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ORAL AND

MAXILLOFACIAL SURGERY

OVERVIEW OF OBSTRUCTIVE SLEEP APNEA—PATHO-

PHYSIOLOGY AND TREATMENT: WHAT WORKS AND

WHAT DOESN’T!

David Yates, DMD, MD Richard A. Finn, DDS

Volume 21, Number 5 November, 2013

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OVERVIEW OF OBSTRUCTIVE SLEEP APNEA - PATHOPHYSIOLOGY AND TREATMENT: WHAT WORKS AND WHAT DOESN’T!

David Yates, DMD, MD and Richard A. Finn, DDS

INTRODUCTION

Sleep induced apnea and disordered breathing refers to intermittent, cyclical reductions or cessations in airflow while asleep.1 This may or may not be related to obstructions present in the airway. Anatomic airway obstruction increases the pressure gradient in the pharynx leading to increased collapsibility of the airway. An individual’s ability to respond to this interruption of airflow and the resulting hypoxia, via abrupt awakenings and arousal, explains the cyclical nature of this disorder. Physiologically, the body responds to hypoxia by increasing sympathetic tone, attempting to maintain airway patency. This is correlated with increased systemic hypertension and possibly with decreased insulin sensitivity, pulmonary hypertension, stroke, and coronary ar-tery disease. These frequent interruptions in the sleep cycle help to explain the common symptoms seen with the disorder, including excessive daytime sleepiness, impaired memory, and concentra-tion.1,2 This paper will be limited to the discussion of obstructive sleep apnea.

APNEA HYPOPNEA INDEx: QUANTIFYING OBSTRUCTIVE SLEEP APNEA (OSA)

The Apnea Hypopnea Index (AHI) is the number of apneas and hypopneas per hour while sleeping. Apneas are defined as cessation in breathing for at least 10 sec-onds. In 2007, the American Academy of Sleep Medicine redefined hypopneas using stricter criteria and there are now a recom-mended (rec) and alternative (alt) definitions for hypopnea. Hypopneas may be classified as: 1) moderate reduction in airflow of more than 30% with an associated O2 desaturation of 4% (rec) or 2) substantial reduction in air-flow of more than 50% with an associated decrease in O2 saturation of more than 3% or arousal (alt).2-5 Upon evaluation of previous studies using the stricter definitions AHIrec, 36% to 48% of patients previously classified

as positive for OSA using the old AHI cri-teria would now be negative. Using AHIalt, 17% to 25% of patients previously classified as positive for OSA using the old AHI criteria would now be negative.3-5

There was also a study, performed by Collop in 2002 that found tremendous vari-ability in polysomnogram scoring by differ-ent sleep technologist.6 These studies cast doubt upon the available literature that used the previous diagnostic criteria to define sleep apnea.3-5 This, in turn, puts into question the co-morbidities, associations, diagnosis, sur-gical and medical treatment modalities that were determined using this data.

Apneas and hypopneas may be due to 1) obstructive events: related to an anatomic obstruction leading to airway collapsibility (respiratory effort present), 2) central events, i.e., a reduction or cessation of brain stem re-spiratory motor output (respiratory effort ab-

Obstructive Sleep Apnea David Yates, DMD, MD; Richard A. Finn, DDS

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sent), or 3) mixed events (the most common), a combination of obstructive and central events.1,7 Severity of sleep apnea is defined by the AHI as mild obstructive sleep apnea (AHI 5-15), moderate obstructive sleep ap-nea (AHI 15-30), and severe obstructive sleep apnea (AHI >30). Central sleep apnea alone is not alleviated by surgical solutions; there-fore, it is vital that surgeons work together with sleep physicians to ensure that they are treating only patients with obstructive sleep apnea.

DEMOGRAPHICS AND RISK FACTORS OF OBSTRUCTIVE SLEEP APNEA

Obstructive sleep apnea is ubiquitous but difficult to diagnose.8,9 The dominant risk factors for obstructive sleep apnea are excess body weight, male gender and aging.2,7 Also significant, but to a lesser extent, are cranio-facial structures, ethnic differences, smok-ing, alcohol consumption prior to sleep, menopausal status, and allergic rhinitis.1,7,10-15

(Table 1)

Signs and symptoms characteristic of sleep apnea include excessive daytime sleepiness (EDS), obesity (especially neck circumference), snoring, witnessed apneas or gasping, hypertension, family history, previ-ous tonsillectomy, and non-restorative sleep.7

(Table 2) In a recent study by Gooneratne, et al. all-cause mortality risk in older adults was shown to increase in patients with EDS and an AHI ≥ 20.16 Interestingly, mortality was not increased in patients with isolated EDS or sleep disordered breathing.17-21

Sleep apnea diagnosis can be difficult when solely relying on symptoms. All of the above symptoms may be found in an OSA patient; however, none are pathognomonic for OSA. This is why collaborating with a sleep physician who can perform polysom-nography is vital.

Pathogenesis of Sleep Apnea

A fascinating aspect of this disorder is that patients with severe OSA are able to breathe without difficulty while awake.1 It has been demonstrated that PaCO2 levels can be substantially lowered in awake OSA patients without significant disruption in breathing, however, if the same patient is in NREM sleep even small decreases in PaCO2 will lead to significant apnea.1,22-24 Additionally, if an air-way obstruction, resulting in negative airway pressure, is induced in an awake patient there is an immediate compensatory increase in the drive to breathe (pharyngeal dilator activa-tion).7 This is not so in the sleeping patient. Rather hypopnea ensues until there is an increase in chemoreceptor stimuli. Only then will arousal occur.1,25-27 It is clear that there is a definite loss of biochemical feedback and neuromuscular control when a patient with OSA enters a sleeping state.

ANATOMICAL CONTRIBUTORS TO OSA

Human Airway

The human pharynx is a complex high-ly specialized structure, associated with 41 skeletal muscles, that is able to perform com-


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Demographic Correlates of Increased OSA Prevalence

Magnitude Mechanism

Male sex ++ Anatomy/ventilation controlAnatomy/neural reflex impairment Age 40 - 70 years ++

Familial AggregationRisk Factors

1. Body Habitus Anatomy/ventilation control stability Overweight and Obesity +++ Central Body Fat Distribution Large Neck Girth 2. Upper Airway Abnormalities Nasopharyngeal Obstruction (+) - (+++) Anatomy Internal nasal valve collapse External nasal valve collapse Hypertrophic turbinates Hpertrophic adenoids Oropharyngeal Obstruction (+) - (+++) Anatomy Hypertrophic tonsils Craniofacial deformities

Suspected Risk Factors 1. Genetics African Race + Unknown: likely anatomy Asian Race + Likely anatomy 2. Menopause + Unknown, anatomy? 3. Alcohol use before sleep ++ Impaired dilator muscle activity 4. Nightime nasal congestion + Airway inflammation/edemea 5. Smoking + Airway inflamation edema

TABLE 1. RISK FACTORS ASSOCIATED WITH OBSTRUCTIVE SLEEP APNEA.

Adapted from Young, et al.8,12,13,14

SnoringExcessive daytime sleepiness associated with non-restorative sleepWitnessed apneas or gaspingObesity (especially neck circumference)Family historyPrevious tonsillectomyHypertension

TABLE 2: SYMPTOMS ASSOCIATED WITH SLEEP APNEA

Adapted from Malhotra and White7


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Figure 1. The balance of forces. Inspiratory negative pressure and extraluminal pressure tend to promote pharyngeal collapse. Upper airway dilator musles and increased lung volume tend to maintain pharyngeal patency. (Adapted from Davies, et al.30 and Malhotra and White.7

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plex behaviors, including deglutition, vocal-ization, and respiration. The anatomical and functional adaptations needed for speech in general, and vowels specifically, prob-ably occurred in the last 40,000 years.28 As Davidson summarizes: “OSA is an anatomic illness caused by the evolutionary changes in the upper respiratory tract to facilitate speech, airway collapsibility was a side effect.” Unfortunately, the cost of such vari-ability is increased flexibility and loss of rigid skeletal support when compared to other spe-cies, leading to collapsibility with even slight variations in luminal pressure.1,7, 28-30 (Fig. 1)

With increased luminal pressure the pharynx behaves like a collapsible tube and follows the pressure-flow relationships out-lined in the Starling Resistor Model. Stud-ies by McNicholas, and Smith and his col-leagues provide a unifying concept of airway obstruction and sleep apnea.31-33 The normal pleural pressures transmitted for quiet breath-

ing from the thorax to pharynx are -4 cm to -8 cm H2O.34 To function properly the pharynx and upper airway must not collapse under this negative pressure during normal inspira-tion. Pcrit is the critical pressure when the pharynx collapses, primarily during inspi-ration. The Pcrit, wherein the pharynx col-lapses during sleep is very different between controls and OSA patients. Passive Pcrit is the pressure at which the inherent mechanical stability is able to maintain an open pharynx, while Active Pcrit is the pressure at which neuromuscular action is able to maintain an open pharynx.

Schwartz, et al. demonstrated that nor-mal individuals have a Pcrit of approxi-mately -12 cm H2O whereas OSA patients have a Pcrit of +3 cm H20 pressure (i.e., the pharynx will collapse at atmospheric pres-sure).35 They also demonstrated that normal individuals, snorers, obstructive hypopneics, and obstructive apneics can all be differen-


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Figure 2. Differentiation of normal individuals, snor-ers, obstructive hypopneics and obstructive apneics by there values of Pcrit during NREM sleep. (Adapted from Schwartz, et al., 1994.35

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tiated by their Pcrit values. (Fig. 2) Further details of Pcrit have been demonstrated,29, 36,37

and the commonality of these findings is that OSA patients have a Passive Pcrit close to 0 cm H2O and an Active Pcrit around -1cm H2O. Kirkness, et al. further demonstrated that factors such as male sex, increasing age, and obesity contribute to the mechanical and neuromuscular instability of the upper airway during sleep.38

Collectively these studies demon-strate that OSA patients have anatomical deficiencies that contribute to a high Passive Pcrit and blunted neuromuscular responses that contribute to a high Active Pcrit. Fac-tors contributing to a blunted neuromuscular response could be decreases in mechano- or chemoreceptor input, overall depressed affer-ent receptors in the sleep state, or decreases in loop gain stability (respiratory stability). Although methodologically these studies are very well done and tightly controlled, only 2 or 3 of possibly 55 muscles have been stud-ied.

Sites of Airway Collapse

In many patients with OSA there are multiple sites of obstruction.1 The sites asso-ciated with airway collapse in OSA patients vary with age, body habitus, and presence of a craniofacial deformity. The primary cause of OSA in children is hypertrophic lymphatic tissue, specifically palatal tonsils and adenoids.39 Obese patients are generally obstructed at the velopharynx (retropalatal region of the oropharynx) whereas non-obese retrognathic patients are obstructed at both the velopharynx and orohypopharynx (retro-glossal region).40

CT and MRI imaging has also demon-strated that the thickness of the lateral pha-ryngeal walls is a major site of obstruction in the adult OSA population.41,42 Maxilloman-dibular advancement, weight loss, and treat-ment with continuous positive airway pres-sure (CPAP) all increase the lateral dimension of the airway.39,43,44 Airway length (measured from the top of the hard palate to the base of the epiglottis) is also increased in the OSA patient. As airway length increases, so do the pressures required to maintain its patency.45,46

Craniofacial Deformities Associated with OSA

Due to the multifactorial etiology and complexity of OSA, the literature has been anything but clear on the association between craniofacial deformities and OSA.47-53 No causality can be established between any cra-niofacial parameter and OSA. A recent paper by Cillo et al. noted that the severity of OSA in the VA population (controlling for sex, age,


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Flexion of the cranial baseMaxillary anteroposterior hypoplasiaMandibular hypoplasia between Go and GndLong face syndrome Vertical maxillary excess High mandibular plane angle Apertognathia Mandibular deficiencyInferiorly positioned hyoid bone

TABLE 3: CEPHALOMETRIC MEASUREMENTS INCONSISTENTLY ASSOCIATED WITH OSA

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and obesity) could not be associated with any of the cephalometric measurements that are commonly thought to be related with the OSA population, including posterior-anterior air-way space, soft palate length, distance of the hyoid from the mandible, mandibular length (Go-Gn), and mandibular plane to sella-nasi-on angle.53 This study demonstrated that for the general population there is very little, if any, association between severity of OSA and craniofacial morphology. Some commonly cited associations found in some studies but not found in others are listed in Table 3.

Factors Contributing to Airway Collapsibility

Obese patients have reduced lung vol-umes due to excessive intra-abdominal fat that decreases their ability to fully expand their chest wall and diaphragm. Chest expan-sion is further inhibited with a recumbent posture during sleep. This decrease in chest wall expansion further compresses the tra-chea leading to tracheal narrowing.1

Surface tension of the liquid lining the pharyngeal mucosa is higher in the OSA patient, which also leads to increased col-lapsibility of the upper airway. Significant decreases in airway collapsibility and an AHI of 20% to 30% have been achieved in OSA patients treated with surfactant therapy.1,54-57

Compared to females, males have a sig-nificantly increased tendency for airway col-lapsibility.38,44,58,59 Males greater pharyngeal airway length and greater amount of soft tis-sue mass in the soft palate and tongue likely accounting for this difference.

Nasal obstruction can also lead to air-way collapse.31,60-65 Obstruction or constric-tion of the upper airway at any site will increase the resistance to airflow and create larger negative intraluminal pressures in the pharynx. The pharyngeal dilator muscles or other mechanisms must then counteract these higher pressures to prevent airway collapse. (Fig. 3) In a non-OSA patient this increased negative pressure is overcome by intrin-sic mechanical stability (Passive Pcrit), an increase in the neuromuscular response (Ac-tive Pcrit) or both. However, OSA patients generally present with airway obstruction and a decreased neuromuscular response, leading to airway collapse.37,66

Figure 3. Starling Resistor Model illustrating the ten-dency toward collapse of the pharynx due to restric-tion of nasal airflow.30

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OSA patients are not apneic during awake states, but during NREM sleep the body is in a hypotonic state in which some degree of neuromuscular control is lost. This loss of neuromuscular control is greater in OSA patients, contributing to their inability to maintain a patent airway.67 In non-OSA subjects during sleep, upper airway resistance is lower when breathing through the nose. Therefore, nasal breathing would normally be expected.68 Only if nasal obstruction leads to airway collapse will the sleeping subject gasp for air via the oral route.31 Multiple stud-ies have confirmed an independent relation-ship between nasal resistance, pharyngeal narrowing, and AHI levels.60,61,69

PHYSIOLOGICAL EFFECTS OF SLEEP APNEA

Cardiovascular Sequelae of Sleep Apnea

OSA produces arterial O2 desaturations and hypercapnia. Carotid chemoreceptors detect these sudden changes and stimulate the release of sympathetic discharge.70,71

Hypoxia results in arousal, which further augments sympathetic discharge. Sympa-thetic discharge leads to a transient increase in vasoconstriction (i.e., blood pressure).72 Continuous exposure to intermittent hypoxic events leads to a long-term increase in sym-pathetic tone.73-75 Additionally, the degree of hypoxia in OSA patients is predictive of the development of atherosclerotic lesions, coro-nary artery disease, and pro-inflammatory factors.76-78

Hypertension

Causality has been established between OSA and hypertension in animal models.1,79-81

The Wisconsin Sleep Cohort has provided compelling evidence that there is a dose-response relationship between hypertension and the severity of OSA.82 However, another large prospective study found no evidence of a dose-response relationship between hypertension and the severity of OSA that was independent of obesity.1,83 Use of CPAP can dramatically reduce hypertension seen in severe OSA patients.84,85 Whereas, oral appli-ances have been associated with only a mod-est decrease in hypertension.86

Stroke

There is an association between stroke and severe OSA (i.e., an AHI > 30).87-89

Additionally, this association appears to be, at least, partially independent of blood pres-sure.87 Use of CPAP in severe OSA patients decreases the incidence of stroke to control group levels.1,90

Hyperlipidemia

Intermittent hypoxia has been shown to cause hyperlipidemia in the rodent model.91

Multiple studies, including the Sleep Heart Health Study (5000 subjects), have demon-strated positive associations between sever-ity of OSA and an increase in serum LDL as well as a corresponding decrease in HDL.92-

94 Effective treatment with CPAP leads to decreases in serum LDL levels and an in-crease in HDL levels.93,94

Cardiac Arrhythmias

Patients with moderate to severe OSA are at an increased risk for arrhythmias.1


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Guilleminault, et al. reported that 50% of OSA patients suffer from arrhythmias (especially bradyarrhythmias, PVCs, and atrial fib/flutter). Interestingly, treatment of OSA eliminated sleep related bradyar-rhythmias and atrial fibrillation/flutter in this population of patients.95 Recurrence of atrial fibrillation after defibrillation is more com-mon in the untreated versus the treated OSA patient.96

Summary of Cardiovascular Sequelae

Numerous studies have demonstrated statistically significant associations between moderate to severe OSA (an AHI between 25 and 30) and cardiovascular disease (espe-cially hypertension, stroke, and arrhythmias). Evidence for associations between OSA and coronary artery disease, left ventricular dys-function, and pulmonary hypertension is less convincing. Cardiovascular events decrease with effective OSA treatment; however, more evidence is needed before definitive conclu-sions can be made.1,95-97

Obstructive Sleep Apnea and Insulin Resistance

The population that suffers from OSA is very similar to the population afflicted with Metabolic Syndrome: namely, many of the patients are obese, suffer from hyperlip-idemia, insulin resistance and hypertension. It has proven difficult to establish causality between insulin resistance and OSA, in part due the similarity between patient popula-tions. Many studies have demonstrated an as-sociation between OSA and insulin resistance, but proving causality has been difficult.98,99

The effect of OSA treatment with CPAP on insulin resistance has had mixed results, some studies have demonstrated improved insulin sensitivity while others have shown no improvement.100,101 In the light of current data no definitive conclusions can be made concerning the relationship between OSA and insulin resistance other than that they are associated and likely more deeply related.1

Neural Injury in Obstructive Sleep Apnea

Typical OSA patients have many comor-bidities with neural injury, including hyper-tension, hyperlipidemia, diabetes, increased atherogenesis, and cardiac arrythymias. As expected, these factors clearly contribute to increased neurovascular injury in this popu-lation of patients. Minoguchi, et al. using brain MRI, found that 25% of individuals with severe sleep apnea had infarctions ver-sus 7% of obese matched controls.102

The more concerning question is: Does OSA alone lead to neuronal loss and cogni-tive impairments? Studies in newborn rat pups have demonstrated that intermittent hypoxia, as seen in OSA patients, can lead to long-term spatial memory deficits even months after the intermittent hypoxia expo-sure.103,104 Similarly, a recent limited study by Halbower, et al. found that children with severe sleep apnea had significant cognitive deficits, including reduced IQ (15 points), poorer verbal working memory and poorer verbal fluency compared to controls.105

Although the majority of studies look-ing at neural injury associated with OSA have been small, many had findings suggest-ing that even limited hypoxia due to severe


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sleep apnea can lead to permanent neural in-jury and associated cognitive deficits.

Unfortunately, studies that have at-tempted to treat patients with OSA-related neurocognitive deficits have, thus far, only shown mild and transient improvement.106 The comorbitities commonly cited in the lit-erature were nicely discussed in a recent re-view article by Dasheiff and Finn.2,107 This article focused on often-cited associations versus the loosely applied “causation” term frequently utilized in literature. Clearly, ad-ditional research is needed.

THE ENDPOINT: UNDERSTANDING THE PATHOGENESIS OF OSA LEADS TO EFFECTIVE TREATMENT

The pharynx is a collapsible tube that is more prone to collapse while OSA patients are asleep but not while they are awake (i.e., dependent on sleep state). Multiple anatomi-cal factors contribute, including internal or external nasal valve collapse (See Selected Readings in Oral and Maxillofacial Surgery, Vol. 12, #1), hypertrophic turbinates, hy-pertrophic adenoids and tonsils (Waldeyer’s ring), fatty deposits, craniofacial abnormali-ties, increased upper airway surface tension, decreased lung volumes, hypotonicity of pharyngeal musculature, and functional eti-ologies (associated with but not yet defined) relating to pharyngeal Pcrit. These factors contribute to airway collapsibility by increas-ing the luminal pressure necessary to main-tain a patent airway.

Effective treatment options include overcoming these resistances with greater inspired forces (i.e., use of CPAP) or re-ducing the obstructions by losing weight,

altering the craniofacial anatomy, increasing lung volumes, decreasing surface tension, or inducing greater tonicity of pharyngeal constrictors.1 CPAP is the gold standard of treatment. It effectively “cures” sleep apnea by eliminating apneas and hypopneas, and it is affordable. Unfortunately, more than 50% of patients are unable to tolerate long-term CPAP use.108 Therefore, effective therapies such as weight loss, positional devices, medi-cations, oral appliances, and surgery would be desirable as an alternative to CPAP. The rest of this paper will address the appropriate surgical indications and therapy for effective OSA treatment.

Goals of Surgical Therapy

Surgical treatment options should be individualized and should specifically target the areas of obstruction that present in each patient. However, the ability of practitioners to consistently and repeatedly identify the same obstruction site from one day to the next and the ability of different observers to identify the same sites of obstruction is still elusive. Instead, the overall aim is to enlarge the airway and decrease its collapsibility.

Treatment planning and appropriate as-sessment of the airway is vital when consid-ering surgery for airway obstruction. An ap-propriate nasopharyngeal, velopharyngeal, and orohypopharyngeal exam is essential. The most useful modalities for performing such an assessment, in our opinion are a thor-ough history, a detailed physical examination (including evaluation of the nasal septum, internal and external nasal valves, tonsil-lar size, mallampati class, facial asymmetry, and cephalometric analysis. It is important to thoroughly assess the entire airway when


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considering surgical intervention. However, Schellenberg, et al’s review of physical find-ings in 420 patients identified only narrowing of the palatopharyngeal fold as a risk factor; retrognathia, macroglossia and overjet did not appear to be risk factors.109

Predictive Parameters for OSA Treatment

The literature has been notoriously mixed when trying to find consistent radio-graphic differences between OSA and non-OSA subjects. Much of this is due to the multifactorial causes of OSA. In a recent review of extensive cephalometric data col-lected and evaluated in OSA patients, Cuccia, et al. attempted to clarify this confusion by separately evaluating obese and non-obese patients.52 Non-obese OSA patients are more likely to be afflicted with a craniofacial de-formity while obese patients with OSA have a normal craniofacial morphology. Addition-ally, soft tissue characteristics are not nec-essarily distinguishable between obese and non-obese patients.52 The following four cephalometric findings were found to be sig-nificant for OSA patients. (Fig. 4)

Hyoid bone position: Both obese and non-obese OSA patients have a low-er hyoid bone position (level of C4-C6) than healthy patients (level of C3-C4).

Relationship of maxilla to mandi-ble: Non-obese OSA patients are likely to have an ANB discrepancy resulting in a Class II occlusion. This parameter was not significant in obese OSA patients.

Intermaxillary divergence: Obese patients with OSA were more likely to have increased intermaxillary

Figure 4. Cephalometric landmarks related to obstructive sleep apnea. 1) Hyoid bone positioning as measured from H (Hyoid) to MP (Mandibular Plane). 2) ANB ° (Angle formed by Point A -> Nasion -> Point B). 3) Intermaxillary divergence is the angle formed by PNS-ANS (Posterior Nasal Spine to An-terior Nasal Spine) and Go-Me (Gonion – Menton). 4) Cranial base measured from S-N (Sella-Nasion).

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divergence. This parameter was not sig-nificant in non-obese OSA patients.

Cranial base length (Sella-Nasi-on): Non-obese patients with OSA were more likely to have a shortened cranial base. This parameter was not significant in obese OSA patients.

SURGICAL INTERVENTION

When evaluating the “success” of one procedure over another, a very critical view must be taken. Many surgeons will call a surgery that results in a decrease of AHI lev-els to less than 20 and AHI reduction of at least 50% a success. This is compared to the American Academy of Sleep Medicine defi-nition of success as an AHI of 5 or less.106 This tendency to link success with a total


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cure is likely due to the ability of CPAP or tracheotomy to have a 100% cure rate.

However, no surgeon is suggesting that CPAP be replaced with surgery. Rather sur-gery should be an adjunctive to CPAP, i.e., an opportunity to increase CPAP compliance by reducing airway resistance and obstruction. Also surgery should be seen as an opportu-nity to alleviate OSA in the large population of patients who are unwilling or unable to tolerate CPAP. Simply because surgery is not able to totally eradicate the disease does not mean that surgical intervention is a failure.110

The vigor with which each position can be defended is clearly demonstrated in a point-counterpoint version in the Journal of Clini-cal Sleep Medicine by Drs. Phillips and Pow-ell.111,112

Septorhinoplasty and Internal and External Nasal Valve Surgery

Nasal breathing is the predominant mode of respiration whether the mouth is open or closed.113,114 Meurice, et al. demon-strated in normal subjects that oral breathing increases the critical pressure and increases pharyngeal collapsibility during sleep more than nasal breathing.115

