Recombinant human activated protein C in the treatment of severe sepsis: an evidence-based review.

Abstract

In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for recombinant human activated protein C that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. Recombinant human activated protein C is recommended in patients at high risk of death (septic shock, sepsis-induced acute respiratory distress syndrome, Acute Physiology and Chronic Health Evaluation II score of >/=25, and sepsis-induced multiorgan failure) and no absolute contraindication related to bleeding risk or relative contraindication that outweighs the potential benefit. The presence or absence of disseminated intravascular coagulation should not influence the decision to administer recombinant human activated protein C. Heparin should be withheld during administration of recombinant human activated protein C.