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Rhinologic pharmacotherapy in rhinoplasty

C. Spencer Cochran, MD, Bradley F. Marple, MD, FAAOA*
Department of Otolaryngology Head and Neck Surgery, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9035, USA

Many potential candidates for rhinoplasty seek initial surgical evaluation for cosmetic reasons, while others seek correction of functional problems with the nose, such as nasal obstruction or congestion. Regardless of the motivation for undergoing rhinoplasty, this population is at risk for concomitant rhinologic disease processes. Thus, a thorough understanding of nasal function and the impact of disease processes is crucial to the overall success of the rhinoplasty surgeon. The nose performs six key functions of the upper airway: respiration, olfaction, humidification, temperature modification, particle filtration, and phonation, as well as having a possible function as a secondary sex organ [1]. Of particular importance to the rhinologist and rhinoplasty surgeon are the functions that are affected by mucosal disease. The nasal mucosa and its mucociliary blanket act as the initial barrier to infection and environmental insult. Nasal mucus is a complex aqueous mixture of glycoproteins, lipids, salts, and other cellular constituents that normally protects nasal epithelia from a wide variety of insults. Aside from its function as a simple mechanical barrier, nasal mucus likely plays an active role in inactivation of many substances that gain access to the nose [2]. Any of these nasal functions can be altered or impaired by structural or functional abnormalities arising from sinonasal disease processes. Thus, rhinoplasty surgeons must be well versed in sinonasal disorders, the available pharmacologic armamentarium, and the impact of these diseases on patient care.

Inflammatory disorders of the nose and paranasal sinuses There is a spectrum of rhinologic disease processes with which the rhinologist and rhinoplasty surgeon alike must be familiar (Box 1). The upper aerodigestive tract, particularly the intranasal mucosa and paranasal sinuses, is a frequent site of both allergic and nonallergic inflammation. Understanding the underlying pathophysiology of the inflammatory disorders can improve the selection of treatments for these conditions and minimize their impact on rhinoplasty patients and outcomes. Allergic rhinitis Allergic rhinitis is a Type I allergic reaction in which allergen-specific immunoglobulin E (IgE) bound to nasal mast cells interacts with an inhalant allergen to produce symptoms that include sneezing, pruritis, congestion, rhinorrhea, and postnasal discharge. Allergic rhinitis has been estimated to affect 40 million Americans, with health care-related expenditures in the billions [3]. Allergy may present as a single rhinologic disease process or may coexist with or contribute to other rhinologic disease processes. For example, allergy produces mucosal edema, which may lead to sinusitis by means of ostial obstruction and set the stage for secondary bacterial infection [4]. While allergic rhinitis is still only partially understood, key elements of its pathophysiology have been elucidated. Initially, an individual who is susceptible to the development of allergic disease encounters a potential allergen. Although at this initial encounter the individual is not capable of developing an allergic reaction, the immune system is triggered to develop a

* Corresponding author. E-mail address: bradley.marple@utsouthwestern.edu (B.F. Marple).

1064-7406/04/$ see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.fsc.2004.04.004

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Box 1. Nasal disorders

 Allergic rhinitis  Nasal polyposis  Nonallergic rhinitis

anticholinergics, anti-leukotrienes, and mast cell stabilizers. Immunomodulation therapies include topical or systemic steroids, immunotherapy, and potentially monoclonal antibodies. Rhinosinusitis Acute rhinosinusitis Acute rhinosinusitis (ARS) denotes an inflammatory state involving the paranasal sinuses as well as the intranasal mucosa. It is defined as a discrete infectious process that lasts less than 4 weeks [6]. Diagnosis of ARS relies on a strong history of two or more major factors, one major factor plus two minor factors, or nasal purulence on examination (Box 3) [7]. Several factors can contribute to the development of rhinosinusitis, such as viral or bacterial infections, allergy, structural abnormalities, cystic fibrosis, cilia defects, and immunosuppression. The mainstays of treatment of bacterial ARS are antibiotics and decongestants. Rhinoplasty is generally contraindicated in the presence of active infection. Chronic rhinosinusitis Chronic rhinosinusitis (CRS) is an inflammatory state differing in duration from acute rhinosinusitis. It is becoming increasingly apparent that CRS is a multifactorial process. In 2002 the Task Force for Defining Chronic Rhinosinusitis [7] defined CRS as a group of disorders characterized by inflammation of the mucosa of the nose and paranasal sinuses of at least 12 weeks duration. While infection may

