Perspectives for the future.
The pathophysiology of sepsis and septic shock is extremely complex and ultimately involves every physiological pathway. The initiating event is the entrance of endotoxin or similar substances into the blood which initiates the release of multiple mediators. These are designed to react locally and to protect the organism. Their constant release, however, sets in motion up- and down regulations, ultimately resulting in "metabolic anarchy". Tumor necrosis factor alpha and other cytokines trigger several systems, especially coagulation to yield DIC, and the complement system. Many treatment modalities have been developed, most recently those which substitute inhibitors of various systems. Antithrombin III concentrates and potentially protein C concentrates are designed to arrest DIC. C1-esterase inhibitor concentrates should intercept the activation of the complement system and the contact phase of coagulation and its relationship to kinin generation. Even newer approaches entail antibodies to tumor necrosis factor alpha or endotoxin itself. The complex process of sepsis will undoubtedly require a multifaceted therapeutic approach.
Mammen
E F
EF
Department of Pathology, Wayne State University School of Medicine, Detroit, MI.
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000990:Antithrombin III / Q000276:immunology / Q000627:therapeutic use; D001777:Blood Coagulation; D003167:Complement Activation; D016207:Cytokines / Q000276:immunology; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D004731:Endotoxins / Q000276:immunology; D005544:Forecasting; D006801:Humans; D011379:Prognosis; D011486:Protein C / Q000276:immunology / Q000627:therapeutic use; D018805:Sepsis / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000401:mortality; D012772:Shock, Septic / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000401:mortality
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D004731:Endotoxins; D011486:Protein C; D000990:Antithrombin III; C068069:nebacumab