Impact of Primary Graft Failure on Outcomes Following Lung Transplantation

doi:10.1378/chest.127.1.161

Chest

Volume 127, Issue 1, January 2005, Pages 161-165

https://doi.org/10.1378/chest.127.1.161 Get rights and content

Study objectives

Primary graft failure (PGF) is a severe acute lung injury syndrome that occurs following lung transplantation. We compared the clinical outcomes of patients who developed PGF with those who did not.

Methods

We conducted a retrospective cohort study including 255 consecutive lung transplant procedures. PGF was defined as (1) diffuse alveolar opacities developing within 72 h of transplantation, (2) an arterial partial pressure of oxygen/fraction of inspired oxygen (Pao₂/Fio₂) ratio of < 200 beyond 48 h postoperatively, and (3) no other secondary cause of graft dysfunction. PGF was tested for acceptance with 30-day and all-cause hospital mortality rates, overall survival, hospital length of stay (HLOS), duration of mechanical ventilation, and best 6-min walk test (6MWT) distance achieved within 12 months.

Setting

Academic medical center.

Results

The overall incidence of PGF was 11.8% (95% confidence interval [CI], 7.9 to 15.9%). The all-cause mortality rate at 30 days was 63.3% in patients with PGF and 8.8% in patients without PGF (relative risk [RR], 7.15; 95% CI, 4.34 to 11.80%; p < 0.001). A total of 73.3% of patients with PGF died during hospitalization vs 14.2% of patients without PGF (RR, 5.18%; 95% CI, 3.51 to 7.63; p < 0.001). The median HLOS in 30-day survivors was 47 days in patients with PGF vs 15 days in those without PGF (p < 0.001), and the mean duration of mechanical ventilation was 15 days in patients with PGF vs 1 day in those without PGF (p < 0.001). By 12 months, a total of 28.5% of survivors with PGF achieved a normal age-appropriate 6MWT distance vs 71.4% of survivors without PGF at 12 months (p = 0.014). The median best 6MWT distance achieved within the first 12 months was 1,196 feet in patients with PGF vs 1,546 feet in those without PGF (p = 0.009).

Conclusions

PGF has a significant impact on mortality, HLOS, and duration of mechanical ventilation following lung transplantation. Survivors of PGF have a protracted recovery with impaired physical function up to 1 year following transplantation.

Section snippets

Study Population

A retrospective cohort study was performed including all 255 consecutive lung transplant procedures performed at our institution between October 1991 and July 2000. One heart-lung transplant and two lung-liver transplants were excluded as it was thought that they would not be representative of outcomes in the population at whole. The follow-up period for survival analysis and clinical outcomes extended to July 2002. We chose this time frame to ensure at least 2 years of follow-up time for all

Results

Thirty of the 252 patients met the criteria for PGF (incidence, 0.118; 95% CI, 0.079 to 0.159). The all-cause mortality rate at 30 days was 63.3% in patients with PGF and 8.8% in patients without PGF (RR, 7.15; 95% CI, 4.34 to 11.80; p < 0.001). Likewise, there was a significant difference in the hospital mortality rates between the groups, with 73.3% of patients with PGF dying during hospitalization and 14.2% of patients without PGF dying (RR, 5.18; 95% CI, 3.51 to 7.63; p < 0.001). Patients

Discussion

In this study, we have illustrated the profound impact of PGF on clinical course following lung transplantation. Our study shows that PGF is associated with a high mortality risk, as patients with PGF have a greater than fivefold increase in the risk of death during hospitalization. Further, the attributable mortality is high, as PGF is the major cause of early death following lung transplantation, contributing to almost half of deaths at 30 days. There is a protracted recovery of functional

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Cited by (194)

Long-Term Survival Following Primary Graft Dysfunction Development in Lung Transplantation
2024, Journal of Surgical Research
Primary graft dysfunction (PGD) is a known risk factor for early mortality following lung transplant (LT). However, the outcomes of patients who achieve long-term survival following index hospitalization are unknown. We aimed to determine the long-term association of PGD grade 3 (PGD3) in patients without in-hospital mortality.
LT recipients were identified from the United Network for Organ Sharing Database. Patients were stratified based on the grade of PGD at 72 h (No PGD, Grade 1/2 or Grade 3). Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan–Meier methods and a multivariable shared frailty model including recipient, donor, and transplant characteristics.
The PGD3 group had significantly increased length of stay, dialysis, and treated rejection post-transplant (P < 0.001). Unadjusted survival analysis revealed a significant difference in long-term survival (P < 0.001) between groups; however, following adjustment, PGD3 was not independently associated with long-term survival (hazard ratio: 0.972; 95% confidence interval: 0.862-1.096). Increased mortality was significantly associated with increased recipient age and treated rejection. Decreased mortality was significantly associated with no donor diabetes, bilateral LT as compared to single LT, transplant in 2015-2016 and 2017-2018, and no post-transplant dialysis.
While PGD3 remains a challenge post LT, PGD3 at 72 h is not independently associated with decreased long-term survival, while complications such as dialysis and rejection are, in patients who survive index hospitalization. Transplant providers should be aggressive in preventing further complications in recipients with severe PGD to minimize the negative association on long-term survival.
Impact of the New Definition of Pulmonary Hypertension on the Prevalence of Primary Graft Dysfunction in Lung Transplant Recipients
2024, Heart Lung and Circulation
Pulmonary hypertension (PH) secondary to lung disease (Group-3 PH) is the second leading cause of PH. The role of PH as a risk factor for primary graft dysfunction (PGD) following lung transplant (LT) is controversial.
To assess the impact that the new definition of PH had on the prevalence of PH in patients with advanced lung disease—candidate for LT, and its association with the occurrence of PGD.
A retrospective study was performed in all patients undergoing cardiac catheterisation referred for consideration as candidates to LT in a centre between 1 January 2017 and 31 December 2022. The baseline and haemodynamic characteristics of patients were analysed, along with the occurrence of PGD and post-transplant course in those who ultimately underwent transplantation.
A total of 396 patients were included. Based on the new 2022 European Society of Cardiology/European Respiratory Society definitions, as many as 70.7% of patients met PH criteria. Since the introduction of the 2022 definition, a significant reduction was observed in the frequency of severe Group-3 PH (41.1% vs 10.3%; p<0.001), with respect to the 2015 definition. As many as 236 patients underwent transplantation. None of the variables associated with PH was identified as a risk factor for PGD.
The new classification did not have any impact on the prevalence of PGD after transplantation. These results exclude that any significant differences exist in the baseline characteristics or post-transplant course of patients with Group-3 PH vs unclassified PH.
Lung transplantation in pulmonary sarcoidosis
2023, Journal of Autoimmunity
Sarcoidosis is a systemic inflammatory disease of unknown etiology and variable clinical course. Pulmonary sarcoidosis is the most common presentation and accounts for most morbidity and mortality related to sarcoidosis. While sarcoidosis generally has good outcomes, few patients experience chronic disease. A minority of patients progress to a specific phenotype of sarcoidosis referred to advanced pulmonary sarcoidosis (APS) which includes advanced fibrosis, pulmonary hypertension and respiratory failure, leading to high morbidity and mortality. In patients with advanced disease despite medical therapy, lung transplantation may be the last viable option for improvement in quality of life. Though post-transplant survival is similar to that of other end-stage lung diseases, it is imperative that patients are evaluated and referred early to transplant centers with experience in APS. A multidisciplinary approach and clinical experience are crucial in detecting the optimal timing of referral, initiating comprehensive transplantation evaluation and listing, discussing surgical approach, and managing perioperative and post-transplant care. This review article seeks to address these aspects of lung transplantation in APS.
Contemporary trends in PGD incidence, outcomes, and therapies
2022, Journal of Heart and Lung Transplantation
We sought to describe trends in extracorporeal membrane oxygenation (ECMO) use, and define the impact on PGD incidence and early mortality in lung transplantation.
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.
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]).
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.
Risk of primary graft dysfunction following lung transplantation in selected adults with connective tissue disease-associated interstitial lung disease
2021, Journal of Heart and Lung Transplantation
Citation Excerpt :
PGD is a form of acute lung injury characterized by hypoxemia and alveolar infiltrates in the allograft(s) that occurs within 72 hours after transplant.15 The highest grade of PGD, grade 3, has been associated with a significantly longer duration of mechanical ventilation and post-transplant hospital LOS, as well as increased 90-day and 1-year mortality compared to absent or lower grades of PGD.16-19 Despite a steady increase in lung transplantation for patients with CTD-ILD,20 little is understood about whether this unique population carries increased risk for the development of severe PGD and whether a higher incidence of PGD, along with other contributing factors, prolongs time to extubation or hospital LOS following transplant.
Previous studies have reported similarities in long-term outcomes following lung transplantation for connective tissue disease-associated interstitial lung disease (CTD-ILD) and idiopathic pulmonary fibrosis (IPF). However, it is unknown whether CTD-ILD patients are at increased risk of primary graft dysfunction (PGD), delays in extubation, or longer index hospitalizations following transplant compared to IPF patients.
We performed a multicenter retrospective cohort study of CTD-ILD and IPF patients enrolled in the Lung Transplant Outcomes Group registry who underwent lung transplantation between 2012 and 2018. We utilized mixed effects logistic regression and stratified Cox proportional hazards regression to determine whether CTD-ILD was independently associated with increased risk for grade 3 PGD or delays in post-transplant extubation and hospital discharge compared to IPF.
A total of 32.7% (33/101) of patients with CTD-ILD and 28.9% (145/501) of patients with IPF developed grade 3 PGD 48-72 hours after transplant. There were no significant differences in odds of grade 3 PGD among patients with CTD-ILD compared to those with IPF (adjusted OR 1.12, 95% CI 0.64-1.97, p = 0.69), nor was CTD-ILD independently associated with a longer post-transplant time to extubation (adjusted HR for first extubation 0.87, 95% CI 0.66-1.13, p = 0.30). However, CTD-ILD was independently associated with a longer post-transplant hospital length of stay (median 23 days [IQR 14-35 days] vs17 days [IQR 12-28 days], adjusted HR for hospital discharge 0.68, 95% CI 0.51-0.90, p = 0.008).
Patients with CTD-ILD experienced significantly longer postoperative hospitalizations compared to IPF patients without an increased risk of grade 3 PGD.
Ventilation parameters and early graft function in double lung transplantation
2021, Journal of Heart and Lung Transplantation
Currently, the primary graft dysfunction (PGD) score is used to measure allograft function in the early post–lung transplant period. Although PGD grades at later time points (T48 hours and T72 hours) are useful to predict mid- and long-term outcomes, their predictive value is less relevant within the first 24 hours after transplantation. This study aimed to evaluate the capability of PGD grades to predict prolonged mechanical ventilation (MV) and compare it with a model derived from ventilation parameters measured on arrival at the intensive care unit (ICU).
A retrospective single-center analysis of 422 double lung transplantations (LTxs) was performed. PGD was assessed 2 hours after arrival at ICU, and grades were associated with length of MV (LMV). In addition, peak inspiratory pressure (P_IP), ratio of the arterial partial pressure of oxygen to fraction of inspired oxygen (P/F ratio), and dynamic compliance (cDyn) were collected, and a logistic regression model was created. The predictive capability for prolonged MV was calculated for both (the PGD score and the model). In a second step, the created model was externally validated using a prospective, international multicenter cohort including 102 patients from the lung transplant centers of Vienna, Toronto, and Budapest.
In the retrospective cohort, a high percentage of extubated patients was reported at 24 hours (35.1%), 48 hours (68.0%), and 72 hours (80.3%) after transplantation. At T0 (time point defined as 2 hours after arrival at the ICU), patients with PGD grade 0 had a shorter LMV with a median of 26 hours (interquartile range [IQR]: 16–47 hours) than those with PGD grade 1 (median: 42 hours, IQR: 27–50 hours), PGD grade 2 (median: 37.5 hours, IQR: 15.5–78.5 hours), and PGD grade 3 (median: 46 hours, IQR: 27–86 hours). However, IQRs largely overlapped for all grades, and the value of PGD to predict prolonged MV was poor. A total of 3 ventilation parameters (P_IP, cDyn, and P/F ratio), determined at T0, were chosen on the basis of clinical reasoning. A logistic regression model including these parameters predicted prolonged MV (>72 hours) with an optimism-corrected area under the curve (AUC) of 0.727. In the prospective validation cohort, the model proved to be stable and achieved an AUC of 0.679.
The prediction model reported in this study combines 3 easily obtainable variables. It can be employed immediately after LTx to quantify the risk of prolonged MV, an important early outcome parameter.

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This research was supported by National Heart, Lung, and Blood Institute grant K23 HL04243, and by the Craig and Elaine Dobbin Pulmonary Research Fund.

Presented in part at the American Thoracic Society International Conference, May 2001, San Francisco, CA.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]).

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Chest

Clinical Investigations: Lung TransplantationImpact of Primary Graft Failure on Outcomes Following Lung Transplantation

Study objectives

Methods

Setting

Results

Conclusions

Section snippets

Study Population

Results

Discussion

Chest

Ann Thorac Surg

J Heart Lung Transplant

Chest

Chest

Chest

Chest

J Heart Lung Transplant

Lung transplantation

N Engl J Med

Interleukin-8 release during early reperfusion predicts graft function in human lung transplantation

Am J Respir Crit Care Med

Clinical Investigations: Lung Transplantation
Impact of Primary Graft Failure on Outcomes Following Lung Transplantation