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

Tianjin Medical University

Status: Completed

Conditions: Pain; Anesthesia

Treatments: Drug: Nalmefene; Drug: Dexmedetomidine injection; Drug: Sufentanil; Drug: Remifentanil; Drug: Normal saline

Study type: Interventional

Funder types: Other

Identifiers

NCT03096730

GWang003

Details and patient eligibility

About

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.

Full 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.

Enrollment: 150 patients

Sex: Female

Ages: 20 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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150 participants in 5 patient groups, including a placebo group

Normal Saline

Placebo Comparator group

Description:

Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil

Treatment:

Drug: Remifentanil

Drug: Normal saline

Sufentanil

Sham Comparator group

Description:

Normal saline is intravenously admistrated before anesthesia induction and intraoperative pain management was with sufentanil

Treatment:

Drug: Normal saline

Drug: Sufentanil

Dexmedetomidine

Active Comparator group

Description:

Dexmedetomidine is intravenously administrated at a dose of 0.5ug/kg 10min before anesthesia induction and intraoperative pain management was with remifentanil

Treatment:

Drug: Remifentanil

Drug: Dexmedetomidine injection

Nalmefene

Active Comparator group

Description:

Nalmefene is intravenously administrated at a dose of 0.2ug/kg before anesthesia induction and intraoperative pain management was with remifentanil

Treatment:

Drug: Nalmefene

Drug: Remifentanil

Dexmedetomidine-Nalmefene

Active Comparator group

Description:

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

Treatment:

Drug: Nalmefene

Drug: Remifentanil

Drug: Dexmedetomidine injection