysis patients • RBV in acute dialysis settings
  • 4. Physiologic Principles of Real Time RBV monitoring
  • 5. Non Invasive Vascular Monitoring: the “critline” • Continuous Hct • Continuous BV change • Continuous O2 saturation • Recirculation • Access Blood Flow
  • 6. • (Overload) Remove more fluid without Intradialytic Morbidity • (Dehydration of Intravascular space) Remove fluid without Intradialytic Morbidity • (Hypoxemia) Ability to Determine and Treat Hypoxemia in HD patients • (ABF) Access Blood Flow measurements (not going to be discussed) Potential Applications of Crit-Lines
  • 8. Crit-Line vs Coulter Counter 5 10 15 20 25 30 35 40 45 50 55 60 65 5 10 15 20 25 30 35 40 45 50 55 60 65 Coulter Counter Hct Crit-LineHct R = .998 SD = ± 1.04 n = 52
  • 9. O2 Saturation Accuracy IL-482 Co-Oximeter Crit-LineO2
  • 10. Total Blood Volume (BV) Red Cell Volume (RCV) Test tube represents circulating blood volume Hct = RCV BV Plasma Volume Fundamental Parameter: Hematocrit (Hct)
  • 11. 0 1 2 3 4 0 -5 -10 -15 -20 -25 27 29 31 33 35 %BV(Loss) Hct Hct = RCV BV X 100 Hematocrit and Blood Volume ∆𝑅𝐵𝑉 = 𝐶0 𝐶 𝑡 −1 × 100%
  • 12. HCT Thresholds, RBV profiles and non-invasive monitoring of compartmental fluid shifts
  • 15. Fluid Removal Profiles 0 1 2 3 4 5 6 7 8 5 10 15 20 25 30 35 400 Adapted from Guyton, AC: Textbook of Medical Physiology, 1991, pg.324 Normal Death Hypovolemia C B AEdema BloodVolume(liters) Extracellular Fluid Volume (liters) Shift Due to: Low O2 Meds UFR Na+ Temp Posture TIME 03:37 HCT 30.7 BV - 0.0 SAT 94 -20 0 -10 5 BV BV Profile A TIME 03:20 HCT 34.7 BV -12.6 SAT 94 -20 0 -10 5 BV BV Profile C TIME 3:08 HCT 37.4 BV -18.4 SAT 91 -20 0 -10 5 BV BV Profile B
  • 16. 0 1 2 3 4 5 6 7 8 5 10 15 20 25 30 35 400 Adapted from Guyton, AC: Textbook of Medical Physiology, 1991, pg.324 Normal Death A Edema BloodVolume(liters) Extracellular Fluid Volume (liters) TIME 03:25 HCT 31.2 BV 0.2 SAT 98 -20 0 -10 5 BV PROFILE A: < 3% RBV/hour
  • 17. 0 1 2 3 4 5 6 7 8 5 10 15 20 25 30 35 400 Adapted from Guyton, AC: Textbook of Medical Physiology, 1991, pg.324 Normal Death BBloodVolume(liters) Extracellular Fluid Volume (liters) TIME 03:25 HCT 34.7 BV -17.3 SAT 94 -20 0 -10 5 BV PROFILE B: < 3 to 8% RBV/hour
  • 18. %BV 1 2 3 4 -20 -10 0 5 A -3 to -8% slope in BV per hour (a “B” profile) is generally safe for patients who have a urinary output of less than 1000 mls per day – unless they reach their HCT Threshold
  • 19. Exceptions to the 3-8% RBV profile Minimal changes in HCT (a flat line) are also acceptable when the patient is: • Near HCT threshold • UFR at minimum (<300-400 ml. per hour) • Polyuric renal failure (why?) • Diarrhea (why?) • Little or no wt gain (assuming their EDW has been correctly set) • Double Amputee (why?) or Poor Ejection Fx (why?)
