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Background: Acute traumatic coagulopathy (ATC) is a well-described phenomenon known to begin shortly after injury. This has profound implications for resuscitation from hemorrhagic shock, as ATC is associated with increased risk for massive transfusion (MT) and mortality. We describe a large-data machine learning-based Coagulation Risk Index (CRI) to test the early prediction of ATC in bleeding trauma patients., Methods: Coagulation Risk Index was developed using continuous vital signs (VSs) available during the first 15 minutes after admission at a single trauma center over 4 years. Data to compute the CRI were derived from continuous features of photoplethymographic and electrocardiographic waveforms, oximetry values, and blood pressure trends. Two groups of patients at risk for ATC were evaluated: critical administration threshold and patients who received an MT. Acute traumatic coagulopathy was evaluated in separate models and defined as an international normalized ratio (INR) >1.2 and >1.5 upon arrival. The CRI was developed using 2 years of cases for training and 2 years for testing. The accuracy of the models is described by area under the receiver operator curve with 95% confidence intervals., Results: A total of 17,567 patients were available for analysis with continuous VS data, 52.8% sustained blunt injury, 30.2% were female, and the mean age was 44.6 years. The ability of CRI to predict ATC in critical administration threshold patients was excellent. The true positive and true negative rates were 95.6% and 88.3%, and 94.9% and 89.2% for INR >1.2 and INR >1.5, respectively. The CRI also demonstrated excellent accuracy in patients receiving MT; true positive and true negative rates were 92.8% and 91.3%, and 100% and 88.1% for INR >1.2 and INR >1.5, respectively., Conclusion: Using continuous VSs and large-data machine learning capabilities, the CRI accurately predicts early ATC in bleeding patients. Clinical application may guide early hemostatic resuscitation. Extension of this technology into the prehospital setting could provide earlier treatment of ATC., Level of Evidence: Retrospective, Prognostic Study; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Introduction: A 2003 landmark study identified the prevalence of early trauma-induced coagulopathy (eTIC) at 28% with a strong association with mortality of 8.9%. Over the last 20 years, there have been significant advances in both the fundamental understanding of eTIC and therapeutic interventions. Methods: A retrospective cohort study was performed from 2018 to 2022 on patients ≥18 using prospectively collected data from two level 1 trauma centers and compared to data from 2003. Demographics, laboratory data, and clinical outcomes were obtained. Results: There were 20,107 patients meeting criteria: 65% male, 85% blunt, mean age 54 ± 21 years, median Injury Severity Score 10 (10, 18), 8% of patients were hypotensive on arrival, with an all-cause mortality 6.0%. The prevalence of eTIC remained high at 32% in patients with an abnormal prothrombin time and 10% with an abnormal partial thromboplastin time, for an overall combined prevalence of 33.4%. Coagulopathy had a major impact on mortality over all injury severity ranges, with the greatest impact with lower Injury Severity Score. In a hybrid logistic regression/Classification and Regression Trees analysis, coagulopathy was independently associated with a 2.1-fold increased risk of mortality (95% confidence interval 1.5-2.9); the predictive quality of the model was excellent [area under the receiver operating characteristic curve (AUROC) 0.932]. Conclusion: The presence of eTIC conferred a higher risk of death across all disease severities and was independently associated with a greater risk of death. Biomarkers of coagulopathy associated with eTIC remain strongly predictive of poor outcome despite advances in trauma care., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Introduction: Poor communication about serious injury in older adults can lead to treatment that is inconsistent with patient preferences, create conflict and strain healthcare resources. We developed a communication intervention called Best Case/Worst Case-intensive care unit (ICU) that uses daily scenario planning, that is, a narrative description of plausible futures, to support prognostication and facilitate dialogue among patients, their families and the trauma ICU team. This article describes a protocol for a multisite, randomised, stepped-wedge study to test the effectiveness of the intervention on the quality of communication (QOC) in the ICU., Methods and Analysis: We will follow all patients aged 50 and older admitted to the trauma ICU for 3 or more days after a serious injury at eight high-volume level 1 trauma centres. We aim to survey one family or 'like family' member per eligible patient 5-7 days following their loved ones' admission and clinicians providing care in the trauma ICU. Using a stepped-wedge design, we will use permuted block randomisation to assign the timing for each site to begin implementation of the intervention and routine use of the Best Case/Worst Case-ICU tool. We will use a linear mixed-effects model to test the effect of the tool on family-reported QOC (using the QOC scale) as compared with usual care. Secondary outcomes include the effect of the tool on reducing clinician moral distress (using the Measure of Moral Distress for Healthcare Professionals scale) and patients' length of stay in the ICU., Ethics and Dissemination: Institutional review board (IRB) approval was granted at the University of Wisconsin, and all study sites ceded review to the primary IRB. We plan to report results in peer-reviewed publications and national meetings., Trial Registration Number: NCT05780918., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The presence of a splenic subcapsular hematoma (SCH) has been associated with higher rates of failure of nonoperative management (FNOM) in patients with blunt splenic injury (BSI), with rates up to 80%. We hypothesized that contemporary rates are lower. A retrospective review was conducted of patients admitted with BSI to a level I trauma center (2016-2021). Patients with SCH who had FNOM were compared to those who did not. There were 661 BSI patients, of which 102 (15.4%) had SCH. Among the SCH patients, 8 (7.8%) had FNOM. Failure of nonoperative management was higher in patients who had a SCH measuring 15 mm or greater. To the best of our knowledge, this is the largest study to date examining the relationship between SCH and FNOM. The presence of a SCH alone is not associated with a high risk for FNOM contrary to previous literature. However, SCH thickness was larger in those who failed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The revised American Association for the Surgery of Trauma (AAST) organ injury scale (OIS) for splenic injury incorporates radiologic features but the implications of this are unknown. We hypothesized that the revised AAST-OIS would better predict outcomes., Methods: Patients with a blunt splenic injury admitted to a Level I trauma center were reviewed from 2016 to 2021. