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Management of non-compressible torso hemorrhage of the abdomen in civilian and military austere environments: a scoping review
Adams, D., McDonald, P. L., Holland, S., Merkle, A. B., Puglia, C., Miller, B., Allison, D. D., Moussette, C., Souza, C. J., Nunez, T., et al
Trauma surgery & acute care open. 2024;9(1):e001189
Abstract
BACKGROUND Non-compressible abdominal hemorrhage (NCAH) is the leading cause of potentially preventable deaths in both civilian and military austere environments, and an improvement in mortality due to this problem has not been demonstrated during the past quarter century. Several innovations have been developed to control hemorrhage closer to the point of injury. OBJECTIVE This review assessed NCAH interventions in civilian and military settings, focusing on austere environments. It identified innovations, effectiveness, and knowledge gaps for future research. METHODOLOGY The Joanna Briggs Institute for Evidence Synthesis methodology guided this scoping review to completion. Studies evaluating NCAH with human participants in civilian and military austere environments that were eligible for inclusion were limited to English language studies published between December 1990 and January 2023. The PCC (Participant, Concept, Context) framework was used for data synthesis. Deductive and inductive thematic analyses were used to assess the literature that met inclusion criteria, identify patterns/themes to address the research questions and identify common themes within the literature. A stakeholder consultation was conducted to review and provide expert perspectives and opinions on the results of the deductive and inductive thematic analyses. RESULTS The literature search identified 868 articles; 26 articles met the inclusion criteria. Textual narrative analysis of the 26 articles resulted in the literature addressing four main categories: NCAH, penetrating abdominal trauma, resuscitative endovascular balloon occlusion of the aorta (REBOA), and ResQFoam. The deductive thematic analysis aimed to answer three research questions. Research question 1 addressed the effectiveness of REBOA, damage control resuscitation, and damage control surgery in managing NCAH in austere environments. No effectiveness studies were found on this topic. Research question 2 identified three knowledge gaps in NCAH management in austere environments. The analysis identified early hemorrhage control, prehospital provider decision-making ability, and REBOA implementation as knowledge gaps in NCAH. Research question 3 identified five innovations that may affect the management of NCAH in the future: transport of patients, advanced resuscitative care, expert consultation, REBOA implementation, and self-expanding foam implementation. The inductive thematic analysis resulted in four recurrent themes from the literature: prehospital care, decision-making, hemorrhage control, and mortality in NCAH. During the stakeholders' consultation, the results of the deductive and inductive thematic analyses were reviewed and agreed on by the stakeholders. Special emphasis and discussion were given to prehospital management, expert opinions in the prehospital environment, decision-making in the prehospital environment, transport and resuscitation in the prehospital setting, REBOA, alternative discussion for research, and research gaps. CONCLUSION NCAH is still a significant cause of preventable death in both military and civilian austere environments, even with ongoing research and interventions aimed at extending survival in such conditions. This scoping review has identified several potential concepts that could reduce the mortality associated with a preventable cause of death due to hemorrhage in austere environments.
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Tranexamic acid in patients with traumatic brain injury: A meta-analysis
Sarhan Boshra, R. M., Abdelrahim, M. E. A., Osama, H.
Revista espanola de anestesiologia y reanimacion. 2024
Abstract
BACKGROUND We performed a meta-analysis to assess the effectiveness and safety of tranexamic acid in patients with traumatic brain injury (TBI). METHODS We searched the literature for articles evaluating the effectiveness and safety of tranexamic acid (TXA) in TBI published between January 2012 and January 2021, and identified 8 studies with a total of 10860 patients: 5660 received TXA and 5200 served as controls. We used a dichotomous or continuous approach with a random or fixed-effect model to assess the efficacy and safety of TXA in TBI, and calculated the mean difference (MD) and odds ratio (OR) with the corresponding 95% confidence interval. RESULTS In patients with TBI, early administration of TXA was associated with a greater relative benefit (MD -2.45; 95% CI = -4.78 to -0.12; p = 0.04) and less total haematoma expansion (MD - 2.52; 95% CI = -4.85 to -0.19; p = 0.03) compared to controls. There were no statistically significant differences in mortality (OR 0.94; 95% CI = 0.85-1.03; p = 0.18), presence of progressive haemorrhage (OR 0.75; 95% CI = 0.56-1.01; p = 0.06), need for neurosurgery (OR 1.15; 95% CI = 0.66-1.98; p = 0.63), high Disability Rating Scale score (OR 0.90; 95% CI = 0.56-1.45; p = 0.68), and incidence of ischaemic or thromboembolic complications (OR 1.34; 95% CI = 0.33-5.46; p = 0.68) between TBI patients treated with TXA and controls. CONCLUSIONS Early administration of TXA in TBI patients may have a greater relative benefit and may inhibit haematoma expansion. There were no significant differences in mortality, presence of progressive haemorrhage, need for neurosurgery, high Disability Rating Scale score, and incidence of ischaemic or thromboembolic complications between TBI patients treated with TXA and controls. Further studies are needed to validate these results.
