Effect of the Pulsatile Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome -comparison of nonpulsatile ECMO-

• Project/Area Number: 19K09407
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Nippon Bunri University (2020-2022); Junshin Gakuen University (2019)
• Principal Investigator: ITOH Hideshi 日本文理大学, 工学部, 教授 (50711462)
• Co-Investigator(Kenkyū-buntansha): 市場 晋吾 東京女子医科大学, 医学部, 教授 (30284102) ; 岡原 重幸 純真学園大学, 医療工学科, 准教授 (50771185) ; 小畑 秀明 岡山理科大学, 工学部, 准教授 (60437118)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ECMO / 重症呼吸不全 / 拍動流 / 定常流 / RV-PA / ARDS / 救急医学 / 集中治療医学 / 呼吸不全 / 体外循環 / 補助循環

Outline of Research at the Start

本研究は「人工肺と血液ポンプを用いた体外循環回路による治療」（Extracorporeal Membrane Oxygenation:ECMO）における拍動流補助循環法による重症呼吸不全の肺機能改善効果を明らかにする。
具体的には、以下の研究を実施する。
１） In-Vitro試験にて肺血管抵抗変化を模擬したオーバーフロー式模擬循環回路にて血液粘性実験を実施し、拍動流ECMOが生体を模擬した肺血管抵抗変化にも対応できることを圧―流量曲線を描いて証明する。
２）重症呼吸不全モデルの小動物実験において、拍動流ECMOと定常流ECMOの比較を実施し、拍動流ECMOの肺機能改善効果について証明する。

Outline of Final Research Achievements

The golden standard of veno-venous ECMO with continuous flow for Acute Respiratory Distress Syndrome. This study aimed to investigate the impact of the right ventricle on pulmonary artery extracorporeal membrane oxygenation (RV-PA ECMO) for acute respiratory dysfunction with/ or without pulsatile flow during the RV-PA ECMO. We used the bronchoalveolar lavage procedure with intrapulmonary administration of warm saline to establish a severe acute respiratory distress syndrome model. The observation of pneumocytes clearly showed less pulmonary edema, pulmonary fibrosis, and inflammation after the RV-PA ECMO treatment. The concentration of IL-6 was less in the pulsatile group than in the non-pulsatile group. Our study demonstrated that the pulsatile RV-PA ECMO was less vasoconstrictive and supplied more effective oxygenated pulmonary flow than the non-pulsatile RV-PA ECMO. The pulsatile RV-PA ECMO ameliorates pulmonary circulation and facilitate recovery from acute respiratory failure.

Academic Significance and Societal Importance of the Research Achievements

本研究結果より、RV-PA ECMOを導入することで従来からあるV-V ECMO(右心房脱血・送血)よりも高効率的に酸素加血を傷害肺へ送ることができる。さらに、拍動流を付加させたRV-PA ECMOを用いることで右心室の過負荷を軽減でき、拍動による肺動脈血管内皮及び肺の毛細血管への刺激によって、肺の炎症を抑制できるだけでなく肺血管抵抗を減少させ、肺血流の増加を得ることができることが判明した。このことから、本研究にある拍動流 RV-PA ECMOは重症呼吸不全の肺機能改善効果が明らかになり、重症呼吸不全に対する治療効果と生存退院向上に寄与することが期待される。

