Management of Obstructive Sleep Apnea

Management of Obstructive Sleep Apnea

Management of Obstructive Sleep Apnea Edited by

Jonas T Johnson

MD, FACS

Department of Otolaryngology and Radiation Oncology University of Pittsburgh School of Medicine Pittsburgh, PA, USA

Jack L Gluckman

MD, FACS

Department of Otolaryngology University of Cincinnati Medical Center Cincinnati, OH, USA

Mark M Sanders

MD, FCCP, FABSM

Pulmonary Sleep Program Department of Pulmonary, Allergy and Critical Care Medicine University of Pittsburgh School of Medicine Pittsburgh, PA, USA Foreword by

Robert Ritch

MD

Chief Glaucoma Service The New York Eye and Ear Infirmary New York USA

Martin Dunitz

© 2002 Martin Dunitz Ltd, a member of the Taylor & Francis Group First published in the United Kingdom in 2001 by Martin Dunitz Ltd, The Livery House, 7–9 Pratt Street, London NW1 0AE Website: http://www.dunitz.co.uk Tel.: +44 (0) 20 7482-2202 Fax.: +44 (0) 20 7267-0159 E-mail: [email protected] This edition published in the Taylor & Francis e-Library, 2002. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission of the publisher or in accordance with the provisions of the Copyright, Designs and Patents Act 1988 or under the terms of any licence permitting limited copying issued by the Copyright Licensing Agency, 90 Tottenham Court Road, London W1P 0LP. Although every effort has been made to ensure that all owners of copyright material have been acknowledged in this publication, we would be glad to acknowledge in subsequent reprints or editions any omissions brought to our attention. Although every effort has been made to ensure that drug doses and other information are presented accurately in this publication, the ultimate responsibility rests with the prescribing physician. Neither the publishers nor the authors can be held responsible for errors or for any consequences arising from the use of information contained herein. For detailed prescribing information or instructions on the use of any product or procedure discussed herein, please consult the prescribing information or instructional material issued by the manufacturer. A CIP record for this book is available from the British Library. ISBN 1 901865 96 7 (Print Edition) Distributed in the USA by Fulfilment Center Taylor & Francis 7625 Empire Drive Florence, KY 41042, USA Toll Free Tel.: +1 800 634 7064 E-mail: cserve@routledge–ny.com Distributed in Canada by Taylor & Francis 74 Rolark Drive Scarborough, Ontario M1R 4G2, Canada Toll Free Tel.: +1 877 226 2237 E-mail: tal–[email protected] Distributed in the rest of the world by ITPS Limited Cheriton House North Way Andover, Hampshire SP10 5BE, UK Tel.: +44 (0) 1264 332424 E-mail: [email protected] ISBN 0-203-42894-3 Master e-book ISBN

ISBN 0-203-44980-0 (Adobe eReader Format)

Contents Contributors

vii

Preface

ix

Acknowledgements

xi

I

Diagnostic considerations

1

Obstructive sleep apnea: the syndrome Steven M Koenig and Paul Suratt

2

3

4

II 5

Non-apneic causes of excessive daytime sleepiness Mark W Mahowald Obstructive sleep apnea in children Carole L Marcus

6

Therapy with oral appliances 111 Wolfgang Schmidt-Nowara

7

Nasal obstruction and nasal surgery David L Steward, Jack Gluckman and Jonas T Johnson

3

21

41

Diagnostic studies for sleep apnea/hypopnea 55 Rajesh Jasani, Mark H Sanders and Patrick J Strollo

121

8

Tracheotomy Jonas T Johnson and Jack Gluckman

9

Uvulopalatopharyngoplasty Aaron E Sher

145

10 Laser uvulopalatopharyngoplasty B Tucker Woodson

155

11 Hypopharyngeal airway surgery Kasey K Li and Nelson B Powell

137

175

Therapy Medical therapy Richard B Berry

81

12 Skeletal facial corrections Walter Hochban

185

vi

Contents

III Future advances 13 Radiofrequency tissue reduction 205 Jonas T Johnson and Jack Gluckman 14 Hypoglossal nerve stimulation Lennart Knaack and Walter Hochban

211

15 Serotonergic medications Richard B Berry

223

Index

235

Contributors Richard B Berry Sleep Laboratory Malcolm Randall VA Medical Center and Pulmonary and Critical Care Division University of Florida Health Science Center Box 100225 Gainesville, FL 32610-0225, USA Jack Gluckman Department of Otolaryngology University of Cincinnati Medical Center P0 Box 670528 Cincinnati, OH 45267-0528, USA Walter Hochban Mund-, Kiefer-, Gesichtschirurgie Schuetzenstrasse 84 D-78315 Radolfzell/Bodensee, Germany Rajesh Jasani Pulmonary Sleep Disorders Program Pulmonary, Allergy and Critical Care Medicine University of Pittsburgh Medical Center Montefiore University Hospital 3459 Fifth Avenue, 12-North Pittsburgh, PA 15213, USA Jonas T Johnson Department of Otolaryngology and Radiation Oncology University of Pittsburgh School of Medicine The Eye and Ear Institute Building 203 Lothrop Street, Suite 500 Pittsburgh, PA 15213, USA

Lennart Knaack Zentrum für Schlafmedizin Dortmund Hermanstrasse 48–52 D-44263 Dortmund–Hörde, Germany Steven M Koenig Pulmonary Division University of Virginia School of Medicine Box 800546 Charlottesville, VA 22908-0546, USA Kasey K Li Stanford Sleep Disorders Clinic and Research Center 750 Welch Road, Suite 317 Palo Alto, CA 94304, USA Mark W Mahowald Minnesota Regional Sleep Disorders Center Hennepin County Medical Center 701 Park Avenue Minneapolis, MN 55415, USA Carole L Marcus Division of Pediatric Pulmonology Park 316 Johns Hopkins Hospital 600 N. Wolfe Street Baltimore, MD 21287-2533, USA Nelson B Powell Stanford Sleep Disorders Clinic and Research Center 750 Welch Road, Suite 317 Palo Alto, CA 94304, USA

viii

Contributors

Mark H Sanders Pulmonary Sleep Disorders Program Pulmonary, Allergy and Critical Care Medicine University of Pittsburgh Medical Center Montefiore University Hospital 3459 Fifth Avenue, 12-North Pittsburgh, PA 15213, USA

Patrick J Strollo Jr Pulmonary Sleep Disorders Program Pulmonary, Allergy and Critical Care Medicine University of Pittsburgh Medical Center Montefiore University Hospital 3459 Fifth Avenue, 12-North Pittsburgh, PA 15213, USA

Wolfgang Schmidt-Nowara University of Texas Southwestern Medical School University of New Mexico and Sleep Medicine Institute Presbyterian Hospital Dallas 8140 Walnut Hill Lane, Suite 100 Dallas, TX 75231, USA

Paul Suratt Pulmonary Division University of Virginia School of Medicine Box 800546 Charlottesville, VA 22908-0546, USA

Aaron E Sher 6 Executive Park Drive Entrance C Albany, NY 12203, USA David L Steward Department of Otolaryngology University of Cincinnati Medical Center P0 Box 670528 Cincinnati, OH 45267-0528, USA

B Tucker Woodson Department of Otolaryngology and Communication Sciences Medical College of Wisconsin 9200 W. Wisconsin Avenue Milwaukee, WI 53226, USA

Preface It is interesting to observe that just twenty-five years ago snoring and obstructive sleep apnea were largely unrecognized and ignored by organized medicine. In the space of just a quarter of a century, a phenomenal ‘new’ field of medicine has developed which greatly impacts quality of life and carries the potential to change our perspective on risk for cardioand cerebrovascular disease. It is estimated that as many as 40% of the population experience socially unacceptable snoring. A significant proportion of these patients have associated sleep-disordered breathing, such as obstructive sleep apnea. The costs in terms of human suffering, social and medical morbidity and mortality, and healthcare, as well as productivity, expense are clearly enormous. Clinicians have not yet fully standardized diagnostic criteria for obstructive sleep apnea,

and efforts to develop evidence-based criteria are ongoing. Therapeutic decision making continues to challenge most physicians and their patients. This textbook attempts to address the current state of the art of the diagnosis and management of snoring and obstructive sleep apnea. The therapeutic use of oral appliances and a variety of surgical procedures indicate the dilemma every patient and treating physician must face in selecting appropriate intervention. Our section on future advances represents but the ‘tip of the iceberg.’ Every primary care physician should be alert to the signs and symptoms of the syndrome of obstructive sleep apnea. Professionals interested in this field must of necessity continue to challenge the past in an effort to improve the future. JTJ JG MHS

Acknowledgements This textbook on the Management of Obstructive Sleep Apnea is dedicated to our many professional colleagues who have contributed so much to our understanding of the diagnosis and treatment of sleep

disordered breathing. We pay special tribute to the thousands of patients who have willingly participated in our ongoing efforts to better understand this syndrome and its therapies.

I

Diagnostic considerations

1 Obstructive sleep apnea: the syndrome Steven M Koenig and Paul Suratt

Epidemiology

Genetics

Obstructive sleep apnea (OSA) was once thought to be an uncommon disorder. However, a recent community-based study estimated that, among randomly chosen middle-aged working adults, sleep-disordered breathing, defined as an apnea-hypopnea score (number of apneas plus hypopneas per hour of sleep) greater than or equal to 5, was found in 9% of women and 24% of men. Moreover, 2% of women and 4% of men met minimal criteria for OSA syndrome, defined as an apnea–hypopnea score of 5 or higher with daytime hypersomnolence.1 In the elderly, estimates of OSA frequency are even greater, ranging from 28% to 67% in men and from 20% to 54% in women.2–5 The prevalence of OSA syndrome in commercial truck drivers has been reported to be as high as 46%.6 In the USA, 20–30% of hypertensive patients have unrecognized sleep apnea.7 Overall, it is estimated that 18 million Americans suffer from OSA syndrome and that the cost of OSA is approximately $42 million annually from hospitalization alone.8 Particularly concerning is the fact that up to 95% of cases of OSA are unsuspected.8

OSA has been shown to aggregate significantly within families, suggesting an inherited basis for this disorder.9–11 The probability of developing OSA appears to increase progressively with increasing numbers of affected family members. While individuals with one affected family member have an estimated 30–58% increased risk for developing OSA, those with three affected family members have an estimated 2–4-fold increased risk.12 Overall, approximately 30–40% of the variability in apneic activity in the population can be explained by variability in familial factors.9 A report of increased prevalence of HLA-A2 in Japanese patients with OSA supports the concept of an inherited defect.13 This increased incidence of OSA in families is not completely explained by familial similarities in body mass index or neck circumference, and persists despite adjustments for other well-known risk factors such as age and male sex.12,13 It has been postulated that inherited craniofacial abnormalities such as a high and narrow hard palate, shorter mandibles, retroposed maxillae and mandibles, longer soft palates and wider uvulae are important in

4

Obstructive sleep apnea: the syndrome Jaw malformation Jaw Malformation

Nasal obstruction

Enlarged tongue

Obesity

Nasal cavities

Floppy epiglottis

Enlarged tonsils and adenoids

Paralysedvocal vocal cord cord Paraivsed

Enlarged soft palate Upper airway tumor Hypopharynx

Velopharynx

Laryngopharynx Gropharynx

Nasopharynx

the pathogenesis of OSA.10,14 However, differences in craniofacial morphology between patients with sleep apnea and control relatives without sleep apnea were small, implying that other factors may be important in familial OSA.9,10,12 Recent studies have noted that family members of subjects with OSA demonstrate blunting of the hypoxic ventilatory response, a greater increase in impedance during inspiratory loading, and a reduced ability to compensate for increased inspiratory loads.12,15 These findings suggest that a genetic susceptibility to OSA may be related to abnormalities in ventilatory control mechanisms and the regulation of upper airway patency.

Pathogenesis and risk factors It is well recognized that narrowing of the human pharynx or upper airway is responsible

Figure 1.1 Diagram of the upper airway showing the different segments of the pharynx and indicating the variety of upper airway abnormalities reported to cause obstructive sleep apnea. (Adapted from Fleetham JA. Upper airway imaging in relation to obstructive sleep apnea. Clin Chest Med 1992;13:400.)

for all the consequences associated with obstructive sleep apnea.16 The pharynx is typically divided into three segments, the nasopharynx (end of the nasal septum to the margin of the soft palate), the oropharynx (free margin of the soft palate to the tip of the epiglottis), which is divided into the retropalatal and retroglossal regions, and the hypopharynx (tip of the epiglottis to the vocal cords) (Figure 1.1). In one study, 75% of patients had more than one site of narrowing, the retropalatal region or velopharynx being the most common site.17 Since a decrease in size or narrowing of the human upper airway or pharynx is the underlying cause of OSA, individuals with this condition must have some abnormality or abnormalities leading to narrowing of their upper airway. According to the ‘balance of pressures’ concept proposed by Remmers et al, there are five major determinants of the size or caliber of the upper airway (Figure 1.2): (1) the baseline pharyngeal area, which is determined by both craniofacial and soft tissue

Pathogenesis and risk factors

Pmusc

Ptis

PL

PL

Ptis

Compliance =

Pmusc

6V 6P

Figure 1.2 Determinants of upper airway caliber. PL = intraluminal pressure; Ptis = pressure in the tissues surrounding the pharyngeal wall; Pmusc = pressure exerted by the pharyngeal dilating muscles; 6V = change in volume; 6P = change in pressure.

structures (Figure 1.1); (2) the compliance or collapsibility of the airway; (3) the pressure within the airway (intraluminal pressure, PL), which on inspiration is negative, due to the upwardly transmitted negative intrapleural pressure, and tends to narrow the airway; (4) the pressure acting on the outside surface of the pharyngeal wall (tissue pressure, Ptis), which can be positive, and also tends to collapse the airway—examples include compression by the lateral pharyngeal fat pad, a large neck, the effect of gravity on submandibular fat, and a large tongue confined to a small oral cavity; and (5) the pressure exerted by the pharyngeal dilating

5

muscles (Pmusc), which is directed outwards, and functions to increase cross-sectional area and decrease pharyngeal compliance.17–19 In addition, there is theoretical evidence that the shape of the upper airway is also important. Compared to the wide, elliptically shaped airway of normal controls, the long axis of which is oriented transversely, the pharynx of patients with OSA is narrow and has its long axis in the anteroposterior direction. Such an orientation could decrease Pmusc by diminishing the mechanical effectiveness of upper airway muscle contraction.20,21 Finally, lung volume independently influences upper airway caliber, resistance and compliance. Decreased lung volume results in a decrease in the area of the pharynx, an increase in its compliance or collapsibility, and the loss of caudal traction or tug on the trachea.22–25 The consequence of the loss of tracheal tug is an increase in upper airway resistance.22 Although narrowing of the human upper airway is the primary event in OSA, the occurrence of oxyhemoglobin desaturation during the abnormal respiratory event is dependent on several other factors. The primary determinants of oxyhemoglobin desaturation with OSA include: (1) the length of the abnormal respiratory event—the longer the event, the more likely it is that oxyhemoglobin desaturation will occur; (2) the type of respiratory event, obstructive events being associated with respiratory effort and therefore greater oxygen consumption than central events with absent respiratory effort; (3) the quantity of oxygen stored in the lungs, which is proportional to the lung volume and the fractional concentration of oxygen in the alveoli (a small lung volume is associated with greater desaturation than a large lung volume); (4) the mixed venous oxygen saturation, the lower this saturation— the more rapid the rate of fall in arterial oxyhemoglobin saturation; (5) the body mass index

6

Obstructive sleep apnea: the syndrome

% Saturation of hemoglobin

100

6SaO2 6SaO2

50

0

0

30

60 PaO2 (mmHg)

90

Figure 1.3 Effect of initial arterial oxygen tension (PaO2) and saturation (SaO2) on extent of arterial oxygen desaturation seen with an apnea or hypopnea. Because of the shape of the oxygen–hemoglobin dissociation curve, the amount of decrease in SaO2 and corresponding PaO2 is different for different starting PaO2s. When the starting PaO2 is near or below the ‘elbow’ of the curve, more oxygen desaturation is seen with a given apnea or hypopnea compared to a starting PaO2 on the ‘plateau’ of the curve.

(BMI) of the subject—obese subjects consume more oxygen per minute than slender subjects; and (6) the baseline arterial oxygen saturation—the lower the value, the closer you are to the knee of the oxyhemoglobin dissociation curve at the start of the abnormal respiratory event, and the more likely you are to desaturate (Figure 1.3).17 Although numerous changes occur during sleep, those most important in the pathogenesis of OSA are the decrease in both Pmusc and lung volume associated with sleep onset.26–28 The latter exacerbates the decreased lung

volume associated with assumption of the supine position. In addition, the effect of gravity on a large neck or parapharyngeal fat may increase Ptis. The overall result is an increase in upper airway resistance due to the decrease in cross-sectional area and increase in compliance or collapsibility of the upper airway.28,29 Stiffer, smaller lungs and resultant atelectasis may also cause a decrease in baseline oxyhemoglobin saturation and the other determinants of the degree of oxyhemoglobin desaturation with an apnea, hypopnea or hypoventilation. The pharynx of persons without OSA has sufficient ‘reserve’ to tolerate this increase in upper airway resistance and collapsibility associated with sleep. In contrast, individuals with OSA have some predisposing condition, either a pharynx with a baseline area that is too small, or an abnormality in one or more of the determinants of upper airway caliber mentioned above. Thus when they fall asleep, their upper airway cannot tolerate this decrease in Pmusc and lung volume and increase in Ptis. The result is an upper airway that narrows enough to have physiologic consequences (see below). Those factors that have been shown to predispose to OSA, and how they interact with the determinants of upper airway caliber described above, are shown in Table 1.1. See also Figure 1.1 for examples of upper airway anatomic abnormalities that can predispose to OSA. Since REM sleep is associated with greater muscle hypotonia compared to non-REM sleep, sleep-disordered breathing is more likely to occur during REM sleep.30 In addition, the more impaired ventilatory responses to hypoxia and hypercapnia contribute to the longer duration of abnormal respiratory events and the presence of post-apneic hypoventilation during REM sleep.31,32 The

Pathogenesis and risk factors

7

Table 1.1 Factors predisposing to the obstructive sleep apnea syndrome and how they interact with the determinants of pharyngeal caliber. Predisposing factor

Awake pharyngeal area

Luminal pressure (PL)

Tissue pressure (Ptis)

Pharyngeal muscle dilating force (Pmusc)

Pharyngeal compliance

Obesity Neuromuscular disease Alcohol Sedative hypnotics Nasal congestion Abnormal anatomy Supine position Sleep deprivation Hypothyroidism Acromegaly

Decreased Decreased Decreased – – Decreased Decreased – Decreased Decreased

– – – – Increased – – – – –

Increased ? – – – – – Increased – Increased Increased

Decreased ? Decreased Decreased Decreased – – – Decreased Decreased –

Increased Increased – – – – – Increased – –

(Adapted from Koenig SM, Suratt PM. Obesity and sleep-disordered breathing. In: Alpert MA, Alexander JD, eds. The Heart and Lung in Obesity. Armong, New York: Futura Publishing Company, 1998:156.)

result is more frequent and more severe episodes of increased upper airway resistance and oxyhemoglobin desaturation compared to non-REM sleep. To predispose to OSA, obesity must influence one or more of the above-mentioned determinants of upper airway caliber, or of degree of oxyhemoglobin desaturation associated with a given abnormal respiratory event. As it turns out, there is evidence that obesity can affect all of these determinants, which explains not only why obesity is the most common factor predisposing to OSA, but why obese individuals with OSA are more likely to have more severe clinical consequences than their non-obese counterparts (Figure 1.4). Although it is unclear whether the predominant mechanism is increased Ptis or simply excessive parapharyngeal tissue without an

increase in Ptis, the majority of studies indicate that, compared to weight-matched controls, obese patients with OSA have a smaller baseline upper airway cross-sectional area. This narrowing is located predominantly in the retropalatal region.19,33 Logic would dictate that excessive adipose tissue should be the cause of this decreased area, and there is evidence to support this hypothesis. Using magnetic resonance imaging (MRI), which can distinguish soft tissue from fat, one study indicated that, compared to weight-matched controls, obese patients with OSA had excess fat deposition in the soft palate, tongue and areas posterior and lateral to the oropharynx at the level of the palate.34 Two other MRI studies confirmed the smaller baseline pharyngeal area in obese subjects with OSA, and also demonstrated the presence of a larger volume

8

Obstructive sleep apnea: the syndrome

OBESITY

Parapharyngeal fat

Thickness, lateral parapharyngeal walls

Abdominal, chest wall, diaphragm fat

Lung volume

Tracheal tug

Baseline UA area

UA compliance

Pmusc

A-P orientation of UA

UA caliber

UAR

Ptis

+

Respiratory load compensation

OSA

Figure 1.4 The pathophysiologic role of obesity in the obstructive sleep apnea syndrome. UA, upper airway; UAR, upper airway resistance; OSA, obstructive sleep apnea; A-P, anterior–posterior; Ptis = pressure in tissues surrounding the pharyngeal wall; Pmusc = pressure exerted by pharyngeal dilating muscles. (Adapted from Koenig SM, Suratt PM. Obesity and sleepdisordered breathing. In: Alpert MA, Alexander JD, eds. The Heart and Lung in Obesity. Armong, New York: Futura Publishing Company, 1998:157.)

of adipose tissue adjacent to the pharyngeal airway.35,36 Moreover, not only did the volume of this parapharyngeal fat correlate with the degree of OSA, but weight loss resulted in a substantial decrease in both pharyngeal adipose tissue volume and the severity of OSA.36 In addition, surgical specimens from

individuals with OSA who underwent uvulopalatopharyngoplasty (UPPP) (see below) have demonstrated increased fat in the soft palate.37 In contrast, although Schwab et al confirmed that airway size is smaller in patients with sleep apnea, their findings

Pathogenesis and risk factors indicated that it was the thickness of the lateral pharyngeal wall and not the size of the soft palate, tongue or parapharyngeal fat pads that was the major anatomic factor causing airway narrowing in apneics.38 Moreover, using a proton spectroscopic technique called hydrogen ultrathin phase-encoded spectroscopy (HUPSPEC) with MRI, he demonstrated that this increased thickness of the lateral pharyngeal walls was not secondary to increased fat infiltration or edema.39,40 He went on to hypothesize that obesity may predispose to sleep apnea by increasing the size of the upper airway soft tissue structures themselves (tongue, soft palate, lateral pharyngeal walls), rather than by the direct deposition of fat in the parapharyngeal fat pads or by compressing the lateral walls by these fat pads. Thus, although most evidence supports a smaller baseline upper airway caliber in obese patients, the exact mechanism of this narrowing remains to be defined. Fat might also encroach on the upper airway lumen and alter its shape without necessarily reducing its diameter. With MRI, differences in pharyngeal shape but not in cross-sectional area have been documented between obese patients and normal-weight controls.21 When the pharynx was viewed in coronal section, the airways of normal awake controls were in the shape of an ellipse, with the long axis oriented transversely. In contrast, awake OSA patients had elliptically shaped airways oriented in an anteroposterior or longitudinal direction. Non-apneic snorers had upper airway shapes intermediate between these two groups. Using CT scanning, Schwab et al made similar findings.19 These results are consistent with reports that the upper airway collapses laterally during sleep when viewed endoscopically or by fast CT.36 Whether the longitudinal orientation of the pharynx in patients with OSA is secondary to

9

lateral encroachment by fat, i.e. an increase in Ptis, or to pharyngeal dilator muscles pulling the airway anteriorly, is unknown. However, as mentioned above, this anteroposterior orientation could diminish the ability of pharyngeal muscles to dilate the upper airway (i.e. decreased Pmusc).20 Several measures have been used to evaluate the compliance or collapsibility of the human upper airway, including acoustic reflection techniques that measure the lung volumerelated change in pharyngeal area, nasopharyngeal resistance and the critical closing pressure of the airway or Pcrit. Pcrit is the luminal pressure at which the cross-sectional area of the upper airway becomes zero. Regardless of the technique employed, numerous studies have suggested that fat surrounding the human upper airway increases the compliance of the pharynx.23–25,41–43 This increased compliance or collapsibility could result from a direct effect on the airway itself or an indirect effect on the function of the upper airway dilator muscles (i.e. decreased Pmusc). Obesity, particularly central or upper body obesity, can also result in decreased lung volume.44,45 Since pharyngeal area and resistance are directly proportional, and compliance is inversely proportional to lung volume, obesity can decrease the baseline area and increase the resistance and compliance of the upper airway simply by its effect on lung volume.22–25 Obesity can also affect the degree of oxyhemoglobin desaturation and hypercapnia associated with a given abnormal respiratory event by several mechanisms: (1) increased baseline oxygen consumption and carbon dioxide production; and (2) decreased lung volume, which increases mismatch of ventilation and perfusion from airway closure and collapse (atelectasis); this results in decreased oxygen stores in the lung, decreased mixed venous oxygen saturation and a lower baseline

10

Obstructive sleep apnea: the syndrome

oxyhemoglobin saturation.46–48 Thus, for a given abnormal respiratory event, an obese individual is more likely than his non-obese counterpart to have oxyhemoglobin desaturation and hypercapnia. Neck circumference is a simple clinical measurement that reflects obesity in the region of the upper airway. Studies have indicated that patients with OSA have larger necks than nonapneic snorers as well as weight-matched controls.49,50 This parameter is related to obesity, apnea severity, tongue and soft palate size, as well as maxillary, mandibular and hyoid bone position, all thought to be important in the pathogenesis of OSA.33,51–56 In addition, of all the anthropometric measurements, including BMI, the neck circumference, particularly if adjusted for height, was the strongest predictor of sleep-disordered breathing.49,57 Hip-to-waist ratio, another measure of central obesity, also exhibits a better correlation with OSA severity than BMI.58 These findings suggest that it is the distribution of fat, in particular upper body obesity, rather than total body fat, that is important to the development of OSA. In one study, only neck circumference and retroglossal space were independent correlates of apnea severity.59 Nonetheless, although a more useful predictor of OSA than BMI and other signs and symptoms, neck circumference alone, even if corrected for height, is neither sufficiently sensitive nor sufficiently specific to avoid the need for further diagnostic testing to establish the diagnosis (r2 = 0.38; sensitivity = 87%; specificity = 79%; positive predictive value = 66%).57

Clinical features Sleep-disordered breathing has two primary outcomes, arousal from sleep and oxyhemoglobin desaturation and hypercapnia. The

Table 1.2 Consequences of arousal from sleep. Sleep fragmentation Excessive daytime sleepiness Personality changes Intellectual deterioration Visual–motor incoordination Impotence Insomnia Restlessness Choking, gagging, gasping, resuscitative snorting

Table 1.3 Consequences of nocturnal hypoxia/hypercapnia. Polycythemia Pulmonary hypertension Cor pulmonale Chronic hypercapnia Morning and nocturnal headache Left-sided congestive heart failure Cardiac dysrhythmias Nocturnal angina Diurnal systemic hypertension

consequences of these abnormalities are depicted in Tables 1.2 and 1.3. Although daytime sleepiness, fatigue, irritability and personality change have been attributed to both nocturnal oxyhemoglobin desaturation and the chronic sleep deprivation caused by sleep fragmentation, arousal from sleep is considered the more important of the two factors.60 Daytime sleepiness and visual–motor incoordination are the presumed cause of the increased rate of automobile (seven-fold) and work-related accidents in patients with OSA

Clinical features compared to the general population.61,62 The most common cardiac dysrhythmia observed in patients with OSA is a cyclic decrease and then increase in heart rate (sinus bradytachyarrhythmia).63,64 Other associated bradydysrhythmias include marked sinus bradycardia (< 30 beats/min), sinus arrest (> 2.5 s) and second-degree atrioventricular (A-V) block. Supraventricular paroxysmal depolarizations (SVPDs), ventricular paroxysmal depolarizations (VPDs), atrial fibrillation, atrial flutter and ventricular tachycardia are also reported. Unless there is coexistent coronary artery disease, increased VPDs and ventricular tachycardia do not typically occur until oxyhemoglobin saturation drops to less than 60–65%.65,66 Patients with sleep-disordered breathing may present with all, or only a few, of the symptoms and signs listed in Tables 1.2 and 1.3. Whether an individual presents with snoring, symptoms of sleep fragmentation, signs of hypoxia/hypercapnia or a combination of these, depends on several factors (Figure 1.5). As has already been mentioned, everything begins with some predisposing abnormality or abnormalities of the upper airway. When this predisposing factor(s) is combined with the decreased pharyngeal dilator muscle activity and lung volume and increased Ptis that accompanies sleep onset, some degree of upper airway narrowing occurs. If the soft portions of the oropharynx and nasopharynx vibrate, snoring will also result. For snoring to occur, you need both the proper structure, e.g. a long floppy uvula and soft palate, as well as exposure to an inspiratory pressure negative enough to set these tissues in motion. The reason why more than 80% of individuals with OSA snore is that the most common site of upper airway abnormality and narrowing is the region around the soft palate.

11

Predisposing factor + Sleep onset

Snoring

Decreased pharyngeal muscle activity and lung volume

Pharyngeal narrowing

Obstructive apnea/hypopnea

Hypoxia and hypercapnia

Inadequate respiratory load compensation Increased ventilatory effort Adequate respiratory load compensation Arousal from sleep

Figure 1.5 Pathophysiology of obstructive sleep apnea. (Adapted from Koenig SM, Suratt PM. Obesity and sleep-disordered breathing. In: Alpert MA, Alexander JD, eds. The Heart and Lung in Obesity. Armong, New York: Futura Publishing Company, 1998:165.)

Depending on the degree of narrowing and resultant increase in upper airway resistance, ventilatory effort may increase to maintain the required ventilation. Because increased ventilatory effort is transmitted to the upper airway in the form of a greater negative intraluminal pressure (PL), the pharynx will become narrower, further increasing upper airway resistance, and a vicious cycle may ensue.

12

Obstructive sleep apnea: the syndrome

Studies have demonstrated that the arousal from sleep that opens the upper airway and terminates an abnormal respiratory event during sleep is much more tightly linked to the tension–time index of the diaphragm than oxyhemoglobin desaturation.67,68 The tension–time index of the diaphragm is an indicator of ventilatory effort. If this ‘ventilatory effort arousal threshold’ is exceeded while the respiratory muscles are still able to compensate for the increased upper airway resistance or load, an arousal from sleep alone, without a decrease in airflow, i.e. without an apnea or hypopnea (see below), will occur. And, without diminished airflow, no oxyhemoglobin desaturation or hypercapnia will result. This condition, which is associated with daytime fatigue, tiredness and sleepiness due to the sleep fragmentation induced by the arousals, has been termed the upper airway resistance syndrome (UARS).69 (see below). Interestingly, several patients with UARS, all women, did not even snore. If ventilatory effort does not exceed its ‘arousal threshold’ prior to the respiratory muscles becoming unable to compensate for the increased upper airway resistance or load, a decrease in airflow and tidal volume occurs; this is called a hypopnea. If airflow ceases completely prior to arousal from sleep, an apnea occurs. An apnea is defined as the complete or near complete cessation of airflow that lasts for at least 10 s.70 A hypopnea is defined as a * 50% decrease in airflow or a < 50% decrease lasting at least 10 s with either an oxyhemoglobin desaturation of * 3% or an arousal from sleep.70 Both abnormal breathing events are associated with similar sequelae, are treated in the same manner, and often occur together in the same patient. There are two possible outcomes of a hypopnea and apnea: a further increase in ventilatory effort followed by an arousal

alone, or hypoxia and hypercapnia, which independently, as well as by further increasing ventilatory effort, usually result in an arousal from sleep. The determinants of whether an apnea or hypopnea result in oxyhemoglobin desaturation and hypercapnia, as well as the severity of these abnormalities if they do occur, are discussed above. Finally, if both the ‘ventilatory effort arousal threshold’ and an individual’s ability to compensate for hypoxia, hypercapnia and respiratory loads are sufficiently blunted, hypoventilation alone, without the periodic arousals that terminate hypopneas, apneas or increased UAR, results. Thus the term OSA is not, strictly speaking, applicable to the entire spectrum of sleep-disordered breathing, but is best reserved for those individuals with the most severe form of the disease. The term obstructive sleep-disordered breathing syndrome (OSDB) better describes the entire spectrum of obstructive breathing abnormalities during sleep (Figure 1.6). At one end of the upper airway resistance continuum there is primary, asymptomatic snoring. This is followed by the UARS, then by the sleep hypopnea syndrome, and finally by the sleep apnea syndrome. The obesity hypoventilation syndrome is used to describe individuals with OSDB who also have daytime hypoventilation and who are typically morbidly obese. The major factors that determine where along the spectrum of OSDB a patient lies are the ‘ventilatory effort arousal threshold’ and the resistive load compensation. Whether hypoventilation, a hypopnea or an apnea eventuates in hypoxia and hypercapnia depends on the individual’s underlying pulmonary function and the duration of the abnormal respiratory event, the latter determined primarily by the ‘ventilatory effort arousal threshold.’ Regarding some of the other long-term consequences of OSDB, several retrospective

Clinical diagnosis Upper airway resistance '

0 Snoring

Arousal

Hypopnea

Apnea

UA vibration

Yes

Yes/No

Yes/No

Yes/No

Ventilatory effort arousal threshold exceeded

No

Yes

No

No

Adequate respiratory load compensation

Yes

Yes

No

No

Clinical syndrome

Primary snoring

UARS

Sleep hypopnea syndrome

Sleep apnea syndrome

Figure 1.6 Spectrum of obstructive sleep-disordered breathing syndrome. UA, upper airway; UARS, upper airway resistance syndrome. The degree of resultant hypoxia and hypercapnia depends on the patient’s underlying cardiopulmonary function (i.e. arterial and mixed venous oxyhemoglobin saturation, lung volumes) and the duration of the abnormal respiratory event. If daytime hypercapnia is present and the patient morbidly obese, the term obesity hypoventilation syndrome is used. (Adapted from Koenig SM, Suratt PM. Obesity and sleep-disordered breathing. In: Alpert MA, Alexander JD, eds. The Heart and Lung in Obesity. Armong, New York: Futura Publishing Company, 1998:167.)

studies have shown that both the OSA syndrome and snoring were associated with an increased prevalence of hypertension, coronary artery disease and cerebral vascular accidents, even when adjustments were made for other risk factors such as weight, age,

13

smoking and sex.71–73 That snoring alone is associated with increased cardiovascular morbidity suggests that even mild degrees of sleep-disordered breathing may have adverse health effects. Finally, in yet another retrospective study, He et al. demonstrated that untreated significant OSA, defined as an apnea index (AI) > 20, was associated with excess mortality.74 Because current morbidity and mortality data are based on retrospective studies, the true impact of sleep-disordered breathing on society remains unknown. A randomized trial is clearly required, and, in fact, is presently ongoing. The mechanism whereby sleep-disordered breathing increases the risk of cardiovascular disease and consequences is unclear. It appears to be mediated by a complex interaction between the mechanical effects of repetitive increased upper airway resistance, the oftenassociated hypoxia and hypercapnia, and their effect on the autonomic nervous system as well as increased platelet aggregation that has been described in untreated sleep apnea.7,75–77

Clinical diagnosis The possibility of sleep-disordered breathing should be considered in any patient with any of the predisposing factors, signs or symptoms mentioned above (Tables 1.1–1.3). Talking with the bed partner, family members, friends or fellow employees can be very helpful, as they will often notice signs, such as apneas or falling asleep unintentionally, that the patient may be unaware of or deny. The next step is to estimate a clinical likelihood or pretest probability of sleep-disordered breathing based on a focused history and physical examination. This evaluation should include searching for alternative explanations for symptoms, such

14

Obstructive sleep apnea: the syndrome

Table 1.4 Features most useful in determining the probability of obstructive sleep-disordered breathing. Male sex Age > 40 Habitual snoring Nocturnal gasping, choking or resuscitative snorting Witnessed apnea BMI > 25 kg/m2, or neck circumference ⭓ 17 inches in males, ⭓ 16 inches in females Systemic hypertension BMI, body mass index.

as insufficient sleep or shiftwork causing excessive daytime sleepiness. Those symptoms and signs that have been shown to be most useful in determining the need for further diagnostic evaluation are listed in Table 1.4. Symptoms of excessive daytime sleepiness, unrefreshing or non-restorative sleep, morning headaches, cognitive impairment, depression, nocturnal esophageal reflux (due to increases in abdominal pressure during upper airway obstruction), nocturia or enuresis (due to increased intra-abdominal pressure and/or secretion of atrial natriuretic hormone), hearing loss, automatic behavior, sleep drunkenness (disorientation, confusion upon awakening), hypnagogic hallucinations and night sweats, although commonly reported, do not distinguish sleep apnea from other nonpulmonary sleep disorders. In any patient presenting with a complaint of daytime sleepiness, the degree of sleepiness should be quantitated. The sleepier the individual, the more likely it is that he has sleep-disordered breathing or some other significant disorder, and the more severe the

Table 1.5 Sleep-inducing situations in sleep apnea patients. Situation

% of patients

Watching television Reading Riding in a car (passenger) Church Visiting friends or relatives Driving in a car Working Waiting at a traffic light

91 85 71 57 54 50 43 32

n = 385 patients. (Adapted from Roth T, Roehrs TA, Carskadon MA, Dement WC. Daytime sleepiness and alertness. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. Philadelphia: WB Saunders Company, 1994:43.)

condition; the severity or the condition influences treatment (see below). A reasonable approach is to divide sleepiness into mild, moderate and severe, based on the frequency of sleep episodes, the degree of impairment of social and occupational function, and the situations in which sleep episodes occur.78 With mild sleepiness, sleep episodes are infrequent, may not occur every day, and occur at times of rest or when little attention is required, such as while watching TV, reading, or traveling as a passenger. Sleepiness is considered severe when it is present daily and when sleep episodes occur even during activities requiring sustained attention, such as eating, conversation, walking and driving. Moderate sleepiness lies somewhere in between these extremes. Table 1.5 presents those sleep-inducing situations most commonly reported by patients with OSA syndrome.

Clinical diagnosis It is important to remember that although the majority of patients with sleep-disordered breathing are sleepy when measured by multiple sleep latency testing (MSLT), daytime sleepiness is underreported.79,80 MSLT is an objective measure of sleepiness (see below). Fatigue may be the only symptom reported. This situation probably results because sleepdisordered breathing develops over a long period, and patients adapt their lifestyles to compensate for it. In addition, sleepiness may be denied because of lack of awareness of risk, embarrassment, or concern regarding punitive actions such as loss of occupation.81 Thus the absence of sleepiness cannot be used to reliably exclude OSA. In addition, sleep-disordered breathing is not the only cause of excessive daytime sleepiness (EDS) (Chapter 2). That is, EDS is not specific for sleep-disordered breathing either. Those physical examination findings that significantly increase the likelihood of sleepdisordered breathing are listed in Table 1.4. Other features that should be searched for include craniofacial and upper airway abnormalities such as retrognathia; tonsillar hypertrophy, especially in children; and an enlarged soft palate. The size and consistency of the tongue, presence of pharyngeal edema or abnormal reddish coloring of the pharynx, appearance of the soft palate, size, length and position of the uvula, evidence of trauma, and nares, including whether they collapse with inspiration, particularly while the patient is supine, should also be noted (Figure 1.1). Unfortunately, subjective impression alone, based on history and physical examination, lacks both sensitivity (52–78%) and specificity (50–79%).82–85 Although plugging clinical variables into regression formulas improves these operating characteristics somewhat (sensitivity 79–92%, specificity 50–51%), many involve complicated mathematical formulas,

15

which limits their usefulness.83,85,86 Moreover, even if the clinical likelihood is low, the posttest probability for OSA, defined as a respiratory disturbance index (RDI) > 10, still varies between 16% and 21%.83,86,87 In addition, since the criterion for the diagnosis of OSA in these studies was an RDI > 10–15, patients with symptoms secondary to UARS would have been missed, decreasing the sensitivity of clinical assessment even further. Whether a post-test probability for OSA of 16–21% is low enough will depend on the threshold at which a physician is willing to accept diagnostic uncertainty. The threshold for pursuing further diagnostic testing will probably be lower in patients with severe daytime sleepiness, comorbid illnesses such as coronary artery disease, a driving accident record and certain occupations, i.e. school bus driver. Recently, a morphometric model that combines measurements of the oral cavity with BMI and neck circumference has been recommended as a screening tool for OSA syndrome.88 This model had a sensitivity of 97.6%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 88.5%. Although these results are quite impressive, verification of this morphometric model by other investigators and in other sleep clinic populations must be performed before it can be recommended. The diagnosis of sleep-disordered breathing should also be considered in any individual with unexplained daytime hypercapnia, polycythemia, pulmonary hypertension or cor pulmonale. Patients with hypercapnia and pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD) typically have a forced expiratory volume in 1 second (FEV1 < 1–1.3 l/min (30% of predicted).89 Pulmonary hypertension predictably occurs in COPD when arterial oxygen tension PaO2 is < 50 mmHg and PaCO2 is

16

Obstructive sleep apnea: the syndrome

> 45 mmHg.90,91 Those with pulmonary hypertension due to restrictive lung disease usually have a forced vital capacity (FVC) < 50% of predicted.92 With systemic sclerosis, a diffusing capacity for carbon monoxide < 43% was a better predictor of pulmonary hypertension than a FVC < 50%, having a sensitivity of 67%.93

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9. Mathur R, Douglas NJ. Family studies in patients with the sleep apnea–hypopnea syndrome. Ann Intern Med 1995;122:174–8. 10. Redline S, Tishler PV, Tosteson TD et al. The familial aggregation of obstructive sleep apnea. Am J Respir Crit Care Med 1995;151:682–7. 11. Pillar G, Lavie P. Assessment of the role of inheritance in sleep apnea syndrome. Am J Respir Crit Care Med 1995;151:688–91. 12. Redline S, Leitner J, Arnold J, Tishler PV, Altose MD. Ventilatory-control abnormalities in familial sleep apnea. Am J Respir Crit Care Med 1997;156:155–60. 13. Redline S, Tosteson T, Tishler PV, Carskadon MA, Millman RP. Studies in the genetics of obstructive sleep apnea. Familial aggregation of symptoms associated with sleep-related breathing disturbances [published erratum appears in Am Rev Respir Dis 1992;145(4 Pt 1):979]. Am Rev Respir Dis 1992;145:440–4. 14. Guilleminault C, Partinen M, Hollman K, Powell N, Stoohs R. Familial aggregates in obstructive sleep apnea syndrome. Chest 1995;107:1545–51. 15. Pillar G, Schnall RP, Peled N, Oliven A, Lavie P. Impaired respiratory response to resistive loading during sleep in healthy offspring of patients with obstructive sleep apnea. Am J Respir Crit Care Med 1997;155:1602–8. 16. Burwell CS, Robin ED, Whaley R, Bickelmann AG. Extreme obesity associated with alveolar hypoventilation. A Pickwickian syndrome. Am J Med 1956;21:811. 17. Powell NB, Guilleminault C, Riley RW. Principles and Practice of Sleep Medicine. Philadelphia: WB Saunders Company, 1994:706–21. 18. Remmers JE, deGroot WJ, Sauerland EK, Anch AM. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol 1978;44:931–8. 19. Schwab RJ, Gefter WB, Hoffman EA, Gupta KB, Pack AI. Dynamic upper airway imaging during awake respiration in normal subjects and patients with sleep-disordered breathing. Am Rev Respir Dis 1993;148:1385–400.

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31. Berthon-Jones M, Sullivan CE. Ventilation and arousal responses to hypoxia in sleeping humans. Am Rev Respir Dis 1982;125:632–9. 32. Douglas NJ, White DP, Weil JV, Pickett CK, Zwillich CW. Hypercapnic ventilatory response in sleeping adults. Am Rev Respir Dis 1982;126:758–62. 33. Rivlin J, Hoffstein V, Kalbfleisch J, McNicholas W, Zamel N, Bryan AC. Upper airway morphology in patients with idiopathic obstructive sleep apnea. Am Rev Respir Dis 1984;129:355–60. 34. Horner RL, Mohiaddin RH, Lowell DG et al. Sites and sizes of fat deposits around the pharynx in obese patients with obstructive sleep apnoea and weight matched controls. Eur Respir J 1989;2:613–22. 35. Shelton KE, Gay SB, Hollowell DE, Woodson H, Suratt PM. Mandible enclosure of upper airway and weight in obstructive sleep apnea. Am Rev Respir Dis 1993;148:195–200. 36. Shelton KE, Woodson H, Gay S, Suratt PM. Pharyngeal fat in obstructive sleep apnea. Am Rev Respir Dis 1993;148:462–6. 37. Stauffer JL, Buick MK, Bixler EO et al. Morphology of the uvula in obstructive sleep apnea. Am Rev Respir Dis 1989;140:724–8. 38. Schwab RJ, Gupta KB, Gefter WB, Metzger LJ, Hoffman EA, Pack AI. Upper airway and soft tissue anatomy in normal subjects and patients with sleep-disordered breathing. Significance of the lateral pharyngeal walls. Am J Respir Crit Care Med 1995;152: 1673–89. 39. Listerud J, Lenkinski RE, Axel L, Roberts M. Hydrogen ultrathin phase-encoded spectroscopy (HUPSPEC). Magnet Reson Imag 1990;14:507–21. 40. Schwab RJ, Prasad A, Gupta KB et al. Fat and water measurements of the upper airway soft tissues in normal subjects and patients with sleep-disordered breathing using magnetic resonance proton spectroscopy. Am Rev Respir Dis 1991;145:A214 (abstract). 41. Bradley TD, Brown IG, Grossman RF et al.

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42.

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Obstructive sleep apnea: the syndrome Pharyngeal size in snorers, nonsnorers, and patients with obstructive sleep apnea. N Engl J Med 1986;315:1327–31. Rubinstein I, Colapinto N, Rotstein LE, Brown IG, Hoffstein V. Improvement in upper airway function after weight loss in patients with obstructive sleep apnea. Am Rev Respir Dis 1988;138:1192–5. Rubinstein I, Hoffstein V, Bradley TD. Lung volume-related changes in the pharyngeal area of obese females with and without obstructive sleep apnoea. Eur Respir J 1989;2:344–51. Enzi G, Baggio B, Vianello A et al. Respiratory disturbances in visceral obesity. Int J Obes 1990;14:26. Muls E, Vryens C, Michels A et al. The effects of abdominal fat distribution measured by computed tomography on the respiratory system in non-smoking obese women. Int J Obes 1990;14:136. Dempsey JA, Reddan W, Balke B et al. Work capacity determinants and physiologic cost of weight-supported breathing in obesity. J Appl Physiol 1966;21:1815–20. Don HG, Crain DB, Wahbo WM et al. The measurement of gas trapped in the lungs at functional residual capacity and the effects of posture. Anesthesiology 1971;35:582–90. Holley HS, Milic-Emili J, Becklake MR et al. Regional distribution of pulmonary ventilation and perfusion in obesity. J Clin Invest 1967;46:475–81. Katz I, Stradling J, Slutsky AS, Zamel N, Hoffstein V. Do patients with obstructive sleep apnea have thick necks? Am Rev Respir Dis 1990;141:1228–31. Pressman MR, Meyer TJ, Kendrick-Mohamed J, Figueroa WG, Greenspon LW, Peterson DD. Night terrors in an adult precipitated by sleep apnea. Sleep 1995;18:773–5. Ferguson KA, Ono T, Lowe AA, Ryan CF, Fleetham JA. The relationship between obesity and craniofacial structure in obstructive sleep apnea. Chest 1995;108:375–81.

52. Shepard JWJ, Gefter WB, Guilleminault C et al. Evaluation of the upper airway in patients with obstructive sleep apnea. Sleep 1991;14:361–71. 53. deBerry-Borowiecki B, Kukwa A, Blanks RH. Cephalometric analysis for diagnosis and treatment of obstructive sleep apnea. Laryngoscope 1988;98:226–34. 54. Bacon WH, Krieger J, Turlot JC, Stierle JL. Craniofacial characteristics in patients with obstructive sleep apnea syndrome. Cleft Palate J 1988;25:374–8. 55. Strelzow VV, Blanks RH, Basile A, Strelzow AE. Cephalometric airway analysis in obstructive sleep apnea syndrome. Laryngoscope 1988;98:1149–58. 56. Partinen M, Guilleminault C, Quera-Salva MA, Jamieson A. Obstructive sleep apnea and cephalometric roentgenograms. The role of anatomic upper airway abnormalities in the definition of abnormal breathing during sleep. Chest 1988;93:1199–205. 57. Davies RJ, Ali NJ, Stradling JR. Neck circumference and other clinical features in the diagnosis of the obstructive sleep apnoea syndrome. Thorax 1992;47:101–5. 58. Grunstein R, Wilcox I, Yang TS, Gould Y, Hedner J. Snoring and sleep apnoea in men: association with central obesity and hypertension. Int J Obes Relat Metab Disord 1993;17:533–40. 59. Davies RJ, Stradling JR. The relationship between neck circumference, radiographic pharyngeal anatomy, and the obstructive sleep apnoea syndrome. Eur Respir J 1990;3:509–14. 60. Colt HG, Haas H, Rich GB. Hypoxemia vs sleep fragmentation as cause of excessive daytime sleepiness in obstructive sleep apnea. Chest 1991;100:1542–8. 61. Findley LJ, Unverzagt ME, Suratt PM. Automobile accidents involving patients with obstructive sleep apnea. Am Rev Respir Dis 1988;138:337–40. 62. Young T, Blustein J, Finn L, Palta M. Sleepdisordered breathing and motor vehicle

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accidents in a population-based sample of employed adults. Sleep 1997;20:608–13. Guilleminault C, Connolly S, Winkle R, Melvin K, Tilkian A. Cyclical variation of the heart rate in sleep apnoea syndrome. Mechanisms, and usefulness of 24 h electrocardiography as a screening technique. Lancet 1984;1:126–31. Miller WP. Cardiac arrhythmias and conduction disturbances in the sleep apnea syndrome. Prevalence and significance. Am J Med 1982;73:317–21. Guilleminault C, Connolly SJ, Winkle RA. Cardiac arrhythmia and conduction disturbances during sleep in 400 patients with sleep apnea syndrome. Am J Cardiol 1983;52:490–4. Shepard JWJ, Garrison MW, Grither DA, Dolan GF. Relationship of ventricular ectopy to oxyhemoglobin desaturation in patients with obstructive sleep apnea. Chest 1985;88:335–40. Vincken W, Guilleminault C, Silvestri L, Cosio M, Grassino A. Inspiratory muscle activity as a trigger causing the airways to open in obstructive sleep apnea. Am Rev Respir Dis 1987;135:372–7. Gleeson K, Zwillich CW, White DP. The influence of increasing ventilatory effort on arousal from sleep. Am Rev Respir Dis 1990;142:295–300. Guilleminault C, Stoohs R, Clerk A, Cetel M, Maistros P. A cause of excessive daytime sleepiness: the upper airway resistance syndrome. Chest 1993;104:781–7. Loube DI, Gay PC, Strohl KP, Pack AI, White DP, Collop NA. Indications for positive airway pressure treatment of adult obstructive sleep apnea patients: a consensus statement. Chest 1999;115:863–6. Hung J, Whitford EG, Parsons RW, Hillman DR. Association of sleep apnoea with myocardial infarction in men. Lancet 1990;336:261–4. Partinen M, Guilleminault C. Daytime sleepiness and vascular morbidity at seven-

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year follow-up in obstructive sleep apnea patients. Chest 1990;97:27–32. Young T, Peppard P, Palta M et al. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med 1997;157:1746–52. He J, Kryger MH, Zorick FJ, Conway W, Roth T. Mortality and apnea index in obstructive sleep apnea. Experience in 385 male patients. Chest 1988;94:9–14. Bokinsky G, Miller M, Ault K, Husband P, Mitchell J. Spontaneous platelet activation and aggregation during obstructive sleep apnea and its response to therapy with nasal continuous positive airway pressure. A preliminary investigation. Chest 1995;108:625–30. Rangemark C, Hedner JA, Carlson JT, Gleerup G, Winther K. Platelet function and fibrinolytic activity in hypertensive and normotensive sleep apnea patients. Sleep 1995;18:188–94. Eisensehr I, Ehrenberg BL, Noachtar S et al. Platelet activation, epinephrine, and blood pressure in obstructive sleep apnea syndrome. Neurology 1998;51:188–95. The International Classification of Sleep Disorders: Diagnostic and Coding Manual. Rochester: American Sleep Disorders Association, 1990. Kribbs NB, Getsy JE, Dinges DF. Investigation and management of daytime sleepiness in sleep apnea. In: Saunders NA, Sullivan CE, eds. Sleeping and Breathing. New York: Marcel Dekker, 1993:575–604. Walsleben JA. The measurement of daytime wakefulness. Chest 1992;101:890–1. Wedderburn AA. Sleeping on the job: the use of anecdotes for recording rare but serious events. Ergonomics 1987;30:1229–33. Hoffstein V, Szalai JP. Predictive value of clinical features in diagnosing obstructive sleep apnea. Sleep 1993;16:118–22. Viner S, Szalai JP, Hoffstein V. Are history and physical examination a good screening test for sleep apnea? Ann Intern Med 1991;115:356–9.

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Obstructive sleep apnea: the syndrome

84. Kapuniai LE, Andrew DJ, Crowell DH, Pearce JW. Identifying sleep apnea from selfreports. Sleep 1988;11:430–6. 85. Gyulay S, Olson LG, Hensley MJ, King MT, Allen KM, Saunders NA. A comparison of clinical assessment and home oximetry in the diagnosis of obstructive sleep apnea. Am Rev Respir Dis 1993;147:50–3. 86. Crocker BD, Olson LG, Saunders NA et al. Estimation of the probability of disturbed breathing during sleep before a sleep study. Am Rev Respir Dis 1990;142:14–18. 87. Flemons WW, Whitelaw WA, Brant R, Remmers JE. Likelihood ratios for a sleep apnea clinical prediction rule. Am J Respir Crit Care Med 1994;150:1279–85. 88. Kushida CA, Efron B, Guilleminault C. A predictive morphometric model for the obstructive sleep apnea syndrome. Ann Intern Med 1997;127:581–7.

89. Burrows B, Strauss RH, Niden AH. Chronic obstructive lung disease: 3. Interrelationships of pulmonary function data. Am Rev Respir Dis 1965;91:861. 90. Harvey RM, Enson Y, Ferrer MI. A reconsideration of the origins of pulmonary hypertension. Chest 1971;59:82. 91. Enson Y, Giuntini C, Lewis ML et al. The influence of hydrogen ion concentration and hypoxia on the pulmonary circulation. J Clin Invest 1964;43:1146. 92. Enson Y, Thomas HMI, Bosken CH et al. Pulmonary hypertension in interstitial lung disease: relation of vascular resistance to abnormal lung structure. Trans Assoc Am Physicians 1975;88:248. 93. Ungerer RG, Tahskin DP, Furst D et al. Prevalence and clinical correlates of pulmonary arterial hypertension in progressive systemic sclerosis. Am J Med 1983;75:65.

2 Non-apneic causes of excessive daytime sleepiness Mark W Mahowald

Introduction There is a tendency to equate the complaint of excessive daytime sleepiness (EDS) with the diagnosis of obstructive sleep apnea (OSA). In fact, OSA is only one of many causes of EDS, and often coexists with and may serve to confound other primary sleep disorders. This is important to recognize, as asymptomatic or coincidental OSA may be identified in patients with other causes of EDS, and may serve to mislead the sleep clinician, resulting in an erroneous diagnosis and ineffective treatment recommendations. Although clinically significant OSA may affect 2–4% of the adult population, observed, but possibly clinically insignificant or confounding OSA may be present in up to 9% of women and 24% of men.1 This means that at least 9–24% of patients who complain of EDS due to other causes will be found to have some degree of OSA upon formal evaluation. However, that degree of OSA may not be sufficient to explain the EDS. The presence of OSA on a sleep study performed on a patient complaining of EDS does not automatically establish cause and effect. It is the sleep professional’s responsibility to determine whether the degree of apnea identified is sufficient to

Case example 1 A 61-year-old, 1.73-m-tall, 158-lb school administrator was evaluated for a long history of severe excessive daytime sleepiness. He had none of the ancillary symptoms of narcolepsy. Polysomnography (PSG) revealed a respiratory disturbance index (RDI) of 22/h, with lowest hemoglobin oxygen saturation of 91%. The obstructive sleep apnea responded nicely to nasal continuous positive airway pressure (CPAP) 7 cm H2O pressure, with no clinical improvement. A repeat sleep study, while using nasal CPAP, confirmed CPAP effectiveness. A multiple sleep latency test (MSLT) the next day revealed a mean sleep latency of 3.0 min, with REM sleep on none of the naps. The true cause of his EDS was longstanding monosymptomatic narcolepsy or idiopathic central nervous system (CNS) hypersomnia, with coincidental OSA. In retrospect, his mild OSA was clearly an inadequate explanation for his longstanding, severe EDS. He responded well to stimulant medication.

22

Non-apneic causes of excessive daytime sleepiness

explain the severity of the patient’s EDS complaint, or whether the apnea is coincidental or contributory to another underlying cause of EDS, such as sleep deprivation or one of the many other medical causes of EDS.

Excessive daytime sleepiness—prevalence and consequences The prevalence of EDS is between 0.3% and 31%.2–5 The complaint of EDS should be taken very seriously, as there are serious consequences, including impaired psychosocial functioning, accidents, reduced work/school performance, and economic and public health consequences.4,6 As more data become available, state and national transportation and labor officials are appropriately becoming more interested in and concerned with the true consequences of EDS in the workplace and behind the wheel. Private and commercial vehicle crashes are frequently due to sleepiness. Factors involved include: sleep deprivation, underlying sleep disorders, duration of drive, and circadian rhythm influences. For the driver, there is a striking and distressing lack of awareness of the precursors to falling asleep.7–9 It is likely that the true incidence of fall-asleep motor vehicle crashes is far greater than reported.10 To add perspective, one full night of sleep deprivation is as impairing for driving as a legally intoxicating blood alcohol level.11 True EDS is always the manifestation of underlying physiologic sleepiness, and, contrary to popular opinion, is rarely, if ever, due to psychological or psychiatric conditions such as depression, laziness, boredom, workavoidance behavior, or other character defects.

In the absence of sleep deprivation, daytime hypersomnia is almost inevitably due to an identifiable and treatable sleep disorder such as sleep apnea, narcolepsy, or idiopathic CNS hypersomnia. Regrettably, despite the high prevalence and dire personal, societal and socio-economic consequences of EDS, a sleep history is routinely ignored in medical practice.12

Evaluation of EDS Evaluation of sleep physiology Polysomnography (PSG)

The technology used for the physiologic diagnosis of sleep disorders employs standard electrophysiologic recording systems and is thoroughly discussed in Chapter 4. Actigraphy

Analysis of sleep diaries may be insufficient to verify a tentative diagnosis in patients with reported insomnia or suspected wake–sleep cycle abnormalities. In such cases, definitive objective data may be obtained by actigraphy, a recently developed technique to record activity during wake and sleep that supplements the subjective sleep log. An actigraph is a small wrist-mounted device which records the activity plotted against time, usually for a week or two. When data collection has been completed, the results are transferred into a personal computer, where software displays activity versus time, demonstrating the rest–activity pattern at a glance. There is direct correlation between the rest–activity recorded by the actigraph and the wake–sleep pattern as determined by PSG.13 Indications for the use of actigraphy include: insomnia, wake–sleep

Evaluation of EDS schedule disorders, and monitoring treatment progress.14,15

Evaluation of daytime alertness–sleepiness Subjective (Sleepiness scales)

Subjective introspective alertness–sleepiness scales such as the Stanford Sleepiness Scale and the Epworth Sleepiness Scale (ESS) have been developed.16,17 The ESS is frequently used as a screening tool for identifying excessive daytime sleepiness, and generally correlates with other measures of sleep propensity.18,19 It must be remembered that such instruments are limited by their lack of sensitivity: there may be a striking discrepancy between the selfperceived sleepiness and the underlying true physiologic sleepiness in a given individual.20,21 In one study, neither patient nor partner ESS ratings were strong predictors of the degree of sleep apnea severity.22 Subjective sleepiness scales may be an inaccurate surrogate for true daytime sleepiness.

23

in quantifying daytime sleepiness and in differentiating the subjective complaints of ‘sleepiness’, ‘tiredness’ and ‘fatigue’. Single nap studies are inadequate, and MSLTs must always be preceded by a formal PSG to document the quality and quantity of sleep immediately preceding the MSLT. In difficult cases, it may be helpful to have 1 week of sleep diaries or actigraphic monitoring preceding the PSG/MSLT to ensure adequate sleep prior to the studies. (See case example 2). It must be remembered that falsely negative MSLTs can and do occur, and that there may be a discrepancy between the subjective complaint of sleepiness and the results of the MSLT.27,28 Stating that a patient does not have EDS on the basis of a ‘normal’ MSLT is analogous to stating that a patient with chest pain does not have cardiac disease on the basis of a normal EKG. Importantly, REM sleep may also occur in subjects with no complaints of excessive daytime sleepiness.29 Clearly, the PSG/MSLT results must be interpreted in light of the entire clinical setting. Maintenance of Wakefulness Test

Objective

Numerous methods have been developed to measure physiologic sleepiness during the waking period.23 Multiple Sleep Latency Test

The MSLT is discussed elsewhere in Chapter 4. Many factors can affect sleep latency during the daytime: prior sleep deprivation, sleep continuity, age, time of day, and medication.24–26 Proper interpretation requires a PSG the preceding night to measure the quality and quantity of sleep obtained immediately prior to the MSLT. The MSLT is a most useful tool

The maintenance of wakefulness test (MWT) is a variation of the MSLT. Unlike during the MSLT, the subject during the MWT is asked to resist sleep while sitting in a chair, rather than asked to fall asleep while lying in bed.30 The MWT appears to offer no specific advantage over the MSLT.31 Alpha Attenuation Test

This is a recently described technique to evaluate daytime sleepiness, based upon the fact that EEG power in the alpha frequency range decreases with eyes closed. The ratio of mean eyes-closed to mean eyes-open alpha power

24

Non-apneic causes of excessive daytime sleepiness

during seated wakefulness is smaller in sleepy subjects.32 Acceptance of this procedure will depend upon more extensive validation studies.

limitations, and, as with many other tests in medicine, the results of either must be interpreted in light of the specific clinical situation.19,34

Pupillography

Static pupillography is based on the fact that the pupils constrict during sleep. The rate of pupillary constriction is determined, and is felt to reflect the degree of underlying sleepiness.33 Pupillography is used infrequently in the evaluation of EDS, as it may be difficult to perform and interpret, and gives no indication as to the cause of the sleepiness. It is clear that all currently available subjective and objective measures of sleepiness have

Case example 2 An 18-year-old female with a remote history of severe depression had undergone two formal sleep studies for the complaint of severe EDS which was destroying her high school career. The first revealed a normal PSG, followed by an MSLT with a very short sleep latency (<< 5 min) and REM sleep on multiple naps. The second (an MSLT not preceded by PSG) was identical. She was treated with stimulant medication, with no benefit. Because her high school was threatening to expel her due to her EDS, she was referred for a second opinion. Owing to the complexity of the history, the initial consultation was with both neurologist and psychiatrist sleep specialists, and was preceded by 2 weeks of actigraphic recording which revealed an extraordinary total sleep time (10–12 h). There was absolutely no evidence of ongoing psychiatric disease. She underwent two

Causes of excessive daytime sleepiness Sleep deprivation By far, the most common cause of EDS in our society is chronic sleep deprivation. We sleep 25% less that our forefathers one century ago.

consecutive PSG studies, each followed by an MSLT. She was allowed to awaken spontaneously (in the afternoon). The first PSG was remarkable only for a total sleep time of 11.5 h with a sleep efficiency of 92%. The next night’s PSG revealed a total sleep time of 12.5 h with a sleep efficiency of 94%. The first MSLT showed a mean sleep latency of 17 min, and the second 20 min, with no REM sleep on any nap during either MSLT. Urine toxicology screens performed on each PSG night were negative. In retrospect, the correct diagnosis was chronic severe sleep deprivation in a patient with an extraordinary sleep requirement. The falsely positive MSLTs performed elsewhere reflected the fact that the patient was awakened prematurely, for the convenience of the laboratory staff, and therefore the MSLT was actually performed during the second half of the patient’s normal sleep period, yielding the expected very brief sleep latencies and the appearance of REM sleep on multiple naps.

Causes of excessive daytime sleepiness There is no evidence that they required more sleep than we do, and nor is there any reason to believe that we require less sleep than them. This sleep deprivation is volitional, often driven by social or economic factors. For instance, approximately 20% of workers in industrialized countries do shiftwork, and it has been shown that night shift workers obtain, on the average, 8 h less sleep per week than day workers.35,36 That amounts to the loss of an entire night’s sleep, every week. The growing availability of 24-h businesses and stock markets, all-night television, E-mail and the internet encourages sleep deprivation. Sufficient sleep is not measured in terms of absolute hours of sleep obtained, but rather by the ability to achieve enough sleep to awaken rested and restored. The total geneticallydetermined sleep requirement for some individuals is 10 h nightly. Therefore, those 10 h sleepers who receive 8 h of sleep nightly may become severely sleep deprived, and therefore severely hypersomnolent. An important concept is that sleep deprivation is cumulative. One does not ‘get used to it’, nor does sleep deprivation-induced sleepiness diminish without make-up sleep.37 Sleep deprivation can easily masquerade as a primary sleep disorder, both clinically and by formal sleep studies.

Sleep-disordered breathing Sleep-disordered breathing takes many different forms, including: obstructive sleep apnea, central sleep apnea, and Cheyne–Stokes respiration, and is thoroughly discussed elsewhere in this volume. The high prevalence of sleepdisordered breathing indicates that it will often coexist with other underlying causes of EDS.

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Narcolepsy Narcolepsy is a relatively frequent disorder, with a prevalence of 0.09%, affecting at least 250 000 Americans. The prevalence approximates that of Parkinson’s disease and multiple sclerosis. There is a clear genetic component, with over 90% of individuals with narcolepsy carrying the HLA-DR2/DQ1 (under current nomenclature, HLA-DR15 and HLA-DQ6) gene (found in less than 30% of the general population).38 This association is present in the different ethnic populations to varying degrees, and represents the highest disease–HLA linkage known in medicine. Clearly, there is a genetic component; however, that component is neither necessary, nor sufficient, to cause narcolepsy. It has been shown that a neuropeptide, hypocretin (also called orexin), is involved in the canine model and in human patients with narcolepsy. Hypocretin-containing neurons are confined to the lateral hypothalamus and project widely throughout the central nervous system. Hypocretin deficiency appears to play a major role in human narcolepsy. Further research will likely result in important diagnostic and therapeutic advances.39–41 The usual age of onset is adolescence or early adulthood, although it ranges from early childhood to senescence (3–72 years of age). There appears to be a bimodal age of onset, with the major peak appearing about age 15, with a secondary peak at 36 years of age. After a relatively brief period of progression as the disease declares itself, it tends to stabilize, but rarely, if ever, completely remits.42,43 EDS is the primary symptom of narcolepsy. There are unwanted or unanticipated sleep episodes which last seconds to minutes and occur at inappropriate times, particularly during periods of reduced environmental stimulation, such as reading, watching television, riding in or driving a motor vehicle, or

26

Non-apneic causes of excessive daytime sleepiness

during classes or meetings. Such feelings of sleepiness are often dramatically, but briefly, reversed by a brief nap. Patients with narcolepsy often complain of memory impairment. This is not due to memory impairment per se, but to the adverse effects of impaired alertness on complex cognitive tasks.44 Aggressive treatment is in order, as the psychosocial and socio-economic consequences of 45,46 narcolepsy are significant. Ancillary symptoms include: cataplexy, hypnagogic hallucinations, and sleep paralysis. Cataplexy occurs in 65–70% of patients with narcolepsy, and is the sudden loss of muscle tone, typically triggered by emotion, such as laughter, anger, excitement, delight, or surprise. Although the muscle weakness of cataplexy may occasionally be complete, resulting in falling down, or being forced to sit, it is more commonly milder and more focal in nature, taking the form of facial sagging, slurred speech, more localized weakness of an extremity, or the feeling that one’s knees may ‘give way’. That cataplexy is simply the inappropriate and isolated intrusion of REM sleep-associated atonia into wakefulness is supported by animal studies.47 Cataplexy may never occur in 30% of patients with narcolepsy. In many people with narcolepsy, the hypersomnia precedes the appearance of the ancillary symptoms, often by decades.48,49 Clearly, the absence of a history of cataplexy in no way rules out the diagnosis of narcolepsy. Rarely, cataplexy or cataplexy-like events may occur in the absence of narcolepsy. Isolated cataplexy may be familial, and is not associated with any of the other clinical or PSG/MSLT features of narcolepsy.50–53 Sleep paralysis is experienced by up to 60% of patients with narcolepsy and consists of totalbody paralysis, with sparing of respiration and eye movements. It lasts from seconds to minutes and is often very frightening to the patient. Sleep

paralysis simply represents the persistence of REM sleep atonia into wakefulness and is extremely common in non-narcoleptics, occurring in over one-third of the general population. It may be familial, and is more common in the setting of sleep deprivation.54–60 When occurring in isolation, it may lead to erroneous diagnoses such as cardiac disease, seizures, or unwarranted psychiatric diagnoses.61 Hypnagogic (at sleep onset) and hypnopompic (upon awakening) hallucinations are seen in 12–50% of cases. These hallucinations are extremely vivid, often frightening dreams which occur during the transition between wakefulness and sleep. They may be associated with total-body paralysis and the sensations of oppression and dread. As with sleep paralysis, such sleep-onset and sleep-offset hallucinatory phenomena are quite common in the nonnarcoleptic population, and may be combined with sleep paralysis (often referred to as the ‘old hag phenomenon’).62–66 Prominent waking hallucinations in patients with narcolepsy have led to erroneous psychiatric diagnoses.67,68 Notably, fewer than half (14–42%) of people with narcolepsy will report all four symptoms of sleep attacks, cataplexy, hypnagogic hallucinations, and sleep paralysis. Automatic behavior occurs in as many as 80% of patients with narcolepsy, and represents the simultaneous or rapidly oscillating occurrence of wake and sleep, during which the individual appears to be awake, but without full awareness. Such spells may result in extremely inappropriate behaviors, and may result in an erroneous diagnosis of partial complex seizures or psychogenic dissociative (fugue) states.69 The underlying pathophysiology of narcolepsy results in impaired control of the boundaries that normally separate the states of wakefulness from REM and non-REM sleep.70 The total sleep time per 24 h in people with

Causes of excessive daytime sleepiness narcolepsy is similar to that in those without narcolepsy.71 However, the control of the onset/offset of both REM and non-REM sleep is impaired. Both the night-time sleep fragmentation and intrusion of sleep into daytime wakefulness may be due to a decreased amplitude of a circadian arousal system.72 Moreover, there is a clear dissociation of various components of the individual wake and sleep states. Cataplexy and sleep paralysis simply represent the isolated and inappropriate intrusion or persistence of REM sleep-related atonia (paralysis) into wakefulness. The hypnagogic or hypnopompic hallucinations are (REM sleep-related) dreams occurring during wakefulness.38 Neuropathological studies in human narcolepsy have revealed a striking reduction in the hypocretin neurons in the lateral hypothalamus. The presence of gliosis in that region suggests an acquired degenerative process, possibly immune-mediated.73 The overwhelming percentage of cases are ‘idiopathic’; however, rare cases of ‘symptomatic’ narcolepsy have been described in patients with associated abnormalities of the diencephalic, hypothalamic or pontine regions of the brain.74 Basal forebrain abnormalities have been reported in canine narcolepsy.75 The diagnosis of narcolepsy may be suspected by history. Although it has been said that the report of cataplexy is pathognomonic of narcolepsy, that is not necessarily the case. A history of ‘classic’ narcolepsy with cataplexy may be the manifestation of a somatoform disorder.76 In view of the nature and duration of treatment with stimulant medications, objective sleep laboratory diagnosis is imperative. Formal sleep studies in narcolepsy include both PSG and MSLT. An all-night PSG must be performed the night before the MSLT to determine the quality and quantity of the preceding night’s sleep. On the MSLT, patients with

27

narcolepsy typically fall asleep in 5 min or less and usually display REM sleep on at least two of the daytime naps, an occurrence rarely seen in normals. The MSLT results must be interpreted in light of the patient’s clinical symptoms and in view of the results of the preceding night’s PSG. In one large study, the combination of a mean latency of less than 5 min and REM sleep on two or more naps had a specificity of 97% for narcolepsy, but the sensitivity was only 70%, meaning that 30% of individuals with those MSLT values did not have narcolepsy.34 Conversely, a ‘negative’ MSLT (or MWT) does not absolutely rule out the possibility of narcolepsy. False-negative MSLTs do occur.77,78 False-positive MSLTs may occur in the setting of prior severe sleep deprivation or in the setting of withdrawal of REM sleepsuppressing agents, such as stimulants (methylphenidate, dexedrine, or cocaine), alcohol, or tricyclic antidepressants. REM sleep may occur on MSLTs in the absence of narcolepsy in patients with myotonic dystrophy, the Prader–Willi syndrome,79–81 or hyperkalemic periodic paralysis.82 To date, there is no reliable objective measure of the compliance with or response to stimulant medication in patients with narcolepsy.83 The response must be evaluated by the patient’s subjective report. The recent discovery of the association between narcolepsy and HLA type is of intense scientific interest and research value; however, the variability of the presence of HLA associations in the general public and in patients with narcolepsy precludes its utility as a diagnostic test.84,85 The associated HLA type is neither necessary nor sufficient for the appearance of narcolepsy. The occurrence of symptomatic narcolepsy due to identifiable CNS abnormalities is extraordinarily rare: further neurologic studies are indicated only in cases in which the history or

28

Non-apneic causes of excessive daytime sleepiness

neurologic examination strongly suggest structural CNS pathology. Stimulant medications such as mazindol, methylphenidate, methamphetamine, dexedrine or modafinil are used to control the hypersomnia. (The recent announcement by the manufacturer of pemoline regarding hepatic necrosis limits its utility.) These stimulants all appear to increase presynaptic activation of dopamine.86 No pharmacokinetic studies have been performed, rendering stated ‘maximum doses’

Case example 3 A 49-year-old home economics teacher was initially evaluated at age 40 for the complaint of EDS associated with cataplexy, hypnagogic hallucinations and sleep paralysis, and had a normal PSG with total sleep time of nearly 9 h and a sleep efficiency of 97%. Snoring, but no sleep-disordered breathing, was present. The MSLT on the following day revealed a mean sleep latency of 9 min, with REM sleep on none of the naps. The patient was treated with stimulant medication with excellent results for 7 years, after which time the hypersomnia gradually recurred. In the interim, she had gained only 10lb, but had undergone menopause. A repeat PSG revealed prominent OSA with an RDI of 51/h, lowest hemoglobin oxygen saturation = 72%, which responded nicely to nasal CPAP. The worsening of symptoms in a patient with EDS previously responsive to treatment should always raise the possibility of the interval development of an additional disorder of EDS, rather than the assumption that the previously diagnosed condition has worsened.

arbitrary and without scientific basis. Many practitioners will titrate the medications to maximally control the symptoms.73 The abuse potential for these agents in the bona fide patient populations for which they are therapeutic has been greatly overrated, as have the cardiovascular and psychiatric consequences.73,83,87–89 Treatment of the ancillary symptoms includes tricyclic antidepressants, serotonin-specific reuptake inhibitors, and ␥-hydroxybutyrate (currently not available in the USA).43

Idiopathic central nervous system hypersomnia Idiopathic CNS hypersomnia may represent a number of different conditions which present as unexplained EDS. This condition is characterized by EDS in the absence of sleep deprivation or other identifiable abnormality during sleep, such as obstructive sleep apnea.90–92 In some cases, the total sleep requirement may be extraordinary, underscoring the heterogeneity of this condition.93 The pathophysiology is unknown. The diagnosis may be suspected by the history of unexplained EDS in the absence of symptoms suggestive of OSA, narcolepsy, or sleep deprivation. Formal studies are mandatory to confirm the absence of unsuspected sleep-related pathologies and to confirm the subjective complaint of EDS. Chronic sleep deprivation must be aggressively ruled out as an explanation for EDS (case example 2). As with narcolepsy, the treatment implications (stimulant medications indefinitely) require formal, objective diagnosis. Bedtime administration of stimulants in some patients with idiopathic CNS hypersommia may make morning awakening easier, without disturbing night-time sleep.94

Causes of excessive daytime sleepiness In idiopathic CNS hypersomnia, the allnight PSG is unremarkable, and the MSLT reveals objective hypersomnia, usually without the occurrence of REM sleep during the naps.90 HLA studies are not indicated. Neuroimaging studies are not indicated in the absence of clinical or neurologic examination findings suggestive of structural CNS abnormalities. It is becoming clear that there is great overlap of symptoms and confusion in establishing a diagnosis between narcolepsy and idiopathic CNS hypersomnia.95,96 A number of patients with narcolepsy and cataplexy may not demonstrate REM sleep on the MSLT, and, conversely, some with idiopathic CNS hypersomnia without cataplexy may have REM sleep on the MSLT. One practical proposed classification is:97 1. Narcolepsy with cataplexy (with or without REM sleep in the MSLT). 2. Hypersomnia without cataplexy (a) with REM sleep on the MSLT (b) without REM sleep on the MSLT.

Sleep inertia/sleep drunkenness upon awakening Sleep inertia refers to a period of impaired performance and reduced vigilance following awakening from the regular sleep episode or from a nap. Some individuals experience a protracted period of confusion and disorientation upon awakening, and may even become hostile or abusive upon vigorous awakening attempts. This impairment may be severe, last from minutes to hours, and be accompanied by polygraphically recorded microsleep episodes.98–100 Recent studies have clearly proven that sleep inertia is a potent phenomenon, resulting in impaired performance and

29

vigilance, averaging 1 h, and requiring 2–4 h to dissipate, in normal, non-sleep-deprived individuals, and is worse following sleep deprivation, one of the known triggers for sleepwalking.101–103 Basic science support of a gradual disengagement from sleep to wakefulness comes from neurophysiologic studies in animals104 and cerebral bloodflow studies in humans.105–107 The persistent reduction, lasting minutes, of the photomyoclonic response upon awakening from non-REM sleep is further confirmation of a less than immediate transition from sleep to wakefulness.108 Impaired performance during the transition from sleep to wakefulness has important implications for rapid decision-making upon forced awakenings (such as a middle-of-the-night telephone call) and for performance following scheduled naps in the workplace.109 There appears to be great interindividual variability in the extent and duration of sleep inertia, both following spontaneous awakening after the major sleep period, and following naps. Sleep inertia may be thought of as the ‘confusional arousal’ potential in all of us, and it may be that disorders of arousal (sleepwalking and sleep terrors) represent an extreme form of sleep inertia. Although there are no large studies, this condition may improve with protriptyline or stimulant administration before bedtime.110,111

Recurrent hypersomnias This rare complaint may be the manifestation of a number of unusual but fascinating conditions including the following. Kleine–Levin syndrome

The Kleine–Levin syndrome is characterized by periodic hypersomnia lasting days to weeks occurring at intervals of days to years with

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Non-apneic causes of excessive daytime sleepiness

intervening normal wake–sleep function and alertness. The classic form is idiopathic, and seen in adolescent males, but may affect both sexes and all age groups. The periodic hypersomnia may be associated with hyperphagia and hypersexuality, and probably represents recurrent hypothalamic dysfunction. The often cited association with adolescent males and unusual behaviors such as hypersexuality and megaphagia have been overrated: it may occur in females, and not be associated with hyperphagia or hypersexuality.112 This syndrome has been reported following mild head injury. No large-scale treatment studies are available. Stimulant medication has been proposed for the symptomatic period, and lithium has been apparently effective prophylactically. Reported response to medication must be viewed with great caution, given the unpredictability of the natural course of this condition. There is a post-traumatic form which, like the idiopathic form, may respond to lithium.113

Menstrual-related hypersomnia

Menstruation-related periodic hypersomnia, as the name implies, is characterized by recurrent periods of hypersomnia related to menstruation, and may represent a variant of the Kleine–Levin syndrome.114 In one case, the hypersomnia was associated with elevations in the serum prolactin level.115

Idiopathic recurring stupor (IRS)

This fascinating condition was first reported in 1990 by Lugaresi’s group. It is characterized by recurrent episodes of stupor, generally beginning in adulthood. The stupors occur at varying intervals, from multiple times weekly to only a few times a year. The duration of the stupor ranges from hours to a few days. There

is a very characteristic EEG pattern—a widely distributed, non-reactive 13–18-Hz EEG activity which has been present in all reported cases. The clinical and EEG manifestations are promptly, but briefly, reversed by flumazenil, a benzodiazepine antagonist.116 Oral flumazenil, available in Europe, has been used to treat some patients with IRS.117 IRS is possibly due to the action of ‘endozepines,’ which are endogenous ligands for the benzodiazepine recognition sites on ␥aminobutyric acid A receptors in the CNS. Endozepines are naturally occurring, nonpeptide, non-benzodiazepine substances that may play a role in CNS processes such as memory and learning, and in pathologic processes such as panic disorders and hepatic encephalopathy. There is good evidence that a benzodiazepine-like substance plays a role in hepatic encephalopathy.118–120 Other ‘false neurotransmitters’ have also been implicated in hepatic encephalopathy.121 In IRS, cerebrospinal fluid (CSF) endozepine 4 levels were 300 times higher during an episode than in control patients. Endozepine 2 levels were slightly elevated. The fact that elevated levels of endozepine 4 were present in both the CSF and blood indicates that this is a systemic disorder, not confined to the CNS.122 The source of endozepine 4, and why its release is intermittent, are not known. Although there are few cases reported in the literature, IRS is probably much more prevalent than currently thought, with many patients being admitted to intensive care units for stupor of unknown etiology, with the stupor being attributed to an overdose of a drug which was not identified by urine toxicology screen. Related conditions include: (1) endogenous opiate poisoning;123 and (2) hyper-endorphin syndrome in a child with necrotizing encephalomyelopathy.124,125 All these conditions represent fascinating experiments of nature which will serve to teach us much about brain function.

Causes of excessive daytime sleepiness Circadian rhythm disturbances Patients with circadian dysrhythmias may complain of hypersomnia. Those with the advanced sleep phase syndrome experience hypersomnia in the evening, while those with the delayed sleep phase syndrome complain of sleep-onset insomnia and severe hypersomnia in the morning, as they have been awakened during the last portion of their sleep period. Treatment options include chronotherapy, phototherapy, and melatonin.126 Persons with blindness are particularly prone to circadian dysrhythmias, and often experience hypersomnia.127

Periodic limb movement disorder (PLMD) PLMD was formerly known as periodic limb movements (PLMs) of sleep or nocturnal myoclonus. PLMD is characterized by periodic (every 20–40 s) movements of the legs during sleep, usually most prominent during the lighter stages of non-REM sleep.128 These movements may be associated with arousals which are often too brief to be perceived by the individual, and may represent spontaneous Babinski or triple spinal flexion reflexes (positive Babinksi responses are normally present during non-REM sleep).129,130 The terms restless legs syndrome (RLS) and PLMD are often confused and, erroneously, used interchangeably. RLS is a clinical symptom often resulting in severe insomnia, whereas PLMD is a PSG finding, which may or may not have clinical significance.131,132 The reason for the confusion is the fact that the majority (80%) of patients with RLS have the PSG finding of PLMD; however, the converse is not true.133 It should be emphasized that the

31

arousals are often associated with the extremity movements, but are not necessarily caused by the movements.134 The cyclic alternating pattern probably plays a role in the periodicity of the leg movements, and, importantly, the arousal often precedes the extremity movement, indicating that the leg movements do not cause the arousal.135,136 Support for this comes from the fact that L-dopa may selectively attenuate the leg movements, without affecting the EEG evidence of arousal (K-alpha complexes).134 There is evidence that periodic limb movements (PLMs) may be generated by motor pattern generators in the spinal cord, as the movements may persist following complete spinal cord transection or spinal cord lesions.137–142 PLMs may be transiently induced by medication (venlafaxine) or epidural or spinal anesthesia.143,144 Periodic limb movements are common in the general population, increasing with advancing age, and may be completely asymptomatic.145 Periodic limb movements are also common in individuals with narcolepsy.146 There is a growing body of evidence that PLMs, as a PSG observation, are of no clinical significance, and that PLMD may not be a distinct syndrome.131,147,148 PLMD (if it is a disorder) is best diagnosed by formal sleep studies. The final diagnosis of PLMD must involve both clinical symptoms and PSG features. Practice parameters for the treatment of RLS and PLMD have been developed by the American Academy of Sleep Medicine.149,150

Medication–induced hypersomnia Certain medications may cause true hypersomnia. The best studied are the conventional

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Non-apneic causes of excessive daytime sleepiness

sedative-hypnotics such as the barbiturates, benzodiazepines, and newer non-benzodiazepine sedative-hypnotics such as zolpidem, zaleplon, and zopiclone (not available in the USA). Many agents such as tricyclic antidepressants and antihistaminic agents may cause sleepiness, but their ability to improve the quality or quantity of sleep have been poorly studied. Although there is a tendency to attribute EDS to other medications, very few objective studies are available to document that non-sedative-hypnotic medications truly cause hypersomnia (see the review by Obermeyer and Benca151). This is particularly true of the non-barbiturate, non-benzodiazepine anticonvulsant agents.152

Medico-legal issues Excessive sleepiness and driving privileges Although it may seem prudent to legislate driving privileges in drivers with primary sleep disorders, it should be kept in mind that by far the largest number of sleepy drivers are those who are volitionally sleep deprived for social or employment reasons (e.g. shiftworkers), and not those who are sleepy due to underlying specific sleep disorders (such as narcolepsy or obstructive sleep apnea). Persons with sleep disorders such as narcolepsy and sleep apnea have an increased incidence of motor vehicle accidents.153–162 Various agencies and governmental bodies have produced guidelines or regulations stating that some of these individuals are unfit to drive. Some states and countries have enacted specific guidelines and regulations. There is a great deal of variability in these

regulations, and they are not based upon scientific data.163

Duty hours of personnel involved in transportation, healthcare, and other industries Sleep deprivation clearly results in impairment of mood, cognition, and performance.164 One celebrated case of malpractice attributed to sleep deprivation in a house-staff officer has led to widespread reform in the duty hours of physicians in training.165,166 Despite this, the objective data on the consequences of sleep derivation in house officers have been varied.167–178 A surgery simulation study clearly indicates that one should prefer to be operated upon by a well-rested surgeon.179

Evaluation of the complaint of hypersomnia In the absence of obvious sleep deprivation, formal sleep studies are usually indicated in all cases of hypersomnia. A MSLT should be performed in every case in which any identified abnormality on the all-night PSG is not clearly sufficient to explain the extent of the daytime symptoms. OSA and PLMs are very common in the asymptomatic population, and their presence on a PSG must be interpreted in the entire clinical context. Notably, although a given patient may have depression, depression is not an explanation for true excessive daytime sleepiness. Sleep disorders and depression certainly may coexist, and sleepiness may masquerade as or exacerbate depression. Sleep diaries and actigraphy may be invaluable in the setting of recurrent hypersomnia or circadian dysrhythmias.

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104. Horner RL, Sanford LD, Pack AI, Morrison AR. Activation of a distinct arousal state immediately after spontaneous awakening from sleep. Brain Res 1997;778:127–34. 105. Koboyama T, Hori A, Sato T, Mikami T, Yamaki T, Ueda S. Changes in cerebral blood flow velocity in healthy young men during overnight sleep and while awake. EEG Clin Neurophysiol 1997;102:125–31. 106. Balkin TJ, Wesensten NJ, Braun AR et al. Shaking out the cobwebs: changes in regional cerebral blood flow (rCBF) across the first 20 minutes of wakefulness. J Sleep Res 1998;21:411A. 107. Winter WC, Bliwise DL, Quershi AI. Post sleep reduction in cerebral blood flow velocity is independent of preceding REM vs NREM sleep. Sleep 1999;22(suppl):S288 (abstract). 108. Meier-Ewert K, Broughton RJ. Photomyoclonic response of epileptic and non-epileptic subjects during wakefulness, sleep and arousal. EEG Clin Neurophysiol 1967;23:142–51. 109. Sallinen M, Harma M, Akerstedt T, Rosa R, Lillqvist O. Promoting alertness with a short nap during a night shift. J Sleep Res 1998;7:240–7. 110. Schmidt HS, Clark RW, Hyman PR. Protriptyline: an effective agent in the treatment of the narcolepsy–cataplexy syndrome and hypersomnia. Am J Psychiatry 1977;134:183–5. 111. Schenck CH, Penn JR, Garcia J, Mahowald MW. Nocturnal sustained-release stimulant therapy of severe morning sleep inertia. Sleep Res 1996;25:71. 112. Smolik P, Roth B. Kleine–Levin syndrome: etiopathogenesis and treatment. Acta Univ Carol Med Monogr 1988;CXXVIII:1–94. 113. Gill RG, Young JPR, Thomas DJ. Kleine–Levin syndrome: report of two cases with onset of symptoms precipitated by head trauma. Br J Psychiatry 1988;152:410–12. 114. Billiard M, Guilleminault C, Dement WC. A menstruation-linked periodic hypersomnia. Neurology 1975;255:436–43.

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115. Bamford CR. Menstrual-associated sleep disorder: an unusual hypersomniac variant associated with both menstruation and amenorrhea with a possible link to prolactin and meclopropamide. Sleep 1993;16:484–6. 116. Lugaresi E, Montagna P, Tinuper P. Idiopathic recurring stupor. Sleep Res 1993;22:229. 117. Lugaresi E, Montagna P, Tinuper P et al. Endozepine stupor. Recurring stupor linked to endozepine-4 accumulation. Brain 1998;121:127–33. 118. Gyr K, Meier R. Flumazenil in the treatment of portal systemic encephalopathy—an overview. Intens Care Med 1991;17:S39–42. 119. Mullen KD, Mendelson WB, Martin JV, Bassett ML, Jones EA. Could an endogenous benzodiazepine ligand contribute to hepatic encephalopathy? Lancet 1988;I:457–9. 120. Olasmaa M, Guidotti A, Costa E et al. Endogenous benzodiazepines in hepatic encephalopathy. Lancet 1989;I:491–2. 121. Yonekura T, Kamata S, Wasa M, Okada A, Kawata S, Tauri S. Simultaneous analysis of plasma phenethylamine, phenylethanolamine, tyramine and octopamine in patients with hepatic encephalopathy. Clin Chim Acta 1991;199:91–8. 122. Rothstein JD, Guidotti A, Tinuper P et al. Endogenous benzodiazepine receptor ligands in idiopathic recurring stupor. Lancet 1992;340:1002–4. 123. Symons IE, Emson PC, Farman JV. Endogenous opoid poisoning? BMJ 1982;284:469–70. 124. Brandt NJ, Terenius L, Jacobsen BB et al. Hyper-endorphin syndrome in a child with necrotizing encephalomyelopathy. N Engl J Med 1980;303:914–16. 125. Snyder SH. Endorphins in necrotizing encephalomyelopathy. N Engl J Med 1980;303:934–5. 126. Mahowald MW, Ettinger MG. Circadian rhythm disorders. In: Chokroverty S, ed.

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147. Youngstedt SD, Kripke DF, Klauber MR, Sepulveda RS, Mason WJ. Periodic leg movements during sleep and sleep disturbances in elders. J Gerontol 1998;53A:M391–4. 148. Nicolas A, Lesperance P, Montplaisir J. Is excessive daytime sleepiness with periodic leg movements during sleep a specific diagnostic category? Eur Neurol 1998;40:22–6. 149. Chesson JLJ, Wise M, Davilla D et al. Practice parameters for the treatment of restless legs syndrome and periodic limb movement disorder. Sleep 1999;22:961–8. 150. Hening W, Allen R, Earley C, Kushida C, Piccietti D, Silber M. The treatment of restless legs syndrome and periodic limb movement disorder. Sleep 1999;22:970–99. 151. Obermeyer WH, Benca RM. Effects of drugs on sleep. Neurol Clin 1996;14:827–40. 152. Malow BA, Bowes RJ, Lin X. Predictors of sleepiness in epilepsy patients. Sleep 1997;20:1105–10. 153. Haraldsson P-O, Carenfelt C, Tingvall C. Sleep apnea syndrome symptoms and automobile driving in a general population. J Clin Epidemiol 1992;45:821–5. 154. Suratt PM, Findley LJ. Driving with sleep apnea. New Eng J Med 1999;340:881–3. 155. Findley LJ, Weiss JW, Jabour R. Drivers with untreated sleep apnea. A cause of death and serious injury. Arch Intern Med 1991;151:1451–2. 156. Findley L, Unverzagt M, Guchu R, Fabrizio M, Buckner J, Suratt P. Vigilance and automobile accidents in patients with sleep apnea or narcolepsy. Chest 1995;108:619–24. 157. Wu H, Yan-Go F. Self-reported automobile accidents involving patients with obstructive sleep apnea. Neurology 1996;46:1254–7. 158. Stoohs RA, Guilleminault C, Itoi A, Dement WC. Traffic accidents in commercial longhaul truck drivers: the influence of sleepdisordered breathing and obesity. Sleep 1994;17:619–23.

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3

Obstructive sleep apnea in children

Carole L Marcus

Introduction Sleep-related upper airway obstruction in childhood can vary from partial upper airway obstruction (such as the upper airway resistance syndrome and obstructive hypoventilation) to complete upper airway obstruction (obstructive sleep apnea). This spectrum of abnormalities has been referred to as the obstructive sleep apnea syndrome (OSAS). OSAS can occur throughout childhood, from infancy through adolescence. Although OSAS is relatively common during childhood, and can result in significant sequelae, it has not been well studied.

improves after tonsillectomy and adenoidectomy.4 Nevertheless, childhood OSAS does not appear to be due to adenotonsillar hypertrophy alone. Several facts suggest that a combination of structural abnormalities (such as adenotonsillar hypertrophy) and neuromuscular abnormalities must be present for OSAS to occur. Most obvious is the fact that patients with OSAS do not obstruct during wakefulness, when the tone of the upper airway muscles is increased. The degree of obstructive apnea is not proportional to the degree of adenotonsillar hypertrophy.5–7 Furthermore, a small percentage of children with adenotonsillar hypertrophy but no other known risk factors for OSAS are not cured by tonsillectomy and adenoidectomy.4 In addition, Guilleminault et

Epidemiology OSAS occurs in approximately 2% of preschool children.1,2 The peak prevalence is at 2–6 years of age, which is the age when the tonsils and adenoidal tissue are the largest in relation to the underlying airway size.3 In contrast to adults, childhood OSAS occurs equally among males and females.1

Etiology In most children, OSAS is associated with adenotonsillar hypertrophy (Figure 3.1), and

Figure 3.1 Oropharynx of a child with OSAS, showing marked tonsillar hypertrophy.

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Obstructive sleep apnea in children

Table 3.1 Medical conditions associated with childhood OSAS. Adenotonsillar hypertrophy Cerebral palsy Choanal stenosis Cleft palate following pharyngeal flap surgery Craniofacial/genetic disorders Achondroplasia Apert syndrome Beckwith–Wiedermann syndrome Crouzon syndrome Down syndrome Hallermann–Streiff syndrome Pierre–Robin syndrome Prader–Willi syndrome Treacher–Collins syndrome Drugs Gastroesophageal reflux in infants Hypothyroidism Laryngomalacia Mucopolysaccharidosis Obesity Muscular dystrophy Sickle cell disease This table lists some of the more common medical conditions that can be associated with OSAS. Many other conditions that are not listed may be associated with childhood obstructive sleep apnea.

al reported a cohort of children who were cured of their OSAS by adenotonsillectomy, but developed a recurrence during adolescence.8 Thus, it appears that childhood OSAS is a dynamic process resulting from a combination of structural and neuromotor abnormalities, rather than from structural abnormalities alone. Therefore, OSAS also occurs in children with other structural abnormalities (such as craniofacial anomalies or obesity) or children with neuromuscular disease (such as cerebral palsy9 or muscular dystrophy10). A list of some of the diseases associated with OSAS is shown in Table 3.1. Clinical differences between children and adults with OSAS are summarized in Table 3.2.

Diagnostic considerations History Most children with OSAS present with a chief complaint of snoring and difficulty in breathing during sleep. Habitual snoring occurs in approximately 10% of children,2,11–14 whereas OSAS occurs in 2%; thus snoring alone is an insensitive indicator of OSAS. The

Table 3.2 Clinical differences between children and adults with OSAS.

Peak age Gender Chief complaint Commonest etiology Primary treatment

Children

Adults

2–6 years Males and females Snoring, difficulty in breathing during sleep Adenotonsillar hypertrophy Tonsillectomy and adenoidectomy

Elderly Predominantly male Excessive daytime sleepiness Obesity CPAP

CPAP, continuous positive airway pressure.

Diagnostic considerations nature of the snoring may be helpful in formulating a diagnosis. Snoring with pauses, followed by gasps, is suggestive of OSAS. However, some children have a pattern of persistent, partial upper airway obstruction known as obstructive hypoventilation (OH; see section on polysomnography, below). These children will have persistent snoring associated with increased work of breathing, but without pauses or gasps. Furthermore, young infants may grunt but not snore. Therefore, it is difficult to make a diagnosis of OSAS based on a history of snoring alone. Parents may describe other signs of OSAS. Children have a very compliant chest wall, and many parents will note impressive retractions or paradoxical inward motion of the rib cage during inspiration when the child is asleep. The child is often a restless sleeper, but this is difficult to quantitate, as most children tend to move about during sleep. The child may sleep with his/her neck hyperextended, or even prefer to sleep sitting up (which is unusual in children, who rarely have orthopnea due to cardiorespiratory disease). Many parents of children with OSAS are so concerned about their child’s breathing that they sit at their child’s bedside all night, or stimulate their child in order to terminate the apneas. Enuresis, particularly if secondary in nature, is associated with OSAS. In contrast to adults, excessive daytime sleepiness is the exception rather than the rule, particularly in young children.15 Excessive daytime sleepiness is, however, seen in some children with severe OSAS, and is more common in the adolescent, particularly if morbidly obese. Younger children often become hyperactive or irritable rather than overtly sleepy. During wakefulness, symptoms related to adenotonsillar hypertrophy may be present. These include mouth breathing, dysphagia or dysarthria. However, these symptoms are not necessarily correlated with OSAS.

43

Physical examination In the majority of children with OSAS, the physical examination during wakefulness is entirely normal. Most children are of normal weight, but children with severe OSAS may have failure to thrive. A minority is obese. Abnormalities related to adenotonsillar hypertrophy may be noted, such as an adenoidal facies or a crowded oropharynx with tonsillar hypertrophy, redundant mucosa or an elongated soft palate. However, these findings are non-specific.16 Studies have failed to show a correlation between upper airway or adenotonsillar size and the degree of OSAS.5–7 Complications of OSAS include growth failure,17 cor pulmonale and neurocognitive deficits (ranging from hyperactivity to school problems,18 seizures19 and mental retardation).19 Children with OSAS have higher blood pressure than predicted, and some may have overt hypertension.20

Laboratory tests Despite the dramatic history sometimes obtained from parents, several studies have shown that childhood OSAS cannot be distinguished from primary snoring on the basis of clinical findings alone.4,15,21–23 The American Academy of Sleep Medicine has stated that ‘the presence and severity of obstructive sleep apnea in patients must be determined before initiating surgical therapy’.24 While this statement alluded to adults, it is relevant to the pediatric age group. In 1996, an expert panel from the American Thoracic Society reviewed the literature and concluded that, in children, ‘a history of loud snoring alone has not been shown consistently to have sufficient diagnostic sensitivity upon which to base a recommendation for surgery’.25 Similarly, studies

44

Obstructive sleep apnea in children

TabIe 3.3 Polysomnographic differences between children and adults with OSAS.

Pattern of obstruction Duration of pathologic obstructive apneas Abnormal obstructive apnea index Abnormal desaturation (%) Abnormal hypercapnia (mmHg) Peak (mmHg) Duration (PETC02 > 50 mmHg; as % TST) State with most obstruction Arousals Sleep architecture

Children

Adults

Cyclic apneas or obstructive hypoventilation Any

Cyclic apneas > 10 s

>1

>5

< 92

< 90

53 > 10%

?a ?a

REM +/– Preserved

REM or non-REM ++ Fragmented

a

Normative data on PCO2 during sleep in adults are not well established. TST, total sleep time; PETCO2, end-tidal PCO2.

have shown that reviewing audiotapes16,26 or videotapes27 of the sleeping child, in addition to the clinical evaluation, does not provide sufficient specificity to confirm the diagnosis of OSAS. Polysomnography has been shown to be cost-effective.22 Nonetheless, many otolaryngologists do not obtain sleep studies prior to surgery, citing such difficulties as cost or lack of available pediatric sleep centers.28,29 With time, more pediatric facilities will hopefully become available. Polysomnography

Polysomnography remains the gold standard for diagnosing OSAS in children.25 With the use of appropriate equipment and personnel, polysomnography can be performed successfully during natural sleep in infants and children of all ages. Provision should be made

for a parent to stay with the child. Vigilant technical support is necessary, as children frequently displace monitoring leads. There are several polysomnographic differences between children with OSAS and adults (Table 3.3). 1. Sleep architecture. Children with OSAS are less likely to have fragmented sleep than adults. In adults, obstructive apneas are usually terminated by cortical arousal. This is a protective mechanism that minimizes gas exchange abnormalities, but results in fragmented sleep, with diminished slow-wave and REM sleep, and resultant daytime sleepiness.30,31 In contrast, children with OSAS frequently do not have cortical arousals associated with obstructive apnea; the younger the child, the fewer the arousals.32 As a result, sleep architecture is preserved,17,33 and

Diagnostic considerations

45

Figure 3.2 All-night summary of a polysomnogram from an 8-yearold child with obstructive sleep apnea. Each apnea is designated by a vertical line. Time is represented on the X-axis. Note that apneas and episodes of arterial oxygen desaturation occur almost exclusively during REM sleep (depicted as the bold bars on the hypnogram). WK, wake; S1–4, sleep stages 1–4, respectively.

daytime sleepiness is uncommon.34 However, there is evidence that children with OSAS may have subcortical arousals,35 which can result in autonomic sequelae such as heart rate changes36 and hypertension.20 2. In children, obstructive apnea is predominantly an REM phenomenon (Figure 3.2).37,38 A recent study of children with severe OSAS showed that the majority of obstructive apneas occurred during REM sleep, although REM sleep accounted for less than a quarter of total sleep time.38 Furthermore, apneas were longer and more numerous during later REM periods than during REM periods earlier in the night. The clinical significance of this finding is that sleep-disordered breathing may be missed if REM time is decreased or absent on screening studies, such as nap studies or on home audio/videotapes.

3. Children may show a pattern of persistent, partial upper airway obstruction associated with hypercapnia and/or hypoxemia, rather than cyclic discrete obstructive apnea (Figures 3.3 and 3.4). This has been termed ‘obstructive hypoventilation’.25 OH is seen most commonly in younger children, perhaps because their high arousal threshold allows for long periods of partial obstruction. Clinically, these children are difficult to diagnose, as they have a history of constant snoring, which is not interrupted by pauses or gasps. However, their parents frequently describe labored breathing during sleep. OH is diagnosed by the presence of episodic elevated end-tidal PCO2 levels in association with snoring and paradoxical breathing. Episodes may be very long (hours). In order to detect obstructive hypoventilation, it is important to monitor the end-tidal PCO2 (PETCO2)

46

Obstructive sleep apnea in children

Figure 3.3 A 2-min portion of a polysomnograph from an 8-year-old child is shown. There are multiple, discrete episodes of obstructive apnea (of up to 25 s duration) associated with cyclical desaturation (to 83%) and EEG arousals. This pattern is similar to that seen in adults with obstructive sleep apnea. LEOG, left electro-oculogram; REOG, right electro-oculogram; C3A2 and O1A2, EEG leads; Chin, submental EMG; NAF, oronasal airflow via a thermistor; THO, thoracic wall movement; ABD, abdominal wall movement; CO2, end-tidal PCO2 waveform; PULSE, oximeter pulse waveform; LEMG, tibial EMG. Time is shown on the X-axis.

Figure 3.4 A 30-s portion of a polysomnograph from a 2year-old child with obstructive hypoventilation is shown. There are no discrete episodes of obstructive apnea, and no evidence of cortical arousal. Paradoxical inward motion of the chest wall during inspiration is present. This is associated with persistent hypercapnia (end-tidal PCO2 (EtCO2) in the 60s) and arterial oxygen desaturation (SaO2 77–85%). Abbreviations as for Figure 3.3.

Diagnostic considerations during pediatric polysomnography. When scoring sleep studies, it should be remembered that normal PCO2 levels are higher during sleep than during wakefulness. A study of normal children showed that a peak PETCO2 > 53 mmHg during sleep is abnormal.39 A more important parameter to measure is the duration of hypoventilation. A PETCO2 > 50 mmHg for more than 10% of total sleep time is abnormal.39 4. Pediatric sleep studies need to be scored and interpreted differently from adult studies. Breathing during sleep changes with age. Therefore, the standards used for the interpretation of polysomnography in adults cannot be extrapolated to infants and children. Children appear to have clinical sequelae associated with milder forms of OSAS than adults, i.e. with fewer and shorter obstructive apneas. The reason for this is unclear, but may be that significant desaturation can occur even with brief apneas. This is because children have a lower functional residual capacity and a faster respiratory rate than adults. The details for pediatric scoring are outlined in the American Thoracic Society consensus statement.25 In adults, apneas > 10s in duration are scored, whereas in children, obstructive apneas of any length are quantitated. For convenience, our laboratory scores obstructions that are two or more respiratory cycles in length. In adults, an apnea index > 5–10/h is considered abnormal. Based on normative data,39 an obstructive apnea index > 1 is considered abnormal in children. However, while an apnea index greater than one is statistically significant, it is not known what level is clinically significant.40 There are no normative data for hypopneas in young children. An arterial oxygen saturation of 92% is considered the lower

47

limit of normal.39 However, it is not uncommon for normal children to have transient desaturation below this level, often in association with central apnea or periodic breathing.41 The upper airway resistance syndrome (UARS) may occur in children.42 Currently, it is diagnosed by measuring the esophageal pressure during polysomnography. Less invasive diagnostic techniques are being developed.43

Nap studies

Daytime nap polysomnography is an alternative to overnight polysomnography. Nap studies, if positive, are highly suggestive of OSAS. However, nap polysomnography has a high false-negative rate and frequently underestimates the degree of sleep-disordered breathing.44 Nap polysomnography is of shorter duration, may not include REM sleep, and may be altered by circadian variations in sleep patterns. In addition, sedation or sleep deprivation, both of which can affect polysomnography results, are frequently necessary to induce sleep.

Home sleep studies

The utility of home or unattended sleep studies has not been well studied in children. Success has been reported from one center.45 However, the polysomnography system used in this study consisted of seven channels in conjunction with videotaping, and is not analogous to commercially available systems. Furthermore, few patients with moderate to severe OSAS were studied. Home studies are potentially advantageous, as they are less disruptive for the patient and family, and may make

48

Obstructive sleep apnea in children

polysomnography more accessible and cheaper. Potential problems include lead displacement, inability to monitor for OH or UARS, and the lack of monitoring for REM sleep with most systems.

Pulse oximetry

Nocturnal pulse oximetry has been evaluated as a screening tool for OSAS.13,46–48 It may be useful if it shows a pattern of cyclic desaturation; however, there is a high false-negative rate. Furthermore, it will miss those children who have obstructive apneas without significant desaturation, but with increased work of breathing or sleep fragmentation.

Ancillary studies

In most children, radiologic evaluation of the upper airway is unnecessary. The tonsils can be evaluated clinically, and the adenoids can be assessed at the time of surgery or via endoscopy. In patients with complex craniofacial anomalies, upper airway endoscopy, cephalometry or CT scans may be helpful to delineate the anatomy and help plan the surgical approach. Patients with severe OSAS should be assessed for pulmonary hypertension by chest X-ray and EKG or echocardiography. Formal testing of cognitive function or assessment of hyperactivity may be appropriate for individual patients.

Treatment considerations

children with severe OSAS should always be treated. On the other hand, there is no evidence that children with primary snoring benefit from treatment. However, children with mild degrees of OSAS present a dilemma. Little is known about the natural course of untreated, mild OSAS in children. Furthermore, it is not known which polysomnographic parameters predict morbidity, and hence what degree of OSAS merits treatment.40 Further study is clearly needed. In the interim, treatment decisions should be based on the constellation of symptoms, physical examination and polysomnography. As most children initially present because they are symptomatic, and as we have seen a number of children with progressive OSAS, but none with spontaneous resolution of OSAS, our tendency is to treat many of the children with mild disease.

Emergency stabilization and treatment Most children with OSAS have been symptomatic for some time prior to diagnosis, and can await elective treatment. Occasionally, a child presents with severe hypoxemia, heart failure, respiratory failure or an altered level of consciousness. In an emergency situation, the patient can be treated with nasopharyngeal tubes that are passed to the level of the tonsils.49 Alternatively, continuous positive airway pressure (CPAP) can be used pending definitive treatment.

When to treat

Tonsillectomy and adenoidectomy

It is not clear which children with sleep-disordered breathing need to be treated. Certainly,

The cardinal treatment for childhood OSAS is tonsillectomy and adenoidectomy (T&A).

Treatment considerations OSAS results from the relative size and structure of the upper airway components, rather than the absolute size of the adenotonsillar tissue. Therefore, both tonsils and adenoids should be removed, even if one or the other appears to be the primary abnormality. An exception is infants, in whom adenoidectomy alone may be sufficient. However, when necessary, T&A is safe and effective in this age group.50 By the same logic, T&A should be the initial treatment of OSAS in children with other predisposing factors, such as obesity51 or Down syndrome,52 although further treatment may be necessary. In children with a submucous cleft palate, adenoidectomy may result in velopharyngeal incompetence; in this group, tonsillectomy alone is a consideration. Although T&A is considered to be relatively minor surgery, significant complications may occur. It is for this reason that T&A is not recommended as treatment for primary snoring. Recent studies have demonstrated complication rates of 6–9%;53–55 complication rates are higher in children with OSAS. Potential complications include immediate perioperative problems (such as pain, dehydration and anesthetic complications), hemorrhage, postoperative respiratory compromise, nasopharyngeal stenosis, velopharyngeal incompetence and death. Postoperative respiratory compromise has been reported to occur in 16–27% of children with OSAS.56–58 The reasons for this include postoperative upper airway edema, increased secretions, respiratory depression secondary to analgesic and anesthetic agents, and postobstructive pulmonary edema.59 High-risk groups include children < 3 years of age, those with severe OSAS, and those with underlying diseases, such as craniofacial anomalies or cerebral palsy.56,57,60 These children are not candidates for outpatient surgery.

49

The majority of children with OSAS will improve postoperatively. Those with severe OSAS,4 or other underlying diseases, should undergo repeat polysomnography 6–8 weeks postoperatively, in order to ensure that additional treatment is not needed.

Continuous positive airway pressure Nasal CPAP is the mainstay of treatment for OSAS in the adult population. Although still not approved by the American Food and Drug Administration for use in children, reports in the literature describe its successful application in more than 266 infants and children.61–64 In our experience, CPAP is well tolerated and effective in the pediatric population, provided that appropriate counseling and support is provided. CPAP use in the young or developmentally delayed child may be difficult. In these cases, behavioral psychology techniques can be useful.65 Another problem with CPAP use in the pediatric population is a shortage of appropriately sized interfaces. Small or weak children may not be able to trigger bilevel or auto-CPAP devices. The sideeffects of CPAP in children are similar to those in adults, and include nasal symptoms, eye irritation or skin lesions. More serious potential side-effects, such as aspiration, pneumothorax or middle ear problems, have not been reported. Central apnea occurs quite commonly in children using CPAP, and is probably due to the prominent Hering–Breuer reflex seen in this age group. If necessary, this can be prevented by providing bilevel pressure with a backup rate. Anecdotal concerns of midfacial depression due to mask pressure have been raised, but definitive data are lacking. In children, unlike in adults, it is

50

Obstructive sleep apnea in children

necessary to frequently re-evaluate pressure levels, as these may change in association with growth of the airway and changes in the airway soft tissue.61 In addition, mask size needs to be evaluated with growth.

Weight loss Unlike adults, most children with OSAS are not obese. However, OSAS is common among morbidly obese children.66 The prevalence of childhood obesity is increasing. Currently, 10% of children in the US are obese.67 Weight loss in obese patients will result in an improvement in the degree of sleep-disordered breathing. However, weight reduction may be extraordinarily difficult for a child to achieve, particularly when the entire family is overweight. Fortunately, many obese children with OSAS will improve following T&A,51 which should be considered as initial treatment. For those obese patients in whom surgery is insufficient, CPAP treatment is indicated while the patient attempts to lose weight.

Uvulopharyngopalatoplasty (UPPP) Few studies have evaluated the safety and efficacy of UPPP in children. It is useful in patients in whom abnormal upper airway neuromuscular tone contributes to OSAS, e.g. patients with cerebral palsy68,69 or Down syndrome.70,71 In addition, it has been reported to be successful in the treatment of an otherwise normal 3-year-old child with OSAS.72 Currently, we would consider UPPP for children with OSAS unresponsive to either T&A or nasal CPAP, especially those children who are obese or have redundant oropharyngeal soft tissue. However, further study is needed.

Craniofacial surgery In patients with craniofacial anomalies, specific surgical procedures may be appropriate, such as supraglottoplasty in patients with severe laryngomalacia73 and mandibular distraction in children with micrognathia. Tongue wedge resection has been reported to be efficacious in patients with macroglossia (e.g. those with Down syndrome or Beckwith–Wiedemann syndrome).70,74

Supplemental oxygen Two studies have evaluated the use of supplemental oxygen in children with OSAS.75,76 Both studies showed an improvement in arterial oxygen saturation, without a worsening of apnea. However, although PCO2 levels did not change for the group as a whole, a few individuals developed significant hypercapnia when breathing supplemental oxygen. Although supplemental oxygen should not be used as a first-line treatment for OSAS, it may be useful in a few individuals in whom surgical or CPAP therapy is unsuccessful, providing that the patient’s PCO2 is monitored closely.

Pharmacologic treatment It is generally accepted that pharmacologic agents are not clinically useful in the management of OSAS in children. Topical treatment of allergic rhinitis can be a useful adjunct to definitive treatment. Although systemic steroids have been used to shrink adenoidal tissue, a recent controlled study showed no significant improvement in sleep-disordered breathing after a 5-day course of prednisone.77

References The use of sedative drugs should be avoided, as these may aggravate OSAS.

Oral appliances The use of oral appliances in the treatment of adults with OSAS is increasing. However, oral appliances have not been studied in detail in pediatric patients, due to the concern that they may adversely affect the facial configuration of the growing child. Some centers have advocated the use of rapid maxillary expansion to treat children with OSAS; however, objective data on this procedure are not yet available.

51

independent disease entity. There has been only one long-term study of childhood OSAS. Guilleminault et al8 re-evaluated adolescents who had been successfully treated with T&A during childhood, and found that a small percentage (13% of those who returned for follow-up) had a recurrence. All were male. This study suggests that either some or all children with OSAS and adenotonsillar hypertrophy have additional subclinical abnormalities, be they structural or neuromuscular, that can lead to recurrence of OSAS if additional risk factors (such as weight gain, or testosterone secretion at puberty) are acquired. Further study is needed.

Acknowledgments Tracheotomy Tracheotomy is the ultimate treatment for OSAS, as it bypasses the site of obstruction. However, it is associated with many complications, including speech problems, chronic tracheitis and interference with the activities of daily life. Fortunately, with the increased use of CPAP and other treatment modalities, tracheotomy is now rarely required for OSAS. It may be needed in children with upper airway obstruction during both wakefulness and sleep, particularly children with craniofacial anomalies or cerebral palsy.

Prognosis and natural course The natural course and long-term prognosis of childhood OSAS are not known. Specifically, it is not known whether childhood OSAS is a precursor of adult OSAS, or whether it is an

Dr Marcus was supported in part by the Pediatric Clinical Research Center #RR00052, the Johns Hopkins Hospital, Baltimore, MD, and NHLBI grant #HL58585-01.

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Obstructive sleep apnea in children adenotonsillectomy on nocturnal hypoxaemia, sleep disturbance, and symptoms in snoring children. Lancet 1990;335:249–53. van Someren VH, Hibbert J, Stothers JK, Kyme MC, Morrison GAJ. Identifying hypoxaemia in children admitted for adenotonsillectomy. BMJ 1989;298:1076. Kravath RE, Pollak CP, Borowiecki B. Hypoventilation during sleep in children who have lymphoid airway obstruction treated by nasopharyngeal tube and T and A. Pediatrics 1977;59:865–71. Leiberman A, Tal A, Brama I, Sofer S. Obstructive sleep apnea in young infants. Int J Pediatr Otorhinolaryngol 1988;16:39–44. Kudoh F, Sanai A. Effect of tonsillectomy and adenoidectomy on obese children with sleepassociated breathing disorders. Acta Otolaryngol 1996; Suppl 523:216–18. Marcus CL, Keens TG, Bautista DB, Von Pechmann WS, Ward SL. Obstructive sleep apnea in children with Down syndrome. Pediatrics 1991;88:132–9. Nicklaus PJ, Herzon FS, Steinle EW. Shortstay outpatient tonsillectomy. Arch Otolaryngol Head Neck Surg 1995;121:521–4. Kendrick D, Gibbin K. An audit of the complications of paediatric tonsillectomy, adenoidectomy and adenotonsillectomy. Clin Otolaryngol 1993;18:115–17. Reiner SA, Sawyer WP, Clark KF, Wood MVV. Safety of outpatient tonsillectomy and adenoidectomy. Otolaryngol Head Neck Surg 1990;102:161–8. Rosen GM, Muckle RP, Mahowald MW, Goding GS, Ullevig C. Postoperative respiratory compromise in children with obstructive sleep apnea syndrome: can it be anticipated? Pediatrics 1994;93:784–8. McColley SA, April MM, Carroll JL, Loughlin GM. Respiratory compromise after adenotonsillectomy in children with obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 1992;118:940–3.

58. Ruboyianes JM, Cruz RM. Pediatric adenotonsillectomy for obstructive sleep apnea. Ear Nose Throat J 1996;75:430–3. 59. Galvis AJ. Pulmonary edema complicating relief of upper airway obstruction. Am J Emerg Med 1987;5:294–7. 60. Wiatrak BJ, Myer CM, Andrews TM. Complications of adenotonsillectomy in children under 3 years of age. Am J Otolaryngol 1991;12:170–2. 61. Marcus CL, Ward SL, Mallory GB et al. Use of nasal continuous positive airway pressure as treatment of childhood obstructive sleep apnea. J Pediatr 1995;127:88–94. 62. Waters KA, Everett FM, Bruderer JW, Sullivan CE. Obstructive sleep apnea: the use of nasal CPAP in 80 children. Am J Respir Crit Care Med 1995;152:780–5. 63. Guilleminault C, Pelayo R, Clerk A, Leger D, Bocian RC. Home nasal continuous positive airway pressure in infants with sleep-disordered breathing. J Pediatr 1995;127:905–12. 64. McNamara F, Sullivan CE. Obstructive sleep apnea in infants and its management with nasal continuous positive airway pressure. Chest 1999;116:10–16. 65. Rains JC. Treatment of obstructive sleep apnea in pediatric patients. Clin Pediatr 1995;34:535–41. 66. Marcus CL, Curtis S, Koerner CB, Joffe A, Serwint JR, Loughlin GM. Evaluation of pulmonary function and polysomnography in obese children and adolescents. Pediatr Pulmonol 1996;21:176–83. 67. Mei Z, Scanlon KS, Grummer-Strawn LM, Freedman DS, Yip R, Trowbridge FL. Increasing prevalence of overweight among US low-income preschool children: the Centers for Disease Control and Prevention pediatric nutrition surveillance, 1983 to 1995. Pediatrics 1998;101:12. 68. Kosko JR, Derkay CS. Uvulopalatopharyngoplasty: treatment of obstructive sleep apnea in neurologically impaired pediatric patients. Int J Pediatr Otorhinolaryngol 1995;32:241–6.

References 69. Seid AB, Martin PJ, Pransky SM, Kearns DB. Surgical therapy of obstructive sleep apnea in children with severe mental insufficiency. Laryngoscope 1990;100:507–10. 70. Donaldson JD, Redmond WM. Surgical management of obstructive sleep apnea in children with Down syndrome. J Otolaryngol 1988;17:398–403. 71. Strome M. Obstructive sleep apnea in Down syndrome children: a surgical approach. Laryngoscope 1986;96:1340–2. 72. Abdu MH, Feghali JG. Uvulopalatopharyngoplasty in a child with obstructive sleep apnea. A case report. J Laryngol Otol 1988;102:5465–8. 73. Marcus CL, Crockett DM, Ward SL. Evaluation of epiglottoplasty as treatment for severe laryngomalacia [published erratum appears in J Pediatr 1991;118(1):168]. J Pediatr 1990;117:706–10.

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74. Morgan WE, Friedman EM, Duncan NO, Sulek M. Surgical management of macroglossia in children. Arch Otolaryngol Head Neck Surg 1996;122:326–9. 75. Marcus CL, Carroll JL, Bamford O, Pyzik P, Loughlin GM. Supplemental oxygen during sleep in children with sleep-disordered breathing. Am J Respir Crit Care Med 1995;152:1297–301. 76. Aljadeff G, Gozal D, Bailey-Wahl SL. Effects of overnight supplemental oxygen in obstructive sleep apnea in children. Am J Respir Crit Care Med 1996;153:51–5. 77. Al-Ghamdi SA, Manoukian JJ, Morielli A, Oudjhane K, Ducharme FM, Brouillette RT. Do systemic corticosteroids effectively treat obstructive sleep apnea secondary to adenotonsillar hypertrophy? Laryngoscope 1997;107:1382–7.

4 Diagnostic studies for sleep apnea/hypopnea Rajesh Jasani, Mark H Sanders and Patrick J Strollo Jr

Airflow Effort

Expiration Inspiration

Pes

Figure 4.1 Obstructive sleep apnea: apnea with continuing respiratory effort, as shown by progressively increasing fluctuations in esophageal pressure (Pes) associated with cessation of airflow. The arrow represents resumption of airflow which usually accompanies an arousal. Airflow

Obstructive sleep apnea–hypopnea syndrome (OSAHS) is a common disorder that represents a significant public health problem, affecting 2–4% of the middle-aged population with a wide range of severity.1,2 The clinical spectrum of OSAHS includes a number of different disorders, possibly resulting from different pathophysiologic mechanisms or representing different points along a continuum of upper airway dysfunction. Although the definition of apnea is unambiguous, identifying those events in which airflow is present but pathologically reduced (hypopnea) is more challenging. There is currently no universally accepted definition for hypopnea.3–6 The application of various clinical techniques possessing different sensitivities to record airflow and breathing effort has further contributed to heterogeneity across sleep laboratories in identifying abnormal breathing events, even when using the same definitions. Ultimate resolution of these issues must await standardization of recording techniques and studies assessing correlations between definitions and health outcomes. To facilitate patient care until this occurs, a task force of The American Academy of Sleep Medicine has recommended terminology and standards of practice for the recording of sleep

and breathing, and assigned evidence-based definitions for abnormal events, parameters and disorders as outlined below and in Figures 4.1–4.5 (‘Chicago Criteria’).7

Effort

Introduction

Expiration Inspiration

Pes

Figure 4.2 Central sleep apnea: cessation of airflow associated with no respiratory efforts, as shown by changes in esophageal pressure (Pes).

Apnea This is defined as cessation of airflow for 10 s or more. Apnea is divided into three patterns. Obstructive apnea

This is apnea during which there is ventilatory effort but no airflow, due to upper airway obstruction (Figure 4.1). Central apnea

This is apnea occurring in the absence of ventilatory effort (Figure 4.2).

Airflow

Diagnostic studies for sleep apnea/hypopnea

Effort

58

Expiration Inspiration

Apnea

Pes

Figure 4.3 Mixed apnea: apnea initially appears as a central apnea (without respiratory effort as evidenced by the constant esophageal pressure (Pes), followed by a period of obstructive apnea (with respiratory effort as evidenced by changes in esophageal pressure). The arrow represents arousal and termination of an event.

This is defined as an event which is characterized by disproportionate reduction of inspiratory airflow relative to inspiratory effort or metabolic needs. The American Academy of Sleep Medicine Task Force7 defined or characterized hypopnea as follows: ‘A clear decrease (> 50%) from baseline in the amplitude of a valid measure of breathing during sleep or an amplitude reduction (< 50%) associated with either an oxyhemoglobin desaturation (> 3%) or an arousal, and the event should last at least 10 seconds.’ Hypopneas, like apneas, can be central or obstructive, although this distinction is infrequently made when reporting clinical sleep studies (Figures 4.4 and 4.5). In routine clinical practice, it may not be necessary to

Effort

Expiration Inspiration

Pes

Figure 4.4 Obstructive sleep hypopnea: decrease in airflow associated with an increase in respiratory effort (Pes, esophageal pressure; arrow represents an arousal).

Airflow

Hypopnea

Effort

This is apnea which is initially due to absent ventilatory effort (a ‘central’ pattern), and subsequently persists despite resumption of ventilatory efforts (an ‘obstructive’ pattern) (Figure 4.3).

Airflow

Mixed apnea

Expiration Inspiration

Pes

Figure 4.5 Central sleep hypopnea: decrease in airflow associated with decrease in respiratory effort.

Introduction differentiate apneas from hypopneas when both types of events have similar pathophysiologic consequences, such as arousal and oxyhemoglobin desaturation.8–10 There are currently no data to suggest different long- or short-term outcome in patients with predominantly hypopneas as compared to apneas.

Apnea, hypopnea and apnea + hypopnea indices Dividing the total number of apneas during a recording period by the total sleep time yields the average number of apneas per hour of sleep, or apnea index (AI). Similarly a variety of other indices, including hypopnea index (HI) and apnea + hypopnea index (AHI) (also termed the respiratory disturbance index (RDI)) are usually employed to quantify OSAHS severity. The concept of ‘index’ permits standardization of event frequency for the number of hours slept. This facilitates comparison of individual patient data with normative as well as pre- and post-treatment values.

Obstructive sleep apnea–hypopnea syndrome The OSAHS is usually defined as excessive daytime somnolence and other sequelae attributable to frequent obstructive apneas or hypopneas during sleep. The criterion of an AHI * 5 is also frequently employed.7 The use of an event frequency of five per hour as a minimal threshold value has been based on epidemiologic data suggesting that adverse health effects, including hypertension, sleepiness and motor vehicle accidents, may be

59

observed at or above this threshold.11–13 Additionally, limited data from intervention studies suggest treatment-associated improvements in vitality, mood and fatigue in patients with AHI between 5 and 30,14 as well as improvement in sleepiness and neurocognitive function in patients with AHI levels of 5–15.15,16 The threshold of AHI that should be employed as a case-finding instrument for the diagnosis of OSAH probably varies with the age of the patient. As discussed in Chapter 3, the presence of one obstructive apnea per hour in a young child may be sufficient to make the diagnosis of obstructive sleep apnea.17–19 Thus, although there are no specific large epidemiologic studies defining the normal distribution of OSAH in the general population, AHI greater than 5–10 is considered to be beyond the broad limits of normal and may justify therapy, particularly in the presence of adverse physiologic or neurocognitive consequences, or attributable difficulty in maintaining alertness.

Upper airway resistance syndrome The upper airway resistance syndrome (UARS) is defined by repetitive and progressively increasing inspiratory efforts with subsequent transient arousal, but without associated reduction in airflow (i.e. not meeting the criteria for hypopnea), hypoventilation or oxygen desaturation20 (Figure 4.6). Controversy exists with regard to whether UARS lies on a continuum between primary (e.g. ‘benign’ snoring; snoring which is not associated with symptoms or known adverse physiologic consequences) and OSAHS, or if it is a distinct clinical syndrome.21 UARS patients have subtle airflow limitation as a

60

Diagnostic studies for sleep apnea/hypopnea

EEG Arousal Airflow

Effort (rib cage)

Effort (abdomen) Effort (Pes cm H2O)

% SaO2

0 –20 –40 –60 100 75 50

10 s

Figure 4.6 Respiratory effort-related arousal (RERA): peak increase in respiratory effort (as shown with more negative esophageal pressure) followed by arousal.

consequence of increased upper airway resistance, but not necessarily a reduction in tidal volume, due to the ‘protective’ compensatory physiologic responses, including increased inspiratory effort. This increased effort is a hallmark of UARS but may not be easily identifiable by the usual clinical monitors such as qualitative measures of chest wall (e.g. rib cage and abdomen).20 However, esophageal manometry or calibrated inductance plethysmography may reveal increasing inspiratory efforts unaccompanied by increased inspiratory flow leading to arousal. Furthermore, more quantitative recording of flow, or recording of pressure fluctuations at the nares (nasal pressure transduction), may reveal inspiratory flow limitation, which is characteristic of increased airway resistance (Figure 4.6).22

UARS patients usually but not universally have crescendo snoring prior to arousal.23 While the UARS and OSAHS are entities which reflect a constellation of physiologic and clinical conditions, individual events in which arousal results from increased inspiratory effort associated with elevated upper airway resistance (e.g. apneas, hypopneas, or elevated airway resistance even in the absence of reduced airflow or tidal volume) have been termed respiratory effort-related arousals (RERAs).24 The American Academy of Sleep Task Force7 defined RERA or UARS as a: ‘Pattern of progressively more negative esophageal pressure, terminated by a sudden change in pressure to a less negative level and an arousal with an event lasting 10 seconds or longer’ (Figure 4.6). Physiologic and clinical

Clinical predictors of OSAH

61

Table 4.1 Types of studies for evaluating sleep apnea (minimum of 6 h of overnight recording). Level 1 Standard PSG

Level 2 Comprehensive portable PSG

Level 3 Modified portable testing

Level 4 Continuous single or dual bioparameter recording

No. of parameters measured EEG EOG Chin EMG EKG/HR Airflow

*7

*7

*4

1–3

C4–A1 or C3–A2 Required Required EKG Required

C4–A1 or C3–A2 Required Required EKG or HR Required

Not measured Not measured Not measured Optional Optional

Respiratory effort

Required

Required

O2 saturation Body position

Required Visual or measured Optional In attendance

Required Measured (optional) Optional Not in attendance

Not measured Not measured Not measured EKG or HR Either one channel of each effort and airflow or two channels of effort Required Measured (optional) Optional Not in attendance

Leg movement Personnel intervention

冦

Optional

Measured Not measured Not measured Not in attendance

EOG, electro-oculogram; HR, heart rate; PSG, polysomnography; EEG, electroencephalogram; EKG, electrocardiogram.

manifestations of RERA or UARS may also be present in some non-snoring individuals, but the exact prevalence is unknown.

