Evolution of ECLS Minneapolis 2016 Boston Children s Hospital Surgical Staff 1965 ECMO Early history Lab, 4 days ECC First cardiac case First newborn case(esperanza) 1965 1971 1972 1975 1980 First sucessful case, ARDS Infant VA Overall Patient Outcomes ELSO Member Centers 2015 6 ELSO Registry July 2015
Runs by Year 100% 80% 60% Card (16 years and over) Card (1 year < 16 years) Card (31 days < 1 year) Card (0-30 days) Adult Pulm Ped Pulm 40% Neo Pulm 20% 0% VA support, no cardiac function Bridge to LVAD, then cardiac recovery 7 ELSO Registry July 2015 Cardiac ECLS algorithm Adult Respiratory Cases Day2-3: CNS OK? Cardiac Function returning? NO: Transplant candidate? YES: Bridge to recovery NO: Bridge to recovery, ($20K) Futility: Stop, Organ donation? Maybe: Bridge to VAD to recovery ($500K) Yes: Donor list Bridge to VAD($500K) Transplant ($500K) Annual Runs 2000 1800 1600 1400 1200 1000 800 600 400 200 0 9000 8000 7000 6000 5000 4000 3000 2000 1000 0 Cumulative Runs 9 10 ELSO Registry July 2015 ECMO II, 2008 Technical improvements Membrane lung: low resistance, easy to prime (10 min) ECMO I, 1990 2008 ECMO II, 2008 Prolonged Life Support System Maquet Mendler design Centrifugal Pump now safe,simple Cannula implantation through Seldinger method
Veno venous ECLS with a double lumen cannula!0 controlled trials of ECMO in Respiratory Failure J Intensive Care Med 2014 UK Adult ECMO Study CESAR. Peek and Firmin 2000 2006 180 ARDS Pts, 30 centers Consent Randomize 90 Conventional 90 Optimal+ECMO 28day Surv 50% 76% 6 mo Surv 47% 63% Peek, Lancet, 2009 ECLS in ARDS ( The CESAR Trial) Prospective Randomized Trial 2008 Peek and Firmin CESAR 2009 300 VO2/VCO2 ml/min 200 CO2 removal O2supply 15 10 IN OUT Content difference 5 ml/dl 100 kg 70 kg 50 kg 100 VO2 @ 3cc/kg LPPV ECCOR 43 cases, 49% survived Gattinoni JAMA 1986 1 2 3 4 5 6 Blood flow: L/min
Ambulatory VV bridge to XP: Hoopes, 2009 Palle Palmer, Stockholm 1997 Tidal volumes long run ECMO 40 yo, viral ARDS, Awake alert on ECMO, total consolidation for 50 days courtesy of Palle Palmer, Karolinska Redefining irreversible lung injury Lung has unexpected regenerative capacity, during prolonged mechanical support, similar to acute kidney injury Late follow up: minimal disability New scientific opportunities New practical problems, similar to dialysis/transplant and VAD /transplant 10 20 years ago Patient Management: ECMO II ECMO I ECMO II Sedation, Paralysis Awake, Spontaneous breathing Intubated Tracheostomy Rest vent settings CPAP, extubate? Specialist 24/7 ICU Nurse, ECMO Team role Lung recruitment? Watch and wait Bleeding: major Bleeding: minor ECMO in 2016:Circuit Safer, simpler, automatic DTI, no heparin Surface prevents thrombosis, no systemic anticoagulation
Technology: Pumps for ECLS Roller Ideal Centrifugal Blow out with high P No No No No Excess suction, hemolysis Pump air, suck air No pump air, suck air No Auto servo No Anticoagulants for ECLS Direct thrombin inhibitors best Heparin DTI ( Bivalirudin, Argatroban) Action Blocks thrombin Blocks thrombin Blocks many steps, Xa AT3 dependent Monitor ACT,TEG ACT, TEG PTT PTT AT3, AntiXa MC3 APS Automatic Perfusion System prototype Dr Bartlett has a financial interest Effect Irregular Smooth, less bleeding Reversible yes, minutes No, 6 hours Cost High with assays, AT3 Moderate Coughlin, JASAIO, 2015:61:652-655 Nitric Oxide surface Argatroban Top Coat on DBHD/N 2 O 2 -containing polym A CONTROL C Argatroban/PEG One large Fibrin clot Fibrin clot B NORel D Argatroban/PEG/NORel Small Fibrin clots No Fibrin clot NO generator for sweep gas UM ECLS Lab Hb and flow in ECLS Typical 80 kg adult: total O2 support 240cc/min Hb gm/dl EC FlowL/min 5.3 15 5.0 14 4.6 13 4.3 12 4.0 11 3.6 10 3.3 9 3.0 8 2.6 Risk of transfusion:minimal Risk of high flow: high ECMO 2026: Circulation support ( VA) Acute Cardiac Failure Post Op MI, Myocarditis, Toxins, PE ECPR for cardiac arrest Acute Circulatory Failure Septic shock, anaphyllaxis Trauma, hemorrhage Organ Donation and Transplantation EDCD Organ perfusion, organ banks
BDD Cold Storage (Hours) Cadaveric Organ Donation (Rapid Recovery) (Unused Organs) Controlled DCD EDCD in situ (Hours) Uncontrolled DCD 42 patients CPR 18 met protocol criteria for ECPR 10 improved(3) or failed ECLS (7) 8 resuscitated on ECLS 5 discharged, neuro intact (61%) Urgent Transplantation Elective Warm Perfusion ex vivo (1 3 days) Bench Rx Immune Rx Drug Eval Organ Banks (Weeks)) Blood Factory Bio Factory Resuscitation Research Organ Banks Imagine an unlimited supply of hearts, lungs, livers, kidneys, bone marrow, and endocrine organs Elective transplantation Immune modulation and perfect matches Gene therapy to the specific organ Bench treatment of cancer and infection Research on human organs, not animals ECLS 2026: Respiratory Support Acute Respiratory Failure Neonatal,Prematurity Acute RDS, pediatric and adult Status asthmaticus, Airway Post transplant Chronic Respiratory Failure Pediatric BPD, CDH Bridge to transplant Acute to chronic ECMO(months) Lung Centers, home ECMO, Wearable lungs,esld/copd palliation Implantable ( Wearable) Artificial Lungs Novalung Ambulung. Portable VV, RA -RA Out of ICU, Lung centers, home ECMO Bridge to recovery, transplant COPD destination therapy Paracorporeal with implanted access With a pump: VV, RA PA Heart perfusion: PA LA. A V for CO2
Portable RA- PA Total support Univ Maryland RA-PA VV total support University of Pittsburgh PA-LA Total support Univ Michigan Ambulatory Lung Assist PA-LA implantation, 5 weeks, bridging to transplant Regensberg, 2007 ECMO III( 2026) AV access 20% cardiac output Total CO2 removal Univ Michigan Awake breathing extubated Indications 50% mortality risk based on algorithms for cardiac, respiratory failure No systemic anticoagulation Automation, servo regultion Cardiac, Shock: bridge to recevery, ECPR, EDCD, bridge to VAD Respiratory: ECMO bridge to recovery, Lung centers, home ECMO, implant lungs
Technology Simple, automated devices Modular components No systemic anticoagulation Future of ECLS Ex vivo organ perfusion, Organ banks Lung Failure Units Applications ARDS algorithm Awake patients Bridge to lung transplant DCD Organs ECPR Sepsis Placenta Implantable Chronic Lungs