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Rationale Cell-free hemoglobin (CFH) in the airspace has been associated with lung injury in patients with acute respiratory distress syndrome but has not previously been assessed as a marker of intraoperative lung injury during lung transplantation. We hypothesized that intra-operative support with extracorporeal membrane oxygenation (ECMO) during lung transplantation would exacerbate intra-operative lung injury as measured by intra-alveolar CFH. Methods We studied 56 consecutive patients enrolled in a prospective multi-center study of intra-operative management of lung transplant recipients. ECMO was used intra-operatively at the discretion of the transplant surgeon. Intra-operative lung injury was quantified by measurement of CFH in bronchoalveolar lavage (BAL) fluid obtained at the end of transplant surgery. Intra-operative ventilator settings (FiO2, tidal volume, positive end-expiratory pressure) after reperfusion were collected, selecting the greatest value for each parameter. PGD at 72h was determined using ISHLT criteria. Associations between clinical variables and biomarkers of lung injury were assessed by multivariable linear regression. Results Intra-operative ECMO was used in 34 (61%) of patients. All patients had detectable airspace CFH at the end of transplant surgery with a median level of 73 mg/dL (IQR 17-172). Patients supported with intra-operative ECMO had reduced BAL CFH compared to those without ECMO support [median 27 (15-102) vs. 146 (40-208), p = 0.011). Next, we determined whether this was driven by changes in mechanical ventilator settings intraoperatively. Patients with ECMO support had similar maximal tidal volumes [median 397 (322-791) vs. 386 (343-475), p = 0.23] and higher PEEP [median 8 (6-10) vs. 6 (5-8), p = 0.01], compared to those without ECMO. BAL CFH was inversely associated with maximal tidal volume and PEEP (p < 0.001 for each), but not with reperfusion FiO2 (p = 0.488). In multivariable analysis, after controlling for reperfusion FiO2, tidal volume, or PEEP, the association between ECMO and BAL CFH was no longer present, suggesting that differences in ventilator settings may have mediated this association. There was no association between intra-operative ECMO and PGD3 at 72h. Conclusions Contrary to our hypothesis, lung transplant recipients supported with intra-operative ECMO have lower airspace levels of CFH compared to those not supported with ECMO. This relationship between CFH and ECMO may have been due to differential impact of tidal volume and PEEP during ECMO. Although the sample size was small, these findings suggest that intraoperative ECMO during lung transplantation may be beneficial by facilitating less injurious ventilation. Future studies will validate these findings in additional patients undergoing lung transplantation.
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Shaver et al. (2026) studied this question.
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