Clinical predictors of OSAHS The clinical features of OSAHS are described in detail in Chapter 1. Several studies have

examined the clinical predictors of OSAHS using various symptoms, signs, risk factors and morphologic parameters. The ‘Berlin Questionnaire’25 examined the presence and frequency of snoring, waketime sleepiness or fatigue, and history of obesity or hypertension, defining a group at high risk for OSAHS by the presence of at least two of these variables. The questionnaire had a sensitivity of 0.86, a specificity of 0.77, a positive predictive value of 0.89, and a likelihood ratio of 3.79 in identifying patients with AHI * 5/h.25 Flemons et al

62

Diagnostic studies for sleep apnea/hypopnea

observed that the AHI correlated linearly with neck circumference, hypertension, habitual snoring and bedpartner reports of nocturnal gasping/choking respirations.26 Employing a morphometric model, Kushida et al found a combination of values for body mass index (BMI), neck circumference and oral cavity measurements to be highly predictive of AHI * 5/h (sensitivity 97.6%, specificity 100%, positive predictive value 100%, and negative predictive value 88.5%).27

Objective diagnostic studies for sleep apnea The variables recorded during diagnostic evaluation for sleep apnea depend upon the type of recording device that is used. A Task Force established by the American Sleep Disorders Association suggested four levels of classification of recording devices for sleep apnea (Table 4.1):28 •

•

•

Level I devices: complete in-laboratory polysomnography including electroencephalogram, electro-oculogram and submental electromyogram, cardiopulmonary monitoring and limb movement monitoring. Level II devices: polysomnography with complete sleep and cardiopulmonary monitoring outside of the laboratory environment (e.g. in the home or on a patient care unit). In contrast to level I, level II studies do not involve the presence of a technologist during the recording. Level III devices: generally record only cardiopulmonary variables, including some measure of breathing effort, airflow, oxygen saturation, and either heart rate

•

(by cardiotachometer) or an electrocardiogram (ECG). Level IV devices: typically record only one to three variables, such as pulse oximetry and ECG. Some devices also provide a recording of airflow. Studies at this level provide the least information.

Polysomnography Polysomnography (PSG) refers to multichannel recording of sleep and breathing variables and, when attended by a trained technician, is the historical and ‘gold standard’ method employed to diagnose OSAHS and other sleeprelated disorders such as periodic limb movements disorder (PLMD) and rapid eye movement sleep behavior disorder. PSG has traditionally been performed overnight. However, the time and labor-intensive nature of attended, overnight PSG and the consequent cost and resource burden of these studies has led to several modifications in the way in which these studies are performed at some centers. One variation is to perform PSG during a daytime nap (nap PSG). Care must be taken when making clinical decisions based on these studies which may be unreliable for the evaluation of sleep architecture and may underestimate the severity of the sleep apnea, particularly if REM sleep or sleep in the supine position is not recorded.29 There are few systematically collected data addressing the value of nap recordings. It appears, however, that a positive study is likely to be valid but a negative study is inadequate to definitively exclude a diagnosis of sleep apnea.30,31 Daytime studies are appropriate in shiftworkers who normally sleep during the daylight hours.

Polysomnography Data collection, derived information and its importance Full PSG typically records sleep stage, breathing effort, airflow, oxyhemoglobin saturation by pulse oximetry (SpO2), an electrocardiogram (ECG), body position, and limb movements.

63

efficiency and prolonged REM latency (‘the first night effect’).42 Although this may be of concern when performing PSG to diagnose a non-pulmonary sleep–wake disorder, the clinical significance of the ‘first night effect’ and night-to-night variability in the frequency of respiratory disturbances in patients who have more than mild OSAHS is believed to be minimal.42,43

Sleep stages and arousal

Sleep stages are monitored by recording the electroencephalogram (EEG), right and left electrooculogram (EOG), and submental electromyogram (EMG). The latter two parameters identify the eye movements and postural muscle hypotonia that characterize and help define REM sleep. Sleep stage percentages and distribution can be calculated, as well as latencies to each of the various stages. In patients with intrinsic lung disease, the apneas and oxyhemoglobin desaturation, even in the absence of specific apnea and hypopnea events, are usually most marked in REM sleep.32–40 Thus, comprehensive assessment for sleepdisordered breathing requires recording during REM sleep. Apneas and hypopneas are terminated by an arousal, which can be identified as a transient (3–14-s) activation of the EEG.41 Arousals, regardless of cause, may result in sleep fragmentation and are believed to be a primary mechanism responsible for daytime hypersomnolence in patients with a variety of sleep disorders (e.g. OSAH, PLMD). Identifying the cause of arousals is essential in establishing a diagnosis and treatment planning. The frequency of arousals (arousal index) becomes an important descriptor of the sleep continuity. The first night of sleep in the unfamiliar laboratory environment may be qualitatively and quantitatively different from sleep at home or during subsequent nights in the laboratory, being characterized by decreased sleep

Monitoring of breathing Airflow changes

Distinguishing a normal breath from an apnea or hypopnea requires a measure of airflow or tidal volume. Various devices have been employed to detect oral and nasal airflow. These include pneumotachography, nasal pressure transduction, use of thermal sensors,44 rapid response carbon dioxide (CO2) analyzers, and laryngeal and tracheal microphones.45–47 The advantages and disadvantages of the various devices are shown in Table 4.2. Recently, recording fluctuation of pressure at the nares with inspiration and expiration has been reported to reflect phasic airflow and demonstrate inspiratory airflow waveform. As with a classic pneumotachograph, variation in the pattern of pressure changes at the nose reflects the pattern of airflow. In this regard, flattening of the inspiratory waveform appears to be a good marker for inspiratory flow limitation and increased upper airway resistance.48 Comparisons of a pneumotachograph recording with nasal pressure, and nasal pressure with thermistor, for the detection of sleep-disordered breathing events, are shown in Figures 4.7 and 4.8, respectively. Respiratory effort monitoring

Absence of airflow in conjunction with absent rib cage and abdominal movements (effort)

64

Diagnostic studies for sleep apnea/hypopnea

Table 4.2 Various techniques for the measurement of airflow changes. Technique

Advantages

Disadvantages

Pneumotachography: Quantitates airflow by providing breath-to-breath measurements, measured by a snug-fitting mask attached with the pneumotachometer (Figure 4.7)

Reference standard for the measurement of airflow changes7 Provides quantitative measurements of airflow and easily integrated to yield tidal volume Can be incorporated into nasal CPAP systems More sensitive than thermal sensors for detecting hypopneas48 (Figure 4.7) Moderate accuracy in measuring ventilation while awake49

Intolerance to mask–pneumotachograph system, especially in minimally sleepy patients Cumbersome to use and may alter sleep architecture

Nasal pressure: Pressure fluctuation at nose during inspiration and expiration reflects indirect measurement of inspiratory and expiratory airflow. Used either with a full-face mask or nasal pressure cannulae connected to a sensitive pressure transducer (Figures 4.7 and 4.8) Thermal sensors (oronasal thermistor or thermocouples): Senses alteration in heat exchange during inspiration and expiration providing indirect measurement of airflow changes44 (Figure 4.8)

Simple and easy to use Well tolerated Less expensive

Expired CO2: Provides indirect measurement of airflow by detecting increased CO2 in expired air

Easy to use Qualitative or semi quantitative indicator of airflow

Tracheal sound: Airflow through trachea produces sound audible via microphone

Qualitative measurement of airflow Inexpensive and easy to use Can be use to quantitate snoring

Less sensitive than pneumotachometer for detecting hypopneas50 Not clear whether sensitivity for the detection of hypopnea would improve if criteria for oxygen desaturation or an arousal were included7 If only nasal pressure cannulae are used, the technique may lack sensitivity if the patient employs predominantly mouth breathing Appears promising, but not recommended as a measurement of a RERA7 Less sensitive than pneumotachometer and nasal pressure48,51 (Figure 4.7) Poor accuracy in recording hypopneas in awake subjects under ideal conditions49 Provides only qualitative information about airflow changes Limited data about the accuracy and precision of these devices Signal quality reduced during nasal CPAP treatment Significant time delay because air is sampled continuously for remote analysis Signal quality reduced during nasal CPAP treatment No data on the accuracy for detecting hypopneas and its correlation with outcomes No data to evaluate the accuracy and precision of expired CO2 Sound amplitude also increases during snoring or partial airflow obstruction No data to evaluate its usefulness and accuracy

CPAP, continuous positive airway pressure; RERA, respiration effort-related arousal.

Polysomnography

65

1.5

Expiration

0.0

Inspiration

Pneumotachograph Nasal prongs (NP) Square root of NP

–1.5 0

10

20

30

40

50

60

Time (s)

Figure 4.7 Comparison between pneumotachograph and nasal prongs: nasal flow recorded simultaneously with a pneumotachograph (solid line) and nasal prongs (dashed line). The dotted line represents the square root of the prongs signal. For comparison, the amplitude of the nasal prongs signal and of its square root were scaled to achieve the same amplitude as with the pneumotachograph in the first breathing cycle. Note that the signal from the nasal prongs overestimates the pneumotachograph signal, and that after the square root correction, the nasal prongs signal was almost coincident with the pneumotachograph signal.48

implies central apnea, whereas the absence of airflow despite persistent chest wall movement with or without paradoxical motion of rib cage and abdomen identifies an obstructive apnea. Respiratory effort can be assessed by quantitative or qualitative respiratory inductance plethysmography (RIP)52 or by qualitative measures including impedance pneumography,53 piezo sensors or strain gauges (Table 4.3). However, the ‘gold

standard’ to quantify inspiratory effort is recording breath-by-breath esophageal pressure fluctuations reflecting swings in intrathoracic pressure using an esophageal balloon/pressure catheter (Table 4.3). Thus, several options exist for monitoring breathing effort. There are, however, few studies addressing the relative efficacy of each in the clinical environment. In view of its noninvasive nature and ease of use, qualitative RIP

66

Diagnostic studies for sleep apnea/hypopnea

EEG EOG EOG EMG

Legs Thermistor Rib Abdomen Nasal cannula SaO2

Figure 4.8 A 120-s section from PSG in one subject with hypopnea that is easily detected on the nasal cannula signal (nasal pressure) but missed by the thermistor. Chest wall and abdominal movements were monitored with piezoelectric strain gauges.

(uncalibrated) is often employed and is generally a reliable clinical tool, although the clinician must recognize the limitations (see Table 4.3). Qualitative RIP may misclassify obstructive apneas as central apneas. If clinically indicated, the clinician should consider repeating PSG using an esophageal catheter in patients in whom qualitative RIP has been employed and in whom only central apnea was identified, in order to confirm this diagnosis. Making the distinction between central and obstructive apnea is important, since the subsequent evaluations and treatment strategies may differ.62

Although there is a wide variety of techniques for measurement of respiratory airflow and effort, there are, at present, insufficient data to develop firm and universal recommendations about which instrumentation is optimal. The situations in which measurements of esophageal pressure should be used as the preferred method quantitatively to assess respiratory effort are uncertain. Additional studies are needed to examine the error rates in identification and typing of respiratory events with different currently employed methodologies. The American Academy of Sleep Medicine Task Force7 has

Polysomnography

67

Table 4.3 Various techniques for the measurement of respiratory efforts. Technique

Advantages

Disadvantages

Esophageal balloon or pressure catheter

Reference standard for measuring respiratory effort7 Reference standard for the detection of central apnea or hypopnea7 Reference standard for the detection of RERA or UARS7 Sleep profile does not appear to be significantly affected in patients with OSAHS54 Provides semiquantitative measurement of ventilation, but most sleep laboratories use uncalibrated RIP (qualitative) Can also provide indirect measurement of airflow (tidal volume is proportional to airflow) Inexpensive Easy to use

Invasive Not universally tolerated May interfere with sleep by reducing total sleep time and sleep efficiency in non-apneic patients54 No studies have compared alternative techniques of measuring respiratory effort or flow limitation with the reference standard Relatively expensive

Respiratory inductance plethysmography (RIP): Detects changes in the circumference of the rib cage and abdomen during breathing; when properly calibrated, the sum of these two signals provides a measure of tidal volume Piezo sensors, strain gauges, and thoracic impedance

Cumbersome nature of the calibration technique and controversy regarding the optimal calibration method55,56 Frequency of central apnea may be overestimated57 Unclear whether it provides quantitative measurements of ventilation throughout sleep period in unrestrained humans who often changes body position58–60 Less reliable than the RIP More sensitive to the changes in body position that may produce reduction in transducer tension61 Few data on which to judge the accuracy of these sensors to qualitatively or semiquantitatively record flow or volume changes compared with reference standards

RERA, respiratory effort-related arousal; UARS, upper airway resistance syndrome; OSAHS, obstructive sleep apneahypopnea syndrome.

recommended reference standard methods as well as other comparative but less sensitive methods for the detection of airflow and respiratory changes as shown in Table 4.2 and 4.3.

The quality of evidence and recommendation grades for various breathing monitoring devices in the detection of sleep-disordered breathing events are described in an original

Diagnostic studies for sleep apnea/hypopnea

Oxyhemoglobin saturation

Monitoring oxyhemoglobin saturation provides the clinician with a parameter of sleep disorder severity and consequently may be useful in management decision-making. Pulse oximeters have proven to be a major asset in the diagnosis and severity assessment of sleep-disordered breathing. It is noninvasive, relatively unobtrusive and, within limitations, discussed below, accurate.63 The clinician should be aware, however, that variation in the oximeter response sampling and response frequency may influence the accuracy in measurements of the oscillatory changes in oxyhemoglobin saturation that are typical of patients with sleep-disordered breathing. Optimal detection of fluctuations in oxyhemoglobin saturation requires that the signal averaging time should not exceed 3 s. A longer averaging time risks underestimation of the severity of the magnitude of desaturation, as shown in Figure 4.9.64 The response time may also vary with the characteristics or the placement of pulse oximeter probes (e.g. the finger or the ear). Clinicians should evaluate both the steady-state and transient responses of oximeters before employing them for cardiopulmonary sleep studies. There is a need to develop standards for such instrumentation in a similar fashion to the standards developed for spirometry.65 The clinician should be aware that pulse oximetry readings may be inaccurate in certain clinical situations, even if the device is functioning properly and is free from the external interference. Abnormal hemoglobin or hemoglobin variants may interfere with the accuracy of pulse oximetry if absorption properties are similar to those of ‘normal’

100 SaO2 (%)

paper by the American Academy of Sleep Medicine Task Force.7

90 80 70

100 SaO2 (%)

68

90 80 70 0

60

120

180

240

Time (s)

Figure 4.9 Example of the SaO2 signals measured with two identical pulse oximeters simultaneously. Top: one oximeter was set to an averaging time (T) of 3 s (control). Bottom: the other oximeter was first set to T = 3 s and subsequently to T = 21 s. The vertical dashed line indicates the time when the setting of T was moved from 3 s to 21 s.

oxyhemoglobin or deoxyhemoglobin. For example since carboxyhemoglobin absorbs approximately the same amount of light as oxyhemoglobin, a pulse oximetry value may not represent oxyhemoglobin (Figure 4.10).66–70 In cases of carbon monoxide poisoning or in chronic, heavy smokers, a falsely reassuring pulse oximetry reading may notably mask reduced oxyhemoglobin saturation. Methemoglobin also absorbs a similar amount of light as oxyhemoglobin,68 and SpO2 tends to be about 85% at higher methemoglobin levels, regardless of the true percentage of oxyhemoglobin (Figure 4.11).66,71–73 When

Polysomnography 100

100 SpO2 80

90

60

80

SpO2 and SaO2 (%)

Saturation SpO2 or O2Hb (%)

69

40 O2Hb

20 FiO2 = 1.0 0 0

20

40

60

80

100

70 60 50

COHb 40

Figure 4.10 Effect of carboxyhemoglobin on measured oxygen saturation by pulse oximetry (SpO2). SpO2 and O2Hb versus carboxyhemoglobin (COHb) at FiO2 = 1.0. SpO2 consistently overestimates saturation in the presence of COHb. At 70% COHb and 30% O2Hb, SpO2 is still around 90%. (Adapted from Barker and Tremper.)69

carboxyhemoglobinemia or methemoglobinemia is suspected, co-oximetry, rather than pulse oximetry is required to accurately measure oxyhemoglobin. Co-oximeters use four rather than two wavelengths of light to detect oxyhemoglobin, deoxyhemoglobin, carboxyhemoglobin, and methemoglobin, but require a sample of arterial blood.74,75 Sickle cell and fetal hemoglobin generally produces pulse oximeter readings similar to those of normal hemoglobin.76–78 Several methods have been proposed to describe a patient’s oxyhemoglobin saturation during sleep. Perhaps the most frequently used is the nadir of O2 saturation, but this value

FiO2 = 1.0

30 0

20

40

60

MetHb (%)

Figure 4.11 Effect of methemoglobin on measured oxygen saturation by pulse oximetry. SpO2 reading (blue circles) and true SaO2 by blood gas (red square along the line) versus MetHb percentage at FiO2 = 1.0. (Adapted from Barker et al.)72

may not be the most physiologically relevant, because it may relate to a single, transient event. Other measures, such as mean overnight oxyhemoglobin saturation or average desaturation per event, have also been used. A convenient graphical format is the cumulative oxyhemoglobin saturation histogram, in which the total percentage of sleep time spent at each saturation is presented.79 From this format, a number of descriptive parameters may be derived, including percentage of time spent with SpO2 below 90%, 80%, 70% and 60% and the SpO2 at which 50% of the time is spent. Unfortunately, we do not currently know the degree and

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duration of desaturation that reflects a health hazard. Apneas and hypopneas often result in oxyhemoglobin desaturation, usually reaching nadir levels within 30 s of the termination of the abnormal breathing event. Oxyhemoglobin saturation monitoring may show recurrent episodes of desaturation and resaturation in a ‘saw-tooth’ pattern in patients with OSAHS. As discussed above the oximeter should be set to the fastest response speed in order to accurately capture the transient peaks and troughs of SpO2. Limb movements

Limb movements are recorded during PSG using a surface EMG of the anterior tibialis muscle. It is important to detect these movements, because they may define PLMD, a primary sleep disorder in which repetitive leg movements or ‘jerks’ precipitate arousals, resulting in daytime sleepiness. It is not infrequent that patients have more than one sleep abnormality. PLMD may be either a comorbid feature of sleep-disordered breathing, or a consequence of OSAH (e.g. arousals due to abnormal breathing events resulting in secondary limb movement). It is important to distinguish primary from secondary limb movements, because of their impact on therapeutic directions. As with other variables, one can calculate the number of limb movement events per hour of sleep and identify those that occur independently from abnormal breathing events in order to define and potentially quantify disease severity (i.e. PLMD). Snoring

The amount and intensity of snoring may be determined with a microphone placed over the upper airway. Snoring can be used as an

additional marker to titrate therapy with positive pressure,80 although inspiratory airflow limitation is a more useful and sensitive marker than snoring alone.81 There is, however, no standardized, commercially available device to calibrate these microphones for clinical use. Body position monitoring

The severity of OSAHS may vary with body position (generally worse in the supine position) and, since this feature may have therapeutic implications, it is important to monitor posture during sleep. Furthermore, recording sleep and breathing in all body positions increases the comprehensive degree of the PSG and may enhance the predictive power of the results. Body position monitors can provide information regarding body position dependency of sleep-disordered breathing.82 Some patients with such supine position dependency may be treated using the ‘sleep-sock’ technique, wherein a tennis ball is placed in a sock which is safety-pinned to the back of the sleeping garment. If the patient assumes the supine position, he or she will be prompted to resume sleeping in lateral recumbency. It should be noted that the long-term effectiveness of this intervention has not been systematically evaluated in large study populations. Electrocardiogram

The ECG is useful to detect arrhythmias or variability in heart rate associated with sleepdisordered breathing.83,84 Identification of dysrhythmias and arrhythmias may affect therapeutic strategies, which may be more or less aggressive depending on the nature of the ECG abnormality (e.g. as it indicates cardiac ischemia or rhythm abnormalities). Moreover,

Polysomnography heart rate acceleration may be a clue to arousal.

Validity of diagnostic polysomnography PSG is considered the ‘gold standard’ for the diagnosis of sleep disorders. However, a negative PSG does not conclusively exclude the diagnosis of OSAHS, especially in adults with a high pretest clinical suspicion of the disease. One prospective study demonstrated that a single negative study was inadequate to exclude OSAHS in patients with one or more of the important clinical markers of the disease, and 6 of 11 such patients had a positive second sleep study. Thus, a second diagnostic PSG should be considered in patients who have an unexpectedly negative first study.

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or treatment efficacy. Newly developed selfadjusting CPAP machines that monitor inspiratory flow may be as effective as sleep technicians in determining the CPAP prescription for home use85 but trained technologists remain a valuable problem-solving and educational resource during the titration process. An apparent value of auto-titrating CPAP devices is to eliminate the burden of manual titration on technicians, thereby permitting greater freedom to provide patient education and support, which hopefully will increase adherence to recommended therapy.86 A more complete discussion of positive-pressure therapy is provided in Chapter 6. PSG can also be used for a follow-up evaluation to determine the adequacy of treatment, the timing of which depends on the nature of the treatment (weight loss, medication, positive-pressure therapy, surgery, oral appliances, assisted ventilation, etc.).

‘Split-night’ PSG studies Assessment of treatment modalities Besides its utility as a diagnostic tool, PSG has been used in the context of titrating continuous positive airway pressure (CPAP) or bilevel positive pressure therapy for OSAHS. During PSG, pressure applied via nasal mask, full facemask or nasal prongs is increased in response to persistent snoring, apneas, hypopneas, desaturations, or arousals. The optimal pressure determined from this type of evaluation is used for the prescription of home therapy. Laboratory PSG (level I) during titration identifies persistent arousals that are not attributable to OSAHS but may be caused by PLMs, and also identifies leaks at the interface or mouth that might impair patient tolerance

Traditionally, patients undergo a diagnostic PSG over a full night in the sleep laboratory, with a subsequent night of study during which positive-pressure titration is performed. However, there has been a recent trend to perform split-night studies, in which the diagnosis of OSAHS is established in the first portion of the night of PSG monitoring and the therapeutic positive pressure and optimal interface are determined during the second portion of the night. The diagnostic portion of the study generally reflects a period of 2–3 h. If moderate to severe OSAHS is diagnosed, the remaining 3–5 h of the study are available for titration. When positive for OSAHS, the first half of the night has been shown to provide a reasonably accurate appraisal of disease severity,87,88 and a single split-night study can also

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establish the correct pressure in a majority of patients.88–91 Patient adherence does not appear to be adversely affected by a half night versus a full night of titration in the laboratory.91–93 This method appears to be a realistic approach to diagnosis and the initiation of therapy, particularly in patients with high pretest clinical probability and enough events (usually more than 30 apneic events) recorded for the diagnostic portion of the split-night study. A partial night diagnostic study that is negative for OSAHS cannot reliably exclude the diagnosis, and therefore recording must be continued for a full night in these instances. MSLT should not be performed after a splitnight study, since the patient will not be in a ‘steady state’ during this time.

Evaluation of sleepiness Hypersomnolent patients may complain of excessive daytime sleepiness (EDS), falling asleep in inappropriate places and under inappropriate circumstances (e.g. while driving, at school, at work, during social activities). The consequences of EDS can be severe, including motor vehicle accidents, workrelated accidents/injuries or household accidents. EDS can be evaluated subjectively by the Epworth Sleepiness Scale (ESS) and objectively by either multiple sleep latency test (MSLT) or maintenance of wakefulness test (MWT). Demonstration of EDS is not required for the diagnosis of OSAHS, so, objective evaluation (MSLT or MWT) is not mandatory in the evaluation of OSAHS. However, if a PSG does not reveal a specific diagnosis, MSLT performed on the subsequent day may provide useful information regarding the presence of a different sleep disorder such as narcolepsy. Similarly, when complaints of sleepiness persist

after adequate treatment for OSAHS is instituted, an MSLT may reveal another sleep disorder requiring a separate treatment approach. The details of the subjective (ESS) and objective (MSLT or MWT) measurement of EDS are discussed in Chapter 2.

Screening and ambulatory monitoring techniques A number of ‘simplified’ approaches have been suggested for screening for or diagnosing individuals with sleep-disordered breathing, but there are few validatory data regarding the cost-effectiveness of all these various screening techniques in the evaluation of sleep-disordered breathing. A study by Chervin et al94 comparing cost-effectiveness of PSG, home study and no testing showed superior costutility of PSG over a period of 5 years since the initial evaluation for sleep apnea, compared to home study or no diagnostic testing. Screening devices include four-channel cardiopulmonary monitoring (level III) and pulse oximetry (level IV). Other less commonly used techniques include tracheal sound recordings,45–47 exhaled CO2 detector to monitor airflow to identify apnea,95 and the static charge-sensitive bed.96,97 With the method of static charge-sensitive bed, a mattress on which the patient sleeps sends signals that relate to the heartbeat (ballistocardiography), breathing movements, and body movements. When combined with oximetry, the static charge-sensitive bed technique may have some utility in detecting apneas, although validation of this device remains at the preliminary stage97 and use in North America appears to be very limited indeed.

Screening and ambulatory monitoring techniques Heart rate (beats/min)

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200 100 75 50 25

Impedance

Thermistor A

SaO22 (percentage) SaO percentage

A

A

100 90 80 70 60 50

Figure 4.12 Typical tracing from a four-channel cardiopulmonary recording. The parameters measured include pulse rate, chest wall impedance, airflow, and oxygen saturation. Obstructive apneas are denoted by the letter A.

Level III devices A 1994 position paper by the American Sleep Disorders Association suggested that level III and IV studies should be restricted to urgent circumstances.98 However, several subsequent studies have suggested that, within limitations, these devices are reliable and potentially useful in the diagnosis and management of OSAHS.99,100 Each of these techniques has particular strengths and weaknesses, and it is

probably optimal to have all the devices available in a large sleep disorders center. A recording from a typical level III device is shown in Figure 4.12. In this example, breathing effort is detected by chest wall impedance monitors, airflow at the nose and mouth by a temperature-sensitive thermistor, and changes in oxyhemoglobin saturation and heart rate by pulse oximetry. The frequency of apneas and hypopneas may be assessed with these devices, although it may be difficult to classify these as

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central or obstructive with certainty. Level III devices do not record sleep, and therefore arousals cannot be identified. These devices have the greatest utility when there is a high clinical, pretest probability of OSAHS with a low clinical likelihood of a significant falsenegative study. Portable recording devices may be used to diagnose OSAHS in the home as well as in sick, hospitalized patients who are too ill to be evaluated in an outpatient laboratory setting. Although it remains to be tested, home recording may also be more convenient and less costly than laboratory studies to assess the adequacy of existing treatment for OSAHS with positive airway pressure, weight loss, surgery, or an oral appliance, although this is unproven. It is controversial whether nasal CPAP can be accurately titrated to the patient’s therapeutic needs using home monitoring. Most sleep specialists believe that the most accurate pressure recommendations can be made after assessment through full PSG, although titration utilizing a fourchannel, level III portable recorder in the home environment has been reported.101 In this study, however, a technologist was present at the bedside to adjust the pressure when appropriate, in response to breakthrough events. The new technological development of auto-adjusting nasal CPAP units may resolve this issue in the future. Studies comparing technician-determined optimal CPAPs and pressures determined by an auto-titrating machine in patients with sleep apnea found no difference between the manually derived pressure determined with full PSG monitoring and the pressure derived by the auto-adjusting device in sleep laboratory or in home settings.85,102 Level III devices have some notable limitations. Interpretation must be performed in the absence of objective measures of sleep. It is

essential that the clinician assess the results of any level III device study in the context of the pretest clinical suspicion for the presence of sleep apnea.103 There also remains a paucity of evidence-based literature supporting the validity of level III devices in the diagnosis of sleepdisordered breathing in otherwise unselected patients (e.g. without excluding individuals with underlying pulmonary or neurologic disorders such as might be seen in the patient population referred to sleep centers).

Level IV devices Application of pulse oximetry alone as an example of a level IV device in the diagnosis of OSAHS is controversial. Although OSAHS can produce a classic oximetry pattern of desaturation–resaturation, there is inadequate sensitivity for routine diagnostic use.28 The sensitivity of oximetry may be increased when combined with a pretest clinical score, but it has been suggested that some patients may still be missed28 due to the relatively low predictive value for the detection of apnea (0.56).104 To determine the accuracy of oximetry alone for diagnosing sleep apnea, Douglas and colleagues105 studied 200 patients with PSG and oximetry. They found 53% sensitivity and 97% specificity for diagnosing sleep-disordered breathing, using event identification criteria of * 4% desaturation/event and >10 events/h.105 In cases where the clinical suspicion is not high, an oximetry study may be adequate to exclude significant OSAHS from consideration, if the criterion for a positive study is the identification of 10 rapid, shortduration desaturations per hour.63,106 Home overnight oximetry is frequently used to assess the efficacy of OSAHS therapy, but investigations employing long-term outcome measures have not been published. Clinicians

Radiographic imaging must be cognizant of the very limited nature of the information provided by this modality, which provides no data relating to sleep continuity. Furthermore, the possibility of sleepdisordered breathing events unaccompanied by oxyhemoglobin desaturation but nonetheless associated with sleep fragmentation cannot be excluded by oximetry. If home oximetry study shows normal SpO2 while the patient is on therapy, and previous sleep apnea symptoms have resolved, then the physician and patient may be somewhat reassured that the therapy is adequate. In this regard, the definition of adequate overnight oxyhemoglobin saturation remains open to question. Finally, a single night of oximetry may not be representative of the patient’s actual response to therapy, and it is unclear if such studies are useful and cost-effective. The value and optimal use of oximetry in the evaluation of patients suspected of having sleep-disordered breathing are not known with certainty.106 Practice parameter guidelines published by the American Sleep Disorders Association in 1994 recommended that level IV devices should not be used for the evaluation of OSAHS.98

Radiographic imaging Although there are no evidence-based data, radiographic imaging may be an adjunct to clinical evaluation, particularly when surgical treatment or dental appliances are considered as treatment options. It has significantly advanced our understanding of the pathogenesis of sleep apnea, and it may also identify various sites of upper airway obstruction to potentially facilitate individualization of treatment strategies. The role of upper airway imaging in the evaluation and management of sleep-disordered breathing seems promising,

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but there is a paucity of evidence-based literature supporting these techniques, and therefore any discussion in this regard is conceptual. There does not appear to be an evidence-based role for routine use of sophisticated imaging techniques in the evaluation of patients with suspected OSAHS. The upper airway can be subdivided anatomically into three regions:107–109 (1) The nasopharynx (the region between the nasal turbinates and the hard palate); (2) The oropharynx, which can be subdivided into the retropalatal region (also called the velopharynx) and the retroglossal region, and; (3) the hypopharynx (the region from the base of the tongue to the larynx). Imaging techniques have revealed that the upper airway is smallest in the oropharynx in both normal subjects and patients with OSAHS, particularly in the retropalatal region.107,110–113 Airway closure during sleep occurs in the retropalatal region in the majority of patients with sleep apnea.114,115 The relevant anatomic structures of this region (tongue, lateral pharyngeal walls, lateral parapharyngeal fat pads) in normal patients and in patients with OSAHS are shown in Figures 4.13 and 4.14. The ideal upper airway imaging modality in OSAHS is one which is inexpensive and noninvasive, and does not involve radiation. In addition, it should be performed in the supine position, with the possibility of dynamic imaging during sleep in order to visualize apneic events, and should provide high-resolution anatomic representations of the airway and soft tissue structures. Such an ideal modality does not exist; the advantages/usefulness and disadvantages/limitations of various techniques are summarized in Table 4.4. Upper airway imaging is not indicated in the routine clinical evaluation, as its value in diagnosing and developing management strategies for OSAHS has not been established.

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Diagnostic studies for sleep apnea/hypopnea B

Figure 4.13 Reduced upper airway size in obstructive sleep apnea: comparison of a mid-sagittal image of a normal subject (A) and a patient with sleep apnea (B). Soft palate and tongue area are larger in the patient with sleep apnea, leading to a reduction in upper airway size. (RP, retropalatal region, from the level of the hard palate to the distal margin of the soft palate; RG, retroglossal region, from the distal margin of the soft palate to the base of the epiglottis).

A

B Figure 4.14 Reduced airway size in obstructive sleep apnea: comparison of an axial image at the minimum airway area (retropalatal region) of a normal subject (A) and a patient with sleep apnea (B). Note the smaller airway size and airway width in the patient with sleep apnea. In addition, the thickness of the lateral pharyngeal wall (distance between the airway and parapharyngeal fat pads) is greater in the patient with sleep apnea.

Radiographic imaging

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Table 4.4 Advantages and disadvantages of various imaging modalities. Technique

Advantages

Disadvantages

Cephalometry: Lateral radiograph of the head and neck

Widely available and easy to perform No weight limitation Less expensive than CT or MRI Evaluates bony abnormalities such as retrognathia Useful in the evaluation of patients undergoing maxillomandibular advancement or placement of dental appliances Useful in predicting palatopharyngoplasty failure116

Fluoroscopy

Dynamic upper airway imaging during wakefulness or, potentially, during sleep

Acoustic reflection: Measurement of airway caliber on the basis of reflected sound waves

Non-invasive No associated radiation Reproducible Possibility of dynamic imaging No weight limitation New devices may permit assessment during sleep

Radiographic equipment; technique and interpretative skills must be standardized Performed only in the sitting or standing position while patients is awake, and may not reflect condition during sleep Two-dimensional evaluation of skeletal and soft tissue structures, no volumetric analytic capabilities Limited information about anterior–posterior structures and no information about lateral soft tissue structures Significant radiation exposure Insensitive to measure changes in airway size or the detailed motion of the soft tissue structures surrounding the upper airway No capability of cross-sectional (axial or sagittal) imaging Performed while the patient is awake, and may not reflect condition during sleep Primarily used as a research tool; clinical usefulness has not been adequately studied Performed while patient is awake, in the sitting position, through the mouth, which alters upper airway anatomy Does not provide high-resolution anatomic representation of the airway or soft tissue structures Invasive Evaluates only airway lumen, not surrounding soft tissue structures Generally performed during wakefulness; cumbersome to do during sleep

Nasopharyngoscopy Widely available and easy to perform No radiation, no weight limitation Can be performed in sitting or supine positions during wakefulness or sleep Muller maneuver, performed during the procedure, may provide insight into the location of upper airway closure by potentially simulating obstructive apneas

continued

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Table 4.4 continued Advantages and disadvantages of various imaging modalities. Technique

Computed tomography

MR imaging

Advantages May be useful in predicting UPPP outcome by determining if retropalatal or retroglossal obstruction occurs during the Muller maneuver117–119 May be useful to identify upper airway lesions (e.g. tumors) Supine imaging Accurate assessment of upper airway cross-sectional area and volume Excellent airway and bony resolution; however, images acquired only in axial plane Three-dimensional reconstruction of craniofacial structures (cranium, mandible, hyoid) and airway May be useful in evaluating patients who undergo bony manipulations (dental appliances and maxillomandibular advancement) Dynamic imaging can be performed with electron beam (ultrafast CT), providing excellent temporal and spatial resolution (images in 50 ms) Helical CT allows for direct acquisition of three-dimensional images Supine imaging, generally during wakefulness Accurate assessment of upper airway cross-sectional area and volume Excellent airway, soft tissue and fat resolution Direct sagittal, coronal and axial images without radiation, so studies can be performed and repeated during wakefulness and sleep Three-dimensional reconstruction of soft tissue structures (tongue, soft palate, lateral parapharyngeal fat pads, lateral pharyngeal walls) and airway (Figures 4.13 and 4.14)

Disadvantages

Relatively expensive Weight limitation of approximately 400 lb Radiation exposure limits ability to perform repeat studies during wakefulness and sleep Poor resolution for upper airway adipose tissue compared with MRI Generally performed during wakefulness and may not reflect condition during sleep

Technique not widely available Expensive Weight limitation of approximately 300 lb Claustrophobia is a problem Cannot be performed in patients with ferromagnetic clips or pacemakers Generally performed during wakefulness and may not reflect condition during sleep

continued

Summary

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Table 4.4 continued Advantages and disadvantages of various imaging modalities. Technique

Disadvantages

Advantages Useful in the evaluation of patients who undergo surgical procedures that alter upper airway soft tissue configuration (e.g. UPPP, geniohyoid advancement) Dynamic imaging possible with ultrafast MRI Potential for soft tissue characterization with spectroscopic imaging studies (e.g. for fat and water) and for magnetic tagging imaging to study the biomechanics for the upper airway

UPPP, uvulopalatopharyngoplasty.

There are no published studies indicating that upper airway imaging improves treatment outcome, and, in addition, those studies examining the pathogenesis of sleep apnea have largely been applied to awake patients, and may not provide an optimal representation of upper airway features and behavior during sleep.

Summary There are several diagnostic techniques and various instruments available for the evaluation of sleep-disordered breathing. The initial evaluation is based on clinical suspicion, possibly incorporating various models, examining particular clinical features, risk factors and morphometric or anthropometric measurements.

PSG is the ‘gold standard’ test for the evaluation of OSAHS, and the clinician must have knowledge of the individual monitored variables and recording as well as the limitations of the currently employed criteria employed in the scoring of abnormal events. In general, patients with high probability of OSAH based on clinical suspicion and predictability models may be candidates for split-night PSG, while the diagnostic approach in patients with low to moderate probability of OSAHS or possible other pulmonary or non-pulmonary sleep–wake disorder requires full-night PSG. Portable monitoring devices also have some use in specific situations, but with clear limitations. Radiographic imaging has potential usefulness in understanding the pathogenesis of sleep-disordered breathing, but its routine use in the evaluation of OSAHS awaits outcome data.

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41. American Sleep Disorders Association. EEG arousals: scoring rules and examples. Sleep 1992;15:173. 42. Agnew Jr. HW, Webb WB, Williams RL. The first night effect: an EEG study of sleep. Pyschophysiology 1966;2(3):263–6. 43. Wittig RM, Romaker A, Zorick FJ, Roehrs TA, Conway WA, Roth T. Night-to-night consistency of apneas during sleep. Am Rev Respir Dis 1984;129(2):244–6. 44. Fisher JG, Garza G, Flickinger R, de la Pena A. An alternate method of recording airflow during sleep. Sleep 1980;2(4):461–3. 45. Krumpe PE, Cummiskey JM. Use of laryngeal sound recordings to monitor apnea. Am Rev Respir Dis 1980;122(5):797–801. 46. Cummiskey J, Williams TC, Krumpe PE, Guilleminault C. The detection and quantification of sleep apnea by tracheal sound recordings. Am Rev Respir Dis 1982;126(2):221–4. 47. Peirick J, Shepard Jr. JW, Automated apnoea detection by computer: analysis of tracheal breath sounds. Med Biol Eng Comput 1983;21:632–5. 48. Norman RG, Ahmed MM, Walsleben JA, Rapoport DM. Detection of respiratory events during NPSG: nasal cannula/pressure sensor versus thermistor. Sleep 1997;20(12):1175–84. 49. Berg S, Haight JS, Yap V, Hoffstein V, Cole P. Comparison of direct and indirect measurements of respiratory airflow: implications for hypopneas. Sleep 1997;20(1):60–4. 50. Fleury B, Rakotonanahary D, Hausser-Hauw C, Lebeau B, Guilleminault C. A laboratory validation study of the dignostic mode of the Autoset system for sleep-related respiratory disorders. Sleep 1996;19(6):502–5 [erratum appears in Sleep 1996;19(7):601]. 51. Farre R, Montserrat JM, Rotger M, Ballester E, Navajas D. Accuracy of thermistors and thermocouples as flow-measuring devices for detecting hypopnoeas. Eur Respir J 1998;11(1):179–82.

52. Cohn MA, Rao AS, Broudy M, et al. The respiratory inductive plethysmograph: a new non-invasive monitor of respiration. Bull Eur Physiopathol Respir 1982;18(4):643–58. 53. Larsen VH, Christensen PH, Oxhoj H, Brask T. Impedance pneumography for long-term monitoring of respiration during sleep in adult males. Clin Physiol 1984;4(4):333–42. 54. Sampson MG, Walskben JA. Effect of esophageal balloon on sleep structure (abstract). Sleep Res 1984;13:211. 55. Chadha TS, Watson H, Birch S, et al. Validation of respiratory inductive plethysmography using different calibration procedures. Am Rev Respir Dis 1982;125(6):644–9. 56. Stradling JR, Chadwick GA, Quirk C, Phillips T. Respiratory inductance plethysmography: calibration techniques, their validation and the effects of posture. Bull Eur Physiopathol Respir 1985;21:317–24. 57. Staats BA, Bonekat HW, Harris CD, Offord KP. Chest wall motion in sleep apnea. Am Rev Respir Dis 1984;130(1):59–63. 58. Gugger M, Gould GA, Whyte KF, et al. Inductive plethysmographs do not accurately measure ventilation during sleep in unrestrained subjects (abstracts). Am Rev Respir Dis 1987;135(suppl):A50. 59. Spier S, England S. The respiratry inductive plethysmograph: bands versus jerkins. Am Rev Respir Dis 1983;127(6):784–5. 60. Zimmerman PV, Connellan SJ, Middleton HC, Tabona MV, Goldman MD, Pride N. Postural changes in rib cage and abdominal volume–motion coefficients and their effect on the calibration of a respiratory inductance plethysmograph. Am Rev Respir Dis 1983;127(2):209–14. 61. Surez M, Bizousky R, Befeler A, Sackner MA. Performance of mecury in silastic strain gauges and respiratory inductive pletyhsmograph as assessed with spirometry (abstract). Am Rev Respir Dis 1987;135(suppl):A49.

References 62. Zolty P, Sanders MH, Pollack IF. Chiari malformation and sleep-disordered breathing: a review of diagnostic and management issues. Sleep 2000;23(5):637–43. 63. Series F, Marc I, Cormier Y, La Forge J. Utility of nocturnal home oximetry for case finding in patients with suspected sleep apnea hypopnea syndrome. Ann Inter Med 1993;119(6):449–53. 64. Farre R, Montserrat JM, Ballester E, Hernandez L, Rotger M, Navajas D. Importance of the pulse oximeter averaging time when measuring oxygen desaturation in sleep apnea. Sleep 1998;21(4):386–90. 65. Gardner R. Snowbird workshop on standardization of spirometry. Am Rev Respir Dis 1979;119:831. 66. Grace RF. Pulse oximetry. Gold standard or false sense of security? Med J Aust 1994;160(10):638–44. 67. Poets CF, Southall DP. Noninvasive monitoring of oxygenation in infants and children: practical considerations and areas of concern. Pediatrics 1994;93(5): 737–46. 68. Mengelkoch LJ, Martin D, Lawler J. A review of the principles of pulse oximetry and accuracy of pulse oximeter estimates during exercise. Phys Ther 1994;74(1):40–9. 69. Barker SJ, Tremper KK. The effect of carbon monoxide inhalation on pulse oximetry and transcutaneous PO2. Anesthesiology 1987;66(5):677–9. 70. Hampson NB. Pulse oximetry in severe carbon monoxide poisoning.Chest 1998;114(4):1036–41. 71. Severinghaus JW, Kelleher JF. Recent developments in pulse oximetry. Anesthesiology 1992;76(6):1018–38. 72. Barker SJ, Tremper KK, Hyatt J. Effects of methemoglobinemia on pulse oximetry and mixed venous oximetry. Anesthesiology 1989;70(1):112–17. 73. Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: etiology,

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pharmacology, and clinical management. Ann Emerg Med 1999;34(5):646–56. Stoneham MD. Uses and limitations of pulse oximetry. Br J Hosp Med 1995;54(1):35–41. Tallon RW. Oximetry: state-of-the-art. Nurs Manage 1996;27(11):43–4. Lindberg LG, Lennmarken C, Vegfors M. Pulse oximetry–clinical implications and recent technical developments. Acta Anaesthesiol Scand 1995;39(3):279–87. Ortiz FO, AldrichTK, Nagel RL, Benjamin LJ. Accuracy of pulse oximetry in sickle cell disease. Am J Respir Crit Care Med 1999;159(2):447–51. Mendelson Y. Pulse oximetry: theory and applications for noninvasive monitoring. Clin Chem 1992;38(9):1601–7. Slutsky AS, Strohl KP. Quantification of oxygen saturation during episodic hypoxemia. Am Rev Respir Dis 1980;121(5):893–5. Berkani M, Lofaso F, Chouaid C, et al. CPAP titration by an auto-CPAP device based on snoring detection: a clinical trial and economic considerations. Eur Respir J 1998;12(4):759–63. Ayappa I, Norman RG, Hosselet JJ, Gruenke RA, Walsleben JA, Rapoport DM. Relative occurrence of flow limitation and snoring during continuous positive airway pressure titration. Chest 1998;114(3):685–90. Cartwright RD. Effect of sleep position on sleep apnea severity. Sleep 1984;7(2):110–14. Pascal-Sebaoun S, Milosevic D, Orvoen-Frija E, Leger D, Basdevant A, Laaban JP. [Value of Holter ECG in the diagnosis of sleep apnea syndrome in patients with massive obesity]. Presse Med 2000;29(1):11–16. Keyl C, Lemberger P, Pfeifer M, Hochmuth K, Geiseler P. Heart rate variability in patients with daytime sleepiness suspected of having sleep apnoea syndrome: a receiveroperating characteristic analysis. Clin Sci (Colch) 1997;92(4):335–43. Lloberes P, Ballester E, Montserrat JM, et al. Comparison of manual and automatic CPAP titration in patients with sleep

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Diagnostic studies for sleep apnea/hypopnea apnea/hypopnea syndrome. Am J Respir Crit Care Med 1996;154(6 Pt 1):1755–8. Stradling JR, Barbour C, Pitson DJ, Davies RJ. Automatic nasal continuous positive airway pressure titration in the laboratory: patient outcomes. Thorax 1997;52(1):72–5. Sanders MH, Black J, Costantino JP, Kern N, Studnicki K, Coates J. Diagnosis of sleepdisordered breathing by half-night polysomnography. Am Rev Respir Dis 1991;144(6):1256–61. Iber C, O’Brien C, Schluter J, Davies S, Leatherman J, Mahowald M. Single night studies in obstructive sleep apnea. Sleep 1991;14(5):383–5. Yamashiro Y, Kryger MH. CPAP titration for sleep apnea using a split-night protocol. Chest 1995;107(1):62–6. Sullivan CE, Issa FG, Berthon-Jones M, McCauley VB, Costas LJ. Home treatment of obstructive sleep apnoea with continuous positive airway pressure applied through a nose-mask. Bull for Physiopathol Respir 1984;20:49–54. Strollo Jr. PJ, Sanders MH, Costantino JP, Walsh SK, Stiller RA, Atwood Jr. CW. Splitnight studies for the diagnosis and treatment of sleep-disordered breathing. Sleep 1996;19(10 Suppl):S255–9. Fleury B, Rakotonanahary D, Tehindrazanarivelo AD, Hausser-Hauw C, Lebeau B. Long-term compliance to continuous positive airway pressure therapy (nCPAP) set up during a split-night polysomnography. Sleep 1994;17(6):512–15. Sanders MH, Kern NB, Costantino JP, et al. Prescription of positive airway pressure for sleep apnea on the basis of a partial-night trial. Sleep 1993;16(8 Suppl):S106–7. Chervin RD, Murman DL, Malow BA, Totten V. Cost-utility of three approaches to the diagnosis of sleep apnea: polysomnography, home testing, and empirical therapy. Ann Intern Med 1999;130(6):496–505.

95. Schmidt-Nowara W. The utility of a CO2 home monitor respisomnograph in the diagnosis of sleep apnea syndrome (abstract). Sleep Res 1985;14:279. 96. Salmi T, Leinonen L. Automatic analysis of sleep records with static charge sensitive bed. Electroencephalogr Clin Neurophysiol 1986;64(1):84–7. 97. Svanborg E, Larsson H. Screening of obstructive sleep apnea with respiration movement and SaO2 monitoring: high diagnostic accuracy in comparison with polygraphic recordings (abstract). Sleep Res 1987;16:587. 98. Standards of Practice Committee of the American Sleep Disorders Association. Practice parameters for the use of portable recording in the assessment of obstructive sleep apnea. Sleep 1994;17(4):372–7. 99. Redline S, Tosteson T, Boucher MA, Millman RP. Measurement of sleep-related breathing disturbances in epidemiologic studies. Assessment of the validity and reproducibility of a portable monitoring device. Chest 1991;100(5): 1281–6. 100. White DP, Gibb TJ, Wall JM, Westbrook PR. Assessment of accuracy and analysis time of a novel device to monitor sleep and breathing in the home. Sleep 1995;18(2):115–26. 101. Waldhorn RE, Wood K. Attended home titration of nasal continuous positive airway pressure therapy for obstructive sleep apnea. Chest 1993;104(6):1707–10. 102. Fletcher EC, Stich J, Yang KL. Unattended home diagnosis and treatment of obstructive sleep apnea without polysomnography. Arch Fam Med 2000;9(2):168–74. 103. Meyer TJ, Eveloff SE, Kline LR, Millman RP. One negative polysomnogram does not exclude obstructive sleep apnea. Chest 1993;103(3):756–60. 104. Farney RJ, Walker LE, Jensen RL, Walker JM. Ear oximetry to detect apnea and differentiate rapid eye movement (REM) and

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non-REM (NREM) sleep. Screening for the sleep apnea syndrome. Chest 1986;89(4):533–9. Douglas NJ, Thomas S, Jan MA. Clinical value of polysomnography. Lancet 1992;339(8789):347–50. Pack AI. Simplifying the diagnosis of obstructive sleep apnea (editorial). Ann Inter Med 1993;119(6):528–9. Schwab RJ, Gupta KB, Gefter WB, Metzger LJ, Hoffman EA, Pack AI. Upper airway and soft tisue anatomy in normal subjects and patients with sleep-disordered breathing. Significance of the lateral pharyngeal walls. Am J Respir Crit Care Med 1995;152(5 Pt 1):1673–89. Hudgel DW. The role of upper airway anatomy and physiology in obstructive sleep apnea. Clin Chest Med 1992;13(3):383–98. van Lunteren E. Muscles of the pharynx: structural and contractile properties. Ear Nose Throat J 1992;13(3):383–98. Galvin JR, Rooholamini SA, Stanford W. Obstructive sleep apnea: diagnosis with ultrafast CT. Radiology 1989;171(3):775–8. Shepard Jr. JW, Thawley SE. Evaluation of the upper airway by computerized tomography in patients undergoing uvulopalatopharyngoplasty for obstructive sleep apnea. Am Rev Respir Dis 1989;140(3):711–16. Schwab RJ, Gefter WB, Hoffman EA, Gupta KB, Pack AI. Dynamic upper airway imaging during awake respiration in normal subjects and patients with sleep disordered

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breathing. Am Rev Respir Dis 1993;148(5):1385–400. Schwab RJ, Gefter WB, Pack AI, Hoffman EA. Dynamic imaging of the upper airway during respiration in normal subjects. J Appl Physiol 1993;74(4):1504–14. Horner RL, Shea SA, McIvor J, Guz A. Pharyngeal size and shape during wakefulness and sleep in patients with obstructive sleep apnoea. Q J Med 1989;72(268):719–35. Suto Y, Matsuo T, Kato T, et al. Evaluation of the pharyngeal airway in patients with sleep apnea: value of ultrafast MR imaging. Am J Roentgenol 1993;160(2):311–14. Riley R, Guilleminault C, Powell N, Simmons FB. Palatopharyngoplasty failure, cephalometric roentgenograms, and obstructive sleep apnea. Otolaryngol Head Neck Surg 1985;93(2):240–4. Sher AE, Thorpy MJ, Shprintzen RJ, Spielman AJ, Burack B, McGregor PA. Predictive value of Muller maneuver in selection of patients for uvulopalatopharyngoplasty. Laryngoscope 1985;95(12):1483–7. Doghramji K, Jabourian ZH, Pilla M, Farole A, Lindholm RN. Predictors of outcome for uvulopalatopharyngoplasty. Laryngoscope 1995;105(3 Pt 1):311–4. Naya M, Vicente E, Llorente E, Marin C, Damborenea J. [Predictive value of the Müller maneuver in obstructive sleep apnea syndrome]. Acta Otorrinolaringol Esp 2000;51(1):40–5.

II Therapy

5

Medical therapy

Richard B Berry

Indications for treatment The indications for treatment of obstructive sleep apnea (OSA) have expanded since the original description of the syndrome. It is now recognized that milder forms of this disorder can be associated with daytime sleepiness1–6 and that treatment can improve symptoms and the quality of life.4–6 Over a decade ago, it was recognized that obstructive hypopnea (reductions in airflow during periods of high upper airway resistance) had the same consequences as obstructive apnea.7 The frequency of apneas and hypopneas are added to determine the apnea hypopnea index (AHI) as an indicator of disease severity. Subsequently, the upper airway resistance syndrome (UARS) was described in patients with daytime sleepiness but little or no apnea, hypopnea, or desaturation. They exhibited repetitive arousals (brief awakenings) associated with episodes of increased inspiratory effort demonstrated by esophageal pressure monitoring. The sleepiness of these patients improved after treatment of the upper airway narrowing. Arousal from respiratory stimuli is related to the level of inspiratory effort and can occur in the absence of apnea or desaturation.8 Experimentally induced repetitive arousals have been demonstrated to cause daytime sleepiness in normal individuals in the absence of arterial oxygen desaturation.9 Thus, daytime sleepiness in

UARS is believed to occur secondary to arousals from increased respiratory effort during periods of high upper airway resistance. The term respiratory effort-related arousals (RERAs) has recently been widely adopted to describe events characterized by increased respiratory effort leading to arousal from sleep which do not meet criteria for apnea or hypopnea.10 The recognition of the importance of RERAs has led to the understanding that the AHI alone may not adequately characterize the degree of respiratory-induced sleep disturbance in individuals with ‘milder OSA’. Rather than being a separate syndrome, most now feel that the upper airway resistance syndrome is simply part of the spectrum moving from non-arousing snoring at the milder end to full-blown sleep apnea at the severe end. While many will agree with this concept, how to utilize RERAs is still somewhat controversial. A consensus conference suggested that the RERA index be added to the AHI to give a true respiratory disturbance index (RDI).11 This assumes that RERAs and apnea/hypopneas disturb sleep equally (not proven). However, as most laboratories do not utilize esophageal pressure monitoring, precise identification of RERAs may be difficult. Recently, the use of nasal pressure or pneumotachograph monitoring of airflow rather than thermistors has been

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utilized to identify periods of airflow limitation (inspiratory flattening). A period of flattening followed by the abrupt return of a round airflow profile has been thought to correctly identify periods of increased upper airway resistance.12 Thus, RERAs could be identified by a pattern of flow limitation followed by arousal and reversal of flow limitation. However, almost all population studies have used thermistors, so little normative information is available with this technique. Another controversial point is whether one should count flow-limited events not associated with arousals. Certainly, not all apneas and hypopneas are associated with clear-cut cortical arousal.8 Events associated only with abrupt change in respiration/heart rate/blood pressure also appear to cause daytime sleepiness.13 If RERAs can be accurately identified, what number should be considered abnormal? Mathur and colleagues demonstrated that normal adults may have an arousal index up to 25/h.14 Therefore, one might guess that an RDI (AHI + RERA index) of around 30/h would be the range at which significant sleep disturbance would occur. Hosselet et al12 identified a flow limitation event index of 30/h as separating symptomatic from asymptomatic individuals. However, they also suggested that an AHI higher than 5/h may be needed for separation of symptomatic individuals when nasal pressure monitoring rather than thermistor flow is used to define the AHI. At this point, no absolute recommendations about what constitutes an abnormal RERA index can made. Definitions of normality, whether based on the AHI, AHI + RERA index, or AHI + a flow limitation index, will certainly depend on the technology used to detect events. What is clear is that a patient with an AHI of 10/h and a RERA index of 30/h is having a significant rate of respiratory arousals per hour, and therefore

it is not surprising that such a patient with ‘mild’ sleep apnea by conventional criteria might be quite symptomatic. In determining an indication for treatment, most physicians evaluate both the RDI (or AHI) and whether or not the patient is symptomatic (daytime sleepiness). Possible detrimental effects from severe hypoxia and evidence of cardiac or neurologic compromise are also considered. Obviously, patients with right heart failure, severe nocturnal hypoxemia or daytime hypercapnia should be treated. In general, the threshold for treating symptomatic patients is lower. For example, a recent consensus conference on positive-pressure treatment suggested that symptomatic patients with an RDI (AHI + RERA index) > 5/h be treated as well as all patients with an RDI > 30/h (with or without symptoms).11 Previous studies of patients with the UARS and two recent studies of patients with an AHI of 5–15/h have clearly demonstrated that patients with milder disease can benefit from treatment, with respect to daytime alertness and quality of life.4–6 Therefore, most physicians would treat sleepy patients with even ‘mild disease’. One caution is that the presence of snoring and mild OSA does not preclude the coexistence of other disorders such as narcolepsy or periodic leg movements in sleep. More than one patient has undergone ‘ineffective’ treatment of mild OSA with nasal CPAP while a another significant sleep disorder went unrecognized and untreated. Most clinicians would also recommend treatment of all patients with moderate to severe OSA (RDI (as defined above) > 30/h or AHI > 20/h), whether or not they are symptomatic. Such patients, if sleepy, should expect clear subjective benefit from successful treatment. A more difficult dilemma is the patient who steadfastly denies any symptoms. Such patients are less likely to perceive a subjective benefit and may be less likely to comply with

Weight loss treatment. What is the evidence for benefit in treating asymptomatic patients with OSA? A frequently quoted retrospective study by He et al15 reported a decrease in survival in untreated OSA patients with an apnea index > 20. Successful treatment with tracheostomy or continuous positive airway pressure (CPAP) normalized the survival. This suggests a benefit from effective treatment apart from symptoms. However, some have challenged the importance of OSA as a health risk.16 More rigorous demonstration of an independent survival risk for untreated OSA awaits results from studies such as the Sleep Heart Health study, which has documented some increase in risk for even relatively mild increases in the AHI.17 Until that time, patients can be told that there is reasonable preliminary evidence that the OSA may negatively impact on other comorbid disorders, such as atherosclerotic heart disease, congestive heart failure and hypertension. Some of this evidence is discussed in more detail in the section on positive-pressure treatment. This chapter will discuss two important medical treatment options: weight loss and positive pressure. As noted below, weight loss alone may be a valid treatment of mild OSA and adjunctive in moderate to severe disease in patients with a wide range of obesity. Positive pressure has traditionally been the treatment of choice for moderate to severe OSA.1,2 Studies have demonstrated that positive pressure can be effective in milder disease, although problems with acceptance and compliance may be even greater than in patients with more severe disease.6

Weight loss Many studies have demonstrated that obesity is a major risk factor for the development of

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OSA. A clinic population study of OSA patients found that approximately two-thirds were obese (body weight > 120% of predicted).1 A population-based study of 6000 Wisconsin state employees (men and women) between 30 and 60 years of age supports the above findings.3 In the Wisconsin study, an increase in body mass index (BMI) of one standard deviation was associated with a fourfold increase in the risk of sleep-disordered breathing (AHI > 5/h). Neck size was the strongest predictor, suggesting that upper body obesity is especially important. Other studies have also suggested that the distribution as well as the total amount of body fat is an important determinant of the risk for developing OSA.18 Given that obesity is an important risk factor for OSA, it is not surprising that weight loss is an important potential treatment. The benefits are not confined to patients with severe obesity, and relatively modest weight loss can have dramatic effects in individual patients.19,20 Nevertheless, to get patients to lose weight and then maintain the weight loss is a difficult task. The mechanisms by which obesity causes OSA or weight loss decreases OSA are still not known. Direct effects on upper airway anatomy (fat deposits in or near the upper airway/changes in pharyngeal muscles) or indirect changes secondary to changes in lung volume are two possible explanations for the effect of obesity on upper airway patency. One magnetic resonance (MR) study of the upper airway in OSA patients found that the amount of fat deposition near the upper airway correlated with the AHI.21 Two OSA patients who improved after weight loss also showed a decrease in fat around the pharynx. Another MR study comparing obese OSA patients and weight-matched controls found an increase in adipose deposition in the OSA patients in areas posterior and lateral to the oropharynx at the

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Figure 5.1 The effect of weight loss on the lateral pharyngeal wall. Axial MR images during wakefulness at the retropalatal region in a normal subject before weight loss (A) and after weight loss (B). After weight loss, there was a decrease in size of the lateral pharyngeal wall and an increase in lateral airway dimensions. (Reprinted with permission, from Schwab.23)

level of the palate.22 Later MR studies have shown that, while obese OSA patients do have more pharyngeal fat, the main change in upper airway size is secondary to the thickness of the lateral pharyngeal muscular walls rather than enlargement of the parapharyngeal fat pad.23 The cause of the thickening of the lateral pharyngeal muscles is not known, but weight loss decreases the thickness (Figure 5.1). The lateral wall changes make the shape of the airways of OSA different from those of normal subjects. In cross-section, the OSA airway is somewhat elliptical with the long axis in the anterior–posterior direction, while in normal subjects the long axis is in the lateral direction. Thus, the upper airway of OSA patients tends to be smaller in size and narrowed in the lateral dimension. Weight loss probably increases the airway size in that dimension.

The size of the upper airway varies with lung volume24 probably secondary to the effects of tracheal displacement (tracheal tug).25 Obesity reduces supine lung volume, and this may be another mechanism by which it reduces upper airway size. Weight loss appears to reduce the lung volume dependence of the pharyngeal area.26 Whatever the mechanism, studies have also shown that the collapsibility of the upper airway is decreased by weight loss, implying that obesity increases the tendency of the upper airway to collapse as well as decreasing the size.27 While early studies showed improvements after major weight reduction,28 other studies have documented that weight loss of even modest proportions (5–10%) can produce significant improvement in sleep apnea.20 The results will vary between patients. A given

Positive airway pressure amount of weight loss may have more effect on upper body obesity in some patients. Even patients with mild obesity (110–115% of ideal body weight) may benefit from weight reduction. Weight loss decreases the AHI but not always to acceptable levels (< 5/h). However, a reduction in collapsibility will often allow a lower level of nasal CPAP to maintain upper airway patency.27 Surgical, behavioral (traditional and very low calorie diets) and medication approaches to weight loss have all been successful in selected groups of patients.19,20,26–29 While some former anorexiant medications have been removed from the market because of an association with pulmonary hypertension, new drugs are rapidly appearing (but are often quite expensive). Surprisingly few studies have addressed the benefits of medicine for weight loss in OSA patients. However, while induction of weight loss is difficult, another major problem has been maintenance of weight loss. Sampol et al studied 216 overweight OSA patients treated by weight reduction alone.30 Twenty-four were cured by this method. After a mean follow-up period of 94 months, 13/24 patients had maintained weight loss. Even in these 13, OSA recurred in 6. Other studies have reported a recurrence of OSA after weight loss.31 Thus, periodic follow-up is required to reinforce weight loss maintenance and to check for symptoms of OSA recurrence. Because different patients have different patterns of weight loss, it is not possible to predict which patients will respond or how much weight loss is needed. In general, weight loss is most effective as a primary treatment in patients with milder OSA. In more severe patients, it is prudent to begin treatment with nasal CPAP while initiating a weight loss program. Noseda et al attempted weight loss while 39 patients were being treated with nasal CPAP for 1 year.

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However, only 3 of the 39 with weight loss could be weaned from CPAP.32 In summary, while weight loss shows promise as a treatment for sleep apnea, its widespread use as a primary treatment for other than mild disease probably awaits effective and safe medicines which will help patients lose and maintain weight loss.

Positive airway pressure Since the original description of nasal CPAP as a treatment for obstructive sleep apnea,33 positive pressure has become the mainstay of treatment for moderate to severe obstructive sleep apnea.2,10,33–36 However, patients with mild OSA,5–6 the upper airway resistance syndrome,4 or even heavy snoring37,38 have also been treated successfully with positive pressure. Since the original description of CPAP, there have been major technological improvements in delivery systems and masks. Objective compliance data are now available on most machines. However, the major challenge to the clinician is still to get patients to first accept and then to comply with positive airway pressure treatment.

Mechanism of action The mechanism of action of positive airway pressure is believed to be primarily a pneumatic splint effect on the upper airway (Figure 5.2). During application of CPAP, upper airway muscle activity decreases, implying a passive distension of the upper airway.39–42 Studies using CT or MRI have documented that CPAP does dilate the upper airway at multiple locations.43–44 In particular, there appears to be a dilation of the lateral

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+

+

+ +

A

– – – – – – –– – – –

+ + +

Figure 5.2 The pneumatic splint mechanism by which nasal positive airway pressure maintains upper airway patency is illustrated here. (A) without a mask; (B) with a nasal mask.