Vasomotor Rhinitis medicamentosa Atrophic  Infectious Acute rhinosinusitis Chronic rhinosinusitis Allergic fungal rhinosinusitis  Structural abnormalities Deviated septum Turbinate hypertrophy Adenoid hypertrophy  Other or system disorders Wegners granulomatosis Sarcoidosis Cocaine-induced destructive lesions

recognition of the allergen, which ultimately leads to the development of T-lymphocytes, B-lymphocytes, and allergen-specific IgE. This process is referred to as sensitization. Upon subsequent exposures, the same allergen can simultaneously bind to two adjacent allergen-specific IgE molecules on the surface of the mast cell, triggering degranulation of the cell and release of histamine and other inflammatory mediators [5]. This reaction is referred to as the early-phase response and leads to the immediate onset of symptoms such as sneezing, rhinorrhea, and congestion. This process, in turn, leads to further recruitment of a number of inflammatory cells such as neutrophils, lymphocytes, and eosinophils. Once at the site of the initial degranulation of the mast cell, these inflammatory cells give rise to a self-sustaining inflammatory reaction known as the late-phase response, which is less severe but more prolonged than the early-phase response [3]. Allergy treatment ideally begins with avoidance, which precludes the formation of antigen-specific IgE and eliminates the initiation point of the allergic cascade. In reality, however, avoidance is difficult to achieve, and patients must rely on medical management to treat their allergy symptoms. Medical therapy involves both target therapy and immunomodulation (Box 2). Targeted forms of therapy address the mediator effects of allergy, whereas immunomodulation prevents initiation and down-regulates the allergic response. Target therapy options include antihistamines, decongestants, mucolytics,

Box 2. Pharmacologic agents for allergic rhinitis Target therapy Antihistamines Decongestants Anticholinergics Anti-leukotrienes Mast cell stabilizers Mucolytics

Immunomodulation Intranasal steroids Systemic steroids Immunotherapy Monoclonal antibodies

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Box 3. Rhinosinusitis Major criteria Facial pain/pressure Nasal obstruction Nasal discharge Hyposmia/Anosmia Purulence in nasal cavity Fever

of topical decongestants after prolonged use. Treatment is supportive and entails absolute abstinence from further topical decongestants. Topical steroids and even systemic steroids may be beneficial to attenuate the mucosal hyperemia and edema. Postrhinoplasty rhinitis Following rhinoplasty, some patients complain of nasal obstruction. Beekhuis [11] reported a 10% incidence of symptomatic nasal obstruction in his series of rhinoplasty patients. Treatment is often expectant, but oral decongestants, topical nasal steroid sprays, and nasal saline irrigation may be of use. Atrophic rhinitis Over-resection of intranasal structures such as the middle or inferior turbinate can lead to atrophy of the nasal mucosa with subsequent symptoms of dryness, crusting, and nasal obstruction. Nasal saline may provide symptomatic relief.

Minor criteria Headache Fever Halitosis Fatigue Dental pain Otalgia/Pressure/Fullness

