Phase I trial on the safety of olprinone for low central venous pressure management aimed at haemorrhage control during open and laparoscopic hepatectomy: a study protocol
Introduction Hepatectomy is the primary treatment for malignant liver tumours. It is crucial to control bleeding during liver parenchymal transection. Methods to reduce central venous pressure (CVP), such as fluid restriction and the use of vasodilators, are essential for minimising bleeding but can...
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BMJ Publishing Group
2025-02-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/15/2/e088307.full |
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| author | Katsuhiko Uesaka Yuya Miura Teiichi Sugiura Ryo Ashida Katsuhisa Ohgi Mihoko Yamada Shimpei Otsuka Yoshiyasu Kato Takuya Oyakawa Eiji Ando Sunao Tamai |
| author_facet | Katsuhiko Uesaka Yuya Miura Teiichi Sugiura Ryo Ashida Katsuhisa Ohgi Mihoko Yamada Shimpei Otsuka Yoshiyasu Kato Takuya Oyakawa Eiji Ando Sunao Tamai |
| author_sort | Katsuhiko Uesaka |
| collection | DOAJ |
| description | Introduction Hepatectomy is the primary treatment for malignant liver tumours. It is crucial to control bleeding during liver parenchymal transection. Methods to reduce central venous pressure (CVP), such as fluid restriction and the use of vasodilators, are essential for minimising bleeding but can lead to haemodynamic instability. Phosphodiesterase-3 (PDEIII) inhibitors such as milrinone have shown efficacy in managing low CVP and maintaining haemodynamic stability. This study investigates olprinone, another PDEIII inhibitor with a potentially strong vasodilatory effect, for its safety and efficacy in CVP management during hepatectomy.Methods and analysis This single-centre phase I trial at Shizuoka Cancer Center evaluates the intraoperative administration of olprinone for open and laparoscopic hepatectomy. The trial employs a 3+3 cohort study design to determine the maximum tolerated dose (MTD) and identify dose-limiting toxicities. The study also assesses the trends in CVP and circulatory dynamics using the FloTrac System, alongside safety evaluations. The trial aims to establish the safety and MTD of olprinone during hepatectomy, potentially offering a method to control CVP without causing haemodynamic instability. This could lead to reduced blood loss, shorter operative time and fewer postoperative complications.Ethics and dissemination The study protocol was approved by the Certified Review Board of Shizuoka Cancer Center (approval number CRB4180010).Trial registration number jRCTs041230110 and jRCTs041230111. |
| format | Article |
| id | doaj-art-64e544a24a7348cabf12beee05b08f31 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-64e544a24a7348cabf12beee05b08f312025-02-08T07:05:10ZengBMJ Publishing GroupBMJ Open2044-60552025-02-0115210.1136/bmjopen-2024-088307Phase I trial on the safety of olprinone for low central venous pressure management aimed at haemorrhage control during open and laparoscopic hepatectomy: a study protocolKatsuhiko Uesaka0Yuya Miura1Teiichi Sugiura2Ryo Ashida3Katsuhisa Ohgi4Mihoko Yamada5Shimpei Otsuka6Yoshiyasu Kato7Takuya Oyakawa8Eiji Ando9Sunao Tamai101 Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan1 Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan1 Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan1 Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan1 Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan1 Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan1 Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan1 Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan2 Division of Oncological Cardiology, Shizuoka Cancer Center, Sunto-gun, Japan3 Division of Anesthesiology, Shizuoka Cancer Center, Sunto-gun, Japan3 Division of Anesthesiology, Shizuoka Cancer Center, Sunto-gun, JapanIntroduction Hepatectomy is the primary treatment for malignant liver tumours. It is crucial to control bleeding during liver parenchymal transection. Methods to reduce central venous pressure (CVP), such as fluid restriction and the use of vasodilators, are essential for minimising bleeding but can lead to haemodynamic instability. Phosphodiesterase-3 (PDEIII) inhibitors such as milrinone have shown efficacy in managing low CVP and maintaining haemodynamic stability. This study investigates olprinone, another PDEIII inhibitor with a potentially strong vasodilatory effect, for its safety and efficacy in CVP management during hepatectomy.Methods and analysis This single-centre phase I trial at Shizuoka Cancer Center evaluates the intraoperative administration of olprinone for open and laparoscopic hepatectomy. The trial employs a 3+3 cohort study design to determine the maximum tolerated dose (MTD) and identify dose-limiting toxicities. The study also assesses the trends in CVP and circulatory dynamics using the FloTrac System, alongside safety evaluations. The trial aims to establish the safety and MTD of olprinone during hepatectomy, potentially offering a method to control CVP without causing haemodynamic instability. This could lead to reduced blood loss, shorter operative time and fewer postoperative complications.Ethics and dissemination The study protocol was approved by the Certified Review Board of Shizuoka Cancer Center (approval number CRB4180010).Trial registration number jRCTs041230110 and jRCTs041230111.https://bmjopen.bmj.com/content/15/2/e088307.full |
| spellingShingle | Katsuhiko Uesaka Yuya Miura Teiichi Sugiura Ryo Ashida Katsuhisa Ohgi Mihoko Yamada Shimpei Otsuka Yoshiyasu Kato Takuya Oyakawa Eiji Ando Sunao Tamai Phase I trial on the safety of olprinone for low central venous pressure management aimed at haemorrhage control during open and laparoscopic hepatectomy: a study protocol BMJ Open |
| title | Phase I trial on the safety of olprinone for low central venous pressure management aimed at haemorrhage control during open and laparoscopic hepatectomy: a study protocol |
| title_full | Phase I trial on the safety of olprinone for low central venous pressure management aimed at haemorrhage control during open and laparoscopic hepatectomy: a study protocol |
| title_fullStr | Phase I trial on the safety of olprinone for low central venous pressure management aimed at haemorrhage control during open and laparoscopic hepatectomy: a study protocol |
| title_full_unstemmed | Phase I trial on the safety of olprinone for low central venous pressure management aimed at haemorrhage control during open and laparoscopic hepatectomy: a study protocol |
| title_short | Phase I trial on the safety of olprinone for low central venous pressure management aimed at haemorrhage control during open and laparoscopic hepatectomy: a study protocol |
| title_sort | phase i trial on the safety of olprinone for low central venous pressure management aimed at haemorrhage control during open and laparoscopic hepatectomy a study protocol |
| url | https://bmjopen.bmj.com/content/15/2/e088307.full |
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