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

Otolaryngol Clin N Am 36 (2003) xixii
Preface
Sleep-disordered breathing
David J. Terris, MD, FACS Guest Editor
Many signicant 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 signicant 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 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00173-1
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failure analysis. Outcome researchers will have an important part to play in the future development of this eld. David J. Terris, MD, FACS Porubsky Professor and Chairman Department of OtolaryngologyHead and Neck Surgery Medical College of Georgia 1120 Fifteenth Street Augusta, GA 30912-4060, USA E-mail address: dterris@mcg.edu
Otolaryngol Clin N Am 36 (2003) 409421
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 eect 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 eld 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 dened by a polysomnogram nding that demonstrates obstruction of the upper airway during sleep. Obstructive sleep apnea syndrome is well recognized and requires both OSA with greater than ve 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: bwoodson@mcw.edu (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 Inu-ENT. 0030-6665/03/$ - see front matter 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(03)00017-3
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an abnormal amount of obstructive ventilatory events has not been identied [2]. Current thought considers a respiratory distress index of greater than 15 as the minimal threshold of disease when symptoms are absent. But such classications 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 dening 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 identied 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 airow. 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 ow. The mechanics of upper airway collapse may be described using both a static model that evaluates
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changes independent of airow and a dynamic model that includes the effects of negative inspiratory pressure and airow [7,11]. Classically, collapse of the upper airway has been thought to occur during inspiration, when negative inspiratory pressure and airow 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 uctuation 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 signicant 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 airow limitation or complete airway collapse.
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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, airow, and intraluminal pressure. If muscle tone, airow, 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 [1820]. The nal 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 airow 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 eects on airway size in patients with snoring and OSA. Several mechanisms, including tissue mass and tracheal
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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 conguration than the supine position. The mechanism of this effect has not been demonstrated yet but likely includes effects of gravity and reex effects. Reex effects should not be dismissed. It is well established that the lateral body position has signicant effects on the nasal cycle. The idea that body position has reex 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 reexes, 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 airow 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 inuencing 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 sufcient to cause signicant ow limitation, in contrast to individuals with severely abnormal upper airway anatomy. In this group,
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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 signicant 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 airow 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 airow limitation and increased work of breathing. The resultant decreased airow 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 reex-mediated.
Other eects 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, signicant 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
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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 reex-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 nding has been demonstrated in laboratory-based studies that show both peak and phasic genioglossus electromyography EMG activity is signicantly 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 reexes 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 reex 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
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demonstrated evidence of both muscle-bundle hypertrophy and muscle-ber 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-ber damage and hypertrophy. Immunohistopathologic changes in muscle-ber 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 dicult. 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 ow 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 Pout Pin denes 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 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 airow (Pow). As noted, airway pressures may be dilating (if positive, such as with expiration or with the application
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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 dierence 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 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 airow on decreasing luminal pressures are determined by its velocity and are described by Bernoullis equation. If airow velocity is zero, then (Pluminal Pairway 0), and if neuromuscular tone is held constant (Ptissue k), then measured airway pressure represents the distending or transmural pressure of the upper airway (Ptm Pairway k). This measured pressure, combined with measures of upper airway size, allows calculation of airway compliance (dA/dP) independent of physiologic inuences. 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 ow 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
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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 ow). In baseline, Pin is greater than Pout, and the collapsible segment is patent. Unobstructed ow (ow, lower left) occurs when Pin is greater than Pout and Pus is greater than Pcrit. In no ow (upper right), water lls the bucket, Pout is greater than Pin (the collapsible tube is obstructed), Pus is less than Pcrit, and there is no airow. Increasing Pus dilates the segment; when this event occurs, ow will resume. In utter (lower right), Pus is greater than Pcrit, and ow must occur; however, Pdownstream is increased (as occurs with increased upper airway resistance during sleep). The orice (*) is exposed to a negative inspiratory pressure (NIP) (Pdownstream < Pcrit), and collapse of this segment occurs. With ow cessation, however, pressure rapidly rises to Pus, and the orice opens. The orice now is exposed to Pdownstream and Bernoulli forces, and collapse occurs. A cycle of rapid opening and closing (utter) 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 ow. 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 Poiseuilles law, which describes ow in noncollapsible tubes. Poiseuilles law states V P1 P2/R, where V ow, P1 pressure upstream, and P2 pressure downstream. The resistance component (R) is determined by length of the tube (L), uid viscosity (g), and the radius (r) of the tube (R resistance 8gL/pr4. Because viscosity and length are constant, changes in resistance are
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primarily related to changes in the area of the tube. Because area is unchanged in a rigid tube, ow in a noncollapsible airway depends signicantly on pressure across the tube (P1 P2 driving pressure). This type of ow contrasts to a collapsible, Starling resistor airway in which ow may be independent of driving pressure. In a Starling resistor, resistance is variable, and resistance and ow 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 ow. Three basic clinical patterns can be observed, which include normal breathing, snoring, and obstruction. Likewise, three possible conditions of ow across a collapsible upper airway exist and may include unimpeded ow, utter, 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 ow, 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 ow occurs. When transmural pressure is less than upstream pressure but greater than downstream pressures (Pus > Ptm > Pds), the condition of utter 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 ow, and the segment becomes exposed to upstream pressure, which dilates the upper airway. When ow 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 ow in the airway. The result is utter. Because of these characteristics, ow in a collapsible tube in patients at risk for OSA is not determined by the dierence between upstream and downstream pressures (driving pressure), but rather by the dierence between upstream pressures and the pressures surrounding the collapsible segment. In a structurally patent airway, the pressure dierence 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 airow.
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Summary Upper airway competence involves complex interactions between anatomy and physiology. The common nal 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 eld. 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.
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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 ones 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 signicant. 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 evidentthat 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 aect the qualitative and quantitative aspects of sleep and daytime function [13]. Of the various sleep disorders, sleep apnea is probably one of the most important and the most common nocturnal problem aicting 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: gohyauhong@hotmail.com (Y.H. Goh). 0030-6665/03/$ - see front matter 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00174-3
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were discovered to have signicant 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% [48], with estimates tending to increase with increasing age. Since the rst 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 specic for sleep apnea, whereas the latter are usually the nonspecic results of abnormal sleep regardless of the cause. To understand the physiologic impact of sleep apnea on wakefulness, it is pertinent to rst examine the respiratory physiology during normal sleep, the arousal responses to respiratory alterations during sleep, the eects 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 inuence breathing and bring about an increase in both ventilation and ventilatory responses. The loss of ventilatory drive that is observed during sleep probably reects the loss of the wakefulness drive to ventilation. During rapid-eye-movement (REM) sleep, the inhibition of both presynaptic and postsynaptic aerent neurons results in an increase in sensory arousal thresholds to external stimuli and postsynaptic inhibition of motor
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neurons that produce postural hypotonia characteristic of REM sleep. This combination of decreased sensory and motor function is believed to account for the signicant 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 [1114]. 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 patients 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 signicant 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 [1518], the phase of sleep when airway resistance typically reaches the maximum [19,20]. The effect of increased airow 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.
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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 nal pathway for arousal from sleep seems to be the level of ventilatory eort [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 effortrelated 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 signicant hypoxemia or signicant hypercapnia.
Eects 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 [3537] 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 signicant 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 signicant 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 nal outcome of any of these events is arousal (visible or not visible on the electroencephalogram [EEG]) and an increase in ventilatory
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eort. 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, dened 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 aecting 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 benet 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.
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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 eld of sleep medicine, the level of ones state of wakefulness is never measured directly. The degree of wakefulness is instead quantied by measuring ones 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 specic 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 (2:006:00 AM), irritability, lethargy, sleepiness, and impaired mental function, such as inability to concentrate and memory lapses, occur. If signicant physiologic sleepiness is allowed to intrude into ones 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
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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 2:006:00 AM and the other between 2:006:00 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 nonspecic 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 reect 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, soporic 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 eects of sleep loss are rather insensitive. Currently, only long and monotonous tasks are
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reliably sensitive in assessing the eects 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 ones likelihood of falling asleep, has gained wide acceptance within the eld 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 patients 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 eects 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 eects on patients mood and behavior. Recognizing the existence of these nonspecic 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.
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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 signicant 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 signicant 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 nonspecic symptoms of lethargy, depression, and cognitive and memory impairment to clinicians in elds such as endocrinology, psychiatry, and neurology. Just how many of these patients with such nonspecic 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 inuenced by a multitude of factors, such as the extent of sleep architecture disruption, the patients 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 difcult 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 trac 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 inuence 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 trafc, industrial, or domestic), a direct link between the two is difcult to prove. The past three decades since the rst 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
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Table 1 Factors aecting 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, Parkinsons 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 eects 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.
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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 fth [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 suered nasal obstruction for a long time and who, we believe, have developed secondary eects somewhere in the systemic phases of the respiratory act. It is a persisting, most often irreversible nding 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) [24] and subsequent identication 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: clete@stanford.edu (C.A. Kushida). 0030-6665/03/$ - see front matter 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00175-5
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were made for children, and in Hills 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 ofcer. He also noted that many children with obstructed airways showed signicant 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 rest the whole body can obtain during the sleep period [4]. He later identied 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 decits 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 rst 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 reects 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
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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 [1821]. 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 signicant 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, dened as the tip of the soft palate to the level of the vocal cords [2426]. The nasopharynx, dened 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 efcient 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 airow generally follows a parabolic curve that arches superiorly through the nasal valve, which is the major site of nasal resistance [21,32,33].
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The internal nasal valve is dened 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 reection between the ULC and the septum, posteriorly by the head of the inferior turbinate, inferiorly by the oor of the nose, and laterally by the bony piriform aperture [34]. Resistance progressively increases over the rst 2 cm of the nose, spread over a ow-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 ow, 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 ow-limiting segment therefore acts like a Starling resistor [35]. Partial collapse of the ULC normally occurs at a ventilatory ow of 30 L/min, preventing further increases in intranasal pressure from augmenting ow [34]. Nasal resistance also can be aected 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 signicant role in the modulation of nasal resistance because apneas and hypopneas
m Fig. 1. Similar to the collapsible hypotonic pharyngeal segment described in the composite theory [7l] of upper airway obstruction during sleep, the ow-limiting segment of the nasal valve, inuenced by nasal reexes, also can act like a Starling resistor in augmenting nasal resistance. Accordingly, only two variables inuence nasal valve closurethe 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 ow (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 airow within this segment, with increased inward pressure of the pharyngeal walls (Bernoulli effect). This pharyngeal narrowing and progressive ow 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 deciencies and neuromuscular abnormalities that may increase future susceptibility to upper airway obstruction and sleep-disordered breathing. GERD gastroesophageal reux disease; Patm atmospheric pressure; PDS downstream pressure; V.M.O. ventilatory motor output; VT tidal volume. *Poiseuilles law.
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can be induced during sleep from chronic mucosal stimulation with an irritant [39]. Several studies have pointed toward the presence of nonspecic inammation [40,41], which may work in synergy with these other factors to inuence nasal resistance [42]. Stimulation of nasal reexes also may inuence upper airway obstruction, because nasal obstruction may disturb reex mechanisms mediated through the trigeminal or vagal nerves. When aerent 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 aring that precedes diaphragmatic activityan 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 inuence 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 xed unilateral nasal obstruction. In turn, there are several indirect mechanisms by which nasal obstruction and increased nasal resistance may aect upper airway resistance and subsequent pharyngeal obstruction [21]. The rst involves alterations in upper airway aerodynamics (Fig. 1). Although upper airway obstruction may begin at end expiration, it is during subsequent inspiration that pharyngeal ow further decreases and ultimately stops, because the pharynx is normally the major limiting factor in inspiratory ow [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 airow in the upper airway may directly affect activity of the respiratory muscles during sleep [21,50], localized polyneuropathy possibly related to vibratory trauma also
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may contribute to airway instability and the development of upper airway obstruction in these patients [21,47,51,52]. Gastroesophageal reux related to excessive diaphragmatic activity may similarly iname 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 inuences 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 ow 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 ow 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 airow 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 nding that nasal occlusion resulted in a signicantly 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 ow 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 eciency 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 reexes may impair upper airway muscle tone further [54,55].
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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 articial 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 specically 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, signicant 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 signicant (P < 0.03). The most frequent ndings, 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 signicant 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) ow resistance. They found that intranasal occlusion increased airway obstruction during sleep, with the minutes of airway obstruction per hour of sleep signicantly increased after nasal occlusion (P < 0.05). Although there was an overall correlation between pulse ow resistance and the number of apneas and hypopneas, this correlation did not reach statistical signicance; interestingly, the patient who developed the most apneas had the highest pulse ow resistance. There was also a trend toward lighter sleep and less slow-wave and REM sleep with nasal occlusion and a statistically signicant 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
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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 airow, 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 benet 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 xed 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, 13.325.0) 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 signicant difference in sleep architecture was seen between the two groups after surgery, sleep fragmentation (as assessed by the number of arousals) was signicantly 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
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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 signicant 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 fty-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 signicantly 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 signicantly higher in the OSAHS group, and although the highest unilateral nasal resistance was not signicantly different between the two groups, basal bilateral nasal resistance did correlate signicantly (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 inuence was less than that of obesity or cephalometric landmarks.
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Rhinitis and sleep-related breathing disorders With allergic and nonallergic rhinitis aecting 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 signicant 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 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 infants jaw is also almost horizontal, and its articulation with the skull is unstable, which allows the relatively exible mandible to displace posteriorly. The tongue, a mobile muscular mass, sits on the oor of the mouth, anchored to the mobile mandible and to the hyoid. At birth and usually for the rst 5 to 6 months of life, the tongue lls 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% condence interval, 1.6616.12) 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
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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 difculties 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 decits [7375]. 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 Downs 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 conguration depends on anatomic bony structures, chronic nasal airow 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,
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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 uctuates 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 brosis, 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 ux, 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 Poiseuilles law, which relates airow 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 closurethe 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 xed obstruction at the level of the nasal valve, requiring more negative intranasal pressure to generate a given amount of nasal airow [34]; for example, the attempt to maintain nasal airow in the setting of small
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Table 1 Conditions and related factors that may contribute to increased nasal resistance and nasal obstruction Nature of problem Mucosala Neuromuscular
Structural
Location Posterior nasal Nasopharyngitis packing Infectious mononucleosis Nasal syphilis Primary tuberculosis Rhinoscleroma (Klebsiella rhinoscleromatis) Diphtheria Midfacial granuloma Wegeners granuloma
Soft tissue obstruction (possibly reversible) Foreign body (reversible)
Bone/cartilage deformity (xed)
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 brosis Asthma Aspirin sensitivity Amyloidosis Cysts Nasal cavity Septum Trauma Polyposis Anterior nasal packing Trauma
Septal deviation Congenital craniofacial anomalies
Turbinates
Trauma Polyposis
Conchal hypertrophy Anterior nasal Congenital craniofacial packing anomalies
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 Trauma Facial paralysis (zygomaticotemporal division of facial nerve)
Nasal valves
Postrhinoplasty Trauma Tip ptosis Cicatricial stenosis
Postrhinoplasty Anterior nasal Tip ptosis packing Paradoxic lateral crura Congenital craniofacial anomalies
Congestion may occur secondary to other causes of nasal obstruction, such as neoplastic lesions, idiopathic polyps, or polyps related to cystic brosis, asthma, aspirin sensitivity, chronic rhinosinusitis, or allergic rhinitis. A deviated nasal septum may cause a sensation of chronic unilateral nasal congestion or congestion that uctuates 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-inammatory drugs. Data from Refs. [21,30,34,38,106].
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vestibular lesions such as cysts or minor septal deections can increase the negative pressure generated at the valve and thus, nasal resistance [21,32]. Conversely, dynamic valvular dysfunction is related to accid 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 rst-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 eectiveness of internal (eg, Nozovent [Prevancure AB; Vastra Frolunda, 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 [8588]. A study by Kerr et al [89], however, showed that among 10 generally obese (body mass index, 25.938.9; 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 signicant improvement in sleep architecture or AHI. There was a reduction in the number of arousals
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per hour, from 52.4 with placebo to 43.7 with treatment (P < 0.04), however. These ndings 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 signicant 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 specied; furthermore, the investigators rather unconventionally dened RDI as the sum of apnea index (AI), hypopnea index (HI), and index of obstructive snoring. Rhinoscopic examination and clinical assessment of pharyngeal collapsibility (Mullers 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 signicantly (22.819.8 [P 0.08] and 8.6-5.8 [P 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 benet 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 dened as having a clinical history of snoring, clinical complaint of excessive daytime sleepiness, and an AHI <15 on original clinical evaluation, and more than ve arousals per hour associated with snores, snorts, or brief cessations of breathing that were shorter than accepted criteria for apnea (<10 sec), without specic mention of arousals related to increased respiratory efforts, which is an essential feature of UARS [93]. The subjects 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
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mass index of 297.4 kg/m2). Signicant 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 signicantly lower on the treatment nights (7.1% 0.7%) compared with placebo nights (8.6% 0.8%, P 0.03). Although this nding 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 eect 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 ve 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, humidication may increase tolerance of positive airway pressure therapy within the critical rst 3 months of therapy. Heated humidication may attenuate the mucosal blood ux associated with the cooling and drying eects 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 insufcient data [76]. Studies have been awed [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 quantication of associated
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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 difcult 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 benet 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 identied 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 benet most from correction of nasal obstruction as a sole intervention may be those with the mildest forms of sleep-disordered breathing without other signicant 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
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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 ecacious rst-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 nding conrms 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 eective treatment, if it is available. The Muller 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 ndings 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: abdlv@ha.org.hk 0030-6665/03/$ - see front matter 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00176-7
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and cine MRI are ideal but not practicable methods in terms of costs, the difculties in the overnight study of a patient with OSAS in a conned space, and the problems of irradiation in CT. Through-the-night inspection of the upper airway of the sleeping patient with the beroptic nasopharyngeal endoscope is an ideal but time- and manpower-consuming technique. It is seldom well tolerated and often results in signicantly disturbing the normal and abnormal sleep patterns. The surgeon naturally prefers to see the actual events during sleep-breathing difculties 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 nights 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 decits, 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 dierent 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 eectively the diagnosed sites of obstruction. Many medium- and long-term failures of surgical treatment lie in the fundamental design of the surgical procedure. The stiness 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
V.J. Abdullah et al / Otolaryngol Clin N Am 36 (2003) 461471 Table 1 Surgical procedures performed for dierent sites of obstructiona Nasal obstruction Septoplasty Turbinoplasty Functional endoscopic sinus surgery (FESS) for nasal polyposis
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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 op One-thirdOne-half laser epiglottic trim All procedures performed at the Prince of Wales Hospital, Chinese University of Hong Kong.
a
a simple tracheostomy can be oered. 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 ecient and cost-eective 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 exible nasopharyngoscopy with the patient awake is performed to exclude static obstructive lesion. A Muller maneuver is performed for correlation. Four milligrams of midazolam are given as an induction bolus with saline ush. The light is dimmed, and the patient is encouraged to sleep. The dose is increased 1 mg at a time with saline ush until the patient sleeps. A minimal 5-minute wait is recommended after the rst bolus and between increments. Increments are needed only if the patient
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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) exible 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 umazenil (Anexate) intravenously (300 500 lg). It is important to be aware that the mean elimination half-life of umazenil, 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 dicult 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 benet 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 ndings 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 9) with single-site snoring had the snore generated by the soft palate, and 54% (n 7) of the two-site snorers had soft palate plus epiglottic snores. Epiglottic and tonsillar
V.J. Abdullah et al / Otolaryngol Clin N Am 36 (2003) 461471 Table 2 Summary of snore-generation sites by VSE recordings in 30 snorers Snore-generation sites Soft palate Tonsils Tongue base Posterior pharyngeal wall Epiglottis No. of patients 26 12 4 2 12
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Percentage of total 87% 40% 13% 6.5% 40%
vibrations seem to feature signicantly in snore generation. In the authors experience with VSE in patients with OSAS, epiglottic utter commonly is seen as the main source of the loud wake-up snore after the obstructive cycle. These ndings 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 umazenil 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 stagecorrelated 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 Single site Two sites Three sites Four sites Five sites No. of patients 12 13 3 1 1 Percentage of total 40% 44% 10% 3% 3%
