2003, Vol.36, Issues 3, Surgery for Sleep Apnea

Otolaryngol Clin N Am 36 (2003) xi–xii

Preface

Sleep-disordered breathing

David J. Terris, MD, FACS Guest Editor

Many significant advances have been made in the evaluation and treatment of sleep-disordered breathing over the past several years. In addition to the advent of radiofrequency-ablative techniques, progress continues to be made in electrical stimulation of upper airway dilators. Of equal importance has been the gradual adjudication of the role of various techniques that otolaryngologists have at their disposal. This issue of The Otolaryngologic Clinics of North America emphasizes this last point, with reassessments of previously described interventions that have found their place in treatment algorithms. A fresh look at the management of pediatric sleep apnea is included, as is a comprehensive review of the available literature concerning gender differences as they relate to the severity and surgical prognosis of sleep apnea. Finally, because otolaryngologists continue to maintain a substantial amount of responsibility for the care of patients with sleep disorders, a significant segment of this issue is devoted to the physiology of sleep-disordered breathing and the physiologic impact of sleep apnea syndromes. Further insight about the management of sleep disorders will require prospective randomized trials (which are beginning to emerge) and thoughtful

0030-6665/03/$ - see front matter Ó 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00173-1

xii

D.J. Terris / Otolaryngol Clin N Am 36 (2003) xi–xii

failure analysis. Outcome researchers will have an important part to play in the future development of this field. David J. Terris, MD, FACS Porubsky Professor and Chairman Department of Otolaryngology–Head and Neck Surgery Medical College of Georgia 1120 Fifteenth Street Augusta, GA 30912-4060, USA E-mail address: [email protected]

Otolaryngol Clin N Am 36 (2003) 409–421

Upper airway physiology and obstructive sleep-disordered breathing Chris Yang, MD, B. Tucker Woodson, MD* Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA

The surgical management of obstructive sleep-disordered breathing (OSDB) is evolving rapidly. With advances in areas of diagnostic and surgical instrumentation, the technology available for surgical treatment of obstructive sleep apnea has never been better. Yet our knowledge of anatomic and physiologic determinants of the upper airway remains inadequate. As a result, our ability to precisely evaluate the airway and our understanding of the effect and mechanisms of pharyngeal surgery remain muddled, inaccurate, and imprecise. The results are too often that surgical outcomes are disappointing for OSDB [1]. The need for future advances in this field dictates a more thorough understanding of this disease process. This article reviews the current concepts of the pathophysiology of OSDB, with special emphasis on anatomic and physiologic factors that lead to upper airway compromise. Background Obstructive sleep-disordered breathing includes obstructive sleep apnea (OSA) and obstructive sleep apnea syndrome (OSAS), which are common disorders that result from upper airway obstruction during sleep. Obstructive sleep apnea is defined by a polysomnogram finding that demonstrates obstruction of the upper airway during sleep. Obstructive sleep apnea syndrome is well recognized and requires both OSA with greater than five obstructive ventilatory events per hour and presence of clinical symptoms. Increasingly, OSA even without apparent clinical symptoms is considered potentially pathologic, but the threshold for determining what constitutes

* Corresponding author. E-mail address: [email protected] (B.T. Woodson). Dr. Woodson is a member of the Medical Advisory Board for Resmed Inc. He has received research support from Gyrus ENT and Influ-ENT. 0030-6665/03/$ - see front matter Ó 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(03)00017-3

410

C. Yang, B.T. Woodson / Otolaryngol Clin N Am 36 (2003) 409–421

an abnormal amount of obstructive ventilatory events has not been identified [2]. Current thought considers a respiratory distress index of greater than 15 as the minimal threshold of disease when symptoms are absent. But such classifications may prove inadequate, because the scope of the pathophysiology of OSDB involves not only airway obstruction but also the consequences arising from arousals, sleep fragmentation, and other factors that result in the varied clinical picture of this disease process. The clinical sequelae of OSDB include hypersomnolence, psychophysiologic dysfunction, cardiovascular morbidity, and snoring. In OSDB, however, the defining event is airway obstruction during sleep, and therefore it is critical to enhance our understanding of upper airway collapse such that superior reconstructive techniques can be developed. Current evidence supports the axiom that abnormal upper airway structure is likely the fundamental abnormality in OSDB [3,4]. In children, this abnormality is most often the result of adenotonsillar hypertrophy. No single structural abnormality has been identified in adults with this disorder, however, and the presence of multiple anatomic and physiologic abnormalities is common [5]. Individually, these abnormalities often are considered disproportionate and not pathologic [6]. Anatomic abnormalities remain the central component in the development of OSDB. Additional interactions between abnormal anatomy and normal or pathologic variables, including ventilatory, neurologic, and other factors, contribute to further compromise an inherently vulnerable upper airway [7]. For instance, subjects with OSDB consistently demonstrate an anatomically small upper airway that is at an increased risk of collapse when a loss of physiologic muscle tone occurs during sleep. The combination of various other static and dynamic forces ultimately determines ability to maintain an adequate upper airway [8].

Static and dynamic forces It is easy when conceptualizing the upper airway to oversimplify complex interactions. Dividing various forces into static and dynamic components helps in better conceptualizing various determinants of airway size. Static determinants of airway size can be thought of as the intrinsic pharyngeal area as determined by craniofacial framework and upper airway soft tissue mass. Dynamic forces include phasic neuromuscular tone and dynamic airflow. Each of these forces has additional levels of controls, complexity, physiology, and pathology, some of which are yet to be described adequately. Known abnormal static features that increase risks of obstruction include smaller maximal upper airway, increased compliance as the airway decreases in size, more positive closing pressures, and increased airway length [3,9,10]. These abnormal static characteristics result in an abnormally collapsible airway when exposed to conditions of dynamic flow. The mechanics of upper airway collapse may be described using both a static model that evaluates


411

changes independent of airflow and a dynamic model that includes the effects of negative inspiratory pressure and airflow [7,11]. Classically, collapse of the upper airway has been thought to occur during inspiration, when negative inspiratory pressure and airflow predominate; however, collapse is not limited to inspiration and also occurs during expiration (Fig. 1) [12]. The critical event actually may occur when passive expiratory collapse or static characteristics predominate.

Sites of upper airway collapse Upper airway collapse during sleep is common and universal in human beings. The phenomenon of OSDB is almost unheard of in any other species. Humans possess a supralaryngeal and pharyngeal airway that is not completely supported by a skeletal or cartilaginous framework. This soft tissue supralaryngeal airway presumably is associated with inferior descent of the larynx in conjunction with the development of speech [13]. Cross-sectional size of this soft tissue conduit is determined by a combination of anatomic structures and by pharyngeal dilator muscle activity (Fig. 2). Variable sites of narrowing occur in the upper airway in OSDB and snoring [14]. Maxillary abnormalities have been implicated increasingly [5,15]. The fact that the

Fig. 1. Phasic fluctuation and cross-sectional airway size are depicted during a single respiratory cycle. At the onset of inspiration (1), airway size increases with activation of inspiratory dilator muscles. Dilatation is countered by negative intraluminal pressures during midinspiration (*). During expiration (2), positive expiratory pressure combined with the effects of phasic muscular contraction and loss of negative intraluminal pressure results in rapid dilation of the upper airway. During midexpiration (**), loss of muscle tone predominates and significant airway collapse occurs. The smallest airway size occurs at end expiration. At this point, if the airway size is critically small, dynamic inspiratory airway forces may result in airflow limitation or complete airway collapse.

412


Fig. 2. The observed size of the upper airway at any moment is a function of multiple interacting variables. The most important variables are structure, muscle tone, airflow, and intraluminal pressure. If muscle tone, airflow, and pressures are controlled, then the observed size approximates actual airway structure.

maxilla is a major contributor to OSDB is no surprise, given the focal role that maxillary development plays in facial growth and development. Other craniofacial abnormalities include decreased mandibular projection, downward and posterior rotation of facial development, increased vertical length of the upper airway, and increased cervical angulation [16,17]. Soft tissue abnormalities include increased tongue size, excessive palatal length, increased lateral wall thickness, enlarged tonsils, increased nasal resistance, rhinitis, and an increased mandibular plane-to-hyoid distance [18–20]. The final common denominator of these structural abnormalities is a smaller and more collapsible cross-sectional airway size [21]. Upper airway shape Upper airway shape is critical in determining airflow and in determining the function of upper airway muscles. Cross-sectional area is critical in determining upper airway resistance [22]. Absolute cross-sectional airway size has only correlated weakly to apnea severity as measured by respiratory distress index, however. Part of this discrepancy is explained by shape differences among individuals. Individuals with OSA tend to have more elliptically shaped upper airways than nonapneic individuals [23]. Apnea is more severe when airways are elliptically shaped, with the long axis in the midsagittal plane. The elliptical shape increases the surface area of the airway and frictional resistance compared with a more circular conduit. Additionally, an airway with a long axis in an anterior posterior direction (in the midsagittal plane) is less affected by contraction of major airway dilators such as the genioglossus muscle. Body and jaw position Body position also has major effects on airway size in patients with snoring and OSA. Several mechanisms, including tissue mass and tracheal


413

tug, may be involved and may contribute to the changes observed [24]. Tissue mass is a major force contributing to collapsing forces to the airway. Because mass and compliance of various structures surrounding the airway differ, it is likely that changing position affects different areas of the airway in different ways. Studies directed at identifying the effects of gravity in nonapneic subjects have demonstrated that the lower pharynx and retroepiglottic airway are affected more than the upper pharynx [25]. In apneic subjects, the isolated effects of gravity have not been evaluated. It is speculated that in apneics with a more unstable upper airway, gravity may contribute to obstruction in multiple segments, depending on the mass of the tissues involved. The upper airway may have marked changes going from the sitting position to the supine position. Similarly, the lateral body position provides a more stable upper airway configuration than the supine position. The mechanism of this effect has not been demonstrated yet but likely includes effects of gravity and reflex effects. Reflex effects should not be dismissed. It is well established that the lateral body position has significant effects on the nasal cycle. The idea that body position has reflex effects on the pharynx is also plausible and may warrant further research.

Nasal pathologic conditions Evaluation of a patent nasal airway is critical in treatment of OSAS. Nasal pathologic conditions may contribute to OSA and pharyngeal collapse in several ways. Nasal obstruction and mouth breathing cause (1) reduction in nasal reflexes, which are important in maintaining muscular tone; (2) jaw opening, with backward rotation of the jaw and inferior displacement of the hyoid, resulting in worsening of pharyngeal collapse; and (3) increase in ‘‘upstream’’ airflow resistance. Upstream airway resistance increases ‘‘downstream’’ collapse. Nasal resistance and obstruction may result from abnormalities of the maxilla and the posterior maxillary airspace [20]. Treatment of nasal obstruction, however, does not alter nasal continuous positive airway pressures [26].

Neuromuscular tone Neuromuscular tone influencing dilation of the upper airway is under complex regulation. Physiologic changes in tone occur phasically with the respiratory cycle and sleep-wake state transitions. During expiration, dilating upper airway muscle tone diminishes, which results in partial upper airway collapse in normal individuals [27]. Yet in nonapneic, anatomically ‘‘normal’’ individuals with minimal static collapse, the phasic loss of upper airway muscle tone during expiration and the loss of muscle tone during sleep are not sufficient to cause significant flow limitation, in contrast to individuals with severely abnormal upper airway anatomy. In this group,

414


static collapse is greater. Combined with further loss of phasic muscle tone occurring during expiration and decreased muscle tone during sleep, abnormal airway anatomy results in complete upper airway obstruction at end expiration [28]. Inspiration then occurs with an already obstructed airway. In individuals with a less abnormal upper airway, static collapse of the upper airway in conjunction with loss of muscle tone can result in significant collapse that exceeds minimal protective threshold at end expiration. Dynamic collapse during inspiration then results in further closure and obstruction. In both groups with OSDB, obstructive events such as these episodes do not occur during wakefulness. The primary reason is that these patients demonstrate augmented motor activity during wakefulness that serves a protective function to prevent airflow limitation [29]. This increased activity is presumably to compensate for a structurally small upper airway. The etiology of this augmented upper muscle activity is yet to be determined, although evidence suggests that upper airway mechanoreceptors (particularly located at the level of the epiglottis) sensitive to negative airway pressure are involved. Because airway patency requires augmented motor activity, greater loss of muscle tone occurs during sleep, resulting in increased ventilatory resistance leading to airflow limitation and increased work of breathing. The resultant decreased airflow results in asphyxia, whereas increased work of breathing and mechanoreceptor stimulation result in CNS arousal and sleep fragmentation. This increased muscle tone activity associated with increases in airway size during wakefulness explains the lack of differences in airway resistance and compliance that is measured in subjects with OSA compared with normal subjects. Part of this increased tonic activity is reflex-mediated.

Other effects of sleep on the upper airway Both rapid-eye-movement (REM) and non-REM sleep are associated with multiple physiologic changes compared with wakefulness. Regarding ventilation, the onset of sleep alters the CNS’ response to hypoventilation, leading to both hypoxia and hypercarbia. Hypoxic ventilatory drive is reduced in non-REM and markedly decreased in REM sleep. Hypercapneic drive also is reduced in non-REM and REM sleep [30]. During non-REM sleep, ventilation is controlled primarily by chemical mechanisms (primarily carbon dioxide). With the onset of fragmented non-REM sleep and wakefulness, significant changes in ventilation occur. The mechanisms are complex and involve oscillations in chemical control of ventilation during sleep combined with changes in carbon dioxide due to upper airway collapse [31]. Arousals and brief awakenings serve to rapidly increase carbon dioxide sensitivity. Ventilatory overshoots occur that then may be followed by ventilatory undershoots. Ventilatory undershoots result in decreased ventilatory drive. The consequence of decreased ventilatory


415

drive is decreased activity of muscles that are tightly linked to respiratory neuronal activity, such as the diaphragm. In general, the upper airway muscles are less tightly linked to ventilatory drive and thus small changes in ventilatory drive may have major effects on their activity. In nonapneic individuals, the consequence of decreased ventilatory drive may be central apneas or central hypopneas, but in patients in whom upper airway muscle drive is crucial in maintaining airway size, even a small loss of upper airway drive may result in airway obstruction. Mechanoreceptor-mediated increases in upper airway muscle tone have been noted to be critical in maintaining upper airway patency in patients with OSDB. Mechanoreceptors are known to serve a role in reflex-mediated compensatory pharyngeal dilator muscle activity when exposed to collapsing negative inspiratory forces [32]. Their importance is greater in patients with OSDB than in normal patients because they must compensate for their poor anatomy. This finding has been demonstrated in laboratory-based studies that show both peak and phasic genioglossus electromyography EMG activity is significantly higher in patients with OSDB compared with normal control patients during wakefulness. The stimulatory effect of negative inspiratory pressure can be ameliorated when continuous positive airway pressure is applied. And when continuous positive airway pressure is applied to patients with OSDB during wakefulness, there is a marked decrease in genioglossus EMG activity, whereas normal subjects display essentially no change [33]. Waking muscle tone decreases after application of topical oropharyngeal anesthesia [34]. The importance of these receptors during sleep is demonstrated by the worsening of obstruction in snorers who have oropharyngeal topical anesthesia during sleep, which suggests that mechanoreceptor-mediated neuromuscular compensation reflexes may be critical in subjects with OSDB but not necessarily in normal subjects. Reopening of the upper airway during obstructive events is associated with an increase in upper airway muscle tone to levels above baseline activity. This increase requires arousal, awakenings, and change in sleep state. As work of breathing increases as a result of increased hypercapneic ventilatory drive, increased mechanoreceptor stimulation occurs as apnea progresses. Increased mechanoreceptor stimulation results in arousal, activation of upper airway muscles, and reopening of the upper airway. Hence, it is mechanoreceptor stimulation that is the primary mediator of cortical arousal and changes in sleep state. Mechanoreceptors also may work to increase the work of breathing in response to ventilatory loads or obstruction. In apneics, ventilatory load detection is impaired. The etiology of this impairment is still under debate, but increasingly, abnormalities of the upper airway reflex mediators are implicated [35]. Some of these abnormalities may be acquired and include evidence of decreases in pharyngeal sensitivity and evidence of pharyngeal nerve damage. These abnormalities are speculated as possibly resulting from the vibratory trauma of snoring [36]. Histopathologic studies have

416


demonstrated evidence of both muscle-bundle hypertrophy and muscle-fiber degeneration and damage. The cause of these changes may include eccentric contraction during stretch and from motor neuron damage. Lengthening or stretching during muscular contraction (eccentric contraction) results in muscle-fiber damage and hypertrophy. Immunohistopathologic changes in muscle-fiber types are also consistent with muscle denervation and reinervation. Electron microscopy and other studies have demonstrated motorneuron damage in OSA. The ultimate result is both muscle hypertrophy that may impinge on airway size and impairment of muscle elastance and strength of contraction.

Balance of forces and Starling resistor The multitude of anatomic and physiologic processes so far described only begins to touch on the true complexity of the upper airway. Integrating these and other factors into a manageable concept is difficult. One method that allows this integration is the concept of ‘‘balance of forces.’’ Dynamic upper airway collapse may be understood further by applying the concepts of the ‘‘Starling resistor,’’ which describes flow in collapsible tubes. Balance-of-forces model At any instant in time, upper airway size is determined by the combined contributions of multiple structural and physiologic variables. The balanceof-forces model allows an accurate description of how multiple variables alter upper airway size (Fig. 3). Airway size is determined by both dilating and collapsing forces. Dilating forces include upper airway muscle tone, mechanical force of the airway wall structure, and positive intraluminal airway pressure. Collapsing forces include tissue mass, surface adhesive forces, and negative intraluminal pressures. The resulting difference in these forces is the distending force, which acts on the wall of the upper airway. When the distending force increases, the airway size increases; when it decreases, the airway size decreases. The distending force of the upper airway is the transmural pressure (Ptm) of the airway. The equation Ptm ¼ Pout Pin defines transmural pressure, where Pout represents the sum of the dilating upper airway forces and Pin represents the sum of the collapsing forces. Another more clinically relevant means to conceive of the forces that act on the upper airway is by considering the skeletal airway structure as a constant and describing the dynamic forces as being either tissue pressures or luminal pressures (Ptm ¼ Ptissue Pluminal). Tissue pressure includes the forces from tissue mass, tissue elastance, surface tension, and neuromuscular dilating and collapsing forces. Luminal pressures include the segmental airway pressure (Pairway) and pressures relating to airflow (Pflow). As noted, airway pressures may be dilating (if positive, such as with expiration or with the application


417

Fig. 3. The balance-of-forces model. Transmural pressure (Ptm) is the force that determines the size of the airway wall. This force is determined by dilating pressures (Pout) and collapsing pressures (Pin). Transmural pressure of the airway wall also can be described as the difference between tissue pressures and intraluminal pressures (see text for details).

of external positive airway pressures) or collapsing (such as during inspiration). Studies have been able to replicate a syndrome identical to OSAS in non-OSA subjects by applying negative pressures to the upper airway during sleep. Although seemingly esoteric, such a model (Ptm ¼ Pluminal Ptissue) provides a means of quantifying upper airway collapse. The compliance (dA/dP) of the upper airway represents the tendency of the upper airway to collapse during respiration. Airway compliance can be calculated, allowing measurement of the intrinsic collapsibility of the upper airway. The effects of airflow on decreasing luminal pressures are determined by its velocity and are described by Bernoulli’s equation. If airflow velocity is zero, then (Pluminal ¼ Pairway þ 0), and if neuromuscular tone is held constant (Ptissue ¼ k), then measured airway pressure represents the distending or transmural pressure of the upper airway (Ptm ¼ Pairway k). This measured pressure, combined with measures of upper airway size, allows calculation of airway compliance (dA/dP) independent of physiologic influences. Airway pressure can be measured and manipulated (such as with nasal continuous positive airway pressure) to assess changes in airway size and compliance. Starling resistor The Starling resistor concept describes flow in collapsible tubes, which serves as an ideal model for the upper airway (Fig. 4). In the human upper airway, the collapsible tube is the supraglottis and pharynx. Upstream

418


Fig. 4. Properties of a Starling resistor. Two rigid tubes are separated by a collapsible segment. The collapsible tube lies within a bucket (baseline). Water can be placed to increase Pout (no flow). In baseline, Pin is greater than Pout, and the collapsible segment is patent. Unobstructed flow (flow, lower left) occurs when Pin is greater than Pout and Pus is greater than Pcrit. In no flow (upper right), water fills the bucket, Pout is greater than Pin (the collapsible tube is obstructed), Pus is less than Pcrit, and there is no airflow. Increasing Pus dilates the segment; when this event occurs, flow will resume. In flutter (lower right), Pus is greater than Pcrit, and flow must occur; however, Pdownstream is increased (as occurs with increased upper airway resistance during sleep). The orifice (*) is exposed to a negative inspiratory pressure (NIP) (Pdownstream < Pcrit), and collapse of this segment occurs. With flow cessation, however, pressure rapidly rises to Pus, and the orifice opens. The orifice now is exposed to Pdownstream and Bernoulli forces, and collapse occurs. A cycle of rapid opening and closing (flutter) occurs.

pressure is ambient pressure and downstream pressure is pleural pressure. During wakefulness, low negative pleural pressures (ie, 5 cm H2O) combined with a large upper airway (the result of multiple balance of forces) result in unimpeded flow. During sleep, changes occur in the balance of forces, and distinct clinical populations occur. In nonapneic, nonsnoring patients, a structurally larger upper airway remains patent. In snorers and apneic subjects, a structurally small upper airway results in a cascade of pathologic events. The Starling resistor concept builds on Poiseuille’s law, which describes flow in noncollapsible tubes. Poiseuille’s law states V ¼ P1 P2/R, where V ¼ flow, P1 ¼ pressure upstream, and P2 ¼ pressure downstream. The resistance component (R) is determined by length of the tube (L), fluid viscosity (g), and the radius (r) of the tube (R ¼ resistance ¼ 8gL/pr4. Because viscosity and length are constant, changes in resistance are


419

primarily related to changes in the area of the tube. Because area is unchanged in a rigid tube, flow in a noncollapsible airway depends significantly on pressure across the tube (P1 P2 ¼ driving pressure). This type of flow contrasts to a collapsible, Starling resistor airway in which flow may be independent of driving pressure. In a Starling resistor, resistance is variable, and resistance and flow are determined primarily by airway size. Airway size is determined by the surrounding forces that act on the airway. In a simple collapsible tube (ie, a tube with a wall without intrinsic structural forces that often is modeled with a penrose drain placed between two rigid tubes) the airway size-determinant forces are primarily the upstream and downstream airway pressures and flow. Three basic clinical patterns can be observed, which include normal breathing, snoring, and obstruction. Likewise, three possible conditions of flow across a collapsible upper airway exist and may include unimpeded flow, flutter, and obstruction. These three conditions are determined by the balance of three groups of pressures exerted on the upper airway. These conditions are the downstream pressure (Pds or negative inspiratory pressure), upstream pressure (Pus or ambient pressure), and the transmural pressure (Ptm). For the condition of unimpeded flow, transmural pressure is greater than both downstream and upstream pressures (Ptm > Pus > Pds). Because transmural pressure is greater than other pressures, airway collapse does not occur, and airway size and resistance are not altered, which contrasts with the condition of obstruction in which transmural pressures are less than both downstream and upstream pressures (Pus > Pds > Ptm). With a negative transmural pressure, airway size is zero and no flow occurs. When transmural pressure is less than upstream pressure but greater than downstream pressures (Pus > Ptm > Pds), the condition of flutter occurs. A choke point or narrowing of the airway occurs in the segment of the collapsible upper airway that is exposed to negative transmural pressure. In this segment, airway size decreases (in an ideal Starling resistor, the resultant airway size is zero). When the airway is closed, there is no flow, and the segment becomes exposed to upstream pressure, which dilates the upper airway. When flow occurs, however, this segment is exposed again to downstream pressure, which acts to collapse this segment. Repeating this cycle results in the choke point being exposed to alternating upstream or downstream pressures, depending on the presence of flow in the airway. The result is flutter. Because of these characteristics, flow in a collapsible tube in patients at risk for OSA is not determined by the difference between upstream and downstream pressures (driving pressure), but rather by the difference between upstream pressures and the pressures surrounding the collapsible segment. In a structurally patent airway, the pressure difference across the collapsible tube wall is of minimal importance; however, in an airway that is more vulnerable to collapse, these forces may become a major determinate of airway cross-sectional area and therefore resistance to airflow.

420


Summary Upper airway competence involves complex interactions between anatomy and physiology. The common final denominator of OSDB is a structurally small and abnormally collapsible upper airway. The mechanisms contributing are often an accumulation of many skeletal or soft tissue abnormalities and respiratory physiology that individually may or may not be pathologic. So far, simplistic models have hampered progress in this field. Successful medical and surgical treatment of OSDB continues to be elusive for too many patients. Great strides remain to be taken, but the possibility seems within reach.

References [1] Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications for the upper airway in adults with obstructive sleep apnea syndrome. Sleep 1996;19:156–77. [2] Shahar E, Whitney C, Redline S, Lee E. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Healthy Study. Am J Respir Crit Care Med 2001;163:19–25. [3] Isono S, Remmers JE, Tanaka A, et al. Anatomy of the pharynx in patients with obstructive sleep apnea and in normal subjects. J Appl Physiol 1997;82:1319–26. [4] Isono S, Remmers JE. Anatomy and physiology of upper airway obstruction. In: Kryger MH, Roth T, Dement WC, editors. Principles and practice of sleep medicine. 2nd edition. Philadelphia: WB Saunders; 1994. p. 642–56. [5] Dempsy JA, Skatrud JB, Jacques AJ, Ewanowski SJ, Woodson T, Hanson PR, et al. Anatomical determinates of sleep disordered breathing across the spectrum of clinical and non-clinical subjects. Chest 2002;122:840–51. [6] Rivlin J, Hoffstein V, Kalbfleisch J, et al. Upper airway morphology in patients with idiopathic obstructive sleep apnea. Am Rev Respir Dis 1984;129:355–60. [7] Redline S, Tishler PV, Hans MG, et al. Differences in sleep disordered breathing in African Americans and Caucasians. Am J Respir Crit Care Med 1997;155:186–92. [8] Tuck S, Remmers J. Mechanical properties of the passive pharynx in Vietnamese potbellied pigs. II. Dynamics. J Appl Physiol 2002;92:2236–44. [9] Gleadhill IC, Schwartz AR, Schubert N, et al. Upper airway collapsibility in snorers and in patients with obstructive hypopnea and apnea. Am Rev Respir Dis 1991;143:1300–3. [10] Pae EK, Lowe AA, Fleetham JA. A role of pharyngeal length in obstructive sleep apnea patients. Am J Orthod Dentofac Orthop 1997;111:12–7. [11] Isono S, Feroah TR, Hajduk EA, Brant R, Whitelaw WA, Remmers JE. Interaction of cross-sectional area, driving pressure, and airflow of passive velopharynx. J Appl Physiol 1997;83:851–9. [12] Sanders MH, Moore SE. Inspiratory and expiratory partitioning of airway resistance during sleep in patients with sleep apnea. Am Rev Respir Dis 1983;127:554–8. [13] Lieberman DE, McCarthy RC. The ontogeny of cranial base angulation in humans and chimpanzees and its implications for reconstructing pharyngeal dimensions. J Human Evolution 1999;36:487–517. [14] Morrison DL, Launois SH, Isono S, et al. Pharyngeal narrowing and closing pressures in patients with obstructive sleep apnea. Am Rev Respir Dis 1993;148:606–11. [15] Cistulli P, Sullivan C. Influence of maxillary morphology on nasal airway resistance in Marfan’s Syndrome. Acta Otolaryngol 2000;120:410–3. [16] Lyberg T, Krogstad O, Djupesland G. Cephalometric analysis in patients with obstructive sleep apnea syndrome: skeletal morphology. J Laryngol Otol 1989;103:287–92.


421

[17] Pracharktam N, Hans MG, Strohl KP, et al. Upright and supine cephalometric evaluation of obstructive sleep apnea syndrome and snoring subjects. Angle Orthod 1994;64:63–74. [18] Lyberg T, Krogstad O, Djupesland G. Cephalometric analysis in patients with obstructive sleep apnoea syndrome: soft tissue morphology. J Laryngol Otol 1989;103:293–7. [19] Young T, Finn L, Kim H. Nasal obstruction as a risk factor for sleep-disordered breathing. Allergy Clin Immunol 1997;99:757–62. [20] Schwab RJ, Gupta KB, Gefter WB, Metzger LJ, Hoffman EA, Pack AI. Upper airway and soft tissue anatomy in normal subjects and patients with sleep-disordered breathing: significance of the lateral pharyngeal walls. Am J Respir Crit Care Med 1995;152:1673–89. [21] Galvin JR, Rooholamini SA, Standford W. Obstructive sleep apnea: diagnosis with ultrafast CT. Radiology 1989;171:775–8. [22] Leiter JC. Upper airway shape: is it important in the pathogenesis of obstructive sleep apnea? Am J Respir Crit Care Med 1996;153:894–8. [23] Rodenstein DO, Dooms G, Thomas Y, Liistro G, Stanesco DC, Culle C, Aubert-Tulkens G. Pharyngeal shape and dimensions in healthy subjects, snorers, and patients with obstructive sleep apnoea. Thorax 1990;45:723–7. [24] Rowley JA, Permutt S, Willey S, et al. Effect of tracheal and tongue displacement on upper airway airflow dynamics. J Appl Physiol 1996;80:2171–8. [25] Fogel R, Malhotra A, Pillar G, et al. Genioglossal activation in patients with obstructive sleep apnea versus control subjects—mechanisms of muscle control. Am J Respir Crit Care Med 2001;164:2025–30. [26] Schechter G, Ware J, Perlstrom J, McBrayer R. Nasal patency and the effectiveness of nasal continuous positive air pressure in obstructive sleep apnea. Otolaryngol Head Neck Surg 1998;118:643–7. [27] Badr SM, Dawak A, Skatrud JB, Morrell MJ, Zahn BR, Babcock MA. Effect of induced hypocapnic hypopnea on upper airway patency in humans during NREM sleep. Respir Physiol 1997;110:33–45. [28] Morrell MJ, Arabi Y, Zahn B, Badr MS. Progressive retropalatal narrowing preceding obstructive apnea. Am J Respir Crit Care Med 1998;158:1974–81. [29] Mezzanote WS, Tangle DJ, White DP. Influence of sleep onset on upper-airway muscle activity in apnea patients versus normal controls. Am Rev Respir Crit Care Med 1996; 153:1880–7. [30] Henke K, Badr M, Skatrud J, Dempsey J. Load compensation and respiratory muscle function during sleep. J Appl Physiol 1992;72:1221–34. [31] Dempsey J, Smith C, Harms C, Chow C, Saupe K. Sleep and breathing state of the art review: sleep-induced breathing instability. Sleep 1996;19:236–47. [32] Nishino T. Physiological and pathophysiological implications of upper airway reflexes in humans. Jpn J Physiol 2000;50:3–14. [33] Deegan PC, Nolan P, Carey M, McNicholas WT. Effects of positive airway pressure on upper airway dilator muscle activity and ventilatory timing. J Appl Physiol 1996;81:470–9. [34] Liistro G, Stanescu D, Veriter C, Rodenstein D, D’Odemont J. Upper airway anesthesia induces airflow limitation in awake humans. Am Rev Respir Dis 1992;146:581–5. [35] Kimmoff RJ, Sforza E, Champagne V, Ofiara L, Gendron D. Upper airway sensation in snoring and obstructive sleep apnea. Am J Respir Crit Care Med 2001;164:250–5. [36] Woodson BT, Garancis JC, Toohill RJ. Histopathologic changes in snoring and obstructive sleep apnea syndrome. Laryngoscope 1991;1010:1318–22.


The physiologic impact of sleep apnea on wakefulness Yau Hong Goh, FRCS, FAMS (ORL)a,* Kheng Ann Lim, FDSRCS, FAMS (OMS)b a

Department of Otolaryngology, Sleep Disorders Unit, Singapore General Hospital, Outram Road, Singapore 169608 b Department of Oral Maxillofacial Surgery, National Dental Centre, 5 Second Hospital Avenue, Singapore 168938

Sleep is a transient state of altered consciousness and perceptual disengagement from one’s environment. Unlike coma, it is an active process involving a host of complex interactions among many cortical, brain stem, diencephalic, and forebrain structures. During this ‘‘rest’’ state, the cerebral metabolism and oxygen consumption within the brain remain significant. Any pathologic condition that interferes with this intriguing cerebral event during sleep therefore disrupts the proper execution of this necessary and vital state of existence. Although the function of sleep is controversial and largely unknown, one observation is evident—that good sleep is critical to a well-functioning awake state. The phenomenon of sleep is associated with profound physiologic alterations. Under normal circumstances, these physiologic changes in the various human systemic functions during sleep occur without any serious consequences. In pathologic states, however, changes that ensue in any of the systemic functions may present serious physiologic risks with consequences that affect the qualitative and quantitative aspects of sleep and daytime function [1–3]. Of the various sleep disorders, sleep apnea is probably one of the most important and the most common nocturnal problem afflicting human beings. The actual incidence of sleep apnea in the world is unknown, and the number of clinically unremarkable patients with occult sleep apnea is speculative. The many patients that the authors frequently encounter in clinical practice who

* Corresponding author. E-mail address: [email protected] (Y.H. Goh). 0030-6665/03/$ - see front matter Ó 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00174-3

424

Y.H. Goh, K.A. Lim / Otolaryngol Clin N Am 36 (2003) 423–435

were discovered to have significant sleep apnea after having been initially investigated for cardiovascular or neurologic complaints, for example, suggest that the true incidence of sleep apnea may be mind-boggling. The problem of sleep apnea is probably grossly under-recognized and underdiagnosed. Several prevalence studies in adult men have estimated prevalence rates of 0.4% to 24% [4–8], with estimates tending to increase with increasing age. Since the first recognition and description of sleep apnea in 1965 [9,10], crucial clinical and laboratory studies on sleep apnea have added new facets to the understanding of the physiologic effects of sleep apnea on humans. The effects of sleep apnea on sleep, the daytime consequences that follow, and the clinical impact of this condition on human life may be far more profound than currently believed. Patients with this condition may present with a variable combination of clinical symptoms affecting both sleep and daytime function; the former tend to be more specific for sleep apnea, whereas the latter are usually the nonspecific results of abnormal sleep regardless of the cause. To understand the physiologic impact of sleep apnea on wakefulness, it is pertinent to first examine the respiratory physiology during normal sleep, the arousal responses to respiratory alterations during sleep, the effects of sleep apnea on sleep architecture, and the role of sleep fragmentation on wakefulness.

Respiratory physiology during normal sleep Breathing during the awake state is regulated by a cluster of complex inter-related factors that includes the following: 1. Voluntary and behavioral factors 2. Mechanical signals from lung, airway, and chest receptors 3. Chemical factors, such as low oxygen or high carbon dioxide levels and acidosis During sleep, however, several important alterations in the physiologic responses to respiratory stimuli occur.

Hypoventilation during sleep In the awake state, both cortical activity and voluntary mental concentration can influence breathing and bring about an increase in both ventilation and ventilatory responses. The loss of ventilatory drive that is observed during sleep probably reflects the loss of the ‘‘wakefulness’’ drive to ventilation. During rapid-eye-movement (REM) sleep, the inhibition of both presynaptic and postsynaptic afferent neurons results in an increase in sensory arousal thresholds to external stimuli and postsynaptic inhibition of motor


425

neurons that produce postural hypotonia characteristic of REM sleep. This combination of decreased sensory and motor function is believed to account for the significant impairment of ventilatory responses during REM sleep. It is this impaired ventilatory response that permits the development of hypoventilation during sleep. Hypoxic and hypercapnic ventilatory response during sleep Not only is the voluntary control of respiration seen in the awake state lost with the emergence of sleep but the usual ventilatory responses to both low oxygen and high carbon dioxide levels also are blunted [11–14]. The marked hypoxemia seen during REM sleep in patients with severe lung and chest disease is due to this phenomenon, which is most depressed during REM sleep. These physiologic responses also may be important in the pathogenesis of upper airway obstruction during sleep and are responsible for a patient’s failure to arouse rapidly during apneas or hypopneas. The change in ventilatory sensitivity to external stimuli during sleep therefore predisposes patients with airway problems to develop clinically significant hypoxia and hypercapnia before arousal occurs. Increased airway resistance and ventilatory response during sleep Besides the blunting of hypoxic and hypercapnic ventilatory responses, sleep also obtunds the ventilatory response to increasing airway resistance. This physiologic phenomenon has been shown to be particularly distinct in non-REM (NREM) sleep [15–18], the phase of sleep when airway resistance typically reaches the maximum [19,20]. The effect of increased airflow resistance on ventilation during REM sleep is not known, however. Arousal responses to respiratory alterations during sleep Isocapnic hypoxia Under normal circumstances, isocapnic hypoxia is a poor stimulus to arousal. Although studies have demonstrated that many subjects are able to remain asleep with oxygen saturation as low as 70% [11,12,21], no difference in arousal threshold has been observed between NREM and REM sleep. Patients with sleep apnea, however, have been shown to exhibit reduced arousal sensitivity to hypoxia during periods of asphyxia [22]. Hypercapnia Although the level of hypercapnia at which arousal is triggered during sleep is highly variable, laboratory studies have shown that most subjects are awakened before the end-tidal carbon dioxide rises by 15 mm Hg above the level in wakefulness [13,23,24]. This response seems to be sensitized by the presence of coexisting hypoxia.

426


Increased airway resistance Inspiratory resistance [25] and occlusion [26] have been shown to be strong precipitants of sleep arousals. The arousal frequency during control sleep periods is most reduced in stage 3 to 4 sleep and remains comparatively lower during slow-wave sleep than in REM sleep with increased inspiratory resistance [27,28]. Although arousal from REM sleep after airway occlusion is far more rapid than arousal from NREM sleep, patients with obstructive sleep apnea tend to have longer apneas during REM sleep [26,29]. Why this phenomenon occurs is still unclear. Whether it is hypoxia, hypercapnia, or increased airway resistance, the final pathway for arousal from sleep seems to be the level of ventilatory effort [30]. Awakening from sleep, whatever the cause, leads to an increase in ventilation, just as sleep onset is associated with a decrease in ventilation. In patients with sleep apnea, this arousal response to the increase in airway resistance has been termed respiratory effort–related arousals and is an important feature of sleep apnea. Patients with this disorder tend to awaken at relatively reproducible levels of pleural pressure, and this arousal may occur without the development of either significant hypoxemia or significant hypercapnia.

Effects of sleep apnea on sleep architecture Sleep apnea [31] is characterized by episodic complete or partial pharyngeal obstruction during sleep. This multilevel disorder is characterized by narrowing at a variable number of pharyngeal locations, the soft palate being the most common site of collapse and narrowing [32,33]. Whether the decrease in the sleep-related pharyngeal neuromuscular activity [34] plays a more dominant role compared with the anatomic narrowing [35–37] of the pharyngeal space is a controversial issue. The extent to which each one of these factors contributes to the pathogenesis of sleep apnea is unknown, although the combined action of these two factors probably plays a significant role in the development of sleep apnea. Decreased upper airway dilator muscle activity [38] and reduction in ventilatory responses to hypercapnia and hypoxia [39] have been shown in 24-hour sleepdeprivation studies. Impaired wakefulness therefore depresses arousability to physiologic challenges. The result is a vicious cycle of a worsening and selfperpetuating breathing disorder during sleep. Depressed physiologic responsiveness due to altered wakefulness is clinically significant for patients with sleep apnea and other breathing disorders because they are all exacerbated by sleepiness [38]. Sleep disruption triggered by apnea results in the production of more intense and severe pathologic apneas. The impact of sleep apnea on sleep architecture can be attributed primarily to tissue vibration during snoring, increase in airway resistance, hypoxia, and hypercapnia. The final outcome of any of these events is arousal (visible or not visible on the electroencephalogram [EEG]) and an increase in ventilatory


427

effort. This intrinsic survival mechanism leads to fragmentation of sleep. It is this sleep fragmentation and the pathophysiologic changes associated with disrupted breathing that currently are believed to account for the symptoms and complications of sleep apnea. Other studies have shown that sleep apnea syndromes may be associated with suppression of slow-wave sleep or REM sleep. Suppression of slow-wave sleep occurs most commonly in children with sleep apnea, whereas REM suppression is more common in adults with sleep apnea syndromes. Successful treatment of this sleep condition results in slow-wave sleep or REM rebounds. The role of sleep fragmentation on wakefulness Increased frequency of arousals causing sleep fragmentation is a common manifestation of a number of sleep disorders and medical conditions involving physical pain or discomfort. Sleep apnea, chronic pain from arthritis and neuralgia, and rhinosinusitis, for example, may be associated with sleep that is punctuated by frequent, brief arousals of 3- to 5-second duration. These arousals are characterized by episodes of EEG speeding or alpha activity, with transient increase in skeletal muscle tone. This outburst of subtle EEG arousals is especially important in the diagnosis of upper airway resistance syndrome [40]. Nonvisible sleep fragmentation, defined as an increase in heart rate of 4 beats per minute or an increase in blood pressure by 4 mm Hg without EEG change in response to sound stimuli, also has been shown to be associated with increased sleepiness on the multiple sleep latency test (MSLT) [20,41]. Less well studied are EEG arousals that may be associated with other subcortical events not seen in the cortical EEG tracing. This abnormality may account for the increase in both the absolute amount of and the proportion of stage 1 sleep, with concomitant reduction of stage 3 to 4 sleep seen in patients with sleep apnea. The association of this event with impaired wakefulness is still not known, however. Regardless of etiology, sleep arousals generally do not result in shortened sleep but rather in sleep fragmentation. It is this fragmentation that is believed to be an important factor affecting impaired daytime wakefulness. Studies have suggested a strong association between sleep fragmentation and daytime sleepiness [42]. Treatment studies also demonstrate a close link between sleep fragmentation and excessive daytime sleepiness. Reduced frequency of arousals from sleep with resultant reduction in the level of sleepiness is seen commonly in patients who are treated successfully for sleep apnea, whereas those who do not subjectively benefit from treatment show no decrease in arousals or sleepiness, despite improved sleeping oxygenation. It must be stressed, however, that lack of fragmented sleep does not exempt one from feeling sleepy. Partial sleep deprivation may be seen occasionally in patients who are unable to sustain sleep from repeated sleep disruption. This condition is seen commonly in patients with anxiety predispositions or superimposed insomnia.

428


Wakefulness and sleepiness The maintenance of wakefulness involves a sophisticated system of feedback mechanisms from the visceral, somatic, and special sensory organs and integration of information in specialized areas within the cerebral cortex and the brain stem. Failure to execute the most minute biochemical processes that are intrinsic to sleep seems to result in the failure to initiate and facilitate the physiologic events necessary to maintain wakefulness during the day. Impaired wakefulness is one of the cardinal symptoms of sleep apnea. Sleep that is compromised qualitatively or quantitatively by this breathing disorder results in an altered state of wakefulness. In the field of sleep medicine, the level of one’s state of wakefulness is never measured directly. The degree of wakefulness is instead quantified by measuring one’s level of sleepiness. It is pertinent to emphasize at this juncture that although sleepy patients have impaired levels of wakefulness, not all patients with impaired wakefulness report sleepiness. The two terms, therefore, should not be regarded as synonymous.

What is sleepiness? Sleepiness is a basic physiologic need state like hunger or thirst that is vital to human survival. Deprivation of sleep causes sleepiness, and as eating and drinking satisfy hunger or thirst, sleeping reverses sleepiness. Under normal circumstances, severe sleep-deprived states do not occur because normal homeostatic and behavioral regulation modulates conditions to facilitate sleeping before severe deprivation states develop. The neurologic substrates of sleepiness and the specific nature of this physiologic need state have yet to be ascertained. Whether sleepiness is a symptom with varying intensity on a onedimensional scale or a multidimensional complaint is a philosophical issue that has generated much discussion. Whether sleepiness and alertness are at opposite ends in a one-dimensional scale is also another debatable issue. It is possible, however, that sleepiness varies from presence to absence and is distinct from alertness. Pivik [43], in particular, theorized that sleepiness may be multidimensional, and REM versus NREM and core versus optional sleepiness are among the different types of sleepiness he proposed. In a typical 24-hour sleep-and-wake biologic time frame, maximum sleepiness typically occurs in the middle of the night during sleep. When nocturnal sleep is not permitted to proceed at the time of maximum biologic sleepiness (2:00–6:00 AM), irritability, lethargy, sleepiness, and impaired mental function, such as inability to concentrate and memory lapses, occur. If significant physiologic sleepiness is allowed to intrude into one’s awake realm during the day, similar symptoms also are experienced. Essentially, there are two important clinical facets, objective and subjective, to sleepiness. Slowing of the alpha rhythm in the EEG seen in MSLT


429

and performance task tests, particularly those related to vigilance, are objective evidence of sleepiness, whereas thoughts, sensations, and emotions that are associated with sleep deprivation are the subjective components of sleepiness. Subjective sleepiness When examining the nature of subjective sleepiness, three important issues must be highlighted. First, an intrinsic biphasic pattern of objective sleep tendency exists in every human being, with two troughs of alertness (one between 2:00–6:00 AM and the other between 2:00–6:00 PM) [44]. How sleepy one is, therefore, depends on when his or her sleepiness is evaluated. Second, although sleep-deprived patients may present with increased tendency to fall asleep at inappropriate times, many may not report sleepiness at all. These patients often report nonspecific symptoms of decreased wakefulness, such as fatigue, lethargy, irritability, inability to concentrate at work, and a loss of sense of well-being. Also, when sleepiness is most intense, these patients may become less aware of the subjective aspects of sleepiness and so may fall asleep without warning. These episodes, called sleep attacks, are experienced commonly when patients with sleep apnea are driving a car. Third, the subjective experience of sleepiness and the behavioral indicators of sleepiness, such as yawning and head nodding, frequently can be suppressed under certain conditions. This sleepy behavior may be reduced or suppressed completely in situations of stress and excitement, high motivation, exercise, and competing needs such as hunger and thirst. Behavioral and subjective indicators thus do not always precisely reflect physiologic sleepiness. When physiologic sleepiness is most intense, however, the ability to avoid overt behavior is reduced markedly. Although a physiologically alert person does not experience sleepiness or appear sleepy even in a sleep-inducing environment, soporific conditions, such as after heavy meals, lazing in cozy rooms, or sitting through a boring lecture, will unmask physiologic sleepiness. Several self-assessment analytic scales have been devised to help clinicians and patients quantify their level of subjective sleepiness. Among the various tools for the measurement of subjective sleepiness, the Stanford sleepiness scale [45] and the Epworth sleepiness scale [46] are probably the most validated. Although most study subjects show good correlation between subjective and objective assessment of sleepiness [47], it also has been shown that patients’ subjective and objective assessment of sleepiness may not be completely consistent [48,49]. The highly subjective nature of subjective sleepiness is indeed a challenging problem for sleep clinicians and researchers. Objective sleepiness Most of the performance tasks used to evaluate the effects of sleep loss are rather insensitive. Currently, only long and monotonous tasks are

430


reliably sensitive in assessing the effects of sleep deprivation, with the exception of the 10-minute visual vigilance task. This test measures taskoriented vigilance lapses (response times 500 msec) and has been shown to correlate well with sleep loss [50,51]. Multiple sleep latency test The MSLT [52] has remained the standard physiologic measure of sleepiness. This test, which assesses one’s likelihood of falling asleep, has gained wide acceptance within the field of sleep and sleep disorders as the standard method of quantifying sleepiness [39]. Besides being a reliable clinical measure of sleepiness, the MSLT has the further advantage of being able to eliminate a patient’s motivation to stay awake during the test. Although subjects are frequently able, through motivation, to compensate for impaired performance after sleep deprivation, they are highly unlikely to stay awake for long in a darkened room during the MSLT. The MSLT is an important clinical tool to identify sleep tendency and the maximum risk for patients in their daily environment. Symptoms of impaired wakefulness not related to sleepiness Apart from reporting sleepiness, patients with sleep apnea may present with symptoms of fatigue, mood disturbance, and loss of sense of well-being. Although the association between sleep apnea and daytime sleepiness has been much studied, little is known about the effects of sleep apnea on non– sleepiness-related symptoms. Longitudinal studies of patients with sleep disturbances have shown an increased risk of developing major depression, anxiety disorders, and substance abuse and nicotine dependence [53,54]. The antidepressant nature of successful sleep apnea treatment in the authors’ clinical practice suggests that sleep disturbance from sleep apnea has profound effects on patients’ mood and behavior. Recognizing the existence of these nonspecific symptoms is necessary when treating obese patients with sleep apnea. These patients frequently require prompt treatment because lingering sleep apnea perpetuates a mental and behavioral state that is a major stumbling block to motivating patients who are attempting weight reduction. More studies are certainly required to evaluate this neuropsychiatric element of sleep apnea.

Clinical implications Between the occurrence of pharyngeal closure and the clinical manifestation of impaired wakefulness exists a complex series of physiologic events involving several systemic functions within the human body. The key link between the airway trigger and the eventual alteration in the level of awake state seems to be the extent of sleep fragmentation from repeated arousals.


431

Although it is well known that patients with impaired wakefulness do not necessarily report sleepiness, the relationship between subjective symptoms of disturbed wakefulness and the severity of sleep apnea is less clear. Patients who were deemed to be simple snorers (without symptoms of impaired wakefulness) on clinical grounds have been shown to have significant obstructive sleep apnea of at least moderate severity during polysomnography [55,56]. Although few patients with full-blown clinical symptoms of sleep apnea have minimal apneas or hypopneas, many otherwise asymptomatic snorers (30%–50%) have significant sleep apnea [57,58]. Patients with altered levels of wakefulness from sleep apnea may not present for treatment in sleep centers but may instead report nonspecific symptoms of lethargy, depression, and cognitive and memory impairment to clinicians in fields such as endocrinology, psychiatry, and neurology. Just how many of these patients with such nonspecific complaints actually have underlying sleep apnea is speculative, but the true incidence of this sleep disorder is probably grossly underdiagnosed. One explanation why patients with impaired wakefulness can present in such a variable manner is that the clinical manifestation of wakefulness is influenced by a multitude of factors, such as the extent of sleep architecture disruption, the patient’s intrinsic factors, and the environmental and external factors listed in Table 1. The ability of patients with sleep apnea to overcome their decreased wakefulness during the awake state by consuming caffeineladen products or to compensate by sleeping for a longer duration and taking afternoon naps, for example, makes the measurement of the daytime effects of sleep apnea extremely difficult and challenging. Factors such as age, gender, and the personality of patients greatly modify the eventual manifestation of their altered state of wakefulness. An important and potentially controversial issue that has been discussed extensively concerns the association of altered wakefulness as a consequence of sleep apnea with accidents. Although reports of associations of sleep apnea with road traffic accidents abound in the medical literature [25,59,60], direct epidemiologic evidence for a causal role of fatigue in car crashes is lacking. At present, there are no well-designed observational epidemiologic studies to estimate the prevalence of impaired wakefulness in the car-driving population and the level of risk it confers [61]. The recent demonstration that driving after sleep deprivation presents a risk similar to that of driving under the influence of alcohol [62,63] has uncovered an entirely new medicolegal aspect to the treatment of patients with sleep apnea. Although it is logical to hold impaired wakefulness responsible for accidents (whether traffic, industrial, or domestic), a direct link between the two is difficult to prove. The past three decades since the first description of obstructive sleep apnea have seen a rapid increase in understanding of this common sleep condition. Unfortunately, this knowledge still is limited by the constraints of the very tool that have helped in our understanding of sleep apnea and other sleep disorders, polysomnography. The economics and logistic considerations of

432


Table 1 Factors affecting wakefulness in patients with sleep apnea 1. Sleep architecture Degree of sleep disturbance (arousal index) Number of sleep arousals (sleep fragmentation) Duration of arousal-free sleep arousals increases restorative effect of sleep Nature of stage-related sleep deprivation The period of disturbance (acute versus chronic) Recovery/compensatory sleep (length of sleep/naps) Associated sleep disorders (eg, periodic leg movement, insomnia) 2. Patient factors Intrinsic factor, individual sleep quotient Personality/psychosocial makeup Age Sex Associated disease (anxiety, Parkinson’s disease, hypothyroidism, CVA) 3. Daytime environment Working environment/occupation Temperature Light Noise 4. Other factors Food/drugs (caffeine, pseudoephedrine, alcohol) Exercise Posture

polysomnography are probably the biggest hurdle to holding large-scale studies for patients with altered levels of wakefulness not typical of sleep apnea (nonsleepy problems). By venturing into newer territories, some day clinicians may uncover a new, direct association between sleep apnea and problems related with altered levels of wakefulness, such as depression, that may not be sleepiness-related. This knowledge may change the way we look at neuropsychiatric conditions in the future. Our present understanding of the physiologic impact of sleep apnea on wakefulness is limited to the effects of sleep apnea on sleepiness. Future breakthroughs in understanding of the non– sleepiness-related problems of impaired wakefulness brought about by sleep apnea will, without doubt, lead to the earlier diagnosis and treatment of this challenging condition.

References [1] Dickerson LW, Huang AH, Nearing BD, et al. Primary coronary vasodilation associated with pauses in heart rhythm during sleep. Am J Physiol 1993;264:R186–96. [2] Parmeggiani PL. Physiological risks during sleep. In: Peter JH, Penzel T, Podszuz T, et al, editors. Sleep and health risk. Berlin: Springer-Verlag; 1991. p. 119–25. [3] Shapiro CMT. Health risks associated with autonomous nervous system malfunction. In: Peter JH, Penzel T, Podszus T, et al, editors. Sleep and health risk. Berlin: Springer-Verlag; 1991. p. 124–36.


433

[4] Bearpark H, Elliot L, Cullen S, et al. Home monitoring demonstrates high prevalence of sleep disordered breathing in men in the Busselton (western Australia) population. Sleep Res 1991;20A:411. [5] Bixler EO, Vgontzas AN, Ten Have T, et al. Effects of age on sleep apnea in men, I: prevalence and severity. Am J Respir Crit Care Med 1998;157:144–8. [6] Lavie P. Sleep apnea in industrial workers. In: Guilleminault C, Lugaresi E, editors. Sleep/wake disorders: natural history, epidemiology, and long-term evolution. New York: Raven Press; 1983. p. 127–35. [7] Telakivi T, Partinen M, Koskenvuo M, et al. Periodic breathing and hypoxia in snorers and controls: validation of snoring history and associations with blood pressure and obesity. Acta Neurol Scand 1987;76:69–75. [8] Young T, Palta M, Dempsey J, et al. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993;328:1230–5. [9] Gastaut H, Tassinari C, Duron B. Etude polygraphique des manifestations episodiques (hypniques et respiratories) du syndrome de Pickwick. Rev Neurol 1965;112:568–79. [10] Jung R, Kuhlo W. Neurophysiological studies of abnormal night sleep and pickwickian syndrome. Prog Brain Res 1965;18:140–59. [11] Berthon-Jones M, Sullivan CE. Ventilatory and arousal responses to hypoxia in sleeping humans. Am Rev Respir Dis 1982;125:632–9. [12] Douglas NJ, White DP, Weil JV, et al. Hypoxic ventilatory response decreases during sleep in normal men. Am Rev Respir Dis 1982;125:286–9. [13] Hedemark LL, Kronenberg RS. Ventilatory and heart rate responses to hypoxia and hypercapnia during sleep in adults. J Appl Physiol 1982;53:307–12. [14] White DP, Douglas NJ, Pickett CK, et al. Hypoxic ventilatory response during sleep in normal women. Am Rev Respir Dis 1982;126:530–3. [15] Gugger M, Molloy J, Gould GA, et al. Ventilatory and arousal responses to added inspiratory resistance during sleep. Am Rev Respir Dis 1989;140:1301–7. [16] Hudgel DW, Mulholland M, Hendricks C. Neuromuscular and mechanical responses to inspiratory resistance loading during sleep. J Appl Physiol 1987;63:603–8. [17] Iber C, Bersenbrugge A, Skatrud JB, et al. Ventilatory adaptions to resistive loading during wakefulness and non-REM sleep. J Appl Physiol 1982;52:607–14. [18] Wiegland L, Zwillich CW, White DP. Sleep and the ventilatory response to resistive loading in normal men. J Appl Physiol 1988;64:1186–95. [19] Hudgel DW, Martin RJ, Johnson B, et al. Mechanics of the respiratory system and breathing pattern during sleep in normal humans. J Appl Physiol 1984;56:133–7. [20] Martin SE, Wraith PK, Deary IJ, et al. The effect of nonvisible sleep fragmentation on daytime function. Am J Respir Crit Care Med 1997;155:1596–601. [21] Gothe B, Goldman MD, Cherniack NS, et al. Effect of progressive hypoxia on breathing during sleep. Am Rev Respir Dis 1982;126:97–102. [22] Sullivan CE, Issa FG. Pathophysiological mechanisms in obstructive sleep apnea. Sleep 1980;3:235–46. [23] Birchfield RI, Sieker HO, Heyman A. Alterations in respiratory function during natural sleep. J Lab Clin Med 1959;54:216–22. [24] Douglas NJ, White DP, Weil JV, et al. Hypercapnic ventilatory response in sleeping adults. Am Rev Respir Dis 1982;126:758–62. [25] Garbarino S, Nobili L, Beelke M, et al. The contributing role of sleepiness in highway vehicle accidents. Sleep 2001;24:203–6. [26] Issa FG, Sullivan CE. Arousal and breathing responses to airway occlusion in healthy sleeping adults. J Appl Physiol 1983;55:1113–9. [27] Netick A, Dugger WJ, Symmons RA. Ventilatory response to hypercapnia during sleep and wakefulness in cats. J Appl Physiol 1984;56:1347–54. [28] Santiago TV, Sinha AK, Edelman NH. Respiratory flow-resistive load compensations during sleep. Am Rev Respir Dis 1981;123:382–7.

434


[29] Gugger M, Bogershausen S, Schaffler L. Arousal response to added inspiratory resistance during REM and non-REM sleep in normal subjects. Thorax 1993;48:125–9. [30] Gleeson K, Zwillich CW, White DP. The influence of increasing ventilatory effort on arousal from sleep. Am Rev Respir Dis 1990;142:295–300. [31] American Academy of Sleep Medicine. Sleep related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 1999;22:667–89. [32] Launois SH, Feroah TR, Campbell WN, et al. Site of pharyngeal narrowing predicts outcome of surgery for obstructive sleep apnea. Am Rev Respir Dis 1993;147:71–94. [33] Morrison DL, Launois SH, Isono S, et al. Pharyngeal narrowing and closing pressures in patients with obstructive sleep apnea. Am Rev Respir Dis 1993;148:606–11. [34] Leiter JC, Knuth SL, Bartlett D Jr. The effect of sleep deprivation on activity of the genioglossus muscle in man. Am Rev Respir Dis 1985;132:1242–5. [35] Guilleminault C, Riley R, Powell N. Obstructive sleep apnea and abnormal cephalometric measurements: implications for treatment. Chest 1984;86:793–4. [36] Horner RL, Shea SA, McIvor J, et al. Pharyngeal size and shape during wakefulness and sleep in patients with obstructive sleep apnea. Q J Med 1989;72:719–35. [37] Rivlin J, Hoffstein V, Kalbfleish J, et al. Upper airway morphology in patients with idiopathic obstructive sleep apnea. Am Rev Respir Dis 1984;129:355–60. [38] Lopes JM, Tabachnik E, Muller NL, et al. Total airway resistance and respiratory muscle activity during sleep. J Appl Physiol 1983;54:773–7. [39] White DP, Douglas NJ, Pickett CK, et al. Sleep deprivation and control of ventilation. Am Rev Respir Dis 1983;128:984–6. [40] Guilleminault C, Stoohs R, Clerk A, et al. From obstructive sleep apnea syndrome to upper airway resistance syndrome—consistency of daytime sleepiness. Sleep 1992;15(Suppl 6): S13–6. [41] Hosslet JJ, Norman RG, Ayappa I, et al. Detection of flow limitation with nasal cannula/ pressure transducer system. Am J Respir Crit Care Med 1998;157:1461–7. [42] Stepanski EJ. The effect of sleep fragmentation on daytime function. Sleep 2002;25:268–76. [43] Pivik RT. The several qualities of sleepiness: psychophysiological considerations. In: Monk T, editors. Sleep, sleepiness and performance. New York: John Wiley & Sons; 1991. p. 3–37. [44] Richardson GS, Carskadon MA, Orav EJ, et al. Circadian variation of sleep tendency in elderly and young adult subjects. Sleep 1982;5:S82–94. [45] Hoddes E, Zarcone VP, Symthe H. Quantification of sleepiness: a new approach. Psychophysiology 1973;10:431–6. [46] Johns MW. Sleepiness in different situations measured by the Epworth Sleepiness Scale. Sleep 1994;17:703–10. [47] Chervin RD, Aldrich MS, Pickett R, Guilleminault C. Comparison of the results of Epworth Sleep Scale and the Multiple Sleep Latency Test. J Psychosom Res 1997;42:145–55. [48] Dement WC, Carskadon MA, Richardson G. Excessive daytime sleepiness in the sleep apnea syndrome. In: Guilleminault C, Dement WC, editors. Sleep apnea syndromes. New York: Alan R Liss; 1978. p. 23–46. [49] Sangal RB, Sangal JM, Belisle C. Subjective and objective indices of sleepiness (ESS and MWT) are not equally useful in patients with sleep apnea. Clin Electroencephalogr 1999; 30:73–5. [50] Dinges DF, Orne MT, Whithouse WG, et al. Temporal placement of a nap for alertness: contributions of circadian phase and prior wakefulness. Sleep 1987;10:313–29. [51] Wilkinson RT, Houghton D. Field test of arousal: a portable reaction timer with data. Hum Factors 1982;24:487–93. [52] Carskadon MA, Dement WC, Mitler MM, et al. Guidelines of the multiple sleep latency test (MSLT): a standard measure of sleepiness. Sleep 1986;9:519–24. [53] Breslau N, Roth T, Rosental L, et al. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Bio Psychiatry 1996;39:411–8.


435

[54] Ford DE, Kamerow DB. Epidemiologic study of sleep disturbance and psychiatric disorders: an opportunity for prevention? JAMA 1989;262:1479–84. [55] Goh YH, Choy DKS. Omission of polysomnography in the treatment of snoring: common reasons and medico-legal implications. J Laryngol Otol 2000;114:519–21. [56] Simmons BF, Guilleminault C, Miles LE. The palatopharyngoplasty operation for snoring and sleep apnea: an interim report. Otol Head Neck Surg 1984;92:375–80. [57] Miles LE, Guilleminault C, Smith LE, et al. Patients who complain only of loud snoring often have significant obstructive sleep apnea. Sleep Res 1983;12:265. [58] Miles LE, Simmons FB. Evaluation of 190 patients with loud and disruptive snoring. Sleep Res 1984;13:154. [59] Fuchs BD, McMaster J, Smull G, et al. Underappreciation of sleep disorders as a cause of motor vehicle crashes. Am J Emerg Med 2001;19:575–8. [60] Masa JF, Rubio M, Findley LJ. Habitually sleepy drivers have a high frequency of automobile crashes associated with respiratory disorders during sleep. Am J Respir Crit Care Med 2000;16(4 Pt 1):1407–12. [61] Connor J, Whitlock G, Norton R, Jackson R. The role of driver sleepiness in car crashes: a systematic review of epidemiological studies. Accid Anal Prev 2001;33:31–41. [62] Hack MA, Choi SJ, Vijayapalan P, Davies RJ, Stradling JR. Comparison of the effects of sleep deprivation, alcohol and obstructive sleep apnoea (OSA) on simulated steering performance. Respir Med 2001;95:594–601. [63] Powell NB, Schechtman KB, Riley RW, et al. The road to danger: the comparative risks of driving while sleepy. Laryngoscope 2001;111:887–93.


Nasal obstruction in sleep-disordered breathing Wynne Chen, MD, Clete A. Kushida, MD, PhD* Stanford University Center of Excellence for Sleep Disorders, 401 Quarry Road, Suite 3301, Stanford, CA 94305, USA

The fifth [aberration] is of great interest. . . At the conclusion of the positive pressure phase [of the nasal pressure curve] there is a period of apnea [no positive or negative pressure] lasting for only a fraction of a second or longer. . . It very often occurs in people who have suffered nasal obstruction for a long time and who, we believe, have developed secondary effects somewhere in the systemic phases of the respiratory act. It is a persisting, most often irreversible finding and is seen even in children and young adults. Correction of the causative nasal obstruction does not often or necessarily change the aberration. —M.H. Cottle [1]

Although several articles have recounted the rich history behind the discovery of obstructive sleep apnea-hypopnea syndrome (OSAHS) [2–4] and subsequent identification of the clinical syndromes now known as the ‘‘sleep-related breathing disorders’’ (SRBDs) [5], it has been generally unrecognized that reports describing the relationship between nasal breathing and sleep quality date back to the 1800s. Sleep disturbances were associated explicitly with nasal obstruction in 1892 when Carpenter [6] described a patient with ‘‘hypertrophic rhinitis’’ who complained of insomnia and frightening dreams, with impairment of the ‘‘faculties of will, intellect, emotion and memory’’ [7]. Fleiss [8] similarly described 130 cases of what he called ‘‘nasal neuroses’’ with the ‘‘incapacity for sustained mental effort, lack of concentrative power, and loss of memory.’’ In 1898, Wells [8] described 10 patients with obstructed nasal breathing, eight of whom complained of excessive sleepiness that resolved after nasal patency was reestablished. He noted that patients were often unaware of the connection between their obstructed nasal breathing and their sleepiness [7] and opined that ‘‘sleep habit’’ should be looked for in mouth breathers. Similar observations also * Corresponding author. E-mail address: [email protected] (C.A. Kushida). 0030-6665/03/$ - see front matter Ó 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00175-5

438

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437–460

were made for children, and in Hill’s paper [9] entitled ‘‘On some causes of backwardness and stupidity in children,’’ he noted that the child ‘‘who frequently suffers from headaches at school, breathes through his mouth instead of his nose, snores and is restless at night, and wakes up with a dry mouth in the morning, is well worthy of the solicitous attention of the school medical officer.’’ He also noted that many children with obstructed airways showed significant improvement in learning abilities after surgical intervention [7]. Yet many of these early observations were largely ignored throughout most of the 1900s [4], until otorhinolaryngologist Maurice Cottle called attention to this relationship in two of his articles published in the 1960s, as described by Lavie [4]. The often marked improvement in sleep quality after nasal surgery and the observed effects of head position on nasal breathing led him to suggest that ‘‘nasal valve changes and turbinate excursions are important factors in initiating head and body movements in sleep, all of which together are greatly responsible for the ÔrestÕ the whole body can obtain during the sleep period’’ [4]. He later identified apneas or ‘‘mid-cycle rest(s)’’ in his study of uninasal pressure-curve recordings in sleeping adults and commented that ‘‘special attention should be paid to the sleeping habits. Sleeping patterns are in great measure dependent on good nasal function.’’ Today it is recognized that the neurocognitive deficits described in the previous paragraph likely were related to underlying sleep-disordered breathing, recurrent arousals with sleep fragmentation, and abnormal sleep architecture [10]. The consequences of such arousals are also well established and include not only excessive daytime sleepiness, delayed reaction times, and impaired performance in neuropsychologic testing but also reduced creativity, decreased quality of life, and increased risk of motor vehicle and occupational accidents [11]. There is also evidence that the conventional measures of sleep disturbance (respiratory variables such as apnea-hypopnea index [AHI], respiratory disturbance index [RDI], and ‘‘macrostructural’’ sleep variables such as rapid-eye-movement [REM] latency) on which the diagnosis of OSAHS had first been made are now inadequate in the evaluation of the milder and more subtle forms of sleep-disordered breathing such as upper airway resistance syndrome (UARS). Increasing attention has been placed on the ‘‘microstructural’’ characteristics of sleep architecture, such as cortical arousals, EEG activation, and the presence of the cyclic alternating pattern (CAP) [12]. An endogenous arousal-related phenomenon consisting of characteristic sequences of electroencephalographic activity, CAP is believed to represent an oscillatory process of unstable sleep [12,13]. An increase in the percentage of CAP time in non-REM sleep (CAP rate [CAPR]) is found in any state of internal or external perturbation of sleep (such as increased upper airway resistance), and reduction in the CAPR to more physiologic values occurs with treatment. The eradication of CAPs reflects consolidation and normalization of sleep structure and autonomic activity [12]. Despite the current recognition that nasal obstruction can interfere with the titration [14,15] and tolerance [16] of nasal positive airway pressure


439

therapy in patients with SRBDs and that the relief of such obstruction may improve patient compliance with this therapy [10,17], the exact role that obstructed nasal breathing plays in the pathogenesis of SRBDs remains presumptive [18–21]. Studies published thus far have been characterized by relatively small numbers of patients, inconsistent study design, methodology, and parameters used to measure sleep disturbance. It seems, however, that correction of nasal obstruction may have its greatest impact on milder forms of sleep-disordered breathing, such as UARS [22]. For infants and young children, nasal obstruction may have a significant effect on ventilation, craniofacial growth, and future risk for SRBD as an adult. The purpose of this article is to review the putative role of nasal obstruction in the pathophysiology of sleep-disordered breathing and to examine the clinical studies that have attempted to corroborate this theory. The consequences of nasal obstruction in infants and children are reviewed, as are the various causes of nasal obstruction as it pertains to sleep-disordered breathing, and reasonable treatment options are presented.

Pathophysiologic implications of nasal obstruction in sleep-related breathing disorders The Starling resistors Although upper airway obstruction has been shown to occur at more than one site and to vary among consecutive apneas in the same individual [23], the primary region of obstruction in SRBDs such as OSAHS is believed to be oropharyngeal-hypopharyngeal, defined as the tip of the soft palate to the level of the vocal cords [24–26]. The nasopharynx, defined as the region between the free edge of the nasal septum and the top of the soft palate, also has been implicated [27,28]. The nose, therefore, may play an important part in upper airway resistance, particularly because it primarily functions as a resistor (Fig. 1) [21] and contributes to 50% of upper airway resistance, adding to that provided by the oropharyngeal tissues and the tongue [21,29]. Because the nasal cavity has a more rigid frame, its resistance is more constant during waking and sleep states when compared with oral breathing. Nasal breathing is more efficient during sleep [30]. As such, the nose functions to match the impedance of the remainder of the upper and lower respiratory tract, thereby controlling the respiratory rate and length of both expiration and inspiration, as well as tidal volume. By prolonging expiration, pulmonary compliance is increased, as are oxygen uptake, alveolar gas exchange, and recovery of water vapor and heat [21]. Conversely, on inspiration, nasal breathing and increased nasal resistance may augment the pressure differential between the atmosphere and intrathoracic space and thus promote upper airway collapse and obstruction [31]. Nasal airflow generally follows a parabolic curve that arches superiorly through the nasal valve, which is the major site of nasal resistance [21,32,33].

440



441

m

The internal nasal valve is defined as the area between the caudal end of the upper lateral cartilages (ULCs) and the cartilaginous septum; this angle is normally 10 to 15 in the Caucasian (leptorrhine) nose and is more obtuse in African-American and Asian (platyrrhine) noses [34]. The entire nasal valve complex is bounded superiorly by the reflection between the ULC and the septum, posteriorly by the head of the inferior turbinate, inferiorly by the floor of the nose, and laterally by the bony piriform aperture [34]. Resistance progressively increases over the first 2 cm of the nose, spread over a ‘‘flow-limiting segment’’ corresponding to the length of the ULC [35,36]. Electromyographic studies [37] show that the function of the dilator naris, nasalis muscle, and apices nasi strongly relates to respiration and probably contributes to nasal valve function [34]. During vigorous inspiration, when the negative nasopharyngeal and intranasal pressure increases to generate more flow, there is a proportional increase in the transmural pressure gradient (normal atmospheric pressure minus intranasal pressure), until the latter reaches a critical value, leading to collapse of the ULC [32]; this ‘‘flow-limiting segment’’ therefore acts like a Starling resistor [35]. Partial collapse of the ULC normally occurs at a ventilatory flow of 30 L/min, preventing further increases in intranasal pressure from augmenting flow [34]. Nasal resistance also can be affected by the air temperature and humidity, posture, the enlargement or constriction of blood vessels in the nose, and mucosal changes, however [38]. Mucosal changes seem to play a significant role in the modulation of nasal resistance because apneas and hypopneas

Fig. 1. Similar to the collapsible hypotonic pharyngeal segment described in the ‘‘composite’’ theory [7l] of upper airway obstruction during sleep, the ‘‘flow-limiting segment’’ of the nasal valve, influenced by nasal reflexes, also can act like a Starling resistor in augmenting nasal resistance. Accordingly, only two variables influence nasal valve closure—the amount of negative pressure generated at the nasal valve and the critical transmural pressure gradient; these variables correspond to static (Stat) and dynamic (Dyn) forms of nasal valve dysfunction (see text). Mucosal changes related to air temperature and humidity and the effects of posture on the nasal cycle also may affect resistance at the nose (Rus), however. This increase in upstream resistance may decrease maximal inspiratory flow (Vmax) by decreasing the upstream pressure (Pus) in the setting of positive pressure surrounding the collapsible pharyngeal segment (Pcrit). Narrowing of the pharyngeal airway may contribute to increased pharyngeal compliance according to the Tube law and increased velocity of airflow within this segment, with increased inward pressure of the pharyngeal walls (Bernoulli effect). This pharyngeal narrowing and progressive flow limitation on inspiratory effort culminate in an obstructive apnea when the upstream nasal pressure (Pus) falls below Pcrit. Underlying genetic susceptibility for respiratory instability during sleep may affect these interactions. Acute mouth opening, with or without transition to oral breathing, also may promote pharyngeal collapse by these mechanisms and promote retrolingual airway obstruction. Chronic mouth breathing in children may lead to craniomandibular deficiencies and neuromuscular abnormalities that may increase future susceptibility to upper airway obstruction and sleep-disordered breathing. GERD ¼ gastroesophageal reflux disease; Patm ¼ atmospheric pressure; PDS ¼ downstream pressure; V.M.O. ¼ ventilatory motor output; VT ¼ tidal volume. *Poiseuille’s law.

442


can be induced during sleep from chronic mucosal stimulation with an irritant [39]. Several studies have pointed toward the presence of nonspecific inflammation [40,41], which may work in synergy with these other factors to influence nasal resistance [42]. Stimulation of nasal reflexes also may influence upper airway obstruction, because nasal obstruction may disturb reflex mechanisms mediated through the trigeminal or vagal nerves. When afferent input for the nasal sensory receptors is acutely decreased, respiratory rhythm is disturbed, leading to apnea [21,43]. Nasal dilator muscles have been shown to work in conjunction with other dilators of the upper airway during sleep, such as the genioglossus muscles. In normal subjects, the nasal alae demonstrate inspiratory bursts of activity, resulting in nasal flaring that precedes diaphragmatic activity—an event that is referred to as preactivation [21,44,45]. The interval between nasal dilator preactivation and initiation of inspiration appears earlier during sleep and hypercapnia [21]. This preactivation is greatest after an apneic event in men with OSAHS, suggesting that preactivation is a compensatory attempt to open the nasal airway before the upper airway pressures are lowered by diaphragmatic contraction, thereby promoting upper airway patency and stability in preparation for the next attempted breath [21]. Body position also may influence upper airway patency, based on the fact that the nasal mucosa and related resistance exhibit not only diurnal but also postural variations [18,46]. The cavernous plexuses within the nasal mucosa are responsible for the nasal cycle and are under autonomic control; whereas nasal resistance is maximal at night and in the early morning [46], the nasal mucosa also exhibits an alternating pattern of left-to-right congestion and decongestion [18]. It also has been demonstrated that nasal resistance increases in the supine and lateral positions (with higher resistance on the dependent side) [46,47]. Relatively asymptomatic nasal obstruction, either unilateral or bilateral, may become symptomatic when recumbent [38,47], and ‘‘paradoxical nasal obstruction’’ [38] may occur in the setting of a fixed unilateral nasal obstruction. In turn, there are several indirect mechanisms by which nasal obstruction and increased nasal resistance may affect upper airway resistance and subsequent pharyngeal obstruction [21]. The first involves alterations in upper airway aerodynamics (Fig. 1). Although upper airway obstruction may begin at end expiration, it is during subsequent inspiration that pharyngeal flow further decreases and ultimately stops, because the pharynx is normally the major limiting factor in inspiratory flow [21]. As described by Badr [48], the pharynx may be hypotonic as a consequence of decreased ventilatory motor output associated with postarousal hypocapnia, sleep stage (REM sleep), and genetic predisposition to respiratory instability [21,49]. Because the capacity to sense pressure and airflow in the upper airway may directly affect activity of the respiratory muscles during sleep [21,50], localized polyneuropathy possibly related to vibratory trauma also


443

may contribute to airway instability and the development of upper airway obstruction in these patients [21,47,51,52]. Gastroesophageal reflux related to excessive diaphragmatic activity may similarly inflame and progressively scar the pharyngeal mucosa [52]. Like the nasal valve, the hypotonic pharynx may act as a Starling resistor, with a collapsible segment that is susceptible to the influences of the surrounding pressure (referred to as the critical closing pressure) and subatmospheric downstream pressure of the thoracic pump muscles, including the diaphragm [48]. Maximal flow through this Starling resistor then would be determined by the resistance of the upstream segment, or nasal resistance, and the critical closing pressure, which is more positive in patients with sleep-disordered breathing. The application of negative nasal pressure then would result in progressive flow limitation and obstructive apnea once nasal pressure is reduced below the critical closing pressure [48]. Narrowing of the pharyngeal airway also would lead to increased pharyngeal compliance according to the Tube law and owing to increased velocity of airflow and increased inward pressure on the pharyngeal walls (Bernoulli effect), promote further pharyngeal narrowing [48]. There also may be a genetic predisposition for sleep-induced respiratory instability, as suggested by the finding that nasal occlusion resulted in a significantly higher frequency of apneic episodes in a study of six sons of patients with OSAHS when compared with age-matched control subjects without familial history of sleep-disordered breathing [49]. It has been suggested that such individuals may progress to more severe forms of SRBDs at a faster rate than those without such a neurobiologic predisposition [21].

The role of mouth opening in upper airway obstruction It also should be kept in mind that mouth opening, with or without transition to oral breathing (as occurs in complete nasal obstruction), may contribute further to upper airway flow limitation and collapse, by the inferior movement of the mandible and associated decrease in pharyngeal diameter. This movement of the mandible also is associated with a reduction in the length of the upper airway dilator muscles that lay between the mandible and the hyoid bone, which decreases their mechanical efficiency in placing them at an unfavorable position on their length-tension curve [53]. The base of the tongue also may fall backward, resulting in a reduction in the posterior pharyngeal space [43,47]. With the additional transition to oral breathing, increased effort is required to overcome the increase in oral airway resistance related to the relaxation of oral and pharyngeal musculature during sleep [30], leading to greater negative pressures in the pharynx and higher risk for collapse [30]. The loss of nasal reflexes may impair upper airway muscle tone further [54,55].

444


The clinical association between nasal obstruction and sleep-related breathing disorders Early studies and the importance of cephalometrics Early studies investigating the role of nasal obstruction in sleepdisordered breathing were uncontrolled and limited by small sample sizes. Studies using artificial models such as nasal packing [56,57] showed that during periods of acute bilateral (complete) nasal obstruction, healthy volunteers exhibited more arousals during sleep and experienced lighter (stage 1) sleep; however, the role played by the transition to oral breathing was not specifically assessed. Lavie et al [58] further examined differences between complete and partial nasal obstruction in 10 healthy adults without otolaryngologic lesions. Studied by overnight polysomnography with either unilateral or bilateral nasal occlusion with nasal tape, significant increases in apneas per hour were noted. The number of apneas increased from a baseline mean of 1.4 (1.9) to 3.1 (3.5) and to 7.9 (12.2) with unilateral and bilateral occlusion, respectively; the difference seen in the setting of bilateral nasal occlusion was found to be statistically significant (P < 0.03). The most frequent findings, however, were periodic breathing of alternating hypopnea and hyperpnea and changes in respiratory rate without noticeable changes in tidal volume, most prominent during light sleep. Two subjects, one male and one female, showed dramatic increases in the number of both obstructive and central apneas during one night of bilateral nasal occlusion, suggesting that they may have had anatomic features that may have predisposed them to more significant upper airway obstruction [59]. This possibility was investigated further by Suratt et al [60], who studied the response of 15 healthy men to acute bilateral intranasal occlusion using gauze impregnated with petrolatum. Overnight polysomnography with esophageal manometry was performed, and oral resistance was measured using pulse (inspiratory) flow resistance. They found that intranasal occlusion increased airway obstruction during sleep, with the minutes of airway obstruction per hour of sleep significantly increased after nasal occlusion (P < 0.05). Although there was an overall correlation between pulse flow resistance and the number of apneas and hypopneas, this correlation did not reach statistical significance; interestingly, the patient who developed the most apneas had the highest pulse flow resistance. There was also a trend toward lighter sleep and less slow-wave and REM sleep with nasal occlusion and a statistically significant increase in both sleep latency and REM latency. The investigators hypothesized that subjects with more narrowed oropharyngeal airways would have more apneas during nasal obstruction than patients with larger airways in the setting of pharyngeal muscle atonia during sleep. Five years later, Series et al [10] revisited this issue in patients with nasal septal deviation, a natural and more chronic model of nasal obstruction. Their study included 20 generally obese (average body mass index of


445

34.0 1.7 kg/m2), older men and women with obstructive sleep apnea, all of whom underwent surgical correction. The subjects also underwent preoperative and postoperative polysomnography with esophageal manometry and had cephalometric measurements (angle from sella to the nasion to subspinal point [SNB], posterior airway space [PAS], behind the tongue base and limited by soft tissues, and distance from mandibular plane to hyoid bone [MP-H]) taken; nasal resistance was measured in 14 subjects who would allow it. Although nasal surgery was effective in improving nasal airflow, with subjective improvement in all subjects and a reduced diurnal nasal resistance in the subjects in whom it was measured, this decrease in nasal resistance did not correlate with respiratory variables; the group as a whole showed no improvement in RDI, total apnea time, or severity of nocturnal desaturations. Both the PAS and MP-H distances were normal in the four patients in whom RDIs did return to normal after surgery, however. The mean AHI (16.7) of these four patients was relatively low when compared with the rest of the group. The authors suggested that overall, nasal surgery showed limited effectiveness in the treatment of sleep apnea in these adults, but it did benefit all patients who had normal PAS and MP-H distances. They believed that this variability in surgical outcomes was related to the presence of other oropharyngeal abnormalities (which, as the authors argued, may have been due to chronic nasal obstruction leading to craniomandibular abnormalities). They sought to verify this hypothesis in a subsequent study [61] examining 14 patients with symptoms suggestive of sleep-disordered breathing who also had symptomatic fixed nasal obstruction in the form of septal deviation or turbinate hypertrophy with or without polyps on examination. All were proven to have mild to moderate OSAHS (AHI, 13.3–25.0) and then were matched by PAS and MP-H measurements into normal and abnormal cephalometry groups. All the patients also underwent preoperative and postoperative polysomnograms, with eight accepting esophageal manometry and 10 subjects also undergoing nasal resistance measurements. After surgery, each patient felt dramatic improvement in nasal ventilation, and a similar decrease in nasal resistance was seen in both groups. Although no significant difference in sleep architecture was seen between the two groups after surgery, sleep fragmentation (as assessed by the number of arousals) was significantly lower in the normal cephalometry group. The frequency of breathing abnormalities (AHI) returned to normal values (<10) in all but one of the subjects in this group and remained unchanged in all those with abnormal PAS and MP-H distances. Correlation with nasal resistance An attempt to correlate nasal resistance with nasal obstruction and sleepdisordered breathing was made by DeVito et al [47] in their investigation

446


into the prevalence of nasal obstruction among 36 of 150 initial subjects referred to their otolaryngologic clinic for possible sleep-disordered breathing; the subjects ultimately were diagnosed as having OSAHS. Based on clinical examination and cephalometric measures, these 36 subjects had evidence of airway obstruction only at the level of the oropharynx, without significant abnormalities in the tongue, jaw, or hyoid bones. Nasal abnormalities included septal deviation with hypertrophy of the inferior and middle turbinates, isolated septal deviation, restriction in the valvular region, and hypertrophy of the inferior turbinates. To account for positional changes in nasal resistance, active anterior rhinomanometry was used to measure nasal resistance in the seated and supine (awake) positions; seven patients had abnormal upright nasal resistance that worsened when supine, nine had normal resistances in a seated position that worsened in a supine position, and 20 had normal resistances both in a seated and a supine position. Although there was an upward trend in RDI with increasing nasal resistance from the seated to the supine position, there was no statistical difference in the AHI among the three groups. Using a more accurate measure of nasal resistance (posterior rhinomanometry with the use of a mask initially used for CPAP, and tongue protrusion), however, Lofaso et al [62] were able to correlate nasal resistance with sleep-disordered breathing in their prospective examination of 541 unselected snorers referred for suspected sleep-disordered breathing. The investigators measured nasal resistance in 528 subjects with or without topical decongestants. Each subject had anthropometric data collected and underwent overnight polysomnography, spirometry, and cephalometric analysis. Two hundred and fifty-nine subjects were found to have OSAHS, based on an AHI of 15 or more (mean, 37.5 23.3). Baseline data revealed that age, sex ratio (men), and body mass index were significantly higher in the OSAHS group than in the non-OSAHS group. Comparisons of cephalometric measurements showed that the angle from the sella to the nasion to the subspinale (SNA) and PAS were similar in both groups, whereas SNB was lower and the posterior nasal spine to the tip of soft palate (PNS-P) and MP-H were higher in the patients with OSAHS. Nasal resistance was significantly higher in the OSAHS group, and although the highest unilateral nasal resistance was not significantly different between the two groups, basal bilateral nasal resistance did correlate significantly (P < 0.0001) with OSAHS severity, and stepwise multiple-regression analysis revealed nasal resistance to be a contributing factor in OSAHS. Although nasal examinations of their subjects were not reported, the investigators concluded that their results supported the hypothesis that nasal obstruction that is either unresponsive (such as septal deviation) or responsive to nasal decongestants (such as vasomotor rhinitis) contributes to sleep-disordered breathing. They suggested that daytime nasal obstruction, whatever the cause, was a risk factor for OSAHS, but its influence was less than that of obesity or cephalometric landmarks.


