Transcript Animal model to study feasibility of VV ECMO using RRT

Animal model to study feasibility of
VV ECMO using RRT platform –
Pilot study
Abhay Divekar, MD, FRCPC, FSCAI
Director Pediatric Cardiac Catheterization Laboratory
University of Iowa Children’s Hospital
Iowa City, IA
Health Sciences Center, Winnipeg, Manitoba
Alex Gutsol, MD
Todd Koga, RTR
Gale Bonin, RN
Helen Cooper, RN
All clinical and research activities performed at the
University of Manitoba, Winnipeg, Canada
Disclosure – Gambro Canada Provided a Prismaflex Unit
for experimental use
Continuous Renal Replacement Therapy Improvised to Provide Extracorporeal Membrane Oxygenation
A Divekar1, R Soni1, M Seshia2,T Drews3, M Kesselman3, G Bonin4, C Press4, M Maas5, J Minski6, T Blydt-Hansen7.
Cardiology1,
Neonatology2,
Critical Care3, Clinical Nurse Specialist CRRT Program4, Cardiac Perfusion5, Respiratory Therapy6, Nephrology7, Department of Pediatrics
Health Sciences Center, Winnipeg, Manitoba, Canada
Full
After
termallinfant
ECMO
needing
is justVV-ECMO
a pump andfor
a
Background
severe PPHN
membrane
secondary
! to MAS
FiO2 100%, PaO2 25-40, PaCO2 60-80, OI 40-80
Inotropic support, “resuscitation” - Dopamine 10 mcg/kg/min
epinephrine 1.0 mcg/kg/min FiO2 100%, PaO2 80-90, PaCO2 50-60,
OI 15; but poor systemic oxygen delivery, lactate 10, poor urine output
Oxy – CRRT - FiO2 40-50%, PaO2 50-70, PaCO2 35-55, OI <15, Lactate 2
Dopamine off, Epinephrine 0.2 mcg/kg/min
RRT platforms have been successfully
used for other indications

Severe sepsis and septic shock


Molecular Adsorbent Recirculating System –
MARS

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Removal of “evil humors”
Extracorporeal liver replacement
ARDS, pulmonary edema
Do we need an oxygenating RRT platform
when ECMO exits?
Are there any potential applications?

Patients requiring CRRT – not needing full
ECMO support

s/p cardiac surgery – AKI – fluid retention

pulmonary edema

RRT increasingly used

? Reduce ventilator needs and avoid iatrogenic injury

Rescue situations ??

“Developing countries” - ? Simpler ECMO
Validation of the system – pilot study

Animal model

Adapting RRT platform for oxygenation

Circuit

Catheters

Oxygenator

Alarms
Animal Model
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
All animal work performed in accordance to CCAC
and University Animal Care Committee guidelines
Domestic Farm Swine 2 - 9 kg (n = 6) and one 50 kg
blood donor
First three animals

Cannulation technique
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
Circuit preparation

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Access and return via same vessel vs. separate vessels
Catheter size and placement
Need to add mannitol
Absolute need for heater-cooler exchanger
Need to normalize prime
Older animals tolerate acute hypoxemic respiratory failure
poorly and therefore need to be place on support rapidly
Animal Model

Three animals weighing 2.4, 2.8 and 5.5 kg formed
the experimental cohort

Induction and maintenance anesthesia - isoflurane
in oxygen

Intubated and mechanically ventilated


achieve normal arterial blood gas
Continuous EKG, invasive arterial pressure,
systemic saturation, core temperature
Animal Model

Femoral vessels and external jugular vessels
were isolated by surgical cutdown

Femoral arterial line

Largest possible double lumen cannula (7-12 Fr) for
return line – femoral vein

Largest possible double lumen cannula (7-12 Fr) for
access – external jugular vein
Animal Model

Unfractionated heparin sulfate 300 U/kg
given after isolating the vessels

ACT maintained at 180-220 secs with
additional heparin boluses
Animal Model

Acute respiratory failure induced by
hypoventilation and normobaric hypoxia (10%
FiO2 – blending in nitrous oxide, oxygen and
medical air)
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Arterial blood gas obtained to demonstrate
respiratory failure
Priming the CRRT circuit
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Prismaflex – Gambro – RRT platform



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
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Flow rate up to 450 ml/min
Pre-packaged ST-100 filter – loaded through
automated steps
Primed with 1000 ml NS with 5000 unit of heparin
CVVHDF mode
Pre blood pump prime with Prismasol4 solution
(100 %) pre-filter
Dialysate solution Prismasol4
Priming Lilliput 2 (D902) hollow fiber
oxygenator

PVC ¼” tubing - venous inlet and arterial
outlet

Primed and de-aired with normal saline

AV loop clamped and ¼ x ¼ inch Cobe
connector (M–F) – spliced in-line

Heater-cooler exchanger
Splicing the hollow
fiber oxygenator
in the return line
pre-air detection
filter
After splicing oxygenator in-line

