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Síndrome da dificuldade respiratória aguda e progressão para choque séptico: abordagem translacional
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A lesão pulmonar com consequente comprometimento das trocas gasosas está na base da origem da SDRA. Esta é uma síndrome caracterizada pelo edema pulmonar, bem como pela inflamação, a qual frequentemente dá lugar a um estado de disfunção multiorgânica. Várias são as doenças e condições que podem precipitar a SDRA, como pneumonia, sépsis ou trauma. A gestão da SDRA foca-se, atualmente, em terapias de suporte tais como a ventilação mecânica, a fluidoterapia e o posicionamento em decúbito ventral. Ainda que se verifiquem progressos quanto ao conhecimento da fisiopatologia da Síndrome da Dificuldade Respiratória Aguda (SDRA), bem como uma aposta notável na investigação de novas abordagens terapêuticas, esta síndrome ainda é, nos dias de hoje, motivo de internamentos prolongados e elevadas taxas de mortalidade. Adicionalmente, é uma síndrome comum em Unidades de Cuidados Intensivos (UCI), pelo que a sua importância é incontornável. Da mesma maneira, também a sépsis e o choque séptico, que frequentemente coexistem em casos de SDRA, representam problemáticas com grande peso em contexto das UCI. Tanto a elevada incidência de casos de sépsis a nível nacional e internacional, como a elevada mortalidade associada a casos mais graves da doença, como o choque séptico, tornam a sépsis uma grave preocupação para a saúde pública. Até agora, os ensaios clínicos e estudos farmacológicos realizados falharam em evidenciar benefícios de vários fármacos. As novas abordagens terapêuticas assumem-se como promissoras de que, num futuro próximo, o tratamento da SDRA seja mais direcionado e eficaz. Estas englobam terapias combinadas, terapia celular e terapias farmacológicas utilizadas em contexto das UCI. Adicionalmente, um crescente interesse em terapias para prevenção da SDRA tem-se vindo a verificar, com o intuito de mitigar a necessidade de recorrer à ventilação mecânica. Neste contexto, na presente monografia são abordadas a SDRA e a sépsis no que concerne às suas definições, mecanismos fisiopatológicos e terapias atualmente disponíveis. É, também, descrita a evolução de casos de SDRA para a condição de choque séptico. Por último, numa abordagem translacional, são referidos os ensaios clínicos que englobam terapias tanto farmacológicas como celulares que estão, atualmente, a decorrer.
Lung injury with consequent impairment of gas exchange is the basis of the Acute Respiratory Distress Syndrome (ARDS). This is a syndrome characterized by pulmonary edema as well as inflammation, which often gives rise to a state of multiorgan dysfunction. Several clinical conditions and disorders can precipitate ARDS, such as pneumonia, sepsis or trauma. The management of ARDS currently focuses on supportive care techniques including mechanical ventilation, fluid therapy and prone positioning. Although progress has been made in understanding the pathophysiology of Acute Respiratory Distress Syndrome (ARDS), and new therapeutic approaches have been undergoing intense study, this syndrome is still a reason for prolonged hospitalizations and. high mortality rates. Additionally, it is a common syndrome in intensive care units (ICU), so its importance is unquestionable. Similarly, sepsis and septic shock, which often coexist in cases of ARDS, represent problems with great weight in the context of ICU. Both the high incidence of sepsis at national and international levels, as well as the high mortality rates associated with more severe cases of sepsis, such as septic shock, make sepsis a serious public health concern. So far, clinical trials of pharmacological approaches have failed to show benefits. These new promising therapeutic approaches are a hope for the establishment of a targeted treatment for ARDS in the near future, including combined therapies, cell therapy and pharmacological therapies used in the contexto of ICU. In addition, a growing interest in the prevention of ARDS has been emerging to mitigate the need for mechanical ventilation. In this context, the present monograph addresses ARDS and sepsis with regard to their definitions, pathophysiological mechanisms and currently available therapies. The evolution of ARDS cases to a septic shock condition is also described. Finally, in a translational approach, clinical trials that include both pharmacological and cellular therapies which are currently underway.
Lung injury with consequent impairment of gas exchange is the basis of the Acute Respiratory Distress Syndrome (ARDS). This is a syndrome characterized by pulmonary edema as well as inflammation, which often gives rise to a state of multiorgan dysfunction. Several clinical conditions and disorders can precipitate ARDS, such as pneumonia, sepsis or trauma. The management of ARDS currently focuses on supportive care techniques including mechanical ventilation, fluid therapy and prone positioning. Although progress has been made in understanding the pathophysiology of Acute Respiratory Distress Syndrome (ARDS), and new therapeutic approaches have been undergoing intense study, this syndrome is still a reason for prolonged hospitalizations and. high mortality rates. Additionally, it is a common syndrome in intensive care units (ICU), so its importance is unquestionable. Similarly, sepsis and septic shock, which often coexist in cases of ARDS, represent problems with great weight in the context of ICU. Both the high incidence of sepsis at national and international levels, as well as the high mortality rates associated with more severe cases of sepsis, such as septic shock, make sepsis a serious public health concern. So far, clinical trials of pharmacological approaches have failed to show benefits. These new promising therapeutic approaches are a hope for the establishment of a targeted treatment for ARDS in the near future, including combined therapies, cell therapy and pharmacological therapies used in the contexto of ICU. In addition, a growing interest in the prevention of ARDS has been emerging to mitigate the need for mechanical ventilation. In this context, the present monograph addresses ARDS and sepsis with regard to their definitions, pathophysiological mechanisms and currently available therapies. The evolution of ARDS cases to a septic shock condition is also described. Finally, in a translational approach, clinical trials that include both pharmacological and cellular therapies which are currently underway.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2019
Palavras-chave
Síndrome da dificuldade respiratória aguda Inflamação Sépsis Choque séptico Mestrado Integrado - 2019