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Table 4 The dierent combinations of snore-generation sites in 30 patients studied with the use of VSE recordings Single site SP 9 T3 Two sites SP+T 3 SP+E 7 T+PP 1 SP+TB 1 SP+E 1 Three sites SP+T+TB 1 SP+T+E 2 Four sites SP+T+TB+E 1 Five sites 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, 1589) selected for surgical assessment, the levels of obstruction and their dierent 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 ndings, 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 decits 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 reect 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 ndings regarding single/multiple-site obstruction in patients with OSAS selected for surgery No. of obstructive sites Single site Two obstructive sites Three obstructive sites Four obstructive sites Five obstructive sites Six obstructive sites No. of patients 13 16 17 20 12 11 Percentages of total 14.61% 17.98% 19.10% 22.47% 13.48% 12.36% Mean BMI 23.8 25.5 24.4 28.3 25.4 27.2
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acceptable pressures, although they may be the best candidates for surgery. The dierent obstructive sites and their combinations are listed in Table 6. As is evident from these ndings, 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 dicult to treat or to treat with any sustained eect. 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 eect of higher-level obstruction. The authors Muller maneuvers correlated poorly with the VSE ndings. The dierent 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 ne-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 exible 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.
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Table 6 The obstructive sites for surgical assessment and the dierent site combinations as seen in VSE for 89 patients
Obstruction sites involved (total, 302) Site No.
Percentage
I II III IV V VI
Palate Lateral pharynx Tonsil Tongue base Epiglottis Hypopharynx
69 64 41 62 37 29
22.8% 21.2% 13.6% 20.5% 12.3% 9.6%
100% No. Percentage Site I+IV I+IV+V I+IV+VI I+IV+V+VI 1.12% 0 0 0 0 0 1 0 0 5 1 0 0 5.62% 1.12% No. Percentage Site No. Percentage I+V 1 I+VI 0 I+V+VI 0 1.12%
Site combinations, number of patients, and percentages Site No. Percentage Site 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
4 4 6 5 1
4.49% 4.49% 6.74% 5.62% 1.12%
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
7 2 2 4 3 0 3 4
7.87% 2.25% 2.25% 4.49% 3.37%
3.37% 4.49%
5 11
5.62% 12.3%
II 1.12% 2.25% II+V II+VI II+V+VI 0 0 0
2.25% 1.12%
Lateral pharynx II+III II+III+IV II+III+V II+III+VI II+III+IV+V II+III+IV+VI II+IV II+IV+V II+IV+VI II+V+VI II+IV+V+VI 0 1 2 0 0 III+V III+VI III+V+VI 1 0 0 1.12%
2 1 0 0 0 1 0
1.12%
III
Tonsil III+IV III+IV+V III+IV+VI III+IV+V+VI IV+VI 0
1 1 0 0 0
1.12% 1.12%
IV
Tongue base IV+V IV+V+VI
4 3 1
4.49% 3.37% 1.12%
Epiglottis V+VI
2 0
2.25%
VI
Hypopharynx
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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 designthe 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 nonrapid-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
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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 reecting 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;96:7034. [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;141:9858. [3] Sher AE, Thorpy MJ, Spielman AJ, Burack B, Mcgregor PA. Predictive value of Muller manoeuvre in selection of patients for uvulopalatopharyngoplasty. Laryngoscope 1985; 95:14837. [4] Pringle MB, Croft CB. A comparison of sleep nasendoscopy and the muller manoeuvre. Clin Otolaryngol 1991;16:55962. [5] Croft CB, Pringle M. Sleep nasendoscopy: a technique of assessment in snoring and obstructive sleep apnoea. Clin Otolaryngol 1991;16:5049. [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;89:92334. [7] Fujita S. UPPP for sleep apnoea and snoring. Ear Nose Throat J 1984;63:7386. [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;15:20916. [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;21:4859. [10] Roblin G, Williams AR, Whittet H. Target-controlled infusion in sleep endoscopy. Laryngoscope 2001;111:1756. [11] Camilleri AE, Ramamurthy L, Jones PH. Sleep nasendoscopy: what benet to the management of snorers? J Laryngol Otol 1995;109:11636. [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; 45:25060.
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, beroptic 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-specic approach. Numerous surgical procedures have been developed to address each of these sites of obstruction and have oered 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: rjtroell@aol.com 0030-6665/03/$ - see front matter 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00177-9
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R.J. Troell / Otolaryngol Clin N Am 36 (2003) 473493
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 elds of cardiology, neurology, oncology, and urology [14]. Temperature-controlled RF delivers RF at 460 kHz by a high-frequency alternating current ow 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 rst 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-dened lesion after 24 hours, with an acute inammatory response and edematous response. Collagen deposition begins approximately 12 days after injury, and at 3 weeks, chronic inammation, brosis, and tissue volume reduction from scar contracture occur. The rst 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.
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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 efcacy reported in the previous animal study were conrmed 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 aecting lesion size.
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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 condent patient-physician relationship. The extent of surgery is mediated by the patients 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 identies areas of airway collapse or obstruction, logically directing surgical treatment to these site-specic areas.
Presurgical evaluation Although the etiology of sleep-disordered breathing is still poorly understood, it is clear that there exist specic 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 dene the exact area of obstruction. There are numerous radiologic tests available to aid in determining the suspected sites of obstruction preoperatively. The authors presurgical evaluation includes a nocturnal polysomnography, a comprehensive head-and-neck physical examination, beroptic nasopharyngoscopy with the Muller maneuver, and a lateral cephalometric radiograph.
Classication of disease severity The understanding of the classication of sleep-disordered breathing is important in communicating with other health professionals. Primary snoring An apnea-hypopnea index (AHI) of less than ve 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.
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Upper airway resistance syndrome An AHI of less than ve 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 ve 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 ow, 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 signicant 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 rst phase of airway reconstruction to allow
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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 signicant 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
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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 efcacy 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 17) compared with the
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VAS subjective patient improvement of nasal patency of 48%. Tolerance to nasal CPAP improved by 28.9% (VAS, 4.96.3) compared with the placebo group (n 5) who decreased CPAP use by 10.4% (VAS, 4.43.3). Inferior turbinate radiofrequency side eects The post-treatment ndings 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 eects, 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 modied by Fujita et al [7,14] and Simmons et al [15]. Unfortunately, the procedure usually is performed under general anesthesia, produces signicant 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.
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Soft palatal reduction procedures 1. Uvulopalatopharyngoplasty 2. Laser-assisted uvulopalatoplasty 3. Uvulopalatal ap 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 syndromethis neurocognitive dysfunction may be conrmed 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 ap (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
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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 eectively. 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 diuses 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 nontemperature-controlled RF.
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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 reection 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-inammatory 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-inammatory properties to relieve swelling. Patients who have a prominent gag reex may benet 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 identied 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 satised with the procedure and would repeat it if necessary.
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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 efcacy 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 nal 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, signicant 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
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procedure. Most subjects experience restless sleep on the rst 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 signicantly 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 als 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 supercial mucosal injuries, when the mucosa is disturbed, patients experience increased discomfort. Palatal stulas 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 signicant 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 insuciency, 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 inuencing hypopharyngeal obstruction 1. Morbid obesity (body mass index >31 kg/m2) 2. Mandibular skeletal deciency (sella-nasion-supramentale (SNB) <76 )
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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
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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 modied 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 patients 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 dierent 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 supercial 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 supercial 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 supercial 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 signicant
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tongue swelling, dysphagia, or postoperative pain. Documenting the specic 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 uid 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 signicantly 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 oor-of-mouth and tongue swelling, which may encroach on the airway. Nonsteroidal anti-inammatory 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 antiinammatory properties to relieve swelling. Occasionally, narcotic analgesia is necessary. Patients with a prominent gag reex who are undergoing the procedure under local anesthesia may benet 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 rst 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 rst human tongue pilot study [23] investigated the feasibility, safety, and possible efcacy 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,
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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 airow. 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 nal patient received only the initial 4000 J of RF energy. Five of these patients were treated successfully, dened 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-ve (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
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RF energy delivery, especially when performed with other upper airway reconstructive procedures. The potential complications are listed below. Tongue-base radiofrequency complications 1. Supercial ulcer formation 2. Infection or cellulitis 3. Tongue abscess 4. Hypoglossal nerve injury 5. Tongue or oor-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 denitive 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 ndings may reveal a normal-appearing tongue or only mild swelling. Needle aspiration, ultrasound scanning, or computer tomography scanning may be required to conrm 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 supercial ulceration; (7) checking the curvature of the tongue base to prevent the electrode tip from being placed close to the supercial 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 supercial 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 signicant post-treatment
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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 rst two post-treatment days, and (4) follow the treatment techniques to limit the risk of infection. In the authors 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 specic role of tongue-base RF in sleep-disordered breathing has not been established. The ecacy of this procedure when performed simultaneously with other hypopharyngeal reconstructive procedures has not been studied. The eect of saline inltration 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 ecacy and side eects of tongue-base RF. Tongue-base radiofrequency: conclusions Tongue-base RF seems to oer 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
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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 dened 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 eective, 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 oers 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 specic 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;6:207. [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;324:160511. [3] LeVeen H, Wapnick S, Piccone V, et al. Tumor eradication by radiofrequency therapy: response in 21 patients. JAMA 1976;253:2198200. [4] Sweet W, Wepsic J. Controlled thermocoagulation of trigeminal ganglion and rootlets for differential destruction of pain bers: I. Trigeminal neuralgia. J Neurosurg 1974;3:14356. [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;111:134855. [6] Powell NB, Riley RW, Troell RJ, et al. Radiofrequency volumetric tissue reduction of the palate in subjects with sleep-disordered breathing. Chest 1998;113:116374.
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[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;89:92330. [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;119:56973. [9] Utley DS, Goode RL, Hakim I. Radiofrequency energy tissue ablation for the treatment of nasal obstruction secondary to turbinate hypertrophy. Laryngoscope 1999;109:6836. [10] Smith TL, Correa AJ, Kuo T, et al. Radiofrequency tissue ablation of the inferior turbinate using a thermocouple feedback electrode. Laryngoscope 1999;109:17605. [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 OtolaryngologyHead 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;111:1538. [13] Ikematsu T. Study of snoring: fourth report. Ther J Jpn Otol Rhinol Laryngol Soc 1968; 4:4345. [14] Fujita S, Conway WA, Zorick F, et al. Evaluation of the effectiveness of uvulopalatopharyngoplasty. Laryngoscope 1985;95:704. [15] Simmons FB, Guilleminault C, Miles L. The palatopharyngoplasty operation for snoring and sleep apnea: an interim report. Otolaryngol Head Neck Surg 1984;4:3757. [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; 122:4104. [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;125:3128. [18] Emery BE, Flexon PB. Radiofrequency volumetric tissue reduction of the soft palate: a new treatment for snoring. Laryngoscope 2000;110:10928. [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;127:11138. [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;122:38794. [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;122:4029. [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. 175184. [23] Powell NB, Riley RW, Guilleminault C. Radiofrequency tongue base reduction in sleepdisordered breathing: a pilot study. Otolaryngol Head Neck Surg 1999;120:65664. [24] Li KK, Powell NB, Riley RW, et al. Radiofrequency tongue base reduction: long-term outcomes. Presented at American Academy of OtolaryngologyHead 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;80:6404. [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;125:30311.
Laser-assisted uvulopalatoplasty revisited

