Contemporary trends in PGD incidence, outcomes, and therapies

Abstract

Background: We sought to describe trends in extracorporeal membrane oxygenation (ECMO) use, and define the impact on PGD incidence and early mortality in lung transplantation.

Methods: Patients were enrolled from August 2011 to June 2018 at 10 transplant centers in the multi-center Lung Transplant Outcomes Group prospective cohort study. PGD was defined as Grade 3 at 48 or 72 hours, based on the 2016 PGD ISHLT guidelines. Logistic regression and survival models were used to contrast between group effects for event (i.e., PGD and Death) and time-to-event (i.e., death, extubation, discharge) outcomes respectively. Both modeling frameworks accommodate the inclusion of potential confounders.

Results: A total of 1,528 subjects were enrolled with a 25.7% incidence of PGD. Annual PGD incidence (14.3%-38.2%, p = .0002), median LAS (38.0-47.7 p = .009) and the use of ECMO salvage for PGD (5.7%-20.9%, p = .007) increased over the course of the study. PGD was associated with increased 1 year mortality (OR 1.7 [95% C.I. 1.2, 2.3], p = .0001). Bridging strategies were not associated with increased mortality compared to non-bridged patients (p = .66); however, salvage ECMO for PGD was significantly associated with increased mortality (OR 1.9 [1.3, 2.7], p = .0007). Restricted mean survival time comparison at 1-year demonstrated 84.1 days lost in venoarterial salvaged recipients with PGD when compared to those without PGD (ratio 1.3 [1.1, 1.5]) and 27.2 days for venovenous with PGD (ratio 1.1 [1.0, 1.4]).

Conclusions: PGD incidence continues to rise in modern transplant practice paralleled by significant increases in recipient severity of illness. Bridging strategies have increased but did not affect PGD incidence or mortality. PGD remains highly associated with mortality and is increasingly treated with salvage ECMO.

Keywords: ECMO; bridge to transplant; lung transplantation; outcomes and lung allocation score; primary graft dysfunction.

Figure 1.. Recipient LAS, PGD incidence and ECMO bridging and salvage strategies over time

Note: 2018 data only includes transplants performed before July. The single case in 2011 was moved to 2012.

Figure 2.. Effects of PGD on length of mechanical ventilation over time

Yellow bar signifies 21 days after lung transplant when a majority of US transplant recipients have been discharged from the hospital.

Figure 3.. Association of salvage ECMO strategy with mortality

Restricted mean survival time analysis of salvage by ECMO type. Stratification was not performed because transplant type (single versus bilateral) was not associated with mortality (p=0.20). Solid line (Blue) represents no salvage, dashed line (Red) VV ECMO salvage, and dotted line (Green) VA ECMO salvage, respectively. Yellow bars set at 1 year (365 days) and 3 years (1095 days) after transplant.