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Activated protein C for the treatment of severe sepsis

G Houston1, B H Cuthbertson

  • 1Intensive Care Unit, Aberdeen Royal Infirmary, Aberdeen, UK. gordonhouston@nhs.net

Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases
|May 7, 2009
PubMed

Insights

Recombinant human activated protein C showed a mortality benefit in severe sepsis patients. However, subsequent trials and controversies raise questions about its efficacy and safety in sepsis management.

Area of Science:

  • Critical Care Medicine
  • Pharmacology
  • Biochemistry

Background:

  • Severe sepsis is a life-threatening condition with high mortality rates.
  • Recombinant human activated protein C (rhAPC) was introduced following the PROWESS trial, showing a significant reduction in mortality.
  • Concerns regarding rhAPC's efficacy and safety profile have emerged from subsequent studies and protocol analyses.

Purpose of the Study:

  • To critically review the evidence supporting and refuting the use of rhAPC in severe sepsis.
  • To address the ongoing controversy surrounding rhAPC's clinical utility.

Main Methods:

  • Systematic review of clinical trials and observational studies.
  • Analysis of data from the PROWESS trial and post-marketing surveillance.
  • Evaluation of the safety and efficacy data of rhAPC in severe sepsis.

Main Results:

  • The PROWESS trial reported a 6.1% absolute mortality reduction with rhAPC.
  • Subsequent trials and meta-analyses have yielded conflicting results regarding efficacy.
  • Concerns have been raised about an increased risk of bleeding events associated with rhAPC use.

Conclusions:

  • The role of rhAPC in severe sepsis management remains controversial.
  • Further research is needed to clarify the risk-benefit profile of rhAPC.
  • Clinical decisions regarding rhAPC should consider the evolving evidence and patient-specific factors.

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