Effect of Dexmedetomidine Combined With Low-dose Nalmefene on Preventing Remifentanil-induced Postoperative Hyperalgesia

August 2, 2021 updated by: Guolin Wang, Tianjin Medical University General Hospital

The Effect of Dexmedetomidine Combined With Low-dose Nalmefene on Preventing Remifentanil-induced Postoperative Hyperalgesia in Patients Undergoing Gynecological Surgery

To explore and compare antihyperalgesic effects of Dexmedetomidine,Nalmefene,and a combination of both received before anesthesia induction.

To evaluate and examine the incidence of adverse effects with the purpose of selecting the optimum dose.

Study Overview

Detailed Description

There are a dramatically increasing number of evidences that administration of the potent, ultra-short-acting opioid remifentanil seems to cause opioid-induced hyperalgesia (OIH) more frequently and predictably compared with the others, likely due to its rapid onset and offset. Therefore, prophylaxis of remifentanil induced hyperalgesia is indispensable to postoperative comfort and satisfaction.

There is no denying the fact that OIH is related to central glutaminergic system and N-methyl-d-aspartate(NMDA)receptor-activation induced central sensitization. Dexmedetomidine is an 2-adrenergic agonist that has been shown to synergize with opioids. Dexmedetomidine inhibits NMDAR excitability by reducing the phosphorylation of N-methyl-D-aspartate receptor 2B subunit phosphorylation of spinal dorsal horn induced by remifentanil, thereby achieving the goal of reducing OIH. Nalmefene is a pure opioid receptor antagonist that antagonizes the Mu receptor, alleviating the central sensitization of NMDA, thereby reducing OIH. At the same time reported in the literature, opioid receptor has a bimode:On the one hand can be mediated by Gs protein-mediated pain, respiratory depression, nausea and vomiting, etc ; on the other hand can be coupled with Gi / Go protein mediated analgesic effect. Low-dose nalmefene (<1.0ug / kg) and other opioid receptor antagonists can antagonize the role of Gs protein-coupled opioid receptors, blocking the pathway of opioid excitatory effects, thereby reducing the incidence of adverse reactions.The following study is carried out to evaluate whether dexmedetomidine combined with nalmefene can be safely and effectively applied to prevent postoperative hyperalgesia induced by remifentanil in patients undergoing Laparoscopic gynecological surgery.

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Tianjin
      • Tianjin, Tianjin, China, 300052
        • Tianjin Medical University General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Patients are scheduled to undergo Gynecological surgery under a short general anesthesia of 1-3 hours.
  2. American Society of Anesthesiologists physical status is I-II.
  3. Written informed consent was obtained from all the subjects.

Exclusion Criteria:

  1. Subject has a diagnosis of Coronary heart disease, bronchial asthma, cardiac, lung, hepatic and renal insufficiency.
  2. Subject has a diagnosis of Severe high blood pressure , diabetes, obesity (BMI>30).
  3. Subject has a history of chronic pain, a history of alcohol or opioid abuse, pre-existing therapy with opioids, intake of any analgesic drug within 48 h before surgery.
  4. .Subject has Pregnancy, psychiatric disease.
  5. Subject has any contraindication for the use of patient-controlled analgesia (PCA).
  6. Inability to understand the Study Information Sheet and provide a written consent to take part in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Normal Saline
Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil
Remifentanil is intravenously administrated
Other Names:
  • Remifentanil Hydrochloride for Injection
Normal saline is intravenously administrated before anesthesia induction
Other Names:
  • 0. 9% Sodium Chloride Injection
Sham Comparator: Sufentanil
Normal saline is intravenously admistrated before anesthesia induction and intraoperative pain management was with sufentanil
Sufentanil is intravenously administrated
Other Names:
  • Sufentanil injection
Normal saline is intravenously administrated before anesthesia induction
Other Names:
  • 0. 9% Sodium Chloride Injection
Active Comparator: Dexmedetomidine
Dexmedetomidine is intravenously administrated at a dose of 0.5ug/kg 10min before anesthesia induction and intraoperative pain management was with remifentanil
Remifentanil is intravenously administrated
Other Names:
  • Remifentanil Hydrochloride for Injection
Dexmedetomidine is intravenously administrated before anesthesia induction
Other Names:
  • Dexmedetomidine
Active Comparator: Nalmefene
Nalmefene is intravenously administrated at a dose of 0.2ug/kg before anesthesia induction and intraoperative pain management was with remifentanil
Remifentanil is intravenously administrated
Other Names:
  • Remifentanil Hydrochloride for Injection
Nalmefene is intravenously administrated before anesthesia induction
Active Comparator: Dexmedetomidine-Nalmefene
A dose of 0.1ug/kg nalmefene and a dose of 0.25ug/kg dexmedetomidine for 10 minutes before anesthesia induction and intraoperative pain management was with remifentanil
Remifentanil is intravenously administrated
Other Names:
  • Remifentanil Hydrochloride for Injection
Dexmedetomidine is intravenously administrated before anesthesia induction
Other Names:
  • Dexmedetomidine
Nalmefene is intravenously administrated before anesthesia induction