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for splenectomy were calculated for high-grade injuries (AAST-OIS grades IV-V) using both schemas., Results: Of the 852 patients analyzed, 48.5% were observed, 24.6% were embolized, and the remaining underwent operative intervention. The median AAST-OIS increased from II to III (p ​< ​0.01). Sensitivity (38.0% vs. 73.7%) and NPV (80.9% vs. 88.2%) for splenectomy increased for high-grade injuries but specificity (93.5% vs 70.1%) and PPV (67.5% vs 46.7%) decreased., Conclusion: The revised AAST-OIS better predicted splenic salvage but is less accurate at predicting need for splenectomy., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report and have received no financial support in relation to this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: Background: Inorganic polyphosphate (polyP) is a procoagulant polyanion. We assessed the impact of polyP inhibition on thrombin generation after trauma using the novel polyP antagonists, macromolecular polyanion inhibitor 8 (MPI 8), and universal heparin reversal agent 8 (UHRA-8). Methods: Plasma thrombin generation (calibrated automated thrombogram, CAT), in 56 trauma patients and 39 controls +/- MPI 8 and UHRA-8 (50 μg/mL), was expressed as lag time (LT, minutes), peak height (PH, nM), and time to peak (ttPeak, minutes), with change in LT (ΔLT) and change in ttPeak (ΔttPeak) quantified. Results expressed in median and quartiles [Q1, Q3], Wilcoxon matched-pairs testing, P < 0.05 significant. Results: Trauma patients had greater baseline PH than controls (182.9 [121.0, 255.2]; 120.5 [62.1, 174.8], P < 0.001). MPI 8 treatment prolonged LT and ttPeak in trauma (7.20 [5.88, 8.75]; 6.46 [5.45, 8.93], P = 0.020; 11.28 [8.96, 13.14]; 11.00 [8.95, 12.94], P = 0.029) and controls (7.67 [6.67, 10.50]; 6.33 [5.33, 8.00], P < 0.001; 13.33 [11.67, 15.33]; 11.67 [10.33, 13.33], P < 0.001). UHRA-8 treatment prolonged LT and ttPeak and decreased PH in trauma (9.09 [7.45, 11.33]; 6.46 [5.45, 8.93]; 14.02 [11.78, 17.08]; 11.00 [8.95, 12.94]; 117.4 [74.5, 178.6]; 182.9 [121.0, 255.2]) and controls (9.83 [8.00, 12.33]; 6.33 [5.33, 8.00]; 16.67 [14.33, 20.00]; 11.67 [10.33, 13.33]; 55.3 [30.2, 95.9]; 120.5 [62.1, 174.8]), all P < 0.001. Inhibitor effects were greater for controls (greater ΔLT and ΔttPeak for both inhibitors, P < 0.001). Conclusion: PolyP inhibition attenuates thrombin generation, though to a lesser degree in trauma than in controls, suggesting that polyP contributes to accelerated thrombin generation after trauma., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Background: Splenic embolization for traumatic vascular abnormalities in stable patients is a common practice. We hypothesize that modern contrast-enhanced computed tomography (CT) over diagnoses posttraumatic splenic vascular lesions, such as intraparenchymal pseudoaneurysms (PSA) that may not require embolization., Methods: We reviewed the experience at our high-volume center with endovascular management of blunt splenic injuries from January 2016 to December 2021. Multidisciplinary review was used to compared initial CT findings with subsequent angiography, analyzing management and outcomes of identified vascular lesions., Results: Of 853 splenic injuries managed overall during the study period, 255 (29.9%) underwent angiography of the spleen at any point during hospitalization. Vascular lesions were identified on 58% of initial CTs; extravasation (12.2%) and PSA (51.0%). Angiography was performed a mean of 22 hours after admission, with 38% done within 6 hours. Embolization was performed for 90.5% (231) of patients. Among the 130 patients with PSA on initial CT, 36 (27.7%) had no visible lesion on subsequent angiogram. From the 125 individuals who did not have a PSA identified on their initial CT, 67 (54%) had a PSA seen on subsequent angiography. On postembolization CT at 48 hours to 72 hours, persistently perfused splenic PSAs were seen in 41.0% (48/117) of those with and 22.2% (2/9) without embolization. Only one of 24 (4.1%) patients with PSA on angiography observed without embolization required delayed splenectomy, whereas 6.9% (16/231) in the embolized group had splenectomy at a mean of 5.5 ± 4 days after admission., Conclusion: There is a high rate of discordance between CT and angiographic identification of splenic PSAs. Even when identified at angiogram and embolized, close to half will remain perfused on follow-up imaging. These findings question the use of routine angioembolization for all splenic PSAs., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Neutrophil extracellular traps (NETs) contribute to trauma-induced coagulopathy. We aimed to develop a murine multiple-injury model that induces thrombo-inflammatory response, that is, NETosis and accelerated thrombin generation., Methods: Wild-type male mice (n = 10, aged 8-12 weeks) underwent multiple injuries (gastrocnemius crush, femur fracture, and laparotomy) and were compared with an uninjured control group (n = 10). Mice were euthanized by cardiac puncture performed 3 hours after injury. Whole blood samples were immediately processed to platelet poor plasma for thrombin generation kinetics (calibrated automated thrombogram), myeloperoxidase (MPO), and von Willebrand factor quantification. Immunohistochemistry of lung tissue was performed to assess for citrullinated histone 3 (CitH3) and MPO. A NETosis cluster was defined as 3+ neutrophils staining for CitH3 at 400× magnification (CitH3 cluster). Data were presented either as mean (SD) or median (interquartile range) with p < 0.05 significant. Sham and trauma treated animals were compared by the two-sample Wilcoxon rank-sum test., Results: Animals subjected to multiple injuries had accelerated thrombin generation compared with controls with greater peak height (61.3 [41.2-73.2] vs. 28.4 [19.5-37.5] nM, p = 0.035) and shorter time to peak (3.37 [2.81-3.81] vs. 4.5 [4.08-4.75] minutes, p = 0.046). Markers of neutrophil activation were greater following multiple injuries than in controls (MPO, 961.1 [858.1-1116.8] vs. 481.3 [438.0-648.9] ng/mL; p = 0.004). NETosis, as evidenced by the aforementioned defined number of CitH3 clusters in the lung, was greater in multiple-injury animals than in controls (mean [SD], 3 [2.9] vs. 0.2 [0.7]; p = 0.009)., Conclusion: This is the first study to demonstrate that NETosis and accelerated thrombin generation can be induced using a murine multiple-injury model, as early as 3 hours following injury., (Copyright © 2023 American Association for the Surgery of Trauma.)

