Effect of Remimazolam Versus Dexmedetomidine on the Incidence of Delirium After Elective Cardiac Surgery with Cardiopulmonary Bypass: a Prospective Randomized Controlled Trial

The study aims to improve the post-open heart surgery lifestyle and overall experience, as well as assess the incidence of delirium using Remimazolam and Dexmedetomidine.

Study Overview

• Status: Not yet recruiting
• Conditions: Delirium - Postoperative
• Intervention / Treatment: Drug: Propofol Group 1; Drug: Remimazolam Intervention; Drug: Dexmedetomidine Intervention

Detailed Description

Delirium is an acute brain dysfunction characterized by an acute onset and fluctuating course of disturbance in attention, awareness, and cognition, It is the most common neurocognitive complication following cardiac surgery, with an incidence rate between 11% and 52%.

The occurrence of delirium correlates strongly with various short- and long-term poor outcomes following cardiac surgery, including prolonged ICU stay and hospitalization and increased risk of hospital readmission. Different risk factors contribute to delirium after cardiac surgery, including advanced age, pre-existing cognitive impairment, diabetes, history of stroke, type of surgery, extended CPB duration, and blood transfusion. Dexmedetomidine is a highly and potently selective α2-adrenoceptor agonist with anxiolytic, sedative, and analgesic properties. It has neuroprotective effects by reducing neuroinflammation, apoptosis, and blood-brain barrier injury via central α2A adrenoceptors, but it can cause hypotension and bradycardia.

Remimazolam, a new ultra-short-acting benzodiazepine, also has a faster onset of action and a higher safety profile. It was recently approved for procedural sedation and general anesthesia. Its metabolism is mainly induced by tissue esterase, independent of liver and kidney function, and its metabolites are inactive. In addition, flumazenil reverses the effects of Remimazolam in the event of adverse events, an advantage not available in non-benzodiazepines. The objective of this clinical trial is to evaluate the efficacy of Remimazolam compared with Dexmedetomidine for preventing postoperative delirium after cardiac surgery.

• Study Type: Interventional
• Enrollment (Estimated): 111
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Moataz Emad Omar, Assistant lecturer; Phone Number: +2001011990789; Email: moataz.emad90@gmail.com
• Study Contact Backup: Name: Ayman Abdel- khalek Mohammed, Lecturer; Phone Number: +2001025675901; Email: aymanglala@aun.edu.eg

Study Locations

• Egypt
  • Assiut, Egypt
    • Assiut University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years.
• Scheduled for cardiac surgery (CABG and/or valve replacement).
• Elective surgery

Exclusion Criteria:

• Patients with known allergies to Remimazolam or Dexmedetomidine
• Refusal to participate.
• History of psychiatric or neurological conditions (schizophrenia, epilepsy, severe dementia, etc.).
• Preoperative inability to communicate (severe visual/auditory dysfunction, language barriers).
• Severe hepatic or renal dysfunction
• Cardiopulmonary bypass time not ≥ 120 minutes
• aortic clamping time not ≥ 90 minutes
• Emergency surgeries
• On preoperative mechanical ventilation and long sedation time
• reoperated patients

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group 1 : propofol group; Postoperative Use	Drug: Propofol Group 1; Postoperative Use: Bolus: 10-20 mg intravenously as needed for sedation initiation. Continuous infusion: 0.3-0.5 mg/kg/hour to maintain light sedation adjusted based on clinical response.
Experimental: Group 2: Remimazolam Intervention; Postoperative Use	Drug: Remimazolam Intervention; Postoperative Use: Initial bolus: 5 mg intravenously upon ICU arrival. Continuous infusion: 0.2-0.3 mg/kg/hour to maintain light sedation with a maximum dose of 0.8 mg/kg/hour. Rescue sedation with propofol or midazolam will be allowed if patients become agitated or if Remimazolam is ineffective in maintaining target sedation.
Experimental: Group 3: Dexmedetomidine Intervention; Postoperative Use	Drug: Dexmedetomidine Intervention; Postoperative Use: Loading dose: 0.5-1 μg/kg over 10-20 minutes after ICU arrival. Continuous infusion: 0.2-0.7 μg/kg/hour for sedation maintenance, adjusted as needed to maintain light sedation. Rescue sedation with propofol or midazolam will be administered if Dexmedetomidine fails to maintain adequate sedation or if patients become agitated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Delirium (POD)	Delirium will be assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) twice daily during the first 5 days after surgery	During the first 5 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of delirium onset and duration ,Sedation level	Time of delirium onset and duration until the end of it.; Sedation level: Assessed using the Richmond Agitation-Sedation Scale (RASS).	During first 5 days after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU length of stay ,Length of Stay in Hospital After Surgery	Results will be presented as median (95% confidence interval)	From end of surgery until discharge from Intensive Care Unit or 30 days after surgery. From end of surgery until discharge from hospital or 30 days after surgery

Collaborators and Investigators

• Sponsor: Assiut University

Publications and helpful links

Helpful Links

• The effect of perioperative dexmedetomidine on postoperative delirium in adult patients undergoing cardiac surgery with cardiopulmonary bypass
• Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine
• The neuroprotective effect of dexmedetomidine and its mechanism
• Remimazolam: First Approval
• Remimazolam besilate, a benzodiazepine, has been approved for general anesthesia
• Incidence and Predictors of Delirium After Cardiac Surgery

Study record dates

Study Major Dates

• Study Start (Estimated): January 10, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: December 17, 2024
• First Submitted That Met QC Criteria: December 25, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 25, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: cradiac surgery with cardiopulmonary bypass
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Hypnotics and Sedatives; Anesthetics, Intravenous; Anesthetics, General; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Dexmedetomidine; Propofol
• Other Study ID Numbers: Elective cardiac surgery

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