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


METHODS
III, therapeutic study.
Department of Emergency and Critical Care, Osaka General Medical Center, Osaka, Japan. yoshi.ogawa@hp-emerg.med.osaka-u.ac.jp
Yoshihito
Y
Ogawa
Kazuma
K
Yamakawa
Hiroshi
H
Ogura
Takeyuki
T
Kiguchi
Tomoyoshi
T
Mohri
Yasushi
Y
Nakamori
Yasuyuki
Y
Kuwagata
Takeshi
T
Shimazu
Toshimitsu
T
Hamasaki
Satoshi
S
Fujimi
D000368:Aged; D004211:Disseminated Intravascular Coagulation / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011994:Recombinant Proteins; D012131:Respiratory Insufficiency / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology; D012189:Retrospective Studies; D018805:Sepsis / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D015996:Survival Rate / Q000639:trends; D018180:Thrombomodulin / Q000008:administration & dosage / Q000627:therapeutic use*
D011994:Recombinant Proteins; D018180:Thrombomodulin