Profound Endothelial Damage Predicts Impending Organ Failure and Death in Sepsis

Maria E. Johansen; Pär I. Johansson; Sisse R. Ostrowski; Morten H. Bestle; Lars Hein; Anne L. G. Jensen; Peter Søe-Jensen; Mads H. Andersen; Morten Steensen; Thomas Mohr; Katrin Thormar; Bettina Lundgren; Alessandro Cozzi-Lepri; Jens D. Lundgren; Jens-Ulrik Jensen

doi:10.1055/s-0034-1398377

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2015; 41(01): 016-025
DOI: 10.1055/s-0034-1398377

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Profound Endothelial Damage Predicts Impending Organ Failure and Death in Sepsis

Maria E. Johansen

¹CHIP, Department of Infectious Diseases and Rheumatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

,

Pär I. Johansson

²Department of Surgery, University of Texas Medical School at Houston, Houston, Texas

³Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, Denmark

,

Sisse R. Ostrowski

³Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, Denmark

,

Morten H. Bestle

⁴Department of Anesthesia and Intensive Care at Nordsjaellands Hospital, Denmark

,

Lars Hein

⁴Department of Anesthesia and Intensive Care at Nordsjaellands Hospital, Denmark

,

Anne L. G. Jensen

⁵Department of Anesthesia and Intensive Care at University Hospital Glostrup, Denmark

,

Peter Søe-Jensen

⁶Department of Anesthesia and Intensive Care at University Hospital Herlev, Denmark

,

Mads H. Andersen

⁷Department of Anesthesia and Intensive Care at University Hospital Aarhus, Denmark

,

Morten Steensen

⁸Department of Anesthesia and Intensive Care at University Hospital Hvidovre, Denmark

,

Thomas Mohr

⁹Department of Anesthesia and Intensive Care at University Hospital Gentofte, Denmark

,

Katrin Thormar

¹⁰Department of Anesthesia and Intensive Care at University Hospital Bispebjerg, Denmark

,

Bettina Lundgren

¹¹Centre of Diagnostic Investigations, Rigshospitalet, Denmark

,

Alessandro Cozzi-Lepri

¹CHIP, Department of Infectious Diseases and Rheumatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

¹²Department of Virology, Royal Free and University College Medical School London, United Kingdom

,

Jens D. Lundgren

¹CHIP, Department of Infectious Diseases and Rheumatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

,

Jens-Ulrik Jensen

¹CHIP, Department of Infectious Diseases and Rheumatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

¹³Department of Clinical Microbiology at Copenhagen University Hospital Hvidovre, Denmark

› Institutsangaben

Abstract

Endothelial damage contributes to organ failure and mortality in sepsis, but the extent of the contribution remains poorly quantified. Here, we examine the association between biomarkers of superficial and profound endothelial damage (syndecan-1 and soluble thrombomodulin [sTM], respectively), organ failure, and death in sepsis. The data from a clinical trial, including critically ill patients predominantly suffering sepsis (Clinicaltrials.gov: NCT00271752) were studied. Syndecan-1 and sTM levels at the time of study enrollment were determined. The predictive ability of biomarker levels on death and organ failures during follow-up were assessed in Cox models adjusted for potential confounders including key organ dysfunction measures assessed at enrollment. Of the 1,103 included patients, 418 died. sTM levels at the time of enrollment independently predicted risk of death in adjusted models (hazard ratio [HR] [highest quartile > 14 ng/mL vs. lowest quartile < 7 ng/mL] 2.2 [95% confidence interval [CI]: 1.2–4.0], p = 0.02, respectively). Conversely, syndecan-1 levels failed to predict death (adjusted HR [> 240 vs. < 70 ng/mL] 1.0 [95% CI: 0.6–1.5], p = 0.67). sTM but not syndecan-1 levels at enrollment predicted risk of multiple organ failure during follow-up (HR [> 14 ng/mL vs. < 7 ng/mL] 3.5 [95% CI: 1.5–8.3], p = 0.005 and 2.0 [95% CI: 0.8–5.0], p = 0.1321, respectively). Profound damage to the endothelium independently predicts risk of multiple organ failure and death in septic patients. Our findings also suggest that the detrimental effect of profound endothelial damage on risk of death operates via mechanisms other than causing organ failures per se. Therefore, damage to the endothelium appears centrally involved in the pathogenesis of death in sepsis and could be a target for intervention.

Keywords

sepsis - endothelial damage - thrombomodulin - syndecan-1

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Referenzen

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