Yosef P. Krespi, MDa,*, Ashutosh Kacker, MDb
a
Department of Otolaryngology/Head and Neck Surgery, St. LukesRoosevelt 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 aects approximately 50% of men and 30% of women. It is estimated that approximately 50% of those aected are habitual snorers (Table 1). Uvulopalatopharyngoplasty (UPPP) was rst introduced by Ilkematsu in 1964 and was later modied by Fujita et al [1] as a surgical treatment for the management of snoring. The application of oce-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 ecacy. 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 [48]. 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: hnsg@aol.com (Y.P. Krespi). 0030-6665/03/$ - see front matter 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(03)00016-1
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Table 1 Grading system of snoring Grade Grade I Grade II Grade III Snoring Occasional Frequent Always (associated with OSA) Characteristics 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 beroptic examination, as a Mullers 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 prole all snoring events into ve 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 signicant 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 48 dB Majority >85 >8 dB
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Absolute contraindications for LAUP include severe sleep apnea, uncontrolled hypertension, severe trismus, cleft palate, velopharyngeal insuciency, 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 eect. 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) ash 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 sh-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 ash 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
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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 eect 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 eective method for treating patients with loud, habitual snoring. Performed as an oce 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 benet 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 [1315]. The reduction of the palate tissues can be performed in a precise, minimally invasive manner. The procedure creates nely controlled zones of coagulation at precise locations beneath the tissue in the upper airway.
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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-utter snoring in habitual snorers [16]. Injection snoreplasty is a simple, safe, and effective ofce 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;89:92334. [2] Kamami YV. Outpatient treatment of sleep apnea syndrome with CO2 laser: laser-assisted UPPP. J Otolaryngol 1994;23:3958. [3] Kamami YV. Outpatient treatment of snoring with CO2 laser: laser-assisted UPPP. J Otolaryngol 1994;23:3914. [4] Krespi YP, Pearlman SJ, Keidar A. Laser-assisted uvula-palatoplasty for snoring. J Otolaryngol 1994;23:32834. [5] Sharp HR, Mitchell DB. Long-term results of laser-assisted uvulopalatoplasty for snoring. J Laryngol Otol 2001;115:897900. [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;30:2125. [7] Neruntarat C. Laser-assisted uvulopalatoplasty: short-term and long-term results. Otolaryngol Head Neck Surg 2001;124:903. [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;25:30510. [9] Ryan CF, Love LL. Unpredictable results of laser assisted uvulopalatoplasty in the treatment of obstructive sleep apnoea. Thorax 2000;55:399404. [10] Lauretano AM, Khosla RK, Richardson G, Matheson J, Weiss JW, Graham C, et al. Efcacy of laser-assisted uvulopalatoplasty. Lasers Surg Med 1997;21:10916. [11] Weingarten CZ, Raviv G. Evaluation of criteria for uvulopalatoplasty (UPP) patient selection using acoustic analysis of oronasal respiration (SNAP testing). J Otolaryngol 1995;24:3527.
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[12] Walker RP, Gopalsami C. Laser-assisted uvulopalatoplasty: postoperative complications. Laryngoscope 1996;106:8348. [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;126:6773. [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: 4029. [15] Flexon FB. Somnoplasty: a treatment for snoring. In: Krause JH, Mirante JP, Christmas DA, editors. Ofce-based surgery in otolaryngology. Philadelphia: WB Saunders; 1999. p. 7986. [16] Brietzke SE, Mair EA. Injection snoreplasty: how to treat snoring without all the pain and expense. Otolaryngol Head Neck Surg 2001;124:50310.
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 OtolaryngologyHead 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 airow mechanics during sleep in patients with OSA and the feasibility of this intervention for the treatment of this disorder.
* Corresponding author. E-mail address: deisele@orca.ucsf.edu (D.W. Eisele). 0030-6665/03/$ - see front matter 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00178-0
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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 eect of the selective stimulation of the genioglossus muscle on upper airway airow 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 conrmation 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 airow 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 signicant apnea-hypopnea indices. Neuromuscular stimulation of the genioglossus muscle resulted in an improvement in inspiratory airow 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 conrmed 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.
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Fig. 1. Mean maximal inspiratory airow (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;81:64352; with permission.)
Selective direct hypoglossal nerve stimulation Another investigation was undertaken to determine the eect 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 airow before, during, and after stimulation was measured during sleep with standard polysomnographic techniques. Lack of arousal from sleep was conrmed 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 airow during stimulation, compared
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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 conrmed 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 airow (VI max) in ve 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;123:5761; with permission.)
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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]. Briey, 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 conrmed 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 ush 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, supercial 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
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Fig. 4. Half-cu 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: 5965; 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 ecacy 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 (nonREM) and REM sleep underwent implantation of the system. Nightly unilateral hypoglossal nerve stimulation was initiated at 4 weeks after system
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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;11:5965; 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. Specically, 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 signicantly. 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
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Fig. 6. Implantable pulse generator placement in an infraclavicular pocket supercial 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;11:5965; 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 benet 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.
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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;127:121623; with permission.)
Further studies are necessary to optimize patient-selection criteria for therapeutic hypoglossal nerve stimulation. Patient selection may be based on baseline dierences 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 eect 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.
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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 airow 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 renements 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;44:9318. [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;140:12859. [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;146:10306. [4] Guilleminault C, Powell N, Bowman B, Stoohs R. The effects of electrical stimulation on obstructive sleep apnea syndrome. Chest 1995;107:6773. [5] Oliven A, Schnall RP, Pillar G, et al. Sublingual electrical stimulation of the tongue during wakefulness and sleep. Respir Physiol 2001;127:21726. [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;78:19506. [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;76:27381. [8] Decker MJ, Haaga J, Arnold JL, et al. Functional electrical stimulation and respiration during sleep. J Appl Physiol 1993;75:105361. [9] Fairbanks DW, Fairbanks DNF. Neurostimulation for obstructive sleep apnea: investigations. Ear Nose Throat J 1993;72:527. [10] Schwartz AR, Eisele DW, Hari A, et al. Electrical stimulation of the lingual musculature in obstructive sleep apnea. J Appl Physiol 1996;81:64352. [11] Eisele DW, Smith PL, Alam DS, Schwartz AR. Direct hypoglossal nerve stimulation in obstructive sleep apnea. Arch Otolarygol Head Neck Surg 1997;123:5761. [12] Goding GS, Eisele DW, Testerman R, et al. Relief of upper airway obstruction with hypoglossal nerve stimulation in the canine. Laryngoscope 1998;108:1629. [13] Eisele DW, Schwartz AR, Smith PL. Electrical stimulation of the upper airway for obstructive sleep apnea. Op Tech Otolaryngol Head Neck Surg 2000;11:5965. [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: 121623.
The limitations of isolated palatal surgery for patients with obstructive sleep apnea
Marc G. Dubin, MD, Brent A. Senior, MD*
Department of OtolaryngologyHead 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 eects. 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 eective at normalizing polysomnographic variables, it is associated with low compliance rates (60%80%) [49], and 15% of patients refuse CPAP after a single nights 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), rst described in 1981 by Fujita et al [12], continues to be the mainstay. Since its introduction, there has been considerable effort expended studying the efcacy 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 conrmed 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: bsenior@med.unc.edu (B.A. Senior). 0030-6665/03/$ - see front matter 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00179-2
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approximately half of the cases of OSA when success is dened as a drop in the AHI by 50%. When more stringent criteria are usedabsolute decline in the apnea index to less than 10 or an AHI less than 20the 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 signicantly 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 denitions of success [1416]. 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 benet 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 identication 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 [1719]. 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 signicant 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 reex 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 dicult 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 identication of the exact sites of collapse should aid the surgeon in procedure selection, thereby improving success rates. In