Pharmacologic agents represent a component of CRS, it is becoming increasingly clear that there is multifactorial causation and interrelationship among many of the inflammatory disorders of the nose and paranasal sinuses [8]. Treatment of CRS is medical, with functional endoscopic sinus surgery (FESS) reserved for treatment failures. Several studies indicate that FESS at the time of rhinoplasty is a viable option in the absence of signs of infection [9]. Allergic fungal rhinosinusitis Allergic fungal rhinosinusitis (AFS) represents an immunologically mediated sinonasal disease process, rather than an infectious process. The inflammation associated with allergic fungal rhinosinusitis is probably related to eosinophil chemotaxis and degranulation. The diagnosis of AFS is established by the characteristics of IgE-mediated hypersensitivity, nasal polyposis, characteristic CT or MRI findings, allergic fungal mucin, and positive fungal stain of sinonasal contents. Long-term control of AFS requires both elimination of fungal antigen (usually requiring surgery) and control of its recurrence through either immunomodulation (immunotherapy or corticosteroids) or fungistatic antimicrobials [10]. Rhinitis Rhinitis medicamentosa Rhinitis medicamentosa refers to rebound rhinitis of the nasal mucosa as the result of sudden cessation Antihistamines Antihistamines are agents that act on H1-receptors to block the local effects of histamine that is released in response to an allergen exposure. Newer antihistamines may also act directly on inflammatory mediators, diminishing their production or negating their effects. Histamines local effects include vasodilation, an increase in vascular permeability, and trigeminal irritation. Early-phase reactions to histamine produce symptoms such as sneezing, rhinorrhea, and congestion. Late-phase reactions include eosinophil recruitment, cellular adhesion, and leukotriene effects. Antihistamines primarily attenuate the allergic rhinitis symptoms of sneezing, pruritis, and rhinorrhea; however, they are not efficacious in alleviating congestion. For this reason, antihistamines and decongestants such as pseudoephedrine are frequently combined. First-generation antihistamines competitively bind H1-receptors (Box 4). Because they are lipophilic, they are able to cross the blood brain barrier and have central nervous system effects such as sedation, decreased cognitive performance, decreased motor coordination, and impairment in central interpretation of vestibular input [12]. In addition, first-generation antihistamines have anticholinergic effects that can cause xerostomia and urinary retention. Paradoxical stimulation by antihistamines may be seen in infants and older patients.

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Box 4. Oral antihistamines First generation Chlorpheniramine Clemastine Diphenhydramine Hydroxyzine Promethazine

Second and third generation Cetirizine Fexofenadine Loratadine Desloratadine Norastemizole

Because of problems with first-generation antihistamines, a new generation of antihistamines began in 1985 with the introduction of terfenadine, followed in 1989 by the commercial availability of astemizole. Like the preparations they replaced, terfenadine and astemizole were found to have side effects and potential drug interactions: the most serious and potentially catastrophic problem with these two drugs was that of ventricular arrhythmias. Because of these adverse effects, a third generation of antihistamines has been developed, including compounds that appear to be free of cardiotoxicity. The earliest members of this class were loratadine and acrivastine. Then came cetirizine (a relatively nonsedating congener of hydroxyzine) and fexofenadine (the acid metabolite of terfenadine, with equal activity but no cardiotoxic side effects). These preparations are generally considered to be nonsedating in normal doses, although loratadine and cetirizine in large doses apparently can cause some degree of sedation [13]. The newer, second- and third-generation antihistamines bind H1-receptors noncompetitively, are lipophobic, and have minimal anticholinergic activity. Hence they are associated with improved performance and fewer side effects such as sedation, psychomotor depression, and anticholinergic effects [14]. Finally, they do not demonstrate the phenomenon of antihistamine tolerance, or tachyphylaxis, which had been observed with first-generation compounds. Because these drugs were new and did not cause unwanted side effects, most clinicians expected them to be more effective than first-generation antihis-

tamines in controlling allergy symptoms. However, terfenadine and astemizole were determined to be equipotent with (not better than) first-generation antihistamines such as chlorpheniramine. Furthermore, efficacy profiles of later-generation antihistamines are similar to those of the sedating antihistamines with regard to attenuation of nasal and ancillary symptoms. They both have little impact on nasal congestion [15,16]. A move toward topical preparations in the treatment of allergic rhinitis has included the development of several antihistamines delivered in this fashion. The first intranasal antihistamine introduced in the United States was azelastine, which appears to be equivalent to other antihistamines in potency. Unfortunately, a high incidence of taste perversion has been noted among patients using it [17]. Topical nasal formulations of levocabastine have been introduced in Canada and Mexico, but introduction is pending in the United States. This preparation is said to be 15,000 times more potent than chlorpheniramine, with duration of effect for 24 hours or more and few if any side effects [18]. As has been noted, the primary effect of antihistamines is to diminish pruritis, sneezing, and rhinorrhea. Because of the similar efficacy of older- and newer- generation antihistamines, selection is based on safety, cost, physicians experience, and individual preference. Rhinoplasty candidates who have symptomatic allergic rhinitis and who are on antihistamines should continue their medication regimen in the perioperative period.

