How to recondition ex vivo initially rejected donor lungs for clinical transplantation: clinical experience from lund university hospital

Abstract

A major problem in clinical lung transplantation is the shortage of donor lungs. Only about 20% of donor lungs are accepted for transplantation. We have recently reported the results of the first six double lung transplantations performed with donor lungs reconditioned ex vivo that had been deemed unsuitable for transplantation by the Scandiatransplant, Eurotransplant, and UK Transplant organizations because the arterial oxygen pressure was less than 40 kPa. The three-month survival of patients undergoing transplant with these lungs was 100%. One patient died due to sepsis after 95 days, and one due to rejection after 9 months. Four recipients are still alive and well 24 months after transplantation, with no signs of bronchiolitis obliterans syndrome. The donor lungs were reconditioned ex vivo in an extracorporeal membrane oxygenation circuit using STEEN solution mixed with erythrocytes, to dehydrate edematous lung tissue. Functional evaluation was performed with deoxygenated perfusate at different inspired fractions of oxygen. The arterial oxygen pressure was significantly improved in this model. This ex vivo evaluation model is thus a valuable addition to the armamentarium in increasing the number of acceptable lungs in a donor population with inferior arterial oxygen pressure values, thereby, increasing the lung donor pool for transplantation. In the following paper we present our clinical experience from the first six patients in the world. We also present the technique we used in detail with flowchart.

Figure 1

Flowchart showing the first part of the ex vivo reconditioning of donor lungs initially rejected donor lungs for clinical transplantation. During the first part of the process, the lungs are not ventilated and the perfusate blood is oxygenated. The temperature of the perfusate is gradually increased with a gradient ≤10°C to 32°C. The initial perfusion flow was 50–100 mL/min. The flow was slowly increased, and the pulmonary pressure was kept at ≤20 mmHg. The left atrium pressure was maintained at 0 mmHg to prevent the development of edema.

Figure 2

Schematic (a) and photograph (b) of the ex vivo lung reconditioning and evaluation system. The blood leaving the remaining dorsal part of the left atrium runs freely out into the box containing the lung. The pulmonary arterial pressure (PAP) is measured continuously. The left atrium pressure (LAP) is maintained at 0 mmHg. Blood gases are measured in the blood before and after the lung. The system is primed with STEEN solution and erythrocyte concentrate.

Figure 3

Flowchart showing the second part of the ex vivo reconditioning of donor lungs initially rejected donor lungs for clinical transplantation. During the second part of the process, the lungs are ventilated and the perfusate blood is oxygenated. When the temperature reaches 32°C, careful ventilation is started at 1 L/min. The ventilation rate is increased with one liter per increasing degree of perfusate from the lung (i.e., increasing lung temperature). The FiO₂ was maintained at 1.0, and the respiratory frequency was gradually increased from 5 to 15–20 per min. The perfusion flow was limited by the pulmonary pressure (≤20 mmHg). The PEEP was gradually increased to 5 cm H₂O at 37°C.

Figure 4

Flowchart illustrating the evaluation of ex vivo reconditioned lungs for clinical transplantation. During the evaluation, the lung is fully ventilated and the perfusate blood is deoxygenated. The gases entering the oxygenator are mixed to obtain values of pCO₂ of 4.5–5 kPa. At this point, the perfusion flow was 4–6 L/min (i.e., full flow). Samples of the perfusate blood are taken before and after passing through the lung (i.e., venous and arterial blood samples) after 5 minutes' exposure to FiO₂ of 0.21, 0.5, and 1.0 in order to measure blood gases. A deflation test is then performed. If the deflation test is normal and the PaO₂ with FiO₂ = 1.0 was 50 kPa or higher, the lungs are accepted for transplantation.

Figure 5

Photograph of the preparation of the donor lungs for ex vivo treatment showing cannulation of the pulmonary artery.