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

Children's National

Status and phase: Completed; Phase 3

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

Treatments: Drug: Dexmedetomidine

Study type: Interventional

Funder types: Other

Identifiers

NCT00480740

IRB# 3908

Details and patient eligibility

About

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.

Full 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.

Enrollment: 41 patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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41 participants in 3 patient groups

Cardiac Transplant

Experimental group

Description:

diagnostic cardiac catheterization in children with a transplanted heart

Treatment:

Drug: Dexmedetomidine

Fontan procedure

Experimental group

Description:

diagnostic cardiac catheterization in children with a transplanted ventricle

Treatment:

Drug: Dexmedetomidine

Normal Physiology

Other group

Description:

diagnostic cardiac catheterization in children with normal cardiac physiology

Treatment:

Drug: Dexmedetomidine