Decongestants Decongestants are available as topical agents or systemic agents, alone or as a component in many over-the-counter cold and allergy preparations. Additionally, decongestant may be formulated with prescription antihistamines (eg, Allegra-D) to relieve nasal congestion, the allergic symptom complex that is not addressed by antihistamines alone. As is the case in over-the-counter combinations, the decongestant most commonly combined with an antihistamine is pseudoephedrine, in a total daily dose of 180 mg to 240 mg. As a group, decongestants exert a sympathomimetic effect by means of a1- and a2-receptor stimulation. They displace norepinephrine from presynaptic sympathetic receptors and block the reuptake of norepinephrine, resulting in smooth muscle contraction and vasoconstriction. Systemic decongestants (pseudoephedrine and phenylpropanolamine) achieve

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peak levels in 1 to 3 hours and have a half-life of 3 to 4 hours. The most common side effect of systemically administered decongestants is cardiovascular stimulation. Pseudoephedrine may produce somewhat less blood pressure elevation than the other available systemic decongestants, although any may be used (albeit with caution) in patients with stable, treated hypertension [19,20]. Other cardiovascular stimulatory effects of these drugs include tachycardia, palpitations, and even arrhythmias. The central nervous system stimulation produced by decongestants is generally manifested as anxiety and insomnia. Additionally, the stimulatory side effects of systemic decongestants are enhanced by tricyclic antidepressants and monoamine oxidase (MAO) inhibitors. The potentiation by MAO inhibitors may persist for up to 2 weeks after these drugs have been discontinued. Hence, systemic decongestants should be administered cautiously and in reduced doses in patients with hypertension, atherosclerotic coronary artery disease, and hyperthyroidism, as well as in patients taking MAO inhibitors and in those with urinary retention. Topical decongestants (oxymetazoline and phenylephrine) have an onset of action of 5 minutes and a duration of more than 6 hours. They have a greater local potency and fewer systemic effects compared with systemic decongestants. A frequent problem associated with prolonged use of topical decongestants is rhinitis medicamentosa; however, the risk of rhinitis medicamentosa can be minimized by limiting topical decongestant use to 3 to 7 days. Topical and systemic decongestants may be a beneficial symptomatic treatment modality in patients after septorhinoplasty to help reduce postoperative congestion and nasal obstruction. Nasal saline Topical nasal saline has been used as an adjunct in the treatment of multiple rhinologic disorders, as well as in postoperative care of patients undergoing rhinoplasty or endoscopic sinus surgery. Anecdotal evidence supports the efficacy of nasal saline. Although there have not been many scientific studies addressing the use of nasal saline, Tomooka [21] reported a statistically significant improvement in nasal symptoms in patients with sinonasal disease who used nasal irrigation. Over the past several years there have been conflicting reports about damage to human nasal epithelia and exacerbation of rhinitis medicamentosa associated with intranasal products containing ben-

