Abstract
Disease-severity scoring systems have been developed for stratification of ICU patients. These systems have been tested and validated in various general medical and surgical ICU patients. However, the validity and efficacy of these systems, especially the newer generation, has not been assessed in patients with sepsis, which is the commonest indication for admission to a medical ICU. Hence, we conducted this study to assess the performance of various ICU scoring systems - Acute Physiology and Chronic Health Evaluation (APACHE) II, III, IV; Simplified Acute Physiology Score (SAPS) II, III; Mortality Prediction Model (MPM) II0, III0; and Sequential Organ Failure Assessment (SOFA) scores - in septic patients admitted to a medical ICU.
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
Summary
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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