Prophylactic Inhaled Nitric Oxide for the Amelioration of Reperfusion Injury in Lung Transplantation

Objectives: The prophylactic administration of inhaled nitric oxide (NO) during reperfusion after lung transplantation has been shown to reduce neutrophil-induced injury in animal models. Questions regarding efficacy in the clinical setting and concerns regarding increased free radical injury remain. Methods: Twenty bilateral sequential lung transplant recipients were randomised to receive 20ppm inhaled NO (NO group) or standard anaesthetic gas mixture (Control group) from the onset of ventilation. Broncho-alveolar lavage was performed immediately prior to implantation and after 30 minutes of reperfusion and analysed for inflammatory cytokine levels and free radical surrogates. Primary graft dysfunction (PGD) scoring was performed prospectively for 72 hours post-transplant. Results: The prophylactic administration of nitric oxide during the first 30 minutes of reperfusion had no statistically significant effect on the development of Grade II–III PGD (5/10 vs.7/10, p=0.36) or gas exchange (AUC 429±296 vs. 336±306, p=0.64) in the NO and Control groups respectively. Pulmonary neutrophil sequestration, as measured by the transpulmonary arterio-venous neutrophil difference, was not influenced by the administration of NO. Pre-implantation lavage IL8 concentration correlated non-significantly, (73.3 ng/mg urea 95% CI 13.3–1,218.3 vs. 30.1 ng/mg urea 95% CI 1.1–157.6, p=0.22) and post-reperfusion IL8 significantly, with the development of PGD (232.9 ng/mg urea 95% CI 8.1–806.5 vs. 9.3 ng/mg urea 95% CI 0.4–65.9, p=0.015) for those with-and without PGD respectively. Prophylactic NO did not significantly alter the up-regulation of IL8, myeloperoxidase, or nitrotyrosine during transplantation. Conclusions: The findings of this study do not support the use of prophylactic inhaled nitric oxide in an attempt to prevent lung reperfusion injury.