Clinical trial NCT02043366: Effect of Butorphanol Combined With Flurbiprofen Axetil on Preventing Hyperalgesia Induced by Remifentanil in Patients
Official title: Effect of Butorphanol Combined With Flurbiprofen Axetil on Preventing Postoperative Hyperalgesia Induced by Remifentanil in Patients Undergoing Lower Abdomimal Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pain
Anesthesia
Keywords: Remifentanil
Opioid-induced hyperalgesia
Postoperative pain
Pain Intensity
Lead sponsor: Tianjin Medical University General Hospital
Sponsor class: OTHER
First posted: 2014-01-23
Enrollment: 180
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

1. Subject is scheduled to undergo lower abdominal surgery under a short general anesthesia of less than 2 hours
2. Subject's American Society of Anesthesiologists physical status is I-II.
3. The subject's parent/legally authorized guardian has given written informed consent to participate.

Exclusion Criteria:

1. Subject has a diagnosis of renal or liver failure.
2. Subject has a diagnosis of Insulin dependent diabetes.
3. Subject is allergy and contraindication to butorphanol or NSAIDs.
4. 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 hours before surgery.
5. Subject has any contraindication for the use of patient-controlled analgesia (PCA).
6. Subject is pregnant or breast-feeding.
7. Subject is obese (body mass index \>30kg/m\^2).

Primary outcomes:
measure: Mechanical Hyperalgesia Threshold on the Dominant Inner Forearm
timeFrame: 24 hours after surgery
Secondary outcomes:
measure: Pain Score (NRS)
timeFrame: 3h, 6h, 12h, and 24h after surgery
measure: Time of First Postoperative Analgesic Requirement
timeFrame: 1 hour post surgery
measure: Occurrence of Side Effects
timeFrame: 24 hours
measure: Total Dose of First Postoperative Analgesic Requirement
timeFrame: 1 hour after surgery
measure: Cumulative Sufentanyl Consumption
timeFrame: 24 hours
measure: Normalized Area of Hyperalgesia Around the Incision
timeFrame: 24 hours after surgery
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University General Hospital
name: Guolin Wang, MD
role: STUDY_DIRECTOR
References:
citation: Zhang L, Shu R, Zhao Q, Li Y, Yu Y, Wang G. Preoperative butorphanol and flurbiprofen axetil therapy attenuates remifentanil-induced hyperalgesia after laparoscopic gynaecological surgery: a randomized double-blind controlled trial. Br J Anaesth. 2016 Oct;117(4):504-511. doi: 10.1093/bja/aew248. Epub 2016 Oct 17.