The Effect of Remimazolam on Opioid Induced Hyperalgesia

The Effect of Remimazolam on Remifentanil-induced Hyperalgesia

The goal of this prospective, randomized, controlled study is to investigate the effect of remimazolam on opioid-induced hyperalgesia (OIH) in patients undergoing single port-laparoscopically assisted urologic surgery.

The main question[s] it aims to answer are:

• [The mechanical hyperalgesia threshold]
• [Area of hyperalgesia around the surgical incision 24 h after surgery (cm^2)]

In three groups: Group RHR (Remimazolam- High-dose Remifentanil), Group DHR (Desflurane-low-dose Remifentanil) or Group DLR (Control).

Study Overview

• Status: Completed
• Conditions: Hyperalgesia, Mechanical
• Intervention / Treatment: Drug: Desflurane; Drug: Remifentanil; Drug: Remimazolam

Detailed Description

Ninety-three (n = 31 per group) American Society of Anesthesiologists I-II patients (age 20-65 years) will be scheduled for single port-laparoscopically assisted urologic surgery.

Group RHR (Remimazolam-Remifentanil): Administer remimazolam at a dose of 6 mg/kg/h initially, followed by 1 mg/kg/h, and remifentanil at 0.3 µg/kg/min.

Group DHR (Desflurane-Remifentanil): Administer desflurane at 1 minimum alveolar concentration (MAC), adjusting the dose by 1 vol% titration to maintain MAP and BIS levels, and remifentanil at 0.3 µg/kg/min.

Group DLR (Control): Administer desflurane at 1 MAC, adjust the dose by 1 vol% titration to maintain mean arterial pressure (MAP) and bispectral index (BIS) levels, and remifentanil at 0.3 µg/kg/min.

Mechanical hyperalgesia threshold, Time to first postoperative analgesic requirement (min), Injected PCA volume containing morphine for 12 h after surgery (ml), Pain intensity: VAS 1 h after surgery, VAS 6 h after surgery, VAS 12 h after surgery VAS 24 h after surgery. Area of hyperalgesia around the surgical incision 24 h after surgery (cm^2) will be checked.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Iksan, Korea, Republic of, 54538
    • Wonkwang University Hospital
  • Jeollabukdo
    • Iksan, Jeollabukdo, Korea, Republic of, 54538
      • Wonkwag UH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

1. Inclusion criteria will include as follows; ASA(American Society of Anesthesiologists)physical status 1-2 patients, Age with 20-65 years, and Single port-laparoscopically assisted urologic surgery.
2. Exclusion criteria will include as follows; a known allergy to remimazolam or remifentanil, a history of drug or alcohol abuse, psychiatric disorders, acute cardiovascular disorders, or unstable hypertension, and other respiratory or neuromuscular pathology, treated with opioid-containing any analgesic drug within 24 h before surgery and contraindications to the self-administration of opioids (i.e., were unable to understand the PCA device).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group DLR; Administer desflurane at 1 MAC, adjust the dose by 1 vol% titration to maintain MAP and BIS levels, and remifentanil at 0.025 µg/kg/min.	Drug: Desflurane; administer desflurane; Other Names: desfuralne; Drug: Remifentanil; administer remifentanil; Other Names: Ulitva
Experimental: Group DHR; Administer desflurane at 1 MAC, adjusting the dose by 1 vol% titration to maintain MAP and BIS levels, and remifentanil at 0.3 µg/kg/min.	Drug: Desflurane; administer desflurane; Other Names: desfuralne; Drug: Remifentanil; administer remifentanil; Other Names: Ulitva
Experimental: Group RHR; Administer remimazolam at a dose of 6 mg/kg/h initially, followed by 1 mg/kg/h, and remifentanil at 0.3 µg/kg/min.	Drug: Remifentanil; administer remifentanil; Other Names: Ulitva; Drug: Remimazolam; Administer remimazolam; Other Names: Byfavo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The mechanical hyperalgesia threshold	The mechanical hyperalgesia threshold (g/mm^2) (preoperative) and 2 cm from the single port incision site (postoperative) at four points (horizontally and perpendicularly).	at 24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first postoperative analgesic requirement	Time to first postoperative analgesic requirement (min)	Within 1 hour after surgery
Injected PCA volume containing morphine for 24 h after surgery	Injected PCA volume containing morphine for 24 h after surgery (ml)	24 hours after surgery
Pain intensity	The Visual analogue scales (VAS)-100 is a line with words describing the extremes of pain from "no pain" to "worst imaginable pain".	1 hour after surgery
Pain intensity	The Visual analogue scales (VAS)-100 is a line with words describing the extremes of pain from "no pain" to "worst imaginable pain".	6 hours after surgery
Pain intensity	The Visual analogue scales (VAS)-100 is a line with words describing the extremes of pain from "no pain" to "worst imaginable pain".	12 hours after surgery
Pain intensity	The Visual analogue scales (VAS)-100 is a line with words describing the extremes of pain from "no pain" to "worst imaginable pain".	24 hours after surgery
Area of hyperalgesia around surgical incision	Area of hyperalgesia around surgical incision (cm^2)	24 hours after surgery

Collaborators and Investigators

• Sponsor: Wonkwang University Hospital
• Investigators: Study Director: Cheol Lee, M.D.,Ph.D., Wonkwang University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2023
• Primary Completion (Actual): September 6, 2023
• Study Completion (Actual): September 15, 2023

Study Registration Dates

• First Submitted: March 28, 2023
• First Submitted That Met QC Criteria: May 9, 2023
• First Posted (Actual): May 19, 2023

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: remifentanil; opioid-induced hyperalgesia; remimazolam
• 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; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Anesthetics, Inhalation; Remifentanil; Desflurane
• Other Study ID Numbers: Wonkwang UH13

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No