William J. Federspiel, PhD Whiteford Professor of … · · 2018-02-22Focus has shifted towards new generation of respiratory assist devices ... Fully integrated and compact blood

The Artificial Lung: Can It Be Realized?

William J. Federspiel, PhD

Whiteford Professor of Bioengineering

Professor of Critical Care Medicine

Director, Medical Devices Laboratory

McGowan Institute of Regenerative Medicine

University of Pittsburgh

Disclosure

William J. Federspiel, PhD

WJF is Co-Founder and Head of the SAB of Alung Technologies, in which he also holds equity. Portions of this talk cover the Hemolung ® Respiratory Assist System (RAS) and other technologies licensed or optioned by Alung from the University of Pittsburgh and invented in part by WJF.

Conclusion: It can be realized but …

Medical Devices Laboratory McGowan Institute of Regenerative Medicine

We are about 20-30 years behind VAD technology

VADs Artificial Lungs

Implantable working unit

YesNo

Extracorporeal

Reliability Years Days-Months

Destination Therapy

YesNoICU

HemocompatibilityVery Good

~ cm2 contact area

Challenge~ m2 contact area

Technology Platform

Mostly Perfected In Infancy


Vs

A ~ 140 m2

A/V ~ 2900 cm-1

~ 1 m VO2 ~ 210 - 3200 ml/min

A ~ 2.5 m2

A/V ~ 28 cm-1

~ 10-30 m VO2 ~ 150 - 250 ml/min

The Natural Lung Versus an Artificial Lung

The natural lung is a remarkable organ for gas exchange

Nature’s Technology “Our” Technology

Hollow Fiber Membrane Modules

Alveolar-Capillary

Microvascular Units

Current Artificial Lungs: ECMO Devices



Active rehabilitation / ambulation during pre-transplant respiratory support can improve post-transplant outcomes.

Where We Are Headed with Next Generation Devices

Focus has shifted towards new generation of respiratory assist devices that allow for easier ambulation.

Fully integrated and compact blood pump/gas exchange devices

University of Maryland Efforts


Ann Thorac Surg 93:274-281,2012

www.breethe.life

University of Michigan & CMU


ASAIO J,2017

• Uses right ventricle as pump

• PA to LA connection

• Compliance reduces load on RV

Aachen Efforts and Hemovent


ASAIO J 61:574-582, 2015

• Pneumatic pumping

• No electrical power/batteries

• Compressed oxygen source

Paracorporeal Ambulatory Assist Lung (PAAL)


Bridge to lung transplant/recovery

Blood flows of 2-3.5 L/min

Pressure generation of 250 mmHg

Oxygenation of 180 ml/min

Oxygenation efficiency > 250 ml/min/m2

Thromboresistant coatings: anticoagulation ACT 1.5-2 x baseline

Minimal hemolysis pfHb < 50 mg/dL

Wearable compact pump-lung

2013


Basic Features of the PAAL System 27 Fr Avalon DLC

compatibility

PMP fiber with 0.65 m2

area; single step potting; bundle fabrication amenable to complete automation

Low gas flow resistance: uses positive pressure; no gas purge required

Pivot-bearing, CFD optimized pump

Controller Drive System

PAAL

UHMWPE Bearing

Ceramic Pivots

Inlet

Impeller

Fiber Bundle

Blood Outlet

Blood InletGas

Inlet

Gas Outlet

PumpImpeller

FiberBundleExit


PAAL In-Vivo Chronic Studies

Chronic 5-day studies in sheep

Oxygenation rates 105-155ml/min

Hemolysis < 20 mg/dL with no change from baseline

ASAIO J 2018

CO2 removal, rather than O2 delivery, can be the primary issue in therapy for acute respiratory failure

Chronic obstructive pulmonary disease

(COPD)

Acute respiratory distress syndrome

(ARDS)

• O2 requirements via non-invasive positive pressure ventilation

• Intubation & MV often necessary due to refractory hypercapnia

• Low tidal volume MV improves mortality (ARDSNet)

• Significant risk of hypercapnia and subsequent respiratory acidosis


Avoid intubation and MV in aeCOPD (200-300K patients/year)

Protective ventilation in ARDS (100-150K patients/year)

Clinical Potential

ECCO2R: Extracorporeal CO2 Removal

Novalung: First Commercial AVCO2 System


Crit Care Med 34:1372-77,2006

Ninety patients with ARDS Blood flow ~ 1.5 LPM; CO2 removal ~ 140 ml/min Hypercapnia reversed by iLA within 2 hrs allowing “less aggressive

“ventilation.

www.ctsnet.org

Cove et al. Critical Care, 2012


Compact, efficient hollow fiber module worn/placed externally

Small dual-lumen cannula (14-16 Fr) inserted in the venous circulation for blood flow

Blood flows of 250-500 ml/min for respiratory support (targeting 40-60% of CO2 production)

Rotating hollow fiber bundle for enhanced gas exchange

Self-pumping driven by rotating fiber bundle

Paracorporeal Respiratory Assist Lung (PRAL)*

“Respiratory Dialysis”

PRAL as envisioned in ~ 2002

*Pitt ECCO2R Efforts: ECCO2R to the Next Level

ASAIO J 51:773-780, 2005

Pittsburgh Start-Up: Alung Technologies


Hemolung RAS(CE Mark 2013)

Hemolung Beginning US Clinical Trial


Prospective, multi-center, open-label, randomized, controlled, 2-arm

Each arm will enroll patients with AE-COPD: 1) Failing NIV 2) Intubated and failing weaning


Compact, efficient respiratory assist device that can be worn paracorporeally and readily allow ambulation

Pump and oxygenator integrated into a single compact unit

Proprietary biocompatible coatings to minimize systemic anticoagulation and complications from thrombosis

Primary Functional Requirements:

Blood pumping from 1-2.5 L/min

Oxygenation of 70%-90% metabolic needs

Maintain low level of blood damage

Provide 1-3 months of continuous support before change-out or termination of therapy

Pittsburgh Pediatric Ambulatory Lung (P-PAL)


Adult Vs. Pediatric Ambulatory Assist Lungs

P-PAL and adult PAAL pump-lungs utilize same/similar internal geometry and components.

Successful in vivo 5-day and on-going 30-day studies of PAAL; Acutein vivo studies of the P-PAL.

Pete Wearden: “If the P-PAL can have an important adult application, commercializing it will be much easier”

A Comprehensive Solution: ModELAS*


*Modular Extracorporeal Lung Assist System:“wearable” lung assist for adults and children

PediatricModELAS

(P-ModELAS)

AdultModELAS

A-ModELASFunction

Blood

FlowrateClinical Goal

Clinical Market

(NA/EU)

P-ModELAS

Pediatric O2

supply and CO2

removal

1-2.5

Liters/min

Bridge to recovery

(acute) or transplant

(chronic)

200-500

A-ModELASAdult O2 supply

and CO2 removal

2-3.5

Liters/min

Bridge to recovery

(severe ARDS) or

transplant (chronic)

20,000-50,000

A,P-

ModELAS

ECCO2R

Minimally

invasive CO2

removal

(respiratory

dialysis)

200-500

mL/min

Bridge to recovery

(ARDS, AE-COPD)

300,000-

500,000

Conclusion: Artificial lungs can be realized but …


We are about 20-30 years behind VAD technology

VADs Artificial Lungs

Implantable working unit

YesNo

Extracorporeal

Reliability Years Days-Months

Destination Therapy

YesNoICU

HemocompatibilityVery Good

~ cm2 contact area

Challenge~ m2 contact area

Technology Platform

Mostly Perfected In Infancy


Acknowledgments and Disclosure

• ALung Technologies is a Pittsburgh based medical start-up company.

• License agreement with the University of Pittsburgh covering portions of the technologies discussed today.

• Commercializing the Hemolung Respiratory Assist System

WJF is Founder, Consultant (Head of SAB) and Stockholder of:

• Medical Devices Laboratory: B. Frankowski, S. Madhani, R. Orizondo, A. May, R. Svitek

• U. Pitt.: J. D’Cunha, P. Wearden, W. Wagner

• Alung: S. Morley, L. Lund, J. Kimmel

• National Institutes of Health: Heart, Lung and Blood Institute • Commonwealth of Pennsylvania• National Tissue Engineering Center (NTEC)• McGowan Institute for Regenerative Medicine

People:

Funding:

The End…..

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William J. Federspiel, PhD Whiteford Professor of … · · 2018-02-22Focus has shifted towards new generation of respiratory assist devices ... Fully integrated and compact blood