Novel therapies for sepsis: a review.
BACKGROUND
Over the past 30 years, efforts have been made to identify therapeutic targets in the host response to infection.


METHODS
A review of the randomized controlled clinical sepsis trials and meta-analyses of glucocorticoids, mediator-specific anti-inflammatory agents, and anticoagulant agents was performed.


RESULTS
The effects of glucocorticoids in sepsis appear to be dose-dependent, with high doses decreasing survival and low doses improving survival. As a class, the mediator-specific anti-inflammatory agents have a small beneficial effect on survival; however, no single agent has demonstrated significant benefit. The treatment effects of these agents appear to be related to the patient's risk of death. As a class, the anticoagulant agents do not improve survival; however, the efficacy of these agents may have been confounded by concurrent heparin therapy. Activated protein C demonstrated a beneficial effect on survival that was dependent on severity of illness.


CONCLUSIONS
Trials of agents directed at altering the host's response during sepsis have had variable results, and it appears that several different factors may alter the efficacy of these agents.
Deans
Katherine J
KJ
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Haley
Michael
M
Natanson
Charles
C
Eichacker
Peter Q
PQ
Minneci
Peter C
PC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000925:Anticoagulants / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D011486:Protein C / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D005938:Glucocorticoids; D011486:Protein C