Sedation With Dexmedetomidine During Cardiac Catheterization

Clinical dose escalation drug trial to evaluate the effect of 3 different doses of
dexmedetomidine on the pulmonary vascular bed in pediatric subjects with elevated pulmonary
vascular resistance. The study will be conducted in 2 parts, with a pilot phase
incorporating stopping rules to optimize safety of the drug in this population. Study
subjects will include pediatric subjects with Pulmonary Hypertension (PHTN).

Part 1: This will be the dose escalation phase of the study. Twenty four evaluable subjects
will be enrolled. Subjects will include pediatric subjects with pulmonary hypertension
(PVR>4WU) undergoing hemodynamic cardiac catheterization and vasoreactivity drug testing.
Cohorts of 8 evaluable subjects will receive dose level 1, dose level 2, or dose level 3
of Dexmedetomidine. The dose will be escalated to the next dose of DEX once all subjects
have been enrolled in the preceding DEX dose cohort, and safety has been established at
that level. Inadequate sedation despite the highest dose of DEX at each level will be
considered a treatment failure on an intention to treat basis. Part 2: This part of the
study will be conducted after the pilot phase is safely completed, and the full complement
of subjects will be recruited.

Inclusion Criteria:

1. Subjects with a diagnosis of pulmonary hypertension

2. Procedure - Planned cardiac catheterization procedure with spontaneous ventilation
and natural airway

3. Patients who want sedation or general anesthetic for the procedure.

4. Age: Subjects ≥8 years and < 21 years

5. Adequate Renal Function defined As:Serum creatinine ≤ 1 mg/dL

6. Adequate Liver Function defined As:Total bilirubin ≤ 1.5 mg/dL alanine
aminotransferase (ALT) ≤ 2 times the upper limit of normal

7. Informed Consent: All parents or legal guardians must sign a written informed
consent.

8. Signed assent when developmentally appropriate

9. Negative pregnancy test in menstruating females and all females ≥ 12 yr

Exclusion Criteria:

1. Refusal of Informed Consent/Assent

2. Subjects with single ventricle physiology

3. Pregnant or lactating females

4. Subjects with syndromes e.g. Trisomy 21 will be excluded due to variability in
pharmacodynamic responses and airway instability during sedation

5. Inappropriate clinical or developmental status to undergo cardiac catheterization
under conditions of spontaneous ventilation with a natural airway

6. Second or third degree heart block

7. Moderate - severe right ventricular dysfunction/failure

8. Subjects who, in the opinion of the investigator, are not appropriate candidates for
an investigational drug study e.g. behavioral or anxiety disorders, inability to lie
supine

9. Concomitant Medications - Investigational Drugs: Subjects who have received another
investigational drug protocol 30 days prior to enrollment in this study

10. Subjects who in the opinion of the investigator may be non compliant with study
schedules or procedures.

11. Non-English speaking subjects will be excluded due to need for direct communication
from clinical and study staff during study procedures and the ability to complete
study tools.