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mechanical Hyperalgesia Threshold on the Dominant Inner Forearm
Time Frame: 24 hours after surgery
The mechanical hyperalgesia threshold was defined as the lowest force (g) necessary to bend a Von Frey filament, which was perceived to be painful by the patient and measured by Von Frey filament at 24 hours postoperatively
24 hours after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Normalized Area of Hyperalgesia Around the Incision
Time Frame: 1hours,3hours,6hours,12hours,24hours after surgery
The skin around the incision is stimulated in steps of 5 mm at intervals of 1 s starting outside of the hyperalgesic area in the direction of the incision. The distance from the incision to the first point where a 'painful', 'sore' or 'sharper' feeling occurred is measured and noted. This measurement is repeated at predefined radial lines around the incision. To eliminate the variable length of incision, this length is subtracted from the longer diameter leaving four radial distances from the end and from the middle of the incision. The normalized area of hyperalgesia is calculated by summing up the areas of the remaining four triangles measured by and Von Frey filament.
1hours,3hours,6hours,12hours,24hours after surgery
Pain Score (Numerical Rating Scale)
Time Frame: 1hours,3hours,6hours,12hours,24hours after surgery
The pain score at rest was evaluated by pain 11-point numerical rating scale : 0 = no pain, 10 = greatest imaginable pain.
1hours,3hours,6hours,12hours,24hours after surgery
Time of First Postoperative Analgesic Requirement
Time Frame: postoperative 1 hours
First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl.
postoperative 1 hours
Cumulative Sufentanyl Consumption
Time Frame: 1hours,3hours,6hours,12hours,24hours after surgery
Each patient was administered analgesics using a PCA pump containing sufentanil (100μg) in normal saline at a total volume of 100 ml after leaving post-anaesthesia care unit . This device was set to deliver a basal infusion of 2 ml/h and bolus doses of 0.5 ml with a 15-min lockout period. Sufentanyl cumulative consumption is recorded 24 hours postoperatively
1hours,3hours,6hours,12hours,24hours after surgery
Occurrence of Side Effects
Time Frame: 24 hours
Occurrence of side effects: nausea, vomiting, dizziness, headache, shivering, pruritus,hypotention/hypertention,bradycardia/tachycardia
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Wang Guolin, MD, Tianjin Medical University General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 6, 2017

Primary Completion (Actual)

December 20, 2017

Study Completion (Actual)

December 30, 2017

Study Registration Dates

First Submitted

March 13, 2017

First Submitted That Met QC Criteria

March 24, 2017

First Posted (Actual)

March 30, 2017

Study Record Updates

Last Update Posted (Actual)

August 3, 2021

Last Update Submitted That Met QC Criteria

August 2, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

data not entered

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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