Use of Recombinant Human Soluble Thrombomodulin in Patients with Sepsis-Induced Disseminated Intravascular Coagulation after Intestinal Perforation

Background: Anticoagulant therapy has been evaluated with respect to its potential usefulness in reducing the high mortality rates associated with severe sepsis, including sepsis-induced disseminated intravascular coagulation (DIC) after intestinal perforation. We examined the hypothesis that recombinant human soluble thrombomodulin (rhTM) is effective in the treatment of patients with septic shock with sepsis-induced DIC after laparotomy for intestinal perforation. Methods: We performed propensity-score and instrumental variable analyses of the Japanese Diagnosis Procedure Combination in-patient database, a nationwide administrative database. The main outcome was 28-day in-hospital all-cause mortality. Results: We categorized eligible patients (n = 2202) from 622 hospitals into the rhTM group (n = 726) and control group (n = 1476). Propensity-score matching created 621 matched pairs of patients with and without rhTM. There was neither significant difference in 28-day mortality between the two groups in the unmatched analysis (rhTM vs. control, 25.3 vs. 23.4%, respectively; difference, 1.9%; 95% CI, −1.9 to 5.7) nor in the propensity-score-matched analysis (rhTM vs. control, 26.1 vs. 24.8%, respectively; difference, 1.3%; 95% CI, −3.6 to 6.1). The logistic analysis showed no significant association between the use of rhTM and the mortality in propensity-score-matched patients (OR, 1.1; 95% CI, 0.82–1.4). The instrumental variable analyses, using the hospital rhTM-prescribing proportion as the variable, found that receipt of rhTM was not associated with the reduction in the mortality (risk difference, −6.7%; 95% CI, −16.4 to 3.0). Conclusion: We found no association between administration of rhTM and 28-day mortality in mechanically ventilated patients with septic shock and concurrent DIC after intestinal perforation.