Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Infection after trauma complicates the patients clinical course. Infection leads to longer critical care and hospital stays, has been associated with increased mortality rates and places considerable cost pressures on health economies. The predictors of infection after severe injury are not known, and the effects on outcomes other than mortality are under-reported. The overall objective of this research was to characterise factors predictive of infection in severely injured patients admitted to critical care. A prospective cohort study of 271 patients investigated admission factors predictive of the development of infection. A second study of 280 patients evaluated post-injury immune cell changes and the association with infection. Thirdly the relationship between early coagulopathy and infections was investigated in 158 patients. Finally a study of 385 patients examined the use of Tranexamic Acid (TXA) and its association with infection and other outcomes. Infection was a significant burden for severely injured patients. Admission hypoperfusion was the only early characteristic associated with the development of infection, and a dose dependent relationship was observed between severity of shock and increased percentage of infection (p<0.01). Lymphopenia prolonged to day four post injury was strongly predictive infection (OR 0.10, CI 0.02-0.48, p<0.01). At 24 hours, the anticoagulant Protein C was lower in those with infection (Infection: 70.2 iu/dL vs. No infection: 83.3 iu/dL p=0.02), and increased fibrinolysis was also associated with infectious complications (Infection: 6156 μg/L vs. No infection: 3324 μg/L p=0.03). There was a trend to a beneficial relationship between TXA and infection, and it was independently associated with reduced organ failure (OR 0.27, CI: 0.10 – 0.73, p=0.01) and mortality (OR 0.16 CI 0.03 - 0.86, p=0.03). In severely injured patients, admission shock, prolonged lymphopenia and early coagulation dysfunction post severe injury were independent predictors of infection. Timely modulation of these responses after trauma may help to reduce the burden of infection.

A pressão sanguínea é responsável pela manutenção de importantes funções corpóreas. Uma perda de sangue que leve à queda brusca dessa pressão resulta em ineficiente perfusão tecidual e, consequentemente, em déficit de oxigênio e acúmulo de metabólitos. Quando em excesso, a perda sanguínea pode levar o paciente ao choque e a complicações anestésicas e cirúrgicas. O uso de um fármaco antifibrinolítico, como o ácido tranexâmico, pode minimizar o sangramento transoperatório, e é preferível à transfusão sanguínea. Este composto já é amplamente utilizado em cirurgias ortopédicas humanas, que apresentam alto grau de sangramento e geralmente requerem a transfusão sanguínea. O objetivo deste trabalho é avaliar a eficácia da utilização do ácido tranexâmico em cães submetidos a cirurgias com grande potencial de perda sanguínea. Foram incluídos 21 cães com ruptura de ligamento ou luxação de patela, com necessidade de osteotomia corretiva, distribuídos em 2 grupos. O primeiro grupo recebeu ácido tranexâmico em bolus, no momento da indução, na dose de 10 mg/kg seguido de infusão contínua na taxa de 1 mg/kg/hora já o segundo recebeu solução salina 0,9% no volume correspondente ao volume do fármaco. A estimativa da perda sanguínea foi feita através da pesagem dos campos cirúrgicos, compressas e gases quando secos e, posteriormente, quando embebidos em sangue, além disso foram dosadas a concentração sérica de lactato, tempos de coagulação, hemograma e hemogasometria, nos dados momentos: TB (basal), T1 (1 hora após a indução anestésica) e T2 (imediatamente ao final do procedimento cirúrgico). Utilizou-se análise de variância para medidas repetidas (ANOVA), seguido pelos testes de Tukey e t-Student, valores de p<0,05 expressam diferença estatística. Não houve diferença estatística entre os grupos em relação a nenhum dos parâmetros avaliados exceto as idades dos animais que foram significativamente mais velhos no grupo GSF quando comparados ao grupo GAT, também não houve diferença em relação à quantidade de sangue perdida nos diferentes grupos. Sendo assim, o ácido tranexâmico não foi eficaz em diminuir a perda sanguínea em cães submetidos a osteotomias corretivas. / Blood pressure is responsible for the maintenance of important body functions. A blood loss leading to low blood pressure results in ineffective tissue perfusion, oxygen deficit and accumulation of metabolites. When in excess, blood loss can lead to hypovolemic shock and surgical and anesthetic complications. The use of an antifibrinolytic drug, such as tranexamic acid, can minimize bleeding during surgery, and it is preferable to blood transfusion. This drug is widely used in human orthopedic surgery, with a high degree of bleeding wich often requires blood transfusion. The aim of this study is to evaluate the effectiveness of the use of tranexamic acid in dogs undergoing surgery with great potential of blood loss. 21 animals with ruptured cruciate ligament or patellar luxation, undergoing corrective osteotomy, were divided in 2 groups. The first group received tranexamic acid as a bolus, at the time of