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Missingness matters: a secondary analysis of thromboelastography measurements from a recent prehospital randomized tranexamic acid clinical trial
Donohue, J. K., Iyanna, N., Lorence, J. M., Brown, J. B., Guyette, F. X., Eastridge, B. J., Nirula, R., Vercruysse, G. A., O'Keeffe, T., Joseph, B., et al
Trauma surgery & acute care open. 2024;9(1):e001346
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Editor's Choice
Abstract
BACKGROUND Tranexamic acid (TXA) has been hypothesized to mitigate coagulopathy in patients after traumatic injury. Despite previous prehospital clinical trials demonstrating a TXA survival benefit, none have demonstrated correlated changes in thromboelastography (TEG) parameters. We sought to analyze if missing TEG data contributed to this paucity of findings. METHODS We performed a secondary analysis of the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport Trial. We compared patients that received TEG (YES-TEG) and patients unable to be sampled (NO-TEG) to analyze subgroups in which to investigate TEG differences. TEG parameter differences across TXA intervention arms were assessed within subgroups disproportionately present in the NO-TEG relative to the YES-TEG cohort. Generalized linear models controlling for potential confounders were applied to findings with p<0.10 on univariate analysis. RESULTS NO-TEG patients had lower prehospital systolic blood pressure (SBP) (100 (78, 140) vs 125 (88, 147), p<0.01), lower prehospital Glascow Coma Score (14 (3, 15) vs 15 (12, 15), p<0.01), greater rates of prehospital intubation (39.4% vs 24.4%, p<0.01) and greater mortality at 30 days (36.4% vs 6.8%, p<0.01). NO-TEG patients had a greater international normalized ratio relative to the YES-TEG subgroup (1.2 (1.1, 1.5) vs 1.1 (1.0, 1.2), p=0.04). Within a severe prehospital shock cohort (SBP<70), TXA was associated with a significant decrease in clot lysis at 30 min on multivariate analysis (β=-27.6, 95% CI (-51.3 to -3.9), p=0.02). CONCLUSIONS Missing data, due to the logistical challenges of sampling certain severely injured patients, may be associated with a lack of TEG parameter changes on TXA administration in the primary analysis. Previous demonstration of TXA's survival benefit in patients with severe prehospital shock in tandem with the current findings supports the notion that TXA acts at least partially by improving clot integrity. LEVEL OF EVIDENCE Level II.
PICO Summary
Population
Patients at risk for haemorrhage receiving tranexamic acid before hospitalization, enrolled in the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport (STAAMP) Trial (n= 903).
Intervention
Prehospital tranexamic acid (TXA) (n= 447).
Comparison
Placebo (n= 456).
Outcome
This study was a secondary analysis of the STAAMP trial, comparing patients that received thromboelastography (TEG) (YES-TEG, n= 837) and patients unable to be sampled (NO-TEG, n= 66) to analyze subgroups in which to investigate TEG differences. NO-TEG patients had lower prehospital systolic blood pressure (SBP) (100 (78, 140) vs. 125 (88, 147)), lower prehospital Glascow Coma Score (14 (3, 15) vs. 15 (12, 15)), greater rates of prehospital intubation (39.4% vs. 24.4%) and greater mortality at 30 days (36.4% vs. 6.8%). NO-TEG patients had a greater international normalized ratio relative to the YES-TEG subgroup (1.2 (1.1, 1.5) vs. 1.1 (1.0, 1.2)). Within a severe prehospital shock cohort (SBP< 70), TXA was associated with a significant decrease in clot lysis at 30 min on multivariate analysis (β= -27.6; 95% CI [-51.3, -3.9].
