The Role of Antiplatelet Drugs in the Management of Sepsis in Critically ill Patients

Abstract

Sepsis is the clinical syndrome that results from a dysregulated inflammatory response to aninfection that is non resolving and deleterious, often leading to organ dysfunction.Because sepsis is defined as a syndrome, it is likely that heterogeneous pathophysiologic processes are contained under this single term. The interaction of microbiological products with a host that is susceptible due to genetic or other factors induces a cascade of immunomodulatory mediators, leading to cellular and organ dysfunction. It is generally accepted that the clinical strategy for improving the outcome of sepsis patients includes the advancement in the knowledge of the pathogenesis of this syndrome as well as the identification of biomarkers to establish risk assessment, predicting the development of individual or multiple organ dysfunctions, guiding antimicrobial therapy, and establishing new and individualized treatment. The principles of the initial management bundle are to provide cardiorespiratory resuscitation and mitigate the immediate threats of uncontrolled infection. Early management of sepsis requires respi¬ratory stabilization. Supplemental oxygen should be given to all patients. A potentially beneficial effect of antiplatelet therapy on septic patients can be explained by several mechanisms. The irreversible inhibition of platelet function caused by these drugs impedes their activation and surface expression of adhesion molecules like selectins and GPIIbIIIa receptors which is a key step in the formation of microvascular thrombi. Aspirin: has shown some specific anti-inflammatory beneficial effects in sepsis. It stimulates the synthesis of (15-epilipoxin A4), which in turn increases nitric oxide synthesis through endothelial nitric oxide synthase and inducible nitric oxide synthase. Nitric oxide inhibits the interactions between leucocytes and endothelial cells, decreasing polymorph neutrophil recruitment. Studies indicate that low-dose aspirin, as it is used in patients with cardiovascular, cerbrovascular, or peripheral vascular diseases, might offer a novel therapeutic option to prevent organ failure. This hypothesis warrants testing in prospective interventional trials. Limitations in safety, efficacy, and tolerability have