Discussion
bleeding, SIRS, intraoperative blood loss, blood loss, reperfusion injury, coagulopathy, Ischemia, TRALI
TRANSFUSION-RELATED ACUTE LUNG INJURY, BLEEDING, BLOOD LOSS, CYSTIC FIBROSIS, INTRAOPERATIVE BLOOD LOSS, COAGULOPATHY, ISCHEMIA
PGD negatively contributes to increased short-term and long-term morbidity and mortality after LuTx [Ischemia–reperfusion injury after lung allograft implantation has been shown to lead to PGD development [Transfusion of a large amount of blood products, especially FFP, to manage intraoperative blood loss during LuTx is an independent risk factor for PGD through transfusion-related acute lung injury (TRALI) [In our study, 5% albumin solution was used solely as volume replacement therapy in the POC group. Albumin is a medium-sized molecule with a molecular weight of 66–69 kDa and is the most abundant protein in human plasma (40 g/l out of a total of 70 g/l). Albumin is synthesized exclusively in the liver and plays an important role in numerous processes. For example, it serves as a major extracellular antioxidant and a major transporter in plasma, responsible for 75% of oncotic plasma pressure. Therefore, albumin solution is considered to be the standard colloidal resuscitation fluid [Fluid management during all types of surgical procedures affects postoperative outcomes [In our study, targeted coagulopathy management and 5% albumin solution administered exclusively as volume replacement therapy during LuTx surgery resulted in significant improvement in lung allograft function in the first postoperative 72 h in the POC study group compared to the non-POC study group measured by Horowitz index. This intervention also resulted in significant decrease of PGD grade 2–3 at time point 72 in POC group. This is of particular interest, as most studies examine the incidence of PGD grade 3 at 72 h. However, in our study there was no statistically significant difference in occurrence of PGD grade 3 between the non-POC and POC group at all tracked time points. Additionally, the mean value of the maximum norepinephrine level during the first 24 h after LuTx was found to be significantly decreased in the POC group. This finding supports the theory that albumin as volume replacement therapy during LuTx surgery may provide greater hemodynamic circulatory stability in the POC group during the first 24 h after surgery through both volume replacement and its hypothesized anti-inflammatory effect on the reduction in SIRS [Our study has several limitations that require rigorous and transparent discussion. First, a major limitation is that our study design contained two interventions in one study protocol (targeted coagulopathy management and 5% albumin in POC study group). As targeted coagulopathy management led to decrease of blood loss and blood products transfusion, the study was preliminarily terminated by the institutional review board due to positive results in favor of the POC approach. This preliminary termination resulted in a relatively small cohort size in each group, precluding further evaluation of effect of the second intervention in the study (5% albumin administration). Moreover, two interventions in one study protocol limits our ability to identify the precise extent of how either the first or second intervention contributed to the study results.Heterogeneity in the patient age distribution between the non-POC group, where patients were older, versus the POC group that contained a greater proportion of younger patients with cystic fibrosis was another limitation. This population difference is important to highlight, as a variety of etiology-based comorbidities can impact intraoperative management and outcomes [To the best of our knowledge, despite abovementioned limitations, the research presented herein represents the first clinical trial attempting to investigate the effect of the perioperative use of targeted bleeding and coagulopathy management combined with 5% albumin administration on lung allograft function after LuTx. Furthermore, our data provide a level of evidence suggesting albumin as an optimal choice for intraoperative resuscitation in lung transplantation that to date has been based on expert opinion in the literature. However, further investigation in this area is highly needed to provide deeper insight into potential beneficial effect of perioperative use of 5% albumin solely as volume replacement therapy during LuTx on PGD incidence. The authors suggest design future trial with 5% albumin solution administrated intraoperatively as the only intervention in study group.