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Abstract

sepsis/septic shock during a seven-month period after implementation of the SS-BPA. The control group consisted of patients meeting the same criteria over a prior sevenmonth period. The primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay (LOS), time to antibiotic administration and proportion of patients that received antibiotics within the target 60 minutes. A multivariable logistic regression analysis was conducted to adjust for potential confounding variables. Results: The baseline characteristics of the study groups were similar, except for SOFA score (median score 5 vs. 4, p=0.05). Time to antibiotics was significantly reduced in the SS-BPA cohort (61.5 vs. 29 minutes, p<0.001). In addition, there was a higher proportion of patients that received antibiotics within 60 minutes (48.6 vs. 76.7%, p<0.001). On multivariable analysis, in-hospital mortality was not significantly reduced in the intervention group (OR 0.64; 95% CI, 0.26-1.57). Multivariable analysis of LOS indicated a significant reduction among patients in the SS-BPA cohort (geometric mean ratio 0.66; 95% CI, 0.53-0.82). Conclusions: Implementation of an EMR-embedded BPA for severe sepsis among ED patients improved timeliness of antibiotic administration and reduced hospital length of stay.Learning Objectives: Epidermal growth factor (EGF) is a cytoprotective peptide that has protective effects on the intestinal mucosa in sepsis. Our previous studies show that both enterocyte-specific overexpression of EGF and systemic administration of EGF to septic immunocompetent mice confer a survival advantage. Crosstalk regularly occurs between the gut epithelium and lymphocytes under homeostatic conditions, and our data show that the CD4+ cell subset is responsible for the anti-apoptotic effect of lymphocytes on the gut epithelium in sepsis. The purpose of this study was to determine if the survival benefit of EGF is CD4-dependent. Methods: Three different groups of mice were subjected to 2x25 cecal ligation and puncture (CLP). All mice received 2 days of antibiotics, and were followed for 7-day survival. Groups were as follows: (1) Rag-/-mice (which lack lymphocytes), half of which received post-CLP EGF (total dose 150ug/kg/day, divided in 2 doses) via systemic administration, half received the same volume of saline.(2) Rag-/-mice and Fabpi-EGF mice (transgenic mice with enterocyte-specific over-expression of EGF). (3) CD4-/-(mice lacking CD4 cells) and C57BL/6 mice, both groups receiving post-CLP EGF via systemic administration. Results: Systemic EGF administration worsened septic survival of Rag-/-mice (12.5% vs. 55%, p<0.01, n=18/group). There was no survival difference between Rag-/-mice and Fabpi-EGF mice (48% vs. 52%, p=0.75, n=25/group). Despite systemic EGF administration, mortality of CD4-/-mice was significantly higher than wild-type controls. All CD4-/-mice died within five days after CLP, whereas only 65% of C57BL/6 died over the course of 7 days (p<0.05, n=16-20). Conclusions: The survival advantage pro...