Finding the bleeding edge: 24-hour mortality by unit of blood product transfused in combat casualties from 2002-2020.

BACKGROUND: Transfusion studies in civilian trauma patients have tried to identify a general futility threshold. We hypothesized that in combat settings there is no general threshold where blood product transfusion becomes unbeneficial to survival in hemorrhaging patients. We sought to assess the relationship between the number of units of blood products transfused and 24-hour mortality in combat casualties. METHODS: A retrospective analysis of the Department of Defense Trauma Registry supplemented with data from the Armed Forces Medical Examiner. Combat casualties who received at least one unit of blood product at US military medical treatment facilities (MTFs) in combat settings (2002-2020) were included. The main intervention was the total units of any blood product transfused, which was measured from the point of injury until 24 hours after admission from the first deployed MTF. The primary outcome was discharge status (alive, dead) at 24 hours from time of injury. RESULTS: Of 11,746 patients included, the median age was 24 years, and most patients were male (94.2%) with penetrating injury (84.7%). The median injury severity score was 17 and 783 (6.7%) patients died by 24 hours. Median units of blood products transfused was 8. Most blood products transfused were red blood cells (50.2%), followed by plasma (41.1%), platelets (5.5%), and whole blood (3.2%). Among the 10 patients who received the most units of blood product (164 units to 290 units), 7 survived to 24 hours. The maximum amount of total blood products transfused to a patient who survived was 276 units. Of the 58 patients who received over 100 units of blood product, 20.7% died by 24 hours. CONCLUSION: While civilian trauma studies suggest the possibility of futility with ultra-massive transfusion, we report that the majority (79.3%) of combat casualties who received transfusions greater than 100 units survived to 24 hours. These results do not support a threshold for futility of blood product transfusion. Further analysis as to predictors for mortality will help in situations of blood product and resource constraints. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Determining resuscitation outcomes in combat casualties: Design of the Deployed Hemostatic Emergency Resuscitation of Traumatic Exsanguinating Shock (Deployed HEROES) study.

BACKGROUND: During the course of the recent conflicts, the recommendations for resuscitation practices have evolved, but there has been no comprehensive comparative effectiveness study of these resuscitation strategies. The objective of this study was to describe the development and study design of the Deployed Hemostatic Emergency Resuscitation of Traumatic Exsanguinating Shock (Deployed HEROES) study-the first comprehensive analysis of military resuscitation practices in the deployed environment from October 2001 to October 2019. METHODS: This retrospective cohort study uses the Department of Defense Trauma Registry, Armed Services Blood Program database, and Military Trauma Mortality Review, while abstractors will use Theater Medical Data Store and Web Interface Patient Records to collect transfusion timing data. This study includes patients, who received blood products or died before receiving blood, treated at US military medical treatment facilities. The primary endpoints are survival at 6 hours, 24 hours, and 30 days postinjury. Secondary outcomes include infection, renal dysfunction, pulmonary dysfunction, and thromboembolic event. Exposure will be defined by blood product transfusion. Study groups will be frequency matched. Cox proportional hazards will compare patients who received warm fresh whole blood, low titer type-O whole blood, or only component therapy, while using adjustment for type of blood product transfused as a time-dependent covariate. Multilevel mixed-effects logistic regression will determine the effect of incompatible plasma in low titer type-O whole blood. RESULTS: An analysis plan for the Deployed HEROES study was developed with the aim of minimizing bias. CONCLUSION: This study will inform the optimal resuscitation strategies, which will potentially have a substantial impact on combat mortality. If whole blood is found to be the optimal transfusion strategy, this finding will be crucial in future operating environments involving dispersed medical assets. These results will provide critical information necessary for combat casualty care guidelines. LEVEL OF EVIDENCE: Prognostic and epidemiological; Level III.

Effect of processing and storage on red blood cell function in vivo.

Red blood cell (RBC) transfusion is indicated to improve oxygen delivery to tissue, and for no other purpose. We have come to appreciate that donor RBCs are fundamentally altered during processing and storage in a manner that both impairs oxygen transport efficacy and introduces additional risk by perturbing both immune and coagulation systems. The protean biophysical and physiological changes in RBC function arising from storage are termed the "storage lesion;" many have been understood for some time; for example, we know that the oxygen affinity of stored blood rises during the storage period and that intracellular allosteric regulators, notably 2,3-bisphosphoglyceric acid and ATP, are depleted during storage. Our appreciation of other storage lesion features has emerged with improved understanding of coagulation, immune, and vascular signaling systems. Here, we review key features of the "storage lesion." Additionally, we call particular attention to the newly appreciated role of RBCs in regulating linkage between regional blood flow and regional O(2) consumption by regulating the bioavailability of key vasoactive mediators in plasma, and discuss how processing and storage disturb this key signaling function and impair transfusion efficacy.