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

The Influence of Epigenetic Modification in OPRM1 on Postoperative Analgesia and Side Effect Induced by μ-opioid Receptor Agonists

To explore the epigenetic mechanism of postoperative analgesia and side effect induced by μ-opioid Receptor Agonists presented with sufentanil among general population.

Study Overview

• Status: Unknown
• Conditions: Epigenetics
• Intervention / Treatment: Drug: Sufentanil; Drug: dexmedetomidine; Drug: propofol; Drug: Rocuronium; Drug: sevoflurane; Drug: remifentanil; Drug: Parecoxib

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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Department of Anaesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: Sufentanil; 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.; Other Names: Sufentanil Citrate Injection; Drug: dexmedetomidine; Patients received intravenous dexmedetomidine 1μg/Kg for induction.; Other Names: Dexmedetomidine Hydrochloride Injection; Drug: propofol; Patients received intravenous propofol 2mg/Kg for induction, and received intavenous pump of propofol (0.3-0.6mg/kg/h) for maintenance.; Other Names: propofol injection; Drug: Rocuronium; Patients received intravenous rocuronium 0.6mg/Kg for induction.; Other Names: Rocuronium Bromide Injection; Drug: sevoflurane; Patients received inhalation of sevoflurane (1-2%) for maintenance.; Drug: remifentanil; Patients received intavenous pump of remifentanil (0.1-0.2ug/kg/min) for maintenance.; Other Names: remifentanil Citrate Injection; Drug: Parecoxib; Parecoxib 40mg was given single intravenously before incision.; Other Names: Dynastat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of methylation in CpG islands located in gene OPRM1	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.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pressure pain threshold (PPT) and pressure pain tolerance (PTO)	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).	1 day
Sex	Patients' sex (male or female) was recorded before surgery.	1 day
Age	Patients' age in years was recorded before surgery.	1 day
Weight	Patients' weight in kilograms was recorded before surgery.	1 day
Height	Patients' height in meters was recorded before surgery.	1 day
History of smoking	Patients' history of smoking (yes or no) was recorded before surgery.	1 day
VAS (static) and VAS (dynamic)	Patients' VAS(static) and VAS(dynamic) score (range 0-10) were recorded at time point of 6hours, 12hours, 24hours, 48hours after surgery.	6hours, 12hours, 24hours, 48hours after surgery.
Ramssay	Patients' Ramssay score (range 1-6) was recorded at time point of 6hours, 12hours, 24hours, 48hours after surgery.	6hours, 12hours, 24hours, 48hours after surgery.
Heart rate (HR)	Patients' HR in bpm was recorded at time point of 6hours, 12hours, 24hours, 48hours after surgery.	6hours, 12hours, 24hours, 48hours after surgery
Blood pressure (BP)	Patients' BP in mmHg was recorded at time point of 6hours, 12hours, 24hours, 48hours after surgery.	6hours, 12hours, 24hours, 48hours after surgery.
Pulse oxygen saturation (SpO2)	Patients' SpO2 in percent was recorded at time point of 6hours, 12hours, 24hours, 48hours after surgery.	6hours, 12hours, 24hours, 48hours after surgery.
PCA pressing frequency	Patients' PCA pressing frequency in time was recorded at time point of 6hours, 12hours, 24hours, 48hours after surgery.	6hours, 12hours, 24hours, 48hours after surgery
PCA consumption	Patients' PCA consumption in ml was recorded at time point of 6hours, 12hours, 24hours, 48hours after surgery.	6hours, 12hours, 24hours, 48hours after surgery
Side effects	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.	6hours, 12hours, 24hours, 48hours after surgery

Collaborators and Investigators

• Sponsor: Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2017
• Primary Completion (Anticipated): May 31, 2017
• Study Completion (Anticipated): May 31, 2017

Study Registration Dates

• First Submitted: March 1, 2017
• First Submitted That Met QC Criteria: April 26, 2017
• First Posted (Actual): May 1, 2017

Study Record Updates

• Last Update Posted (Actual): May 1, 2017
• Last Update Submitted That Met QC Criteria: April 26, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: sufentanil; DNA methylation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anticonvulsants; Anticoagulants; Cyclooxygenase 2 Inhibitors; Anesthetics, Inhalation; Neuromuscular Agents; Chelating Agents; Sequestering Agents; Calcium Chelating Agents; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Remifentanil; Propofol; Dexmedetomidine; Sevoflurane; Bromides; Rocuronium; Sufentanil; Dsuvia; Citric Acid; Sodium Citrate; Parecoxib
• Other Study ID Numbers: ALing

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No