zalkonium chloride (BKC). BKC is a quaternary ammonium compound that has been used to maintain the sterility of a variety of prescription and over-thecounter products, including nasal saline. In a recent review of eighteen studies of the effects of BKC, Marple [2] found that the available literature has failed to establish a clear cause-and-effect relationship between BKC at concentrations less than 0.1% and clinically significant detrimental effects on nasal epithelium. He concluded that intranasal products containing BKC are safe and well tolerated for both short- and long-term use. Anticholinergics Topical anticholinergic preparations (ipratropium bromide) decrease parasympathetic tone locally to decrease watery rhinorrhea, a common complaint in patients with allergic rhinitis. These preparations do not, however, reduce congestion, irritation, itching, or sneezing. Ipratropium bromide is now available in 0.03% and 0.06% strengths in a metered-dose pump spray for intranasal use. The 0.06% strength is primarily used to alleviate the initial rhinorrhea of the common cold, whereas the 0.03% concentration is used to control rhinorrhea caused by vasomotor rhinitis, perennial nonallergic rhinitis, perennial allergic rhinitis, and gustatory rhinitis [22,23]. The most important factor in the success of this treatment is a dose sufficient to control symptoms early in the day, with additional dosing as necessary [24]. The recommended dosing regimen is two sprays in each nostril in the morning on rising, with subsequent doses of two sprays in midafternoon and in the evening if needed. Often, the morning dose alone suffices. In these circumstances, the use of the topical anticholinergic is not curative but will often control symptoms that are extremely bothersome to the patient. Side effects from topical nasal ipratropium are minimal, and its long-term use does not appear to present a problem. Leukotriene receptor antagonists Although histamine is the primary culprit in the allergic reaction, leukotrienes are a group of inflammatory mediators that play a supporting role in sinonasal inflammation. Leukotrienes, formerly referred to collectively as slow reacting substances of anaphylaxis, were isolated in 1983 and consist of a family of inflammatory mediators that are end-products of the arachidonic acid cascade produced in response to degranulation of the mast cell.

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The biologic effects of the cysteinyl leukotrienes (LTC4, LTD4, LTE4) can act to trigger a number of processes important to inflammation of respiratory mucosa, including chemotaxis of inflammatory cells (eg, neutrophils, lymphocytes, eosinophils), increased permeability of vessels, and vasodilation [25,26]. Identification of the leukotrienes as an important mediator of allergic inflammation piqued interest in the potential that blocking their effect might have on the allergic response. Leukotriene modifying agents were found first to have a positive effect in the control of asthma, then to have a beneficial rhinologic application in treating allergic rhinitis, aspirin sensitivity (Samters triad), and idiopathic nasal polyposis. Several studies have proved their efficacy in alleviating the congestive symptoms of allergic rhinitis, as well as sneezing and rhinorrhea [27]. Because these agents improve mucus production and congestion, the treatment effect of a leukotriene inhibitor with an H1-antagonist may be additive. Montelukast, a leukotriene receptor antagonist, acts to inhibit the action of leukotrienes at the endorgan receptor site. Studies comparing this preparation with placebo have demonstrated a statistically significant impact on both daytime and nighttime symptoms of allergy. Moreover, this class of medications has demonstrated the ability to decrease the number of activated eosinophils resident within inflamed mucosa [28]. Given the relative novelty of this class of medications and the limited amount of data currently available regarding their impact on allergic rhinitis, there is much to learn about how they may be used to improve patient outcomes. Initial information appears to support the use of leukotriene receptor antagonists in the treatment of symptomatic allergy, especially for symptoms of rhinorrhea and nasal congestion. The impact of this class of medications on eosinophils may indicate a broader role for them in the future treatment of inflammatory disorders of the nose and paranasal sinuses.

immediately after allergen exposure, they are good for anticipated situational allergy if used 3 to 7 days before exposure to the inciting antigen. Of course, cromolyn (or any intranasally administered drug) must adequately reach the nasal mucosa to be effective. Hence it may not be feasible for use by patients with severe septal deviation or marked turbinate hypertrophy. Not only will polyps prevent cromolyn from achieving adequate contact with nasal mucosa, but the cromolyn has no effect on the polyps. Rather, it prevents the allergic event when applied beforehand, and to a much lesser degree may ameliorate symptoms of an allergic event in progress. It must be reapplied every 4 to 6 hours to remain effective. Despite these shortcomings, cromolyn is especially effective for patients with allergy to welldefined inhalants that are unavoidable and are not encountered on a continuous basis. Also, cromolyn is exceptionally safe and is probably one of the best methods of providing relief to pregnant women with mild to moderate symptoms of allergic rhinitis.