+

B

dimensions of the upper airway.44 Dynamic imaging studies of the upper airway have also shown that the smallest area occurs at end exhalation.45 This may explain why application of expiratory positive airway pressure alone induces some improvement in upper airway patency.46 Positive airway pressure may also have some indirect effects on the upper way via changes in lung volume.47 However, it appears that this is not the major mechanism by which positive airway pressure maintains upper airway patency.48,49 As the level of positive pressure is increased, first apnea, and then hypopnea and desaturation, are abolished. At higher pressure levels, snoring is also prevented. However, evidence of airflow limitation and high upper airway resistance may still persist. Sometimes, only a few additional centimeters of H2O pressure are required for normalizing inspiratory effort (esophageal pressure swings).50

Methods of delivery of positive pressure Currently available modes of delivering positive airway pressure are listed in Table 5.1. CPAP remains the standard method to provide

Table 5.1 Positive-pressure devices and patient interfaces. Positive-pressure devices Patient interfaces Continuous positive airway pressure (CPAP) Bilevel pressure Auto-titrating CPAP Volume-cycled ventilation

Nasal masks Nasal prongs (pillows) Full facemasks (oronasal)

positive pressure for upper airway stabilization.2,11,33–36,50,51 A blower unit provides a flow of air sufficient to maintain a constant pressure during the respiratory cycle and to overcome leaks in the system. A nasal mask is the common interface.52 The palate moves forward against the tongue, preventing oral leaks (Figure 5.2). Nasal prongs (pillows) and full facemasks53–55 are also utilized in some patients. In general, a good seal is more difficult to obtain with full facemasks (oronasal) than with nasal masks. All systems have a facility to wash out exhaled carbon dioxide. This is usually accomplished by a controlled leak through a hole or set of holes in the mask or in a small

Positive airway pressure

A

B

C

D

95

E

Figure 5.3 Several current types of interfaces for positive-pressure delivery are shown here. (A) Nasal pillows (prongs) (Breeze™ headgear, Mallinckrodt: Minneapolis, MN, USA). (B) Nasal mask (Contour™, Respironics: Pittsburgh, PA, USA). (C) Nasal mask (UltraMirage™, ResMed: San Diego, CA, USA). (D) Nasal mask (Simplicity™, Respironics: Pittsburgh, PA, USA). (E) A full facemask (Mirage™, ResMed: San Diego, CA, USA).

section of tubing connecting the hose from the blower unit to the mask (Whisper Swivel™, Respironics). In Figure 5.3, several different types of masks are shown, including nasal and full facemasks and nasal prongs (pillows). Bilevel pressure, in which different pressures are delivered in inspiration (inspiratory positive airway pressure (IPAP)) and expiration (expiratory positive airway pressure (EPAP)) has also been shown to be effective.56 The machine cycles into the expiratory mode when inspiratory airflow reaches a threshold value, and cycles into inspiration when inspiratory flow is detected. Bilevel pressure may allow airway stabilization with a lower pressure during exhalation. In addition, this method can deliver non-invasive pressure support (IPAP – EPAP) as well as maintain upper airway patency.57 While bilevel pressure devices are more expensive than CPAP blower units, they can certainly increase acceptance of positive pressure in some cases. Patients requiring high pressure, those with hypoventilation, some patients with mouth leaks, or patients with chronic obstructive pulmonary or muscle weakness of any cause, may accept

bilevel pressure but not CPAP. However, for unselected OSA patients, there is no evidence that bilevel pressure increases compliance.58 In both CPAP and bilevel pressure, a fixed prescription pressure is given, based on some type of pressure titration study. A third method of delivering positive pressure is an auto-titrating device (‘smart CPAP’).59–64 This type of machine adjusts pressure according to set algorithms that vary between commercial devices. The devices monitor one or more of the following: vibration in the airways (snoring), flow (apnea and hypopnea), inspiratory flow shape (flattening), impedance (forced oscillation) or a combination (snoring, flow, flattening). In most devices, a lower and upper bound for pressures may also be set. Many auto-titrating units can store pressure and leak information in downloadable memory. The delivered airway pressures and leak and flow characteristics during the night are then available. One can prescribe a fixed prescription pressure using a traditional CPAP blower on the basis of pressures needed during the auto-titration night(s). For example, one could use the maximum or 90–95th percentile pressure

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(90–95% of time at that pressure or below). Auto-titrating units could potentially allow a technician to titrate more patients or perform unattended titration, either in the hospital or at home. Some units, by recording the number of respiratory events, also provide a means of diagnosis. Alternatively, the same devices could be used for chronic treatment (auto-adjusting). By varying the airway pressure according to changing requirements during the night, autotitrating devices could potentially increase compliance, as a lower mean pressure may be administered. To date, there has not been convincing evidence that these units will increase compliance enough in unselected patients to justify the extra cost. These issues will be discussed in the titration and compliance sections to follow. A final, rarely used method of positive pressure is to utilize volume cycle ventilation with positive end expiratory pressure (PEEP) via a nasal or full facemask interface. The method has been most frequently used in the initial treatment of severe OSA associated with respiratory failure in patients with an acceptable level of consciousness.65 One problem is that most ventilators will alarm repeatedly with the small leaks inevitable in this setting. Recent models of some ventilators now allow raising the threshold for the leak alarm, and may be more useful for this mask ventilation. As some bilevel pressure flow devices can now generate up to 35 cmH2O, volume-cycled ventilation may not be required for even the most severe patients. The relative advantages of the above modes of positivepressure application will be discussed below.

Determination of prescription pressure Traditionally, the level of positive pressure prescribed for the patient is chosen during full-

or partial-night study in the laboratory during conventional polysomnography. The partialnight titration follows an initial diagnostic portion (split study). While the partial night approach is effective for 60–80% of patients66–68 and has economic benefits, it does shorten both diagnostic and positive-pressure titration portions of the study. In patients showing predominant events in either the supine position or during REM sleep, a shortened diagnostic portion may contain little supine or REM sleep and therefore result in an underestimation of the severity of sleep apnea. Many laboratories encourage the patient to sleep supine as much as possible and to include at least one REM period in the diagnostic portion of the study. Split-night studies also shorten the CPAP titration. Sometimes, inadequate REM sleep or little sleep in the supine position are recorded at the final pressure. This may be important, because higher pressures are usually needed to stabilize the upper airway in the supine position and during REM sleep.69 The protocols for titration also vary between laboratories. One must understand that a CPAP trial is both a determination of efficacy and a desensitization to wearing a mask and sleeping with positive pressure. In general, the sleep technician must gauge both the effectiveness of a given level of pressure and tolerance. Thus, temporary reductions in pressure are sometimes required to allow a patient to return to sleep. Many laboratories utilize a positive-pressure treatment table, demonstrating in tabular form the amount and type of apnea/hypopnea, the stages of sleep present, predominant body position, and arterial oxygen saturation at a given pressure or pressure range. For example, in Table 5.2a, one sees that adequacy of treatment at the final pressure was not documented in the supine position during REM sleep. In Table 5.2b, a more ideal titration is shown.

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Table 5.2 Examples of positive-pressure treatment tables. (a) CPAP Monitoring time (min) Non-REM (min) REM (min) AHI (/h) % of events Obstructive + mixed apnea Central apnea Hypopnea Body position

0 (diagnostic) 180 150 10 75

5.0 40 20 10 60

7.5 60 40 10 30

10 60 40 0 20

12.5 40 30 0 10

100 0 0 Supine

90 0 10 Supine

50 0 50 Lateral

10 0 90 Lateral

0 5 95 Lateral

0 (diagnostic) 120 90 0 75

5.0 60 35 10 60

7.5 60 45 10 30

10 60 30 10 15

12.5 80 20 40 5

75 5 20 Supine

60 0 40 Supine

50 0 50 Lateral

35 5 60 Supine

0 5 95 Supine

(b) CPAP Monitoring time (min) Non-REM (min) REM (min) AHI (/h) % of events Obstructive + mixed apnea Central apnea Hypopnea Body position

A commonly used titration endpoint (see Table 5.3) is to increase positive pressure until apnea, hypopnea, desaturation and snoring are abolished or dramatically reduced. An additional goal is the elimination of RERAs. However, it is not always clear to a technician exactly what is causing repetitive arousals. Direct measurement of esophageal pressure deflections can allow titration until the pressure swings are less than 10 cmH2O.50 Such monitoring is not widely utilized. Others have suggested that the presence of flattening in the inspiratory flow contour (flow limitation) is evidence of persistent elevation in upper airway resistance70 (Figure 5.4). Thermistors do not provide an accurate

Table 5.3 Titration endpoints. Elimination of apnea, hypopnea, desaturation Elimination of snoring Elimination of respiratory effort-related arousals (RERAs) Elimination of increased respiratory effort (requires esophageal pressure monitoring) Elimination of airflow limitation (requires accurate airflow monitoring)

estimate of either flow or the flow versus time profile. Most diagnostic positive-pressure devices have an output utilizing a built-in

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CPAP (cm H2O)

14 13 12 11 10

Total flow (l/min)

50 40 30 20 10

Press. Esoph. (cm H2O)

0 4 2 0 –2 –4 Resistance = 12

–6 0

5

Resistance = 29 10

15

20

25

30

Time (seconds)

Figure 5.4 Airflow limitation (inspiratory flattening) during reduction of nasal pressure is shown coincident with increases in esophageal pressure deflections (increased upper airway resistance). (Reprinted from Condos et al.70 with permission.)

pneumotachograph to provide an accurate estimate of flow and system leak. Respiratory impedance determined by the forced oscillation technique has recently been proposed as an alternative to using the airflow profile (flattening) to detect high residual amounts of upper airway resistance.71 Most would recommend that positive pressure should be increased until RERAs are eliminated. Should positive pressure be increased until no flow limitation is present?

The presence of some flow limitation may not be detrimental. Meurice et al72 compared titration to overcome apnea, hypopnea, desaturation and snoring (standard endpoint with a protocol to eliminate flow limitation (PFL)). They found that the PFL group required about an additional 1.5 cmH2O. At the end of a 3week home CPAP treatment trial, the two groups were restudied. There was no difference in sleep quality or daytime vigilance tests between the two groups. The PFL group had a

Positive airway pressure higher nightly compliance (on average greater than 1 h), and the standard endpoint group showed more variability in improvement in sleep latency on the maintenance of wakefulness test (MWT). The difference in compliance makes it difficult to prove that the PFL titration endpoint resulted in better reversal of daytime sleepiness. However, one might propose that the higher compliance was secondary to an increased perceived benefit. In any case, the study does suggest that the addition of a few cm H2O pressure will not reduce compliance. A reasonable pressure titration approach would be to increase pressure to abolish arousals associated with flow limitation or severe flow limitation, even in the absence of arousals. Further upward pressure titration to abolish milder degrees of flow limitation could be attempted so long as this did not induce patient intolerance or intractable air leaks. Ultimately, the prescription pressure is always a compromise between what is optimum for maintaining airway patency and high-quality sleep and what the patient will tolerate (side-effects). Titration protocols for bilevel pressure also vary between sleep centers. A simple and effective approach is to titrate up (IPAP = EPAP) until apnea is abolished.56–57 Then the IPAP is increased until hypopnea, desaturation and respiratory arousals are abolished. In some patients in whom an increase in IPAP is not completely successful or mask leaks/pressure intolerance preclude a higher IPAP, additional increases in EPAP may be tried (Figure 5.5). In patients with hypoventilation or a persistently low arterial oxygen saturation despite upper airway patency, one might try further increases in IPAP to improve oxygenation or increase the tidal volume. An estimation of tidal volume is available on many laboratory diagnostic bilevel devices. The IPAP–EPAP difference is the level of pressure support.

A (a) Flow (L/s)

99

Inspiration 1.0 0 1.0

Pressure (cm H2O)

15 10

(b) B

Inspiration Flow 1.0 (L/s) 0 1.0

Pressure (cm H2O)

15 12.5

Figure 5.5 Bilevel pressure titration. Two sequential tracings (A) and (B) in the same patient. (A) At a bilevel pressure of IPAP = 15, EPAP = 10 cmH2O, apnea was present. After an increase in the EPAP to 12.5 cmH2O apnea resolved. (Adapted from Sanders and Kern.56)

Increases in pressure support provide an inspiratory ‘boost’ and may augment tidal volume. The appearance of central apneas during a positive-pressure titration is sometimes a challenging problem. Central apneas can follow arousals from mask or mouth leaks, arousals related to pressure intolerance, or respiratory-related arousals (persistent high upper airway obstruction). The cause of the arousals may not always be obvious to the technician. In such a case, a trial of slightly lower or higher pressure may be tried, based on the perceived cause of the arousals. If the arousals are secondary to pressure intolerance or leaks, a slightly lower pressure may be indicated. Alternatively, if arousals are secondary to high respiratory effort (RERAs), an increase in pressure may be beneficial. Postarousal central apnea is thought to occur

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because the PCO2 level on return to sleep is below the apneic threshold.73 This is especially likely if arousal also triggers brief hyperventilation. Central apneas may also occur in the absence of preceding arousals. The persistence of central apnea after tracheostomy in both non-REM and REM sleep was well described during initial studies of tracheostomy treatment of severe OSA patients.74 The amount of central apneas decreased over time once upper airway stabilization was effected. Non-post-arousal central apneas in patients with severe OSA during CPAP titration may be secondary to a reduction in sleeping PCO2 (with airway stabilization) to a value near the apneic threshold. Aggressive attempts to increase ventilation during sleep, such as a switch to bilevel pressure, may even make the amount of central apneas worse. Positive airway pressure has been demonstrated to be effective in some patients with idiopathic central sleep apnea.75 These non-hypercapnic patients tend to have low daytime PCO2 values. One mechanism by which CPAP induces improvement in this group may be an induction of a mild increase in PCO2.76 Another possible mechanism is prevention of high upper airway resistance, which may trigger central apnea by a negative-pressure reflex76 or by causing arousal. One can increase the level of positive pressure in OSA patients in an attempt to treat central apneas. However, this may not be always be successful or even necessary. For example, brief central apneas can also occur during periods of REM rebound. If they do not cause arousal or desaturation, they are probably best left untreated. One of the most dramatic changes occasionally seen during CPAP titration is the conversion of obstructive or mixed apnea to central apnea of the Cheyne–Stokes type in patients with underlying congestive heart failure.77 The pattern of Cheyne–Stokes central apnea differs

from that of ‘idiopathic central apneas’. In Cheyne–Stokes breathing (CSB), the ventilatory phase between central apneas is typically longer and shows a definite crescendo– decrescendo pattern (Figure 5.6). In patients with OSA and CSB, positive pressure should be titrated to prevent obstruction. Sometimes, further upward titration will prevent CSB, possibly by increasing PCO2. However, more commonly, no level of pressure will abolish CSB, although arterial oxygen saturation and sleep continuity are often improved (decreased

Nasal H22O O Nasal CPAP CPAP 12 12 cm cmH 20 sec Airflow Chest Abdomen SaO2

90%

96% 20 sec

Airflow A A Compressed view of consecutive apneas

Figure 5.6 A central apnea of the Cheyne–Stokes type that appeared during a CPAP titration. At this pressure, obstructive and mixed apneas were eliminated. Higher pressures did not abolish central apneas. A compressed view of several contiguous central apneas shows the crescendo–decrescendo pattern. Note that arousals occurred several breaths after the cessation of apnea (A). In Cheyne–Stokes central apnea, arousal tends to occur at the maximum of ventilatory effort. (Adapted from Berry RB, Sleep Medicine Pearls. Philadelphia; Hanley & Belfus, page 181.)

Positive airway pressure arousals). Based on the experience of investigators who treat pure CSB secondary to congestive heart failure, a reasonable recommendation is to increase the level of positive pressure until obstruction is abolished or to 10–12 cmH2O (whichever is higher). This level of pressure commonly improves cardiac function in many patients and may ultimately reduce CSB.78

Alternative methods of titration and prescription pressure stability over time Because traditional in-laboratory positivepressure titrations are expensive, other methods of determining an optimum pressure have been explored. Hoffstein and developed a prediction colleagues79,80 equation: CPAP = –5.121 + 0.13 ⫻ BMI + 0.16 ⫻ NC + 0.04 ⫻ AHI. This equation incorporates the BMI (BMI = weight in kg/ (height in meters)2), the neck circumference (NC) in centimeters at the cricothyroid membrane, and the AHI. Calculations from this formula lack sufficient accuracy to replace in-laboratory titration. However, the equation may serve as a rough guide. In-home titration by a nurse or spouse has also been attempted, and many patients with respiratory failure undergo titrations in intensive care units (ICUs) with the endpoint to prevent desaturation. When stable, patients can undergo a traditional in-laboratory titration for fine tuning the prescription pressure. As discussed above, auto-titrating units have a built-in algorithm for pressure titration. Therefore, they could be used as a technician ‘extender’ in the sleep laboratory or for unattended titrations in hospital or at home. Studies comparing auto-CPAP titrations with traditional polysomnographic titrations have

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generally found close agreement in the prescription pressure for moderate to severe patients.60–64 Auto-titrating units with airflow limitation in their algorithm are quite sensitive to milder degrees of airway narrowing and may result in slightly higher pressures than traditional polysomnography performed with thermistors. Of note is the fact that many of the studies comparing auto-titration with traditional titration have been performed in a sleep laboratory. Technicians in many cases made mask adjustments to minimize leaks. In addition, patients with a number of conditions were often excluded. For example, patients with underlying congestive heart failure (and possible CSB), hypoventilation or the overlap syndrome (OSA + chronic obstructive pulmonary disease (COPD)) were often not included. Problems with auto-titrating devices have been described in such patients with cardiopulmonary disease.81 Certainly the autotitrating devices are not designed to treat arterial oxygen desaturation that occurs despite a patent upper airway. In the USA, unattended CPAP titration is either not reimbursed or reimbursed at a lower level. For all of these reasons, unattended auto-CPAP titration cannot be recommended for routine titration of CPAP. The auto-titrating devices might allow a technician to titrate more patients at a time in a laboratory environment. The technician would still be available for reassurance, education, mask adjustment, and recognition of complications. Retitration at home with an auto-titrating device to verify the adequacy of the current prescription pressure might be another potential use for these devices if reimbursement is not an issue. There are a number of other factors complicating the use of auto-titration devices. Units using airway vibration for titration may not work in patients who do not snore or who have

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had a uvulopalatopharyngoplasty (UPPP). Some units are not designed to work with all types of humidifiers or masks. In general, auto-titrating

Leak (l/sec) (L/sec)

Pressure (cmH2O)

A (a)

Leak (l/sec) (L/sec)

Pressure (cmH2O)

B (b)

20 8 0 1

0

0

1

2

3

4

5

6

20 8 0 1

0

0

1

2

3 4 5 Hours in study

6

7

Figure 5.7 Auto-CPAP printout table. Each division in the pressure graph represents 4 cm of H2O pressure. Mask pressure and total leak during two AutoSet automatic pressure titration studies. (A) Pressure started at default pressure of 4 cmH2O. There was a brisk rise in pressure approximately 10 min into the study, corresponding to sleep onset. Thereafter, pressure varied between 4 and 10 cmH2O. Recommended pressure was 9 cmH2O. Mask leak remained minimal throughout the study. (B) A period of high mask leak at 5 h into the study was associated with a brief inappropriate rise in pressure, corrected by the subject reseating the mask. Recommended pressure was 10 cmH2O. (Reprinted with permission, Teschler H, Bethon-Jones M, Thompson AB et al. Automated continuous positive airway pressure titration for obstructive sleep apnea syndrome. Am J Respir Crit Care Med 1996;154:734–40.)

devices have problems adapting to large leaks or central apnea. When attended or unattended auto-titration is performed to determine a fixed prescription pressure, it is imperative to view a pressure and leak versus time printout (Figure 5.7). High pressures are delivered in response to leaks and may not be needed with proper mask adjustment. No matter how it is determined, the ‘optimum pressure’ may be influenced over time by a number of factors. Some have suggested that a lower pressure may be required with continuous treatment,82 while others have documented stability over time.83 If a decrease in pressure is required, one explanation may be an increase in upper airway size secondary to decreased edema.84 In a given patient, changes in nasal resistance (colds, allergy) and weight fluctuations could also affect the required pressure. While some have cited that ethanol can increase pressure requirements, two studies have shown that moderate ingestion does not cause a significant increase in required level of pressure.85,86 This is probably because, with CPAP, upper airway muscles are already relaxed. However, ethanol ingestion is still to be discouraged, as intoxicated patients may not apply the mask correctly, remove the mask during the night, or fail to notice mask leaks. If apnea occurs, event duration will be longer, as ethanol increases the arousal threshold to airway occlusion.87

Adjunctive treatments including supplemental oxygen There are times when the optimal level of pressure is not tolerated by the patient, or upper airway patency is not restored at the highest pressure that the blower can produce (morbidly obese patients). At other times, the optimal level of pressure cannot be maintained

Positive airway pressure secondary to intractable mask leaks or leaks through the mouth. In such cases, one may consider the use of adjunctive treatments. One treatment that is often overlooked is the ability of elevation of head of the bed or the side sleeping position to enhance the effectiveness of a given level of CPAP. Neill et al found that the level of pressure needed to maintain upper airway patency was reduced by as much as 5 cmH2O by elevating the head of the bed 30º.88 In obese patients, elevation of the head of the bed may be more effective than the lateral sleeping position. Although not studied systematically, simultaneous treatment with an oral appliance may also reduce the level of positive pressure needed to maintain upper airway patency. Obviously, weight loss can also be a useful adjunctive treatment. Unfortunately, it takes time and, as discussed above, is difficult to maintain. Another potential approach is the augmentation of upper airway muscle activity by pharmacologic means. There is a single case report of enhancement of effectiveness of a given level of CPAP by addition of protriptyline.89 This non-sedating antidepressant may produce an augmentation of upper airway muscle activity;90 however, it causes urinary retention in a high percentage of men. There is some evidence that selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine or paroxetine, may also be effective at increasing upper airway patency in some patients with OSA.90 The possible future use of serotonin-enhancing medications is discussed in Chapter 15. At this time, such pharmacologic adjunctive therapy must be considered experimental. In patients with a low awake PO2 or severe obesity, desaturation may persist even after upper airway patency is effected. This is especially common during REM sleep on initial CPAP titrations, and the degree of desaturation may be severe.91 If a trial of

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increased CPAP pressure does not help, the addition of supplemental oxygen is one approach. Two other alternatives in this situation are delivery of pressure support via bilevel pressure or the use of volume-cycled ventilation. In our experience, some patients requiring oxygen during the initial CPAP titration with its large REM rebound may be adequately treated with CPAP alone several weeks later. In patients with the overlap syndrome (OSA and COPD) and low awake arterial oxygen saturations, supplemental oxygen is commonly required in addition to positive pressure.92 Oxygen may be added to the circuit either at the mask or at the outflow port of the blower unit. The effective FiO2 for a given liter flow of oxygen depends on the amount of flow from the CPAP device. In devices where the controlled leak is proximal to the mask, a lower flow rate of oxygen may be required if oxygen is added to the mask.35 In general, higher flow rates of oxygen are needed if the total flow from the blower unit is high (high mask or oral leaks).

Benefits of upper airway stabilization Stabilization of the upper airway often results in a large rebound in the amount of slow-wave and REM sleep on the titration night. Virtual elimination of obstructive and mixed apnea, hypopnea, desaturation and RERAs occurs with an optimal pressure level.3,33–36 Patients having such results often report feeling better and less sleepy after a single night of CPAP.93 Indeed, multiple uncontrolled studies have documented that optimal CPAP use is associated with an increase in sleep latency on the multiple sleep latency test (MSLT), although not always into the normal range. A larger increase in the sleep latency on the maintenance

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of wakefulness test (MWT) is seen after CPAP treatment.94 Improvement in daytime sleepiness may require more prolonged treatment in some patients.95 A review by Wright et al questioned the scientific evidence for the efficacy of CPAP as a treatment for OSA because of a lack of placebo-controlled studies that documented improved patient outcomes.16 This challenge has been answered by two placebo-controlled trials showing clear improvements in subjective and objective sleepiness as well as the quality of life compared to control groups.6,34 One of the studies used subtherapeutic CPAP (1 cmH2O) as the placebo.34 An improvement in subjective but not objective sleepiness was seen in the group treated with subtherapeutic CPAP. Thus, clinicians taking care of patients should remember that even CPAP may have a ‘placebo’ effect. However, a much larger improvement in both subjective and objective sleepiness was noted in the therapeutic CPAP treatment group. Another study found that patients with mild OSA (AHI 5–15/h) benefited from CPAP treatment more than from an oral placebo.6 Both studies also documented an improvement in mood and quality of life indices. The study of mild patients did report a low hours/night rate of objective compliance with CPAP. Studies comparing CPAP treatment with conservative therapy (weight loss, sleep hygiene) in patients with mild OSA5 and moderate to severe OSA96 have also documented clear advantages to CPAP treatment. Jokic et al found that while patients with positional sleep apnea had acceptable treatment with both position therapy (backpack inducing the side sleep position) and nasal CPAP, a significant fraction of the patients at the end of the study actually preferred CPAP.97 Withdrawal of CPAP for even one night can cause a return of sleepiness.98 Similarly, withdrawal of CPAP for

three nights has been shown to impair the arousal response (increased arousal threshold) to airway occlusion.99 Positive-pressure treatment also results in benefits besides improvements in daytime alertness and mood. In patients with daytime hypercapnia (obesity hypoventilation syndrome or OSA + COPD), adequate treatment is often associated with a reduction in daytime PCO2.100,101 Non-invasive positivepressure treatment may also avoid intubation in patients with OSA and acute hypercapnic respiratory failure.102 Studies of the awake hypercapnic ventilatory response have shown a parallel shift in the ventilation versus PCO2 line with CPAP treatment.103 That is, the slope was unchanged but the ventilation at a given PCO2 was higher. In patients with both OSA and asthma, treatment of OSA may actually improve control of lower airways disease.104 A retrospective study of survival in patients with moderate to severe OSA (apnea index > 20/h) found an improvement in survival on CPAP compared to untreated controls. Thus, while the study was neither prospective nor randomized, it remains some of the best evidence for a survival benefit with treatment in patients with moderate to severe OSA. The reason for an improved survival is not known but may be secondary to multiple detrimental effects of untreated OSA on the progression or consequences of atherosclerotic heart disease, hypertension, or heart failure. A good therapeutic CPAP result typically decreases catecholamine excretion,105 sympathetic activity,106 and nocturnal pulmonary and systemic blood pressure.107,108 Daytime blood pressure may also decrease in some patients.109 Patients with coronary artery or cerebrovascular disease may also benefit from adequate treatment of the OSA. Nasal CPAP reverses OSAinduced increases in fibrinogen110 and platelet

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Table 5.4 Side-effects and interventions. Positive-pressure side-effects

Interventions

Mask interface Air leaks Conjunctivitis Discomfort

Proper mask fitting Proper mask application (education) Different brand/type of mask Customized mask Alternate between different mask types Nasal prongs/ pillows Tape barrier for skin protection Different headgear Low pressure alarm If snoring on CPAP then increase pressure

Skin breakdown Unintentional mask removal Nasal symptoms Epistaxis 冧 Pain, dryness Congestion/obstruction

Nasal saline Humidification Nasal steroid inhaler Antihistamines (if allergic component) Humidification (heated) Night-time decongestants Full facemasks (oronasal) Nasal ipratropium bromide Antihistamines (if allergic component) Frequent filter changes

Rhinitis/rhinorrhea Mouth symptoms Mouth leaks Mouth dryness

Humidification (prevent increased nasal resistance) Treatment of nasal problems Chin straps (?) Full facemask Lower pressure/bilevel pressure

Pressure problems Pressure intolerance

Difficulty exhaling Snoring on positive pressure Feeling of not getting enough flow Inability to maintain upper airway patency at pressure limit

冧

Miscellaneous problems Machine noise Claustrophobia Questionable compliance Persistent desaturation despite patent upper airway

Ramp Bilevel pressure Auto-titrating device Lower prescription pressure—accept higher AHI Lower pressure + adjunctive measures Weight loss, elevated head of bed, side sleeping position, simultaneous oral appliance (?) Bilevel pressure Raise pressure 1–2 cmH2O Fix high leak if present Bilevel pressure Volume-cycled ventilation Adjunctive treatments Supplemental oxygen Long tubing with machine removed from bedroom Different brand of blower Desensitization Nasal prongs Time meter Downloadable time at pressure information Spouse education Try increase in CPAP 1–2 cmH2O Bilevel pressure Add supplemental oxygen

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activation.111 A study of OSA patients with cardiomyopathy demonstrated an improvement in the ejection fraction after successful OSA treatment with nasal CPAP.112 Patients with arrhythmias or heart block may also improve.113 CPAP treatment also reduces nocturnal naturesis and typically reduces episodes of nocturia.114 The mechanism may be a reduction in atrial natriuretic peptide (ANP) secretion, although other factors may also be involved.

Side-effects of positive-pressure treatment Several studies have enumerated the many side-effects with positive-pressure treatment.35,36,115,116 If left untreated, side-effects from positive airway pressure may cause a lower chance of acceptance and lower rates of compliance.117 Side-effects and possible interventions are listed in Table 5.4. Prevention and/or elimination of side-effects at the introduction of CPAP appears to be very important. Patients complying over the first 1–3 months tend to continue to accept positive-pressure treatment.118,119 Weaver and coworkers found that a difference in the pattern of use by compliant and non-compliant patients is noted as early as 4 days of treatment.120 Many sideeffects are secondary to the mask interface. In one study, intolerance of the mask was the most common reason for discontinuing CPAP treatment.119 Obtaining an adequate mask fit may require trials of several different brands and types of masks. While most companies make a few sizes of masks, there are many sizes of faces. Obtaining an adequate seal at the bridge of the nose is an especially difficult problem. Adequate mask positioning is also essential, as is elimination of overtightening of head straps. Often, moving the mask up or

down slightly will produce a better seal than further tightening. Poor mask fit leads to leaks which are both uncomfortable (especially into the eyes) and may result in an inadequate pressure. Conjunctivitis has been described during CPAP use.121 Overtightening of head straps can result in severe skin abrasion, especially on the bridge of the nose (‘CPAP divot’). Turning in bed can also change the mask position, resulting in loss of mask seal. Improvements in mask material and flexibility in the mask–hose connection have been used in an attempt to reduce these problems. Swivel arms to allow hose movement with minimal mask movement have also been introduced to approach this problem. Some companies offer thermolabile materials that, when heated, conform to the shape of the face. Other masks utilize thin material that balloons out against the face under pressure. Nasal prongs (nasal pillows) can sometimes provide a useful alternative for patients unable to get a good seal around the nasal bridge. Adequate care of masks (cleaning) and replacement of masks when old (and less flexible) is also necessary. Nasal symptoms, including congestion, rhinorrhea, pain, dryness, and epistaxis, are all potential problems with positive-pressure treatment. Many OSA patients have underlying nasal congestion that may be worsened by treatment. Nasal congestion may make breathing through the nose uncomfortable and result in oral breathing (leaks). In theory, positive pressure can be applied nasally, because the palate moves forward against the back of the tongue, sealing off the oral passage (Figure 5.2). However, if an oral leak does occur, this removes humidity from the system and can lead to nasal dryness. This mucosal dryness further increases nasal bloodflow (and resistance), leading to even higher mouth leaks.122,123 Nasal congestion may be treated with nasal steroid inhalers, antihistamines (if

Positive airway pressure an allergic component is present), and, as a last resort, bedtime decongestants. The addition of humidification can prevent nasal dryness and pain and may also prevent an escalation of mouth leaks in some patients.123,124 While cold passover humidification may reduce mild symptoms of dryness in some patients, heated humidification is usually required if severe nasal symptoms or mouth leaks occur. Massie et al demonstrated that heated humidification improves compliance, and both heated and passover humidification improved satisfaction with CPAP.124 A full facemask may also prevent a loss of humidity from mouth leaks. In some patients with intractable nasal congestion, a full facemask may be needed. This is especially useful during initial inlaboratory titrations that would otherwise have to be aborted51–53 because of severe nasal obstruction. After intensive treatment of nasal problems and addition of humidity, some patients can later be switched back to a nasal mask. Until recently, the types of commercially available full facemask were limited. Several better-fitting alternatives are now available. Some patients develop rhinorrhea during CPAP treatment or immediately following cessation of treatment. This is usually controlled with intranasal ipratropium bromide. Mouth leaks can be a severe problem during the initial CPAP titration or with home use of CPAP. They may awaken the patient or prevent maintenance of airway patency. During in-laboratory titration, most diagnostic units provide an estimate of the total leak. If the patient is observed to have an open mouth during episodes of high leaks, a mouth leak is obvious. On the polysomnographic tracings, one often sees normal chest and abdominal movements with a low and erratic nasal flow signal. Mouth leaks should always

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be suspected if patients complain of severe mouth dryness during home use. While chin straps may be tried, their efficacy is probably marginal. Treatment of nasal congestion may improve mouth leaks by lowering nasal resistance. In some patients, adding heated humidification can minimize mouth leaks, as noted above. Full facemasks are another approach. In individual patients, using a slightly lower pressure or switching to bilevel pressure, which allows maintenance of airway patency with a lower pressure in exhalation, may also help control mouth leaks. One study suggested that patients who have undergone a UPPP before CPAP treatment are more likely to develop mouth leaks.125 This is presumably secondary to the defect in the palate. Machine noise was once a common problem, but newer models are much quieter. One could recommend longer tubing and removal of the blower unit from the bedroom. Other side-effects are the noise and discomfort from the stream of air leaving the controlled leak in the mask or mask–hose interface. This can sometimes also bother the bedmate. Again, recent improvements in blower design have attempted to minimize this problem. Some patients also ‘unconsciously’ remove the mask during the night. A few units now have low-pressure alarms. Intolerance to the level of positive pressure is also a common side-effect, especially at higher treatment pressures. There are several approaches to handle the problem. Most machines have a ‘ramp system’, in which the pressure is slowly increased over 5–30 min to the prescription pressure.36,51 While this approach seems reasonable, no study has validated the usefulness of the ramp alternative. Another approach is to utilize bilevel pressure. A third approach is to use adjunctive treatments that are outlined above. These may reduce the required level of positive pressure.

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A fourth approach is to try an auto-titrating CPAP device. This should allow airway stabilization with a lower mean pressure for the entire night. A fifth approach is to settle for a less than optimal prescription pressure. There is some evidence that with prolonged use of CPAP there may be a reduction in the pressure needed to maintain upper airway patency. One must also remember that if positive pressure fails, the other therapeutic alternatives may not be able to equal the efficacy of a less than optimal CPAP pressure. Claustrophobia is an especially difficult side-effect to treat. An occasional patient will respond to nasal prongs. Others may need desensitization to the mask and CPAP pressure during the day.126 While never studied systematically some laboratories have even used anxiolytics during the initial CPAP trial in non-hypercapnic patients. In addition, a few patients do not tolerate a low initial ramp pressure. They seem to do better with no ramp or an increase in the initial ramp pressure. We have recently seen two patients with the sudden onset of claustrophobia after being on CPAP for some time. In one case, the blower unit made noise but never reached the prescription pressure. The other patient had decided to remove the controlled leak device from his system and was rebreathing CO2.

Acceptance and compliance Acceptance of positive pressure implies that the patient is willing to use this treatment. Compliance, also termed adherence, means that the patient will use the device nightly for a sufficient time to obtain a benefit. Acceptance of a positive-pressure titration depends on educating the patient about the need for treatment and the lack of other treatments of equivalent efficacy. Such education is not

likely to be effective in the middle of the night. The second major factor in increasing acceptance is to minimize side-effects on the positive-pressure titration night. Careful mask fitting, the use of humidification if mucosal dryness or a mouth leak is prominent, pretreatment of nasal congestion, and slow upward titration of pressure, are strategies that can be tried to increase acceptance. Bilevel pressure may also be tried for patients requiring high pressures. Some patients will request a termination of CPAP titration during a split study, but will accept a repeat full-night CPAP titration after discussion of alternatives with a physician. Overall, up to 5–15% of patients will not accept or tolerate a CPAP titration. Other patients will not accept positive pressure after their experience with CPAP during titration. In one study, up to 30% of patients either did not accept CPAP or discontinued its use.119 McArdle et al found that, at 5 years, 68% of patients were still using their CPAP. Patients who were compliant in the first 3 months were more likely to continue to use positive pressure on a long-term basis.118 Numerous studies have addressed compliance with positive-pressure treatment. Initial studies of self-reported use found 60–80% compliance with CPAP treatment.115,116 Subsequent studies have showed that objectively measured compliance is often significantly less than reported compliance.127,128 In one study, only 46% of patients used their CPAP for more than 70% of the days and more than 4 h/day.127 Thus, obtaining objective compliance data is essential in any outcomes study of positive-pressure treatment. The discouraging early objective data sparked interest in finding methods to increase compliance. A European cooperative study found that 79% of patients met objective compliance criteria (> 4.0 h of nightly use at pressure on 70% of days) over the initial 3 months of treatment.129 Of note is

Positive airway pressure the fact that all centers used three nights of inhospital acclimatization to CPAP and aggressive early treatment of problems. Patients were seen monthly, and compliance as well as the benefits of treatment were discussed. The somewhat higher short-term compliance in this study suggests that intensive interventions can result in better compliance. To address this question more systematically, Hoy et al prospectively compared intensive support and standard support of patients being started on CPAP. Intensive support improved mean objective nightly CPAP use over 6 months by about 1.5 h.130 Intensive support included three nights of CPAP use in the hospital, involvement of the patient’s spouse in all education, and home visits by nurses. Another study found that weekly telephone calls discussing problems and simple interventions encouraging compliance were more effective131 than standard low-level contact. Possible interventions to improve compliance are listed in Table 5.5. Patients with better compliance would be assumed to have better control of their daytime sleepiness. However, the minimum level of compliance needed for reasonable control of symptoms may vary between patients. For example, in the above study of intensive versus standard support, while the mean hourly compliance differed, the sleep latency on the MWT did not (both were in the normal range).130 While most positive-pressure devices have time meters, many modern devices allow downloading of more detailed compliance information. They can show in detail the pattern of use, including time at pressure. In Figure 5.8, a daily compliance record shows that the patient does not use his CPAP on weekends. The measurement of time at pressure might be more accurate for determining meaningful compliance than simple run

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Table 5.5 Methods to enhance acceptance/compliance. 1.

2. 3. 4. 5. 6. 7. 8. 9. 10.

Intensive education about importance of treatment and treatment alternatives before sleep study Careful mask fitting, testing for leaks/comfort before sleep study Pretreatment of nasal congestion if present Availability/routine use of humidification Involvement of spouse in education/ CPAP training Early interventions for sideeffects/discomforts Frequent contact with support personnel in first few weeks Monthly contact with physician during start of treatment Objective compliance monitoring–time meters, download usage Change mode of pressure delivery/prescription pressure as needed

time meters. However, the above European compliance study found compliance by hour meter and time at pressure to be similar.129 Evidently, most patients do not take the time to run their machines simply to appear compliant. In any case, objective compliance monitoring allows sleep physicians to intervene, encourages patient responsibility, and prevents needless studies to evaluate patients with persistent sleepiness who are not being honest about their level of compliance.

Modes of positive-pressure delivery and compliance There appears to be no firm evidence that bilevel pressure will substantially increase the

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Medical therapy Blwr. time 02h 56m 03h 30m 04h 10m 04h 00m 06h 18m 02h 12m 07h 21m 07h 00m 08h 05m 02h 17m 04h 24m 07h 03m 06h 25m 07h 40m 05h 43m 07h 18m 07h 20m 12 14 16 18 20 22 24 2 4 6 8 10 12 Time

Graph based on 04/29/99 – 05/18/99 (20 days) (93.7 blwr hrs) 100 90 80 Percent of days

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70 60 50 40 30 20 10 0 0

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Device usage (hours)

Figure 5.8 Compliance data for a patient who claimed that he used positive pressure every night. On the left, daily time at pressure information is shown. The red bars denote less than the threshold compliance level (here set at 4 h per night). The green bars denote higher than the threshold level of compliance. Note that the patient sometimes skipped entire nights of CPAP use. The graph on the right shows that the patient used his CPAP for 4 h or more on about 65% of the nights during the time period analyzed. (Encore compliance program, Respironics.)

overall rate of compliance with positive pressure in unselected patients.57 However, most physicians have found that some individual patients will accept and comply better with this form of positive pressure. For example, some patients with COPD find bilevel pressure much more comfortable. Perhaps the lack of a tremendous improvement in compliance in many patients with bilevel pressure is not surprising, as many of the side-effects with positive pressure may also occur at relatively low pressures. One would also suspect that

patients in whom the IPAP–EPAP difference was small would not be able to tell much difference from traditional fixed-pressure CPAP. A few studies have showed a modest advantage in compliance with auto-titrating devices.62,63 Konermann et al randomized patients to fixed-level CPAP or auto-titrating CPAP after an in-laboratory CPAP titration with the appropriate device. They excluded patients requiring more than 14 cmH2O. A significant advantage was found in the

Positive airway pressure nights-per-week that auto-CPAP was utilized (5.7 versus 6.5), but not the mean hours per night. Interestingly, the mean mask pressure in the auto-titrating CPAP group differed from that in the fixed CPAP group by only about 1.6 cmH2O. Perhaps this small difference explains why larger differences in compliance were not present. Alternatively, patients with positional apnea (events substantially reduced in the lateral sleep position) or events only during REM sleep might have a substantially lower mean nightly pressure when using an auto-titrating device. At the present time, the added expense (typically $500 or more) has precluded routine use of these devices, despite some evidence for a very modest increase in compliance. However, in individual patients with poor tolerance or compliance with traditional CPAP, auto-adjusting units may certainly be worth trying.

Patients still sleepy on positivepressure treatment Patients who report a deterioration in daytime alertness while on CPAP present a challenging problem. If the patient’s bedmate reports any snoring or apnea while the patient uses positive pressure, this is an important clue that the prescription pressure is too low. An appreciable weight gain may also suggest that the prescription pressure may need to be raised. Other possibilities, such as mask leak, mouth leak, poor compliance, or another sleep disorder (periodic limb movements in sleep or narcolepsy), must be considered. Unfortunately, patient reports of compliance are unreliable. Thus, the first step is to document compliance with an objective method. If compliance appears adequate, another approach is to utilize an auto-titrating unit for one or several nights to check the required

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pressure. An empirical increase in the prescription pressure by a few cmH2O may also be tried if an inadequate-pressure problem is suspected (recent weight gain, etc.). A repeat sleep study–pressure titration is indicated if these interventions do not prove informative and sleepiness persists. If narcolepsy is suspected, one approach is to perform a nighttime study at the prescription pressure (documenting good sleep) and a MSLT on the following day while using CPAP.132 An MSLT showing a short sleep latency and two or more REM periods despite good nocturnal sleep supports a diagnosis of narcolepsy (in addition to OSA).

Positive airway pressure treatment in the future One can expect that technological innovations will continue to improve blower units and mask interfaces. The price of auto-titrating CPAP will undoubtedly be reduced and they will probably be more widely used for treatment. One can also expect that the diagnostic capabilities of machines will increase. Hopefully, governmental agencies will require that all blower units have, at a minimum, a run time clock for checking compliance. On the other hand, a rigid standard for the mean hourly usage to qualify for reimbursement may be a detrimental intrusion. The amount of usage needed to obtain a benefit may vary between patients. In addition, we do not know the minimum usage necessary to reverse or avoid sequelae. It is also obvious from objective compliance studies that more effort needs to be directed to optimizing therapy during the early nights of CPAP use. In the USA, the physician reading the sleep study, the physician directing patient care (often a primary care physician), and the home healthcare

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company providing positive-pressure device delivery and follow-up, are often separated by distance and organizational units. Communication is often suboptimal and treatment poorly coordinated. As practice often follows reimbursement in the USA, funding agencies will hopefully require more attention to outcomes, compliance, and the optimal coordinated delivery of positive-pressure treatment.

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continuous positive airway pressure in decompensated hypercapnic respiratory failure as a complication of sleep apnea. Chest 1993;104:770–4. Berthon-Jones M, Sullivan CE. Time course of change in ventilatory response to CO2 with long-term CPAP therapy for obstructive sleep apnea. Am Rev Respir Dis 1987;135:144–7. Chan CS, Woolcock AJ, Sullivan CE. Nocturnal asthma: role of snoring and obstructive sleep apnea. Am Rev Respir Dis 1988;137:1502–4. Hedner J, Darpo B, Ejnell H, Carlson J, Caidahl K. Reduction in sympathetic activity after long-term CPAP treatment in sleep apnoea: cardiovascular implications. Eur Respir J 1995;8:222–9. Waradekar NV, Sinoway LI, Zwillich CW, Leuenberger UA. Influence of treatment on muscle sympathetic nerve activity in sleep apnea. Am J Respir Crit Care Med 1996;153:1333–8. Akashiba T, Minemura H, Yamamoto H, Kosaka N, Saito O, Horie T. Nasal continuous positive airway pressure changes blood pressure ‘non-dippers’ to ‘dippers’ in patients with obstructive sleep apnea. Sleep 1999;22:849–53. Sforza E, Krieger J, Weitzenblum E, Apprill M, Lampert E, Ratamaharo J. Long term effects of treatment with nasal continuous positive airway pressure on daytime lung function and hemodynamics in patients with obstructive sleep apnea. Am Rev Respir Dis 1990;141:866–70. Fletcher EC. Can the treatment of sleep apnea syndrome prevent the cardiovascular consequences? Sleep 1996;19:S67–70. Chin K, Ohui M, Kita H et al. Effects of NCPAP therapy on fibrinogen levels in obstructive sleep apnea syndrome. Am J Respir Crit Care Med 1996;153: 1972–6. Bokinsky G, Miller M, Ault K, Husband P, Mithchell J. Spontaneous platelet activation

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114.

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118.

119.

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and aggregation during obstructive sleep apnea and its response to therapy with nasal continuous positive airway pressure. Chest 1995;108:625–30. Malone S, Liu PP, Holloway R, Rutherford R, Xie A, Bradley TD. Obstructive sleep apnea in patients with dilated cardiomyopathy: effects of continuous positive airway pressure. Lancet 1991;338:1480–4. Koehler U, Fus E, Grimm W et al. Heart block in patients with obstructive sleep apnoea: pathogenetic factors and effects of treatment. Eur Respir J 1998;11:434–9. Krieger J, Follenius M, Sforza E, Brandenberger G, Peter JD. Effects of treatment with nasal continuous positive airway pressure on atrial naturetic peptide and arginine vasopressin release during sleep in patients with sleep apnea. Clin Sci (Colch) 1991;80:443–9. Nino-Murcia G, McCann CC, Bliwise DL, Guilleminault C, Dement WC. Compliance and side effects in sleep apnea patients treated with nasal continuous positive airway pressure. West J Med 1989;150:165–9. Hoffstein V, Viner S, Mateika S, Conway J. Treatment of obstructive sleep apnea with nasal continuous positive airway pressure. Patient compliance, perception of benefits, and side effects. Am Rev Respir Dis 1992;145:841–5. Engleman HM, Martin SE, Douglas NJ. Compliance with CPAP therapy in patients with the sleep apnea/hypopnea syndrome. Thorax 1994;49:263–6. McArdle N, Devereux G, Heidarnejad H, Engleman HM, Mackay TW, Douglas NJ. Long term use of CPAP therapy for sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med 1999;159:1108–14. Rolfe I, Olson LG, Sanders NA. Long-term acceptance of continuous positive airway pressure in obstructive sleep apnea. Am Rev Respir Dis 1991;144:1130–3.

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120. Weaver TE, Kribbs NB, Pack AI et al. Night to night variability in CPAP use over the first three months of treatment. Sleep 1997;20:278–83. 121. Stauffer JL, Fayter NA, MacLurg BJ. Conjunctivitis from nasal CPAP apparatus. Chest 1998;86:802. 122. Hayes MJ, McGregor FB, Roberts DN, Schroter RC, Pride NB. Continuous nasal positive airway pressure with a mouth leak: effect on nasal mucosal blood flux and nasal geometry. Thorax 1995;50:1179–82. 123. Richards GN, Cistulli PA, Ungar RG, Berthon-Jones M, Sullivan CE. Mouth leak with nasal continuous positive airway pressure increases nasal airway resistance. Am J Respir Crit Care Med 1996;154:182–6. 124. Massie CA, Hart RW, Peralez K, Richards G. Effects of humidification on nasal symptoms and compliance in sleep apnea patients using continuous positive airway pressure. Chest 1999;116:403–8. 125. Mortimore IL, Bradley PA, Murray JA, Douglas NJ. Uvulopharyngopalatoplasty may compromise nasal CPAP therapy in sleep apnea syndrome. Am J Respir Crit Care Med 1996;154:1759–62. 126. Edinger JD, Radtke RA. Use of in vivo desensitization to treat a patient’s

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claustrophobic response to nasal CPAP. Sleep 1993;16:678–80. Kribbs NB, Pack AI, Kline LR et al. Objective measurement of patterns of nasal CPAP use by patients with obstructive sleep apnea. Am J Respir Crit Care Med 1993;147:887–95. Reeves-Hoche MK, Meck R, Zwillich CW. Nasal CPAP: an objective evaluation of patient compliance. Am J Respir Crit Care Med 1994;149:149–54. Pépin JL, Krieger J, Rodenstein D et al. Effective compliance during the first 3 months of continuous positive airway pressure. A European prospective study of 121 patients. Am J Respir Crit Care Med 1999;160:1124–9. Hoy CJ, Vennelle M, Kingshott RN, Engleman HM, Douglas NJ. Can intensive support improve continuous positive airway pressure use in patients with the sleep apnea/hypopnea syndrome? Am J Respir Crit Care Med 1999;159:1096–100. Chervin RD, Theut S, Bassetti C, Aldrich MS. Compliance of nasal CPAP can be improved by simple interventions. Sleep 1997;20:284–9. American Sleep Disorders Association. The clinical use of the multiple sleep latency test. Sleep 1992;15:268–76.

6

Therapy with oral appliances

Wolfgang Schmidt-Nowara

Introduction Of the three major therapies for snoring and obstructive sleep apnea (OSA), oral appliances (OAs) are the most recent to have become available. Although OA use is steadily increasing, this mode of therapy is still met with scepticism by some clinicians and resistance by some healthcare payers. In fact, a substantial and growing clinical literature documents the efficacy of this treatment, and it no longer seems reasonable to question whether OAs work. Instead, the only reasonable debate at this time is where to position OA therapy in the spectrum of patient problems and treatment alternatives. This chapter will attempt to do so with a summary of the current understanding of OA therapy for snoring and sleep apnea and with recommendations for their use.

Conceptual development of oral appliance therapy The concept of a dental or oral appliance to facilitate airway patency is not new. At the turn of the century, Pierre Robin proposed this type of treatment in infants with respiratory distress due to micrognathia, a syndrome now known

eponymously by his name.1 Throughout the twentieth century, patent applications can be found for dental devices designed to treat snoring. With the discovery of sleep apnea in the 1960s, with the subsequent appreciation of its substantial prevalence, and with the difficulty of getting patients to accept other therapies, i.e. continuous positive airway pressure (CPAP) and tracheostomy and other operations, the interest in other treatments became acute. Reports of successful therapy of OSA with OAs began to appear in the medical literature in the 1980s.2–4 The 1990s saw a steady succession of clinical reports which clearly documented that OAs can be effective therapy for OSA, that their use is relatively safe, and that, compared to CPAP, patients usually prefer them. Anatomic and functional studies of the upper airway have explored the mechanism of this treatment effect. A review of this clinical literature in 19955 was accompanied by an influential practice parameter developed by the American Academy of Sleep Medicine6 Other updates have appeared since then.7–9 Appliance design and protocols for appliance use have evolved.

Types of oral appliance OA is a generic term for any device inserted in the oral cavity for the purpose of modifying

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Therapy with oral appliances

A

B

Figure 6.1 (A,B) A mandible-advancing oral appliance, adjustable with a screw mechanism (arrow), custom made from a patient’s dental models in a dental laboratory (Klearway appliance, Great Lakes Orthodontics Ltd, Tonawanda, NY, USA). Note the full dental coverage of both arches. (By courtesy of Dr A. Lowe.)

the airway to relieve snoring and OSA. The types of OA in use today are limited to the mandible-advancing devices and tongue devices. Appliances designed to lift the soft palate, depress the base of the tongue or modify intraoral pressures have fallen by the wayside, due to inefficacy and poor patient tolerance. The mandible-advancing type of OA represents the great majority of OAs in use today, and it is the type of appliance studied in almost all published reports. An example is shown in Figure 6.1. This appliance attaches to both dental arches and repositions the mandible forward of the centric position. Maxillary and mandibular components are connected by an intraoral wire harness that determines the position of the mandibular arch relative to the

maxillary arch. Many similar devices have been developed. A comprehensive listing can be found in a current textbook of sleep medicine.10 The device in Figure 6.1 is adjustable, allowing ‘titration’ of mandibular advance for effect and comfort. All modern OAs of this type have incorporated this feature. The OA illustrated in Figure 6.1 is an example of an adjustable ‘custom’ appliance, meaning that the mandibular advance can be adjusted by means of a screw mechanism and that the appliance is fabricated from dental models in a dental laboratory. Another type of mandible-advancing OA can be made from prefabricated molds containing a thermolabile material (Figure 6.2). These so called ‘boiland-bite’ appliances can be fitted to the patient

Types of oral appliance

Figure 6.2 A mandible-advancing oral appliance, adjustable, prefabricated ‘boil-and-bite’ type, ready for fitting to a patient’s teeth after warming (Therasnore appliance, Distar Inc., Albuquerque, NM, USA).

in the clinic, allowing immediate delivery of the appliance and usually at a lower cost. The illustrated appliance (Figure 6.2) is the adjustable version of a family of ‘boil-andbite’ appliances, with several publications

121

documenting good efficacy and acceptance by patients.11,12 Boil-and-bite appliances tend to be more bulky and less comfortable, are not as easily adjusted, and are less durable over time. Attachment to both arches may be less secure than with custom appliances, resulting in problems with retention during the entire sleep period. In some, the mandibular attachment does not involve the entire arch, accentuating the stress to the lower incisors. The author considers these disadvantages to be substantial and prescribes these appliances only for occasional use, or for a trial of the OA concept before committing to the full cost of a custom appliance, and in other settings when cost is a major constraint. Nevertheless, many patients have used these appliances for long periods of time as the principal treatment for sleep apnea, with good results. Several tongue appliances are available today, but only the tongue-retaining device has been evaluated in published reports by one group of investigators (Figure 6.3),2,5 and their last report appeared in 1991. These papers show a success rate comparable to those of

Figure 6.3 (A,B) The tongue retaining device (Pro-Positioners, Racine, WI, USA). The tip of the tongue is retained in the bulb of the appliance by suction.

A

B

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Therapy with oral appliances

other OAs. Tongue devices should be considered when an OA is selected but the dentition is inadequate for the stress of a mandibleadvancing OA. Tongue devices are difficult to use, and it takes a dedicated patient to learn to use them consistently all night. This probably accounts for the fact that tongue devices represent only a small fraction of all OAs in use. For this reason, in the rest of this discussion, OA will refer to mandible-advancing appliances unless another type is specifically designated.

Efficacy and use Beginning with case reports, followed by numerous case series, and more recently with several well-controlled clinical trials, a substantial literature documents the efficacy of OAs. Typical published studies report polysomnography before and with use of a mandible-advancing OA in patients with mild to moderate obstructive sleep apnea. This case series study design is more subject to bias than the standard randomized control trial, because of the lack of an untreated control group and the possibility that improvement may be unrelated to treatment. However, in at least one study, when OAs were removed after treatment, OSA was present with severity comparable to baseline, whereas during treatment the apnea–hypopnea index (AHI) was significantly lower than baseline and in OA-removed conditions (Figure 6.4). Furthermore, a randomized controlled trial of OA included a sham treatment arm,13 which should address the methodologic criticisms that have been directed at this literature. Treatment effects in all reports, including the shamcontrolled study, are robust, and the outcomes of all studies are remarkably consistent, indicating that the effects cannot reasonably be attributed to chance.

120 100 80 AHI 60 40 20 0 Pre/out

Post/in

Post/out

Treatment/Orthosis

Figure 6.4 Improvement in AHI with a SnoreGuard oral appliance and return to baseline severity with appliance removal. Note that more severe patients (AHI 40+) are less likely to achieve AHI < 20. (Adapted from Schmidt-Nowara et al.11)

Table 6.1 lists selected studies, including the author’s original report in 1991,11 a state-ofthe-art review in 1995,5 and three more recent studies of adjustable appliances.13–15 In each study, OAs were effective in most, but not all, patients. For example, in the review of 20 papers, comprising studies in 304 patients,5 51% of patients achieved normal levels (AHI < 10) and 70% demonstrated a reduction in pretreatment AHI of 50%, a success criterion frequently used in the surgical literature. The three recent studies13–15 appear to have produced a lower mean AHI and arguably a higher proportion of successfully treated patients, suggesting that titration of an adjustable appliance offers the prospect of more effective treatment. However, in every report some patients are left with an unacceptable level of apnea. Ineffective treatment occurs more frequently in patients with severe OSA (Figure 6.4). Other reasons for treatment

Efficacy and use

123

Table 6.1 Efficacy of oral appliances in obstructive sleep apnea in selected studies. Reference

Patients n

11

20

5

304

13

24

14

75

15

38 20 18

Appliance type

SnoreGuard, non-adjustable MAD, TRD, non-adjustable MAD, sham, adjustable TAP, adjustable Klearway, adjustable AHI 15–30 AHI 30+

AHI without/with OA mean

Treatment response AHI ⭐ 15 (%)

< 50% initial AHI (%)

47/20

40

75

43/19

51*

70

30/14

75

–

44/12

55

81

33/12

71

–

80 61

– –

*

AHI <10–15 AHI, apnea–hypopnea index; OA, oral appliance; MAD, mandible-advancing device; SnoreGuard appliance (Distar, Albuquerque, NM, USA); TRD, tongue retaining device (Pro-Positioners, Racine, WI, USA); TAP, Thornton Anterior Positioner (Airway Mangement, Inc., Dallas, TX, USA); Klearway appliance (Great Lakes Orthodontics Ltd, Tonawanda, NY, USA).

failure include limited mandibular mobility, dental or temporomandibular joint (TMJ) discomfort, and other poorly characterized factors probably reflecting properties of the airway and the propensity to collapse. In addition to reducing OSA, OAs are very effective in reducing snoring. In the previously mentioned review paper,5 satisfactory reduction or elimination of snoring was reported in more than 90% of patients. An adjustable appliance reduced snoring to less than loud in 97% of patients.14 Sleepiness is usually corrected to the extent that sleep apnea is successfully controlled. Early reports suggested that OA treatment was less successful in more severe OSA, defined as AHI less than 30–50, was less effective in the supine position, had only modest effect on

minimum oxygen saturation, and could be effective in patients failing uvulopalatopharyngoplasty (UPPP).5,11 Subsequent reports have confirmed and strengthened these findings.8 Several papers have shown correlations with cephalographic parameters and treatment success.8,16 These correlations can help with the selection of patients for OA therapy, although exceptions are well documented. The safety of OA use is good, with the proviso that care needs to be supervised by a dentist with special expertise. Despite initial concern about TMJ pain, reports show this to be an infrequent complication, 8% in one study,17 presumably because patients stop therapy before significant injury occurs. Excessive salivation is an early and universal sideeffect that abates with continued use. A change

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Therapy with oral appliances

in the occlusal relationship is the most common complication, occurring in 14% of 132 patients evaluated in one study.17 This complication can often be managed with specific exercises without discontinuing therapy. Patients usually use an OA regularly, once the initial adjustment is completed. In a questionnaire survey of 121 patients, on average 350 days after starting OA use, 86% reported nightly use and only 13% were dissatisfied with this form of therapy.14 A report of a novel compliance monitor imbedded into an OA indicates use for an average of 6.8 hours per night.15 Expulsion of the appliance during sleep is minimized in modern appliances by special lining materials that firmly adhere to the dental surfaces. The most common reason for discontinuing OA use is lack of efficacy.

60 50

40 AHI 30

20

10

0 PreCPAP

CPAP

A 60 50

40

Comparison of OA to other therapies

AHI 30

20

OAs have been compared to CPAP in four randomized studies, three with crossover and one with parallel group design12,18–20 Comprising a total of 126 patients, mostly of mild to moderate severity, these studies tell a consistent story. CPAP controls OSA in all patients, whereas some OA treatments are ineffective (Figure 6.5). This advantage of CPAP is offset by its lower acceptance compared to OA therapy. When efficacy and treatment acceptance and adherence are considered together to define treatment effectiveness, both therapies are effective in approximately two-thirds of patients. However, patients with good response to both therapies consistently prefer OA therapy. In two crossover studies, 20 of 22 successful OA users preferred OA to CPAP12,19 and in a third study, 19 of 21 patients chose OA for long-term treatment.20

10

0 Pre-OA

Oral appliance

B Figure 6.5 Improvement in AHI with nasal CPAP (A) is better when compared to a SnoreGuard oral appliance (B). (Adapted from Ferguson et al.12)

Direct comparison of OAs to surgical therapy has been performed in one randomized controlled study comparing a mandibular advancing OA to UPPP.21 Of the patients, 37 treated with OA therapy and 43 treated with surgery were evaluated at 12-month follow-up.

Treatment protocols A 50% reduction in AI or a reduction in AHI to 10 or less occurred in 95% and 78% of the OA group respectively. These success rates were significantly higher than the respective rates of 70% and 51% in the UPPP group. Quality of life assessments at 12 months were improved to the same degree in both groups, except that the surgical group reported a higher level of ‘contentment.’22 Perhaps this indicates that the greater success rate of OA is to some extent offset by the inconvenience of nightly therapy.

Mechanisms Mandible-advancing OAs are thought to open the airway by forward traction on soft tissues attached to the mandible. The evidence for this mechanism is convincing. Examination by endoscopy, lateral cephalograms and MR all show increases in the retropalatal and retroglossal airspace with OA emplacement.9 Although none of these observations were made during sleep, one endoscopic study found the same effects during anesthesia.23 Presumably with increased airway size, resistance and the degree of negative inspiratory pressure are reduced, and by this means the frequency of upper airway obstructions during sleep is reduced. OAs may also work by preventing mandibular retrusion during sleep.24,25 This may explain why a very small advance from the centric position can often be effective. Mandibular advance also increases the tension on upper airway muscles, reducing airway compliance, and by this mechanism may resist airway collapse.

Treatment protocols The decision to use OA therapy is influenced by numerous factors, including access to

125

experienced clinicians and the goodwill of healthcare payers. With respect to medical indications, the practice parameters of the American Academy of Sleep Medicine serve as a good starting point (Table 6.2). The author suggests that cases of upper airway resistance syndrome be included in the indications, since this condition is closely related to primary snoring and mild OSA. Additional factors contribute to the decision in individual cases (Table 6.3). A critical factor

Table 6.2 Indications for oral appliance therapy of snoring and sleep apnea. 1. 2. 3. 4.

Primary snoring without sleep apnea Mild obstructive sleep apnea Moderate to severe OSA if CPAP rejected and surgery not appropriate Upper airway resistance syndrome version of OSA

Indications 1–3 adapted from AASM Practice Parameters.6

Table 6.3 Relative indications for and against oral appliance use for obstructive sleep apnea. For OA therapy

Against OA therapy

Snoring main symptom AHI < 30 CPAP refusal Surgery failure Frequent travel Mask claustrophobia

Sleepiness main symptom AHI 30+ Poor dentition Active TMJ problem Gags easily Morbid obesity Severe oxygen desaturation

OA, oral appliance; TMJ, temporomandibular joint.

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Therapy with oral appliances

is the state of dentition, since mandibular devices stress the dental attachments. Symptom presentation, OSA severity, past experience with OSA therapies and treatment objectives should also be considered as factors contributing to a treatment decision. Patient preference is important, but the patient should be fully informed. When patients are presented with a choice of CPAP, throat surgery, or OA use, many indicate a preference for OA, but the physician must add the weight of professional experience and clinical science to help with this decision. The author often suggests an OA as the primary therapy when snoring is the chief complaint, symptoms of sleep disturbance are modest, AHI is less than 30, and hypoxemia is not a significant problem. When sleepiness is the chief complaint, CPAP is a better choice, because the treatment response helps improve treatment adherence. In addition to using OAs as primary treatment, OAs may also be useful in CPAP users as an adjunct for travel when a patient does not wish to be burdened by the CPAP equipment. OA therapy should involve a dentist. Dentists are best qualified to assess the adequacy of the dentition, to fabricate the appliance, and to supervise adjustment. Conversely, the diagnosis of snoring and OSA and the assessment of treatment response require medical expertise. Medical and dental licensing and liability concerns may affect which aspects of care practitioners from the two professions may assume.26 Ideally, a model of collaboration between dentist and physician should provide the best care for the patient. The fabrication of an appliance is only the first step in the treatment. Although OAs are usually made with an initial amount of advance, in most cases adjustment is required to achieve the desired treatment effect and an acceptable level of comfort. This process may

take several weeks to months. The endpoint of this titration period should be the resolution of symptoms and adequate control of OSA. The latter requires objective monitoring. The author and his dental colleagues use oximetry at baseline and after adjustment for this purpose.

Conclusion OAs have become an important alternative in the treatments for OSA. Although not uniformly effective, they can achieve treatment goals in up to two-thirds of selected patients. In the broad spectrum of OSA severity, OAs complement CPAP as a non-surgical therapy, since OAs are more effective in less severe cases where CPAP adherence is low. Conversely, more severe cases with severe hypoxemia and sleepiness that may be undertreated by OAs are more likely to adapt well to CPAP. OAs and palatal surgery are often considerations in the same patient. When CPAP is rejected and uncertainty about treatment persists, an OA may be a reasonable choice, since OA therapy does not produce a permanent change and can be terminated at any time. Full disclosure of the risks and benefits of each treatment will allow the patient to make the best choice.

Case report A 54-year-old man presented for help with snoring and poor sleep. An ear, nose and throat evaluation 4 years earlier produced an oximetry test showing mild sleep apnea. Surgery of the nasal septum improved nasal breathing but did not correct snoring and daytime fatigue.

References Sleepiness assessed by the Epworth Sleepiness Scale (ESS) was moderate, with a score of 10 on a 24-point scale. Examination showed a body mass index of 25, normal craniofacial development, a patent nasal airway, a crowded Malampati class III oral airway, and displacement of the palatal attachment towards the midline, producing a narrow nasopharyngeal introitus. Polysomnography showed loud snoring, AHI 10, and 27 breathing-related arousals per hour. The patient requested OA therapy. A dentist provided a TAP appliance (Thornton Anterior Positioner, Airway Management, Inc., Dallas, TX, USA), which the patient adjusted to a position of effect and comfort under supervision. At follow-up 4 months later, snoring was relieved, ESS was 7, sleep was refreshing, and fatigue was corrected. Oximetry with the appliance showed 12/h oxygen desaturations no less than 2% and a minimum saturation of 89%.

Study questions 1. What was the probability of treatment success when OA therapy was proposed? 2. What side-effects may develop with continued OA use and what is the probability of each? 3. In this patient, what would be the probability of effective treatment, i.e. successful treatment with good adherence, with CPAP and with palatal surgery?

References 1. Robin P. Glossoptosis due to atresia and hypotrophy of the mandible. Am J Dis Child 1934;48:541–7.

