Abstract
Background: Patients with acute respiratory distress syndrome (ARDS) often develop disseminated intravascular coagulation (DIC), which can worsen clinical outcomes. Anticoagulant therapy such as human soluble recombinant thrombomodulin (rTM) treatment may help to resolve DIC and improve prognoses. This study analyzes the influence of rTM treatment on in-hospital mortality in patients with both ARDS and DIC. Methods: In a retrospective cohort study, we examined 75 patients with ARDS and DIC who had been admitted to the intensive care units of 3 university hospitals between March 1, 2008 and February 29, 2016. Data were extracted from clinical records. Subjects were divided into a control group comprising 38 patients who were not administered rTM and an rTM group comprising 37 patients who were administered rTM. Kaplan-Meier survival analysis was performed to produce survival curves and the log-rank test was used to compare survival between the 2 groups. We conducted a Cox proportional hazards regression analysis where the dependent variable was in-hospital mortality and the main independent variable of interest was the use of rTM; the hazard ratio of rTM use was calculated. Results: The variables of with P values below 0.2 were age (P=0.15), source of sepsis (P=0.17), rTM use (P=0.02) and AT concentrate use (P=0.17) between the survivors and non-survivors. There was no significant difference in the ARDS severity levels between the rTM group and the control group (P=0.71). In-hospital mortality was significantly lower (P=0.02) in the rTM group (37.8%) than in the control group (65.8%). The hazard ratio of rTM use for mortality was 0.49 (95% confidence interval: 0.26-0.95; P=0.03). In addition, the log-rank test showed that the rTM group had significantly better survival than the control group (P=0.04). Conclusion: Our study indicates that rTM treatment significantly improved prognoses in patients with both ARDS and DIC.
Highlights
Patients with acute respiratory distress syndrome (ARDS) often develop disseminated intravascular coagulation (DIC), which can worsen clinical outcomes
A phase III clinical trial of recombinant thrombomodulin (rTM) treatment for DIC associated with hematologic malignancies and infection reported that patients treated with rTM had a significantly higher DIC resolution rate when compared with patients treated with unfractionated heparin; there was no significant difference in 28-day mortality between the 2 treatment modalities [7]
The most common level of ARDS severity in the control group and rTM group was moderate ARDS (47.4% and 56.8%, respectively), followed by mild ARDS (31.6% and 27.0%, respectively) and severe ARDS (21.1% and 16.2%, respectively); there was no significant difference among these severity levels (P=0.71)
Summary
Patients with acute respiratory distress syndrome (ARDS) often develop disseminated intravascular coagulation (DIC), which can worsen clinical outcomes. Anticoagulant therapy such as human soluble recombinant thrombomodulin (rTM) treatment may help to resolve DIC and improve prognoses. Acute respiratory distress syndrome (ARDS) refers to the development of acute noncardiogenic pulmonary edema due to an increase in pulmonary vascular permeability It is not uncommon for patients with ARDS to develop disseminated intravascular coagulation (DIC) [1] and patients with DIC develop ARDS with fairly high frequency [1,2]. Human soluble recombinant thrombomodulin (rTM) is composed of the active extracellular domain of thrombomodulin, which forms a reversible complex with thrombin to convert plasma protein C into its activated form This in turn inactivates coagulation factors and reduces the pro-inflammatory effects of thrombin.
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