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Doctoral Thesis
DOI
10.11606/T.5.2018.tde-02072018-152418
Document
Author
Full name
Juliana Mynssen da Fonseca Cardoso
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2018
Supervisor
Committee
Montero, Edna Frasson de Souza (President)
Abib, Simone de Campos Vieira
Rasslan, Roberto
Schanaider, Alberto
Utiyama, Edivaldo Massazo
Title in Portuguese
Efeito da N-acetilcisteína associada ao ácido tranexâmico na coagulopatia em modelo suíno de politrauma
Keywords in Portuguese
Ácido tranexâ.
Modelos animais
N-acetilcisteína
Transtornos da coagulação sanguínea
Tromboelastometria
Abstract in Portuguese
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.
Title in English
Effect of N-acetylcystein in association with tranexamic acid in the coagulopathy of a multi-trauma swine model
Keywords in English
Blood coagulation disorders
Models animal
N-acetylcysteine
Thromboelastometry
Tranexamic acidmico
Abstract in English
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
 
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Publishing Date
2018-07-03
 
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