The Effect of Ultra-low-dose Naloxone on Remifentanil-induced Postoperative Hyperalgesia - A Randomized Controlled Study

Study Overview
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Brief Summary
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High-dose remifentanil infused intraoperative ironically results in postoperative hyperalgesia. Ultra-low dose nalxone is demonstrated to prevent these opioid-induced hyperalgesia in animal model. In this clinical trial in patients undergoing general anesthesia with remifentanil, we evaluate the effects of ultra-low-dose naloxone on remifentanil-induced hyperalgesia

Detailed Description
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We enrolled adult patients undergoing thyroidectomy under general anesthesia with desflurane and remifentanil. Remifentanil was administered via target-controlled infusion and anesthetic depth was maintained keeping the BIS between 40 and 60. Patients were randomized into one of three groups depending on intraoperative doses of remifentanil and naloxone: effect-site concentrations of remifentanil 1 ng/ml (control group), 4 ng/ml (remifentanil group), and 4 ng/ml combined with infusion rate 0.8 ng/kg/min of naloxone (remifentanil and naloxone group). Postoperative mechanical pain thresholds, pain intensity, and analgesic consumption were examined during 48 h of postoperative period. The primary outcome was mechanical pain threshold measured on the peri-incisional area 24 h after surgery.

Official Title
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The Effect of Ultra-low-dose Naloxone on Remifentanil-induced Postoperative Hyperalgesia - A Randomized Controlled Study

Conditions
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Pain

Intervention / Treatment
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* Drug: High dose Remifentanil
* Drug: Naloxone
* Drug: Low dose remifentanil
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients who are scheduled to undergo elective thyroidectomy Exclusion Criteria: consent refusal, obesity, pregnancy, hx. of thyroid surgery, neurological disorders, psychiatric disorders, hx. of drug abuse or chronic use of opioids or sedative drugs, intake of any analgesic drug within 12h before surgery.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: group LR<br>low dose remifentanil (1 ng/ml of Ce) with normal saline infusion | Drug: Low dose remifentanil<br>* remifentanil infusion at 1ng/ml of Ce<br>Drug: Normal Saline<br>* normal saline infusion<br>|
| Active Comparator: group HR<br>High dose remifentanil infusion (4ng/ml of Ce) with normal saline infusion | Drug: High dose Remifentanil<br>* remifentanil infusion at 4ng/ml of Ce<br>Drug: Normal Saline<br>* normal saline infusion<br>|
| Experimental: group HR-N<br>remifentanil infusion at 4ng/ml of Ce with naloxone infusion | Drug: High dose Remifentanil<br>* remifentanil infusion at 4ng/ml of Ce<br>Drug: Naloxone<br>* naloxone infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical pain thresholds | Mechanical pain thresholds were assessed by von Frey filaments. The patients were asked to close their eyes during the test, and an investigator made the filament pressing the skin perpendicularly against the skin until bowing and being maintained for 1.5 seconds. The filament size was started from 0.4 g and was increased to the point until the patient perceives a clear change in sensation. | 24hr after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical pain thresholds |  | 48hr after surgery | 
| pain score |  | verbal numerical rating scale at 24 hr after surgery | 
| pain score |  | verbal numerical rating scale at 48 after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute pain, postoperative, surgery