Hemodynamic and Pharmacokinetic Analysis of Oxymetazoline Absorption

Study Overview
=================
Brief Summary
-----------------
Oxymetazoline is an α-adrenergic agonist that is commonly used as a topical sympathomimetic agent in over-the-counter decongestant sprays. It is used extensively at Nationwide Children's Hospital for surgical procedures to produce vasoconstriction and reduce bleeding. Although there is generally limited vascular absorption, when administered in larger doses, uptake of oxymetazoline can lead to significant systemic hemodynamic effects. The NCH anesthesia department recently reported a case of oxymetazoline induced postoperative hypertension in a three-year-old child following inferior turbinate reduction and adenoidectomy. Current practice at NCH is to soak pledgets with full strength oxymetazoline and insert a varying number of pledgets during surgical procedures or instill oxymetazoline drops into the nose prior to nasotracheal intubation. There is no pediatric data regarding the method of administration and the absorption of oxymetazoline or the dose-response relationship of oxymetazoline serum levels on blood pressure and heart rate. These studies would be the first to determine safe and appropriate doses of oxymetazoline in the pediatric population.

Official Title
-----------------
The Hemodynamic and Pharmacokinetic Analysis of Oxymetazoline Absorption During Functional Endoscopic or Turbinate Reduction Surgery and From the Nasal Mucosa During Operative Dentistry

Conditions
-----------------
Dental Anesthesia, Nasal Surgical Procedures, Intranasal Drug Administration

Intervention / Treatment
-----------------
* Drug: Oxymetazoline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients ages 2 through 12 yrs. Scheduled for: operative dentistry, functional endoscopic sinus surgery, or turbinate reduction (with or without tonsillectomy and/or adenoidectomy). Exclusion Criteria: Treatment with oral decongestants or antihistamines within 24 hours of surgery. Taking anticoagulants. History of nasal trauma. History of epistaxis (nose bleeds). History of hypertension or cardiac disease. Allergy to oxymetazoline.

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ENT - full strength<br>Full strength oxymetazoline pledgets packed in the nose (total volume 20 ml). | Drug: Oxymetazoline<br> <br> * Other names: Afrin;|
| Experimental: ENT - 1/2 strength<br>½ strength oxymetazoline pledgets packed in the nose (total volume 20 ml). | Drug: Oxymetazoline<br> <br> * Other names: Afrin;|
| Experimental: DENTAL - Full strength 1.0 mL<br>Full strength oxymetazoline 1.0 mL to each naris (total =1000 mcg). | Drug: Oxymetazoline<br> <br> * Other names: Afrin;|
| Experimental: DENTAL - Full strength 0.5 mL<br>Full strength oxymetazoline 0.5 mL to each naris (total = 500 mcg). | Drug: Oxymetazoline<br> <br> * Other names: Afrin;|
| Experimental: DENTAL - ½ strength 0.5 mL<br>½ strength oxymetazoline 0.5 mL to each naris (total = 250 mcg). | Drug: Oxymetazoline<br> <br> * Other names: Afrin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxymetazoline plasma concentration |  | 5, 10, 20, 45, 90 & 150 mins. after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate | Assessing for bradycardia | Every 2-5 mins. for a maximum of 240 mins. | 
| Blood pressure | Assessing for hypertension. | Every 2-5 mins. for a maximum of 240 mins. |