Clinical risk factors for primary graft dysfunction after lung transplantation

Abstract

Rationale: Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies have yielded conflicting results for PGD risk factors.

Objectives: We sought to identify donor, recipient, and perioperative risk factors for PGD.

Methods: We performed a 10-center prospective cohort study enrolled between March 2002 and December 2010 (the Lung Transplant Outcomes Group). The primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD at 48 or 72 hours post-transplant. The association of potential risk factors with PGD was analyzed using multivariable conditional logistic regression.

Measurements and main results: A total of 1,255 patients from 10 centers were enrolled; 211 subjects (16.8%) developed grade 3 PGD. In multivariable models, independent risk factors for PGD were any history of donor smoking (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.6; P = 0.002); FiO2 during allograft reperfusion (OR, 1.1 per 10% increase in FiO2; 95% CI, 1.0-1.2; P = 0.01); single lung transplant (OR, 2; 95% CI, 1.2-3.3; P = 0.008); use of cardiopulmonary bypass (OR, 3.4; 95% CI, 2.2-5.3; P < 0.001); overweight (OR, 1.8; 95% CI, 1.2-2.7; P = 0.01) and obese (OR, 2.3; 95% CI, 1.3-3.9; P = 0.004) recipient body mass index; preoperative sarcoidosis (OR, 2.5; 95% CI, 1.1-5.6; P = 0.03) or pulmonary arterial hypertension (OR, 3.5; 95% CI, 1.6-7.7; P = 0.002); and mean pulmonary artery pressure (OR, 1.3 per 10 mm Hg increase; 95% CI, 1.1-1.5; P < 0.001). PGD was significantly associated with 90-day (relative risk, 4.8; absolute risk increase, 18%; P < 0.001) and 1-year (relative risk, 3; absolute risk increase, 23%; P < 0.001) mortality.

Conclusions: We identified grade 3 PGD risk factors, several of which are potentially modifiable and should be prioritized for future research aimed at preventative strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 00552357).

Trial registration: ClinicalTrials.gov NCT00552357.

Figure 1.

Flow diagram for subject enrollment. Of 2,011 transplants performed at the participating centers, 1,255 were enrolled in the Lung Transplant Outcomes Group cohort. “Not consented” refers to patients who were transplanted before being approached for consent. “Consented but not enrolled due to logistics” includes patients who were unable to give a blood sample as part of the study.

Figure 2.

Standardized grade 3 primary graft dysfunction (PGD) risk for donor, recipient, and perioperative variables. Standardized risk of grade 3 PGD represents the postestimation marginalized standardized risks for grade 3 PGD and was calculated based on the final logistic regression model. Dots represent the point estimate for adjusted standardized risk from a logistic regression equation containing donor smoking, reperfusion Fi_O2, total ischemic time, recipient sex and parity, World Health Organization categorized severity of pulmonary hypertension, volume of packed red blood cell (PRBC) transfusion, recipient body mass index (BMI), use of cardiopulmonary bypass, transplant type, center, and preoperative diagnosis, with the bar representing 95% confidence intervals. Standardized risks represent the estimated risk of grade 3 PGD if all variables were kept stable except for altering the variable of interest; for example, the estimated grade 3 PGD risk if all of the patients alternatively received or did not receive cardiopulmonary bypass.

Figure 3.

Standardized incidence of grade 3 primary graft dysfunction (PGD) across the 10 centers. Standardized risk of grade 3 PGD represents the postestimation marginalized standardized risks for grade 3 PGD and was calculated based on the final logistic regression model. Dots are the point estimates and error bars represent the 95% confidence intervals.