Appraisal of four novel approaches to the prevention and treatment of sepsis.
OBJECTIVE
Four novel approaches to the management of sepsis are discussed.


CONCLUSIONS
Drotrecogin alfa (activated) has FDA-approved labeling for use in the treatment of severe sepsis. Risk of bleeding and identification of the most suitable patients have been the major issues related to use of this drug. Tight glycemic control and early goal-directed therapy (EGDT) are promising supportive strategies. Both have challenged existing views regarding safe glucose levels and the usefulness of increased oxygen delivery in sepsis. The routine maintenance of euglycemia is resource intensive, however, and benefits during treatment of sepsis are unclear. Very early initiation of measures to optimize hemodynamic variables and the ability to identify patients with cryptic shock appear to be key reasons for successful EGDT. The use of corticosteroids for septic shock has been extensively researched and has provoked controversy. Selection of patients likely to benefit on the basis of relative adrenal insufficiency and prolonged treatment may account for recently observed positive results. A model for combining the four strategies is proposed.


CONCLUSIONS
Novel strategies for treating sepsis include drotrecogin alfa (activated), tight glycemic control, EGDT, and low-dose corticosteroids.
Kumar
Atul
A
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis 55455-0343, USA.
Mann
Henry J
HJ
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000379:methods / Q000639:trends*; D004311:Double-Blind Method; D006801:Humans; D007262:Infusions, Intravenous; D015337:Multicenter Studies as Topic; D011486:Protein C / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018805:Sepsis / Q000401:mortality / Q000517:prevention & control* / Q000628:therapy*; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated