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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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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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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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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.
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Volume replacement in the resuscitation of trauma patients with acute hemorrhage: an umbrella review
Gianola, S., Castellini, G., Biffi, A., Porcu, G., Napoletano, A., Coclite, D., D'Angelo, D., Di Nitto, M., Fauci, A. J., Punzo, O., et al
International journal of emergency medicine. 2023;16(1):87
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Abstract
BACKGROUND The use of intravenous fluid therapy in patients with major trauma in prehospital settings is still controversial. We conducted an umbrella review to evaluate which is the best volume expansion in the resuscitation of a hemorrhagic shock to support the development of major trauma guideline recommendations. METHODS We searched PubMed, Embase, and CENTRAL up to September 2022 for systematic reviews (SRs) investigating the use of volume expansion fluid on mortality and/or survival. Quality assessment was performed using AMSTAR 2 and the Certainty of the evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS We included 14 SRs investigating the effects on mortality with the comparisons: use of crystalloids, blood components, and whole blood. Most SRs were judged as critically low with slight overlapping of primary studies and high consistency of results. For crystalloids, inconsistent evidence of effectiveness in 28- to 30-day survival (primary endpoint) was found for the hypertonic saline/dextran group compared with isotonic fluid solutions with moderate certainty of evidence. Pre-hospital blood component infusion seems to reduce mortality, however, as the certainty of evidence ranges from very low to moderate, we are unable to provide evidence to support or reject its use. The blood component ratio was in favor of higher ratios among all comparisons considered with moderate to very low certainty of evidence. Results about the effects of whole blood are very uncertain due to limited and heterogeneous interventions in studies included in SRs. CONCLUSION Hypertonic crystalloid use did not result in superior 28- to 30-day survival. Increasing evidence supports the scientific rationale for early use of high-ratio blood components, but their use requires careful consideration. Preliminary evidence is very uncertain about the effects of whole blood and further high-quality studies are required.
PICO Summary
Population
Trauma patients with haemorrhagic shock (14 systematic reviews).
Intervention
Crystalloids, packed red blood cells, fresh frozen plasma, platelets, liquid plasma, lyophilized plasma, low titre 0-negative whole blood.
Comparison
A comparison or combination of the above (including different ratios).
Outcome
For crystalloids, inconsistent evidence of effectiveness in 28- to 30-day survival (primary endpoint) was found for the hypertonic saline/dextran group compared with isotonic fluid solutions with moderate certainty of evidence. Pre-hospital blood component infusion seems to reduce mortality, however, as the certainty of evidence ranges from very low to moderate, the authors are unable to provide evidence to support or reject its use. The blood component ratio was in favour of higher ratios among all comparisons considered with moderate to very low certainty of evidence. Results about the effects of whole blood are very uncertain due to limited and heterogeneous interventions in studies included in systematic reviews.
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Tranexamic Acid for Traumatic Injury in the Emergency Setting: A Systematic Review and Bias-Adjusted Meta-Analysis of Randomized Controlled Trials
Fouche, P. F., Stein, C., Nichols, M., Meadley, B., Bendall, J. C., Smith, K., Anderson, D., Doi, S. A.
Annals of emergency medicine. 2023
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Abstract
STUDY OBJECTIVE Traumatic injury causes a significant number of deaths due to bleeding. Tranexamic acid (TXA), an antifibrinolytic agent, can reduce bleeding in traumatic injuries and potentially enhance outcomes. Previous reviews suggested potential TXA benefits but did not consider the latest trials. METHODS A systematic review and bias-adjusted meta-analysis were performed to assess TXA's effectiveness in emergency traumatic injury settings by pooling estimates from randomized controlled trials. Researchers searched Medline, Embase, and Cochrane Central for randomized controlled trials comparing TXA's effects to a placebo in emergency trauma cases. The primary endpoint was 1-month mortality. The methodological quality of the trials underwent assessment using the MASTER scale, and the meta-analysis applied the quality-effects method to adjust for methodological quality. RESULTS Seven randomized controlled trials met the set criteria. This meta-analysis indicated an 11% decrease in the death risk at 1 month after TXA use (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.84 to 0.95) with a number needed to treat of 61 to avoid 1 additional death. The meta-analysis also revealed reduced 24-hour mortality (OR 0.76, 95% CI 0.65 to 0.88) for TXA. No compelling evidence of increased vascular occlusive events emerged (OR 0.96, 95% CI 0.73 to 1.27). Subgroup analyses highlighted TXA's effectiveness in general trauma versus traumatic brain injury and survival advantages when administered out-of-hospital versus inhospital. CONCLUSIONS This synthesis demonstrates that TXA use for trauma in emergencies leads to a reduction in 1-month mortality, with no significant evidence of problematic vascular occlusive events. Administering TXA in the out-of-hospital setting is associated with reduced mortality compared to inhospital administration, and less mortality with TXA in systemic trauma is noted compared with traumatic brain injury specifically.
PICO Summary
Population
Patients with traumatic injuries in emergency settings (7 randomised controlled trials).
Intervention
Tranexamic acid (TXA).
Comparison
Placebo.
Outcome
The primary endpoint was 1-month mortality. The meta-analysis indicated an 11% decrease in the death risk at 1 month after TXA use (odds ratio [OR] 0.89; 95% confidence interval (CI) [0.84, 0.95]) with a number needed to treat of 61 to avoid 1 additional death. The meta-analysis also revealed reduced 24-hour mortality (OR 0.76; 95% CI [0.65, 0.88]) for TXA. No compelling evidence of increased vascular occlusive events emerged (OR 0.96; 95% CI [0.73, 1.27]). Subgroup analyses highlighted TXA's effectiveness in general trauma versus traumatic brain injury and survival advantages when administered out-of-hospital versus in-hospital.
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Factors that influence the administration of tranexamic acid (TXA) to trauma patients in prehospital settings: a systematic review
Nicholson, H., Scotney, N., Briscoe, S., Kirby, K., Bedson, A., Goodwin, L., Robinson, M., Taylor, H., Thompson Coon, J., Voss, S., et al
BMJ open. 2023;13(5):e073075
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Abstract
OBJECTIVE In the UK there are around 5400 deaths annually from injury. Tranexamic acid (TXA) prevents bleeding and has been shown to reduce trauma mortality. However, only 5% of UK major trauma patients who are at risk of haemorrhage receive prehospital TXA. This review aims to examine the evidence regarding factors influencing the prehospital administration of TXA to trauma patients. DESIGN Systematic literature review. DATA SOURCES AMED, CENTRAL, CINAHL, Cochrane Database of Systematic Reviews, Conference Proceedings Citation Index-Science, Embase and MEDLINE were searched from January 2010 to 2020; searches were updated in June 2022. CLINICALTRIALS gov and OpenGrey were also searched and forward and backwards citation chasing performed. ELIGIBILITY CRITERIA All primary research reporting factors influencing TXA administration to trauma patients in the prehospital setting was included. DATA EXTRACTION AND SYNTHESIS Two independent reviewers performed the selection process, quality assessment and data extraction. Data were tabulated, grouped by setting and influencing factor and synthesised narratively. RESULTS Twenty papers (278 249 participants in total) were included in the final synthesis; 13 papers from civilian and 7 from military settings. Thirteen studies were rated as 'moderate' using the Effective Public Health Practice Project Quality Assessment Tool. Several common factors were identified: knowledge and skills; consequences and social influences; injury type (severity, injury site and mechanism); protocols; resources; priorities; patient age; patient sex. CONCLUSIONS This review highlights an absence of high-quality research. Preliminary evidence suggests a host of system and individual-level factors that may be important in determining whether TXA is administered to trauma patients in the prehospital setting. FUNDING AND REGISTRATION This review was supported by Research Capability Funding from the South Western Ambulance Service NHS Foundation Trust and the National Institute for Health Research Applied Research Collaboration South West Peninsula. PROSPERO REGISTRATION NUMBER CRD42020162943.
PICO Summary
Population
Any trauma patients in prehospital settings (20 studies, n= 278,249).
Intervention
Exposure: Factors influencing the decision to administer tranexamic acid (TXA).
Comparison
Outcome
This systematic review included 13 studies from civilian settings and 7 studies from military settings. This review highlighted a lack of high-quality research addressing the factors that influence prehospital TXA administration, particularly in children or patients with isolated head injuries. Common factors identified suggested a host of system and individual-level factors including: knowledge and skills, consequences and social influences, injury type (including severity, injury site and mechanism of injury), protocols, resources, priorities, patient age, and patient sex.
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Pre-hospital freeze-dried plasma for critical bleeding after trauma: A pilot randomized controlled trial
Mitra B, Meadley B, Bernard S, Maegele M, Gruen RL, Bradley O, Wood EM, McQuilten ZK, Fitzgerald M, St Clair T, et al
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2023
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Abstract
OBJECTIVES Transfusion of a high ratio of plasma to packed red blood cells (PRBC), to treat or prevent acute traumatic coagulopathy, has been associated with survival after major trauma. However, the effect of pre-hospital plasma on patient outcomes has been inconsistent. The aim of this pilot trial was to assess the feasibility of transfusing freeze-dried plasma with red blood cells (RBC) using a randomized controlled design in an Australian aeromedical pre-hospital setting. METHODS Patients attended by Helicopter Emergency Medical Service (HEMS) paramedics with suspected critical bleeding after trauma managed with pre-hospital RBC were randomized to receive two units of freeze-dried plasma (Lyoplas N-w) or standard care (no plasma). The primary outcome was the proportion of eligible patients enrolled and provided the intervention. Secondary outcomes included preliminary data on effectiveness, including mortality censored at 24 hours and at hospital discharge, and adverse events. RESULTS During the study period of 01 June to 31 October 2022, there were 25 eligible patients, of whom 20 (80%) were enrolled in the trial and 19 (76%) received the allocated intervention. Median time from randomization to hospital arrival was 92.5 mins (IQR 68-101.5). Mortality may have been lower in the freeze-dried plasma group at 24h (RR 0.24; 95%CI: 0.03 - 1.73) and at hospital discharge (RR 0.73; 95%CI: 0.24 - 2.27). No serious adverse events related to the trial interventions were reported. CONCLUSIONS This first reported experience of freeze-dried plasma use in Australia suggests pre-hospital administration is feasible. Given longer prehospital times typically associated with HEMS attendance, there is potential clinical benefit from this intervention and rationale for a definitive trial.
PICO Summary
Population
Patients attended by Helicopter Emergency Medical Service (HEMS) paramedics with suspected critical bleeding after trauma (n= 20).
Intervention
Two units of freeze-dried plasma (Lyoplas N-w), (n= 9).
Comparison
Standard care (no plasma), (n= 11).
Outcome
The primary outcome was the proportion of eligible patients enrolled and provided the intervention. Secondary outcomes included preliminary data on effectiveness, including mortality censored at 24 hours and at hospital discharge, and adverse events. Nineteen patients (76%) received the allocated intervention. Median time from randomization to hospital arrival was 92.5 mins (IQR 68-101.5). Mortality may have been lower in the freeze-dried plasma group at 24h (RR 0.24; 95% CI [0.03, 1.73]) and at hospital discharge (RR 0.73; 95% CI [0.24, 2.27]. No serious adverse events related to the trial interventions were reported.
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The Restrictive Red Blood Cell Transfusion Strategy for Critically Injured Patients (RESTRIC) trial: a cluster-randomized, crossover, non-inferiority multicenter trial of restrictive transfusion in trauma
Hayakawa, M., Tagami, T., Kudo, D., Ono, K., Aoki, M., Endo, A., Yumoto, T., Matsumura, Y., Irino, S., Sekine, K., et al
Journal of intensive care. 2023;11(1):34
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Abstract
BACKGROUND The efficacies of fresh frozen plasma and coagulation factor transfusion have been widely evaluated in trauma-induced coagulopathy management during the acute post-injury phase. However, the efficacy of red blood cell transfusion has not been adequately investigated in patients with severe trauma, and the optimal hemoglobin target level during the acute post-injury and resuscitation phases remains unclear. Therefore, this study aimed to examine whether a restrictive transfusion strategy was clinically non-inferior to a liberal transfusion strategy during the acute post-injury phase. METHODS This cluster-randomized, crossover, non-inferiority multicenter trial was conducted at 22 tertiary emergency medical institutions in Japan and included adult patients with severe trauma at risk of major bleeding. The institutions were allocated a restrictive or liberal transfusion strategy (target hemoglobin levels: 7-9 or 10-12 g/dL, respectively). The strategies were applied to patients immediately after arrival at the emergency department. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%. RESULTS The 28-day survival rates of patients in the restrictive (n = 216) and liberal (n = 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02 (95% confidence interval: 0.49-2.13). Significant non-inferiority was not observed. Transfusion volumes and hemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days. CONCLUSIONS Although non-inferiority of the restrictive versus liberal transfusion strategy for 28-day survival was not statistically significant, the mortality and complication rates were similar between the groups. The restrictive transfusion strategy results in a lower transfusion volume. TRIAL REGISTRATION NUMBER umin.ac.jp/ctr: UMIN000034405, registration date: 8 October 2018.
