The Influence of Epigenetic Modification in OPRM1 on Postoperative Analgesia and Side Effect Induced by μ-opioid Receptor Agonists
试验速览
- 阶段
- 4 期
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Quantification of methylation in CpG islands located in gene OPRM1
研究概览
简要总结
To explore the epigenetic mechanism of postoperative analgesia and side effect induced by μ-opioid Receptor Agonists presented with sufentanil among general population.
详细描述
Patients were interviewed the day before surgery, and taught about the use of PCA pump and VAS. Pressure pain threshold(PPT) and pressure pain tolerance(PTO) were collected before surgery.
Dexmedetomidine1μg/Kg，sufentanil 0.5μg/Kg， propofol 2mg/Kg and rocuronium 0.6mg/Kg were given intravenously for induction. Anesthesia was maintained with inhalation of 1% sevoflurane and infusion of remifentanil (0.2-0.4ug/kg/min) and propofol (6-10mg/kg/h). Aterial blood pressure(ABP)，central venous pressure(CVP)，SPO2， HR，ETCO2，T and Narcotrend were monitored. Before incision, parecoxib 40mg was given intravenously, and PCA with sufentanil 1ug/ml was started immediately after surgery, suing a controlled infusion pump. The pump was programmed to use a loading dose of 2ml, background infusion at 2m/h, PCA dose of 1ml, lockout time of 10min, and maximal dose of 12ml with 1 h period.
VAS(static), VAS(dynamic), Ramssay, HR, NBP, SpO2, PCA pressing frequency, PCA comsumption were recorded 6h, 12h, 24h, 48h after surgery. Side effects such as nausea, vomiting, respiratory depression; pruritus; abdominal distention; urinary retention and dizziness were also recorded, and corresponding treatment were given.
EDTA anti-coagulated blood was collected from a central venous catheter during the operation. Genomic DNA was extracted from the blood samples, and characteristics and degree of DNA methylation of the gene OPRM1 were analysed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Screening
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •American Society of Anesthesiologists physical status Ⅰ-Ⅱ ;
- •Weight 50-75 kg;
排除标准
- •Long history of alcohol or analgesic drugs(including opioid ) abuse;
- •Heavy smoking;
- •Motion sickness;
- •Long history of PONV;
- •Chronic pain;
- •Complicated with severe heart、brain or kidney disease.
研究组 & 干预措施
patients undergoing pancreatectomy
patients undergoing pancreatectomy received dexmedetomidine 1μg/Kg，sufentanil 0.5μg/Kg， propofol 2mg/Kg，rocuronium 0.6mg/Kg for induction.And received sevoflurane(1-2%), remifentanil(0.1-0.2ug/kg/min) and propofol(0.3-0.6mg/kg/h) for maintenance. Parecoxib 40mg was given single intravenously before incision. And PCA with sufentanil 1ug/ml was started immediately after surgery.
干预措施: Sufentanil (Drug)
patients undergoing pancreatectomy
patients undergoing pancreatectomy received dexmedetomidine 1μg/Kg，sufentanil 0.5μg/Kg， propofol 2mg/Kg，rocuronium 0.6mg/Kg for induction.And received sevoflurane(1-2%), remifentanil(0.1-0.2ug/kg/min) and propofol(0.3-0.6mg/kg/h) for maintenance. Parecoxib 40mg was given single intravenously before incision. And PCA with sufentanil 1ug/ml was started immediately after surgery.
干预措施: dexmedetomidine (Drug)
patients undergoing pancreatectomy
patients undergoing pancreatectomy received dexmedetomidine 1μg/Kg，sufentanil 0.5μg/Kg， propofol 2mg/Kg，rocuronium 0.6mg/Kg for induction.And received sevoflurane(1-2%), remifentanil(0.1-0.2ug/kg/min) and propofol(0.3-0.6mg/kg/h) for maintenance. Parecoxib 40mg was given single intravenously before incision. And PCA with sufentanil 1ug/ml was started immediately after surgery.
干预措施: propofol (Drug)
patients undergoing pancreatectomy
patients undergoing pancreatectomy received dexmedetomidine 1μg/Kg，sufentanil 0.5μg/Kg， propofol 2mg/Kg，rocuronium 0.6mg/Kg for induction.And received sevoflurane(1-2%), remifentanil(0.1-0.2ug/kg/min) and propofol(0.3-0.6mg/kg/h) for maintenance. Parecoxib 40mg was given single intravenously before incision. And PCA with sufentanil 1ug/ml was started immediately after surgery.
干预措施: Rocuronium (Drug)
patients undergoing pancreatectomy
patients undergoing pancreatectomy received dexmedetomidine 1μg/Kg，sufentanil 0.5μg/Kg， propofol 2mg/Kg，rocuronium 0.6mg/Kg for induction.And received sevoflurane(1-2%), remifentanil(0.1-0.2ug/kg/min) and propofol(0.3-0.6mg/kg/h) for maintenance. Parecoxib 40mg was given single intravenously before incision. And PCA with sufentanil 1ug/ml was started immediately after surgery.
干预措施: sevoflurane (Drug)
patients undergoing pancreatectomy
patients undergoing pancreatectomy received dexmedetomidine 1μg/Kg，sufentanil 0.5μg/Kg， propofol 2mg/Kg，rocuronium 0.6mg/Kg for induction.And received sevoflurane(1-2%), remifentanil(0.1-0.2ug/kg/min) and propofol(0.3-0.6mg/kg/h) for maintenance. Parecoxib 40mg was given single intravenously before incision. And PCA with sufentanil 1ug/ml was started immediately after surgery.
干预措施: remifentanil (Drug)
patients undergoing pancreatectomy
patients undergoing pancreatectomy received dexmedetomidine 1μg/Kg，sufentanil 0.5μg/Kg， propofol 2mg/Kg，rocuronium 0.6mg/Kg for induction.And received sevoflurane(1-2%), remifentanil(0.1-0.2ug/kg/min) and propofol(0.3-0.6mg/kg/h) for maintenance. Parecoxib 40mg was given single intravenously before incision. And PCA with sufentanil 1ug/ml was started immediately after surgery.
干预措施: Parecoxib (Drug)
结局指标
主要结局
Quantification of methylation in CpG islands located in gene OPRM1
时间窗: 3 months
EDTA anti-coagulated blood was collected before induction. Genomic DNA was extracted according to the manufacturer's protocol, and CpG islands in the OPRM1 gene region were identified by CpG Island Explorer 2.0 software. Quantification of DNA methylation of all CpG sites from position +528 to +1649 in CpG islands was analysed.
次要结局
- Age(1 day)
- VAS (static) and VAS (dynamic)(6hours, 12hours, 24hours, 48hours after surgery.)
- Pulse oxygen saturation (SpO2)(6hours, 12hours, 24hours, 48hours after surgery.)
- History of smoking(1 day)
- Heart rate (HR)(6hours, 12hours, 24hours, 48hours after surgery)
- Pressure pain threshold (PPT) and pressure pain tolerance (PTO)(1 day)
- Weight(1 day)
- Height(1 day)
- Ramssay(6hours, 12hours, 24hours, 48hours after surgery.)
- PCA pressing frequency(6hours, 12hours, 24hours, 48hours after surgery)
- Sex(1 day)
- Blood pressure (BP)(6hours, 12hours, 24hours, 48hours after surgery.)
- PCA consumption(6hours, 12hours, 24hours, 48hours after surgery)
- Side effects(6hours, 12hours, 24hours, 48hours after surgery)
研究者
Ai Ling
attending doctor
Huazhong University of Science and Technology