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Orthopaedic Trauma and Anemia: Conservative versus Liberal Transfusion Strategy: A Prospective Randomized Study
Mullis, B. H., Mullis, L. S., Kempton, L. B., Virkus, W., Slaven, J. E., Bruggers, J.
Journal of orthopaedic trauma. 2024;38(1):18-24
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Editor's Choice
Abstract
OBJECTIVES To determine whether it is safe to use a conservative packed red blood cell transfusion hemoglobin (Hgb) threshold (5.5 g/dL) compared with a liberal transfusion threshold (7.0 g/dL) for asymptomatic musculoskeletal injured trauma patients who are no longer in the initial resuscitative period. METHODS Design: Prospective, randomized, multicenter trial. SETTING Three level 1 trauma centers. PATIENT SELECTION CRITERIA Patients aged 18-50 with an associated musculoskeletal injury with Hgb less than 9 g/dL or expected drop below 9 g/dL with planned surgery who were stable and no longer being actively resuscitated were randomized once their Hgb dropped below 7 g/dL to a conservative transfusion threshold of 5.5 g/dL versus a liberal threshold of 7.0 g/dL. OUTCOME MEASURES AND COMPARISONS Postoperative infection, other post-operative complications and Musculoskeletal Functional Assessment scores obtained at baseline, 6 months, and 1 year were compared for liberal and conservative transfusion thresholds. RESULTS Sixty-five patients completed 1 year follow-up. There was a significant association between a liberal transfusion strategy and higher rate of infection (P = 0.01), with no difference in functional outcomes at 6 months or 1 year. This study was adequately powered at 92% to detect a difference in superficial infection (7% for liberal group, 0% for conservative, P < 0.01) but underpowered to detect a difference for deep infection (14% for liberal group, 6% for conservative group, P = 0.2). CONCLUSIONS A conservative transfusion threshold of 5.5 g/dL in an asymptomatic young trauma patient with associated musculoskeletal injuries leads to a lower infection rate without an increase in adverse outcomes and no difference in functional outcomes at 6 months or 1 year. LEVEL OF EVIDENCE Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
PICO Summary
Population
Musculoskeletal trauma patients with planned surgery (n= 99).
Intervention
Liberal transfusion threshold of 7.0 g/dL (n= 49).
Comparison
Conservative transfusion threshold of 5.5 g/dL (n= 50).
Outcome
Overall, 46/49 (93.9%) of the liberal group had a transfusion versus 23/50 (46.0%) of the conservative group had a transfusion after resuscitation and after enrollment in this study. Following resuscitation and enrollment in the study, patients in the liberal group received a median of 1 unit of blood transfused (range 0–12) and patients in the conservative group received a median of 0 units of blood (range 0–14). Sixty-five patients completed 1- year follow-up. There was a significant association between a liberal transfusion strategy and higher rate of infection, with no difference in functional outcomes at 6 months or 1 year.
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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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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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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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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.
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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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Editor's Choice
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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Editor's Choice
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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Editor's Choice
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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The Impact of Time to Hemostatic Intervention and Delayed Care for Patients with Traumatic Hemorrhage: A Systematic Review
Lamb T, Tran A, Lampron J, Shorr R, Taljaard M, Vaillancourt C
The journal of trauma and acute care surgery. 2023
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Editor's Choice
Abstract
BACKGROUND Uncontrolled bleeding is a common cause of preventable mortality in trauma. While intuitive that delays to hemostasis may lead to worse outcomes, the impacts of these delays remain incompletely explored. This systematic review aimed to characterize the extant definitions of delayed hemostatic intervention and to quantify the impacts of delays on clinical outcomes. METHODS We searched EMBASE, MEDLINE, and Web of Science from inception to August 2022. Studies defining "delayed intervention" and those comparing times to intervention among adults presenting to hospital with blunt or penetrating injuries who required major hemostatic intervention were eligible. The co-primary outcomes were mortality and the definition of delay to hemostasis employed. Secondary outcomes included units of packed red blood cells received, length of stay in hospital, and length of stay in intensive care. RESULTS We identified 2,050 studies, with 24 studies including 10,168 patients meeting inclusion criteria. The majority of studies were retrospective observational cohort studies and most were at high risk of bias. A variety of injury patterns and hemostatic interventions were considered, with 69.6% of studies reporting a statistically significant impact of increased time to intervention on mortality. Definitions of delayed intervention ranged from ten minutes to four hours. Conflicting data were reported for impact of time on receipt of blood products, while one study found a significant impact on intensive care length of stay. No studies assessed length of stay in hospital. CONCLUSIONS The extant literature is heterogeneous with respect to injuries included, methods of hemostasis employed, and durations of delay examined. While the majority of the included studies demonstrated a statistically significant relationship between time to intervention and mortality, an evidence-informed definition of delayed intervention for bleeding trauma patients at large has not been solidified. Additional, standardized research is needed to establish targets which could reduce morbidity and mortality. LEVEL OF EVIDENCE Level IV, Systematic Review.
