Preemptive therapy with steroids but not macrolides improves gas exchange in caustic-injured donor lungs

Background: Donor lungs are susceptible to aspiration in the period before and after brain death. We hypothesized that preemptive anti-inflammatory treatment may result in better graft performance as evaluated during ex vivo lung perfusion (EVLP).

Methods: Pigs (27.4 ± 8.3kg) were divided into four groups (n = 6). Group [S] was treated with steroids (methylprednisolone 10 mg/kg), group [M] with macrolides (clarithromycin 250 mg), and group [P] with placebo (saline). In all groups, treatment was given i.v. 25, 18, and 1 h before instillation of 4 mL/kg gastric juice (GJ). Group [C] without GJ instillation served as a control group. Two hours after the onset of acute lung injury, lungs were flushed, explanted, and stored cold for 75 min. Graft performance was then assessed during EVLP for 2 h. Aerodynamic and hemodynamic parameters and oxygenation capacity (∆PO(2)) were recorded every 30 min (T30-T120). BAL samples were collected and analyzed for total and differential cells, IL-6, IL-1β, 8- isoprostane, and CRP levels. Wet-to-dry weight ratio [W/D] was measured and tissue samples were collected for histology.

Results: ΔPO(2) in [S] was comparable to [C] and was higher versus [M] (P < 0.05) and [P] (P < 0.01). No differences were observed in pulmonary vascular resistance, lung compliance, and mean airway pressure. No additional edema was noticed after 2 h of EVLP. Cellular and biomolecular changes in BAL fluid and histologic alterations were comparable among the three study groups.

Conclusion: Preemptive treatment of donors with steroids but not macrolides improves gas exchange in a porcine lung injury model independently from its anti-inflammatory activity.