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Ex-Vivo Single Lung <strong>Perfusion</strong><br />
Techniques:<br />
Expanding the <strong>Perfusion</strong>ist Role<br />
during Lung Transplantation<br />
George Justison CCP 1 , Leo Carr CCP 1 , Miral Sadaria MD 2 ,<br />
Phillip Smith MD 2 , Michael Weyant MD 2 .<br />
George A Justison CCP<br />
Manager <strong>Perfusion</strong><br />
1 Specialty Care, Nashville, TN.<br />
1,2 University of Colorado Hospital<br />
Aurora, CO
Disclosures<br />
This project was supported by a generous grant of equipment<br />
and supplies by :<br />
Sorin Group USA, Arvada CO<br />
Vitrolife, Göteborg, Sweden<br />
Puritan Bennett, Covidien, Mansfield, MA<br />
This project received a waiver from the Colorado Multiple<br />
Institutional Review Board<br />
I will discuss equipment and/or techniques which have not<br />
received clearance by the FDA for sale or use in the US.<br />
"I declare on behalf of myself and all authors the following:<br />
We have no material, financial, or other relationship with any<br />
healthcare-related business or other entity whose products or<br />
services may be discussed in, or directly affected in the<br />
marketplace by, this manuscript."
Lung Transplantation<br />
• 35% of patients die on waiting list<br />
• 8 out of 10 lungs offered are unsuitable<br />
• Aspiration associated injury<br />
• Ventilator associated pneumonia<br />
• Barotrauma<br />
• Poor fluid/ventilator management during the<br />
brain death process<br />
• ISHLT gas exchange guidelines<br />
• PaO2 > 300mmHg, FiO2 100%, PEEP 5 cmH2O<br />
Punch JD, Hayes DH, LaPorte LB, McBride V, Seely MS. Organ donation and utilization in the United States, 1996-2005. Am J Transplant 2007;7:1327-38.<br />
Cypel M, Yeung J, Hirayama S, et al. Technique for prolonged normothermic ex vivo lung perfusion. J Heart Lung Transplant 2008;27:1319-25.
Ex-Vivo Lung <strong>Perfusion</strong> (EVLP)<br />
• Described by Steen et. al (2003)<br />
• Short term support and evaluation of DCD<br />
donor lungs<br />
• Steen S., Liao Q., Wierup, PN., et al. Transplantation of lungs from nonheart<br />
beating donors after functional assessment ex vivo. Ann Thorac<br />
Surg 2003;76:244-52.<br />
• First successful human transplant of an exvivo<br />
reconditioned lung (2007)<br />
• Steen S., Ingemansson R., Eriksson L., et al. First human<br />
transplantation of a nonacceptable donor lung after reconditioning ex<br />
vivo. Ann Thorac Surg 2007;83:2191-5.
Prolonged EVLP<br />
Cypel M, Yeung J, Hirayama S, et al. Technique for prolonged<br />
normothermic ex vivo lung perfusion. J Heart Lung Transplant<br />
2008;27:1319-25.<br />
• Prolonged (12 h) normothermic perfusion<br />
• Low Flow (40% of normal CI)<br />
• Acellular STEEN Solution
Ex-Vivo Lung <strong>Perfusion</strong> (EVLP)<br />
• Cold Lung Storage<br />
• Impaired cellular<br />
metabolism<br />
• Eliminates substantial<br />
reparative processes<br />
• Must support patient<br />
immediately from cold<br />
storage to reperfusion<br />
• EVLP<br />
• Isolated perfusion<br />
• Normothermic<br />
• Prolonged evaluation<br />
• Eliminates donorrecipient<br />
hemodynamic<br />
mismatch<br />
• Time for therapeutic<br />
strategies
University of Colorado Single<br />
EVLP Protocol<br />
• CMIRB waiver<br />
• 5 single human lungs declined for transplant<br />
• PaO2 < 300 mmHg<br />
• Barotrauma<br />
• Suspected pneumonia<br />
• Harvested using standard techniques<br />
• Perfadex® retrograde flush<br />
• Large LA, PA, tracheal cuffs<br />
• Cold ice storage
LA Cuff<br />
PA Cuff<br />
Trachea
EVLP Cannulation<br />
• Large silicone cuffs cut to fit LA, PA<br />
• Running 4-0 monofilament suture<br />
• Integral pressure monitoring channel<br />
• 3/8 inch connection
Elements of EVLP Circuit<br />
• Sorin EOS 905<br />
• Revolution® pump<br />
• Pall LG6 leukocyte filter<br />
• A/V CDI 500<br />
• Sorin Smart 3/8” A-V<br />
loop<br />
• Medtronic Bio Cal<br />