PICO Summary
Population
Patients with traumatic haemorrhage (24 studies, n= 10,168).
Intervention
Systematic review to characterize the extant definitions of delayed haemostatic intervention and to quantify the impacts of delays on clinical outcomes.
Comparison
Outcome
The majority of studies were retrospective observational cohort studies and most were at high risk of bias. A variety of injury patterns and haemostatic interventions were considered, with 69.6% of studies reporting a statistically significant impact of increased time to intervention on mortality. Definitions of delayed intervention ranged from ten minutes to four hours. Conflicting data were reported for impact of time on receipt of blood products, while one study found a significant impact on intensive care length of stay. No studies assessed length of stay in hospital.
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10.
Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury: The CRYOSTAT-2 Randomized Clinical Trial
Davenport, R., Curry, N., Fox, E. E., Thomas, H., Lucas, J., Evans, A., Shanmugaranjan, S., Sharma, R., Deary, A., Edwards, A., et al
Jama. 2023
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Editor's Choice
Abstract
IMPORTANCE Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute fibrinogen deficiency. Management is fibrinogen replacement with cryoprecipitate transfusions or fibrinogen concentrate, usually administered relatively late during hemorrhage. OBJECTIVE To assess whether survival could be improved by administering an early and empirical high dose of cryoprecipitate to all patients with trauma and bleeding that required activation of a major hemorrhage protocol. DESIGN, SETTING, AND PARTICIPANTS CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study. Patients were enrolled at 26 UK and US major trauma centers from August 2017 to November 2021. Eligible patients were injured adults requiring activation of the hospital's major hemorrhage protocol with evidence of active hemorrhage, systolic blood pressure less than 90 mm Hg at any time, and receiving at least 1 U of a blood component transfusion. INTERVENTION Patients were randomly assigned (in a 1:1 ratio) to receive standard care, which was the local major hemorrhage protocol (reviewed for guideline adherence), or cryoprecipitate, in which 3 pools of cryoprecipitate (6-g fibrinogen equivalent) were to be administered in addition to standard care within 90 minutes of randomization and 3 hours of injury. MAIN OUTCOMES AND MEASURES The primary outcome was all-cause mortality at 28 days in the intention-to-treat population. RESULTS Among 1604 eligible patients, 799 were randomized to the cryoprecipitate group and 805 to the standard care group. Missing primary outcome data occurred in 73 patients (principally due to withdrawal of consent) and 1531 (95%) were included in the primary analysis population. The median (IQR) age of participants was 39 (26-55) years, 1251 (79%) were men, median (IQR) Injury Severity Score was 29 (18-43), 36% had penetrating injury, and 33% had systolic blood pressure less than 90 mm Hg at hospital arrival. All-cause 28-day mortality in the intention-to-treat population was 26.1% in the standard care group vs 25.3% in the cryoprecipitate group (odds ratio, 0.96 [95% CI, 0.75-1.23]; P = .74). There was no difference in safety outcomes or incidence of thrombotic events in the standard care vs cryoprecipitate group (12.9% vs 12.7%). CONCLUSIONS AND RELEVANCE Among patients with trauma and bleeding who required activation of a major hemorrhage protocol, the addition of early and empirical high-dose cryoprecipitate to standard care did not improve all cause 28-day mortality. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04704869; ISRCTN Identifier: ISRCTN14998314.
PICO Summary
Population
Bleeding patients with trauma enrolled in the CRYOSTAT-2 trial, at 26 UK and US major trauma centers (n= 1,604).
Intervention
Usual care plus 3 early pools of cryoprecipitate (n= 799).
Comparison
Standard care (n= 805).
Outcome
The primary outcome was all-cause mortality at 28 days in the intention-to-treat population. Data from 1,531 (95%) patients were included in the primary analysis population. All-cause 28-day mortality in the intention-to-treat population was 26.1% in the standard care group vs. 25.3% in the cryoprecipitate group (odds ratio, 0.96; 95% CI [0.75, 1.23]). There was no difference in safety outcomes or incidence of thrombotic events in the standard care vs. cryoprecipitate group (12.9% vs. 12.7%).