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most patients, however, it is dicult 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 beroptic airway endoscopy with the Muller maneuver and cephalometrics, among others. The role of cephalometrics in predicting the site of anatomic obstruction has led to contradictory data [2226], which is not surprising given the fact that these static measurements of bony and soft tissue anatomy most likely do not reect 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 identied by these methods [27]. Methods that would identify distal sites of collapse will aid in predicting which patients actually will benet 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, somnouoroscopy, several authors have attempted to radiographically localize the site of obstruction during sleep [27,30,31]. In one study, patients who had closure identied 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, Mullers 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 difcult 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 Mullers 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 diculty 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
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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 diculty in precisely determining the anatomic site of obstruction in patients with OSA leads to challenges in predicting which patients will benet 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 benet 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 dened 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 [4143]. 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 (ve patients), seroma (three patients), arrhythmia (four patients), and unstable angina (one patient) [44]. In this same review, signicant preoperative comorbidities also were described and included hypertension (31%), arrhythmia (5.5%), coronary artery disease
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(3.3%), pulmonary disease (7.7%), reux esophagitis (4.4%), and depression (10%) [44]. In one limited prospective study, it was shown that patients continue to demonstrate a signicant 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;92:6317. [3] Braver H, Block A, Perri M. Treatment for snoring: combined weight loss, sleeping on side, and nasal spray. Chest 1995;107:12838. [4] Engleman H, Martin S, Douglas J. Compliance with CPAP therapy in patients with sleep apnoea/hypopnea syndrome. Thorax 1994;49:2636. [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;147:88795. [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;159:110814. [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; 107:37581. [8] Reeves-Hoche M, Meck R, Zwillich C. Nasal CPAP: an objective evaluation of patient compliance. Am J Respir Crit Care Med 1994;149:14954. [9] Pirsig W. Obstructive sleep apnea. In: McCaffrey T, editor. Rhinologic diagnosis and treatment. Stuttgart: Theime; 1997. p. 22969. [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:426. [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;97:338. [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;89:92334. [13] Sher A, Schectman K, Piccirillo J. The efcacy of surgical modications of the upper airway in adults with obstructive sleep apnea syndrome. Sleep 1995;19:15677. [14] Hochban W, Brandenburg U, Peter J. Surgical treatment of obstructive sleep apnea by maxillomandibular advancement. Sleep 1994;17:6249. [15] Riley R, Powell N, Guilleminault C. Obstructive sleep apnea syndrome: a review of 306 consecutively treated surgical patients. Otolaryngol Head Neck Surg 1993;108:11725. [16] Riley R, Powell N, Guilleminault C. Obstructive sleep apnea and the hyoid: a revised surgical procedure. Otolaryngol Head Neck Surg 1994;111:71721.
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[17] Guilleminault C, Hayes B, Smith L, et al. Palatopharyngoplasty and obstructive sleep apnea syndrome. Bull Euro Physiopathol Respir 1983;19:5959. [18] Hoffstein V. How and why should we stabilize the upper airway? Sleep 1996;19:S5760. [19] Simmons F, Guilleminault C, Silvestri R. Snoring and some obstructive sleep apnea can be cured by oropharyngeal surgery-palopharyngoplasty. Arch Otolaryngol 1983;109:5037. [20] Wetmore S, Scrima L, Snyderman N, et al. Postoperative evaluation of sleep apnea after uvulopalatopharyngoplasty. Laryngoscope 1986;96:73841. [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;92:12731. [22] Doghramji K, Jabourian Z, Pilla M, et al. Predictors for uvulopalatopharyngoplasty. Laryngoscope 1995;105:3114. [23] Gislason T, Lindholm C, Almqvist M. Uvulopalatopharyngoplasty in the sleep apnea syndrome: predictors of results. Arch Otolaryngol Head Neck Surg 1985;114:4551. [24] Riley R, Guilleminault C, Powell N, et al. Palatopharyngoplasty failure: cephalometric roentgenograms and obstructive sleep apnea. Otolaryngol Head Neck Surg 1985;93:2404. [25] Ryan C, Dickson R, Blokmanis A, et al. Upper airway measurements predict response to uvulopalatopharyngoplasty in obstructive sleep apnea. Laryngoscope 1990;100:24853. [26] Yao M, Utley D, Terris D. Cephalometric parameters after multilevel pharyngeal surgery for patients with obstructive sleep apnea. Laryngscope 1998;108:78995. [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;147:1829. [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;140:7116. [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;143:9426. [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;101:11028. [31] Katsantonis G, Walsh J. Somnouoroscopy: its role in the selection of candidates for uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg 1986;94:5660. [32] DeBerry-Borowiecki B, Kukwa A, Blanks R. Indications for palatopharyngoplasty. Arch Otolaryngol 1985;111:65963. [33] Sher A, Thorpy M, Shprintzen R, et al. Predictive value of Muller maneuver in selection of patients for uvulopalatopharyngoplasty. Laryngoscope 1985;95:14837. [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; 107:94651. [35] Katsantonis G, Mass C, Walsh J. The predictive efcacy of the muller maneuver in uvulopalatopharyngoplasty. Laryngoscope 1989;99:67780. [36] Li K, Riley R, Powell N, et al. Obstructive sleep apnea surgery: patient perspective and polysomnographic results. Otolaryngol Head Neck Surg 2000;123:5725. [37] Johnson N, Chinn J. Uvulopalatopharyngoplasty and inferior sagittal mandibular osteotomy with genioglossus advancement for treatment of obstructive sleep apnea. Chest 1994; 105:27883. [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;145:52732. [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;104:13628. [40] Senior B, Rosenthal L, Lumley A, et al. Efcacy of uvulopalatopharyngoplasty in unselected patients with mild obstructive sleep apnea. Otolaryngol Head Neck Surg 2000; 123:17982.
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[41] Fairbanks D. Uvulopalatopharyngoplasty complication and avoidance strategies. Otolaryngol Head Neck Surg 1990;102:23945. [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; 8:113942. [43] Simmons F, Guilleminault C, Dement W, et al. Surgical management of airway obstruction during sleep. Laryngoscope 1977;87:32638. [44] Riley R, Powell N, Guilleminault C, et al. Obstructive sleep apnea surgery: risk management and complications. Otolaryngol Head Neck Surg 1997;117:64852. [45] Burgess L, Derderian S, Morin G, et al. Postoperative risk following uvulopalatopharyngoplasty for obstructive sleep apnea syndrome. Otolaryngol Head Neck Surg 1992; 106:816.
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 dened 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 dened 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, conrming that daytime sleepiness in children with OSAS is the exception, not the rule [6]. Instead of being sleepy, the child may have nonspecic behavioral difculties 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-decit disorder. In an eort to clarify the relationship between poor sleep quality and daytime functioning, Gozal [7] evaluated a cohort of poorly performing children in the rst grade. In this prospective study, 297 rst graders who were in the lowest tenth percentile of their class were screened for OSAS
* Pediatric OtolaryngologyHead and Neck Surgery, Lucile Packard Childrens Hospital at Stanford, 725 Welch Road, Palo Alto, CA 94304-5654, USA. E-mail address: amessner@stanfordmed.org 0030-6665/03/$ - see front matter 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00180-9
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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 groups 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 ndings 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 eort (nasal aring 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 rst-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 conrmed the familial incidence of 21% of rstdegree 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 rst-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 signicant obstructive sleep disorder in a pediatric patient can be dicult. The most
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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 airow, respiratory eort, 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 eective 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 rst-night eect, that is, a change in a patients sleep architecture due to unfamiliar surroundings, has been postulated. It seems that the rst-night eect is rarely signicant. 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 signicantly 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 nding 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 specic 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
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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 difcult 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 signicant 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 rst 24 hours after surgery was similar in both groups. Follow-up of the children, however, revealed a signicantly 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 eort 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 tonsillectomya partial tonsillectomyusing 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 signicantly less pain than the total tonsillectomy group, the two groups were not equivalent; the intracapsular tonsillectomy group was signicantly 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
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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 rst, 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 signicantly 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 signicantly longer with the HS, and pain scores trended lower on postoperative days 2, 3, and 4 but were not statistically signicant. 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 signicantly 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 signicantly 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 nding 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
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OtolaryngologyHead and Neck Surgery and found a signicant 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 signicant 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 signicant 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 1220) had the highest signicant 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 eort 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 childs 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 rst 24 hours after tonsillectomy surgery. In an eort to reduce the postoperative pain, a single dose of dexamethasone can be given intraoperatively to decrease vomiting, improve oral intake, and decrease postoperative pain [3133]. 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 signicantly higher percentage of a normal diet on the rst 6 postoperative days, with no difference in pain scores between the treatment groups [34]. Postoperatively, a telephone call
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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 uticasone was found to decrease the apnea-hypopnea index from an average of 10.7 to 5.8 in a small group of subjects (n 13) [36]. This nding 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 signicant 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 diculties 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 318) 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 eect 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 childs sleep disturbance, physical symptoms, emotional symptoms, daytime activity, and caregiver concerns. The OSD-6 specically 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]. Specically, 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.)
