- Who is available from the study to assist us with questions as they come up for the protocol?
- How long can preservation time be per stage?
- How long does the EVLP process take from initiation to completion?
- Will the study centers receive an alert when a lung is sent for EVLP?
- Is there any reference that needs to be followed for procuring the lungs for this study?
- Who is responsible for transportation arrangements to and from LBE facilities?
- Can a single lung be perfused on your system?
- Is ECMO an exclusion criterion?
- If a patient previously had a right single transplant and then needs a transplant on the left, are they eligible for the study?
- What is the definition of PGD for double lungs and single lungs?
- What type of training do the Specialists have?
Who is available from the study to assist us with questions as they come up for the protocol?
Lung Bioengineering works with a clinical research organization (CRO), a resource for questions related to data collection and/or analysis and adverse events. In general, study centers should first consult with the CRO when questions about the protocol arise.
The Lung Bioengineering team will be available to consult with study center physicians/surgeons about suitability criteria for lungs undergoing EVLP or post-EVLP suitability for transplantation.
If you would like to request additional information or submit a question, please use the “contact us” form and one of our team members will follow up with you directly.
How long can preservation time be per stage?
CIT-1, from donor aortic cross clamp to the start of the EVLP process at LBE facilities, must be 10 hours or less.
EVLP time, from initiation to completion of EVLP procedure may be a minimum of 3 hours and a maximum of 6 hours.
CIT-2, from completion of EVLP to the first stitch in the anastomosis of the first lung, must be less than or equal to 6 hours. For sequential bilateral procedures, CIT-2 for the second lung must be less than or equal to 10 hours.
How long does the EVLP process take from initiation to completion?
EVLP begins once lung perfusion starts on the EVLP circuit. The EVLP procedure runs for a minimum of 3 hours up to a maximum of 6 hours.
Will the study centers receive an alert when a lung is sent for EVLP?
The involved transplant program will receive electronic alerts when a lung arrives at LBE facilities. At the conclusion of the EVLP procedure, the study center will receive another alert telling the transplant physician to log in and enter their disposition of the lung (accept or decline for transplant) in the client portal of the CMX.
Is there any reference that needs to be followed for procuring the lungs for this study?
The protocol has no requirements for the way that the lungs are procured. However, we do have a “Lung Retrieval and Preservation for EVLP” reference that has recommendations for lung retrieval specifically for EVLP. It is recommended to review this reference and to share it with your colleagues who perform the lung retrieval.
Who is responsible for transportation arrangements to and from LBE facilities?
The transplant center and/or OPO are in charge of arranging air transportation and LBE is responsible for ground local transportation to the EVLP facility. If for whatever reason transportation arrangements cannot be made expeditiously, Lung Bioengineering is able to assist in air and ground transportation logistics. An EVLP Specialist contacts the appropriate transplant center personnel to ensure that lungs are imported and exported as quickly as possible. The air and/or ground transportation cost involved with the import of lungs to LBE facilities from the donor location are paid for by LBE regardless of EVLP outcome to transplant. Air and/or ground transportation cost for exporting lungs to an accepting clinical trial site are also paid by LBE. For reimbursement of transportation costs, LBE must be aware of the method of transportation in advance of any lung import/export activity, and the cost to be paid by LBE must be reasonable.
Can a single lung be perfused on your system?
Yes. A single lung can be perfused on the Centralized Lung Evaluation System.
Is ECMO an exclusion criterion?
No, ECMO is not an exclusionary criterion. Pre-transplant ECMO status will be tracked for all enrolled subjects as control group subjects will be matched on several criteria, including ECMO.
If a patient previously had a right single transplant and then needs a transplant on the left, are they eligible for the study?
Yes, they are eligible for the study because it is NOT a same side re-transplant.
What is the definition of PGD for double lungs and single lungs?
Primary Graft Dysfunction (PGD) Score
The subject’s PGD Score is to be determined upon admission to the ICU after transplantation, as well as 24, 48, and 72 hrs post-transplant following the 2016 ISHLT PGD definition.1 PGD Score will be as graded using the parameters in Table 2, where the P/F ratio is PaO2/FiO2.
Table 2 | Primary Graft Dysfunction Grading
| Grade | P/F Ratio | Pulmonary Edema on Chest X-ray |
|---|---|---|
| 0 | ANY | No |
| 1 | >300 | Yes |
| 2 | 200 TO 300 | Yes |
| 3 | <200 | Yes |
Grade severity notes: Patients with no evidence of pulmonary edema on chest X-ray are considered grade 0. Absence of invasive mechanical ventilation should be graded according to the PaO2/FIO2 ratio, using methods similar to those receiving mechanical ventilation. If PaO2 is not available for calculation of a PaO2/FIO2 ratio, then an oxygen saturation/FIO2 ratio should be calculated and the 200 and 300 PGD grading cutoffs should be adjusted to 235 and 315. Use of nitric oxide, aerosolized epoprostenol, or other pharmacologic agents that may improve oxygenation should not change grading methods. Use of extracorporeal lung support (ECLS) with bilateral pulmonary edema on chest X-ray image should be graded as grade 3 and ECLS use should be explicitly recorded. The use of ECLS for non-hypoxic indications without pulmonary edema on chest X-ray imaging should be considered un- gradable and explicitly recorded separately. Time window notes: PGD is graded at 4 time-points over the first 72 hours after transplantation (T0, T24, T48 and T72 hours). T0 is defined as the time of the first blood draw for blood gas testing after admission to the ICU, which should take place within 6 hours of reperfusion of the last lung transplanted. T24, T48 and T72 have time windows ± 6 hours. If multiple blood gas values are available, the worst PaO2/FIO2 ratio in a given assessment should be used. Other notes: PaO2/FIO2 should ideally be measured on positive end-expiratory pressure of 5cm H2O at FIO2 of 1.0 while patients are on mechanical ventilation; however, grading should not be altered for other settings.
Grade severity notes: Patients with no evidence of pulmonary edema on chest X-ray are considered grade 0. Absence of invasive mechanical ventilation should be graded according to the PaO2/FIO2 ratio, using methods similar to those receiving mechanical ventilation. If PaO2 is not available for calculation of a PaO2/FIO2 ratio, then an oxygen saturation/FIO2 ratio should be calculated and the 200 and 300 PGD grading cutoffs should be adjusted to 235 and 315. Use of nitric oxide, aerosolized epoprostenol, or other pharmacologic agents that may improve oxygenation should not change grading methods. Use of extracorporeal lung support (ECLS) with bilateral pulmonary edema on chest X-ray image should be graded as grade 3 and ECLS use should be explicitly recorded. The use of ECLS for non-hypoxic indications without pulmonary edema on chest X-ray imaging should be considered un- gradable and explicitly recorded separately.
Time window notes: PGD is graded at 4 time-points over the first 72 hours after transplantation (T0, T24, T48 and T72 hours). T0 is defined as the time of the first blood draw for blood gas testing after admission to the ICU, which should take place within 6 hours of reperfusion of the last lung transplanted. T24, T48 and T72 have time windows ± 6 hours. If multiple blood gas values are available, the worst PaO2/FIO2 ratio in a given assessment should be used.
Other notes: PaO2/FIO2 should ideally be measured on positive end-expiratory pressure of 5cm H2O at FIO2 of 1.0 while patients are on mechanical ventilation; however, grading should not be altered for other settings.
1. Snell GI, et al. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction, part I: Definition and grading-A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2017 Oct;36(10):1097-1103.
What type of training do the Specialists have?
EVLP Specialists candidates are selected from applicants having organ procurement and evaluation experience, including OPO personnel and surgeons. Specialist candidates are then qualified by a combination of intensive training with the development team at Toronto General Hospital, and a Lung Bioengineering-specific competency and qualification program upon their return.
Specialist candidates have extensive training through an in-residence program at TGH, culminating in successful completion of an Ex Vivo Lung Specialist Final Exam. This training program was developed by the team that developed the Toronto EVLP Method, and is therefore specifically focused on this mode of EVLP.
The practical, hands-on experience includes observing and participating in ongoing research (animal) EVLP procedures. Additionally, the specialist candidate will observe and participate in clinical (human) EVLP procedures performed at Toronto General Hospital. This includes assembly of the EVLP components, troubleshooting all equipment, cannulation and intubation of lungs, maintaining a lung on EVLP, explaining donor lung physiology and suitability for EVLP, and interpreting key assessment parameters during the EVLP procedure.