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

Disclosure – Gambro Canada Provided a Prismaflex Unitfor experimental use

All clinical and research activities performed at the University of Manitoba, Winnipeg, Canada

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

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

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 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

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)

Arterial blood gas obtained to demonstrate respiratory failure

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

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 oxygenatorin the return linepre-air detection filter

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

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

Results

Sat

Sat

Sat

PaO2 PaO2

PaO2

PaCO2

PaCO2

PaCO2

7 Fr

7 Fr

7 Fr

7 Fr

7 Fr

7 Fr

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

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

Anemia

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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

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

Acknowledgements

The Winnipeg Rh Institute Foundation

Gambro Canada

Sorin Medical

Section of Pediatric Nephrology, Health Sciences Center, Winnipeg, Manitoba

Question and Answers

ResultsAnimal - 2.4 kg

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ResultsAnimal - 2.8 kg

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ResultsAnimal - 5.5 kg

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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)

Results

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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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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)

Anemia

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Hypoxic O2 Content O2 Content Actual O2 Content assuming no dilution O2 Content Assuming Hb 14