Kazuma Yamakawa1,2, Satoshi Gando3,4, Hiroshi Ogura2, Yutaka Umemura2, Daijiro Kabata5, Ayumi Shintani5, Atsushi Shiraishi6, Daizoh Saitoh7, Seitato Fujishima8, Toshihiko Mayumi9, Shigeki Kushimoto10, Toshikazu Abe11,12, Yasukazu Shiino13, Taka-Aki Nakada14, Takehiko Tarui15, Toru Hifumi16, Yasuhiro Otomo17, Kohji Okamoto18, Joji Kotani19, Yuichiro Sakamoto20, Junichi Sasaki21, Shin-Ichiro Shiraishi22, Kiyotsugu Takuma23, Ryosuke Tsuruta24, Akiyoshi Hagiwara25, Tomohiko Masuno26, Naoshi Takeyama27, Norio Yamashita28, Hiroto Ikeda29, Masashi Ueyama30, Satoshi Fujimi1. 1. Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan. 2. Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. 3. Department of Anesthesiology and Critical Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan. 4. Acute and Critical Care Center, Department of Acute and Critical Care Medicine, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan. 5. Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan. 6. Emergency and Trauma Center, Kameda Medical Center, Kamogawa, Chiba, Japan. 7. Division of Traumatology, Research Institute, National Defense Medical College, Tokorozawa, Saitama, Japan. 8. Center for General Medicine Education, Keio University School of Medicine, Kanagawa, Japan. 9. Department of Emergency Medicine, School of Medicine, University of Occupational and Environmental Health Japan, Fukuoka, Japan. 10. Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, Sendai Japan. 11. Department of General Medicine, Juntendo University, Tokyo, Japan. 12. Health Services Research and Development Center, University of Tsukuba, Tokyo, Japan. 13. Department of Acute Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan. 14. Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan. 15. Department of Trauma and Critical Care Medicine, Kyorin University School of Medicine, Mitaka, Tokyo, Japan. 16. Department of Emergency and Critical Care Medicine, St. Luke's International Hospital, Tokyo, Japan. 17. Trauma and Acute Critical Care Center, Medical Hospital, Tokyo Medical and Dental University, Tokyo, Japan. 18. Department of Surgery, Center for Gastroenterology and Liver Disease, Kitakyushu City Yahata Hospital, Kitakyushu, Japan. 19. Division of Disaster and Emergency Medicine, Department of Surgery Related, Kobe University Graduate School of Medicine, Kobe, Japan. 20. Emergency and Critical Care Medicine, Saga University Hospital, Saga, Japan. 21. Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan. 22. Department of Emergency and Critical Care Medicine, Aizu Chuo Hospital, Aizu, Japan. 23. Emergency & Critical Care Center, Kawasaki Municipal Hospital, Kawasaki, Kanagawa, Japan. 24. Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Yamaguchi, Japan. 25. Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan. 26. Department of Emergency and Critical Care Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan. 27. Advanced Critical Care Center, Aichi Medical University Hospital, Aichi-gun, Aichi, Japan. 28. Advanced Emergency Medical Service Center, Kurume University Hospital, Kurume, Fukuoka, Japan. 29. Department of Emergency Medicine, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan. 30. Department of Trauma, Critical Care Medicine, and Burn Center, Japan Community Healthcare Organization, Chukyo Hospital, Nagoya, Aichi, Japan.
Abstract
BACKGROUND: Anticoagulant therapy has seldom been achieved in randomized trials targeting nonspecific overall sepsis patients. Although the key components to identify the appropriate target in sepsis may be disseminated intravascular coagulation (DIC) and high disease severity, the interaction and relation of these two components for the effectiveness of therapy remain unknown. OBJECTIVE: This article identifies the optimal target of anticoagulant therapy in sepsis. METHODS: We used a prospective nationwide cohort targeting consecutive adult severe sepsis patients in 59 intensive care units in Japan to assess associations between anticoagulant therapy and in-hospital mortality according to DIC (International Society on Thrombosis and Haemostasis [ISTH] overt and Japanese Association for Acute Medicine DIC scores) and disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] and Sequential Organ Failure Assessment scores). Multivariable Cox proportional hazard regression analysis with nonlinear restricted cubic spline including a two-way interaction term (treatment × each score) and three-way interaction term (treatment × ISTH overt DIC score × APACHE II score) was performed. RESULTS: The final study cohort comprised 1,178 sepsis patients (371 received anticoagulants and 768 did not). The regression model including the two-way interaction term showed significant interaction between intervention and disease severity as indicated by the ISTH overt DIC score and APACHE II score (p = 0.046 and p = 0.101, respectively). Three-way interaction analysis revealed that risk hazard was suppressed in the anticoagulant group compared with the control group in the most severe subset of both scores. CONCLUSION: Anticoagulant therapy was associated with better outcome according to the deterioration of both DIC and disease severity, suggesting that anticoagulant therapy should be restricted to patients having DIC and high disease severity simultaneously. Georg Thieme Verlag KG Stuttgart · New York.
BACKGROUND: Anticoagulant therapy has seldom been achieved in randomized trials targeting nonspecific overall sepsispatients. Although the key components to identify the appropriate target in sepsis may be disseminated intravascular coagulation (DIC) and high disease severity, the interaction and relation of these two components for the effectiveness of therapy remain unknown. OBJECTIVE: This article identifies the optimal target of anticoagulant therapy in sepsis. METHODS: We used a prospective nationwide cohort targeting consecutive adult severe sepsispatients in 59 intensive care units in Japan to assess associations between anticoagulant therapy and in-hospital mortality according to DIC (International Society on Thrombosis and Haemostasis [ISTH] overt and Japanese Association for Acute Medicine DIC scores) and disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] and Sequential Organ Failure Assessment scores). Multivariable Cox proportional hazard regression analysis with nonlinear restricted cubic spline including a two-way interaction term (treatment × each score) and three-way interaction term (treatment × ISTH overt DIC score × APACHE II score) was performed. RESULTS: The final study cohort comprised 1,178 sepsispatients (371 received anticoagulants and 768 did not). The regression model including the two-way interaction term showed significant interaction between intervention and disease severity as indicated by the ISTH overt DIC score and APACHE II score (p = 0.046 and p = 0.101, respectively). Three-way interaction analysis revealed that risk hazard was suppressed in the anticoagulant group compared with the control group in the most severe subset of both scores. CONCLUSION: Anticoagulant therapy was associated with better outcome according to the deterioration of both DIC and disease severity, suggesting that anticoagulant therapy should be restricted to patients having DIC and high disease severity simultaneously. Georg Thieme Verlag KG Stuttgart · New York.