Fitzpatrick studied the effect of oral versus nasal breathing during sleep in a ran-domized, single cross-over design and dem-onstrated that oral breathing increases airway resistance and results in severe OSA, whereas nasal breathing does not.116 Obstructed nasal breathing has been identified as an indepen-dent risk factor for OSA in a large study of 540 OSA patients through stepwise multiple regression analysis.117

In a Japanese study of almost 8000 patients, Udaka, et al. showed that OSA patients with chronic nasal obstruction had a 5.22 higher odds ratio for habitual observed apneas and 2.17 higher odds ratio for excessive daytime sleepiness, compared with those without nasal obstruction (P<0.001).118 Experimental nasal obstruction during sleep consistently results in the precipitation of OSA as measured by AHI.119-121

Chen and Kushida reviewed the role of nasal obstruction in sleep disordered breath-ing and emphasized the contribution of air-flow obstruction at different sites throughout the nasopharynx.122 Nasal surgery has proven effective in decreasing excessive daytime sleepiness, decreasing CPAP pressures, and improving sleep quality,119,120,123-126 but nasal surgery has been inconsistently effective in decreasing AHI.127-129

Series, et al. reported significant decreases in AHI in moderate OSA patients following septoplasty, turbinectomy and pol-ypectomy.129 Other studies, however, have demonstrated less than optimal improve-ment in OSA parameters following surgery for nasal obstruction.124-126 (See also Selected Readings in Oral and Maxillofacial Surgery, Vol. 14, #4) The clinical utility of functional nasal surgery in decreasing EDS, improving sleep quality, improving quality of life, and decreasing CPAP pressures versus improve-ment in the AHI seems to be a disconnect.

Currently, studies that have evaluated surgery for nasal obstruction have been most-ly limited to septoplasty or turbinectomies. Very few have evaluated results following nasal valve surgery. Septoplasty alone has


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only a modest and statistically insignificant ability to improve nasal airflow, whereas in-ternal and external nasal valve reconstruc-tions are associated with significant decreas-es in resistance and 200% to 260% increases in airflow.127-130 Constantian and Clardy in a series of 160 private patients, studied with rhinomanometry, demonstrated a 490% im-provement in airflow in patients treated at multiple intranasal sites.130 Future studies are needed to evaluate outcomes following nasal valve surgery in conjunction with septoplasty for the OSA patient.

Soft Palate Procedures

Tonsillectomy is a proven effective therapy for treatment of OSA in patients with tonsillar hypertrophy. This has been clearly established in the pediatric literature; how-ever, tonsillar hypertrophy is relatively rare in the adult population.131 A recent case se-ries by Verse, et al. found that adult patients who presented with tonsillar hypertrophy and OSA had a 80% surgical success rate (defined as AHI levels less than 20 and AHI reduction of at least 50%) for severely apneic OSA patients and 100% for mildly apneic OSA patients.132 For the few adult patients with tonsillar hypertrophy, tonsillectomy can drastically improve their OSA.

Uvulopalatopharyngoplasty (UPPP) has not proven to be an effective therapy for the majority of sleep apnea patients. UPPP includes the removal of the tonsils, posterior soft palate/uvula, and closure of the tonsil-lar pillars.133 Approximately 41% of patients who undergo this procedure obtain an AHI of fewer than 20 events per hour. Additionally, imaging and physical characteristics have

been unsuccessful in guiding the surgeon to appropriately select those patients who might benefit from this therapy.7,134 Caples, et al. in a metanalysis found that UPPP reduced AHI by 33%, from a pre-op mean of 40.3 to 29.8.

Laser Assisted Uvulopalatoplasty (LAUP) has not proven to be an effective therapy for the majority of sleep apnea patients. LAUP is performed via laser incisions, causing scarifi-cation of the soft palate and uvula that leads to shortening and tightening. There are mixed findings, most studies reporting modest re-ductions135 in AHI (i.e. from 18.6 to 14.7); however, multiple studies have demonstrat-ed an increase in AHI following surgery.136,137 There is also an overall complication rate of 3.45%.

