腹部緊急手術を施行した敗血症性DIC症例に関する検討
トロンボモジュリン製剤である遺伝子組換え型ヒトトロンボモジュリンは，敗血症性DICの治療薬として近年注目されてきているが，腹部緊急手術後の使用に注目した研究は少ない。そこで，当院で過去約3年間に経験した腹部緊急手術を要した敗血症性DIC症例を対象に，同製剤の使用と周術期の治療成績を後方視的に検討した。投与群24例，非投与群19例であり，投与群でAPACHE Ⅱ scoreが有意に高く (p＝0.02），術後ICU入室率，人工呼吸器使用率が高かった (p＜0.001，p＝0.004）。出血性合併症や死亡率に有意差はなく，投与群では敗血症性DIC診断後の新鮮凍結血漿の投与量が少なかった (p＝0....
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| Published in | Nihon Fukubu Kyukyu Igakkai Zasshi (Journal of Abdominal Emergency Medicine) Vol. 35; no. 3; pp. 195 - 200 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本腹部救急医学会
2015
Japanese Society for Abdominal Emergency Medicine |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1340-2242 1882-4781 |
| DOI | 10.11231/jaem.35.195 |
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| Abstract | トロンボモジュリン製剤である遺伝子組換え型ヒトトロンボモジュリンは，敗血症性DICの治療薬として近年注目されてきているが，腹部緊急手術後の使用に注目した研究は少ない。そこで，当院で過去約3年間に経験した腹部緊急手術を要した敗血症性DIC症例を対象に，同製剤の使用と周術期の治療成績を後方視的に検討した。投与群24例，非投与群19例であり，投与群でAPACHE Ⅱ scoreが有意に高く (p＝0.02），術後ICU入室率，人工呼吸器使用率が高かった (p＜0.001，p＝0.004）。出血性合併症や死亡率に有意差はなく，投与群では敗血症性DIC診断後の新鮮凍結血漿の投与量が少なかった (p＝0.02）。以上により，同製剤は腹部緊急手術の周術期でも安全に使用できることが確認され，敗血症性DIC診断後の輸血量を減らせる可能性が示唆された。 |
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| AbstractList | トロンボモジュリン製剤である遺伝子組換え型ヒトトロンボモジュリンは，敗血症性DICの治療薬として近年注目されてきているが，腹部緊急手術後の使用に注目した研究は少ない。そこで，当院で過去約3年間に経験した腹部緊急手術を要した敗血症性DIC症例を対象に，同製剤の使用と周術期の治療成績を後方視的に検討した。投与群24例，非投与群19例であり，投与群でAPACHE Ⅱ scoreが有意に高く (p＝0.02），術後ICU入室率，人工呼吸器使用率が高かった (p＜0.001，p＝0.004）。出血性合併症や死亡率に有意差はなく，投与群では敗血症性DIC診断後の新鮮凍結血漿の投与量が少なかった (p＝0.02）。以上により，同製剤は腹部緊急手術の周術期でも安全に使用できることが確認され，敗血症性DIC診断後の輸血量を減らせる可能性が示唆された。 Although several studies on recombinant soluble human thrombomodulin (rhTM) have been reported, the safety/efficacy of rhTM for sepsis-associated disseminated intravascular coagulation (DIC) after emergency laparotomy remains controversial. We retrospectively reviewed the treatment and clinical characteristics of patients with sepsis-associated DIC who underwent emergency laparotomy between 2012 and 2014 at our institution. In all, 24 patients were treated with rhTM, while the remaining 19 were not. There were no significant differences in the background characteristics of the patients between the two groups, however, the APACHE Ⅱ score, admission rate to the intensive care unit, and respiratory utilization were higher in the cases treated with rhTM (p=0.02, p<0.001, and p=0.004, respectively). There was no significant association between rhTM use, mortality and complications including postoperative hemorrhage. The administration rate of fresh frozen plasma (FFP) was lower in the group that was treated with rhTM (p=0.02). This study demonstrates that rhTM may be used safely, even after emergency laparotomy, and may be associated with a reduced amount of FFP transfusion. トロンボモジュリン製剤である遺伝子組換え型ヒトトロンボモジュリンは，敗血症性DICの治療薬として近年注目されてきているが，腹部緊急手術後の使用に注目した研究は少ない。そこで，当院で過去約3年間に経験した腹部緊急手術を要した敗血症性DIC症例を対象に，同製剤の使用と周術期の治療成績を後方視的に検討した。投与群24例，非投与群19例であり，投与群でAPACHE Ⅱ scoreが有意に高く (p＝0.02），術後ICU入室率，人工呼吸器使用率が高かった (p＜0.001，p＝0.004）。出血性合併症や死亡率に有意差はなく，投与群では敗血症性DIC診断後の新鮮凍結血漿の投与量が少なかった (p＝0.02）。以上により，同製剤は腹部緊急手術の周術期でも安全に使用できることが確認され，敗血症性DIC診断後の輸血量を減らせる可能性が示唆された。 |
| Author | 加瀬, 建一 山元, 良 小林, 健二 篠崎, 浩治 |
| Author_FL | Shinozaki Hiroharu Kobayashi Kenji Kase Kenichi Yamamoto Ryo |
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| Author_xml | – sequence: 1 fullname: 篠崎, 浩治 organization: 栃木県済生会宇都宮病院外科 – sequence: 1 fullname: 山元, 良 organization: 栃木県済生会宇都宮病院救急科 – sequence: 1 fullname: 小林, 健二 organization: 栃木県済生会宇都宮病院救急科 – sequence: 1 fullname: 加瀬, 建一 organization: 栃木県済生会宇都宮病院救急科 |
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| Copyright | 2014, Japanese Society for Abdominal Emargency Medicine |
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| DocumentTitleAlternate | Treatment of Sepsis-associated Disseminated Intravascular Coagulation after Emergency Laparotomy |
