Incidence of primary graft dysfunction is higher according to the new ISHLT 2016 guidelines and correlates with clinical and molecular risk factors

Abstract

Background: Primary graft dysfunction (PGD) is the most important determinant of morbidity and mortality after lung transplantation, but its definition has evolved over the past decade. The implications of this refinement in clinical definition have not been evaluated. In this single-center study, we compared PGD incidence, risk factors, and outcomes using the 2005 and the updated-2016 International Society of Heart and Lung Transplantation guidelines for PGD grading in lung transplant patients. Methods: In this retrospective study, we extracted data from the medical records of 127 patients who underwent lung transplantation between 1/1/2016-12/31/2018. PGD was defined as PGD3 present at 48 and/or 72 hours post-reperfusion. We used the 2005 and the updated 2016 guidelines to assess clinical risk factors, outcomes, and baseline biomarkers for PGD. Results: On the basis of the 2016 and 2005 guidelines, we identified PGD in 37% and 26% of patients, respectively. PGD was significantly associated with extracorporeal life support, large body mass index, and restrictive lung disease using the 2016 but not the 2005 guidelines. Based on the 2016 guidelines, pretransplant levels of several biomarkers were associated with PGD; using the 2005 guidelines, only increased interleukin-2 levels were significantly associated with PGD. No preoperative biomarkers were associated with PGD using either guidelines after adjusting for clinical variables. Postoperative morbidity and 1-year mortality were similar regardless of guidelines used. Conclusions: Our findings suggest that refinements in the PGD scoring system have improved the detection of graft injury and associated risk factors without changing its ability to predict postoperative morbidity and mortality.

Plasma protein biomarkers for primary graft dysfunction after lung transplantation: a single-center cohort analysis

“…We found a correlation between sRAGE levels and the severity of PGD in one of 12 pairwise comparisons. Pretransplant samples showed lower levels of sRAGE in patients with greater PGD severity, which is consistent with findings reported by Daoud et al 5 . sRAGE levels were increased in postoperative samples at T24–72 h in our study.…”

“…Moreover, the rates of PGD in this series were higher than those reported in large multicenter studies 24 , but the risk factors and outcomes associated with PGD were similar. The higher rates in our study may be due to the use of the updated 2016 ISHLT scoring guidelines, which increase detection of PGD, particularly in extubated patients 5 . However, our PGD rates were not entirely different from those in a recent international multicenter www.nature.com/scientificreports/ cohort 25 .…”

“…Clinical outcomes data were entered into the Baylor-St. Luke’s Medical Center lung transplant database. All perioperative chest radiographs and blood gas results were reviewed by an expert PGD grader, and PGD scores were assigned based on strict adherence to the 2016 International Society for Heart and Lung Transplantation (ISHLT) consensus guidelines and caveats, including use of a saturation scale for patients who were extubated without arterial blood gasses 4 , 5 . PGD scores were determined at T0, T24, T48, and T72 h timepoints, which correspond to 6, 24, 48, and 72 h after lung reperfusion with a range of ± 6 h, except for T0 (with a range of ± 2 h).…”

“…Short of identifying a cure, the ability to accurately map a molecular signature for detecting PGD could enhance the overall treatment of patients. The clinical implementation of biomarkers specific to the pathogenesis of PGD would improve early detection, predict the clinical course of PGD, and, importantly, provide an objective metric to gauge the efficacy of interventions 3 – 5 .…”

Effect of mode of intraoperative support on primary graft dysfunction after lung transplant

“…A recent study by our group showed that the updated guidelines could increase detection of PGD by 42%. 22 In addition, intraoperative ECMO was not included in the LTOG analysis, and there could certainly be differences among patient populations. Substantial differences in PGD outcomes across studies are not uncommon and can be explained by differences in guidelines, the timing of blood gas collections, availability of oxygen saturation and blood gas data in extubated patients, differences in interpretation of chest radiograph results, and differences in ventilator-related parameters.…”