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Effectiveness of Tranexamic Acid in Trauma Patients: A Systematic Review
Meza Monge, K., Domene, S. S., Diaz Mendoza, D. L., Vidal-Gallardo, A., Alfaro Llique, A. M., Rodriguez, M., Premchandra, P., Anwar Pandya, S., Arruarana, V. S., Aleman Paredes, K., et al
Cureus. 2024;16(1):e52111
Abstract
Tranexamic acid (TXA), a fibrinolytic agent, effectively inhibits plasminogen activation, thereby reducing fibrinolysis and hemorrhage. This study focused on its application in trauma patients undergoing emergency surgery, a critical area due to trauma's significant role in mortality. Our investigation involved a meticulous screening of randomized controlled trials from databases including Scopus, PubMed, Web of Science, and Cochrane. The findings indicate that TXA intervention is promising in enhancing outcomes for trauma patients. However, the drug's effectiveness may vary based on the specific nature of the medical condition. In summary, robust evidence suggests that TXA can diminish blood loss, lower transfusion rates, reduce complications, and improve hemoglobin and hematocrit levels in surgical patients. Consequently, TXA should be considered a crucial medication, readily available to mitigate morbidity and mortality in surgical settings. Future research should explore factors influencing TXA's effectiveness in traumatic brain injury cases and across a broad spectrum of surgical scenarios in diverse patient populations. This would further guide clinicians in refining and optimizing the use of TXA.
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Tranexamic acid in pediatric hemorrhagic trauma
Borgman, M. A., Nishijima, D. K.
The Journal of Trauma and Acute Care Surgery. 2023;94(1S Suppl 1):S36-s40
Abstract
There is strong evidence in adult literature that tranexamic acid (TXA) given within 3 hours from injury is associated with improved outcomes. The evidence for TXA use in injured children is limited to retrospective studies and one prospective observational trial. Two studies in combat settings and one prospective civilian US study have found association with improved mortality. These studies indicate the need for a randomized controlled trial to evaluate the efficacy of TXA in injured children and to clarify appropriate timing, dose and patient selection. Additional research is also necessary to evaluate trauma-induced coagulopathy in children. Recent studies have identified three distinct fibrinolytic phenotypes following trauma (hyperfibrinolysis, physiologic fibrinolysis, and fibrinolytic shutdown), which can be identified with viscohemostatic assays. Whether viscohemostatic assays can appropriately identify children who may benefit or be harmed by TXA is also unknown.
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Cost-Effectiveness of Cell Salvage in Trauma Blood Transfusions
Beeton G, Zagales I, Ngatuvai M, Atoa A, Wajeeh H, Hoops H, Smith CP, Elkbuli A
The American surgeon. 2023;:31348231175124
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Editor's Choice
Abstract
INTRODUCTION Despite the increasing amount of evidence supporting its use, cell salvage (CS) remains an underutilized resource in operative trauma care in many hospitals. We aim to evaluate the utilization of CS in adult trauma patients and associated outcomes to provide evidence-based recommendations. METHODS A systematic review was conducted using PubMed, Google Scholar, and CINAHL. Articles evaluating clinical outcomes and the cost-effectiveness of trauma patients utilizing CS were included. The primary study outcome was mortality rates. The secondary outcomes included complication rates (sepsis and infection) and ICU-LOS. The tertiary outcome was the cost-effectiveness of CS. RESULTS This systematic review included 9 studies that accounted for a total of 1119 patients that received both CS and allogeneic transfusion (n = 519), vs allogeneic blood transfusions only (n = 601). In-hospital mortality rates ranged from 13% to 67% in patients where CS was used vs 6%-65% in those receiving allogeneic transfusions only; however, these findings were not significantly different (P = .21-.56). Similarly, no significant differences were found between sepsis and infection rates or ICU-LOS in those patients where CS usage was compared to allogeneic transfusions alone. Of the 4 studies that provided comparisons on cost, 3 found the use of CS to be significantly more cost-effective. CONCLUSIONS Cell salvage can be used as an effective method of blood transfusion for trauma patients without compromising patient outcomes, in addition to its possible cost advantages. Future studies are needed to further investigate the long-term effects of cell salvage utilization in trauma patients.
PICO Summary
Population
Adult trauma patients (9 studies, n= 1,119).
