Introduction: 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. Methods: 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. Results: 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. Conclusions: 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: Thrombelastography is a laboratorial test that measures viscoelastic changes of the entire clotting process. There is growing interest in its clinical use in trauma resuscitation, particularly for managing acute coagulopathy of trauma and assisting decision making concerning transfusion. This review focuses on the clinical use of thrombelastography in trauma, with practical points to consider on its use in civilian and military settings. Methods: A search in the literature using the terms “thrombelastography AND trauma” was performed in PUBMED database. We focused the review on the main clinical aspects of this viscoelastic method in diagnosing and treating patients with acute coagulopathy of trauma during initial resuscitation. Results: Thrombelastography is not a substitute for conventional laboratorial tests such as INR and aPTT but offers additional information and may guide blood transfusion. Thrombelastography can be used as a point of care test but requires multiple daily calibrations, should be performed by trained personnel and its technique requires standardization. While useful partial results may be available in minutes, the whole test may take as long as other conventional tests. The most important data provided by thrombelastography are clot strength and fibrinolysis. Clot strength measure can establish whether the bleeding is due to coagulopathy or not, and is the key information in thrombelastography-based transfusion algorithms. Thrombelastography is among the few tests that diagnose and quantify fibrinolysis and thus guide the use of anti-fibrinolytic drugs and blood products such as cryoprecipitate and fibrinogen concentrate. It may also diagnose platelet dysfunction and hypercoagulability and potentially prevent inappropriate transfusions of hemostatic blood products to non-coagulopathic patients. Conclusions: Thrombelastography has characteristics of an ideal coagulation test for use in early trauma resuscitation. It has limitations, but may prove useful as an additional test. Future studies should evaluate its potential to guide blood transfusion and the understanding of the mechanisms of trauma coagulopathy.

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.

Background: 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. N-acetylcysteine (NAC) has the potential to downregulate both processes. This review focuses on the potential neuroprotective utility of NAC and N-acetylcysteine amide (NACA) post-TBI. Methods: 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. Results: 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. Conclusion: 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.

BACKGROUND: Treatment of acute trauma coagulopathy has shifted toward rapid replacement of coagulation factors with frozen plasma (FP). There are logistic difficulties in providing FP. Freeze-dried plasma (FDP) may have logistical advantages including easier storage and rapid preparation time. This review assesses the feasibility, efficacy, and safety of FDP in trauma. STUDY DESIGN AND METHODS: Studies were searched from Medline, Embase, Cochrane Controlled Trials Register, ClinicalTrials.gov, and Google Scholar. Observational and randomized controlled trials (RCTs) assessing FDP use in trauma were included. Trauma animal models addressing FDP use were also included. Bias was assessed using validated tools. Primary outcome was efficacy, and secondary outcomes were feasibility and safety. Meta-analyses were conducted using random-effect models. Evidence was graded using Grading of Recommendations Assessment, Development, and Evaluation profile. RESULTS: Twelve human studies (RCT, 1; observational, 11) and 15 animal studies were included. Overall, studies demonstrated moderate risk of bias. Data from two studies (n = 119) were combined for meta-analyses for mortality and transfusion of allogeneic blood products (ABPs). For both outcomes, no difference was identified. For mortality, pooled odds ratio was 0.66 (95% confidence interval, 0.29–1.49), with I ² = 0%. Use of FDP is feasible, and no adverse events were reported. Animal data suggest similar results for coagulation and anti-inflammatory profiles for FP and FDP. CONCLUSION: Human data assessing FDP use in trauma report no difference in mortality and transfusion of ABPs in patients receiving FDP compared with FP. Data from animal trauma studies report no difference in coagulation factor and anti-inflammatory profiles between FP and FDP. Results should be interpreted with caution because most studies were observational and have heterogeneous population (military and civilian trauma) and a moderate risk of bias. Well-designed prospective observational studies or, preferentially, RCTs are warranted to answer FDP’s effect on laboratory (coagulation factor levels), transfusion (number of ABPs), and clinical outcomes (organ dysfunction, length of stay, and mortality). LEVEL OF EVIDENCE: Systematic review and meta-analysis, level IV.

Objectives The Tactical Combat Casualty Care (TCCC) guidelines detail resuscitation practices in prehospital and austere environments. We sought to review the content and quality of the current TCCC and civilian prehospital literature and characterize knowledge gaps to offer recommendations for future research. Methods MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials were searched for studies assessing intervention techniques and devices used in civilian and military prehospital settings that could be applied to TCCC guidelines. Screening and data extraction were performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quality appraisal was conducted using appropriate tools. Results Ninety-two percent (n=57) of studies were observational. Most randomized trials had low risk of bias, whereas observational studies had higher risk of bias. Interventions of massive hemorrhage control (n=17) were wound dressings and tourniquets, suggesting effective hemodynamic control. Airway management interventions (n=7) had high success rates with improved outcomes. Interventions of respiratory management (n=12) reported low success with needle decompression. Studies assessing circulation (n=18) had higher quality of evidence and suggested improved outcomes with component hemostatic therapy. Hypothermia prevention interventions (n=2) were generally effective. Other studies identified assessed the use of extended focused assessment with sonography in trauma (n=3) and mixed interventions (n=2). Conclusions The evidence was largely non-randomized with heterogeneous populations, interventions, and outcomes, precluding robust conclusions in most subjects addressed in the review. Knowledge gaps identified included the use of blood products and concentrate of clotting factors in the prehospital setting. Level of evidence Systematic review, level III.