Blood prime - Donor blood collected and stored in ACD blood
bags from a 50 kg swine
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Pigs have weak blood group antigens do not need cross match
no lawyers either !
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Add mannitol to blood bag (1 g/kg)
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Sweep flow 1 lit, 100% FiO2
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Normalize prime (pre-blood pump replacement solution and
dialysate solution) – 30 min BFR 100 ml/min, PBP – 500 ml/min,
Dialysate 500 ml/min
Initiation of VV - ECMO
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Start at 75 ml/min and increase by 50 ml/min
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Maximum flow of 400 ml/min
Limiting access/return line/filter pressure
Obtain ABG, pre and post oxygenator blood
gas analysis
Record all monitored and software calculated
pressures
Record all alarms
Results
Blood gas result at intermediate flow rate
PaO2
Sat
PaCO2
90
Sat
82
Sat
80
79
PaCO2
Sat
74
72
70
60
PaCO2
56
50
mm Hg
PaO2
PaO2
43
41
40
39
PaCO2
40
37
PaO2
37
32
30
30
26
25
25
23
20
10
0
Animal 2.4 kg
Animal 2.8 kg
Animal 5.5 kg
83 ml/kg/min
71 ml/kg/min
45 ml/kg/min
Blood gas result at maximum flow rate achieved
PaO2
Sat
PaCO2
100
95
93
92
90
80
74
70
65
60
56
mm Hg
57
50
43
40
40
37
32
30
26
25
20
10
0
25
25
22
19
Animal 2.4 kg
Animal 2.8 kg
Animal 5.5 kg
133 ml/kg/min
125 ml/kg/min
56 ml/kg/min
Access and return line pressures
Flow rate in ml/kg/min
400
335
321
300
284
7 Fr
7 Fr
7 Fr
200
169
Pressure in mm Hg
312
170
100
Return pressure
Animal 2.4 kg
0
Animal 2.8 kg
-25
Access Pressure
7 Fr
Animal 5.5 kg
-75
-100
-128
-150
7 Fr
-200
7 Fr
-216 -202
-300
-400
40
50
60
70
80
90
100
110
120
130
140
Results
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Animal model of acute hypoxemic respiratory failure
useful to study and adapt RRT platform for VV
ECMO
Very efficient at CO2 removal
With adequate flow rates can support veno-venous
membrane oxygenation
Minimal recirculation with access from external
jugular vein and return via the femoral vessels
Circuit resistance (tubing size, stop-cocks, filter) and
catheter size major limitation to flow
Limitations of experimental setup
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Pilot project – limited number of animals
Only short term (hours) data available
 Longer term data in terms of filter clotting/change
needed
Limited cannula choice
Hemolysis not evaluated
Sweep flow and % FiO2 not adjusted
Only one type of oxygenator evaluated
Anemia
16
Anemia
14
12
10
8
6
4
2
0
Hypoxic O2 Content
O2 Content Actual
O2 Content assuming no dilution
O2 Content Assuming Hb 14
Limitation if the modification is used with
the circuit as is

Circuit shutdown for malfunction and warning
alarms

72 hours mandatory filter change

Tubing/circuit resistance
Future Work

Circuit design

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
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Access and return cannula

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novel design with DL cannula
femoral cannulation in small infants may compromise venous
drainage and therefore have limited clinical application
Optimal oxygenator


Minimize sites of resistance, ? Large tubing size
Optimal filter
High flow stopcock
Prevent automatic clamping of the return line for malfunction and
warning alarms
Study a larger group of animals in each group and
for a longer duration
Acknowledgements

The Winnipeg Rh Institute Foundation

Gambro Canada

Sorin Medical

Section of Pediatric Nephrology, Health
Sciences Center, Winnipeg, Manitoba
Question and Answers
Animal - 2.4 kg
Results
100
90
80
70
60
50
40
30
20
10
0
Results
Animal - 2.8 kg
100
90
80
70
60
50
40
30
20
10
0
Animal - 5.5 kg
Results
100
90
80
70
60
50
40
30
20
10
0
Results
Pre and post oxygenator blood gas analysis - 2.4 kg animal
1000
100
10
1
Preoxygenator (200)
Postoxygenator(200)
Preoxygenator (300)
Postoxygenator (300)
pO2
29
534
35
487
Sat
53
100
70
100
pCO2
33
18
27
18
Results
Pre and post oxygenator blood gas analysis 2.8 kg animal
1000
100
10
1
Preoxygenator
(200)
Postoxygenator(20
0)
Preoxygenator
(300)
Postoxygenator
(300)
Preoxygenator
(350)
Postoxgenator
(350)
pO2
32
458
39
370
43
316
Sat
46
100
69
100
81
100
pCO2
47
23
36
24
29
19
Results
Pre and Post oxygenator blood gas analysis - 5.5 kg animal
1000
100
10
1
Preoxgenator
(150)
Postxygenator
(150)
Preoxgenator
(250)
Postxygenator
(250)
Preoxygenator
(310)
Postoxygenator
(310)
pO2
28
440
26
300
28
475
Sat
48
100
53
100
62
100
pCO2
37
18
28
17
24
16
16
Anemia
14
12
10
8
6
4
2
0
Hypoxic O2 Content
O2 Content Actual
O2 Content assuming no dilution
O2 Content Assuming Hb 14