The understanding of coagulopathies in trauma has increased interest in thromboelastography (TEG®) and thromboelastometry (ROTEM®), which promptly evaluate the entire clotting process and may guide ...blood product therapy. Our objective was to review the evidence for their role in diagnosing early coagulopathies, guiding blood transfusion, and reducing mortality in injured patients.
We considered observational studies and randomized controlled trials (MEDLINE, EMBASE, and Cochrane databases) to February 2014 that examined TEG®/ROTEM® in adult trauma patients. We extracted data on demographics, diagnosis of early coagulopathies, blood transfusion, and mortality. We assessed methodologic quality by using the Newcastle-Ottawa scale (NOS) for observational studies and QUADAS-2 tool for diagnostic accuracy studies.
Fifty-five studies (12,489 patients) met inclusion criteria, including 38 prospective cohort studies, 15 retrospective cohort studies, two before-after studies, and no randomized trials. Methodologic quality was moderate (mean NOS score, 6.07; standard deviation, 0.49). With QUADAS-2, only three of 47 studies (6.4%) had a low risk of bias in all domains (patient selection, index test, reference standard and flow and timing); 37 of 47 studies (78.8%) had low concerns regarding applicability. Studies investigated TEG®/ROTEM® for diagnosis of early coagulopathies (n = 40) or for associations with blood-product transfusion (n = 25) or mortality (n = 24). Most (n = 52) were single-center studies. Techniques examined included rapid TEG® (n =12), ROTEM® (n = 18), TEG® (n = 23), or both TEG® and rapid TEG® (n = 2). Many TEG®/ROTEM® measurements were associated with early coagulopathies, including some (hypercoagulability, hyperfibrinolysis, platelet dysfunction) not assessed by routine screening coagulation tests. Standard measures of diagnostic accuracy were inconsistently reported. Many abnormalities predicted the need for massive transfusion and death, but predictive performance was not consistently superior to routine tests. One observational study suggested that a ROTEM®-based transfusion algorithm reduced blood-product transfusion, but TEG®/ROTEM®-based resuscitation was not associated with lower mortality in most studies.
Limited evidence from observational data suggest that TEG®/ROTEM® tests diagnose early trauma coagulopathy and may predict blood-product transfusion and mortality in trauma. Effects on blood-product transfusion, mortality, and other patient-important outcomes remain unproven in randomized trials.
BACKGROUND
Deaths by exsanguination in trauma are preventable with hemorrhage control and resuscitation with allogeneic blood products (ABPs). The ideal transfusion ratio is unknown. We compared ...efficacy and safety of high transfusion ratios of FFP:RBC and PLT:RBC with low ratios in trauma.
STUDY DESIGN AND METHODS
Medline, Embase, Cochrane, and Controlled Clinical Trials Register were searched. Observational and randomized data were included. Risk of bias was assessed using validated tools. Primary outcome was 24‐h and 30‐day mortality. Secondary outcomes were exposure to ABPs and improvement of coagulopathy. Meta‐analysis was conducted using a random‐effects model. Strength and evidence quality were graded using GRADE profile
RESULTS
55 studies were included (2 randomized and 53 observational), with low and moderate risk of bias, respectively, and overall low evidence quality. The two RCTs showed no mortality difference (odds ratio OR, 1.35; 95% confidence interval CI, 0.40‐4.59). Observational studies reported lower mortality in high FFP:RBCs ratio (OR, 0.38 95% CI, 0.22‐0.68 for 1:1 vs. <1:1; OR, 0.42 95% CI, 0.22‐0.81 for 1:1.5 vs. <1:1.5; and OR, 0.47 95% CI, 0.31‐0.71 for 1:2 vs. <1:2, respectively). Meta‐analyses in observational studies showed no difference in exposure to ABPs. No data on coagulopathy for meta‐analysis was identified.
CONCLUSIONS
Meta‐analyses in observational studies suggest survival benefit and no difference in exposure to ABPs. No survival benefit in RCTs was identified. These conflicting results should be interpreted with caution. Studies are mostly observational, with relatively small sample sizes, nonrandom treatment allocation, and high potential for confounding. Further research is warranted.
Elevated catecholamine levels might be associated with unfavorable outcome after traumatic brain injury (TBI). We investigated the association between catecholamine levels in the first 24 h ...post-trauma and functional outcome in patients with isolated moderate-to-severe TBI.
