Long Term Impact of Primary Graft Dysfunction after Lung Transplantation

According to the International Society for Heart and Lung Transplantation (ISHLT) Registry, graft failure accounted for 24.7% of deaths within 30 days of transplantation among adult lung recipients between 1992 and 2012 [1]. Although important details distinguishing different causes of early graft failure may be missing from the Registry data, it is likely that primary graft dysfunction (PGD) is the leading cause of early graft failure. PGD was initially described in 1973 when autologous lung reimplantation in canines was associated with functional defects in the early post-operative period even when re-implantation was “technically flawless.” Serial radiographs after re-implantation and biopsy specimens demonstrated pulmonary edema despite normal pulmonary angiograms [2]. These findings led investigators to suspect ischemia followed by reperfusion as the cause of this graft injury. Forty years later, the predominant explanation for the mechanism of tissue damage characteristic of PGD still underscores the role of ischemia-reperfusion injury [3,4]. This early injury after lung transplantation is thought to include an acute phase, involving macrophage-mediated microvascular endothelial damage, and a delayed phase, mediated by neutrophil and monocyte graft infiltration [5]. Nonetheless, it is likely that PGD represents the end-result of multiple insults that begin with donor brain death and possible neurogenic pulmonary edema, aspiration, and ventilator-induced lung injury followed by ischemia when the donor organ is retrieved and reperfusion at the time of implantation. PGD is characterized clinically and radiographically by hypoxemia and pulmonary edema occurring in the first 72 hours after transplantation [4]. Histologically, PGD manifests as an acute lung injury that is characterized by diffuse alveolar damage in its most severe form. There is a spectrum of severity varying from mild abnormalities in pulmonary function to severe hypoxemic respiratory failure requiring intensive support. Fortunately, a minority of lung transplant recipients develops severe PGD while others have mild or moderate impairment in pulmonary function. The majority of recipients improve over time with supportive care, but some patients have progressive or persistently severe graft dysfunction and ultimately die or require re-transplantation. However, survivors who appear to recover completely from the acute injury have worse long-term outcomes than recipients who did not develop PGD. This manuscript will review the clinical presentation and management of PGD and focus on its impact on long-term outcomes after lung transplantation.