Clinical trial NCT02043366
Conditions: Pain Anesthesia
Keywords: Remifentanil Opioid-induced hyperalgesia Postoperative pain Pain Intensity
Sponsor: Tianjin Medical University General Hospital
Start date: 2014-02-01; Completion date: 2015-08-01
Enrollment: 180 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Purpose:

To explore and compare antihyperalgesic effects of butorphanol, flurbiprofen axetil, 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.

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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. Prostaglandins can promote glutamate release from both astrocytes and spinal cord dorsal horns with subsequent activation of the NMDA receptors, and flurbiprofen axetil, as non-steroidal anti-inflammatory drugs (NSAIDs), not only functionally antagonizes the NMDA receptor activation via inhibition of prostaglandins, but also is a targeted drug which gathers at the site of inflammation, thus greatly enhances the analgesic effect. While butorphanol has both spinal analgesic and sedative functions because of predominantly central κ-receptor agonist activation, other advantages of butorphanol include few side effects, very low addiction potential, and low toxicity on account of a partial agonist-antagonist activity to μ-receptor. Moreover, antihyperalgesic activity of κ opioids at the site of inflammation has been reported in various acute pain models. The following study is carried out to evaluate whether butorphanol combined with flurbiprofen axetil can be safely and effectively applied to preventing postoperative hyperalgesia induced by remifentanil in patients undergoing lower abdominal surgery.

Arms: arm 1: Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil arm 2: Butorphanol is intravenously administrated at a dose of 20μg/ kg before anesthesia induction and intraoperative pain management was with remifentanil arm 3: Flurbiprofen axetil is intravenously administrated at a dose of 1.0mg/ kg before anesthesia induction and intraoperative pain management was with remifentanil arm 4: Flurbiprofen axetil is intravenously administrated at a dose of 1.0mg/ kg before the skin closure and intraoperative pain management was with remifentanil arm 5: A dose of 10μg/ kg butorphanol and a dose of 0.5mg/ kg flurbiprofen axetil are intravenously administrated before anesthesia induction and intraoperative pain management was with remifentanil arm 6: Normal saline is intravenously administrated before anesthesia induction and intraoperative pain management was with sufentanil
Interventions: intervention 1: Normal Saline intervention 2: Butorphanol intervention 3: Flurbiprofen axetil intervention 4: Remifentanil intervention 5: Sufentanil
Intervention descriptions: intervention 1: Normal Saline is intravenously administrated before anesthesia induction intervention 2: Butorphanol is intravenously administrated intervention 3: Flurbiprofen axetil is intravenously administrated intervention 4: Remifentanil is intravenously administrated intervention 5: Sufentanil is intravenously administrated

Protocol documents: