Hemodynamic and pharmacokinetic analysis of oxymetazoline use during nasal surgery in children

Abstract

Objectives/Hypothesis: Oxymetazoline is an α-adrenergic agonist that is commonly used as a topical hemostatic agent in the operating room during ear, nose, and throat surgery. There are limited data on oxymetazoline pharmacokinetics in children who undergo general anesthesia. We assessed the hemodynamic effects and systemic absorption of topically applied oxymetazoline in children undergoing various nasal procedures. Study Design: Prospective trial. Methods: Children ages 2 to 17 years undergoing functional endoscopic sinus surgery, turbinate resection, or adenoidectomy were enrolled. The surgeon placed oxymetazoline-soaked pledgets (1.5 mL of 0.05% solution) according to our usual clinical practice. Blood samples for oxymetazoline assay were drawn at 5, 10, 20, 45, 90, and 150 minutes, and hemodynamic data were recorded at 5-minute intervals. Data analysis included mixed-effects regression and population pharmacokinetic/pharma-codynamic modeling. Results: The analysis included 27 patients, age 7 ± 4 years, who received between 2 and 12 pledgets (3–18 mL) of oxymetazoline. Relative bioavailability compared to the spray formulation was 2.3 (95% confidence interval [CI]: 1.6–3.2), with slow absorption from the mucosal surface (absorption half-life 64 minutes; 95% CI: 44–90). Mean arterial pressure did not increase with oxymetazoline instillation at the observed oxymetazoline serum concentrations (0.04–7.6 μg/L). Conclusions: Despite concerns regarding oxymetazoline administration to mucosal membranes, we found that hemodynamic changes were clinically negligible with our usual clinical use of pledgets soaked in oxymetazoline. Compared to data on oxymetazoline in spray formulation, bioavailability was increased twofold with pledgets, but systemic absorption was very slow, contributing to low serum concentrations and limited hemodynamic effects.

Conceptual Model for Using Imidazoline Derivative Solutions in Pulpal Management

“…Delivery can be achieved through the use of microbrush (~0.015 mL of solution) or defined volume soaking of small cotton balls (1 drop~0.05 mL) common in primary tooth pulpotomy procedures. As stated previously defined volume soaked pledgets on nasal mucosa had minimal systemic effects in children and it is postulated that there is a self-limiting bioavailability of oxymetazoline through local vasoconstriction [ 1 , 27 ]. This concept can be applied to pulpal tissue, where near immediate hemostasis of the small pulp exposure will limit systemic absorption of the ImD.…”

“…The purpose of this review is to formulate a conceptual model on the potential management of pulpal tissue by imidazoline derivatives (ImDs) based on a review of the literature that examines the hemostatic properties and mechanistic actions of these compounds in other human tissues. Commercial ImDs are formulated in solution with antimicrobial preservatives in order to act as ‘parenteral topical agents’ and used to manage ophthalmic inflammation, nasal congestion, and to control bleeding during otolaryngology surgery [ 1 , 2 ]. While systematic reviews of IMDs in medicine are published [ 3 , 4 , 5 ] this critical review proposes an advancement in dental pulpal management by examining the pharmacology and biochemistry of ImDs, which have been largely understudied for direct dental application [ 6 , 7 , 8 , 9 ].…”

“…Current evidence suggests that controlled dosage of ImDs, such as light soaking of nasal pledgets, is safe and preferred over other vasoconstrictors, such as catecholamines, for surgical hemostasis in children [ 2 , 24 ]. Blood pressure, heart rate, and respiratory rates are well maintained in children during otolaryngology surgeries when ImDs dosing is premeasured [ 1 , 25 , 26 ]. It has been postulated that defined volume soaked pledgets of oxymetazoline held against the nasal mucosa cause such profound vasoconstriction that the drug has very slow absorption and limited systemic effects [ 1 , 27 ].…”

“…Blood pressure, heart rate, and respiratory rates are well maintained in children during otolaryngology surgeries when ImDs dosing is premeasured [ 1 , 25 , 26 ]. It has been postulated that defined volume soaked pledgets of oxymetazoline held against the nasal mucosa cause such profound vasoconstriction that the drug has very slow absorption and limited systemic effects [ 1 , 27 ].…”

In Response to Hemodynamic and Pharmacokinetic Analysis of Oxymetazoline Use During Nasal Surgery in Children

“…Thank you for your comments regarding our article "Hemodynamic and Pharmacokinetic Analysis of Oxymetazoline Use During Nasal Surgery in Children". 1 The authors are grateful that you found our study informative, as your work has been the motivation for our interest in this subject. 2 Currently, the United States Food and Drug Administration (FDA) approves oxymetazoline use in patients who are ≥6 years of age.…”