447

Rhinitis and sleep-related breathing disorders With allergic and nonallergic rhinitis affecting more than 20% of the US population [63], it is not surprising that this naturally occurring model of nasal obstruction also has been used to investigate the role of nasal obstruction in sleep-disordered breathing. Extensively reviewed by Scharf and Cohen [31], nasal obstruction does seem to contribute to sleep-disordered breathing in predisposed individuals. Most recently, Houser et al [22] retrospectively examined 50 subjects with seasonal or perennial allergic rhinitis and found significant differences in congestion factors at cross-sectional area 1 of the nose (the anterior portion of the inferior turbinate or the nasal valve) between those with mild OSAHS (mean RDI of 14.5) and those without sleep apnea (P ¼ 0.03).

Nasal obstruction in infants and children, allergic rhinitis, and developmental implications Mouth breathing in infants and children The issues of rhinitis, nasal obstruction, and attendant mouth breathing are particularly important in infants and children. For infants, the transition from nasal to oral breathing is particularly dangerous because of the close approximation of the soft palate, tongue, and epiglottis [64]. The infant’s jaw is also almost horizontal, and its articulation with the skull is unstable, which allows the relatively flexible mandible to displace posteriorly. The tongue, a mobile muscular mass, sits on the floor of the mouth, anchored to the mobile mandible and to the hyoid. At birth and usually for the first 5 to 6 months of life, the tongue fills the oral cavity unless the infant is crying or gasping, and thus, breathing occurs preferentially through the nasal passages [65]. Nasal obstruction, such as that caused by bilateral choanal atresia, therefore can lead to complete upper airway obstruction [66]. Cyclic cyanosis ensues, which is relieved rapidly by crying or mouth opening. A recent study in young children by McColley et al [67] has shown an increase in frequency of OSAHS in habitual snorers with allergic sensitization. A history of sinus problems (adjusted odds ratio, 5.21; 95% confidence interval, 1.66–16.12) also recently was found to be an independent predictor of sleep-disordered breathing in children and adolescents as part of a genetic-epidemiology study of sleep-disordered breathing [68]. Tonsillar and adenoidal hypertrophy Children with allergic rhinitis often become mouth breathers and snore at night as a result of nasal obstruction and adenoidal hypertrophy [69], with congestion of the inferior turbinate [70]. This occurrence corresponds with the peak prevalence of childhood OSAHS, occurring between 2 and 8 years

448


of age, when the tonsils and adenoids are the largest in relation to underlying airway size. Increased nasal resistance, as measured by anterior rhinometry, has been found to correlate with severity of sleep apnea in children with adenotonsillar hypertrophy [71]. Because of the difficulties in distinguishing simple snoring from sleep apnea [72], children who snore always should be evaluated for signs and symptoms of sleep-disordered breathing, such as failure to thrive, daytime sleepiness, behavioral problems, and neurocognitive deficits [73–75]. Although several studies have shown that symptoms of sleep-disordered breathing in children often completely resolve after adenotonsillectomy [73,76], incomplete resolution of symptoms may occur in the setting of other diseases, such as Down’s syndrome, and craniofacial anomalies such as the Pierre Robin sequence [76]. Alternatively, OSAHS symptoms may recur years later in some children, particularly in those in whom only a unilateral tonsillectomy is performed [76] or in whom more subtle craniofacial variances exist [77]. Children successfully treated with adenotonsillectomy for OSAHS should be followed closely for the recurrence of signs and symptoms of sleepdisordered breathing, particularly in families with bite abnormalities that may reach their full manifestation only during puberty [76,78]. Craniofacial and upper airway development Apart from genetic facial predisposition, chronic nasal obstruction in young children may lead to acquired craniofacial abnormalities, which may further compromise the stability of the upper airway [61]. Lowering of the mandible to establish the oral airway and requisite posture of the mandible and lower tongue position may alter the relationship of the dental arches, causing an increased lower facial height and a narrow, high palatal vault [79]. These children exhibit facial changes referred to as the ‘‘adenoid face’’ or ‘‘long-face syndrome’’ [80], with a long and narrow facial appearance, retrognathia, micrognathia, and a high, narrowly arched palate [81]. Experimental studies of complete nasal obstruction with oral breathing in young primates have revealed alterations in the tonic and phasic electromyographic activity of the upper airway (geniohyoid and genioglossus muscles), mandibular, and facial muscles. Changes in mandibular growth observed in mouth-breathing monkeys (posterior rotation of the mandible with lower position of the chin) can be associated with these changes in muscular activity, and because pharyngeal configuration depends on anatomic bony structures, chronic nasal airflow obstruction may lead to similar neuromuscular and craniomandibular abnormalities in humans.

Causes of nasal obstruction A careful history focusing on nasal symptoms and prior nasal surgery or trauma should complement the physical examination of the facial muscles,


449

nasal valve and nasal passages, oral cavity and oropharynx, as well as an assessment of the craniofacial skeleton [30,55,82]. Representative causes of nasopharyngeal obstruction can be broadly divided into structural, mucosal, and neuromuscular etiologies (Table 1). Alternatively, they may be separated into congenital and acquired [83] or congestive versus noncongestive etiologies [30]. Among these etiologies, nasal obstruction related to nasal congestion and pathologic conditions related to the nasal valve deserve special mention. Nasal congestion Nasal congestion involves the cavernous tissues of the turbinates and is caused most commonly by allergic rhinitis, vasomotor rhinitis, chronic sinusitis, and upper respiratory tract viral infections [30]. As reviewed by Corey et al [30], the most commonly associated structural abnormality is septal deviation, which can cause the sensation of chronic unilateral nasal congestion or congestion that fluctuates with the nasal cycle. The inferior turbinates may exhibit a compensatory hypertrophy on the contralateral side and therefore may lead to bilateral nasal obstruction [30,84] Polyps, nasal or nasopharyngeal, or those associated with cystic fibrosis, asthma, or aspirin sensitivity also may be associated with nasal congestion [30]. The symptoms of nonallergic rhinitis with eosinophilia syndrome (NARES) are similar to those of perennial allergic rhinitis, and NARES may represent a reaction to an unknown agent or an overlap syndrome with vasomotor rhinitis. States of hormonal flux, such as those that occur during pregnancy and puberty, are associated with nasal mucosal engorgement and obstruction; hypothyroidism also can cause rhinitic symptoms [30]. Static and dynamic lesions Nasal valve dysfunction may contribute to symptoms in 13% of adults reporting chronic nasal obstruction [34]. The behavior of the nasal valve as a Starling resistor must be kept in mind when discussing its dysfunction, as well as Poiseuille’s law, which relates airflow to the radius of the nasal passages, raised to the fourth power (Fig. 1) [34]. Dilator muscles of the nose can modulate the size of the nasal valve and can decrease the anterior nasal resistance [21], as previously mentioned. Similar to conditions in the pharyngeal airway, however, it is important to realize that only two variables determine nasal valve closure—the amount of negative pressure generated at the nasal valve and the critical transmural pressure gradient, a function of the mechanical properties of the cartilage and soft tissues. Nasal valve pathology can cause either static or dynamic dysfunction. Static dysfunction is caused by fixed obstruction at the level of the nasal valve, requiring more negative intranasal pressure to generate a given amount of nasal airflow [34]; for example, the attempt to maintain nasal airflow in the setting of small

Nasopharynx Adenoid hypertrophy Tumor Nasopharyngeal CA Hamartoma Nasopharyngeal stenosis Tonsillectomy/adenoidectomy Pharyngoplasty or palatopharyngoplasty Cicatricial bullous pemphigoid Syphilis/treatment Congenital Congenital craniofacial anomalies Choanal atresia Antrochoanal polyps Polyps Cystic fibrosis Asthma Aspirin sensitivity Amyloidosis Cysts Nasal cavity Septum Trauma Polyposis

Location

Soft tissue obstruction (possibly reversible)

Trauma

—

Anterior nasal packing

Septal deviation Congenital craniofacial anomalies

Neuromuscular

Posterior nasal Nasopharyngitis — packing Infectious mononucleosis Nasal syphilis Primary tuberculosis Rhinoscleroma (Klebsiella rhinoscleromatis) Diphtheria Midfacial granuloma Wegener’s granuloma

Foreign body (reversible)

Mucosala

—

Bone/cartilage deformity (fixed)

Structural

Nature of problem

Table 1 Conditions and related factors that may contribute to increased nasal resistance and nasal obstruction

450 W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437–460

Postrhinoplasty Trauma Tip ptosis Cicatricial stenosis

Trauma Polyposis

Postrhinoplasty Anterior nasal Tip ptosis packing Paradoxic lateral crura Congenital craniofacial anomalies

Conchal hypertrophy Anterior nasal Congenital craniofacial packing anomalies

Trauma

Allergic rhinitis Vasomotor rhinitis NARES Infectious rhinitis (viral or bacterial) Rhinitis medica mentosa Reaction to BB, ASA, NSAIDS, and so forth Secondary to DNS or lesions/polyps Trauma Metabolic/endocrine Pregnancy Puberty Hypothyroidism Facial paralysis (zygomaticotemporal division of facial nerve)

—

Congestion may occur secondary to other causes of nasal obstruction, such as neoplastic lesions, idiopathic polyps, or polyps related to cystic fibrosis, asthma, aspirin sensitivity, chronic rhinosinusitis, or allergic rhinitis. A deviated nasal septum may cause a sensation of chronic unilateral nasal congestion or congestion that fluctuates with the nasal cycle and may be associated with compensatory hypertrophy of the contralateral inferior turbinate. Abbreviations: ASA, aspirin; BB, beta-blockers; DNS, deviated nasal septum; NARES, nonallergic rhinitis with eosinophilia syndrome; NSAIDS, nonsteroidal anti-inflammatory drugs. Data from Refs. [21,30,34,38,106].

a

Nasal valves

Turbinates

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437–460 451

452


vestibular lesions such as cysts or minor septal deflections can increase the negative pressure generated at the valve and thus, nasal resistance [21,32]. Conversely, dynamic valvular dysfunction is related to flaccid or absent structural support of the sidewall and results in closure of the nasal valve at lower transmural pressures [34]. Laxity in the soft tissues or cartilage and facial muscle weakness or paralysis may predispose one to such nasal closure [21,32,34].

Treatment modalities Pharmacologic treatment options for rhinitis Decongestants are appropriate in treating nasal obstruction related to rhinitis, and when related to allergies, avoidance of allergens and environmental control are also appropriate. In addition, pharmacotherapy with antihistamines, topical intranasal corticosteroids, mast-cell stabilizers, and immunotherapy also may help [30,31]. Later-generation antihistamines are preferred, because the first-generation (or ‘‘classic’’) antihistamines such as diphenhydramine, chlorpheniramine, and the phenothiazine promethazine are lipophilic and thus sedating; not only may they worsen underlying sleep-disordered breathing but they also may suppress REM sleep and produce a marked compensatory rebound above baseline levels after withdrawal of these agents [30,31]. This rebound has been associated with an increase in both amount and intensity of REM sleep and thus sleep instability and fragmentation [31]. Apparatus-related therapy Nasal dilatation devices directed toward the nasal valve area also have been used to reduce nasal resistance. As such, the effectiveness of internal (eg, Nozovent [Prevancure AB; Va¨stra Fro¨lunda, Sweden]) and external (eg, Breathe Right Nasal Strips [CNS; Bloomington, MN]) dilators has been studied, but studies have been limited by relatively small numbers of subjects and variability in methodology. Several negative studies have been published [85–88]. A study by Kerr et al [89], however, showed that among 10 generally obese (body mass index, 25.9–38.9; mean, 32.0 kg/m2) men with moderate (mean AHI of approximately 20 respiratory events per hour) sleep apnea, six of whom had evidence of chronic nasal obstruction related to septal deviation, narrowed nasal valves, mucosal swelling, or a combination of these factors, nasal resistance decreased in all of those who used a topical nasal vasoconstrictor and internal dilators (vestibular stents). Although treatment was associated with subjective improvement in sleep quality, with a mean drop in nasal resistance (as measured by posterior rhinomanometry) to 73% (P < 0.001), there was no significant improvement in sleep architecture or AHI. There was a reduction in the number of arousals


453

per hour, from 52.4 with placebo to 43.7 with treatment (P < 0.04), however. These findings suggest that there may have been an improvement in upper airway resistance in these patients, because the most important mechanism of arousal in sleep-disordered breathing may be increased respiratory efforts and magnitude of intrapleural pressure swings [90]. Alternatively, more significant changes in AHI may have been detected if the investigators had accounted for other risk factors for sleep-disordered breathing, such as pharyngeal obstruction, body weight, and age [91]. This possibility was addressed by Gosepath et al [91], examined this possibility by studying the effects of Breathe Right nasal strips on RDI among 26 subjects with a history of sleep-disordered breathing and impaired nasal breathing. The subjects were older (mean age, 52 years), and although all had an RDI of 10 per hour or higher, the distribution and mean were not specified; furthermore, the investigators rather unconventionally defined RDI as the sum of apnea index (AI), hypopnea index (HI), and ‘‘index of obstructive snoring.’’ Rhinoscopic examination and clinical assessment of pharyngeal collapsibility (Mu¨ller’s maneuver) were performed, and each subject was studied with overnight polysomnography; most of them also were examined by anterior rhinomanometry and acoustic rhinometry with and without topical decongestion. Although only 19 subjects showed a decrease in RDI, as a group, the average values of both AI and HI did fall significantly (22.8–19.8 [P ¼ 0.08] and 8.6-5.8 [P ¼ 0.013], respectively). The four patients in whom the most dramatic reductions in RDI were seen (to less than 10 per hour) were those who started with low values (RDIs between 10.3 and 16.7 that fell to between 2.2 and 6.3 [58%–81% reductions]), and thus had the mildest disease. Similarly, the average RDI of the participants who did show a reduction in RDI with the nasal strips was lower than that of the groups that did not (27.4 per hour versus 43.5 per hour), suggesting that the patients with more severe sleep-disordered breathing experienced less benefit from the Breathe Right nasal strips. In an attempt to extend this hypothesis to patients with the mildest SRBD, Bahammam et al [13] studied the effects of Breathe Right nasal strips on 18 subjects with the diagnosis of UARS without nasal pathology. However, no esophageal manometry was used, given the risk of sleep disruption and reduction in the nasal cross-sectional area, which could possibly counteract the effect of the treatment [92]. Therefore, the participants were defined as having a ‘‘clinical history of snoring, clinical complaint of excessive daytime sleepiness, and an AHI <15 on original clinical evaluation, and more than five arousals per hour associated with snores, snorts, or brief cessations of breathing that were shorter than accepted criteria for apnea (<10 sec),’’ without specific mention of arousals related to increased respiratory efforts, which is an essential feature of UARS [93]. The subjectsÕ mean RDI was 8.9 per hour. Nevertheless, they were given a ‘‘placebo’’ or regular Breathe Right strips and studied with overnight polysomnography and multiple sleep latency testing. Twelve subjects were men, and most were overweight (mean body

454


mass index of 297.4 kg/m2). Significant increases in nasal cross-sectional area were seen by acoustic rhinometry, and the percentage of stage 1 sleep, expressed as a percentage of total sleep time, was also significantly lower on the treatment nights (7.1% 0.7%) compared with placebo nights (8.6% 0.8%, P ¼ 0.03). Although this finding suggested reduced sleep disruption, no changes could be detected in the AI or in sleepiness by multiple sleep latency testing. External nasal dilators may have an effect on more subtle measures of sleep disruption, such as CAP, however. In a study using Breathe Right strips in nine snorers without subjective nasal congestion who may have had mild sleep-disordered breathing, Scharf et al [94] showed that CAP may be reduced. Although the subjects studied were described as snorers with AHIs of less than five per hour without ‘‘clinically suspected levels of OSA (to make mild snoring the secondary diagnosis),’’ they may have had upper airway resistance or UARS, because esophageal manometry data were not available. As studied for two consecutive nights with or without Breathe Right strips, there was a reduction in CAPR during stage 1 and 2 sleep on the experimental nights compared with the control nights (28.4% 15.7% versus 37.9% 18.4%, P < 0.05). Positive airway pressure therapy and temperature-controlled radiofrequency reduction of turbinate hypertrophy In patients who are being treated with either nasal continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) for sleepdisordered breathing, humidification may increase tolerance of positive airway pressure therapy within the critical first 3 months of therapy. Heated humidification may attenuate the mucosal blood flux associated with the cooling and drying effects of such therapy [16] and may be particularly important in patients with allergic rhinitis [95]. Submucosal temperaturecontrolled radiofrequency reduction of inferior turbinate hypertrophy also may improve CPAP tolerance and adherence [17]. Its role as an alternative to nasal CPAP therapy in mild forms of sleep-disordered breathing requires further study, however [96]. Surgical interventions Although case reports [97,98] have suggested that correction of nasal obstruction such as that due to septal deviation may improve subjective daytime complaints of OSAHS, subsequent surgical studies have not been helpful in assessing the true effectiveness of nasal surgery in the treatment of sleep-disordered breathing, mainly because of insufficient data [76]. Studies have been flawed [10] by the relatively small number of patients studied [99]; the fact that nasal surgery often is associated with other surgical procedures, such as tonsillectomy [100]; and the lack of quantification of associated


455

pharyngeal abnormalities and objective data regarding nasal resistance and respiratory variables such as AHI or RDI [100,101]. Although the use of a strict criterion for surgical success, such as improvement in AHI by at least 50% with an absolute value below 20 per hour has been recommended [102,103], this goal may be difficult to achieve in mild forms of sleepdisordered breathing. Even when attainable in more severe cases of sleepdisordered breathing, such improvement may not be clinically relevant, because daytime sleepiness and sleep fragmentation still may persist [104]. It has been suggested that measures of effectiveness used in assessing other modes of treatment, such as nasal CPAP, be applied to surgical interventions as well [104]. These measures would include assessment of parameters such as microarousals, CAP, and upper airway resistance. Because there is currently no accepted criteria to predict who will benefit from nasal surgery, the study by Series et al [61] suggests that at least in mild sleepdisordered breathing, patients with narrowing of the posterior airway space and increased distance from the mandible to the hyoid bone may be poor candidates for such intervention. Summary It has been 30 years since Cottle suggested that ‘‘sleeping patterns are in great measure dependent on good nasal function’’ [1]. During this time, we have identified the OSAHS and related forms of sleep-disordered breathing such as UARS, and better appreciate the clinical sequelae of recurrent arousals and sleep fragmentation. Yet the exact role that obstructed nasal breathing plays in the pathogenesis of such sleep disorders remains presumptive, and robust clinical studies to corroborate this theory remain elusive; however, patients who may benefit most from correction of nasal obstruction as a sole intervention may be those with the mildest forms of sleep-disordered breathing without other significant predisposing anatomic abnormalities. Clearly, more stringently controlled studies [17,105] are needed, particularly in these types of patients. Until such time, it is reasonable to address issues of nasal obstruction as an adjunct to surgical and nonsurgical treatment in all patients who are diagnosed with a sleep-related breathing disorder. References [1] Cottle MH. Nasal breathing pressures and cardio-pulmonary illness. Eye Ear Nose Throat Mon 1972;51:331–40. [2] Lavie P. Nothing new under the moon: historical accounts of sleep apnea syndrome. Arch Intern Med 1984;144:2025–8. [3] Kryger MH. Fat, sleep and Charles Dickens: literary and medical contributions to the understanding of sleep apnea. Clin Chest Med 1985;6:555–62. [4] Lavie P. Rediscovering the importance of nasal breathing in sleep or, shut your mouth and save your sleep. J Laryngol Otol 1987;101:558–63.

456


[5] American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 1999;22:667–89. [6] Carpenter JE. Mental aberration and attending hypertrophic rhinitis with subacute otitus media. JAMA 1892;19:539–42. [7] Lavie P. Historical note: nasal obstructions, sleep, and mental function. Sleep 1983;6:244–6. [8] Wells WA. Some nervous and mental manifestions occurring in connection with nasal disease. Am J Med Sci 1898;116:677–92. [9] Hill W. On some causes of backwardness and stupidity in children. BMJ 1889;2:711–12. [10] Series F, Pierre SS, Carrier G. Effects of surgical correction of nasal obstruction in the treatment of obstructive sleep apnea. Am Rev Respir Dis 1992;146:1261–5. [11] Malhotra A, White DP. Obstructive sleep apnea. Lancet 2002;360:237–45. [12] Parrino L, Smerieri A, Boselli M, Spaggiari MC, Terzano MG. Sleep reactivity during acute nasal CPAP in obstructive sleep apnea syndrome. Neurology 2000;54:1633–40. [13] Bahammam AS, Tate R, Manfreda J, Kryger MH. Upper airway resistance syndrome: effect of nasal dilation, sleep stage, and sleep position. Sleep 1999;22:592–8. [14] Lafond C, Series F. Influence of nasal obstruction on auto-CPAP behaviour during sleep in sleep apnoea/hypopnoea syndrome. Thorax 1998;53:780–3. [15] Friedman M, Yanyeri H, Lim JW, Landsberg R, Vaidyanathan K, Caldarelli D. Effect of improved nasal breathing on obstructive sleep apnea. Otolaryngol Head Neck Surg 2000; 122:71–4. [16] Zozula R, Rosen R. Compliance with continuous positive airway pressure therapy: assessing and improving treatment outcomes. Curr Opin Pulm Med 2001;7:391–8. [17] Powell NB, Zonato AI, Weaver EM, et al. Radiofrequency treatment of turbinate hypertrophy in subjects using continuous positive airway pressure: a randomized doubleblind, placebo-controlled clinical pilot trial. Laryngoscope 2001;111:1783–90. [18] Cole P, Haight JS. Mechanisms of nasal obstruction in sleep. Laryngoscope 1984;94 (12 Pt 1):1557–9. [19] Schwartz AR, Smith PL, Wise RA. Induction of upper airway occlusion in sleeping individuals with subatmospheric nasal pressure. J Appl Physiol 1988;64:535–42. [20] Gleeson K, Zwillich CW, Bendrick TW, White DP. Effect of inspiratory nasal loading on pharyngeal resistance. J Appl Physiol 1986;60:1882–6. [21] Mirza N, Lanza DC. The nasal airway and obstructed breathing during sleep. Otolaryngol Clin North Am 1999;32:243–62. [22] Houser SM, Mamikoglu B, Aquino BF, Moinuddin R, Corey JP. Acoustic rhinometry findings in patients with mild sleep apnea. Otolaryngol Clin North Am 2002;126:475–80. [23] Boudewyns AN, Heyning PHVD, Backer WAD. Site of upper airway obstruction in obstructive apnoea and influence on sleep stage. Eur Respir J 1997;10:2566–72. [24] Chaban R, Cole P, Hoffstein V. Site of upper airway obstruction in patients with idiopathic obstructive sleep apnea. Laryngoscope 1988;98:641–7. [25] Shepard JW, Thawley SE. Localization of upper airway collapse during sleep in patients with obstructive sleep apnea. Am Rev Respir Dis 1989;141:1350–5. [26] Miyazaki S, Itasaka Y, Ishikawa K, Togawa K. Acoustic analysis of snoring and the site of airway obstruction in sleep related respiratory disorders. Acta Otolaryngol (Stockh), 1998;Suppl 537:47–51. [27] Shellock FG, Schatz CJ, Julien P. Occlusion and narrowing of the pharyngeal airway in obstructive sleep apnea: evaluation by ultrafast spoiled GRASS MR imaging. AJR 1992;158:1019–24. [28] Morrison DL, Launois SH, Isono S, Feroah TR, Whitelaw WA, Remmers JE. Pharyngeal narrowing and closing pressures in patients with obstructive sleep apnea. Am Rev Respir Dis 1993;148:606–11. [29] Papsidero MJ. The role of nasal obstruction in obstructive sleep apnea syndrome. ENT Journal 1993;72:82–4.


457

[30] Corey JP, Houser SM, Ng BA. Nasal congestion: a review of its etiology, evaluation, and treatment. Ear Nose Throat J 2000;79:690–3, 696, 698. [31] Scharf MB, Cohen AP. Diagnostic and treatment implications of nasal obstruction in snoring and obstructive sleep apnea. Ann Allergy Asthma Immunol 1998;81:279–90. [32] Tarabichi M, Fanous N. Finite element analysis of airflow in the nasal valve. Arch Otolaryngol Head Neck Surg 1993;119:638–42. [33] Proctor DF. The upper airways: nasal physiology and defense of the lungs. Am Rev Respir Dis 1977;115:97–129. [34] Schlosser RJ, Park SS. Functional nasal surgery. Otolaryngol Clin North Am 1999;32: 37–51. [35] Haight JSJ, Cole P. The site and function of the nasal valve. Laryngoscope 1983;93:49–55. [36] Bridger GP, Proctor DF. Maximum nasal inspiratory flow and nasal resistance. Ann Otolaryngology 1970;79:481–8. [37] Bruintjes TD, vanOlhen AF, Hillen B. Electromyography of the human nasal muscles. Eur Arch Otorhinolaryngol 1996;253:464–9. [38] Olsen KD, Kern EB. Nasal influences on snoring and obstructive sleep apnea. Mayo Clin Proc 1990;65:1095–105. [39] White DP, Cadieux RJ, Lombard RM. The effects of nasal anesthesia on breathing during sleep. Am Rev Respir Dis 1985;132:972–5. [40] Rubinstein I. Nasal inflammation in patients with obstructive sleep apnea. Laryngoscope 1995;105:175–7. [41] Olopade CO, Christon JA, Zakkar M. Exhaled pentane and nitric oxide levels in patients wtih obstructive sleep apnea. Chest 1997;111:1500–4. [42] Anch AM, Remmers JE, Bunce H. Supraglottic airway resistance in normal subjects and patients with occlusive sleep apnea. J Appl Physiol 1982;53:1158–63. [43] Metes A, Ohki M, Cole P, Haight JS, Hoffstein V. Snoring, apnea and nasal resistance in men and women. J Otolaryngol 1991;20:57–61. [44] Strohl KP, O’Cain CF, Slutsky AS. Alae nasi activation and nasal resistance in healthy subjects. J Appl Physiol 1982;52:1432–7. [45] Williams AJ, Santiago S. The nose and obstructive sleep apnea [editorial]. Chest 1993;104:993a. [46] Atkins M, Tasker V, Clayton N, Stone P, Woodcock A. Nasal resistance in obstructive sleep apnea. Chest 1994;105:1133–5. [47] DeVito A, Berrettini S, Carabelli A, et al. The importance of nasal resistance in obstructive sleep apnea syndrome: a study with positional rhinomanometry. Sleep Breath 2001;5:3–11. [48] Badr MS. Pathophysiology of upper airway obstruction during sleep. Clin Chest Med 1998;19:21–32. [49] Lavie P, Rubin AE. Effects of nasal obstruction on respiration in sleep: evidence of inheritability of sleep apnea proneness. Acta Otolaryngol 1984;97:127–30. [50] Rochester DF, Braun NT. The diaphragm and dyspnea. Am Rev Respir Dis 1979;119: 77–80. [51] Woodson BT, Garancis JC, Toohill RJ. Histopathologic changes in snoring and obstructive sleep apnea syndrome. Laryngoscope 1991;101(12 Pt 1):1318–22. [52] Guilleminault C, Quo SD. Sleep-disordered breathing: a view at the beginning of the new millenium. Dent Clin N Am 2001;45:643–56. [53] Meurice JC, Marc I, Carrier G. Effects of mouth opening on upper airway collapsibility in normal sleeping subjects. Am J Respir Crit Care Med 1996;153:255–9. [54] McNicholas WT, Coffey M, Boyle T. Effects of nasal airflow on breathing during sleep in normal humans. Am Rev Respir Dis 1993;147:620–3. [55] Woodson BT. Predicting which patients will benefit from surgery for obstructive sleep apnea: the ENT exam. Ear Nose Throat J 1999;78:792–5,798–800. [56] Olsen KD, Kern EB, Westbrook PR. Sleep and breathing disturbance secondary to nasal obstruction. Otolaryngol Head Neck Surg 1981;89:804–10.

458


[57] Zwillich CW, Pickett C, Hanson FN, Weil JV. Disturbed sleep and prolonged apnea during nasal obstruction in normal men. Am Rev Respir Dis 1981;124:158–60. [58] Lavie P, Fischel N, Zomer J, Eliaschar I. The effects of partial and complete mechanical occlusion of the nasal passages on sleep structure and breathing in sleep. Acta Otolaryngol 1983;95:161–6. [59] Sher AE. Obstructive sleep apnea syndrome: a complex disorder of the upper airway. Otolaryngol Clin North Am 1990;23:593–608. [60] Suratt PM, Turner BL, Wilhoit SC. Effect of intranasal obstruction on breathing during sleep. Chest 1986;90:324–9. [61] Series F, Pierre SS, Carrier G. Surgical correction of nasal obstruction in the treatment of mild sleep apnoea: importance of cephalometry in predicting outcome. Thorax 1993; 48:360–3. [62] Lofaso F, Coste A, d’Ortho MP, et al. Nasal obstruction as a risk factor for sleep apnoea syndrome. Eur Respir J 2000;16:639–43. [63] Schumacher MJ. Nasal congestion and airway obstruction: the validity of available objective and subjective measures. Curr Allergy Asthma Reports 2002;2:245–51. [64] Wynne JW. Obstruction of the nose and breathing during sleep [editorial]. Chest 1982;82:657–8. [65] Tonkin SL, Gunn TR, Bennet L, Bofel SA, Gunn AJ. A review of the anatomy of the upper airway in early infancy and its possible relevance to SIDS. Early Hum Dev 2002; 66:107–21. [66] Handley GH, Reilly JS. Nasal obstruction in children. Otolaryngol Clin North Am 1989; 22:383–96. [67] McColley SA, Carroll JL, Curtis S. High prevalence of allergic sensitization in children with habitual snoring and obstructive sleep apnea. Chest 1997;111:170–3. [68] Redline S, Tishler PV, Schluchter M, Aylor J, Clark K, Graham G. Risk factors for sleepdisordered breathing in children: associations with obesity, race, and respiratory problems. Am J Respir Crit Care Med 1999;159:1527–32. [69] Lack G. Pediatric allergic rhinitis and comorbid disorders. J Allergy Clin Immunol 2001;108:9S–15S. [70] Kim YK, Kang JH, Yonn KS. Acoustic rhinometric evaluation of nasal cavity and nasopharynx after adenoidectomy and tonsillectomy. Int J Pediatr Otorhinolaryngol 1998;44:215–20. [71] Rizzi M, Onorato J, Andreoli A, et al. Nasal resistances are useful in identifying children with severe obstructive sleep apnea before polysomnography. Int J Pediatr Otorhinolaryngol 2002;65:7–13. [72] Carroll JL, McColley SA, Marcus CL, Curtis S, Loughlin GM. Inability of clinical history to distinguish primary snoring from obstructive sleep apnea syndrome in children. Chest 1995;108:610–8. [73] American Academy of Pediatrics. Clinical practice guidelines: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 2002;109:704–12. [74] Marcus CL. Sleep-disordered breathing in children. Am J Respir Crit Care Med 2001; 164:16–30. [75] Chervin RD, Archbold KH, Dillon JE, et al. Inattention, hyperactivity, and symptoms of sleep-disordered breathing. Pediatrics 2002;109:449–56. [76] Pirsig W, Verse T. Long-term results in the treatment of obstructive sleep apnea. Eur Arch Otolaryngol 2000;257:570–7. [77] Finkelstein Y, Wexler D, Berger G, Nachmany A, Shapiro-Feinberg M, Ophir D. Anatomical basis of sleep-related breathing abnormalities in children with nasal obstruction. Arch Otolaryngol Head Neck Surg 2000;126:593–600. [78] Guilleminault C, Partinen M, Praud JP, Quera-Salva MA, Powell N, Riley R. Morphometric facial changes and obstructive sleep apnea in adolescents. J Pediatr 1989;114:997–9.


459

[79] Smith RM, Gonzalez C. The relationship between nasal obstruction and craniofacial growth. Pediatr Clin North Am 1989;36:1423–34. [80] Cooper BC. Nasorespiratory function and orofacial development. Otolaryngol Clin North Am 1989;22:413–41. [81] Chervin RD, Guilleminault C. Obstructive sleep apnea and related disorders. Neurol Clin 1996;14:583–609. [82] Goldberg AN, Schwab RJ. Sleep apnea,. part I: identifying the patient with sleep apnea—upper airway assessment and physical examination. Otolaryngol Clin North Am 1998;31:919–30. [83] Pincus RL. Nasopharyngeal obstruction. Otolaryngol Clin North Am 1989;22:367–82. [84] Roblin DG, Eccles R. What, if any, is the value of septal surgery? Clin Otolaryngol 2002;27:77–80. [85] Hoijer U, Ejness H, Hender J. The effects of nasal dilatation on snoring and obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 1992;118:281–4. [86] Metes A, Cole P, Hoffstein V, Miljeteig H. Nasal airway dilation and obstructed breathing in sleep. Laryngoscope 1992;102:1053–5. [87] Hoffstein V, Mateika S, Metes A. Effect of nasal dilation on snoring and apneas during different stages of sleep. Sleep 1993;16:360–5. [88] Schonhofer B, Franklin KA, Brunig H, Wehde H, Kohler D. Effect of nasal-valve dilation on obstructive sleep apnea. Chest 2000;118:587–90. [89] Kerr P, Millar T, Buckle P, Kryger M. The importance of nasal resistance in obstructive sleep apnea syndrome. J Otolaryngol 1992;21:189–95. [90] Gleeson K, Zwillich C, White DP. The influence of increasing ventilatory effort on arousal from sleep. Am Rev Respir Dis 1990;142:295–300. [91] Gosepath J, Amedee RG, Romantschuck S, Mann WJ. Breathe Right nasal strips and the respiratory disturbance index in sleep related breathing disorders. Am J Rhinol 1999; 13:385–9. [92] Virkkula P, Silvola J, Lehtonen H, Salmi T, Malmberg H. The effect of esophageal pressure monitoring on nasal airway resistance. Otolaryngol Head Neck Surg 2001; 125:261–4. [93] Wheatley JR. Definition and diagnosis of upper airway resistance syndrome. Sleep 2000;23(Suppl 4):S193–6. [94] Scharf MB, McDannold MD, Zaretsky NT, Hux GT, Brannen DE, Berkowitz DV. Cyclic alternating pattern sequences in non-apneic snorers with and without nasal dilatation. Ear Nose Throat J 1996;75:617–9. [95] Winck JC, Delgado JL, Almeida JM, Marques JA. Heated humidification during nasal continuous positive airway pressure for obstructive sleep apnea syndrome: objective evaluation of efficacy with nasal peak inspiratory flow measurements. Am J Rhinol 2002; 16:175–7. [96] Guilleminault C, Kim Y-d, Palombini L, Li K, Powell N. Upper airway resistance syndrome and its treatment. Sleep 2000;23(Suppl 4):S197–200. [97] Heimer D, Scharf SM, Liberman A, Lavie P. Sleep apnea syndrome treated by repair of deviated nasal septum. Chest 1983;84:184–5. [98] Irvine BW, Dayal VS, Phillipson EA. Sleep apnea due to nasal valve obstruction. J Otolaryngol 1984;13:37–8. [99] Dayal VS, Phillipson EA. Nasal surgery in the management of sleep apnea. Ann Otol Rhinol Laryngol 1985;94:550–4. [100] Rubin AH, Eliaschar I, Joachim Z, Alroy G, Lavie P. Effects of nasal surgery and tonsillectomy on sleep apnea. Bull Eur Physiopathol Respir 1983;19:612–5. [101] Lavie P, Zomer J, Eliaschar I, et al. Excessive daytime sleepiness and insomnia: association with deviated nasal septum and nocturnal breathing disorders. Arch Otolaryngol Head Neck Surg 1982;108:373–7.

460


[102] Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper airway in adults with obstructive sleep apnea syndrome. Sleep 1996;19:156–77. [103] Verse T, Maurer JT, Pirsig W. Effect of nasal surgery on sleep-related breathing disorders. Laryngoscope 2002;112:64–8. [104] Pepin JL, Veale D, Mayer P, Bettega G, Wuyam B, Levy P. Critical analysis of the results of surgery in the treatment of snoring upper airway resistance syndrome (UARS), and obstructive sleep apnea (OSA). Sleep 1996;19(9 Suppl):S90–100. [105] Sackett DL. Rules of evidence and clinical recommendations for the management of patients. Can J Cardiol 1993;9:487–9. [106] Oneal RM, Beil RJ, Schlesinger J. Surgical anatomy of the nose. Otolaryngol Clin N Am 1999;32:145–81.


Video sleep nasendoscopy: the Hong Kong experience V.J. Abdullah, FRCS, FHKAMa,*, Y.K. Wing, MRCPsych, FHKAMb, C.A. van Hasselt, FRCS, FHKAMa a

Division of Otolaryngology, Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong b Department of Psychiatry, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong

The study of upper airway dynamics in obstructive sleep apnea syndrome (OSAS) has always posed a challenge to the interested clinician. Until the dynamics of obstructive sleep apnea are well understood, the treatment options cannot be comprehensive. To date, continuous positive airway pressure (CPAP) remains the most efficacious first-line treatment because it stents open the entire upper airway without a need to know. Many patients are, nevertheless, not amenable to its lifelong use. They should not be disregarded, particularly if surgical or nonsurgical options other than CPAP can alleviate, if not cure, the symptoms caused by their condition. The much-disfavored tracheostomy, with its associated problems, always helps in treating OSAS and has achieved the best long-term survival rate [1,2]. This finding confirms the importance of understanding the dynamics of the upper airway above the glottis in OSAS, especially if effective surgery is to be designed. From the surgical viewpoint, the clear establishment of the obstructive sites is crucial for the planning of effective treatment, if it is available. The Mu¨ller maneuver, once a popular technique of selecting patients for uvulopalatopharyngoplasty [3], is at best an easy-to-perform estimation of tissue collapse in the upper airway under inspiratory suction. The findings may differ quite dramatically from the sleep-breathing situation [4]. Cine CT

* Corresponding author. Department of ENT, NTEC Chinese University of Hong Kong, Alice Ho Miu Ling Nethersole Hospital, 11 Chuen On Road, Tai Po, New Territories, Hong Kong SAR. E-mail address: [email protected] 0030-6665/03/$ - see front matter Ó 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00176-7

462

V.J. Abdullah et al / Otolaryngol Clin N Am 36 (2003) 461–471

and cine MRI are ideal but not practicable methods in terms of costs, the difficulties in the overnight study of a patient with OSAS in a confined space, and the problems of irradiation in CT. Through-the-night inspection of the upper airway of the sleeping patient with the fiberoptic nasopharyngeal endoscope is an ideal but time- and manpower-consuming technique. It is seldom well tolerated and often results in significantly disturbing the normal and abnormal sleep patterns. The surgeon naturally prefers to see the actual events during sleep-breathing difficulties to guide his or her plans for the appropriate surgical intervention. Video sleep nasendoscopy (VSE) [5] in the (albeit simulated) sleep-breathing situation is the authors’ preferred technique for assessing surgical candidates. It is probably the most accurate assessment of the situation or the most effective in revealing the worst situation that stands to be corrected. The indications In the authors’ establishment, VSE is reserved for research protocols, selected snorers, and the OSAS surgical candidates as selected by the multidisciplinary team, which comprises respiratory physicians, psychiatrists, neurologists, otolaryngologists, pediatricians (for the pediatric cases), and physiotherapists for the weight-control program for those who are obese. It is not used for the diagnosis of OSAS, and it is interpreted in the light of a full night’s polysomnographic (PSG) sleep study. The authors’ criteria for surgical intervention in adult patients are as follows: they must be PSG-proven snorers; patients with upper airway resistance syndrome; patients with OSAS and a body mass index (BMI) of less than 30; and patients with correctable craniofacial deficits, such as ‘‘South China chin,’’ retrognathia that is common in the Cantonese population in the authors’ locality. At the authors’ institution, surgical candidates should be less than 60 years of age. All surgical candidates are required to have tried CPAP with the present-day selection of masks for at least 6 months. The procedures performed at the authors’ institution for the different VSE-established sites of obstruction in patients with OSAS are summarized in Table 1. Video sleep nasendoscopy is useful only if there is a surgical procedure to treat effectively the diagnosed sites of obstruction. Many medium- and long-term failures of surgical treatment lie in the fundamental design of the surgical procedure. The stiffness or extra room achieved by scarring, tightening, or widening procedures are unable to counter the natural laxity of pharyngeal tissue, which yields to the upper airway negative pressure with time, resulting in re-obstruction. In obese patients with multiple medical problems and multilevel obstruction, the authors’ experience with surgery has been disappointing. These patients are not subjected to VSE; they are patiently counseled and recommended for treatment with CPAP. Bilevel positive airway pressure (BIPAP) is recommended for patients with obesity hypoventilation who are under the supervision of respiratory physicians, or


463

Table 1 Surgical procedures performed for different sites of obstructiona Nasal obstruction Septoplasty Turbinoplasty Functional endoscopic sinus surgery (FESS) for nasal polyposis Velopharyngeal obstruction Limited uvulopalatopharyngoplasty (tonsillectomy, uvulectomy, and tonsillar pillar suture) Tonsillar obstruction Tonsillectomy Lateral pharyngeal wall Tonsillectomy and pillar suture Tongue base obstruction Hyoid hitch Phase I surgery for nonreceding chin Sliding genioplasty for receding chin Radiofrequency tongue base reduction (under evaluation) Distraction osteogenesis under evaluation in children Phase II surgery not performed to date Epiglottic flop One-third–One-half laser epiglottic trim a

All procedures performed at the Prince of Wales Hospital, Chinese University of Hong Kong.

a simple tracheostomy can be offered. In the authors’ unit, VSE also has been assessed for the establishment of CPAP level and has proven to be of great promise as an efficient and cost-effective means of CPAP titration. The procedure of video sleep nasendoscopy Patients who are surgical candidates are admitted as ‘‘day cases.’’ An intravenous site is established for access during the procedure. The patient is monitored for transcutaneous oxygen saturation, electrocardiogram abnormalities, and blood pressure. At present, simultaneous PSG and electroencephalographic monitoring is used for research protocols in the authors’ unit. The sleep endoscopy laboratory is equipped with oxygen, suction, a conveniently adjustable BIPAP/CPAP machine, and the standard resuscitation equipment. The more patent nostril is selected, and 10% xylocaine spray is delivered to the nasal cavity and the nasopharynx using a long cannula. A flexible nasopharyngoscopy with the patient awake is performed to exclude static obstructive lesion. A Mu¨ller maneuver is performed for correlation. Four milligrams of midazolam are given as an induction bolus with saline flush. The light is dimmed, and the patient is encouraged to sleep. The dose is increased 1 mg at a time with saline flush until the patient sleeps. A minimal 5-minute wait is recommended after the first bolus and between increments. Increments are needed only if the patient

464


shows no sign of sleep onset. The ceiling dose in the authors’ unit is limited to 7.5 mg intravenously, after which point the patient is deemed to have failed sedation. The average dose in the authors’ experience is 0.06 mg/kg in OSAS cases. The dose for snorers is variable, and the authors have applied the same ceiling dose of 7.5 mg for this group of patients. Once the patient is asleep, obstructive episodes are observed and the endoscopic examination is carried out after at least two episodes or cycles of obstruction and arousal. If the oxygen saturation (SaO2) should fall below 70%, the CPAP mask is applied and examination is resumed after 5 minutes of unobstructed breathing. The endoscopic examination is performed using an Olympus P4 (Olympus Optical Co. Ltd., Japan) flexible nasopharyngoscope inserted through the anesthetized nostril. In the location of obstructive sites, attention is paid to the following levels: Soft palate Lateral pharyngeal wall Tonsils Tongue base Epiglottis Hypopharynx (the pyriform fossae squashing in around the larynx) Once the level or levels of obstruction are established, the patient is reversed with the slow injection of flumazenil (Anexate) intravenously (300– 500 lg). It is important to be aware that the mean elimination half-life of flumazenil, which is 35.5 minutes, is shorter than that of midazolam, which is 107 minutes. Nevertheless, it helps to shorten the duration of sedation. The patient then is turned on his or her side, and the airway is monitored in the recovery area and then in the high-dependency area of the ward. Snorers Snorers are the most difficult group of patients to sedate optimally for viewing asleep because they are usually not hypersomnolent. They are easy to oversedate. The authors are performing less VSEs in this group of patients because most would benefit from any of the present range of soft palate and uvula procedures. When the authors do perform VSE in this group of patients to tailor-make surgical procedures after their PSGs, the patients are sedated with a protocol similar to that of patients with OSAS, with the midazolam ceiling dose set at 7.5 mg, and no obstructive or desaturation events should be seen throughout the procedure. Tables 2, 3, and 4 summarize the authors’ study of video-captured nasoendoscopic findings of snore-generation sites in 30 successfully sedated snorers (28 men and 2 women; mean age, 41.4 years). It was interesting that in this study, 75% (n ¼ 9) with single-site snoring had the snore generated by the soft palate, and 54% (n ¼ 7) of the two-site snorers had soft palate plus epiglottic snores. Epiglottic and tonsillar


465

Table 2 Summary of snore-generation sites by VSE recordings in 30 snorers Snore-generation sites

No. of patients

Percentage of total

Soft palate Tonsils Tongue base Posterior pharyngeal wall Epiglottis

26 12 4 2 12

87% 40% 13% 6.5% 40%

vibrations seem to feature significantly in snore generation. In the authors’ experience with VSE in patients with OSAS, epiglottic flutter commonly is seen as the main source of the loud wake-up snore after the obstructive cycle. These findings also support the concept that the use of palatalstiffening procedures for snorers is likely to be effective in most patients.

