The Effects of Different Loading Doses of Dexmedetomidine on The Bispectral Index-Guided Propofol Sedation in Patients Undergoing Advanced Upper Gastrointestinal Endoscopic Procedures: A Randomized Control Study

Propofol is currently the most common drug used but has drawbacks like narrow therapeutic window and potential complications.

Dexmedetomidine is an attractive alternative due to its unique properties like minimal respiratory depression.

Studies are ongoing to find the optimal use of dexmedetomidine for these procedures. A combination of propofol and dexmedetomidine might be ideal, but the best balance between the two drugs needs further investigation.

Study Overview

• Status: Recruiting
• Conditions: Procedural Sedation; GIT Endoscopy
• Intervention / Treatment: Drug: Precedex (Dexmedetomidine) 200 MCG in 2 ML Injection; Other: C group: Patients received saline infusion over 10 minutes

Detailed Description

Advanced upper gastrointestinal tract procedures such as Endoscopic retrograde cholangiopancreatography (ERCP) & Endoscopic ultrasound (EUS) are very important diagnostic and therapeutic procedures for the diagnosis & management of many pancreatobiliary pathologies whether benign or malignant (1-4). These procedures require moderate-deep sedation with the patient lying in the lateral or semi-prone position to provide the operator easier access & insertion while permitting fluoroscopic visualisation (1-4).

Propofol sedation is currently the most popular drug used for advanced endoscopic procedures because of its shorter half-life which results in a shorter recovery time than conventional sedation (benzodiazepine &/or opioid) (5). Propofol was administered initially by intermittent boluses but later on was superseded by continuous infusion guided by clinical scoring, e.g., Ramsey sedation score (6), by target-controlled infusion (TCI) (7) or more recently by bispectral index (BIS) monitoring (8).

Propofol, however, has a narrow therapeutic window that may cause fluctuation of the level of sedation from moderately deep sedation to near general anesthesia. Not only that but also propofol sedation is associated with many other complications including apnoea, airway obstruction desaturation, hypotension, bradycardia, gagging, restlessness, regurgitation & vomiting & delayed recovery (9).

Dexmedetomidine, a highly specific, potent and selective α2-adrenoceptor agonist, was originally introduced as a sedative for critically ill mechanically ventilated patients [9]. In addition to sedation, it has a group of unique properties in the form of analgesia, reduction of sympathetic tone and attenuation of the neuroendocrine and hemodynamic responses to anesthesia and surgery with minimal respiratory depression, making it an attractive agent for perioperative sedation especially in remote areas outside the operating theatres (6,10).

The quest to replace propofol coupled with the unique sedo-analgesic properties of dexmedetomidine resulted in the interest in the use of dexmedetomidine for providing sedation for advanced endoscopic procedure (6,10).

In 2021, Srivastava et al (6), studied the effects dexmedetomidine as a sole sedative agent in the form of a loading dose of 1 µg.kg-1 followed by 0.5 µg.kg-1.hr-1 continuous infusion. They reported that although this dexmedetomidine regimen produced adequate sedation in many patients yet it was associated with a relatively high sedation failure rate requiring rescue propofol boluses (6). Moreover, dexmedetomidine was associated with bradycardia & hypotension (6,7,11).

It was 2013, When Wang et al (12), examined the propofol sparing effect of various dexmedetomidine loading doses ranging between 0.25 & 1 µg.kg-1 followed by a fixed infusion of 0.5 µg.kg-1.hr-1 and reported a dose dependent reduction of propofol requirements for induction of sedation (12). However, they did not investigate the impact of these dexmedetomidine doses on the total propofol consumption for the whole procedure, the incidence of adverse events or the recovery profile of such a combination in the context of sedation for advanced endoscopic procedures. Thus, the" sweet spot" (13), where there is a maximal synergism between propofol and dexmedetomidine, is still to be identified.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sameh M. Elaidy, Msc.; Phone Number: +20 1111776906; Email: sameh.elaidy@hotmail.com
• Study Contact Backup: Name: Nabawya Kamel, Proffessor; Phone Number: +20 1066175989; Email: n.kamal21@hotmail.com

Study Locations

• Egypt
  • Giza
    • Cairo, Giza, Egypt, 12411
      • Recruiting
      • Theodor Bilharz Research Institute
      • Contact: Sanaa Botros, Professor; Phone Number: +20 1008009411; Email: sanaabotros113@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients aged 18-65
• Both sexes
• ASA I-II
• BMI <35

Exclusion Criteria:

• Patients' refusal to participate
• ASA III-IV
• BMI > 35
• Patients who are considered high aspiration risk, e.g., gastric outlet obstruction
• Allergy to any medications used
• Diabetics
• Any patient receiving cardioactive drugs, e.g., Beta blockers, Calcium channel blockers, Inhaled B2 bronchodilators)
• Patients with Pacemakers or heart rate below 50 beat/min
• Pregnant women
• Habitual Drug abusers
• Patients who had to be intubated during the procedure.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: The Dexmedetomidine Group D1; D1 group will receive 1µg.kg as a loading dose over 10 minutes, followed by maintenance 0.5 µg.kg.	Drug: Precedex (Dexmedetomidine) 200 MCG in 2 ML Injection; The Effects of Different Loading Doses of Dexmedetomidine on The Bispectral Index-Guided Propofol Sedation in Patients Undergoing Advanced Upper Gastrointestinal Endoscopic Procedures: A Randomized Control Study
Experimental: The Dexmedetomidine Group D 0.5; D 0.5 group will receive 0.5 µg.kg as a loading dose over 10 minutes, followed by maintenance 0.5 µg.kg	Drug: Precedex (Dexmedetomidine) 200 MCG in 2 ML Injection; The Effects of Different Loading Doses of Dexmedetomidine on The Bispectral Index-Guided Propofol Sedation in Patients Undergoing Advanced Upper Gastrointestinal Endoscopic Procedures: A Randomized Control Study
Experimental: The Dexmedetomidine Group D0.25; D 0.25 group will receive 0.25 µg.kg as a loading dose over 10 minutes, followed by maintenance 0.5 µg.kg	Drug: Precedex (Dexmedetomidine) 200 MCG in 2 ML Injection; The Effects of Different Loading Doses of Dexmedetomidine on The Bispectral Index-Guided Propofol Sedation in Patients Undergoing Advanced Upper Gastrointestinal Endoscopic Procedures: A Randomized Control Study
Placebo Comparator: The Dexmedetomidine Group D 0; D 0 group will receive a placebo saline infusion over 10 minutes and then will receive 50 ml of normal saline as a placebo	Other: C group: Patients received saline infusion over 10 minutes; the group will receive normal saline infusion over 10 minutes.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
• Recovery time of each group: the time from ending the infusions till a modified Aldrete score (MAS) score of ≥ 9 is reached.	4 months

Collaborators and Investigators

• Sponsor: Theodor Bilharz Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: May 9, 2024
• First Submitted That Met QC Criteria: May 13, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: 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; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: PT (704)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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