The Epigenetic Modification in OPRM1 on Postoperative Analgesia and Side Effect Induced by Sufentanil

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.

• Sufentanil (Drug), also known as Sufentanil Citrate Injection: Patients received intravenous sufentanil 0.5μg/kg for induction,and received PCA after surgery with sufentanil 1ug/ml using a controlled infusion pump, which 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 within 1 hour period.
• dexmedetomidine (Drug), also known as Dexmedetomidine Hydrochloride Injection: Patients received intravenous dexmedetomidine 1μg/Kg for induction.
• propofol (Drug), also known as propofol injection: Patients received intravenous propofol 2mg/Kg for induction, and received intavenous pump of propofol (0.3-0.6mg/kg/h) for maintenance.
• Rocuronium (Drug), also known as Rocuronium Bromide Injection: Patients received intravenous rocuronium 0.6mg/Kg for induction.
• sevoflurane (Drug): Patients received inhalation of sevoflurane (1-2%) for maintenance.
• remifentanil (Drug), also known as remifentanil Citrate Injection: Patients received intavenous pump of remifentanil (0.1-0.2ug/kg/min) for maintenance.
• Parecoxib (Drug), also known as Dynastat: Parecoxib 40mg was given single intravenously before incision.

Primary outcomes

• Quantification of methylation in CpG islands located in gene OPRM1 [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

• Pressure pain threshold (PPT) and pressure pain tolerance (PTO) [1 day]: Patients' Pressure pain threshold(PPT) and pressure pain tolerance(PTO) in Kg/cm2 were measured before surgery using electronic pressure algometer (YISIDA-DS2, Hongkong, China).
• Sex [1 day]: Patients' sex (male or female) was recorded before surgery.
• Age [1 day]: Patients' age in years was recorded before surgery.
• Weight [1 day]: Patients' weight in kilograms was recorded before surgery.
• Height [1 day]: Patients' height in meters was recorded before surgery.
• History of smoking [1 day]: Patients' history of smoking (yes or no) was recorded before surgery.
• VAS (static) and VAS (dynamic) [6hours, 12hours, 24hours, 48hours after surgery.]: Patients' VAS(static) and VAS(dynamic) score (range 0-10) were recorded at time point of 6hours, 12hours, 24hours, 48hours after surgery.
• Ramssay [6hours, 12hours, 24hours, 48hours after surgery.]: Patients' Ramssay score (range 1-6) was recorded at time point of 6hours, 12hours, 24hours, 48hours after surgery.
• Heart rate (HR) [6hours, 12hours, 24hours, 48hours after surgery]: Patients' HR in bpm was recorded at time point of 6hours, 12hours, 24hours, 48hours after surgery.
• Blood pressure (BP) [6hours, 12hours, 24hours, 48hours after surgery.]: Patients' BP in mmHg was recorded at time point of 6hours, 12hours, 24hours, 48hours after surgery.
• Pulse oxygen saturation (SpO2) [6hours, 12hours, 24hours, 48hours after surgery.]: Patients' SpO2 in percent was recorded at time point of 6hours, 12hours, 24hours, 48hours after surgery.
• PCA pressing frequency [6hours, 12hours, 24hours, 48hours after surgery]: Patients' PCA pressing frequency in time was recorded at time point of 6hours, 12hours, 24hours, 48hours after surgery.
• PCA consumption [6hours, 12hours, 24hours, 48hours after surgery]: Patients' PCA consumption in ml was recorded at time point of 6hours, 12hours, 24hours, 48hours after surgery.
• Side effects [6hours, 12hours, 24hours, 48hours after surgery]: Side effects such as nausea, vomiting, respiratory depression, pruritus, abdominal distention, urinary retention and dizziness (yes or no) were recorded at time point of 6hours, 12hours, 24hours, 48hours after surgery, and corresponding treatment were given.

Sex: All, ages: 35 Years to 60 Years

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.

• Xu Hui, Study chair, Department of Anaesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology