Efficacy of Dexmedetomidine Versus Clonidine to Control Delirium in Patients Undergoing CABG

Efficacy of Dexmedetomidine Versus Clonidine to Control Delirium in Patients Undergoing Coronary Artery Bypass Grafting

This prospective, randomised, double blinded, controlled clinical trial will be conducted in 147 patients between 60 yr and 70 yr , ASA physical status II and III, undergoing CABG. Patients will be randomly allocated to either dexmedetomidine or clonidine (control) groups .Upon arrival to ICU, in the dexmedetomidine group, patients will receive an infusion of 0.5-0.7 μg/kg/h then 1.4 μg/kg/h if Richmond assessment sedation score from +1 to +4

Taking into consideration if the heart rate less than 60 per minute or persistent hypotension reduce infusion rate by 0.2 μg/kg/h.

Once the patient will be extubated, wean the infusion by 0.1μg/kg/h till reaching 0.2μg/kg/h. Slow the weaning rate if evidence of withdrawal reactions as agitation or hypertension occur. In clonidine group, the patients will receive 0.5μg/kg then 0.1-0.2 μg/kg/h.Primary end point of the study is the incidence of delirium.The secondary endpoints will be the the duration of extubation, the length of ICU stay, need for inotropic support or vasopressors, hospital stay , mean arterial blood pressure and heart rate , hospital mortality rate , all additional sedatives including overall doses of morphine and haloperidol the incidence of adverse events as bradycardia

Study Overview

• Status: Completed
• Conditions: Delirium on Emergence
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Clonidine

Detailed Description

After Ethics committee approval, and a written informed consent will be taken from every patient, . Patients with a history of mental illness, severe dementia, delirium or undergoing emergency procedures will be excluded.

Anesthesia management will be standardized to minimize any effect of anesthetic type on neurological outcomes. Premedication with midazolam will be limited to a maximum of 0.05 mg/kg.

Anesthesia will be induced with 12 μg/kg fentanyl, 5-7mg/kg thiopental sodium, and 0.15 mg/kg pancuronium and maintained with 1% to 2.0% isoflurane. The heart rate and blood pressure will be maintained within 20% of the baseline values. Anticoagulation will be achieved with heparin to maintain an activated clotting time above 480 s.The CPB circuit will be primed with 1.8 l lactated Ringer's solution and 50 ml of 20% mannitol. Management of CPB will include systemic temperature drift to 32 C, targeted mean perfusion pressure between 60 and 80 mmHg, and pump flow rates of 2.2 l/min/m2 . Myocardial protection will be achieved with antegrade cold blood cardioplegia. A 32-μ m filter (Avecor Affinity, USA)will be used in the arterial perfusion line. Before separation from CPB, patients will be rewarmed to 36 to 37C. After separation from CPB, heparin will be neutralized with protamine sulfate, 1 mg/100 U heparin, to reach an activated clotting time within 10% of baseline.All patients will be transferred to ICU after surgery. Patients will be randomly allocated to either dexmedetomidine or clonidine (control) groups according to a computer-generated randomization code, with allocation ratio 1:1 .Opaque sealed envelopes will be done according to the randomization schedule and opened by a physician not involved in the study . Upon arrival to ICU, in the dexmedetomidine group, patients will receive an infusion of 0.5-0.7 μg/kg/h then 1.4 μg/kg/h if Richmond assessment sedation score from +1 to +4

+4 Combative ,+3 Very agitated ,+2 Agitated,+1 Restless, 0 Alert and calm, -1 Drowsy , -2 Light sedation, -3 Moderate sedation, -4 Deep sedation, -5 Unarrousable A four millilitres vial of dexmedetomidine ( 100 micrograms per ml)will be drawn up and diluted in 46 ml of normal saline.The infusion of dexmedetomidine will be continued for a maximum period of 24 h. Taking into consideration if the heart rate less than 60 per minute or persistent hypotension reduce infusion rate by 0.2 μg/kg/h.Dexmedetomidine infusion will not be discontinued before extubation. Once the patient will be extubated, wean the infusion by 0.1μg/kg/h till reaching 0.2μg/kg/h. Slow the weaning rate if evidence of withdrawal reactions as agitation or hypertension occur. In clonidine group, the patients will receive 0.5μg/kg then 0.1-0.2 μg/kg/h.

Five ampoules of clonidine(750 μg) was drawn up and diluted in 45ml of normal saline.