Mucolytics Mucolytics, such as guaifenesin, decrease mucous viscosity and increase mucous volume by means of a vagal nerve mediated increase in parasympathetic tone. Wawrose et al [30] found a significant decrease in congestion and thinner postnasal drip among patients with CRS, and Morgan and Petty [31] showed improvement in frequency of cough and chest discomfort in patients with Chronic Obstructive Pulmonary Disease (COPD). However, Druce [32] found no support for guaifenesins ability to reduce viscosity. The role of mucolytics as a symptomatic adjunct to treatment of sinonasal disorders and in postoperative care remains unclear.

Corticosteroids Mast cell stabilizers Cromolyn sodium (Nasalcrom, Intal) and nedocromil (Tilade) exert direct effects on mast cells by inhibiting their calcium-dependent degranulation in response to allergen exposure, although the exact mechanism of their action remains a matter of conjecture. The result is the prevention of an allergic reaction when these stabilizers are used before an antigen exposure [29]. These agents may also exert a late-phase inhibition of eosinophils and neutrophils. Although they are ineffective when administered Corticosteroids, both systemic and topical, are potent anti-inflammatory agents with general applications in the management of tissue inflammation, whether it is related to postsurgical changes, allergic phenomena, or infection. Rhinology too has embraced the efficacy of steroids, as evidenced by the widespread acceptance of topical nasal steroids as first-line agents in the management of allergic rhinitis and by their increased use in managing chronic sinonasal inflammation. Although the targeted forms of therapy address mediator effects of inflammation, corticosteroids ex-

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ert an immunodulatory effect to prevent initiation and down-regulate the inflammatory responses. Steroids reduce the influx of inflammatory cells, attenuate the availability of inflammatory mediators, and reduce the development of hyperresponsiveness. Corticosteroids, by virtue of their lipophilic nature, enter the target cell directly and bind to a steroid receptor. The steroid-bound receptor alters mRNA transcription and ultimately protein translation to alter the expression of inflammatory mediators. Corticosteroids exhibit a profound inhibitory effect on production of proinflammatory cytokines such as interleukin-1 (IL-1), IL-2, IL-2R, Interferon alpha (INFa), and Tumor necrosis factor (TNF). In allergic rhinitis, corticosteroids efficacy in mitigating early- and late-phase reactions has been well established. Topical intranasal steroids Topical nasal steroids act locally on the nasal mucosa, and because their anti-inflammatory action is nonspecific, they are useful in the treatment of both allergic and nonallergic rhinitis. Whereas systemic corticosteroids almost exclusively affect the late-phase allergic reaction, pretreatment with topical nasal corticosteroids for up to a week has a beneficial effect on both acute- and late-phase allergic reactions. Topical steroids affect eosinophils by decreasing recruitment and immigration and increasing apoptosis. Additionally, they attenuate the effect of basophils and mast cells by decreasing the amount of histamine. However, it is worth emphasizing that these compounds do not prevent the allergic reaction, but simply blunt the effects of the mediators thus released. Effective dosing entails regular use of topical nasal steroids, though there is some efficacy achieved with single dose administration. The effective use of nasal steroids (as of any nasal preparation) begins with the drugs being able to penetrate the nasal cavity and come in contact with the target mucosa. For this reason, patients with severe septal deviation or markedly hypertrophic inferior turbinates will benefit considerably less from the use of nasal corticosteroids than will patients without such obstruction. A systemic decongestant, or a brief course of a topical decongestant, may be necessary in conjunction with nasal steroids (especially at the initiation of therapy) to ensure adequate penetration past congested areas. Although steroid nasal sprays are effective in the treatment of small nasal polyps and the prevention of polyp regrowth after nasal and sinus surgery, large polyp masses that block the nasal passage will not generally yield to topical therapy.

