Case Report: Optimal utilization of marginal lung allografts by considering donor-recipient PGD risk compatibility and by mitigating allograft and recipient inflammatory risk

Abstract

Reducing the risk of high-grade primary graft dysfunction (PGD) is vital to achieve acceptable short- and long-term outcomes for recipients following lung transplantation. However, the utilization of injured lung allografts, which may confer a higher risk of PGD, must be considered due to the disparity between the increasing number of patients requiring lung transplantation and the limited donor pool. We describe a case in which highly marginal lung allografts were utilized with a good post-transplant outcome. Donor-recipient PGD risk compatibility was taken into consideration. Normothermic ex vivo lung perfusion (EVLP) was utilized to functionally assess the allografts. A second cold ischemia time following EVLP was avoided by converting the EVLP mode to a hypothermic oxygenated perfusion setup from which the lungs were transplanted directly. We attempted to mitigate lung ischemia-reperfusion injury in the recipient by employing cytokine adsorption both during the EVLP and intraoperatively during the implant procedure. In this case report, we describe our hypothermic oxygenated perfusion setup on EVLP for the first time. Furthermore, we describe the utilization of cytokine adsorption in two phases of the same transplant process.

Keywords: EVLP; cytokine adsorption; hypothermic oxygenated lung perfusion; lung ischemia-reperfusion injury; lung transplant continuum; lung transplantation outcome; primary graft dysfunction.

Figure 1

(A) A schematic diagram of the time intervals and events encountered in a standard DBD/EVLP procedure to contrast with (B) where the events and time intervals are given for a DBD/EVLP/hypothermic oxygenated perfusion procedure as was performed in this case. (A) The standard procedure of a static EVLP where a first cold ischemia time (CIT) is followed by a period of ex vivo lung perfusion (EVLP) to test and optimize lung function. This is then followed by a second period of static cold storage and cold ischemia (CIT 2) and a period of warm ischemia (WIT, warm ischemia time) during the surgical implantation in the recipient. (B) The time intervals and events in hypothermic oxygenated perfusion (HOPE) on the EVLP setup where CIT 2 is avoided. Actual times for the case are given in row B. During HOPE on EVLP, the lungs were cooled to 12°C, ventilation of the lungs was stopped, CPAP was applied in this case at 10 cmH₂O, and the perfusion was reduced to 800 ml/min. The lungs were directly transplanted from the HOPE EVLP setup. In this case, the right lung was transplanted first, leaving the left lung on the HOPE EVLP setup with an open left atrium.

Figure 2

The PaO₂/FiO₂ ratio of the lung allografts during the transplant process from procurement in the donor to 72 h after reperfusion in the recipient. NB: The x-axis is not linear, the procurement and recipient phases are in hours, EVLP time is in minutes, and the post-transplant phase is in hours. SCS, static cold storage; EVLP, ex vivo lung perfusion. (A) X-ray at T120 mins of EVLP depicting a distribution of perfusate suggestive of hydrostatic lung edema. (B) Chest x-ray of the recipient on admission to the ICU immediately post-transplant. (C) Chest x-ray of the recipient at 72 h post-transplant.

Figure 3

PGD risk estimation on the basis of recipient, donor, and surgical risk factors as taken in the context of a specific transplant continuum. The donor in this case is designated high risk due to the presence of severe edema (weight 1,492 g) and a P/F ratio of less than 300 mmHg. (A) Transplant continuum of the originally designated recipient with an estimation of a high cumulative PGD risk. The recipient was designated as “high risk” on the basis of (i) high lung allocation score (73), (ii) high-risk diagnosis (interstitial lung disease), (iii) high pre-operative disease severity (acutely worsening clinical state), and (iv) pulmonary hypertension (mean pulmonary artery pressure of 39 mmHg). Surgery was estimated as high risk due to (i) the necessity for size reduction of the graft in combination with (ii) the need for extracorporeal support during the operation. (B) The transplant continuum of the second (reserve) recipient with the estimation of the cumulative PGD risk as “acceptable.” The recipient was designated as “low risk” on the basis of (i) a low lung allocation score (33), (ii) a low-risk diagnosis (combined emphysema and fibrosis), and (iii) mild pulmonary hypertension (mean pulmonary artery pressure of 26 mmHg). Surgery was estimated as intermediate risk due to the need for extracorporeal support during the operation.