  • 20. Intradialytic Hypotension and the “C” profile Time (hours) %BV SystolicBloodPressure             0 1 2 3 4 0 10 -10 -20 -30 0 25 50 75 100 125 150 UFR = 1428 ml/hr    UF Off BP cuff: post- facto measurement RBV : predictive measurement
  • 21. HCT Threshold • Definition: The HCT at which the patient experiences symptoms of morbidity. • Maximum degree of hemoconcentration ( UFR) a patient may tolerate before symptoms occur • Rule of thumb…. Until you establish a Threshold set the HCT Limit at 15% of the starting HCT. • Review it every 3 weeks: it can change as the RBC mass changes with EPO titration.
  • 22. Just because a patient “Crashes” It does NOT Mean they are “DRY”!!! Time (hr) %BV 1 2 3 4 -20 -10 0 5 8.0 L Removed 7.0 L Goal
  • 23. 0 1 2 3 4 Time (hours) 0 10 -10 -20 -30 BVChange(%) 1 2 Refill: An Indicator of Over-hydration Dynamic crit line monitoring : try to investigate after a crash or when challenging DRY WET
  • 24. Causes of Intradialytic Hypotension • Posture • Low O2 saturation • Medications / Antihypertensives • Incorrect Ultrafiltration rate • Hypotonic environment / Hypoalbumemia • Dialysate at body temperature or warmer: core body heating • Splanchnic vasodilatation secondary to food ingestion • Electrolyte / Acid-Base Imbalances • Severe anemia / Occult hemorrhage • Unstable cardiovascular status / Arrhythmias / Pericardial tamponade / MI • Septicemia • Dialyzer reaction, Hemolysis and Air embolism
  • 25. 6 reasons for a “wet crash” • O2 below 90% for Graft or fistula and below 60% for a CVC • Position • UFR higher than plasma refill • Medications that cause vasodilatation • Temperature • Hypotonic internal environment: i.e.: low Na+
  • 26. Effects of Intradialytic Hypotension • Tissue Hypoxia • Adenosine release causing decrease in PVR • Changes in Mental status / Seizures / Stroke • Vision changes • Silent cardiac ischemia / MI • Ischemia / Infarct to the gut • Decrease in Residual Renal Function • Ischemia = decrease in URR
  • 27. 02 Delivery 20+ % of HD patients have intradialytic Hypoxemia; up to70% are sleep apneics. 0 1 2 3 4 Time (hours) 80 85 90 95 OxygenSaturation Sleep Apnea Profile Sleep Complimentary Oxygen Delivery Issues
  • 28. • Oxygen saturation: The percent to which the hemoglobin is filled with oxygen. • Must interpret in relationship to HGB / HCT • 90 to 100% is considered normal for arterial sats: thru access needles • > 60 % for mixed venous sats: CVC lines Oxygen Saturation
  • 29. Intradialytic Oxygen Therapy Increasing Oxygen: • Increases Vascular tone / Vasoconstriction • Increases Peripheral Vascular Resistance • Increases Plasma Refill One of the measures suggested for preventing/treating IDH
  • 30. Application of RBV for Fluid, EDW and BP management in ESRD
  • 31. Water : The Most Important Uremic Toxin ? • A patient at their EDW should be: - asymptomatic and - normotensive - on minimum blood pressure medications - while preserving organ perfusion and - maintaining existing residual renal function
  • 32. Volume Overload Indices In Stable Hemodialysis Patients Blood Purif 2013;35:202–208 𝑆𝑙𝑜𝑝𝑒4ℎ = ∆𝐵𝑉 (%/ℎ) 𝑈𝐹(𝐿) 𝑆𝑒𝑠𝑠𝑖𝑜𝑛 𝐷𝑢𝑟𝑎𝑡𝑖𝑜𝑛 (ℎ𝑜𝑢𝑟𝑠)
  • 33. Curves A,B,C or 1—6 ? Blood Purif 2013;35:202–208
  • 34. Curves A,B,C or 1—6? Blood Purif 2013;35:202–208 Take home points: • Slope4h : highest dynamic range • A flat curve is truly a sign of FO • Only 11% of the variability of the BVM marker can be explained by FO.