Research Products

• [Journal Article] Chemotherapy-induced leukopenic septic shock treated with veno-arterial extracorporeal membrane oxygenation: A case report (2023)
  • Author(s): Hoshino A, Ichiba S, Ishikawa J, Seino Y, Yoshida T, Sato N, Nomura T
  • Journal Title: Clin Case Rep. Volume: 11(2) Issue: 2
  • DOI: 10.1002/ccr3.6979
  • Peer Reviewed / Open Access
• [Journal Article] 人工肺 ─総説 2022 (2022)
  • Author(s): 原伸太郎，市場晋吾
  • Journal Title: Jinko Zoki Volume: 51 Issue: 3 Pages: 141-144
  • DOI: 10.11392/jsao.51.141
  • ISSN: 0300-0818, 1883-6097
  • Year and Date: 2022-12-15
• [Journal Article] Use of Jonsen's Four Topic Approach in the Treatment Policy of COVID-19-Associated Severe Respiratory Failure under Prolonged Venovenous Extracorporeal Membrane Oxygenation: A Case of Ethical Approach (2022)
  • Author(s): 山本 舞、市場 晋吾、坂西 佐久子、星野 あつみ、嶋田 正子、矢口 有乃、野村 岳志
  • Journal Title: Journal of Tokyo Women's Medical University Volume: 92 Issue: 3 Pages: 103-109
  • DOI: 10.24488/jtwmu.92.3_103
  • ISSN: 0040-9022, 2432-6178
  • Year and Date: 2022-06-25
  • Peer Reviewed / Open Access
• [Journal Article] 特集 生理学2 Part 4 循環 8.経皮的循環補助の生理学(ECMO/IMPELLA/IABP)-各装置の適応,臓器への影響,管理,合併症 (2022)
  • Author(s): 市場 晋吾、服部 英敏、山田 有希子、清野 雄介
  • Journal Title: INTENSIVIST Volume: 14 Issue: 2 Pages: 331-348
  • DOI: 10.11477/mf.3102200970
  • ISSN: 1883-4833, 2186-7852
  • Year and Date: 2022-04-01
  • Peer Reviewed
• [Journal Article] 人工臓器の最前線(vol.6) 呼吸不全に対する膜型人工肺(VV-ECMO) withコロナの時代に向けて (2022)
  • Author(s): 星野あつみ, 市場晋吾
  • Journal Title: 医学のあゆみ Volume: 282（11） Pages: 1023-1030
• [Journal Article] ECMO装着患者の搬送 集約化のための安全な重症患者搬送を目指して (2022)
  • Author(s): 藤田健亮，市場晋吾
  • Journal Title: LiSA Volume: 29（７） Pages: 676-685
• [Journal Article] 補助循環(ECMO、IABP、Impella) (2022)
  • Author(s): 市場晋吾，菊池規子
  • Journal Title: 集中治療医学レビュー2022-'23 Volume: 2022-23' Pages: 166-174
• [Journal Article] Early short course of neuromuscular blocking agents in patients with COVID-19 ARDS: a propensity score analysis (2022)
  • Author(s): Li Bassi G, Gibbons K, Dalton HJ, White N, Corley A, Hinton S, Forsyth S, Laffey JG, Fan E, Fanning JP, Panigada M, Bartlett R, Brodie D, Burrell A, Chiumello D, Elhazmi A, Esperatti M, Grasselli G, Hodgson C, Ichiba S, Luna C, Marwali E, Merson L, Murthy S, Nichol A, Ogino M, Pelosi P, Torres A, Ng PY, Fraser JF
  • Journal Title: Crit Care Volume: 26(1) Issue: 1 Pages: 141-141
  • DOI: 10.1186/s13054-022-03983-5
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Early predictors of oxygenator exchange during veno-venous extracorporeal membrane oxygenation: A retrospective analysis (2022)
  • Author(s): Umei Nao、Ichiba Shingo、Genda Yuki、Mase Hiroshi、Sakamoto Atsuhiro
  • Journal Title: The International Journal of Artificial Organs Volume: 45 Issue: 11 Pages: 927-935
  • DOI: 10.1177/03913988221118382
  • Peer Reviewed
• [Journal Article] The Need for an Adult Intensive Care Unit Boot Camp for Residents and Fellows: A Cross-Sectional Survey among Intensive Care Unit Directors (2022)
  • Author(s): Umei N, Nishimura M, Ichiba S, Sakamoto A, Berg BW
  • Journal Title: J Nippon Med Sch. Volume: 89(4) Pages: 443-453
  • Peer Reviewed / Open Access
• [Journal Article] A case of severe respiratory failure due to interstitial pneumonia successfully bridged to lung transplantation from a brain-dead donor using 109-day veno-arterial extracorporeal membrane oxygenation (2022)
