الفهرس 
Introduction and Aim of WorkOnly 14 pages are availabe for public view
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Abstract
Sepsis is a life-threatening sequential organ failure resulting from an unregulated host response to infection, whereas septic shock is a subgroup of sepsis with higher short-term mortality. Neostigmine, a peripherally acting choline esterase inhibitor, has improved survival in animal models of sepsis. However, its feasibility, efficacy, and safety in sepsis or septic shock patients have not been yet investigated. Many biomarkers including presepsin, procalcitonin (PCT) and c-reactive protein (CRP) have been suggested as promising diagnostic and prognostic biomarker in sepsis. This study aims first to investigate the efficacy and safety of neostigmine as a new adjunctive therapy in patients with sepsis or septic shock. Secondly, to evaluate the diagnostic and prognostic utility of presepsin, PCT, and CRP in patients with suspected sepsis. Subjects and Method A total of 167 adult patients with sepsis or septic shock were assessed for eligibility; only 50 patients were randomized to receive a continuous infusion of neostigmine (0.2 mg/h for five days; neostigmine arm, n= 25) or 0.9% saline (control arm, n= 25) in addition to the standard therapy. The primary outcome was to observe the change in Sequential Organ Failure Assessment (SOFA) score 5 days after therapy initiation. Secondary outcomes included the percentage of shock reversal, mortality rates and changes in PCT level. Safety outcomes were also measured, such as percentage of patients who required atropine. Receiver-operating characteristic (ROC) curve analyses were executed with area under the curve (AUC) for diagnosis and prognosis of sepsis. Results The median change in SOFA scores improved significantly in the neostigmine arm compared to the control arm (p = 0.007). Progression from sepsis to septic shock was more frequent in the control arm than in the neostigmine arm (p = 0.01). The incidence of shock reversal in patients with septic shock was significantly lower in the control arm than in the neostigmine arm (p = 0.04). Differences in 28-day mortality rates did not reach statistical significance between the control and neostigmine arms. The percentage change in PCT level was similar in both arms (p = 0.74). Presepsin showed the highest AUC; 0.884 (95% CI: 0.780 – 0.988) for diagnostic properties. AUC of PCT added to Acute Physiology and chronic Health Evaluation (APACHE II) score and SOFA score was the highest for predicting prognosis [0.82 (95% confidence interval (CI): 0.7 -.937)].Conclusion In conclusion, neostigmine adjunctive therapy may be safe and effective when administered in patients with sepsis or septic shock. Presepsin showed superiority to PCT, and CRP in sepsis diagnosis. The addition of PCT to clinical scores showed the highest predictive ability for predicting prognosis of sepsis.