Dataset Information

Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: A prospective cohort study.

ABSTRACT:

Background

Almost all studies that have investigated the immune response to trauma have analysed blood samples acquired post-hospital admission. Thus, we know little of the immune status of patients in the immediate postinjury phase and how this might influence patient outcomes. The objective of this study was therefore to comprehensively assess the ultra-early, within 1-hour, immune response to trauma and perform an exploratory analysis of its relationship with the development of multiple organ dysfunction syndrome (MODS).

Methods and findings

The immune and inflammatory response to trauma was analysed in 89 adult trauma patients (mean age 41 years, range 18-90 years, 75 males) with a mean injury severity score (ISS) of 24 (range 9-66), from whom blood samples were acquired within 1 hour of injury (mean time to sample 42 minutes, range 17-60 minutes). Within minutes of trauma, a comprehensive leukocytosis, elevated serum pro- and anti-inflammatory cytokines, and evidence of innate cell activation that included neutrophil extracellular trap generation and elevated surface expression of toll-like receptor 2 and CD11b on monocytes and neutrophils, respectively, were observed. Features consistent with immune compromise were also detected, notably elevated numbers of immune suppressive CD16BRIGHT CD62LDIM neutrophils (82.07 x 106/l ± 18.94 control versus 1,092 x 106/l ± 165 trauma, p < 0.0005) and CD14+HLA-DRlow/- monocytes (34.96 x 106/l ± 4.48 control versus 95.72 x 106/l ± 8.0 trauma, p < 0.05) and reduced leukocyte cytokine secretion in response to lipopolysaccharide stimulation. Exploratory analysis via binary logistic regression found a potential association between absolute natural killer T (NKT) cell numbers and the subsequent development of MODS. Study limitations include the relatively small sample size and the absence of data relating to adaptive immune cell function.

Conclusions

Our study highlighted the dynamic and complex nature of the immune response to trauma, with immune alterations consistent with both activation and suppression evident within 1 hour of injury. The relationship of these changes, especially in NKT cell numbers, to patient outcomes such as MODS warrants further investigation.

SUBMITTER: Hazeldine J

PROVIDER: S-EPMC5515405 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Publications

Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: A prospective cohort study.

Hazeldine Jon J Naumann David N DN Toman Emma E Davies David D Bishop Jonathan R B JRB Su Zhangjie Z Hampson Peter P Dinsdale Robert J RJ Crombie Nicholas N Duggal Niharika Arora NA Harrison Paul P Belli Antonio A Lord Janet M JM

PLoS medicine 20170718 7

<h4>Background</h4>Almost all studies that have investigated the immune response to trauma have analysed blood samples acquired post-hospital admission. Thus, we know little of the immune status of patients in the immediate postinjury phase and how this might influence patient outcomes. The objective of this study was therefore to comprehensively assess the ultra-early, within 1-hour, immune response to trauma and perform an exploratory analysis of its relationship with the development of multip ...[more]

