Effect of Ketalar or Dexmedetomidine on Increased Sensitivity to Pain Following Treatment With Remifentanil

Comparison of the Effect of Ketalar or Dexmedetomidine on Increased Sensitivity to Pain Induced Following Treatment With Remifentanil in Patients Undergoing a Laparoscopic Cholecystectomy

Analgesia is one of the pillars of anesthesia. One of the common opiates for pain relief, with a short half-life, is Remifentanil. However, following Remifentanil treatment an increased sensitivity to pain [hyperalgesia] appears. The aim of the study is to compare the effects between complementary treatments, like Ketalar and Dexmedetomidine, in preventing increased sensitivity to pain after Remifentanil treatment

Study Overview

• Status: Recruiting
• Conditions: Cholecystectomy
• Intervention / Treatment: Drug: Ketalar; Drug: Dexmedetomidine

Detailed Description

Analgesia is one of the pillars of anesthesia. For many years, opiates were the basic ingredient in pain relief. The effectiveness of these substances in pain relief caused them to be overused which resulted in a global epidemic of addiction, morbidity and mortality due to the overuse of these drugs. Some of the options for realizing a reduction in the use of opiates include the use of drugs with a more predictable pharmacological profile and a short half-life, such as Remifentanil. This opiate is stronger than Morphine and its half-life remains within a few minutes, without accumulation even after prolonged infusion. Therefore, it seems that the use of remifentanil is ideal, especially for prolonged anesthesia.

One of the severe complications following treatment with Remifentanil is the appearance of increased sensitivity to pain [hyperalgesia] which results from a central sensitivity to pain and is expressed by stimulation of sensory receptors for pain in the nervous system (nociceptive sensitization). In order to alleviate the feeling of pain following the increased sensitivity to pain after treatment with opiates, as well as with Remifentanil, complementary treatments, such as Ketalar and dexmedetomidine, were offered. This study will compare the ability of Ketalar or Dexmedetomidine in alleviating increased sensitivity to pain after treatment with Remifentanil in patients who are candidates for laparoscopic cholecystectomy.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sara Bar Yehuda, PhD; Phone Number: 972528981004; Email: sarabar1@shamir.gov.il
• Study Contact Backup: Name: Zoya Haitov Ben Zikri, MD; Phone Number: 972537346186; Email: ZoyaC@shamir.gov.il

Study Locations

• Israel
  • Be'er Ya'aqov, Israel, 70300
    • Recruiting
    • Shamir (Asaf Harofe) Medical Center
    • Contact: Zoya Haitov Ben Zikri, MD; Phone Number: 972537346186; Email: ZoyaC@shamir.gov.il
    • Contact: Sara Bar Yehuda, PhD; Phone Number: 972528981004; Email: sarabar1@shamur.gov.il

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients who are about to undergo alaparoscopic cholecystectomy under general anesthesia

Exclusion Criteria:

• Patients with sensitivity to the anesthetic
• Patients with chronic pain who are in regular treatment
• Urgent surgery
• Patients with ischemic heart disease
• Patients with known bradycardia
• Patients with a pacemaker
• Prolonged use of opiates
• Kidney/liver function problems

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ketalar; All patients will undergo general anesthesia using Fentanyl at a dose of 2 mcg/kg, Rocuronium at a dose of 0.6 mg/kg, Isoflurane during surgery and Remifentanil at a dose of 0.2-0.25 mcg/kg/min, 30 Minutes before the end of the operation, Morphine will be given at a dose of 0.1 mg/kg. Each patient will receive paracetamol during surgery. In addition to the general anesthesia, the patients in the Ketalar group will also receive a bolus of Ketalar at a dose of 0.3 mg/kg in induction + Propofol and Fentanyl and during the operation, continuous Ketalar at a dose of 5 mcg/kg/minute.	Drug: Ketalar; a dissociative anesthetic used medically for induction and maintenance of anesthesia; Other Names: Ketamine
Active Comparator: Dexmedetomidine; In addition to the general anesthesia, the patients in the Dexmedetomidine group will also receive a bolus of Ketalar at a dose of 0.3 mg/kg in induction + Propofol and Fentanyl and during the operation, continuous Ketalar at a dose of 5 mcg/kg/minute. In addition to the general anesthesia, the patients in the Dexmedetomidine group will also receive a bolus of Dexmedetomidine at a dose of 0.5 mg/kg for fifteen minutes + Propofol and Fentanyl, and during the operation, continuous Dexmedetomidine at a dose of 0.3 mcg/kg/hour.	Drug: Dexmedetomidine; an agonist of α2-adrenergic receptors in certain parts of the brain used for sedation; Other Names: Precedex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Level	A record of pain level will be made using the Visual Analogue Scale. The score is determined by marking on 10-cm line between 0 - "no pain" to 10 - "the highest pain".	Up to two hours after the end of the anesthesia process
Pain killer consumption	Treatment with morphine for pain relief	Up to two hours after the end of the anesthesia process

Collaborators and Investigators

• Sponsor: Assaf-Harofeh Medical Center
• Investigators: Study Director: Sara Bar Yehuda, PhD, Shamir (Asaf Harofe) Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2024
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): August 30, 2026

Study Registration Dates

• First Submitted: June 19, 2024
• First Submitted That Met QC Criteria: June 19, 2024
• First Posted (Actual): June 25, 2024

Study Record Updates

• Last Update Posted (Actual): August 7, 2024
• Last Update Submitted That Met QC Criteria: August 5, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Ketamine; Dexmedetomidine
• Other Study ID Numbers: 0173-23-ASF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD will be = will be provided as needed after receiving approval from the authorities of the Shamir (Asaf Harofe) medical center

Drug and device information, study documents

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