induction, at a dose of 10mg/kg followed by continuous infusion at the rate of 1mg/kg/hour. The second group, received saline solution 0.9% in volume corresponding to the volume of the drug. The estimation of blood loss was made by weighing the surgical drapes and gauzes when dry and then when soaked in blood, besides was dosed in addition serum lactate, coagulation times, blood count and blood gas analysis at three specific moments during the procedure: TB (baseline), T1 (1 hour after anesthesia induction) and T2 (immediatly before the end of procedure. Statistical analysis was performed by ANOVA for repeated measurements, followed by Tukey and t-Students test, values with p<0,05 were considered significant. There were no statistical difference between the groups regarding any of the parameters except the ages of the animals that were significantly older at the GSF group when compared to the GAT group. Regarding the blood loss, there were no difference as well. Therefore the tranexamic acid was not effective in reducing blood loss in dogs undergoing corrective osteotomies.

A pressão sanguínea é responsável pela manutenção de importantes funções corpóreas. Uma perda de sangue que leve à queda brusca dessa pressão resulta em ineficiente perfusão tecidual e, consequentemente, em déficit de oxigênio e acúmulo de metabólitos. Quando em excesso, a perda sanguínea pode levar o paciente ao choque e a complicações anestésicas e cirúrgicas. O uso de um fármaco antifibrinolítico, como o ácido tranexâmico, pode minimizar o sangramento transoperatório, e é preferível à transfusão sanguínea. Este composto já é amplamente utilizado em cirurgias ortopédicas humanas, que apresentam alto grau de sangramento e geralmente requerem a transfusão sanguínea. O objetivo deste trabalho é avaliar a eficácia da utilização do ácido tranexâmico em cães submetidos a cirurgias com grande potencial de perda sanguínea. Foram incluídos 21 cães com ruptura de ligamento ou luxação de patela, com necessidade de osteotomia corretiva, distribuídos em 2 grupos. O primeiro grupo recebeu ácido tranexâmico em bolus, no momento da indução, na dose de 10 mg/kg seguido de infusão contínua na taxa de 1 mg/kg/hora já o segundo recebeu solução salina 0,9% no volume correspondente ao volume do fármaco. A estimativa da perda sanguínea foi feita através da pesagem dos campos cirúrgicos, compressas e gases quando secos e, posteriormente, quando embebidos em sangue, além disso foram dosadas a concentração sérica de lactato, tempos de coagulação, hemograma e hemogasometria, nos dados momentos: TB (basal), T1 (1 hora após a indução anestésica) e T2 (imediatamente ao final do procedimento cirúrgico). Utilizou-se análise de variância para medidas repetidas (ANOVA), seguido pelos testes de Tukey e t-Student, valores de p<0,05 expressam diferença estatística. Não houve diferença estatística entre os grupos em relação a nenhum dos parâmetros avaliados exceto as idades dos animais que foram significativamente mais velhos no grupo GSF quando comparados ao grupo GAT, também não houve diferença em relação à quantidade de sangue perdida nos diferentes grupos. Sendo assim, o ácido tranexâmico não foi eficaz em diminuir a perda sanguínea em cães submetidos a osteotomias corretivas. / Blood pressure is responsible for the maintenance of important body functions. A blood loss leading to low blood pressure results in ineffective tissue perfusion, oxygen deficit and accumulation of metabolites. When in excess, blood loss can lead to hypovolemic shock and surgical and anesthetic complications. The use of an antifibrinolytic drug, such as tranexamic acid, can minimize bleeding during surgery, and it is preferable to blood transfusion. This drug is widely used in human orthopedic surgery, with a high degree of bleeding wich often requires blood transfusion. The aim of this study is to evaluate the effectiveness of the use of tranexamic acid in dogs undergoing surgery with great potential of blood loss. 21 animals with ruptured cruciate ligament or patellar luxation, undergoing corrective osteotomy, were divided in 2 groups. The first group received tranexamic acid as a bolus, at the time of induction, at a dose of 10mg/kg followed by continuous infusion at the rate of 1mg/kg/hour. The second group, received saline solution 0.9% in volume corresponding to the volume of the drug. The estimation of blood loss was made by weighing the surgical drapes and gauzes when dry and then when soaked in blood, besides was dosed in addition serum lactate, coagulation times, blood count and blood gas analysis at three specific moments during the procedure: TB (baseline), T1 (1 hour after anesthesia induction) and T2 (immediatly before the end of procedure. Statistical analysis was performed by ANOVA for repeated measurements, followed by Tukey and t-Students test, values with p<0,05 were considered significant. There were no statistical difference between the groups regarding any of the parameters except the ages of the animals that were significantly older at the GSF group when compared to the GAT group. Regarding the blood loss, there were no difference as well. Therefore the tranexamic acid was not effective in reducing blood loss in dogs undergoing corrective osteotomies.