Intervention
Cell salvage and allogeneic transfusion.
Comparison
Allogeneic blood transfusion.
Outcome
In-hospital mortality rates ranged from 13% to 67% in patients where cell salvage was used vs. 6%-65% in those receiving allogeneic transfusions only. These findings were not significantly different. No significant differences were found between sepsis and infection rates or intensive care unit length-of-stay in those patients where cell salvage usage was compared to allogeneic transfusions alone. Of the four studies that provided comparisons on cost, three found the use of cell salvage to be significantly more cost-effective.
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Re-analysis of the PolyHeme Phase III trial dataset: Lessons for future haemoglobin-based oxygen carrier trauma trials
Mackenzie CF, Dubé GP, Pitman AN
Injury. 2023
Abstract
INTRODUCTION To assist design of future HBOC clinical trials for pre-hospital and prolonged field care, the haemoglobin-based-oxygen carrier (HBOC) Phase III trauma trial database comparing PolyHeme to blood transfusion was re-analysed to identify causes of adverse early outcomes versus the 30-day mortality outcome of the original trial. We questioned if failure of PolyHeme (10 g/dl) to increase haemoglobin concentration and dilutional coagulopathy versus blood, caused higher Day 1 mortality in the PolyHeme arm of the trial. METHODS New analyses of the original trial database, including Fisher's exact test, examined impact of interval changes in total haemoglobin [THb], coagulation, fluid volumes administered and mortality on Day 1 in the Control (pre-hospital crystalloids, then blood after trauma centre admission) and PolyHeme arms of the trial. RESULTS Admission [THb] was significantly greater (p<0.05) in PolyHeme (12.3 [SD = 1.8] g/dl) versus Control (11.5 [SD= 2.9] g/dl) patients. This early [THb] advantage was reversed within 6 h. Early mortality was negatively correlated with [THb] and maximum 1.4 h after hospital admission (17/365 for Control vs. 5/349 for PolyHeme). The mortality trend began reversing, when Control arm received blood. Coagulopathy was more common in the PolyHeme arm. Mortality rate was 2-fold greater for patients with coagulopathy in the control arm (18% vs. 9%, p = 0.1008) and 4-fold greater in PolyHeme arm (33% vs. 8.5%, p < 0.001). In a subgroup analysis of patients with major haemorrhage (n = 55), mortality was significantly higher in PolyHeme patients [12/26 (46.2%) versus 4/29 (13.8%) in control cohort (p = 0.018)], related to mean 10 liters more IV fluid administration and more severe anaemia (6.2 g/dL vs. 9.2 g/dL) in the PolyHeme cohort. CONCLUSIONS PolyHeme (10 g/dL) diminished pre-hospital anaemia. The inability of PolyHeme to reverse acute anaemia in a subset of major haemorrhage patients was due to volume overload secondary to high PolyHeme doses, resulting in dilution of clotting factors and low circulating THb (versus transfused controls) during the first 12 h of the trial. Haemodilution was associated with prolonged administration of PolyHeme, while blood transfusion was available to Control patients following hospital admission. Coagulopathy exacerbated bleeding, anaemia, contributing to excess mortality in the PolyHeme arm. Future trials for prolonged field care should evaluate HBOC with higher haemoglobin concentration, lower volume administration and transition upon trauma centre admission to blood plus coagulation factors or whole blood.