  • Author(s): Ikeda Tokuji、Ichiba Shingo、Sasaki Takashi、Sato Masaaki、Konoeda Chihiro、Okamoto Tsukasa、Miyazaki Yasunari、Nakajima Jun、Sakamoto Atsuhiro
  • Journal Title: Journal of Artificial Organs Volume: 26 Issue: 1 Pages: 84-88
  • DOI: 10.1007/s10047-022-01341-4
  • Peer Reviewed
• [Journal Article] EXTRACORPOREAL MEMBRANE OXYGENATION FOR ACUTE RESPIRATORY AND CARDIAC FAILURE (2021)
  • Author(s): Hideshi ITOH, Nguyen The Binh, Le Ngoc Thanh, Hitomi Ando, Naohiro Inagawa, Shingo Ichiba
  • Journal Title: The Vietnam Journal of Cardiovascular and Thoracic Surgery Volume: 33 Pages: 55-64
  • DOI: 10.47972/vjcts.v33i.565
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Iliopsoas hematoma in patients undergoing venovenous ECMO (2021)
  • Author(s): Taniguchi H, Ikeda T, Takeuchi I, Ichiba S
  • Journal Title: Am J Crit Care Volume: 30 Issue: 1 Pages: 55-63
  • DOI: 10.4037/ajcc2021351
  • Peer Reviewed
• [Journal Article] COVID-19 Critical Care Consortium. An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients (2021)
  • Author(s): 4.Li Bassi G, Suen JY, Dalton HJ, White N, Shrapnel S, Fanning JP, Liquet B, Hinton S, Vuorinen A, Booth G, Millar JE, Forsyth S, Panigada M, Laffey J, Brodie D, Fan E, Torres A, Chiumello D, Corley A, Elhazmi A, Hodgson C, Ichiba S, Luna C, Murthy S, Nichol A, Ng PY, Ogino M, Pesenti A, Trieu HT, Fraser JF
  • Journal Title: Crit Care Volume: 25 Issue: 11 Pages: 199-199
  • DOI: 10.1097/cce.0000000000000567
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expanding controlled donation after the circulatory determination of death: stronger emphasis on different cultural, religious, and legal backgrounds is needed (2021)
  • Author(s): Muller T, Brodie D, Lorusso R, MacLaren G, Ichiba S
  • Journal Title: Intensive Care Med Volume: 47 Issue: 6 Pages: 724-725
  • DOI: 10.1007/s00134-021-06405-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lung transplant after long-term veno-venous extracorporeal membrane oxygenation: a case report (2021)
  • Author(s): Yoshiyasu N, Sato M, Anraku M, Ichiba S, Nakajima J
  • Journal Title: J Cardiovasc Surg Volume: 16 Issue: 1 Pages: 246-246
  • DOI: 10.1186/s13019-021-01614-8
  • Peer Reviewed / Open Access
• [Journal Article] Catheter related thrombosis after cardiac surg-ery in patients with central venous and pulmonary artery catheters inserted into the right internal jugular vein: a single-center, prospective, observational study (2021)
  • Author(s): 7.Idei M, Seino Y, Sato N, Saishu Y, Goto S, Namekawa M, Moriwaki S, Ishikawa J, Kamei D, Nakagawa M, Ichiba S, Nomura T
  • Journal Title: Heart vessels Volume: 37 Issue: 4 Pages: 691-696
  • DOI: 10.1007/s00380-021-01955-3
  • Peer Reviewed / Open Access
• [Journal Article] Hospital survival outcomes in acute respiratory distress syndrome patients receiving veno-venous extracorporeal membrane oxygenation for longer than 28 days: A retrospective study (2021)
  • Author(s): Umei N, Ichiba S, Genda Y, Mase H, Sakamoto A
  • Journal Title: Artif Organs Volume: 45 Issue: 12 Pages: 1533-1542
  • DOI: 10.1111/aor.14051
  • Peer Reviewed
• [Journal Article] COVID-19とECMO/血液浄化装置の管理 (2021)
  • Author(s): 鈴木健一, 中山拓也, 市場晋吾
  • Journal Title: 日本急性血液浄化学会雑誌 Volume: 12 Pages: 15-19
