Reducing Ischemia–Reperfusion Injury in Clinical Lung Transplantation

Abstract Objective Acute graft dysfunction secondary to ischemia–reperfusion injury (IRI) continues to be the most common cause of early mortality after lung transplantation. The perioperative management with aprotinin could decrease the incidence of severe IRI. Methods A retrospective analysis was conducted of the data from 180 patients who underwent either single lung (56%) or bilateral sequential lung transplantation for similar end-stage lung disease between 1997 and 2005. The most recent 68 patients were managed perioperatively with the high-dose aprotinin infusion regimen (aprotinin group). The ISHLT grade III injury score was used for the diagnosis of severe IRI, which is based on a Pa o2 –FI o2 ratio of less than 200 mmHg. Results Grade III injury was observed in 18% of the patients who were not managed with aprotinin (control group, 152 grafts, 64% single transplants, 68% male, 54 ± 8 years of age). Early ECMO support was required in 25% of these patients. The associated mortality rate was 40%. Despite significantly longer cold ischemic times (290 ± 14 minutes vs 231 ± 14 minutes), older donors (42 ± 12 years of age), and more frequently observed severely elevated systolic PAP of greater than 60 mmHg (60% vs 48%) as well as more frequently required extracorporeal circulatory support (24%* vs 12%) in the aprotinin group, the incidence of severe IRI (8%) and associated mortality (9%) was markedly reduced. Conclusions The use of aprotinin in LTX surgery, which had strong beneficial effects on patient outcomes, significantly decreased the incidence of severe posttransplant IRI.