PICO Summary
Population
Adult patients with severe trauma at risk of major bleeding, enrolled in the RESTRIC cluster-randomized, crossover trial at 22 tertiary emergency medical institutions in Japan (n= 422).
Intervention
Restrictive transfusion strategy (n= 222).
Comparison
Liberal transfusion strategy (n= 200).
Outcome
The restrictive and liberal red blood cell strategy groups included 216 and 195 patients in the intention-to-treat analysis, respectively. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%. The 28-day survival rates of patients in the restrictive (n= 216) and liberal (n= 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02; 95% confidence interval [0.49, 2.13]. Significant non-inferiority was not observed. Transfusion volumes and haemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days.
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Prehospital plasma is associated with survival principally in patients transferred from the scene of injury: A secondary analysis of the PAMPer trial
Lewis RE, Muluk SL, Reitz KM, Guyette FX, Brown JB, Miller RS, Harbrecht BG, Claridge JA, Phelan HA, Yazer MH, et al
Surgery. 2022
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Editor's Choice
Abstract
BACKGROUND We sought to characterize if prehospital transfer origin from the scene of injury (SCENE) or from a referral emergency department (REF) alters the survival benefit attributable to prehospital plasma resuscitation in patients at risk of hemorrhagic shock. METHODS We performed a secondary analysis of data from a recently completed prehospital plasma clinical trial. All of the enrolled patients from either the SCENE or REF groups were included. The demographics, injury characteristics, shock severity and resuscitation needs were compared. The primary outcome was a 30-day mortality. Kaplan-Meier analysis and Cox-hazard regression were used to characterize the independent survival benefits of prehospital plasma for transport origin groups. RESULTS Of the 501 enrolled patients, the REF group patients (n = 111) accounted for 22% with the remaining (n = 390) originating from the scene. The SCENE group patients had higher injury severity and were more likely intubated prehospital. The REF group patients had longer prehospital times and received greater prehospital crystalloid and blood products. Kaplan-Meier analysis revealed a significant 30-day survival benefit associated with prehospital plasma in the SCENE group (P < .01) with no difference found in the REF group patients (P = .36). The Cox-regression verified after controlling for relevant confounders that prehospital plasma was independently associated with a 30-day survival in the SCENE group patients (hazard ratio 0.59; 95% confidence interval 0.39-0.89; P = .01) with no significant relationship found in the REF group patients (hazard ratio 1.03, 95% confidence interval 0.4-3.0). CONCLUSION Important differences across the SCENE and REF cohorts exist that are essential to understand when planning prehospital studies. Prehospital plasma is associated with a survival benefit primarily in SCENE group patients. The results are exploratory but suggest transfer origin may be an important determinant of prehospital plasma benefit.
PICO Summary
Population
Severely injured trauma patients enrolled in the PAMPer trial (n= 501).
Intervention
Thawed plasma (n= 230).
Comparison
Standard pre-hospital air medical care (n= 271).
Outcome
For this secondary analysis of the PAMPer trial, the study population was composed of 390 (78%) patients with an air medical transfer origin from the scene of injury (SCENE) and 111 (22%) patients transferred from an outside referral emergency department (REF). Randomization to plasma or standard of care was equally distributed across each transfer origin group. The SCENE group had higher injury severity and were more likely intubated pre-hospital. The REF group had longer pre-hospital times and received greater pre-hospital crystalloid and blood products. Kaplan-Meier analysis revealed a significant 30-day survival benefit associated with pre-hospital plasma in the SCENE group with no difference found in the REF group. The Cox-regression verified after controlling for relevant confounders that pre-hospital plasma was independently associated with a 30-day survival in the SCENE group with no significant relationship found in the REF group.
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Effects of tranexamic acid treatment in severely and non-severely injured trauma patients
Ageron FX, Shakur-Still H, Roberts I
Transfusion. 2022
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Editor's Choice
Abstract
BACKGROUND Urgent treatment with tranexamic acid (TXA) reduces bleeding deaths but there is disagreement about which patients should be treated. We examine the effects of TXA treatment in severely and non-severely injured trauma patients. STUDY DESIGN AND METHODS We did an individual patient data meta-analysis of randomized trials with over 1000 trauma patients that assessed the effects of TXA on survival. We defined the severity of injury according to characteristics at first assessment: systolic blood pressure of less than 90 mm Hg and a heart rate greater than 120 beats per minute or Glasgow Coma Scale score of less than nine or any GCS with one or more fixed dilated pupils. The primary measure was survival on the day of the injury. We examined the effect of TXA on survival in severely and non-severely injured patients and how these effects vary with the time from injury to treatment. RESULTS We obtained data for 32,944 patients from two randomized trials. Tranexamic acid significantly increased survival on the day of the injury (OR = 1.22, 95% CI 1.11-1.34; p < .01). The effect of tranexamic acid on survival in non-severely injured patients (OR = 1.25, 1.03-1.50) was similar to that in severely injured patients (OR = 1.22, 1.09-1.37) with no significant heterogeneity (p = .87). In severely and non-severely injured pateints, treatment within the first hour after injury was the most effective. DISCUSSION Early tranexamic acid treatment improves survival in both severely and non-severely injured trauma patients. Its use should not be restricted to the severely injured.