  • NAID: 40022771623
  • Peer Reviewed
• [Journal Article] 今, 臨床工学技士が知っておきたいCOVID-19 up-to-date（第3回）. COVID-19症例におけるECMOの成績. (2021)
  • Author(s): 市場晋吾
  • Journal Title: Clinical Engineering Volume: 32 Pages: 484-491
• [Journal Article] 体外循環と補助循環の基礎と臨床 -循環と呼吸の補助循環, 基礎と臨床-. (2021)
  • Author(s): 市場晋吾
  • Journal Title: Clinical Engineering. Volume: 32 Pages: 477-483
• [Journal Article] An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients (2021)
  • Author(s): Li Bassi G, Suen JY, Dalton HJ, Liquet B, Hinton S, Millar JE, Forsyth S, Panigada M, Laffey J,Corley A, Hodgson C, Ichiba S, Luna C, Murthy S, Nichol A, Ng PY, Ogino M, Pesenti A, Trieu HT, Fraser JF; COVID-19 Critical Care Consortium
  • Journal Title: Crit Care. Volume: 25 Issue: 1 Pages: 199-199
  • DOI: 10.1186/s13054-021-03518-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Online Prediction of Normal Blood Viscosity During Cardiopulmonary Bypass Using Hematocrit- and Temperature-Dependent Model (2020)
  • Author(s): Okahara Shigeyuki、Miyamoto Satoshi、Soh Zu、Itoh Hideshi、Takahashi Shinya、Tsuji Toshio
  • Journal Title: IEEE Access Volume: 8 Pages: 5611-5621
  • DOI: 10.1109/access.2019.2963355
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 体外式膜型人工肺装着時における人工呼吸回路選択の検討 (2020)
  • Author(s): 鈴木 英正, 鈴木 健一, 市場 晋吾
  • Journal Title: 人工呼吸 Volume: 37(1) Pages: 103-106
  • Peer Reviewed
• [Journal Article] 重症呼吸不全に対するVV-ECMOの適応と管理 (2020)
  • Author(s): 藤田健亮、市場晋吾
  • Journal Title: Heart View Volume: 24(4) Pages: 360-366
  • Peer Reviewed
• [Journal Article] 【集中治療医学レビュー 最新主要文献と解説 2020-'21】II章 集中治療における検査・技術 補助循環(ECMO、IABP、Impella) (2020)
  • Author(s): 市場晋吾
  • Journal Title: 集中治療医学レビュー Volume: 2020-21' Pages: 128-133
  • Peer Reviewed
• [Journal Article] ECMO管理中の鎮静・鎮痛 (特集 ECMOを極める(1)ER導入編) -- (ECMOの管理を極める) (2020)
  • Author(s): 藤田 健亮, 梅井 菜央, 源田 雄紀, 間瀬 大司, 市場 晋吾
  • Journal Title: 救急医学 Volume: 44(2) Pages: 213-221
  • NAID: 40022162488
  • Peer Reviewed
• [Journal Article] Awake ECMOの管理 (特集 ECMOを極める(1)ER導入編) -- (ECMOの管理を極める) (2020)
  • Author(s): 池田 督司, 市場 晋吾, 増山 素道
  • Journal Title: 救急医学 Volume: 44(2) Pages: 222-228
  • NAID: 40022162492
  • Peer Reviewed
• [Journal Article] 重症呼吸不全に対するVV-ECMOの適応と管理 (2020)
  • Author(s): 藤田健亮, 市場晋吾
  • Journal Title: Heart View; 24(4): 360-366, 2020. Volume: 24 Pages: 360-366
  • Peer Reviewed
• [Journal Article] 成人重症呼吸不全に対するECMOにおける終末期医療の実際と問題点 (2019)
  • Author(s): 市場晋吾
  • Journal Title: 人工呼吸; 36(2): 124-129, 2019. Volume: 36 Pages: 124-129
  • Peer Reviewed
• [Journal Article] Respiratory ECMO Teamを組織する (2019)
  • Author(s): 池田督司, 市場晋吾
  • Journal Title: ICUとCCU; 43(10): 559-565, 2019. Volume: 43 Pages: 559-565
  • Peer Reviewed
• [Journal Article] 重症呼吸不全に対する体外式肺補助(ECMO) (2019)
  • Author(s): 市場晋吾
  • Journal Title: 救急・集中治療; 31: 574-579, 2019. Volume: 31 Pages: 574-579
  • Peer Reviewed
• [Presentation] 重症呼吸不全に対するECMOの肺血管抵抗に及ぼす影響ー定常流と拍動流の比較ー (2023)
  • Author(s): 安東倫美，伊藤英史，市場晋吾，小畑秀明
  • Organizer: 第39回日本医工学治療学会
• [Presentation] 腹臥位中の集中治療 当院におけるVV-ECMO下の腹臥位管理法 (2023)
  • Author(s): 工藤 弦, 堀部 達也, 加島 広太, 菊地 剛, 志真 奈緒子, 青山 要平, 野村 岳志, 市場 晋吾, 若林 秀隆
  • Organizer: 第50回日本集中治療医学会
• [Presentation] 集中治療における重症心不全に対する補助循環によるブリッジ-VA-ECMO,ECPELLA,VAD- 当院における心原性ショックに対するMCSブリッジ戦略 (2023)
  • Author(s): 山田 有希子, 市原 有起, 飯塚 慶, 齋藤 聡, 菊池 規子, 服部 英敏, 萩原 誠久, 市場 晋吾, 野村 岳志, 新浪 博士