• Puritan Bennett 840<br />
ventilator<br />
• Deoxygenating Gas<br />
• 86% N, 8% CO2, 6% O2
STEEN Solution<br />
• Composition<br />
• Normal human albumin<br />
• Dextran<br />
• Extracellular electrolyte (Low K+)<br />
• Prime EVLP 1500 mL<br />
• Exchange 100 mL / hour<br />
For research only in the US
EVLP <strong>Perfusion</strong> Protocol<br />
<strong>Perfusion</strong> Minutes Temp o C % Flow PAP LAP Ventilator Deoxygenator<br />
10 20 10 10 to 15 3 to 5 OFF OFF<br />
20 30 20 10 to 15 3 to 5 OFF OFF<br />
30 32-35 30 10 to 15 3 to 5 ON ON<br />
40 37 50 10 to 15 3 to 5 ON ON<br />
50 37 80 10 to 15 3 to 5 ON ON<br />
60 + 37 100 10 to 15 3 to 5 ON ON<br />
• Double lung flow: 40% donor CI of 2.4-3.0 L/min/m 2<br />
• Single lung flow: 60% DL Right Lung, 40% DL Left Lung<br />
• Ventilator: 6-8 mL/Kg, 60% Right Lung, 40% Left Lung<br />
• 7 breaths/min., PEEP 5 cmH 2 O, FiO 2 21%<br />
• Ventilator recruitment to PEEP 25 cmH 2 O q 30 minutes<br />
• Deoxygenator gas flow to maintain PaCO 2 35-45 mmHg
PVR PaO2 Data<br />
Lung Prior to Hours of <strong>Perfusion</strong><br />
# Procurement 1 2 3 4 5 6 7 8 9 10 11 12<br />
1 262 350 435 431<br />
PaO2 with FiO2<br />
100% (mmHg)<br />
2 400 475 467 454<br />
3 430 430 415 399<br />
4 189 408 369 360<br />
5 237 341 341 322<br />
1 667 286 369 185 185 185 123 235 178 117 234 178<br />
Pulmonary<br />
Vascular<br />
Resistance<br />
(dynes/s/cm5)<br />
2 1905 1600 1725 1796 1796 1633 970 1143 1161 1161 1290 1161<br />
3 839 896 855 855 842 782 1137 1118 1209 647 529 529<br />
4 744 780 867 809 899 809 791 818 791 791 696 703<br />
5 879 1011 870 783 681 609 711 744 426 539 522 455
PaO2 Trend<br />
p = 0.03
PVR Trend<br />
p < 0.001
Structural Integrity after 12<br />
hours of single lung EVLP
Importance of CILM<br />
• Steady venous state<br />
• pCO2 35-45 mmHg<br />
• pO2 30-40 mmHg<br />
• Titrate deoxygenator<br />
• Immediate evaluation<br />
of lung function<br />
• Hours 2, 6, 12 > Fio2<br />
to 100%<br />
• pH<br />
• Guide for STEEN<br />
replacement
EVLP Troubleshooting Guide<br />
Condition Problem Solution<br />
Low perfusate pH<br />
Low perfusate pCO 2<br />
High LAP<br />
High PAP<br />
1. Vasoconstriction<br />
2. High PVR<br />
1. Endothelial damage<br />
2. Alveolar fluid retention<br />
1. Increased hydrostatic<br />
pressure.<br />
2. Pulmonary edema.<br />
1. Low perfusion flow<br />
2. Pulmonary edema<br />
3. Inadequate flush<br />
Replace STEEN Solution<br />
(Avoid Sodium Bicarbonate)<br />
Increase deoxygenator gas<br />
flow<br />
1. Check cannula position<br />
2. Lower reservoir<br />
1. Check cannula position.<br />
2. Increase retrograde flush<br />
to remove residual clots.<br />
3. Check flow rate.<br />
• Challenges with Single Lung EVLP<br />
• Maintaining low flow (200-400 mL/min) with a centrifugal pump<br />
• Maintaining PAP LAP guidelines<br />
• Pressure excursions during ventilator recruitment maneuvers and<br />
sustained PEEP.
XVIVO <strong>Perfusion</strong> System (XPS TM )<br />
• Self contained<br />
portable system for<br />
EVLP<br />
• “Sterile” lung side<br />
• <strong>Perfusion</strong><br />
Management side<br />
This product is not FDA approved for sale in the<br />
US
XPS TM Features:<br />
Touch-screen display<br />
In-line gas monitoring<br />
(pCO 2 , pO 2 , pH)<br />
ICU Ventilator<br />
CardioHelp XVIVO<br />
Heater/cooler (15-39 o C)<br />
This product is not FDA approved for sale in the<br />
US
This product is not FDA approved for sale in the<br />
US
Zych, B, Marczin N., Carby M., Ex Vivo <strong>Perfusion</strong>-A way to Salvage Lungs for<br />
Transplantation?. Brit. J Transplantation., Volume 4 Issue 3: 10-6<br />
“ Staffing with trained perfusionists is a prerequisite to starting a<br />
clinical programme and will have an impact on elective services”<br />
• Antibiotic therapy of donor lungs<br />
• Non heart beating DCD lung transplantation<br />
• Gene therapy and immune modulation
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