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2. Cartwright R, Samelson C. The effects of a nonsurgical treatment for obstructive sleep apnea–the tongue-retaining device. JAMA 1982;248:705–9. 3. Soll BA, George PT. Treatment of obstructive sleep apnea with a nocturnal airway patency appliance. N Engl J Med 1985;313:386–7. 4. Kloss W, Meier-Ewert K, Schaefer H. Zur Therapie des obstruktiven Schlaf-ApnoeSyndroms. Fortschritte Neurol Psychiatrie 1986;54:267–71. 5. Schmidt-Nowara W, Lowe A, Wiegand L, Cartwright R, Perez-Guerra F, Menn S. Oral appliances for the treatment of snoring and obstructive sleep apnea: a review. Sleep 1995;18:501–10. 6. American Sleep Disorders Association Standards of Practice Committee. Practice parameters for the treatment of snoring and obstructive sleep apnea with oral appliances. Sleep 1995;18:511–13. 7. Clark GT. Mandibular advancement devices and sleep-disordered breathing. Sleep Med Rev 1998;2:163–74. 8. Schmidt-Nowara W. Recent developments in oral appliance therapy of sleep-disordered breathing. Sleep Breathing 1999;3:103–6. 9. Lowe AA, Schmidt-Nowara W. Oral appliance therapy for snoring and apnea. In Pack AI, ed. Pathogenesis, Diagnosis and Treatment of Sleep Apnea. New York: Marcel Dekker, in press. 10. Lowe AA. Oral appliances for sleep breathing disorders. In: Kryger M, Roth T, Dement W, eds. Principles and Practice of Sleep Medicine, 3rd edn. Philadelphia: WB Saunders, 2000: 929–39. 11. Schmidt-Nowara W, Meade T, Hays M. Treatment of snoring and obstructive sleep apnea with a dental orthosis. Chest 1991;99:1378–85. 12. Ferguson KA, Ono T, Lowe AA, Keenan SP, Fleetham JA. A randomized crossover study of an oral appliance vs nasal-continuous positive airway pressure in the treatment of

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13.

14.

15.

16.

17.

18.

19.

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mild–moderate obstructive sleep apnea. Chest 1996;109:1269–75. Mehta A, Qian J, Petocz P, Darendeliler M, Cistulli P. A randomized controlled study of a mandibular advancement splint for obstructive sleep apnea. Am J Respir Crit Care Med 2001;163:1457–61. Pancer J, Al-Faifi S, Al-Faifi M, Hoffstein V. Evaluation of variable mandibular advancement appliance for treatment of snoring and sleep apnea. Chest 1999;116:1511–18. Lowe A, Sjoeholm T, Ryan C, Fleetham J, Ferguson K, Remmers J. The effects of Klearway oral appliance on airway size and obstructive sleep apnea. Sleep 2000;23: S172–8. Mayer G, Meier-Ewert K. Cephalometric predictors for orthopaedic mandibular advancement in obstructive sleep apnea. Eur J Orthodont 1995;17:35–43. Pantin CC, Hilman DR, Tennant M. Dental side effects of an oral device to treat snoring and obstructive sleep apnea. Sleep 1999;22:237–40. Fleetham J, Lowe A, Vazquez J, Ferguson K, Flemons W, Remmers J. A long term randomized parallel multicentre study of an oral appliance vs. nCPAP in the treatment of obstructive sleep apnea. Am J Respir Crit Care Med 1998;157:A285. Ferguson KA, Ono T, Lowe AA, Al-Majed S, Love LL, Fleetham JA. A short term controlled trial of an adjustable oral appliance for the treatment of mild–moderate obstructive sleep apnea. Thorax 1997;52:362–8.

20. Clark GT, Blumenfeld I, Yoffe N, Peled E, Lavie P. A cross-over study comparing the efficacy of continuous positive airway pressure with anterior mandibular positioning devices on patients with obstructive sleep apnea. Chest 1996;109:1477–83. 21. Wilhelmsson B, Tegelberg A, WalkerEngstrom M et al. A prospective randomized trial of a dental appliance compared to uvulopalatopharyngoplasty in the treatment of obstructive sleep apnea. Acta Otolaryngol 1999;119:503–9. 22. Walker-Engstrom M, Wilhelmsson B, Tegelberg A, Dimenas E, Rinqvist I. Quality of life assessment of treatment with dental appliances or UPPP in patients with mild to moderate obstructive sleep apnea: a prospective randomized 1-year follow-up study. Sleep Res 2000;9:303–8. 23. Isono S, Tanaka A, Sho Y, Konno A, Nishino T. Advancement of the mandible improves velopharyngeal patency. J Appl Physiol 1995;79:2132–8. 24. Miyamoto K, Ozbek MM, Lowe AA et al. Mandibular posture during sleep in healthy adults. Arch Oral Biol 1998;43:269–75. 25. Miyamoto K, Ozbek M, Lowe A et al. Vertical mandibular posture during sleep in patients with obstructive sleep apnea. Arch Oral Biol 1999;44:657–64. 26. Cooper NA. Legal perspective: licensing and liability issues regarding the use of oral appliances in the treatment of obstructive sleep apnea. Sleep Breathing 2000;4:89–93.

7

Nasal obstruction and nasal surgery

David L Steward, Jack Gluckman and Jonas T Johnson

Introduction Physicians and laypersons alike have long suspected nasal obstruction to be a cause of snoring and disturbed sleep.1 A nineteenth century report in the English literature notes the association between disturbed sleep and impairment of the nasal airway, as well as the relationship between nasal obstruction and daytime somnolence.2 However, the mechanism by which this occurs and the role of surgical management remain elusive. This chapter will address the etiology, diagnosis and management options for patients with nasal obstruction and sleep-disordered breathing. The primary role of the nasal airway is to function as an involuntary variable resistor to match pulmonary impedance, minimize turbulent airflow, and optimize gas exchange within the alveoli.3–5 In contrast, mouth breathing is associated with decreased airway resistance, turbulent airflow, and poor ventilation and oxygenation.6 Evidence for nasal obstruction causing obstructive sleep apnea (OSA) has been derived from studies of normal subjects who developed snoring, hypopnea and apnea after experimentally induced nasal obstruction.7–10 Additionally, a study of mouth opening during sleep showed increased upper airway collapsibility.11 While acute nasal obstruction results

in sleep-disordered breathing in otherwise normal subjects, this does not necessarily mean that nasal obstruction is the cause of OSA. However, a population study of nearly 5000 people found that those complaining of nasal obstruction were statistically more likely to complain of excessive daytime somnolence and habitual snoring.12 The same study demonstrated that habitual snorers have significantly reduced nasal airflow when compared to non-snorers. Additionally, those who reported nasal obstruction due to allergy were 1.8 times more likely to have moderate to severe sleep-disordered breathing than those without.12 A separate study of patients with seasonal allergic rhinitis and OSA demonstrated significantly increased nasal resistance and apneic episodes during symptomatic periods.13 A simplified explanation of the mechanism by which nasal obstruction may contribute to OSA is based upon a theoretical spectrum of sleep-disordered breathing progressing from snoring to OSA. Nasal airway pathology causes increased nasal resistance. As nasal resistance increases, the pressure differential across the pharynx also increases, causing turbulent airflow and subsequent soft tissue vibration.14 Attempts to bypass the increased nasal resistance by mouth breathing also result in increased airflow turbulence. This turbulent vibratory pattern is audibly recognized as

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Nasal obstruction and nasal surgery

snoring. Histopathologic studies demonstrate that in this situation nasal and pharyngeal soft tissues undergo inflammation, interstitial edema, muscle bundle disruption, and neural degeneration.5,15,16 The progression from snoring and upper airway resistance syndrome (UARS) to OSA occurs when the negative pressure within the pharyngeal airway overcomes the pharyngeal dilatory forces, with resultant collapse of pharyngeal soft tissue.17,18 This may in part be mediated by a loss of afferent neural input5,15,19 as well as pharyngeal dilator muscle hypotonia. Some individuals may be genetically more susceptible to these effects, resulting in a more rapid progression to OSA.10 As appealing as this explanation is, studies have not found a linear correlation between nasal resistance and severity of sleep-disordered breathing.12,20 This may be in part due to different pressure thresholds for pharyngeal soft tissue collapse in different patients. Additionally, the measurement of nasal resistance has generally been performed on patients while awake and upright, rather than asleep and supine.20 Nevertheless, nasal obstruction is more likely to be an etiologic cofactor of OSA rather than the sole precipitant.21

Nasal airway anatomy and physiology

Nasal valve area

}

The nasal airway may be thought of as a bilateral tube from the anterior nares to the posterior choanae with narrowing at the nasal valve, middle meatus, and posterior choanae. The nasopharynx constitutes the common passageway for air flowing from the nasal cavity into the pharyngeal airway with narrowing at the velopharynx.

The nasal cycle is a normal physiologic process by which the nose undergoes alternating left and right congestion and decongestion through autonomic regulation of cavernous venous plexuses within the ‘pseudo-erectile’ nasal mucosa. The cycle occurs every 40 min to 4 h. The nasal cycle is altered by body posture and leads to unilateral nasal airflow during sleep, optimizing pulmonary compliance and function. Hypoxia, hypercapnea and increased sympathetic tone cause vasoconstriction and reduced nasal resistance. Hypocapnea, cold air, irritants and decreased sympathetic tone cause vasodilation and increased resistance. Additionally, certain hormonal states such as pregnancy affect the nasal cycle.22 The nasal valve is generally the narrowest portion of the nasal passage, accounting for about 50% of total resistance to respiratory airflow.23,24 The nasal valve is a slit-like space bounded by the upper and lower lateral cartilages superiorly, the septum medially, the inferior turbinate laterally, and the pyriform aperture inferiorly (Figures 7.1 and 7.2). This is a functional valve regulating resistance, and thus airflow, via nasal dilator musculature

Ala Nasal sill

Figure 7.1 Inferior view of the nasal valve area.

Nasal obstruction

Keystone area Frontal process of maxilla

131

Figure 7.2 Lateral view of nasal anatomy.

Rhinion

Upper lateral cartilage Pyriform aperture Sesamoid cartilages Dome (shaded area) Accessory cartilages Medial crus Lower lateral Lateral crus cartilage

{

Nasal spine

(Figure 7.3) and autonomic regulation of venous plexuses along the inferior turbinate and nasal septum.22

Levator Levatorlabii labiisuperioris superior alaeque Alaeque nasi nasi m. m. Procerus m.

Nasalis m. (pars transversa)

The middle meatus is the site of approximately two-thirds of the nasal airflow. Airflow regulation in this region is also under autonomic control via regulation of the mucosa along the septum medially and the middle turbinate laterally.22 The posterior choana is bounded laterally by the posterior portion of the inferior turbinate and medially by the septum. While inferior turbinate and septal mucosal engorgement is under autonomic control, the posterior choana is not a significant area of normal airflow regulation. The nasopharynx is separated inferiorly from the oropharynx by the soft palate, and bounded posteriorly by the adenoid pad. Nasal resistance within the nasopharynx may in part be regulated by palatal and pharyngeal musculature.

Dilator naris m.

Depressor septi m.

Figure 7.3 Lateral view of nasal dilator musculature.

Nasal obstruction Nasal obstruction to airflow may occur in any of the four previously discussed areas.

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Nasal obstruction and nasal surgery

Obstruction may be pathologic or physiologic, and static or dynamic. It may occur secondary to bony, cartilaginous, mucosal or neuromuscular pathology. The etiology may be congenital, infectious, inflammatory, neoplastic, traumatic, systemic, or functional, and is often multifactorial. The nasal valve area may cause obstruction through functional collapse of the lateral nasal wall during inspiration. This is due to weak lateral cartilaginous support. This may be idiopathic but is common after nasal trauma or rhinoplasty. Less commonly, dysfunction of the nasal dilator muscles or lack of coordination with other inspiratory musculature may cause nasal valve obstruction. Inferior turbinate hypertrophy results from mucosal inflammation, or less commonly bony overgrowth, and is a common cause of anterior nasal obstruction. Anterior cartilaginous septal deviation and mucosal inflammation may contribute to obstruction. While cadaveric studies reveal septal deviation in about 80% of people,25 most remain asymptomatic. Congenital or acquired pyriform aperture stenosis or nasolacrimal duct cysts are unusual causes of obstruction. The middle meatal area may be obstructed by bony or mucosal pathology of the septum or middle turbinate. While ‘pseudo-erectile’ septal mucosa is often misinterpreted as septal deviation, the bony–cartilaginous junction is a common site for septal deviation. Occasionally, an enlarged or aerated middle turbinate (concha bullosa) will contribute to nasal obstruction in this region. Additionally, inflammatory masses such as polyps may cause significant obstruction. Less commonly, neoplastic masses or papillomas result in obstruction. The posterior nasal choana is a common site of congenital obstruction. This atresia may be bony or soft tissue. Acquired stenosis is

uncommon. Posterior inferior turbinate hypertrophy from chronic mucosal inflammation may also contribute to posterior obstruction. Nasopharyngeal obstruction may result from adenoid hypertrophy, or less commonly from acquired stenosis complicating adenoidectomy. Neoplastic disease may cause complete obstruction, as may congenital masses such as Tornwaldt’s cysts. Pharyngeal hypotonia may cause obstruction during inspiration. More commonly, soft palatal hypotonia and mucosal hypertrophy result in velopharyngeal collapse during inspiration, resulting in nasopharyngeal obstruction.26,27

Diagnosis The following discussion focuses on the diagnosis of nasal obstruction in association with sleep-disordered breathing. Unfortunately, objective assessment of nasal patency often does not correlate well with a patient’s subjective assessment. It is therefore important for the physician to be sure to take the symptomatology into consideration. A good history includes: symptoms of obstruction, hyposmia, allergy, and infection; past medical, surgical and traumatic history; and medication use. Physical examination includes anterior rhinoscopy both before and after topical nasal decongestion. Assessment of nasal valve obstruction is aided by the Cottle maneuver, whereby the skin overlying the maxilla is retracted laterally. Bilateral nasal endoscopy is best performed with a flexible scope, which aids in evaluation of the nose, nasopharynx, oropharynx, hypopharynx, and larynx. Nasal evaluation should identify the sites of obstruction as well as the underlying etiologies, in order to adequately direct treatment.

Treatment Ancillary testing may occasionally aid in diagnosis and provide objective assessment of nasal obstruction. Imaging may be indicated for chronic infection or polyposis, and to rule out neoplastic disease. Cephalometry may help in diagnosing craniofacial abnormalities. Rhinomanometry and acoustic rhinometry can be used to calculate nasal resistance, but are limited in their clinical utility. For patients with allergy, testing may be indicated to direct desensitization.

Treatment Treatment for nasal obstruction in association with sleep-disordered breathing may be divided into medical, behavioral, mechanical, surgical and combined therapy. Appropriate therapy requires accurate diagnosis and should be directed at the underlying etiology of obstruction.

Medical Medical therapy of nasal obstruction may be topical or systemic, and is directed at mucosal disease. It is based upon the accurate diagnosis of the cause of obstruction. A placebocontrolled, double-blind study of 20 patients with perennial allergic rhinitis (without OSA, obesity, or septal deviation) found statistically significant subjective improvement in nasal congestion and sleep, along with a trend towards improvement in daytime sleepiness, in the group of patients treated with topical steroids.28 Thus, for patients with allergic rhinitis, topical nasal steroid spray is indicated. Additionally, for some patients with allergic rhinitis, topical or systemic antihistamines, short-course systemic steroids and allergic

133

desensitization may be beneficial. First-generation antihistamines may have a negative impact due to their sedative effect, so second-generation antihistamines are recommended for systemic therapy.29 Systemic decongestants are effective for patients who can tolerate them. However, consideration of their hypertensive side-effects is critical in this population, because of a high incidence of concomitant hypertension or hypertension induced by obstructive sleep. Topical decongestant sprays are contraindicated for chronic use, but may be beneficial during acute upper respiratory infection. Antibiotic therapy is indicated for patients with chronic sinusitis. In severe nasopharyngeal acid reflux disease, systemic therapy with proton pump inhibitors may be worthwhile.

Behavioral Behavior modification may be helpful in selected cases. Patients should be counseled to lose weight when appropriate.30,31 Patients should be counseled to avoid alcohol, benzodiazepines and other sedatives prior to sleep, because of reduced respiratory drive, muscle hypotonia, and increased nasal resistance.32–35 If sleep-disordered breathing occurs only in the supine position, techniques to encourage sleeping in a prone or lateral position may also be useful.36–39 Patients with allergy may benefit from antigen avoidance and techniques to minimize exposure, such as use of mattress covers. Patients with excessive daytime sleepiness or a history of falling asleep while driving should discontinue driving and operating heavy machinery until after successful treatment.40–43 Lastly, tobacco smoking is strongly associated with OSA,12 resulting from increased nasal resistance and/or night-time nicotine withdrawal, and smoking cessation should always be recommended.

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Nasal obstruction and nasal surgery

Figure 7.4 An external nasal dilator (Courtesy of Breathe Right® Nasal Strips, CNS, Inc., Minneapolis, MN, USA).

Figure 7.5 An example of an internal nasal dilator (Courtesy of Nozovent, Scandinavian Naturals, Inc., Perkasie, PA, USA and Tonya Hines, The Neuroscience Institute, University of Cincinnati, Cincinnati, OH, USA).

Mechanical

Factors that correlated with a positive effect were: inferior turbinate hypertrophy, septal deviation, and/or allergic rhinitis; minimal or no pharyngeal obstruction; and age < 55 years. The authors proposed using an external dilator polysomnogram to select patients in whom nasal therapy (dilator or surgery) may resolve mild apnea.54 One study using internal nasal dilators in 11 patients with snoring, and/or OSA, demonstrated a reduction in the mean apnea index (AI) from 18 (range 1.8–60) to 6.4 (range 1.3–15), with a mean decrease in AI of 47%. Snoring noise was also decreased in snorers.55 A second study of an internal nasal dilator for patients with snoring and/or OSA but without evidence of nasal obstruction on physical examination found no benefit in snoring or apnea.56

Mechanical devices include internal and external nasal dilators (Figures 7.4 and 7.5), nasal and facial continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP),44–47 and intraoral appliances.48–51 Nasal dilators are designed to reduce nasal resistance at the nasal valve. External dilators have been shown to decrease snoring intensity especially in those patients without OSA.52 Additionally, external dilators have been shown to reduce arousal instability in mild snorers without OSA.53 A recent study of patients with nasal obstruction and OSA (respiratory disturbance index (RDI) > 10) demonstrated reduction in the RDI in 19 of 26 patients (73%) using external dilators.

Treatment Surgical When considering surgical therapy for sleepdisordered breathing in the presence of subjective or objective evidence of nasal obstruction, the following issues are relevant: 1. Is there any indication for nasal surgery alone in the relief of snoring and/or OSA? 2. Should nasal surgery be performed in conjunction with other surgical therapy for snoring and/or OSA? 3. Is there any role for nasal surgery to improve the efficacy and tolerance of CPAP? 4. If nasal surgery is indicated, what procedure(s) should be recommended?

Snoring Nasal surgery has been shown to benefit patients with snoring and even some with sleep apnea.57–61 A study of seven patients with snoring and daytime somnolence, but without OSA, demonstrated objective improvement in daytime somnolence (using sleep latency testing) and decreased snoring. All patients underwent septoplasty and turbinoplasty.1 A recent study of 50 patients with nasal obstruction, snoring and OSA demonstrated subjective improvement in snoring in 34% of patients treated with septoplasty with or without turbinoplasty.62 A study of 29 snoring patients treated with septoplasty and inferior turbinoplasty (and polypectomy when indicated) found a 69% subjective success rate in snoring. However, of the 14 patients with OSA, only 50% had subjective improvement in snoring.63 Fairbanks employs a topical nasal decongestant spray test to preoperatively identify patients who obtain relief from snoring during spray nights. Using this selec-

135

tion criterion, he reports a 75% success rate in treating snoring with nasal surgery alone.58,64 Thus, nasal surgery alone for the treatment of snoring may result in subjective improvement in snoring in about 70% of patients without OSA, and between 33% and 50% of patients with OSA. Test use of a topical nasal decongestant spray may help determine those likely to benefit from nasal surgery alone. However, since no objective data on snoring reduction after nasal surgery are available, suspicion is warranted in interpreting the subjective data. A study comparing subjective and objective snoring improvement after uvulopalatopharyngoplasty (UPPP) found no significant objective improvement despite 80% of patients reporting improved snoring and sleep quality, and 20% of bed partners also reporting no more interference with sleep.65

Obstructive sleep apnea The data regarding the efficacy of nasal surgery alone in the treatment of OSA are even less convincing. A study of 20 patients with OSA reported that 20% of patients were cured with nasal surgery alone (septoplasty, inferior turbinectomy, and/or polypectomy).57 However, a recent study of 50 patients with nasal obstruction and OSA, treated with septoplasty with or without turbinoplasty, found that patients with mild OSA had statistically worsened RDI, while moderate to severe OSA patients had no significant change.62 A study of 40 patients with OSA, included 23 treated with septoplasty, reported a successful reduction in RDI of > 50% in 8 patients (35%).66 Thus it appears that there is no role for routine treatment of OSA with nasal surgery alone, except possibly in cases of massive polyposis.

136

Nasal obstruction and nasal surgery

Combined nasal and pharyngeal surgery Combining nasal surgery with other surgical therapy for snoring and/or OSA is attractive, in that the patient may undergo only one general anesthetic. UPPP, combined with nasal surgery, has shown a 97% subjective rate of snoring improvement in a review of 180 patients.67 However, a study of 347 patients found a 14% complication rate when septoplasty and turbinectomy were performed with UPPP, compared to a 2% complication rate when UPPP was performed alone. These authors recommended staging procedures.68 A study of UPPP alone in the treatment of snoring in 100 patients found similar subjective improvement (96%) except in patients with high nasal resistance by rhinomanometry, where improvement was 78%. They recommended UPPP followed by nasal surgery for those who fail to improve with the UPPP.69 Thus, if nasal surgery is deemed necessary in addition to other surgical therapy for snoring, consideration should be given to staging the procedures, due to a higher complication rate with combined surgery. If concurrent nasal and pharyngeal surgery is performed, the nasal portion should be performed last to prevent bleeding from obscuring visualization. Nasal packing should be avoided, or ventilated nasal stents should be used.70

Nasal surgery to improve CPAP tolerance Nasal surgery has been advocated for patients with nasal obstruction who have difficulty tolerating nasal CPAP. This is a result of the poor compliance with nasal CPAP despite proven benefit in treating sleep-disordered

breathing. However, CPAP compliance is multifactorial, and no single problem accounts for the patient non-compliance.71–76 Yet, unlike UPPP, which can increase problems with mouth leakage during nasal CPAP use, nasal surgery generally reduces nasal resistance and is not associated with worsening of CPAP compliance.77 A study of 50 patients with nasal obstruction and OSA demonstrated a statistically significant reduction in CPAP pressure levels after nasal surgery (septoplasty with or without inferior turbinoplasty).62 A recent placebo-controlled study specifically addressed the role of improving CPAP tolerance using radiofrequency treatment to perform inferior turbinoplasty. CPAP tolerance subjectively improved by 29% in patients treated with radiofrequency compared to a 10% worsening in patients treated with placebo. Objective outcome measures were not statistically significant.78

Procedures The decision regarding what type of nasal surgery to recommend in cases of nasal obstruction associated with sleep-disordered breathing is complex. Certainly, in patients who have symptomatic nasal obstruction refractory to medical management and have sleep-disordered breathing, nasal surgery is indicated for the management of the obstruction and may secondarily improve the sleep disorder. Selection of the appropriate surgical procedure is based upon accurate diagnosis of the level(s) and cause(s) of obstruction. Septoplasty (Figures 7.6–7.9) may be the most common procedure used to treat nasal obstruction associated with sleep-disordered breathing. It is recommended in cases of severe deviation with symptomatic obstruction refractory to medical therapy. Despite

Treatment

137

Area of mucosal elevation Remove or score cartilage

Secure with 3-0 vicryl

165-3 165-6

Elevator

Swing back into midline

Figure 7.6 A small incision is made inside the nose, which allows the surgeon to elevate the mucosa from the periosteum, and perichondrium from the bone and cartilage of the nose.

Figure 7.7 Bowing of the nasal septum can sometimes be corrected by resecting part of the bowed septum.

Resected area of cartilage

165-7 165-9

Cartilage scored on concave side

Scored cartilage

Overriding cartilage to be resected

Sutures Maxillary spine

Excess overriding cartilage excised

Figure 7.8 When the anterior cartilage is badly deviated, it can sometimes be scored on the concave side. This allows the cartilage to resume a more normal flat shape. Both excessive overriding cartilages must be excised.

Figure 7.9 When overriding cartilage is part of the obstruction problem, this can be excised.

138

Nasal obstruction and nasal surgery

objective evidence of reduced nasal resistance after septoplasty, 22% of patients continue to report symptoms of nasal obstruction.79,80 Efficacy of septoplasty in the management of snoring and OSA is discussed above. Inferior turbinate surgery may be performed alone, or in conjunction with other nasal surgery. Recently, turbinectomy has fallen out of favor, and various techniques for turbinoplasty have been described, including: outfracturing; submucosal resection; and submucosal ablation with electrocautery or radiofrequency energy.81 Attention is generally focused anteriorly, in the region of the nasal valve. A randomized study of 50 patients undergoing septoplasty or septoplasty with contralateral inferior turbinoplasty for nasal obstruction, found no subjective or objective evidence of improvement with the addition of turbinoplasty.80 Thus, the role of turbinoplasty remains controversial. Use of the Cottle maneuver, in conjunction with a trial of external nasal dilators, may aid in identifying patients with nasal valve collapse.54 Surgery to prevent nasal valve collapse has been reported for the treatment of OSA in two patients;82 however, conclusive data are lacking. Use of cartilage spreader grafts between the upper lateral cartilage and septum is standard therapy for this problem.83 A recent report of nasal alar rim reconstruction using cartilaginous struts placed along the caudal alar rim suggests equal or improved efficacy with less technical difficulty.84 Middle meatal surgery is indicated for nasal obstruction in cases of chronic sinusitis and sinonasal polyposis refractory to medical therapy. Rarely, resection of a concha bullosa or enlarged middle turbinate may be indicated to relieve symptoms of nasal obstruction associated with sleep-disordered breathing.22 Adenoidectomy is indicated in the management of nasal obstruction and snoring or OSA

secondary to adenoid hypertrophy. This, coupled with tonsillectomy, is often curative in the pediatric population. The goal of surgery is patent posterior nasal choanae.22 UPPP has been shown to reduce nasal airway resistance by eliminating obstruction in the region of the nasopharynx and possibly reducing anterior nasal mucosal imflammation.85

Conclusion Evaluation of symptoms and signs of nasal airway obstruction is an essential component in the assessment of the patient with snoring and/or OSA. While nasal obstruction may cause snoring and be a cofactor in the development of OSA, it is rarely the sole cause. Treatment of nasal obstruction associated with sleep-disordered breathing should initially be medical and behavioral. Snoring patients with nasal obstruction refractory to medical and behavioral therapy may be candidates for mechanical devices (external nasal dilators, nasal CPAP, or intraoral appliances) or nasal surgery. Test use of a topical nasal decongestant spray and/or an external nasal dilator may help to identify those likely to achieve subjective benefit from nasal surgery alone. Combining nasal and palatal surgery markedly increases the complication rate, and consideration should be given to staging procedures. Patients with nasal obstruction and OSA are best treated with nasal CPAP, except possibly in: young patients with significant adenoid obstruction; massive nasal polyposis; or neoplastic disease. In patients unable to tolerate nasal CPAP due to nasal symptoms related to nasal obstruction, nasal surgery may reduce CPAP pressure levels and subjectively improve CPAP tolerance. When

Conclusion

139

Nasal obstruction and sleep-disordered breathing

Polysomnography

Snoring

OSA

Medical therapy therapy Medical Behavioral therapy therapy Behaviour

CPAP

Tolerate CPAP?

Improved?

Yes

No

Yes

No

Continue therapy

Topical decongestant test External dilator test

Continue CPAP

Nasal symptoms or high CPAP pressures?

Symptoms improved?

Yes

No

Nasal surgery or external nasal dilator

CPAP, IOA or UPPP

Yes

No

Nasal surgery and/or medical therapy to increase CPAP tolerance

OSA OSA surgery, surgery, IOA, and/or and/or IOA, behavioral behavioural therapy therapy

Figure 7.10 A suggested protocol for the management of nasal obstruction and sleep-disordered breathing. Exceptions may include patients with adenoid hypertrophy, massive polyps, neoplasm, or severe structural deformity causing obstructive symptoms during daytime. OSA, obstructive sleep apnea; CPAP, continuous positive airway pressure; UPPP, uvulopalatopharyngoplasty; IOA, intraoral appliance.

140

Nasal obstruction and nasal surgery

nasal surgery is planned, it should be directed towards the area and underlying etiology causing the obstruction. A protocol is suggested for the patient with nasal obstruction and sleep-disordered breathing (Figure 7.10).

11.

12.

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LB. The effects of nasal dilation on snoring and obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 1992;118(3):281–4. Hoffstein V, Mateika S, Metes A. Effect of nasal dilation on snoring and apneas during different stages of sleep. Sleep 1993;16:360–5. Series F, St Pierre S, Carrier G. Effects of surgical correction of nasal obstruction in the treatment of obstructive sleep apnea. Am Rev Respir Dis 1992;146:1261–5. Fairbanks DN. Effect of nasal surgery on snoring. South Med J 1985;78:268–70. Hester TO, Phillips B, Archer SM. Surgery for obstructive sleep apnea: effects on sleep, breathing and oxygenation. South Med J 1985;78:268–70. Fairbanks DNF. Snoring: surgical vs nonsurgical management. Laryngoscope 1984;94:1188–92. Silvoniemi P, Suonpaa J, Sipila J, Grenman R, Erkinjuntti M. Sleep disorders in patients with severe nasal obstruction due to septal deviation. Acta Otolaryngol 1997;529:199–201. Friedman M, Tanyeri H, Lim JW, Landsberg R, Vaidyanathan K, Caldarelli D. Effect of improved nasal breathing on obstructive sleep apnea. Otolaryngol Head Neck Surg 2000;122:71–4. Woodhead CJ, Allen MB. Nasal surgery for snoring. Clin Otolaryngol 1994;19:41–4. Fairbanks DN. Predicting the effect of nasal surgery on snoring: a simple test. Ear Nose Throat J 1991;70:50–2. Miljeteig H, Mateika S, Haight JS, Cole P, Hoffstein V. Subjective and objective assessment of uvulopalatopharyngoplasty for treatment of snoring and obstructive sleep apnea. Am J Respir Crit Care Med 1994;150(5 pt 1):1286–90. Caldarelli DD, Cartwright RD, Lilie JK. Obstructive sleep apnea: variations in surgical management. Laryngoscope 1985;95(9 pt 1):1070–3.

References 67. Piche J, Gagnon NB. Snoring, apnea, and nasal resistance. J Otolaryngol 1996;25(3):150–4. 68. Mickelson SA, Hakim I. Is postoperative intensive care monitoring necessary after uvulopalatopharyngoplasty? Otolaryngol Head Neck Surg 1998;119(4):352–6. 69. Virkkula P, Lehtonen H, Malmberg H. The effect of nasal obstruction on outcomes of uvulopalatopharyngoplasty. Acta Otolaryngol Suppl 1997;529:195–8. 70. Olsen KD. The role of nasal surgery in the treatment of obstructive sleep apnea. Op Tech Otolaryngol Head Neck Surg 1991;2:63–8. 71. Reeves-Hoche MK, Hudgel DW, Meck R et al. Continuous versus bilevel positive airway pressure for obstructive sleep apnea. Am J Respir Crit Care Med 1995;151:443–9. 72. Kribbs NB, Pack AI, Kline LR et al. Objective measurement of patterns of nasal CPAP use by patients with obstructive sleep apnea. Am Rev Respir Dis 1993;147:887–95. 73. Reeves-Hoche MK, Meck R, Zwillich CW. Nasal CPAP: an objective evaluation of patient compliance. Am J Respir Crit Care Med 1994;149:149. 74. Engleman HM, Martin SE, Douglas NJ. Compliance with CPAP therapy in patients with sleep apnoea/hypopnoea syndrome. Thorax 1994;49:263. 75. Rauscher H, Formanek D, Popp W, Zwick H. Self reported vs. measured compliance with nasal CPAP for obstructive sleep apnea. Chest 1993;103:1675. 76. Meurice JC, Dore P, Paquereau J et al. Predictive factors of long-term compliance with nasal continuous positive airway pressure treatment in sleep apnea syndrome. Chest 1994;105:429.

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77. Mortimore IL, Bradley PA, Murray JA, Douglas NJ. Uvulopalatopharyngoplasty may compromise nasal CPAP therapy in sleep apnea syndrome. Am J Respir Crit Care Med 1996;154(6 pt 1):1759–62. 78. Powell NB, Riley RW, Zonato AI, Li KK, Troell RJ. Radiofrequency treatment of turbinate hypertrophy to improve nasal CPAP usage. Otolaryngol-Head & Neck Surg 1999;121:P54. 79. Gordon ASD, McCaffrey TV, Kern EB et al. Rhinomanometry for preoperative and postoperative assessment of nasal obstruction. Otolaryngol Head Neck Surg 1989;101:20–6. 80. Illum P. Septoplasty and compensatory inferior turbinate hypertrophy: long-term results after randomized turbinoplasty. Eur Arch Otorhinolaryngol Suppl 1997;1:S89–92. 81. Li KK, Powell NB, Riley RW, Troell RJ, Guilleminault C. Radiofrequency volumetric tissue reduction for treatment of turbinate hypertrophy: a pilot study. Otolaryngol Head Neck Surg 1998;119(6):569–73. 82. Irvine BW, Dayal VS, Phillipson EA. Sleep apnea due to nasal valve obstruction. J Otolaryngol 1984;13:37–8. 83. Toriumi DM. Open rhinoplasty. Facial Plastics Clin North Am 1993;1:102–8. 84. Troell RJ, Powell NB, Riley RW, Li KK. Evaluation of a new procedure for nasal alar rim and valve collapse: nasal alar rim reconstruction. Otolaryngol Head Neck Surg 2000;122(2):204–11. 85. Kawano K, Usui N, Kanazawa H, Hara I. Changes in nasal and oral respiratory resistance before and after uvulopalatopharyngoplasty. Acta Otolaryngol Suppl 1996;523:236–8.

8

Tracheotomy

Jonas Johnson and Jack Gluckman

Introduction Patients with obstructive sleep apnea (OSA) have a normally patent airway when awake. During sleep there is obstruction at a site or sites in the upper airway which results in hypoxemia and multiple arousals. Theoretically, tracheotomy is the ideal treatment for OSA, particularly if the tracheotomy tube can be covered or plugged during the day and opened during sleep. As the ‘perfect’ solution for OSA it is essential that the diagnosis of OSA be made prior to intervening with tracheotomy. Tracheotomy is imperfect as treatment for most patients with OSA. This is reflective of the fact that patients and their families perceive a tracheotomy to be unsightly and intrusive. It is difficult to camouflage and serves to ‘label’ the patient. Nevertheless, tracheotomy is highly effective in the management of OSA, resulting in immediate relief of symptoms, and should be considered in patients with severe life-threatening disease and when other approaches have failed. Patients with other sleep-related disorders are unlikely to benefit from tracheotomy. Similarly, patients with so-called central sleep apnea in whom there is inadequate respiratory drive would be unlikely to benefit from a tracheotomy. Prior to planning surgical

intervention, consultation with the sleep laboratory and careful evaluation of the polysomnogram is an essential component of treatment planning.

Historical review Guilleminault et al reported the results of 50 patients with OSA treated with tracheotomy.1 Apnea indices were uniformly greater than 65 events per hour. All patients reported dramatic reduction in apnea-associated symptomatology. Subsequent study in the sleep laboratory with the tracheotomy open and patent showed that apnea indices had been reduced to fewer than five per hour per individual. Occlusion of the tracheotomy tube resulted in recurrence of OSA. Other authors have noted similar, almost uniformly successful outcomes following tracheotomy for OSA.2,3 Patients experienced improved alertness with less daytime somnolence. Some patients have experienced reduction of hypertension and associated weight loss. Motta et al studied six patients with hemodynamic monitoring before and after tracheotomy.2 The variables evaluated included heart rate, pulmonary artery

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pressure, femoral artery pressure and arterial oxygen tension. Following tracheotomy, significant reductions were noted in pulmonary artery pressure and mean femoral artery pressure. There was also an increase in arterial oxygen tension.

Indications Tracheotomy is indicated in patients with severe OSA who have been unresponsive to or non-compliant with other therapeutic interventions. There does not exist a standard apnea index or respiratory disturbance index for which tracheotomy is uniformly indicated. Patients with severe symptomatology, such as pathologic and dangerous hypersomnolence, may be thankful for the immediate relief offered by tracheotomy. Patients with cor pulmonale, apnea-associated cardiac arrhythmia and severe oxygen desaturation may realize significant benefit subsequent to tracheotomy. Additionally, some surgeons feel that perioperative tracheotomy reduces the potential for postoperative morbidity and mortality in patients with severe sleep apnea who require pharyngeal surgery. In general, patients with OSA with documented apnea indexes in excess of 50 events per hour should be offered a tracheotomy if they cannot comply with the regular use of continuous positive airway pressure (CPAP). Severely affected patients may be managed perioperatively more safely with tracheotomy if they elect to undergo surgery directed at the upper airway. Patients with documented severe apnea, who have previously undergone airway surgery and failed to respond, are also candidates with whom tracheotomy should be discussed.

Technique General factors Surgeons and anesthesiologists alike are cautioned to avoid sedation in patients with severe OSA. Preoperative evaluation of mandibular excursion and the condition of the dentition as well as flexible transnasal evaluation of the airway allow the surgeon and anesthesiologist alike to prepare for administration of anesthesia and subsequent general endotracheal intubation. Simple abundance of soft tissue (tongue) should not impede intubation in experienced hands. Other factors which may make intubation even more difficult, such as retrognathia or temporomandibular joint ankylosis, call for flexible fiberoptic transnasal intubation or tracheotomy performed under local anesthesia. Tracheotomy is a surgical procedure widely performed by surgeons trained in a variety of disciplines. It is generally acknowledged to be quick and simple in appropriately trained hands. Tracheotomy in the ‘average’ patient with severe OSA may challenge these generally held concepts. Some patients present with morbid obesity resulting in excessive soft tissue overlying the trachea and often multiple folds of soft tissue (double and triple chins) which may serve to occlude the tracheotomy tube. Standard tracheotomy tubes may not fit. The potential for granuloma formation, soft tissue excoriation and an imperfect hygienic situation is high. In view of the fact that tracheotomy performed for OSA is intended for long-term use, a ‘permanent’ skin-lined stoma is preferable to the technique utilizing an endotracheal tube that most surgeons are conversant with (Figure 8.1A,B,C,D). The additional difficulty and time required to

Technique develop a skin-lined stoma in a morbidly obese patient suggest that general anesthesia with intubation and airway protection is the preferred approach. The technique used in performing the tracheotomy in the patients with OSA must be reflective of the intended duration of use of the tracheotomy and the patient’s particular morphology. In some instances, a tracheotomy is intended to be temporary to accompany other procedures in high-risk patients. Under these circumstances, it may be the intention of the surgeon to remove the tracheotomy when the patient has recovered from the other procedures and has shown documented relief of OSA. A standard tracheotomy may be undertaken under these circumstances; however, a special long-length tube may be required in some patients. A permanent skinlined tracheostomy is preferred if the intention is to support the patient with a tracheotomy long term. A variety of techniques to form a permanent skin-lined track have been described.4–6 In each case, a skin paddle is outlined and mobilized. The skin paddle invariably requires defatting such that it can be advanced and sutured directly to the tracheal margin. Preoperative estimation of the depth of soft tissue may help in acquisition of a properly sized tracheotomy tube. The availability of a tube with an inner cannula is invaluable in nursing care and preparing for discharge training. During performance of the procedure, meticulous attention to hemostasis with ligature or oversewing of bleeders is encouraged. The thyroid should be divided at the isthmus, oversewn and mobilized laterally to prevent it from compromising the stoma. Similarly, it may be necessary to displace the strap muscles laterally with a suture to the tendon of the sternomastoid muscle. A superiorly based tracheal flap using the third and

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fourth anterior rings is sutured to the upper skin flap. Eliachar has described a self-sustaining, tube-free tracheotomy which would suit most patients with OSA. A tube-free tracheotomy would minimize some of the unwanted complaints that patients have regarding conventional tracheotomy. This would be ideal if patients could generate speech and cough without the need to occlude the stoma or to use stents or valves. The Eliachar technique is performed through an omegashaped incision situated over the intended tracheotomy site (Figure 8.1E). Subsequently, skin flaps are elevated and adipose tissue is excised. This technique requires extensive undermining to allow tension-free mobilization of the flaps. The thyroid isthmus is transected and oversewn. The thyroid lobes are sutured laterally underneath the muscle (Figure 8.1F). When excessive submental fat is present, it must be excised, sometimes including an oval strip of skin (Figure 8.1G). The skin flaps are then advanced to provide a tension-free approximation to the margins of the tracheal fenestra (Figure 8.1H). An essential component comprises two suspensory sutures designed to sustain the elevation of the lower skin flap. These sutures (2–0 silk) are passed through the subcutaneous tissue of the undersurface of the flap and subsequently through the tendons overlying the sternoclavicular joint. A supplementary sling procedure is designed to allow tube-free tracheotomy function for effective cough and speech. This procedure is advocated as a staged adjuvant technique for patients who are unable to adequately constrict and seal the primary stoma. Interested readers are encouraged to consult the primary report.4 Postoperatively, patients are maintained in the hospital for monitoring and home care teaching prior to discharge. Some patients

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} 1.5 cm

}

3–6 cm

A B C

D

E

Figure 8.1 (A) An inferiorly based flap is elevated. Subcutaneous fat is excised. The flap is sutured directly to the trachea, skin to mucosa. (B) Schematic lateral view of the stoma. (C) An alternative design is the use of two laterally based flaps. Again, the fat is excised and the skin is sutured directly to the mucosa. (D) In the obese neck, this design improves the vascularity and the length of the flap. (E) With the patient supine and the neck in moderate extension, an incision is designed one finger’s breadth above the clavicles, with its vertex overlapping the cricoid arch.

Technique

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Suspended skin Excised panus

F

G

H

I

Figure 8.1 continued (F) The thyroid lobes and the strap muscles are everted sideways away from the trachea and sutured to the undersurface of the sternal tendon of the sternocleidomastoid muscle. The superiorly based anterior tracheal wall flap is elevated. (G) Excess fat, which may occlude the stoma, must be excised. When indicated, an oval strip of skin is suspended away from the stoma and sutured to the hyoid bone. Two continuous-suction drain tubes are inserted through the lower skin flap. (H) The lower skin flap is extensively undermined and advanced in a cephalad direction to provide tension-free approximation to the planned lower margins of the tracheal fenestra. (I) Side-view of the stage reached in (H).

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have such excessive submental soft tissue that this needs to be taped or otherwise supported to avoid direct obstruction of the tracheotomy tube. Local hygiene requires application of antibiotic ointment and occasional resection of granulation tissue. Sudden relief of chronic upper airway obstruction may lead to postobstructive pulmonary edema and adult respiratory distress syndrome. Chronic subtotal respiratory obstruction is transmitted to the pulmonary alveoli as increased alveolar pressure. When this is relieved by tracheotomy, there may be an outpouring of interstitial fluid into the alveoli (congestive heart failure). Patients with right heart failure and severe cardiopulmonary compromise should be identified prospectively and placed on a respirator in the immediate postoperative period, employing positive end expiratory pressure (PEEP). The patients can be then weaned over the ensuing 18–36 h.

Tracheotomy tube considerations The choice of a tracheotomy tube for longterm use in the patient with OSA must first reflect the patient’s specific needs. The ideal tracheotomy tube can be opened at night to allow breathing during sleep and occluded all day, such that the patient will be able to talk around it and can pursue a nearly normal active life. The ideal tube is comfortable, atraumatic and has a low profile, allowing it to be easily covered with clothing. The tracheotomy plug should be easy to use and securely attachable. A removable intercannula for cleaning is ideal. Patients exhibiting massive obesity create special challenges to

achieve a ‘fit.’ Additionally, local hygiene is a serious challenge in the early convalescent period, until such time as there is complete healing between the skin of the neck and the mucosa of the trachea, thereby forming a mature tract. Until this is achieved, chronic drainage and foreign body granuloma formation is the rule rather than the exception. The circumferential stoma tends to contract and stenose. All of these issues serve to challenge the care-giver to provide a reliable system which can be cared for at home by the average patient. New tubes with inner cannulae are available. Extra-long tracheotomy tubes which are shapeable are currently available, but do not allow routine use of an inner cannula. Many of the standard tracheotomy tubes have excessive anterior projections and some do not allow reliable attachment of a tracheotomy plug. Stoma buttons, while theoretically ideal, are sometimes poorly retained and extruded. The Montgomery cannula works well in many patients. The reader needs to communicate directly with the manufacturers in selecting the best-suited device for each individual patient. Eliachar et al describe a system of biocompatible medical grade silicone stents which are smooth, flexible, and non-irritating to skin and mucosa.7 The stent shaft serves to connect skin to mucosa and obviates the need for an inner cannula. Internal and external flanges resist expulsion during speech and cough. These tubes are adapted with a fitted plug. The stent is unplugged during sleep. These tubes, available through Hood Laboratories (Pembroke, MA, USA) come in a variety of sizes and profiles. Montgomery has introduced a tube system which also works as a grommet with no tube actually in the airway. A series of washers allows custom fitting to a variety of neck sizes.

References

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Conclusion

Tube displacement is a potential complication in the early postoperative period. Inasmuch as these patients do not have total respiratory obstruction while awake, replacement of the tube is not an emergency and should be undertaken by experienced staff with adequate instrumentation and lighting to ensure that the tube is properly replaced. Creation of a false passage and pneumothorax are unnecessary sequelae of hasty maneuvers. Crusts, granulation tissue and other wound care problems respond to local hygiene, frequent tube cleaning and changes, and occasional laser vaporization of granulation. Fletcher describes recurrence of sleep apnea in a patient with OSA treated with tracheotomy.8 This patient experienced initial relief of OSA following tracheotomy. Four years later and after an approximate 50 lb weight gain, the patient developed recurrence of nocturnal apnea. Further evaluation demonstrated that the patient had central apnea which required home nocturnal positive-pressure ventilation via cuff tracheostomy tube. Some investigators have proposed a common factor leading to either obstructive or central nocturnal apnea. Central apneas may result from the interaction between hypercarbia and hypoxemia. If hypoxemia results in hyperpnea causing the arterial CO2 level to go below the apneic CO2 threshold, the result may be central apnea. Fletcher suggested that cases such as this may lend support to a common mechanism for all sleep apnea. The ultimate goal may be to find treatment for both types of apnea which improves the problem at the controller level rather than the site of obstruction. Currently, the site of obstruction is treated by CPAP and surgery.

He et al report that mortality of OSA is reduced following tracheotomy. Tracheotomy is as effective as nasal CPAP in reduction of cardiopulmonary morbidity attributed to OSA.9 Tracheotomy is perceived to be an intrusive, mutilating intervention. Most patients and families are motivated to explore alternative therapies. When symptoms are severe and other treatments have failed or are unacceptable tracheotomy may be a great help in the care of some of the most difficult patients with OSA. The duration of commitment to tracheotomy may reasonably be based upon the response to other therapies such as weight reduction, tongue surgery, or maxillomandibular advancement. Patient acceptance may sometimes be enhanced under these circumstances.

References 1.

2.

3.

4.

5.

Guilleminault C, Simmons B, Motta J et al. Obstructive sleep apnea syndrome and tracheostomy. Long-term follow-up experience. Arch Intern Med 1981;141:985–8. Motta J, Guilleminault C, Schroeder JS, Dement WC. Tracheostomy and hemodynamic changes in sleep-induced apnea. Ann Intern Med 1978;89: 454–8. Simmons FB. Tracheostomy in the sleep apnea syndrome. Ear Nose Throat J 1984;63:222–6. Eliachar I, Zohar S, Golz A, Joachims H, Goldsher M. Permanent tracheostomy. Head Neck Surg 1984;7:99–103. Sahni R, Blakley B, Maisel RH. ‘How I do it’ —head and neck and plastic surgery. A

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6.

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targeted problem and its solution. Flap tracheostomy in sleep apnea patients. Laryngoscope 1985;95:221–3. Mickelson SA. Upper airway bypass surgery for obstructive sleep apnea syndrome. Otolaryngol Clin North Am 1998;31(6):1013–23. Eliachar I. Unaided speech in long-term tubefree tracheostomy. Laryngoscope 2000;110:749–60.

8.

9.

Fletcher EC. Recurrence of sleep apnea syndrome following tracheostomy. A shift from obstructive to central apnea. Chest 1989;96:205–9. He J, Kryger MH, Zorick FJ, Conway W, Roth T. Mortality and apnea index in obstructive sleep apnea. Experience in 385 male patients. Chest 1988;94:9–14.

9

Uvulopalatopharyngoplasty

Aaron E Sher

Uvulopalatopharyngoplasty (UPPP), introduced by Fujita in 1981, was the first surgical procedure specifically developed to treat patients with obstructive sleep apnea syndrome (OSAS).1 Classical otorhinolaryngologic techniques (nasal septal reconstruction, turbinate mucosal cauterization, turbinate outfracture, and tonsillectomy) previously applied to eliminate sleep-related upper airway collapse produced variable and often inadequate results.2 Only tracheotomy was uniformly successful in eliminating OSAS. Fujita, seeking an effective surgical alternative to tracheotomy, expanded on the work of Ikematsu, who previously reported a surgical approach to alleviate snoring.3 As originally described and variously modified by subsequent authors, UPPP includes tonsillectomy in patients who have not previously undergone tonsillectomy. However, prior tonsillectomy does not preclude UPPP, which can then be performed by excision of mucosa which lines the tonsillar fossa after tonsillectomy. The anterior and posterior tonsillar pillars are trimmed, rotated across the tonsillar fossa, and applied to line the denuded fossa. The posterior margin of the soft palate and uvula are ablated. Modifications of the original surgical procedure substitute electrocautery and laser ablation for traditional surgical techniques.4

Technique UPPP is accomplished under general anesthesia. The patient is placed in the supine position with the neck slightly extended and the McIvar mouth gag is introduced to expose the oropharynx. When the patient has residual tonsils, UPPP should be accompanied by bilateral tonsillectomy. In either case, the anterior pillar is resected. I seek to resect approximately 1 cm of anterior pillar superiorly. This is tapered toward the junction of the anterior pillar and the tongue base inferiorly. Subsequent to this, the free edge of the soft palate is transected horizontally. Make an effort to develop a 90º angle between the vertical incision resecting the anterior pillar and the horizontal incision which resects the soft palate. The soft palate resection ordinarily removes approximately 1.2–1.4 cm of tissue measured at the narrowest spot (Figure 9.1). This includes complete amputation of the uvula. Hemostasis is achieved with electrocautery or suture ligature. Significant bleeding is rarely encountered. There does exist a small vessel in the midline of the uvula and another that enters the soft palate at the lateral aspect of soft palate. Both are easily controlled with electrocautery. When hemostasis is satisfactory, the posterior tonsil pillar is advanced and sutured to the

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Figure 9.1 The UPPP is designed to resect approximately 1 cm of the anterior pillar and the free edge of the soft palate. The soft palate resection usually averages 1.2–1.4 cm of tissue.

Figure 9.2 The posterior tonsil pillar is mobilized laterally to close it with a suture to the residual oropharynx. The free edge of the soft palate is closed on itself.

residual oropharyngeal mucosa (Figure 9.2). The most critical and important stitch is the corner suture which serves to re-establish the shape of the oropharyngeal opening. This suture should be passed deeply enough to assure that it does not tear out. An over-andover technique seems to ensure this. A reabsorbable suture which stays in place for a minimum of 10 days prevents early dehiscence. It is essential that the surgeon use enough knots properly squared such that it does not untie in the first few postoperative hours due to swallowing and the moisture present in the oropharynx. Closure of the tonsillar pillars more inferiorly is elective. Lastly, the free edge of the soft palate is closed upon itself. An attempt is made to advance the nasopharyngeal mucosa to meet the oropharyngeal mucosa. This serves to promote healing and to ensure hemostasis. Postoperatively, patients are observed for a minimum of 3–4 h, subsequent to which the overwhelming majority can be discharged to home with instructions regarding diet and limitation of exercise. Most patients can tolerate only a soft, bland diet for the first week to 10 days. Attempts to drink too quickly are almost always associated with nasal emission. The majority of patients quickly accommodate to this, and nasal emission of fluids is rarely a problem beyond the first 10 days. Pain is controlled with an elixir containing acetominophen and a semisynthetic narcotic analgesic. Patients may ambulate, but are encouraged not to use the first few postoperative days as an opportunity to begin an exercise program.

Complications Hemorrhage following a tonsillectomy is a well-reported and understood complication. Its incidence should be no greater following

Results UPPP and tonsillectomy than following tonsillectomy alone. Most of the raw surfaces are closed following surgery for OSAS. The incidence of bleeding seems to be lower. Most patients lose 10–15 lb in the first 10 days following surgery. This is a reflection of the severity of their sore throat, and is welcomed in most instances. Nasal emission of fluid is an annoyance that rarely persists; however, a surgeon should be cautioned to resist excessive removal of soft palate. When the resection exposes the muscles of the soft palate, the risk of nasal emission goes up. The most dreaded complication of UPPP is the development of nasopharyngeal stenosis. This complication is almost always secondary to excessive removal of posterior pharyngeal tissue. The operator should never remove the posterior tonsillar pillars. Similarly, adenoidectomy should not be done with simultaneous UPPP. Under either circumstance, a circumferential wound is established which is the basis for scar contracture and the development of nasopharyngeal stenosis.

Results Mean short-term outcome data for UPPP are derived by meta-analysis of 37 case series, each of which reports on at least nine surgical subjects and assesses surgical outcomes through clear and unambiguous outcome measures, i.e. a pre- and postoperative polysomnogram (PSG).2 The mean decrease in apnea index (AI) in more than 500 patients was 55% from a mean preoperative AI of 45 apneas per hour. The mean decrease in respiratory (or apnea–hypopnea) index (RDI) in approximately 500 patients was 38% from a mean preoperative RDI of 60 apneas and hypopneas per hour. In 14 papers defining

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surgical response as 50% decrease in AI, the reponse rate for 352 patients was 65%. In 16 papers defining surgical response by 50% decrease in RDI, the response rate for 375 patients was 53%. For 168 patients in nine reports, success was defined by the more restrictive and more recently applied criteria of: 50% decrease in AI to postoperative AI less than 10 apneas per hour, or 50% decrease in RDI to postoperative RDI less than 20 apneas and hypopneas per hour. Forty-three per cent of patients achieved success by the former definition, and 39% achieved success by the latter definition. If achievement of either of these criteria defines surgical success, 41% of patients respond to UPPP.2 There was no significant preoperative difference between responders and non-responders in terms of age, AI, RDI, minimum oxygen saturation, or body weight. Long-term follow-up is provided in a small number of studies. Fifty patients were followed for a mean of 46 months after UPPP. Six months postoperatively, 60% were responders (response defined by *50% reduction of preoperative RDI to less than 20 apneas and hypopneas per hour). Twenty-one months postoperatively, 39% of patients remained responders, relapse resulting from weight gain. Forty-six months postoperatively, 50% were classified responders. Weight loss, abstinence from alcohol and positional conditioning were cited in those who sustained late improvement.5 Twenty-five patients subjected to UPPP had a 6-month postoperative response rate of 64% (response defined by 50% decrease to postoperative RDI of less than 10) and a longterm (4–8 years postoperatively) response rate of 48%. No difference in preoperative RDI, body mass index (BMI), or change in BMI was found between long-term responders and nonresponders.6 Fifteen patients with response rate (response defined by greater than 50%

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reduction in RDI) of 67% at 3–6 months postoperatively demonstrated a response rate of only 33% at greater than 5 years postoperatively (mean 88 months).7

Complications Early surgical complications compiled in a meta-analysis of 640 patients for whom complications were delineated included postoperative bleeding (1%), successfully managed perioperative upper airway obstruction (0.3%), and death secondary to upper airway obstruction (0.2%). Late complications are velopharyngeal insufficiency (VPI) of greater than 1 month in duration (2%), nasopharyngeal stenosis (1%), and voice change (1%). However, since more than half of the papers in the meta-analysis do not comment on complications, it is not possible to determine the true incidence of complications in the population.2 In two series which focused on complications of UPPP, the death rate for unsuccessfully managed upper airway obstruction was 1%.8,9 The incidence of postoperative VPI was dependent on the definition of VPI applied. The incidence of VPI 2 years after UPPP in 71 patients was: 39% with subclinical reflux of liquids apparent only on nasal endoscopy; 16% with nasal reflux when the patient bends over a water fountain to drink; 7% with subclinical nasal reflux, i.e. patient feels bubbles in the nose after drinking gaseous beverages; and 3% with ‘mild’ nasal reflux for liquids.10 Of 91 patients 1 year after UPPP, 31% reported persistent ‘dry throat’, while 10% reported ‘swallowing abnormalities’.9 A model of the upper airway in OSAS likens it to a simple collapsible tube. The tendency to collapse can be expressed quantitatively in terms of a critical pressure (Pcrit), the pressure surrounding the area of collapse. If atmospheric

pressure is designated zero, then airway collapse will occur whenever Pcrit is a positive number (indicating that it is higher than atmospheric pressure). Pcrit levels are higher during sleep than during wakefulness in both normal individuals and OSAS patients. This is the result of diminished tone in airway-supporting musculature. In normals, Pcrit rises from awake values that are more negative than –41 cmH2O to sleep values of –13 cmH2O.11–13 This means that, in normal individuals, atmospheric pressure is greater than Pcrit even during sleep, and the pharynx does not collapse. In OSAS patients, the spectrum of awake values of Pcrit is –40 to –17 cmH2O, and Pcrit during sleep is +2.5 cmH2O.11,12,14,15 Although the pharyngeal airway of awake OSAS patients tends to be more collapsible than that of awake normals, Pcrit does not cross the critical line of zero (i.e. atmospheric pressure) except when the individual with OSAS has sleep onset and OSAS results.11 Patients who have varying degrees of partial pharyngeal collapse have intermediate, but negative levels of Pcrit during sleep: –6.5 cmH2O for asymptomatic snorers, and –1.6 cmH2O for patients with hypopneas but no apneas.11,15 In general, Pcrit at values more negative than –5 cmH2O is associated with relief of sleepdisordered breathing.11 Examples of the decrement in Pcrit that are achieved by non-surgical interventions are –6 cmH2O through the loss of 15% of body weight, –3 to –4 cmH2O through protriptyline treatment, and –4 to –5 cmH2O through sleeping in a position other than supine.11 When 13 patients underwent UPPP, Pcrit decreased from a level of 0 to a level of –3 cmH2O. In those patients who had greater than 50% decrease in RDI in nonREM sleep, Pcrit decreased from –1 cmH2O to –7 cmH2O. The degree of improvement in sleep-disordered breathing was correlated

Results significantly with the change of Pcrit (p = 0.001), and the decrease in RDI was determined by the magnitude of the fall in Pcrit rather than by the initial level of Pcrit. No significant change in Pcrit was detected in nonresponders.16 Collapse of the pharynx during sleep occurs at a discrete (less than 1 cm) locus. Data derived from studies of the pharynx with awake endoscopy, awake endoscopy with Müller maneuver, asleep (drug-induced) endoscopy, asleep (natural and drug-induced) endoscopy with nasal continuous positive airway pressure (CPAP), asleep fluoroscopy, computed tomographic (CT) scan and manometry suggest that the pattern of static pharyngeal narrowing and/or dynamic pharyngeal collapse is localized and patient specific.16–18 Failure of UPPP may result from residual or secondary airway compromise at remote loci not surgically addressed. A model considers the pharynx as consisting of two loci: (1) retropalatal—located posterior to the soft palate; and (2) retrolingual—located posterior to the vertical portion of the tongue. The pharynx is preoperatively classified as follows: (1) type I—only the retropalatal region is compromised; (2) type II—both retropalatal and retrolingual regions are compromised; and (3) type III—only the retrolingual region is compromised.19 Association of pharyngeal type with UPPP outcome was accomplished by meta-analysis of UPPP outcomes in 168 patients in nine reports in which the preoperative pattern of pharyngeal narrowing or collapse was specified to be type I, II or III.2 Pharyngeal classification is achieved by application of one of the following techniques: awake fiberoptic endoscopy with or without Müller maneuver, asleep endoscopy with nasal CPAP, lateral cephalometry, airway manometry, or pharyngeal CT. For all patients (types I, II and III

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combined), 43% achieved at least a 50% decrease in AI and postoperative AI less than 10 apneas and hypopneas per hour, and 39% achieved at least a 50% decrease in RDI and postoperative RDI of less than 20 apneas and hypopneas per hour. If achievement of either of these criteria defines surgical success, 41% of patients responded to UPPP.2 However, the mean percentage decrease in AI for type I was 75% (from a mean preoperative AI of 39 apneas per hour), while for types II and III, the mean percentage decrease in RDI was 23% (from a mean preoperative AI of 60 apneas and hypopneas per hour). The mean decrease in RDI for type I was 33% (from a mean preoperative RDI of 57 apneas and hypopneas per hour), while for types II and III the mean percentage decrease in RDI was 7% (from a mean preoperative RDI of 65 apneas and hypopneas per hour). The percentage of patients attaining at least 50% decrease in RDI to a postoperative RDI of less than 20 apneas and hypopneas per hour (or, alternatively, 50% decrease in AI to a postoperative AI of less than 10 apneas per hour, as reported in some papers), was 52% for type I patients and 5% for type II and type III patients.2 The variable degree of success of UPPP, which can be described in terms of change in AI, RDI or Pcrit, may reflect, at least in part, patient variability in upper airway anatomy and physiology. Patients classified as type I are more likely to have adequate change in parameters of success than those classified as type II or III. While UPPP diminishes the tendency for upper airway collapse in the retropalatal region, type II and III patients may continue to suffer collapse in the lower, or retrolingual, portion of the pharynx. This hypothesis is supported by data indicating salvage of patients who fail UPPP and subsequently undergo successful surgical

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modification which alters the retrolingual region of the pharynx (lingual ablation, genioglossal advancement, hyoid myotomy and suspension, mandibular advancement, maxillo-mandibular advancement).2 However, even patients classified as type I have successful UPPP only 52% of the time. There are at least three alternative, though not mutually exclusive, explanations for this observation: (1) the techniques utilized to classify patients into types I, II and III are not sufficiently robust and periodically result in incorrect classification; (2) there are nuances of pharyngeal structure and function in patients correctly classified as type I which may mandate variable degrees of surgical modification at the palatal level (i.e. UPPP may not be an adequately robust surgical procedure to effectively treat all type I patients); and/or (3) there are nuances of pharyngeal structure and function in patients classified as type I which may mandate surgical modification at both the palatal and retrolingual levels (perhaps reflecting shift of the focus of pharyngeal collapse from retropalatal pre-UPPP to retrolingual post-UPPP). Support for all three explanations follows. Techniques utilized by clinicians to classify patients into types I, II and III have recognized limitations. Lateral cephalometry and fiberoptic endoscopy of the upper airway (with or without Müller maneuver) are the most widely applied techniques. Both are applied in the awake patient, while OSAS occurs in the sleeping patient under significantly different neurophysiologic conditions. Both are commonly applied in the seated patient, whereas the sleeping patient rarely assumes this position. Lateral cephalometry is adynamic and views the airway in only two dimensions, whereas airway collapse in OSAS is dynamic and occurs in three dimensions. While fiberoptic endoscopy offers the advantage of providing a

three-dimensional perspective, its intepretation is highly subjective. If the Müller maneuver is applied, the response may be confounded by the fact that the degree of negative pressure applied by the patient is not measured. Furthermore, the relationship between collapse of the awake pharynx challenged by the Müller maneuver and that of the passive pharynx in sleep remains in question. Indeed, different investigators describe varying degrees of success and failure in prognosticating UPPP outcome when fiberoptic endoscopy is used to preoperatively characterize the pharyngeal airway.2,20–22 Furthermore, studies comparing fiberoptic endoscopy with pharyngeal manometry, and other studies comparing either technique in wakefulness with the same technique applied in sleep, demonstrate disagreement in identifying pharyngeal dynamics.23–25 It has been demonstrated that nuances of pharyngeal structure and function in patients correctly classified as type I may mandate a degree of surgical modification at the palatal level beyond UPPP (i.e. UPPP may not be adequately robust for all type I patients). Transpalatal advancement pharyngoplasty (TPAP) is a procedure which enlarges the retropalatal airway by resection of the posterior hard palate and advancement of the soft palate, in an anterior direction, into the defect.26 It differs from UPPP, in which the hard palate is not altered. Sequential performance of UPPP and TPAP results in incremental decrease in Pcrit to a level below that resulting from UPPP alone. Four patients who underwent UPPP had a mean postoperative Pcrit of 5 cmH2O, a level at which OSAS would be expected to persist. TPAP increased the postUPPP retropalatal airway cross-sectional area by 321% (29 to 95 cm2, p < 0.01), and Pcrit was incrementally diminished to –4 cmH2O (p < 0.01).27

References It has been demonstrated that there are nuances of pharyngeal structure and function in patients classified as type I which may mandate surgical modification at both the retropalatal and retrolingual levels (possibly reflecting shift of the locus of pharyngeal collapse from retropalatal pre-UPPP to retrolingual post-UPPP). The shift of locus has been suggested by endoscopic and manometric analysis of the upper airway in wakefulness and sleep.23–25 The salvage of UPPP failures by surgical procedures which alter the retrolingual airway has previously been cited.2 The current perspective on surgery for OSAS regards UPPP as one component of the surgical armamentarium for OSAS. Airway vulnerability to collapse in OSAS is believed to involve different regions of the airway, and UPPP addresses primarily the retropalatal region. It is expected that UPPP will prove adequate for cure in only a fraction of patients. In the remainder, UPPP is applied in conjunction with other surgical modifications, either concomitantly or in stages. UPPP is applied when retropalatal narrowing is perceived to be a component of airway compromise. Other anatomic modifications are dictated when appraisal of the upper airway suggests retrolingual compromise. Review of the literature on UPPP reveals several deficiencies. Criteria for surgical success and failure have evolved over the two decades since Fujita’s introduction of UPPP. This evolution is reflected in the criteria for success applied in the succession of papers reviewed. Fujita established as the criterion for success a decrease in AI of at least 50% from its preoperative value. Current perceptions of the pathophysiology of OSAS mandate a more restrictive criterion for success, one that takes into account not only apneas but also hypopneas and subobstructive events that result in arousal. The ideal definition of response may require

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development of a paradigm (applied preoperatively and postoperatively) which integrates parameters of sleep architecture, arousal and excessive daytime sleepiness with measures of respiratory disturbance and oxygenation. Such a complex descriptor of disease severity might be designed in a manner akin to the TNM tumor classification of the head and neck. Identification of which metrics and levels of severity best reflect thresholds of morbidity and mortality will be clarified by such investigations as the ongoing NIH Sleep Heart Health Study. However, the current lack of universal criteria for reporting results poses difficulty in interpretation and comparison of surgical as well as non-surgical outcomes. There are steps underway to standardize outcome reporting.28 Bias is frequently introduced into the surgical literature by retrospective study design and non-random loss to follow-up. The number of patients exposed to the surgical procedure often far exceeds the number having both preoperative and postoperative PSG. Studies are not randomized and generally do not have control groups. Sample size tends to be low, and statistical power is low. Missing data and missing and inconsistent definitions are common. Most papers report only short-term follow-up and infrequently report long-term follow-up. Few papers associate PSG data with patient-based assessment of quality of life.29

References 1. Fujita S, Conway W, Zorick F et al. Surgical correction of anatomical abnormalities in obstructive sleep apnea syndrome: uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg 1981;89:923–34. 2. Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper

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airway in adults with obstructive sleep apnea syndrome. Sleep 1996;19(2):156–77. Ikematsu T. Clinical study of snoring. 4th Report. Therapy [in Japanese]. J Jpn Otol Rhinol Laryngol Soc 1964;64:434–5. Ikematsu T, Simmons FB, Fairbanks DNF et al. Uvulopalato-pharyngoplasty: variations. In: Fairbanks DNF, Fujita S, eds. Snoring and Obstructive Sleep Apnea, 2nd edn. New York: Raven Press, 1994: 97–145. Larsson LH, Carlsson-Nordlander B, Ssvanborg E. Four-year follow-up after uvulopalatopharyngoplasty in 50 unselected patients with obstructive sleep apnea syndrome. Laryngoscope 1994;104:1362–8. Janson C, Gislason T, Bengtsson H et al. Long-term follow-up of patients with obstructive sleep apnea treated with uvulopalatopharyngoplasty. Arch Otolaryngol Head Neck Surg 1997;123: 257–62. Lu S-J, Chang S-Y, Shiao G-M. Comparison between short-term and long-term postoperative evaluation of sleep apnoea after uvulopalatopharyngoplasty. J Laryngol Otol 1995;109:308–12. Esclamado RM, Glenn MG, McCulloch TM et al. Perioperative complications and risk factors in the surgical treatment of obstructive sleep apnea syndrome. Laryngoscope 1989;99:1125–9. Haavisto L, Suonpaa J. Complications of uvulopalatopharyngoplasty. Clin Otolaryngol 1994;19:243–7. Zohar Y, Finkelstein Y, Talmi YP et al. Uvulopalatopharyngoplasty: evaluation of postoperative complications, sequelae, and results. Laryngoscope 1991;101:775–9. Winakur SJ, Smith PL, Schwartz AR. Pathophysiology and risk factors for obstructive sleep apnea. Semin Respir Crit Care Med 1998;19:999–1112. Suratt PM, Wilhoit SC, Cooper K. Induction of airway collapse with subatmospheric pressure in awake patients with sleep apnea. J Appl Physiol 1984;57:140–6.

13. Schwartz AR, Smith PL, Wise RA et al. Induction of upper airway occlusion in sleeping individuals with subatmospheric nasal pressure. J Appl Physiol 1988;64:535–42. 14. Horner RL, Mohiaddin RH, Lowell DG et al. Sites and sizes of fat deposits around the pharynx in obese patients with obstructive sleep apnoea and weight matched controls. Eur Respir J 1989;2:613–22. 15. Gleadhill IC, Schwartz AR, Schubert N et al. Upper airway collapsibility in snorers and in patients with obstructive hypopnea and apnea. Am Rev Respir Dis 1991;143: 1300–3. 16. Schwartz AR, Schiebert N, Rothman W et al. Effect of uvulopalatopharyngoplasty on upper airway collapsibility in obstructive sleep apnea. Am Rev Respir Dis 1992;145: 527–32. 17. Shepard JW Jr, Gefter WB, Guilleminault C et al. Evaluation of the upper airway in patients with obstructive sleep apnea. Sleep 1991;14(4): 361–71. 18. Launois SH, Feroah TR, Campbell WN et al. Site of pharyngeal narrowing predicts outcome of surgery for obstructive sleep apnea. Am Rev Respir Dis 1993;147:182–9. 19. Fujita S. Midline laser glossectomy with lingualplasty: a treatment of sleep apnea syndrome. Op Tech Otolaryngol Head Neck Surg 1991;2:127–31. 20. Aboussouan LS, Golish JA, Wood BG et al. Dynamic pharyngoscopy in predicting outcome of uvulopalatopharyngoplasty for moderate and severe obstructive sleep apnea. Chest 1995;107:946–51. 21. Doghramji K, Jabourian ZH, Pilla M et al. Predictors of outcome for uvulopalatopharyngoplasty. Laryngoscope 1995;105:311–14. 22. Petri N, Suadicani P, Wildschiodtz G et al. Predictive value of Muller maneuver, cephalometry and clinical features for the outcome of uvulopalatopharyngoplasty. Acta Otolaryngol (Stockh) 1994;114:565–75.

References 23. Woodson BT, Wooten MR. Comparison of upper airway evaluation during wakefulness and sleep. Laryngoscope 1994;104:821–8. 24. Woodson BT, Wooten MR. Manometric and endoscopic localization of airway obstruction after uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg 1994;111:38–43. 25. Skatvedt O. Localization of site of obstruction in snorers and patients with obstructive sleep apnea syndrome: a comparison of fiberoptic nasopharyngoscopy and pressure measurements. Acta Otolaryngol (Stockh) 1993;113:206–9. 26. Woodson BT, Toohill RJ. Transpalatal advancement pharyngoplasty for obstructive sleep apnea. Laryngoscope 1993;103: 269–76.

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27. Woodson BT. Retropalatal airway characteristics in uvulopalatopharyngoplasty compared with transpalatal advancement pharyngoplasty. Laryngoscope 1997;107:735–40. 28. American Academy of Sleep Medicine Task Force on Sleep Related Breathing Disorders in Adults. Recommendations for syndrome definition and measurement techniques in clinical research. Sleep 1999;5:667–89. 29. Schechtman KB, Sher AE, Piccirillo JF. Methodological and statistical problems in sleep apnea research: the literature on uvulopalatopharyngoplasty. Sleep 1995;18(8):659–66.

10 Laser uvulopalatoplasty B Tucker Woodson

There are many treatment options available for sleep-disordered breathing (SDB) and obstructive sleep apnea (OSA). These include positional therapy, weight loss, medical treatment of underlying or predisposing conditions, devices, and surgery. The primary treatment of OSA is nasal continuous positive airway pressure (CPAP). Oral appliances and surgery are alternatives for the treatment of OSA and are also primary treatments for snoring. Surgical treatment, when successful, may correct some of the structural etiologies of the disorders. This chapter describes laserassisted uvulopalatoplasty (LAUP) as a surgical treatment option. There are three features of a ‘ideal’ surgery for OSA syndrome. These include: (1) low morbidity; (2) minimal cost; and (3) demonstrated clinical effectiveness.1 LAUP achieves the first two of these three criteria. The third and most important (i.e. effectiveness) remains uncertain. Most individuals agree that acute perioperative morbidity and the serious complication rate of LAUP are low. LAUP’s direct costs are relatively low compared to other surgical procedures. The controversy over effectiveness will be answered only from critically reviewed outcome studies. This chapter will attempt to address important concepts and to describe the current status of the medical literature relating to LAUP.

Therapeutic goals for OSA are to ‘cure’ the disorder, eliminate symptoms, and reduce the risk of sequelae from the disease. Currently, there are no true ‘cures’ of the disorder. Successful treatments reduce obstructive events and symptoms to a subclinical level. Following successful surgery, patients do not require the daily compliance that other modalities require. However, on which outcomes do we assess successful treatment? The symptoms which form the primary focus of surgery are snoring and excessive daytime sleepiness. Hypertension, increased risks of stroke and cardiovascular disease and increased risk of mortality are the medical sequelae associated with OSA.2–4 Successful treatment should reduce these risks. No LAUP studies have addressed these outcomes. Most data on LAUP address only symptomatic outcomes, with snoring as the most common symptom reported. Effectiveness on sleepiness is infrequently noted. Only a few studies report objective respiratory data, which are crucial to assess effectiveness for LAUP. Better outcome data on LAUP are needed. The needed prospective randomized studies are difficult to perform. The current understanding of LAUP’s effectiveness often comes from uncontrolled retrospective case series. Conclusions from these studies must be guarded.

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An additional goal of surgery is to reconstruct the airway. Successful snoring surgery reduces vibration and flutter. Successful apnea surgery reduces upper airway obstruction and airflow limitation during sleep. LAUP’s effect on airflow limitation and airway obstruction are yet to be determined. Since it is not possible to completely re-evaluate every new and minor modification of a surgical procedure, assessment of LAUP effectiveness at this time must be based on available clinical studies, extrapolated data from similar procedures, and our understanding of the pathophysiology of SDB and the upper airway. Kamami proposed LAUP in 1991 as a treatment for snoring.5 Subsequently, the procedure has been advocated and applied to treat OSA.6,7 The clinical application of LAUP was rapid following use for snoring, was done prior to any systematic study, and resulted in controversy. The American Sleep Disorders Association (ASDA) published an initial position paper with reservations on the procedure until adequate published data established its safety and efficacy.8 This position has not been significantly altered, although LAUP has been demonstrated as a safe outpatient, ambulatory procedure.9 Nonetheless, LAUP remains controversial, because data on efficacy are still sparse. Few procedures in otolaryngology and sleep medicine have created such polarity, with such distinct advocates and critics.

Background It is generally accepted that palatal operations are the most common procedures used to treat SDB and OSA. The two most common palatal operations performed have been uvulopalatopharyngoplasty (UPPP) and LAUP. Historically, both were developed to treat snoring.

The success rate in treating snoring is high. Each reports an 80% success rate.5,10 Both procedures have been empirically applied to treat OSA. Successful outcomes for OSA have been much lower than outcomes for snoring. Prior to LAUP and even before the description of OSA, Ikamatsu described palatopharyngoplasty to reduce snoring.11 Ikamatsu’s development was spurred by the clinical observation of redundant pharyngeal tissues in snorers. By modification and removal of tissues of the uvula, palate, and pharynx, snoring was reduced in many individuals without impairing swallowing or speech. Similar observations of redundant tissues in apneic patients by Fujita led him to modify UPPP to treat OSA.12 Although success was only partial, UPPP provided an alternative to tracheotomy.13 LAUP was first described by Kamami in 1991 as a treatment for snoring. The development of LAUP was, in part, spurred by the advent of surgical technologies, which created widely available office-based carbon dioxide lasers. The carbon dioxide laser enabled hemostatic removal and ablation of mucosa and soft tissue. This could be performed with only local anesthesia in an outpatient or office-based setting without the need for inpatient hospitalization. LAUP has several characteristics that differentiate it from traditional UPPP. Initial descriptions of LAUP were as a staged serial procedure. This was in contrast to UPPP, which was done in a single operative setting. LAUP’s tissue ablation centered chiefly on the palate, velum, and uvula. As first described, LAUP was a palatoplasty and not a pharyngoplasty. Finally, the intention of LAUP is to heal by secondary intent. This contrasted to UPPP, which created palatal flaps that were advanced and closed primarily using sutures. Kamami’s first LAUP technique involved using a CO2 laser to create two vertical trenches in the soft palate. These were lateral

Background to the uvula and extended approximately 1 cm from the free margin of the distal soft palate. The trenches were then widened and the uvula narrowed and shortened (but not removed). The wound then healed secondarily. Clinically,

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shortening of the palate and uvula was observed. Procedures were then repeated as needed. Although each procedure removed only a small amount of tissue, repeated sessions created additive effects.

A

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Figure 10.1 Techniques of laser-assisted uvulopalatoplasty (LAUP) are depicted. All may be performed under local anesthesia. The technique of Kamami is depicted in the upper level (A). Parallel trenches lateral to the uvular muscle are created and the uvula shortened by approximately 50%. A modified ‘UPPP technique’ is shown in the middle level (B). Lateral trenches are widened, and more aggressive removal of the uvula is performed. In the lower level (C), the mucosal stripping technique is depicted. The uvula is excised (cross-hatch) and midline palatal mucosa is removed down to muscle (stripes).

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Multiple modifications have been proposed for LAUP since its inception. Tissue ablation with LAUP is not limited to the palate but may involve the tonsillar pillars and pharynx.14 Variations include but are not limited to complete or partial removal of the uvula, aggressive widening of lateral trenches in the palate, or even distal excision of the palate similar to UPPP (Figure 10.1). The procedure is not limited to the CO2 laser but may be performed using other types of lasers or any tool that will remove or ablate tissue while also providing adequate hemostasis.15 Considering this wide array of techniques, the term ‘LAUP’ is applied to a series of procedures all of which trace their development to the initial descriptions by Kamami. The procedures must have the following characteristics: (1) the capability of being repeatedly performed; (2) it must surgically modify the uvula and soft palate; and (3) healing must be by secondary intention. Alternatively, single-stage pharyngoplasties that are sutured primarily are considered to be modifications of techniques initially described by Fujita (i.e. UPPP). It is speculated but unproven that multiple LAUP procedures may modify the upper airway commensurately with other palatopharyngoplasty techniques. An additive effect is suggested by a progressive snoring reduction demonstrated with successive procedures.16 However, additive effectiveness in reducing OSA has not been demonstrated. A major dilemma in performing LAUP is the criterion used to identify a treatment endpoint. As a snoring procedure, the endpoint of treatment was determined with resolution of patient’s self-reports of snoring, the loss of the ability of the patient to ‘snort’, or the development of side-effects such as temporary velopharyngeal incompetence.17 For snoring, these criteria are adequate; however, for OSA, the presence or absence of snoring is a

questionable endpoint. It is well established that snoring may be eliminated in patients following LAUP and UPPP with persistent obstructive apnea.7,13 The current standard method of determining surgical endpoint uses snoring reduction, elimination of voluntary snorting or new onset of velopharyngeal dysfunction as the outcomes to stop treatment. None of these is demonstrated as related to objective OSA outcomes, yet their use continues.

Advantages and disadvantages of LAUP LAUP has several real and potential advantages over more conventional techniques. Because the CO2 laser may cut, ablate and coagulate the tissues, the procedure is readily adaptable to an ambulatory office-based setting. LAUP may be performed under local anesthesia without the need for sedation, general anesthesia, or an operating room environment. There is no hospitalization required. This is significantly different from UPPP, where few if any patients are treated in the office. This lowers the risk to the patient and the potential cost of the procedure. In addition, the incidence of velopharyngeal dysfunction is low. Presumably this is because, as LAUP is a serial procedure, tissue removal is less. The procedure is terminated with appearance of velopharyngeal dysfunction. Surgery can be slowly ‘titrated’ to the needs of the patient as an alternative to a ‘one-step’ UPPP. LAUP was marketed as a procedure causing little pain compared to traditional surgeries. However, when objectively compared, LAUP and UPPP pain are similar.18 Both are associ-

Advantages and disadvantages of LAUP ated with severe pain. Based on a 10-point visual analog scale, peak pain rated near 10 in studies reporting pain (7.7 and 10). Peak pain occurred from day 2 to day 7, and varied by surgeon and likely patient. No method of pain control has been demonstrated to be superior. A claim of less pain appears not to have been substantiated. However, LAUP pain may be variable. Successive procedures cause less pain than the first. Even if pain is severe, most patients are treated ambulantly with little or no time off work. Side-effects and complications of LAUP are usually minor or infrequent. Dysphagia, velopharyngeal insufficiency and minor bleed-

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ing are uncommon following LAUP.9,19,20 Severe bleeding requiring hospitalization or transfusion is rare. General anesthesia is rarely required for LAUP. Time off work is minimal. Disadvantages of LAUP include concerns about effectiveness for OSA, severe pain associated with the procedure, and worries about treating patients in a non-observed postoperative environment. Is OSA worsened? Acutely, it is. Terris et al demonstrated that LAUP worsened respiratory disturbance index (RDI), but did not significantly narrow the retropalatal airway as measured postoperatively with MRI.21 Postoperative RDI doubled and lowest oxygen saturation decreased.

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Figure 10.2 The pattern of healing following traditional LAUP. Following LAUP, palatal trenches are created and the uvula shortened (A). With healing, the trenches close. This shortens the distance between points A and B, and creates lateral tension in the palate. The uvula is observed to retract (B). The effects on the nasopharynx are variable, but trenches in the palate (red) reduce the circumference of the pharyngeal isthmus. This may narrow the velopharyngeal area (C).

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Because of these concerns, most authors who use LAUP to treat OSA recommend the perioperative use of nasal CPAP following LAUP procedures. With this recommendation, perioperative respiratory complications appear to be rare following LAUP.22 The long-term effects of LAUP are unknown. Palatal scarring occurs after the procedure.23,24 This initially increases tension and reduces snoring (Figure 10.2). Airway narrowing may or may not occur. If airway narrowing does occur, the potential decrease in collapsibility due to decreased compliance may be lost, with softening of scar tissue that occurs over 12–24 months.24 This would worsen apnea (Figure 10.3). Extensive thermal damage created by the laser also damages all three layers of the soft palate and may result in chronic inflammation, ulceration, and loss of seromucinous glands. The latter may

Figure 10.3 A nasopharyngeal view of the velopharyngeal inlet open (A) and narrowed (C) as occurs during partial airway collapse. Note that the narrowest portion of the pharyngeal isthmus is at the velopharyngeal inlet. With palatal resection, the velopharyngeal inlet is moved rostrally. In the vertically oriented velum (D), a shorter palate will have little effect on upper airway size. In the more horizontally oriented velum (B), palate shortening may increase area size.

explain common complaints of pharyngeal dryness after LAUP.23

Complications The complication rate of LAUP is low. Complications may be grouped as acute surgical, perioperative, or late. Acute complications may include hemorrhage, anesthetic reaction, vasovagal reactions, aspiration, laser burn, or damage to teeth.5,6,9,25–28 Unpublished reports indicate that these may occur in less than 1% of patients. Bleeding requiring local cautery is not common, with reports of 1–1.2% incidence. Perioperative reports indicate that bleeding acutely or in the first 7–10 days is uncommon. Minor bleeding not requiring treatment may occur in 2–3% of patients.

Pharyngeal anatomy Severe bleeding is rare, with many large series not reporting this complication and smaller series reporting a 1% bleeding rate requiring treatment. Infection may be underreported (0.5–3% infection rate), since criteria may vary among surgeons. Acute velopharyngeal symptoms (either nasal reflux or speech-related velopharyngeal insufficiency (VPI)) are variable. Symptoms were reported in 10–14% in one series (29 patients); however, larger series have reported only 0–0.5% temporary VPI or nasal reflux.28,29 Long-term VPI that requires further treatment is rare and virtually unreported. Lesser degrees of dysfunction have not been systemically evaluated. The most common complication and complaint following LAUP is the sensation of a dry throat or thickened mucus. The prevalence of this ranges from 12% to 21%.28,29 The etiology of this is unclear. It may result from impaired mucociliary clearance, scarring, pharyngeal paresthesia, pharyngeal phantom sensation, loss of the uvula, actual changes in mucus production, or other unknown causes. Treatment is often difficult. In summary, LAUP’s advocates cite the advantages of local anesthesia, low complication rates and lower costs in an ambulant setting. Critics cite the lack of objective data supporting the effectiveness of the procedure for OSA, the cost of the laser, and the significant perioperative pain.

Pharyngeal anatomy LAUP’s goal is to modify the pharyngeal valve for OSA in order to augment patency while not impairing speech and swallowing. Critical sites of airway obstruction and the effects of LAUP are unknown. Increasing pharyngeal airway stability may be achieved by increasing airway size, decreasing airway compliance, or altering

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Nose Flow Hard palate Soft palate

Mouth

Figure 10.4 Airflow and pressure drops across a flowlimiting collapsible airway segment release kinetic energy, which results in vibration and flutter of soft tissues. The primary source of vibratory snoring is the soft palate. The severity of flutter and vibration is a function of the length of the soft palate, the compliance of the soft tissues, and the pressure drop across the flow-limiting segment.

upper airway shape. The defining feature of obstruction is airflow limitation. Airflow limitation is dependent not only on the size of the airway but also on the airway’s compliance and shape, the pressure drop across the segment, surface tension forces, inspiratory effort, Bernoulli forces, and airway length.30 Increasing airway size and decreasing airway collapsibility are important. Modifying collapsing or critical closing pressures are associated with and may even predict UPPP success or failure.30,31 Which aspects of LAUP technique best modify the upper airway are unknown. The actual mechanisms of snoring are complex and are only partially understood (Figure 10.4) Snoring is reduced or altered by several potential mechanisms. The noise of snoring results from flutter and vibration of

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the uvula, soft palate and tissues of the pharyngeal lateral wall bands.32 The flutter and noise frequency is determined by tissue elasticity and palatal length.33 The pressure drops across the flow-limiting segments drives snoring by releasing kinetic energy. The combination of increased airway resistance and compliance, and increased negative inspiratory pressure, determine the pressure drop across the flow-limiting segment. Surgery affects snoring by stiffening or shortening tissues of the palate or pharynx or alternatively by reducing airflow limitation or ventilatory effort. Precisely which mechanism is effective in LAUP patients is unknown. Several different pharyngeal shapes have been described. Finkelstein et al classified the upper pharynx into flat or circular types (Figure 10.5). Studies of airway shape in OSA also describe a third type with a narrow

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Figure 10.5 Patterns of pharyngeal collapse. The coronal type (A) is closed in an anterior–posterior direction. Circular airways (B) are physiologically most stable. Theoretically, circular airways offer the least resistance to airflow for any given cross-sectional area. (C) A sagittal pattern of collapse may occur from contributions of the lateral pharyngeal wall.

oropharynx.34,35 Therefore, the three general shapes of the pharyngeal segment include: (1) a coronally shaped velopharynx which is flat in an anterior–posterior dimension, with its long axis lying in the coronal plane; (2) a circular pharynx; and (3) a sagittal oropharynx with its long axis oriented in the sagittal plane. Closure in the coronal pharynx is often in the anterior–posterior dimension. Closure in the sagittal pharynx may be circular or result predominantly from movement of the lateral pharyngeal walls to the midline. Collapse of the lateral pharyngeal walls may result from hypertrophy of the lateral walls or from tonsillar hypertrophy. The adult pharyngeal airway is phylogenetically unique among mammals. Instead of being tightly interdigitated to the skull base, the larynx in humans descends into the neck.36 In contrast to other mammals and infants, the adult human upper airway is composed of a significant supralaryngeal soft tissue pharynx. The patency of this pharynx is maintained by the activity of pharyngeal dilator muscles.37 A loss of muscle tone during sleep places the pharynx at risk of partial or complete obstruction. Since patients with OSA syndrome have smaller and more compliant upper airways, they are predisposed to airway collapse.38,39 No single abnormality defines OSA or SDB. The common denominator is a small airway size (Figure 10.6). Many variables contribute to an abnormal upper airway involving both the facial skeleton and soft tissues.40,41 Findings associated with this segment in OSA syndrome include a long and wide soft palate. Often, there is enlargement of the uvula, and there may be webbing of palatal mucosa. Collapse of the lateral pharyngeal walls contributes to both OSA and snoring. The size and thickness of the lateral walls are increased in OSA compared to normals.42 In addition, the pharyngeal airway may be encroached

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Airway length from hard palate (mm)

Figure 10.6 The cross-sectional airway size measured from the hard palate inferiorly is shown in normals and in patients with OSA. For both groups, the smallest pharyngeal segment is 10 mm below the hard palate, in the area of the pharyngeal isthmus. With loss of muscle tone or with increased negative inspiratory pressures, this segment is most vulnerable to collapse.

upon by enlargement of surrounding pharyngeal musculature. This includes the palatopharyngeus, stylopharyngeus, and prevertebral muscles. Maxillary retrusion compromises the pharyngeal isthmus anteriorly. Abnormalities of the upper cervical vertebrae may compromise the segment posteriorly. The segment most vulnerable to collapse is the pharyngeal isthmus bordered by the soft palate and uvula anteriorly, lateral pharyngeal walls laterally,

4

Figure 10.7 The actions of the tensor palatini (1), levator palatini (2), palatoglossus (3) and palatopharyngeus (4). Muscular shortening or anatomic shortening of the levator palatini muscle may result in posterior and superior movement of the velum, closing the airway.

and nasopharyngeal wall posteriorly.43 This is the area altered by LAUP. Muscles comprising the velum include the tensor and levator veli palatini, musculus uvulae, palatopharyngeus, palatoglossus, superior, middle and inferior constrictors, stylopharyngeus, and salpingopharyngeus.44 Most of the physiologic actions of the pharyngeal muscles narrow the pharynx. The variable effects of LAUP may result from differing anatomy. Muscles ablated during LAUP may include the musculus uvulae, palatopharyngeus, palatoglossus, and levator veli palatini. The musculus uvulae’s physiologic functions are to add bulk to the palate, increasing its thickness, and to elevate the palate. Shortening of the levator veli palatini elevates and posteriorly displaces the velum (Figure 10.7). Muscle shortening also

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moves the lateral walls medially. The palatopharyngeus adducts the posterior tonsillar pillars, constricts the pharyngeal isthmus, narrows the velopharynx, and elevates the larynx. Finally, the palatoglossus muscle pulls the tongue postero-superiorly and constricts the oropharynx at the anterior tonsillar pillars. The palatoglossus also lowers and tenses the velum. The combined effect of surgically modifying these muscles is unknown but

conceptually may be either beneficial or detrimental, depending on the underlying anatomy. During the LAUP procedure, muscle is both excised and damaged. This is followed by scarring, contracture, and shortening. If anatomic shortening parallels the action of physiologic shortening, constriction and pharyngeal narrowing may occur with laser ablation. If extreme, stenosis may result (Figure 10.8).

44 4 4

4

4

2

2

1

1

2 1

3

A

3

2 1

33 3 3

B

Figure 10.8 The effects of shortening of the palatopharyngeus (A) and palatoglossus (B) are shown in a coronal plane. Shortening of the muscles closes the oropharyngeal and the pharyngeal isthmus. Muscles may also act as dilators, depending on the muscle resting position during contraction. When the pharynx is closed, contraction of both muscles will dilate the airway. When the pharynx is wide open, contraction of muscles will constrict the airway.

Patient selection

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Figure 10.9 A mechanism for creating pharyngeal stenosis with excision of lateral wall tissues. Removal of mucosa posterior to the fold of the posterior tonsillar pillar reduces lateral pharyngeal wall width. Since the pharynx is fixed posteriorly, lateral shortening must result in posterior displacement of the palate and pharyngeal folds.

Another mechanism of LAUP’s effect is to modify the myomucosal envelope. By contracture and scarring of the mucosa, the underlying shape and configuration of the pharynx may be modified. This modification is the mechanism of effect of palatal stripping procedures. Basic science studies have demonstrated that tensile forces in the palate are increased following palatal stripping.25 Excessive removal of mucosa may also worsen the upper airway structure. A major risk of stenosis occurs when lateral pharyngeal wall mucosa is excised. Damage to this vulnerable strip of mucosa has long been recognized as a cause of nasopharyngeal stenosis following tonsillectomy and adenoidectomy (Figure 10.9). Finkelstein et al45 have raised troubling concerns about the possible effects of LAUP on postoperative upper airway structure. In a non-randomized study of patients before and after LAUP and UPPP, oropharyngeal configuration was measured with photographs. A small sample was also measured postoperatively with cephalometric X-rays. Although the photographs were not quantitative, both LAUP techniques used in the study created oropharyngeal stenosis. Quantitative measures of airway size following UPPP (when scar

contracture may presumably be less) were much larger than following LAUP. Both of these results must be evaluated with caution, since preoperative selection may have biased postoperative outcomes. However, the possibility of anatomic stricture is real following LAUP.

Patient selection No consensus exists in selecting patients for LAUP. Contraindications for the procedure include significant tonsillar hypertrophy, an excessive gag reflex, or obstruction at nonpalatal locations in the upper airway. Patients with clinically significant nasal obstruction should have this corrected prior to LAUP. Patients with clinically significant OSA and inability to use nasal CPAP following surgical procedures should probably have other procedures performed, or have LAUP performed with intensive postoperative monitoring for respiratory complications. Indications for LAUP vary. All would agree that patients undergoing LAUP should be informed that its effectiveness has not been

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determined. Attempts to identify and exclude patients with non-palatal levels of airway obstruction should be made. This may include physical examination, endoscopy using Müller’s maneuver, cephalometric X-rays, sedated endoscopy, or manometry during sleep. Several authors have proposed that body mass index (BMI) discriminates patient responders from non-responders. Improved outcomes of snoring subjects have been observed in patients with a BMI below 25–28 kg/m2.46 This is in contrast to OSA outcomes, where BMI did not discriminate responders from non-responders.28,29 Paradoxically, although almost all authors use Müller’s maneuver to select patients for LAUP, patient response by level of collapse on endoscopic Müller’s maneuver did not differ in OSA patients.27 Cephalometric X-rays have been evaluated in several studies. Utley et al47 did not observe differences in success in a small number of patients. However, using digital fluoroscopy, Tsushima et al48 classified good and poor LAUP responders. Hyoid bone position was more inferiorly displaced and postoperative posterior airspace was smaller in non-responder groups. Different outcomes in these studies may reflect small sample groups, different criteria used to define success, and differences in other non-controlled demographics. Level of obstruction during sleep has been evaluated manometrically by Skadtvelt.49 Although high success rates were observed with this technique, other groups have failed to improve surgical success using similar techniques.50 Also, Skadtvelt’s LAUP surgical technique may actually represent UPPP performed with the laser rather than LAUP. Application of results to more traditional LAUP techniques may not be valid. Optimism about using manometry to select LAUP patients must be tempered. Treatment response based on apnea severity has been variable. Some authors have had

higher success rates with less severe OSA measured by either RDI or AI.7,26–28 Other authors have not observed significant differences in success dependent on OSA severity. In summary, no current consensus exists on selecting patients for LAUP. Lacking such a consensus, LAUP should be applied conservatively. Those patients with the highest probability of success are probably non-obese, with mild OSA and a predominant complaint of snoring. All patients with OSA require postoperative sleep testing following the procedure to assess effectiveness. These studies need to be performed at least 6 weeks following surgery and after body weight has stabilized. Owing to the frequent changes in BMI that occur following surgery, a 3–6 month equilibration period is probably of benefit prior to obtaining a postoperative polysomnogram.

LAUP techniques Several LAUP techniques have been described. Few have been objectively evaluated or compared.15,25,29 No one technique is ‘better’ than another. Individual surgeons have preferences based on their experience. The choice of technique may vary with anatomy, levels of obstruction, and severity of disease. No accepted scheme or classification of LAUP has been widely applied. Techniques, however, may be classified into three types. These include the ‘French’ technique of Kamami, with serial uvula resection along with simultaneous palatal trenches to shorten the palate, the ‘palatal excision’ technique, with uvula resection, excision of distal palate, and midline ‘mucosal stripping’. Studies suggesting airway stenosis with use of the palatal trench technique are worrisome (Figure 10.10).45 If such stenosis were to occur, OSA could be

LAUP techniques

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A

Figure 10.10 Two different configurations of the palatopharyngeus muscle. When anteriorly placed and vertically oriented, scarring and shortening of the palatopharyngeus muscle results in stiffening of the palate without a change in airway size. When obliquely oriented, scarring and shortening of this muscle will result in narrowing of the pharynx.

B

C worsened in some patients. In fact, the failure of studies using the palatal trench technique to show statistically significant improvement is consistent with a hypothesis that some patients may have worsened sleep apnea. It may be noteworthy that those studies suggesting statistical improvement in groups of patients undergoing LAUP have used the ‘UPPP’-type technique. Obviously, there are inadequate data to compare studies or techniques (Figures 10.11 and 10.12).

Figure 10.11 Preoperative (A), postoperative (B) and longterm postoperative (C) photographs of a traditional LAUP procedure with conservative removal of tissue. There is marked medialization of the posterior pillar and palatopharyngeus muscle. This is consistent with anatomic shortening of the muscle. No significant change in position of the anterior tonsillar pillar is seen.

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B

A Figure 10.12 A more aggressive LAUP with widening of the lateral trenches is shown (A). With a UPPP-type procedure, the uvula may be completely amputated. After healing, the uvula has retracted (B) and there has been a significant medialization of the anterior pillars. Scarring of the palate may result in less vibration and flutter, affecting the noise of snoring. LAUP’s effects on the airway are dependent on the underlying anatomy as well as surgical technique.

LAUP overview

LAUP for snoring

A review of the English language surgical literature has identified 35 papers published with results presented on nine patients or more. The majority of these papers address snoring as an outcome. Data on physiologic outcomes such as respiratory events, daytime functioning, blood pressure and other cardiovascular effects are severely lacking. Some data have been presented comparing different LAUP techniques. However, the combined literature does present considerable evidence on complications associated with LAUP. Based on this literature review, LAUP may treat both snoring and OSA; however, a definitive statement of effectiveness cannot be made. Since only some patients respond successfully to the treatment, improved patient evaluation and selection may improve outcomes. Methods to identify optimal candidates have yet to be established.

In the non-apneic population, snoring is common. It is also the cardinal symptom of OSA and is often the OSA patient’s presenting complaint. The severity of snoring may not always relate to the patient’s complaint of sleepiness or OSA. Furthermore, snoring is often minimized by the medical establishment as being cosmetic. Yet, multiple studies associate snoring with both cardiovascular risk and sleepiness independent of OSA. When watching the sleep of a stentorian snorer, common sense dictates that neither health nor sleep are well served. Clearly, not all snoring is pathologic. However, successful treatment of nonapneic ‘benign’ snorers often results in dramatic effects on social functioning, sleep, and general health. In cases where more conservative treatments have not been successful, surgical treatment of snoring is medically indicated.

LAUP for obstructive sleep apnea A key problem in treating snoring is having a consensus on the definition of snoring itself. Snoring may be defined as an objectionable noise that results from vibration and flutter of the pharynx during sleep. Snoring, therefore, has two components: noise and objectionable complaints. Controversy exists as to which component should be measured when evaluating snoring outcomes. There is also uncertainty as to which should be used as an endpoint of surgical treatment. A patient who has a major change in noise amplitude, yet continues to have complaints of snoring, will require further treatment. In this case, a successful objective measure would be a clinical failure. Alternatively, a patient with only a minor change in the overall amplitude and quality of the snoring noise but who has the complaints eliminated would neither seek nor require further treatment. This would be an objective failure but a clinical success. Therefore, although the noise of snoring is critical, its simple amplitude does not truly define ‘clinical’ snoring. Acoustics analysis before and after LAUP demonstrates small changes in snoring peak amplitude. Distribution of the snoring frequency does change. A major change is the shift of snoring fundamental frequencies to higher and presumably less bothersome sounds.51 Such a change in snoring intensity and frequency has also been correlated with a shifting of the anatomic location of the pressure drop that occurs with snoring. Frequency is higher and amplitude is lower when obstruction occurs at the tongue base and tonsils.52 Data from Hoffstein et al53 indicate that there is very little agreement between objectively measured snoring sounds and snoring complaints. There is also little agreement between different observers and the nature of snoring sounds. It appears that snoring is almost individually defined and a very

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personal complaint. Therefore, defining snoring using solely objective criteria will continue to be elusive.

LAUP for obstructive sleep apnea LAUP has demonstrated effects on both subjective and objective outcomes for OSA. A consensus on LAUP’s effectiveness remains controversial, due to significant gaps in the medical literature. Problems include a lack of consistent outcome measures, large numbers of patients lost to follow-up, and retrospective case series. Furthermore, patient selection criteria and LAUP surgical techniques are often poorly described. This makes extrapolating findings to other patient populations difficult.6,7,15,20,22,26–28,47–49,54,55 Surprisingly, little has changed since the initial ASDA position paper on LAUP was published in 1994.8,56 One of the biggest obstacles to interpreting LAUP results continues to be the large numbers of patients who are lost to followup. When only a small number of patients are available for follow-up, data presented may not represent the overall population studied. The burden of proof rests on the advocates of the procedure, and no studies have adequately addressed this. Many reasons may explain poor polysomnographic followup. Patients are reluctant to pursue further treatment due to prior treatment failure and/or severe pain. They perceive the test as bothersome and an academic exercise if their primary complaint of snoring has been resolved. Last, out-of-pocket costs may deter some patients. Discrepancy in LAUP results may reflect the different techniques used. The best outcomes

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of LAUP were reported by Mickelson and Pribitkin using a UPPP variant of LAUP. This contrasts with studies using a trench technique, where statistically significant results have not been obtained. Multiple variables may confound the results of the studies. One variable that may influence studies is that many patients’ preoperative polysomnograms pre-date LAUP by a considerable time. Walker et al noted that polysomnograms pre-date LAUP by over 18 months.7 Since data suggest the potential of significant worsening of OSA over this time frame, LAUP results may be skewed to miss a possible treatment effect. A recent well done prospective study demonstrated 30% success but also 30% worsening (>100% increase) after LAUP.57 LAUP improves subjective outcome. Excessive daytime sleepiness has improved with both visual analog measures and Epworth Sleepiness Scales. In a small number of patients who only underwent LAUP for OSA, multiple sleep latency test improved from 5–10 min.28

LAUP future directions As an ambulatory procedure, LAUP may be performed under local anesthesia, at a relatively low cost. LAUP, if effective, would have potential advantages over UPPP; both in lower cost and lower complication rates. Unfortunately, this has not been established, and randomized trials measuring relevant outcomes are required. Since LAUP may worsen OSA, it should be performed with caution until questions are answered.

References 1. Powell N, Riley R, Troell R et al. Radiofrequency volumetric reduction of the tongue. Chest, 1997;111:1348–55.

2. Hla K, Young T, Bidwell T et al. Sleep apnea and hypertension. Ann Intern Med 1994;120:382–8. 3. Hung J, Whitford E, Parsons R et al. Association of sleep apnoea with myocardial infarction in men. Lancet 1990;336:261–4. 4. He J, Kryger M, Zorick F et al. Mortality and apnea index in obstructive sleep apnea: experience in 385 male patients. Chest 1988;94(1):9–14. 5. Kamami Y. Outpatient treatment of snoring with CO2 laser: laser-assisted UPPP. J Otolaryngol 1994;23(6):391–4. 6. Kamami Y. Outpatient treatment of sleep apnea syndrome with CO2 laser: laser-assisted UPPP. J Otolaryngol 1994;23(6): 395–8. 7. Walker R, Grigg-Damberger M, Gopalsami C. Laser-assisted uvulopalatoplasty for snoring and obstructive sleep apnea: results in 170 patients. Laryngoscope 1995;105:938–43. 8. Standards of Practice Committee of the American Sleep Disorders Association. Practice parameters for the use of laser assisted uvulopalatoplasty. Sleep 1994;17:744–8. 9. Walker R, Gopalsami C. Laser-assisted uvulopalatoplasty: postoperative complications. Laryngoscope 1996;106:834–8. 10. Gtontved A, Jorgensen K, Petersen S. Results of uvulopalatopharyngoplasty in snoring. Acta Otolaryngol 1992;492(Suppl):11–14. 11. Ikamatsu T. Palatopharyngoplasty and partial uvulectomy method of Ikematsu: a 30 year clinical study of snoring. In: Fairbanks D, Fujita S, Ikematsu T, Simmons FB, eds. Snoring and Sleep Apnea. 1st edn. New York: Rivlin Press, 1987: 130–4. 12. Fujita S, Conway W, Zorick F et al. Surgical correction of anatomic abnormalities of obstructive sleep apnea syndrome: uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg 1981;89:923–34. 13. Fujita S, Conway WA, Zorick FJ et al. Evaluation of the effectiveness of the

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24. Courey M, Fomin D, Smith T et al. Histologic and physiologic effects of electrocautery, CO2 laser, and radiofrequency injury in the porcine soft palate. Laryngoscope 1999;109:1316–19. 25. Kotecha B, Paun S, Leong P et al. Laser assisted uvulopalatoplasty: an objective evaluation of the technique and results. Clin Otolaryngol 1998;23:354–9. 26. Lauretano A, Khosla R, Richardson G et al. Efficacy of laser-assisted uvulopalatoplasty. Lasers Surg Med 1997;21:109–16. 27. Mickelson S, Ahuja A. Short-term objective and long-term subjective results of laserassisted uvulopalatoplasty for obstructive sleep apnea. Laryngoscope 1999;109:362–7. 28. Pribitkin E, Schutte S, Keane W et al. Efficacy of laser-assisted uvulopalatoplasty in obstructive sleep apnea. Otolaryngol Head Neck Surg 1998;119:643–7. 29. Ingrams D, Spraggs P, Pringle M et al. CO2 laser palatoplasty: early results. J Laryngol Otol 1996;110:754–6. 30. Isono S, Akiko S, Tanaka A et al. Efficacy of endoscopic static pressure/area assessment of the passive pharynx in predicting uvulopalatopharyngoplasty outcomes. Laryngoscope 1999;109:769–74. 31. Schwartz A, Schubert N, Rothman W et al. Effect of uvulopalatopharyngoplasty on upper airway collapsibility in obstructive sleep apnea. Am Rev Respir Dis 1992;145:527–32. 32. Liistro G, Stanescu D, Veriter C et al. Pattern of snoring in obstructive sleep apnea patients and heavy snorers. Sleep 1991;14:517–25. 33. Huang L. Mechanical modeling of palatal snoring. J Acoust Soc Am 1995;97(6):3642–8. 34. Finkelstein Y, Talmi Y, Nachmani A et al. On the variability of velopharyngeal valve anatomy and function: a combined peroral and nasoendoscopic study. Plastic Reconstructive Surg 1992;89(4):631–9. 35. Schwab R, Gupta K, Gefter W et al. Upper airway and soft tissue anatomy in normal subjects and patients with sleep-disordered

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breathing. Significance of the lateral pharyngeal walls. Am J Respir Crit Care Med 1995;152:1673–89. Laitman J, Reidenberg J. Specializations of the human upper respiratory and upper digestive systems as seen through comparative and developmental anatomy. Dysphagia 1993;8:318–25. White D. Pathophysiology of obstructive sleep apnoea. Thorax 1995;50:797–805. Isono S, Remmers J, Tanaka A et al. Anatomy of the pharynx in patients with obstructive sleep apnea and in normal subjects. J Appl Physiol 1997;82:1319–26. Gleadhill I, Schwartz A, Schubert N et al. Upper airway collapsibility in snorers and in patients with obstructive hypopnea and apnea. Am Rev Respir Dis 1991;143:1300–3. Lyberg T, Krogstad O, Djupesland G. Cephalometric analysis in patients with obstructive sleep apnoea syndrome: skeletal morphology. J Laryngol Otol 1989;103: 287–292. Lyberg T, Krogstad O, Djupesland G. Cephalometric analysis in patients with obstructive sleep apnoea syndrome: soft tissue morphology. J Laryngol Otol 1989;103: 293–7. Caballero P, Alvarez-Sala R, Garcia-Rio F. CT in the evaluation of the upper airway in healthy subjects and in patients with obstructive sleep apnea syndrome. Chest 1998;113:111–16. Morrison D, Launois S, Isono S et al. Pharyngeal narrowing and closing pressures in patients with obstructive sleep apnea. Am Rev Respir Dis 1993;148:606–11. McWilliams B, Morris H, Shelton R. The nature of the velopharyngeal mechanisms. In: McWilliams BJ, ed. Cleft Palate Speech. 2nd edn. St Louis: Mosby, 1990: 197–235. Finkelstein Y, Shapiro-Feinberg M, Stein G et al. Uvulopalatopharyngoplasty vs laserassisted uvulopalatoplasty. Arch Otolaryngol Head Neck Surg 1997;123:265–76. Rollheim J, Miljeteig H, Osnes T. Body mass index less than 28 kg/m2 is a predictor of

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11 Hypopharyngeal airway surgery Kasey K Li and Nelson B Powell

Introduction Hypopharyngeal obstruction is a major contributing factor in obstructive sleep apnea (OSA). Hypopharyngeal obstruction stems from the prominence or relaxation of the base of the tongue, and lateral pharyngeal wall collapse, and occasionally involves the aryepiglottic folds or epiglottis.1–3 ‘Disproportionate’ skeletal anatomy in the form of a narrowed mandibular arch and/or mandibular deficiency can also be a significant factor leading to hypopharyngeal obstruction.4 The complex interplay of the soft and hard tissues that contribute to hypopharyngeal obstruction, the importance of the hypopharynx to speech and swallowing, as well as the subsequent edematous response after surgical intervention, present a formidable challenge to the sleep surgeon. The Stanford Surgical Protocol incorporates a conservative, stepwise treatment philosophy along with a risk management strategy to minimize the risks of surgery. This protocol has been refined and modified since we first described the mandibular advancement procedure for the treatment of hypopharyngeal obstruction in 1983.5

Rationale for hypopharyngeal surgery Hypopharyngeal obstruction has been documented in OSA by EMG studies, cephalometric radiography, CT scanning, MRI and videofluoroscopy.3,6–9 These diagnostic studies have improved our understanding of the mechanism of hypopharyngeal obstruction, in that it can result from the prominence or collapse of the base of the tongue, lateral pharyngeal wall, the aryepiglottic folds or epiglottis, as well as the disproportionate mandibular anatomy. Tracheotomy was the first treatment to manage OSA in ‘Pickwickian’ subjects. Tracheotomy is a highly effective therapy in the management of hypopharyngeal obstruction, as it bypasses this region completely. Since the first tracheotomy performed by Kuhlo et al,10 various procedures have been developed to improve airway obstruction in the hypopharynx (Table 11.1). These procedures were developed based on the understanding of the anatomy and physiology of the maxillofacial skeletal relationships and the genioglossus–hyoid complex as they relate to airway size during wakefulness and sleep. Since these surgical approaches were

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Table 11.1 Surgical procedures for treatment at the hypopharyngeal region. Mandibular osteotomy with genioglossus advancement Hyoid myotomy with suspension Maxillomandibular advancement Tongue base resection Tracheotomy (bypass all upper airway obstructions) Radiofrequency volumetric reductiona Electrical stimulationb Suture to tongue basec a b

c

New technology with multi-center studies in progress. Experimental and investigational with studies in progress. New technology with studies in progress.

specifically designed to alleviate hypopharyngeal obstruction, accurate presurgical evaluations are essential for the appreciation of the anatomic abnormality present. This allows for the utilization of a surgical protocol that results in improved clinical outcomes. At our center, a thorough head and neck evaluation combined with fiberoptic pharyngolaryngoscopy is performed to isolate and direct treatment at the region or regions of obstruction. A lateral cephalometric radiograph is also utilized to assist in treatment planning. Although cephalometric radiography is only a static two-dimensional method of evaluating a dynamic three-dimensional area, it does provide useful information on the posterior airway space. The posterior airway space measurement on lateral cephalometric radiographs has been shown to correlate with the volume of hypopharyngeal airway on three-dimensional CT scans.11 In addition, it is a valuable study to assess the relationship of

N

S

Ba PNS ANS A P PAS

Go B

MP H Gn

Figure 11.1 Cephalometric analysis. The normative values are as follows: SNA 82˚ (SD ± 2), maxilla to cranial base; SNB 80˚ (SD ± 2), mandible to cranial base; PAS 11 mm (SD ± 1), posterior airway space; PNS–P 37 mm (SD ± 3), length of soft palate; MP–H 15.4 mm (SD ± 3), distance of hyoid from inferior mandible. Ba, basion; Gn, gnathion; Go, gonion; ANS, anterior nasal spine; PNS, posterior nasal spine.

the maxillofacial skeleton and the hyoid bone with the airway (Figure 11.1).

Stanford protocol The Stanford two-phase surgical protocol (Figure 11.2) combines the evaluation, the indications for treatment, and the treatment philosophies to manage upper airway obstruction in OSA. This two-phase approach was

Stanford protocol Presurgical evaluation (physical examination, cephalometric analysis, fiberoptic pharyngoscopy)

Phase I (site of obstruction)

UPPP (type 1 oropharynx)

UPPP + GAHM (type 2 oropharynx – hypopharynx) (Type

GAHM (type 3 hypopharynx)

Postoperative polysomnogram (6 months) (failure)

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Figure 11.2 The Stanford protocol. UPPP, uvulopalatopharyngo plasty; MMA, maxillomandibular advancement; GAHM, genioglossus advancement/hyoid myotomy.

Phase II MMA

Table 11.2 Criteria for cure. Postsurgical RDI and LSAT equal to CPAP results For patients without CPAP results Postsurgical RDI of 20 or less and at least a reduction of RDI by 50%, i.e. an RDI of 26 would need to be reduced to 13 Postsurgical SaO2 must be normal or with only a few brief falls below 90% Normalization of sleep architecture Subjective complaints of EDS neutralized RDI, respiratory disturbance index; CPAP, continuous positive airway pressure; EDS, excessive daytime sleepiness; LSAT, lowest oxygen saturation.

established to minimize surgical interventions and avoid unnecessary surgery while achieving a cure. After the completion of phase I surgery, patients are allowed a period of healing for 4–6 months, and a postoperative polysomnogram is obtained to evaluate outcome. Since continuous positive airway pressure (CPAP) is considered the ‘gold standard’ treatment

modality, we have instituted a surgical goal to define cure (Table 11.2). This strict criterion enables us to compare our surgical results with CPAP results. Patients with persistent OSA following phase I surgery are offered phase II surgery (maxillomandibular advancement). Clearly, not all of the patients undergo phase I surgery prior to phase II surgery. Patients with severe OSA and significant mandibular deficiency, or patients who have already undergone uvulopalatopharyngoplasty (UPPP) may proceed directly to phase II surgery. Therefore, it is important to review all possible treatment options and explain the rationale for upper airway reconstruction. In our opinion, combining phase I and phase II surgery should be avoided due to the potential for unnecessary surgery, as well as the increased surgical morbidity and postoperative airway compromise. Our concern for postoperative airway compromise has prompted us to further establish a CPAP surgical protocol.12 Nasal CPAP is prescribed 2 weeks prior to surgery in patients with a respiratory disturbance index (RDI) greater than or equal to 40 and oxygen desaturation of 80%

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or less. The patients are maintained on CPAP postoperatively until 2 weeks prior to the postoperative polysomnogram (4–6 months). In patients with severe OSA (RDI > 60 and SaO2 < 60%), temporary tracheotomy is considered.

Phase I surgery Since the mandible, tongue and hyoid complex are major determinants of the airway dimension at the hypopharyngeal level,4,13 mandibular osteotomy with genioglossus advancement and hyoid myotomy and suspension have evolved for the reconstruction of this region. Anterior repositioning of the genioglossus muscle is achieved through a conservative mandibular osteotomy that advances the genial tubercle without movement of the teeth or mandible. It improves the tension of the genioglossus muscle and decreases its collapsibility during sleep, thus alleviating airway obstruction. The rationale for altering the hyoid position in the treatment of tongue base obstruction is the fact that, anatomically, the hyoid complex is an integral part of the hypopharynx. Anterior movement of the hyoid complex improves the posterior airway space, and numerous reports have supported the concept that surgical intervention at the hyoid level improves the hypopharyngeal airway.14–17 In 1984, we described the inferior mandibular osteotomy with hyoid myotomy and suspension for hypopharyngeal reconstruction.18 The technique has evolved over the years to improve outcome and minimize morbidity. The current technique of mandibular osteotomy with genioglossus advancement involves a limited osteotomy intraorally to isolate and advance the genial tubercle. It is a

minimally invasive procedure that is routinely completed within 30 min. Although hyoid myotomy with suspension also improves hypopharyngeal obstruction and is included in the phase I surgical protocol, it is not always performed simultaneously with genioglossus advancement. This is because the majority of patients with OSA have diffuse airway obstruction, and genioglossus advancement is generally combined with UPPP. The added insult to the infrahyoid region by combining the genioglossus advancement and hyoid myotomy and suspension results in increased edema, and was thought to be inappropriate in some patients. We have also found that the hypopharyngeal airway obstruction is resolved with only genioglossus advancement in some patients, so a hyoid procedure may not always be necessary. Furthermore, in some elderly patients (> 60 years old), airway edema following simultaneous genioglossus advancement and hyoid myotomy and suspension can result in prolonged dysphagia that may require days to resolve. For these reasons, we perform hyoid myotomy and suspension only in some patients as a separate surgical step.

Surgical procedures Mandibular osteotomy with genioglossus advancement The operation is designed to reposition the genial tubercle forward, thus improving the tension of the tongue musculature and limiting its posterior displacement during sleep. The limiting factor in this forward movement is the thickness of the mandibular symphysis.

Surgical procedures Preoperative radiographic analysis, including a lateral cephalometric radiograph and a panoramic dental X-ray, is necessary to assist the surgeon in surgical planning. The cephalometric radiograph will document skeletal deformities and soft tissue airway narrowing. It will further assist in the evaluation of the genial tubercle position and the airway changes following surgery. The panoramic radiograph will demonstrate the course of the inferior alveolar nerve canal, the mental foramen, and the position of the mandibular tooth roots, as well as detect potential pathologic processes of the mandible. The procedure begins with a mucosal incision approximately 7–8 mm below the mucogingival junction. A subperiosteal dissection is performed to expose the mandibular symphysis. The genial tubercle and genioglossus muscle can be identified by finger palpation in the floor of the mouth and with the aid of the lateral cephalometric radiograph. It is recommended that the superior horizontal bone cut be at least 5 mm below the mandibular root apices to decrease the likelihood of tooth paresthesia. The inferior horizontal bone cut should be designed to preserve approximately 10 mm of the inferior border of the mandible to reduce the risk of a pathologic mandibular fracture. The lateral and vertical bone cuts should be within the confines of the canine roots. Prior to completing the osteotomy, a titanium screw is placed in the outer cortex in order to manipulate the genial tubercle fragment. Bleeding is controlled with electrocautery and a hemostatic agent such as Gelfoam® (Pharmacia and Upjohn Company, Kalamazoo, Michigan, USA). The fragment is advanced and rotated 60–90º to prevent retraction back into the floor of the mouth. The outer cortex and marrow are removed and the inner cortex is rigidly fixed with a lag screw (Figure 11.3).

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A

B Figure 11.3 The mandibular osteotomy with genioglossus advancement procedure. (A) Anterior view. (B) Lateral view.

Hyoid myotomy and suspension Our initial hyoid procedure involved the suspension of the hyoid to the mandible.18 We have modified the procedure several times in an attempt to minimize surgical trauma. The current hyoid myotomy and suspension technique involves suspending the hyoid to the superior thyroid cartilage (Figure 11.4).19 We

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Hypopharyngeal airway surgery Figure 11.4 The hyoid myotomy and suspension procedure.

have found that the current technique is less invasive and the results have been comparable to those of the earlier procedures. The current hyoid myotomy and suspension is approached with a horizontal skin incision made over the hyoid bone. Surgical dissection is performed through the suprahyoid musculature to the body of the hyoid bone. The infrahyoid and suprahyoid muscles are partially dissected off the body of the hyoid bone to allow mobilization of the hyoid complex. Occasionally, the stylohyoid ligament may need to be released from the lesser cornu to improve the degree of mobilization. Limiting the dissection within the lesser cornu will minimize the risk of superior laryngeal nerve injury. The hyoid is secured to the superior thyroid cartilage with four permanent sutures. A passive surgical drain is placed for 1–2 days to prevent seroma or hematoma formation.

Perioperative management Patients with OSA have an increased risk for postoperative airway compromise. As stated

earlier, nasal CPAP should be attempted at least 2 weeks prior to surgery to reverse sleep debt and prevent REM rebound in the postoperative period. Anesthesia induction and intubation should be performed with the surgeons present. In patients with a difficult airway, especially in obese patients with an increased neck circumference (> 46 cm) and associated skeletal deformities (mandibular deficiency and low hyoid bone), an awake fiberoptic intubation or tracheotomy should be considered.20 All patients should be extubated awake in the operating room immediately following surgery. Intensive care unit (ICU) monitoring should be considered in patients undergoing multiple procedures (UPPP combined with genioglossus advancement and/or hyoid myotomy and suspension), or in patients with significant coexisting medical problems such as hypertension and coronary artery disease. Nasal CPAP or humidified oxygen (35%) via face tent should be used on all patients, and oximetry monitoring is performed throughout the hospitalization. Blood pressure should be monitored closely, and hypertension treated aggressively with intravenous antihypertensive medications

Phase II surgery to minimize postoperative bleeding and edema. The use of narcotics should be closely monitored due to the increased potential for airway compromise.21,22 Our protocol consists of intravenous morphine sulfate (MS) or meperidine HCl administered by a nurse in graduated doses (e.g. MS 1–8 mg every 1–3 h as necessary) in the ICU while monitoring respiratory rate, oxygen saturation and mental status. Intramuscular meperidine HCl and oxycodone elixir are used after the patients are transferred to the floor on the second postoperative day. Oral hydrocodone is used following discharge. Patients are discharged if there is a stable airway, adequate oral intake of fluids, and satisfactory pain control. The use of nasal CPAP is recommended after discharge, and humidified oxygen is prescribed for 2 weeks in patients with severe OSA syndrome who cannot tolerate nasal CPAP.

Phase I surgical protocol clinical outcomes Our surgical results were reported in 1992 (Table 11.3).23 Two hundred and thirty-nine patients underwent phase I surgery, with most of the patients requiring intervention at the pharyngeal and hypopharyngeal levels. The overall cure rate was 61% (145/239 patients). The surgical results were comparable to nasal CPAP results. The mean preoperative RDI was 48.3, and the mean postoperative RDI 9.5 (nasal CPAP RDI 7.2, p = NS). The lowest oxygenation saturation (LSAT) improved from 75% to 86.6% (nasal CPAP LSAT 86.4%, p = NS). There was a higher cure rate with mild to moderately severe disease (approximately 70%) as compared to severe

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disease (42%). Most of the patients who failed phase I therapy had severe OSA (mean RDI 61.9) and morbid obesity (mean body mass index (BMI) 32.3 kg/m2). The postoperative morbidity was low. The mean hospital stay was 2.1 days. The complications associated with genioglossus advancement and hyoid suspension were infection (< 2%), injury of tooth roots requiring root canal therapy (< 1%), permanent paresthesia and anesthesia of the mandibular incisors (< 6%), and seroma (< 2%). Major complications such as mandibular fracture, alteration of speech, alteration of swallow or aspiration were not encountered.

Phase II surgery Craniomaxillofacial skeletal abnormality is a well-recognized predictor in OSA.1,24,25 Many patients with OSA have maxillomandibular deficiency resulting in diminished airway size that leads to nocturnal obstruction. In 1983, we reported the use of mandibular advancement surgery in the treatment of OSA.5 The forward movement of the mandible improved hypopharyngeal obstruction. We subsequently investigated the effect of maxillomandibular advancement (MMA) on the airway and have utilized this procedure as the second phase of our surgical protocol.26 MMA achieves enlargement of the pharyngeal and hypopharyngeal airway by physically expanding the skeletal framework. In addition, the forward movement of the maxillomandibular complex improves the tension and collapsibility of the suprahyoid and velopharyngeal musculature. The majority of patients who entered the phase II surgical protocol had completed the phase I protocol and had failed to respond fully. These patients had already

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undergone reconstruction of the airway at the nasal, pharyngeal and hypopharyngeal levels. Phase I surgical failure usually involves persistent obstruction of the hypopharyngeal level (occasionally combined with pharyngeal-level obstruction). The MMA procedure creates further tension and physical room in the upper airway, relieving residual obstructions. In order to maximize airway expansion, a major advancement of the maxillomandibular complex is required to facilitate a successful result. However, it is important to achieve maximal advancement while maintaining a stable dental occlusion and a balanced esthetic appearance. Over the past 17 years, patients with and without ‘disproportionate’ craniomaxillofacial features have undergone MMA for persistent severe OSA due to incomplete response to phase I surgery. Although patients with craniomaxillofacial abnormalities such as maxillary and/or mandibular deficiencies usually have improved facial esthetics following surgery, we found that many patients with normal cephalometric measurements preoperatively also have an improved facial appearance following MMA. This is because many of our patients are middle-aged adults who are already showing signs of facial aging due to soft tissue sagging. Skeletal expansion of the maxilla and mandible enhances appearance by improving soft tissue support.

Phase II surgical protocol clinical outcomes An analysis of 175 patients between 1988 and 1995 demonstrated that 166 patients had a successful outcome, with a cure rate of 95% (Table 11.4). The mean preoperative RDI was 72.3. The mean postoperative RDI was 7.2. The surgical results were comparable to nasal

Table 11.3 Surgical protocol results: phase I.

Surgery groups

Patient success/ total patients

Success rate (%)

GAHM + UPPP GAHM UPPP Total

133/223 4/6 8/10 145/239

60 66 80 61

Table 11.4 Surgical outcomes, phase II—MMA.

Surgery groups Failed phase I Skeletal deformity (without UPPP) Failed UPPPa Total a

Patient success/ total patients

Success rate (%)

83/86 10/11

97 91

73/78 166/175

94 95

Outside referral—severe OSA syndrome.

CPAP results (nasal CPAP RDI 8.2, p = NS). The mean LSAT improved from 64.0% to 86.7% (nasal CPAP LSAT 87.5%, p = NS). Eighty-six patients who failed the phase I surgical protocol underwent MMA. The mean age of patients was 43.5 years. The cure rate in this group was 97% (83/86 patients). Most of the patients who failed the phase I protocol but declined MMA were older, with a mean age of 51.8 years. The mean hospital stay was 2.4 days. The surgical morbidity included transient anesthesia of the lower lip, chin and cheek in all of the patients. There was an 87% resolution between 6 and 12 months. There was no postoperative

References bleeding or infection. Mild malocclusion encountered in some patients was treated satisfactorily with dental occlusal adjustment. No major skeletal relapse occurred. To date, 59 patients (49 men) have had long term follow-up results. The mean age was 47.1 years. The mean BMI was 31.1 kg/m2. Nineteen patients had only subjective (quality of life) results. These patients refused long-term polysomnograpy for various reasons, including inconvenience, time and cost. Sixteen of the 19 patients continued to report subjective success with minimal to no snoring, no observed apnea, and no recurrence of excessive daytime sleepiness (EDS). All patients reported stable (unchanged) weight to mild weight gain (< 5 kg). Three patients reported recurrence of snoring and excessive daytime sleepiness (EDS). Long-term polysomnographic data were available in 40 patients (33 men). The mean age was 45.6 years. The mean BMI was 31.4 kg/m2. The preoperative RDI and LSAT were 71.2 and 67.5%, respectively. The 6-month postoperative RDI was 9.3 and the LSAT was 85.6%. The mean follow-up period was 50.7 months, and long-term RDI and LSAT were 7.6 and 86.3%, respectively. The mean weight at the long-term follow-up was 32.2 kg/m2 (p = 0.002). Four patients had recurrent OSA. The 6-month RDI in these four patients was 10.5, but the longterm RDI (61 ± 24.7 months) was 43.0. The LSAT decreased from 87.5% to 81.8%.

Conclusion A systematic and conservative approach to the management of hypopharyngeal airway obstruction has been described. The surgical techniques have been modified and refined over the past 17 years. A thorough presurgical evaluation to identify airway collapse is

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mandatory to allow for the utilization of the Stanford protocol, which results in improved clinical outcomes. This logical stepwise surgical approach in airway reconstruction will minimize surgical interventions and avoid unnecessary operations. The incorporation of the risk management protocol will minimize treatment complications.

References 1. Riley RW, Guilleminault C, Powell NB et al. Palatopharyngoplasty failure, cephalometric roentgenograms, and obstructive sleep apnea. Otolaryngol Head Neck Surg 1985;93:240–4. 2. Kletzker GR, Bastian RW. Acquired airway obstruction from histologically normal, abnormally mobile supraglottic soft tissues. Laryngoscope 1990;100:375–9. 3. Schwab RJ, Gefter WB, Hoffman EA. Dynamic upper airway imaging during awake respiration in normal subjects and patients with sleep-disordered breathing. Am Rev Respir Dis 1993;148:1385–400. 4. Rojewski TE, Schuller DE, Clark RW et al. Videoendoscopic determination of the mechanism of obstruction in obstructive sleep apnea. Otolaryngol Head Neck Surg 1984;92:127–31. 5. Powell N, Guilleminault C, Riley R, Smith L. Mandibular advancement and obstructive sleep apnea syndrome. Bull Eur Physiopathol Respir 1983;19:607–10. 6. Remmers JE, deGroot WJ, Sauerland EK, Anch AM. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol 1978;44:931–8. 7. Riley R, Powell N, Guilleminault C. Cephalometric roentgenograms and computerized tomographic scans in obstructive sleep apnea. Sleep 1986;9:514–15.

