Newer techniques for extracorporeal lung support. Antonio Pesenti University of Milano Bicocca Italy

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1 Newer techniques for extracorporeal lung support Antonio Pesenti University of Milano Bicocca Italy

2 Conflict Of Interest Grants from Maquet, Drager Consultant for Maquet, Novalung Gambro Patents in CO2 removal technology Patent in respiratory monitoring

3 Extracorporeal CO 2 removal (ECCO 2 R) Role of ECCO 2 R? Why improving ECCO 2 R How to improve ECCO 2 R?

4 Extracorporeal CO2 removal (ECCO2R) Role of ECCO2R? Why improving ECCO2R How to improve ECCO2R? Clinical cases

5 Why Future V-V >15 F Future: >40 >50

6 Improving extracorporeal CO2 removal Constraints Normal blood contains 25 mmol/l CO2 Normal VCO2 10 mmol / min 0.5 l of blood carries total VCO2 Changing CO2 contents changes ph

7 Improving extracorporeal CO2 removal Targets: Safety Easy to apply Simple operation Performance ( CO2 removed/ Blood flow)

8 Improving extracorporeal CO2 removal Minimizing blood flow: Minimizes cannulation problems Minimizes extracorporeal circulation risks Regional anticoagulation?

9 Improving extracorporeal CO2 removal Minimizing blood flow: Minimizes cannulation problems Minimizes extracorporeal circulation risks Regional anticoagulation?

10 Extracorporeal CO2 removal (ECCO2R) Role of ECCO2R? Why improving ECCO2R How to improve ECCO2R?

11 Extracorporeal CO2 removal (ECCO2R) Role of ECCO2R? Why improving ECCO2R How to improve ECCO2R? HOW TO GET A LOT OF CO2 OUT FROM A SMALL AMOUNT OF BLOOD

12 How to improve CO2 removal? Two main approaches: Carbonic anhydrase Acidification

13 CO 2 blood content (%) CO 2 blood content % dissolved CO 2 (pco2 x 0.03) Membrane lung works on ΔPCO2 90% HCO H + H 2 CO 3 CO 2 + H 2 O 5 0 5% carbamino compounds Venous blood ~650 ml CO 2 /l blood

14 CO 2 blood content (%) CO 2 blood content % dissolved CO 2 (pco2 x 0.03) CA accelerates the equilibrium ( both directions) 90% HCO H + H 2 CO 3 CO 2 + H 2 O 5 0 5% carbamino compounds Venous blood ~650 ml CO 2 /l blood

15 Kimmel JD ; J Mater Sci: Mater Med (2013) 24:2611

16 CO 2 blood content (%) ACID Changes the equilibrium and increases PCO Acid 90% HCO 3- + H + H 2 CO 3 CO 2 + H 2 O 5 0

17 MEMBRANE BLOOD SIDE GAS SIDE ph = 7.39 PCO2 = 40 mmhg HCO3- = 24 mmol/l BE = 0 ph = 6.57 PCO2 = 208 mmhg HCO3- = 18.7 mmol/l BE = - 10 VCO2 increases

18 Which ACID? Non-metabolizable Metabolizable - Hydrochloric acid - Lactic acid - Citric acid Equally effective on extracorporeal VCO2

19 Which ACID? Metabolizable - Lactic acid > Quickly metabolized > Not harmful > Easy to measure at the bedside

20 Exp. n 1 How much acidification? L-lactic acid 4,5% (0.5 N) 6 pigs 37±2 Kg 1 meq/min 2 meq/min 5 meq/min Gas Flow FiO2 100% 10 l/min Zanella, Pesenti et al, Intensive Care Med, : Blood Flow 500 ml/min Quadrox D

21 CO 2 removal(ml/min) Exp. n 1 >> How much acidification? % + 30% + 64% Adult CO 2 production 121ml 131ml 171ml ml Acid Infusion (meq/min) Blood flow = 500 ml/min Zanella et al, Intensive Care Med, 2009; 35:

22 Exp. n 2 >> Long term safety and efficacy meq/l 5 Arterial [Lactate] preacid 1h 24h 1h stop 48h 1h stop Maximum ph drop 0.04 No complications, No hemolysis Zanella, Anesthesiology 2014: 120: 416

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24 Exp. N 4 >> ML on dialysate circuit Evaluating efficacy and safety of enhanced extracoropreal CO 2 removal through acidification and ventilation of dialysate Blood Flow 250 ml/min Gas flow 10 l/min 100% O 2 8 randomized 1-h steps repeated 3 times: 4 dialysate flows (200/ 400/ 600/ 800 ml/min) ± lactic acid infusion Lactic Acid 2.5 meq/min Zanella, et J Heart Lung Transplant 2014, 33: 536

25 Which ACID? Non-metabolizable Metabolizable - Hydrochloric acid - Lactic acid - Citric acid Cannot be metabolized Progressive accumulation A removal system is required

26 How to acidify blood without infusion of exogenous compunds? Basic Acid Electrodialysis Image from :

27 Am J Respir Crit Care Med 2015

28 Respiratory Electrodialysis

29 Minute Volume L/min 9 8 Respiratory electrodialysis Minute Volume 7 6 *% 5 4 *%$ First Baseline ECCO 2 R Respiratory Electrodialysis Final Baseline

30 VCO 2 ml/min 300 Respiratory electrodialysis CO 2 removal *% $ NL VCO *%$ ML VCO First Baseline ECCO 2 R Respiratory Final Baseline Electrodialysis

31 Arterial ph Arterial pco 2 mmhg Respiratory electrodialysis First Baseline First Baseline ECCO 2 R ECCO 2 R Respiratory Electrodialysis Respiratory Electrodialysis Final Baseline Final Baseline

32 VCO2 ML (ml/min) : Respiratory electrodialysis : Standard ECCO 2 R Extracorporeal Blood flow l/min