Clinical trial NCT00480740: The Pharmacology and Hemodynamics of Dexmedetomidine in Children With Congenital Heart Disease
Official title: The Pharmacology of Dexmedetomidine in Children With Congenital Heart Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiac Transplant
Patent Ductus Arterious
Atrial Septal Defect
Bidirectional Cavopulmonary Anastomosis
Keywords: Dexmedetomidine
Congenital heart disease
pharmacokinetics
pharmacodynamics
pediatric
Bidirectional cavopulmonary anastomosis
Fontan physiology
Cardiac transplant
Lead sponsor: Children's National Research Institute
Sponsor class: OTHER
First posted: 2007-05-31
Enrollment: 41
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in Hemodynamic Variables Recorded During Administration of Sevoflurane + Dexmedetomidine.
timeFrame: Up to 24 hours following cardiac catheterization
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
Study officials:
affiliation: Children's National Research Institute
name: Julia C Finkel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Finkel JC, Johnson YJ, Quezado ZM. The use of dexmedetomidine to facilitate acute discontinuation of opioids after cardiac transplantation in children. Crit Care Med. 2005 Sep;33(9):2110-2. doi: 10.1097/01.ccm.0000178183.21883.23.
citation: Finkel JC, Elrefai A. The use of dexmedetomidine to facilitate opioid and benzodiazepine detoxification in an infant. Anesth Analg. 2004 Jun;98(6):1658-1659. doi: 10.1213/01.ANE.0000113547.34160.A5.