Sepsis and Septic Shock in Critically Ill Patients
Septic shock is the leading cause of death in critically ill patients. Mortality rates of individuals who develop septic shock are approximately 45%.
Organ failure and death are believed to result from tissue hypoperfusion and dysregulation of the immune response. However, these mechanisms are poorly understood. The most commonly accepted theory is that an unbalanced and excessive inflammatory response to infection leads to cellular damage and tissue hypoperfusion, with resultant organ dysfunction. Another theory involves development of a relative immunocompromised state that results from dysregulation of the immune response and inability to eradicate infectious microorganisms. It is likely that both mechanisms play important roles in the development of organ failure and death in sepsis. Regardless of the underlying mechanism, sepsis has a tremendous impact on society with respect to healthcare expenditures and mortality.
Standard treatment guidelines for sepsis encompass early goal-directed fluid resuscitation, with vasopressor and inotropic support and blood products when needed to ensure adequate end-organ perfusion. Timely source isolation and treatment of the infectious organism is paramount.
Because sepsis may represent an exaggerated inflammatory response, a great deal of research has focused on anti-inflammatory strategies, most of which have failed to yield a substantial or consistent benefit. Stress-dose corticosteroids, glucose control, and activated protein C are currently guideline-recognized methods for treatment of sepsis.
Additional research has focused on nutritional supplementation with endogenous and exogenous antioxidants, including selenium, zinc, vitamin E or tocopherol, vitamin C, glutamine, glutathione, eicosapentaenoic and docosahexaenoic acids, R-α-lipoic acid, melatonin, and N-acetylcysteine. These modalities hold promise as inexpensive adjunctive therapies in sepsis. Although strong evidence is lacking, these agents have biological plausibility, and no significant adverse effects have been reported.
Low serum selenium levels have been associated with organ dysfunction, infection, and ICU mortality. A 40% reduction in plasma selenium concentrations has been observed in severe sepsis, which may contribute to an impaired antioxidant defense. Oxidant stress may play a key role in the host-mediated inflammatory response that is ultimately detrimental to survival. In septic shock, this process results in endothelial damage leading to increased vascular permeability and tissue injury.