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

Phase 3

Completed

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

Interventions: Drug: Dexmedetomidine

Registration Number: NCT00480740

Lead Sponsor: Children's National Research Institute

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 41

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cardiac Transplant	Dexmedetomidine	diagnostic cardiac catheterization in children with a transplanted heart
Fontan procedure	Dexmedetomidine	diagnostic cardiac catheterization in children with a transplanted ventricle
Normal Physiology	Dexmedetomidine	diagnostic cardiac catheterization in children with normal cardiac physiology

Primary Outcome Measures

Name	Time	Method
Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine.	Up to 24 hours following cardiac catheterization	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.

Secondary Outcome Measures