Opioids were titrated to reach pain score 3 out of 10. Pain will be assessed using a standard 10-cm visual analog scale (0, no pain; 10, worst and unbearable pain). Patients received 2 mg morphine as rescue analgesic.

Primary end point of the study is the incidence of delirium, which is defined as a disturbed level of consciousness that develops over a period of hours or days and fluctuates over time.

Delirium will be assessed preoperatively (baseline)and postoperatively, in ICU every 2 hours using the confusion assessment method (CAM) for ICU.(7) When patients are discharged from ICU to the ward, delirium will be assessed using CAM every 8 hours for the next 5 days. The CAM-ICU is used for both ventilated and extubated patients. It included a fourstep algorithm : (1) an acute onset of changes or fluctuations in the course of mental status, (2)inattention, (3) disorganized thinking, and (4) an altered level of consciousness. Patients are delirious if both (1) and (2) were found inanition to either feature (3)or (4). Patients are stated either CAM positive (delirium present) or CAM negative (delirium absent). Incidence of delirium was confirmed by the psychiatry consultant. The onset and duration of delirium will be also recorded. The CAM-ICU and CAM testers were involved in the study . IV haloperidol(2.5-5 mg PRN), will be used as a first-line treatment in delirious patients, a regular dose 1 mg ads until symptoms resolve.

The secondary endpoints will be the the duration of extubation, the length of ICU stay, need for inotropic support or vasopressors, hospital stay , mean arterial blood pressure and heart rate , hospital mortality rate , all additional sedatives including overall doses of morphine and haloperidol, finally the incidence of adverse events as bradycardia, heart block , the need for pacemaker , nausea and vomiting will be recorded as well.

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11566
    • Ain Shams University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

60-70 yrs age ASA II, III Scheduled for CABG -

Exclusion Criteria:

History of mental illness Delirium or dementia patient refusal to participate Emergency procedures Any contraindications to study drugs

-

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
Active Comparator: dexmedetomidine group; Upon arrival to ICU, in the dexmedetomidine group, patients will receive an infusion of 0.5-0.7 μg/kg/h then 1.4 μg/kg/h if Richmond assessment sedation score from +1 to +4 +4 Combative ,+3 Very agitated ,+2 Agitated,+1 Restless, 0 Alert and calm, -1 Drowsy , -2 Light sedation, -3 Moderate sedation, -4 Deep sedation, -5 Unarrousable Taking into consideration if the heart rate less than 60 per minute or persistent hypotension reduce infusion rate by 0.2 μg/kg/h. Once the patient will be extubated, wean the infusion by 0.1μg/kg/h till reaching 0.2μg/kg/h. Slow the weaning rate if evidence of withdrawal reactions as agitation or hypertension occur.	Drug: Dexmedetomidine; an infusion of 0.5-0.7 μg/kg/h then 1.4 μg/kg/h if Richmond assessment sedation score from +1 to +4 ,if the heart rate less than 60 per minute or persistent hypotension reduce infusion rate by 0.2 μg/kg/h.; Other Names: demedetomidine hydrochloride
Sham Comparator: clonidine group; In clonidine group, the patients will receive 0.5μg/kg then 0.1-0.2 μg/kg/h if Richmond assessment sedation score from +1 to +4 Five ampoules of clonidine(750 μg) will be drawn up and diluted in 45ml of normal saline.	Drug: Clonidine; an infusion of 0.5μg/kg then 0.1-0.2 μg/kg/h if Richmond assessment sedation score from +1 to +4.; Other Names: clonidine hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the incidence of delirium	disturbed level of consciousness that develops over a period of hours or days and fluctuates over time.	every 4 hours in first day in ICU then every 8h for the next day, after discharge from ICU to the ward it will be checked every 8h for 5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
length of ICU stay	time to stay in ICU discharge to the ward	2 days

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Study Chair: Ayman Shoeb, professor, Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Actual): February 28, 2019
• Study Completion (Actual): February 28, 2019

Study Registration Dates

• First Submitted: March 20, 2018
• First Submitted That Met QC Criteria: March 20, 2018
• First Posted (Actual): March 27, 2018

Study Record Updates

• Last Update Posted (Actual): July 11, 2019
• Last Update Submitted That Met QC Criteria: July 10, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: dexmedetomidine, clonidine, postoperative, CABG
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Emergence Delirium; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Sympatholytics; Dexmedetomidine; Clonidine
• Other Study ID Numbers: FMASU R 16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD including protocol will be shared
• IPD Sharing Time Frame: about one year
• IPD Sharing Access Criteria: prevention of delirium post cardiac surgery
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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