Topical administration of medication delivered by pharyngeal or throat sprays is routinely recommended after surgery for conditions of the larynx and pharynx of horses.1–7 These pharyngeal spray medications are typically administered through a nasopharyngeal catheter and contain anti-inflammatory medications and carrier solutions.8 Use of pharyngeal spray is not limited to postsurgical management; it can also be combined with systemically administered drugs for medical treatment of diseases of the pharynx and larynx. Additionally, medications can be administered by pharyngeal spray routes to induce local anesthesia of the larynx for examination and surgical procedures. Although topical medications are frequently applied to the pharynx and larynx after surgery,1–4,9–12 there is little evidence to support their use, and the authors are aware of no studies in which investigators have documented the distribution and efficacy of these products or critically evaluated administration techniques.
Efficacy and distribution of pharyngeal medications administered via oral versus nasopharyngeal methods are unknown. Horses can be resistant to repeated passage of a catheter through the nasal passages, and application of a twitch or assistance by additional personnel might be required for nasopharyngeal administration of medications. In contrast, horses are often more amenable to oral administration of medications, which is a method of administration that can be conducted more easily by 1 person. If oral administration of anti-inflammatory medications results in adequate topical pharyngeal and laryngeal distribution, then this method could provide a viable alternative for horses that are not amenable to nasopharyngeal administration.
The objective of the study reported here was to determine the distribution of contrast medium administered orally or directly into the nasopharynx by use of the same methods as those used for solutions intended as topical medications for the larynx and pharynx. Specfically, we sought to determine by use of radiographic assessment the distribution of contrast medium administered orally versus into the nasopharynx via a nasopharyngeal catheter in standing, unsedated horses. Endoscopy of the nasopharynx, laryngopharynx, and larynx was used to confirm radiographic findings for contrast distribution.
Materials and Methods
Animals
Five adult horses (3 Quarter Horses, 1 Thoroughbred, and 1 Arabian) were included in the study. Horses ranged from 4 to 26 years of age. Each horse was deemed healthy on the basis of the medical history and results of physical examination, with no abnormalities detected in the pharynx and larynx during videoendoscopic examination. The design of the study reported here was similar to that of a study13 conducted to evaluate topical delivery of barium sulfate into the nasal airways by use of 4 administration methods (nasal drops, syringe, spray, and sinus wash). For the present study, a power calculation was performed to identify the number of subjects required to detect an 80% difference in topical distribution within the larynx, which resulted in a median of 4 animals necessary to identify a difference in proportions (similar to the aforementioned study13). The experimental protocol was approved by the Institutional Animal Care and Use Committee of Colorado State University (protocol 12-3308A).
Experimental procedures
A study with a crossover design was conducted. Both nasopharyngeal and oral administration of contrast material was performed on each horse; a minimum of 17 hours was allowed to elapse between subsequent treatments. The order for method of administration was discretionary for each horse. Distribution of contrast material was assessed via radiographic and endoscopic examinations. Digital radiographic examination by use of a lateral view positioned over the pharynx and larynx was performed before administration of contrast medium to provide a baseline result for comparison. Radiographic examination was repeated 17 to 24 hours after administration of contrast medium to ensure no residual medium was present at the time the subsequent treatment was administered. Horses were not sedated and were minimally restrained, with the head and neck maintained in a neutral position for all procedures as previously reported,14 such that the neck was not flexed or extended.
Administration of contrast medium
Administration of contrast medium into the nasopharyngeal region was performed by use of a 10F polypropylene cathetera inserted into the nasopharynx via the ventromedial nasal meatus. Depth for catheter insertion was determined by measuring the distance between the opening of the nares and the ipsilateral ocular medial canthus. This distance was recorded and marked on the catheter prior to insertion. An aliquot (12 mL) of 60% (wt/vol) barium sulfate solutionb was administered via nasopharyngeal catheter over a period of 5 to 10 seconds. A lateral radiograph was obtained immediately after administration of contrast medium.
Oral administration consisted of administration of 12 mL of barium sulfate by use of a syringe placed in the mouth at the oral commissure; contrast medium was administered over a period of 5 to 10 seconds. A lateral radiograph was obtained immediately after administration of contrast medium.