PMID: 28719602

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Project description:Importance:Traumatic brain injury (TBI) is a massive public health problem. While evidence-based guidelines directing the prehospital treatment of TBI have been promulgated, to our knowledge, no studies have assessed their association with survival. Objective:To evaluate the association of implementing the nationally vetted, evidence-based, prehospital treatment guidelines with outcomes in moderate, severe, and critical TBI. Design, Setting, and Participants:The Excellence in Prehospital Injury Care (EPIC) Study included more than 130 emergency medical services systems/agencies throughout Arizona. This was a statewide, multisystem, intention-to-treat study using a before/after controlled design with patients with moderate to critically severe TBI (US Centers for Disease Control and Prevention Barell Matrix-Type 1 and/or Abbreviated Injury Scale Head region severity ?3) transported to trauma centers between January 1, 2007, and June 30, 2015. Data were analyzed between October 25, 2017, and February 22, 2019. Interventions:Implementation of the prehospital TBI guidelines emphasizing avoidance/treatment of hypoxia, prevention/correction of hyperventilation, and avoidance/treatment of hypotension. Main Outcomes and Measures:Primary: survival to hospital discharge; secondary: survival to hospital admission. Results:Of the included patients, the median age was 45 years, 14?666 (67.1%) were men, 7181 (32.9%) were women; 16?408 (75.1% ) were white, 1400 (6.4%) were Native American, 743 (3.4% ) were Black, 237 (1.1%) were Asian, and 2791 (12.8%) were other race/ethnicity. Of the included patients, 21?852 met inclusion criteria for analysis (preimplementation phase [P1]: 15?228; postimplementation [P3]: 6624). The primary analysis (P3 vs P1) revealed an adjusted odds ratio (aOR) of 1.06 (95% CI, 0.93-1.21; P?=?.40) for survival to hospital discharge. The aOR was 1.70 (95% CI, 1.38-2.09; P?<?.001) for survival to hospital admission. Among the severe injury cohorts (but not moderate or critical), guideline implementation was significantly associated with survival to discharge (Regional Severity Score-Head 3-4: aOR, 2.03; 95% CI, 1.52-2.72; P?<?.001; Injury Severity Score 16-24: aOR, 1.61; 95% CI, 1.07-2.48; P?=?.02). This was also true for survival to discharge among the severe, intubated subgroups (Regional Severity Score-Head 3-4: aOR, 3.14; 95% CI, 1.65-5.98; P?<?.001; Injury Severity Score 16-24: aOR, 3.28; 95% CI, 1.19-11.34; P?=?.02). Conclusions and Relevance:Statewide implementation of the prehospital TBI guidelines was not associated with significant improvement in overall survival to hospital discharge (across the entire, combined moderate to critical injury spectrum). However, adjusted survival doubled among patients with severe TBI and tripled in the severe, intubated cohort. Furthermore, guideline implementation was significantly associated with survival to hospital admission. These findings support the widespread implementation of the prehospital TBI treatment guidelines. Trial Registration:ClinicalTrials.gov identifier: NCT01339702.

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Project description:BackgroundTraumatic brain injury (TBI) can result in an acute coagulopathy including platelet dysfunction that can contribute to ongoing intracranial hemorrhage. Previous studies have shown adenosine diphosphate (ADP)-induced platelet aggregation to be reduced after TBI. In addition, circulating microvesicles (MVs) are increased following TBI and have been shown to play a role in post-TBI coagulopathy and platelet function. We hypothesized that post-TBI MVs would affect platelet aggregation in a murine head injury model.MethodsModerate TBI was performed using a weight-drop method in male C57BL6 mice. Whole blood, plasma, MVs, and MV-poor plasma were isolated from blood collected 10 minutes following TBI and were mixed separately with whole blood from uninjured mice. Platelet aggregation was measured with Multiplate impedance platelet aggregometry in response to ADP. The ADP P2Y12 receptor inhibitor, R-138727, was incubated with plasma and MVs from TBI mice, and platelet inhibition was again measured.ResultsWhole blood taken from 10-minute post-TBI mice demonstrated diminished ADP-induced platelet aggregation compared with sham mice. When mixed with normal donor blood, post-TBI plasma and MVs induced diminished ADP-induced platelet aggregation compared with sham plasma and sham MVs. By contrast, the addition of post-TBI MV-poor plasma to normal blood did not change ADP-induced platelet aggregation. The observed dysfunction in post-TBI ADP platelet aggregation was prevented by the pretreatment of post-TBI plasma with R-138727. Treatment of post-TBI MVs with R-138727 resulted in similar findings of improved ADP-induced platelet aggregation compared with nontreated post-TBI MVs.ConclusionAdenosine diphosphate-induced platelet aggregation is inhibited acutely following TBI in a murine model. This platelet inhibition is reproduced in normal blood by the introduction of post-TBI plasma and MVs. Furthermore, observed platelet dysfunction is prevented when post-TBI plasma and MVs are treated with an inhibitor of the P2Y12 ADP receptor. Clinically observed post-TBI platelet dysfunction may therefore be partially explained by the presence of the ADP P2Y12 receptor within post-TBI MVs.Level of evidenceLevel III.

Dataset Information

Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: A prospective cohort study.

Background

Methods and findings

Conclusions

Publications

Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: A prospective cohort study.

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