Recombinant human soluble thrombomodulin in sepsis-induced disseminated intravascular coagulation: a multicenter propensity score analysis.
OBJECTIVE
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.
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, 2-15, Yamadaoka, Suita, Osaka, 565-0871, Japan. k.yamakawa0911@gmail.com
Kazuma
K
Yamakawa
Hiroshi
H
Ogura
Satoshi
S
Fujimi
Miki
M
Morikawa
Yoshihito
Y
Ogawa
Tomoyoshi
T
Mohri
Yasushi
Y
Nakamori
Yoshiaki
Y
Inoue
Yasuyuki
Y
Kuwagata
Hiroshi
H
Tanaka
Toshimitsu
T
Hamasaki
Takeshi
T
Shimazu
D018806:APACHE; D000368:Aged; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D007564:Japan; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D057216:Propensity Score; D012044:Regression Analysis; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D012189:Retrospective Studies; D018805:Sepsis / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D062606:Tertiary Care Centers; D018180:Thrombomodulin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D018180:Thrombomodulin