A cohort of 174 patients who sustained isolated blunt TBI was prospectively enrolled from three Level-1 Trauma Centers. Epinephrine (Epi) and norepinephrine (NE) concentrations were measured at admission (baseline), 6, 12 and 24 h post-injury. Outcome was assessed at 6 months by the extended Glasgow Outcome Scale (GOSE) score. Fractional polynomial plots and logistic regression models (fixed and random effects) were used to study the association between catecholamine levels and outcome. Effect size was reported as the odds ratio (OR) associated with one logarithmic change in catecholamine level.
At 6 months, 109 patients (62.6%) had an unfavorable outcome (GOSE 5-8 vs. 1-4), including 51 deaths (29.3%). Higher admission levels of Epi were associated with a higher risk of unfavorable outcome (OR, 2.04, 95% CI: 1.31-3.18, p = 0.002) and mortality (OR, 2.86, 95% CI: 1.62-5.01, p = 0.001). Higher admission levels of NE were associated with higher risk of unfavorable outcome (OR, 1.59, 95% CI: 1.07-2.35, p = 0.022) but not mortality (OR, 1.45, 95% CI: 0.98-2.17, p = 0.07). There was no relationship between the changes in Epi levels over time and mortality or unfavorable outcome. Changes in NE levels with time were statistically associated with a higher risk of mortality, but the changes had no relation to unfavorable outcome.
Elevated circulating catecholamines, especially Epi levels on hospital admission, are independently associated with functional outcome and mortality after isolated moderate-to-severe TBI.
Transfusion in trauma is often empiric or based on traditional lab tests. Viscoelastic tests such as thromboelastography (TEG®) and rotational thromboelastometry (ROTEM®) have been proposed as ...superior to traditional lab tests. Due to the similarities between the two tests, general opinion seems to consider them equivalent with interchangeable interpretations. However, it is not clear whether the results can be similarly interpreted. This review evaluates the comparability between TEG and ROTEM and performs a descriptive review of the parameters utilized in each test in adult trauma patients.
PUBMED database was reviewed using the keywords "thromboelastography" and "compare", between 2000 and 2011. Original studies directly comparing TEG® with ROTEM® in any area were retrieved. To verify the individual test parameter used in studies involving trauma patients, we further performed a review using the keywords "thromboelastography" and "trauma" in the PUBMED database.
Only 4 studies directly compared TEG® with ROTEM®. One in liver transplantation found that transfusion practice could differ depending on the device in use. Another in cardiac surgery concluded that all measurements are not completely interchangeable. The third article using commercially available plasma detected clinically significant differences in the results from the two devices. The fourth one was a head-to-head comparison of the technical aspects. The 24 articles reporting the use of viscoelastic tests in trauma patients, presented considerable heterogeneity.
Both tests are potentially useful as means to rapidly diagnose coagulopathy, guide transfusion and determine outcome in trauma patients. Differences in the activators utilized in each device limit the direct comparability. Standardization and robust clinical trials comparing the two technologies are needed before these tests can be widely recommended for clinical use in trauma.
No new therapies for traumatic brain injury (TBI) have been officially translated into current practice. At the tissue and cellular level, both inflammatory and oxidative processes may be exacerbated ...post-injury and contribute to further brain damage.
acetylcysteine (NAC) has the potential to downregulate both processes. This review focuses on the potential neuroprotective utility of NAC and
-acetylcysteine amide (NACA) post-TBI.
Medline, Embase, Cochrane Library, and ClinicalTrials.gov were searched up to July 2017. Studies that examined clinical and laboratory effects of NAC and NACA post-TBI in human and animal studies were included. Risk of bias was assessed in human and animal studies according to the design of each study (randomized or not). The primary outcome assessed was the effect of NAC/NACA treatment on functional outcome, while secondary outcomes included the impact on biomarkers of inflammation and oxidation. Due to the clinical and methodological heterogeneity observed across studies, no meta-analyses were conducted.
Our analyses revealed only three human trials, including two randomized controlled trials (RCTs) and 20 animal studies conducted using standardized animal models of brain injury. The two RCTs reported improvement in the functional outcome post-NAC/NACA administration. Overall, the evidence from animal studies is more robust and demonstrated substantial improvement of cognition and psychomotor performance following NAC/NACA use. Animal studies also reported significantly more cortical sparing, reduced apoptosis, and lower levels of biomarkers of inflammation and oxidative stress. No safety concerns were reported in any of the studies included in this analysis.
Evidence from the animal literature demonstrates a robust association for the prophylactic application of NAC and NACA post-TBI with improved neurofunctional outcomes and downregulation of inflammatory and oxidative stress markers at the tissue level. While a growing body of scientific literature suggests putative beneficial effects of NAC/NACA treatment for TBI, the lack of well-designed and controlled clinical investigations, evaluating therapeutic outcomes, prognostic biomarkers, and safety profiles, limits definitive interpretation and recommendations for its application in humans at this time.
Military Forward Aeromedical Evacuation and civilian Helicopter Emergency Medical Services are widely used to conduct Primary Aeromedical Retrieval. Crew composition in Primary Aeromedical Retrieval ...missions varies considerably. The ideal composition is unknown. Thus, we conducted a descriptive systematic review on mortality and other outcomes for different Primary Aeromedical Retrieval crew compositions.
Medline, Embase, and Cochrane Controlled Trials Register were searched up to January 2020. Results were reported per Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Studies of adult trauma air transported by different crews were included. Population, injury severity, crew composition, procedures, and outcomes, including mortality, were abstracted. Risk of bias was assessed using previously validated tools. A lack of reported effect measures precluded a quantitative analysis.
Sixteen studies met inclusion criteria (3 prospective studies, 1 case-control, and 12 retrospective). Overall, studies reported a mortality benefit associated with advanced health care providers. This was most apparent in patients with severe but survivable injuries. In this population, early rapid sequence induction, endotracheal intubation, mechanical ventilation, thoracostomies, blood products transfusion, and treatment of hemorrhagic shock are better performed by advanced providers and may improve outcomes. The quality of evidence reported a moderate risk of bias in the included studies.
Overall, findings were divergent but showed a trend to decreased mortality in patients treated by advanced providers with interventions beyond the basic paramedic level. This trend was most significant in patients with severe but survivable injuries. These results should be cautiously interpreted because most studies were observational, had small sample sizes, and had a high potential for confounding factors.
Artificial intelligence (AI), a branch of machine learning (ML) has been increasingly employed in the research of trauma in various aspects. Hemorrhage is the most common cause of trauma-related ...death. To better elucidate the current role of AI and contribute to future development of ML in trauma care, we conducted a review focused on the use of ML in the diagnosis or treatment strategy of traumatic hemorrhage. A literature search was carried out on PubMed and Google scholar. Titles and abstracts were screened and, if deemed appropriate, the full articles were reviewed. We included 89 studies in the review. These studies could be grouped into five areas: (1) prediction of outcomes; (2) risk assessment and injury severity for triage; (3) prediction of transfusions; (4) detection of hemorrhage; and (5) prediction of coagulopathy. Performance analysis of ML in comparison with current standards for trauma care showed that most studies demonstrated the benefits of ML models. However, most studies were retrospective, focused on prediction of mortality, and development of patient outcome scoring systems. Few studies performed model assessment via test datasets obtained from different sources. Prediction models for transfusions and coagulopathy have been developed, but none is in widespread use. AI-enabled ML-driven technology is becoming integral part of the whole course of trauma care. Comparison and application of ML algorithms using different datasets from initial training, testing and validation in prospective and randomized controlled trials are warranted for provision of decision support for individualized patient care as far forward as possible.
IntroductionAcute traumatic coagulopathy (ATC) in bleeding trauma patients increase in-hospital mortality. Fibrinogen concentrate (FC) and prothrombin complex concentrate (PCC) are two purified ...concentrates of clotting factors that have been used to treat ATC. However, there is a knowledge gap on their use compared with the standard of care, the transfusion of plasma.Methods and analysisThe factors in the initial resuscitation of severe trauma 2 trial is a multicentre, randomised, parallel-control, single-blinded, phase IV superiority trial. The study aims to address efficacy and safety of the early use of FC and PCC compared with a plasma-based resuscitation. Adult trauma patients requiring massive haemorrhage protocol activation on hospital arrival will receive FC 4 g and PCC 2000 IU or plasma 4 U, based on random allocation. The primary outcome is a composite of the cumulative number of all units of red cells, plasma and platelets transfused within 24 hours following admission. Secondary outcomes include measures of efficacy and safety of the intervention. Enrolment of 350 patients will provide an initial power >80% to demonstrate superiority for the primary outcome. After enrolment of 120 patients, a preplanned adaptive interim analysis will be conducted to reassess assumptions, check for early superiority demonstration or reassess the sample size for remainder of the study.Ethics and disseminationThe study has been approved by local and provincial research ethics boards and will be conducted according to the Declaration of Helsinki, Good Clinical Practice guidelines and regulatory requirements. As per the Tri-Council Policy Statement, patient consent will be deferred due to the emergency nature of the interventions. If superiority is established, results will have a major impact on clinical practice by reducing exposure to non-virally inactivated blood products, shortening the time for administration of clotting factors, correct coagulopathy more efficaciously and reduce the reliance on AB plasma.Trial registration number NCT04534751, pre results.
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