Dexmedetomidine in Seizure Patients

Study Overview
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Brief Summary
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Dexmedetomidine is an alpha-2 agonist commonly used during neurosurgery due to its unique properties as a sedative and anxiolytic with minimal respiratory depression. Neurosurgical patients frequently come to the operating room on anticonvulsant therapy with a history of seizures. The investigators clinical experience suggests that these patients are resistant to the sedative effects of dexmedetomidine. This effect may represent a pharmacokinetic interaction between the anticonvulsant medications and dexmedetomidine or the higher dexmedetomidine dose requirement could result from abnormal pharmacodynamics due to the underlying seizure disorder. The investigators study aims to investigate the pharmacokinetic and pharmacodynamic differences of dexmedetomidine between patients receiving and not receiving enzyme-inducing anticonvulsant therapy and to identify a potential mechanism for these differences.

Official Title
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The Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Patients With Seizure Disorders

Conditions
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Seizure Disorders

Intervention / Treatment
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* Drug: Dexmedetomidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65, BMI 20-25 kg/m2 Anticonvulsant Group: Diagnosis of seizure disorder taking carbamazepine or phenytoin for a minimum of 2 weeks Control Group: Healthy volunteers taking no medications Exclusion Criteria: Positive urine pregnancy test or lactating History of allergy to dexmedetomidine or alpha -2 agonists History of liver, renal or thyroid disease History of cardiovascular disease including history of arrhythmia or congestive heart failure History of drug or alcohol abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Dexmedetomidine|Dexmedetomidine will be administered to 2 groups: (1) Seizure disordered patients on anticonvulsants and (2) Healthy volunteers (Control group)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum level of dexmedetomidine | Serum levels of dexmedetomidine will be taken at specific intervals during and after a step-wise computer controlled infusion of dexmedetomidine. | 0-8 hour period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient State Index (PSI) and Entropy | PSI and/or state entropy will be recorded at specific intervals during and after a step-wise computer controlled infusion of dexmedetomidine. | 0-8h | 
| Visual Analog Scale score | VAS scores will be recorded at specific intervals during and after a step-wise computer controlled infusion of dexmedetomidine. | 0-8h | 
| Ramsay Sedation Score | Ramsay sedation scores will be recorded at specific intervals during and after a step-wise computer controlled infusion of dexmedetomidine. | 0-8h | 
| Observer's Assessment of Alertness/Sedation Score (OAA/S) | OAA/S scores will be recorded at specific intervals during and after a step-wise computer controlled infusion of dexmedetomidine. | 0-8h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, Dexmedetomidine, Seizure