Fluid resuscitation in ovine sepsis: re-examining the role of a common resuscitation therapy

Fluid resuscitation continues to be recommended as the first-line resuscitative therapy for all patients with severe sepsis and septic shock. The current acceptance of the therapy is based in part on long history and familiarity with its use in the resuscitation of other forms of shock, as well as on an incomplete and incorrect understanding of the pathophysiology of sepsis. Recently, the safety of intravenous fluids in patients with sepsis has been called into question with both prospective and observational data suggesting improved outcomes with less fluid or no fluid. The current evidence for the continued use of fluid resuscitation for sepsis remains contentious with no prospective evidence demonstrating benefit to fluid resuscitation as a therapy in isolation. This article reviews the historical and physiological rationale for the introduction of fluid resuscitation as treatment for sepsis and highlights a number of significant concerns based on current experimental and clinical evidence. The research agenda should focus on the development of hyperdynamic animal sepsis models which more closely mimic human sepsis and on experimental and clinical studies designed to evaluate minimal or no fluid strategies in the resuscitation phase of sepsis. © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Background Sepsis is a significant global health problem. e worldwide incidence of sepsis is increasing, with current estimates between 20 and 30 million cases annually [1–5]. e mortality of septic shock, the most severe form of sepsis, continues to be higher than 50% [5, 6]. e cost associated with a single admission of a patient with sepsis has been estimated to be in excess of Euro 20,000 [7, 8]. e treatment of sepsis has not significantly changed over the past 40 years, with the currently used therapies of antibiotics, source control, fluid resuscitation and judicious use of vasopressors recommended in a familiar form in the literature as far back as 1970 [9]. Fluid resuscitation remains the most enduring of sepsis treatments predating even antibiotics. Its beginnings date to the European cholera epidemic of the 1830s, where it was first used to replace the losses associated with cholera diarrhoea [10]. In modern practice, fluid resuscitation has developed to encompass both corrections of absolute and relative hypovolemic states with the additional goal of augmenting cardiac output to restore organ perfusion pressure and improve oxygen transport to cells [5, 11, 12]. Unfortunately, there is no agreed uniform definition of fluid resuscitation in the literature. Fluid administration is not necessarily the same as fluid resuscitation. It is important to differentiate between fluid substitution and volume substitution in intensive care patients, a distinction that has not always been appreciated sufficiently in the design of fluid studies [13]. For the sake of simplicity and consistency, we define fluid resuscitation for sepsis in this review as the administration of intravenous fluids to correct sepsis-induced tissue hypoperfusion. is definition is consistent with the surviving sepsis guidelines and implies a targeted approach to a clinical problem [12]. e following article reviews the rationale for the introduction of fluid resuscitation as treatment for sepsis and highlights a number of significant concerns based on current experimental and clinical evidence. Open Access *Correspondence: Liambyrne.syd@gmail.com 2 Intensive Care Unit, The Canberra Hospital, Canberra, Australia Full list of author information is available at the end of the article