Effect of Dexmedetomidine Combined With Low-dose Nalmefene on Preventing Remifentanil-induced Postoperative Hyperalgesia
Condition: Pain; Anesthesia
MeSH terms: Hyperalgesia
Study type: Interventional

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.
    

Intervention name(s): Normal saline; Remifentanil; Sufentanil; Dexmedetomidine injection; Nalmefene
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Normal saline is intravenously administrated before anesthesia induction; Remifentanil is intravenously administrated; Sufentanil is intravenously administrated; Dexmedetomidine is intravenously administrated before anesthesia induction; Nalmefene is intravenously administrated before anesthesia induction
Other intervention name(s): 0. 9% Sodium Chloride Injection; Remifentanil Hydrochloride for Injection; Sufentanil injection; Dexmedetomidine
Intervention MeSH terms: Sufentanil; Dexmedetomidine; Remifentanil; Dsuvia; Nalmefene
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Remifentanil; Opioid-induced hyperalgesia; Postoperative pain; pain intensity