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.
The management of acquired coagulopathy in multiple clinical settings frequently involves fibrinogen supplementation. Cryoprecipitate, a multidonor product, is widely used for the treatment of ...acquired hypofibrinogenemia following massive bleeding, but it has been associated with adverse events. We aimed to review the latest evidence on cryoprecipitate for treatment of bleeding.
We conducted a narrative review of current literature on cryoprecipitate therapy, describing its history, formulations and preparation, and recommended dosing. We also reviewed guideline recommendations on the use of cryoprecipitate in bleeding situations and recent studies on its efficacy and safety.
Cryoprecipitate has a relatively high fibrinogen content; however, as it is produced by pooling fresh frozen donor plasma, the fibrinogen content per unit can vary considerably. Current guidelines suggest that cryoprecipitate use should be limited to treating hypofibrinogenemia in patients with clinical bleeding. Until recently, cryoprecipitate was deemed unsuitable for pathogen reduction, and potential safety concerns and lack of standardized fibrinogen content have led to some professional bodies recommending that cryoprecipitate is only indicated for the treatment of bleeding and hypofibrinogenemia in perioperative settings where fibrinogen concentrate is not available. While cryoprecipitate is effective in increasing plasma fibrinogen levels, data on its clinical efficacy are limited.
There is a lack of robust evidence to support the use of cryoprecipitate in bleeding patients, with few prospective, randomized clinical trials performed to date. Clinical trials in bleeding settings are needed to investigate the safety and efficacy of cryoprecipitate and to determine its optimal use and administration.
The anticoagulated trauma patient presents a particular challenge to the critical care physician. Our understanding of these patients is defined and extrapolated by experience with patients on ...warfarin pre-injury. Today, many patients who would have been on warfarin are now prescribed the Direct Oral Anticoagulants (DOACs) a class of anticoagulants with entirely different mechanisms of action, effects on routine coagulation assays and approach to reversal.
Trauma registry data from Toronto's (Ontario, Canada) two Level 1 trauma centres were used to identify patients on oral anticoagulation pre-injury from June 1, 2014 to June 1, 2015. The trauma registry and medical records were reviewed and used to extract demographic and clinical data.
We found 81 patients were on oral anticoagulants pre-injury representing 3.2% of the total trauma population and 33% of the orally anticoagulated patients were prescribed a DOAC prior to presentation. Comparison between the DOAC and warfarin groups showed similar age, mechanisms of injury, indications for anticoagulation, injury severity score and rate of intracranial hemorrhage. Patients on DOACs had higher initial mean hemoglobin vs warfarin (131 vs 120) and lower serum creatinine (94.8 vs 129.5). The percentage of patients receiving a blood transfusion in the trauma bay and total in-hospital transfusion was similar between the two groups however patients on DOACs were more likely to receive tranexamic acid vs patients on warfarin (32.1% vs 9.1%) and less likely to receive prothrombin concentrates (18.5% vs 60%). Patients on DOACs were found to have higher survival to discharge (92%) vs patients on warfarin (72%).
Patients on DOACs pre-injury now represent a significant proportion of the anticoagulated trauma population. Although they share demographic and clinical similarities with patients on warfarin, patients on DOACs may have improved outcomes despite lack of established drug reversal protocols and challenging interpretation of coagulation assays.
III; Study Type: Retrospective Review.
Hypothermia is present in up to two-thirds of patients with severe injury, although it is often disregarded during the initial resuscitation. Studies have revealed that hypothermia is associated with ...mortality in a large percentage of trauma cases when the patient's temperature is below 32 °C. Risk factors include the severity of injury, wet clothing, low transport unit temperature, use of anesthesia, and prolonged surgery. Fortunately, associated coagulation disorders have been shown to completely resolve with aggressive warming. Selected passive and active warming techniques can be applied in damage control resuscitation. While treatment guidelines exist for acidosis and bleeding, there is no evidence-based approach to managing hypothermia in trauma patients. We synthesized a goal-directed algorithm for warming the severely injured patient that can be directly incorporated into current Advanced Trauma Life Support guidelines. This involves the early use of warming blankets and removal of wet clothing in the prehospital phase followed by aggressive rewarming on arrival at the hospital if the patient's injuries require damage control therapy. Future research in hypothermia management should concentrate on applying this treatment algorithm and should evaluate its influence on patient outcomes. This treatment strategy may help to reduce blood loss and improve morbidity and mortality in this population of patients.
