Recombinant human soluble thrombomodulin in sepsis-induced disseminated intravascular coagulation: a multicenter propensity score analysis

• Published in: Intensive care medicine Vol. 39; no. 4; pp. 644 - 652
• Main Authors: Yamakawa, Kazuma, Ogura, Hiroshi, Fujimi, Satoshi, Morikawa, Miki, Ogawa, Yoshihito, Mohri, Tomoyoshi, Nakamori, Yasushi, Inoue, Yoshiaki, Kuwagata, Yasuyuki, Tanaka, Hiroshi, Hamasaki, Toshimitsu, Shimazu, Takeshi
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.04.2013; Springer; Springer Nature B.V
• Subjects: Acuity; Aged; Anesthesiology; Anticoagulants; APACHE; Care and treatment; Cohort analysis; Comparative analysis; Critical care; Critical Care Medicine; Disseminated intravascular coagulation; Disseminated Intravascular Coagulation - drug therapy; Disseminated Intravascular Coagulation - etiology; Disseminated Intravascular Coagulation - mortality; Emergency Medicine; Female; Health aspects; Hospital Mortality; Hospitals; Humans; Infection; Intensive; Intensive care; Intensive Care Units; Japan; Male; Medical referrals; Medicine; Medicine & Public Health; Middle Aged; Mortality; Multicenter Studies as Topic; Original; Pain Medicine; Pediatrics; Pneumology/Respiratory System; Propensity Score; Regression Analysis; Respiration, Artificial - statistics & numerical data; Retrospective Studies; Sepsis; Sepsis - complications; Sepsis - drug therapy; Sepsis - mortality; Tertiary Care Centers; Thrombomodulin - administration & dosage; Thrombomodulin - therapeutic use; Treatment Outcome; Ventilators; Japan; Sepsis; Retrospective studies; Thrombomodulin; Outcome assessment; Anticoagulant therapy; DIC
• ISSN: 0342-4642; 1432-1238; 1432-1238
• DOI: 10.1007/s00134-013-2822-2

Purpose Evidence of efficacy and safety of, and especially mortality related to, recombinant human thrombomodulin (rhTM) treatment for sepsis-induced disseminated intravascular coagulation (DIC) is limited. We hypothesized that patients with sepsis-induced DIC receiving treatment with rhTM would have improved mortality compared with those with similar acuity who did not. Methods This retrospective cohort study conducted in three tertiary referral hospitals in Japan between January 2006 and June 2011 included all patients with sepsis-induced DIC who required ventilator management. Primary endpoint was in-hospital mortality, with duration of intensive care unit treatment, changes in DIC scores and rate of bleeding complications as secondary endpoints. Regression technique was used to develop a propensity model adjusted for baseline imbalances between groups. Results Eligible were 162 patients with sepsis-induced DIC; 68 patients received rhTM and 94 did not. Patients receiving rhTM had higher severity of illness according to baseline characteristics. After adjusting for these imbalances by stratified propensity score analysis, treatment with rhTM was significantly associated with reduced in-hospital mortality (adjusted hazard ratio, 0.45; 95 % confidential interval, 0.26–0.77; p  = 0.013). An association between rhTM treatment and higher numbers of intensive care unit-free days, ventilator-free days, and vasopressor-free days were observed. DIC scores were significantly decreased in the rhTM group compared with the control group in the early period after rhTM treatment, whereas the incidence of bleeding-related adverse events did not differ between the two groups. Conclusions Therapy with rhTM may be associated with reduced in-hospital mortality in adult mechanically ventilated patients with sepsis-induced DIC.