title: The puzzle of sepsis: fitting the pieces of the inflammatory response with treatment.
abstract: Sepsis is a complex syndrome characterized by simultaneous activation of inflammation and coagulation in response to microbial insult. These events manifest as systemic inflammatory response syndrome (SIRS)/sepsis symptoms through release of proinflammatory cytokines, procoagulants, and adhesion molecules from immune cells and/or damaged endothelium.Conventional treatments have focused on source control, antimicrobials, vasopressors, and fluid resuscitation; however, a new treatment paradigm exists: that of treating the host response to infection with adjunct therapies including early goal directed therapy, drotrecogin alfa (activated), and immunonutrition. The multimechanistic drotrecogin alfa (activated) has been shown to reduce mortality in the severely septic patient when combined with traditional treatment. Therapies targeting improved oxygen and blood flow and reduction of apoptosis and free radicals are under investigation. Early sepsis diagnosis through detection of pro calcitonin, C reactive protein, sublingual CO2, and genetic factors may be beneficial. Ultimately, intervention timing may be the most important factor in reducing severe sepsis mortality.
authors.affiliation: Eli Lilly and Company, US Medical, Critical Care, Indianapolis, IN, USA. JaneLC@lilly.com
authors.forename: Jane
authors.initials: J
authors.lastname: Cunneen
authors.forename: Martina
authors.initials: M
authors.lastname: Cartwright
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D017209:Apoptosis / Q000276:immunology; D001777:Blood Coagulation / Q000276:immunology; D003167:Complement Activation / Q000276:immunology; D003422:Critical Care / Q000379:methods* / Q000639:trends; D016207:Cytokines / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005440:Fluid Therapy / Q000379:methods; D006801:Humans; D007249:Inflammation; D018836:Inflammation Mediators / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D009102:Multiple Organ Failure / Q000209:etiology; D018529:Nutritional Support / Q000379:methods; D011486:Protein C / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012151:Resuscitation / Q000379:methods; D018805:Sepsis / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
chemical_list: D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D018836:Inflammation Mediators; D011486:Protein C; D011994:Recombinant Proteins; D014662:Vasoconstrictor Agents; C421124:drotrecogin alfa activated