A reunião de revista "Telemedicina Baseada em Evidência - Cirurgia do Trauma e Emergência" (TBE-CiTE) realizou uma revisão crítica da literatura e selecionou três artigos atuais sobre o tratamento do ...trauma renaldefinido como graus III a V pela classificação da Associação Americana de Cirurgia do Trauma (AAST). O primeiro trabalho propõe subestratificação da lesão renal AAST grau IV em 4a (baixo risco) e 4b (alto risco). O segundo trabalho revisa o atual sistema de classificação de lesão renal AASTpara incluir lesões vasculares segmentares e estabelecer uma definição mais detalhada dos graus IV e V. O último artigo analisa a angiografia diagnóstica e angioembolização na fase aguda do trauma renal utilizando dados americanos. A reunião de revista TBE-CiTE elaborou as conclusões e recomendações para o tratamento do trauma renal de alto grau.
A reunião de revista "Telemedicina Baseada em Evidência - Cirurgia do Trauma e Emergência" (TBE-CiTE) realizou uma revisão crítica da literatura e selecionou os três artigos mais relevantes e atuais ...sobre a indicação de tomografia de crânio em pacientes pediátricos com trauma craniencefálico leve (TCE). O primeiro trabalho identificou pacientes vítimas de TCE leve com fatores de alto e baixo risco de apresentarem lesões intracranianas vistas à tomografia computadorizada (TC) de crânio e com necessidade de intervenção neurocirúrgica. O segundo trabalho avaliou o uso das recomendações do "National Institute of Clinical Excellence" em pacientes pediátricos com TCE, e utilizou como variáveis de desfecho a realização de TC ou internação hospitalar. O último artigo analisou e identificou os pacientes onde a TC de crânio seria desnecessária e, portanto, não deve ser feita rotineiramente. Baseado nessa revisão crítica da literatura e a discussão com especialistas, o TBE-CiTE concluiu que é importante evitar a exposição desnecessária de crianças com TCE leve à radiação ionizante da TC de crânio. O grupo favoreceu a utilização do guideline do PECARN onde ECG de 14, alteração do nível de consciência ou fratura do crânio palpável são indicações de TC de crânio, ou quando a experiência do médico, achados múltiplos ou piora dos sintomas ocorrerem.
Management of stab wounds to the anterior abdominal wall Rezende-Neto, João Baptista; Vieira Jr, Hélio Machado; Rodrigues, Bruno De Lima ...
Revista do Colégio Brasileiro de Cirurgiões,
01/2014, Volume:
41, Issue:
1
Journal Article
Peer reviewed
Open access
The meeting of the Publication "Evidence Based Telemedicine - Trauma and Emergency Surgery" (TBE-CiTE), through literature review, selected three recent articles on the treatment of victims stab ...wounds to the abdominal wall. The first study looked at the role of computed tomography (CT) in the treatment of patients with stab wounds to the abdominal wall. The second examined the use of laparoscopy over serial physical examinations to evaluate patients in need of laparotomy. The third did a review of surgical exploration of the abdominal wound, use of diagnostic peritoneal lavage and CT for the early identification of significant lesions and the best time for intervention. There was consensus to laparotomy in the presence of hemodynamic instability or signs of peritonitis, or evisceration. The wound should be explored under local anesthesia and if there is no injury to the aponeurosis the patient can be discharged. In the presence of penetration into the abdominal cavity, serial abdominal examinations are safe without CT. Laparoscopy is well indicated when there is doubt about any intracavitary lesion, in centers experienced in this method.
