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

Sponsor

Seoul National University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02856087

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

18.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Pain	Drug: High dose Remifentanil Drug: Naloxone Drug: Low dose remifentanil Drug: Normal Saline	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

92 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Nov 1, 2014

Actual Primary Completion Date :

Apr 1, 2015

Actual Study Completion Date :

Apr 1, 2015

Arms and Interventions

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

Arm

Intervention/Treatment

Placebo Comparator: group LR

low dose remifentanil (1 ng/ml of Ce) with normal saline infusion

Drug: Low dose remifentanil

remifentanil infusion at 1ng/ml of Ce

Drug: Normal Saline

normal saline infusion

Active Comparator: group HR

High dose remifentanil infusion (4ng/ml of Ce) with normal saline infusion

Drug: High dose Remifentanil

remifentanil infusion at 4ng/ml of Ce

Drug: Normal Saline

normal saline infusion

Experimental: group HR-N

remifentanil infusion at 4ng/ml of Ce with naloxone infusion

Drug: High dose Remifentanil

remifentanil infusion at 4ng/ml of Ce

Drug: Naloxone

naloxone infusion

Outcome Measures

Primary Outcome Measures

Mechanical pain thresholds [24hr after surgery]
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.

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.