Obstructive sleep apnea syndrome This group of patients is easy to sedate, and most will sleep with the initial 4 mg of midazolam with their hypersomnolence. Their respiratory events have to be watched carefully throughout the procedure, and CPAP should be administered to them or their sedation should be reversed with flumazenil if SaO2 levels fall below 70% or if arrhythmic episodes develop other than the usual mild cyclical slowing and recovery of heart rate with the obstructive episodes. The authors recommend that one waits for two obstructive cycles before viewing the events. In experienced hands, the viewing usually takes no longer than 15 minutes. With the help of intermittent CPAP, sleep stage–correlated events can be recorded when simultaneous PSG is used for study purposes. The authors are in the process of data collection for this group of patients. Between October of 1992 and January of 2002, the authors performed 893 sleep nasoendoscopy procedures for different research and investigation protocols and did not experience an adverse event. The authors’ data on patients with OSAS indicated that 87% of the patients had multilevel obstruction. In a recent study the authors conducted on 93 patients with a mean respiratory disturbance index of 48.4 Table 3 Summary of single/multiple snore-generation sites by VSE recordings in 30 snorers No. of snoring sites

No. of patients

Percentage of total

Single site Two sites Three sites Four sites Five sites

12 13 3 1 1

40% 44% 10% 3% 3%

466


Table 4 The different combinations of snore-generation sites in 30 patients studied with the use of VSE recordings Single site

Two sites

Three sites

Four sites

Five sites

SP 9 T3

SP+T 3 SP+E 7 T+PP 1 SP+TB 1 SP+E 1

SP+T+TB 1 SP+T+E 2

SP+T+TB+E 1

SP+T+TB+PP+E 1

Abbreviations: SP, soft palate; T, tonsils; PP, posterior pharyngeal wall; TB, tongue base; E, epiglottis.

(respiratory disturbance index range, 15–89) selected for surgical assessment, the levels of obstruction and their different combinations were analyzed in detail. Of the 93 patients, four patients (4.3%) failed sedation. The 89 patients analyzed comprised 11 women (mean age, 46.9 years) and 78 men (mean age, 39.7 years). The mean BMI of the 89 patients was 27.2; the mean BMI for the female patients was 26.7 and that for the male patients was 27.4. The number and percentages of single/multiple-site obstruction and the mean BMI of each subgroup are presented in Table 5. As can be seen from the findings, the percentage of patients with singlesite obstruction is low, at 14.61%. Despite the observable trend of a higher BMI being associated with four or more sites of obstruction as compared with single-site obstruction, no conclusion can be fairly drawn from this select group of patients. Many of these potential surgical candidates with lower BMIs would have obvious or subtle facial skeletal deficits as the main contributor to their OSAS. Aside from one patient with a respiratory disturbance index of 15 with two-site obstruction adequately treated with phase I surgery, all patients were in the moderate/severe obstructive sleep apnea range. Interestingly, the number of obstructive levels does not necessarily reflect the severity of OSAS and vice versa. In the selected few with single-level tonsillar obstruction, a simple tonsillectomy is curative for severe OSAS. In the authors’ institution, many of the milder cases are not seen because they are referred for dental devices or CPAP at lower Table 5 The summary of VSE findings regarding single/multiple-site obstruction in patients with OSAS selected for surgery No. of obstructive sites

No. of patients

Percentages of total

Mean BMI

Single site Two obstructive sites Three obstructive sites Four obstructive sites Five obstructive sites Six obstructive sites

13 16 17 20 12 11

14.61% 17.98% 19.10% 22.47% 13.48% 12.36%

23.8 25.5 24.4 28.3 25.4 27.2


467

acceptable pressures, although they may be the best candidates for surgery. The different obstructive sites and their combinations are listed in Table 6. As is evident from these findings, the three obstructive sites that are featured with equal frequency are the soft palate, the lateral pharyngeal wall, and the tongue base. Within the present-day surgical spectrum, the lateral pharyngeal wall at the oropharyngeal level is the least-attended-to site. The tonsils usually are not the source of the problem. This is the area that is most difficult to treat or to treat with any sustained effect. The authors have observed side-to-side, concentric, and oblique collapse of this region. In terms of single-site obstruction, the soft palate is obstructed as often as the tongue base. The hypopharynx, interpreted as the pyriform fossa squeezing concentrically around the larynx, interestingly is never featured as a single-site obstruction. This level of collapse is likely to be a secondary effect of higher-level obstruction. The authors’ Mu¨ller maneuvers correlated poorly with the VSE findings. The different combinations of obstructive sites are challenging to the interested surgeon. It is the humbling truth that the lasting cure for all these levels of obstruction is not necessarily in place at this point in time. The continued study of the upper airway dynamics is an important adjunct to the fine-tuning of present-day surgical procedures and the design of new procedures for OSAS. Video sleep nasendoscopy and continuous positive airway pressure titration Video sleep nasendoscopy can be used to establish the CPAP pressure in patients with OSAS. This procedure can be conveniently performed at the end of the VSE examination by placing a CPAP mask gently over the nose of the patient, with the flexible endoscope in situ. Despite the presence of the endoscope, a seal can be achieved easily (Fig. 1). The authors have a picturein-picture oximetric tracing on the video monitor screen to facilitate pressure establishment while watching the changes in the upper airway. The aim is to achieve unobstructed breathing at the lowest level of CPAP pressure with minimal snoring. It is interesting that a large airway lumen is not usually necessary to achieve this goal in most of the authors’ patients. In the authors’ study of 43 cases (40 men and 3 women), a 67% precise correlation of established CPAP pressure values was achieved using the authors’ technique when compared with those methods established manually overnight in the sleep laboratory. If 1 cm H2O is accepted as the error margin, a 77% correlation is achieved, and 90% correlation is achieved if 2 cm H2O is the accepted error margin. The technique is simple and quick. It is still the authors’ preference to titrate CPAP pressure manually overnight in the sleep laboratory. The authors have found this technique to be more reliable than the autotitrators. The VSE technique, nevertheless, can be a cost-effective method of CPAP titration when perfected, because it takes no longer than 10 minutes to perform.

I

Palate I+II I+II+III I+II+IV I+II+V I+II+VI I+II+III+IV I+II+III+V I+II+III+VI I+II+IV+V I+II+IV+VI I+II+V+VI I+II+III+IV+V I+II+III+IV+VI I+II+III+V+VI I+II+IV+V+VI I+II+III+IV+V+VI

4.49% 4.49% 6.74% 5.62% 1.12%

7.87% 2.25% 2.25% 4.49% 3.37%

3.37% 4.49%

5.62% 12.3%

4 4 6 5 1

7 2 2 4 3 0 3 4

5 11

I+III I+III+IV I+III+V I+III+VI I+III+IV+V I+III+IV+VI I+III+V+VI I+III+IV+V+VI

Site combinations, number of patients, and percentages Site No. Percentage Site

100%

22.8% 21.2% 13.6% 20.5% 12.3% 9.6%

69 64 41 62 37 29

I II III IV V VI

Palate Lateral pharynx Tonsil Tongue base Epiglottis Hypopharynx

Percentage

Obstruction sites involved (total, 302) Site No.

0 0 0 0 0 1 0 0 1.12%

I+IV I+IV+V I+IV+VI I+IV+V+VI

No. Percentage Site 5 1 0 0

5.62% 1.12%

1.12%

No. Percentage I+V 1 I+VI 0 I+V+VI 0

No. Percentage Site

Table 6 The obstructive sites for surgical assessment and the different site combinations as seen in VSE for 89 patients 468 V.J. Abdullah et al / Otolaryngol Clin N Am 36 (2003) 461–471

Lateral pharynx II+III II+III+IV II+III+V II+III+VI II+III+IV+V II+III+IV+VI

Tonsil III+IV III+IV+V III+IV+VI III+IV+V+VI

Tongue base IV+V IV+V+VI

Epiglottis V+VI

Hypopharynx

II

III

IV

V

VI

0

2 0

4 3 1

1 1 0 0 0

2 1 0 0 0 1 0

2.25%

4.49% 3.37% 1.12%

1.12% 1.12%

1.12%

2.25% 1.12%

IV+VI

III+V III+VI III+V+VI

II+IV II+IV+V II+IV+VI II+V+VI II+IV+V+VI

0

1 0 0

0 1 2 0 0

1.12%

1.12% 2.25%

II+V II+VI II+V+VI

0 0 0 V.J. Abdullah et al / Otolaryngol Clin N Am 36 (2003) 461–471 469

470


Fig. 1. Continuous positive airway pressure mask on the nose and endoscope for VSE-guided CPAP titration.

The future of video sleep nasendoscopy Ever since Croft and Pringle described their technique of sleep nasendoscopy [5], reception has been mixed. Criticisms were generated by the disappointing results of the once-popular uvulopalatopharyngoplasty [6,7] for which this technique was used to select the appropriate candidates for the procedure. The second reason for skepticism is the use of sedation in VSE. Sedation is unnatural sleep and may relax the tongue muscles, thus worsening the pharyngeal collapse. Uvulopalatopharyngoplasty failed because of its design—the created scar lies in a region that is massaged constantly by the act of swallowing. The stiffness could not possibly last for long. Uvulopalatopharyngoplasty also fell into disrepute because only a few patients with OSAS have single-site obstruction at the soft palate, and this operation was once performed for all patients with OSAS. Different agents have been used for sleep endoscopic examination: halothane in children [8], midazolam [5], diazepam [9], and propofol [10]. The Osaka group evaluated diazepam-induced sleep nasendoscopy under PSG control in 50 patients. The non–rapid-eye-movement parameters were observed to be equal to those of their nocturnal PSG, and the only difference was in the duration of rapid-eye-movement sleep [9]. Supporters of VSE for surgical evaluation are more than a few [11,12]. In the days to come, the optimal sedation for sleep endoscopy will require PSG-controlled evaluation. Surface electromyography would help to clarify the suspected tongue-base relaxation effect. The


471

authors believe that the small, controlled dose used in the protocol would be hypnotic in the hypersomnolent patients with OSAS rather than musclerelaxing. Polysomnographic data are being collected for midazolam. The authors’ 10-year experience with the use of VSE in more than 800 cases supports its safety, if it is performed correctly. At present, however, sleep nasendoscopy should be used only for surgical evaluation, which should be interpreted in the light of a nocturnal PSG. Through a simulated sleepbreathing situation, sleep nasendoscopy undoubtedly provides quality information on the upper airway dynamics that is closest to reflecting the true situation in a cost-effective manner. To the surgeon, this information is invaluable.

References [1] Partinen M, Jamieson A, Guilleminault C. Long term outcome for obstructive sleep apnea syndrome patients: mortality. Chest 1989;96:703–4. [2] Guilleminault C, Simmons FB, Motta J, Cummiskey J, Rosekind M, Schroeder JS, et al. Obstructive sleep apnea syndrome and tracheostomy: long-term follow-up experience. Arch Intern Med 1981;141:985–8. [3] Sher AE, Thorpy MJ, Spielman AJ, Burack B, Mcgregor PA. Predictive value of Muller manoeuvre in selection of patients for uvulopalatopharyngoplasty. Laryngoscope 1985; 95:1483–7. [4] Pringle MB, Croft CB. A comparison of sleep nasendoscopy and the muller manoeuvre. Clin Otolaryngol 1991;16:559–62. [5] Croft CB, Pringle M. Sleep nasendoscopy: a technique of assessment in snoring and obstructive sleep apnoea. Clin Otolaryngol 1991;16:504–9. [6] Fujita S, Conway W, Zorick F, Roth T. Surgical correction of anatomic abnormalities in obstructive sleep apnea syndrome: uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg 1981;89:923–34. [7] Fujita S. UPPP for sleep apnoea and snoring. Ear Nose Throat J 1984;63:73–86. [8] Croft CB, Thomson HG, Samuels MP, Southall DP. Endoscopic evaluation and treatment of sleep-associated upper airway obstruction in infants and young children. Clin Otolaryngol 1990;15:209–16. [9] Sadaoka T, Kakitsuba N, Fujiwara Y, Kanai R, Takahashi H. The value of sleep nasendoscopy in the evaluation of patients with suspected sleep related breathing disorders. Clin Otolaryngol 1996;21:485–9. [10] Roblin G, Williams AR, Whittet H. Target-controlled infusion in sleep endoscopy. Laryngoscope 2001;111:175–6. [11] Camilleri AE, Ramamurthy L, Jones PH. Sleep nasendoscopy: what benefit to the management of snorers? J Laryngol Otol 1995;109:1163–6. [12] Takeda K. Sleep nasendoscopy in the selection of surgical treatments for simple snoring and sleep apnea syndrome. Journal of the Medical Society of Toho University 1998; 45:250–60.


Radiofrequency techniques in the treatment of sleep-disordered breathing Robert J. Troell, MD Plastic Surgery Institute, 653 North Town Center Drive, Suite 308, Las Vegas, NV 89144, USA

The pathophysiology of sleep-disordered breathing is collapse or obstruction of the upper airway during sleep. This obstruction may occur at any site along the upper airway passages to include the nasal cavity, nasopharynx, oropharynx, hypopharynx, and larynx. Diagnosis requires a nocturnal polysomnogram to document the presence and severity of sleepdisordered breathing. The presurgical evaluation includes a comprehensive head-and-neck physical examination, fiberoptic nasopharyngoscopy, and lateral cephalometric to determine the site or sites of upper airway obstruction. This analysis is essential in directing surgical therapy in a site-specific approach. Numerous surgical procedures have been developed to address each of these sites of obstruction and have offered the surgeon an armamentarium of options, each with its own set of advantages, disadvantages, and success rates. Radiofrequency (RF) tissue volumetric reduction was developed to reduce tongue-base obstruction by way of an outpatient, minimally invasive procedure using local anesthesia and causing minimal discomfort with a low complication rate. The research to bring this technique to fruition demonstrated the usefulness of temperature-controlled RF for other areas of the upper airway. Radiofrequency may be used to treat nasal obstruction by reducing the size of the inferior turbinate. Soft palatal reduction is an alternative treatment for primary snoring, upper airway resistance syndrome, and mild obstructive sleep apnea syndrome. The current medical information reviewing the use of RF in tissue volumetric reduction in the upper airway for nasal obstruction, primary snoring, and sleep-disordered breathing is reviewed.

E-mail address: [email protected] 0030-6665/03/$ - see front matter Ó 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00177-9

474

R.J. Troell / Otolaryngol Clin N Am 36 (2003) 473–493

Background and biophysics of radiofrequency The RF energy ablation of soft tissues has been applied successfully, in the past, to humans by specialists in the fields of cardiology, neurology, oncology, and urology [1–4]. Temperature-controlled RF delivers RF at 460 kHz by a high-frequency alternating current flow into the tissue, creating ionic agitation. This ionic agitation heats the tissue and as the temperature rises higher than 47 C, protein coagulation and tissue necrosis ensue. In the first study evaluating RF for sleep-disordered breathing, a porcine study [5] evaluated the relationship of lesion size to total RF energy delivery and subsequent tissue volume reduction. The maximum lesion size is two thirds the diameter of the RF electrode or approximately 7 mm, and the maximum length of the lesion is between 1.5 to 1.75 cm (Fig. 1). Heat is transported by way of conduction to tissue farther away from the electrode and extends the size of the lesion. The computer algorithm controls the power to maximize the lesion size, resulting in tissue coagulation with no charring. The healing process was analyzed through a serial histologic analysis in the porcine model and demonstrated favorable wound healing with a well-defined lesion after 24 hours, with an acute inflammatory response and edematous response. Collagen deposition begins approximately 12 days after injury, and at 3 weeks, chronic inflammation, fibrosis, and tissue volume reduction from scar contracture occur. The first human clinical study evaluating the use of RF was in the soft palate for snoring and sleep-disordered breathing, and the investigators

Fig. 1. Biophysical properties of RF.


475

concluded that the technique was safe with minimal complications. Bleeding, infection, speech disturbances, and swallowing problems were not observed. Results of RF for snoring reduction revealed that the pretreatment snoring level was reduced by an overall mean of 77% [6]. The safety and efficacy reported in the previous animal study were confirmed in the human palate.

Radiofrequency device The medical RF device (Gyrus ENT LLC, Memphis, TN) is delivered at 460 kHz using an RF generator with custom-fabricated needle electrodes. The essential RF energy parameters of power (watts), temperature limits (Celsius), resistance (Ohms), treatment time (seconds), and total energy delivery in joules (watt seconds) are controlled by a computer algorithm. The necessary feedback for temperature adjustment is provided by multiple microthermocouples embedded along the electrode. The 22-gauge RF electrodes have a 10-mm active tip. A protective thermal sheath is used on the proximal portion of the electrode to eliminate surface damage. The maximum temperature gradient is regulated to less than 90 C, with a target temperature between 80 C to 85 C. The computer algorithm maximizes the RF lesion size (Fig. 2).

Fig. 2. Radiofrequency factors affecting lesion size.

476


Treatment philosophy A full disclosure to the patient describing the available procedures, the success rates, the potential risks and complications, and the possibility of a staged surgical approach or multiple procedures fathers good medicine and a confident patient-physician relationship. The extent of surgery is mediated by the patient’s acceptance, severity of symptoms, severity of objective obstruction, level of upper airway collapse, and the severity of the site of obstruction. The philosophy of ‘‘treatment to cure’’ mandates follow-up on all procedures. The systemic presurgical evaluation in sleep-disordered breathing identifies areas of airway collapse or obstruction, logically directing surgical treatment to these site-specific areas.

Presurgical evaluation Although the etiology of sleep-disordered breathing is still poorly understood, it is clear that there exist specific anatomic abnormalities that obstruct the upper airway during sleep. The three major areas of obstruction are the nose, the palate, and the hypopharynx. Fujita et al [7] described the areas of collapse as retropalatal (type I), retropalatal and retrolingual (type II), or solely retrolingual (type III). An anatomic obstruction at one or all of these levels may create increased airway resistance and varying degrees of sleep-related obstruction. It is impossible to direct therapy logically without isolating the area of obstruction; unfortunately, it is not always possible preoperatively to define the exact area of obstruction. There are numerous radiologic tests available to aid in determining the suspected sites of obstruction preoperatively. The author’s presurgical evaluation includes a nocturnal polysomnography, a comprehensive head-and-neck physical examination, fiberoptic nasopharyngoscopy with the Mu¨ller maneuver, and a lateral cephalometric radiograph.

Classification of disease severity The understanding of the classification of sleep-disordered breathing is important in communicating with other health professionals. Primary snoring An apnea-hypopnea index (AHI) of less than five events per hour of sleep with no oxygen saturation (SaO2) less than 90% during sleep or a peak negative end-inspiratory esophageal pressure or inspiratory nadir (Pes) of less negative than 10 cm H2O. These patients do not report excessive daytime sleepiness.


477

Upper airway resistance syndrome An AHI of less than five events per hour of sleep with an SaO2 of greater than or equal to 90% during total sleep time and an inspiratory nadir Pes more negative than 10 cm H2O. Patients without an esophageal pressure monitor displayed frequent arousals associated with snoring or increased diaphragmatic electromyogram activity. Two thirds of these patients snore, and all have an accompanying complaint of excessive daytime sleepiness. Obstructive sleep apnea syndrome An AHI of greater than five events per hour of sleep. These patients usually have accompanying oxyhemoglobin desaturations below 90% and neurobehavioral symptoms, most commonly excessive daytime sleepiness. Review of nasal obstruction Nasal obstruction may be the primary complaint or it may be a factor in producing primary snoring or sleep-disordered breathing. The pathophysiology of nasal obstruction causing upper airway collapse is an increased nasal resistance, an increased velocity of air flow, an increased negative intraluminal pressure, and resultant partial obstruction and vibration of tissues of the upper airway predisposed to collapse, including the soft palate, tongue, and lateral pharyngeal walls. Nasal obstruction may be caused by nasal rim or nasal valve collapse, septal deviation, adenoid hypertrophy, nasal polyps or tumors, and inferior turbinate hypertrophy. Patients with mild sleep-disordered breathing with an AHI less than 15 may be treated successfully with nasal surgery alone. Nasal surgery may improve the sleep study parameters in patients with obstructive sleep apnea of moderate or severe disease, but it will not successfully treat these patients. If inferior turbinate hypertrophy is the cause of the nasal obstruction, RF is an excellent treatment modality. The technique can be performed on an outpatient basis with local anesthesia, with a minimal risk of post-treatment complications and minimal discomfort. Performing nasal surgery simultaneously with other procedures of the upper airway in patients other than those with mild disease may increase the risk of airway compromise. The production of significant postoperative edema or the use of nasal packing prevents the use of nasal continuous positive airway pressure (CPAP), which is used to stent the airway open during sleep-induced upper airway collapse. Nasal septal deviation, turbinate hypertrophy, and nasal ala and valve collapse are corrected by septoplasty, turbinoplasty, and nasal valve cartilage implants, respectively. Adenoid hypertrophy is treated by adenoidectomy. Nasal obstruction may be addressed in a staged fashion 6 to 8 weeks postoperatively from the first phase of airway reconstruction to allow

478


adequate healing of the procedures most likely to remedy their disease. It also may be performed initially to provide a patient with the best possibility to tolerate nasal CPAP in those with significant nasal obstruction. In patients with mild severity of sleep-disordered breathing, nasal surgery may be combined with soft palatal surgery, but this approach is not recommended in those patients with moderate or severe disease, because of the risk of the patient not being able to use nasal CPAP in the immediate postoperative period, when the upper airway swelling is at its height. The rationale for nasal surgery is to improve nasal patency, which establishes physiologic breathing and minimizes oral breathing during sleep. Oral breathing during sleep causes the tongue to be positioned posteriorly, increasing the risk of upper airway obstruction. Also, resolving nasal obstruction reduces nasal resistance and improves the negative intraluminal pressure, which generates upper airway collapse. Inferior turbinate radiofrequency indications Nasal obstruction is caused by inferior turbinate enlargement. There are numerous other methods of turbinate reduction that are available alternatives, including the following: Inferior turbinate reduction techniques 1. Traditional total turbinectomy 2. Traditional partial turbinectomy 3. Submucous resection 4. Submucous diathermy 5. Cryotherapy 6. Laser vaporization 7. Coblation 8. RF Radiofrequency can be used along the entire length of the inferior turbinate, depending on the location and magnitude of the turbinate hypertrophy. This technique has been attempted by the author for the middle turbinate, but because the thickness of the submucosa is much thinner than the inferior turbinate, direct surgical excision is the preferred technique for a concha bollosum or middle turbinate hypertrophy. Surgical technique of inferior turbinate radiofrequency Radiofrequency of the inferior turbinate can be performed on an outpatient basis or in the operating room associated with other operative procedures, such as a nasal septoplasty. In an outpatient setting, the patient is placed in the sitting position. The anterior nasal cavity is anesthetized with a topical local anesthetic without epinephrine and then cotton pledgets with the same solution are placed along the anterior and middle aspects of the


479

inferior turbinate. After approximately 5 minutes, the anterior aspect of the inferior turbinate is injected with between 3 to 5 mL of 1% or 2% lidocaine without epinephrine. The injection provides anesthesia and enlarges the diameter of the turbinate to prevent mucosal injury while the RF energy is being delivered. Between 350 to 550 J of energy are delivered to the anterior and, if required, middle aspects of the inferior turbinate. After the probe is removed, a cotton pledget with oxymetazoline (HC 0.05%) is placed along the inferior turbinate for hemostasis. Inferior turbinate radiofrequency results The initial human study [8] evaluating the efficacy of RF for the treatment of nasal obstruction caused by inferior turbinate hypertrophy was a prospective nonrandomized study of 22 adult volunteers (18 men). The mean age was 41.1 years 10.7. The subjects were diagnosed with nasal obstruction solely from inferior turbinate hypertrophy that had failed to respond to conservative medical management. A mean RF energy delivery per treatment was 382 J 102, with a mean temperature of 77 C 8.4 and mean duration of RF energy of 102.9 minutes 57. A subjective visual analog score (VAS) of nasal obstruction was completed 8 weeks after treatment, with 21 of 22 patients (95%) having improved nasal symptoms. The patients experienced mild edema for 24 to 48 hours after treatment, and 20 of 22 (91%) reported post-treatment discomfort, with a visual analog pain score of 1 1.8. Three subjects (14%) used analgesics, with a total of six 500-mg acetaminophen tablets administered. No bleeding, crusting, dryness, adhesions, or infections were noted. Additional outcome studies have revealed similar improvement in nasal patency. Utley et al [9] evaluated 10 patients using a 15-mm RF probe (no longer available), with two lesions per turbinate. A mean RF energy delivery on the left turbinate of 492 J 72 and 429 J 104 and on the right of 412 J 103 and 465 J 13 revealed a subjective improvement of 75% on the left and 68% on the right. Eight of nine patients no longer required allergic medications, and no narcotics were required postoperatively. Smith et al [10] evaluated 11 patients using a 10-mm RF probe, with one lesion per turbinate. The mean RF energy delivery on the left of 423 J 17 and on the right of 428 J 13 revealed an improvement in subjective nasal obstruction VAS from 7.5 to 3.3. Six of 11 patients reported mild pain during the treatment, but only one acetaminophen tablet was administered. Powell et al [11] evaluated the use of inferior turbinate reduction to improve compliance with nasal CPAP in patients with nasal obstruction. The double-blinded, prospective study evaluated 22 patients (12 women) with a mean age of 54.3 years, body mass index of 29.3 kg/m2, and a mean AHI of 33.5. A mean of 413 J of RF energy was delivered to each inferior turbinate. The investigators discovered an overall reduction in size of the inferior turbinate by 27% on a four-point scale (n ¼ 17) compared with the

480


VAS subjective patient improvement of nasal patency of 48%. Tolerance to nasal CPAP improved by 28.9% (VAS, 4.9–6.3) compared with the placebo group (n ¼ 5) who decreased CPAP use by 10.4% (VAS, 4.4–3.3). Inferior turbinate radiofrequency side effects The post-treatment findings after inferior turbinate RF include nasal swelling for 24 to 72 hours. No wound care or limitation of daily activities is necessary. Narcotic analgesics are not required, and few patients administer acetaminophen. Bleeding, crusting, dryness, adhesions, and infection are rare complications. Final reduction is complete in 3 to 4 weeks, and retreatment can be performed if nasal obstruction persists. Rhee et al [12] evaluated nasal function after RF treatment to the inferior turbinate. No ciliary dysfunction was appreciated using the saccharin transit time and ciliary beat frequency tests. Butanol threshold testing revealed improved olfaction, probably from improved nasal patency. Mucous rheologic properties were unchanged. Improved nasal obstruction was compared with laser vaporization and revealed an improvement of 81.3% in the RF group and 87.5% in the laser group. Inferior turbinate radiofrequency: conclusions Inferior turbinate RF is a technically simple, minimally invasive procedure that can be performed as an outpatient procedure under local anesthesia with improved nasal obstruction, minimal side effects, and unchanged ciliary and mucous properties. Review of soft palatal obstruction Primary snoring, upper airway resistance syndrome, obstructive sleep apnea syndrome, and obesity-hypoventilation syndrome encompass a spectrum of sleep-related upper airway obstruction. Patients with primary snoring seek treatment because of the social annoyance and disruption of sleep of a bed partner. The etiology of primary snoring in approximately 85% of patients is partial airway obstruction from soft palatal redundancy causing tissue vibration, with resultant sound production [13]. The initial procedure devised to address primary snoring was the uvulopalatopharyngoplasty designed by Ikematsu [13] and modified by Fujita et al [7,14] and Simmons et al [15]. Unfortunately, the procedure usually is performed under general anesthesia, produces significant postoperative pain, and has short- and long-term failures for both snoring resolution and persistent obstructive sleep apnea. There have been numerous other soft palatal reduction procedures that have been discovered (see following list); unfortunately, each procedure has its limitations and disadvantages.


481

Soft palatal reduction procedures 1. Uvulopalatopharyngoplasty 2. Laser-assisted uvulopalatoplasty 3. Uvulopalatal flap 4. Cautery-assisted palatal-stiffening operation 5. Transpalatal advancement 6. Coblation 7. Injection snoreplasty 8. RF Alternatively, since the early 1980s, there have been numerous nonprescription, noninvasive medical management options, including nasal CPAP, oral appliances, nasal appliances, and medications. There are more than 300 patented appliances for snoring and sleep-disordered breathing. These devices have yielded either limited success or are fraught with low compliance rates. Minimally invasive procedures, including RF volumetric tissue reduction of the soft palate, injection snoreplasty, and coblation, have gained favor with both patients and surgeons because of the ability to perform them as an outpatient procedure under local anesthesia with minimal posttreatment discomfort, a limited complication rate, and good surgical results. Soft palatal radiofrequency indications Most patients with primary snoring and sleep-disordered breathing are candidates for surgical intervention. Patients must be medically and psychologically stable and wish to undergo a surgical procedure. Patients should be informed of the treatment philosophy. Surgical indications for soft palatal RF include the following: (1) socially disruptive snoring; (2) neurobehavioral derangements and excessive daytime sleepiness caused by sleep fragmentation as a result of soft palatal collapse in upper airway resistance syndrome and mild obstructive sleep apnea syndrome—this neurocognitive dysfunction may be confirmed to be due to upper airway collapse with resolution of these symptoms by a nasal CPAP trial; (3) mild sleep-disordered breathing with an AHI or respiratory disturbance index less than 20, with mild soft palatal redundancy or tonsillar hypertrophy; and (4) patients with persistent snoring after other soft palatal reduction procedures have been unsuccessful, such as laser assisted uvulopalatoplasty (LAUP), uvulopalatopharyngoplasty, and uvulopalatal flap (UPF). Soft palatal radiofrequency limitations Patients with a long, thick uvula most likely will require sharp amputation of part or all of the uvula to treat a redundant soft palate successfully. Patients with a thin, soft palate, especially the banding between the posterior tonsillar pillar and the uvula, are poor candidates for RF because the mean ablative

482


lesion diameter is 7 mm. The technique will result in a perforation of the soft palate or lateral scarring and contraction of this band of tissue, narrowing the oropharyngeal introitus. Patients with other than mild sleep-disordered breathing most likely will require other surgical procedures, especially those addressing the hypopharynx, to treat their disease severity effectively. Soft palatal radiofrequency surgical technique The soft palate is sprayed with 20% benzocaine as a topical anesthetic. A local anesthetic as a gel (2% lidocaine) is placed on a cotton-tipped applicator at the initial soft palatal injection site. A 27- or 30-gauge needle is used to inject 2.0 mL of 0.25% bupivacaine (Marcaine) 1:100,000 with epinephrine at this superior palatal midline site. The local anesthetic diffuses over approximately 5 to 7 minutes caudally, making additional inferior and lateral injections nearly painless. The soft palate from the uvular base to the posterior nasal spine and the paramedian area extending approximately 2 cm laterally from the midline is selected for treatment. The temperature-controlled RF energy delivery maximizes the size of the lesion compared with non-temperature-controlled RF delivery systems (Fig. 3). A 22-gauge RF needle electrode (10-mm active length with a 10-mm protective sheath) in a custom-fabricated device allows placement of the electrode under the palatal mucosa in the area selected for treatment. This electrode is bent with a crimping tool on an individual patient basis to contour to the curvature of the soft palate. Radiofrequency energy then is

Fig. 3. Soft palatal lesion size comparison: temperature- and non–temperature-controlled RF.


483

delivered for 60 to 170 seconds. Four potential sites of treatment during each treatment are selected, dependent on the size of the soft palate. The recommended maximum amount of energy delivered to the superior midline soft palate is 750 J; the recommended maximum amount to the uvular base and the paramedian areas is 350 J. Patients who previously have undergone other palatal procedures can tolerate higher energy levels laterally, up to 550 J, with limited risk of mucosal erosion or perforation. An assessment of the thickness of the soft palate should be performed before treatment to determine the maximal safe dose of RF energy and to limit the risk of soft palatal perforation. In patients with a long uvula, sharp amputation of the uvular tissue up to the muscle reflection may improve the success rate without any additional post-treatment discomfort. If the muscle is cut, then the patient experiences heightened pain and may require narcotic analgesic administration. Nonsteroidal anti-inflammatory medications are an excellent choice for postoperative pain, especially the new generation of Cox-II inhibitors. These medications have the same pain relief as hydrocodone combined with acetaminophen, with the anti-inflammatory properties to relieve swelling. Patients who have a prominent gag reflex may benefit from a pretreatment 10- to 20-mg oral dose of oral diazepam. Although they are not necessary, oral antibiotics or corticosteroids may be used postoperatively. The author does not use antibiotics after soft palatal RF and has not identified any patients with soft palatal cellulitis. A short course of oral methylprednisolone (Medrol), for 3 to 5 days, may be used to limit soft palatal edema, especially in those patients with a long uvula or thick soft palate.

Soft palatal radiofrequency results The initial human soft palatal RF study [6] revealed a reduction of snoring by 77%, in 22 subjects with a pretreatment subjective snoring VAS mean score of 8.3 1.8 and a post-treatment mean score of 1.9 1.2. The mean number of treatment sessions per patient was 3.6 1.2, with a total mean of 5 2 sites and mean RF energy delivered per treatment session of 688 106 J. A follow-up study [16] 12 to 18 months (mean, 14 months) later reported that subjective snoring scores relapsed by 29% overall. Thirteen patients (59%) reported continual success without relapse of snoring or daytime sleepiness. Nine patients (41%) noted relapse of snoring from 2.1 1.1 to 5.7 2.7. Eight of these patients underwent further RF sessions with a reduction of snoring from 5.8 2.9 to 3.3 3.1. Six patients received one treatment session, and two patients received two treatment sessions. The mean RF energy delivered per treatment session was 786 114 J, and each patient received a minimum of one and a maximum of three separate RF ablations per treatment session. Overall, 21 of the 22 patients (95%) were satisfied with the procedure and would repeat it if necessary.

484


A prospective, nonrandomized multicenter study [17] of 113 patients validated the use of RF applied to the soft palate for snoring reduction. The snoring VAS scores went from a mean of 7.8 2.1 pretreatment to 3.2 2.3 after treatment by delivering a mean of 1977.6 887 J with a mean of 2.4 1.2 treatment sessions per patient. The average follow-up period after treatment was 8 weeks. Another prospective, nonrandomized study [18] evaluated 43 patients undergoing soft palatal RF and revealed a 71% reduction of subjective snoring. Nineteen patients had a single midline lesion created, with RF delivering a mean of 698 52 J per treatment, a total mean of 2165 1057 J per patient with a mean of 3.3 1.6 treatment sessions per patient. Reduction in subjective snoring occurred from 7.8 1.8 to 2.3 2.1 (70.5%). Twenty-four patients had three separate lesions, one midline and left and right lateral sites, per treatment session, with RF delivering a mean of 1254 191 J per treatment, a total mean of 2196 1158 J per patient with a mean of 1.8 0.9 treatment sessions per patient. Reduction in subjective snoring occurred from 8.9 1.7 to 2.5 0.8 (71.9%). Another study comparing single-lesion versus multilesion soft palatal RF in 47 patients [19] revealed a more-than-twice-as-likely cure rate for snoring after two RF treatment sessions, with 61% of multilesion patients and 25% of single-lesion patients being treated successfully. The authors concluded that multilesion RF, using higher energy levels per treatment, is safe and increased the efficacy without increasing complications relative to single-lesion therapy. A study of 12 patients [20] undergoing midline RF to the soft palate revealed an improvement of subjective snoring from 8.3 2.1 to a posttreatment snoring level of 2.1 1.4 or a 75% reduction of snoring. These patients required an average of 2.3 treatment sessions per patient, with between 495 and 693 J per treatment session. The mean follow-up period was 5.1 weeks after the final RF procedure. The available soft palatal RF studies reveal a 70% to 77% subjective snoring reduction, with minimal pain and complications. The author prefers to deliver enough energy per treatment session as possible without producing mucosal erosions, significant uvular and soft palatal swelling, and post-treatment pain to require narcotic analgesics. One or two lesions are created at the initial treatment session, and the amount of soft tissue swelling and post-treatment subjective pain is assessed. If the patient experiences minimal swelling and pain, then high midline palatal, uvular base, and paramedian lesions are created at the second treatment session as dictated by the palatal anatomy.

Soft palatal radiofrequency complications The advantage of the RF technique of the soft palate, which is used principally for primary snoring, is the minimally invasive nature of the


485

procedure. Most subjects experience restless sleep on the first post-treatment night in response to palatal swelling and mild discomfort. The post-treatment discomfort of RF of the soft palate was compared with laser-assisted uvulopalatoplasty and uvulopalatopharyngoplasty [21]. The mean number of days with pain after RF, LAUP, and uvulopalatopharyngoplasty was 2.6, 13.8, and 14.3, respectively. The mean number of days requiring narcotic pain medication for RF, LAUP, and uvulopalatopharyngoplasty was 0.2, 11.8, and 12.4, respectively, whereas the total narcotic equivalent was 0.3, 7.4, and 29.6 days, respectively. Soft palatal RF produced significantly less post-treatment pain than either LAUP or uvulopalatopharyngoplasty, making this procedure well tolerated by patients. The discomfort experienced with this procedure is related to the number of lesions, the amount of energy delivered, and the presence of a mucosal injury. Powell et al’s initial study [6] revealed a mucosal injury rate of 7.6%, with other studies revealing mucosal injury rates as high as 45% [18]. Except for superficial mucosal injuries, when the mucosa is disturbed, patients experience increased discomfort. Palatal fistulas or perforations also may occur. This complication can be avoided by decreasing the amount of energy delivered in thin soft palates and by refraining from placing the RF probe lateral to the uvular and levator veli palatini muscles (Fig. 4). Uvular slough also may occur, which can lead to increased posttreatment pain. Because the goal of RF therapy is to shrink and tighten the soft tissue of the soft palate, this incident is not a complication unless significant pain is created. Decreasing the amount of energy delivered to the uvular base and the distance away from the uvular base may aid in diminishing this occurrence. Most studies evaluating soft palatal RF did not note bleeding, infection, speech disturbances, or swallowing problems. Soft palatal swelling may produce a globus sensation, but it usual resolves in 2 to 4 days. Dysphagia, velopalatal insufficiency, and nasopharyngeal stenosis have not been reported. Except for some post-treatment mild discomfort, swelling, and a low incidence of mucosal erosions, complications are minimal.

Overview of hypopharyngeal obstruction The pathophysiology of sleep-disordered breathing is collapse or obstruction of the upper airway during sleep. This obstruction may be partly or entirely due to the hypopharynx, and there are preoperative factors that may suggest the hypopharyngeal area as a site of collapse (see following list) [22]. Factors influencing hypopharyngeal obstruction 1. Morbid obesity (body mass index >31 kg/m2) 2. Mandibular skeletal deficiency (sella-nasion-supramentale (SNB) <76 )

486


Fig. 4. Soft palatal musculature anatomy. PNS – Posterior Nasal Spine.

3. 4. 5. 6.

Severe sleep-disordered breathing (AHI >40) Minimal soft palatal redundancy Retrodisplaced tongue or lateral wall collapse on nasopharyngoscopy Narrowed posterior airway space on lateral cephalometric radiograph (posterior airway space <11 mm)

Once the hypopharynx is suggested to be a site of collapse of the upper airway in sleep-disordered breathing, determining reconstructive procedure is the next step (see following list). Tongue-base RF is an alternative treatment to decrease the volume of the tongue and to improve the posterior airway space. Hypopharyngeal surgical procedures 1. Genioglossus advancement 2. Hyoid myotomy and suspension 3. Partial glossectomy or lingualplasty 4. Repose tongue suspension 5. Maxillomandibular advancement 6. Tongue-base RF Tongue-base radiofrequency indications Patients diagnosed with obstructive sleep apnea for whom the preoperative evaluation suggests tongue-base collapse as the cause of the hypopharyngeal obstruction are candidates for RF. Patients need to be in


487

stable medical condition, understand that the procedure is a multiple-stage process, and appreciate the potential complications. Post-treatment airway concerns and requirements for monitoring need to be addressed by the surgeon. Patients with complaints of dysphagia or dysarthria preoperatively may undergo a modified barium-swallow or speech-therapy evaluation before considering these therapeutic options. Those patients with underlying diabetes mellitus should be counseled regarding the increased risk of tongue abscess formation. Two treatment approaches exist: (1) performing RF alone and (2) performing RF with other base-of-tongue procedures, such as the genioglossus advancement or hyoid suspension procedures. Tongue-base radiofrequency technique The technique can be performed as an outpatient or an inpatient procedure in a monitored setting. Depending on the severity of the patient’s sleep-disordered breathing, post-treatment airway protection with nasal CPAP or a tracheotomy should be considered. The oral cavity is prepared with 0.12% oral chlohexidene (Peridex), and either oral or parenteral cephalexin is administered before placing the electrode. If under local anesthesia, the tongue is sprayed with 20% benzocaine as a topical anesthetic. A local anesthetic as a gel (2% lidocaine) is placed on a sterile, cotton-tipped applicator at the tongue-injection sites. A 25- or 27-gauge needle is used to inject 5.0 mL of 0.25% bupivacaine (Marcaine) with 1:100,000 epinephrine into each site. A different sterile needle is used at each site of injection. Treatment sites should be spaced a minimum of 1.5 cm apart. Lingual nerve blocks may be used but are not necessary. The author does not inject saline into the treatment area because there is no study to date verifying the increased tissue destruction with this method. There is an increased risk of infection with each additional injection at the lesion site by bringing potential superficial tongue debris and bacteria into the area to be ablated. A 22-gauge RF needle electrode (10 mm of active length with a 10-mm protective sheath) in a custom-fabricated device allows placement of the electrode under the superficial tongue musculature in the area selected for treatment. This electrode may be additionally bent on an individual patient basis to contour to the curvature of the tongue. Continual pressure on the electrode and visualization that the insulation sheath is not retracting out of the tongue tissue reduce the risk of superficial tissue injury. A singleor dual-channel tongue probe may be selected to deliver the RF energy. If the dual-channel probe is selected, the author prefers to bend the probe proximal to the retractable sheath to separate the two RF lesions farther apart. Potential sites of treatment include the midline, paramedian, and ventral tongue areas. As an inpatient procedure, up to 750 J in four sites, with 3000 J total delivery, can be administered safely without significant

488


tongue swelling, dysphagia, or postoperative pain. Documenting the specific tongue sites of treatment is prudent so that future RF tongue sessions do not place the RF electrode in previously ablated tongue tissue. In an outpatient setting, it is prudent to deliver only two sites of RF energy secondary to the risk of postoperative swelling and airway compromise in an unmonitored setting at home. Also, too much RF energy can result in dysphagia to the point at which oral intake of fluid is impaired, necessitating a hospital admission for hydration. The recommended maximum amount of energy delivered per site is between 750 to 1000 J. The amount of swelling and postoperative discomfort significantly increases with RF energy delivered at more than 750 J per treatment site. If tonguebase RF is being performed simultaneously with other base-of-tongue procedures such as the genioglossus advancement, decreasing the amount of RF energy may be warranted to prevent severe floor-of-mouth and tongue swelling, which may encroach on the airway. Nonsteroidal anti-inflammatory medications are an excellent choice for postoperative pain, especially the new generation of Cox- II inhibitors. These medications have the same pain relief as hydrocodone combined with acetaminophen, with the antiinflammatory properties to relieve swelling. Occasionally, narcotic analgesia is necessary. Patients with a prominent gag reflex who are undergoing the procedure under local anesthesia may benefit from a pretreatment 10- to 20-mg dose of diazepam. Although they are not necessary, corticosteroids may be used postoperatively. The author does not use methylprednisolone because of the concern of tongue abscess formation. If postoperative swelling and airway compromise are of concern, using nasal CPAP, monitoring the patient on an inpatient basis with pulse oximetry, or intensive care monitoring is preferred. Tongue-base radiofrequency results In the first report evaluating RF for sleep-disordered breathing, a porcine study [5] evaluated the relationship of lesion size to total RF energy delivery and subsequent tissue volume reduction. The study showed that tongue musculature volume could be reduced safely using RF energy in a precise and controlled manner with minimal risk of mucosal injury or infection. The first human tongue pilot study [23] investigated the feasibility, safety, and possible efficacy of RF in the treatment of sleep-disordered breathing. Eighteen patients who were treated incompletely for sleep-disordered breathing with other upper airway reconstruction procedures enrolled in the study, and all of them underwent at least a uvulopalatopharyngoplasty. The mean preoperative AHI of 39.6 improved to a mean of 17.8 (55%) after treatment, the mean apnea index of 22.1 improved to a mean of 4.1 (80%), and the mean preoperative SaO2 nadir of 81.9% improved to 88.3% (12%) after treatment. The mean energy delivery per treatment session was 1543 J,


489

for a mean total energy delivery of 8490 J. Tongue volume, as assessed with magnetic resonance imaging, was reduced by 17%, with an improvement of the posterior airway space by 15%. Speech and swallowing, as evaluated by VAS scores, were unchanged. Pain was controlled by oral hydrocodone for up to 4 days. The only complication in 181 treatment sessions was one tongue abscess, which resolved after incision and drainage. A long-term follow-up study [24] of these same patients revealed that 16 patients completed the follow-up at a mean of 28 months after the initial treatment. Sleep studies were performed using a new nasal cannula by Sleep Solutions (Redwood City, CA) that can quantitate airflow. This technique is believed to be more accurate in identifying hypopneas. The follow-up data revealed that the apnea index remained the same at 5.4, but the overall AHI relapsed to 28.7 and the SaO2 nadir relapsed to 85.8%. There were no changes in the quality-of-life scale (SF-36), Epworth sleepiness scale, or speech or swallowing VAS scores. The conclusion was that the success of tongue-base RF may reduce with time with the primary relapse in the hypopnea index. The limitation of the study was the use of different monitoring devices to document hypopneas. A prospective, nonrandomized study [25] evaluated 10 sleep apneic patients who underwent uvulopalatopharyngoplasty and nasal surgery (when indicated), along with tongue-base RF under general anesthesia. Two additional RF sessions were performed postoperatively in an outpatient setting. Nine of the 10 patients received a cumulative dose of approximately 12,000 J. The final patient received only the initial 4000 J of RF energy. Five of these patients were treated successfully, defined as an AHI less than 20 with at least a 50% reduction in AHI. The mean preoperative AHI of 29.5 14.8 improved to a mean AHI of 18.8 14.6, and the mean apnea index of 8.7 6.4 improved to a mean apnea index of 3.7 4.9. A multi-institutional study [26] evaluated 73 patients with underlying obstructive sleep apnea; 56 (76.7%) of these patients completed tongue-base RF and follow-up polysomnography. Sixty-five (92.9%) had prior pharyngeal surgery. A mean of 5.4 1.8 treatment sessions were performed, with a mean of 3.1 0.9 lesions per treatment session and an overall energy delivery of 13,394 5459 J. The mean AHI of 40.5 21.5 decreased to a mean of 32.8 22.6 after treatment. The investigators concluded that RF tongue reduction diminishes the severity of obstructive sleep apnea with subjective outcomes comparable to nasal CPAP. Tongue-base radiofrequency complications Tongue-base RF is a treatment of tongue-base collapse in patients with sleep-disordered breathing. These patients have inherent postoperative airway concerns with upper airway reconstructive surgery. To avoid postoperative airway obstruction after tongue-base RF, the surgeon should consider in-patient monitoring, nasal CPAP use, and limiting the amount of

490


RF energy delivery, especially when performed with other upper airway reconstructive procedures. The potential complications are listed below. Tongue-base radiofrequency complications 1. Superficial ulcer formation 2. Infection or cellulitis 3. Tongue abscess 4. Hypoglossal nerve injury 5. Tongue or floor-of-mouth swelling 6. Upper airway obstruction Infection is an uncommon complication, with progression to a tongue abscess in less than 1% of treatment lesions. Some of these suppurative infections drain spontaneously, some may be treated by needle aspiration, but definitive treatment usually requires incision and drainage. The symptoms are a rapid onset of severe tongue pain, usually only mild or moderate swelling, and occasional cervical adenopathy or swelling. Diagnosis requires a high index of suspicion, because the initial physical examination findings may reveal a normal-appearing tongue or only mild swelling. Needle aspiration, ultrasound scanning, or computer tomography scanning may be required to confirm the diagnosis. To diminish the risk of infection, the following precautions can be taken: (1) pretreatment with oral antibiotics, usually cephalexin, and a 3-day prophylactic antibiotic course; (2) instructing the patient to gargle with 0.12% oral chlorhexidene (Peridex) for at least 1 minute immediately before treatment; (3) use of sterile technique as much as possible; (4) use of a new sterile needle with each injection site; (5) avoidance of steroids, which may lower the immune response; (6) ensuring that the electrode is seated completely into the tongue musculature to prevent a superficial ulceration; (7) checking the curvature of the tongue base to prevent the electrode tip from being placed close to the superficial aspect of the tongue; (8) wiping the electrode tip using sterile technique between treatment lesion sites to remove debris; (9) not delivering greater than 1000 J of energy per treatment site; and (10) considering other treatment alternatives in patients with diabetic mellitus. Following these recommendations limits the incidence of tongue superficial ulcerations and infection. To avoid hypoglossal nerve injury, the surgeon should limit the ablation sites to no more than 2 cm lateral to midline. The neurovascular bundle is approximately 2 to 3 cm from the surface epithelium and approximately 3 cm lateral from midline in a normal-sized tongue (Fig. 5). With decreased tongue volumes, the RF lesions should not extend beyond 1.5 to 2.0 cm from midline to prevent hypoglossal nerve injury. Four studies revealed no hypoglossal nerve injuries, whereas one study had only mild and transient tongue deviations, which resolved completely postoperatively. Tongue discomfort, odynophagia, and dysphagia may occur for 3 to 5 days after treatment. To lower the incidence of significant post-treatment


491

Fig. 5. Tongue cross-sectional anatomy.

discomfort, the physician should (1) limit the energy per treatment site to 750 J, (2) limit the treatment sites to four per treatment session, (3) use crushed ice by mouth as much as possible for the first two post-treatment days, and (4) follow the treatment techniques to limit the risk of infection. In the author’s experience with more than 200 base-of-tongue RF treatments following these recommendations, no patient has had a tongue ulcer, infection, abscess, lingual neuralgia, or hypoglossal nerve injury. The incidence of these complications is largely technique-dependent. Tongue-base radiofrequency limitations The specific role of tongue-base RF in sleep-disordered breathing has not been established. The efficacy of this procedure when performed simultaneously with other hypopharyngeal reconstructive procedures has not been studied. The effect of saline infiltration into the area to be ablated in altering the lesion size has not been delineated. Finally, there are only limited results on the long-term efficacy and side effects of tongue-base RF. Tongue-base radiofrequency: conclusions Tongue-base RF seems to offer promising results in upper airway reconstruction in patients with sleep-disordered breathing. The technique can be performed as an outpatient or inpatient procedure, under local or general

492


anesthesia, with minimal risks of complications and minimal quality-of-life changes. Upper airway reconstruction surgery follow-up Three to 4 months after completing upper airway reconstruction, patients undergo a polysomnogram to determine surgical outcome. Surgical success is defined as an AHI of less than 20 with at least a 50% reduction compared with the preoperative study and the lowest oxyhemoglobin saturation levels equivalent to those seen with nasal CPAP or greater than 90%. In addition to objective polysomnographic data, patients should experience improvement in their snoring and sleep hygiene. Elimination of the daytime hypersomnolence corresponds to reports of better-quality sleep, improved ability to concentrate, elimination of the necessity of naps, and improved work performance. The surgeon should use the procedures that are the most effective, with the lowest morbidity, and technically reproducible for him or her. Radiofrequency in upper airway reconstruction: conclusions Radiofrequency for upper airway reconstructive surgery in sleepdisordered breathing for the nasal inferior turbinate, the soft palate, and the tongue base offers additional therapeutic options in the surgical armamentarium in an area in which there were once limited options. The procedures are technically simple and minimally invasive; they are associated with reduced postoperative pain compared with traditional surgical approaches; and they can be performed in an outpatient setting under local anesthesia with a low complication rate and generally good therapeutic results. Future studies will aid in delineating the specific role of RF in nasal obstruction and sleep-disordered breathing. References [1] Issa M, Oesterling J. Transurethral needle ablation (TUNA): an overview of radiofrequency thermal therapy for the treatment of benign prostatic hyperplasia. Curr Opin Urol 1996;6:20–7. [2] Jackman WM, Wang XZ, Friday KJ, et al. Catheter ablation of accessory atrioventricular pathways (Wolff-Parkinson-White syndrome) by radiofrequency current. N Engl J Med 1991;324:1605–11. [3] LeVeen H, Wapnick S, Piccone V, et al. Tumor eradication by radiofrequency therapy: response in 21 patients. JAMA 1976;253:2198–200. [4] Sweet W, Wepsic J. Controlled thermocoagulation of trigeminal ganglion and rootlets for differential destruction of pain fibers: I. Trigeminal neuralgia. J Neurosurg 1974;3:143–56. [5] Powell NB, Riley RW, Troell RJ, et al. Radiofrequency volumetric reduction of the tongue: a porcine pilot study for the treatment of obstructive sleep apnea syndrome. Chest 1997;111:1348–55. [6] Powell NB, Riley RW, Troell RJ, et al. Radiofrequency volumetric tissue reduction of the palate in subjects with sleep-disordered breathing. Chest 1998;113:1163–74.


493

[7] Fujita S, Conway W, Zorick F, et al. Surgical correction of anatomic abnormalities in obstructive sleep apnea syndrome: uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg 1981;89:923–30. [8] Li KK, Powell NB, Riley RW, Troell RJ, Guilleminault C. Radiofrequency volumetric tissue reduction of turbinate hypertrophy: a pilot study. Otolaryngol Head Neck Surg 1998;119:569–73. [9] Utley DS, Goode RL, Hakim I. Radiofrequency energy tissue ablation for the treatment of nasal obstruction secondary to turbinate hypertrophy. Laryngoscope 1999;109:683–6. [10] Smith TL, Correa AJ, Kuo T, et al. Radiofrequency tissue ablation of the inferior turbinate using a thermocouple feedback electrode. Laryngoscope 1999;109:1760–5. [11] Powell NB, Riley RW, Zonato AI, et al. Radiofrequency treatment of turbinate hypertrophy to improve nasal CPAP usage. Presented at the American Academy of Otolaryngology–Head and Neck Surgery annual meeting, Washington, DC; September 2000. [12] Rhee CS, Kim DY, Won TB, et al. Changes of nasal function after temperature-controlled radiofrequency tissue volume reduction for the turbinate. Laryngoscope 2001;111:153–8. [13] Ikematsu T. Study of snoring: fourth report. Ther J Jpn Otol Rhinol Laryngol Soc 1968; 4:434–5. [14] Fujita S, Conway WA, Zorick F, et al. Evaluation of the effectiveness of uvulopalatopharyngoplasty. Laryngoscope 1985;95:70–4. [15] Simmons FB, Guilleminault C, Miles L. The palatopharyngoplasty operation for snoring and sleep apnea: an interim report. Otolaryngol Head Neck Surg 1984;4:375–7. [16] Li KK, Powell NB, Riley RW, Troell RJ, Guilleminault C. Radiofrequency volumetric reduction of the palate: an extended follow-up study. Otolaryngol Head Neck Surg 2000; 122:410–4. [17] Sher AE, Flexon PB, Hillman D, et al. Temperature-controlled radiofrequency tissue volume reduction in the human soft palate. Otolaryngol Head Neck Surg 2001;125:312–8. [18] Emery BE, Flexon PB. Radiofrequency volumetric tissue reduction of the soft palate: a new treatment for snoring. Laryngoscope 2000;110:1092–8. [19] Ferguson M, Smith TL, Zanation AM, et al. Radiofrequency tissue volume reduction: multilesion vs single-lesion treatments for snoring. Arch Otolaryngol Head Neck Surg 2001;127:1113–8. [20] Coleman SC, Smith TL. Midline radiofrequency tissue reduction of the palate for bothersome snoring and sleep-disordered breathing: a clinical trial. Otolaryngol Head Neck Surg 2000;122:387–94. [21] Troell RJ, Powell NB, Riley RW, et al. Comparison of postoperative pain between laserassisted uvulopalatoplasty, uvulopalatophayngoplasty, and radiofrequency volumetric tissue reduction of the palate. Otolaryngol Head Neck Surg 2000;122:402–9. [22] Troell RJ, Powell NB, Riley RW. Hypopharyngeal airway obstruction for obstructive sleep apnea syndrome. In: Millman RP, editor. Seminars in respiratory and critical care medicine, vol. 19. New York: Thieme Medical Publishers; 1998. p. 175–184. [23] Powell NB, Riley RW, Guilleminault C. Radiofrequency tongue base reduction in sleepdisordered breathing: a pilot study. Otolaryngol Head Neck Surg 1999;120:656–64. [24] Li KK, Powell NB, Riley RW, et al. Radiofrequency tongue base reduction: long-term outcomes. Presented at American Academy of Otolaryngology–Head and Neck Surgery annual meeting, Denver Colorado, September 2001. [25] Nelson LM. Combined temperature-controlled radiofrequency tongue reduction and UPPP in apnea surgery. ENT J 2001;80:640–4. [26] Woodson BT, Nelson L, Mickelson S, et al. A multi-institutional study of radiofrequency volumetric tissue reduction for OSAS. Otolaryngol Head Neck Surg 2001;125:303–11.


Laser-assisted uvulopalatoplasty revisited Yosef P. Krespi, MDa,*, Ashutosh Kacker, MDb a

Department of Otolaryngology/Head and Neck Surgery, St. Luke’s–Roosevelt Hospital Center, 425 West 59th Street, 10th Floor, New York, NY 10019, USA b Department of Otolaryngology and Head and Neck Surgery, New York Presbyterian Hospital, Weill College of Medicine, York Avenue and 68th Street, New York, NY 10021, USA

Snoring is a social problem and a precursor to the more ominous syndrome of obstructive sleep apnea (OSA). It affects approximately 50% of men and 30% of women. It is estimated that approximately 50% of those affected are habitual snorers (Table 1). Uvulopalatopharyngoplasty (UPPP) was first introduced by Ilkematsu in 1964 and was later modified by Fujita et al [1] as a surgical treatment for the management of snoring. The application of office-based laser technology to surgery for snoring and mild OSA led to the introduction of laser-assisted uvulopalatoplasty (LAUP) in the middle to late 1980s. Since then, controversies have arisen, especially with respect to its efficacy. Kamani [2,3], who is credited with the introduction of LAUP, published data showing remarkable results for its use as treatment for both snoring and OSA. Similar short-term results were published by other authors using either a single-stage or multiple-stage LAUP procedure [4–8]. Recently published data tend to contradict earlier results, with patients showing poorer results or results that worsened with time [9,10]. Also, because of the indiscriminate use of LAUP, complications (in the form of nasopharyngeal stenosis) were reported. Since then, our understanding of snoring and sleep apnea has improved, which has led to changes in patient selection and improved results. Diagnosis The diagnosis of snoring is determined primarily by history. The character and consistency of the snoring are evaluated to determine its severity and possible associated OSA. The physical examination includes a complete evaluation of the nose, nasopharynx, oral cavity, oropharynx, hypopharynx, * Corresponding author. E-mail address: [email protected] (Y.P. Krespi). 0030-6665/03/$ - see front matter Ó 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(03)00016-1

496

Y.P. Krespi, A. Kacker / Otolaryngol Clin N Am 36 (2003) 495–500

Table 1 Grading system of snoring Grade

Snoring

Characteristics

Grade I Grade II

Occasional Frequent

Grade III

Always (associated with OSA)

Overtired, alcohol intake, lying on the back All positions, continues through out night, heard from one room away Heard throughout the entire home

and larynx. Flexible fiberoptic examination, as a Mu¨ller’s maneuver, helps in localizing the site of origin of the snoring or OSA.

Use of sleep study to characterize snoring The authors use the SNAP Laboratories’ (Glenview, IL) sleep-study snoring analysis to identify and localize the source of snoring and to detect and quantify sleep apnea [11]. This information is used to select and tailor the procedure.

Snoring analysis The sleep study performed by SNAP Laboratories is unique in its ability to identify and spectrally profile all snoring events into five categories. Clinical correlation studies have shown that these categories help to identify the likely sites of sound generation and airway compromise. Type 1 and type 2 snoring are believed to be predominantly of palatal origin. The incidence (percentage) of each type of snoring and its relative loudness is determined. Another parameter included in the SNAP analysis is the snoring index (frequency of snoring and fundamental frequency of snoring). The most useful parameters for identifying significant velopharyngeal (palatal) snoring, are the percent and relative loudness of palatal snoring. The following guidelines (see box) are used to assess the relative velumlike component of overall snoring amplitude and distribution. Criteria for patient selection Patients with grade II or III snoring with mild apnea in whom the snoring is localized to the palate on a sleep study are the ideal candidates for LAUP.

Types 1 and 2 (%) Amplitude distribution Minimal <65 <4 dB Moderate <85 4–8 dB Majority >85 >8 dB


497

Absolute contraindications for LAUP include severe sleep apnea, uncontrolled hypertension, severe trismus, cleft palate, velopharyngeal insufficiency, and an uncooperative patient. Procedure of laser-assisted uvulopalatoplasty Currently, the senior author (YPK) uses a single-stage, graded, interactive procedure in which he performs a stepwise reduction of the uvula and soft palate. After each step, the patient is asked to snort to re-create the snoring sound. The procedure is continued until this sound can no longer be created by snorting. Anesthesia for laser-assisted uvulopalatoplasty Laser-assisted uvulopalatoplasty is performed in an upright, sitting position in an otolaryngology examination chair. The topical anesthetic used is 20% benzocaine, which is sprayed in the posterior oral cavity; an injection of lidocaine 1% with 1:100,000 epinephrine and bupivacaine 0.5% also is given. Surgical procedure Surgical use of the carbon dioxide laser is commenced after waiting 10 minutes for the anesthesia to take effect. A special pharyngeal hand piece with a backstop is used to incise the soft palate. The power setting is 18 to 20 W, continuous mode. The tongue is retracted inferiorly with an ebonized tongue blade with the integrated smoke-evacuation channel. Through-andthrough, full-thickness, vertical trenches measuring 1.0 to 1.5 cm are made on the free edge of the soft palate on either side of the uvula. These trenches are created using a focused beam in a continuous mode. The patient is instructed to take a deep breath, and the laser is activated during slow exhalation to avoid inhalation of the plume. Shortening and thinning of the uvula are performed with the SwiftLase (Sharplan Lasers, Allendale, NJ) flash scanner attached to the carbon dioxide (CO2):laser, using 18 to 20 W. The uvula is reduced to 60% to 90% of its original dimensions by coring it out from the bottom up. Overall, the surgical goal is to reduce the length and to reshape the soft palate and uvula. Care must be taken not to burn excessively the mucosa overlying the soft palate and uvula. The uvula is shortened by ablating the muscle from within, creating a ‘‘fish-mouth’’ appearance, because the mucosae of the base of the uvula on the nasal and oral surfaces are preserved. This procedure is performed best with SwiftLase. The advantages of using the SwiftLase flash scanner are absence of char, precise layer-by-layer surface ablation, and the ability of the SwiftLase to seal small blood vessels. Excision of the uvula (amputation) at its base using the carbon dioxide laser with a focus beam may cause undesired bleeding from the uvula and soft

498


palate vessels. Light bleeding during surgery occurred in approximately 3% of the patients. This complication is controlled easily by applying silver nitrate. Patients with obstructive sleep apnea syndrome with redundant pharyngeal folds and enlarged tonsils can be helped by the reduction of the upper portion of the pharyngeal folds and the tonsils using the SwiftLase. Complications A moderate-to-severe sore throat is the major side effect after LAUP [12]. The pain intensity reaches its peak 4 to 5 days postoperatively, with complete relief of symptoms approximately 8 to 10 days after surgery. The pain usually is controlled with hydration, anesthetic gel, and oral analgesics. There was no late or delayed bleeding in the authors’ series. Healing occurs by formation of an eschar 3 to 5 days after the procedure. Complete healing takes place after the slough of the eschar in approximately 10 to 12 days. Vasovagal episodes were encountered in 2% of the patients after injection of the local anesthetic. Laser-assisted uvulopalatoplasty was combined with other procedures, such as submucous resection of the septum, laser turbinectomy, laser-assisted serial tonsillectomy, or laser lingual tonsillectomy, in approximately 20% of the authors’ patients. Discussion Laser-assisted uvulopalatoplasty is an effective method for treating patients with loud, habitual snoring. Performed as an office procedure under local anesthesia, laser-assisted uvulopalatoplasty has proven to be a safe and reliable method of relieving this sociomedical problem. Because the procedure is performed under local anesthesia and in stages, patients report minimal pain, eliminating the need for adults to miss work or to be incapacitated for several weeks, as is the case after UPPP. In most patients, a reduction in snoring occurs immediately. One major advantage of LAUP over UPPP is the ability of LAUP to titrate tissue removal to achieve optimal benefit without the danger of overcorrection. Complications seen in patients undergoing LAUP include postoperative hemorrhage, local infection, temporary palatal incompetence, and temporary loss of taste. More serious complications include hypernasal speech, permanent palatal incompetence, nasopharyngeal stenosis, airway compromise, or death. Alternate options to LAUP include dental obturators, radiofrequency reduction of the palate, injection snoreplasty, and the conventional UPPP. The somnoplasty system uses radiofrequency energy to reduce and tighten excess tissue in the upper airway that is responsible for snoring [13–15]. The reduction of the palate tissues can be performed in a precise, minimally invasive manner. The procedure creates finely controlled zones of coagulation at precise locations beneath the tissue in the upper airway.


499

During a 3- to 8-week period, the treated tissue is resorbed, reducing excess tissue volume and opening the airway. Advantages of somnoplasty include an easy, pain-free procedure and the lack of serious adverse effects. The disadvantages include the fact that multiple procedures are required to obtain good results and the cost of the hand piece. Injection snoreplasty is a new procedure in which sodium tetradecyl sulfate 3% (Tromboject 3%) (Omega Labs, Montreal, CA) (a sclerosing agent) is injected into the soft palate to reduce or eliminate palatal-flutter snoring in habitual snorers [16]. Injection snoreplasty is a simple, safe, and effective office treatment for primary snoring. Advantages as compared with current snoring procedures include simplicity, low cost, decreased posttreatment pain levels, and minimal or no convalescence. Currently, Sotradecol is not approved by the Food and Drug Administration for this use. Summary When performed correctly in a properly selected patient, LAUP provides good and lasting results in snoring improvement. A sleep study with snoring analysis helps in patient selection. Laser-assisted uvulopalatoplasty can be performed adequately in one sitting. References [1] Fujita S, Conway W, Zorick F, Roth T. Surgical correction of anatomic abnormalities in obstructive sleep apnea syndrome: uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg 1981;89:923–34. [2] Kamami YV. Outpatient treatment of sleep apnea syndrome with CO2 laser: laser-assisted UPPP. J Otolaryngol 1994;23:395–8. [3] Kamami YV. Outpatient treatment of snoring with CO2 laser: laser-assisted UPPP. J Otolaryngol 1994;23:391–4. [4] Krespi YP, Pearlman SJ, Keidar A. Laser-assisted uvula-palatoplasty for snoring. J Otolaryngol 1994;23:328–34. [5] Sharp HR, Mitchell DB. Long-term results of laser-assisted uvulopalatoplasty for snoring. J Laryngol Otol 2001;115:897–900. [6] Seemann RP, DiToppa JC, Holm MA, Hanson J. Does laser-assisted uvulopalatoplasty work? An objective analysis using pre- and postoperative polysomnographic studies. J Otolaryngol 2001;30:212–5. [7] Neruntarat C. Laser-assisted uvulopalatoplasty: short-term and long-term results. Otolaryngol Head Neck Surg 2001;124:90–3. [8] Osman EZ, Osborne JE, Hill PD, Lee BW, Hammad Z. Uvulopalatopharyngoplasty versus laser assisted uvulopalatoplasty for the treatment of snoring: an objective randomised clinical trial. Clin Otolaryngol 2000;25:305–10. [9] Ryan CF, Love LL. Unpredictable results of laser assisted uvulopalatoplasty in the treatment of obstructive sleep apnoea. Thorax 2000;55:399–404. [10] Lauretano AM, Khosla RK, Richardson G, Matheson J, Weiss JW, Graham C, et al. Efficacy of laser-assisted uvulopalatoplasty. Lasers Surg Med 1997;21:109–16. [11] Weingarten CZ, Raviv G. Evaluation of criteria for uvulopalatoplasty (UPP) patient selection using acoustic analysis of oronasal respiration (SNAP testing). J Otolaryngol 1995;24:352–7.

500


[12] Walker RP, Gopalsami C. Laser-assisted uvulopalatoplasty: postoperative complications. Laryngoscope 1996;106:834–8. [13] Blumen MB, Dahan S, Wagner I, De Dieuleveult T, Chabolle F. Radiofrequency versus LAUP for the treatment of snoring. Otolaryngol Head Neck Surg 2002;126:67–73. [14] Troell RJ, Powell NB, Riley RW, Li KK, Guilleminault C. Comparison of postoperative pain between laser-assisted uvulopalatoplasty, uvulopalatopharyngoplasty, and radiofrequency volumetric tissue reduction of the palate. Otolaryngol Head Neck Surg 2000;122: 402–9. [15] Flexon FB. Somnoplasty: a treatment for snoring. In: Krause JH, Mirante JP, Christmas DA, editors. Office-based surgery in otolaryngology. Philadelphia: WB Saunders; 1999. p. 79–86. [16] Brietzke SE, Mair EA. Injection snoreplasty: how to treat snoring without all the pain and expense. Otolaryngol Head Neck Surg 2001;124:503–10.


Tongue neuromuscular and direct hypoglossal nerve stimulation for obstructive sleep apnea David W. Eisele, MDa,*, Alan R. Schwartz, MDb, Philip L. Smith, MDb a

Department of Otolaryngology–Head and Neck Surgery, University of California, San Francisco, 400 Parnassus Avenue, Suite A-730, San Francisco, CA 94143-0342, USA b Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Bayview Circle, Baltimore, MD 21224, USA

Obstructive sleep apnea (OSA) is caused by recurrent episodes of upper airway obstruction during sleep associated with periodic arousals from sleep and oxyhemoglobin desaturations. Sleep disturbance and abnormal oxygenation are believed to cause the primary clinical sequelae of OSA that include daytime hypersomnolence, arterial and pulmonary hypertension, and cardiopulmonary failure. Therapy for OSA is directed toward the relief of upper airway obstruction so that the clinical manifestations of the disorder are alleviated or prevented. Although numerous methods have been used to restore upper airway patency during sleep for patients with OSA, no single treatment modality has been shown to provide complete reversal of upper airway obstruction during sleep in all patients with this disorder. The cause of OSA, which is considered to be related to diminished genioglossus muscle activity during sleep, is not addressed by current therapies [1]. To address this problem, the authors conducted investigations into the effect of neuromuscular stimulation of the tongue muscles and direct hypoglossal nerve stimulation on upper airway patency during sleep in patients with OSA. This article summarizes the authors’ investigations of selective neuromuscular tongue and direct hypoglossal nerve stimulation on upper airway airflow mechanics during sleep in patients with OSA and the feasibility of this intervention for the treatment of this disorder.

* Corresponding author. E-mail address: [email protected] (D.W. Eisele). 0030-6665/03/$ - see front matter Ó 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00178-0

502

D.W. Eisele et al / Otolaryngol Clin N Am 36 (2003) 501–510

Neuromuscular stimulation of the tongue Multiple prior investigations have addressed the concept of electrical stimulation of the tongue in OSA. Approaches have included attempts to stimulate the tongue with surface electrodes placed in the upper neck skin [2,3], sublingual mucosa [4,5], base-of-tongue mucosa [6], and soft palate [7]. Percutaneous wire electrodes, directed near the hypoglossal nerve, also have been used [8,9]. The methods used in these studies, however, lacked selectivity in stimulating the genioglossus muscle or hypoglossal nerve and induced recurrent arousals from sleep. A generalized arousal from sleep resulting in pharyngeal muscle activation could have caused the improvements in pharyngeal airway patency reported in these earlier investigations. In light of the limitations of these studies, the authors began investigations into electrical stimulation of the tongue muscles with three primary objectives. First, methods were developed to selectively stimulate the genioglossus muscle in volunteers and patients with OSA. Second, the effect of the selective stimulation of the genioglossus muscle on upper airway airflow dynamics during sleep was determined in patients with OSA. Third, patients were sought for OSA treatment with an implantable electrical-stimulation system. Initially, methods for selective neuromuscular stimulation of the tongue muscles with transorally directed hook-wire electrodes were developed. Tongue motor responses with this method were correlated with tongue motor responses resulting from selective hypoglossal nerve stimulation performed during open-neck surgical procedures. This correlation provided confirmation of proper transoral electrode placement into the genioglossus muscle based on the motor response observed with stimulation. The observed response to neuromuscular and selective hypoglossal nerve stimulation of the genioglossus muscle was tongue protrusion and deviation of the tongue to the contralateral side. Neuromuscular stimulation of the genioglossus muscle then was examined during sleep in patients with OSA [10]. The level of maximal airflow before, during, and after stimulation was measured with standard polysomnographic recording techniques. Arousal from sleep during or after stimulation was excluded by monitoring electroencephalography, electromyography, the pattern of respiration, and the heart rate. All patients with OSA studied were morbidly obese with significant apnea-hypopnea indices. Neuromuscular stimulation of the genioglossus muscle resulted in an improvement in inspiratory airflow of approximately 200 to 250 mL/s (Fig. 1). The improvement in airway patency was limited to the duration of stimulation of the genioglossus muscle. Importantly, the results of this study confirmed that electrical stimulation of the upper airway could be achieved during sleep in patients with OSA without arousal from sleep. The airwayopening effect produced by stimulation was noted to be directly related to genioglossus neuromuscular activation rather than global arousal from sleep.


503

Fig. 1. Mean maximal inspiratory airflow (VI max) levels for eight patients with OSA before, during, and after neuromuscular stimulation of the genioglossus muscle during sleep. (From Schwartz AR, Eisele DW, Hari A, et al. Electrical stimulation of the lingual musculature in obstructive sleep apnea. J Appl Physiol 1996;81:643–52; with permission.)

Selective direct hypoglossal nerve stimulation Another investigation was undertaken to determine the effect of direct hypoglossal nerve stimulation on upper airway patency in patients with OSA during sleep [11]. A tripolar half-cuff electrode (Medtronic 3990; Medtronic, Minneapolis, MN) was used. This electrode was designed to limit the electrical current to the nerve and to prevent nerve entrapment. The hypoglossal nerve was exposed through an upper neck incision in patients with OSA. Two loci of hypoglossal nerve stimulation, the distal branch to the genioglossus muscle and the main nerve trunk, were examined. The level of maximal inspiratory airflow before, during, and after stimulation was measured during sleep with standard polysomnographic techniques. Lack of arousal from sleep was confirmed by monitoring electroencephalography, electromyography, the respiratory pattern, and the heart rate. Electrical stimulation of the hypoglossal nerve at both stimulation loci resulted in a marked improvement in inspiratory airflow during stimulation, compared

504


with unstimulated breaths, without patient arousal from sleep (Fig. 2). It was concluded from this study that airway obstruction in patients with OSA was alleviated by hypoglossal nerve stimulation, not only when the genioglossus muscle was stimulated but also when the tongue retrusor muscles were coactivated with the genioglossus muscle.

Implantable hypoglossal nerve-stimulation system After the publication of the above-mentioned studies that confirmed the success of electrical-stimulation methods for opening the airway in patients with OSA without arousal from sleep and additional animal studies [12], a Food and Drug Administration-approved feasibility study was undertaken to investigate the treatment of patients with OSA with a fully

Fig. 2. Mean maximal inspiratory airflow (VI max) in five patients with OSA before, during, and after hypoglossal nerve stimulation during sleep. Filled circles indicate stimulation of the hypoglossal nerve branch to the genioglossus muscle. Open circles indicate main trunk hypoglossal nerve stimulation. (From Eisele DW, Smith PL, Alam DS, Schwartz AR. Direct hypoglossal nerve stimulation in obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 1997;123:57–61; with permission.)


505

Fig. 3. Schematic diagram of Inspire I Hypoglossal Nerve Stimulation System (Medtronic, Minneapolis, MN).

implantable hypoglossal nerve-stimulation system. This system, the Inspire I (Medtronic) (Fig. 3) consists of components that were designed to reliably predict the onset of the inspiratory phase of respiration and to stimulate the hypoglossal nerve during inspiration. The system components include an implantable pulse generator (IPG), a respiratory pressure sensor, and a tripolar, half-cuff peripheral nerve-stimulation electrode. The IPG contains a programmable microprocessor. Stimulus frequency, duration, and amplitude can be adjusted transcutaneously by the physician programmer. The peripheral nerve lead and the respiratory pressure sensor interface with the IPG. Surgical implantation of the hypoglossal nerve-stimulation system is described in detail elsewhere [13,14]. Briefly, the system is implanted under general anesthesia through three surgical incisions: an upper lateral neck incision, a lower midline neck incision, and an infraclavicular incision. The hypoglossal nerve is exposed by dissection through an upper neck incision. The stimulation electrode is placed on the peripheral hypoglossal nerve branch to the genioglossus muscle (Fig. 4). Proper placement on the desired nerve is confirmed by stimulation of the nerve with a hand-held pulse generator and observation of tongue protrusion and deviation to the contralateral side. Through a midline lower neck incision, the pressure transducer is placed flush with the posterior aspect of the manubrium through a drill hole, and the transducer housing is secured to the manubrium with a miniscrew (Fig. 5). An infraclavicular pocket, superficial to the pectoralis major muscle fascia, is created by way of an infraclavicular incision (Fig. 6). A tunneling device then is used to tunnel the nerve-electrode lead and the pressure-transducer lead to the IPG pocket. The leads then are connected to the IPG, and the wounds are closed. The system is checked for functional integrity before awakening the patient from anesthesia. Further testing of

506


Fig. 4. Half-cuff stimulation electrode placement around distal branch of the hypoglossal nerve to the genioglossus muscle. (From Eisele DW, Schwartz AR, Smith PL. Electrical stimulation of the upper airway for obstructive sleep apnea. Op Tech Otolaryngol Head Neck Surg 2000;11: 59–65; with permission.)

the system is deferred for 1 month to allow for adequate healing and stabilization of the implanted system.

Therapeutic hypoglossal nerve stimulation in obstructive sleep apnea Recently, a multi-institutional, prospective trial to investigate the therapeutic efficacy of the Medtronic Inspire I hypoglossal nerve-stimulation system for OSA was completed [14]. Eight middle-aged, moderately overweight men with moderate to severe OSA during non-rapid-eye-movement (non–REM) and REM sleep underwent implantation of the system. Nightly unilateral hypoglossal nerve stimulation was initiated at 4 weeks after system


507

Fig. 5. Pressure transducer placement through a drill hole in the manubrium. (From Eisele DW, Schwartz AR, Smith PL. Electrical stimulation of the upper airway for obstructive sleep apnea. Op Tech Otolaryngol Head Neck Surg 2000;11:59–65; with permission.)

implantation. Patients initiated electrical stimulation with a self-controlled programming unit. A pre-set delay in system activation allowed patients to initiate sleep before the start of electrical stimulation. Sleep and breathing patterns were examined at baseline and at 1, 3, and 6 months postoperatively. Results of this clinical trial indicated that unilateral hypoglossal nerve stimulation decreased the severity of the OSA throughout the entire study period. Specifically, stimulation reduced the mean apneahypopnea indices in non-REM and REM sleep compared with baseline values (Fig. 7). The severity of oxyhemoglobin desaturations was reduced significantly. All patients were able to tolerate long-term stimulation at night, and there were no adverse effects related to system implantation or nerve stimulation. Small, consistent increases in stimulus parameters were required early in the protocol to maintain therapeutic responses to stimulation. After 3 months, however, little further increase in stimulus intensity

508


Fig. 6. Implantable pulse generator placement in an infraclavicular pocket superficial to the pectoralis major muscle fascia. The nerve-electrode lead and pressure-transducer lead are tunneled to the IPG pocket and connected to the IPG. (From Eisele DW, Schwartz AR, Smith PL. Electrical stimulation of the upper airway for obstructive sleep apnea. Op Tech Otolaryngol Head Neck Surg 2000;11:59–65; with permission.)

was required, suggesting that the nerve-electrode interface had stabilized during this early postoperative period. The results of this prospective study demonstrate the feasibility and therapeutic benefit of unilateral hypoglossal stimulation in OSA. Some system technical issues require resolution before broader application of a stimulation system for the treatment of OSA. Electrode breakage or respiratory sensor malfunction occurred in some patients, resulting in compromise of long-term stimulation. Patients who remained free from stimulator malfunction, however, were able to continue to use the device as primary therapy for OSA.


509

Fig. 7. Non-REM apnea-hypopnea indices for a night without stimulation (baseline) and for entire-night and continuous periods with hypoglossal nerve stimulation. Patients’ values for the entire night are the mean of values at 1, 3, and 6 months and last follow-up. (From Schwartz AR, Bennett ML, Smith PL, et al. Therapeutic electrical stimulation of the hypoglossal nerve in obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 2001;127:1216–23; with permission.)

Further studies are necessary to optimize patient-selection criteria for therapeutic hypoglossal nerve stimulation. Patient selection may be based on baseline differences in upper airway collapsibility or the site of pharyngeal obstruction. Therapeutic responses may be augmented by the use of multisite stimulation, such as bilateral hypoglossal nerve stimulation, or stimulation of other combinations of upper airway and cervical muscles. Most importantly, the effect of electrical stimulation of the upper airway on measures of daytime sleepiness, performance, and cardiopulmonary function must be assessed before this treatment modality can be established as a therapeutic option for OSA.

