SEVERITY OF HEMORRHAGE AND THE SURVIVAL BENEFIT ASSOCIATED WITH PLASMA: RESULTS FROM A RANDOMIZED PREHOSPITAL PLASMA TRIAL.

INTRODUCTION Recent randomized clinical trial evidence demonstrated a survival benefit with the use of prehospital plasma in patients at risk of hemorrhagic shock. We sought to characterize the survival benefit associated with prehospital plasma relative to the blood transfusion volume over the initial 24 hours. We hypothesized that the beneficial effects of prehospital plasma would be most robust in those with higher severity of hemorrhage. METHODS We performed a prespecified secondary analysis using data derived from a prospective randomized prehospital plasma trial. Blood component transfusion volumes were recorded over the initial 24 hours. Massive transfusion (MT) was defined a priori as receiving ≥ 10 units of red cells in 24hrs. We characterized the 30-day survival benefit of prehospital plasma and the need for MT and overall 24-hour red cell transfusion volume utilizing Kaplan-Meier survival analysis and Cox proportional hazard regression. RESULTS There were 501 patients included in this analysis with 230 randomized to prehospital plasma with 104 patients requiring MT. Mortality in patients who received MT were higher compared to those that did not (MT vs. NO-MT, 42% vs 26%, p=0.001). Kaplan-Meier survival curves demonstrated early separation in the NO-MT subgroup (log rank p=0.008) with no survival benefit found in the MT group (log rank p=0.949). Cox regression analysis verified these findings. When 24-hour red cell transfusion was divided into quartiles, there was a significant independent association with 30-day survival in patients who received 4-7 units (HR 0.33, 95% CI 0.14-0.80, p=0.013).The survival benefits of prehospital plasma was demonstrated only in patients with red cell requirements below the transfusion level of MT. Patients who received 4-7 units of red cells demonstrated the most robust independent survival benefit attributable to prehospital plasma transfusion. Prehospital plasma may be most beneficial in those patients with moderate transfusion requirements and mortality risk.Secondary AnalysisLevel of Evidence- I.

[1]  A. Peitzman,et al.  Prehospital Blood Product and Crystalloid Resuscitation in the Severely Injured Patient: A Secondary Analysis of the Prehospital Air Medical Plasma Trial. , 2019, Annals of surgery.

[2]  K. Inaba,et al.  A comparison of resuscitation intensity and critical administration threshold in predicting early mortality among bleeding patients: A multicenter validation in 680 major transfusion patients , 2018, The journal of trauma and acute care surgery.

[3]  C. Callaway,et al.  Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock , 2018, The New England journal of medicine.

[4]  James G. Chandler,et al.  Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial , 2018, The Lancet.

[5]  Jaakko Reinikainen,et al.  Time-varying covariates and coefficients in Cox regression models. , 2018, Annals of translational medicine.

[6]  K. Brohi,et al.  The Evolving Science of Trauma Resuscitation. , 2018, Emergency medicine clinics of North America.

[7]  Jeffrey T. Howard,et al.  Association of Prehospital Blood Product Transfusion During Medical Evacuation of Combat Casualties in Afghanistan With Acute and 30-Day Survival , 2017, JAMA.

[8]  C. Wade,et al.  Syndecan-1: A Quantitative Marker for the Endotheliopathy of Trauma. , 2017, Journal of the American College of Surgeons.

[9]  B. Tilley,et al.  Earlier Endpoints are Required for Hemorrhagic Shock Trials Among Severely Injured Patients , 2017, Shock.

[10]  C. Wade,et al.  Control the damage: morbidity and mortality after emergent trauma laparotomy. , 2016, American journal of surgery.

[11]  C. Wade,et al.  Traumatic Endotheliopathy: A Prospective Observational Study of 424 Severely Injured Patients , 2016, Annals of surgery.

[12]  A. Ho,et al.  The Many Faces of Survivor Bias in Observational Studies on Trauma Resuscitation Requiring Massive Transfusion. , 2015, Annals of emergency medicine.

[13]  A. Peitzman,et al.  Taking the Blood Bank to the Field: The Design and Rationale of the Prehospital Air Medical Plasma (PAMPer) Trial , 2015, Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors.

[14]  R. Kozar,et al.  Syndecan-1 restitution by plasma after hemorrhagic shock , 2015, The journal of trauma and acute care surgery.

[15]  A. Peitzman,et al.  Pre-trauma center red blood cell transfusion is associated with improved early outcomes in air medical trauma patients. , 2015, Journal of the American College of Surgeons.

[16]  A. Peitzman,et al.  Red Blood Cell Transfusion Is Associated With Reduced Mortality and Coagulopathy in Severely Injured Patients With Blunt Trauma , 2014 .

[17]  David B Hoyt,et al.  Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. , 2015, JAMA.

[18]  T. Fabian,et al.  The new metric to define large-volume hemorrhage: Results of a prospective study of the critical administration threshold , 2015, The journal of trauma and acute care surgery.

[19]  Peter Rhee,et al.  Increasing Trauma Deaths in the United States , 2014, Annals of surgery.

[20]  J. Holcomb,et al.  Fresh Frozen Plasma Lessens Pulmonary Endothelial Inflammation and Hyperpermeability After Hemorrhagic Shock and Is Associated With Loss of Syndecan 1 , 2013, Shock.

[21]  T. Fabian,et al.  Redefining massive transfusion when every second counts , 2013, The journal of trauma and acute care surgery.

[22]  J. Holcomb,et al.  Modulation of Syndecan-1 Shedding after Hemorrhagic Shock and Resuscitation , 2011, PloS one.

[23]  Michael A Dubick,et al.  Damage control resuscitation: directly addressing the early coagulopathy of trauma. , 2007, The Journal of trauma.