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Prehospital Tranexamic Acid for Severe Trauma
Gruen, R. L., Mitra, B., Bernard, S. A., McArthur, C. J., Burns, B., Gantner, D. C., Maegele, M., Cameron, P. A., Dicker, B., Forbes, A. B., et al
The New England journal of medicine. 2023
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Editor's Choice
Abstract
BACKGROUND Whether prehospital administration of tranexamic acid increases the likelihood of survival with a favorable functional outcome among patients with major trauma and suspected trauma-induced coagulopathy who are being treated in advanced trauma systems is uncertain. METHODS We randomly assigned adults with major trauma who were at risk for trauma-induced coagulopathy to receive tranexamic acid (administered intravenously as a bolus dose of 1 g before hospital admission, followed by a 1-g infusion over a period of 8 hours after arrival at the hospital) or matched placebo. The primary outcome was survival with a favorable functional outcome at 6 months after injury, as assessed with the use of the Glasgow Outcome Scale-Extended (GOS-E). Levels on the GOS-E range from 1 (death) to 8 ("upper good recovery" [no injury-related problems]). We defined survival with a favorable functional outcome as a GOS-E level of 5 ("lower moderate disability") or higher. Secondary outcomes included death from any cause within 28 days and within 6 months after injury. RESULTS A total of 1310 patients were recruited by 15 emergency medical services in Australia, New Zealand, and Germany. Of these patients, 661 were assigned to receive tranexamic acid, and 646 were assigned to receive placebo; the trial-group assignment was unknown for 3 patients. Survival with a favorable functional outcome at 6 months occurred in 307 of 572 patients (53.7%) in the tranexamic acid group and in 299 of 559 (53.5%) in the placebo group (risk ratio, 1.00; 95% confidence interval [CI], 0.90 to 1.12; P = 0.95). At 28 days after injury, 113 of 653 patients (17.3%) in the tranexamic acid group and 139 of 637 (21.8%) in the placebo group had died (risk ratio, 0.79; 95% CI, 0.63 to 0.99). By 6 months, 123 of 648 patients (19.0%) in the tranexamic acid group and 144 of 629 (22.9%) in the placebo group had died (risk ratio, 0.83; 95% CI, 0.67 to 1.03). The number of serious adverse events, including vascular occlusive events, did not differ meaningfully between the groups. CONCLUSIONS Among adults with major trauma and suspected trauma-induced coagulopathy who were being treated in advanced trauma systems, prehospital administration of tranexamic acid followed by an infusion over 8 hours did not result in a greater number of patients surviving with a favorable functional outcome at 6 months than placebo. (Funded by the Australian National Health and Medical Research Council and others; PATCH-Trauma ClinicalTrials.gov number, NCT02187120.).
PICO Summary
Population
Adult patients with severe trauma and at risk for trauma induced coagulopathy, enrolled in the PATCH-Trauma trial in 15 emergency medical services in Australia, New Zealand, and Germany (n= 1,310).
Intervention
Tranexamic acid (n= 661).
Comparison
Placebo (n= 646).
Outcome
Survival with a favorable functional outcome at 6 months occurred in 307 of 572 patients (53.7%) in the tranexamic acid group and in 299 of 559 (53.5%) in the placebo group (risk ratio, 1.00; 95% confidence interval (CI), [0.90, 1.12]. At 28 days after injury, 113 of 653 patients (17.3%) in the tranexamic acid group and 139 of 637 (21.8%) in the placebo group had died (risk ratio, 0.79; 95% CI [0.63, 0.99]. By 6 months, 123 of 648 patients (19.0%) in the tranexamic acid group and 144 of 629 (22.9%) in the placebo group had died (risk ratio, 0.83; 95% CI [0.67, 1.03]. The number of serious adverse events, including vascular occlusive events, did not differ meaningfully between the groups.
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Association of Fibrinolysis Phenotype with Patient Outcomes following Traumatic Brain Injury
Durbin, S., Brito, A., Johnson, A., Cotton, B., Rowell, S., Schreiber, M.
The journal of trauma and acute care surgery. 2023
Abstract
BACKGROUND Impaired coagulation is associated with elevated risk of mortality in trauma patients. Prior studies have demonstrated increased mortality in patients with hyperfibrinolysis (HF) and fibrinolysis shutdown (SD). Additionally, prior studies have demonstrated no effect of tranexamic acid (TXA) on fibrinolysis phenotypes. We examined the association of admission fibrinolysis phenotype with traumatic brain injury (TBI) patient outcomes. METHODS Data were extracted from a placebo-controlled multicenter clinical trial. Patients ≥15 years old with TBI (Glasgow Coma Scale 3-12) and systolic blood pressure ≥ 90 mmHg were randomized in the out-of-hospital setting to receive placebo bolus/placebo infusion (Placebo), 1 gram (g) TXA bolus/1 g TXA infusion (Bolus Maintenance [BM]); or 2 g TXA bolus/placebo infusion (Bolus Only [BO]). Fibrinolysis phenotypes on admission were determined by clot lysis at 30 minutes (LY30): SD ≤0.8%, physiologic 0.9-2.9%, HF ≥3%. Logistic regression was used to control for age, sex, penetrating injury, ISS, maximum head AIS, and TXA treatment group. RESULTS 747 patients met inclusion criteria. Fibrinolysis shutdown was the most common phenotype in all treatment groups and was associated with increased age, ISS and presence of intracranial hemorrhage (ICH). Inpatient mortality was 15.2% for SD and HF, and 10.6% for physiologic (p = 0.49). No differences in mortality, disability rating scale at 6 months, acute kidney injury, acute respiratory distress syndrome, or multi-organ failure were noted between fibrinolysis phenotypes. CONCLUSION SD is the most common phenotype expressed in moderate to severe TBI. In TBI, there is no association between fibrinolysis phenotype and mortality or other major complications. LEVEL OF EVIDENCE diagnostic test/criteria, III.
