Oral Melatonin VS Nebulized Dexmedetomidine Premedication on Attenuation of Hemodynamic Response to Direct Laryngoscopy and Tracheal Intubation in Hypertensive Patients

Comparative Study Between Oral Melatonin and Nebulized Dexmedetomidine Premedication on Attenuation of Hemodynamic Response to Direct Laryngoscopy and Tracheal Intubation in Hypertensive Patients: A Prospective Randomized Trial

The aim of this study is to compare the efficacy of oral melatonin versus nebulized dexmedetomidine in attenuating the hemodynamic response to direct laryngoscopy and endotracheal intubation in controlled hypertensive patients prepared for general anesthesia

Study Overview

• Status: Not yet recruiting
• Conditions: Tracheal Intubation Morbidity; Laryngoscopy; Hemodynamic Response
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Melatonin

Detailed Description

Laryngoscopy and endotracheal intubation are associated with sympathetic stimulation and induce hemodynamic changes with consequent increase in heart rate (HR) and blood pressure (BP) which may lead to myocardial infarction, cardiac arrhythmias, cardiac failure and cerebrovascular accidents in patients with underlying cardiovascular or cerebrovascular diseases.

Dexmedetomidine is a centrally acting α-2 adrenergic agonist with sedative, hypnotic, analgesic, anxiolytic, anti-sialagogue, antinociceptive and sympatholytic action. Premedication with dexmedetomidine through intravenous, intramuscular and intranasal route has been shown to effectively attenuate hemodynamic response to laryngoscopy and endotracheal intubation. Nebulization provides an alternative route of dexmedetomidine premedication with high bioavailability through both nasal (65%) and oral mucosa (82%) and avoids a venipuncture as a prerequisite. Recent studies have shown nebulization as a novel route of dexmedetomidine administration for attenuation of hemodynamic response to endotracheal intubation.

Melatonin is a natural substance produced mainly in the pineal gland of all mammals and vertebrates. It is rapidly distributed and eliminated after intravenous administration. After oral administration, plasma concentration peaks after 60 min and is then eliminated. It exerts its hypnotic effects through the activation of the Melatonin receptors type I and II (MT1, MT2). It has shown potent analgesic effects in a dose dependent manner in experimental studies. It may induce relaxation of the arterial wall smooth muscle by increasing nitric oxide levels. Therefore, premedication with sublingual/oral Melatonin is associated with pre-operative anxiolysis and sedation without impairment of orientation, psychomotor skills, or impact on quality of recovery, moreover, it attenuates the hemodynamic stress response to laryngoscopy and tracheal intubation.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Aya GAE Ismaeil, MBBCH; Phone Number: +201159716507; Email: ayagamal9009@gmail.com
• Study Contact Backup: Name: Alaa MF Abo Hagar, PHD; Phone Number: +201099220281; Email: alaa.abohagar@med.tanta.edu.eg

Study Locations

• Egypt
  • El-Gharbia Govenorate
    • Tanta, El-Gharbia Govenorate, Egypt, 31527
      • Tanta University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age (40-60) years of both genders.
• Controlled hypertensive patients.
• Categorized as ASA physical status II.
• Planning to do an elective surgery under General Anesthesia.

Exclusion Criteria:

• Patient refusal to participate in the study.
• Patient with expected difficult intubation.
• Body Mass Index (BMI) > 30 kg/m2.
• History of allergy to the drugs of the study.
• Patients with Heart rate<50 or Heart block.
• End stage renal and hepatic disease.
• Patients on beta blocker, oral hypoglycemics, anti-depressants, anti-convulsants, anti- psychotics and thyroid medications.
• Pregnant or lactating females.

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: Dexmedetomidine group; Participants in this group will receive nebulized dexmedetomidine (1μg/kg) one hour before induction of anesthesia	Drug: Dexmedetomidine; Nebulized Dexmedetomidine (1μg/kg); Other Names: Precedex
Experimental: Melatonin group; Participants in this group will receive melatonin oral tablet (5mg) one hour before induction of anesthesia	Drug: Melatonin; Oral Melatonin tablet (5mg); Other Names: Circadin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Heart Rate (HR)	Heart Rate will be assessed using pulse oximeter in pre-operative room (baseline), before the induction of anesthesia, immediately before laryngescopy or intubation, 1 minute after induction, 3 minutes after induction, 5 minutes after induction, every 30 minutes till the end of operation.	Till the end of surgery (up to 2 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Systolic and Diastolic blood pressure	Systolic and diastolic blood pressure will be recorded in pre-operative room (baseline), before the induction of anesthesia, immediately before laryngescopy or intubation, 1 minute after induction, 3 minutes after induction, 5 minutes after induction, every 30 minutes till the end of operation.	Till the end of surgery (up to 2 hours)
Sedation levels using Ramsay Sedation Scale	Sedation levels will be assessed using Ramsay Sedation Scale (1, Anxious and agitated, restless, or both; 2, Cooperative, oriented, and calm; 3 Responsive to commands only; 4 Exhibiting brisk response to light glabellar tap or loud auditory stimulus; 5, Exhibiting a sluggish response to light glabellar tap or loud auditory stimulus; 6, Unresponsive) before administration of the study drugs, before induction of anesthesia (60 minutes after drug taken), every 30 minutes post operative till 2 hours after surgery.	Till 2 hours after the surgery
Intraoperative requirement of fentanyl	Additional fentanyl bolus dosages of 1 µg/kg IV will be administered if heart rate or mean arterial blood pressure elevated more than 20% of the baseline (after exclusion of other causes than pain).	Intraoperatively

Collaborators and Investigators

• Sponsor: Tanta University
• Investigators: Principal Investigator: Aya GAE Ismaeil, MBBCH, Faculty of Medicine, Tanta University, Egypt

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: April 11, 2025
• First Submitted That Met QC Criteria: April 11, 2025
• First Posted (Actual): April 20, 2025

Study Record Updates

• Last Update Posted (Actual): April 20, 2025
• Last Update Submitted That Met QC Criteria: April 11, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Hypertension; Melatonin; Dexmedetomidine; Hemodynamic response; Tracheal Intubation; Direct laryngoscope
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Hypnotics and Sedatives; Antioxidants; Protective Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Dexmedetomidine; Melatonin
• Other Study ID Numbers: 36264MS867/3/25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data will be available upon a reasonable request from the corresponding author after the end of study for one year.
• IPD Sharing Time Frame: After the end of study for one year.
• IPD Sharing Access Criteria: The data will be available upon a reasonable request from the corresponding author
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

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.: Yes