Effects and the mechanism of action by remifentanil in the brain protection strategy

• Project/Area Number: 24390364
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: The University of Tokyo
• Principal Investigator: Uchida Kanji 東京大学, 医学部附属病院, 准教授 (60302709)
• Co-Investigator(Kenkyū-buntansha): YAMADA Yoshitsugu 東京大学, 医学部附属病院, 教授 (30166748) ; IMAI Hideaki 東京大学, 医学部附属病院, 講師 (70359587)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2015: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2014: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: レミフェンタニル / 脳保護 / 術後予後 / 開頭手術 / 炎症 / サイトカイン / 虚血再還流 / 白血球 / 手術侵襲

Outline of Final Research Achievements

Propensity-matched analysis of administrative claims database indicated that the use of remifentanil associated with improved outcome of the patients undergoing surgical clipping of intracranial aneurysm. Use of remifentanil associated with reduced postoperative death with odds ratio of 0.52 ( 95% CI 0.37-0.74 p<0.001). Animal craniotomy model using rats revealed that the use of intraoperative remifentanil associated with suppressed recruitment of white blood cells to the peripheral blood. We have also standardized GM-CSF autoantibody ELISA and quantify reactivity of circulating neutrophils to exogenous GM-CSF to evaluate GM-CSF bioactivity that is important to the innate immunity agains the invading pathogen, as well as repair of the wound.