With the increasing use of intranasal steroids for the treatment of allergic rhinitis and chronic disease, there has been much debate about their safety and the potential for local or systemic side effects. Intranasal steroids have been associated with several local side effects, including epistaxis, dryness, and burning. Local side effects may occur with any nasal steroid preparation. In addition to local discomfort caused by preservatives and vehicles, side effects frequently involve nasal crusting and dryness, epistaxis, headache, and sore throat. Excoriation or ulceration of the nasal septum, potentially leading to frank septal perforation, may follow nasal steroid therapy. In addition to irritation from propellants and a thinning of the nasal mucosa from the steroid, the most likely contributory factor is trauma to the septum. This trauma can be avoided by careful instructions to patients to direct the tip of nasal steroid sprays away from the septum (pointing it toward the corner of the eye), thereby avoiding contact. While there have been reports of septal perforations, several studies have demonstrated no evidence of mucosal atrophy, mucosal metaplasia, or impairment of mucociliary function [33,34]. The systemic availability of the topical steroids is variable. Wilson et al [35] showed that 24-hour mean plasma cortisol levels are similar across all groups. Benninger et al [36] recently reviewed the safety of intranasal steroids and concluded that they are not associated with systemic side effects such as hypophyseal pituitary axis (HPA) axis suppression and linear growth, in addition to local side effects.

Intranasal corticosteroid injection The submucosal injection of a repository corticosteroid at the anterior tip of the inferior turbinates results in a slow uptake of the material with spreading to the adjacent nasal mucosa, offering symptomatic relief of allergic rhinitis (and other forms of rhinitis) that begins within a few hours and persists for 4 to 6 weeks. The slow absorption of the injected steroid does not generally result in suppression of endogenous cortisol production, indicating that the effect is local rather than systemic [37]. A review in 1981 of all published and available unpublished data on visual loss following intranasal steroid injection indicated that the mechanism involved was either retinal vasospasm or embolization of the injected material into the retinal circulation through collateral channels from the nose to the eye [38]. Suggestions for preventing such complications included preparation of the nasal mucosa by applying a topical vasoconstrictor/anesthetic solution, use of a

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fine needle for injection, avoidance of steroid preparations with large particle size and high viscosity, placement of the injection just beneath the mucosa in the anterior tip of the inferior turbinate (as far away from retinal collaterals as possible), and use of a very gentle technique during injection. Following these guidelines, one of the authors has performed more than 20,000 such injections over almost 30 years, with no visual complications [39]. The results of an intraturbinal corticosteroid injection are usually noted within a few hours of the injection, and if triamcinolone acetonide has been injected, they last for 4 to 6 weeks. This procedure is extremely helpful for symptom relief in patients with severe nasal allergic symptoms limited to a single season. If several injections per year are necessary, the patient is probably a candidate for maintenance therapy with topical steroids.

apparent efficacy, no clear guidelines exist in the literature regarding the use of antibiotics in aesthetic surgery [44]. A frequently cited reason for the use of antibiotics in septorhinoplasty is the use of intranasal splints and the fear stemming from reports of Toxic Shock Syndrome following septorhinoplasty.

Treatment strategies Because of the prevalence of allergic rhinitis and its contributory effect on other inflammatory sinonasal disease processes, adequate control of symptoms should precede surgical intervention. Optimizing the patients allergic symptoms before surgery will improve patient satisfaction in the postoperative period. Patients with allergic rhinitis are not a homogeneous group, and each requires individual consideration in the choice of a pharmacotherapeutic treatment regimen to maximize symptomatic relief. Combining the individual attributes of each class of medication and matching these attributes to the individual patient will help achieve this goal. This matching can be done by recognizing some rather general features of the patients allergic history. Those features that help differentiate patients include quality of symptoms (irritative symptoms versus congestion), degree of predictability of the allergen exposure (eg, predictable intermittent, nonpredictable intermittent, prolonged seasonal, or prolonged perennial), and the degree of inflammation (perhaps most important in the case of prolonged exposure to an antigen). Adherence to such a strategy will decrease the tendency to use medications to address inappropriate symptoms as well as decrease duplication of medications within a class. The patient with allergic rhinitis does not typically achieve relief of all symptoms with the use of a single medication. Antihistamines relieve the irritative symptoms (itching, sneezing, and rhinorrhea) that typify this disorder and have the added benefit of being rapid in their onset of action. As a result, a second- or third-generation antihistamine may be used either to treat prophylactically or as a rescue medication to relieve symptoms after their onset. It is important to recognize that antihistamines fail effectively to address congestion. Decongestants are necessary to relieve nasal stuffiness. Often these treatments are combined, and although the use of individual antihistamines and decongestants allows the patient more leeway in treating individual symptoms as they occur, the use of a single tablet or capsule once or twice daily is appealing to

