Perioperative Dexmedetomidine and Long-term Survival After Cancer Surgery

Официальное название

Impact of Perioperative Dexmedetomidine on Long-term Survival in Older Patients After Cancer Surgery: a Multicenter Randomized Trial

Обзор

Along with aging population, cancer incidence and mortality are increasing. However, despite advances in oncology and surgery, long-term survival of cancer patients is far from optimal. Dexmedetomidine is a highly selective alpha 2 adrenergic receptor agonist with sedative, analgesic, and anxiolytic effects. Studies showed that perioperative use of dexmedetomidine reduces delirium and some non-delirium complications after surgery. In long-term follow-up studies of older patients who, for other reasons, were randomized to receive either dexmedetomidine or placebo during intra- or postoperative period, dexmedetomidine use was associated with improved long-term survival. This multicenter randomized trial aims to investigate the effect of perioperative dexmedetomidine on long-term outcomes in older patients undergoing cancer surgery.

Подробное описание

Along with aging population, cancer incidence and mortality are increasing. Surgical resection remains the mainstay treatment for solid organ cancer. However, despite advances in oncology and surgery, long-term survival of cancer patients is far from optimal. For example, the 5-year survival rate of cancer patients is about 36.9% in China, and the survival rate decreases for about 10% each year in older patients after cancer surgery. How to improve long-term survival after cancer surgery remains an urgent problem to be solved.

Cancer death usually occur after cancer recurrence or metastasis. The development of cancer recurrence or metastasise after surgical resection depends on the balance between the anti-cancer defense function of host and the invasiveness of residual cancer cells. Studies showed that surgery, while resecting cancer mass, also releases cancer cells into the circulation. Surgical stress also impairs cell-mediated immunity and promote cancer growth.

Dexmedetomidine is a highly selective alpha 2 adrenergic receptor agonist with sedative, analgesic, and anxiolytic effects. Studies showed that intraoperative use of dexmedetomidine reduces anesthetic and opioid consumption and relieves surgery-related stress response and inflammation. Studies also showed that perioperative use of dexmedetomidine reduces delirium, a commonly occurred complication in older patients, and some non-delirium complications after surgery.

The effect of perioperative dexmedetomidine on long-term outcomes after cancer surgery remains unclear. In a long-term follow-up of older patients who were randomized to receive either low-dose dexmedetomidine or placebo during intensive care unit stay, dexmedetomidine use was associated with improved survival within 2 years. In a recent long-term follow-up of older patients who were randomized to receive either dexmedetomidine or placebo during surgery, dexmedetomidine use was associated with improved recurrence-free survival.

The investigators hypothesize that perioperative use of dexmedetomidine may improve long-term survival after cancer surgery. This multicenter randomized trial aims to investigate the effect of perioperative dexmedetomidine on long-term outcomes in older patients undergoing cancer surgery.

Вмешательства

• Препарат Dexmedetomidine
  A loading dose of dexmedetomidine (0.6 μg/kg) will be administered over 10-15 minutes before anaesthesia induction, followed by a continuous infusion at a rate of 0.5 μg/kg/hr till 1 hour before the end of surgery. Patient-controlled dexmedetomidine supplemented sufentanil analgesia will be provided after surgery: the formula contains a mixture of sufentanil (1.25 μg/ml) and dexmedetomidine (1.25 μg/ml), diluted with normal saline to a total volume of 160 ml; the analgesic pump is set to adminis
• Препарат Placebo
  Volume-matched normal saline will be administered in the same rate and volume for the same duration as in the dexmedetomidine group during anesthesia. Patient-controlled sufentanil analgesia will be provided after surgery: the formula contains sufentanil (1.25 μg/ml), diluted with normal saline to a total volume of 160 ml; the analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with patient-controlled bolus of 2 ml each time and a lockout time of 8 minutes.

Первичные конечные точки

• Progression-free survival after surgery [Срок оценки: Up to 3 years after surgery of the last enrolled patient.]