Research Products

• [Journal Article] 誤嚥性肺炎の病態と治療 (2016)
  • Author(s): 内田寛治
  • Journal Title: 麻酔 Volume: 65 Pages: 13-22
• [Journal Article] Recovery from extreme hemodilution (hemoglobin level of 0.6g/dL) in cadaveric liver transplantation. (2015)
  • Author(s): Kariya T, Ito N, Kitamura T, Yamada Y.
  • Journal Title: Anesthesia and analgesia case report Volume: 10 Issue: 10 Pages: 132-134
  • DOI: 10.1213/xaa.0000000000000132
  • Peer Reviewed
• [Journal Article] A standardized blood test for the routine clinical diagnosis of impaired GM-CSF signaling using flow cytometry. (2014)
  • Author(s): Kusakabe Y, Uchida K, Hiruma T, Suzuki Y, Totsu T, Suzuki T, Carey BC, Yamada Y, Trapnell BC.
  • Journal Title: J Immunol Methods. Volume: 413 Pages: 1-11
  • DOI: 10.1016/j.jim.2014.07.009
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Up-Regulation of Cluster of Differentiation (CD) 11b Expression on the Surface of Canine Granulocytes with Human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) (2014)
  • Author(s): Nakagaki K, Nunomura Y, Uchida K, Nakata K, Tazawa R
  • Journal Title: Journal of Veterinary Medical Science Volume: 76 Pages: 1173-6
  • NAID: 130004432194
  • Peer Reviewed / Open Access
• [Journal Article] Effects of Remifentanil on In-Hospital Mortality and Length of Stay Following Clipping of Intracranial Aneurysm: A Propensity Score-matched Analysis. (2014)
  • Author(s): Uchida K, Yasunaga H, Sumitani M, Horiguchi H, Fushimi K, Yamada Y
  • Journal Title: J Neurosurg Anesthesiol Volume: in press
  • Peer Reviewed
• [Journal Article] Perioperative factors affecting the occurrence of acute complex regional pain syndrome following limb bone fracture surgery: data from the Japanese Diagnosis Procedure Combination database. (2014)
  • Author(s): Sumitani M, Yasunaga H, Uchida K, Horiguchi H, Nakamura M, Ohe K, Fushimi K, Matsuda S, Yamada Y
  • Journal Title: Rheumatology Volume: in press
  • Peer Reviewed
• [Journal Article] Standardized serum GM-CSF autoantibody testing for the routine clinical diagnosis of autoimmune pulmonary alveolar proteinosis (2014)
  • Author(s): Uchida K, Nakata K, Carey B, Chalk C, Suzuki T, Sakagami T, Koch DE, Stevens C, Inoue Y, Yamada Y, Trapnell BC.
  • Journal Title: J Immunol Methods Volume: 402 Issue: 1-2 Pages: 57-70
  • DOI: 10.1016/j.jim.2013.11.011
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 顆粒球マクロファージコロニー刺激因子(GM-CSF)シグナルと生体防御・臓器保護 (2013)
  • Author(s): 内田寛治
  • Journal Title: 麻酔 Volume: 62 Pages: 265-274
  • Peer Reviewed
• [Journal Article] Impact of remifentanil use on early postoperative outcomes following brain tumor resection or rectal cancer surgery. (2012)
  • Author(s): Uchida K
  • Journal Title: Journal of Anesthesia Volume: 26 Issue: 5 Pages: 711-720
  • DOI: 10.1007/s00540-012-1397-3
  • NAID: 10031123494
  • Peer Reviewed
• [Journal Article] Analysis of cytotoxicity induced by proinflammatory cytokines in the human alveolar epithelial cell line A549. (2012)
  • Author(s): Muroya M, Chang K, Uchida K, Bougaki M, Yamada Y
  • Journal Title: Bioscience Trends Volume: 6 (2) Pages: 70-80
  • NAID: 130004572568
  • Peer Reviewed
• [Journal Article] Standardization of perioperative management on hepato-biliary-pancreati c surgery. (2012)
  • Author(s): Gao J, Song P, Tamura S, Hasegawa K, Sugawara Y, Kokudo N, Uchida K, Orii R QiF, Dong J, Tang W
  • Journal Title: Drug Discoveries & Therapeutics Volume: 6 (2) Pages: 108-111
• [Journal Article] 手術患者リスク評価と周術期管理に関連した周術期アウトカム (2012)
  • Author(s): 内田寛治
  • Journal Title: 麻酔 Volume: 61 Pages: 514-25
• [Presentation] Possible systemic immune paralysis in patients undergoing aseptic, limited surgical stress (2016)
  • Author(s): Y. Tamai, K. Uchida, Y. Kusakabe, K. Chang, S. Taketomi, H. Inui, S. Tanaka, Y. Yamada
  • Organizer: American Thoracic Society Annual Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2016-05-14
  • Int'l Joint Research
• [Presentation] Peritoneal sepsis impairs efficient recruitment of neutrophils into the alveolar space and augment lung injury after nosocomial infection (2016)
  • Author(s): T. Hiruma, K. Uchida, B.C. Trapnell, Y. Kusakabe, Y. Yamamura, T. Totsu, K. Chang, K. Nakamura, K. Doi, S. Nakajima, N. Yahagi, Y. Yamada
  • Organizer: American Thoracic Society Annual Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2016-05-14
  • Int'l Joint Research
• [Presentation] 頭蓋内腫瘍合併症例の腹腔鏡補助下S状結腸切除術において、頭蓋内圧評価に視神経鞘径モニタリングを行った1例 (2015)
  • Author(s): 阿部 真友子、篠川 美希、内田 寛治、山田 芳嗣
  • Organizer: 日本麻酔科学会東京・関東甲信越支部合同学術集会
  • Place of Presentation: パシフィコ横浜 神奈川県横浜市
  • Year and Date: 2015-09-05
• [Presentation] 敗血症に引き続く緑膿菌肺炎のマウスモデルに対するインターフェロンβの治療的効果とそのメカニズム. (2015)
  • Author(s): 比留間 孝広, 内田 寛治, 日下部 良臣, 山村 睦朗, 矢作 直樹, 山田 芳嗣
  • Organizer: 日本麻酔科学会
  • Place of Presentation: 神戸ポートピアホテル 兵庫県神戸市
  • Year and Date: 2015-05-28
• [Presentation] 肺傷害発症と重症化のメカニズム―臨床応用への可能性―肺血管透過性の関与とその制御. (2015)
  • Author(s): 内田寛治
  • Organizer: 日本麻酔科学会
  • Place of Presentation: 神戸ポートピアホテル 兵庫県神戸市
  • Year and Date: 2015-05-28
  • Invited
• [Presentation] 全身麻酔下帝王切開術の1施設における疫学 (2012)
  • Author(s): 池田貴充、内田寛治、折井亮、山田芳嗣
  • Organizer: 日本臨床麻酔学会
  • Place of Presentation: ビッグパレット福島他(郡山市)
  • Year and Date: 2012-11-01
• [Presentation] MRIを用いた経口補水液の種類による胃消失時間の違いの検討 (2012)
  • Author(s): 中村誠、内田寛治、坊垣昌彦、室屋充明、山田芳嗣
  • Organizer: 日本臨床麻酔学会
  • Place of Presentation: ビッグパレット福島他(郡山市)
  • Year and Date: 2012-11-01
• [Presentation] 肺胞蛋白症の全肺洗浄の麻酔;全国疫学調査の結果 (2012)
  • Author(s): 岡上泰子、内田寛治、―和多俊男、井上義一、山田芳嗣
  • Organizer: 日本麻酔科学会第59回学術集会
  • Place of Presentation: 神戸国際会議場他(神戸市)
  • Year and Date: 2012-06-08
• [Presentation] 肝肺症候群を有する生体肝移植症例の検討 (2012)
  • Author(s): 尾藤まりあ、折井亮、坊垣昌彦、内田寛治、山田芳嗣
  • Organizer: 日本麻酔科学会第59回学術集会
  • Place of Presentation: 神戸国際会議場他(神戸市)
  • Year and Date: 2012-06-08
• [Presentation] 肝移植手術患者における動脈圧波形解析と肺動脈カテーテルによるモニタリングの比較 (2012)
  • Author(s): 朝元雅明、折井亮、坊垣昌彦、東賢志、内田寛治、山田芳嗣
  • Organizer: 日本麻酔科学会第59回学術集会
  • Place of Presentation: 神戸国際会議場他(神戸市)
  • Year and Date: 2012-06-08
• [Presentation] GM-CSF刺激による好中球のCDllibの上昇率で術後患者や重症感染症患者の免疫能を評価する (2012)
  • Author(s): 日下部良臣、内田寛治、B.C.Trapnell、山田芳嗣
  • Organizer: 日本麻酔科学会第59回学術集会
  • Place of Presentation: 神戸国際会議場他(神戸市)
  • Year and Date: 2012-06-07
• [Presentation] 医療コストのフィードバックを用いた医療コスト教育の試み (2012)
  • Author(s): 冨岡俊也、牛尾倫子、阿部博昭、市原剛央、内田寛治、山田芳嗣
  • Organizer: 日本麻酔科学会第59回学術集会
  • Place of Presentation: 神戸国際会議場他(神戸市)
  • Year and Date: 2012-06-07
• [Presentation] Dried Blood Spot Card Testing For Diagnostic, Epidemiological And Lon gitudinal Evaluation Of Pulmonary Alveolar Proteinosis: The us National PAP Registry Study (2012)
  • Author(s): Carey B, Chalk C, Uchida K, Suzuki T, Nakata K, Inoue Y, Trapnell B
  • Organizer: American thoracic society annual meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2012-05-23
• [Presentation] Validation And Mechanism of Flow-Based Whole Blood Assay To Evaluate Phagocyte Immune Function (2012)
  • Author(s): Kusakabe Y, Uchida K, Trapnell BC, Yamada Y
  • Organizer: American thoracic society annual meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2012-05-22