Fresh Red Blood Cell Transfusion and Short-Term Pulmonary, Immunologic, and Coagulation Status A Randomized Clinical Trial AT A GLANCE COMMENTARY Scientific Knowledge on the Subject

Rationale: Transfusion-related pulmonary complications are leading causes of morbidity and mortality attributed to transfusion. Observational studies suggest an important role for red blood cell (RBC) storage duration in these adverse outcomes. Objectives: To evaluate the impact of RBC storage duration on shortterm pulmonary function as well as immunologic and coagulation status in mechanically ventilated patients receiving RBC transfusion. Methods: This is a double-blind, randomized, clinical trial comparing fresh (<5 d of storage) versus standard issue single-unit RBC transfusion in adult intubated and mechanically ventilated patients. The primary outcome is the change in pulmonary gas exchange as assessed by the partial pressure of arterial oxygen to fraction of inspired oxygen concentration ratio ( Since the first successful attempt at blood storage almost a century ago, advances in extracorporeal red blood cell (RBC) preservation have incrementally prolonged the viability of stored RBCs. With contemporary preservative solutions, the accepted duration of RBC storage has now been extended to 42 days (1). In the past two decades, there has been increased interest in the time-dependent changes in RBC quantity and quality during this storage period. The various changes that occur within both the RBC and storage media during ex vivo preservation have been collectively termed the RBC "storage lesion." Importantly, alterations that occur during the RBC storage process are believed potentially responsible for many of the adverse effects associated with blood product administration (2). Among these concerns is a potentially increased risk of transfusion-related acute lung injury (TRALI) (3-6) as well as risk-adjusted mortality (7-10). Multiple publications have suggested that these associations become more significant with increased duration of RBC storage While the majority of TRALI cases are believed to be the result of an interaction between donor anti-HLA or anti-leukocyte antibodies and the cognate antigen on recipient leukocytes (20), a second "two-hit" model for TRALI has also been described (21). This model suggests that in a "primed" host, infusion of Author Contributions: D.J.K. contributed to the acquisition of data, and analysis and interpretation of the study results. R.K. contributed to the study design and procedures and the acquisition of the data. R.B.W. contributed to the study conception and design as well as the interpretation of the data. G.A.W. contributed to the study procedures and acquisition of the study data. C.M.v.B. contributed to the study conception and design as well as the study procedures. J.L.W. contributed to the study procedures as well as the interpretation of the study results. M.M. contributed to the analysis and interpretation of the data and study results R.D.H. contributed to the study conception and design as well as the interpretation of the study results. O.G. contributed to the study conception and design as well as the analysis and interpretation of the study results. All of the listed authors contributed to drafting and revising the manuscript and all have provided approval to the final version of the submitted manuscript. What This Study Adds to the Field In this investigation, the impact of a single unit of fresh red blood cell transfusion on markers of pulmonary, inflammatory, and coagulation status was similar to the impact seen with the transfusion of a single unit of standard issue red blood cells