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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 difculties 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 signicantly improved after T&A, and only 8% of children scored in the abnormal range postoperatively.
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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 conrmed 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 conrming 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, 636 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 conrm the signicant benet gained after a child undergoes a T&A. References
[1] Rosen CL. Obstructive sleep apnea syndrome (OSAS) in children: diagnostic challenges. Sleep 1996;19:S27477. [2] American Thoracic Society. Standards and indications for cardiopulmonary sleep studies in children. Am J Respir Crit Care Med 1996;153:86678. [3] Guilleminault C, Pelayo R, Clerk A, et al. Recognition of sleep-disordered breathing in children. Pediatrics 1996;98:87182. [4] Downey R 3d, Perkin RM, MacQuarrie J. Upper airway resistance syndrome: sick, symptomatic but underrecognized. Sleep 1993;16:6203. [5] American Sleep Disorders Association. International classication of sleep disorders, revised: diagnostic and coding manual. Rochester (MN): American Sleep Disorders Association; 1997. p. 1957. [6] Gozal D, Wang M, Pope DW Jr. Objective sleepiness measures in pediatric obstructive sleep apnea. Pediatrics 2001;108:6937. [7] Gozal D. Sleep-disordered breathing and school performance in children. Pediatrics 1998;102:61620. [8] Gozal D, Pope DW Jr. Snoring during early childhood and academic performance at ages thirteen to fourteen years. Pediatrics 2001;107:13949. [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;102:117884. [10] Fernandes do Prado LB, Li X, Thompson R, et al. Body position and obstructive sleep apnea in children. Sleep 2002;25:6671. [11] Ovchinsky A, Rao M, Lotwin I, et al. The familial aggregation of pediatric obstructive sleep apnea syndrome. Arch Otol Head Neck Surg 2002;128:8158.
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[12] Phillips B, Cook Y, Schmitt F. Sleep apnea: prevalence of risk factors in a general population. South Med J 1989;82:10902. [13] Redline S, Tishler PV, Tosteson TD, et al. The familial aggregation of obstructive sleep apnea. Am J Respir Crit Care Med 1995;151:6827. [14] Douglas NJ, Luke M, Mathur R. Is the sleep apnoea/hypopnoea syndrome inherited? Thorax 1993;48:71921. [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;140:58994. [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;125:3536. [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;109:70412. [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;118:3605. [20] Nunez DA, Provan J, Crawford M. Postoperative tonsillectomy pain in pediatric patients: electrocautery (hot) vs. cold dissection and snare tonsillectomya randomized trial. Arch Otol Head Neck Surg 2000;126:83741. [21] Koltai PJ, Solares CA, Mascha EJ, et al. Intracapsular partial tonsillectomy for tonsillar hypertrophy in children. Laryngoscope 2002;112:179. [22] Walker RA, Syed ZA. Harmonic scalpel tonsillectomy versus electrocautery tonsillectomy: a comparative pilot study. Otolaryngol Head Neck Surg 2001;125:44955. [23] Wiatrak BJ, Willging JP. Harmonic scalpel for tonsillectomy. Laryngoscope 2002;112: 146. [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;128:6726. [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;111:21669. [26] Strong EB, Rubinstein B, Senders CW. Pathologic analysis of routine tonsillectomy and adenoidectomy specimens. Otolaryngol Head Neck Surg 2001;125:4737. [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;58:1138. [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;126:14447. [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;127:12715. [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;44:11523. [31] Steward DL, Welge JA, Myer CM. Do steroids reduce morbidity of tonsillectomy? Metaanalysis of randomized trials. Laryngoscope 2001;111:17128. [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;126:30715.
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[34] Moir MS, Bair E, Shinnick P, et al. Acetaminophen versus acetaminophen with codeine after pediatric tonsillectomy. Laryngoscope 2000;220:18247. [35] Rosbe KW, Jones D, Jalisi S, et al. Efcacy of postoperative follow-up telephone calls for patients who underwent adenotonsillectomy. Arch Otolaryngol Head Neck Surg 2000; 126:71821. [36] Brouillette RT, Manoukian JJ, Ducharme FM, et al. Efcacy of uticasone nasal spray for pediatric obstructive sleep apnea. J Pediatr 2001;138:83844. [37] Friedman O, Chidekel A, Lawless ST, et al. Postoperative bilevel positive airway pressure ventilation after tonsillectomy and adenoidectomy in childrena preliminary report. Int J Pediatr Otorhinolaryngol 1999;51:17780. [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;41:1639. [39] Cohen SR, Simms C, Burstein FD, et al. Alternatives to tracheostomy in infants and children with obstructive sleep apnea. J Pediatr Surg 1999;34:1826. [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;119:47685. [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;126:14239. [42] Franco RA, Rosenfeld RM, Rao M. Quality of life for children with obstructive sleep apnea. Otolaryngol Head Neck Surg 2000;123:916. [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; 128:48996. [44] Goldstein NA, Post JC, Rosenfeld RM, et al. Impact of tonsillectomy and adenoidectomy on child behavior. Arch Otolaryngol Head Neck Surg 2000;126:4948. [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;128:7705. [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;153:337.
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 aicted 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 dierences 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 rst 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 [24]. 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: rwalke2@lumc.edu 0030-6665/03/$ - see front matter 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00181-0
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R.P. Walker / Otolaryngol Clin N Am 36 (2003) 531538
[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 dened as an apnea-hypopnea score of ve 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 dene a diagnosis of sleep apnea syndrome was an apnea-hypopnea score of ve 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 dierences 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 ndings of Young et al do not support this hypothesis, however. For both men and women, the signicant 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
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Papers, is difcult 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 patients focus is usually on the snoring sound he or she produces and the disruption of his or her bed partners sleep. Men are brought in by their wives to be xed, whereas women often present without prompting because of their embarrassment about their snoring. It is the physicians 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 reux; and (4) daytime stimulant use, for example, caeine 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 specic to women includes pregnancy status and the use of hormonereplacement therapy (HRT). Most female patients diagnosed with OSAS are postmenopausal [1115]. 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 signicantly 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 Turners syndrome and polycystic ovary syndrome in whom hormonal status is altered. Turners 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].
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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 exible 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 dicult 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 signicantly higher BMI when compared with the male patients at presentation [10]. The BMI versus RDI was evaluated to determine whether gender modied 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 ndings 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 signicantly 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 patients BMI is used to determine his or her weight status (Table 1). Another term often used, morbid obesity, is dened 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 signicantly 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-classication system Category Underweight Healthy weight Overweight Obesity (class 1) Obesity (class 2) Severe obesity (class 3) BMI (kg/m2) Less than 18.5 18.524.9 25.029.9 30.034.9 35.039.9 40 or more
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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 dierences in the physical examination is critical when determining a treatment plan for patients with OSAS. Recent research has identied the following trends in physical dierences between men and women with OSAS: 1. 2. 3. 4. Women have a signicantly 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 ndings 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 signicant. Mohsenin [26] reported polysomnographic ndings 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. OConnor 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) nonpositional-related obstructive sleep apnea, and (3) rapid-eye-movementrelated apnea. Women were found to have rapid-eye-movementrelated 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 ndings 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-movementrelated 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 signicantly in surgical publications. Another
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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 als 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 specically, but the individual raw data were presented. Seven of the 36 patients were female. The authors 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 Ahujas series demonstrates a nonsignicant decrease in the RDI (P 0.2834) and an increase in the lowest oxygen saturation (P 0.3830) after LAUP treatment for OSAS. In general, a successful surgical outcome is dened as a postoperative RDI of 10 or less. Of these patients, 43% had an RDI of 10 or less after treatment. In the authors series of 16 female patients, a signicant decrease in the RDI (P 0.0042) and a nonsignicant increase in the lowest oxygen saturation (P 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 reect LAUP procedure results; results from other palatal surgery, specically uvulopalatopharyngoplasty, are not available. Based on these early ndings, 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 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 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.
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Acknowledgments The author thanks Dr. Chellam Gopalsami and Lisa Harrison for their assistance in preparing this manuscript. References
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[24] Kapsimalis F, Kryger M. Gender and obstructive sleep apnea syndrome, part 1: clinical features. Sleep 2002;25:4129. [25] Brooks LJ, Strohl KP. Size and mechanical properties of the pharynx of healthy men and women. Am Rev Respir Dis 1992;146:13947. [26] Mohsenin V. Gender differences in the expression of sleep-disordered breathingrole of upper airway dimensions. Chest 2001;120:14427. [27] Leech J, Onal E, Dulberg C, et al. A comparison of men and women with occlusive sleep apnea syndrome. Chest 1988;94:9837. [28] OConnor C, Thornley K, Kanly P. Gender differences in the polysomnographic features of obstructive sleep apnea. Am J Respir Crit Care Med 2000;161:146572. [29] Mickelson S, Ahuja A. Short-term objective and long-term subjective results of laserassisted uvulopalatoplasty for obstructive sleep apnea. Laryngoscope 1999;109:3627. [30] Millman R, Carlisle C, Rosenberg C, et al. Simple predictors of uvulopalatopharyngoplasty outcome in treatment of obstructive sleep apnea. Chest 2000;118:102530. [31] Riley RW, Powell NB, Guilleminault C. Obstructive sleep apnea syndrome: a review of 306 consecutively treated surgical patients. Otolaryngol Head Neck Surg 1993;108:11725.
Evidence-based medicine in sleep apnea surgery