PICO Summary
Population
Severely and non-severely injured trauma patients enrolled in the two large randomised controlled trials: CRASH-2 and CRASH-3 (n= 32,944).
Intervention
Tranexamic acid (n= 16,499).
Comparison
Placebo (n= 16,445).
Outcome
Tranexamic acid significantly increased survival on the day of the injury (odd ratio (OR)= 1.22). The effect of tranexamic acid on survival in non-severely injured patients (OR= 1.25) was similar to that in severely injured patients (OR= 1.22) with no significant heterogeneity. In severely and non-severely injured patients, treatment within the first hour after injury was the most effective.
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10.
Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): a pilot randomized trial
Nishijima DK, VanBuren JM, Linakis SW, Hewes HA, Myers SR, Bobinski M, Tran NK, Ghetti S, Adelson PD, Roberts I, et al
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2022
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Editor's Choice
Abstract
BACKGROUND The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage; however, the drug has not been evaluated in a trial in injured children. We evaluated the feasibility of a large-scale trial evaluating the effects of TXA in children with severe hemorrhagic injuries. METHODS Severely injured children (0 up to 18(th) birthday) were randomized into a double-blind randomized trial of 1) TXA 15 mg/kg bolus dose, followed by 2 mg/kg/hr infusion over 8 hours, 2) TXA 30 mg/kg bolus dose, followed by 4 mg/kg/hr infusion over 8 hours, or 3) normal saline placebo bolus and infusion. The trial was conducted at 4 pediatric Level I trauma centers in the United States between June 2018 and March 2020. We enrolled patients under federal exception from informed consent (EFIC) procedures when parents were unable to provide informed consent. Feasibility outcomes included the rate of enrollment, adherence to intervention arms, and ability to measure the primary clinical outcome. Clinical outcomes included global functioning (primary), working memory, total amount of blood products transfused, intracranial hemorrhage progression, and adverse events. The target enrollment rate was at least 1.25 patients per site per month. RESULTS A total of 31 patients were randomized with a mean age of 10.7 years (standard deviation [SD] 5.0 years) and 22 (71%) patients were male. The mean time from injury to randomization was 2.4 hours (SD 0.6 hours). Sixteen (52%) patients had isolated brain injuries and 15 (48%) patients had isolated torso injuries. The enrollment rate using EFIC was 1.34 patients per site per month. All eligible enrolled patients received study intervention (9 patients TXA 15 mg/kg bolus dose, 10 patients TXA 30 mg/kg bolus dose, and 12 patients placebo) and had the primary outcome measured. No statistically significant differences in any of the clinical outcomes were identified. CONCLUSION Based on enrollment rate, protocol adherence, and measurement of the primary outcome in this pilot trial, we confirmed the feasibility of conducting a large-scale, randomized trial evaluating the efficacy of TXA in severely injured children with hemorrhagic brain and/or torso injuries using EFIC.
PICO Summary
Population
Severely injured children enrolled in the TIC-TOC trial across four centers in US (n= 31).
Intervention
15 mg/kg of tranexamic acid (TXA) dose, followed by 2 mg/kg/hr infusion (n= 9).
Comparison
30 mg/kg of TXA dose, followed by 4 mg/kg/hr infusion (n= 10). Saline placebo and infusion (n= 12).
Outcome
All patients had their primary outcome measured. Feasibility outcomes included the rate of enrollment, adherence to intervention arms, and ability to measure the primary clinical outcome. Clinical outcomes included global functioning (primary), working memory, total amount of blood products transfused, intracranial hemorrhage progression, and adverse events. The mean time from injury to randomization was 2.4 hours (SD 0.6 hours). Sixteen (52%) patients had isolated brain injuries and 15 (48%) patients had isolated torso injuries. No statistically significant differences in any of the clinical outcomes were identified.