Abstract

The use of pharmacological and physical antipyretic therapies to reduce fever in febrile patients is common in hospital settings. Actual evidence on the frequency of antipyretic use is limited, however, both in general hospital populations and, more specifically, in adult intensive care [1-3]. We undertook a prospective point prevalence study with the aim of identifying the prevalence of physical and pharmacological antipyretic therapies in intensive care patients with sepsis and inflammation. We also recorded the indication for antipyretic therapies, temperature measurement site, and mean temperatures on the study day.

Highlights

  • Fibrinolytic shutdown plays a pivotalrole in the pathogenesis of multiple organ dysfunction syndrome (MODS) in disseminated intravascular coagulation (DIC)

  • Beneficial action is mainly believed through improvement of major antioxidant selenoenzymes, but could on the contrary be related to a therapeutic oxidant action reducing activity of hyperactivated circulating phagocytic cells [4]

  • It has been suggested that the absence of beneficial effect of high-dose Na SeO continuously administered [2] might be related to toxicity, especially on the lung, of too much selenium (Se) as mentioned in recent parenteral nutrition guidelines in intensive care

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Summary

Introduction

Fibrinolytic shutdown plays a pivotalrole in the pathogenesis of multiple organ dysfunction syndrome (MODS) in disseminated intravascular coagulation (DIC). In a separate set of experiments investigating the MOA, AB103 administration (5 mg/kg, given without antibiotics 2 hours post CLP) was associated with: a reduction in Th-1 cytokine levels in peritoneum (TNFα, IL-3, IL-17 and Rantes) and plasma (IL-3 and IL-6); a reduction in splenocyte proliferation, stimulated ex vivo with anti-CD3 and anti-CD28 antibodies; a reduction in neutrophil recruitment to the spleen, liver and kidney, as determined by MPO activity; and a reduced bacterial load in peritoneum, blood and tissues (kidney, liver, spleen) Conclusion These data demonstrate that attenuation of CD28 signaling is a viable therapeutic approach to the treatment of sepsis. Therapeutic dosing of AZD9773 bid from 24 to 60 hours (schedule/dose/route as previously) did not result in significantly different survival outcomes versus either DigiFab or imipenem alone (n = 60 per group) Conclusion These data demonstrate for the first time that TNFα neutralization in a murine CLP model improves survival in a severe sepsis setting.

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