Recombinant human soluble thrombomodulin improves mortality and respiratory dysfunction in patients with severe sepsis

J Trauma Acute Care Surg. 2012 May;72(5):1150-7. doi: 10.1097/TA.0b013e3182516ab5.

Abstract

Background: Respiratory dysfunction associated with severe sepsis is a serious condition leading to poor prognosis. Activation of coagulation is a consequence of and contributor to ongoing lung injury in severe sepsis. The purpose of this study was to examine the efficacy of recombinant human soluble thrombomodulin (rhTM), a novel anticoagulant agent, for treating patients with sepsis-induced disseminated intravascular coagulation (DIC) in terms of mortality and respiratory dysfunction.

Methods: This study comprised 86 consecutive patients with sepsis-induced DIC who required ventilator management. The initial 45 patients were treated without rhTM (control group), and the following 41 patients were given rhTM (0.06 mg/kg/d) for 6 days (rhTM group). Patients were followed up for 90 days after study entry. Sequential Organ Failure Assessment (SOFA) score and lung injury score were recorded until 7 days after entry.

Results: The baseline characteristic of severity of illness was significantly higher in the rhTM group than in the control group. Nevertheless, 90-day mortality rate in the rhTM group was significantly lower than that in the control group (37% vs. 58%, p = 0.038). There was a significant difference in the serial change of SOFA score from baseline to day 7 between the two groups (p = 0.009). Both the respiratory component of the SOFA score and the lung injury score in the rhTM group were significantly lower compared with the control group (p = 0.034 and p < 0.001, respectively).

Conclusions: rhTM may have a significant beneficial effect on mortality and respiratory dysfunction in patients with sepsis-induced DIC.

Level of evidence: III, therapeutic study.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Disseminated Intravascular Coagulation / complications
  • Disseminated Intravascular Coagulation / drug therapy
  • Disseminated Intravascular Coagulation / mortality*
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Prognosis
  • Recombinant Proteins
  • Respiratory Insufficiency / drug therapy*
  • Respiratory Insufficiency / epidemiology
  • Respiratory Insufficiency / etiology
  • Retrospective Studies
  • Sepsis / complications
  • Sepsis / drug therapy
  • Sepsis / mortality*
  • Survival Rate / trends
  • Thrombomodulin / administration & dosage
  • Thrombomodulin / therapeutic use*

Substances

  • Recombinant Proteins
  • Thrombomodulin