Introduction: The necessity of angioembolization for all splenic pseudoaneurysms (PSAs) is unknown after blunt trauma. We compared the outcomes of patients with PSAs managed with splenic artery embolization (EMBO) versus no embolization (NO-EMBO)., Methods: We retrospectively reviewed all patients with blunt splenic trauma and PSA on initial computed tomography scan admitted to an academic, urban, Level I trauma center from 2016 to 2021. Patients who had emergent splenectomy or died before discharge were excluded. Demographics, injury and computed tomography characteristics, and details regarding angiography, if pursued, were collected. The primary outcome was failure of nonoperative management (FNOM), as defined by need for delayed splenectomy for the EMBO group versus delayed splenectomy or embolization for the NO-EMBO group., Results: One hundred and fifty-six patients were in the final study population, of which 96 (61.5%) were in the EMBO group and 60 (38.5%) were in the NO-EMBO group. Patient demographics and mechanism of injury were similar between the two cohorts. The two cohorts had similar imaging findings, however, EMBO patients had more compartments with hemoperitoneum (2 versus 1, P < 0.01). Patients who underwent embolization had a lower FNOM rate (3.1% versus 13.3%, P = 0.02)., Conclusions: Splenic artery embolization in the setting of PSA is associated with lower rates of FNOM versus nonembolization. It is unclear if addressing the PSA itself with embolization drives the decreased FNOM rate., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Cryoprecipitate (CP) can augment hemostasis after hemorrhagic shock (HS). Similar to fresh frozen plasma (FFP), CP may provide short-term endothelial protection. We tested a new 5-day postthaw CP (5-day pathogen-reduced cryoprecipitate [5PRC]) and lyophilized pathogen-reduced cryoprecipitate (LPRC) to overcome challenges of early administration and hypothesized that 5PRC and LPRC would provide lasting organ protection in a rodent model of HS., Methods: Mice underwent trauma/HS (laparotomy then HS), mean arterial pressure (MAP) 35 × 90 minutes, and then 6 hours of hypotensive resuscitation (MAP, 55-60 mm Hg) with lactated Ringer's solution (LR), FFP, CP, 5PRC, or LPRC and compared with shams. Animals were followed for 72 hours. Organs and blood were collected. Data are presented as mean ± SD and analysis of variance with Bonferroni post hoc., Results: Mean arterial pressure was comparable between experimental groups at baseline, preresuscitation, and 6 hours per protocol. However, volume needed to resuscitate to target MAP over 6 hours was less than half for CP, 5PRC, LPRC, and FFP compared with LR, suggesting that CP products can serve as effective resuscitative agents. Mean arterial pressure at 72 hours was also significantly higher in the CP, 5PRC, and FFP groups compared with LR. Resuscitation with CP, 5PRC, and LPRC provided lasting protection from gut injury and enhanced syndecan immunostaining comparable with FFP, while LR mice demonstrated persistent organ dysfunction. Sustained endothelial protection was demonstrated by lessened lung permeability, while cystatin C was an indicator of kidney function, and liver aspartate aminotransferase and alanine transaminase returned to sham levels in all groups., Conclusion: Cryoprecipitate products can provide lasting organ protection comparable with FFP in a sustained rodent model of trauma/HS and hypotensive resuscitation. The availability of 5PRC and LPRC will allow for investigation into the immediate use of cryoprecipitate for severely injured patients. As lyophilized products such as cryoprecipitate become available clinically, their use has important implications for prehospital, rural, and battlefield usage., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The endotheliopathy of trauma involves a complex interplay between the glycocalyx, von Willebrand factor, and platelets that leads to abnormalities in coagulation, inflammation, and endothelial cell (EC) function. The current review presents a synopsis of EC function under homeostatic conditions, the structure and function of the endothelial glycocalyx; mechanisms of EC injury and activation after trauma; pathological consequences of the EoT at the cellular level; and clinical implications of the EoT. Recent evidence is presented that links the EoT to extracellular vesicles and hyperadhesive ultralarge von Willebrand factor multimers through their roles in coagulopathy. Lastly, potential therapeutics to mitigate the EoT are discussed. Most research to date has focused on blood products, primarily plasma, and its contribution to restoring postinjury EC dysfunction. Additional therapeutic adjuvants that target the glycocalyx, ultralarge von Willebrand factor, low ADAMTS-13, and pathologic extracellular vesicles are reviewed. Much of the pathobiology of EoT is known, but a better mechanistic understanding can help guide therapeutics to further repair the EoT and improve patient outcomes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Obesity is associated with higher mortality following trauma, although the pathogenesis is unclear. Both obesity and trauma are associated with syndecan-1 shedding and metalloproteinase-9 (MMP-9) activation, which can adversely affect endothelial cell function. We recently demonstrated that fibrinogen stabilizes endothelial cell surface syndecan-1 to reduce shedding and maintain endothelial barrier integrity. We thus hypothesized that MMP-9 activation and syndecan-1 shedding would be exacerbated by obesity after trauma but attenuated by fibrinogen-based resuscitation., Materials and Methods: ApoE null ( -/- ) mice were fed a Western diet to induce obesity. Mice were subjected to hemorrhage shock and laparotomy then resuscitated with Lactated Ranger's (LR) or LR containing fibrinogen and compared to null and lean sham wild type mice. Mean arterial pressure (MAP) was monitored. Bronchial alveolar lavage protein as an indicator of permeability and lung histopathologic injury were assessed. Syndecan-1 protein and active MMP-9 protein were measured., Results: MAP was similar between lean sham and ApoE -/- sham mice. However, following hemorrhage, ApoE -/- mice resuscitated with fibrinogen had significantly higher MAP than LR mice. Lung histopathologic injury and permeability were increased in LR compared to fibrinogen resuscitated animals. Compared with lean sham mice, both active MMP-9 and cleaved syndecan-1 level were significantly higher in ApoE -/- sham mice. Resuscitation with fibrinogen but not lactated Ringers largely reduced