Plasma Free Hemoglobin Potentiates the Association between Reperfusion FiO2 and Primary Graft Dysfunction after Lung Transplantation

Abstract

<h3>Purpose</h3> Free hemoglobin (freeHgb) is a potent oxidant released from red cells in conditions such as sepsis, hemolysis, hemodialysis and cardiopulmonary bypass. We determined whether plasma freeHgb is elevated in lung transplant recipients and whether levels are associated with primary graft dysfunction (PGD). We also tested whether the potential oxidative injury associated with freeHgb is potentiated by high FiO2 at reperfusion. <h3>Methods and Materials</h3> Patients were lung recipients in the Lung Transplant Outcomes Group cohort and included 40 cases with Grade 3 PGD at 72h after transplant and 80 controls with no PGD, frequency matched for diagnosis (COPD, IPF) and procedure (single, bilateral). Plasma freeHgb was measured pre-op, and at 6 and 24h after reperfusion. PGD status was determined by ISHLT criteria. <h3>Results</h3> FreeHgb was detectable in 91% of pre-op, 97% of 6h and 85% of 24h samples. Pre-op [median 30 mg/dL (IQR 20-50 )] and 6h [30 (10-80)] levels were similar, but fell at 24h [20 (10-40), p=0.002]. Post-op freeHgb levels were similar between cases and controls although levels were higher in those who underwent cardiopulmonary bypass [80 (40–150) vs 20 (10–40), p<0.001]. By contrast, pre-op freeHgb levels were associated with PGD (p=0.043 for trend across freeHgb quartiles). In addition, pre-op freeHgb levels potentiated the association of high reperfusion FiO2 (≥0.40) with PGD (p=0.008, Figure). <h3>Conclusions</h3> High pre-op levels of plasma freeHgb associate with PGD, particularly when FiO2 is high at reperfusion. FreeHgb may be a mediator of oxidative injury during ischemia reperfusion and high levels of inspired O2 may potentiate this oxidative injury.