The systemic inflammatory response syndrome and the critically ill surgical patient

Systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) continue to have unacceptably high rates of mortality despite significant advances in our understanding of the pathophysiology of these diseases and the development of novel therapeutic biotechnologies. Recent advances have focused on molecular interactions between the inciting agent and the host mediator and effector systems. As a result, we have come to view SIRS and MODS as manifestations of a severely dysregulated immune response to injury, occurring at numerous points in the cascade of initiator, mediator, and effector molecules. The gastrointestinal tract is implicated as a potential source of perpetuating agents that fuel the spiral of SIRS and MODS. Selective gastrointestinal decontamination decreases infectious morbidity but does not significantly impact mortality. Alternatively, support of gastrointestinal immune functions through specific nutritional therapies and the early initiation of an enterally delivered diet improve outcome in critically ill patients. Despite the central importance of cytokine and other mediator systems, aberrations in their function should be viewed as only one aspect of the complex pathophysiology of these diseases. Advances in molecular biology have allowed the manipulation of key mediators in the cytokine cascade. Disappointingly, clinical trials targeting these mediators have not yielded improvements in outcome. Diversity in patient populations and the individual response to injury limits the application of animal studies to the clinical situation. A more thorough understanding of the interactions between various mediator systems will allow the development of rationally based immunotherapies. Leukocyte-induced endothelial cell injury is emerging as an important pathogenic mechanism that contributes to SIRS and MODS. Therapeutic strategies aimed at attenuating cellular injury by maximizing oxygen delivery and minimizing oxidant stress have shown promising results in experimental settings. Through new and ever-expanding scientific information, our knowledge of these diseases has evolved. The challenge will be to integrate this new knowledge into conceptually based paradigms and therapies that will benefit patients.