The Influence of Epigenetic Modification in OPRM1 on Postoperative Analgesia and Side Effect Induced by μ-opioid Receptor Agonists
Overview
- Phase
- Phase 4
- Intervention
- Sufentanil
- Conditions
- Epigenetics
- Sponsor
- Huazhong University of Science and Technology
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Quantification of methylation in CpG islands located in gene OPRM1
- Last Updated
- 9 years ago
Overview
Brief Summary
To explore the epigenetic mechanism of postoperative analgesia and side effect induced by μ-opioid Receptor Agonists presented with sufentanil among general population.
Detailed Description
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.
Investigators
Ai Ling
attending doctor
Huazhong University of Science and Technology
Eligibility Criteria
Inclusion Criteria
- •American Society of Anesthesiologists physical status Ⅰ-Ⅱ ;
- •Weight 50-75 kg;
Exclusion Criteria
- •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.
Arms & Interventions
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.
Intervention: Sufentanil
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.
Intervention: dexmedetomidine
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.
Intervention: propofol
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.
Intervention: Rocuronium
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.
Intervention: sevoflurane
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.
Intervention: remifentanil
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.
Intervention: Parecoxib
Outcomes
Primary Outcomes
Quantification of methylation in CpG islands located in gene OPRM1
Time Frame: 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.
Secondary Outcomes
- 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)