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8. Suratt PM, Dee P, Atkinson RL et al. Fluoroscopic and computed tomographic features of the pharyngeal airway in obstructive sleep apnea. Am Rev Respir Dis 1983;127:487–92. 9. Shepard JW, Thawley SE. Evaluation of the upper airway by computerized tomography in patients undergoing uvulopalatopharyngoplasty for obstructive sleep apnea. Am Rev Respir Dis 1989;140:711–16. 10. Kuhlo W, Doll E, Franck MD. Erfolgreiche Behandlung eines Pickwick Syndroms durch eine Dauertrachekanuele. Dtsch Med Wochenschr 1969;94:1286–90. 11. Riley RW, Powell NB. Maxillofacial surgery and obstructive sleep apnea syndrome. Otolaryngol Clin North Am 1990;23:809–26. 12. Powell N, Riley R, Guilleminault C. Obstructive sleep apnea, continuous positive airway pressure, and surgery. Otolaryngol Head Neck Surg 1988;99:362–9. 13. Lowe A, Gionhaku N, Tadeuchi K et al. Three dimensional reconstructions of the tongue and airway in adult subjects with obstructive sleep apnea. Am J Orthodont 1986;90:364–74. 14. Kaya N. Sectioning the hyoid bone as a therapeutic approach for obstructive sleep apnea. Sleep 1984;7:77–8. 15. Van de Graaf WB, Gottfried SB, Mitra J et al. Respiratory function of hyoid muscles and hyoid arch. J Appl Physiol 1984;57:197–204. 16. Patton TJ, Thawley SE, Water RC et al. Expansion hyoid-plasty: a potential surgical procedure designed for selected patients with obstructive sleep apnea syndrome. Experimental canine results. Laryngoscope 1983;93:1387–96. 17. Patton TJ, Ogura JH, Thawley SE. Expansion hyoidplasty. Otolaryngol Head Neck Surg 1984;92:509–19.

18. Riley RW, Guilleminault C, Powell NB, Derman S. Mandibular osteotomy and hyoid bone advancement for obstructive sleep apnea: a case report. Sleep 1984;7:79–82. 19. Riley RW, Powell NB, Guilleminault C. Obstructive sleep apnea and the hyoid: a revised surgical procedure. Otolaryngol Head Neck Surg 1994;111:717–21. 20. Riley RW, Powell NB, Guilleminault C, Pelayo R, Treoll RJ, Li KK. Obstructive sleep apnea surgery: risk management and complications. Otolaryngol Head Neck Surg 1997;117:648–52. 21. Esclamado RM, Glenn MG, McCulloch TM et al. Perioperative complications and risk factors in the surgical treatment of obstructive sleep apnea syndrome. Laryngoscope 1989;99:1125–9. 22. Gabrielczyk MR. Acute airway obstruction after uvulopalatopharyngoplasty for obstructive sleep apnea syndrome. Anesthesiology 1988;69:941–3. 23. Riley RW, Powell NB, Guilleminault C. Obstructive sleep apnea syndrome: a review of 306 consecutively treated surgical patients. Otolaryngol Head Neck Surg 1993;108:117–25. 24. Jamieson A, Guilleminault C, Partinen M, Quera-Salva MA. Obstructive sleep apneic patients have craniomandibular abnormalities. Sleep 1986;9:469–77. 25. DeBerry-Borowiecki B, Kukwa A, Blanks R. Cephalometric analysis for diagnosis and treatment of obstructive sleep apnea. Laryngoscope 1988;98:226–34. 26. Riley RW, Powell N, Guilleminault C. Current surgical concepts for treating obstructive sleep apnea syndrome. J Oral Maxillofac Surg 1987;45:149–57.

12 Skeletal facial corrections Walter Hochban

Introduction Owing to the multiple etiologies of sleeprelated breathing disorders (SRBDs) e.g. obstructive sleep apnea (OSA) with numerous different parameters influencing upper airway collapse,1–3 it appears highly unlikely that every patient is a suitable candidate for all treatment options. Unlike medical treatment options, which may be implemented as therapeutic trials generally without significant risk of morbidity and mortality, the potential risks of surgery require a greater degree of certainty of success before proceeding. The skeletal dimensions of the face, particularly the position of the jaws, have a major influence on the shape and patency of the upper airway. Numerous inherited or acquired clinical syndromes with craniofacial changes (Pierre–Robin, Treacher–Collins, Goldenhar, Hallermann–Streiff, Pfeiffer, Apert and Crouzon syndromes) are significantly associated with SRBD. Mandibular deficiency represents the most frequent form of dysgnathia. Even moderate variations of maxillomandibular size, and jaw and head position, may induce SRBD in patients with retrognathia. The occurrence of SRBD is increased if retrognathia is associated with certain craniofacial and morphologic characteristics, e.g. vertical and dolichofacial (‘long face’). This results in a steep mandibular base which promotes a

dorsal and caudal displacement of the chin and the adjacent tongue base and suprahyoid musculature. Mouth opening with rotation of the mandible along the hinge axis accentuates this displacement. Thus, surgical correction of certain craniofacial types is a valuable tool for the treatment of SRBD. The historical development in recent years towards a systematic approach to treat OSA by skeletal facial corrections started about two decades ago with single case reports,4–8 in spite of the fact that surgical corrections of skeletal facial deformities such as dysgnathias were already well established in craniomaxillofacial surgery. During the 1980s the high percentage of failure after UPPP led to the search for more efficient treatment modalities and work on the indications for different surgical options for successful treatment of OSA.9–13

Preoperative diagnostic essentials A careful clinical investigation of the complete upper airway by a trained specialist is essential prior to any kind of treatment, even if only conservative treatment is considered. Clinical examination is important not only with respect to possible surgical intervention, but

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also to exclude underlying pathologic conditions, e.g. tumors, prior to instituting conservative treatment with nasal continuous positive airway pressure ventilation (nCPAP). These are found in less than 5% of the sleep apnea patients.14–19 With respect to surgical procedures, status of the teeth, their position and the maxillomandibular relationship are important to rule out possible skeletal disorders. A large series of case reports supports the importance of clinical evaluation of skeletal disorders, mainly of the mandible, as possible factors in the pathophysiology of OSA.20–25 A multitude of static and dynamic investigation procedures have been used to locate the site of obstruction and predict successful outcome prior to surgical intervention. Rhinomanometry and acoustic rhinometry are only useful to diagnose impairment of nasal breathing.26 CT as well as MRI scanning, as mentioned earlier,27 do not provide reliable information about the dynamic process of the upper airway in OSA. Information about the different pharyngeal sizes, for instance, does not have any therapeutic consequences for the surgical treatment of OSA. The only valuable diagnostic tool for those considering skeletal surgery is cephalometry.28,29 Cephalometrically, in about 40% of OSA patients (predominantly non-obese patients) characteristic craniofacial patterns can be identified.28,29 Under the assumption that SRBD presents a more functional than mechanical problem, functional dynamic evaluation such as pressure, flow, or Pcrit measurements are better tests. Besides routine polysomnographic evaluation, additional dynamic techniques permit an investigation of SRBD qualitatively and also quantitatively and may be useful for preoperative evaluation. Esophagus pressure measurements represent the gold standard method for the assessment of upper airway occlusion during sleep.30,31 For the detection of mixed

apneas (with a long central component) and a moderately increased upper airway resistance, esophageal pressure swings sensitively reflect an increasing respiratory effort, which is essential for the decision to operate or not. Upper airway pressure measurements with a multisensor catheter are able to locate the site of collapse,32–36 but there is great variability, and upper airway obstruction usually involves more than one specific site of obstruction. The same problem occurs with pharyngeal fiberoptic endoscopy;37,38 with or without additional use of the Müller maneuver the selective surgical correction of specific sites of obstruction leads only to a change of the site of obstruction.39 In our experience, both techniques are only valuable for specific minor secondary refinements after major improvement of pharyngeal collapse by skeletal corrections. The measurement of the critical pharyngeal closing pressure (Pcrit) makes it possible to quantify pharyngeal collapse.40–43 Skeletal advancement usually reduces Pcrit by about 8 cmH2O (own measurements), which means that patients who need greater reduction of Pcrit (e.g. due to considerable obesity) are obviously not good candidates for this kind of surgery. In the clinical setting, these kinds of measurements are not routine and, unfortunately, at present there is no clear-cut protocol for evaluation of these patients. However, in the future these measurements may help the clinician predict the success of different therapies for OSA.44

Patient selection and indication for surgical treatment (MMO) In cases where the number of obstructive events exceeds a certain level (e.g. apnea index

Patient selection and indication for surgical treatment (MMO) (AI) > 10, apnea-hypopnea index (AHI) > 20, respiratory disturbance index (RDI) > 20) it seems not to be important whether these events are more or less complete obstructions. Even short respiratory disturbances which do not fulfill the classic criteria of apneas or hypopneas interact with sleep and may provoke a considerable number of arousals. There is no question that simple primary snoring (International Classification on Sleep Disorders, 780.53–1)45 is not an indication for major skeletal corrections, but—beyond a certain threshold (RDI > 20 ?)—it does not matter whether we have an upper airway resistance syndrome (UARS) or mere complete OSA. Pharyngeal properties, e.g. pharyngeal collapsibility, are of much greater importance for the preoperative prediction of postoperative success, which certainly means complete elimination of all obstructive events. A reduc-

Aa

Bb

195

tion of 50% is not relevant—even if this reduction is statistically significant—unless the number of events is reduced below a critical level (AHI < 10/h, RDI < 20/h). As stated earlier, skeletal maxillary and mandibular advancement are able to reduce critical pharyngeal closing pressure, Pcrit, by about 8 cmH2O. Therefore, patients with extremely high Pcrit may not be good candidates for this kind of surgery. Often, these patients with high Pcrit are extremely obese, and considerable obesity is a hint that any craniofacial changes may be of minor importance in the etiology of OSA. During the primary visit at the sleep laboratory, in addition to a careful routine clinical examination, standardized lateral X-rays are taken and cephalometry is performed. This simple procedure may give an indication of whether craniofacial changes (retrognathic, dolichofacial appearance) may influence upper

Cc

Figure 12.1 (A) ‘Normal’ mesofacial type—no primary indication for skeletal corrections. (B) Dolichofacial type with pharyngeal narrowing—primary indication for maxillomandibular advancement osteotomy. (C) Retrognathic type with class II malocclusion—primary indication for maxillomandibular advancement osteotomy with correction of malocclusion.

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Table 12.1 Indications for surgical treatment of OSA by maxillomandibular advancement.

Table 12.2 Contraindications for surgical treatment of OSA by maxillomandibular advancement.

Obstructive SRBD Relevant SRBD (RDI > 20) Cephalometric pharyngeal obstruction (PAS/ML < 10 mm) Retrognathic facial type (angle SNB < 77º) Dolichofacial type (angle ML/NSL > 34º)

Non-obstructive SRBD Obstructive SRBD of extremely long duration (?) Mixed SRBD with long central/only short obstructive parts Wide pharyngeal space (PAS/ML > 15 mm) No skeletal facial changes Considerable obesity (BMI >t32 kg/m2?) Alcohol/drug abuse Old age (due to changing sleep pattern with old age) (?)

SRBD, sleep-related breathing disorder; RDI, respiratory disturbance index; PAS, posterior airway space; ML, mandibular plane; SNB, sella–nasion–B-point of mandible; NSL, nasion–sella line.

SRBD, sleep-related breathing disorder; PAS, posterior airway space; BMI, body mass index.

airway function and patency. Surgical treatment by skeletal advancement is considered if patients fulfill certain cephalometric criteria: (1) retrognathic appearance (angle sella–nasion–B-point of mandible, SNB < 77°, for instance) and/or dolichofacial appearance (steep mandibular plane, e.g. angle ML–NSL > 34°)—in most of these patients, a pharyngeal narrowing (posterior airway space (PAS) < 10 mm) is seen concomitantly (Figure 12.1); (2) patients with less obvious skeletal changes are considered for surgery if they prove to have a highly narrow PAS and are not extremely obese (body mass index (BMI) < 32 kg/m2). In patients with an AHI or an RDI of 20 events per hour of sleep or more, the question arises whether these events are more or less obstructive SRBD (Table 12.1). Non-obstructive SRBD should be excluded from any surgical treatment. Surgery is not the treatment of choice for periodic respiration, since the underlying pathomechanism of this disorder is attributed to deteriorated chemoreceptor function. Most of the patients have mixed SRBD. If these patients have a predominantly central component and only a minimal obstructive component, it is questionable whether they

are candidates for surgery. Another group of patients who may fulfill all criteria for surgery might present with very long apneas. In these cases, where it takes a long time until the apneic events are terminated by an arousal, central changes such as diminished chemoreceptor sensitivity must be assumed. Therefore, surgical success is unlikely (Table 12.2). Craniofacial changes and obesity are not mutually exclusive. In an obese patient, it is difficult to determine whether SRBD is the consequence of obesity or the craniofacial changes. Successful treatment of the obesity may reduce the SRBD to a level where no surgery is necessary. The advisable strategy for obese patients with craniofacial changes should be to first treat the weight problem. Surgical intervention is normally only considered for our patients with a BMI of 32 kg/m2 or less. Another uncertain factor is age, because of changing sleep patterns with age. Our oldest patient was 67 at the time of surgery. At a 5year follow-up, he was asymptomatic with an

Surgical principles and techniques RDI < 10/h. Excessive alcohol use or drug abuse should be an exclusion criterion, as is a wide pharyngeal airway space at all levels without any skeletal changes.

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A A

Surgical principles and techniques The importance of abnormal skeletal craniofacial configuration as an important causal factor is well known.4–13,21–25,46–53 In addition to standard techniques, recent developments include gradual distraction osteogenesis in the face according to the Ilizarov principle, which in extreme cases may be an alternative to conventional osteotomy especially in growing children.54

B B

Mandibular advancement Over the years, various techniques have been described for mandibular advancement surgery (vertical oblique ramus osteotomy with and without bone graft, C-osteotomy, inverted L-osteotomy, etc.). Our standard approach for mandibular advancement osteotomy is the bilateral retromolar sagittal split osteotomy as originally described by Obwegeser and Dalpont in the 1950s55–57 via an intraoral approach (Figure 12.2a). A lingual horizontal osteotomy of the lingual table of the ascending ramus is performed cranial to the entrance of the inferior alveolar nerve, and then a vertical osteotomy of the outer cortex is performed distal to the molars. Between these two osteotomy lines, the mandibular angle is split sagittally. The neurovascular bundle of the inferior alveolar nerve stays within the central distal part of the

Figure 12.2 (A) Mandibular advancement by bilateral retromolar sagittal split osteotomy via an intraoral approach. (B) Modification according to Hunsuck.

mandible. Whenever possible, particularly if the advancement is to be minor, a modification, as described by Hunsuck,58 where the lingual cortical aspect of the posterior border of the ascending ramus is preserved to the

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Figure 12.3 Maxillary advancement by Le Fort-l osteotomy.

proximal segment, is used (Figure 12.2b). This means that the attachments of the medial pterygoid muscles can be preserved. The proximal segments with the temporomandibular joints stay in place, and the distal toothbearing mandibular segment with the adjacent suprahyoid and genioglossal muscles is advanced. After proper positioning of the segments is achieved, fixation is accomplished by transoral bicortical positioning miniscrews. Originally developed for the correction of bite discrepancies (class II malocclusion), the amount of advancement is determined by the dental occlusion. For the surgical treatment of OSA, a mandibular advancement of at least 7–8 mm is mandatory, and we routinely perform mandibular advancement of 10 mm.

Maxillary advancement Maxillary advancement in patients with OSA can best be accomplished by Le Fort-I

Figure 12.4 Fixation of the mandibular segments is achieved by transoral bicortical mini-screws and fixation of the maxilla with miniplates at the piriform aperture and the zygomaticoalveolar buttresses.

Surgical principles and techniques osteotomy with the down-fracture technique59 (Figure 12.3). Via an intraoral approach, a subperiosteal mobilization exposes the maxillary pillars from the piriform aperture to the pterygopalatine fossa and the nasal floor. The piriform aperture, maxillary sinus walls, zygomaticoalveolar buttresses and nasal septum are osteotomized at the Le Fort-I level, and the tooth-bearing segment of the maxilla and the palatal plate down-fractured. After mobilization and advancement, fixation in the new position is achieved with miniplates at the piriform aperture and the zygomaticoalveolar buttresses (Figure 12.4). During the procedure, after down-fracture of the maxilla, additional nasal septal corrections can be performed very easily if necessary. In cases with normal dental occlusion (class I occlusion) (in our series more than 80% of the patients), maxillary advancement corresponds to

A A

C

B B

D

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mandibular advancement of 10 mm. In patients with class II malocclusion, maxillary advancement is arranged according to the planned correction of dental malocclusion. Nevertheless, maxillary advancement also considerably influences velopharyngeal muscle patency. Therefore, maxillary advancement should achieve at least 5–6 mm in these special cases.

Genioplasty In most cases (90% of our patients), maxillomandibular advancement is the only surgical intervention needed. In addition to mandibular advancement osteotomy, however, advancement of the genial tubercles with the adjacent genioglossal and geniohyoid muscles may support the effect of protrusion (Figure 12.5). Via an intraoral approach, a horizontal

Figure 12.5 Advancement of the genial tubercle (A,B) may support the effect of protrusion (C,D).

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sliding osteotomy of the chin is performed and the distal segment is advanced and fixed in the new position with wires or miniplates. In contrast to conventional esthetic genioplasty, the muscles must stay in place at the posterior mental spine. If cosmetic changes are not desired, a subapical window osteotomy of the mentum may be chosen with advancement of the posterior cortical table with the genial tubercle and the adjacent muscles only; the anterior cortical table and the cancellous bone is cut off to avoid chin augmentation, and the remaining cortical part is rotated and fixed with screws for proper tension of the muscles. Both procedures can be easily combined with maxillary and mandibular advancement if desired. In our series, genioplasty was only performed as a second-stage procedure in less than 10% of the patients, due to lack of success after primary maxillomandibular advancement. During surgery, muscles, ligaments and tendons attached to the jaw must be equally advanced and straightened. This results in a modification of pharyngeal and palatal muscles as well as lingual, genioglossal and suprahyoid muscles. Thus, the effectiveness of maxillomandibular advancement is most probably caused by tension of suprahyoid and velopharyngeal muscles, even if the additional place for the tongue and the enlarged posterior airway might have some importance.

Surgical treatment concepts Step-by-step surgery tends to look for isolated sites of obstruction which are surgically corrected in a first step. This means that patients with an isolated obstruction of the

velopharynx at the level of the soft palate receive a uvulopalatopharyngoplasty (UPPP),60 while patients with an obstruction at the base of the tongue undergo an anterior repositioning of the genioglossus muscle and the hyoid bone by chin advancement osteotomy and hyoid myotomy and suspension (GAHM). Patients with obstructions at both the velo- and hypopharynx undergo both procedures. With this ‘phase I surgery’ Riley et al60 reported a success rate (reduction of AHI by > 50%/AHI < 20 events/h) of more than 60% in 249 patients. The non-responders tended to be more obese and have more severe mandibular deficiency than the responders, and the likelihood of a response tended to be diminished with increasing preoperative AHI. Nevertheless, the reproducibility of such results remains to be confirmed. Other study groups worldwide have not been able to confirm these good results using phase I surgery, with a short-term follow-up success rate of less than 40%.61–64 After unsuccessful phase I surgery Riley et al60 recommend as a second step maxillomandibular advancement osteotomy, their success rate being 97%. Our concept is different.65,66 A success rate of 40–60% after phase I surgery for OSA means that every second patient had no benefit from this kind of surgery. In Europe, patients will not accept a surgical procedure with a 50% chance for success, if they have excellent conservative treatment alternatives. Furthermore, additional maxillary advancement as a second-stage procedure after UPPP may enhance possible side-effects and complications of UPPP, such as velopharyngeal insufficiency and nasal regurgitation. Whereas maxillomandibular osteotomy paradoxically leads to less complaints of pain than phase I surgery or UPPP, pain and unsuccessful results after first-step procedures adversely affect patients’ confidence and compliance.

Results In our experience, the advancement of the maxillomandibular complex should be at least 7–8 mm in the sagittal direction to be reliably effective. To be on the safe side, a sagittal advancement of the mandible of at least 10 mm should be attempted. In cases with extreme mandibular deficiency with class II bite discrepancy (more than 10 mm), mandibular advancement only may suffice for bite correction as well as for correction of OSA. In patients with predominantly dolichofacial appearance, counter-clockwise rotation of the maxillomandibular complex may support efficacy, due to further advancement of the genial tubercle with the adjacent suprahyoid muscles (the pogonion is advanced and rotated in a frontocranial direction). More advancement does not necessarily mean more efficacy. The main influence of skeletal advancement is less the mechanical enlargement of the maxillofacial complex (viscerocranium) than the functional influence on the upper airway muscles, which are stretched and straightened by advancement of their origins. In our opinion, velopharyngeal soft tissue resection should be reserved for secondary refinements in patients with OSA or for patients with primary snoring only.

Results Abolition of all obstructive events may be an ambitious goal and can not be guaranteed in every case. However, success must be defined as adequate reduction of the number of apneas, hypopneas and arousals down to a physiologic level comparable to the results with nCPAP therapy. Reduction of 50% of the events may not be enough, even if this reduction is significant. In our opinion postopera-

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60 AI AHI RDI

50 40 30 20 10 0

Pre-op

n = 54 CPAP

Post-op

1-yr Post-op

Figure 12.6 Results of maxillomandibular advancement in 63 consecutive patients with a 1-year follow-up compared to CPAP: RDI/AHI/AI (events/h).

tive AHI should be reduced to below 10 events/h or RDI below 20 events/h. Furthermore a physiologic profile of sleep stages should be re-established. Even more important are the subjective symptoms of the patients, such as daytime sleepiness etc.67,68 In properly selected patients with moderate or severe OSA, surgical maxillomandibular advancement yields a success rate of 90% without any further secondary corrections.65,66 Comparable results are also reported from other centers.13,60,61 In about 10% of our patients, additional surgical procedures (adenotonsillectomy, UPPP, genioplasty) were necessary. Our case series of 63 consecutive patients (4 women and 59 men), all with a preoperative AHI > 20/h, demonstrates the strategy and the results obtained (Figures 12.6–12.8). Preoperative median BMI was 27 kg/m2, with a range from 22 to 36 kg/m2. Preoperative mean SNB angle was 75°

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80

ST3/4

70 60

ST1/2

REM

50 40 30 20 10 0

Pre-op

n = 54 CPAP

Post-op

1-yr Post-op

Figure 12.7 Results of maxillomandibular advancement in 63 consecutive patients with a 1-year follow-up compared to CPAP: sleep stages 1/2, 3/4, and REM (%).

90 80 70 60 50 40 30 20 10 0

O2<90%

n = 60 Pre-op

O2-MIN

n = 54 CPAP

n = 60 Post-op

n = 53 1-yr Post-op

Figure 12.8 Results of maxillomandibular advancement in 63 consecutive patients with a 1-year follow-up compared to CPAP: minimal oxygen saturation (%)/sleep time (%) with oxygen saturation < 90%.

(SD ± 4°), and PAS (ML) 8 mm (SD ± 2 mm). Mean ML/NSL was preoperatively 35°, with a wide range (SD ± 7°), because most of the

patients were simply retrognathic and only some of them were classic dolichofacial. Fiftyseven of 63 patients had primary maxillomandibular advancement only, without secondary refinements such as UPPP or genioplasty; 12 of them had accompanying corrections of bite discrepancies. Of these 12 with correction of bite discrepancies, 1 had mandibular advancement only. For the other 11, maxillary advancement was within a range of 4–10 mm, and mandibulary advancement within a range of 10–15 mm. All other patients received simultaneous maxillomandibular advancement of 10 mm each (Figures 12.9 and 12.10 give examples of 2 patients). After these primary procedures, sufficient success with reduction of AHI below 10 was achieved at the immediate postoperative polysomnographic follow-up for 59 of the 63 patients. Four patients improved considerably but still had an AHI above 10. They all were treated by secondary procedures: 2 received both UPPP and genioplasty with additional advancement of the genial tubercle, 1 patient had genioplasty only, due to persistent obstructions at the hypopharyngeal level, and another patient had only UPPP combined with palatorrhaphy, due to persistent velopharyngeal obstructions. At long-term follow-up, 35 patients were followed for 5 years or more;69 2 further patients needed secondary corrections (1 isolated UPPP after 2 years and 1 with UPPP and genioplasty after 5 years).66,68 Comparison of pre- and postoperative polysomnographic findings suggests that most patients’ conditions clearly improved after surgery. Obstructive apneas occurred but sporadically. The results by surgery are comparable to the results under nCPAP therapy, which is offered to all our patients prior to surgery for at least 3 months.

Results

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C

A

B

F

D

E

I

G

H

Figure 12.9 Example of a patient before (A–C) and after (D–F) maxillomandibular advancement (10 mm), with a 9-year follow-up (G–I).

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Skeletal facial corrections Figure 12.10 (A,B) Example of a patient before and after maxillary advancement of 9 mm and mandibular advancement of 14 mm with simultaneous correction of class ll malocclusion.

A

B

Nevertheless, only 54 of the 63 accepted prior CPAP treatment. Regarding the 1-year followup results, OSA was clearly improved, as indicated by a postoperative AHI of less than 10/h in 61 of 63 patients. One case with a poor result was probably due to insufficient maxillary advancement of only 4 mm in extreme velopharyngeal obstruction. A second-stage procedure with UPPP and palatorrhaphy, due to persistent velopharyngeal obstructions, did improve the situation but did not yield sufficient success. Retrospectively, a further maxillary advancement would probably have been sensible in this case and could have saved velopharyngeal soft tissue reduction in this patient. The second failure was a patient with preexisting OSA, of very long duration, mainly mixed SRBD with long central and only short obstructive events at the end of the apnea. At immediate postoperative control, apneas disappeared and obstructions receded, but at the 1-year control, a considerable number of

central events remained. Obviously, this patient was not a good candidate for surgical treatment. The proportions of slow-wave sleep and percentage non-REM1 are closely associated with sleep quality and daytime alertness. A severe nocturnal breathing disorder is frequently associated with a strong reduction of slow-wave sleep and an increase in nonREM1. In the population presented here, the distribution of sleep stages was normal throughout the whole postoperative period (Figure 12.7). The alterations in the SaO2 saturation as well as the percentages of slowwave sleep indicate that the remaining obstructive respiratory events were not clinically relevant (Figure 12.8). Specific complications due to maxillary or mandibular osteotomy are well described in appropriate textbooks.59 Applying the principles of maxillary and mandibular osteotomy with advancement to the treatment of OSA should not create further complications. But it

Practical points should be kept in mind that OSA has potential cardiovascular side-effects (e.g. blood pressure rise). Whereas maxillary or mandibular osteotomy are normally applied in young, healthy patients, this may cause increased risk for bleeding out of the osteotomy site from the maxillary sinus. Therefore, maxillomandibular osteotomy in OSA should be performed under stationary conditions under immediate postoperative control with pulse oximetry during the first night; intensive care is not necessary. Definitive postoperative polysomnographic control should be postponed for at least 2 weeks until swelling has receded. Furthermore, mandibular advancement of 10 mm or even more is more than is normally needed to correct class II malocclusion. Therefore, temporary hypesthesia or paresthesia of the lower lip—a typical complication of mandibular osteotomy, even if temporary—seemed to occur more often (about 30%) and be more prolonged (3–6 months) in OSA patients compared to young patients with class II malocclusion.

Summary Prior to surgery, nocturnal assessment of respiratory and sleep parameters is crucial for a discrimination of existing SRBD and prior conditions for further therapy. Cardiorespiratory polysomnography allows an evaluation of whether nocturnal respiratory disturbances are associated with upper airway obstructions or are, rather, central in nature. Even short treatment of patients with a conservative therapy can also unmask existing central nervous respiratory regulation disorders. Additional investigations in the functional evaluation of pharyngeal properties (e.g. Pcrit measurement) may offer further help in the

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decision of whether to operate or not. In addition to cardiorespiratory polysomnography, there should be routine cephalometric evaluation of all patients with OSA. Under these conditions, we advocate—alternatively to conservative nCPAP ventilation— in patients with maxillary and especially mandibular deficiency or dolichofacial type, in combination with cephalometrically detectable pharyngeal narrowing, surgical treatment primarily by maxillomandibular advancement. A stepwise procedure as sometimes advocated—e.g. first UPPP and, if unsuccessful, then maxillomandibular advancement as a second-stage procedure—is not justified, in our opinion, in these cephalometrically selected patients. Owing to the selection criteria—retrognathia or dolichofacial type—maxillomandibular advancement often also improves the facial appearance of the patients. Under the assumption that the effectiveness of maxillomandibular advancement results from straightening of the suprahyoid and velopharyngeal muscles and tendons by advancement of their skeletal attachments, worsening over years might occur. Despite stable results at 5-year followup in 30 patients, with the exception of one patient, we do not know what will happen after 10 or 20 years. Long-term follow-up is absolutely essential.

Practical points 1. Examination and diagnosis of SRBD should also include cephalometric evaluation of the viscerocranium as a frequent cause of pharyngeal obstruction. Cephalometric evaluation, which is a cheap and simple diagnostic tool, must be mandatory at least prior to any surgical consideration.

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2. In addition to polysomnographic evaluation, testing of the daytime performance of the patients with respect to vigilance and daytime performance should be routinely established, especially for patients with surgical treatment. 3. Pharyngeal soft tissue resection (e.g. UPPP) with all its variations may be suitable treatment for snoring or even snoring with arousal, but is not advisable for the treatment of SRBD. Patients should be clearly informed that this kind of surgery for SRBD is experimental in humans, without a predictable outcome. 4. For patients with cephalometric evidence of certain craniofacial patterns such as a retrognathic or vertical dolichofacial type, surgical treatment of OSA by maxillomandibular advancement can be considered as a first treatment.

Research agenda 1. We know a lot about possible pathophysiological consequences of SRBD for blood pressure, but knowledge of the etiopathology of pharyngeal obstruction in SRBD is low. After the fundamental research by Renners et al70 in the late 1970s no basic research can be found in the literature on causes, mechanics and possible influences on pharyngeal obstruction during sleep. Further research, therefore, should focus on functional properties of the upper airway with special attention to the neurophysiological and muscular functions. Understanding the basic physiological mechanisms of pharyngeal patency or collapse during sleep will help to develop selective pharmacologic agents to stimulate the specific neuromuscular units for the upper airway.

2. At present, since maxillomandibular advancement is the surgical procedure with the highest success for the treatment of OSA, further research should investigate whether the indications for it should be restricted to selected cases with certain craniofacial characteristics (retrognathic or dolichofacial appearance) or spread to a larger group of patients.

References 1. Deegan PC, McNicholas WT. Pathophysiology of obstructive sleep apnea. Eur Respir J 1997;8:1161–78. 2. Deegan PC, McNicholas WT. Pathophysiology of obstructive sleep apnea. Eur Respir Monogr 1998;10:28–62. 3. Hochban W, Ehlenz K, Conradt R, Brandenburg U. Obstructive sleep apnoea in acromegaly: the role of craniofacial changes. Eur Respir J 1999;14:196–202. 4. Piecuch JF. Costocondral grafts to temporomandibular joints (abstract). Presented at the 60th Annual Meeting, American Association of Oral and Maxillofacial Surgeons, Chicago 1978. 5. Priest JH. Mandibular advancement for treatment of sleep apnea secondary to upper airway obstruction (abstract). Presented at the 60th Annual Meeting, American Association of Oral and Maxillofacial Surgeons, Chicago 1978. 6. Kuo PC, West RA, Bloomquist DS, McNeil RW. The effect of mandibular osteotomy in three patients with hypersomnia sleep apnea. Oral Surg Oral Med Oral Pathol 48;1979:385–92. 7. Bear SE, Priest JH. Sleep apnea syndrome: correction with surgical advancement of the mandible. J Oral Surg 38;1980:543–9. 8. Wittig R, Wolford G, Conway W et al. Mandibular advancement as a treatment of

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sleep apnea syndrome. Sleep Res 1983;12:296 (abstract). Riley RW, Powell NB, Guilleminault C, Nino-Murcia G. Maxillary, mandibular, and hyoid advancement: an alternative to tracheostomy in obstructive sleep apnea syndrome. Otolaryngol Head Neck Surg 1986;94;:584–8. Riley RW, Powell NB, Guilleminault C. Maxillofacial surgery and obstructive sleep apnea: a review of 80 patients. Otolaryngol Head Neck Surg 1989;101:353–61. Riley RW, Powell NB. Maxillofacial surgery and obstructive sleep apnea syndrome. Otolaryngol Clin North Am 1990;23:809–26. Riley RW, Powell NB, Guilleminault C. Maxillary, mandibular, and hyoid advancement for treatment of obstructive sleep apnea: a review of 40 patients. J Oral Maxillofac Surg 1990;48:20–6. Waite PD, Wooten V, Lachner J, Guyette RF. Maxillomandibular advancement surgery in 23 patients with obstructive sleep apnea syndrome. J Oral Maxillofac Surg 1989;47:1256–61. Veitch D, Rogers M, Blanshard J. Parapharyngeal mass presenting with sleep apnoea. J Laryngol Otol 1989;103:961–3. Stafford N, Youngs R, Waldron J, Baer S, Randall C. Obstructive sleep apnoea in association with retrosternal goitre and acromegaly. J Laryngol Otol 1986;100:861–3. Rodgers GK, Chan KH, Dahl RE. Antral choanal polyp presenting as obstructive sleep apnea syndrome. Arch Otolaryngol Head Neck Surg 1991;117:914–16. Jasper RD, Goldberg MH, Zborowski RG. Lymphangioma and cystic hygroma. Correction of facial growth disharmony and obstructive sleep apnea. Int J Oral Maxillofac Surg 1989;18:152–4. Herlihy JP, Whitlock WL, Dietrich RA, Shaw T. Sleep apnea syndrome after irradiation of the neck. Arch Otolaryngol Head Neck Surg 1989;115:1467–9.

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19. Goldman JM, Barnes DJ, Pohl DV. Obstructive sleep apnoea due to a dermoid cyst of the floor of the mouth. Thorax 1990;45:76. 20. Yoshizawa H, Nagao M, Nakano M et al. A case of malignant rheumatoid arthritis associated with obstructive sleep apnea due to mandibular lesions. Ryumachi 1991;31: 290–314. 21. Vila CN, Sanz JA, Robredo MB, Verdaguer MJJ, Monturiol RJM, Lopez AJM. Sleep apnea syndrome in an adult patient with mandibular hypoplasia. Int J Oral Maxillofac Surg 1988;18:32–4. 22. Valero A, Alroy G. Hypoventilation in acquired micrognathia. Arch Intern Med 1965;115:307–10. 23. Richter M, Chausse JM, Berner M. Sleep obstructive apnea syndrome and temporomandibular ankylosis. Maxillofacial correction for adults and children. Rev Stomatol Chir Maxillofac 1989;90:313–19. 24. Pollak PT, Vincken W, Munro IR, Cosio MG. Obstructive sleep apnea caused by hemarthrosis-induced micrognathia. Eur J Respir Dis 1987;70:117–21. 25. Colmenero C, Esteban R, Albarino AR, Colmenero B. Sleep apnoea syndrome associated with maxillofacial abnormalities. J Laryngol Otol 1991;105:94–100. 26. Kunkel M, Hochban W. Acoustic rhinometry: rationale and perspectives. J Cranio Maxillofac Surg 1994;22:244–9. 27. Horner RL, Shea SA, McIvor J, Guz A. Pharyngeal size and shape during wakefulness and sleep in patients with obstructive sleep apnoea. Q J Med 1989;72:719–35. 28. Hochban W, Brandenburg U. Morphology of the viscerocranium in obstructive sleep apneasyndrome—cephalometric evaluation of 400 patients. J Cranio Maxillofac Surg 1994;22:205–13. 29. Hochban W. Das obstruktive SchlafapnoeSyndrom: Diagnostik und Therapie unter besonderer Berücksichtigung craniofazialer Anomalien. Berlin: Blackwell-Verlag, 1995.

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30. Skatvedt O. Continuous pressure measurements during sleep to localize obstructions in the upper airways in heavy snorers and patients with obstructive sleep apnoea syndrome. Eur Arch Otolaryngol 1995;252:11–14. 31. Woodson BT, Feroah T, Connolly LA, Toohill RJ. A method to evaluate upper airway mechanics in snorers. Am J Otolaryngol 1997;18:306–14. 32. Boudewyns AN, Van de Heyning PH, De Backer WA. Site of upper airway obstruction in obstructive apnoea and influence of sleep stage. Eur Respir J 1997;10:2566–72. 33. Chaban R, Cole P, Hoffstein V. Site of upper airway obstruction in patients with idiopathic obstructive sleep apnoea. Laryngoscope 1998;98:641–7. 34. Wasicko MJ, Erlichman JS, Leiter JC. Control of segmental upper airway resistance in patients with obstructive sleep apnoea. J Appl Physiol 1993;74:2694–703. 35. Hudgel DW. Variable site of airway narrowing among obstructive sleep apnoea patients. J Appl Physiol 1986;61:1403–9. 36. Tvinnereim M, Miljeteig H. Pressure recordings. A method for detecting site of upper airway obstruction in obstructive sleep apnoea syndrome. Acta Otolaryngol (Stockh) 1991;492(suppl):132–40. 37. DeBerry-Borowiecki B, Pollack CP, Weitzmann ED, Rakoff S, Imperato J. Fibrooptic study of pharyngeal airway patency during sleep in patients with HSAH. Laryngoscope 1978;88:1310–13. 38. Crumley RL, Stein M, Gamsu G, Golden J, Dermon S. Determination of obstructive site in obstructive sleep apnea. Laryngoscope 1987;97:301–8. 39. Metes A, Hoffstein V, Mateika S, Cole P, Haight JS. Site of airway obstruction in patients with obstructive sleep apnea before and after uvulopalatopharyngoplasty. Laryngoscope 1991;101:1102–8. 40. Schwartz AR, Smith PL, Kashima HK, Proctor DF. Respiratory function of the upper

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References 51. Triplett WW, Lund BA, Westbrook PR, Olsen KD. Obstructive sleep apnea syndrome in patients with class II malocclusion. Mayo Clin Proc 1989;64:644–52. 52. Metes A, Direnfeld V, Haight JS, Hoffstein V. Resolution of obstructive sleep apnea following facial surgery. J Otolaryngol 1991;20:342–4. 53. Sultan MR, Coleman JJ 3rd. Salvage of successful mandibular advancement for obstructive sleep apnea using a bipedicle osteocutaneous scapular free flap. Ann Plast Surg 1991;27:61–5. 54. Hochban W, Hoch B. Obstructive sleep apnea in children: an interdisciplinary approach with special regard to craniofacial disorders. Pneumologie 1998;52:147–53. 55. Trauner R, Obwegeser H. The surgical correction of mandibular prognathism and retrognathia with consideration of genioplasty I. Oral Surg Oral Med Oral Pathol 1957;10:677–89. 56. Trauner R, Obwegeser H. The surgical correction of mandibular prognathism and retrognathia with consideration of genioplasty II. Oral Surg Oral Med Oral Pathol 1957;10:787–92. 57. Dal Pont G. Retromolar osteotomy for the correction of prognathism. J Oral Surg 1961;19:42–7. 58. Hunsuck EE. A modified intra-oral sagittal splitting technique for correction of mandibular prognathism. J Oral Surg 26;1968:249–52. 59. Bell WH, Proffit WR, White RP. Surgical Correction of Dentofacial Deformities. Philadelphia: WB Saunders, 1980. 60. Riley RW, Powell NB, Guilleminault C. Obstructive sleep apnea syndrome: a review of 306 consecutively treated surgical patients. Otolaryngol Head Neck Surg 1993;108:117–25. 61. Bettega G, Pépin JL, Veale D, Raphael B, Lévy P. Maxillofacial surgery for obstructive sleep apnea. Eur Respir J 1997;10(suppl):177S.

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62. Bittencourt LR, Palombini LO, Morgado P. Clinical and polysomnographic (PSG) findings in surgically treated patients with obstructive sleep apnea (OSA). Am J Respir Crit Care Med 1997;155:A677. 63. Hinkle RM, Berendts BP, Schmidt HS. Uvulopalatopharyngoplasty combined with genioglossus advancement and hyoid myotomy with suspension (UP3GAHM) for the treatment of OSA. Somnologie 1997;1(suppl):1–48. 64. Morgado PF, Gregório LC, Miranda SL, Bittencourt LR, Nery LE, Tufik S. Surgical treatment for obstructive sleep apnea: polysomnographic results of 50 patients submitted to the Stanford’s phase I technique. Somnologie 1997;1(suppl):1–51. 65. Hochban W, Brandenburg U, Peter JH. Surgical treatment of obstructive sleep apnea by maxillo-mandibular advancement. Sleep 1994;17:624–9. 66. Hochban W, Conradt R, Brandenburg U, Heitmann J, Peter JH. Surgical maxillofacial treatment of obstructive sleep apnea. Plast Reconstr Surg 1997;99:619–26. 67. Conradt R, Hochban W, Heitmann J, Cassel W. Sleep fragmentation and daytime vigilance in patients with OSA treated by surgical maxillomandibular advancement compared to CPAP-therapy. J Sleep Res 1998;7:217–23. 68. Conradt R, Hochban W, Brandenburg U, HeitmannJ, Peter JH. Long term results after surgical treatment of obstructive sleep apnea by maxillomandibular advancement. Eur Respir J 1997;10:123–8. 69. Hochban W, Conradt R, Heitmann J, Brandenburg U, Peter JH. 5–Jahresergebnisse nach chirurgischer Behandlung von OSA. Somnologie 1999;3(suppl1):25. 70. Isono S, Remmers JE. Anatomy and physiology of the upper airway obstruction. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine, Philadelphia: WB Saunders, 1994:642–56.

III Future advances

13 Radiofrequency tissue reduction Jonas T Johnson and Jack Gluckman

Introduction Circle

The use of radiofrequency (RF) in medicine and surgery has been applied to a variety of clinical situations in the last two decades. Low-voltage diathermy is used for uterine cervical curettage. RF was first used in the field of cardiology for ablation of aberrant conduction pathways in 1987. Transurethral devices are used today for management of prostatic hypertrophy. RF is also used for neuroablation in the management of pain disorders and for palliation of malignancies. The translation of this technology to otolaryngology seems natural. A computerized delivery system which monitors time, temperature and energy delivered was patented by Somnus Technologies, Sunnyvale, California, USA. The use of RF volumetric reduction of the soft palate for the treatment of mild sleepdisordered breathing and snoring was introduced in 1997. This technique employs an insulated needle which delivers high-frequency (300–1000 kHz) energy to the anesthetized soft palate. The heat delivered results in thermocoagulation, subsequent to which the treated area is absorbed and fibrosed. The heat is greatest near the electrode and reduces dramatically (the inverse of the radius to the fourth power) with increasing distance. Generally, the lesion is ellipsoid (Figure 13.1) Powell

B

Ellipse

A' A

A

B B'

Figure 13.1 The energy from radiofrequency is related to the distance from the source resulting in an ellipsoid area of tissue destruction. AA', major axis; BB', minor axis.

et al characterized the histologic findings in an animal model. Nerve tissue and vessels surrounding the RF-induced lesion remained viable, and a 26% tissue volume reduction was achieved when treating the tongue.1

Palatal radiofrequency reduction Investigators have employed RF volumetric reduction in treating the palate for socially

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unacceptable snoring. Coleman and Smith assessed the safety and efficacy of RF tissue reduction of the palate in a cohort of 12 healthy volunteers with socially disruptive snoring.2 A significant reduction in the level of snoring, as rated by the bed partner, occurred in all patients. An average of 2.3 treatment sessions was required. Post-treatment pain was considered absent or minimal in 11 of 12 patients and was managed with acetaminophen. These authors employed one midline tissue reduction at each procedure. An average energy of 693 J was employed at the first treatment. The second and third treatments averaged approximately 500 J. Hukins et al subsequently reported RF volume reduction of the palate in a cohort of 20 patients with simple snoring or mild obstructive sleep apnea (OSA) (apnea– hypopnea index of ) 15).3 Eighteen of 20 patients reported improvement in subjective snoring; however, only 8 patients reported an improvement of at least 50%. Adverse effects of treatment included mucosal ulcers, which developed in 3 patients. These authors employed three RF treatments to the soft palate at intervals of at least 2 weeks. Six hundred and fifty joules were delivered to the midline of the soft palate and areas described as proximal, middle and distal thirds of the soft palate. The authors observed that reductions in snoring following treatment of the middle and distal thirds of the soft palate were more commonly observed, and this seemed to indicate that the thinner free edge of the palate was more responsive to therapy. Treatment of the thinner distal soft palate was, however, more commonly associated with mucosal burn and complaints of subjective pain. Li et al reported extended follow-up in a cohort of patients treated with RF volumetric reduction of the palate.4 Twenty-two patients were evaluated for a mean of 14 months

following treatment. Subjective snoring scores relapsed by 29% overall. These patients had received a mean of 3.6 treatment sessions per patient. The total energy administered per patient was 688 J ± 106 per treatment session (total 2377 ± 869 J per patient). Eight of nine patients with relapse of snoring underwent further RF treatment, and a statistically significant reduction in snoring was reported in this retreated group of patients.

Indications RF is primarily indicated for the outpatient management of non-apneic snoring. We and others have observed success in the treatment of patients with mild to moderate OSA. In either case, success seems to be predicated upon correct identification of the palate as a site of obstruction and/or snoring. Selection of patients for volumetric reduction of palatal tissue aimed at the relief of socially unacceptable snoring remains problematic. Fiberoptic nasopharyngoscopic evaluation undertaken during wakefulness is of limited use. Sleep nasoendoscopy may have some promise as a technique to localize snoring. Quinn et al reported that noise generation at a site other than the soft palate may be observed in as many as 30% of adult snorers.5 This observation may explain the variability in clinical response to palatal soft tissue reduction. Patients with snoring attributable to non-palatal sources would not be expected to improve with palatal treatment.

Technique RF reduction of the soft palate is an outpatient procedure undertaken with local anesthesia. Preliminary mouthwash with an antimicrobial

Palatal radiofrequency reduction

Tonsil

+

+

Uvula

+

Soft palate

Tongue

Figure 13.2 Most authors recommend that the palate be treated along its distal edge. The treatment should not be given directly into the uvula. solution and application of topical anesthetic is undertaken. The patient is comfortably positioned in the treatment chair, and 1% lidocaine is infiltrated submucosally into the

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middle and distal third of the soft palate in the areas to be treated (Figures 13.2, 13.3). In general, the administration of 3–5 cm3 of lidocaine is advocated. This serves to give effective anesthesia. Additionally, the volume of infiltrate seems to distend the palate, reducing the risk of an inadvertent mucosal thermal burn. The ideal technique of energy administration is in a state of evolution. Response to RF is probably related to total energy delivered (in joules) and the location of the lesion. Lesions placed nearer the distal third of the palate may be more effective.3 The lesion should not be placed directly into the uvula or at the base of the uvula where it joins the palate. This results in venous and lymphatic obstruction in the uvula, resulting in massive edema and, in some cases, complete sloughing of the uvula. Placement of the lesion in close proximity to the mucosa results in a painful mucosal burn. A transmural lesion may result in a through-and-through palatal fistula. The optimum time for reassessment and retreatment is unclear. A minimum of 1 month seems necessary before the need for retreatment can be evaluated. Response to therapy in

Figure 13.3 Administration of radiofrequency to a lesion in the soft palate. The necrotic area is subsequently reabsorbed, resulting in tissue fibrosis and shrinkage of the length of the soft palate.

216

Radiofrequency tissue reduction

terms of fibrosis and reabsorption of treated tissue may take up to 3 months.

Radiofrequency tongue base reduction A prospective non-randomized trial of RF reduction of tongue base tissue was reported by Powell et al.6 All had failed palatal surgery for OSA and had residual OSA. Detailed physical examination and cephalometry suggested a residual tongue base component of obstruction. Volumetric MRI scanning was performed before and after therapy. Treatments were undertaken with local anesthesia. Each treatment consisted of RF administration to two sites near the circumvallate papillae separated by 1.5–2.0 cm. Treatment intervals were spaced at a minimum of 3 weeks. RF was delivered for a mean of 270 s at 465 kHz. Patients received a total treatment time of 15–20 min. Polysomnographic data were recorded prior to treatment and after completion of therapy. Eighteen patients completed the study. The mean time from the first treatment until completion of therapy was approximately 28 weeks. The final evaluation occurred 12–30 weeks after the final treatment. The 18 patients underwent 99 treatment sessions, with a mean of 1.82 lesions produced per session. The mean number of sessions was 5.5, and the mean energy delivered was 1543 J at each session. Cumulative total energy for each subject at completion was 8494 ± 2687 J. Three patients with very severe sleep apnea received a mean cumulative total of 10 849 ± 3436 J of energy. Comparative MRI scans were available for 14 patients. These demonstrated a mean reduction in tongue volume of 17.4 cm3. Three

adverse events were reported during the course of this study. Two were mild and self-limiting, but one patient developed infection of the tongue base requiring tracheotomy with incision and drainage. Sleep studies demonstrated a reduction in the respiratory disturbance index (RDI) of 55% (mean apnea index was reduced from 39.5 to 17.8). In 7 of the 18 patients, the final RDI was less than 10 and these patients were judged to be cured. The authors speculate that additional cumulative energy may have improved the cure rate in the other patients. Speech, swallowing and taste were assessed on a visual analog scale before and after therapy and were judged to be unchanged. All patients had some pain following each individual session requiring therapy for 3–4 days post-treatment.

Indications These data were presented to the Food and Drug Administration (FDA) and resulted in the approval of the somnoplasty device for the treatment of OSA due to tongue base obstruction (November 1998). It is indicated for OSA attributed to tongue base collapse compromising the retrolingual space. The ideal site, size and frequency of lesion application are under investigation. In their preliminary report, Powell et al suggested a mean total energy of 8500 J where necessary. Our subsequent experience suggests that many patients may require twice that much energy.

Technique The procedure is undertaken in the outpatient setting, with the patient comfortably

+ + +

+ + +

+ + +

Radiofrequency tongue base reduction

Figure 13.4 Tongue base lesions are distributed in the midline and paramedian positions around the area of the circumvallate papillae. An effort is made to avoid retreatment of the identical spot from month to month.

seated in an upright position. Pretreatment with an antimicrobial mouthwash and topical anesthetic may be appropriate. One per cent lidocaine is infiltrated into the tongue base in the area of the circumvallate

217

papillae in the areas to be treated. Two to four lesions of 800/1000 J each are administered at each setting. Treatments are spaced a minimum of 4 weeks apart. An effort is made to record the site of each treatment, to avoid retreating identical sites (Figure 13.4). The treatments are administered in the midline and paramedian positions (Figure 13.5). Mucosal burns are probably related to lesions created in a superficial location. All patients experience some moderate posttreatment pain which lasts 7–10 days and is effectively relieved with acetaminophen or acetaminophen plus codeine. Topical application of ice or ice water seems to be helpful immediately after treatment. Significant tongue edema is rarely observed, and hospitalization seems unnecessary. Tongue base abscess, which develops at the site of the lesion, has been rarely observed, but is a potential complication necessitating that patients be informed of the signs and symptoms (swelling and pain with dysphagia) and provided with ready access to the physician’s office. Treatment may require hospitalization, antibiotics with incision and drainage, plus or minus tracheotomy.

Figure 13.5 This diagram demonstrates how radiofrequency to a lesion in the tongue results in an area of coagulative necrosis. This area is subsequently reabsorbed, resulting in tissue shrinkage and fibrosis of the tongue.

218

Radiofrequency tissue reduction

Conclusion

References

RF tissue reduction for OSA is an intriguing and appealing alternative for some patients presenting with symptomatic sleep disordered breathing attributable to excessive length or floppiness of the soft palate, or redundant soft tissue in the tongue base compromising the retrolingual space. The technique is associated with relatively minor discomfort and only occasional side-effects, most of which are mild and self-limiting. Abscess associated with tissue necrosis has been reported, and may require incision and drainage with concurrent airway support. The technique of RF soft tissue reduction requires multiple treatment sessions. Assessment of success is complicated by surgeons’ inability to accurately localize the site of obstruction in all patients. This and similar tissue reduction approaches will continue to be the source of much investigation in the near future.

1.

2.

3.

4.

5.

6.

Powell NB, Riley RW, Troell RJ et al. Radiofrequency volumetric reduction of the tongue. A porcine pilot study for the treatment of obstructive sleep apnea syndrome. Chest 1997;111:1348–55. Coleman SC, Smith TL. Midline radiofrequency tissue reduction of the palate for bothersome snoring and sleep-disordered breathing: a clinical trial. Otolaryngol Head Neck Surg 2000;122:387–94. Hukins CA, Mitchell IC, Hillman DR. Radiofrequency tissue volume reduction of the soft palate in simple snoring. Arch Otolaryngol Head Neck Surg 2000;126: 602–6. Li KK, Powell NB, Riley RW, Troell RJ, Guilleminault C. Radiofrequency volumetric reduction of the palate: an extended followup study. Otolaryngol Head Neck Surg 2000;122:410–4. Quinn SJ, Daly N, Ellis PD. Observation of the mechanism of snoring using sleep nasendoscopy. Clin Otolaryngol 1995;20:360–4. Powell NB, Riley RW, Guilleminault C. Radiofrequency tongue base reduction in sleep-disordered breathing: a pilot study. Otolaryngol Head Neck Surg 1999;120:656–64.

14 Hypoglossal nerve stimulation for the treatment of obstructive sleep apnea Lennart Knaack and Walter Hochban

Introduction Although it has been demonstrated that obstructive sleep apnea (OSA) is influenced by specific anatomic properties, craniofacial characteristics and body mass index (BMI), it remains unclear how these mechanisms mediate upper airway (UA) collapse during sleep. It has been generally accepted that UA collapse is a consequence of a disordered neuromuscular coordination of the pharynx in patients with OSA. Neuromuscular coordination of pharyngeal musculature depends on the sleep–wake state. During sleep, neuromuscular control mechanisms (phasic and tonic activities) coordinate the requirements of numerous muscle groups in order to maintain respiratory function.1–4 The genioglossus is the major muscle of the tongue base, and spans a large portion of the anterior pharyngeal wall. Several studies indicate that unilateral genioglossal protrusion might improve pharyngeal patency by lowering UA collapsibility. Recently, it has been demonstrated that electrical stimulation of the distal branch of the hypoglossal nerve can be employed to protrude the tongue via a contraction of the genioglossus muscle.

The effect of upper airway muscle activity on airway patency The UA consists of multiple muscles which are involved in neuromuscular respiratory coordination. Inspiration consists of a well-coordinated muscle activation beginning with activation of the palatal musculature and extending more caudally to the oropharynx, the hyoid and the larynx.5 UA collapse in OSA is variable and extends to different portions of oral, pharyngeal and laryngeal anatomic segments.3,6,7 Static and dynamic techniques, such as a CT scan or multilumen catheter measurements, can be employed to detect the variable sites of UA collapse.8–14 While some studies have demonstrated that the site of collapse is located predominantly in the lower pharynx, others have found the collapse to be retropalatal or retroglossal. Shepard and Thawley showed that 78% of patients with OSA developed a retroglossal collapse in REM sleep.10 A relapse of the tongue due to decreased muscular tone of the genioglossus muscle during sleep can occlude the retroglossal oropharynx.14 Although data of Isono and coworkers

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Hypoglossal nerve stimulation

indicated UA stiffening and widening following coactivation of tongue-protruding (genioglossus) and -retracting (styloglossus and hyoglossus) muscles, the effects of simultaneous activation of these upper airway antagonists are controversial.15 It has been generally accepted that unilateral activity of the genioglossus protrudes the tongue and dilates the pharyngeal airway. The genioglossus is innervated by the distal branch of the twelfth cranial motor nerve (N. hypoglossus). Several studies have investigated the effects of electrical stimulation of the UA muscles and function by contracting the muscle directly or via nerve stimulation.16–23

Electrical neuromuscular stimulation of upper airway muscles Mikki et al reported that cutaneous functional electrical stimulation (FES) in the submental region reduced the number and length of sleepdisordered breathing events in humans.24 Although this investigation had several methodologic problems, it demonstrated the possible usefulness of electrical stimulation in the management of OSA. Edmonds et al investigated the effects of transcutaneous electrical stimulation (TES) in the submental and subhyoid region in order to increase UA dilator muscle tone.25 Both studies showed that the method of TES was not selective enough to activate UA dilating muscles and required a stimulation intensity that provoked arousal throughout the night, independent of sleep stage. The observation that genioglossus activation dilates the pharyngeal airway and decreases both UA collapsibility and resistance26 raised interest in developing therapeutic electrical

stimulation. To overcome the effects of stimulation-induced arousals, Decker et al developed a protocol for percutaneous placement of finewire electrodes using a needle placement method. This technique comprised the placement of fine wire electrodes near the neurovascular bundle of the hypoglossal nerve (controlled by axial tomography (CAT) scan). Their investigation demonstrated that FES could produce tongue protrusion, but with an unpredictable increase in the size of the oropharynx, which reflects the fact that neither surface nor fine wire stimulation had a consistent effect in terminating OSA during sleep.27 Although several studies have suggested that various muscles control airflow dynamics in the UA, the genioglossus muscle plays a major role in maintaining UA patency. Schwartz and Rowley investigated the influence of hypoglossal nerve stimulation on UA resistance and collapsibility in a feline model of an isolated upper airway.26,28,29 To estimate the effectiveness of electrical stimulation of the distal hypoglossal nerve, Schwartz et al analyzed critical pharyngeal closing pressure (Pcrit) and resistance to the site of the collapsing airway (Rus) during bilateral hypoglossal nerve stimulation over a range of frequencies from 0 to 100 Hz. Their findings were that proximal hypoglossal nerve stimulation did not improve airflow or Pcrit, whereas, stimulation of the distal hypoglossal branch provoked tongue protrusion, thereby lowering UA collapsibility and improving maximum inspiratory airflow (Vimax). So far, electrical stimulation of the genioglossus transcutaneously or with intraorally applied electrodes has been of questionable value, lacking muscular selectivity. Furthermore, it is unclear whether electrical stimulation had caused cortical arousal that might be responsible for the re-establishment of airway patency.

Approaches for clinical treatment of OSA Schwartz, Smith and coworkers investigated OSA patients with a new protocol to exclude these factors.16–18 The aim of the study was to quantitatively investigate UA function (Pcrit and Rus) during electrical stimulation and to control sleep quality while neuromuscular stimulation was performed. Therefore, UA resistance and airflow were measured under conditions with or without electrical stimulation of tongue-protruding and -retracting muscles (hyoglossus, styloglossus and genioglossus). To improve muscular selectivity, intraoral intramuscular electrodes were applied to the patients. UA parameters were recorded under variable stimulation parameters, such as amplitude (voltage), frequency and pulse width. It was clearly demonstrated that, compared to prior studies, lower motor thresholds were needed to obtain muscular responses during electrical stimulation. In addition, these patients maintained a good sleep quality with a lower number of cortical arousals during electrical stimulation. In summary, the investigators found that anteriorly placed electrodes (fixed in the belly of the genioglossus) protruded the tongue, thereby improving airflow and lowering Pcrit in OSA. Posteriorly placed electrodes activated the styloglossus and hyoglossus and retracted the tongue. This retraction impaired UA function, by increasing Pcrit and decreasing inspiratory airflow during sleep. These preliminary data suggest that electrical stimulation of the UA might be potentially effective for the treatment of OSA.16–18

Approaches for clinical treatment of OSA Preliminary experiments indicated that a half-cuff electrode placed directly on the

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hypoglossal nerve improves airflow to a level of ~400 ml/s.16 Eisele et al investigated the effect of direct hypoglossal nerve stimulation in patients with OSA.19 To determine the motor responses resulting from direct electrical stimulation of the hypoglossal nerve, they investigated 15 patients who were undergoing a surgical procedure for cancer resection that involved exposing the hypoglossal nerve (n = 10) and normal volunteers (n = 5). The investigators alternately stimulated the main trunk, which supplies tongue retractor muscles, and the distal branch, which selectively innervates the genioglossus, by using a half-cuff tripolar electrode. It was demonstrated that stimulation of the distal branch caused tongue protrusion, whereas stimulation of the main trunk had no effect on maximal inspiratory airflow. The arousal threshold for stimulation exceeded the motor recruitment threshold by 0.8 ± 0.4 V. As a result of stimulation, inspiratory airflow increased in all patients by 184.5 ± 61.7 ml/s. The authors surmised that direct hypoglossal nerve stimulation might improve airflow in patients with OSA without affecting sleep quality.19 Based on experiences from phrenic nerve stimulation, these findings initiated scientific effort to develop an implantable electrode which can be fixed around the distal branch of the hypoglossal nerve to stimulate the nerve in synchronization with respiratory parameters. Whereas preceding studies investigated the acute effects of electrical stimulation on UA function, Podszus et al published data about the first patient with a chronically implantable electrode.20,21 They used an intermittently stimulating system (Inspire I: Medtronic Inc., Minneapolis, MN, USA) and also included a radiofrequency receiver and a pulse wave generator, which induces phasic electrical stimuli to the nerve. Stimulation was also

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Hypoglossal nerve stimulation

performed during inspiration (30 Hz, pulse width 100 µs, burst duration 1.5–2 s). Electrical bursts were synchronized to the onset of inspiration, utilizing inductive plethysmography. This method generated signals of respiratory belts which were conducted to the radiofrequency receiver. Sustained increases in airflow were achieved during stimulation for a period of more than 1 h. Airflow responses were greatest when electrical bursts preceded or coincided with inspiratory onset during permanent stimulation. O’Hearn et al also implanted an identical system in one patient.22 Stimulation was performed during non-REM sleep. In comparison to the baseline data, the apnea–hypopnea index (AHI) decreased from 92 to 17 events per hour. Vimax improved from 0 to 308 ± 22 ml/s, and Pcrit as a measure of UA collapsibility decreased from +1.6 ± 0.7 to –3.9 ± 1.0 cmH2O, whereas UA resistance was not affected. Although the data demonstrated the potential feasibility of electrical stimulation of the genioglossus and its stabilizing effect on UA patency, it has been shown that respiratory synchronization is susceptible to movement artifacts and positional maneuvers during sleep, when respiratory belts were employed to detect the onset of inspiration. Therefore, new methods had to be developed to improve respiratory sensing to coordinate electrical bursts with inspiration.

Hypoglossal nerve

Lead

Stimulation

Sensor Lead

Stimulator Connector

Figure 14.1 The Inspire I hypoglossal nerve-stimulating system developed for the treatment of obstructive sleep-disordered breathing works as follows. Respiratory pressure swings (piezo pressure sensor) are monitored and conducted via a sensing lead to the pulse generator. After analyzing respiratory waveforms, electrical bursts are generated, synchronized with the onset of inspiration. The electrical stimuli are conducted via a lead and an electrode to the distal hypoglossal nerve.

The implantable hypoglossal stimulating device

breathing when it is synchronized with the onset of inspiration. Therefore, a hypoglossal pacemaker device has been developed, which contains a piezo pressure sensor to detect respiratory pressure swings (Figure 14.1). The implantable pacemaker device (Inspire I) consists of three components (Figure 14.2):

Previous studies indicated that electrical stimulation of UA airway muscles only effectively reduces obstructive sleep-disordered

1. The pressure sensor. 2. The programmable pulse-generating system. 3. The impulse-conducting tripolar electrode.

The implantable hypoglossal stimulating device

Figure 14.2 Fully implantable pacemaker system (Inspire I).

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The piezo pressure sensor is implanted in the sternum, where it monitors intrathoracic pressure during the respiratory cycle (Figure 14.3). The pulse-generating system contains a threshold detector to monitor the inspiratory onset. A programmable algorithm is implemented to detect the slope changes of the respiratory waveform (intrathoracic respiratory pressure swings) in order to detect expiratory onset. The parameters of this sensing system are used for the timing of electrical bursts, which are delivered synchronized to the onset and entire duration of the inspiratory phase. Electrical burst parameters are programmable for voltage amplitude, pulse width and frequency. The pulse-generating system contains a power source and is programmable via telemetry, which allows the adjustment of sensing and stimulating parameters. The electrical impulses are delivered via a

Figure 14.3 Printout of respiratory pressure swings (undisturbed waveform). Arrows indicate period of respiratory synchronized electrical stimulation.

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Hypoglossal nerve stimulation

Figure 14.4 Schematic illustration of the half-cuff electrode and a cross-sectional image of the hypoglossal nerve.

lead ending in a half-cuff silicone tripolar electrode wrapped around the hypoglossal nerve (Figure 14.4). The patient uses a selfcontrolled programmer to initiate or terminate electrical stimulation at will. A preset delay function of 0–30 min allows the patients to fall asleep before electrical stimulation starts to protrude the tongue.

Surgical procedure

the hypoglossal nerve divides inconsistently into 2–5 branches. Stimulation of the more proximal trunk of the hypoglossal nerve is not of value, because stimulation of innervation to the pharyngeal muscle complex and the styloglossal or hyoglossal muscles may provoke pharyngeal closure instead of opening. Detaching and undermining the nerve over a distance of 10 mm allows the cuff to be wrapped around the nerve (Figure 14.5). At this stage, the correct placement of the electrode and its effectiveness concerning tongue protrusion must be tested by stimulation demonstrating that the pharynx is not occluded. To prevent secondary dislocation during movement, the cuff and the lead are secured with sutures. 2. A second incision is made at the upper end of the manubrium sterni. The pressure transducer is inserted into a fossa carefully erected by dissecting the posterior layer of the manubrium subperiosteally, taking care not to injure the great vessels (Figure 14.6). The pressure sensor is prevented from being displaced with a small titanium screw or wire fixation.

The surgical procedure for the implantation of the device consists of three steps: 1. The distal portion of the hypoglossal nerve has to be prepared for placement of the tripolar electrode cuff. This can be easily achieved via a submandibular incision. Beneath the submandibular gland, the hypoglossal nerve can easily be identified under the digastric muscle. Retracting the mylohyoid muscle, the distal portion of the nerve divides into one or two major and 2–4 minor divisions. Careful dissection is essential to avoid bleeding from the ranine vein and to prevent damage to the nerve. Cadaver dissections have demonstrated that

Figure 14.5 Exposed hypoglossal nerve encoded by the half-cuff electrode.