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| PublicationTitle_FL | J Abdom Emerg Med 日本腹部救急医学会雑誌 日腹部救急医会誌 Journal of Abdominal Emergency Medicine Nihon Fukubu Kyukyu Igakkai Zasshi |
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| References | 14) Nagato M, Okamoto K, Abe Y, et al: Recombinant human soluble thrombomodulin decreases the plasma high-mobility group box-1 protein levels, whereas improving the acute liver injury and survival rates in experimental endotoxemia. Crit Care Med 2009; 37: 2181-2186. 4) 齋藤大蔵，岡本好司，真弓俊彦，ほか：急性期DIC診断基準 第二次他施設共同前向き試験結果報告 治療効果の分析．日救急医会誌2007; 18: 268-272 7) Kitchens CS: Thrombocytopenia and thrombosis in disseminated intravascular coagulation (DIC). Hematology 2009; 2009: 240-246. 15) Saito H, Maruyama I, Shimazaki S, et al: Efficacy and safety of recombinant human soluble thrombomodulin（ART-124) in disseminated intravascular coagulation: Results of a phase Ⅲ, randomized, double-blind clinical trial. J Thromb Haemost 2007; 5: 31-41. 9) Owen WG, Esmon CT: Functional properties of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. J Biol Chem 1981; 256: 5532-5535. 10) Conway EM: Thrombomodulin and its role in inflammation. Semin Immunopathol 2012; 34: 107-125. 18) Ogawa Y, Yamanaka K, Ogura H, et al: Recombinant human soluble thrombomodulin improves mortality and respiratory dysfunction in patients with severe sepsis. J Trauma Acute Care Surg 2012; 72: 1150-1157. 5) Vincent JL, Ramesh MK, Ernest D, et al: A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Soluble Thrombomodulin, ART-123, in Patients With Sepsis and Suspected Disseminated Intravascular Coagulation. Crit Care Med 2013; 41: 2069-2079. 19) Fink MP: Recombinant Soluble Thrombomodulin as an Adjunctive Treatment for Sepsis and Disseminated Intravascular Coagulation: Relatively Safe and Possibly Effective. Crit Care Med 2013; 41: 2221-2223. 2) 日本集中治療医学会Sepsis Registry委員会：日本版敗血症診療ガイドラインThe Japanese Guidelines for the Management of Sepsis．日集中医誌 2013; 20: 124-173 3) Kawano N, Yoshida S, Ono N, et al: Clinical Features and Outcomes of 35 Disseminated Intravascular Coagulation Cases Treated with Recombinant Human Soluble Thrombomodulin at a Single Institution. J Clin Exp Hematop 2011; 51: 101-107. 13) Hagiwara S, Iwasaka H, Matsumoto S, et al: In vivo and in vitro effects of the anticoagulant, thrombomodulin, on the inflammatory response in rodent models. Shock 2010; 33: 282-288. 16) Yamakawa K, Fujimi S, Mohri T, et al: Treatment effects of recombinant human soluble thrombomodulin in patients with severe sepsis: A historical control study. Crit Care 2011; 15: R123. 6) 丸藤 哲，齋藤大蔵，石倉宏恭，ほか：急性期DIC診断基準で診断された敗血症性DICに対するアンチトロンビンの効果．日救急医会誌2013; 24: 105-115 8) 澤野宏隆，重光胤明，吉永雄一，ほか：敗血症性DICにおけるリコンビナントトロンボモジュリンと安置トロンビン製剤の併用療法の有用性．日救急医会誌2013; 24: 119-131 17) Kato T, Sakai T, Kato M, et al: Recombinant human soluble thrombomodulin administration improves sepsis-induced disseminated intravascular coagulation and mortality: A retrospective cohort study. Thromb J 2013; 11: 3. 11) Lin SM, Wang YM, Lin HC, et al: Serum thrombomodulin level relates to the clinical course of disseminated intravascular coagulation, multiorgan dysfunction syndrome, and mortality in patients with sepsis. Crit Care Med 2008; 36: 683-689. 1) Dellinger RP, Levy MM, Rhodes A, et al: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013; 41: 580-637. 12) Abeyama K, Stern DM, Ito Y, et al: The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel anti-inflammatory mechanism. J Clin Invest 2005; 115: 1267-1274. |
