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Animal model to study feasibility of VV ECMO
using RRT platform – Pilot study
Abhay Divekar, MD, FRCPC, FSCAIDirector Pediatric Cardiac Catheterization Laboratory
University of Iowa Children’s HospitalIowa City, IA
Alex Gutsol, MD Todd Koga, RTR Gale Bonin, RN Helen Cooper, RNHealth Sciences Center, Winnipeg, Manitoba
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Disclosure – Gambro Canada Provided a Prismaflex Unitfor experimental use
All clinical and research activities performed at the University of Manitoba, Winnipeg, Canada
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Continuous Renal Replacement Therapy Improvised to Provide Extracorporeal Membrane OxygenationContinuous Renal Replacement Therapy Improvised to Provide Extracorporeal Membrane OxygenationA DivekarA Divekar11, R Soni, R Soni11, M Seshia, M Seshia22,T Drews,T Drews33, M Kesselman, M Kesselman33, G Bonin, G Bonin44, C Press, C Press44, M Maas, M Maas55, J Minski, J Minski66, T Blydt-Hansen, T Blydt-Hansen77..
CardiologyCardiology11, Neonatology, Neonatology22, Critical Care, Critical Care33, Clinical Nurse Specialist CRRT Program, Clinical Nurse Specialist CRRT Program44, Cardiac Perfusion, Cardiac Perfusion55, Respiratory Therapy, Respiratory Therapy66, Nephrology, Nephrology77, Department of Pediatrics , Department of Pediatrics
Health Sciences Center, Winnipeg, Manitoba, CanadaHealth Sciences Center, Winnipeg, Manitoba, Canada
BackgroundAfter all ECMO is just a pump and a membrane !
Full term infant needing VV-ECMO for severe PPHN
secondary to MASFiO2 100%, PaO2 25-40, PaCO2 60-80, OI 40-80
Inotropic support, “resuscitation” - Dopamine 10 mcg/kg/minepinephrine 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 2Dopamine off, Epinephrine 0.2 mcg/kg/min
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RRT platforms have been successfully used for other indications Severe sepsis and septic shock
Removal of “evil humors”
Molecular Adsorbent Recirculating System – MARS
Extracorporeal liver replacement
ARDS, pulmonary edema
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Do we need an oxygenating RRT platform when ECMO exits?
Are there any potential applications?
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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
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Validation of the system – pilot study Animal model
Adapting RRT platform for oxygenation
Circuit
Catheters
Oxygenator
Alarms
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Animal Model 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 Access and return via same vessel vs. separate vessels Catheter size and placement
Circuit preparation 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
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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
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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
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Animal Model
Unfractionated heparin sulfate 300 U/kg
given after isolating the vessels
ACT maintained at 180-220 secs with
additional heparin boluses
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Animal Model
Acute respiratory failure induced by hypoventilation and normobaric hypoxia (10% FiO2 – blending in nitrous oxide, oxygen and medical air)
Arterial blood gas obtained to demonstrate respiratory failure
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Priming the CRRT circuit
Prismaflex – Gambro – RRT platform 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
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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
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Splicing the hollow fiber oxygenatorin the return linepre-air detection filter
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After splicing oxygenator in-line Blood prime - Donor blood collected and stored in ACD blood
bags from a 50 kg swine
Pigs have weak blood group antigens do not need cross match no lawyers either !
Add mannitol to blood bag (1 g/kg)
Sweep flow 1 lit, 100% FiO2
Normalize prime (pre-blood pump replacement solution and dialysate solution) – 30 min BFR 100 ml/min, PBP – 500 ml/min, Dialysate 500 ml/min
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Initiation of VV - ECMO Start at 75 ml/min and increase by 50 ml/min
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
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Results
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Sat
Sat
Sat
PaO2 PaO2
PaO2
PaCO2
PaCO2
PaCO2
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7 Fr
7 Fr
7 Fr
7 Fr
7 Fr
7 Fr
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Results
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
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Limitations of experimental setup 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
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Anemia
0
2
4
6
8
10
12
14
16
Hypoxic O2 Content O2 Content Actual O2 Content assuming no dilution O2 Content Assuming Hb 14
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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
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Future Work Circuit design
Minimize sites of resistance, ? Large tubing size Optimal filter High flow stopcock
Access and return cannula novel design with DL cannula femoral cannulation in small infants may compromise venous
drainage and therefore have limited clinical application Optimal oxygenator
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
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Acknowledgements
The Winnipeg Rh Institute Foundation
Gambro Canada
Sorin Medical
Section of Pediatric Nephrology, Health Sciences Center, Winnipeg, Manitoba
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Question and Answers
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ResultsAnimal - 2.4 kg
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ResultsAnimal - 2.8 kg
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ResultsAnimal - 5.5 kg
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Results
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10
100
1000
Pre and post oxygenator blood gas analysis - 2.4 kg animal
pO2 29 534 35 487
Sat 53 100 70 100
pCO2 33 18 27 18
Preoxygenator (200) Postoxygenator(200) Preoxygenator (300) Postoxygenator (300)
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Results
1
10
100
1000
Pre and post oxygenator blood gas analysis 2.8 kg animal
pO2 32 458 39 370 43 316
Sat 46 100 69 100 81 100
pCO2 47 23 36 24 29 19
Preoxygenator (200)
Postoxygenator(200)
Preoxygenator (300)
Postoxygenator (300)
Preoxygenator (350)
Postoxgenator (350)
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Results
1
10
100
1000
Pre and Post oxygenator blood gas analysis - 5.5 kg animal
pO2 28 440 26 300 28 475
Sat 48 100 53 100 62 100
pCO2 37 18 28 17 24 16
Preoxgenator (150)
Postxygenator (150)
Preoxgenator (250)
Postxygenator (250)
Preoxygenator (310)
Postoxygenator (310)
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Anemia
0
2
4
6
8
10
12
14
16
Hypoxic O2 Content O2 Content Actual O2 Content assuming no dilution O2 Content Assuming Hb 14