Impact of Epidural Anesthesia-analgesia on Long-term Outcome in Elderly Patients After Surgery: 5-year Follow-up of a Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,802
- 试验地点
- 5
- 主要终点
- Overall survival after surgery.
研究概览
简要总结
Surgical resection is one of the most important treatments for resectable cancer; on the other hand, cancer recurrence and/or metastasis are the major reasons of treatment failure. The development of recurrence/metastasis after cancer surgery mostly depends on the balance between the immunity of human body and the capability of implantation, proliferation and neovascularization of the residual cancer. Preclinical and retrospective clinical studies suggest that anaesthetic management may affect the long-term outcomes after cancer surgery. The investigators hypothesize that use of epidural anesthesia-analgesia may improve long-term survival in elderly patients after major surgery for cancer.
详细描述
Surgical resection is the main treatment for potentially curable solid organ cancer. However, it is unavoidable that some cancer cells are disseminated into the circulatory or lymphatic system during surgery. And quite a number of patients develop cancer recurrence and/or metastasis after surgery, which are associated with poor long-term outcomes. The development of cancer recurrence and/or metastasis after surgery is mostly dependent on the balance between the anti-tumor immune function of the human body and the ability of implantation, proliferation and neovascularization of the residual cancer cells.
Multiple surgical factors may influence the balance between the anti-cancer immune function and cancer recurrence. For example, the presence of the primary cancer inhibits angiogenesis, whereas cancer resection eliminates this safeguard against angiogenesis; surgical manipulation releases cancer cells into the circulation; surgery-related stress response inhibits natural killer (NK) cell activity and can promote the development of cancer metastasis; local and systemic release of growth factors during surgery may also promote cancer recurrence both locally and at distant sites.
Available studies showed that general anaesthesia/anesthetics may influence the cellular immune function and long-term outcomes. For example, it was found that ketamine and thiopental, but not propofol, suppressed NK cell activity; all three drugs caused a significant reduction in NK cell number; isoflurane and halothane inhibit interferon (IFN) stimulation of NK cell cytotoxicity; nitrous oxide interferes with DNA, purine, and thymidylate synthesis and depresses neutrophil chemotaxis; opioids have been reported to suppress cell-mediated and humoral immunity.
Considering the potential harmful effects of general anesthesia/anesthetics, there is an increasing interest on the effect of regional anaesthesia. Retrospective studies investigating the relationship between epidural anesthesia and outcome after cancer surgery gave different results. In a meta-analysis, regional anesthesia is associated with improved survival (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.74-0.96, P = 0.013), but not cancer recurrence/metastasis (HR 0.88, 95% Cl 0.64-1.22, P = 0.457). The investigators hypothesize that combined use of epidural anesthesia may produce favorable effects on the long-term survival in elderly patients undergoing major cancer surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Elderly patients (age 60-90 years);
- •Scheduled to undergo noncardiac thoracic or abdominal surgery with an expected duration of 2 hours or longer. For those who undergo thoracoscopic or laparoscopic surgery, the expected length of incision must be 5 centimeters or more;
- •Agree to receive patient-controlled postoperative analgesia.
排除标准
- •Refuse to participate;
- •Previous history of schizophrenia, epilepsy or Parkinson disease, or unable to complete preoperative assessment due to severe dementia, language barrier or end-stage disease;
- •History of myocardial infarction or stroke within 3 months before surgery;
- •Presence of any contraindication to epidural anesthesia and analgesia, including abnormal vertebral anatomy, previous spinal trauma or surgery, severe chronic back pain, coagulation disorder (prothrombin time or activated partial prothrombin time longer than 1.5 times of the upper normal limit, or platelet count of less than 80 * 10^9/L), local infection near the site of puncture, and severe sepsis;
- •Severe heart dysfunction (New York Heart Association functional classification 3 or above), severe hepatic insufficiency (Child-Pugh grade C), or severe renal insufficiency (serum creatinine of 442 umol/L or above, with or without serum potassium of 6.5 mmol/L or above, or requirement of renal replacement therapy);
- •Any other conditions that are considered unsuitable for study participation.
研究组 & 干预措施
Combined epidural-general anesthesia
Patients assigned to this group (experimental group) receive combined epidural-general anesthesia and postoperative patient-controlled epidural analgesia.
干预措施: Combined epidural-general anesthesia (Drug)
General anesthesia
Patients assigned to this group (control group) receive general anesthesia and postoperative patient-controlled intravenous analgesia.
干预措施: General anesthesia (Drug)
结局指标
主要结局
Overall survival after surgery.
时间窗: Up to median 5 years after surgery.
Time from surgery to the date of all-cause death.
次要结局
- Cancer-specific survival after surgery.(Up to median 5 years after surgery.)
- Recurrence-free survival after surgery.(Up to median 5 years after surgery.)
- Event-free survival after surgery.(Up to median 5 years after surgery.)
研究者
Dong-Xin Wang
Professor
Peking University First Hospital