Pharmacokinetic Study of Intranasal Dexmedetomidine in Pediatric Patients With Congenital Heart Disease

The high anxiety levels that children may experience during the preoperative period may be
associated with negative medical, psychological, and social consequences. To reduce this
stress, and to facilitate separation from parents and the induction of anesthesia, children
are often given a sedative prior to undergoing a procedure. Dexmedetomidine is a highly
selective a2-adrenergic receptor agonist with sedative, anxiolytic, and analgesic properties.
While off-label in its use, the administration of dexmedetomidine by the intranasal route has
become a popular and effective technique for sedation in children because it is non-invasive,
easy to administer, well tolerated, and relatively fast in onset. Despite this, little
consistent data have been published on its onset time, duration of action, or optimal dose.
The only available pharmacokinetic (PK) data on dexmedetomidine in pediatric patients is in
children who were administered IV dexmedetomidine. We are proposing a prospective open-label
inter-subject cohort dose-escalation pharmacokinetic study to obtain peak dexmedetomidine
drug concentration level in plasma and the corresponding time point following intranasal
administration in the pediatric patient with cardiac disease.

Inclusion Criteria:

1. Male or female subjects age ≥1 mo to ≤6 yo.

2. Subjects must have congenital heart disease.

3. American Society of Anesthesiology (ASA) Physical Status 1-3.

4. Subjects scheduled for elective cardiac interventional or diagnostic catheterization
anticipated to last ≥ 3hours.

5. Subjects must have reliable intravascular access from which to draw blood samples.

Exclusion Criteria:

1. History of allergic reaction or sensitivity to dexmedetomidine.

2. Nasal pathology preventing the administration of drug.

3. Patients that are on maintenance medications that could inhibit or induce the CYP2A6
enzyme.

4. Cardiac conduction abnormalities defined as second or third degree heart block or
pacemaker dependence.

5. Bradycardia, defined by age, upon arrival in the preoperative care area.

6. Hepatic dysfunction defined as a history of hepatic dysfunction AND an Alanine
Aminotransferase (ALT) value greater than 2 times normal in the 6 months prior to
study drug administration.

7. The subject has received dexmedetomidine or clonidine within 1 week of the study date.

8. BMI >30.

9. Patients previously enrolled in this study.

10. Any investigational drug use within 30 days prior to enrollment.

11. Wards will not be eligible.