NCT03096730

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

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

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 150 (actual)
• Sponsor: Tianjin Medical University General Hospital · Academic / Other
• Sex: Female
• Age: 20 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• Pain
• Anesthesia

Interventions

Type	Name	Description
DRUG	Normal saline	Normal saline is intravenously administrated before anesthesia induction
DRUG	Remifentanil	Remifentanil is intravenously administrated
DRUG	Sufentanil	Sufentanil is intravenously administrated
DRUG	Dexmedetomidine injection	Dexmedetomidine is intravenously administrated before anesthesia induction
DRUG	Nalmefene	Nalmefene is intravenously administrated before anesthesia induction

Timeline

• Start date: 2017-02-06
• Primary completion: 2017-12-20
• Completion: 2017-12-30
• First posted: 2017-03-30
• Last updated: 2021-08-03
• Results posted: 2021-08-03

Locations

1 site across 1 country: China