A reunião de Revista "Telemedicina Baseada em Evidências - Cirurgia do Trauma e Emergência" (TBE-CiTE) através de revisão da literatura selecionou três artigos recentes sobre o tratamento do paciente vítima de agressão por arma branca na parede abdominal. O primeiro trabalho observou o papel da tomografia computadorizada (TC) no tratamento do paciente com agressão por arma branca na parede abdominal. O segundo analisou o uso da laparoscopia diagnóstica em detrimento do exame físico seriado para avaliar os pacientes com necessidade de laparotomia terapêutica. O terceiro fez uma avaliação da exploração cirúrgica do ferimento abdominal, uso do lavado peritoneal diagnóstico e TC na identificação precoce de lesões significativas e o melhor momento para intervenção. Houve consenso para a indicação de laparotomia na presença de instabilidade hemodinâmica, ou sinais de peritonite, ou evisceração. O ferimento deve ser explorado sob anestesia local e se não houver lesão da aponeurose o doente pode receber alta. Na presença de penetração na cavidade abdominal, o exame seriado do abdome é seguro, sem a necessidade de TC. A laparoscopia está bem indicada quando existe dúvida de lesão intracavitária em centros com experiência nesse método.
Background
Coagulopathic bleeding is frequently present after major trauma. However, trauma‐induced coagulopathy (TIC) remains incompletely understood. This laboratory analysis of blood samples ...derived from our completed trial on fibrinogen in the initial resuscitation of severe trauma (FiiRST) was conducted to evaluate TIC and associated responses to fibrinogen replacement.
Study design and methods
We conducted a retrospective evaluation of TIC in 45 FiiRST trial patients based on rotational thromboelastometry (ROTEM), international normalized ratio (INR), and biomarkers for hemostasis and endotheliopathy. Whole blood was analyzed by ROTEM. Plasma was analyzed for INR and biomarkers.
Results
Overall, 19.0% and 30.0% of the FiiRST trial patients were coagulopathic on admission defined by EXTEM maximum clot firmness out of the range of 40–71 mm and INR >1.2, respectively. The FiiRST patients showed lower fibrinogen, factor II and V levels, protein C and antiplasmin activities, higher activated protein C, tissue plasminogen activator, d‐dimer, and thrombomodulin concentrations at admission than healthy controls. Most of the biomarkers changed their activities during 48‐h hospitalization, but were at abnormal levels even 48‐h after admission. The fibrinogen treatment reduced hypofibrinogenemia and increased factor XIII level, but had no significant effects on other biomarkers levels. Limited development of endotheliopathy was indicated by syndean‐1, thrombomodulin, and sE‐selectin.
Conclusions
About 19%–30% of the trauma patients in the FiiRST trial were coagulopathic on hospital admission depending on the definition of TIC. Analyses of the TIC biomarkers demonstrated that hemostasis would not return to normal after 48‐h hospitalization, and fibrinogen replacement improved hypofibrinogenemia.
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BACKGROUND:Thrombelastography (TEG) fibrinolysis shutdown after trauma is associated with increased mortality due to hypercoagulability-associated organ failure. However, a lack of mechanistic data ...has precluded the development of novel interventions to treat shutdown.
OBJECTIVES:To define the pathophysiology of TEG shutdown in severely injured, bleeding patients through secondary analysis of the PROPPR trial.
METHODS:Fibrinolysis was characterized in PROPPR subjects using admission TEG lysis at 30 min (LY30) or plasmin-antiplasmin (PAP) levels. LY30 categories were low (<0.9%), moderate (0.9–2.9%), or high (≥ 3%). PAP was classified as low (<1,500 μg/L), moderate (1,500–20,000 μg/L), or high (>20,000 μg/L). Demographics, outcomes, admission TEG values, platelet count and function, standard coagulation tests, and coagulation proteins were compared.
RESULTS:Five hundred forty-seven patients had TEG data and 549 patients had PAP data available. Low LY30 was associated with reduced platelet count and aggregation, poorer TEG clot formation, prolonged clotting times, and reduced fibrinogen and alpha2 antiplasmin. Compared to moderate PAP, low PAP subjects had similar platelet parameters, TEG values, fibrinogen, and alpha2 antiplasmin, but reduced tPA, and elevated PAI-1. D-Dimer values increased as PAP increased, however patients with low LY30 had elevated D-Dimer compared with moderate LY30 patients. Most low LY30 deaths were due to TBI (45%) and hemorrhage (42%) versus one of each cause (TBI, hemorrhage, MOF) in low PAP patients.
CONCLUSIONS:Low TEG LY30 does not reflect shutdown of enzymatic fibrinolysis with hypercoagulability, but rather a coagulopathic state of moderate fibrinolysis with fibrinogen consumption and platelet dysfunction that is associated with poor outcomes.
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.
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