these changes., Conclusions: Fibrinogen as a resuscitative adjunct in ApoE -/- mice after hemorrhage shock augmented MAP and reduced histopathologic injury and lung permeability, suggesting fibrinogen protects the endothelium by inhibiting MMP-9-mediated syndecan-1 cleavage in obese mice., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Recent studies in severely injured patients suggest an important role of von Willebrand Factor (VWF) and ADAMTS13 in the endotheliopathy of trauma (EoT). We hypothesized that the early use of cryoprecipitate would be effective as an endothelial protector by supplementing physiologic VWF and ADAMTS13 to reverse the EoT. We tested a pathogen-reduced lyophilized cryoprecipitate (LPRC) that could expedite the early administration of cryoprecipitate in the battlefield., Methods: A mouse multiple-trauma model with uncontrolled hemorrhage (UCH) from liver injury was utilized followed by hypotensive resuscitation (mean arterial pressure, 55-60) × 3 hours with lactated Ringer's (LR), fresh frozen plasma (FFP), conventional pathogen-reduced cryoprecipitate (CC), and LPRC. Blood was collected for measurement of syndecan-1, VWF, and ADAMTS13 by ELISA. Lungs were stained for histopathologic injury and syndecan-1 and bronchial alveolar lavage (BAL) fluid harvested for protein as an indicator of permeability. Statistical analysis was by ANOVA followed by Bonferroni correction., Results: Following multiple trauma and UCH, blood loss was similar across groups. Mean volume of resuscitation was higher in the LR group compared with the other resuscitation groups. Lung histopathologic injury, syndecan-1 immunostaining and BAL protein were higher with LR compared with resuscitation with FFP and CC, while LPRC further reduced BAL compared with FFP and CC. The ADAMTS13/VWF ratio was significantly lower in LR but improved with FFP and CC, comparable to shams while LPRC further increased this ratio., Conclusion: The protective effects of CC and LPRC were comparable to FFP in ameliorating the EoT in our murine multiple trauma and UCH model. Lyophilized cryoprecipitate may also provide additional benefit by enhancing the ADAMTS13/VWF ratio. These data provide evidence of the safety and efficacy of LPRC and warrants further investigation for its potential application in military settings once approved for human administration., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The American Association for the Surgery of Trauma Colon Organ Injury Scale (OIS) was updated in 2020 to include a separate OIS for penetrating colon injuries and included imaging criteria. In this multicenter study, we describe the contemporary management and outcomes of penetrating colon injuries and hypothesize that the 2020 OIS system correlates with operative management, complications, and outcomes., Methods: This was a retrospective study of patients presenting to 12 Level 1 trauma centers between 2016 and 2020 with penetrating colon injuries and Abbreviated Injury Scale score of <3 in other body regions. We assessed the association of the new OIS with surgical management and clinical outcomes and the association of OIS imaging criteria with operative criteria. Bivariate analysis was done with χ 2 , analysis of variance, and Kruskal-Wallis, where appropriate. Multivariable models were constructed in a stepwise selection fashion., Results: We identified 573 patients with penetrating colon injuries. Patients were young and predominantly male; 79% suffered a gunshot injury, 11% had a grade V destructive injury, 19% required ≥6 U of transfusion, 24% had an Injury Severity Score of >15, and 42% had moderate-to-large contamination. Higher OIS was independently associated with a lower likelihood of primary repair, higher likelihood of resection with anastomosis and/or diversion, need for damage-control laparotomy, and higher incidence of abscess, wound infection, extra-abdominal infections, acute kidney injury, and lung injury. Damage control was independently associated with diversion and intra-abdominal and extra-abdominal infections. Preoperative imaging in 152 (27%) cases had a low correlation with operative findings ( κ coefficient, 0.13)., Conclusion: This is the largest study to date of penetrating colon injuries and the first multicenter validation of the new OIS specific to these injuries. While imaging criteria alone lacked strong predictive value, operative American Association for the Surgery of Trauma OIS colon grade strongly predicted type of interventions and outcomes, supporting use of this grading scale for research and clinical practice., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

We aimed to determine whether early (<6 hours) vs delayed (≥6 hours) splenic angioembolization (SAE) after blunt splenic trauma (grades II-V) impacted splenic salvage rates at a level I trauma center (2016-2021). The primary outcome was delayed splenectomy by timing of SAE. Mean time of SAE was determined for those who failed vs those who had successful splenic salvage. We retrospectively identified 226 individuals, from which 76 (33.6%) were in the early group and 150 (66.4%) were in the delayed group. The early group had higher AAST grade, greater amount of hemoperitoneum on CT, and 3.9x greater odds of undergoing delayed splenectomy (P = .046). Time to embolization was shorter in the group that failed splenic salvage (5 vs 10 hours, P = .051). On multivariate analysis, timing of SAE had no effect on splenic salvage. This study supports performing SAE on an urgent rather than emergent basis in stable patients after blunt splenic injury.

This retrospective, single-site study at a level I trauma center (2016-2021) sought to determine whether repeat CT had an impact on clinical decision making after splenic angioembolization following blunt splenic trauma (grades II-V). The primary outcome was need for intervention after subsequent imaging (defined as angioembolization and/or splenectomy) by high- or low-grade injury. Of the 400 individuals examined, 78 (19.5%) underwent intervention after repeat CT, from which 17% were in the low-grade group (grades II and III) and 22% were in the high-grade group (grades IV and V). Individuals in the high-grade group were 3.6 times more likely to undergo delayed splenectomy than those in the low-grade group ( P = .006). Delayed intervention after surveillance imaging in blunt splenic injury is driven mostly by the identification of new vascular lesions and leads to greater rates of splenectomy in high-grade injuries. Surveillance imaging should be considered for all AAST injury grades II or higher.

