The Pharmacology and Hemodynamics of Dexmedetomidine in Children With Congenital Heart Disease

Study Overview
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Brief Summary
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The purpose of this study is to examine the pharmacokinetics, pharmacodynamics, and pharmacogenomics of dexmedetomidine in the following three pediatric patient populations: patients with bi-directional cavopulmonary anastomosis or a Fontan procedure, patients who have had a cardiac transplant, and patients with otherwise normal physiology who are undergoing closure of a patent ductus arteriosis or atrial septal defect.

Detailed Description
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While opioid analgesia is currently the mainstream for management of pain in the perioperative setting, it often leads to significant morbidity, including opioid tolerance and hyperalgesia. Looking at ways to decrease the need for opioids with the use of adjunct medications allows for the long-term goal of decreasing physiologic tolerance in children. This is especially relevant in the pediatric congenital heart population. Dexmedetomidine is in a class of drugs known as alpha-2 agonists and is known to provide analgesia, attenuate opioid tolerance and inhibit the sympathetic stress response. While there are numerous published case studies of dexmedetomidine validating its effectiveness and safety, the pharmacologic and pharmacodynamic profile has not been established. This study will examine the hemodynamics, pharmacokinetics, and pharmacogenomics of dexmedetomidine in patients with congenital heart disease. The dose-ranging effect of dexmedetomidine will also be investigated. The three groups being studied will be: patients with bi-directional cavopulmonary anastomosis or a Fontan procedure, patients who have had a cardiac transplant, and patients with otherwise normal physiology who are undergoing closure of a patent ductus arteriosis or atrial septal defect. Comparison: Compare both invasive and noninvasive hemodynamic parameters at baseline sevoflurane and during maintenance dosing on dexmedetomidine. The pharmacokinetics of dexmedetomidine in the pediatric population following escalating loading doses and continuous infusion at timed intervals will be estimated. The efficacy of dexmedetomidine will be estimated by the amount of rescue doses of propofol that are given.

Official Title
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The Pharmacology of Dexmedetomidine in Children With Congenital Heart Disease

Conditions
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Cardiac Transplant, Patent Ductus Arterious, Atrial Septal Defect, Bidirectional Cavopulmonary Anastomosis

Intervention / Treatment
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* Drug: Dexmedetomidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age is birth to 18 years > or = 6 kg. American Society of Anesthesiology (ASA) I, II, or III undergone prior cardiac transplant, Fontan or has a patent ductus arterious or atrial septal defect. scheduled for cardiac catheterization Exclusion Criteria: subject or family history of malignant hyperthermia known hepatic disorder determined by history physical exam or laboratory tests pregnant or lactating female receiving inotropic agents or has a pacemaker weighs less than 6 kg.

Ages Eligible for Study
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Maximum Age: 18 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: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cardiac Transplant<br>diagnostic cardiac catheterization in children with a transplanted heart | Drug: Dexmedetomidine<br>* Dexmedetomidine load of 1 microgram/kilogram over 10 minutes, followed by a 1 microgram/kilogram/hour infusion during the time of catheterization<br>* Other names: Precedex;|
| Experimental: Fontan procedure<br>diagnostic cardiac catheterization in children with a transplanted ventricle | Drug: Dexmedetomidine<br>* Dexmedetomidine load of 1 microgram/kilogram over 10 minutes, followed by a 1 microgram/kilogram/hour infusion during the time of catheterization<br>* Other names: Precedex;|
| Other: Normal Physiology<br>diagnostic cardiac catheterization in children with normal cardiac physiology | Drug: Dexmedetomidine<br>* Dexmedetomidine load of 1 microgram/kilogram over 10 minutes, followed by a 1 microgram/kilogram/hour infusion during the time of catheterization<br>* Other names: Precedex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine. | Non-inferiority was shown when differences at steady-state (dexmedetomidine + sevoflurane) compared to baseline (sevoflurane alone) and its associated 95% confidence interval fell completely within the range of plus or minus 20%.The 95% confidence interval was normalized by subtracting the baseline values. Bispectral Index: monitors electroencephalographic and electromyographic parameters to monitor the depth of anesthesia. | Up to 24 hours following cardiac catheterization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dexmedetomidine, Congenital heart disease, pharmacokinetics, pharmacodynamics, pediatric, Bidirectional cavopulmonary anastomosis, Fontan physiology, Cardiac transplant