510


Summary Recent studies have shown that neuromuscular stimulation of the genioglossus muscle and direct stimulation of the hypoglossal nerve can be performed selectively and safely. Such stimulation, delivered below the arousal threshold, can modulate airflow during sleep in patients with OSA. The feasibility and potential of upper airway stimulation for the treatment of OSA have been demonstrated. Further studies and stimulation-system refinements are presently underway, with hopes of establishing upper airway stimulation as a therapeutic option for this challenging disorder.

References [1] Remmers JE, de Groot WJ, Sauerland EK, Anch AM. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol 1978;44:931–8. [2] Miki H, Hida W, Chonan T, et al. Effects of submental electrical stimulation during sleep on upper airway patency in patients with obstructive sleep apnea. Am Rev Respir Dis 1989;140:1285–9. [3] Edmonds LC, Daniels BK, Stanson AW, et al. The effects of transcutaneous electrical stimulation during wakefulness and sleep in patients with obstructive sleep apnea. Am Rev Respir Dis 1992;146:1030–6. [4] Guilleminault C, Powell N, Bowman B, Stoohs R. The effects of electrical stimulation on obstructive sleep apnea syndrome. Chest 1995;107:67–73. [5] Oliven A, Schnall RP, Pillar G, et al. Sublingual electrical stimulation of the tongue during wakefulness and sleep. Respir Physiol 2001;127:217–26. [6] Schnall RP, Pillar G, Kelsen SG, Oliven A. Dilatory effects of upper airway muscle contraction induced by electrical stimulation in awake humans. J Appl Physiol 1995;78:1950–6. [7] Schwartz RS, Salome NN, Ingmundon PT, Rugh JD. Effects of electrical stimulation to the soft palate on snoring and obstructive sleep apnea. J Prosthet Dent 1996;76:273–81. [8] Decker MJ, Haaga J, Arnold JL, et al. Functional electrical stimulation and respiration during sleep. J Appl Physiol 1993;75:1053–61. [9] Fairbanks DW, Fairbanks DNF. Neurostimulation for obstructive sleep apnea: investigations. Ear Nose Throat J 1993;72:52–7. [10] Schwartz AR, Eisele DW, Hari A, et al. Electrical stimulation of the lingual musculature in obstructive sleep apnea. J Appl Physiol 1996;81:643–52. [11] Eisele DW, Smith PL, Alam DS, Schwartz AR. Direct hypoglossal nerve stimulation in obstructive sleep apnea. Arch Otolarygol Head Neck Surg 1997;123:57–61. [12] Goding GS, Eisele DW, Testerman R, et al. Relief of upper airway obstruction with hypoglossal nerve stimulation in the canine. Laryngoscope 1998;108:162–9. [13] Eisele DW, Schwartz AR, Smith PL. Electrical stimulation of the upper airway for obstructive sleep apnea. Op Tech Otolaryngol Head Neck Surg 2000;11:59–65. [14] Schwartz AR, Bennett ML, Smith PL, et al. Therapeutic electrical stimulation of the hypoglossal nerve in obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 2001;127: 1216–23.


The limitations of isolated palatal surgery for patients with obstructive sleep apnea Marc G. Dubin, MD, Brent A. Senior, MD* Department of Otolaryngology–Head and Neck Surgery, 610 Burnett-Womack Building, Campus Box 7070, University of North Carolina, Chapel Hill, NC 27599-7070, USA

The goals of the treatment of obstructive sleep apnea (OSA) should be aimed at alleviating symptoms while decreasing morbidity and mortality in a manner that minimizes side effects. For example, approximately 70% of patients with OSA are obese. It has been shown that weight loss improves and in some cases cures sleep-related breathing disorders and is clearly a lowmorbidity treatment modality [1,2]. It also has been shown, however, that the improvement in apnea-hypopnea index (AHI) with weight loss, particularly in moderate to severe sleep apnea, is only partial [3]. Although other medical treatments for OSA exist, including pharmacotherapy and dental appliances, the standard treatment for OSA continues to be continuous positive airway pressure (CPAP). Although highly effective at normalizing polysomnographic variables, it is associated with low compliance rates (60%–80%) [4–9], and 15% of patients refuse CPAP after a single night’s use in the laboratory [10,11]. For this sizable group of patients in whom medical management alone has been of limited value, surgery becomes essential in the management algorithm. Many surgical procedures have been described during the past 20 years, but of these procedures, uvulopalatopharyngoplasty (UPPP), first described in 1981 by Fujita et al [12], continues to be the mainstay. Since its introduction, there has been considerable effort expended studying the efficacy of this procedure and the role that it should play in the management of OSA. Unfortunately, the results of these studies have shown that UPPP as an isolated intervention for the treatment of OSA has met with mediocre results. This fact is confirmed by evaluating the data of its most ardent supporters using the best selection criteria available. In an excellent review of the literature, Sher et al [13] have shown that UPPP is effective in only

* Corresponding author. E-mail address: [email protected] (B.A. Senior). 0030-6665/03/$ - see front matter Ó 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00179-2

512

M.G. Dubin, B.A. Senior / Otolaryngol Clin N Am 36 (2003) 511–517

approximately half of the cases of OSA when success is defined as a drop in the AHI by 50%. When more stringent criteria are used—absolute decline in the apnea index to less than 10 or an AHI less than 20—the success rate is lowered to 40.7% [13]. These data are in marked contrast to the data on the use of UPPP as part of a multistaged approach to multilevel anatomic obstruction. These series report significantly better results: up to 79% success with phase I (UPPP, genioglossal advancement, hyoid suspension) interventions and 90% to 95% success with phase II (additional maxillarymandibular advancement) interventions using similar definitions of success [14–16]. The limitations of UPPP as an isolated procedure for the treatment of OSA center on the challenge of determining the anatomic site of obstruction in an individual with OSA. As is evident by a review of the literature, even when all attempts are made to predict which patients will benefit from UPPP, successful control of OSA cannot be guaranteed [13]. As with many procedures for the treatment of OSA, UPPP has a relatively high morbidity associated with it, and its complications can be life threatening. In contrast, medical management of OSA with CPAP has a relatively high rate of treatment success with few complications, although with mediocre compliance. Sites of obstruction and their identification The etiology of anatomic obstruction in OSA is believed to be an imbalance between the forces acting to maintain airway patency (the force of the pharyngeal muscles) and the negative inspiratory forces generated by the diaphragm [17–19]. This mismatch may be due to a clear anatomic abnormality (ie, micrognathia, macroglossia, or hypertrophy of the tonsils and adenoids) but more often is subtle. It has been demonstrated that patients who have OSA have pharyngeal collapse that is more significant than in control subjects when the same amount of negative suction pressure is applied [20]. Additionally, patients with sleep apnea have been shown to have failure of reflex activation of pharyngeal dilators in response to airway occlusion [18]. In determining the site of obstruction, two problems come to light: Where is the pharyngeal area of greatest collapse, and how can this area be determined accurately? The exact location of pharyngeal collapse is often difficult to ascertain with certainty. More confounding is the fact that the area is often not a single area at all but involves a combination of retropalatal and retroglossal collapse. Similarly, the collapse may be oriented in an anterior-posterior dimension or in a lateral-medial dimension (or a combination). Emphasizing this point, in one series of 200 patients with OSA, only three were found to have a single anatomic abnormality by routine otolaryngologic examination [21]. Theoretically, accurate identification of the exact sites of collapse should aid the surgeon in procedure selection, thereby improving success rates. In


513

most patients, however, it is difficult to identify the anatomic locations amenable to surgical correction. This challenge in identifying the areas of anatomic abnormality has led to the development of diagnostic techniques, including fiberoptic airway endoscopy with the Mu¨ller maneuver and cephalometrics, among others. The role of cephalometrics in predicting the site of anatomic obstruction has led to contradictory data [22–26], which is not surprising given the fact that these static measurements of bony and soft tissue anatomy most likely do not reflect the dynamic changes in pressure that result in airway collapsibility. The role of CT in the assessment of the site of anatomic narrowing has been similarly unsuccessful. There was clearly no difference in static cross-sectional area of the pharyngeal lumen in patients who responded to UPPP and those who did not [27,28]. Attempts at predicting the site of collapse using intrapharyngeal pressure recordings also have been unsuccessful. Various studies have failed to correlate palatal collapse by pressure manometry with a successful outcome from UPPP [27,29,30]. It has been hypothesized by at least one author that only the most proximal site of obstruction can be identified by these methods [27]. Methods that would identify distal sites of collapse will aid in predicting which patients actually will benefit from an isolated surgical intervention that addresses only the proximal palatal obstruction, or if additional surgical modalities may be warranted [27]. Using a related technique, somnofluoroscopy, several authors have attempted to radiographically localize the site of obstruction during sleep [27,30,31]. In one study, patients who had closure identified at the level of the soft palate were more likely than the population as a whole to improve after UPPP (67% versus 42%) [31]. Unfortunately, despite these limited data, this technique is not readily available. With this in mind, Mu¨ller’s maneuver seems to offer the best and easiest analysis of dynamic airway collapsibility. This maneuver assesses the extent of anterior-posterior collapsibility and lateral collapsibility along various points of the upper aerodigestive tract (ie, retropalatal or retroglossal). With this information, the examiner should be able to begin the difficult task of assessing which areas may be amenable to surgical correction in a multistage process. There are several studies that suggest that patients who demonstrate nasopharyngeal collapse on Mu¨ller’s maneuvers are more likely to improve after UPPP [32,33]. Additional data have demonstrated that the maneuver may more accurately identify poor responders to surgical intervention with UPPP, although other studies state that the utility of the maneuver as a predictive technique is low [22,26,34,35]. Owing to the difficulty in predicting a single site of obstruction with relative accuracy, most surgeons currently advocate a multiphase approach in the surgical treatment of OSA, with UPPP playing an integral role. Increased success rates are seen when multiple procedures are used that address various sites of obstruction [15,36]. Palatal obstruction is addressed

514


with UPPP, and base-of-tongue obstruction frequently is addressed with genioglossus advancement and hyoid myotomy suspension or base-oftongue reduction. This procedure then is followed by maxillary-mandibular advancement for treatment failures [15,36]. The success of these approaches adds support for the argument that the limited success of UPPP when performed in isolation is due to its inability to adequately address the multiple sites of obstruction in patients with OSA. Additional patient-selection criteria Clearly, the difficulty in precisely determining the anatomic site of obstruction in patients with OSA leads to challenges in predicting which patients will benefit from palatal surgery in isolation. There are numerous other patient factors that have been implicated in contributing to OSA, however, that are measured easily and theoretically could increase the likelihood of selecting patients who would benefit from UPPP. Unfortunately, for all of the data collected during a polysomnograph, none has been correlated consistently with a successful outcome for an isolated UPPP [37,38]. Increasing body mass index or weight of the individual has been shown to decrease the likelihood of success of a UPPP, however [29,39]. It also has been shown that with more severe OSA (by both AHI and apnea index), UPPP tends to be less successful [13,39]. In light of these data, it was hypothesized that less severe OSA may be more amenable to surgical correction with UPPP. In a study by Senior et al [40], only 40% of patients with mild OSA (AHI >5 and <20) who were treated with UPPP with or without septoplasty responded (response being defined as a decline of 50% in AHI). Interestingly, in the same series, the patients who did not respond had an elevation of their AHI from 16.6 5 to 26.7 18.4 [40]. Based on these data, it is concluded that the anatomy of mild OSA is also complex and is not always corrected with isolated UPPP. Complications A discussion on the limitations of UPPP in the surgical management of OSA would be incomplete without mentioning the complications of the procedure and its associated morbidity. Early reports in the literature described cases of acute airway obstruction, and in some cases, death after UPPP in the setting of sedating drugs [41–43]. In one retrospective review of 135 patients, cited complications included one death, failed intubation (seven patients), hemorrhage (three patients), and arrhythmia (one patient). In another review of 210 patients, the most frequent complications included bleeding (four patients), infection (five patients), seroma (three patients), arrhythmia (four patients), and unstable angina (one patient) [44]. In this same review, significant preoperative comorbidities also were described and included hypertension (31%), arrhythmia (5.5%), coronary artery disease


515

(3.3%), pulmonary disease (7.7%), reflux esophagitis (4.4%), and depression (10%) [44]. In one limited prospective study, it was shown that patients continue to demonstrate a significant number of hypopneas and apneas in the early postoperative period after UPPP when polysomnography was performed [45]. Summary Obstructive sleep apnea is a condition for which palatal surgery in isolation has been shown to have limited success. In comparison, palatal procedures combined with other surgical approaches that address the multiple sites of obstruction in the upper aerodigestive tract seem to have improved success in the carefully selected patient. References [1] Guilleminault C. Clinical features and evaluation of obstructive sleep apnea. In: Kryger MH, Roth T, Dement WC, editors. Principles and practice of sleep medicine. Philadelphia: WB Saunders; 1994. [2] Suratt P, McTier R, Findley L, et al. Changes in breathing and the pharynx after weight loss in obstructive sleep apnea. Chest 1987;92:631–7. [3] Braver H, Block A, Perri M. Treatment for snoring: combined weight loss, sleeping on side, and nasal spray. Chest 1995;107:1283–8. [4] Engleman H, Martin S, Douglas J. Compliance with CPAP therapy in patients with sleep apnoea/hypopnea syndrome. Thorax 1994;49:263–6. [5] Kribbs N, Pack A, Kline L, et al. Objective measurement of patterns of nasal CPAP use by patients with obstructive sleep apnea. Am Rev Respir Dis 1993;147:887–95. [6] McArdle N, Devereux G, Heidarnejad H, et al. Long-term use of CPAP therapy for sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med 1999;159:1108–14. [7] Pepin J, Leger P, Veale D, et al. Side effects of nasal continuous positive airway pressure in sleep apnea syndrome (a study of 193 patients in two French sleep centers). Sleep 1995; 107:375–81. [8] Reeves-Hoche M, Meck R, Zwillich C. Nasal CPAP: an objective evaluation of patient compliance. Am J Respir Crit Care Med 1994;149:149–54. [9] Pirsig W. Obstructive sleep apnea. In: McCaffrey T, editor. Rhinologic diagnosis and treatment. Stuttgart: Theime; 1997. p. 229–69. [10] Krieger J. Long-term compliance with nasal continuous positive airway pressure (CPAP) in obstructive sleep apnea patients and non-apneic snorers. Sleep 1992;15s:42–6. [11] Waldhorn R, Herrick T, Nguyen M, et al. Long-term compliance with nasal continuous positive airway pressure therapy of obstructive sleep apnea. Chest 1990;97:33–8. [12] Fujita S, Conway W, Zorick F, et al. Surgical correction of anatomic abnormalities in obstructive sleep apnea syndrome: uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg 1981;89:923–34. [13] Sher A, Schectman K, Piccirillo J. The efficacy of surgical modifications of the upper airway in adults with obstructive sleep apnea syndrome. Sleep 1995;19:156–77. [14] Hochban W, Brandenburg U, Peter J. Surgical treatment of obstructive sleep apnea by maxillomandibular advancement. Sleep 1994;17:624–9. [15] Riley R, Powell N, Guilleminault C. Obstructive sleep apnea syndrome: a review of 306 consecutively treated surgical patients. Otolaryngol Head Neck Surg 1993;108:117–25. [16] Riley R, Powell N, Guilleminault C. Obstructive sleep apnea and the hyoid: a revised surgical procedure. Otolaryngol Head Neck Surg 1994;111:717–21.

516


[17] Guilleminault C, Hayes B, Smith L, et al. Palatopharyngoplasty and obstructive sleep apnea syndrome. Bull Euro Physiopathol Respir 1983;19:595–9. [18] Hoffstein V. How and why should we stabilize the upper airway? Sleep 1996;19:S57–60. [19] Simmons F, Guilleminault C, Silvestri R. Snoring and some obstructive sleep apnea can be cured by oropharyngeal surgery-palopharyngoplasty. Arch Otolaryngol 1983;109:503–7. [20] Wetmore S, Scrima L, Snyderman N, et al. Postoperative evaluation of sleep apnea after uvulopalatopharyngoplasty. Laryngoscope 1986;96:738–41. [21] Rojewski T, Schuller D, Clark R, et al. Videoendoscopic determination of the mechanism of obstruction in obstructive sleep apnea. Otolaryngol Head Neck Surg 1984;92:127–31. [22] Doghramji K, Jabourian Z, Pilla M, et al. Predictors for uvulopalatopharyngoplasty. Laryngoscope 1995;105:311–4. [23] Gislason T, Lindholm C, Almqvist M. Uvulopalatopharyngoplasty in the sleep apnea syndrome: predictors of results. Arch Otolaryngol Head Neck Surg 1985;114:45–51. [24] Riley R, Guilleminault C, Powell N, et al. Palatopharyngoplasty failure: cephalometric roentgenograms and obstructive sleep apnea. Otolaryngol Head Neck Surg 1985;93:240–4. [25] Ryan C, Dickson R, Blokmanis A, et al. Upper airway measurements predict response to uvulopalatopharyngoplasty in obstructive sleep apnea. Laryngoscope 1990;100:248–53. [26] Yao M, Utley D, Terris D. Cephalometric parameters after multilevel pharyngeal surgery for patients with obstructive sleep apnea. Laryngscope 1998;108:789–95. [27] Launois S, Feroah T, Campbell W, et al. Site of pharyngeal narrowing predicts outcome of surgery for obstructive sleep apnea. Am Rev Respir Dis 1993;147:182–9. [28] Shepard J, Thawley S. Evaluation of the upper airway by computerized tomography in patients undergoing uvulopalatopharyngoplasty for obstructive sleep apnea. Am Rev Respir Dis 1989;140:711–6. [29] Hudgel D, Horasick T, Katz R, et al. Uvulopalatopharyngoplasty in obstructive apnea: value of preoperative localization of site of upper airway narrowing during sleep. Am Rev Respir Dis 1991;143:942–6. [30] Metes A, Hoffstein V, Mateika S, et al. Site of airway obstruction in patients with obstructive sleep apnea before and after uvulopalatopharyngoplasty. Laryngoscope 1991;101:1102–8. [31] Katsantonis G, Walsh J. Somnofluoroscopy: its role in the selection of candidates for uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg 1986;94:56–60. [32] DeBerry-Borowiecki B, Kukwa A, Blanks R. Indications for palatopharyngoplasty. Arch Otolaryngol 1985;111:659–63. [33] Sher A, Thorpy M, Shprintzen R, et al. Predictive value of Muller maneuver in selection of patients for uvulopalatopharyngoplasty. Laryngoscope 1985;95:1483–7. [34] Aboussauan L, Golish J, Wood B, et al. Dynamic pharyngoscopy in predicting outcome of uvulopalatopharyngoplasty for moderate and severe obstructive sleep apnea. Chest 1995; 107:946–51. [35] Katsantonis G, Mass C, Walsh J. The predictive efficacy of the muller maneuver in uvulopalatopharyngoplasty. Laryngoscope 1989;99:677–80. [36] Li K, Riley R, Powell N, et al. Obstructive sleep apnea surgery: patient perspective and polysomnographic results. Otolaryngol Head Neck Surg 2000;123:572–5. [37] Johnson N, Chinn J. Uvulopalatopharyngoplasty and inferior sagittal mandibular osteotomy with genioglossus advancement for treatment of obstructive sleep apnea. Chest 1994; 105:278–83. [38] Schwartz A, Schubert N, Rothman W, et al. Effect of uvulopalatopharyngoplasty on upper airway collapsibility in obstructive sleep apnea. Am Rev Respir Dis 1992;145:527–32. [39] Larsson L, Carlsson-Nordlander B, Svanborg E. Four year follow-up after uvulopalatopharyngoplasty in 50 unselected patients with obstructive sleep apnea syndrome. Laryngoscope 1994;104:1362–8. [40] Senior B, Rosenthal L, Lumley A, et al. Efficacy of uvulopalatopharyngoplasty in unselected patients with mild obstructive sleep apnea. Otolaryngol Head Neck Surg 2000; 123:179–82.


517

[41] Fairbanks D. Uvulopalatopharyngoplasty complication and avoidance strategies. Otolaryngol Head Neck Surg 1990;102:239–45. [42] Hishikawa Y, Furuya E, Wakamatsu H, et al. A polygraphic study of hypersomnia with periodic breathing and primary alveolar hypoventilation. Bull Physiopathol Respir 1970; 8:1139–42. [43] Simmons F, Guilleminault C, Dement W, et al. Surgical management of airway obstruction during sleep. Laryngoscope 1977;87:326–38. [44] Riley R, Powell N, Guilleminault C, et al. Obstructive sleep apnea surgery: risk management and complications. Otolaryngol Head Neck Surg 1997;117:648–52. [45] Burgess L, Derderian S, Morin G, et al. Postoperative risk following uvulopalatopharyngoplasty for obstructive sleep apnea syndrome. Otolaryngol Head Neck Surg 1992; 106:81–6.


Treating pediatric patients with obstructive sleep disorders: an update Anna H. Messner, MD* Division of Otolaryngology/Head and Neck Surgery, Room R135, Edwards Building, Stanford University, Stanford, CA 94305-5328, USA

It is a truth universally known that a person who sleeps poorly at night is tired the following day. Although this ‘‘truth’’ may hold for adults, it usually does not hold for young children with obstructive sleep apnea syndrome (OSAS) [1]. Obstructive sleep apnea syndrome is defined as a ‘‘disorder of breathing during sleep characterized by prolonged partial upper airway obstruction and/or intermittent complete obstruction (obstructive apnea) that disrupts normal ventilation during sleep and normal sleep patterns’’ [2]. Importantly, pediatric patients can show symptoms of obstructive sleep disorder even in the absence of frank apneas (upper airway resistance syndrome) [3,4]. Obstructive sleep apnea syndrome must be differentiated from primary snoring, which is defined as snoring without obstructive apnea, frequent arousals from sleep, or gas-exchange abnormalities [5]. One indicator of excessive daytime sleepiness is how quickly children fall asleep during the day. In a study of 54 children diagnosed on polysomnogram (PSG) as having OSAS, only 7 (13%) were found to fall asleep in less than 10 minutes when they were evaluated in a sleep laboratory during the day, confirming that daytime sleepiness in children with OSAS is the exception, not the rule [6]. Instead of being sleepy, the child may have nonspecific behavioral difficulties such as abnormal shyness, hyperactivity, developmental delay, and aggressive behavior. The possibility of a sleep disorder should be considered in any child being evaluated for an attention-deficit disorder. In an effort to clarify the relationship between poor sleep quality and daytime functioning, Gozal [7] evaluated a cohort of poorly performing children in the first grade. In this prospective study, 297 first graders who were in the lowest tenth percentile of their class were screened for OSAS

* Pediatric Otolaryngology–Head and Neck Surgery, Lucile Packard Children’s Hospital at Stanford, 725 Welch Road, Palo Alto, CA 94304-5654, USA. E-mail address: [email protected] 0030-6665/03/$ - see front matter Ó 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00180-9

520

A.H. Messner / Otolaryngol Clin N Am 36 (2003) 519–530

using a parental questionnaire and a single-night recording of pulse oximetry and transcutaneous partial pressure of carbon dioxide. Those who were found to have abnormalities on the studies (54 of 297) were encouraged to seek medical intervention; 24 of these children underwent tonsillectomy and adenoidectomy (T&A). The performance of the children who underwent T&A was compared to the 30 children who did not undergo T&A, and in second grade the treatment group’s mean grades increased significantly. The author concluded that OSAS is associated with an adverse effect on learning. Further evidence that OSAS may affect daytime functioning is seen in another article by Gozal and Pope [8]. This retrospective questionnaire compared snoring in early childhood in matched groups of 13- and 14-year-olds who were in the top or bottom quartile of their class. Children with lower academic performance in middle school were found to have been more likely to have snored during early childhood and to require T&A for snoring as compared to their better-performing schoolmates. The authors concluded that these findings support the idea that a ‘‘learning debt’’ may develop with sleep-disordered breathing during early childhood and hamper subsequent school performance. Nocturnal symptoms of OSAS include snoring, pauses in breathing, gasping for breath, increased respiratory effort (nasal flaring and supraclavicular, suprasternal, and intercostal retractions), enuresis, and excessive sweating. Frequently, children with OSAS resist going to bed [9]. In adults, sleep apnea is worse when the patient is in the supine position. Conversely, children with OSAS seem to breathe best when they are in the supine position [10]. Severe OSAS can lead to cor pulmonale. Etiology of obstructive sleep apnea syndrome in children It has been theorized that obstructive sleep disorders are familial. Genetic transmission of risk factors such as a high-arched palate, micrognathia, or adenotonsillar hypertrophy may play an etiologic role. A questionnaire-type telephone survey by Ovchinsky et al [11] showed that 20.4% of first-degree relatives of 115 index cases with pediatric obstructive sleep apnea had symptoms highly suggestive of obstructive sleep apnea. Because the general incidence of this syndrome is from 3% to 4%, the study supports the concept that there are genetic mechanisms at work in the development of the disorder [12]. This study confirmed the familial incidence of 21% of firstdegree relatives of index cases with OSAS who were found to have OSAS as reported by Redline et al [13]. In a combined questionnaire-PSG study by Douglas et al [14], a similar (25%) incidence of OSAS was seen again in the first-degree relatives of patients with apnea. Evaluation of the child with symptoms of obstructive sleep apnea syndrome With the wide range of symptoms, the diagnosis of a significant obstructive sleep disorder in a pediatric patient can be difficult. The most


521

widely recognized and best single laboratory test to support the diagnosis of obstructive sleep disorder is the nocturnal PSG. A pediatric PSG uses the same technology to record the same information as is recorded in adults. The recording includes electroencephalography, chin electromylogram, right and left electro-oculogram, electrocardiogram, limb movements, and breathing measurements. The breathing measurements usually monitored are airflow, respiratory effort, and pulse oximetry. End-tidal carbon dioxide and esophageal pressure measurements are used in some but not all laboratories. Although the PSG unquestionably is the most effective tool available to determine the presence and severity of an obstructive sleep disorder, some have questioned the reliability of a single-night study. The possibility of a ‘‘first-night’’ effect, that is, a change in a patient’s sleep architecture due to unfamiliar surroundings, has been postulated. It seems that the first-night effect is rarely significant. In a study by Katz et al [15], 30 children with symptoms of sleep-disordered breathing underwent two nocturnal PSGs performed 7 to 27 days apart. The mean of the respiratory variables, including apnea index, apnea-hypopnea index, arterial oxygen saturation, and end-tidal partial pressure of carbon dioxide, was not significantly different from night to night. No child changed diagnosis from primary snoring to OSAS (or the reverse) as a result of the second PSG. This finding led to the conclusion that a single PSG night is an adequate measure of OSAS in children with symptoms of sleep-disordered breathing. Currently, the relationships among various parameters of the PSG (apneahypopnea index, number of respiratory-related arousals per hour of sleep, minimum oxygen saturation, number of oxygen desaturations <90% per hour of sleep, and the maximum end-tidal carbon dioxide value) and neuropsychologic parameters (intelligence, memory, attention and impulsivity, and academic performance) are being studied. Preliminary evidence suggests that memory impairment is correlated strongly with the degree of hypoxemia as indicated by the minimum arterial oxygen saturation value, whereas impairment in adaptive behavior is correlated with the degree of sleep disruption as indicated by the respiratory arousal index. Intelligence and academic achievement are not related to any specific PSG parameter, but instead are best correlated with a composite of the parameters described [16]. There is controversy concerning the necessity of a PSG in all pediatric patients with symptoms of OSAS [17]. In April of 2002, the Section on Pediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome of the American Academy of Pediatrics published a clinical practice guideline that addressed the diagnosis and management of childhood OSAS [18]. Concerning the diagnosis of patients with OSAS, the guideline recommends the following: ‘‘(1) all children should be screened for snoring; (2) complex high-risk patients should be referred to a specialist; (3) patients with cardiorespiratory failure cannot await elective evaluation; and (4) diagnostic evaluation is useful in discriminating between primary snoring

522


and OSAS, the gold standard being polysomnography.’’ The guideline concludes that history and physical examination are poor at differentiating primary snoring from OSAS. Other screening techniques, such as videotaping, nocturnal pulse oximetry, and daytime nap polysomnography were considered helpful if results are positive, but have a poor predictive value if results are negative [19]. Unfortunately, the lack of pediatric sleep laboratories makes this guideline difficult to follow. Tonsillectomy techniques There is little debate that the primary treatment for most children with OSAS is T&A [18]. Head-and-neck surgeons are constantly searching for better ways to perform a tonsillectomy. Although the standard cold (scissors, knife) or hot (electrocautery) techniques are quick, effective, and safe, the patient invariably experiences significant postoperative pain. The best operative technique to minimize postoperative pain has long been and continues to be controversial, and thus various techniques are compared constantly in the medical literature. Nunez et al [20] compared electrocautery (hot) versus cold dissection and snare tonsillectomy prospectively in a group of 54 children. Not surprisingly, cold dissection resulted in double the intraoperative blood loss (33.7 mL versus 15.1 mL). Recovery in the first 24 hours after surgery was similar in both groups. Follow-up of the children, however, revealed a significantly greater analgesic consumption, longer time to return to eating a normal diet, and more consultations with the family practitioner for throat pain for children in the hot-dissection group. In an effort to decrease the postoperative pain experience and to decrease the amount of bleeding intraoperatively, several new techniques have been described recently. A supplemental issue of Laryngoscope was dedicated to ‘‘Innovative Techniques for Adenotonsillar Surgery in Children.’’ In it, Koltai et al [21] reviewed their experience with intracapsular tonsillectomy—a partial tonsillectomy—using powered instrumentation. The purpose of the partial as opposed to the routine tonsillectomy is to preserve the tonsil capsule, thus leaving the pharyngeal muscles covered, and, it is hoped, causing the patient to experience less postoperative pain. A retrospective review of 150 patients who underwent intracapsular tonsillectomy was compared with 162 children who underwent standard tonsillectomy during the same time period. A telephone survey was used to collect data concerning the postoperative course. Although the children in the intracapsular group had significantly less pain than the total tonsillectomy group, the two groups were not equivalent; the intracapsular tonsillectomy group was significantly younger (mean, 6.0 versus 8.9 years). A prospective, randomized study by the same group is pending. The ultrasonic dissector coagulator (Harmonic scalpel [HS]; Ethicon Endo-Surger, Cincinnati, OH) is a relatively new surgical tool that uses


523

ultrasonic technology to cut and coagulate tissues at lower temperatures than that used with the electrocautery, thereby minimizing tissue damage (and possibly, postoperative pain). Two studies have compared HS tonsillectomy to electrocautery tonsillectomy. The first, a prospective, randomized study performed by Walker and Syed [22], used a questionnaire to compare the postoperative course after tonsillectomy with the HS (155 patients) with that after electrocautery (161 patients). Intraoperative blood loss and postoperative hemorrhage were equivalent in the two groups. Patients treated with the HS had a significantly earlier return to normal diet and activity. An upcoming study of 120 children undergoing tonsillectomy who were randomly assigned to the HS (61 patients) and electrocautery (59 patients) also showed equivalent blood loss in the two groups [23]. Operating time was significantly longer with the HS, and pain scores trended lower on postoperative days 2, 3, and 4 but were not statistically significant. Thus far, there does not seem to be enough evidence showing decreased postoperative pain with the HS, considering its additional cost and prolonged operating time, to justify its use during routine tonsillectomy. A recently published study compared electrocautery tonsillectomy versus plasma-mediated ablation (cold ablation) of the tonsil [24]. Plasma-mediated ablation energizes protons to break molecular bonds between tissues. This method results in less thermal injury, which theoretically may reduce postoperative pain. In this prospective, randomized, blinded study, 34 children aged 4 to 7 years underwent tonsillectomy. Postoperative pain scores were recorded for 10 days, and a histopathologic evaluation of the excised tonsils was performed. Mean surgical time was increased for the cold-ablation group (23.8 minutes versus 16.2 minutes), whereas estimated blood loss was similar. Histopathologic analysis of the tonsils showed that the mean depth of injury was significantly greater in the electrocautery group. Two of the children undergoing cold-ablation removal of their tonsils required unplanned admissions for airway obstruction. Measures of postoperative pain were not significantly different between the two groups, leading the authors to conclude that plasma-mediated ablation ‘‘as it is presently delivered should not replace monopolar electrosurgery for routine tonsillectomy.’’ Pathologic evaluation of the tonsil/adenoid specimen After the tonsils and adenoids are removed, the circulating nurse in the operating room typically asks the surgeon if he or she would like the specimen sent for pathologic evaluation. For the pediatric patient undergoing a routine T&A for OSAS, this step seems to be unnecessary. In a recent study by Younis et al [25], 2438 tonsil-specimen reports were reviewed retrospectively, and none was found to have a histopathologic finding other than the expected lymphoid hyperplasia. In addition, Strong et al [26] found no occult neoplasms in 1583 specimens reviewed at their institution. They surveyed 4715 members of the American Academy of

524


Otolaryngology–Head and Neck Surgery and found a significant increase in respondents ordering ‘‘gross only’’ and ‘‘no pathology.’’ A notable exception to the ‘‘gross-only’’ or ‘‘no-pathology’’ policy concerns children who have undergone liver transplantation. Lymphoid hypertrophy is common in this group, and an obstructive sleep disorder can result. On removing the tonsils or adenoids, the specimen always should be sent for pathologic review. Post-transplant lymphoproliferative disease can result in these patients after infection with Epstein-Barr virus. Histologic changes can range from tonsillar hyperplasia to large-cell lymphoma, necessitating changes in the immunosuppressive therapy [27,28]. Postoperative complications Postoperative hemorrhage has been and continues to be the most important complication after tonsillectomy surgery. A recent retrospective study of 1438 patients found that 51 patients (3.5%) required intervention (termed a significant hemorrhage) for their bleeding [29]. One hundred twelve (7.8%) of all patients in this study had returned for an evaluation when the caregiver saw blood of any volume. Patients who were younger than the age of 3 had fewer significant hemorrhages than the older children, with only 0.9% (3 of 317) requiring postoperative medical intervention. In the 4-to-11 age group, 969 underwent tonsillectomy and 34 (3.5%) required intervention. The oldest group (ages 12–20) had the highest significant postoperative hemorrhage rate, with 9.2% (14 of 152) requiring care. The most common time from surgery to initial evaluation for hemorrhage was 6 days. As stated earlier, children inevitably experience pain after a tonsillectomy. In an effort to objectively measure post-tonsillectomy pain, a standard questionnaire was developed so that analgesic requirements could be titrated [30]. This questionnaire asked caregivers to report on the child’s drinking, eating, talking, dribbling, crying, activity, and mood, and assigned points to each response so that higher scores indicate more severe pain. Interestingly, child complaints of pain did not correlate well with the other items in the survey, and when this question was removed, the survey had higher internal consistency. The pain scores also did not correlate with the amount of pain medicine given in the first 24 hours after tonsillectomy surgery. In an effort to reduce the postoperative pain, a single dose of dexamethasone can be given intraoperatively to decrease vomiting, improve oral intake, and decrease postoperative pain [31–33]. The doses given in the cited studies range from 0.15 to 1.0 mg/kg; the optimal dose is not known. Acetaminophen is a standard postoperative medication given to children after tonsillectomy. In a prospective, randomized, double-blind study of acetaminophen compared to acetaminophen with codeine, the children who used acetaminophen alone consumed a significantly higher percentage of a normal diet on the first 6 postoperative days, with no difference in pain scores between the treatment groups [34]. Postoperatively, a telephone call


525

3 to 4 weeks after surgery by an otolaryngology nurse, instead of the traditional postoperative visit, has been shown to be cost-effective and desirable to parents [35].

Nonsurgical treatment of pediatric obstructive sleep apnea syndrome For the patient and family who want to avoid surgery, one option may be topical steroids. In a recent study, 6 weeks of topical fluticasone was found to decrease the apnea-hypopnea index from an average of 10.7 to 5.8 in a small group of subjects (n ¼ 13) [36]. This finding was compared to a similarly sized control group of subjects who had an increase from 10.9 to 13.1 in their apneahypopnea index, although there was no significant change in tonsil size, adenoid size, and symptoms score between the two groups. Occasionally, patients with obesity, neuromuscular disorders (cerebral palsy), and craniofacial disorders will have respiratory difficulties in the immediate postoperative period. Frequently, these patients can be managed in the pediatric intensive care unit with continuous positive airway pressure or bilevel positive airway pressure (BiPAP) [37]. This same group of patients (and occasionally, other children with severe OSAS) frequently have residual OSAS after a T&A is performed. The study by Padman et al [38] supports the use of BiPAP in these patients with persistent OSAS. They described 10 children (aged 3–18) who underwent pre-BiPAP and postBiPAP sleep studies. With BiPAP, the apnea index decreased from 19.7 to 0.82, the lowest oxygen saturation increased from 75.6% to 89.5%, and breath length increased from 3.22 to 3.68 seconds. In severe cases of OSAS in which BiPAP is not possible, a tracheotomy may be necessary, although it often can be avoided in the child with craniofacial anomalies who undergoes craniofacial skeletal expansion and soft tissue reduction [39,40].

Patient quality of life before and after tonsillectomy and adenoidectomy Several recent studies have examined the effect of T&A on patient quality of life (QOL). Published, validated, reliable QOL surveys relating specifically to tonsillectomy include the OSD-6 (Fig. 1) developed by de Serres et al [41] and the OSA-18 (Fig. 2) developed by Franco et al [42]. Both instruments survey caregivers on their child’s sleep disturbance, physical symptoms, emotional symptoms, daytime activity, and caregiver concerns. The OSD-6 specifically addresses speech or swallowing problems. The OSA18 was found to correlate with the respiratory disturbance index on nap polysomnography in the 61 children studied. A before-and-after adenotonsillectomy study using the OSD-6 instrument detected large improvements in at least short-term QOL in most children [43]. Specifically, large, moderate, and small improvements in QOL were seen in 74.5%, 6.1%, and 7.1% of children, respectively. The most

Fig. 1. The OSD-6. (From deSerres LM, Derkay C, Astley S, et al. Measuring quality of life in children with obstructive sleep disorders. Arch Otolaryngol Head Neck Surg 2000;126:1426; with permission.)


527

Fig. 2. The OSA-18. (From Franco RA, Rosenfeld RM, Rao M. Quality of life for children with obstructive sleep apnea. Otol Head Neck Surgery 2000;123:10; with permission.)

improved areas were sleep disturbance, caregiver concern, and physical suffering. Five percent of children had a poorer QOL after surgery. Similarly, the OSA-18 instrument was used in addition to the Child Behavior Checklist (CBCL) by Goldstein et al [44] in a before-and-after adenotonsillectomy study. A pilot study using the CBCL showed that 10 of 36 children (28%) undergoing T&A for chronic upper airway obstruction scored in the abnormal range for behavior. Using both the CBCL and the OSA-18 to evaluate 64 children who underwent T&A for treatment of sleep-disordered breathing or recurrent tonsillitis, behavioral and emotional difficulties in children with sleep-disordered breathing were found to improve after surgery [45]. Again, 25% of children demonstrated behavioral and emotional problems preoperatively on the CBCL. The total problem scores and most domains significantly improved after T&A, and only 8% of children scored in the abnormal range postoperatively.

528


In addition to improved behavior after a T&A, families can be informed preoperatively that frequently the child will gain weight postoperatively. A recent study confirmed that growth hormone secretion is impaired in children with OSAS [46]. After adenotonsillectomy, children with OSAS normalize their growth hormone secretion and gain weight. Further confirming evidence was provided in a retrospective cohort study by Soultan et al [47]. In this retrospective study, 45 children who underwent tonsillectomy and/or adenoidectomy for OSAS an average of 15 months previously (range, 6–36 months). Thirty-one children (69%) had substantial weight gain postoperatively, including 10 of 17 who were obese or morbidly obese at the time of surgery. Summary Obstructive sleep apnea syndrome in children continues to be an important subject for otolaryngologists because of the high prevalence of the disease. The evaluation of a child with OSAS remains controversial, although there is little controversy that T&A is the optimal treatment for these children. The search for the optimal T&A technique is ongoing, although now either ‘‘cold’’ tonsillectomy or ‘‘hot’’ tonsillectomy is standard. Quality-of-life studies confirm the significant benefit gained after a child undergoes a T&A. References [1] Rosen CL. Obstructive sleep apnea syndrome (OSAS) in children: diagnostic challenges. Sleep 1996;19:S274–77. [2] American Thoracic Society. Standards and indications for cardiopulmonary sleep studies in children. Am J Respir Crit Care Med 1996;153:866–78. [3] Guilleminault C, Pelayo R, Clerk A, et al. Recognition of sleep-disordered breathing in children. Pediatrics 1996;98:871–82. [4] Downey R 3d, Perkin RM, MacQuarrie J. Upper airway resistance syndrome: sick, symptomatic but underrecognized. Sleep 1993;16:620–3. [5] American Sleep Disorders Association. International classification of sleep disorders, revised: diagnostic and coding manual. Rochester (MN): American Sleep Disorders Association; 1997. p. 195–7. [6] Gozal D, Wang M, Pope DW Jr. Objective sleepiness measures in pediatric obstructive sleep apnea. Pediatrics 2001;108:693–7. [7] Gozal D. Sleep-disordered breathing and school performance in children. Pediatrics 1998;102:616–20. [8] Gozal D, Pope DW Jr. Snoring during early childhood and academic performance at ages thirteen to fourteen years. Pediatrics 2001;107:1394–9. [9] Owens J, Opipari L, Nobile C, et al. Sleep and daytime behavior in children with obstructive sleep apnea and behavioral sleep disorders. Pediatrics 1998;102:1178–84. [10] Fernandes do Prado LB, Li X, Thompson R, et al. Body position and obstructive sleep apnea in children. Sleep 2002;25:66–71. [11] Ovchinsky A, Rao M, Lotwin I, et al. The familial aggregation of pediatric obstructive sleep apnea syndrome. Arch Otol Head Neck Surg 2002;128:815–8.


529

[12] Phillips B, Cook Y, Schmitt F. Sleep apnea: prevalence of risk factors in a general population. South Med J 1989;82:1090–2. [13] Redline S, Tishler PV, Tosteson TD, et al. The familial aggregation of obstructive sleep apnea. Am J Respir Crit Care Med 1995;151:682–7. [14] Douglas NJ, Luke M, Mathur R. Is the sleep apnoea/hypopnoea syndrome inherited? Thorax 1993;48:719–21. [15] Katz ES, Greene MG, Carson KA, et al. Night-to-night variability of polysomnography in children with suspected obstructive sleep apnea. J Pediatr 2002;140:589–94. [16] Glaze DG, Bautista M, Chapieski ML, et al. Obstructive sleep apnea: impact on cognition, behavior and quality of life. In: Abstracts of the American Society of Pediatric Otolaryngology annual meeting, Boca Raton, FL, May 14, 2002, p. 17. [17] Messner AH. Evaluation of obstructive sleep apnea by polysomnography prior to pediatric adenotonsillectomy. Arch Otolaryngol Head Neck Surg 1999;125:353–6. [18] Section on Pediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome. American Academy of Pediatrics. Clinical practice guideline: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 2002;109:704–12. [19] Saeed MM, Keens TG, Stabile MW, et al. Should children with suspected obstructive sleep apnea syndrome and normal nap sleep studies have overnight sleep studies? Chest 2000;118:360–5. [20] Nunez DA, Provan J, Crawford M. Postoperative tonsillectomy pain in pediatric patients: electrocautery (hot) vs. cold dissection and snare tonsillectomy—a randomized trial. Arch Otol Head Neck Surg 2000;126:837–41. [21] Koltai PJ, Solares CA, Mascha EJ, et al. Intracapsular partial tonsillectomy for tonsillar hypertrophy in children. Laryngoscope 2002;112:17–9. [22] Walker RA, Syed ZA. Harmonic scalpel tonsillectomy versus electrocautery tonsillectomy: a comparative pilot study. Otolaryngol Head Neck Surg 2001;125:449–55. [23] Wiatrak BJ, Willging JP. Harmonic scalpel for tonsillectomy. Laryngoscope 2002;112: 14–6. [24] Shah UK, Galinkin J, Chiavacci R, et al. Tonsillectomy by means of plasma-mediated ablation: prospective, randomized, blinded comparison with monopolar electrosurgery. Arch Otol Head Neck Surg 2002;128:672–6. [25] Younis RT, Hesse SV, Anand VK. Evaluation of the utility and cost-effectiveness of obtaining histopathologic diagnosis on all routine tonsillectomy specimens. Laryngoscope 2001;111:2166–9. [26] Strong EB, Rubinstein B, Senders CW. Pathologic analysis of routine tonsillectomy and adenoidectomy specimens. Otolaryngol Head Neck Surg 2001;125:473–7. [27] De Diego JI, Prim MP, Hardisson D, et al. Post-transplant lymphoproliferative disease in tonsils of children with liver transplantation. Int J Pediatr Otorhinolaryngol 2001;58:113–8. [28] Broughton S, McClay JE, Murray A, et al. The effectiveness of tonsillectomy in diagnosing lymphoproliferative disease in pediatric patients after liver transplantation. Arch Otolaryngol Head Neck Surg 2000;126:1444–7. [29] Liu JH, Anderson KE, Willging JP, et al. Posttonsillectomy hemorrhage: what is it and what should be recorded? Arch Otol Head Neck Surg 2001;127:1271–5. [30] Myatt HM, Myatt RA. The development of a paediatric quality of life questionnaire to measure post-operative pain following tonsillectomy. Int J Pediatr Otorhinolaryngol 1998;44:115–23. [31] Steward DL, Welge JA, Myer CM. Do steroids reduce morbidity of tonsillectomy? Metaanalysis of randomized trials. Laryngoscope 2001;111:1712–8. [32] Hanasono MM, Messner AH, Mikulec AM, et al. Preoperative steroids in tonsillectomy patients using hot and cold surgical techniques. In: Program of the American Society of Pediatric Otolaryngology annual meeting, Boca Raton, FL, May 14, 2002, p. 55 [33] Giannoni C, White S, Enneking FK. Does dexamethasone with preemptive analgesia improve pediatric tonsillectomy pain? Otolaryngol Head Neck Surg 2002;126:307–15.

530


[34] Moir MS, Bair E, Shinnick P, et al. Acetaminophen versus acetaminophen with codeine after pediatric tonsillectomy. Laryngoscope 2000;220:1824–7. [35] Rosbe KW, Jones D, Jalisi S, et al. Efficacy of postoperative follow-up telephone calls for patients who underwent adenotonsillectomy. Arch Otolaryngol Head Neck Surg 2000; 126:718–21. [36] Brouillette RT, Manoukian JJ, Ducharme FM, et al. Efficacy of fluticasone nasal spray for pediatric obstructive sleep apnea. J Pediatr 2001;138:838–44. [37] Friedman O, Chidekel A, Lawless ST, et al. Postoperative bilevel positive airway pressure ventilation after tonsillectomy and adenoidectomy in children—a preliminary report. Int J Pediatr Otorhinolaryngol 1999;51:177–80. [38] Padman R, Hyde C, Foster P. The pediatric use of bilevel positive airway pressure therapy for obstructive sleep apnea syndrome: a retrospective review with analysis of respiratory parameters. Clin Pediatr 2002;41:163–9. [39] Cohen SR, Simms C, Burstein FD, et al. Alternatives to tracheostomy in infants and children with obstructive sleep apnea. J Pediatr Surg 1999;34:182–6. [40] Cohen SR, Ross DA, Burstein FD, et al. Skeletal expansion combined with soft-tissue reduction in the treatment of obstructive sleep apnea in children: physiologic results. Otolaryngol Head Neck Surg 1998;119:476–85. [41] de Serres LM, Derkay C, Astley S, et al. Measuring quality of life in children with obstructive sleep disorders. Arch Otolaryngol Head Neck Surg 2000;126:1423–9. [42] Franco RA, Rosenfeld RM, Rao M. Quality of life for children with obstructive sleep apnea. Otolaryngol Head Neck Surg 2000;123:9–16. [43] de Serres LM, Derkay C, Sie K, et al. Impact of adenotonsillectomy on quality of life in children with obstructive sleep disorders. Arch Otolaryngol Head Neck Surg 2002; 128:489–96. [44] Goldstein NA, Post JC, Rosenfeld RM, et al. Impact of tonsillectomy and adenoidectomy on child behavior. Arch Otolaryngol Head Neck Surg 2000;126:494–8. [45] Goldstein NA, Fatima M, Campbell TF, et al. Child behavior and quality of life before and after tonsillectomy and adenoidectomy. Arch Otolaryngol Head Neck Surg 2002;128:770–5. [46] Nieminen P, Lopponen T, Tolonen U, et al. Growth and biochemical markers of growth in children with snoring and obstructive sleep apnea. Pediatrics 2002;109:e55. [47] Soultan Z, Wadowski S, Rao M, et al. Effect of treating obstructive sleep apnea by tonsillectomy and/or adenoidectomy on obesity in children. Arch Pediatr Adolesc Med 1999;153:33–7.


Surgery for sleep-disordered breathing in female patients Regina Paloyan Walker, MD* Department of Otolaryngology, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA

The average physician and layperson envision Joe, the fat boy of the Pickwick Club, when the medical condition obstructive sleep apnea syndrome (OSAS) is discussed. Charles Dickens depicted Joe as a morbidly obese, hypersomnolent boy who snored. Initial research and clinical guidelines that have been established for the evaluation and treatment of this disorder have been based primarily on patients who resemble Joe. During the past 10 years, however, it has become apparent that young and old, male and female, and obese and nonobese patients may be afflicted with sleepdisordered breathing (SDB). Presenting symptoms may vary depending on the age and gender of the patient. A child with OSAS may be hyperactive, whereas an adult with the same condition typically has the opposite symptom of hypersomnolence. Clinical response to positive airway pressure and surgical treatment varies as well. The astute physician needs to recognize these differences when evaluating and treating patients with sleep disorders.

Epidemiology of sleep-disordered breathing: male versus female sleep-disordered breathing Young et al [1] were the first group to perform a large population-based study of sleep apnea that included women. Prior to this publication in 1993, other large population-based studies of OSAS included only male patients [2–4]. In addition to these population-based studies, reports that focused on the clinical population of patients with OSAS again focused on the male patients. Review articles from the 1970s and 1980s suggested that the maleto-female ratio for OSAS in a clinical population varied from 10:1 to 60:1

* 40 South Clay Street, Suite 135, West Hinsdale, IL 60521, USA. E-mail address: [email protected] 0030-6665/03/$ - see front matter Ó 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00181-0

532

R.P. Walker / Otolaryngol Clin N Am 36 (2003) 531–538

[5]. The conclusion that was extrapolated from these articles was that OSAS was a disorder of male patients. The article published by Young et al [1] changed the perception of this disease. This group of investigators studied 602 patients (352 men, 250 women) who were from a middle-aged and working population in Wisconsin. The results of this study revealed that 9% of women and 24% of men had SDB. Sleep-disordered breathing was defined as an apnea-hypopnea score of five or more. They also estimated that 2% of women and 4% of men, in a middle-aged working population, have OSAS. The diagnostic criterion that was used to define a diagnosis of sleep apnea syndrome was an apnea-hypopnea score of five or more that was associated with daytime hypersomnolence. Young et al showed that approximately 33% of the sleep apnea population is made up of women. In another study, Ohayon et al [6] conducted a telephone-interview survey of 4972 people in the United Kingdom that concluded that approximately 30% of patients with OSAS are women. Clinical population studies examine only the population that presents to physicians for evaluation of symptoms, whereas population-based studies focus on the general population. At this time, population-based studies are reporting that one third of the apnea population is female. Yet in studies published in the 1990s that evaluated a clinical population, only 10% to 25% of the patients were female [7,8]. Therefore, gender-related differences are much less pronounced in recent population-based studies than previous clinical studies indicated. Gender differences in symptoms of obstructive sleep apnea syndrome In 1996, Young et al [9] addressed the gender bias in the sleep apnea population using data from the Wisconsin Sleep Cohort Study. Multiple hypotheses were evaluated to attempt to explain why sleep apnea is underdiagnosed in women. One hypothesis is that the diagnosis of women with sleep apnea is missed because they have different symptoms than men. The findings of Young et al do not support this hypothesis, however. For both men and women, the significant predicators of SDB are snoring, breathing pauses, and hypersomnolence. Although these classic symptoms are found in both men and women, women reported higher rates of morning headaches, depression, and anxiety at presentation in addition to classic symptoms. Morning headaches were reported more commonly in women than in men in a surgical population of apneic patients as well [10]. Morning headaches, depression, and anxiety are not as well recognized as the ‘‘classic symptoms’’ of sleep apnea. Another hypothesis that has been proposed is that the reporting of these ‘‘atypical’’ complaints may lead physicians to consider other diagnostic possibilities. For example, if an obese female patient reports fatigue, typically thyroid function studies are obtained. If an obese male patient reports fatigue, however, it is much more likely that a polysomnogram will be ordered. The stereotype of ‘‘Joe the fat boy,’’ from Dickens’ Pickwick


533

Papers, is difficult to erase. Physicians need to be educated about the prevalence of SDB in female patients and the need to take sleep histories in women as well.

Preoperative evaluation Sleep history Many patients present to an otolaryngologist with the simple complaint of snoring. Unless a sleep history is taken, symptoms of sleep apnea often are not mentioned by the patient. The patient’s focus is usually on the snoring sound he or she produces and the disruption of his or her bed partner’s sleep. Men are ‘‘brought in’’ by their wives to be ‘‘fixed,’’ whereas women often present without prompting because of their embarrassment about their snoring. It is the physician’s responsibility to inquire about the other sleep habits and daytime symptoms before the treatment of snoring can occur, however. In addition, the history should include (1) typical bedtime and arousal time; (2) the use of sleep aids, such as sedatives or alcohol; (3) a history of nocturnal reflux; and (4) daytime stimulant use, for example, caffeine intake. Sleepiness is a subjective complaint that can be evaluated more objectively with a standard questionnaire such as the Epworth or Stanford Sleepiness Scale. Additional information pertaining to history that is specific to women includes pregnancy status and the use of hormonereplacement therapy (HRT). Most female patients diagnosed with OSAS are postmenopausal [11–15]. The use of HRT may have a protective effect in the postmenopausal woman. The prevalence of sleep apnea is similar in premenopausal and postmenopausal women on HRT (0.6% and 0.5%, respectively). The prevalence is significantly higher in postmenopausal women who are not receiving HRT (2.7%), however. With recent research showing that HRT may not be as useful as once believed, it is plausible that the number of apneic women will increase as women choose to proceed through menopause without HRT. Although a pregnant patient rarely would undergo any kind of elective surgical procedure, it seems that the hormonal changes that take place during a pregnancy have a protective effect toward SDB [16,17]. Other special cases include women with Turner’s syndrome and polycystic ovary syndrome in whom hormonal status is altered. Turner’s syndrome is a common X-linked aneuploidy (XO) characterized by a female phenotype, retarded growth, infertility, and craniofacial abnormalities, in some cases [18]. The upper airway abnormalities and the hormonal status predispose this group of women to SDB. Women with polycystic ovary syndrome are predisposed to SDB because of the obesity and androgen excess typically seen in patients with this disorder [19]. Exogenous administration of testosterone to female and male patients has been reported to increase the respiratory disturbance index (RDI) or to induce sleep apnea in a small group of patients [20,21].

534


Physical examination The physical examination of the patient with SDB should include vital signs, height, weight, neck circumference, and a complete head-and-neck examination. In general, a flexible endoscopic examination is needed to assess the laryngeal airway and hypopharynx. A body mass index (BMI) should be calculated (the weight in kilograms divided by the square of the height in meters). The neck circumference usually is measured at the cricothyroid membrane, although in the obese neck, the laryngeal landmarks are often difficult to discern. Obesity is the most important predisposing factor in OSAS [1,4,22]. In the author and colleagues’ surgical study of 686 patients (111 women and 575 men) diagnosed with OSAS, female patients had a significantly higher BMI when compared with the male patients at presentation [10]. The BMI versus RDI was evaluated to determine whether gender modified the effect of BMI on RDI. It was found that for women, there was a weaker correlation between BMI and RDI as compared with men. Young et al [9] reported similar findings in the Wisconsin Sleep Cohort Study, in which 551 men and 388 women were studied. Women with an RDI of 15 or more had a significantly greater BMI when compared with men. Classically, men have a predominantly android or upper-body fat distribution, and women have a gynecoid or lower-body fat distribution [23]. Women with a diagnosis of OSAS are typically more obese than their male counterparts. A patient’s BMI is used to determine his or her weight status (Table 1). Another term often used, morbid obesity, is defined as a BMI greater than 35 kg/m2. A BMI can be calculated quickly in a clinic setting using a BMI chart. Upper-body obesity, seen predominantly in men, may partly explain why men have OSAS more frequently than women. The overall neck circumference, commonly much larger in men than women, is correlated with airway obstruction in men [24]. This upper-body obesity would lead one to predict that men with OSAS have a smaller pharynx than women with the same disorder. The opposite is true. Brooks and Strohl [25] found that normal men have a significantly larger pharynx than women. Men also have been shown to have a larger change in the pharyngeal area with lung-volume change.

Table 1 Weight-classification system Category

BMI (kg/m2)

Underweight Healthy weight Overweight Obesity (class 1) Obesity (class 2) Severe obesity (class 3)

Less than 18.5 18.5–24.9 25.0–29.9 30.0–34.9 35.0–39.9 40 or more


535

Normal men may have a greater tendency to collapse their airways, which may account for the gender differences in the development of SDB. Mohsenin [26] demonstrated that in middle-aged men and women with a diagnosis of OSAS, women had a smaller pharynx than did men. This study demonstrated that pharyngeal size was correlated with apnea severity in men but not in women with OSAS. The awareness of gender-related differences in the physical examination is critical when determining a treatment plan for patients with OSAS. Recent research has identified the following trends in physical differences between men and women with OSAS: 1. 2. 3. 4.

Women have a significantly higher BMI as compared with men. Women have lower-body obesity and men have upper-body obesity. Men have larger necks than women. Women have a smaller pharynx than men.

Polysomnographic findings Female patients with a diagnosis of OSAS have been noted to have a lower RDI when compared with men [10]. In a group of 686 patients (111 women and 575 men) who presented for a surgical evaluation, the mean RDI for women was 37, versus 42 in men. This difference was statistically significant. Mohsenin [26] reported polysomnographic findings in 130 patients referred for evaluation of SDB. The RDI was lower in the female patients (24 versus 62 in men). Leech et al [27] noted that among 118 patients with OSAS (77 men and 41 women), women have more hypopneas rather than apneas, and the length of their apneic events was shorter. O’Connor et al [28] categorized patients as having one of three main patterns of apnea: (1) obstructive sleep apnea that occurred in the supine position, (2) non–positional-related obstructive sleep apnea, and (3) rapid-eye-movement–related apnea. Women were found to have rapid-eye-movement–related apnea more often than male patients (62% versus 24%). In contrast, supine and non-positional apnea patterns were much more common in men. The polysomnographic findings in women diagnosed with OSAS differ from male patients with the same disorder. The RDI is lower in women, the proportion of the RDIs made up of hypopneas is greater, and rapid-eye-movement–related apnea is more common in women. Surgical treatment Little information can be obtained from the surgical literature regarding response rates of women undergoing various surgical procedures for the treatment of OSAS. Just as there is no standardization within the medical community regarding interpretation of a polysomnogram, the analysis of postoperative data varies significantly in surgical publications. Another

536


limitation of studying female patients undergoing surgical treatment is the paucity of patients. In most surgical series examining uvulopalatopharyngoplasty or laser assisted uvulopalatoplasty (LAUP), less than 20% of the patients are women [10,29,30]. Meaningful data on more extensive procedures in women, such as genioglossus advancement with hyoid myotomy-suspension and maxillary-mandibular advancement, are not available. In Riley et al’s classic report [31] on 306 surgical patients, only 35 were women. Despite all of these limitations and the critical need for further investigation, some information is available. Mickelson and Ahuja [29] reported their results on 36 patients with OSAS who underwent laser-assisted uvulopalatoplasty. In this series, the female data were not analyzed specifically, but the individual raw data were presented. Seven of the 36 patients were female. The author’s group [10] also studied patients with OSAS who underwent LAUP treatment. Preoperative and postoperative data from both series are shown in Table 2. Mickelson and Ahuja’s series demonstrates a nonsignificant decrease in the RDI (P ¼ 0.2834) and an increase in the lowest oxygen saturation (P ¼ 0.3830) after LAUP treatment for OSAS. In general, a successful surgical outcome is defined as a postoperative RDI of 10 or less. Of these patients, 43% had an RDI of 10 or less after treatment. In the author’s series of 16 female patients, a significant decrease in the RDI (P ¼ 0.0042) and a nonsignificant increase in the lowest oxygen saturation (P ¼ 0.1141) were noted. Of these 16 patients, 81% had a postoperative RDI of 10 or less. At this time, only preliminary data are available on the surgical treatment of female patients. These data only reflect LAUP procedure results; results from other palatal surgery, specifically uvulopalatopharyngoplasty, are not available. Based on these early findings, palatal surgery treatment for female patients with OSAS is certainly a viable option. Initial impressions suggest that women respond as well as or more favorably to palatal surgery when compared with male patients. Further studies are necessary before any guidelines can be established for female patients.

Table 2 Female patients with OSAS treated with LAUP Mickelson and Ahuja [29] (n ¼ 7) Mean SD Age BMI Preoperative RDI Postoperative RDI Preoperative LSAT Postoperative LSAT

58.1 35.2 26.1 17.9 76.1 80.9

8.6 11.8 13.8 13.6 11.3 11.8

Walker et al [10] (n ¼ 16) Mean SD 54.6 32.4 18.7 6.5 84.0 86.7

12.7 7.8 13.9 7.5 4.7 4.2

Abbreviations: BMI, body mass index (kg/m2); LSAT, lowest oxygen saturation; RDI, respiratory distrubance index (events/hour); SD, standard deviation.


537

Acknowledgments The author thanks Dr. Chellam Gopalsami and Lisa Harrison for their assistance in preparing this manuscript. References [1] Young T, Palta M, Dempsey J, et al. The occurrence of sleep disordered breathing among middle-aged adults. N Engl J Med 1993;328:1230–5. [2] Gislason T, Almqvist M, Eriksson G, et al. Prevalence of sleep apnea syndrome among Swedish men: an epidemiological study. J Clin Epidemiol 1988;41:571–6. [3] Haraldsson PO, Carenfelt C, Tingvall C. Sleep apnea syndrome symptoms and automobile driving in a general population. J Clin Epidemiol 1992;45:821–5. [4] Stradling JR, Crosby JH. Predictors and prevalence of obstructive sleep apnea and snoring in 1001 middle aged men. Thorax 1991;46:85–90. [5] Chaudhary BA, Speir WA Jr. Sleep apnea syndromes. South Med J 1982;75:39–45. [6] Ohayon MM, Guilleminault C, Priest RG, et al. Snoring and breathing pauses during sleep: telephone interview survey of a United Kingdom population sample. BMJ 1997; 314:860–3. [7] Hoffstein V, Szalai P. Predictive value of clinical features in diagnosing obstructive sleep apnea. Sleep 1993;16:118–22. [8] Kapsimalis F, Kryger M. Gender and obstructive sleep apnea syndrome, part 2: mechanisms. Sleep 2002;25:499–506. [9] Young T, Hutton R, Finn L, et al. The gender bias in sleep apnea diagnosis: are women missed because they have different symptoms? Arch Intern Med 1996;156:2445–51. [10] Walker R, Durzao-Arvizu R, Wachter B, et al. Preoperative differences between male and female patients with sleep apnea. Laryngoscope 2001;111:1501–5. [11] Bixler E, Vgontza A, Lin H, et al. Prevalence of sleep-disordered breathing in women— effects of gender. Am J Respir Crit Care Med 2001;163:608–13. [12] Dancey RD, Hanley PJ, Soong C, et al. Impact of menopause on the prevalence and severity of sleep apnea. Chest 2001;120:151–5. [13] Guilleminault C, Quera-Salva MA, Partinen M, et al. Women and obstructive sleep apnea syndrome. Chest 1988;93:104–9. [14] Guilleminault C, Stoohs R, Jim Y, et al. Upper airway sleep-disordered breathing in women. Ann Intern Med 1995;122:493–501. [15] Smith R, Ronald J, Delaive K, et al. What are obstructive apnea patients being treated for prior to this diagnosis? Chest 2002;121:164–72. [16] Brownell LG, West P, Kryger MH. Breathing during sleep in normal pregnant woman. Am Rev Respir Dis 1986;133:38–41. [17] Maasilta P, Bachour A, Teramo K, et al. Sleep-related disordered breathing during pregnancy in obese women. Chest 2001;120:1448–54. [18] Orliaguet O, Pepin JL, Bettega G, et al. Sleep apnoea and Turner’s syndrome. Eur Respir J 2001;17:153–5. [19] Fogel RB, Malhorta A, Pillar G, et al. Increased prevalence of obstructive sleep apnea in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 2001;86:1175–80. [20] Johnson MW, Anch AM, Remmers JE. Induction of the obstructive sleep apnea syndrome in a woman by exogenous androgen administration. Am Rev Respir Dis 1984;129:1023–5. [21] Schneider BK, Pickett C, Zwillich CW, et al. Influence of testosterone on breathing during sleep. J Appl Physiol 1986;61:618–23. [22] O’Donnell CP, Schwartz AR, Smith PL. Upper airway collapsibility: the importance of gender and adiposity. Am J Respir Crit Care Med 2000;162:1606–7. [23] Millman R, Carlisle C, McGarvey S. Body fat distribution and sleep apnea severity in women. Chest 1995;107:362–6.

538


[24] Kapsimalis F, Kryger M. Gender and obstructive sleep apnea syndrome, part 1: clinical features. Sleep 2002;25:412–9. [25] Brooks LJ, Strohl KP. Size and mechanical properties of the pharynx of healthy men and women. Am Rev Respir Dis 1992;146:1394–7. [26] Mohsenin V. Gender differences in the expression of sleep-disordered breathing—role of upper airway dimensions. Chest 2001;120:1442–7. [27] Leech J, Onal E, Dulberg C, et al. A comparison of men and women with occlusive sleep apnea syndrome. Chest 1988;94:983–7. [28] O’Connor C, Thornley K, Kanly P. Gender differences in the polysomnographic features of obstructive sleep apnea. Am J Respir Crit Care Med 2000;161:1465–72. [29] Mickelson S, Ahuja A. Short-term objective and long-term subjective results of laserassisted uvulopalatoplasty for obstructive sleep apnea. Laryngoscope 1999;109:362–7. [30] Millman R, Carlisle C, Rosenberg C, et al. Simple predictors of uvulopalatopharyngoplasty outcome in treatment of obstructive sleep apnea. Chest 2000;118:1025–30. [31] Riley RW, Powell NB, Guilleminault C. Obstructive sleep apnea syndrome: a review of 306 consecutively treated surgical patients. Otolaryngol Head Neck Surg 1993;108:117–25.


Evidence-based medicine in sleep apnea surgery K. Christopher McMains, MD, David J. Terris, MD, FACS* Department of Otolaryngology–Head and Neck Surgery, Medical College of Georgia, 1120 Fifteenth Street, Augusta, GA 30912-4060, USA

Historical perspective Guilleminault et al [1] coined the term obstructive sleep apnea (OSA) to describe patients with disrupted nocturnal breathing. Kuhlo et al [2] performed the first tracheotomy to bypass upper airway obstruction in 1969, which represented the first definitive surgical procedure to treat OSA. Fujita et al [3] introduced the uvulopalatopharyngoplasty (UPPP) for treatment of OSA in 1979. Sullivan et al [4] published the first study of continuous positive airway pressure (CPAP) for nonsurgical treatment of OSA in 1981. As with tracheotomy, CPAP eliminates excessive daytime sleepiness (EDS) and cardiopulmonary sequelae of OSA [5], including normalization of blood pressure [6]. Only complete compliance was shown to be sufficient to confer treatment benefits from CPAP [7], and incomplete compliance with CPAP proved prevalent [8–10]. Despite increased compliance with autotitrating CPAP, a substantial proportion of patients remained ineffectively treated on CPAP [11]. This finding led to a shift in focus toward surgical treatment of OSA. In a meta-analysis, Sher et al [12] noted success of UPPP in 41% of all patients, whereas in patients with tongue base obstruction, success was achieved in only 6% of cases. This finding is supported further by Isono et al [13], who demonstrated that collapsibility at the level of the retroglossal airway is the most significant determinant of UPPP outcome. In the wake of objective failure of UPPP in many patients, it became clear that multiple anatomic sites contribute to obstruction [14–16]. Methods for evaluating levels of obstruction were sought to improve preoperative assessment and surgical outcomes. The methods the studies used included

* Corresponding author. E-mail address: [email protected] (D.J. Terris). 0030-6665/03/$ - see front matter Ó 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00182-2

540

K.C. McMains, D.J. Terris / Otolaryngol Clin N Am 36 (2003) 539–561

the Mu¨ller maneuver, cephalometric analysis, CT, and volumetric MRI. The Mu¨ller maneuver offers some insight into the level of obstruction and dimensions of obstruction, although it does not accurately predict surgical success [17]. Cephalometric analysis correlates with three-dimensional CT analysis [18]. CT provides good airway and bony resolution, although it does not provide delineation of the upper airway soft tissue as well as the MRI [19]. Sagittal MRI allows evaluation of the palate and tongue base to the posterior pharyngeal wall [20]. MRI provides good soft tissue resolution and supine evaluation in multiple dimensions; however, weight, claustrophobia, pacemaker placement, and expense can limit its application. In response to the limitations of UPPP, Riley et al [21] introduced the Stanford Protocol (Fig. 1), which involved inferior sagittal osteotomy of the mandible and hyoid myotomy and suspension. Later, Riley et al [22] published results from a two-phase protocol, which involved UPPP for palatal obstruction and genioglossus advancement with hyoid myotomy or suspension for tongue base obstruction in phase I. This method achieved success as measured by polysomnography in 70% to 80% of patients with mild to moderate OSA, although success was obtained in only 42% of patients with severe OSA. Additionally, surgical treatment improved sleep architecture and increased lowest oxygen-saturation levels to those achieved by CPAP. For patients with residual OSA as determined by postoperative sleep study who were interested in further treatment, phase II involved maxillarymandibular advancement osteotomy and achieved a 97% success rate [22]. Updates on clinical outcomes from the Stanford group continue to report similar outcomes for phase I [23] and phase II [24]. Recent years have seen a proliferation of procedures aimed at a surgical cure for OSA. Laser-assisted uvuloplasty has been investigated and proved to be an effective treatment for snoring [25], but there are conflicting data on its efficacy in the treatment of OSA [26]. Preliminary studies on tongue-base suspension sutures demonstrate a modest effect on objective measures [27] and small improvement in functional outcomes, sleepiness, and snoring [28]. Radiofrequency energy has been used to decrease the volume of palatal tissue [29], turbinate tissue [30,31], and tongue base [32–34], with mixed results. Bariatric surgery also has been used to affect the degree of obesity and, secondarily, OSA. This tremendous assortment of treatment modalities and methods of reporting outcomes raises two fundamental questions: What constitutes failure or success and why do specific interventions succeed or fail by these measures? Pathologic features of obstructive sleep apnea To fully understand treatment approaches to OSA, a thorough understanding of the pathologic features of OSA is necessary. Current understanding suggests that obstruction and cessation of ventilation result from anatomic and neurologic factors working to collapse the airway,


541

Fig. 1. Staged surgical protocol. From Likk, Powell NB, Riley RW, Troell R, Guilleminault C. Overview of phase I surgery for obstructive sleep apnea syndrome. Ear Nose Throat J 1999;78:836–45; with permission.

overriding those working to dilate the airway. This effect is known as the ‘‘balance-of-forces’’ model [35]. In OSA, these events include apneas, complete cessation of ventilation, hypopneas, significantly reduced ventilation secondary to partial obstruction, or respiratory effort–related arousal, which are defined as inspiratory efforts against increased upper airway resistance that cause transient arousals but do not reach the threshold for either apnea or hypopnea [36]. Formerly, it was believed that hypersomnolence resulted from hypoxemia or hypercapnea associated with

542


these events. It is now understood that hypersomnolence results from sleep fragmentation [37]. Respiratory drive and tonic control of airway musculature differ in the sleep and awake states. A ‘‘wakefulness drive,’’ which responds to nonmetabolic inputs, modulates changes during the awake state. When this influence is removed during sleep, respiratory drive relies solely on metabolic inputs to chemoreceptors that allow a higher pCO2 set point. Transition from wakefulness to sleep results in an immediate decrease in respiratory drive. This decrease is followed sequentially by hypoxemia, a brisk respiratory response, arousal, and a large compensatory breath. Therefore, the transition between states represents a time of considerable importance for the patient with OSA because of the vulnerability of the upper airway [38,39]. Additionally, rapid-eye-movement–phase sleep constitutes a higher percentage of sleep during the last third of the night [40] and is associated with decreased muscle tone. The effect of this change in tonic control is increased collapsibility during this phase of sleep. Anatomically, resistance can occur intranasally or at the level of the palate (type I), at both the palate and the base of the tongue (type II), or at the base of the tongue alone (type III) [41]. As compared with control patients, there is increased pharyngeal resistance during wakefulness in patients with OSA [42–45]. As compared with the wakeful state, pharyngeal airway resistance triples during sleep [42–48]. With arousal and concomitant return of the wakefulness drive, dilator muscle activity increases, airway resistance decreases, and airflow resumes [42–49]. Several specific anatomic differences exist between control patients and patients with sleep apnea. Smaller upper airways have been observed in patients with OSA [15,47,50]. The cross-sectional area of the pharynx has been shown to be inversely proportional to the severity of OSA [15]. Pharyngeal anterior-posterior axis length greater than lateral axis length predisposes to airway collapse [51]. In contrast to the pharynx in control patients, the pharynx in patients with OSA is collapsible to a greater degree [52] and collapses under subatmospheric pressure conditions [53]. Lateral walls are the structures most likely to collapse in all subject groups. Thickness of the lateral pharyngeal muscular walls is cited as being responsible for collapse [54]. The palate of patients with OSA has significantly increased muscle and fat mass as compared with control patients [55]. Evidence suggests that there is a relationship between OSA and local pharyngeal fat deposits. Additionally, increased fat load in the collapsible pharyngeal segment has been demonstrated when compared with control patients [47]. These anatomic and physiologic tendencies lead to poor sleep efficiency and downstream physiologic effects. As a result, much of the available data suggest that OSA negatively affects several measures of health. Several authors have shown an association between OSA and cardiovascular disease. The National Commission on Sleep Disorders Research


543

estimates that there are 38,000 cardiovascular deaths per year in the United States secondary to OSA [56]. Obstructive sleep apnea is believed to lead to pulmonary and systemic hypertension [57,58]. In individuals with an apneahypopnea index (AHI) greater than or equal to 15, increased systolic and diastolic blood pressure was noted during both sleep and wakefulness when compared with individuals with AHIs less than 15 [59]. Hung et al [60] showed increased cardiovascular mortality in patients with apnea indices (AIs) greater than 5.3. Obstructive sleep apnea has been implicated in cor pulmonale, arrhythmia, cerebrovascular accident (CVA), and polycythemia as well [56]. Obstructive sleep apnea has been implicated as a causal factor in motor vehicle accidents. In one study, an AHI greater than 5 yielded a three-fold increase in motor vehicle accidents, whereas an AHI greater than 15 yielded a seven-fold increase [33,61]. It is worth noting that an AHI greater than 15 falls within the definition of clinical success used by several authors. Reaction times of motorists with OSA were compared with and found to be worse than those of alcohol-impaired drivers [62]. Obstructive sleep apnea has been linked to increased mortality. In middleaged patients with sleep-disordered breathing (SDB), decreased survival was demonstrated, regardless of disease severity [63]. He et al [64] showed increased mortality in patients with AIs greater than 20. Despite similarity in overall mortality in the post-uvulopalatopharyngoplasty (UP3) population, there is a relative risk of three for hypertension and subsequent death from cardiovascular disease (CVD) in patients with OSA as compared with control patients [65]. In a review published in 1997, Wright et al [66] contravened conventional wisdom by questioning the health effects of OSA. They found contradictory evidence regarding SDB and cardiovascular disease or CVA. They regarded the evidence linking OSA to EDS as stronger but still inconclusive. Since that time, much work has been done to further examine the role of OSA in cardiovascular and overall health, most notably through the Framingham and Sleep Heart Health Study. In the Framingham study, SDB was associated with increased right ventricular wall thickness, although neither right atrial dimensions, right ventricular dimensions, or right ventricular systolic function was affected [67]. Obstructive sleep apnea is associated with overall increased health care use [68]. Nieto et al [69] demonstrated an association between hypertension and SDB, as defined by AHI and percent time with oxygen saturation in arterial blood below 90%. Obstructive sleep apnea was shown to have mild to moderate effects on ‘‘heterogeneous manifestations of CVD’’ with even a slight increase in AHI. A stronger association with congestive heart failure (CHF) and stroke was shown [70]. In a recent review, Young and Peppard [71] wrote of the data: ‘‘collectively they provide evidence that we cannot dismiss the hypothesis that SDB causes CVD.’’ Other authors argue that correlations among respiratory disturbance index (RDI) and body mass index (BMI), hypertension diabetes mellitus (HTN, DM), and lipid

544


levels cloud any conclusions as to whether increased risk of CVD results from SDB or concomitant risk factors [72]. Despite mounting evidence, debate about the true effect of OSA on health continues.

Measures of success and failure Several mechanisms have been used for diagnosing OSA, assessing its severity, and assessing the response to treatment. These mechanisms include purely subjective patient-reported measures, subjective physician-graded measures, and objective monitoring. A brief review of the major modalities follows. Epworth sleepiness scale Principal among the symptoms resulting from OSA is EDS. Using EDS in assessment of disordered sleep presents the difficulties of subjective reporting. Additionally, EDS is not limited to patients with OSA. It was found in 21% in patients with RDIs less than 5 versus 35% of patients with RDIs greater than 30 [73]. The Epworth sleepiness scale (ESS), first described by Johns, is an instrument used to evaluate severity of symptoms from OSA in a semiquantitative way [74]. The ESS is a self-administered survey of a patient’s likelihood of dozing during eight activities. For each activity, the patient rates his or her chances of falling asleep while engaged in the activity. Scores range from 0 (never dozing in a situation) to 3 (always dozing). Quality-of-life scales (general and disease-specific) In early work, global measures of health were used to assess the effect of OSA. These measures originally were designed to measure aggregate health characteristics and to provide synoptic information regarding a patient’s own perception of health. The Medical Outcome Survey Short Form (SF-36) includes eight domains to measure health and well-being [75]. Briones et al [76] showed a correlation among the ESS score and vitality, role-emotional, and general health domains, whereas the multiple sleep latency test correlated with the vitality domain. Another study using the SF-36 showed improvement in energy and vitality and mental and physical functioning domains, although another measure used in the study failed to identify these effects [77]. Mild to moderate SDB was associated with a decreased vitality measure on the SF-36, whereas severe SDB was associated with a global decrease in quality of life (QOL) [78]. Oxygen desaturation negatively affects the QOL measured by SF-36 as well [79]. All dimensions of QOL were diminished significantly on the SF-36 in patients with OSA as compared with control patients. Improvement in QOL was related more to the degree of perceived disability than to the RDI or arousal index [80].


545

The Nottingham Health Survey demonstrated significant differences in energy, pain, sleep, social isolation, and physical mobility in patients with OSA as compared with control patients; however, no difference in EDS between these groups was noted. No difference in QOL was identified among patients with different levels of severity with OSA [81]. Concern about the ability of nonspecific measures to elucidate subtle QOL changes specific to OSA led to development of disease-specific measures of QOL. The Calgary Sleep Apnea Quality-of-Life Index demonstrated validity in assessment of OSA. It also demonstrated a higher responsiveness index and effect size than did the SF-36 [82]. The Functional Outcomes Sleep Questionnaire was designed to assess the effect of sleep-related symptomatology on five daily activities. It demonstrated validity in evaluating functional disability as it relates to sleep disturbance and response to treatment [83]. The Obstructive Sleep Apnea Patient-Oriented Severity Index (Table 1) was designed for use in the OSA Treatment Outcome Pilot Study. It involves responses to questions regarding five subscales to which importance and magnitude of effect are assigned. A symptom impact score is generated from the product of the importance and the magnitude. The OSA Treatment Outcome Pilot Study study demonstrated worse QOL in all domains except bodily pain [84]. A revised version, the SNORE-25, excluded seven items from the first and dispensed with symptom-impact scoring, reporting average magnitude score instead. This instrument correlates well with the patient’s subjective response to treatment [85]. Multiple sleep latency test The multiple sleep latency test (MSLT) evaluates degree of impairment of daytime alertness [86]. This test involves recording the time of sleep initiation for multiple naps separated by at least 2 hours during a patient’s normal waking period. This instrument can be used to diagnose upper airway resistance syndrome (UARS) [87] or as an assessment of treatment effect. In the absence of UARS, the MSLT is used to diagnose narcolepsy. It generally is considered the ‘‘gold standard’’ for evaluating daytime somnolence and sleep latency. Moderate correlation exists between ‘‘irresistible sleepiness,’’ which describes the sensation of being overcome by sleep, and MSLT; however, ‘‘irresistible sleepiness’’ failed to identify pathologic MSLT in patients with SDB [88]. Mu¨ller maneuver: palate, base of tongue, and lateral walls The Mu¨ller maneuver originated from attempts to evaluate various levels of upper airway obstruction. The examiner views the upper airway through the nasopharyngoscope at rest and with maximal inspiratory effort against closed nose and mouth. The base of tongue, lateral pharyngeal walls, and

546


Table 1 Items on the Obstructive Sleep Apnea Patient-Oriented Severity Index Sleep 1. 2. 3. 4. 5. 6. 7.

problems Trouble falling asleep Waking during sleep Loud/excessive snoring Restlessness during sleep Waking ‘‘too early’’ in morning Waking up feeling tired Bed wetting

Awake problems 8. Fatigue or tiredness 9. Frequent yawning 10. Sleepiness while driving 11. Memory and/or concentration problems 12. Productivity limited at certain times of day 13. Often late for meetings or appointments 14. Participation in community, volunteer, religious, or spiritual activities limited Medical problems 15. Amount of medical care required for OSA 16. Interaction of OSA with other medical problems 17. Travel by automobile to other regions or parts of country limited because of fear of medical problem 18. Unable to have sexual relations because of medical problem 19. Financial burden as a result of illness Emotional and personal problems 20. Dread/fear going to bed 21. Nerves are ‘‘right on surface’’ 22. Inability to relax, always anxious 23. Marital strain, stress, and tension 24. ‘‘Foul’’ mood 25. Unable to experience closeness with spouse and/or others 26. Lack of desire for sexual relations 27. Feeling that future is hopeless Occupational impact 28. Competence questioned 29. Reliability questioned 30. Inability or difficulty getting new job 31. Loss of job 32. Modification in job because of excessive sleepiness From Piccirillo JF, Gates GA, Schectman KB. Obstructive sleep apnea treatment outcomes pilot study. Otolaryngol Head Neck Surg 1998;118:833–44; with permission.

palate are examined for collapse. The examiner rates collapsibility of each structure from 0 (minimal collapse) to 4+ (complete collapse). Mu¨ller maneuver score was shown to be correlated moderately with preoperative SDB severity, and its reproducibility was verified between examiners [27]. Collapse of the palate was correlated highly with RDI, whereas lateral wall


547

collapse was correlated moderately, and base-of-tongue collapse was not correlated [89]. P close P close is the pressure at which the upper airway collapses. This value is a significant discriminating feature between normal subjects and patients with abnormal collapsibility, as is seen in OSA [90]. In apneics, P close tends toward higher values than in control subjects. Airway collapse can occur at the level of the palate or tongue base. Positive P close predicted treatment effect in patients with OSA. For patients with positive P close, nocturnal oxygenation was normalized after UPPP in 27%, whereas oxygenation corrected 73% of OSA in patients with negative P close [13]. Tracheal traction [91], UPPP, and palatal advancement result in a decrease in closing pressure [92]. Cephalometrics Cephalometric radiographs are obtained and evaluated in a standardized manner [93]. Relationships of different structures to one another have been assessed for predictive value in diagnosing OSA and evaluating surgical outcome. Changes in ANB and SNB angles were correlated with postoperative changes in AHI [94]. Other studies correlated postoperative outcomes with increased posterior airway length, increased hyoid-mandibular length, and increased posterior airway space (PAS) [95,96]. Li et al [97] report an increase in pharyngeal length and depth of 48% and 53%, respectively, after maxillomandibular advancement and report a high success rate for these procedures. Conflicting data were described by Yao et al [89], who found that cephalometric radiographs reflect anatomic changes postoperatively, but these changes did not correlate with efficacy as measured by improvements in the AHI. Polysomnogram The polysomnogram (PSG) was first described in 1974 by Holland et al [98]. Since that time, PSG has become the ‘‘gold standard’’ in diagnosis and follow-up of sleep apnea because it provides objective data on sleep and respiratory status. Originally, the only events evaluated were apnea; however, analysis has expanded to include hypopneas and respiratory event-related arousals (RERAs), as described previously. The diagnosis most frequently is made on the basis of the sum of these events per hour or RDI. In the level I study, information gathered includes pulse oximetry, electrocardiography, nasal or oral airflow, respiratory effort, extremity electromyography, submental electromyography, electro-oculogram, positionally dependent sleep changes, and electroencephalographic evidence of arousal [99]. Despite

548


collecting information on oxygen desaturation, arousals, limb movements, sleep architecture, and cardiac events, diagnosis most often is made by RDI alone. With the pressures of medical economics, other less costly studies have been explored that endeavor to adequately diagnose OSA without incurring similar costs. These studies range from fully monitored home studies to overnight oximetry, although each has limitations in the data collected. In a nap study, the AHI and oxygen desaturation index detected correlates with the severity of OSA as determined by PSG [100]. Data reported from portable PSG correlated with those obtained with a laboratorybased control for AHI and diagnosis, although there was reduced confidence in respiratory scoring secondary to signal quality [101]. Parra et al [102] showed 89% concordance between AHI measured by a home device and traditional PSG. Kapur et al [103] reported that unattended home sleep studies were acceptable for the evaluation and diagnosis of OSA in 90.6% of cases.