Radiographic examination
Digital radiographic equipmentc was used to obtain precontrast and postcontrast lateral radiographs of the combined pharyngeal and laryngeal regions for each administration. Lateral radiographs of the laryngeal region were obtained at 100 kVp and 2.0 mAs. Images were transferred to the Colorado State University picture-archiving and communication system for storage and subsequent evaluation. A board-certified veterinary radiologist (AV-M), who was unaware of the method of contrast administration, graded the regional distribution of contrast medium on radiographs by use of the following grading system: grade 0 = radiopaque contrast medium not visible, grade 1 = mild amount of contrast medium visible, grade 2 = moderate amount of contrast medium visible, and grade 3 = marked amount of contrast medium visible. Areas of interest were examined and graded separately; these included the nasopharynx (dorsal surface of the soft palate), oropharynx (ventral surface of the soft palate), laryngopharynx, and larynx. When contrast medium was detected in these regions, the anatomic distribution was specified.
Endoscopy
Videoendoscopyd was used to confirm the pharyngeal and laryngeal appearance in all horses. Endoscopic examination of the nasopharynx, laryngopharynx, and larynx was performed within 5 minutes after administration of contrast medium. Endoscopy was performed by a board-certified veterinary surgeon (ESH) and a resident in a veterinary surgical training program (ACC). Endoscopic examinations were video recorded, and another board-certified veterinary surgeon (BSL), who was unaware of the method of administration of contrast medium, analyzed these at a later date. Presence or absence of contrast material was determined for the locations of nasopharynx, laryngopharynx, and larynx.
Viscosity assessment
A viscometere was used to determine viscosity of the 60% barium sulfate solution as well as a pharyngeal spray solution (compounded and used clinically at our institution) that consisted of dexamethasone sodium phosphatef (0.5 mg/mL), DMSO (393 mg/mL), and glycerin (188 mg/mL). A commercially available pharyngeal spray solutiong was also evaluated.
Statistical analysis
Detection of contrast medium during radiographic examination was compared between nasopharyngeal catheter and oral administration methods by use of a Fisher exact test. Values of P < 0.05 were considered significant.
Results
Animals
Horses tolerated oral and nasopharyngeal administration of contrast medium well, without signs of coughing or other complications. Swallowing was observed in all horses during administration of contrast medium regardless of the method of administration. Examination of all radiographs obtained before oral or nasopharyngeal administration of contrast medium confirmed an absence of contrast medium.
Nasopharyngeal administration
Median distance for nasopharyngeal insertion of the catheter was 30 cm (range, 28 to 33 cm). Examination of radiographs obtained after nasopharyngeal administration revealed contrast medium in the nasopharynx and dorsal surface of the soft palate of 5 horses, oropharynx of 2 horses, laryngopharynx of 3 horses, and larynx of 5 horses (Figure 1). Contrast medium was also visible in the trachea of 1 horse and esophagus of 5 horses. Median grade for uptake of contrast medium was 3 (range, 1 to 3) for the nasopharynx, 0 (range, 0 to 2) for the oropharynx, 1 (range, 0 to 1) for the laryngopharynx, and 1 (range, 1 to 2) for the larynx. When contrast medium was visible within the pharynx, it was described as highlighting the soft palate of all 5 horses. When contrast medium was visible within the larynx, it was described as highlighting the epiglottis of all 5 horses and the aryepiglottic folds of 3 horses.
Lateral radiographic views obtained after nasopharyngeal (A) or oral (B) administration of contrast medium to a representative horse. In panel A, notice the moderate amount of contrast medium highlighting the nasopharynx (including the dorsal surface of the soft palate [arrow]) and larynx. In panel B, notice the marked intensity of the contrast medium highlighting the ventral surface of the soft palate within the oropharynx (arrows).
Citation: American Journal of Veterinary Research 78, 9; 10.2460/ajvr.78.9.1098
Oral administration
Examination of radiographs obtained after oral administration of contrast medium revealed contrast medium within the oropharynx of 4 horses and the larynx of 1 horse (Figure 1). Contrast medium was also visible in the esophagus of 3 horses. Median grade for uptake of contrast medium was 1 (range, 0 to 3) for the oropharynx and 0 (range, 0 to 1) for the larynx. Contrast medium visible in the larynx was described as highlighting the tip of the epiglottis. Contrast medium was not observed radiographically within the nasopharynx, laryngopharynx, or trachea after oral administration.
Comparison of distribution of contrast medium
Contrast medium was significantly more likely to be detected radiographically in the nasopharynx (P = 0.008) and larynx (P = 0.048) after nasopharyngeal catheter administration than after oral administration. Radiographic detection of contrast medium did not differ significantly in the oropharynx (P = 0.524) and laryngopharynx (P = 0.167) after administration via either method.
Endoscopy
Endoscopy performed within 5 minutes after nasopharyngeal administration of contrast medium revealed that contrast medium was visible on the nasopharyngeal, laryngopharyngeal, and laryngeal surfaces of all horses (Figure 2). Endoscopy performed within 5 minutes after oral administration of contrast medium did not reveal visible contrast medium on the nasopharyngeal surfaces. However, contrast medium was endoscopically visible within the laryngopharynx adjacent to the esophageal opening of 2 horses and within the larynx on the dorsal portion of the corniculate process of the arytenoid cartilages of 1 horse after oral administration. The oropharynx was not assessed during endoscopic examination.
Endoscopic images of the nasopharynx, laryngopharynx, and larynx after nasopharyngeal (A) or oral (B) administration of contrast medium to a representative horse. In panel A, contrast medium is visible on the surfaces of the nasopharynx, laryngopharynx, and larynx, whereas in panel B, contrast medium is visible within the laryngopharynx on the dorsal portion of the corniculate process of the arytenoid cartilages.
Citation: American Journal of Veterinary Research 78, 9; 10.2460/ajvr.78.9.1098
Viscosity assessment
Viscosity of the barium sulfate contrast medium used in the study was 0.027 Pa•s. Viscosity of the pharyngeal spray compounded and used clinically by our institution was 0.020 Pa•s. Viscosity of the commercially available pharyngeal spray solutiong was below the lower limit of quantitation of the viscometer (< 0.010 Pa•s).
Discussion
In the study reported here, nasopharyngeal administration of barium sulfate contrast solution resulted in distribution within the pharynx (including the dorsal surface of the soft palate) and larynx. Results for the present study indicated that effective coverage of these regions can be achieved by administration of 12 mL of liquid through a nasopharyngeal catheter over a 5- to 10-second period and confirmed that nasopharyngeal administration of pharyngeal spray is an adequate delivery method for treatment of conditions of the pharynx and larynx, which supported its use as a method for delivery of medications after palatal and laryngeal surgery and the purported claims of treatment success.1–3,10,12 In the present study, oral administration of barium contrast medium resulted in distribution of contrast medium to the larynx of only 1 horse. However, oral administration provided coverage of the ventral surface of the palate in 4 of 5 horses, which suggested that oral administration of pharyngeal spray medications might be appropriate for treatment of conditions of the palate or for use after palatal surgeries when nasopharyngeal administration cannot be tolerated. Similar to its use in equine medicine, topical administration of treatments is widely used in human otolaryngology, with goals for the combination of the pharmacological solution and delivery method being complete mucosal distribution and a prolonged contact time.15 A primary benefit of topical administration is the achievement of high local concentrations of medications at the site of action.16,17
Viscosity of the barium sulfate contrast solution was similar to that of a pharyngeal spray compounded and used clinically at our institution. Selecting a liquid with comparable viscosity to evaluate distribution of a pharyngeal spray was essential because augmentation of the viscosity of topical mucosal preparations is a critical element for improving residence time and allowing the opportunity for greater pharmacological uptake and activity. Other bioadhesive delivery systems (such as those involving chitosan or starch microspheres) markedly improve residence time on nasal mucosa by counteracting mucociliary clearance16 and could be used to increase the time available for drug absorption after delivery of a pharyngeal spray in horses. Penetration enhancement, via thixotropic deoxycholate-hydrogels, might further improve effects of drug carrier solutions used in horses.18 Evaluation of residence time for pharyngeal sprays is of interest for determining local drug delivery to the pharynx and larynx of horses.
It is generally accepted that pharyngeal sprays are beneficial, and their use has been extensively evaluated in other species; however, little is known about solution properties and components for use in horses. The pharyngeal sprays evaluated in the present study contained chelated silver, glycerin, DMSO, and dexamethasone. Intranasal administration of nanosilver can reduce inflammation in mice with allergic rhinitis19; however, effects of the low viscosity of the chelated silver solutiong on distribution and residence time in the larynx and pharynx are not known. Glycerin is likely to be largely responsible for the viscosity of the compounded pharyngeal spray used clinically at our institution. Esterified glycerin has been used in clinical trials of humans with allergic rhinitis and has been found to be safe and to prevent allergic symptoms, particularly nasal congestion, by providing surface protection from allergens on the nasal mucosa.20 Although DMSO is often used in equine medicine for its anti-inflammatory properties, DMSO solutions (concentrations between 90 and 900 mg/mL) applied topically to the nasal mucosa of guinea pigs have been associated with irritation.21 Similar inflammatory responses were not identified for DMSO concentrations < 45 mg/mL21; therefore, a reduction of this component in the pharyngeal spray solution might be warranted. Topical administration of dexamethasone is beneficial for healing by decreasing granulation formation and stroma thickness without impeding epithelial differentiation in animals with experimentally induced paranasal sinus injury.22 Systemic effects of dexamethasone in pharyngeal spray solutions used in horses are currently unknown, but dexamethasone could impact animal health and drug testing compliance in performance horses, in which urine and serum are routinely screened. Dexamethasone administered intranasally twice daily over a 6-week period suppressed cortisol concentrations in approximately one-third of patients in a recent study23 of people receiving treatment for chronic rhinosinusitis. Serious health effects related to systemic absorption have been reported in children receiving intranasally administered corticosteroids.24,25 In human medicine, topical administration of dexamethasone as treatment for rhinitis has largely been replaced by use of other corticosteroids (eg, beclomethasone) because of the effects of dexamethasone on the hypothalamic-pituitary-adrenal axis.26 Whereas much is known about use of pharyngeal sprays in other species, further investigations and optimization of the use of pharyngeal spray solutions would complement the present study on pharyngeal spray delivery methods in horses.