Background: Propensity-matched methods are increasingly being applied to the American College of Surgeons TQIP database to evaluate hemorrhage control interventions. We used variation in systolic blood pressure (SBP) to demonstrate flaws in this approach., Study Design: Patients were divided into groups based on initial SBP (iSBP) and SBP at 1 hour (2017 to 2019). Groups were defined as follows: iSBP 90 mmHg or less who decompensated to 60 mmHg or less (immediate decompensation [ID]), iSBP 90 mmHg or less who remained greater than 60 mmHg (stable hypotension [SH]), and iSBP greater than 90 mmHg who decompensated to 60 mmHg or less (delayed decompensation [DD]). Individuals with Head or Spine Abbreviated Injury Scale score 3 or greater were excluded. Propensity score was assigned using demographic and clinical variables. Outcomes of interest were in-hospital mortality, emergency department death, and overall length of stay., Results: Propensity matching yielded 4,640 patients per group in analysis #1 (SH vs DD) and 5,250 patients per group in analysis #2 (SH vs ID). The DD and ID groups had 2-fold higher in-hospital mortality than the SH group (DD 30% vs 15%, p < 0.001; ID 41% vs 18%, p < 0.001). Emergency department death rate was 3 times higher in the DD group and 5 times higher in the ID group (p < 0.001), and length of stay was 4 days shorter in the DD group and 1 day shorter in the ID group (p < 0.001). Odds of death were 2.6 times higher for the DD vs SH group and 3.2 times higher for the ID vs SH group (p < 0.001)., Conclusions: Differences in mortality rate by SBP variation underscore the difficulty of identifying individuals with a similar degree of hemorrhagic shock using the American College of Surgeons TQIP database despite propensity matching. Large databases lack the detailed data needed to rigorously evaluate hemorrhage control interventions., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Injuries to the inferior vena cava (IVC), while uncommon, have a high mortality despite modern advances. The goal of this study is to describe the diagnosis and management in the largest available prospective data set of vascular injuries across anatomic levels of IVC injury., Methods: The American Association for the Surgery of Trauma PROspective Observational Vascular Injury Treatment (PROOVIT) registry was queried from November 2013 to January 2019. Demographics, diagnostic modalities, injury patterns, and management strategies were recorded and analyzed. Comparisons between anatomic levels were made using non-parametric Wilcoxon rank-sum statistics., Results: 140 patients from 19 institutions were identified; median age was 30 years old (IQR 23-41), 75% were male, and 62% had penetrating mechanism. The suprarenal IVC group was associated with blunt mechanism (53% vs 32%, P = .02), had lower admission systolic blood pressure, pH, Glasgow Coma Scale (GCS), and higher ISS and thorax and abdomen AIS than the infrarenal injury group. Injuries were managed with open repair (70%) and ligation (30% overall; infrarenal 37% vs suprarenal 13%, P = .01). Endovascular therapy was used in 2% of cases. Overall mortality was 42% (infrarenal 33% vs suprarenal 66%, P<.001). Among survivors, there was no difference in first 24-hour PRBC transfusion requirement, or hospital or ICU length of stay., Conclusions: Current PROOVIT registry data demonstrate continued use of ligation extending to the suprarenal IVC, limited adoption of endovascular management, and no dramatic increase in overall survival compared to previously published studies. Survival is likely related to IVC injury location and total injury burden.

Surgical science has driven innovation and inquiry across adult and pediatric disciplines that provide critical care regardless of location. Surgically originated but broadly applicable knowledge has been globally shared within the pages Critical Care Medicine over the last 50 years., Competing Interests: Dr. Coopersmith reports funding form the National Institute of Health (NIH) under grants GM072808, GM104323, and AA027396. Drs. Napolitano and Efron have previously served as Council members of the Society of Critical Care Medicine. Drs. Coopersmith, Efron, and Kaplan all serve on the editorial board of Critical Care Medicine. Dr. Cannon received funding from UptoDate; he disclosed that he is a consultant for CSL Behring. Drs. Kozar’s and Coopersmith’s institutions received funding from the NIH. Dr. Kozar’s institution received funding form the Department of Defense (DoD). Dr. Sugrue received funding from Novus Scientific and Smith and Nephew. Dr. Tiserhman’s institution received funding from the DoD (W81XWH-07-1-068 and W81XWH-18-1-0601); he disclosed that he is co-author of a patent for “Emergency Preservation and Resuscitation Method”; he disclosed the off-label product use of cardiopulmonary bypass equipment and saline. Dr. Coopersmith received support for article research from the NIH. Dr. Kaplan received funding from Society of Critical Care Medicine. Dr. Tisherman is a co-author of a patent for “Emergency Preservation and Resuscitation Method.” The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: It has been shown that microRNA-19b (miR-19b) binds to and degrades syndecan-1 after hemorrhagic shock (HS) and contributes to endothelial dysfunction in vitro and in vivo. The objective of the current study was to assess longitudinal changes in miR-19b and syndecan-1 in HS patients., Methods: Blood samples from HS patients (blood pressure <90 mm Hg and ≥2 U blood) were collected upon admission, completion of hemostasis, and after 24 hours for miR-19b (quantitative reverse transcription PCR) and syndecan-1 (enzyme-linked immunosorbent assay) and compared with controls and minimally injured (Injury Severity Score, ≤9). Inflammatory cytokines were measured (Luminex [Thermo Fisher, Waltham, MA]). Correlations between syndecan-1, miR-19b, inflammatory markers, and patient outcomes were performed. Logistic regression models were developed for outcomes., Results: Thirty-four HS patients were studied: age, 46 (19-89) years; male, 82%; penetrating, 35%; Injury Severity Score, 24 ± 10; and blood products at 24 hours, 21 ± 19 U. MicroRNA-19b was increased upon arrival and further increased over time: 4.6 → 6.7 → 24.1-fold change compared with 0.1 and 1.2 for minimally injured patients and controls, respectively. Syndecan-1 was increased to 42.6 → 50 → 