Вторичные конечные точки (2)

• Incidence of postoperative delirium. [Срок оценки: During the first 4 postoperative days.]
• Incidence of cognitive dysfunction at 6 months and 1 year postoperatively. [Срок оценки: At 6 months and 1 year postoperatively.]

Критерии участия

Критерии включения

• Aged 60 years or older.
• Scheduled to undergo radical surgery for cancer under general anesthesia, with an expected surgical duration of 2 hours or longer.
• Required patient-controlled intravenous analgesia after surgery.

Критерии исключения

• Inability to communicate preoperatively due to visual, auditory, verbal. or other reasons.
• Surgery for breast cancer or intracranial tumor.
• Preoperative severe sinus bradycardia (<50 beats per minute), sick sinus syndrome，or second-degree or above atrioventricular block without pacemaker.
• Severe hepatic dysfunction (Child-Pugh class C).
• Severe renal dysfunction (requirement of renal replacement therapy before surgery).
• Enrolled in other clinical studies.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Китай · 39 центров

• The First Affiliated Hospital of China University of Science and Technology — Хэфэй
• The First Affiliated Hospital of University of Science and Technology of China (Anhui Prov — Хэфэй
• Peking University First Hospital — Пекин
• Tsinghua University Yuquan Hospital — Пекин
• Cancer Hospital Chinese Academy of Medical Sciences — Пекин
• The First Affiliated Hospital of Army Medical University (Southwest Hospital) — Чунцин
• Fujian Provincial Hospital — Фучжоу
• The First Affiliated Hospital of Fujian Medical University — Фучжоу
• … и ещё 31 центр

Публикации

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• Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25. PMID 26808342
• Zhang DF, Su X, Meng ZT, Li HL, Wang DX, Xue-Ying Li, Maze M, Ma D. Impact of Dexmedetomidine on Long-term Outcomes After Noncardiac Surgery in Elderly: 3-Year Follow-up of a Randomized Controlled Trial. Ann Surg. 2019 Aug;270(2):356-363. doi: 10.1097/SLA.0000000000002801. PMID 29742525
• Du YT, Li YW, Zhao BJ, Guo XY, Feng Y, Zuo MZ, Fu C, Zhou WJ, Li HJ, Liu YF, Cheng T, Mu DL, Zeng Y, Liu PF, Li Y, An HY, Zhu SN, Li XY, Li HJ, Wu YF, Wang DX, Sessler DI; Peking University Clinical Research Program Study Group. Long-term Survival after Combined Epidural-General Anesthesia or General Anesthesia Alone: Follow-up of a Randomized Trial. Anesthesiology. 2021 Aug 1;135(2):233-245. doi: PMID 34195784
• Fokas E, Engenhart-Cabillic R, Daniilidis K, Rose F, An HX. Metastasis: the seed and soil theory gains identity. Cancer Metastasis Rev. 2007 Dec;26(3-4):705-15. doi: 10.1007/s10555-007-9088-5. PMID 17786535
• Khuri SF, Henderson WG, DePalma RG, Mosca C, Healey NA, Kumbhani DJ; Participants in the VA National Surgical Quality Improvement Program. Determinants of long-term survival after major surgery and the adverse effect of postoperative complications. Ann Surg. 2005 Sep;242(3):326-41; discussion 341-3. doi: 10.1097/01.sla.0000179621.33268.83. PMID 16135919
• Sessler DI. Long-term consequences of anesthetic management. Anesthesiology. 2009 Jul;111(1):1-4. doi: 10.1097/ALN.0b013e3181a913e1. No abstract available. PMID 19512884
• Yamaguchi K, Takagi Y, Aoki S, Futamura M, Saji S. Significant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection. Ann Surg. 2000 Jul;232(1):58-65. doi: 10.1097/00000658-200007000-00009. PMID 10862196

Идентификаторы

NCT: NCT06030804 · 2023-227

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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