  • Organizer: 第50回日本集中治療医学会
• [Presentation] VV-ECMOからの離脱にINTELLiVENT-ASVを使用した一例 (2023)
  • Author(s): 山本 舞, 星野 あつみ, 救仁郷 達也, 石川 淳哉, 清野 雄介, 吉田 拓生, 佐藤 暢夫, 幸野 真樹, 市場 晋吾, 野村 岳志
  • Organizer: 第50回日本集中治療医学会
• [Presentation] 化学療法後の好中球減少症を伴う敗血症性ショックに対し、VA-ECMOを使用し救命し得た成人症例 (2023)
  • Author(s): 星野 あつみ, 山本 舞, 出井 真史, 石川 淳哉, 清野 雄介, 吉田 拓生, 佐藤 暢夫, 中川 雅史, 市場 晋吾, 野村 岳志
  • Organizer: 第50回日本集中治療医学会
• [Presentation] RV-PA ECMO実験モデルは確立できるか？ (2022)
  • Author(s): 伊藤英史，市場晋吾，小畑秀明，岡原重幸，安東倫美，川端晃幸
  • Organizer: 第38回日本医工学治療学会
• [Presentation] 赤血球の形状変化による人工肺圧勾配の上昇 (2022)
  • Author(s): 岡原重幸, 宮本聡史, 吉野将, 高橋秀暢, 伊藤英史, 曽智, 辻敏夫
  • Organizer: 第60回日本人工臓器学会
• [Presentation] 人工心肺中のヘマトクリットレベルに対する血液粘度-温度特性 (2022)
  • Author(s): 岡原 重幸, 宮本 聡史, 吉野 将, 高橋 秀暢
  • Organizer: 第47回日本体外循環技術医学会
• [Presentation] 10年後にも役立つECMO治療の基礎 (2022)
  • Author(s): 市場晋吾
  • Organizer: 第60回日本人工臓器学会
  • Invited
• [Presentation] 重症呼吸不全に対するECMOの最新知見 (2022)
  • Author(s): 市場晋吾
  • Organizer: 第39回日本医工学治療学会
  • Invited
• [Presentation] Impact on Cardiopulmonary Bypass Management for Double Outlet Right Ventricle Repair: compare univentricular repair with biventricular repair (2020)
  • Author(s): Hideshi ITOH
  • Organizer: 16th International Conferences on pediatric mechanical circulatory support systems and pediatric cardiopulmonary bypass
  • Int'l Joint Research
• [Presentation] Pitfalls and problems in pediatric perfusion (2019)
  • Author(s): Hideshi ITOH
  • Organizer: The 52nd anniversary scientific conference in E hospital, Hanoi, Vietnam
  • Int'l Joint Research / Invited
• [Presentation] Perfusion education in Japan (2019)
  • Author(s): Hideshi ITOH
  • Organizer: The 52nd anniversary scientific conference in E hospital, Hanoi, Vietnam
  • Int'l Joint Research / Invited
• [Presentation] Use of microbubbles as an approach to blood oxygenation. (2019)
  • Author(s): Shingo Ichiba
  • Organizer: The ASAIO (American Society for Artificial Internal Organs) 65th Annual Conference, 2019. San Francisco, USA.
  • Int'l Joint Research
• [Presentation] Prevention and early detection of LV distension in VA ECMO. (2019)
  • Author(s): Shingo Ichiba
  • Organizer: The 4th Asia-Pacific Extracorporeal Life Support Organization (ELSO) Conference, 2019. Bangkok, Thailand.
  • Int'l Joint Research
• [Presentation] A blood viscosity estimation method based on pressure-flow characteristics of an oxygenator during cardiopulmonary bypass (2019)
  • Author(s): Shigeyuki Okahara, Hideshi ITOH
  • Organizer: The 52nd anniversary scientific conference in E hospital, Hanoi, Vietnam
  • Int'l Joint Research
• [Presentation] Connecting CRRT to the ECMO Circuit (2019)
  • Author(s): Shingo Ichiba
  • Organizer: The 4th Asia-Pacific Extracorporeal Life Support Organization (ELSO) Conference, Bangkok, Thailand.
• [Presentation] 重症呼吸不全に対するECMOのTips and Pitfalls. (2019)
  • Author(s): 市場晋吾
  • Organizer: 日本医工学治療学会第35回学術大会, 2019. 東京
  • Invited
• [Presentation] ECLS in Japan -Respiratory ECMO-. (2019)
  • Author(s): Shingo Ichiba
  • Organizer: The 3rd Chinese Society of Extracorporeal Life Support, Chengdu, China.
• [Book] 市場晋吾、清水敬樹 (2020)
  • Author(s): ECMO 実践ハンドブックー世界標準の成人ECMO管理
  • Total Pages: 200
  • Publisher: 羊土社
• [Book] ECMO実践ハンドブック-世界標準の成人ECMO管理. (2020)
  • Author(s): 市場晋吾、清水敬樹
  • Total Pages: 200
  • Publisher: 羊土社
  • ISBN: 9784758118613