51.5 ng/mL over time compared with 14.7 and 23.5 for minimally injured and controls, respectively. Values for both biomarkers remained significantly increased through 24 hours and were associated with a persistent increase in inflammatory cytokines. Admission syndecan-1 significantly predicted mortality, coagulopathy, and massive transfusion., Conclusion: We have shown for the first time that miR-19b and syndecan-1 were biomarkers for endothelial dysfunction independent of resuscitation. MicroRNA-19b did not demonstrate a strong correlation with syndecan-1 nor outcomes. Admission syndecan-1, however, remains a strong prognostic marker, but its elevation over time suggests a versatile role following HS that requires further investigation., Level of Evidence: Prognostic/Epidemiological; Level II., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Our previous data demonstrated that miR-19b expression was increased in human lung microvascular endothelial cells in-vitro-, in-vivo and in patients with hemorrhagic shock, leading to a decrease in syndecan-1 mRNA and protein and resulting in loss of endothelial barrier function. However, the mechanism underlying increased miR-19b expression remains unclear. The objective of the current study was to determine if c-Jun mediates the early responsive microRNA, miR-19b, to cause endothelial barrier dysfunction., Method: Human lung microvascular endothelial cells (HLMEC) or HEK293T cells were transfected with c-Jun overexpressing vector, c-Jun siRNA, miR-19b promoter vector, miR-19b mutated promoter vector, miR-19b oligo inhibitor, then subjected to hypoxia/reoxygenation as in-vitro model of hemorrhagic shock. Levels of protein, miRNA, and luciferase activity were measured. Transwell permeability of endothelial monolayers were also determined. Plasma levels of c-Jun were measured in injured patients with hemorrhagic shock., Result: Hypoxia/reoxygenation induced primary (pri-)miR-19b, mature miR-19b, and c-Jun expression over time in a comparable timeframe. c-Jun silencing by transfection with its specific siRNA reduced both pri-miR-19b and mature miR-19b levels. Conversely, c-Jun overexpression enhanced H/R-induced pri-miR-19b. Studies using a luciferase reporter assay revealed that in cells transfected with vectors containing the wild-type miR-19b promoter and luciferase reporter, c-Jun overexpression or hypoxia/ reoxygenation significantly increased luciferase activity. c-Jun knockdown reduced the luciferase activity in these cells, suggesting that the miR-19b promoter is directly activated by c-Jun. Further, chromatin immunoprecipitation assay confirmed that c-Jun directly bound to the promoter DNA of miR-19b and hypoxia/reoxygenation significantly increased this interaction. Additionally, c-Jun silencing prevented cell surface syndecan-1 loss and endothelial barrier dysfunction in HLMECs after hypoxia/reoxygenation. Lastly, c-Jun was significantly elevated in patients with hemorrhagic shock compared to healthy controls., Conclusion: Transcription factor c-Jun is inducible by hypoxia/reoxygenation, binds to and activates the miR-19b promoter. Using an in-vitro model of hemorrhagic shock, our findings identified a novel cellular mechanism whereby hypoxia/ reoxygenation increases miR-19b transcription by inducing c-Jun and leads to syndecan-1 decrease and endothelial cell barrier dysfunction. This finding supports that miR-19b could be a potential therapeutic target for hemorrhage shock., (© 2022. The Author(s).)

Abstract: Introduction: Neutrophil extracellular traps (NETs) trigger thrombin generation. We aimed to characterize the effects of deoxyribonuclease (DNAse) on NET components (cell-free DNA [cfDNA] and histones) and thrombin generation after trauma. Methods: Citrated plasma samples were collected from trauma patients and healthy volunteers. Thrombin generation (calibrated automated thrombogram) was measured as lag time (LT, in minutes), peak height (in nM), and time to peak thrombin generation (in minutes). Citrullinated histone 3 (CitH3) and 4 (CitH4) were measured by enzyme-linked immunosorbent assay; cfDNA by PicoGreen (all in nanograms per milliliter). Samples analyzed +/- DNAse (1,000 U/mL). Results expressed as median and quartiles [Q1, Q3], Wilcoxon testing, P < 0.05 significant. Results: We enrolled 46 patients (age, 48 [31, 67] years; 67% male) and 21 volunteers (age, 45 [28, 53] years; 43% male). Deoxyribonuclease treatment of trauma plasma led to shorter LT (3.11 [2.67, 3.52] min; 2.93 [2.67, 3.19] min), shorter time to peak thrombin generation (6.00 [5.30, 6.67] min; 5.48 [5.00, 6.00] min), greater peak height (273.7 [230.7, 300.5] nM; 288.7 [257.6, 319.2] nM), decreased cfDNA (576.9 [503.3, 803.1] ng/mL; 456.0 [393.5, 626.7] ng/mL), decreased CitH3 (4.54 [2.23, 10.01] ng/mL; 3.59 [1.93, 7.98] ng/mL), and increased H4 (1.30 [0.64, 6.36] ng/mL; 1.75 [0.83, 9.67] ng/mL), all P < 0.001. The effect of DNAse was greater on trauma patients as compared with volunteers for LT (ΔLT, -0.21 vs. -0.02 min, P = 0.007), cfDNA (ΔcfDNA -133.4 vs. -84.9 ng/mL, P < 0.001), and CitH3 (ΔCitH3, -0.65 vs. -0.11 ng/mL, P = 0.004). Conclusion: Deoxyribonuclease treatment accelerates thrombin generation kinetics in trauma patient samples as compared with healthy volunteers. These findings suggest that NETs may contribute to the hypercoagulable state observed in trauma patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by the Shock Society.)

In 2020, the American Association for the Surgery of Trauma (AAST) published a revision of the organ injury scale (OIS) for bowel injuries. The update included for the first time a separate OIS for penetrating colon injuries as well as imaging criteria. To validate the new OIS and its correlation with outcomes, we performed a retrospective review of patients with penetrating colon injuries (AIS<3 in other body regions) between 2016 and 2020 at a single institution. Sixty-six patients met inclusion criteria. Most were young (29 years median) and male (90%). All underwent operative intervention and 23 (34%) had pre-operative imaging. Imaging grade was higher than operative grade in 11 patients (48%). Higher AAST operative grade was associated with a higher likelihood of resection and anastomosis or colostomy, need for damage control laparotomy, and development of intra-abdominal abscess and acute kidney injury. A multicenter study is underway to confirm these findings.

