Primary Graft Dysfunction

Abstract

Primary graft dysfunction (PGD) is a form of acute lung injury after transplantation characterized by hypoxemia and the development of alveolar infiltrates on chest radiograph that occurs within 72 hours of reperfusion. PGD is among the most common early complications following lung transplantation and significantly contributes to increased short-term morbidity and mortality. In addition, severe PGD has been associated with higher 90-day and 1-year mortality rates compared with absent or less severe PGD and is a significant risk factor for the subsequent development of chronic lung allograft dysfunction. The International Society for Heart and Lung Transplantation released updated consensus guidelines in 2017, defining grade 3 PGD, the most severe form, by the presence of alveolar infiltrates and a ratio of PaO2:FiO2 less than 200. Multiple donor-related, recipient-related, and perioperative risk factors for PGD have been identified, many of which are potentially modifiable. Consistently identified risk factors include donor tobacco and alcohol use; increased recipient body mass index; recipient history of pulmonary hypertension, sarcoidosis, or pulmonary fibrosis; single lung transplantation; and use of cardiopulmonary bypass, among others. Several cellular pathways have been implicated in the pathogenesis of PGD, thus presenting several possible therapeutic targets for preventing and treating PGD. Notably, use of ex vivo lung perfusion (EVLP) has become more widespread and offers a potential platform to safely investigate novel PGD treatments while expanding the lung donor pool. Even in the presence of significantly prolonged ischemic times, EVLP has not been associated with an increased risk for PGD.

Predictors of early mortality after lung transplantation for idiopathic pulmonary arterial hypertension

“…The higher early mortality in these patients stems from an increased incidence of serious postoperative complications 10,11 . Both a diagnosis of PAH and increasing pulmonary artery pressure are established risk factors for severe PGD, the most common cause of early deaths after lung transplant 13,21 . The odds ratio for severe PGD among PAH recipients was 3.5 relative to COPD in the large multicenter prospective Lung Transplant Outcomes (LTOG) study 22 .…”

“…10,11 Both a diagnosis of PAH and increasing pulmonary artery pressure are established risk factors for severe PGD, the most common cause of early deaths after lung transplant. 13,21 The odds ratio for severe PGD among PAH recipients was 3.5 relative to COPD in the large multicenter prospective Lung Transplant Outcomes (LTOG) study. 22 The basis for this observation is felt to be due, in part, to the effects of longstanding RV dysfunction with consequent underfilling, atrophy and transient dysfunction of the left ventricle (LV).…”

Management of primary graft dysfunction after lung transplantation with extracorporeal life support: an evidence-based review

“…Recent research has challenged this convention by relaxing the preservation temperature to 10 degrees Celsius and widening the cold ischemic time to greater than 8 hours ( 11 ). The donor lungs are transported while inflated with an FiO 2 between 0.3 to 0.5 to facilitate aerobic metabolism—a practice that may also increase the production of reactive oxygen species ( 10 , 12 ). Allograft ischemia is further potentiated by hypoperfusion, as bronchial arteries are typically not re-anastomosed during transplant.…”

Pulmonary, circulatory and renal considerations in the early postoperative management of the lung transplant recipient

“…Primary graft dysfunction (PGD) is a form of non-cardiogenic pulmonary edema within the first 72 h after lung transplantation caused by pathological findings of acute lung injury with diffuse alveolar damage in the most severe cases 33 . Diagnosis is made based on the presence of radiographic opacities consistent with pulmonary edema ( Figure 2 ) in the absence of other causes, such as left heart failure, pneumonia, pulmonary venous obstruction, hemorrhage, or hyperacute rejection 34 .…”

“…Several risk factors have been described with variable associations for the development of PGD that can be divided into donor-related, recipient-related 36 , peri-operative, and post-transplant ( Table 3 ) 33 . LTOG analysis identified eight independent variables ( Table 3 ) 8 .…”