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

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

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Low dose remifentanil; Drug: Normal Saline; Drug: High dose Remifentanil; Drug: Naloxone

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 Type: Interventional
• Enrollment (Actual): 92
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / 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: Normal Saline; normal saline infusion; Drug: High dose Remifentanil; remifentanil infusion at 4ng/ml of Ce
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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Publications and helpful links

General Publications

• Koo CH, Yoon S, Kim BR, Cho YJ, Kim TK, Jeon Y, Seo JH. Intraoperative naloxone reduces remifentanil-induced postoperative hyperalgesia but not pain: a randomized controlled trial. Br J Anaesth. 2017 Dec 1;119(6):1161-1168. doi: 10.1093/bja/aex253.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (ACTUAL): April 1, 2015
• Study Completion (ACTUAL): April 1, 2015

Study Registration Dates

• First Submitted: August 2, 2016
• First Submitted That Met QC Criteria: August 2, 2016
• First Posted (ESTIMATE): August 4, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): November 16, 2016
• Last Update Submitted That Met QC Criteria: November 15, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: surgery; acute pain; postoperative
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Sensation Disorders; Somatosensory Disorders; Hyperalgesia; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Remifentanil; Naloxone
• Other Study ID Numbers: YSjeon_naloxone

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO