Pediatric Artificial Lung (PAL) Work sponsored by NIH RO1-HD-015434 - - PowerPoint PPT Presentation

Pediatric Artificial Lung (PAL)

Ronald B. Hirschl, M.D. Professor and Head, Pediatric Surgery Mott Children’s Hospital University of Michigan

No disclosures Work sponsored by NIH RO1-HD-015434

Pediatric Chronic Respiratory Failure

• CDH:

 56% die or meet criteria for BPD at 30 days.  The cost of CDH is $250 million annually  Beyond age 4-5 years patients lead reasonably normal lives.  Example: LTx in newborn with CDH and excised at 5 years.

• Hypoxemia, CO2 retention, and

pulmonary hypertension.

• CDH, BPD, ACD, interstitial lung

disease, and fibrosis following necrotizing pneumonia and ARDS.

DeAnda A , et al. J Ped Surg, 33:655, 1998

Pediatric Chronic Respiratory Failure

• ECMO is being

discontinued for futility at a lower rate which is resulting in longer runs.

Posluszny J, et al. Ann Surg 263:573, 2016

• Johns Hopkins—Case
• f ECMO 605 days

with survival

• 974 adult ELSO Registry with respiratory

failure from 1989 to 2013

• ECLS course > 14 days, median course of

21 days (range: 14-208 days).

Pediatric Chronic Respiratory Failure

• A simple PAL might :
• Provide gas exchange, offload the RV, decrease

pulmonary pressures

• Allow discharge from the ICU and even potentially to

home.

• Eventually may serve as a destination device.
• ECMO is complicated, labor

intensive, and expensive.

• ECMO mortality is 26% in

neonates and 43% in children

Pediatric Chronic Respiratory Failure

• LTx common for cystic fibrosis in older children
• LTx rare in ARDS on ECMO and in

newborns/infants with refractory PHTN

• 27% of pediatric LTx performed in children < 11

years of age and ~3% in infants < 1 year of age

 Brendan C, et al. J Heart Lung Transplant. 32:989, 2013  Puri V, et al. JTCVS. 140:427, 2010  Aurora P, et al. J Heart Lung Transplant 29:1129, 2010

Lung Transplant in Pediatric Chronic Respiratory Failure

• PAL would permit extubation, ambulation
• Allow months to recover from acute disease and

deconditioning

• Provide a contingency for graft failure

Schmid F, et al., Ped Pulm 51:1222, 2016 Fuehner, T., et al., AJRCCM, 185:763, 2012 Wong, JYW, et al., Am J Transplant, 15: 2256, 2015

N = 26, 80% Surv N = 34, 50% Surv

• 4 year old
• BMPR2

mutation

• PAH
• RAAo

10 20 30 40 50 60 B1 B2 1 2 3 4 5 6 7 Elapsed Time, Day PCO2, mmHg 100 200 300 400 500 600 PO2, mmHg PCO2 PO2

PA  LA in Pulmonary HTN

Mean PVR: 5.91 to 2.64 Woods Units, p=.001

PVR (mPAP-mLAP/CO)

1 2 3 4 5 6 7 8 9 10 11 Device Clamped Device Flow Wood's Units

Sato, Ann Thor Surg. 84:988, 2007

• 38 year old
• PAH and RHF
• ECMO62 days

PA-LA

• Bridge to

double LTx

PAL Management of PAH

Strueber M, et al. Am J Transplant 9: 853–857, 2009

• 30 year old
• PAH and PVOD
• ECMO18 days

PA-LA

• Succumbed to

sepsis Camboni D, et al. ASAIO Journal 55: 304, 2009

Pediatric Artificial Lung

• High efficiency
• Low resistance
• Simple, no pump
• Total gas exchange requirements of

patient

• Unload right ventricle
• Minimize blood element trauma
• Serve as bridge to lung

transplantation, recovery, destination

• 4 patients supported with pulmonary artery to

left atrium lung assist device

• One neonate and 3 children under the age of 2

Hogansen, D, et al. J Thor Cardiovasc Surg 147:420, 2014

Age Diagnosis preop PASP* (mmHg) Preop SBP (mmHg) PASP during device support** (mmHg) Percent drop in PASP 23 days ACD 75 50 55 27% 2 months AV canal, R lung hypoplasia 125 85 51 59% 9 months ACD 100 75 46 54% 23 months PPH 93 75 not measured n/a Age Diagnosis ECMO support (days) Lung device support (days) Extubated (days post device insertion) Outcome 23 days ACD 5 54 15 death (hemorrhagic CVA 44 days) 2 months AV canal, R lung hypoplasia 0.1 74 72 death (renal failure,CVA) 9 months ACD 9 5 n/a lung transplant 23 months PPH 17 23 9 weaned to medical management, mild CVA

ACD, alveolar capillary dysplasia; AV canal, atrioventricular canal; PPH, primary pulmonary hypertension

Pediatric paracorporeal lung assist device

Hogansen, D, et al. J Thor Cardiovasc Surg 147:420, 2014

Left atrial cannulation strategy with transatrial graft

Patient Left atrial cannula LA thrombus 23months 22F metal R angle none 23 days 16F metal R angle large 3 months 16F metal R angle small 9 months 10mm Gore graft none

Berlin cannula with transatrial Gore graft sewn to interatrial septum Berlin cannula to main pulmonary artery

Hogansen, D, et al. J Thor Cardiovasc Surg 147:420, 2014

• Guidelines for implantation and management of

paracorporeal lung assist device in children

• Current indications: primary or secondary

pulmonary hypertension with systemic or suprasystemic PA pressures.

Gazit A, et al.Ped Transplant 20:256, 2016

Pediatric paracorporeal lung assist device

Pediatric Artificial Lung: Ovine Model of Pediatric Lung Failure Pathophysiology Trahanas, J, et al.ASAIO Journal 2017; 63:216–222

• Seven (25-40 Kg) sheep
• Thoracotomy with RPA

tourniquet placement

• Occlusion of RPA on POD #1

Pediatric Artificial Lung: Ovine Model of Pulmonary Hypertension

• Five lambs (29.4 ± 3.1 kg), left thoracotomy.
• 10 mm grafts sewn onto PA and LA and connected by a

shunt, tourniquet on the right PA

• The next day, baseline data collected
• The right PA was then occluded and data collected
• PAL (Novalung) attached and data collected

Alghanem F, et al. ASAIO J 63:223, 2017

Pediatric Artificial Lung: Ovine Model of Pulmonary Hypertension

Alghanem F, et al. ASAIO J 63:223, 2017

M Lung Design

Particle Image Velocimetry CFD

M Lung Design

M Lung Efficiency

Fiber SA = 0.28 m2

Nitric Oxide Surface Coating With S-nitroso-N- acetylpenicillamine (SNAP) Prevents Platelet Consumption and Clot Formation During ECLS

Brisbois EJ, et al. Acta Biomaterialia 37:111, 2016

• NO donor mimics range of endothelium NO release
• 8 rabbit AV ECLS no heparin, n=4 control, n=4 SNAP
• Platelets at 64% of baseline (control = 12%)
• 67% reduction in circuit chamber thrombus formation

PAL Servoregulation of CO2

• Automatically controls gas flow based on exhaust gas CO2.
• Proportional-integral-derivative (PID) feedback controller to

modulate the sweep flow

• A graphical user interface and software controller were

programmed using Microsoft Visual

Cannula Development Those that do the work

Pediatric Chronic Respiratory Failure

• Survival is ~50% at 5 years in pediatric lung txp

 Brendan C, et al. J Heart Lung Transplant. 32:989, 2013