Recombinant human soluble thrombomodulin and mortality in severe pneumonia patients with sepsis-associated disseminated intravascular coagulation: an observational nationwide study.
BACKGROUND
The association between recombinant human soluble thrombomodulin (rhTM) use and mortality in patients with sepsis-associated disseminated intravascular coagulation (DIC) remains controversial.


OBJECTIVE
To examine the hypothesis that rhTM could be effective in the treatment of patients with sepsis-associated DIC following severe pneumonia.


METHODS
Propensity score and instrumental variable analyses using a nationwide administrative database, the Japanese Diagnosis Procedure Combination inpatient database, were used. The main outcome was 28-day in-hospital all-cause mortality.


RESULTS
Eligible patients (n = 6342) from 936 hospitals were categorized into the rhTM group (n = 1280) or control group (n = 5062). Propensity score matching created a matched cohort of 1140 pairs with and without rhTM. No significant difference in 28-day mortality was documented between the two groups in the unmatched analysis (rhTM vs. control, 37.0%, 474/1280 vs. 36.9%, 1866/5062; odds ratio [OR], 1.00; 95%CI, 0.98-1.03), nor in the propensity-matched analysis (37.6%, 429/1140 vs. 37.0%, 886/1140; OR, 1.01; 95%CI, 0.93-1.10). The logistic regression analysis did not show a significant association between the use of rhTM and 28-day mortality in propensity-matched patients (OR, 1.00; 95%CI, 0.87-1.22). An analysis using the hospital rhTM-prescribing rate as an instrumental variable found that receipt of rhTM was not associated with reduction in mortality at 28 days (risk difference, 0.008; 95% CI, -0.08-0.98).


CONCLUSIONS
This large retrospective nationwide study demonstrated that there might be little association between the use of rhTM and mortality in severe pneumonia patients with sepsis-associated DIC. A multinational randomized trial is required to confirm this.
Department of Clinical Epidemiology and Health Economics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; Department of Emergency and Critical Care Medicine, Nippon Medical School, Tokyo, Japan.
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T
Tagami
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Matsui
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Horiguchi
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Fushimi
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Yasunaga
D000368:Aged; D000369:Aged, 80 and over; D016208:Databases, Factual; D004211:Disseminated Intravascular Coagulation / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007564:Japan / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011014:Pneumonia / Q000401:mortality*; D057216:Propensity Score; D016016:Proportional Hazards Models; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D018805:Sepsis / Q000175:diagnosis / Q000401:mortality*; D012720:Severity of Illness Index; D018180:Thrombomodulin / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D011994:Recombinant Proteins; C546931:THBD protein, human; D018180:Thrombomodulin
anticoagulants; disseminated intravascular coagulation; outcomes assessment; pneumonia; sepsis