Acid In Trauma Patients Research Articles

Effectiveness of Tranexamic Acid in Trauma Patients: A Systematic Review.

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.

Should pre-hospital intramuscular tranexamic acid be given to trauma patients at risk of significant haemorrhage?

There are situations in the pre-hospital setting where gaining intravenous or intraosseous access is impossible or delayed. This can delay the administration of tranexamic acid to bleeding trauma patients, which may reduce its effectiveness. We sought to investigate whether some patients would benefit from early administration of tranexamic acid via the intramuscular route. Relevant observational and interventional studies were identified and summarised using a BestBET format. The current evidence supports clinicians considering intramuscular tranexamic acid in trauma patients at risk of haemorrhage when there may be significant delay in administration via intravenous or intraosseous routes.

Pre-hospital administration of tranexamic acid in trauma patients: A systematic review and meta-analysis

Background The Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage-2 (CRASH-2) trial proved that tranexamic acid (TXA) is a time-dependent drug, having a better outcome if given within 1-hour of injury. In order to test this theory, studies have been conducted to examine the effect of TXA in the pre-hospital setting. We conducted a systematic search and meta-analysis to evaluate the role of TXA administration in the civilian pre-hospital setting on patient outcomes. Methods Embase, Medline, CINAHL and Cochrane were searched for randomized control trials (RCTs), retrospective, and prospective studies that examined the effect of TXA on patients in the pre-hospital setting versus a control group. Outcome measures were overall mortality rate and thromboembolic events. Two authors extracted the data independently. To appraise the included studies, we used the NIH quality assessment tool for cohort and cross-sectional studies. Results are presented as Risk Ratio (RR), a random-effect model was implemented, and the I2 test was used to assess heterogeneity. Results The search identified 1886 papers, but only five retrospective studies met the inclusion/exclusion criteria and were selected for further analysis. A meta-analysis confirmed that TXA reduced the overall mortality rate (pooled risk ratio of 0.74 (95% CI 0.45, 1.25)) and thromboembolic events (risk ratio of 0.71 (95% CI 0.35, 1.44)). Conclusion The pooled effects for both outcome measures favour the administration of TXA in the pre-hospital setting, although none of the findings reported a significant effect. Our study highlights the need for additional high-quality evidence to validate the significance of these findings. Level of evidence Level III, therapeutic study.

Prehospital administration of tranexamic acid in trauma patients: A 1:1 matched comparative study from a level 1 trauma center

PurposeThe purpose of this study was to test the efficacy of prehospital administration of tranexamic acid (TXA) to injured patients on mortality, thromboembolic events and need for blood transfusion in a level 1 trauma center. MethodsWe conducted a retrospective study comparing adult trauma patients receiving or not receiving prehospital TXA between January 2017 and September 2018. Patients not receiving TXA but transfused within 4 h of admission were 1:1 matched to TXA-treated patients for age, sex, injury severity score, head abbreviated injury score, prehospital heart rate and systolic blood pressure. ResultsIn total 204 patients were included (102 TXA and 102 control), with a mean age of 31 years. On admission, shock index (p = 0.03) and serum lactate (p = 0.001) were greater in the control group, whereas the initial base deficit, hemoglobin levels and EMS time were comparable in both groups. The odd ratio (OR) for shock index ≥0.9 after TXA administration was 0.44 (95% CI 0.23–0.84). The median amount of blood transfusion was greater in the control group [eight units (range 1–40) vs three (range 0–40), p = 0.01] as well as the use of massive blood transfusion [OR 0.35 (95% CI 0.19–0.67)]. In the TXA group, VTE was higher [OR 2.0 (95% CI 0.37–11.40)]; whereas the overall mortality was lower [OR 0.78 (95% CI 0.42–1.45)] without reaching statistical significance. ConclusionsPrehospital TXA administration is associated with less in-hospital blood transfusion and massive transfusion protocol (MTP). There is no significant increase in the thromboembolic events and mortality, however, further evaluation in larger clinical trials is needed.

