Laboratory models of sepsis and septic shock

Abstract

That there are so many models of sepsis and septic shock is tacit evidence that none of them are perfect. Although sepsis presents in many forms clinically, most clinicians would probably agree that virtually all severely septic patients manifest respiratory failure and ventilator dependence. Furthermore, failure of organs other than the lungs typically occurs days to weeks after the onset of the septic process. Although early deaths occur commonly in some situations (e.g., meningococcemia, pneumococcal bacteremia in asplenic individuals, Gram-negative bacteremia in the setting of profound granulocytopenia), most deaths due to sepsis occur after a protracted course in an intensive care unit. Thus, for certain important experiments, there is a need for an animal model of severe chronic sepsis characterized by these features: persistent hypermetabolism, low systemic vascular resistance, respiratory failure severe enough to require mechanical ventilation, late (nonpulmonary) organ system failure, and death. Obviously, creation of such a model will require a major commitment of resources, because it will require, in essence, the creation of an animal intensive care unit. Nevertheless, we believe that progress in sepsis-related research would be substantially facilitated were such a model available. Even without such a model, progress will continue in this field. A wide variety of good animal models are already available to investigators. In the next decade, as new methods, such as the powerful tools of molecular biology, are applied to problems related to the sepsis syndrome, these models will be invaluable in improving our understanding of pathophysiology and in developing new and more effective approaches toward therapy.