| References_xml | – reference: 11) Lin SM, Wang YM, Lin HC, et al: Serum thrombomodulin level relates to the clinical course of disseminated intravascular coagulation, multiorgan dysfunction syndrome, and mortality in patients with sepsis. Crit Care Med 2008; 36: 683-689. – reference: 1) Dellinger RP, Levy MM, Rhodes A, et al: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013; 41: 580-637. – reference: 4) 齋藤大蔵，岡本好司，真弓俊彦，ほか：急性期DIC診断基準 第二次他施設共同前向き試験結果報告 治療効果の分析．日救急医会誌2007; 18: 268-272． – reference: 12) Abeyama K, Stern DM, Ito Y, et al: The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel anti-inflammatory mechanism. J Clin Invest 2005; 115: 1267-1274. – reference: 17) Kato T, Sakai T, Kato M, et al: Recombinant human soluble thrombomodulin administration improves sepsis-induced disseminated intravascular coagulation and mortality: A retrospective cohort study. Thromb J 2013; 11: 3. – reference: 7) Kitchens CS: Thrombocytopenia and thrombosis in disseminated intravascular coagulation (DIC). Hematology 2009; 2009: 240-246. – reference: 18) Ogawa Y, Yamanaka K, Ogura H, et al: Recombinant human soluble thrombomodulin improves mortality and respiratory dysfunction in patients with severe sepsis. J Trauma Acute Care Surg 2012; 72: 1150-1157. – reference: 2) 日本集中治療医学会Sepsis Registry委員会：日本版敗血症診療ガイドラインThe Japanese Guidelines for the Management of Sepsis．日集中医誌 2013; 20: 124-173． – reference: 5) Vincent JL, Ramesh MK, Ernest D, et al: A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Soluble Thrombomodulin, ART-123, in Patients With Sepsis and Suspected Disseminated Intravascular Coagulation. Crit Care Med 2013; 41: 2069-2079. – reference: 3) Kawano N, Yoshida S, Ono N, et al: Clinical Features and Outcomes of 35 Disseminated Intravascular Coagulation Cases Treated with Recombinant Human Soluble Thrombomodulin at a Single Institution. J Clin Exp Hematop 2011; 51: 101-107. – reference: 8) 澤野宏隆，重光胤明，吉永雄一，ほか：敗血症性DICにおけるリコンビナントトロンボモジュリンと安置トロンビン製剤の併用療法の有用性．日救急医会誌2013; 24: 119-131． – reference: 6) 丸藤 哲，齋藤大蔵，石倉宏恭，ほか：急性期DIC診断基準で診断された敗血症性DICに対するアンチトロンビンの効果．日救急医会誌2013; 24: 105-115． – reference: 16) Yamakawa K, Fujimi S, Mohri T, et al: Treatment effects of recombinant human soluble thrombomodulin in patients with severe sepsis: A historical control study. Crit Care 2011; 15: R123. – reference: 19) Fink MP: Recombinant Soluble Thrombomodulin as an Adjunctive Treatment for Sepsis and Disseminated Intravascular Coagulation: Relatively Safe and Possibly Effective. Crit Care Med 2013; 41: 2221-2223. – reference: 13) Hagiwara S, Iwasaka H, Matsumoto S, et al: In vivo and in vitro effects of the anticoagulant, thrombomodulin, on the inflammatory response in rodent models. Shock 2010; 33: 282-288. – reference: 14) Nagato M, Okamoto K, Abe Y, et al: Recombinant human soluble thrombomodulin decreases the plasma high-mobility group box-1 protein levels, whereas improving the acute liver injury and survival rates in experimental endotoxemia. Crit Care Med 2009; 37: 2181-2186. – reference: 10) Conway EM: Thrombomodulin and its role in inflammation. Semin Immunopathol 2012; 34: 107-125. – reference: 15) Saito H, Maruyama I, Shimazaki S, et al: Efficacy and safety of recombinant human soluble thrombomodulin（ART-124) in disseminated intravascular coagulation: Results of a phase Ⅲ, randomized, double-blind clinical trial. J Thromb Haemost 2007; 5: 31-41. – reference: 9) Owen WG, Esmon CT: Functional properties of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. J Biol Chem 1981; 256: 5532-5535. |
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| Snippet | トロンボモジュリン製剤である遺伝子組換え型ヒトトロンボモジュリンは，敗血症性DICの治療薬として近年注目されてきているが，腹部緊急手術後の使用に注目した研究は... Although several studies on recombinant soluble human thrombomodulin (rhTM) have been reported, the safety/efficacy of rhTM for sepsis-associated disseminated... |
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| SubjectTerms | DIC トロンボモジュリン 敗血症 緊急手術 |
| Title | 腹部緊急手術を施行した敗血症性DIC症例に関する検討 |
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