Haemorrhage is a leading cause of trauma morbidity and mortality, with many deaths potentially preventable. Hyperfibrinolysis is a central characteristic of trauma-induced coagulopathy (TIC) which develops rapidly and is associated with poor outcomes. Tranexamic acid (TXA) improves survival in trauma haemorrhage but its uptake worldwide remains variable, in part because its effects on the coagulation system during trauma haemorrhage have not been described. Further uncertainty regarding patient selection for TXA therapy has emerged following the description of an early viscoelastic haemostatic assay (VHA) diagnosed hypofibrinolytic phenotype in whom TXA may potentiate thrombotic complications. The patient characteristics and mechanisms leading to this apparent hypofibrinolytic phenotype are poorly understood. Over 900 trauma patients prospectively recruited to a multicentre observational cohort study had blood drawn within 2-hours of injury for VHA and fibrinolysis plasma protein analysis. Patients were categorised according to VHA maximum lysis (ML) and D-dimer (DD) levels. Patients with MLLOW exhibited heterogeneity in clinical and injury characteristics and outcomes. Those who died were severely injured, with a high incidence of traumatic brain injury and a 7-fold higher D-dimer. Patients with MLLOW+DDHIGH had a hyperfibrinolytic biomarker profile, with the fibrinolytic mediator S100A10 identified as a potential driver of fibrinolysis, which can ex-vivo artificially reduce ML. Empiric TXA could benefit this occult hyperfibrinolytic phenotype. Over two subsequent observational studies, the effects of TXA on the coagulation system during trauma haemorrhage and the effect of TXA infusion and timing of treatment on thrombotic events were investigated. Early empiric TXA avoided VHA-hyperfibrinolysis and provided a degree of protection from TIC. Whilst univariate analysis suggested increased thromboses with later TXA treatment in patients receiving TXA bolus+infusion, neither the TXA infusion nor time to bolus were associated with thrombotic events after multivariate analysis. A single TXA bolus may provide a lower effective therapeutic dose with reduced complications.

BACKGROUND: Tranexamic acid (TXA) has become highly utilized in total joint arthroplasties for its anti-fibrinolytic effect. Recently, intra-articular application of TXA has become popular for its avoidance of systemic distribution within the body. With a more direct application to the surgical site, there is interest to see if topical application will provide hemostasis without increasing rates of venous or arterial thrombotic events and infections. In particular, there is lack of published data describing the safety of TXA in patients who have a significant disposition towards thromboembolic events. METHODS: This study was a retrospective chart-review (RCR) to assess the safety and efficacy of intra-articular TXA (IA-TXA) in total knee and hip arthroplasty patients. IA-TXA 2g/50mL NS was administered to patients who were contraindicated for IV-TXA usage based on our hospital’s guidelines (history of VTE events, mitral or aortic valve replacement with additional risk factors for stroke, active cancer, genetic or acquired thrombophilia, significant cardiac disease, serum creatinine > 2.8 mg/dL). Primary efficacy outcomes were total blood loss on post-operative day 1 (POD1), overall perioperative blood loss, and changes in hemoglobin/hematocrit values over the hospital stay. Primary safety outcomes were the incidence of arterial or venous thrombosis and wound infections. The study compared patients who received IA-TXA (study group) to patients who did not receive TXA (control group). The study included TKA patients=156 (Control=72 Study=83), anterior THA patients=57 (Control=20 Study=37), and posterior THA patients=59 (Control=27 Study=32). RESULTS: TKA patients administered IA-TXA showed a significant decrease in POD1 blood loss compared to the control group [305.84 mL, p = 0.004]. Additionally, the control patients showed significantly lower levels of overall hematocrit than those who had received IA-TXA [0.9 units, p = 0.041]. However, IA-TXA did not cause a reduction in blood loss in either the anterior or posterior THA patients. No statistically significant differences existed between treatment and control groups for transfusion rates or post-operative complications (VTE events and infections). CONCLUSION: IA-TXA 2g/50mL is effective in reducing blood loss in TKA patients; however, further research is needed regarding IA-TXA use in THA patients. The lack of efficacy in THA may have been related to the dosage used, the volume instilled, the timing of administration, or technique of administration.