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Prehospital tranexamic acid is associated with a dose-dependent decrease in syndecan-1 after trauma: A secondary analysis of a prospective randomized trial
Gruen DS, Brown JB, Guyette FX, Johansson PI, Stensballe J, Li SR, Leeper CM, Eastridge BJ, Nirula R, Vercruysse GA, et al
The journal of trauma and acute care surgery. 2023
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Editor's Choice
Abstract
BACKGROUND In the Study of Tranexamic Acid During Air and Ground Prehospital Transport (STAAMP) Trial, prehospital tranexamic acid (TXA) was associated with lower mortality in specific patient subgroups. The underlying mechanisms responsible for a TXA benefit remain incompletely characterized. We hypothesized that TXA may mitigate endothelial injury and sought to assess whether TXA was associated with decreased endothelial or tissue damage markers among all patients enrolled in the STAAMP Trial. METHODS We collected blood samples from STAAMP Trial patients and measured markers of endothelial function and tissue damage including syndecan-1, soluble thrombomodulin (sTM), and platelet endothelial cell adhesion molecule-1 (PECAM-1) at hospital admission (0 hours) and 12, 24, and 72 hours after admission. We compared these marker values for patients in each treatment group during the first 72 hours, and modeled the relationship between TXA and marker concentration using regression analysis to control for potential confounding factors. RESULTS We analyzed samples from 766 patients: 383 placebo, 130 abbreviated dosing, 119 standard dosing, and 130 repeat dosing. Lower levels of syndecan-1, TM, and PECAM measured within the first 72 hours of hospital admission were associated with survival at 30 days (P < 0.001). At hospital admission, syndecan-1 was lower in the TXA group (28.30 [20.05, 42.75] vs. 33.50 [23.00, 54.00] P = 0.001) even after controlling for patient, injury, and prehospital factors (P = 0.001). For every 1 g increase in TXA administered over the first 8 hours of prehospital transport and hospital admission, there was a 4 ng/mL decrease in syndecan-1 at 12 hours controlling for patient, injury, and treatment factors (P = 0.03). CONCLUSIONS Prehospital TXA was associated with decreased syndecan-1 at hospital admission. Syndecan-1 measured 12 hours after admission was inversely related to the dose of TXA received. Early pre- and in-hospital TXA may decrease endothelial glycocalyx damage or upregulate vascular repair mechanisms in a dose-dependent fashion. LEVEL OF EVIDENCE Level II, Secondary analysis of a prospective randomized trial.
PICO Summary
Population
Injured patients who received prehospital tranexamic acid (TXA) and were at risk for haemorrhage enrolled in the STAAMP randomised controlled trial (n= 766).
Intervention
Abbreviated dose: 1g of TXA (n= 130). Standard dose: 2g of TXA (n= 119). Repeat dose: 3g of TXA (n= 130).
Comparison
Placebo (saline), (n= 383).
Outcome
Blood samples were collected to measure markers of endothelial function and tissue damage including syndecan-1, soluble thrombomodulin (sTM), and platelet endothelial cell adhesion molecule-1 (PECAM-1) at hospital admission and 12, 24, and 72 hours after admission. Lower levels of syndecan-1, TM, and PECAM measured within the first 72 hours of hospital admission were associated with survival at 30 days. At hospital admission (mean ng/mL [IQR]), syndecan-1 was lower in the TXA group than the placebo group (28.30 [20.05, 42.75] vs. 33.50 [23.00, 54.00]) even after controlling for patient, injury, and prehospital factors. For every 1g increase in TXA administered over the first 8 hours of prehospital transport and hospital admission, there was a 4 ng/mL decrease in syndecan-1 at 12 hours controlling for patient, injury, and treatment factors.