Journal of Critical Care
Volume 26, Issue 6 , Pages 539-545, December 2011

Severe protein C deficiency is associated with organ dysfunction in patients with severe sepsis☆☆

  • Andrew D. Shaw, MB

      Affiliations

    • Department of Anesthesiology, Duke University, DUMC 3094, Durham, NC 27710, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 919 286 6938; fax: +1 919 286 6853.
  • ,
  • George M. Vail, MD

      Affiliations

    • Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
  • ,
  • Douglas J. Haney, PhD

      Affiliations

    • Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
  • ,
  • Jin Xie, MS

      Affiliations

    • Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
  • ,
  • Mark D. Williams, MD

      Affiliations

    • Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA

published online 07 July 2011.

Abstract 

Purpose

The aim of this study was to assess the relationship between protein C levels and temporal changes in organ dysfunction.

Materials and Methods

Using data from the placebo arm of Recombinant Human Activated PROtein C Worldwide Evaluation in Severe Sepsis trial (N = 775), we compared the development of organ dysfunction over time, in adult severe sepsis patients with and without severe protein C deficiency.

Results

At study enrollment (baseline), patients with and without severe protein C deficiency were similar in age and likelihood of comorbidities. Patients with severe protein C deficiency had lower arterial blood pressure (P = .0006), greater serum creatinine concentration (P < .0001), elevated markers of thrombosis and inflammation, and impairment of fibrinolysis (P < .0001). The baseline PaO2/FiO2 ratio was not significantly different between the 2 groups. Seven days after study enrollment, cardiovascular and renal function remained significantly worse in patients with severe protein C deficiency (P < .0001), and respiratory dysfunction was greater (P < .0001). Baseline protein C deficiency was seen to be associated with subsequent pulmonary, renal, and hematologic organ failure.

Conclusions

Severe protein C deficiency in patients with severe sepsis is associated with both the incidence and severity of organ dysfunction and subsequent worsening of organ function and may be a useful predictor of organ failure in severe sepsis.

Keywords: Sepsis, Protein C, Organ dysfunction, SOFA, Outcome

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 Financial support: This work was sponsored by Eli Lilly and Company.

☆☆ Competing interests: Author Ms. Xie is employed by and is a stockholder in Eli Lilly and Company. Drs. Vail, Haney, and Williams are previous employees of Eli Lilly and Company. Dr. Shaw has received speaker bureau and advisory board fees from Eli Lilly and Company.

PII: S0883-9441(11)00208-5

doi:10.1016/j.jcrc.2011.05.006

Journal of Critical Care
Volume 26, Issue 6 , Pages 539-545, December 2011