Examining the effectiveness of fluid bolus therapy in the treatment of septic shock and prevention of organ failure in a large animal model

Abstract

Fluid resuscitation is a widely recommended and used therapy in the management of septic shock. Despite widespread use there is limited evidence demonstrating efficacy. Recently the first randomised controlled study examining the effectiveness of fluid resuscitation in septic shock was published suggesting it was in fact harmful. This PhD will examine the effectiveness of fluid resuscitation in a large animal model of endotoxemic shock with the aim of establishing if it is an effective therapy for reversing shock and preventing organ failure. The first chapter will review the history of fluid resuscitation as a therapy as well as the current evidence supporting its use. The second chapter describes the issues surrounding previous animal models and development of a large animal model of hyperdynamic endotoxemic shock. The third chapter describes the results of the the experiments comparing fluid resuscitation in endotoxemic shock with a model of resuscitation without fluid resuscitation. The fourth and fifth chapters examine fluid resuscitations effect on specific organ and physiological function (lung and coagulation). Overall the thesis supports the conclusion that fluid resuscitation is an ineffective therapy in the management of septic shock and may lead to significant iatrogenic harm.