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 posttransplant. 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 ¼ 0.002); FI O 2 during allograft reperfusion (OR, 1.1 per 10% increase in FI O 2 ; 95% CI, 1.0-1.2; P ¼ 0.01); single lung transplant (OR, 2; 95% CI, 1.2-3.3; P ¼ 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 ¼ 0.01) and obese (OR, 2.3; 95% CI, 1.3-3.9; P ¼ 0.004) recipient body mass index; preoperative sarcoidosis (OR, 2.5; 95% CI, 1.1-5.6; P ¼ 0.03) or pulmonary arterial hypertension (OR, 3.5; 95% CI, 1.6-7.7; P ¼ 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). What This Study Adds to the FieldWe performed a multicenter, prospective cohort study of 1,255 lung transplant recipients across 10 US transplant centers. We identified receipt of an organ from a donor with any smoking history, elevated FI O 2 during allograft reperfusion, preoperative sarcoidosis or pulmonary arterial hypertension, use of cardiopulmonary bypass, single lung transplant, large-volume blood product transfusion, elevated pulmonary arterial pressures, and overweight or obese recipient body habitus as risk factors for grade 3 PGD. Several of these risk factors are potentially modifiable, and thus may suggest preventative strategies, whereas other risk factors should be prioritized for future mechanistic research efforts.

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 posttransplant. 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 ¼ 0.002); FI O 2 during allograft reperfusion (OR, 1.1 per 10% increase in FI O 2 ; 95% CI, 1.0-1.2; P ¼ 0.01); single lung transplant (OR, 2; 95% CI, 1.2-3.3; P ¼ 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 ¼ 0.01) and obese (OR, 2.3; 95% CI, 1.3-3.9; P ¼ 0.004) recipient body mass index; preoperative sarcoidosis (OR, 2.5; 95% CI, 1.1-5.6; P ¼ 0.03) or pulmonary arterial hypertension (OR, 3.5; 95% CI, 1.6-7.7; P ¼ 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). What This Study Adds to the FieldWe performed a multicenter, prospective cohort study of 1,255 lung transplant recipients across 10 US transplant centers. We identified receipt of an organ from a donor with any smoking history, elevated FI O 2 during allograft reperfusion, preoperative sarcoidosis or pulmonary arterial hypertension, use of cardiopulmonary bypass, single lung transplant, large-volume blood product transfusion, elevated pulmonary arterial pressures, and overweight or obese recipient body habitus as risk factors for grade 3 PGD. Several of these risk factors are potentially modifiable, and thus may suggest preventative strategies, whereas other risk factors should be prioritized for future mechanistic research efforts.

Pulmonary hypertension presents a particular challenge in critically ill patients, because typical therapies such as volume resuscitation and mechanical ventilation may worsen hemodynamics in patients with pulmonary hypertension and right ventricular failure. Patients with decompensated pulmonary hypertension, including those with pulmonary hypertension associated with cardiothoracic surgery, require therapy for right ventricular failure. Very few human studies have addressed the use of vasopressors and pulmonary vasodilators in these patients, but the use of dobutamine, milrinone, inhaled nitric oxide, and intravenous prostacyclin have the greatest support in the literature. Treatment of pulmonary hypertension resulting from critical illness or chronic lung diseases should address the primary cause of hemodynamic deterioration, and pulmonary vasodilators usually are not necessary.