Evaluation of tranexamic acid in trauma patients: A retrospective quantitative analysis

IntroductionTranexamic acid (TXA) has been shown to decrease mortality in adult trauma patients with or at significant risk of hemorrhage when administered within 3 h of injury. The use and appropriateness of TXA in adult trauma patients presenting to Royal Columbian Hospital (RCH) was investigated. MethodsThis retrospective chart review utilized the British Columbia Trauma Registry to identify 100 consecutive trauma patients that presented to the emergency department at RCH between April 2012 to June 2015 and met the following indications for TXA: systolic blood pressure <90 mm Hg and/or heart rate >110 bpm and presentation within 8 h of injury. Primary outcomes included: percentage that met indications for TXA, received TXA according to the CRASH-2 protocol, received a pre-hospital dose, and received TXA ≤1, >1 to ≤3, or >3 h from injury. ResultsDuring the given time period, 117 subjects (2.7%) met indications for TXA. 67 patients (57%) received TXA in any dose, with 10 subjects (8.5%) receiving TXA according to the CRASH-2 protocol. Of the 67 patients who received any TXA, 76% did so ≤3 h. 22 patients (19%) received TXA as a pre-hospital dose. Conclusions<10% of adult trauma patients that met the indication for TXA received it according to the CRASH-2 protocol. Of those patients that received TXA, 76% did so within 3 h. Further inquiry to identify reasons trauma patients are not receiving TXA as well as quality improvement initiatives in trauma care are required. Level of evidenceIII Study typeTherapeutic

Optimisation of the dosage of tranexamic acid in trauma patients with population pharmacokinetic analysis.

Tranexamic acid is used both pre-hospital and in-hospital as an antifibrinolytic drug to treat or prevent hyperfibrinolysis in trauma patients; dosing, however, remains empirical. We aimed to measure plasma levels of tranexamic acid in patients receiving pre-hospital anti-hyperfibrinolytic therapy and to build a population pharmacokinetic model to propose an optimised dosing regimen. Seventy-three trauma patients were enrolled and each received tranexamic acid 1g intravenously pre-hospital. A blood sample was drawn after arrival in the emergency department, and we measured the plasma tranexamic acid concentration using liquid chromatography-mass spectrometry, and modelled the data using non-linear mixed effect modelling. Tranexamic acid was administered at a median (IQR [range]) time of 43 (30-55 [5-135]) min after trauma. Plasma tranexamic acid levels were determined on arrival at hospital, 57 (43-70 [20-148])min after pre-hospital administration of the drug. The measured concentration was 28.7 (21.5-38.5 [8.7-89.0])μg.ml-1 . Our subjects had sustained severe trauma; injury severity score 20 (16-29 [5-75]), including penetrating injury in 2.8% and isolated traumatic brain injury in 19.7%. The pharmacokinetics were ascribed a two-compartment open model with body-weight as the main covariate. As tranexamic acid concentrations may fall below therapeutic levels during initial hospital treatment, we propose additional dosing schemes to maintain a specific target blood concentration for as long as required. This is the first study to investigate plasma level and pharmacokinetics of tranexamic acid after pre-hospital administration in trauma patients. Our proposed dosing regimen could be used in subsequent clinical trials to better study efficacy and tolerance profiles with controlled blood concentrations.

Prehospital administration of tranexamic acid in trauma patients.

BackgroundEvidence on prehospital administration of the antifibrinolytic tranexamic acid (TXA) in civilian trauma populations is scarce. The aim was to study whether prehospital TXA use in trauma patients was associated with improved outcomes.MethodsThe prehospital database of the ADAC (General German Automobile Club) Air Rescue Service was linked with the TraumaRegister of the German Trauma Society to reidentify patients documented in both registries. Primarily admitted trauma patients (2012 until 2014) who were treated with TXA during the prehospital phase were matched with patients who had not received prehospital TXA, applying propensity score-based matching.ResultsThe matching yielded two identical cohorts (n = 258 in each group), since there were no significant differences in demographics or injury characteristics (mean Injury Severity Score 24 ± 14 [TXA] vs. 24 ± 16 [control]; p = 0.46). The majority had sustained blunt injury (90.3 % vs. 93.0 %; p = 0.34). There were no differences with respect to prehospital therapy, including rates of intubation, chest tube insertion or both administration of i.v. fluids and catecholamines. During ER treatment, the TXA cohort received fewer numbers of red blood cells and plasma units, but without reaching statistical significance. Incidences of organ failure, sepsis or thromboembolism showed no significant differences as well, although data were incomplete for these parameters. Early mortality was significantly lower in the TXA group (e.g., 24-h mortality 5.8 % [TXA] vs. 12.4 % [control]; p = 0.01), and mean time to death was 8.8 ± 13.4 days vs. 3.6 ± 4.9 days, respectively (p = 0.001). Overall hospital mortality was similar in both groups (14.7 % vs. 16.3 %; p = 0.72). The most pronounced mortality difference was observed in patients with a high propensity score, reflecting severe injury load.ConclusionsThis is the first civilian study, to our knowledge, in which the effect of prehospital TXA use in trauma patients has been examined. TXA was associated with prolonged time to death and significantly improved early survival. Until further evidence emerges, the results of this study support the use of TXA during prehospital treatment of severely injured patients.

