The Effect of Remimazolam on Opioid Induced Hyperalgesia

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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The Effect of Remimazolam on Remifentanil-induced Hyperalgesia

Conditions
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Hyperalgesia, Mechanical

Intervention / Treatment
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* Drug: Remimazolam
* Drug: Desflurane
* Drug: Remifentanil


Participation Criteria
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Eligibility Criteria
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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. 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).

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 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
Interventional Model Description: Group RHR (Remimazolam- High doses of 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-High doses of Remifentanil): 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. Group DLR (Desflurane-Low-dose of Remifentanil): 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group DLR<br>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<br>* administer desflurane<br>* Other names: desfuralne;Drug: Remifentanil<br>* administer remifentanil<br>* Other names: Ulitva;|
| Experimental: Group DHR<br>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<br>* administer desflurane<br>* Other names: desfuralne;Drug: Remifentanil<br>* administer remifentanil<br>* Other names: Ulitva;|
| Experimental: Group RHR<br>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: Remimazolam<br>* Administer remimazolam<br>* Other names: Byfavo;Drug: Remifentanil<br>* administer remifentanil<br>* Other names: Ulitva;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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remifentanil, remimazolam, opioid-induced hyperalgesia