K. Christopher McMains, MD, David J. Terris, MD, FACS*
Department of OtolaryngologyHead 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 rst tracheotomy to bypass upper airway obstruction in 1969, which represented the rst denitive 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 rst 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 sufcient to confer treatment benets from CPAP [7], and incomplete compliance with CPAP proved prevalent [810]. Despite increased compliance with autotitrating CPAP, a substantial proportion of patients remained ineffectively treated on CPAP [11]. This nding 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 nding is supported further by Isono et al [13], who demonstrated that collapsibility at the level of the retroglossal airway is the most signicant 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 [1416]. 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: dterris@mcg.edu (D.J. Terris). 0030-6665/03/$ - see front matter 2003, Elsevier Science (USA). All rights reserved. doi:10.1016/S0030-6665(02)00182-2
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the Muller maneuver, cephalometric analysis, CT, and volumetric MRI. The Muller 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 eective treatment for snoring [25], but there are conicting data on its efcacy 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 [3234], 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 specic 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,
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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;78:83645; with permission.
overriding those working to dilate the airway. This eect is known as the balance-of-forces model [35]. In OSA, these events include apneas, complete cessation of ventilation, hypopneas, signicantly reduced ventilation secondary to partial obstruction, or respiratory effortrelated arousal, which are dened 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
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these events. It is now understood that hypersomnolence results from sleep fragmentation [37]. Respiratory drive and tonic control of airway musculature dier in the sleep and awake states. A wakefulness drive, which responds to nonmetabolic inputs, modulates changes during the awake state. When this inuence 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-movementphase 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 [4245]. As compared with the wakeful state, pharyngeal airway resistance triples during sleep [4248]. With arousal and concomitant return of the wakefulness drive, dilator muscle activity increases, airway resistance decreases, and airow resumes [4249]. Several specic anatomic dierences 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 signicantly 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 efciency 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
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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 denition 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 dened 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
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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 diculties 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), rst 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 patients 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 eect of OSA. These measures originally were designed to measure aggregate health characteristics and to provide synoptic information regarding a patients 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 signicantly 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].
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The Nottingham Health Survey demonstrated signicant dierences in energy, pain, sleep, social isolation, and physical mobility in patients with OSA as compared with control patients; however, no dierence in EDS between these groups was noted. No dierence in QOL was identied among patients with dierent levels of severity with OSA [81]. Concern about the ability of nonspecic measures to elucidate subtle QOL changes specic to OSA led to development of disease-specic 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 eect size than did the SF-36 [82]. The Functional Outcomes Sleep Questionnaire was designed to assess the effect of sleep-related symptomatology on ve 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 ve 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 rst and dispensed with symptom-impact scoring, reporting average magnitude score instead. This instrument correlates well with the patients 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 patients 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]. Muller maneuver: palate, base of tongue, and lateral walls The Muller 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
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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 difculty getting new job 31. Loss of job 32. Modication 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;118:83344; with permission.
palate are examined for collapse. The examiner rates collapsibility of each structure from 0 (minimal collapse) to 4+ (complete collapse). Muller maneuver score was shown to be correlated moderately with preoperative SDB severity, and its reproducibility was veried between examiners [27]. Collapse of the palate was correlated highly with RDI, whereas lateral wall
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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 signicant 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. Conicting data were described by Yao et al [89], who found that cephalometric radiographs reect anatomic changes postoperatively, but these changes did not correlate with efcacy as measured by improvements in the AHI. Polysomnogram The polysomnogram (PSG) was rst 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 airow, respiratory effort, extremity electromyography, submental electromyography, electro-oculogram, positionally dependent sleep changes, and electroencephalographic evidence of arousal [99]. Despite
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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 condence 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 dicult to guarantee eective 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 patients 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 eectiveness 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 dened 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 eect from aging and minor weight gain [106]. Failure after UP3 was related to preoperative BMI and postoperative weight gain [107]. Bariatric surgery
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has been explored in the treatment of OSA, with variable results. Several authors report that bariatric surgery provides signicant long-term reduction in weight and OSA severity [108110], whereas other reports suggest a considerable relapse rate among treated patients [111]. Aggressive weightreduction programs represent an important component of comprehensive OSA treatment. Signicant dierences 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 signicantly 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 ve 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 signicantly to obstruction. Bettega et al [117] wrote, No data are available on the effects of phase I surgical techniques on dilator muscle activity, contraction efciency, 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 signicantly 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 signicantly with UPPP failure [121]. Exploration of airway-lengthening procedures may exploit the insight gained through Thuts research to the benet of patients with OSA. Recognition of the inuence exerted by other diseases and syndromes may contribute to the challenge of eective OSA treatment. Disproportionate anatomy among the base of the tongue, narrow mandible, and hypoplastic mandible aect upper airway dynamics [16]. This disproportion can be seen in syndromic patients and in isolation from other abnormalities.
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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 eectiveness, 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 nding suggests an inuence from desaturation independent of RDI; however, ODI has been shown to be specic 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 specic 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 signicant 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 benets of restored sleep architecture. Patient perception of treatment may dier dramatically from objective data provided by PSG. The fact that tracheotomy and CPAP can decrease QOL secondary to inconvenience, discomfort, and social stigma despite eective 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-identied 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
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difculty in obtaining postoperative sleep studies is that symptomatic improvement decreases a patients desire to undergo additional testing [130]. In a study of patients with mild OSA, no additional benet 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 ndings [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 Prole [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 conicting data regarding the relationship to OSA dened 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 denitions of these occurrences have been made [86], considerable variability in denition, evaluation, and reporting continues to cloud comparisons [139]. Various cutoffs are used in individual studies for diagnosis, benet, 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 nonrapid-eye-movement sleep with oxygen saturation below 90%. The use of different denitions for respiratory disturbance, criteria for diagnosis, and measures of success is perhaps the most signicant 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 inuences, 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 signicant difference between rst- and second-night sleep studies [144] and reclassication of disease or severity in only a few patients based on subsequent night-sleep studies [145]. Although data conict 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.
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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 signicant 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 elds of endeavor. Much progress has been made already in the eld of assessment. Clear denition of respiratory disturbances will help establish uniform reporting and more reliable, valid comparisons among dierent studies. To date, relative contributions of apneas, hypopneas, and RERAs have not been well dened. Research into the relative contributions of dierent types of respiratory disturbance to symptomatology and downstream health eects may provide insight into the true eect 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 eorts on the part of the medical community to raise public awareness of OSA will aect health behaviors and social stigmata assigned to various treatment modalities. Such educational eorts 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.
K.C. McMains, D.J. Terris / Otolaryngol Clin N Am 36 (2003) 539561 553
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, 916, >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):1620; with permission.)
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The complexity of OSA and its variability of expression within individuals make identication of one best method of assessment and treatment dicult. 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
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2003, Vol.36, Issues 3, Surgery For Sleep Apnea