Why surgical procedures fail The complex interacting factors causing dysfunction in OSA make it difficult to guarantee effective treatment in an individual patient. The perfect treatment for OSA would eliminate sleep disturbance, reverse dangerous physiologic changes, restore restful sleep, eliminate symptoms, and be well tolerated by patients. The principal failure of CPAP is the patient’s inability to tolerate treatment. Tracheotomy bypasses airway obstruction at all levels, yielding objective results comparable to CPAP, but it also is poorly tolerated by many patients owing to inconvenience and social stigma. Paradoxically, UPPP may, in some cases, decrease the maximal pressure tolerated by way of CPAP by creating oral air escape and decreasing the effectiveness of treatment [104]. The importance of patient selection based on careful examination affects the likelihood of success. In early work, Sher et al [17] showed that selecting patients with pharyngeal changes isolated to the region of the tonsillar fossae and soft palate increased the success rate of UPPP. For patients completing phase II surgical treatment, more than 90% have a successful surgical result as measured by RDI; however, many patients who do not have successful surgery as defined by PSG do not elect to complete phase II surgery, limiting the generalizability of results reported in OSA surgery [105]. Answers to the questions ‘‘What prevents a successful result in earlier stages of surgical treatment?’’ and ‘‘How does one maximize the likelihood of a given patient achieving a cure for his or her disease?’’ may lie in the variability of OSA. The association of OSA and obesity cannot be disputed. Major weight gain was associated with surgical failures, although there was no negative effect from aging and minor weight gain [106]. Failure after UP3 was related to preoperative BMI and postoperative weight gain [107]. Bariatric surgery


549

has been explored in the treatment of OSA, with variable results. Several authors report that bariatric surgery provides significant long-term reduction in weight and OSA severity [108–110], whereas other reports suggest a considerable relapse rate among treated patients [111]. Aggressive weightreduction programs represent an important component of comprehensive OSA treatment. Significant differences in disease presentation and characteristics are seen between male and female patients with OSA. Presenting symptoms for men included snoring and stoppage of breathing, whereas women reported headache on awakening [112]. In another study of SDB, both genders presented with similar symptoms of snoring and EDS. This same study showed that, despite having significantly smaller oropharyngeal airways, women had much milder disease than men. Additionally, upper airway size correlated with severity of disease only for men [113]. A higher death rate is noted among women with AHIs greater than five than in similarly affected men [114]. In a study of obese patients, Vgontzas et al [115] reported OSA in 40% of men and only 3% of women. The association between BMI and RDI is weaker in women than in men. Another study of morbidly obese patients showed that 77% of men and only 7% of women had OSA [116]. Taken together, these observations suggest important gender differences in sleep disorders. Further exploration of the nature of these differences may result in a higher percentage of surgical successes. Collapse of the lateral pharyngeal wall contributes significantly to obstruction. Bettega et al [117] wrote, ‘‘No data are available on the effects of phase I surgical techniques on dilator muscle activity, contraction efficiency, and upper airway collapsibility.’’ This view is disputed by Schwab et al [93], who reported that skeletal advancement surgery increased tension on constrictors, thereby decreasing lateral wall collapse. Li et al [24] found that maxillomandibular osteotomy improves the tension and collapsibility of the suprahyoid and velopharyngeal musculature. In a later study, Li et al [118] reported that maxillomandibular osteotomy improves retrodisplacement of the tongue and more dramatically improves lateral wall stability. Thut et al [119] showed that elongation of the airway had the greatest effect on collapsibility. Pharyngeal length increases significantly in patients with OSA as compared with control patients when changing from the upright to the supine position [120]. A distance of less than 21 mm from the mandibular plane to the hyoid was associated significantly with UPPP failure [121]. Exploration of airway-lengthening procedures may exploit the insight gained through Thut’s research to the benefit of patients with OSA. Recognition of the influence exerted by other diseases and syndromes may contribute to the challenge of effective OSA treatment. ‘‘Disproportionate anatomy’’ among the base of the tongue, narrow mandible, and hypoplastic mandible affect upper airway dynamics [16]. This disproportion can be seen in syndromic patients and in isolation from other abnormalities.

550


Allergy also may play a role in the pathogenesis of OSA [122]. Allergic response not only increases airway resistance intranasally, it may result in edema of pharyngeal segments and predispose to collapse. Hypoventilation syndrome can occur concomitantly with OSA and cause continued sleep disturbance despite treatment of obstruction. Recognizing and addressing these and other comorbidities may affect surgical outcomes positively. Best current metrics Despite using RDI as a standard for diagnosis and treatment effectiveness, there is some suggestion that RDI may not completely describe all aspects of the disease. Piccirillo elucidates the principal limitations in the use of PSG for diagnosis and evaluation of response in OSA [123]: 1. Assignment of severity based on RDI, not oxygen desaturation index (ODI), sleep fragmentation, or patient symptoms. This criticism is supported by Kingshott et al [124], who demonstrated that neither apneas nor hypopneas account for more than a small percentage of the variation in objective or subjective sleepiness. Respiratory disturbance index showed poor correlation with EDS, neuropsychologic functioning, or rates of motor vehicle accidents [61]. Oxygen desaturations negatively affect QOL measured by SF-36 as well [79]. This finding suggests an influence from desaturation independent of RDI; however, ODI has been shown to be specific for OSA diagnosed by PSG [125], whereas ODI coupled with CT90 (percentage of time saturation levels remain below 90%) and oximetry is both sensitive and specific for OSA by PSG [126]. Sleep fragmentation results from short-alpha electroencephalogram arousals during sleep that correlate with increased work of breathing [127]. Although RDI and minimum oxygen saturation in arterial blood were improved on therapeutic CPAP, no significant difference in sleep architecture was seen between therapeutic CPAP and placebo CPAP [128]. Therefore, patients ‘‘effectively’’ treated as assessed by RDI alone may not receive the physical benefits of restored sleep architecture. Patient perception of treatment may differ dramatically from objective data provided by PSG. The fact that tracheotomy and CPAP can decrease QOL secondary to inconvenience, discomfort, and social stigma despite effective bypass or splinting of obstruction highlights the distinction between PSG data and patient perception [129]. This disparity has been demonstrated for laser assisted uvulopalatoplasty [26], UPPP [130], and dental appliances [131]. Epworth sleepiness scale shows correlation with patient-identified sleepiness but does not correlate with MSLT [132], AHI, or minimum oxygen saturation in arterial blood [133]. In contrast, other studies have found an association between RDI and QOL measures [134]. Li et al [129] showed correlation among RDI, minimum oxygen saturation in arterial blood, and visual analog scale reporting of symptoms. Most patients report subjective improvement in symptoms after UP3, although this subjective improvement does not correlate with AI or sleep architecture for many patients. One suggestion regarding the


551

difficulty in obtaining postoperative sleep studies is that symptomatic improvement decreases a patient’s desire to undergo additional testing [130]. In a study of patients with mild OSA, no additional benefit was seen with CPAP treatment compared with placebo on SF-36 or functional outcomes of sleep questionnaire, suggesting that the placebo effect may obscure subjective reporting of findings [135]. Additionally, snorers without OSA have decrements in QOL to almost the same degree as patients who carry the diagnosis of OSA as measured on the Nottingham Health Profile [136]. Response bias has been shown to affect medical outcomes survey data [137]. Differing data on PSG data and subjective data are competing and cloud conclusions on the relationship among these measures. 2. There is a lack of correlation between AHI and overall health status [81] or QOL [138]. The conflicting data regarding the relationship to OSA defined by PSG and various measures of health are presented in a previous section (‘‘Pathologic features of obstructive sleep apnea’’). Data addressing the relationship between PSG results and QOL also are presented previously in this section. Although not uniformly disproved, questions about the strength of each of these relationships persist. 3. Apneas and hypopneas are not reported in a uniform way. Although efforts to standardize definitions of these occurrences have been made [86], considerable variability in definition, evaluation, and reporting continues to cloud comparisons [139]. Various cutoffs are used in individual studies for diagnosis, benefit, and cure, which further complicate interpretation of PSG data. Different methods of recording AHI yield dramatically different diagnosis and assignment of severity [140]. For example, thermistors have the potential to be less sensitive to hypopneas than other methods of recording [116]. Sher [141] states that intraesophageal manometry is the most effective method of distinguishing apnea from hypopnea. In contrast, Skatvedt et al [142] showed no statistical difference between patients undergoing PSG with and without pressure monitoring in any sleep-quality parameter except duration of non–rapid-eye-movement sleep with oxygen saturation below 90%. The use of different definitions for respiratory disturbance, criteria for diagnosis, and measures of success is perhaps the most significant limitation in evaluating and comparing outcomes from different treatments. 4. Frequency of apneas and hypopneas may vary from night to night. Because sleep quality may vary from night to night owing to myriad physical and psychosocial influences, a one-night study may be inaccurate [143]. A corollary to this contention is that monitoring may cause considerable arousal artifact secondary to mask placement or perception of other monitoring devices. This criticism has been refuted by some studies that show no significant difference between first- and second-night sleep studies [144] and reclassification of disease or severity in only a few patients based on subsequent night-sleep studies [145]. Although data conflict on this point as well, attention to this possibility may guide decisions regarding repeating sleep studies or proceeding with surgical treatment in cases that fall close to diagnostic cutoffs.

552


Steps have been taken already to incorporate some of these principles in diagnosis and treatment of OSA. The composite clinical-severity index, described by Piccirillo et al [84], includes ESS, BMI, presence of redundant pharyngeal tissue, RDI, and minimum oxygen saturation in assignment of disease severity (Figs. 1 and 2). A second generation of this instrument, the SNORE-25, has been developed, and an initial study has been reported [85]. Although exploration of this type of multidimensional analysis is in its infancy, this approach represents a significant step toward thorough assignment by considering both objective and subjective measures.

Future strategies Future strategies for OSA treatment will involve the evolution of methods of assessment and treatment. Although related, these areas are distinct fields of endeavor. Much progress has been made already in the field of assessment. Clear definition of respiratory disturbances will help establish uniform reporting and more reliable, valid comparisons among different studies. To date, relative contributions of apneas, hypopneas, and RERAs have not been well defined. Research into the relative contributions of different types of respiratory disturbance to symptomatology and downstream health effects may provide insight into the true effect of treatment. Despite its utility as an objective measure, traditional PSG reported in terms of RDI alone has limitations. Recognition of these limitations has already motivated the development of instruments that include multiple pertinent variables. Additionally, continued exploration of the neural interface between sleep and awake states may provide new frontiers in OSA treatment. Future advances in treatment will likely parallel those made in assessment. On the nonsurgical front, vigorous educational efforts on the part of the medical community to raise public awareness of OSA will affect health behaviors and social stigmata assigned to various treatment modalities. Such educational efforts have been reported to increase compliance with CPAP treatment [146]. Finding new and unique approaches to prevent collapse while decreasing morbidity will likely drive additional treatment advances. Continued work on lateral wall collapse offers one area of potential improvement. Procedures designed to lengthen the airway may provide a breakthrough in prevention of collapse. Early success has been reported in electrical stimulation of the genioglossus, resulting in decreased pharyngeal critical pressure [147]. Work will likely continue on application of radiofrequency energy in OSA. Other devices also may demonstrate utility in treatment of OSA. Jokic et al [148] reported decreasing surface tension and, as a result, AHI by applying a topical lubricant to upper airway tissues. Further work in these areas will likely add to the armamentarium of OSA treatment.

Fig. 2. Creation of clinical-severity staging system. Panels A through C demonstrate the sequential conjunction and consolidation of key physical examination variables, ESS, and PSG variables to ultimately create the clinical severity index. (A) Pattern of consolidation of redundant pharyngeal tissue and BMI to form composite physical-severity index. Categories of BMI and redundant pharyngeal tissue are conjoined to create the three-category (alpha, beta, and gamma) physical-severity index. (B) Pattern of consolidation of ESS and physical-severity index to form composite functional-severity index. Categories of physical-severity index (alpha, beta, and gamma) are conjoined with three categories of the ESS (<9, 9–16, >16) to create the functional-severity index. (C) Pattern of consolidation of minimum O2 saturation during apnea and RDI to form the composite PSG-severity index. Categories of the two key PSG variables, minimum O2 saturation during apnea and RDI, are conjoined to create the three-category (1, 2, and 3) PSG-severity index. (D) Pattern of consolidation of functional-severity index and PSG-severity index to form the composite clinical-severity index. The three categories (A, B, and C) of the functional-severity index and the three categories (1, 2, and 3) of the PSG-severity index are conjoined to create the three-category (I, II, and III) composite clinical-severity index. (From Piccirillo JF. Outcomes research and obstructive sleep apnea. Laryngoscope 2000;110(3 Pt 3):16–20; with permission.)

K.C. McMains, D.J. Terris / Otolaryngol Clin N Am 36 (2003) 539–561 553

554


The complexity of OSA and its variability of expression within individuals make identification of one ‘‘best method’’ of assessment and treatment difficult. As new techniques for treatment continue to evolve, methods of reporting will continue to evolve to more thoroughly illuminate the complex relationships at work in OSA. References [1] Guilleminault C, van den Hoed J, Mitler MM. Clinical overview of the sleep apnea syndrome. In: Guilleminault C, Dement WC, editors. Sleep apnea syndromes. New York: Alan R Liss; 1978. p. 1–12. [2] Kuhlo W, Doll E, Franck MC. Successful management of Pickwickian syndrome using long-term tracheostomy. Dtsch Med Wochenschr 1969;94:1286–90. [3] Fujita S, Conway W, Zorick F, Roth T. Surgical correction of anatomic abnormalities in obstructive sleep apnea syndrome: uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg 1981;89:923–34. [4] Sullivan CE, Issa FG, Berthon-Jones M, Eves L. Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares. Lancet 1981;1:862–5. [5] Sullivan CE, Berthon-Jones M, Issa FG. Remission of severe obesity-hypoventilation syndrome after short-term treatment during sleep with nasal continuous positive airway pressure. Am Rev Respir Dis 1983;128:177–81. [6] Guilleminault C, Stoohs R. Arousal, increased respiratory efforts, blood pressure and obstructive sleep apnoea. J Sleep Res 1995;4(S1):117–24. [7] Collop NA, Block AJ, Hellard D. The effect of nightly nasal CPAP treatment on underlying obstructive sleep apnea and pharyngeal size. Chest 1991;99:855–60. [8] Sanders MH, Moore SE, Eveslage J. CPAP via nasal mask: a treatment for occlusive sleep apnea. Chest 1983;83:144–5. [9] Waldhorn RE, Herrick TW, Nguyen MC, O’Donnell AE, Sodero J, Potolicchio SJ. Long-term compliance with nasal continuous positive airway pressure therapy of obstructive sleep apnea. Chest 1990;97:33–8. [10] Kribbs NB, Pack AI, Kline LR, Smith PL, Schwartz AR, Schubert NM, et al. Objective measurement of patterns of nasal CPAP use by patients with obstructive sleep apnea. Am Rev Respir Dis 1993;147:887–95. [11] Series F, Marc I. Efficacy of automatic continuous positive airway pressure therapy that uses an estimated required pressure in the treatment of the obstructive sleep apnea syndrome. Ann Intern Med 1997;127(8 Pt 1):588–95. [12] Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper airway in adults with obstructive sleep apnea syndrome. Sleep 1996;19:156–77. [13] Isono S, Shimada A, Tanaka A, Tagaito Y, Utsugi M, Konno A, et al. Efficacy of endoscopic static pressure/area assessment of the passive pharynx in predicting uvulopalatopharyngoplasty outcomes. Laryngoscope 1999;109:769–74. [14] Crumley RL, Stein M, Gamsu G, Golden J, Dermon S. Determination of obstructive site in obstructive sleep apnea. Laryngoscope 1987;97(3 Pt 1):301–8. [15] Rivlin J, Hoffstein V, Kalbfleisch J, McNicholas W, Zamel N, Bryan AC. Upper airway morphology in patients with idiopathic obstructive sleep apnea. Am Rev Respir Dis 1984;129:355–60. [16] Rojewski TE, Schuller DE, Clark RW, Schmidt HS, Potts RE. Videoendoscopic determination of the mechanism of obstruction in obstructive sleep apnea. Otolaryngol Head Neck Surg 1984;92:127–31. [17] Sher AE, Thorpy MJ, Shprintzen RJ, Spielman AJ, Burack B, McGregor PA. Predictive value of Muller maneuver in selection of patients for uvulopalatopharyngoplasty. Laryngoscope 1985;95:1483–7.


555

[18] Riley RW, Powell NB. Maxillofacial surgery and obstructive sleep apnea syndrome. Otolaryngol Clin North Am 1990;23:809–26. [19] Schwab RJ, Goldberg AN. Upper airway assessment: radiographic and other imaging techniques. Otolaryngol Clin North Am 1998;31:931–68. [20] Dundar A, Gerek M, Ozunlu A, Yetiser S. Patient selection and surgical results in obstructive sleep apnea. Eur Arch Otorhinolaryngol 1997;254(Suppl 1):S157–61. [21] Riley RW, Powell NB, Guilleminault C. Inferior sagittal osteotomy of the mandible with hyoid myotomy-suspension: a new procedure for obstructive sleep apnea. Otolaryngol Head Neck Surg 1986;94:589–93. [22] Riley RW, Powell NB, Guilleminault C. Obstructive sleep apnea syndrome: a review of 306 consecutively treated surgical patients. Otolaryngol Head Neck Surg 1993;108:117–25. [23] Li KK, Powell NB, Riley RW, Troell R, Guilleminault C. Overview of phase I surgery for obstructive sleep apnea syndrome. Ear Nose Throat J 1999;78:836–45. [24] Li KK, Riley RW, Powell NB, Troell R, Guilleminault C. Overview of phase II surgery for obstructive sleep apnea syndrome. Ear Nose Throat J 1999;78:851–7. [25] Mickelson SA. Laser-assisted uvulopalatoplasty for obstructive sleep apnea. Laryngoscope 1996;106(1 Pt 1):10–3. [26] Ryan CF, Love LL. Unpredictable results of laser assisted uvulopalatoplasty in the treatment of obstructive sleep apnoea. Thorax 2000;55:399–404. [27] Terris DJ, Hanasono MM, Liu YC. Reliability of the Muller maneuver and its association with sleep-disordered breathing. Laryngoscope 2000;110:1819–23. [28] Woodson BT, Derowe A, Hawke M, Wenig B, Ross EB Jr, Katsantonis GP, et al. Pharyngeal suspension suture with repose bone screw for obstructive sleep apnea. Otolaryngol Head Neck Surg 2000;122:395–401. [29] Powell NB, Riley RW, Troell RJ, Li K, Blumen MB, Guilleminault C. Radiofrequency volumetric tissue reduction of the palate in subjects with sleep-disordered breathing. Chest 1998;113:1163–74. [30] Back LJ, Hytonen ML, Malmberg HO, Ylikoski JS. Submucosal bipolar radiofrequency thermal ablation of inferior turbinates: a long-term follow-up with subjective and objective assessment. Laryngoscope 2002;112:1806–12. [31] Utley DS, Goode RL, Hakim I. Radiofrequency energy tissue ablation for the treatment of nasal obstruction secondary to turbinate hypertrophy. Laryngoscope 1999;109: 683–6. [32] Li KK, Powell NB, Riley RW, Guilleminault C. Temperature-controlled radiofrequency tongue base reduction for sleep-disordered breathing: long-term outcomes. Otolaryngol Head Neck Surg 2002;127:230–4. [33] Powell NB, Riley RW, Guilleminault C. Radiofrequency tongue base reduction in sleepdisordered breathing: a pilot study. Otolaryngol Head Neck Surg 1999;120:656–64. [34] Woodson BT, Nelson L, Mickelson S, Huntley T, Sher A. A multi-institutional study of radiofrequency volumetric tissue reduction for OSAS. Otolaryngol Head Neck Surg 2001;125:303–11. [35] Woodson BT, Naganuma H. Comparison of methods of airway evaluation in obstructive sleep apnea syndrome. Otolaryngol Head Neck Surg 1999;120:460–3. [36] Loube DI, Andrada TF. Comparison of respiratory polysomnographic parameters in matched cohorts of upper airway resistance and obstructive sleep apnea syndrome patients. Chest 1999;115:1519–24. [37] Kryger MH. Sleep apnea: from the needles of Dionysius to continuous positive airway pressure. Arch Intern Med 1983;143:2301–3. [38] Dempsey JA, Skatrud JB, Safwan BM, et al. Effects of sleep on the regulation of breathing and respiratory muscle function. In: Crystal RG, West JB, editors. The lung: scientific foundations. New York: Raven Press; 1991. [39] Khoo MC. Periodic breathing. In: Crystal RG, West JB, editors. The lung: scientific foundations. New York: Raven Press; 1991.

556


[40] Troell RJ, Riley RW, Powell NB, Li K. Surgical management of the hypopharyngeal airway in sleep disordered breathing. Otolaryngol Clin North Am 1998;31:979–1012. [41] Fujita S. Pharyngeal surgery for obstructive sleep apnea and snoring. In: Fairbanks DNF, Fujita S, Ikematsu T, et al, editors. Snoring and obstructive sleep apnea. New York: Raven Press; 1987. p. 101. [42] Anch AM, Remmers JE, Bunce H 3rd. Supraglottic airway resistance in normal subjects and patients with occlusive sleep apnea. J Appl Physiol 1982;53:1158–63. [43] Kuna ST, Remmers JE. Neural and anatomic factors related to upper airway occlusion during sleep. Med Clin North Am 1985;69:1221–42. [44] Stauffer JL, Zwillich CW, Cadieux RJ, Bixler EO, Kales A, Varano LA, et al. Pharyngeal size and resistance in obstructive sleep apnea. Am Rev Respir Dis 1987;136:623–7. [45] Suratt PM, McTier RF, Wilhoit SC. Collapsibility of the nasopharyngeal airway in obstructive sleep apnea. Am Rev Respir Dis 1985;132:967–71. [46] Winakur SJ, Smith PL, Schwartz AR. Pathophysiology and risk factors for obstructive sleep apnea. Seminars in Respiratory and Critical Care Medicine 1998;19:999–1112. [47] Horner RL, Mohiaddin RH, Lowell DG, Shea SA, Burman ED, Longmore DB, et al. Sites and sizes of fat deposits around the pharynx in obese patients with obstructive sleep apnoea and weight matched controls. Eur Respir J 1989;2:613–22. [48] Mezzanotte WS, Tangel DJ, White DP. Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism). J Clin Invest 1992;89:1571–9. [49] Tangel DJ, Mezzanotte WS, White DP. Influence of sleep on tensor palatini EMG and upper airway resistance in normal men. J Appl Physiol 1991;70:2574–81. [50] Suratt PM, Dee P, Atkinson RL, Armstrong P, Wilhoit SC. Fluoroscopic and computed tomographic features of the pharyngeal airway in obstructive sleep apnea. Am Rev Respir Dis 1983;127:487–92. [51] Leiter JC. Upper airway shape: is it important in the pathogenesis of obstructive sleep apnea? Am J Respir Crit Care Med 1996;153:894–8. [52] Malhotra A, Pillar G, Fogel R, Beauregard J, Edwards J, White DP. Upper-airway collapsibility: measurements and sleep effects. Chest 2001;120:156–61. [53] Suratt PM, Wilhoit SC, Cooper K. Induction of airway collapse with subatmospheric pressure in awake patients with sleep apnea. J Appl Physiol 1984;57:140–6. [54] Schwab RJ, Gupta KB, Gefter WB, Metzger LJ, Hoffman EA, Pack AI. Upper airway and soft tissue anatomy in normal subjects and patients with sleep-disordered breathing: significance of the lateral pharyngeal walls. Am J Respir Crit Care Med 1995;152(5 Pt 1): 1673–89. [55] Stauffer JL, Buick MK, Bixler EO, Sharkey FE, Abt AB, Manders EK, et al. Morphology of the uvula in obstructive sleep apnea. Am Rev Respir Dis 1989;140:724–8. [56] National Commission on Sleep Disorders Research. Wake up America: a national sleep alert. Washington (DC): Government Printing Office; 1993. [57] Fletcher EC, DeBehnke RD, Lovoi MS, Gorin AB. Undiagnosed sleep apnea in patients with essential hypertension. Ann Intern Med 1985;103:190–5. [58] Kales A, Bixler EO, Cadieux RJ, Schneck DW, Shaw LC 3rd, Locke TW, et al. Sleep apnoea in a hypertensive population. Lancet 1984;2:1005–8. [59] Young T, Peppard P, Palta M, Hla KM, Finn L, Morgan B, Skatrud J. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med 1997;157:1746–52. [60] Hung J, Whitford EG, Parsons RW, Hillman DR. Association of sleep apnoea with myocardial infarction in men. Lancet 1990;336:261–4. [61] Young T, Blustein J, Finn L, Palta M. Sleep-disordered breathing and motor vehicle accidents in a population-based sample of employed adults. Sleep 1997;20:608–13. [62] Beninati W, Harris CD, Herold DL, Shepard JW Jr. The effect of snoring and obstructive sleep apnea on the sleep quality of bed partners. Mayo Clin Proc 1999;74:955–8.


557

[63] Noda A, Okada T, Yasuma F, Sobue T, Nakashima N, Yokota M. Prognosis of the middle-aged and aged patients with obstructive sleep apnea syndrome. Psychiatry Clin Neurosci 1998;52:79–85. [64] He J, Kryger MH, Zorick FJ, Conway W, Roth T. Mortality and apnea index in obstructive sleep apnea: experience in 385 male patients. Chest 1988;94:9–14. [65] Lysdahl M, Haraldsson PO. Long-term survival after uvulopalatopharyngoplasty in nonobese heavy snorers: a 5- to 9-year follow-up of 400 consecutive patients. Arch Otolaryngol Head Neck Surg 2000;126:1136–40. [66] Wright J, Johns R, Watt I, Melville A, Sheldon T. Health effects of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure: a systematic review of the research evidence. BMJ 1997;314:851–6. [67] Guidry UC, Mendes LA, Evans JC, Levy D, O’Connor GT, Larson MG, et al. Echocardiographic features of the right heart in sleep-disordered breathing: the Framingham Heart Study. Am J Respir Crit Care Med 2001;164:933–8. [68] Kapur VK, Redline S, Nieto FJ, Young TB, Newman AB, Henderson JA. The relationship between chronically disrupted sleep and healthcare use. Sleep 2002;25:289–96. [69] Nieto FJ, Young TB, Lind BK, Shahar E, Samet JM, Redline S, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA 2000;283:1829–36. [70] Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Javier Nieto F, et al. Sleepdisordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 2001;163:19–25. [71] Young T, Peppard P. Sleep-disordered breathing and cardiovascular disease: epidemiologic evidence for a relationship. Sleep 2000;23(Suppl 4):S122–26. [72] Newman AB, Nieto FJ, Guidry U, Lind BK, Redline S, Pickering TG, et al. Relation of sleep-disordered breathing to cardiovascular disease risk factors: the Sleep Heart Health Study. Am J Epidemiol 2001;154:50–9. [73] Gottlieb DJ, Whitney CW, Bonekat WH, Iber C, James GD, Lebowitz M, et al. Relation of sleepiness to respiratory disturbance index: the Sleep Heart Health Study. Am J Respir Crit Care Med 1999;159:502–7. [74] Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14:540–5. [75] Stewart AL, Ware JE Jr. Measuring functioning and well-being. The Medical Outcomes Study Approach. Duke University Press; Durham, NC: 1991. [76] Briones B, Adams N, Strauss M, Rosenberg C, Whalen C, Carskadon M, et al. Relationship between sleepiness and general health status. Sleep 1996;19:583–8. [77] Jenkinson C, Stradling J, Petersen S. Comparison of three measures of quality of life outcome in the evaluation of continuous positive airways pressure therapy for sleep apnoea. J Sleep Res 1997;6:199–204. [78] Baldwin CM, Griffith KA, Nieto FJ, O’Connor GT, Walsleben JA, Redline S. The association of sleep-disordered breathing and sleep symptoms with quality of life in the Sleep Heart Health Study. Sleep 2001;24:96–105. [79] Akashiba T, Kawahara S, Akahoshi T, Omori C, Saito O, Majima T, et al. Relationship between quality of life and mood or depression in patients with severe obstructive sleep apnea syndrome. Chest 2002;122:861–5. [80] D’Ambrosio C, Bowman T, Mohsenin V. Quality of life in patients with obstructive sleep apnea: effect of nasal continuous positive airway pressure—a prospective study. Chest 1999;115:123–9. [81] Fornas C, Ballester E, Arteta E, Ricou C, Diaz A, Fernandez A, et al. Measurement of general health status in obstructive sleep apnea hypopnea patients. Sleep 1995;18: 876–9. [82] Flemons WW, Reimer MA. Measurement properties of the Calgary sleep apnea quality of life index. Am J Respir Crit Care Med 2002;165:159–64.

558


[83] Weaver TE, Laizner AM, Evans LK, Maislin G, Chugh DK, Lyon K, et al. An instrument to measure functional status outcomes for disorders of excessive sleepiness. Sleep 1997;20:835–43. [84] Piccirillo JF, Gates GA, White DL, Schectman KB. Obstructive sleep apnea treatment outcomes pilot study. Otolaryngol Head Neck Surg 1998;118:833–44. [85] Piccirillo JF. Outcomes research and obstructive sleep apnea. Laryngoscope 2000;110 (3 Pt 3):16–20. [86] American Sleep Disorders Association Standards of Practice Committee Indications for Polysomnography Task Force. Practice parameters for the indications for polysomnography and related procedures: an American Sleep Disorders Association report. Sleep 1997;20:406–22. [87] Chervin RD, Guilleminault C. Obstructive sleep apnea and related disorders. Neurol Clin 1996;14:583–609. [88] Rinaldi R, Vignatelli L, D’Alessandro R, Bassein L, Sforza E, Plazzi G, et al. Validation of symptoms related to excessive daytime sleepiness. Neuroepidemiology 2001;20: 248–56. [89] Yao M, Utley DS, Terris DJ. Cephalometric parameters after multilevel pharyngeal surgery for patients with obstructive sleep apnea. Laryngoscope 1998;108:789–95. [90] Isono S, Remmers JE, Tanaka A, Sho Y, Sato J, Nishino T. Anatomy of pharynx in patients with obstructive sleep apnea and in normal subjects. J Appl Physiol 1997; 82:1319–26. [91] Rowley JA, Permutt S, Willey S, Smith PL, Schwartz AR. Effect of tracheal and tongue displacement on upper airway airflow dynamics. J Appl Physiol 1996;80:2171–8. [92] Woodson BT. Retropalatal airway characteristics in uvulopalatopharyngoplasty compared with transpalatal advancement pharyngoplasty. Laryngoscope 1997;107:735–40. [93] Schwab RJ, Gefter WB, Hoffman EA, Gupta KB, Pack AI. Dynamic upper airway imaging during awake respiration in normal subjects and patients with sleep disordered breathing. Am Rev Respir Dis 1993;148:1385–400. [94] Vilaseca I, Morello A, Montserrat JM, Santamaria J, Iranzo A. Usefulness of uvulopalatopharyngoplasty with genioglossus and hyoid advancement in the treatment of obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 2002;128:435–40. [95] Ryan CF, Dickson RI, Lowe AA, Blokmanis A, Fleetham JA. Upper airway measurements predict response to uvulopalatopharyngoplasty in obstructive sleep apnea. Laryngoscope 1990;100:248–53. [96] Woodson BT, Conley SF, Dohse A, Feroah TR, Sewall SR, Fujita S. Posterior cephalometric radiographic analysis in obstructive sleep apnea. Ann Otol Rhinol Laryngol 1997;106:310–3. [97] Li KK, Troell RJ, Riley RW, Powell NB, Koester U, Guilleminault C. Uvulopalatopharyngoplasty, maxillomandibular advancement, and the velopharynx. Laryngoscope 2001;111:1075–8. [98] Holland J, Dement W, Raynall D. Polysomnography: a response to a need for improved communication. Presented at the 14th Annual Meeting of the Association of Psychophysiological Study of Sleep, Jackson Hole, WY, June 1974. [99] Coleman J. Sleep studies: current techniques and future trends. Otolaryngol Clin North Am 1999;32:195–210. [100] Sergi M, Rizzi M, Greco M, Andreoli A, Bamberga M, Castronovo C, et al. Validity of diurnal sleep recording performed by an ambulatory device in the diagnosis of obstructive sleep apnoea. Respir Med 1998;92:216–20. [101] Mykytyn IJ, Sajkov D, Neill AM, McEvoy RD. Portable computerized polysomnography in attended and unattended settings. Chest 1999;115:114–22. [102] Parra O, Garcia-Esclasans N, Montserrat JM, Garcia Eroles L, Ruiz J, Lopez JA, et al. Should patients with sleep apnoea/hypopnoea syndrome be diagnosed and managed on the basis of home sleep studies? Eur Respir J 1997;10:1720–4.


559

[103] Kapur VK, Rapoport DM, Sanders MH, Enright P, Hill J, Iber C, et al. Rates of sensor loss in unattended home polysomnography: the influence of age, gender, obesity, and sleep-disordered breathing. Sleep 2000;23:682–8. [104] Mortimore IL, Bradley PA, Murray JA, Douglas NJ. Uvulopalatopharyngoplasty may compromise nasal CPAP therapy in sleep apnea syndrome. Am J Respir Crit Care Med 1996;154(6 Pt 1):1759–62. [105] Schechtman KB, Sher AE, Piccirillo JF. Methodological and statistical problems in sleep apnea research: the literature on uvulopalatopharyngoplasty. Sleep 1995;18:659–66. [106] Li KK, Powell NB, Riley RW, Troell RJ, Guilleminault C. Long-term results of maxillomandibular advancement surgery. Sleep Breath 2000;4:137–40. [107] Larsson LH, Carlsson-Nordlander B, Svanborg E. Four-year follow-up after uvulopalatopharyngoplasty in 50 unselected patients with obstructive sleep apnea syndrome. Laryngoscope 1994;104(11 Pt 1):1362–8. [108] Charuzi I, Lavie P, Peiser J, Peled R. Bariatric surgery in morbidly obese sleep-apnea patients: short- and long-term follow-up. Am J Clin Nutr 1992;55(2 Suppl):594S–6S. [109] Scheuller M, Weider D. Bariatric surgery for treatment of sleep apnea syndrome in 15 morbidly obese patients: long-term results. Otolaryngol Head Neck Surg 2001;125: 299–302. [110] Sugerman HJ, Fairman RP, Sood RK, Engle K, Wolfe L, Kellum JM. Long-term effects of gastric surgery for treating respiratory insufficiency of obesity. Am J Clin Nutr 1992;55(2 Suppl):597S–601S. [111] Wittels EH, Thompson S. Obstructive sleep apnea and obesity. Otolaryngol Clin North Am 1990;23:751–60. [112] Walker RP, Durazo-Arvizu R, Wachter B, Gopalsami C. Preoperative differences between male and female patients with sleep apnea. Laryngoscope 2001;111:1501–5. [113] Mohsenin V. Gender differences in the expression of sleep-disordered breathing: role of upper airway dimensions. Chest 2001;120:1442–7. [114] Young T. Analytic epidemiology studies of sleep disordered breathing—what explains the gender difference in sleep disordered breathing? Sleep 1993;16(8 Suppl):S1–2. [115] Vgontzas AN, Tan TL, Bixler EO, Martin LF, Shubert D, Kales A. Sleep apnea and sleep disruption in obese patients. Arch Intern Med 1994;154:1705–11. [116] Rajala R, Partinen M, Sane T, Pelkonen R, Huikuri K, Seppalainen AM. Obstructive sleep apnoea syndrome in morbidly obese patients. J Intern Med 1991;230:125–9. [117] Bettega G, Pepin JL, Veale D, Deschaux C, Raphael B, Levy P. Obstructive sleep apnea syndrome: fifty-one consecutive patients treated by maxillofacial surgery. Am J Respir Crit Care Med 2000;162(2 Pt 1):641–9. [118] Li KK, Guilleminault C, Riley RW, Powell NB. Obstructive sleep apnea and maxillomandibular advancement: an assessment of airway changes using radiographic and nasopharyngoscopic examinations. J Oral Maxillofac Surg 2002;60:526–30; discussion, 531. [119] Thut DC, Schwartz AR, Roach D, Wise RA, Permutt S, Smith PL. Tracheal and neck position influence upper airway airflow dynamics by altering airway length. J Appl Physiol 1993;75:2084–90. [120] Pae EK, Lowe AA, Fleetham JA. A role of pharyngeal length in obstructive sleep apnea patients. Am J Orthod Dentofacial Orthop 1997;111:12–7. [121] Millman RP, Carlisle CC, Rosenberg C, Kahn D, McRae R, Kramer NR. Simple predictors of uvulopalatopharyngoplasty outcome in the treatment of obstructive sleep apnea. Chest 2000;118:1025–30. [122] Boehlecke BA. Epidemiology and pathogenesis of sleep-disordered breathing. Curr Opin Pulm Med 2000;6:471–8. [123] Piccirillo JF. More information needed about the long-term health consequences of mild to moderate obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 2001;127: 1400–1.

560


[124] Kingshott RN, Vennelle M, Hoy CJ, Engleman HM, Deary IJ, Douglas NJ. Predictors of improvements in daytime function outcomes with CPAP therapy. Am J Respir Crit Care Med 2000;161(3 Pt 1):866–71. [125] Douglas NJ, Thomas S, Jan MA. Clinical value of polysomnography. Lancet 1992; 339:347–50. [126] Gyulay S, Olson LG, Hensley MJ, King MT, Allen KM, Saunders NA. A comparison of clinical assessment and home oximetry in the diagnosis of obstructive sleep apnea. Am Rev Respir Dis 1993;147:50–3. [127] Troell RJ, Riley RW, Powell NB, Li K. Long-term results of surgical management of sleep disordered breathing: are our patients really benefiting? Otolaryngol Clin North Am 1998;31:1031–5. [128] Loredo JS, Ancoli-Israel S, Dimsdale JE. Effect of continuous positive airway pressure vs placebo continuous positive airway pressure on sleep quality in obstructive sleep apnea. Chest 1999;116:1545–9. [129] Li KK, Riley RW, Powell NB, Gervacio L, Troell RJ, Guilleminault C. Obstructive sleep apnea surgery: patient perspective and polysomnographic results. Otolaryngol Head Neck Surg 2000;123:572–5. [130] Simmons FB, Guilleminault C, Miles LE. The palatopharyngoplasty operation for snoring and sleep apnea: an interim report. Otolaryngol Head Neck Surg 1984;92:375–80. [131] Walker-Engstrom ML, Wilhelmsson B, Tegelberg A, Dimenas E, Ringqvist I. Quality of life assessment of treatment with dental appliance or UPPP in patients with mild to moderate obstructive sleep apnoea: a prospective randomized 1-year follow-up study. J Sleep Res 2000;9:303–8. [132] Benbadis SR, Mascha E, Perry MC, Wolgamuth BR, Smolley LA, Dinner DS. Association between the Epworth sleepiness scale and the multiple sleep latency test in a clinical population. Ann Intern Med 1999;130(4 Pt 1):289–92. [133] Chervin RD, Aldrich MS. The Epworth Sleepiness Scale may not reflect objective measures of sleepiness or sleep apnea. Neurology 1999;52:125–31. [134] Moore P, Bardwell WA, Ancoli-Israel S, Dimsdale JE. Association between polysomnographic sleep measures and health-related quality of life in obstructive sleep apnea. J Sleep Res 2001;10:303–8. [135] Barnes M, Houston D, Worsnop CJ, Neill AM, Mykytyn IJ, Kay A, et al. A randomized controlled trial of continuous positive airway pressure in mild obstructive sleep apnea. Am J Respir Crit Care Med 2002;165:773–80. [136] Reda M, Ullal U, Wilson JA. The quality of life impact of snoring and the effect of laser palatoplasty. Clin Otolaryngol 2000;25:570–6. [137] Bardwell WA, Ancoli-Israel S, Dimsdale JE. Response bias influences mental health symptom reporting in patients with obstructive sleep apnea. Ann Behav Med 2001; 23:313–7. [138] Weaver EM, Kapur VK, Yueh B. Correlations between polysomnography parameters and quality of life measures in sleep apneics [abstract]. Sleep 2000;23:A59. [139] Moser NJ, Phillips BA, Berry DT, Harbison L. What is hypopnea, anyway? Chest 1994;105:426–8. [140] Series F, Marc I. Nasal pressure recording in the diagnosis of sleep apnoea hypopnoea syndrome. Thorax 1999;54:506–10. [141] Sher AE. An overview of sleep disordered breathing for the otolaryngologist. Ear Nose Throat J 1999;78:694–5698–700, 703–6. [142] Skatvedt O, Akre H, Godtlibsen OB. Nocturnal polysomnography with and without continuous pharyngeal and esophageal pressure measurements. Sleep 1996;19:485–90. [143] Pitman SD, Pillar G, Malhotra A, Fogel R, White DP. Night-to-night variability of apnea severity abstract. Sleep 2000;23:A373. [144] Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleepdisordered breathing among middle-aged adults. N Engl J Med 1993;328:1230–5.


561

[145] Mendelson WB. Use of the sleep laboratory in suspected sleep apnea syndrome: is one night enough? Cleve Clin J Med 1994;61:299–303. [146] Zozula R, Rosen R. Compliance with continuous positive airway pressure therapy: assessing and improving treatment outcomes. Curr Opin Pulm Med 2001;7:391–8. [147] Schwartz AR, Eisele DW, Hari A, Testerman R, Erickson D, Smith PL. Electrical stimulation of the lingual musculature in obstructive sleep apnea. J Appl Physiol 1996; 81:643–52. [148] Jokic R, Klimaszewski A, Mink J, Fitzpatrick MF. Surface tension forces in sleep apnea: the role of a soft tissue lubricant: a randomized double-blind, placebo-controlled trial. Am J Respir Crit Care Med 1998;157(5 Pt 1):1522–5.

2003, Vol.36, Issues 3, Surgery for Sleep Apnea

Recommend Documents