Identifying Sepsis Populations Benefitting from Anticoagulant Therapy: A Prospective Cohort Study Incorporating a Restricted Cubic Spline Regression Model.


Journal

Thrombosis and haemostasis
ISSN: 2567-689X
Titre abrégé: Thromb Haemost
Pays: Germany
ID NLM: 7608063

Informations de publication

Date de publication:
Nov 2019
Historique:
pubmed: 14 8 2019
medline: 9 4 2020
entrez: 14 8 2019
Statut: ppublish

Résumé

 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.  This article identifies the optimal target of anticoagulant therapy in sepsis.  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.  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 (  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.

Sections du résumé

BACKGROUND 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 OBJECTIVE
 This article identifies the optimal target of anticoagulant therapy in sepsis.
METHODS 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 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 (
CONCLUSION CONCLUSIONS
 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.

Identifiants

pubmed: 31408900
doi: 10.1055/s-0039-1693740
doi:

Substances chimiques

Anticoagulants 0

Types de publication

Journal Article Multicenter Study Observational Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

1740-1751

Informations de copyright

Georg Thieme Verlag KG Stuttgart · New York.

Déclaration de conflit d'intérêts

None declared.

Auteurs

Kazuma Yamakawa (K)

Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan.
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

Satoshi Gando (S)

Department of Anesthesiology and Critical Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Acute and Critical Care Center, Department of Acute and Critical Care Medicine, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan.

Hiroshi Ogura (H)

Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

Yutaka Umemura (Y)

Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

Daijiro Kabata (D)

Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan.

Ayumi Shintani (A)

Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan.

Atsushi Shiraishi (A)

Emergency and Trauma Center, Kameda Medical Center, Kamogawa, Chiba, Japan.

Daizoh Saitoh (D)

Division of Traumatology, Research Institute, National Defense Medical College, Tokorozawa, Saitama, Japan.

Seitato Fujishima (S)

Center for General Medicine Education, Keio University School of Medicine, Kanagawa, Japan.

Toshihiko Mayumi (T)

Department of Emergency Medicine, School of Medicine, University of Occupational and Environmental Health Japan, Fukuoka, Japan.

Shigeki Kushimoto (S)

Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, Sendai Japan.

Toshikazu Abe (T)

Department of General Medicine, Juntendo University, Tokyo, Japan.
Health Services Research and Development Center, University of Tsukuba, Tokyo, Japan.

Yasukazu Shiino (Y)

Department of Acute Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.

Taka-Aki Nakada (TA)

Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Takehiko Tarui (T)

Department of Trauma and Critical Care Medicine, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.

Toru Hifumi (T)

Department of Emergency and Critical Care Medicine, St. Luke's International Hospital, Tokyo, Japan.

Yasuhiro Otomo (Y)

Trauma and Acute Critical Care Center, Medical Hospital, Tokyo Medical and Dental University, Tokyo, Japan.

Kohji Okamoto (K)

Department of Surgery, Center for Gastroenterology and Liver Disease, Kitakyushu City Yahata Hospital, Kitakyushu, Japan.

Joji Kotani (J)

Division of Disaster and Emergency Medicine, Department of Surgery Related, Kobe University Graduate School of Medicine, Kobe, Japan.

Yuichiro Sakamoto (Y)

Emergency and Critical Care Medicine, Saga University Hospital, Saga, Japan.

Junichi Sasaki (J)

Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.

Shin-Ichiro Shiraishi (SI)

Department of Emergency and Critical Care Medicine, Aizu Chuo Hospital, Aizu, Japan.

Kiyotsugu Takuma (K)

Emergency & Critical Care Center, Kawasaki Municipal Hospital, Kawasaki, Kanagawa, Japan.

Ryosuke Tsuruta (R)

Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Yamaguchi, Japan.

Akiyoshi Hagiwara (A)

Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.

Tomohiko Masuno (T)

Department of Emergency and Critical Care Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.

Naoshi Takeyama (N)

Advanced Critical Care Center, Aichi Medical University Hospital, Aichi-gun, Aichi, Japan.

Norio Yamashita (N)

Advanced Emergency Medical Service Center, Kurume University Hospital, Kurume, Fukuoka, Japan.

Hiroto Ikeda (H)

Department of Emergency Medicine, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan.

Masashi Ueyama (M)

Department of Trauma, Critical Care Medicine, and Burn Center, Japan Community Healthcare Organization, Chukyo Hospital, Nagoya, Aichi, Japan.

Satoshi Fujimi (S)

Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan.

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