Pretransplant Medications and Primary Graft Dysfunction Risk in Lung Transplant Recipients

Abstract

PurposePrimary graft dysfunction (PGD) is a serious complication of lung transplantation marked by acute lung injury and reperfusion edema in the immediate post-transplant period, but the effect of pretransplant medication use on PGD risk is not known. We hypothesized that some pretransplant medications could be associated with PGD risk, particularly those with anti-inflammatory activity (macrolide antibiotics, statins) and vasoactives (anti-hypertensives, pulmonary vasodilators).MethodsWe reviewed a previously published cohort of adult patients who underwent lung transplant in our program between 2004 and 2016. The primary outcome was the development of grade 3 PGD (PGD3) at 48- or 72-hours post-transplant. We assessed use of medication classes from listing records, with a sample of these verified against transplant admission records. We evaluated the relationship between pretransplant medication class and PGD3 using Fisher's exact testing and multivariable logistic regression, adjusting for known PGD risk factors including recipient pulmonary diagnosis, body mass index, mean pulmonary arterial pressure, donor age and donor smoking status.Results19% of 330 patients who underwent lung transplant during the study timeframe developed PGD3. Phosphodiesterase inhibitor (PDE5i), endothelin receptor antagonist, proton pump inhibitor, and beta blocker (BB) use showed unadjusted associations with PGD3 risk, and PDE5 and BB use remained associated after adjustment (table 1). BB use remained significantly associated after further correction for left ventricular end diastolic pressure.ConclusionOur exploratory analysis showed no association between pretransplant use of medications with anti-inflammatory properties - including macrolides and statins - and PGD3 risk, but PDE5i and BB use increased PGD risk despite adjustment for indication, suggestive vasoactive medications may play a role. These associations would benefit from further study. Primary graft dysfunction (PGD) is a serious complication of lung transplantation marked by acute lung injury and reperfusion edema in the immediate post-transplant period, but the effect of pretransplant medication use on PGD risk is not known. We hypothesized that some pretransplant medications could be associated with PGD risk, particularly those with anti-inflammatory activity (macrolide antibiotics, statins) and vasoactives (anti-hypertensives, pulmonary vasodilators). We reviewed a previously published cohort of adult patients who underwent lung transplant in our program between 2004 and 2016. The primary outcome was the development of grade 3 PGD (PGD3) at 48- or 72-hours post-transplant. We assessed use of medication classes from listing records, with a sample of these verified against transplant admission records. We evaluated the relationship between pretransplant medication class and PGD3 using Fisher's exact testing and multivariable logistic regression, adjusting for known PGD risk factors including recipient pulmonary diagnosis, body mass index, mean pulmonary arterial pressure, donor age and donor smoking status. 19% of 330 patients who underwent lung transplant during the study timeframe developed PGD3. Phosphodiesterase inhibitor (PDE5i), endothelin receptor antagonist, proton pump inhibitor, and beta blocker (BB) use showed unadjusted associations with PGD3 risk, and PDE5 and BB use remained associated after adjustment (table 1). BB use remained significantly associated after further correction for left ventricular end diastolic pressure. Our exploratory analysis showed no association between pretransplant use of medications with anti-inflammatory properties - including macrolides and statins - and PGD3 risk, but PDE5i and BB use increased PGD risk despite adjustment for indication, suggestive vasoactive medications may play a role. These associations would benefit from further study.