Surgical procedure

A

225

A Sensor

Anchor Manubrium

Manubrium Sensor Brochiocephaic

Anterior side

Posterior side

Sternum

B Figure 14.6 (A) Piezo pressure sensor inserted into the sternum. (B) Schematic illustration of the pressure sensor, anchored into the upper part of the manubrium sterni.

B Figure 14.7 (A) Infraclavicular pocket for the pulse generator. (B) Pulse generator (Inspire I).

3. Finally, an infraclavicular subcutaneous suprapectoral pocket is created to place the pulse-generating device, which is connected subcutaneously to the hypoglossal nerve electrode and to the pressure sensor in the sternum with thin leads (Figure 14.7). All the leads are coated with silicone and secured to the tissue to allow free mobility.

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Hypoglossal nerve stimulation

Clinical outcome of chronic hypoglossal nerve stimulation To evaluate the outcome of the surgical procedure, technical feasibility, effects of electrical stimulation on UA function and clinical results, patients were included in a standardized protocol consisting of baseline and frequent follow-up sleep studies. After physical recovery and healing, an initial sleep study was performed to set electrical parameters and to adapt the patients to chronic electrical stimulation. Subsequent sleep studies were performed to verify technical settings and to perform polysomnographic and clinical investigations.

Technical outcome In general, the first follow-up 4 weeks after surgery demonstrated that respiratory sensing, impulse generation and electrical transmission worked effectively. Telemetric data on the pressure sensor mostly showed physiologic respiratory waveforms. In some cases, the pressure sensor signal occasionally showed waveform disturbances, which were associated with a dissociation of electrical bursts and inspiratory onset. In some cases, waveform artifacts did not generate electrical impulses, and therefore did not stimulate isolated breaths (Figure 14.8). Presumably, these phenomena were generated or affected by sleep posture, sleep stage-dependent breathing pattern (REM) or cardiac artifacts. Further follow-up showed that electrical parameters had to be adjusted. For instance, the motor threshold shifted between the range from 2.8 V to 3.2 V. It was speculated whether connective tissue growth between the nerve

Figure 14.8 Polysomnographic data with (on) and without (off) electrical stimulation. Electrical stimulation improves upper airway function, which is indicated by improvement of airflow during stimulation (on).

and the electrode or electrode damage caused this shift. In contrast, one electrode that was removed after mechanical damage that fractured the middle part of the tripolar cuff did not show significant connective tissue ingrowth between the cuff and the exposed hypoglossal nerve. In the feasibility study (n = 8) for Inspire I, malfunction of two pulse generators, one sensor shut down and electrode failure, was reported.

Clinical results The major finding of this feasibility study was that unilateral hypoglossal nerve stimulation markedly reduced sleep-disordered breathing in patients with OSA (Figure 14.8). The reduction was effective in both, non-REM and REM sleep. Neither the mechanical tongue protrusion nor the electrical burst affected sleep quality significantly. As a result of improved

Therapeutic perspective for the future? sleep quality, slow-wave sleep increased significantly compared to baseline sleep studies. The electrical parameters (amplitude, pulse frequency and pulse width) did not affect motor function of the tongue during daytime. All patients felt comfortable after surgery, and no infection, bleeding or nerve damage occurred. Intraoperative complications (injury to major vessels or damage to the nerve) did not occur. As a foreign body is inserted, the risk of infection should be kept to a minimum; surgery should be performed under careful aseptic conditions. Animal studies demonstrated in one case increased scarring around the electrode cuff placed at the hypoglossal nerve, thus extruding the nerve out of the cuff of the electrode, and necessitating increased stimulation thresholds. Nevertheless, this has not been observed in any of the patients treated so far. As further long-term follow-up has become available, no further side-effects have been noticed. Unexpected growth of the genioglossus muscle did not occur. Although clinical results demonstrated significant effects of unilateral hypoglossal nerve stimulation on UA patency, unexpected factors, such as the influence of sleep posture and sleep stages, impaired the effectiveness of chronic neuromuscular stimulation. For instance, in one patient, obstructive sleep-disordered breathing was totally abolished while sleeping on the side, whereas when the patient was lying on his back, apnea activity remained nearly unaffected. This patient presented different effects of electrical stimulation in the supine compared to the side sleep posture in all follow-up sleep studies. While lying on his side, maximum inspiratory airflow improved by between 100 and 250 ml/s, whereas in the supine position, airflow improvement was less than 50 ml/s. To quantify the potential therapeutic effects on UA function with and without electrical

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stimulation, we calculated Pcrit (critical pharyngeal closing pressure) as a measure of UA collapsibility during sleep. The mean Pcrit in the supine sleep position was lowered from +2 cmH2O to +0.7 cmH2O thereby indicating no therapeutic effect in this sleep posture under atmospheric pressure levels. In the side body position, the mean Pcrit was lowered from –0.8 cmH2O to –3.5 cmH2O, demonstrating a clinical improvement of inspiratory airflow under atmospheric conditions. The Sleep Disorders Center of the Johns Hopkins University has shown that electrical stimulation improves the Pcrit non-REM and supine sleep posture in a range between 3 and 5 cmH2O.22 It has been demonstrated that, independent of sleep stage, unilateral chronic electrical stimulation of the distal hypoglossal nerve reduces the AHI by about 75% of the baseline indices (n = 8) (unpublished data).

Therapeutic perspective for the future? Current results of the feasibility study indicate that unilateral neuromuscular stimulation of the genioglossus muscle might be effective as an alternative treatment of OSA. It has been demonstrated that the implantable system, acting as a respiratory synchronized genioglossus pacemaker, improves UA collapsibility, thereby reducing sleep-disordered breathing. It should be the aim of further investigations to improve the technical and clinical efficiency of this novel method as a potential alternative treatment. Specific criteria for patient selection must be defined. Further studies should implement functional and static investigation of the upper airway. Recently published results of Pcrit measurements prior to and during electrical stimulation of the genioglossus provide

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Hypoglossal nerve stimulation

evidence that patients with moderate collapse might benefit from electrical stimulation, whereas severely obese patients are not eligible. On the other hand, dynamic techniques (e.g. esophageal multilumen catheter and the assessment of pharyngeal pressure–area measurements) and static techniques (e.g. cephalometry, CT scan) provide us with information about UA dimensions and the possible role of the genioglossus muscle in the pathogenesis of UA collapse for each patient. Furthermore, it should be investigated how electrical stimulation influences UA properties and shape in all sleep stages and body positions and in patients with different UA dimensions.30,31

References 1. Schwartz AR, Smith PL, Kashima HK, Proctor DF. Respiratory function of the upper airways. In: Murray JF, Nadel JA eds. Textbook of Respiratory Medicine, 2nd edn. Philadelphia: WB Saunders, 1994:1451–70. 2. Horner RL. Motor control of the pharyngeal musculature and implications for the pathogenesis of obstructive sleep apnea. Sleep, 1996;19(10):827–53. 3. Hudgel DW, Surratt P. The human airway during sleep. In: Saunders NA, Sullivan CE, eds. Sleep and Breathing, 2nd edn. New York: Marcel Dekker, 1994:191–208. 4. Schwartz AR, Schubert N, Rothman W et al. Effect of uvulopalatopharyngoplasty on upper airway collapsibility in obstructive sleep apnea. Am Rev Respir Dis 1992;145:527–32. 5. Strohl KP, Hensley MJ, Hallet M, Saunders NA, Ingram RH Jr. Activation of upper airway muscles before onset of respiration in normal subjects. J Appl Physiol 1980;49:638–42.

6. Isono S, Remmers JE. Anatomy and physiology of the upper airway obstruction. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine, Philadelphia: WB Saunders, 1994:642–56. 7. Hudgel DW. Variable site of airway narrowing among obstructive sleep apnoea patients. J Appl Physiol 1986;61:1403–9. 8. Boudewyns AN, Van de Heyning PH, De Backer WA. Site of upper airway obstruction in obstructive apnoea and influence of sleep stage. Eur Respir J 1997;10:2566–72. 9. Pépin JI, Ferreti G, Veale D et al. Somnofluoroscopy, computed tomography and cephalometry in the assessment of the airway in obstructive sleep apnoea. Thorax 1992;47:150–6. 10. Shepard JW, Thawley SE. Localisation of upper airway collapse during sleep in patients with obstructive sleep apnoea. Am Rev Respir Dis 1990;141:1350–5. 11. Chaban R, Cole P, Hoffstein V. Site of upper airway obstruction in patients with idiopathic obstructive sleep apnoea. Laryngoscope 1988;98:641–7. 12. Tvinnereim M, Miljeteig H. Pressure recordings. A method for detecting site of upper airway obstruction in obstructive sleep apnoea syndrome. Acta Otolaryngol (Stockh) Suppl 1991;492:132–40. 13. DeBerry-Borowiecki B, Pollack CP, Weitzmann ED, Rakoff S, Imperato J. Fibrooptic study of pharyngeal airway patency during sleep in patients with HSAH. Laryngoscope 1978;88:1310–13. 14. Günther E, Jäger L, Kastenbauer E, Resier M. Fast functional MRI and polysomnography in OSA patients: a new approach to obstruction detection? In: Ribári O, Hirschberg A, eds. 3rd European Congress of the European Federation of Oto-Rhino-Laryngological Societies EUFOS. 1996:295–9. 15. Isono S, Tanaka A, Nishino T. Effects of tongue electrical stimulation on pharyngeal mechanics in anaesthetized patients with

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obstructive sleep apnoea. Eur Respir J 1999;14:1258–65. Schwartz AR, Eisele DW, Hari A, Testerman R, Erickson D, Smith P. Electrical stimulation of the lingual musculature in obstructive sleep apnea, J Appl Physiol 1996;81(2):643–52. Smith PL, Eisele DW, Podszus T et al. Electrical stimulation of upper airway musculature. Sleep 1996;19(10):284–7. Eisele DW, Schwartz AR, Hari A, Thut DC, Smith PL. The effects of selective nerve stimulation on upper airway airflow mechanics. Arch Otolaryngol Head Neck Surg 1995;121:1361–4. Eisele DW, Smith PL, Alam DS, Schwartz AR. Direct hypoglossal nerve stimulation in obstructive sleep apnea. Arch Otololaryngol Head Neck Surg 1997;123:57–61. Podszus T, Peter JH, Hochban W et al. Electrical hypoglossal (HG) nerve stimulation in obstructive sleep apnea (OSA). Am J Respir Crit Care Med 1995;151:538. Podszus T, Peter JH, Hochban W et al. Treatment of obstructive sleep apnea with hypoglossal nerve stimulation. Eur Respir J 1995;8(suppl 19):343. O’Hearn DJ, Schneider H, LeBlanc K et al. Effect of unilateral hypoglossal stimulation on upper airway function. Am J Respir Crit Care Med 1998;157(3):284. De Backer WA, Boudewyns A, Van de Heyning P. Hypoglossal nerve (HGN) stimulation using a fully implantable pulse generator. Clinical experiance in 2 OSA patients. Am J Respir Crit Care Med 1998;157(3):284. Mikki H, Hida W, Chonan T, Kikuchi Y, Takishima T. Effects of submental electrical

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stimulation during sleep on upper airway patency in patients with obstructive sleep apnea. Am Rev Respir Dis 1989;140:1285–9. Edmonds LC, Daniels BK, Stanson AW, Sheedy II PF, Shepard JR. The effects of transcutaneous electrical stimulation during wakefulness and sleep in patients with obstructive sleep apnea. Am Rev Respir Dis 1992;146:1030–6. Schwartz AR, Thut DC, Russ B et al. Effect of electrical stimulation of the hypoglossal nerve on airflow mechanics in the isolated upper airway. Am Rev Respir Dis 1992;147: 1144–50. Decker MJ, Haaga J, Arnold JL, Atzberger D, Strohl KP. Functional electrical stimulation and respiration during sleep. J Appl Physiol 1993;75(3):1053–61. Rowley JA, Bernesta CW, Smith PL, Schwartz AR. Neuromuscular activity and upper airway collapsibility (mechanism of action in the decerebrate cat). Am J Respir Crit Care Med 1997;156:515–21. Gold AR, Schwartz AR. The pharyngeal critical pressure: the whys and hows of using nasal continuous positive airway pressure diagnostically. Chest 1996;110:1077–88. Hochban W, Brandenburg U. Morphology of the viscerocranium in obstructive sleep apnea —cephalometric evaluation of 400 patients. J Craniomaxfac Surg 1994;22:205–13. Neill AM, Angus SM, Sajkov D, McEvoy RD. Effects of sleep posture on upper airway stability in patients with obstructive sleep apnoea. Am J Respir Crit Care Med 1997;155:199–204.

15 Serotonergic medications Richard B Berry

Upper airway muscle activity falls at sleep onset even in normal individuals and is associated with an increase in upper airway resistance. The activity of muscles showing phasic (inspiratory) activity, such as the genioglossus, returns to waking levels or higher with the establishment of stable sleep.1 The genioglossus muscle protrudes the tongue and is an important upper airway dilator. The tone of other muscles exhibiting mainly constant (tonic) activity, such as the tensor veli palatini (a palatal muscle), remains below the wakefulness level during non-rapid eye movement (NREM) sleep. Patients with obstructive sleep apnea (OSA) have higher than normal upper airway muscle activity during wakefulness to compensate for unfavorable upper airway anatomy.2 At sleep onset they may have a greater than normal decrement in upper airway muscle activity, depending on the muscles studied.3–5 The fall in upper airway muscle activity is associated with upper airway closure (apnea) or narrowing (hypopnea). During the latter portion of obstructive apnea, there is a progressive increase in the activity of the genioglossus and other phasic upper airway muscles as respiratory effort increases. However, these increases in muscle activity do not restore airway patency, since they are balanced by higher intra-luminal suction pressure.4,5 Apnea termination occurs in conjunction with a large preferential increase

in upper airway muscle activity associated with arousal. The cause of the fall in upper airway muscle activity at sleep onset is unknown. Withdrawal of facilitatory serotoninergic and noradrenergic input to upper airway motor nuclei from medullary or pontine sites may be one mechanism.6 Medications that augment upper airway muscle activity could therefore provide a potential treatment for OSA. The ideal agent would selectively increase upper airway dilator muscle activity (compared to respiratory muscles) during sleep without disturbing sleep quality. Studies in animal preparations have shown that direct application of serotonin, norepinephrine, TRH and other agents to the hypoglossal motor nucleus augments cranial nerve XII activity.6,7 The portion of the nerve from the ventromedial part of the hypoglossal nucleus innervates the genioglossus. The role of serotonin has attracted the most experimental interest. The hypoglossal nuclei receive innervation from a number of brain stem areas including the serotonergic neurons in the caudal raphe. The activity of these neurons (and the level of serotonin at the hypoglossal motor nuclei) decreases on transition from wakefulness to NREM sleep and reaches the lowest point in REM sleep.8 However, this decrease is somewhat gradual and would not explain the abrupt fall in genioglossus activity

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at sleep onset. Nevertheless, the parallel fluctuation of serotonin levels and muscle activity suggests a clinically useful relationship, and serotonergic medications could potentially augment the activity of the genioglossus and other upper airway muscles. While studying the effects of site-specific application of serotonin is useful to understanding the pharmacology of upper airway muscle control, potential clinical applications require an understanding of the systemic effects of serotonergic medications. Systemically administered serotonin enhancing medications may have effects at multiple brainstem sites. The net effect on upper airway muscle activity may depend on a complex set of interactions that we currently do not understand. Serotonin does not cross the blood brain barrier. However, serotonin precursors such as tryptophan or 5-hydroxy-tryptophan (5HTP) do and could potentially increase brainstem serotonin. Nonselective (protriptyline) or selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, or sertraline could also increase serotonin effects by preventing reuptake. The actions of sertonin are mediated by binding to specific receptors on cells. Many types of serotonin receptors have been identified. Receptors on hypoglossal motor neurons, which mediate augmentation, are type 2c or 2a. Drugs that bind serotonin receptors and produce serotonin like effects (direct agonists) are a third way of enhancing upper airway muscle activity. The normal sleep associated fall in serotonin at brainstem sites during sleep might affect the activity of direct agonists less than SSRIs. Another potential advantage of serotonin agonists is that medications could target specific receptor types (and locations). Finally, combinations of precursors, SSRIs, and direct serotonergic agonists might be more effective than single agents.

In animal preparations acute systemic administration of serotonin precursors (5HTP), reuptake inhibitors (protriptyline, sertraline) and direct agonists (buspirone) augments hypoglossal or genioglossus activity.9,10 While studies have shown that serotonin acting at 2c receptors on the hypoglossal motor nuclei augments activity,7 activation of other receptor types at other locations may also augment upper airway activity: for example, the partial 1a receptor agonist buspirone also augments hypoglossal nerve activity.9 At the present time there are no direct 2c agonists that are approved for clinical use. However, mCPP, a metabolite of the antidepressant trazodone, does have 2c agonist activity. One study of the effects of serotonin enhancement in the English bulldog model of sleep apnea made use of a combined treatment approach using trazodone:11 a combination of tryptophan (a sertonin precursor) and high doses of trazadone decreased the amount of sleep disordered breathing in NREM and REM sleep. While trazodone also has some serotonin reuptake inhibition activity and receptor 2C antagonist activity, the authors hypothesized that the direct agonist effects of the metabolite mCPP may have predominated at the high doses used and produced upper airway muscle augmentation. However, the relative role that tryptophan and trazodone each played in decreasing sleep disordered breathing in the bulldogs was not determined. This study also showed a clear increase in effects at higher doses (dose-related response). In human studies, tryptophan,12 buspirone,13 protriptyline14 and the SSRIs fluoxetine14 and paroxetine15 have all been reported to decrease apnea in some of the OSA patients studied. Hanzel and co-workers14 found a reduction in the apnea + hypopnea index (AHI) during NREM sleep after administration of 20 mg of fluoxetine in 5 of 12 of the patients they studied. The results were similar with

Serotonergic medications protriptyline but fluoxetine was better tolerated. Another study by Kraiczi and coworkers15 of 20 patients with mild-to-moderate OSA found that treatment with 20 mg of paroxetine (a potent SSRI) decreased the AHI during NREM sleep from 37.6 events/hour on placebo nights to 27.1 on treatment nights (p < 0.02). This study used a double-blind randomized cross-over protocol with a 6-week treatment duration and a 4-week washout period between paroxetine or placebo. It is possible that augmentation of upper airway muscle activity occurred in all patients in these studies but was inadequate to stabilize the upper airway in the non-responding patients. Another problem with the existing human studies of serotonergic treatment of OSA is that the effects of various doses have not been examined; lack of response could have been secondary to a sub-therapeutic dose. To date, little is known about the effects of SSRIs or other serotonergic agonists on the activity of individual upper airway muscles during sleep in humans. A single study published in abstract form found that the SSRI fluoxetine did not augment genioglossus activity or decrease upper airway resistance during NREM sleep in a group of normal subjects.16 In contrast, a study of the effects of acute administration of paroxetine on genioglossus muscle activity in a group of patients with severe OSA found evidence of genioglossus augmentation (Figure 15.1).17 Following a single dose of 40 mg of paroxetine, there was higher peak inspiratory genioglossus activity at a given level of ventilatory drive (esophageal pressure deflection) during obstructive apnea in NREM sleep than with placebo. Unfortunately, this augmentation was not sufficient to reduce the AHI. In summary, studies in OSA suggest that serotonergic agents may provide a modest augmentation of upper airway muscle activity and a reduction in obstructive events during

233

i ii iii

A i ii

iii

B Figure 15.1 Two tracings from the same patient recorded on nights after ingestion of either (A) placebo or (B) 40 mg of paroxetine. Airflow (i), the moving time average of genioglossus (% maximum) (ii), and esophageal pressure (cm H2O) (iii) are shown. The two obstructive apneas of similar duration illustrate that at similar esophageal pressure deflections during the last 3 efforts (1, 2, 3) the peak inspiratory activity of the moving time average of the genioglossus is higher on the paroxetine night. (Reprinted with permission from Berry et al.17.)

NREM sleep in some patients. The fact that paroxetine reduced the AHI in patients with moderate15 but not severe17 OSA suggests that patients with milder disease might benefit the most from SSRI medications. However, a clinical trial of SSRIs in patients with mild OSA has not been performed. In addition, the SSRIs also tend to disturb sleep. It has not been clearly demonstrated that sleep quality is improved in OSA patients with these medications. In contrast, the sleep quality of English

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bulldogs treated with tryptophan and trazadone did improve.12 Certainly, serotonergic medications cannot be considered an established treatment for OSA. A combination of SSRIs with serotonin precursors and/or direct serotonin receptor agonists may prove more effective than using SSRIs alone; however, this approach remains to be validated. While much has been learned over the last decade, our understanding of the pharmacology of upper airway muscle control is in its infancy. Perhaps when more is learned about the sites of action of serotonin and other neurotransmitters affecting upper airway muscle activity, the dose–response relationships, and the relevant receptor types, more effective treatment regimens and medications can be designed.

References 1. Tangel DJ, Mezzanotte WS, Sandberg EJ, White DP. Influences of NREM sleep on the activity of tonic vs. inspiratory phasic muscles in normal humans. J Appl Physiol 1992;73:1058–66. 2. Mezzanote WS, Tangel DJ, White DP. Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism). J Clin Invest 1992;89:1571–9. 3. Mezzanotte WS, Tangel DJ, White DP. Influence of sleep onset on upper-airway muscle activity in apnea patients versus normal controls. Am J Respir Crit Care Med 1996;153:1880–7. 4. Remmers JE, DeGroot WJ, Sauerland EK, Anch AM. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol 1978;44:931–8. 5. Carlson SM, Onal E, Carley DW, Lopata M, Basner RC. Palatal muscle electromyogram activity in obstructive sleep apnea. Am J Respir Crit Care Med 1995;152:1022–7.

6. Horner RJ. Motor control of pharyngeal musculature and implications for the pathogenesis of obstructive sleep apnea. Sleep 1996;19:827–53. 7. Kubin L, Tojima H, Taguchi O, Reigner C, Pack AI, Davies RO. Serotonergic excitatory drive to hyoglossal motorneurons in the decerebrate cat. Neurosci Lett 1992;139:243–8. 8. Heym J, Steinfels GF, Jacobs BJ. Activity of serotonin containing neurons in the nucleus pallidus of freely moving cats. Brain Res 1982;251:259–76. 9. Richmonds CR, Hudgel DW. Hypoglossal and phrenic motorneuron responses to serotonergic active agents in rats. Respiration Physiology 1996;106:153–60. 10. Veasey SC, Fenik P, Woch G, Pack AI. The effects of systemic serotonergics on hypoglossal motorneuronal activity. Am J Respir Crit Care Med 1998;157:A655. 11. Veasey SC, Fenik PV, Panckeri KA, Pack AI, Hendricks JC. The effects of trazodone with L tryptophan on sleep-disordered breathing in the English bulldog. Am J Respir Crit Care Med 1999;160:1659–67. 12. Schmidt HS. L-Tryptophan in the treatment of impaired respiration in sleep. Bull Europ Respir Physiol 1982;19:625–9. 13. Mendelson WB, Maczaj M, Holt J. Buspirone administration to sleep apnea patients. J Clin Psychopharmacol 1991;11:71–2. 14. Hanzel DA, Proia NG, Hudgel DW. Response of obstructive sleep apnea to fluoxetine and protriptyline. Chest 1991;100:416–21. 15. Kraiczi H, Hedner J, Dalof P, Ejnell H, Carlson J. Effect of serotonin uptake inhibition on breathing during sleep and daytime symptoms in obstructive sleep apnea. Sleep 1999;22:61–7. 16. Slamowitz DI, Shea SA, Edward JK, Akahoshi T, White DP. Serotonergic and cholinergic influences on pharyngeal muscles. Sleep 1998;21:140A. 17. Berry RB, Yamaura EM, Gill K, Reist C. Acute effects of paroxetine on genioglossus activity in Obstructive Sleep apnea. Sleep 1999;22:1087–92.

Index abnormal respiratory events clinical features 12, 13 obesity 9 oxyhemoglobin desaturation 5–6 REM sleep 6–7 abscesses 217, 218 acceptance 106, 108–9, 121, 124 acetaminophen 217 acoustic reflection 9, 77 actigraphy 22, 24 adenoidectomy 132, 138, 155, 173 adenoids 48–9, 50, 51 adenotonsillar hypertrophy 41–2, 43, 51 adherence see compliance, therapeutic adjunctive treatments 102–3, 105, 107 adjustable oral appliances 120–1, 123 adult obstructive sleep apnea syndrome, childhood comparison 42 AHI see apnea–hypopnea index AI see apnea index airflow cardiopulmonary monitoring 73 indications for treatment 90 obstructive sleep apnea–hypopnea syndrome 62 polysomnography 63–8 positive pressure titration 97, 98 screening devices 72 alertness–sleepiness evaluation 23–4 allergies 129, 133 alpha attenuation test 23–4 alveolar pressure 150 ambulatory monitoring 72 anatomy nasal airway 130–1, 137, 138 soft palate 215 upper airway 4–5, 169–73 anesthesia 146, 215, 216, 217 animal models 213, 231, 232 anterior cartilage 137 anterior tonsillar pillars 153, 154, 175 antibiotics 133 anticonvulsants 32 antidepressants 32, 103 antihistamines 32, 133 anxiolytics 108

apnea, definition 12, 58 apnea index (AI) 13, 59 childhood obstructive sleep apnea syndrome 47 laser uvulopalatoplasty 174 nasal obstruction 134 oral appliances 125 positive airway pressure 104 skeletal facial corrections 194–5 tracheotomy 145, 146 uvulopalatopharyngoplasty 155, 157, 159 apnea–hypopnea index (AHI) 59 see also respiratory disturbance index indications for treatment 89, 90, 91 intermittent hypoglossal nerve stimulation 222 obstructive sleep apnea–hypopnea syndrome 61–2 oral appliances 122–3, 124, 125, 126, 127 palatal radiofrequency reduction 214 positive pressure titration 101 serotonergic medications 232, 233 skeletal facial corrections 195, 200, 201, 202, 204 weight loss 91, 93 arousal from sleep childhood obstructive sleep apnea syndrome 44 clinical features 11, 12 consequences 10 indications for treatment 89–90 polysomnography 63 positive pressure titration 99 trachetomy 145 uvulopalatopharyngoplasty 159 arousal index 63, 90 arrhythmias continuous positive airway pressure 106 electrocardiography 70–1 sinus bradytachyarrhythmia 11 tracheotomy 146 arterial oxygen saturation childhood obstructive sleep apnea syndrome 46, 47, 48, 50

indications for treatment 89 oxyhemoglobin desaturation 6 positive pressure titration 99, 100, 103 arterial oxygen tension 146 atelactasis 6, 9 atherosclerosis 91, 104 atonia 26 atrial fibrillation 11 atrial flutter 11 atrial natriuretic peptide 106 atrioventricular block 11 auto-titrating continuous positive airway pressure 94, 95–6, 101–2, 105, 108, 110–11 Babinski responses 31 ‘balance of pressures’ concept 4–5 bed elevation 103 behavioural therapy 133, 139 ‘Berlin Questionnaire’ 61 bilateral retromolar sagittal split osteotomy 197–8 bilevel positive airway pressure (BiPAP) acceptance 108 compliance 109–10 delivery methods 94, 95, 96 nasal obstruction 134 obstructive sleep apnea–hypopnea syndrome 71 side-effects 105, 107 titration 99, 100, 103 bleeding 167, 168–9, 187, 189 blood pressure 43, 104, 188 BMI see body mass index body mass index (BMI) apnea–hypopnea index 62 clinical diagnosis 15 hypopharyngeal airway surgery 189, 191 laser uvulopalatoplasty 174 neck size 10 oral appliances 127 oxyhemoglobin desaturation 5–6 positive pressure titration 101 skeletal facial corrections 196, 201 upper airway collapse 219

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Index

body mass index (BMI) (cont.) uvulopalatopharyngoplasty 155 weight loss 91 body position, polysomnography 70 ‘boil-and-bite’ oral appliances 120–1 bradydysrhythmias 11 brainstem 231, 232 breathing difficulties childhood obstructive sleep apnea syndrome 42–3, 45, 48, 50 obstructive sleep apnea–hypopnea syndrome 62 breathing effort level III recording devices 73 obstructive sleep apnea–hypopnea syndrome 62 polysomnography 63–8 buspirone 232 caliber, upper airway 4–5, 6–7, 9, 77 calibrated inductance plethysmography 60 carbon dioxide detection 63, 64, 72 carbon dioxide laser 164, 166 carbon monoxide poisoning 68 carboxyhemoglobin 68–9 cardiac arrythmia 146 cardiac dysrhythmia 11 cardiomyopathy 106 cardiopulmonary disorders 101, 150 cardiopulmonary monitoring 62, 72 cardiovascular morbidity 13 CAT see controlled by axial tomography cataplexy 26, 27, 29 caudal traction 5 central apnea airflow 65, 66 auto-titrating devices 102 continuous positive airway pressure 49 positive pressure titration 99–100 tracheotomy 151 central nervous system (CNS) idiopathic recurring stupor 30 narcolepsy 25 central sleep apnea definition 57, 58 excessive daytime sleepiness 25 trachetomy 145 central sleep hypopnea, definition 58 cephalometry hypopharyngeal obstruction 184, 187 laser uvulopalatoplasty 174 nasal obstruction 133 oral appliances 123, 125

oropharynx 173 radiofrequency tongue base reduction 216 skeletal facial corrections 194, 195, 196, 205, 206 upper airway 77, 157, 158 cerebral palsy 50, 51 cerebrovascular disease 104 chest wall impedance 73 Cheyne–Stokes breathing (CSB) 25, 100–1 Cheyne–Stokes central apnea 100 children obstructive sleep apnea syndrome 41–51 oral appliances 119 chin advancement osteotomy 200 choking 10 chronic obstructive pulmonary disease (COPD) 15–16 chronic subtotal respiratory obstruction 150 chronic upper airway obstruction 150 chronically implantable electrodes 221–7 circadian rhythm disturbances 31, 32 circumvallate papillae 216, 217 claustrophobia 108 clinical diagnosis see diagnosis clinical examination, skeletal facial corrections 193–4, 205 clinical features 10–13 clinical predictors 61–2 co-oximetry 69 coagulative necrosis 217 collapsibility genioglossus muscle 186 upper airway 5, 6, 9, 92 body mass index 219 hypoglossal nerve stimulation 219–29 hypopharyngeal surgery 189 laser uvulopalatoplasty 168, 169, 170–3 nasal obstruction 129 retroglossal region 219 skeletal facial corrections 193, 194, 195, 206 uvulopalatopharyngoplasty 153, 156–7, 158–9 compliance, therapeutic continuous positive airway pressure 111, 136, 146 oral appliances 124 positive airway pressure 105, 106, 108–11 upper airway 5, 6, 7, 9

computed tomography (CT) childhood obstructive sleep apnea syndrome 48 hypopharyngeal obstruction 184 skeletal facial corrections 194 upper airway 9, 78, 219 uvulopalatopharyngoplasty 157 congestion, nasal 105, 106–7, 108 congestive heart failure 91, 101 conjunctivitis 105, 106 connective tissue ingrowth 226 continuous positive airway pressure (CPAP) see also positive airway pressure case example 21 childhood obstructive sleep apnea syndrome 48, 49–50, 51 devices 94 hypopharyngeal airway surgery 185–6, 189, 190 indications for treatment 90, 91 laser uvulopalatoplasty 168, 173 level III recording devices 74 nasal obstruction 134, 136, 138, 139 oral appliances 124, 125–6 polysomnography 64, 67, 71 skeletal facial corrections 201, 202, 204, 205 tracheotomy 146, 151 treatment 93–4 uvulopalatopharyngoplasty 157 weight loss 93 controlled by axial tomography (CAT) scan 220 coordinated muscle action 219 COPD see chronic obstructive pulmonary disease cor pulmonale 15 coronary artery disease 13, 104, 188 cortical arousal 44–5, 46, 90 Cottle maneuver 132, 138 CPAP see continuous positive airway pressure cranial nerve XII activity 231 craniofacial anomalies childhood obstructive sleep apnea syndrome 42, 48, 49, 51 nasal obstruction 133 obstructive sleep apnea syndrome 42 skeletal facial corrections 193, 195–6, 206 craniofacial surgery 50 craniomaxillofacial skeleton see also maxillomandibular advancement

Index hypopharyngeal airway surgery 189 skeletal facial corrections 193 crescendo–decrescendo pattern 100 critical closing pressure 9 hypoglossal nerve stimulation 220, 221, 227 skeletal facial corrections 194, 195, 205 upper airway 156–7, 158 cumulative oxyhemoglobin saturation 69 cumulative total energy 216 cutaneous functional electrical stimulation see functional electrical stimulation daytime alertness 111 daytime hypercapnia 90, 104 daytime hypersomnia 22 daytime hypersomnolence 3 daytime sleepiness alertness–sleepiness 23–4 childhood obstructive sleep apnea syndrome 44–5 clinical diagnosis 14–15 clinical features 10, 12 continuous positive airway pressure 109 nasal obstruction 133 oral appliances 126–7 positive pressure titration 99 treatment indications 89 upper airway stabilization 104 daytime somnolence nasal obstruction 129 nasal surgery 135 obstructive sleep apnea–hypopnea syndrome 59 polysomnography 63 tracheotomy 145 decongestants 105, 107, 133, 135, 139 definitions apnea 12, 58 hypopnea 57, 58–9 obstructive sleep apnea–hypopnea syndrome 59 snoring 177 delivery, positive airway pressure 109–11 dental discomfort 123 dentists 126 depression 32 diagnosis 13–14 childhood obstructive sleep apnea syndrome 42–8 level IV recording devices 74–5

nasal obstruction 132–3 obstructive sleep apnea–hypopnea syndrome 62 polysomnography 71 skeletal facial corrections 193–4, 205 diaphragm 12 diathermy see radiofrequency tissue reduction discomfort 105, 106 disproportionate skeletal anatomy 183, 190 distal hypoglossal nerve 220, 221 dolichofacial type 195, 196, 201, 202, 206 Down syndrome 49, 50 driving privileges 32 dryness 105, 106, 107, 108 duty hours 32 dysgnathia 193 dysphagia 167, 186, 217 dysrhythmias 70–1 edema 15, 49, 102, 150, 186, 189 EDS see excessive daytime sleepiness EEG see electroencephalography electrical stimulation 219 hypoglossal nerve 219–29 electrocardiography (ECG) 62, 63, 70 electrodes half-cuff 221, 224 implantable 221–7 impulse-conducting tripolar electrodes 222–5 placement method 220 electroencephalography (EEG) 62, 63 electrooculography (EOG) 62, 63 Eliachar technique 147 ellipsoid areas of tissue reduction 213 emergency stabilization 48 EMG see electromyography endogenous opiate poisoning 30 endoscopy 125, 132, 157, 174 endotracheal intubation 146 endozepines 30 endpoint, laser uvulopalatoplasty 166, 177 enuresis 43 EOG see electrooculography epidemiology 3, 41, 59 epiglottis 4, 183 epistaxis 105, 106 Epworth Sleepiness Scale (ESS) 23, 72, 127, 178 esophageal pressure evidence-based definitions 57–8

237

indications for treatment 89 positive pressure titration 97, 98 respiratory effort 65, 66, 67 respiratory effort-related arousal 60 skeletal facial corrections 194 ESS see Epworth Sleepiness Scale etiology 41–2 evaluation 32 evidence-based definitions 57–8 excessive daytime sleepiness (EDS) 15 childhood obstructive sleep apnea syndrome 43 circadian rhythm disturbances 31 consequences 22 duty hours 32 evaluation 22–4 hypersomnolence 72 hypopharyngeal airway surgery 185, 191 idiopathic central nervous system hypersomnia 28–9 laser uvulopalatoplasty 178 legal issues 32 medication-induced hypersomnia 31–2 narcolepsy 25–8, 29 nasal obstruction 133 non-apneic causes 21–32 periodic limb movement disorder 31 prevalence 22 recurrent hypersomnias 29–30 sleep deprivation 24–5 sleep drunkenness 29 sleep inertia 29 sleep-disordered breathing 25 uvulopalatopharyngoplasty 159 excessive daytime somnolence 59 see also daytime somnolence expiratory positive airway pressure (EPAP) 94, 95, 99, 110 external nasal dilators 134, 138 facemasks auto-titrating devices 101, 102 positive airway pressure 94, 95, 96, 103 side-effects 105, 107 titration 99 facial corrections see skeletal facial corrections familial factors 3 fat neck size 10 pharyngeal 5, 6, 7–8, 9, 75–6 weight loss 91–2 FDA see Food and Drug Administration

238

Index

feline model 220 femoral artery pressure 146 fenestra, tracheal 147, 149 FES see functional electrical stimulation fiberoptic endoscopy 157, 158 fiberoptic nasopharyngoscopy 214 fiberoptic pharyngolaryngoscopy 184 fibrinogen activation 104, 106 fine-wire electrodes 220 ‘first night effect’ 63 fluoroscopy 77, 157, 174 fluoxetine 232, 233 Food and Drug Administration (FDA) 216 forced vital capacity (FVC) 16 ‘French’ technique 174 functional electrical stimulation (FES) 220 FVC see forced vital capacity genetics 3–4, 25 genial tubercle 187, 199, 200, 201, 202 genioglossus electrical stimulation 221–8 hypopharyngeal airway surgery 186–7, 188, 189 serotonin medications 232, 233 skeletal facial corrections 198, 199 sleep activity 231 upper airway collapse 219, 220 genioplasty 199–200, 202 granuloma formation 146, 150 half-cuff electrodes 221, 224 hallucinations 26 heart failure 104 heart rate childhood obstructive sleep apnea syndrome 45 clinical features 11 obstructive sleep apnea–hypopnea syndrome 62 polysomnography 70–1 screening devices 72 tracheotomy 145 hemoglobin variants 68 hemostasis hypopharyngeal airway surgery 187 laser uvulopalatoplasty 166 uvulopalatopharyngoplasty 153 heredity 3–4 Hering–Breuer reflex 49 HI see hypopnea index hip-to-waist ratio 10 home sleep studies 47–8

hormones 130 hours of work 32 humidification 108 Hunsuck modification 197 hydrochloric acid 189 hydrogen ultrathin phase-eroded spectroscopy (HUPSPEC) 9 5-hydroxy-tryptophan (5HTP) 232 hyoglossus muscle 221 hyoid bone 184, 186, 187–8, 189, 200 hyper-endorphin syndrome 30 hypercapnia childhood obstructive sleep apnea syndrome 45–7, 50 clinical diagnosis 15 clinical features 11, 12, 13 consequences 10 nasal cycle 130 obesity 9, 10 REM sleep 6 hypercarbia 151 hyperkalemic periodic paralysis 27 hypersomnia circadian rhythm disturbances 31 evaluation 32 excessive daytime sleepiness 26 idiopathic central nervous system 28–9 medication-induced 31–2 recurrent 29–30, 32 hypersomnolence 25, 72, 146 see also daytime hypersomnolence hypertension childhood obstructive sleep apnea syndrome 43, 45 continuous positive airway pressure 104 hypopharyngeal airway surgery 188 indications for treatment 91 nasal obstruction 133 obstructive sleep apnea–hypopnea syndrome 61–2 snoring 13 tracheotomy 145 hypertrophy 170 hyperventilation 100 hypnagogic hallucinations 26 hypocapnia 130 hypocretin 25, 27 hypoglossal motor nucleus 231 hypoglossal nerve stimulation 219–29 clinical results 226–7 feline model 220 surgical procedure 224–5 hypopharyngeal airway surgery 183–91

perioperative management 188–9 phase I 186, 189, 190 phase II 189–91 Stanford protocol 184–6 techniques 186–8 hypopharynx 4, 75, 132, 200 hypopnea see also apnea–hypopnea index childhood obstructive sleep apnea syndrome 47 clinical features 12 definition 12, 57, 58–9 indications for treatment 89 obstructive sleep apnea–hypopnea syndrome 57 oxyhemoglobin desaturation 6 positive pressure titration 97, 98, 99 serotonergic medications 231 upper airway stabilization 103 uvulopalatopharyngoplasty 155, 157, 159 hypopnea index (HI) 59 hypoventilation 6, 12, 99, 101 hypoxemia 45–7, 48, 90, 126, 145, 151 hypoxia clinical features 11, 12, 13 indications for treatment 90 nasal cycle 130 REM sleep 6 idiopathic central apnea 100 idiopathic central nervous system hypersomnia 21, 28–9 idiopathic recurring stupor (IRS) 30 imaging see magnetic resonance imaging impedance 73, 95, 98 impedance pneumography 65 implantable electrodes 221–7 impotence 10 impulse-conducting tripolar electrodes 222–5 indications for treatment 89–91 oral appliances 125–6 skeletal facial corrections 194–7 tracheotomy 146 infection 216, 227 inferior constrictor muscles 171 inferior turbinate 130–1, 132 infraclavicular pocket 225 inner cannulae 150 insomnia 10 inspiratory effort hypopnea 58 upper airway 94 upper airway resistance syndrome 60

Index inspiratory flattening 90, 95, 97, 98 inspiratory positive airway pressure (IPAP) 95, 99, 110 Inspire I hypoglossal nerve-stimulating system 222 intellectual deterioration 10 intensive support 109 intermittent hypoglossal nerve stimulation 221–7 internal nasal dilators 134 intraluminal pressure 5, 11 intraoral appliances 120, 134, 139 intraoral approach 197, 199 intubation 146, 147 ipratropium 105, 107 IRS see idiopathic recurring stupor Kleine–Levin syndrome 29–30 laryngomalacia 50 larynx 132, 172 laser uvulopalatoplasty (LAUP) 163–78 advantages 166–7 complications 167, 168–9 disadvantages 167–8 patient selection 173–4 results 177 snoring 176–7 technique 164–6, 174–6 upper airway anatomy 169–73 lateral cartilage 130, 131, 132, 138 lateral cephalometry 157 lateral pharyngeal wall 9, 76, 92, 183 lateral trenches 165, 166, 176 Le Fort-I osteotomy 198–9 leaks, masks 105, 106–7 legal issues 32 levator veli palatini 171 level I recording devices 62 level II recording devices 62 level III recording devices 62, 72, 73–4 level IV recording devices 62, 72, 74–5 lidocaine 215, 217 limb movement 62, 63, 70 lingual horizontal osteotomy 197–8 lithium 30 local anesthetics 215, 216, 217 lowest oxygenation saturation (LSAT) 185, 189, 190, 191 luminal pressure 7 lung volume 5, 6, 9, 11, 92 machine noise 105, 107 macroglossia 50 magnetic resonance (MR) imaging fat 7, 9

obesity 91–2 radiofrequency tongue base reduction 216 upper airway 78–9 maintenance of wakefulness test (MWT) 23, 72, 99, 103–4, 109 mandibular advancement hypopharyngeal obstruction 183, 184 oral appliances 120–1, 122–3, 124, 125–6 skeletal facial corrections 195, 197–8, 199–202, 204–5 mandibular deficiency 193 mandibular distraction 50 mandibular osteotomy 186–7 manometry 157, 158, 174 manubrium sterni 224–5 masks see facemasks; nasal masks maxillary advancement 198–9, 200, 202, 204 maxillofacial skeleton 184 maxillomandibular advancement (MMA) hypopharyngeal airway surgery 184, 185, 189, 190 skeletal facial corrections 195–6, 199, 200–3, 205, 206 maxillomandibular size 193, 194 maximum inspiratory airflow 220 mCCP 232 mean apnea index 216 mechanical devices, nasal obstruction 134 medical therapy, nasal obstruction 133, 139 medication, serotonergic 231–4 medication-induced hypersomnia 31–2 menstrual-related hypersomnia 30 meperidine hydrochloric acid 189 methemoglobin 68–9 micrognathia 50, 119 microphones 70 middle meatus 131, 138 middle turbinate 131, 132 mild sleepiness 14 mixed apnea 58, 103 MMA see maxillomandibular advancement moderate sleepiness 14 monosymptomatic narcolepsy 21 Montgomery cannula 150 morphine sulfate 189 mouth symptoms 105, 107 MR see magnetic resonance imaging MSLT see multiple sleep latency test

239

mucosal burns 217 mucosal disease 133 mucosal stripping 174 mucosal ulcers 214 Müller maneuver 157, 158, 174, 194 multilumen catheter measurements 219, 228 multiple sleep latency test (MSLT) 15 continuous positive airway pressure 111 excessive daytime sleepiness 21, 23, 24, 72 hypersomnia 32 idiopathic central nervous system hypersomnia 29 narcolepsy 27–8 ‘split-night’ PSG 72 upper airway stabilization 103 muscle activity airway patency 219–20 hypoglossal nerve stimulation 219–29 sleep levels 231 muscle dilating force see pharyngeal dilating muscles muscle group coordination 219 MWT see maintenance of wakefulness test myomucosal envelope 173 myotonic dystrophy 27 nap polysomnography 62 nap studies 47 narcolepsy driving 32 excessive daytime sleepiness 25–8, 29 indications for treatment 90 multiple sleep latency test 72 positive airway pressure 111 periodic limb movements 31 nares 15 narrowing see also hypopnea pharynx 4–5, 6, 11 nasal airway 130–1 nasal cycle 130 nasal dilator muscles 130–1, 132 nasal dilators 134, 138 nasal fluid emission 154, 155 nasal masks 94, 95, 96, 105, 106–7 nasal obstruction 129, 131–2 diagnosis 132–3 management protocol 139, 140 treatment 133–8 nasal pressure 63, 64, 66, 89–90

240

Index

nasal prongs polysomnography 65, 71 positive airway pressure 94, 95, 105, 106, 108 nasal reflux 156, 169 nasal stents 136 nasal symptoms 105, 106 nasal valve 130 nasopharyngeal stenosis 155, 156, 173 nasopharyngoscopy 77 nasopharynx 4, 130, 131 laser uvulopalatoplasty 167, 168 nasal obstruction 132, 138 oral appliances 127 radiographic imaging 75 snoring 11 upper airway 9 uvulopalatopharyngoplasty 154 natural course 51 neck size clinical diagnosis 15 hypopharyngeal airway surgery 188 obstructive sleep apnea–hypopnea syndrome 62 positive pressure titration 101 tracheotomy 150 upper airway 5, 6, 10 weight loss 91 necrosis 215 nerve stimulation, hypoglossal 219–29 neuromuscular control mechanisms 219 neuromuscular disease 42 neurotransmitters 231–4 nocturia 106 nocturnal naturesis 106 non-invasive pressure support 95 non-palatal noise generation 214 non-rapid eye movement sleep (NREM) 226, 227, 231, 232, 233 norepinephrine 231 ‘normal’ mesofacial type 195 NREM see non-rapid eye movement sleep OA see oral appliances obesity bed elevation 103 childhood obstructive sleep apnea syndrome 43, 49, 50 hypopharyngeal airway surgery 189 lung volume 9 neck size 10 obstructive sleep apnea–hypopnea syndrome 61 oxyhemoglobin desaturation 6, 9, 10 pathogenesis 7–8

skeletal facial corrections 195, 196, 200 tracheotomy 146, 147, 148, 150 weight loss 91–2 obesity hypoventilation syndrome 12, 13, 104 objective measurement 62, 72 objective sleepiness scales 23, 24 obstructive hypoventilation (OH) 41, 43, 45–7, 48 obstructive sleep apnea, definition 57, 58 obstructive sleep apnea syndrome (OSAS) children 41–51 uvulopalatopharyngoplasty 153, 156, 158, 159 obstructive sleep apnea–hypopnea syndrome (OSAHS) 57 clinical predictors 61–2 continuous positive airway pressure 71 definition 59 excessive daytime sleepiness 72 indices 59 level III devices 73 level IV recording devices 74–5 polysomnography 62, 63, 70, 71–2, 79 radiographic imaging 75–9 ‘split-night’ polysomnography 71–2 upper airway resistance syndrome 59–61 obstructive sleep hypopnea, definition 58 obstructive sleep-disordered breathing syndrome (OSDB) 12–13, 14 OH see obstructive hypoventilation oral appliances (OA) 51, 103, 119–27 orexin see hypocretin oropharynx 4 childhood obstructive sleep apnea syndrome 41, 43 fat 7 laser uvulopalatoplasty 172, 173 nasal airway 131 nasal obstruction 132 obesity 91 radiographic imaging 75, 76 snoring 11 upper airway shape 170 uvulopalatopharyngoplasty 154 OSAHS see obstructive sleep apnea–hypopnea syndrome OSDB see obstructive sleep-disordered breathing syndrome

osteotomy 186–7, 197–9, 200, 204–5 outpatient procedures 214–17 overlap syndrome 101, 103 oximetry 69, 126, 127, 188 see also pulse oximetry oxygen storage 5, 9 oxygen supplementation 102, 103 oxyhemoglobin desaturation 5–6 arousal from sleep 12 cardiac dysrhythmias 11 consequences 10 obesity 9 REM sleep 7 oxyhemoglobin saturation cardiopulmonary monitoring 73 hypopnea 58 level IV recording devices 75 obstructive sleep apnea–hypopnea syndrome 62 polysomnography 63, 68–70 pacemaker devices, implantable 222–7 pain laser uvulopalatoplasty 166–7 palatal radiofrequency reduction 214 positive airway pressure side-effects 105, 106 radiofrequency tongue base reduction 217 skeletal facial corrections 200 ‘palatal excision’ technique 174 palatal radiofrequency reduction 213–16 palatal trench technique 174–5 palatoglossus 171, 172 palatopharyngeus 171, 172, 175 palatorrhaphy 202, 204 paroxetine 232, 233 pathogenesis 4–10 pathophysiology 11 patient selection 173–4, 194–7 PEEP see positive end expiratory pressure percutaneous electrodes 220 periodic limb movement disorder (PLMD) excessive daytime sleepiness 31, 32 indications for treatment 90 polysomnography 62, 63, 70 perioperative management childhood obstructive sleep apnea syndrome 49 hypopharyngeal airway surgery 188–9 tracheotomy 146 upper airway obstruction 156

Index personality changes 10 PFL see protocol to eliminate flow limitation pharmacology 32, 47, 50–1, 103, 231–4 pharyngeal dilating muscles clinical features 11 laser uvulopalatoplasty 170 nasal obstruction 130 pathogenesis 6 upper airway 5, 7, 8, 9 pharyngeal dryness 168 pharyngeal fat 5, 6, 75, 76, 91–2 pharyngeal isthmus 167, 168, 171–2 pharyngeal pressure-area measurements 228 pharyngeal valve 169 pharynx edema 15 laser uvulopalatoplasty 166, 168, 170 narrowing 4–5 nasal resistance 129 phase I surgery 185, 186, 188–9, 190, 200 phase II surgery 185, 189–91 phrenic nerve stimulation 221 physical examination 43 piezo pressure sensors 65, 66, 67, 222–5 piriform aperture 198, 199 placebo-controlled trials 104 platelet activation 104, 106 PLMD see periodic limb movement disorder pneumatic splint effect 93, 94 pneumotachography 63, 64, 65, 89–90 polycythemia 15 polysomnography (PSG) childhood obstructive sleep apnea syndrome 44–7, 48 definition 62 excessive daytime sleepiness 21, 22, 23, 24 hypersomnia 32 hypoglossal nerve stimulation 226 hypopharyngeal airway surgery 185, 191 idiopathic central nervous system hypersomnia 29 laser uvulopalatoplasty 177–8 level IV recording devices 74 narcolepsy 27–8 nasal obstruction 134, 139 obstructive sleep apnea–hypopnea syndrome 62, 63, 70, 71–2, 79

oral appliances 122, 127 periodic limb movement disorder 31 positive airway pressure 96, 101 radiofrequency tongue base reduction 216 screening techniques 72 skeletal facial corrections 194, 202, 205, 206 ‘split-night’ PSG 71–2 trachetomy 145 uvulopalatopharyngoplasty 155, 159 validity 71 position therapy 104 positive airway pressure 91, 93–112 see also continuous positive airway pressure acceptance 106, 108–9 adjunctive treatments 102–3 compliance 105, 106, 108–11 daytime alertness 111 delivery 94–6, 109–11 future prospects 111–12 mechanism of action 93–4 prescription pressure 111 side-effects 105, 106–8, 110 supplemental oxygen 103 treatment table 96–7 upper airway stabilization 103–6 positive end expiratory pressure (PEEP) 96, 150 posterior airway space 196 posterior choana 131, 132 posterior tonsillar pillars 153–4, 155, 172, 173, 175 postoperative period childhood obstructive sleep apnea syndrome 49 laser uvulopalatoplasty 174 tracheotomy 147, 150 uvulopalatopharyngoplasty 154, 155 velopharyngeal insufficiency 156 posture 70, 227 Prader–Willi syndrome 27 prescription pressure 96–102, 105, 107, 108, 111 pressure continuous positive airway pressure 103 positive airway pressure side-effects 105, 107–8 positive pressure titration 99 sensors 65, 66, 67, 222–5 upper airway 4–5 prevertebral muscles 171 primary snoring 13 prognosis 51

241

programmable pulse-generating systems 222–5 protocol to eliminate flow limitation (PFL) 98–9 proton pump inhibitors 133 protriptyline 103, 156, 232, 233 protrusion 199–200 ‘pseudo-erectile’ septal mucosa 130, 132 PSG see polysomnography pulmonary artery pressure 145–6 pulmonary hypertension 15–16, 48, 93 pulse oximetry childhood obstructive sleep apnea syndrome 48 level III recording devices 73 level IV recording devices 74 obstructive sleep apnea–hypopnea syndrome 62 oxyhemoglobin saturation 68 polysomnography 63 skeletal facial corrections 205 sleep-disordered breathing 72 pulse rate 73 pulse-generating systems 222–5 pupillography 24–5 pyriform aperture 130, 131 radiofrequency receivers 221–2 radiofrequency tissue reduction 213–18 radiofrequency tongue base reduction 216–17 radiography 75–9, 187 ramp system 105, 107 rapid eye movement (REM) sleep 6–7 see also non-rapid eye movement sleep childhood obstructive sleep apnea syndrome 44, 45, 47, 48 excessive daytime sleepiness 21, 23–4, 28 hypoglossal nerve stimulation 226, 227 idiopathic central nervous system hypersomnia 29 narcolepsy 26–7 polysomnography 62, 63 positive airway pressure 96, 100, 103, 111 serotonergic medications 231, 232 skeletal facial corrections 202 upper airway stabilization 103 rapid maxillary expansion 51 rapid response carbon dioxide analyzers 63, 64

242

Index

RDI see respiratory disturbance index receptors, serotonin 232 recording devices 62, 72, 73–4, 75 recurrent hypersomnias 29–30, 32 REM see rapid eye movement RERA see respiratory effort-related arousal resistance to the site of the collapsing airway 220, 221 respiratory cycle 223–8 respiratory disturbance index (RDI) 15 see also apnea–hypopnea index excessive daytime sleepiness 21, 28 hypopharyngeal airway surgery 185–6, 189, 190 indications for treatment 89, 90 laser uvulopalatoplasty 167, 174 nasal obstruction 134, 135 radiofrequency tongue base reduction 216 skeletal facial corrections 195, 196–7, 201 tracheotomy 146 uvulopalatopharyngoplasty 155, 157 respiratory effort 65–8, 97 respiratory effort-related arousal (RERA) 60–1 indications for treatment 89–90 polysomnography 64, 67 positive pressure titration 97, 98, 99 upper airway stabilization 103 respiratory function 219 respiratory impedance 98 respiratory inductance plethysmography (RIP) 65–7 restless legs syndrome (RLS) 31 restlessness 10 retroglossal region 4, 10, 75, 76, 125, 219 retrognathia clinical diagnosis 15 skeletal facial corrections 193, 195, 196, 202, 206 tracheotomy 146 retrolingual pharynx 157, 158, 159 retropalatal region 4, 7, 75, 76 see also velopharynx laser uvulopalatoplasty 167 oral appliances 125 uvulopalatopharyngoplasty 157, 158–9 weight loss 92 RF see radiofrequency rhinitis 133, 134 rhinomanometry 133, 136 rhinometry 194

rhinorrhea 105, 106, 107 RIP see respiratory inductance plethysmography (RIP) risk factors 3, 4–10, 13, 61 RLS see restless legs syndrome safety, oral appliances 123 salivation 123 salpingopharyngeus 171 screening techniques 72 sedation 32, 47, 51, 133 selective serotonin reuptake inhibitors (SSRIs) 103, 232, 233, 234 sensitivity 15, 61 septoplasty 135–8 septum, nasal 130–1, 132, 137, 138 serotonergic medications 231–4 sertraline 232 severe sleepiness 14 shape of upper airway 5, 170 side-effects, positive airway pressure 105, 106–8, 110 sinus arrest 11 sinus bradycardia 11 sinus bradytachyarrhythmia 11 site-specific serotonin 232 size of upper airway 8–9 skeletal facial corrections 193–206 diagnosis 205 patient selection 194–7 phase I surgery 200 results 201–5 techniques 197–201 treatment indications 194–7 skin flaps 147, 148–9 skin paddle 147 skin-lined stoma 146–7, 148 sleep apnea syndrome 13 sleep architecture childhood obstructive sleep apnea syndrome 44–5 hypopharyngeal airway surgery 185 polysomnography 62 uvulopalatopharyngoplasty 159 sleep deprivation 22, 24–5, 26, 32, 47 sleep drunkenness 29 sleep fragmentation 10, 11, 12, 63, 75 sleep hypopnea syndrome 13 sleep inertia 29 sleep nasoendoscopy 214 sleep paralysis 26 sleep physiology 22–3 sleep stage-dependent breathing pattern see rapid eye movement sleep sleep stages 63

sleep–wake state 219 sleep-disordered breathing (SDB) body position 70 clinical diagnosis 13, 15 clinical features 12 excessive daytime sleepiness 25 laser uvulopalatoplasty 163, 164, 170 level IV recording devices 74–5 nasal obstruction 132–3, 136 uvulopalatopharyngoplasty 156 sleep-inducing situations 14 sleep-related breathing disorders (SRBD) 193–4, 196, 204, 205, 206 ‘sleep-sock’ technique 70 smoking 133 SnoreGuard oral appliance 122, 123, 124 snoring auto-titrating continuous positive airway pressure 95 childhood obstructive sleep apnea syndrome 42–3, 45, 48 clinical features 11 definition 177 hypertension 13 laser uvulopalatoplasty 164, 166, 168, 169–70, 174, 176–7 nasal dilators 134 nasal obstruction 129, 130, 138, 139 nasal surgery 135–6 oral appliances 119, 123, 125–6 palatal radiofrequency reduction 214–16 polysomnography 70 positive airway pressure 93, 97, 98 skeletal facial corrections 195 sleep nasoendoscopy 214 socially disruptive snoring 214 soft palate 4, 215 childhood obstructive sleep apnea syndrome 43 clinical diagnosis 15 clinical features 11 fat 7, 8, 9 laser uvulopalatoplasty 164–5, 166, 168, 170, 171 nasal airway 131 neck size 10 oral appliances 120 palatal radiofrequency reduction 213–16 radiographic imaging 75, 76 snoring 169–70

Index transpalatal advancement pharyngoplasty 158 uvulopalatopharyngoplasty 153, 154, 155 soft tissue nasal resistance 129, 130 snoring 169–70 tracheotomy 146, 147 upper airway 170 somnoplasty devices 216 specificity 15, 61 split-night studies 71–2, 79, 96, 108 SRBD see sleep-related breathing disorders SSRIs see selective serotonin reuptake inhibitors standard support 109 Stanford protocol 184–6 Stanford Sleepiness Scale 23 static charge-sensitive bed method 72 stenosis 155, 156, 172, 173, 174–5 stents 150 sternum 224–5 stimulant medications 28, 29, 30 stoma 146–7, 148, 150 strain gauges 65, 67 strap muscles 147, 149 styloglossus muscle 221 stylopharyngeus 171 subapical window osteotomy 200 subhyoid region 220 subjective sleepiness scales 23, 24 subjective snoring scores 214 submental electromyography 62, 63 submental region 220 subtherapeutic continuous positive airway pressure 104 supplemental oxygen 50, 102, 103 supraglottoplasty 50 supraventricular paroxysmal depolarizations (SVPDs) 11 surface electromyography, limb movements 70 surgery combined nasal and pharyngeal 136 hypoglossal nerve stimulator implantation 224–5, 227 hypopharyngeal airway 183–91 laser uvulopalatoplasty 163–4, 174–6 nasal obstruction 135–40 oral appliances 124–5, 126 radiofrequency tissue reduction 213–18 skeletal facial corrections 196, 197–201

tracheotomy 146–50 uvulopalatopharyngoplasty 153–5, 156–9 suspension, hyoid bone 187–8, 189, 200 SVPDs see supraventricular paroxysmal depolarizations symphysis, mandibular 186 systemic sclerosis 16 temporomandibular joint (TMJ) 146, 198 oral appliances 123 tension-time index 12 tensor palatini 171 TES see transcutaneous electrical stimulation thermal monitoring 63, 64, 66, 73 thermistors airflow 97 indications for treatment 89–90 positive pressure titration 101 Thornton Anterior Positioner oral appliance 127 tissue reduction 5, 7, 8, 11, 164–6, 213–18 titrating continuous positive airway pressure 71, 96–102, 108–11 TMJ see temporomandibular joint tobacco smoking 133 tongue base abscess 217, 218 base reduction 216–17 oral devices 120, 121–2, 123 protrusion 220, 221, 226 retraction 221 wedge resection 50 tongue-retaining oral appliances 121–2, 123 tonsillar hypertrophy 15, 41–2, 170, 173 see also adenotonsillar hypertrophy tonsillar pillars 153–4, 155, 166, 172, 173, 175 tonsillectomy 48–9, 51, 138, 153, 154–5, 173 topical anesthetics 215 Tornwaldt’s cysts 132 TPAP see transpalatal advancement pharyngoplasty tracheal sound 64, 72 tracheal tug 92 tracheotomy 145–51 childhood obstructive sleep apnea syndrome 51 history 145–6

243

hypopharyngeal airway surgery 188 hypopharyngeal obstruction 183, 184 indications for treatment 91 perioperative 146 technique 146–50 troubleshooting 151 tubes 146, 147, 150, 151 transcutaneous electrical stimulation (TES) 220 transpalatal advancement pharyngoplasty (TPAP) 158 trauma 15 trazadone 232, 234 treatment childhood obstructive sleep apnea syndrome 48–51 indications 89–91 oral appliances 125–6 skeletal facial corrections 194–7 tracheotomy 146 nasal obstruction 133–8 oral appliances 122–7 polysomnography 71 positive airway pressure 91, 93–112 weight loss 91–3 trenches 164–5, 167, 174, 176 TRH 231 tripolar electrodes 222–5 tryptophan 232, 234 tug 5, 92 turbinoplasty 135–6, 138 turbulent airflow 129 twelfth cranial motor nerve 220 type I pharynx 157, 158, 159 type II pharynx 157, 158 type III pharynx 157, 158 UARS see upper airway resistance syndrome unilateral genioglossal protrusion 219, 220 upper airway 4–5 apnea definitions 58 auto-titrating devices 101, 102 bed elevation 103 caliber 9 childhood obstructive sleep apnea syndrome 43, 45–7, 48 collapsibility 5, 6, 9, 92 body mass index 219 hypoglossal nerve stimulation 219–29 hypopharyngeal surgery 189 laser uvulopalatoplasty 168, 169, 170–3

244

Index

upper airway (cont.) muscle activity effects 219–20 nasal obstruction 129 retroglossal region 219 skeletal facial corrections 193, 194, 195, 206 uvulopalatopharyngoplasty 153, 156–7, 158–9 continuous positive airway pressure 93–4 hypoglossal nerve stimulation 221 narrowing 4–5, 6, 11 obesity 91 oral appliances 125 positive pressure titration 97, 100 radiographic imaging 75–9 shape 170 stabilization 103–6 weight loss 91–3 upper airway resistance syndrome (UARS) 12, 13 childhood obstructive sleep apnea syndrome 47, 48 children 41 clinical diagnosis 15 indications for treatment 89–90 nasal obstruction 130 obstructive sleep apnea–hypopnea syndrome 59–61 oral appliances 125 polysomnography 67 positive airway pressure 93, 94 skeletal facial corrections 195

UPPP see uvulopalatopharyngoplasty uvula clinical diagnosis 15 laser uvulopalatoplasty 165, 166, 167, 170, 171, 174 palatal radiofrequency reduction 215 snoring 170 uvulopalatopharyngoplasty 153 uvulopalatopharyngoplasty (UPPP) 8, 153–9 auto-titrating devices 102 childhood obstructive sleep apnea syndrome 50 complications 154–5, 156–9 continuous positive airway pressure 107 hypopharyngeal airway surgery 188 laser uvulopalatoplasty comparison 164–6, 173, 175 nasal obstruction 135, 136, 138, 139 oral appliances 123, 124–5 radiographic imaging 79 results 155–6 skeletal facial corrections 193, 200, 202, 206 Stanford protocol 185, 186 technique 153–5 uvulopalatoplasty, laser 163–78 validity 71 velopharyngeal insufficiency (VPI) 156, 167, 169

velopharynx 4 see also retropalatal region childhood obstructive sleep apnea syndrome 49 hypopharyngeal airway surgery 189 laser uvulopalatoplasty 166, 167, 168, 169, 170, 172 nasal airway 130 nasal obstruction 132 skeletal facial corrections 199, 200, 202, 204 velum 171–2 venous oxygen saturation 5, 9, 13 ventilatory effort 11–12, 58, 170 ventilatory effort arousal threshold 12, 13 ventricular paroxysmal depolarizations (VPDs) 11 ventricular tachycardia 11 viscerocranium 201, 205 visual–motor incoordination 10 volume-cycled ventilation 94, 96, 103 volumetric radiofrequency tissue reduction 213–18 VPDs see ventricular paroxysmal depolarizations VPI see velopharyngeal insufficiency weight loss 50, 91–3, 103, 133, 145, 155 zygomaticoalveolar buttresses 198, 199