Impact of Inhalational Versus Intravenous Anesthesia Maintenance Methods on 5-year Survival in Elderly Patients After Cancer Surgery: a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,228
- 试验地点
- 15
- 主要终点
- Over survival after surgery.
研究概览
简要总结
Surgery is one of the major treatment methods for patients with solid organ cancer. And, alone with the ageing process, more and more elderly patients undergo surgery for cancer. Evidence emerges that choice of anesthetics, i.e., either inhalational or intravenous anesthetics, may influence the outcome of elderly patients undergoing cancer surgery. From the point of view of immune function after surgery and invasiveness of malignant tumor cells, propofol intravenous anesthesia may be superior to inhalational anesthesia. However, the clinical significance of these effects remains unclear. Retrospective studies indicated that use of propofol intravenous anesthesia was associated higher long-term survival rate. Prospective studies exploring the effect of anesthetic choice on long-term survival in cancer surgery patients are urgently needed.
详细描述
It is estimated that 234.2 million major surgical procedures are undertaken every year worldwide. Surgery is one of the major treatment methods for patients with solid organ cancer. And, alone with the ageing process, more and more elderly patients undergo surgery for cancer. However, evidence emerges that choice of anesthetics, i.e., either inhalational or intravenous anesthetics, may influence the outcome of elderly patients undergoing cancer surgery.
A. Effects of anesthetics on immune function after surgery
The choice of general anesthetics might influence human's immune function after surgery. An international multicenter team investigated the effects of propofol-paravertebral anesthesia vs sevoflurane-opioid anesthesia on the immune function in patients after breast cancer surgery. In a small sample size (n = 32) randomized controlled trail published in 2010, postoperative serum concentrations of interleukin (IL)-1 (protumorigenic cytokine) and matrix metalloproteinases (MMP)-3/9 (associated with cancer cell invasion and metastasis) were significantly lower (P = 0.003 and 0.011, respectively), whereas that of IL-10 (antitumorigenic cytokines) was significantly higher in the propofol group than in the sevoflurane group (P = 0.001). In another small sample size (n = 10) randomized controlled trail published in 2014, serum obtained from patients who received propofol anesthesia led to greater human donor natural killer (NK) cell cytotoxicity in vitro when compared with serum from those who received sevoflurane anesthesia. In a recent small sample size (n = 28) randomized controlled trial, the levels of NK and T helper cell infiltration in breast cancer tissue were significantly higher in patients receiving propofol anesthesia than those receiving sevoflurane anesthesia (P = 0.015 and 0.03, respectively).
Similar findings were reported in patients with other malignant tumors. In a small randomized controlled trial, 30 patients with non-small-cell lung cancer randomly received either propofol or isoflurane anesthesia. The results showed that cluster of differentiation (CD)4+CD28+ percentage (P < 0.0001) and the ratio of interferon-gamma:interleukin-4 (P = 0.001) all increased significantly with propofol but no change with isoflurane anesthesia; indicating that propofol promotes activation and differentiation of peripheral T-helper cells. In another randomized controlled trial, 60 patients undergoing surgery for tongue cancer surgery randomly received total propofol, mixed (propofol induction and sevoflurane maintenance) anesthesia or total sevoflurane anesthesia. The results showed that the percentages of CD3+, CD3+CD4+, and NK cells and the ratio of CD4+/CD8+ were significantly decreased in the two sevoflurane groups, but not in the total propofol group; suggesting that propofol has less effects on cellular immune response than sevoflurane. There are also studies that reported neutral results.
The above studies suggest that, when compared with inhalational anesthesia, propofol intravenous anesthesia may have favorable effects on the immune function in patients after cancer surgery. However, care must be taken when explaining these results: (1) the sample sizes of the available studies were small; (2) the relationship between postoperative immune function changes and long-term outcomes remains unclear.
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
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 90 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants will be included if they meet all the following criteria:
- •Age ≥ 65 years and < 90 years;
- •Primary malignant tumor;
- •Do not receive radiation therapy or chemotherapy before surgery;
- •Scheduled to undergo surgery for the treatment of tumors, with an expected duration of 2 hours or more, under general anesthesia;
- •Agree to participate, and give signed written informed consent.
排除标准
- •Patients will be excluded if they meet any of the following criteria:
- •Preoperative history of schizophrenia, epilepsy, parkinsonism or myasthenia gravis;
- •Inability to communicate in the preoperative period (coma, profound dementia, language barrier, or end-stage disease);
- •Critical illness (preoperative American Society of Anesthesiologists physical status classification ≥ IV);
- •Severe hepatic dysfunction (Child-Pugh class C), or severe renal dysfunction (undergoing dialysis before surgery);
- •Neurosurgery.
研究组 & 干预措施
Sevoflurane group
Anesthesia will be induced intravenously with midazolam (0.015-0.03 mg/kg), sufentanil, propofol, and rocuronium.
Sevoflurane will be administered by inhalation for anesthesia maintenance. The concentration of inhaled sevoflurane will be adjusted to maintain the bispectral index (BIS) value between 40 and 60. Analgesia will be supplemented with remifentanil (administered by continuous infusion), sufentanil (administered by intermittent injection/continuous infusion), or fentanyl (administered by intermittent injection).
Towards the end of surgery, sevoflurane inhalational concentration will be decreased and fentanyl/sufentanil will be administered when necessary. Sevoflurane inhalation will be stopped at the end of surgery.
干预措施: Sevoflurane (Drug)
Propofol group
Anesthesia will be induced intravenously with midazolam (0.015-0.03 mg/kg), sufentanil, propofol, and rocuronium.
Propofol will be administered by intravenous infusion for anesthesia maintenance. The infusion rate of propofol will be adjusted to maintain the BIS value between 40 and 60. Analgesia will be supplemented with remifentanil (administered by continuous infusion), sufentanil (administered by intermittent injection/continuous infusion), or fentanyl (administered by intermittent injection).
Towards the end of surgery, propofol infusion rate will be decreased and fentanyl/sufentanil will be administered when necessary. Propofol infusion will be stopped at the end of surgery.
干预措施: Propofol (Drug)
结局指标
主要结局
Over survival after surgery.
时间窗: Up to 5 years after surgery
Time from surgery to the date of all-cause death.
次要结局
- Event-free survival after surgery(Up to 5 years after surgery)
- Recurrence-free survival after surgery(Up to 5 years after surgery)
研究者
Dong-Xin Wang
Professor
Peking University First Hospital