Abstractintroduction: Although a number of studies have demonstrated increased release of extracellular vesicles (EVs) and changes in their origin differentials after trauma, the biologic significance of EVs is not well understood. We hypothesized that EVs released after trauma/hemorrhagic shock (HS) contribute to endotheliopathy and coagulopathy. To test this hypothesis, adoptive transfer experiments were performed to determine whether EVs derived from severely injured patients in shock were sufficient to induce endothelial dysfunction and coagulopathy. Methods: Total EVs were enriched from plasma of severely injured trauma/HS patients or minimally injured patients by ultracentrifugation and characterized for size and numbers. Under isoflurane anesthesia, noninjured naive C57BL/6J mice were administered EVs at varying concentrations and compared with mice receiving equal volume vehicle (phosphate-buffered saline (PBS)) or to mice receiving EVs from minimally injured patients. Thirty minutes after injection, mice were sacrificed, and blood was collected for thrombin generation (thrombin-antithrombin, thrombin-antithrombin complex [TAT] assay) and syndecan-1 by enzyme-linked immunoabsorbent assay (ELISA). Lungs were harvested for examination of histopathologic injury and costained with von Willebrand factor and fibrin to identify intravascular coagulation. Bronchial alveolar lavage fluid was aspirated from lungs for protein measurement as an indicator of the endothelial permeability. Data are presented as mean ± SD, P < 0.05 was considered significant, and t test was used. Results: An initial proof-of-concept experiment was performed in naive mice receiving EVs purified from severely injured trauma/HS patients (Injury Severity Score [ISS], 34 ± 7) at different concentrations (5 × 106 to 3.1 × 109/100 μL/mouse) and compared with PBS (control) mice. Neither TAT nor syndecan-1 levels were significantly different between groups at 30 minutes after EV infusion. However, lung vascular permeability and histopathologic injury were significantly higher in the EV group, and lung tissues demonstrated intravascular fibrin deposition. Based on these data, EVs from severely injured trauma/HS patients (ISS, 32 ± 6) or EVs from minimally injured patients (ISS, 8 ± 3) were administered to naive mice at higher concentrations (1 × 109 to 1 × 1010 EV/100 μL/mouse). Compared with mice receiving EVs from minimally injured patients, plasma TAT and syndecan-1 levels were significantly higher in the trauma/HS EV group. Similarly, bronchial alveolar lavage protein and lung histopathologic injury were higher in the trauma/HS EV group, and lung tissues demonstrated enhanced intravascular fibrin deposition. Conclusion: These data demonstrate that trauma/HS results in the systemic release of EVs, which are capable of inducing endotheliopathy as demonstrated by elevated syndecan-1 and increased permeability and coagulopathy as demonstrated by increased TAT and intravascular fibrin deposition. Targeting trauma-induced EVs may represent a novel therapeutic strategy., Competing Interests: The authors report no conflict of interests., (Copyright © 2022 by the Shock Society.)

Background: Splenorrhaphy was once used to achieve splenic preservation in up to 40% of splenic injuries. With increasing use of nonoperative management and angioembolization, operative therapy is less common and splenic injuries treated operatively are usually high grade. Patients are often unstable, making splenic salvage unwise. Modern surgeons may no longer possess the knowledge to perform splenorrhaphy., Methods: The records of adult trauma patients with splenic injuries from September 2014 to November 2018 at an urban level I trauma center were reviewed retrospectively. Data including American Association for the Surgery of Trauma splenic organ injury scale, type of intervention, splenorrhaphy technique, and need for delayed splenectomy were collected. This contemporary cohort (CC) was compared to a historical cohort (HC) of splenic injuries at a single center from 1980 to 1989 (Ann Surg 1990; 211: 369)., Results: From 2014 to 2018, 717 adult patients had splenic injuries. Initial management included 157 (21.9%) emergent splenectomy, 158 (22.0%) angiogram ± embolization, 371 (51.7%) observation, and only 10 (1.4%) splenorrhaphy. The HC included a total of 553 splenic injuries, of which 313 (56.6%) underwent splenectomy, while splenorrhaphy was performed in 240 (43.4%). Those who underwent splenorrhaphy in each cohort (CC vs HC) were compared., Conclusion: The success rate of splenorrhaphy has not changed. However, splenorrhaphy now involves only electrocautery with topical hemostatic agents and is used primarily in low-grade injuries. Suture repair and partial splenectomy seem to be "lost arts" in modern trauma care.

Background: COVID-19-associated coagulopathy is incompletely understood., Objectives: To characterize thrombin generation, Von Willebrand Factor (VWF), neutrophil extracellular traps (NETs), and their role in COVID-19 risk stratification in the emergency department (ED)., Patients/methods: Plasma samples from 67 ED COVID-19 patients were compared to 38 healthy volunteers (HVs). Thrombin generation (calibrated automated thrombogram, CAT) was expressed as lag time (LT, min), peak height (PH, min), and time to peak (ttPeak, min). Citrullinated nucleosomes and histones were quantified with ELISA, VWF antigen and activity (IU/dL) through latex immunoassay, Factor VIII (IU/dL) through one-stage optical clot detection, and VWF multimers with Western blot densitometry. Wilcoxon testing and multivariable logistic regression were performed. Results presented as median [Q1, Q3]; p < 0.05 significant., Results: COVID-19 patients had longer LT (4.00 [3.26, 4.67]; 2.95 [2.67, 3.10], p < 0.001) and ttPeak (7.33 [6.33, 8.04]; 6.45 [6.00, 7.50], p = 0.004), greater VWF antigen (212 [158, 275]; 110 [91, 128], p < 0.001) and Factor VIII levels (148 [106, 190]; 106 [86, 129], p < 0.001), with decreased high molecular weight multimers (Normalized multimer ratio 0.807 [0.759, 0.869]; 0.891 [0.858, 0.966], p < 0.001), than HVs. COVID-19 patients requiring admission from the ED had longer LT and ttPeak with greater VWF antigen and Factor VIII levels than those not admitted. Two and three variable models of CAT parameters and VWF correlated with COVID-19 and admission status (C-statistics 0.677 to 0.922)., Conclusions: Thrombin generation kinetics and VWF levels, independent of NETs, may have a role in predicting admission need for COVID-19 patients., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: EpiCypher is a commercial developer and supplier of platforms like those used in this study: recombinant semi-synthetic nucleosomes (dNucs), antibody validation platforms, and nucleosome based H3Cit assays (e.g. EpiCypher Catalog No. R&D143001). ALJ is an inventor on patents covering use of recombinant nucleosomes carrying histone or DNA modifications for antibody validation and assay quantification. All other authors declare no conflict of interest., (© 2021 The Authors.)