Systemic steroids Systemic steroids are often used perioperatively for control of edema. For rhinoplasty patients, some advocate the use of systemic steroids to reduce postoperative edema [40]. Additionally, corticosteroids are an important means of treating various types of rhinosinusitis, and they are often used perioperatively for surgical treatment of AFS and CRS. However, when administered systemically, they possess a potential for significant adverse effects. Pharmacologic doses of systemic corticosteroids may suppress endogenous cortisol production. After the administration of 20 mg to 30 mg of prednisone or the equivalent for 1 week, an additional week is required for adrenal recovery; after prolonged highdose therapy, 1 year may be required for recovery of function [41].

Antibiotics The role of antibiotics has been firmly established for the treatment of rhinosinusitis. Their use in surgery, however, remains a point of controversy. Randomized controlled trials have shown that prophylactic antibiotics are effective in preventing certain surgical wound infections. Classen et al [42] found that the prophylactic administration of antibiotics in the preoperative period was associated with the lowest risk of surgical wound infections. Antibiotics are frequently used in rhinoplasty. Lyle [43] reports a 200% increase in the use of perioperative antibiotics in rhinoplasty between 1985 and 2000. Despite their widespread use and

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many patients as a matter of convenience (it also requires no clinical judgments on their part). Nasal corticosteroids have become the mainstay of treatment of patients with more severe or chronic nasal allergic symptoms. In comparisons of the effectiveness of antihistamines versus nasal steroids versus both drugs in combination, nasal steroids were more effective than antihistamines in relieving most allergy symptoms, and combined therapy was even more effective. When patients have severe or chronic symptoms that necessitate medication on a daily basis, it is appropriate to switch to the use of a nasal steroid. The steroid should be used daily throughout the expected season of allergen exposure, with antihistamines or decongestants relegated to a role of augmentation as as-needed medications. Furthermore, the effectiveness of nasal corticosteroids is optimized by use in a regular fashion over a period of up to several weeks. Conversely, nasal corticosteroids, when compared with antihistamines, are a less appropriate rescue choice to arrest symptoms after their onset. Patients with mild symptoms may require little more than the use of a mast cell stabilizer, such as cromolyn, before an anticipated allergen exposure. These medications are most useful when employed preemptively in the management of allergic rhinitis. Conversely, the effect of mast cell stabilizers is diminished when initial use follows the onset of an allergic reaction. Moreover, the reactive use of this class of medication fails to address the issue of congestion. In situations where rhinorrhea does not respond to either nasal steroids or topical ipratropium, a combination of the two may be effective. The patient should be maintained on a nasal corticosteroid in the usual dosage, adding ipratropium daily with the usual morning dose and supplemental doses of ipratropium once or twice later in the day as needed. The same approach may be used in patients whose rhinorrhea is only partially relieved with antihistamines and who (for whatever reason) are not candidates for nasal steroid therapy.

cesses may warrant an otolaryngologic evaluation before proceeding with surgery. A thorough medical history and examination elucidate sinonasal disease conditions that may not improve after septorhinoplasty but potentially could respond to pharmacologic therapy.

References
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Summary Rhinoplasty surgeons inevitably encounter therapeutic considerations in managing their patients, and a thorough understanding of nasal function, as well as of disorders of the nose and sinuses, is requisite for positive clinical outcomes. Patients suffering from allergic rhinitis are not precluded from undergoing rhinoplasty, whereas other disease pro-

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