Abstract

BackgroundRecent research has identified an increased rate of mortality associated with fluid bolus therapy for severe sepsis and septic shock, but the mechanisms are still not well understood. Fluid resuscitation therapy administered for sepsis and septic shock targets restoration of the macro-circulation, but the pathogenesis of sepsis is complex and includes microcirculatory dysfunction.ObjectiveThe objective of the study is to systematically review data comparing the effects of different types of fluid resuscitation on the microcirculation in clinically relevant animal models of lipopolysaccharide-induced sepsis.MethodsA structured search of PubMed/MEDLINE and EMBASE for relevant publications from 1 January 1990 to 31 December 2015 was performed, in accordance with PRISMA guidelines.ResultsThe number of published papers on sepsis and the microcirculation has increased steadily over the last 25 years. We identified 11 experimental animal studies comparing the effects of different fluid resuscitation regimens on the microcirculation. Heterogeneity precluded any meta-analysis.ConclusionsFew animal model studies have been published comparing the microcirculatory effects of different types of fluid resuscitation for sepsis and septic shock. Biologically relevant animal model studies remain necessary to enhance understanding regarding the mechanisms by which fluid resuscitation affects the microcirculation and to facilitate the transfer of basic science discoveries to clinical applications.

Highlights

  • Sepsis is a syndrome induced by infection that is characterized by physiologic, pathologic, and biochemical abnormalities [1], causing a substantial primary disease burden and co-morbidity [2]

  • Few animal model studies have been published comparing the microcirculatory effects of different types of fluid resuscitation for sepsis and septic shock

  • Relevant animal model studies remain necessary to enhance understanding regarding the mechanisms by which fluid resuscitation affects the microcirculation and to facilitate the transfer of basic science discoveries to clinical applications

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Summary

Introduction

Sepsis is a syndrome induced by infection that is characterized by physiologic, pathologic, and biochemical abnormalities [1], causing a substantial primary disease burden and co-morbidity [2]. Treatment guidelines focus upon the normalization of macro-circulatory perturbations, with less attention to restoring microcirculatory dysfunction, which can only be resuscitated in the early period and has been shown to occur early in the disease process [10] and to persist in the later stages of volume-resuscitated sepsis and septic shock [10,11,12,13,14,15,16,17,18]. The microcirculation is an elaborate network of blood vessels, comprised of arterioles, venules, and capillaries that are lined with a dynamic endothelial-glycocalyx layer [19] This network together forms the largest organ system in the body [20]. Fluid resuscitation therapy administered for sepsis and septic shock targets restoration of the macro-circulation, but the pathogenesis of sepsis is complex and includes microcirculatory dysfunction

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