Artificial Lung: A New Inspiration

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Artificial Lung: A New Inspiration Joseph B. Zwischenberger MD Johnston-Wright Professor and Chairman: Department of Surgery j.zwische@uky.edu The University of Kentucky Lexington, Kentucky

Presenter Disclosure Information Joseph B. Zwischenberger, M.D. Research supported in part through Competitive funding: National Institutes of Health (SBIR,STTR,T-32) Contracts: MC3, Ann Arbor Mi Medarray Inc. Ann Arbor Mi Avalon Laboratories, LLC, Grand rapids Mi Patent: Avalon Elite

Introduction Respiratory failure is now the 3 rd leading cause of death in the USA Despite advances, death from acute respiratory failure remains ~ 40% ARDS NET Trial demonstrated decreased mortality with Low Tidal Volume Ventilation (6 ml/kg vs. 12 ml/kg)

Treatments for Severe Hypoxemic Respiratory Failure High PEEP vs. Low PEEP Recruitment Maneuvers Pressure Control Ventilation Airway Pressure Release Ventilation High Frequency Oscillatory Ventilation High Frequency Percussive Ventilation All transiently improve oxygenation but NONE HAVE PRODUCED A MORTALITY BENEFIT!! Esan et.al. CHEST 2010, 137(5):1203-1216

VENOARTERIAL ECMO: Bartlett 1979

VENOVENOUS ECMO Single, Double Lumen Cannula For total gas exchange alone Zwischenberger/Drake 1989

ELSO Registry: 7/2011 Total # % Survived Neonate Respiratory 24,770 85 Cardiac 4,375 61 Pediatric Respiratory 4,009 65 Cardiac 5,423 64 Adult Respiratory 2,620 63 Cardiac 1,680 53 Total 46,509 74

Oxygen transfer Carbon Dioxide Removal

CO 2 Removal CO 2 removal and O 2 transfer are uncoupled: CO 2 is transferred across the 2 membrane gas exchanger Low Frequency Ventilation: O 2 diffuses across the native lungs Ted Kolobow 1977

AVCO 2 R: Carbon Dioxide Removal (get the bad air out) with a low-resistance gas exchanger in a simple arterio-venous shunt Zwischenberger 1996

AVCO 2 R Outcome 5/5 completed 72 hr trial 3/5 Discharged 2 minor complications Ann Thorac Surg 1999; 68:181-187 8/8 completed 72 hr trial for ARDS with hypercapnia 5/8 Discharged No major complications Intensive Care Med (2001) 27:1340-46

Arteriovenous CO 2 Removal NOVALUNG (Europe): Overall Survival 70% percutaneous cannulation of femoral artery and vein

Impact of CO 2 Homeostasis CO 2 flux is greatly reduced by AVCO 2 R, and may be important in: organ tissue neutrophil apoptosis resolution of inflammation maintaining a normal alveolar milieu

Paracorporeal Artificial Lung: PA- PA Configuration 100% flow through device Full lung metabolic function No risk of stroke or R L shunt High right heart power requirement 2004 Right Heart Failure!! ASAIO 2004 Wang/Zwischenberger

Assisted RA-PA Artificial Lung 1. Right ventricular assist device (RA-PA) 100% of cardiac output through the Paracorporeal Artificial Lung to prevent right heart failure 2. Requires only one PA anastomosis 3. Insertion without CPB 4. Spares pulmonary hilum for subsequent transplant ASAIO 2006 Wang/Zwischenberger

Ambulatory,Compact, and Paracorporeal Successful to 4 weeks Artificial Lung Pump Driver Outlet Cannula Inlet Cannula MicroMed Pump Zwischenberger/Wang STSA 2006

Problem Alert!! RA access and PA anastomosis too delicate for ambulation Goal:To develop a minimally invasive double lumen cannula for a Paracorporeal Artificial Lung to: Avoid Thoracotomy Avoid Major Vessel Central Access Avoid recirculation Based on VV ECMO cannulation

Wang-Zwisch DLC Avalon Elite

Avalon Elite Catheter Placement: image guidance required

Newborn with Meconium Aspiration on Avalon Elite VVDL ECMO 6 days: No Recirculation Blue blood out Red blood in

ECMO in 2006 Complex Labor intensive Expensive Time Limited Thrombogenic System failures (Why are they still BLUE??)

Safer ECMO Technology: 2011 how it looks Low resistance gas exchangers Low pressure, low trauma pumps Self regulating circuit Image-guided vascular access Double lumen cannula Non-thrombogenic coatings

Goal: Ambulatory Paracorporeal Artificial Lung

56 yo idiopathic pulmonary fibrosis:uncomplicated bilateral lung tx 3/08 12/08 Trichosporon pneumonia, post-infectious obliterative bronchiolitis. Listed for redo transplant Feb 08. Alert 3-3-09 Chuck Hoopes (UCSF ): the first Ambulatory Lung Assist patient using Avalon Cannula, Quadrox and Centrimag!! IVC TV SVC IVC RV Total gas exchange - no recirculation SVC

Exercise at the bedside

ECMO as bridge to lung Transplant Cleveland Clinic Experience n=7 2 - non intubated resp failure (ambulatory) 5 - intubated with inadequate ventilation 6/7 lung transplant, 1/7 died on wait list 1 single, 5 double lung transplant all weaned from ECMO within 24 hrs, 1 death day 26 5/7 survivors 1-16 mo Yun et al ISHLT 2010

This is ECMO? walking bypass RA to Ao cannulation (BiV failure, PHTN s/p PEA..to HLTx) walking ECMO dual lumen Avalon VV (hypoxia, hypercarbea secondary BOS.. to redo BLTx) ambulatory right heart bypass PA to LA cannulation (RV failure, hypoxia, PHTN s/p PEA..to BLTx)

Pulmonary transplant and orphan diseases pulmonary veno-occlusive disease (PVOD) Urisman et al (2011) Rapidly progressive pulmonary venoocclusive disease in young women on oral contraceptives. Pathology, in press. (A) Small sized vein demonstrates marked intim proliferation and narrowing of the lumen (B) Tw adjacent veins contain organizing thrombi (200X magnification)

Failing Fontan: Percutaneous cannula based CP Assist Device (CPAD) AvalonElite TM DLC: Insert from jugular vein to SVC-extracardiac conduit. Blood drains through side openings in SVC and end openings in conduit-ivc. Wang/Zwisch 2011

Wang/Zwisch 2012 Percutaneous RVAD

Organ Block Support Donor lung evaluation

Artificial Lung: A New Inspiration Joseph B. Zwischenberger MD Johnston-Wright Professor and Chairman: Department of Surgery j.zwische@uky.edu The University of Kentucky Lexington, Kentucky