Investigation of the Strategy of Preventing Post-operative Opioid-induced Hyperalgesia

Investigation of the Strategy of Preventing Post-operative Opioid-induced Hyperalgesia by Remifentanil Infusion

The concept of Enhanced Recovery After Surgery(ERAS) has been prevalent in recent years. In the ERAS guideline, short-acting anesthetics, instead of long-acting opioid anesthetics, were recommended during surgery to decrease post-operative complication and length of hospital stay. Propofol-remifentanil based total intravenous anesthesia (TIVA) can provide quicker emergence and decreased post-operative nausea and vomiting. However, the prescription of opioid (especially remifentanil) may induce opioid-induced hyperalgesia (OIH) and increase the requirement of analgesics. Previous studies provided some strategies to prevent OIH. The purpose of this study is to investigate the effect of adding remifentanil(1 mcg/kg) after emergence and endotracheal extubation in breast cancer females receiving breast surgery under propofol-remifentanil based TIVA for the prevention of OIH.

Study Overview

• Status: Completed
• Conditions: Opioid-Induced Disorders
• Intervention / Treatment: Drug: Remifentanil

Detailed Description

1. After obtaining informed consent, patients will be randomized into two groups.
2. All patients receive remifentanil-propofol based TIVA and Bispectral index (BIS) monitor during breast surgery. In the end of surgery, intravenous NSAID(keto) 30mg and local anestehsia (Marcaine) infiltration around the surgical wound will be prescribed to reduce post-operative pain.
3. group R(intervention): remifentanil 1mcg/kg diluted with 0.9% saline to 50ml and drip for 30 minutes after emergence and extubation of endotracheal tube
4. group N(no intervention): 0.9% saline 50ml drip for 30 minutes after emergence and extubation of endotracheal tube
5. In post-anesthesia room: record the numerical rating scale (NRS); requirement of additional analgesics (rescue medication), blood pressure, heart rate, pulse oximeter, degree of nausea, vomiting
6. In ward: record the numerical rating scale (NRS) and total analgesics consumption

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 114
    • Tri-Service General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject's ASA (American Society of Anesthesiologists) Physical Status Classification: I (A normal healthy patient)~III(A patient with severe systemic disease)
• Subject has breast cancer and scheduled for breast surgery using total-intravenous anesthesia(TIVA)

Exclusion Criteria:

• Subject's ASA (American Society of Anesthesiologists) Physical Status Classification >3
• Subject doesn't receive total-intravenous anesthesia(TIVA) during surgery
• Subject has psychiatric disease
• allergic to opioid or propofol
• History of alcoholism
• History of drug abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: remifentanil; After emergence and extubation of endotracheal tube, remifentanil 1mcg/kg were diluted with 0.9% saline to 50 ml, added in IV bag, and drip for 30 minutes.	Drug: Remifentanil; remifentanil 1mcg/kg added in 0.9% saline and diluted to 50ml; Other Names: Remifentanil ALVOGEN powder
No Intervention: no intervention; After emergence and extubation of endotracheal tube, 0.9% saline 50ml were added in IV bag and drip for 30 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numerical Rating Score (NRS) for pain score in post-anesthesia room (PAR)	1.The pain after breast surgery is moderate and suppose to be reduced after combined prescription of NSAID and local analgesics. Post-operative pain is supposed to be related with hyperalgesia. 2.Record the degree of post-operative pain by Numerical Rating Scale (Numerical Rating Scale)(0-10; 0= no pain; 10=pain as bad as can be)	0 minutes
Numerical Rating Score (NRS) for pain score in post-anesthesia room (PAR)	1.The pain after breast surgery is moderate and suppose to be reduced after combined prescription of NSAID and local analgesics. Post-operative pain is supposed to be related with hyperalgesia. 2.Record the degree of post-operative pain by Numerical Rating Scale (Numerical Rating Scale)(0-10; 0= no pain; 10=pain as bad as can be)	30 minutes
The amount analgesic requirement in post-anesthesia room (PAR)	1.The pain after breast surgery is moderate and suppose to be reduced after combined prescription of NSAID and local analgesics during surgery. Post-operative pain is supposed to be related with hyperalgesia. 2.Record the degree of post-operative pain by record additional analgesics amount (rescue medication, mg) in PAR	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
degree of post-operative nausea in post-anesthesia room (PAR)	Record the degree of nausea in PAR: mild, moderate, severe	30 minutes
degree of post-operative vomiting in post-anesthesia room (PAR)	Record the degree of vomiting in PAR: mild, moderate, severe	30 minutes
post-operative blood pressure in post-anesthesia room (PAR)	Record the blood pressure(mmHg) in PAR	0 minutes
post-operative systolic blood pressure in post-anesthesia room (PAR)	Record the systolic blood pressure(mmHg) in PAR	0 minutes
post-operative systolic blood pressure in post-anesthesia room (PAR)	Record the systolic blood pressure(mmHg) in PAR	30 minutes
post-operative diastolic blood pressure in post-anesthesia room (PAR)	Record the diastolic blood pressure(mmHg) in PAR	30 minutes
post-operative heart rate in post-anesthesia room (PAR)	Record the heart rate (beat/min) in PAR	0 minutes
post-operative heart rate in post-anesthesia room (PAR)	Record the heart rate (beat/min) in PAR	30 minutes
post-operative pulse oximeter in post-anesthesia room (PAR)	Record the pulse oximeter(SpO2; %) in PAR	0 minutes
postoperative pulse oximeter in post-anesthesia room (PAR)	Record the pulse oximeter(SpO2; %) in PAR	30 minutes
Numerical Rating Score (NRS) for pain score in ward	Record the degree of post-operative pain by Numerical Rating Scale (NRS)(0-10; 0= no pain; 10=pain as bad as can be)	1 hour after transferring to ward
Numerical Rating Score (NRS) for pain score in ward	Record the degree of post-operative pain by Numerical Rating Scale (NRS)(0-10; 0= no pain; 10=pain as bad as can be)	2 hours after transferring to ward
Numerical Rating Score (NRS) for pain score in ward	Record the degree of post-operative pain by Numerical Rating Scale (NRS)(0-10; 0= no pain; 10=pain as bad as can be)	4 hours after transferring to ward
Numerical Rating Score (NRS) for pain score in ward	Record the degree of post-operative pain by Numerical Rating Scale (NRS)(0-10; 0= no pain; 10=pain as bad as can be)	8 hours after transferring to ward
Numerical Rating Score (NRS) for pain score in ward	Record the degree of post-operative pain by Numerical Rating Scale (NRS)(0-10; 0= no pain; 10=pain as bad as can be)	24 hours after transferring to ward
total analgesics requirement in ward	Record total analgesic requirement (mg) in ward	24hr after transferring to ward

Collaborators and Investigators

• Sponsor: Tri-Service General Hospital
• Investigators: Study Chair: Jyh-cherng Yu, MD, Tri-Service General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2019
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): February 1, 2020

Study Registration Dates

• First Submitted: January 13, 2019
• First Submitted That Met QC Criteria: January 18, 2019
• First Posted (Actual): January 22, 2019

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: opioid-induced hyperalgesia, remifentanil
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Sensation Disorders; Somatosensory Disorders; Hyperalgesia; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Acids, Acyclic; Carboxylic Acids; Piperidines; Propionates; Remifentanil
• Other Study ID Numbers: 2-107-05-162

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Numerical rating scale, rescue analgesic amount

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No