Abstract
Sepsis is regarded as one of the main causes of death among the critically ill. Pathogen infection results in a host-mediated pro-inflammatory response to fight infection; as part of this response, significant endogenous reactive oxygen (ROS) and nitrogen species (RNS) production occurs, instigated by a variety of sources, including activated inflammatory cells, such as neutrophils, platelets, and cells from the vascular endothelium. Inflammation can become an inappropriate self-sustaining and expansive process, resulting in sepsis. Patients with sepsis often exhibit loss of aspects of normal vascular homeostatic control, resulting in abnormal coagulation events and the development of disseminated intravascular coagulation. Diagnosis and treatment of sepsis remain a significant challenge for healthcare providers globally. Targeting the drivers of excessive oxidative/nitrosative stress using antioxidant treatments might be a therapeutic option. This review focuses on the association between excessive oxidative/nitrosative stress, a common feature in sepsis, and loss of homeostatic control at the level of the vasculature. The literature relating to potential antioxidants is also described.
Highlights
Sepsis is a life-threatening condition that affects 30 million people worldwide per year and is considered one of the main causes of death amongst critically ill patients
The reduction in platelet aggregation seen in patients with sepsis is more pronounced depending on the severity sepsis, stage of disease, and the presence of Neutrophils are white blood cells that play a critical role in the immune response as well as in sepsis, which is associated with an excessive activation of neutrophils
Production resulting from an overstimulation of the inflammatory response beyond the limits of homeostatic control, in part due to depletion of finite antioxidant reserves, results tion resulting from an overstimulation of the inflammatory response beyond the limits of homeostatic control, in part due to depletion of finite antioxidant reserves, results in a prooxidant environment
Summary
Sepsis is a life-threatening condition that affects 30 million people worldwide per year and is considered one of the main causes of death amongst critically ill patients. Around two-thirds of patients with sepsis are treated in intensive care units (ICUs), with an annual estimated cost at £15.6 billion [4]. This represents a significant component of annual healthcare budgets; the need for further support for recovering patients as provided by primary care providers places an even greater burden budget. This review aims to explore the potential role for ROS and RNS as initiators for adverse clotting and bleeding events in sepsis. Efforts to target these processes using antioxidant therapies will be discussed
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