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Otolaryngol Clin N Am 36 (2003) xixii

David J. Terris, MD, FACS Guest Editor

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Otolaryngol Clin N Am 36 (2003) 409421

Upper airway physiology and obstructive sleep-disordered breathing

C. Yang, B.T. Woodson / Otolaryngol Clin N Am 36 (2003) 409421

C. Yang, B.T. Woodson / Otolaryngol Clin N Am 36 (2003) 409421

C. Yang, B.T. Woodson / Otolaryngol Clin N Am 36 (2003) 409421

C. Yang, B.T. Woodson / Otolaryngol Clin N Am 36 (2003) 409421

C. Yang, B.T. Woodson / Otolaryngol Clin N Am 36 (2003) 409421

C. Yang, B.T. Woodson / Otolaryngol Clin N Am 36 (2003) 409421

C. Yang, B.T. Woodson / Otolaryngol Clin N Am 36 (2003) 409421

C. Yang, B.T. Woodson / Otolaryngol Clin N Am 36 (2003) 409421

C. Yang, B.T. Woodson / Otolaryngol Clin N Am 36 (2003) 409421

C. Yang, B.T. Woodson / Otolaryngol Clin N Am 36 (2003) 409421

C. Yang, B.T. Woodson / Otolaryngol Clin N Am 36 (2003) 409421

C. Yang, B.T. Woodson / Otolaryngol Clin N Am 36 (2003) 409421

Otolaryngol Clin N Am 36 (2003) 423435

The physiologic impact of sleep apnea on wakefulness

Y.H. Goh, K.A. Lim / Otolaryngol Clin N Am 36 (2003) 423435

Y.H. Goh, K.A. Lim / Otolaryngol Clin N Am 36 (2003) 423435

Y.H. Goh, K.A. Lim / Otolaryngol Clin N Am 36 (2003) 423435

Y.H. Goh, K.A. Lim / Otolaryngol Clin N Am 36 (2003) 423435

Y.H. Goh, K.A. Lim / Otolaryngol Clin N Am 36 (2003) 423435

Y.H. Goh, K.A. Lim / Otolaryngol Clin N Am 36 (2003) 423435

Y.H. Goh, K.A. Lim / Otolaryngol Clin N Am 36 (2003) 423435

Y.H. Goh, K.A. Lim / Otolaryngol Clin N Am 36 (2003) 423435

Y.H. Goh, K.A. Lim / Otolaryngol Clin N Am 36 (2003) 423435

Y.H. Goh, K.A. Lim / Otolaryngol Clin N Am 36 (2003) 423435

Y.H. Goh, K.A. Lim / Otolaryngol Clin N Am 36 (2003) 423435

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Otolaryngol Clin N Am 36 (2003) 437460

Nasal obstruction in sleep-disordered breathing

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W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

Soft tissue obstruction (possibly reversible) Foreign body (reversible)

Bone/cartilage deformity (xed)

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

Septal deviation Congenital craniofacial anomalies

Conchal hypertrophy Anterior nasal Congenital craniofacial packing anomalies

Postrhinoplasty Trauma Tip ptosis Cicatricial stenosis

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W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

W. Chen, C.A. Kushida / Otolaryngol Clin N Am 36 (2003) 437460

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