Trauma é a maior causa de óbito entre adultos jovens no Brasil e no mundo, considerado um problema grave de saúde mundial. Atualmente, o controle da hemorragia é feito com uma reanimação hemostática, que preconiza a hipotensão permissiva, limita o uso de cristalóides, estimula o uso precoce de hemoderivados e medicamentos que possam minimizar o sangramento. Entretanto, a administração precoce de componentes do sangue, apresenta limitações de armazenamento, transporte, disponibilidade, compatibilidade, reações transfusionais e custo. Assim, devem ser desenvolvidas estratégias medicamentosas que possam beneficiar o paciente politraumatizado no tratamento do sangramento e na coagulopatia traumática. Por isso, decidiuse avaliar o efeito da administração precoce de N-acetilcisteína (NAC) e do ácido tranexâmico (TXA) em associação com Ringer lactato e seus efeitos na coagulação. Foi utilizado modelo experimental de choque hemorrágico e politrauma em 36 suínos, machos, da raça Landrace, com peso médio de 28,34 kg e distribuídos em cinco grupos: Controle (n=5), Ringer lactato (n=5), NAC (n=6), TXA (n=6) e NAC+TXA (n=6). Os animais foram submetidos à anestesia geral, fratura de fêmur, choque hemorrágico controlado e, por fim, a uma lesão hepática com hemorragia não controlada. Foram analisados os parâmetros fisiológicos, testes laboratoriais e tromboelastometria. Todos os animais submetidos ao experimento apresentaram taquicardia, hipotensão arterial, hipotermia, acidose, redução de plaquetas e hemoglobina e alteração nos testes de coagulação e viscoelásticos. O grupo NAC+TXA apresentou melhora do pH e excesso de base nas fases mais tardias do experimento quando comparados com os demais grupos (p < 0,05). No tempo Final, observou-se uma redução do fibrinogênio menor no grupo tratado com NAC+TXA. Na análise da tromboelastometria, os grupos tratados com TXA e NAC+TXA apresentaram o ML menor do que os tratados apenas com Ringer lactato ou NAC (p < 0,05). As análises do estudo sugerem um efeito benéfico da NAC em associação com TXA na melhora da acidose e fibrinólise. / Trauma is the major cause of death among young adults in Brazil and is considered a worldwide public health problem. Today, hemorrhage control begins with a homeostatic approach which preconizes permissive hypotension, limits the use of crystalloids, uses early transfusion and drugs that can minimize bleeding. However, early administration of blood components implies concerns, which includes storage, transport, availability, compatibility, transfusion reactions and cost. Therefore, there must be strategies that could bring benefits to the patient victim of trauma with bleeding and traumatic coagulopathy. Thus, it was decided to evaluate the potential of early administration of N-acetylcysteine (NAC) and Tranexamic Acid (TXA) associated or not to Ringer lactate and its potential benefits in coagulopathy. A model of multiple trauma and hemorrhagic shock previously described was used to evaluate these aspects in 36 male pigs, Landrace race, with an average weight of 28,34 kg and randomized into five groups: Control (n=5), Ringer lactate (n=5), NAC (n=6), TXA (n=6) and NAC + TXA (n=6). The animals were submitted to general anesthesia, a femur fracture, followed by controlled hemorrhagic shock, and an uncontrolled hepatic hemorrhage. Physiological parameters, standard laboratory tests and thromboelastometry were analyzed. All the animals showed tachycardia, low blood pressure, hypothermia, acidosis, lower platelets and hemoglobina levels and viscoelastics tests. The group NAC + TXA showed improvement in pH and base excess at the final phase of the experiment when compared with the others groups (p < 0.05). At the final phase, fibrinogen was lower reduced in the NAC + TXA group. In the thromboelastometry, the groups TXA and NAC + TXA had lower ML (Maximum Lysis) than the groups Ringer lactate and NAC. The study suggests a beneficial effect of NAC in association with TXA in improving acidosis and fibrinolysis

Diss. (sammanfattning) Linköping : Linköpings universitet, 2004. / Härtill 5 uppsatser.

Trauma é a maior causa de óbito entre adultos jovens no Brasil e no mundo, considerado um problema grave de saúde mundial. Atualmente, o controle da hemorragia é feito com uma reanimação hemostática, que preconiza a hipotensão permissiva, limita o uso de cristalóides, estimula o uso precoce de hemoderivados e medicamentos que possam minimizar o sangramento. Entretanto, a administração precoce de componentes do sangue, apresenta limitações de armazenamento, transporte, disponibilidade, compatibilidade, reações transfusionais e custo. Assim, devem ser desenvolvidas estratégias medicamentosas que possam beneficiar o paciente politraumatizado no tratamento do sangramento e na coagulopatia traumática. Por isso, decidiuse avaliar o efeito da administração precoce de N-acetilcisteína (NAC) e do ácido tranexâmico (TXA) em associação com Ringer lactato e seus efeitos na coagulação. Foi utilizado modelo experimental de choque hemorrágico e politrauma em 36 suínos, machos, da raça Landrace, com peso médio de 28,34 kg e distribuídos em cinco grupos: Controle (n=5), Ringer lactato (n=5), NAC (n=6), TXA (n=6) e NAC+TXA (n=6). Os animais foram submetidos à anestesia geral, fratura de fêmur, choque hemorrágico controlado e, por fim, a uma lesão hepática com hemorragia não controlada. Foram analisados os parâmetros fisiológicos, testes laboratoriais e tromboelastometria. Todos os animais submetidos ao experimento apresentaram taquicardia, hipotensão arterial, hipotermia, acidose, redução de plaquetas e hemoglobina e alteração nos testes de coagulação e viscoelásticos. O grupo NAC+TXA apresentou melhora do pH e excesso de base nas fases mais tardias do experimento quando comparados com os demais grupos (p < 0,05). No tempo Final, observou-se uma redução do fibrinogênio menor no grupo tratado com NAC+TXA. Na análise da tromboelastometria, os grupos tratados com TXA e NAC+TXA apresentaram o ML menor do que os tratados apenas com Ringer lactato ou NAC (p < 0,05). As análises do estudo sugerem um efeito benéfico da NAC em associação com TXA na melhora da acidose e fibrinólise. / Trauma is the major cause of death among young adults in Brazil and is considered a worldwide public health problem. Today, hemorrhage control begins with a homeostatic approach which preconizes permissive hypotension, limits the use of crystalloids, uses early transfusion and drugs that can minimize bleeding. However, early administration of blood components implies concerns, which includes storage, transport, availability, compatibility, transfusion reactions and cost. Therefore, there must be strategies that could bring benefits to the patient victim of trauma with bleeding and traumatic coagulopathy. Thus, it was decided to evaluate the potential of early administration of N-acetylcysteine (NAC) and Tranexamic Acid (TXA) associated or not to Ringer lactate and its potential benefits in coagulopathy. A model of multiple trauma and hemorrhagic shock previously described was used to evaluate these aspects in 36 male pigs, Landrace race, with an average weight of 28,34 kg and randomized into five groups: Control (n=5), Ringer lactate (n=5), NAC (n=6), TXA (n=6) and NAC + TXA (n=6). The animals were submitted to general anesthesia, a femur fracture, followed by controlled hemorrhagic shock, and an uncontrolled hepatic hemorrhage. Physiological parameters, standard laboratory tests and thromboelastometry were analyzed. All the animals showed tachycardia, low blood pressure, hypothermia, acidosis, lower platelets and hemoglobina levels and viscoelastics tests. The group NAC + TXA showed improvement in pH and base excess at the final phase of the experiment when compared with the others groups (p < 0.05). At the final phase, fibrinogen was lower reduced in the NAC + TXA group. In the thromboelastometry, the groups TXA and NAC + TXA had lower ML (Maximum Lysis) than the groups Ringer lactate and NAC. The study suggests a beneficial effect of NAC in association with TXA in improving acidosis and fibrinolysis

No description available.