Pregabalin Versus Dexmedetomidine for Delirium Prevention After Cardiac Surgery

Study Overview
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Brief Summary
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The aim of this study is to compare the effect of perioperative administration of pregabalin versus dexmedetomidine on the prevalence and lasting duration of delirium in elderly patients after cardiac surgery.

Detailed Description
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Pregabalin is a beta-isobutyl of GABA with chemical similarity to gabapentin . Pregabalin binds to the alpha-2-delta subgroup of calcium channels, thereby reducing excitatory neurotransmitter release and preventing hyperalgesia and central sensitization . Pregabalin is used as anticonvulsant but has also been used as analgesic for neuropathic pain and, lately, for postoperative pain, in an attempt to reduce opioid consumption and prevent progression to chronic pain. Dexmedetomidine with its broad range of effects including easily controllable sedation, analgesia, and anxiolysis still enables the caring medical team to interact with the patient. It reduces the activity while still maintaining the reactivity of neurons in the locus coeruleus. Therefore, it is an appealing alternative to traditional sedatives such as propofol and benzodiazepines.

Official Title
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Pregabalin Versus Dexmedetomidine for Delirium Prevention After Cardiac Surgery: A Randomized Double-Blind Trial

Conditions
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Pregabalin, Dexmedetomidine, Delirium

Intervention / Treatment
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* Drug: Pregabalin
* Drug: Dexmedetomidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 65 years of age both genders American Society of Anesthesiologists (ASA) physical status classification II or III scheduled for cardiac surgery. Exclusion Criteria: Patients who had history of psychiatric diseases; inability to communicate; previous history of POD; preoperative sick sinus syndrome. Allergy/sensitivity to pregabalin or dexmedetomidine. Severe bradycardia (heart rate <50 beat per minute). Second-degree or above atrioventricular block without pacemaker. Severe hepatic or renal insufficiency. Previous cardiac or thoracic surgery. Known diagnosis of depression or other major psychiatric diseases. Cognitive impairment or inability to cooperate with the study. Renal insufficiency, and history of substance abuse.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: pregabalin group<br>patients will receive pregabalin capsules (75 mg) will be given 2 h prior to induction of anesthesia and every 12 h for 24h postoperatively by nasogastric tube or orally. Patients will receive IV saline as placebo with the same rate of dexmedetomidine. | Drug: Pregabalin<br>* patients will receive pregabalin capsules (75 mg) will be given 2 h prior to induction of anesthesia and every 12 hours<br>|
| Active Comparator: dexmedetomidine group<br>patients in the dexmedetomidine group will receive after induction of GA a bolus dose of 0.4 μg/kg dexmedetomidine (over a period of 10 to 20 min) followed by an infusion of 0.2 to 0.7 μg/kg/h. Patients will receive placebo 2 h prior to induction of anesthesia and every 12 h for 24h postoperatively by nasogastric tube or orally. If patients are hemodynamically unstable, the bolus dose will be omitted. The infusion of dexmedetomidine will be continued for a maximum period of 24 h. Dexmedetomidine infusion will be not discontinued before extubation. | Drug: Dexmedetomidine<br>* patients will receive dexmedetomidine after induction of GA a bolus dose of 0.4 μg/kg dexmedetomidine (over a period of 10 to 20 min) followed by an infusion of 0.2 to 0.7 μg/kg/h<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Delirium | Assessment of delirium will be performed preoperatively and postoperatively at 12-h intervals or as needed according to the patient's condition using the confusion assessment method (CAM) | 24hour postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain score | Postoperative pain (using VAS) at rest and movement will be measured at PACU, 1h, 2hr. 4hr, 6hr, 8hr, 12hr, 18hr, and 24hrs postoperative. The Visual Analogue Scale (VAS) measures pain intensity. The VAS consists of a 10cm line, with two end points representing 0 ('no pain') and 10 ('pain as bad as it could possibly be'). | 24 hours postoperatively | 
| Postoperative opioid consumption | Patients will receive single 3 mg dose of intravenous morphine and patient control analgesia (PCA) will be started with a programmable PCA pump using the following settings: basal morphine infusion 1 mg/h, bolus dose 1 mg, and lockout time 20 minutes. | 24 hours postoperatively | 
| Sedation | Sedation level will be recorded using Sedation Agitation Scale | 24 hours postoperatively | 
| Length of hospital stay | Patients will stay in hospital for one month | One month postoperatively |