Procoagulant and fibrinolytic activity after polytrauma in rat.

The purpose of this study was to determine whether trauma-induced coagulopathy is due to changes in 1) thrombin activity, 2) plasmin activity, and/or 3) factors that stimulate or inhibit thrombin or plasmin. Sprague-Dawley rats were anesthetized with 1-2% isoflurane/100% oxygen, and their left femoral artery and vein were cannulated. Polytrauma included right femur fracture, and damage to the small intestines, the left and medial liver lobes, and right leg skeletal muscle. Rats were then bled 40% of blood volume. Plasma samples were taken before trauma, and at 30, 60, 120, and 240 min. Polytrauma and hemorrhage led to a significant fall in prothrombin levels. However, circulating thrombin activity did not change significantly over time. Antithrombin III and α2 macroglobulin fell significantly by 2 h, then rose by 4 h. Soluble thrombomodulin was significantly elevated over the 4 h. Circulating plasmin activity, plasminogen, and D-dimers were elevated for the entire 4 h. Tissue plasminogen activator (tPA) was elevated at 30 min, then decreased below baseline levels after 1 h. Plasminogen activator inhibitor-1 was significantly elevated at 2-4 h. Neither tissue factor pathway inhibitor nor thrombin activatable fibrinolysis inhibitor changed significantly over time. The levels of prothrombin and plasminogen were 30-100 times higher than their respective active enzymes. Polytrauma and hemorrhage in rats lead to a fibrinolytic coagulopathy, as demonstrated by an elevation in plasmin activity, D-dimers, and tPA. These results are consistent with the observed clinical benefit of tranexamic acid in trauma patients.

Applying results from clinical trials: tranexamic acid in trauma patients.

This paper considers how results from clinical trials should be applied in the care of patients, using the results of the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial of tranexamic acid in bleeding trauma patients as a case study. We explain why an understanding of the mechanisms of action of the trial treatment, and insight into the factors that might be relevant to this mechanism, is critical in order to properly apply (generalise) trial results and why it is not necessary that the trial population is representative of the population in which the medicine will be used. We explain why cause (mechanism)-specific mortality is more generalizable than all-cause mortality and why the risk ratio is the generalizable measure of the effect of the treatment. Overall, we argue that a biological insight into how the treatment works is more relevant when applying research results to patient care than the application of statistical reasoning.

Safety and efficacy of tranexamic acid in trauma patients at high risk for venous thromboembolism

Safety and efficacy of tranexamic acid in trauma patients at high risk for venous thromboembolism

Insulin stimulates branched chain amino acid uptake and diminishes nitrogen flux from skeletal muscle of injured patients

Resistance to insulin-mediated glucose disposal occurs in uninjured skeletal muscle of trauma patients but the effect of insulin on the accelerated proteolysis of trauma is unknown. We examined the influence of insulin on forearm amino acid and substrate exchange in five normals and four trauma patients using the hyperinsulinemic glucose clamp technique. Forearm substrate and amino acid flux ( Q, n M/100 ml tissue/min), the product of blood flow and arterial deep venous concentration difference, was calculated before and during insulin infusion. Total nitrogen release (NQ, n M/100 ml tissue/min) was calculated as the algebraic sum of all nitrogen groups contained in the amino acids released. Among normal subjects, total nitrogen release from the forearm did not change (581 ± 197 n M/100 ml tissue/min to 1167 ± 455) during insulin infusion nor did total branched chain amino acid flux (0 ± 30 nM/100 ml/min to 106 ± 36). Under conditions of hyperinsulinemia, neither glutamine nor alanine changed in control subjects. In trauma patients, total nitrogen release (3843 ± 1383 n M/100 ml/min) was inhibited during insulin administration (819 ± 314, P < 0.05). Total branched chain amino acid flux went from a net release of 460 ± 134 n M/100 ml/min to a net uptake of 10 ± 82 ( P < 0.05). In patients, statistically significant ( P < 0.05) differences were seen in individual amino acids as well. Forearm nitrogen flux was directly related to total branched chain amino acid flux in patients ( r 2 = 0.89). Additional studies in normals ( n = 4) at higher insulin infusion rates confirmed that these effects were unique to injured subjects and not an effect of the insulin dose. Insulin attenuates the accelerated release of skeletal muscle amino acid in trauma patients. This effect may be mediated in part by facilitated branched chain amino acid uptake. The manipulation of both insulin and branched chain amino acid concentrations may provide a method to reduce post-traumatic protein catabolism.