Background: Rapid triage and intervention to control hemorrhage are key to survival following traumatic injury. Patients presenting in hemorrhagic shock may undergo resuscitative thoracotomy (RT) or resuscitative endovascular balloon occlusion of the aorta (REBOA) as adjuncts to rapidly control bleeding. We hypothesized that machine learning along with automated calculation of continuously measured vital signs in the prehospital setting would accurately predict need for REBOA/RT and inform rapid lifesaving decisions., Methods: Prehospital and admission data from 1,396 patients transported from the scene of injury to a Level I trauma center via helicopter were analyzed. Utilizing machine learning and prehospital autonomous vital signs, a Bleeding Risk Index (BRI) based on features from pulse oximetry and electrocardiography waveforms and blood pressure (BP) trends was calculated. Demographics, Injury Severity Score and BRI were compared using Mann-Whitney-Wilcox test. Area under the receiver operating characteristic curve (AUC) was calculated and AUC of different scores compared using DeLong's method., Results: Of the 1,396 patients, median age was 45 years and 68% were men. Patients who underwent REBOA/RT were more likely to have a penetrating injury (24% vs. 7%, p < 0.001), higher Injury Severity Score (25 vs. 10, p < 0.001) and higher mortality (44% vs. 7%, p < 0.001). Prehospital they had lower BP (96 [70-130] vs. 134 [117-152], p < 0.001) and higher heart rate (106 [82-118] vs. 90 [76-106], p < 0.001). Bleeding risk index calculated using the entire prehospital period was 10× higher in patients undergoing REBOA/RT (0.5 [0.42-0.63] vs. 0.05 [0.02-0.21], p < 0.001) with an AUC of 0.93 (95% confidence interval [95% CI], 0.90-0.97). This was similarly predictive when calculated from shorter periods of transport: BRI initial 10 minutes prehospital AUC of 0.89 (95% CI, 0.83-0.94) and initial 5 minutes AUC of 0.90 (95% CI, 0.85-0.94)., Conclusion: Automated prehospital calculations based on vital sign features and trends accurately predict the need for the emergent REBOA/RT. This information can provide essential time for team preparedness and guide trauma triage and disaster management., Level of Evidence: Therapeutic/care management, Level IV., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Damage-associated molecular patterns (DAMPs) stimulate endothelial syndecan-1 shedding and neutrophil extracellular traps (NET) formation. The role of NETs in trauma and trauma-induced hypercoagulability is unknown. We hypothesized that trauma patients with accelerated thrombin generation would have increased NETosis and syndecan-1 levels., Methods: In this pilot study, we analyzed 50 citrated plasma samples from 30 trauma patients at 0 h (n = 22) and 6 h (n = 28) from time of injury (TOI) and 21 samples from healthy volunteers, for a total of 71 samples included in analysis. Thrombin generation was quantified using calibrated automated thrombogram (CAT) and reported as lag time (LT), peak height (PH), and time to peak (ttPeak). Nucleosome calibrated (H3NUC) and free histone standardized (H3Free) ELISAs were used to quantify NETs. Syndecan-1 levels were quantified by ELISA. Results are presented as median [interquartile range] and Spearman rank correlations., Results: Plasma levels of H3NUC were increased in trauma patients as compared with healthy volunteers both at 0 h (89.8 ng/mL [35.4, 180.3]; 18.1 ng/mL [7.8, 37.4], P = 0.002) and at 6 h (86.5 ng/mL [19.2, 612.6]; 18.1 ng/mL [7.8, 37.4], P = 0.003) from TOI. H3Free levels were increased in trauma patients at 0 h (5.74 ng/mL [3.19, 8.76]; 1.61 ng/mL [0.66, 3.50], P = 0.002) and 6 h (5.52 ng/mL [1.46, 11.37]; 1.61 ng/mL [0.66, 3.50], P = 0.006). Syndecan-1 levels were greater in trauma patients (4.53 ng/mL [3.28, 6.28]; 2.40 ng/mL [1.66, 3.20], P < 0.001) only at 6 h from TOI. H3Free and syndecan-1 levels positively correlated both at 0 h (0.376, P = 0.013) and 6 h (0.583, P < 0.001) from TOI. H3NUC levels and syndecan-1 levels were positively correlated at 6 h from TOI (0.293, P = 0.041). TtPeak correlated inversely to H3 NUC (-0.358, P = 0.012) and syndecan-1 levels (-0.298, P = 0.038) at 6 h from TOI., Conclusions: Our pilot study demonstrates that trauma patients have increased NETosis, measured by H3NUC and H3Free levels, increased syndecan-1 shedding, and accelerated thrombin generation kinetics early after injury., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Background: The benefits of plasma as an adjunct to the treatment of haemorrhagic shock are well established; however, the mechanism by which plasma modulates the endotheliopathy of trauma remains unclear. Our recent data demonstrated a novel role of microRNA-19b in post-haemorrhagic shock endothelial dysfunction via targeting of syndecan-1. Additionally, fibrinogen, as a key component of plasma or an isolated haemostatic protein, protects the endothelium by stabilizing syndecan-1. We therefore hypothesized that fibrinogen would inhibit microRNA-19b to mitigate the endotheliopathy of trauma in a murine model of haemorrhagic shock., Materials and Methods: C57BL/6J mice were subjected to haemorrhagic shock (mean arterial pressure 35±5 mmHg for 90 minutes) followed by resuscitation with lactated Ringer's, fresh frozen plasma, fibrinogen or no resuscitation. MicroRNA-19b and syndecan-1 mRNA were measured in lung tissue by qRT-PCR. Lungs were stained for histopathologic injury, and broncheoalveolar lavage was collected for protein as a permeability indicator., Results: Pulmonary microRNA-19b was increased after haemorrhagic shock and lactated Ringers, but reduced to sham levels by plasma and fibrinogen. Conversely, pulmonary syndecan-1 mRNA was downregulated by haemorrhagic shock and lactated Ringers, but returned to sham levels by plasma and fibrinogen. Plasma and fibrinogen-based resuscitation reduced lung injury compared to haemorrhagic shock and lactated Ringers while fibrinogen also reduced broncheoalveolar lavage protein., Discussion: We have demonstrated a novel mechanism by which fibrinogen, a key component of plasma and haemostatic agent, inhibits miR-19b, possibly by mitigating the endotheliopathy of trauma. Complete demonstration of the mechanism of fibrinogen inhibition of endotheliopathy via microRNA, however, remains to be elucidated. These findings support the early and empiric use of fibrinogen in post-haemorrhagic shock resuscitation.