  • 35. Crit-Line Intradialytic Monitoring Benefit (CLIMB) Study J Am Soc Nephrol 16: 2162–2169, 200 Can Crit-Line monitoring improve fluid removal and reduce morbidity in ESRD?
  • 36. CLIMB Study Flowchart and Study Characteristics J Am Soc Nephrol 16: 2162–2169, 200
  • 37. Implementation of the intervention in CLIMB was variable and inconsistent J Am Soc Nephrol 16: 2162–2169, 200
  • 38. Application of RBV did not modify BP in CLIMB J Am Soc Nephrol 16: 2162–2169, 200
  • 39. Application of RBV increased mortality and hospitalizations J Am Soc Nephrol 16: 2162–2169, 200 Mortality at 6 mo was greater in the Crit-Line than the conventional monitoring group (8.7 and 3.3%, respectively; P 0.021 by log-rank test).
  • 40. Using RBV to manage BP & estimated EDW in stable chronic dialysis patients Hypertension. 2010;55:305-311 Hypertension. 2009;53: 500–507 Prevalent HD patients (>3 mos on HD) with interdialytic ambulatory BP > 135/85 Intervention probed pts EDW by decreasing until symptoms occurred
  • 41. Using RBV to manage BP & estimated EDW in stable chronic dialysis patients Hypertension. 2010;55:305-311 Hypertension. 2009;53: 500–507 When EDW is not probed, pts w/o change in slope had no change in BP When EDW is probed, pts who go from flap to steep had the largest, most robust BP changes “Flat” < 1.33%/hr Prespecified analysis of a trial in which change in EDW => affects slope Does not establish that tracking of slope is useful in adjusting dry weight
  • 42. Problems with the measurement of RBV Blood Purif 2012;33:177–182 RBV ≠ Absolute Blood Volume Fahraeus effect (F-cell) = hematocrit mixed blood / central hematocrit varies during HD • Postural changes in the first 30 mins • Observed decrease in RBV under- estimates changes in total blood volume ? Not as good in preventing hypotension ? Better at managing overload
  • 43. RBV and ScvO2 in Acute Dialysis Settings
  • 44. RBV Monitoring in Acute Dialysis In the ICU Kidney International, Vol. 62 (2002), pp. 1075–1080 Only prospective study to date included 20 patients dialyzing in the ICU for a total of 57 treatments (less than 2 weeks worth of data in our service) ?? Any takers for a quality project
  • 45. RBV Monitoring of Acute Dialysis In the ICU Kidney International, Vol. 62 (2002), pp. 1075–1080
  • 46. Access: Catheter Normal 60-80 % SvO2 Venous Blood Lower O2 Saturation
  • 47. ScvO2 ScvO2 Venous Blood Lower O2 Saturation Cardiac Output (L/min) = Oxygen consumption (ml/minute) Art O2 content - Ven O2 Content  ScvO2 = CO = BP (BP = CO X PVR)
  • 48. Continuous monitoring of SvO2 is a sensitive parameter of cardiac output C. O. = Heart Rate x Stroke Volume Nephrol Dial Transplant (2017) 1– doi: 10.1093/ndt/gfx271 Unanswered questions: 1. could changes in acute patients (dialyzing with CVCs) be inferred to stand for myocardial stunning? 2. Could we trend SvO2 to prevent IDH in acute dialysis patients?
  • 49. Conclusions • The value of RBV monitoring remains highly uncertain • Inconsistent application of RBV monitoring may even be associated with worse clinical outcomes • At present the device seems more able to identify volume overloaded patients than prevent hypotension • Standardization of measurements are important given postural changes around the start of dialysis • Further studies are needed to probe the utility of other device channels (e.g. SvO2) in acute and chronic settings • Modifications of the standard critline readout to estimate the absolute blood volume may be useful in future applications