Barium sulfate contrast medium was visible radiographically and endoscopically within the larynx and pharynx of horses of the present study. Radiopaque contrast agents have been used to evaluate distribution of topically applied medications in nasal sinuses of humans and to compare delivery methods,27,28 although the study reported here, to the authors’ knowledge, was the first in which use of pharyngeal spray methods for horses has been evaluated. Radiographic examination allowed simultaneous evaluation of the distribution of contrast medium in the nasopharynx, oropharynx, laryngopharynx, and larynx. Endoscopic evaluation complemented the radiographic examination and was more sensitive for detection of contrast medium within the laryngopharynx, regardless of the method of administration, although endoscopic evaluation of the oropharynx was not conducted. Observers who were not aware of the method of administration separately identified contrast medium in endoscopic and radiographic examinations. Additional observers for each examination type and evaluation of interobserver agreement would have added to the present study. Additional radiographic views or CT images obtained from horses in the standing position might have allowed improved visibility of contrast medium in relation to the anatomic structures, compared with visibility via conventional radiographic examination, endoscopic examination, or technetium Tc 99m–enhanced scintigraphy29; however, CT is not performed on unsedated animals at our institution. If CT had been performed, that might have allowed evaluation of the relative surface area of the oropharynx and nasopharynx, and it would have further indicated whether volume of infusate should be adjusted. It is unclear whether use of an identical volume of infusate for oral and nasopharyngeal administration methods, as was performed in the present study, was appropriate or whether this component of the methods biased the outcomes. The transit areas and contact surfaces for each infusate method have not been clearly described for horses and could differ from those described for humans.30 The objective of the present study was to determine the distribution of barium sulfate contrast medium administered via a nasopharyngeal catheter and orally to mimic the distribution of a pharyngeal spray clinically administered to horses; however, contrast medium administered by use of these methods could also improve soft tissue contrast in the pharynx and larynx to aid in investigation of pathological conditions of the airways13; this should be evaluated in a future study.
Effects of airway disease of horses on delivery and retention of pharyngeal sprays and their impact on safety and efficacy are unknown. In the present study, nasopharyngeal administration of contrast medium resulted in excellent coverage of the surface of the pharynx and larynx of healthy horses, which supported its use for a variety of conditions in these regions that are responsive to topical medications. Oral administration of contrast medium resulted in distribution primarily in the oropharynx and laryngopharynx of healthy horses. These results suggested that oral administration could be appropriate for treatment of conditions affecting these areas (eg, palatitis). Dorsal displacement of the soft palate and epiglottic disease often occur jointly,5,6 which might affect the efficacy of medications administered orally in affected patients. Further investigations are necessary to determine whether distribution of a pharyngeal spray is altered in the presence of disease that affects regions of the pharynx and larynx and whether modifications to administration methods might improve efficacy in both healthy and diseased horses.
Acknowledgments
Supported in part by the Colorado State University Advances in Equine Health Fund.
Presented in abstract form at the 60th Annual American Association of Equine Practitioners Conference, Salt Lake City, December 2014.
ABBREVIATIONS
| DMSO | Dimethyl sulfoxide |
Footnotes
Argyle suction catheter 8890703518, Covidien, Mansfield, Mass.
E-Z-Paque, E-Z-EM Canada Inc, Lake Success, NY.
Duocon M-150 Collimator, Siemens, Munich, Germany.
Olympus mobile workstation P14s0, Olympus America Inc, Lombard, Ill.
Viscolead Pro series L VL300003 rotational viscometer, Fungilab, Hauppauge, NY.
Dexamethasone-SP, Bimeda-MTC Animal Health Inc, Cambridge, ON, Canada.
Equisilver veterinary antimicrobial silver respiratory solution, Equisilver, Louisville, Ky.
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