Prehospital plasma is associated with distinct biomarker expression following injury.

Danielle S Gruen,Yoram Vodovotz,Joshua B Brown,Brian S Zuckerbraun,Francis X Guyette,Herb A Phelan,Brian G Harbrecht,Brian J Daley,Jinling Yin,Derek A Barclay,Timothy R Billiar,Pär I Johansson,Jeffrey A Claridge,Richard S Miller,Jason L Sperry,Matthew D Neal,Jakob Stensballe

doi:10.1172/jci.insight.135350

Abstract

BACKGROUNDPrehospital plasma improves survival in severely injured patients transported by air ambulance. We hypothesized that prehospital plasma would be associated with a reduction in immune imbalance and endothelial damage.METHODSWe sampled blood from 405 trauma patients enrolled in the Prehospital Air Medical Plasma (PAMPer) trial upon hospital admission (0 hours) and 24 hours post admission across 6 U.S. sites. We assayed samples for 21 inflammatory mediators and 7 markers associated with endothelial function and damage. We performed hierarchical clustering analysis (HCA) of these biomarkers of the immune response and endothelial injury. Regression analysis was used to control for differences across study and to assess any association with prehospital plasma resuscitation.RESULTSHCA distinguished two patient clusters with different injury patterns and outcomes. Patients in cluster A had greater injury severity and incidence of blunt trauma, traumatic brain injury, and mortality. Cluster A patients that received prehospital plasma showed improved 30-day survival. Prehospital plasma did not improve survival in cluster B patients. In an adjusted analysis of the most seriously injured patients, prehospital plasma was associated with an increase in adiponectin, IL-1β, IL-17A, IL-23, and IL-17E upon admission, and a reduction in syndecan-1, TM, VEGF, IL-6, IP-10, MCP-1, and TNF-α, and an increase in IL-33, IL-21, IL-23, and IL-17E 24 hours later.CONCLUSIONPrehospital plasma may ameliorate immune dysfunction and the endotheliopathy of trauma. These effects of plasma may contribute to improved survival in injured patients.TRIAL REGISTRATIONNCT01818427.FUNDINGDepartment of Defense; National Institutes of Health, U.S. Army.

Highlights

Injury and the associated hemorrhagic shock are leading causes of death [1]
In an adjusted analysis of the most seriously injured patients, prehospital plasma was associated with an increase in adiponectin, IL-1β, IL-17A, IL-23, and IL-17E upon admission, and a reduction in syndecan-1, TM, vascular endothelial growth factor (VEGF), IL-6, inducible protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), and TNF-α, and an increase in IL-33, IL-21, IL-23, and IL-17E 24 hours later
Prehospital plasma may ameliorate immune dysfunction and the endotheliopathy of trauma. These effects of plasma may contribute to improved survival in injured patients

Summary

Introduction

Injury and the associated hemorrhagic shock are leading causes of death [1]. Emerging evidence suggests that damage-control resuscitation strategies — which prioritize blood-component products, including plasma, platelets, and packed RBCs (PRBCs) over crystalloid fluids — improve survival following severe injury [2, 3]. It was hypothesized that the administration of plasma in civilian prehospital settings would improve survival as compared with conventional crystalloid resuscitation. The Prehospital Air Medical Plasma (PAMPer) trial, a pragmatic, multicenter, cluster-randomized, phase 3 superiority trial, demonstrated that prehospital plasma fluid resuscitation reduces 30-day mortality in severely injured trauma patients at risk for hemorrhagic shock and transported by air ambulance [6]. Prehospital plasma improves survival in severely injured patients transported by air ambulance. We hypothesized that prehospital plasma would be associated with a reduction in immune imbalance and endothelial damage

Methods

Results

Conclusion