Radiofrequency ablation has not prov-en to be an effective therapy in sleep apnea patients. Radiofrequency ablation of the soft palate, tongue or both produces only mild changes in AHI (from 23.4 to 14.1), with only slight changes in excessive daytime sleepiness (from 9.7 to 6.7).133

Soft palate implants have not proven to be an effective modality for treatment of OSA. In this procedure, Dacron® rods are inserted into the soft palate under local anes-thesia. Caples, et al. noted that modest reduc-tions in AHI have been noted (26%), but very few studies have been conducted.133

Genioglossal and Hyoid Procedures

Genioglossal advancement with hyoid myotomy holds promise for moderate reduc-tions in AHI. Neruntarat, et al. reported a re-duction in AHI from 48 to14 in 46 patients after 39 months of follow-up.138


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Maxillo-Mandibular Advancement (MMA)

MMA is a consistently effective treat-ment modality for OSA. Maxillary advance-ment by a Le Fort 1 osteotomy, advances the soft palate with its associated muscles, con-tributing to an increase in the velopharyngeal airway space. Similarly, mandibular advance-ment by bilateral sagittal split rami oste-otomies, advances the anterior belly of the digastric, mylohyoid, geniohyoid and genio-glossus muscles, positioning the tongue and hyoid more anteriorly, and thereby, increas-ing the orohypopharyngeal airway space.139

There are a limited number of practi-tioners performing this procedure for OSA, and due to its perceived morbidity and cost it is typically reserved for the patient who has failed every other treatment modality avail-able (not including tracheostomy). Interest-ingly, the degree of maxillary advancement, but not mandibular advancement, was most closely related to surgical success.

Although many studies have shown significant improvement of subjective symp-toms and AHI with MMA, the majority of these had relatively small sample sizes and none were prospective randomized con-trolled trials.140 However, this limited data suggests that MMA may provide the greatest improvement in OSA symptoms, AHI, and overall quality of life compared to all other surgical options.133,139-142

A recent meta-analysis by Caples, et al. concluded that substantial and consistent reductions in AHI were found with MMA (Fig. 5) with few adverse outcomes.133 They

Figure 5. Changes in Apnea/Hypopnea Index (AHI) before and after maxillo-mandibular advancement from 9 studies reviewed by Caples, et al.133

____________________________________looked at 9 case series (234 subjects), all with severe OSA (mean AHI 54.4/h). After MMA overall reduction of AHI was 87%, with a mean post-op AHI of 7.7. Similarly, Holty and Guilleminault in a more inclusive meta-analysis of 627 adults treated with MMA, of which 67% had previous Level I soft tissue procedures, found an increase in the lowest nocturnal O2 saturation from 71.9% to 87.7%, an improved Epworth Sleepiness Scale (Table 4) from 13.2 to 5.1, and a reduction in AHI from 63.9 to 9.5. The overall percent-ages of subjects with AHIs of < 15, <10, <5 after MMA were 77.6%, 63.4%, and 43.2%, respectively.140 When all patients with an AHI of less than 30 were combined the increase was 66.7%.

A surprising finding in this study was the dentofacial normalcy of the group-mean SNA of 80° and SSB of 77°. The only pre-dictors of a cure (AHI less than 5) included: greater maxillary advancement, larger pos-terior airway space (> 14mm), younger age (< 30 years), and a lower pre-surgery AHI. No pre-op or post-op cephalometric findings were predictive of a cure, other than posterior airway space.140 Also of note, 50% of patients


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TABLE 4; EPWORTH SLEEPINESS SCALE: 139

How likely are you to doze or fall asleep in the following situations, in con-trast to just feeling tired? This refers to your usual way of life in recent times. Even if you have not done some of these things recently try to work out how they would have affected you. Use the following scale to choose the most appropriate number for each situation: 0 = would never dose; 1 = slight chance of dozing; 2 = moderate chance of dozing; 3 = high chance of dozing.

Not sleepy < 10 Sleepy = 10-16 Very Sleepy ≥ 16

SITUATION SCORESitting and ReadingWatching TVSitting inactive in a public place (e.g., a theater or meeting)As a passenger in a car for one hour without a breakLying down to rest in the afternoon when circumstances permitSitting and talking to someoneSitting quietly after lunch without alcoholIn a car, while stopped for a few minutes in traffic

TOTAL /24

____________________________________

reported a younger facial appearance, 36% reported a more esthetic facial appearance, and 9% report a less esthetic face.

MMA has a major surgical complication of rate of 1%, a minor complication rate of 3.1%, a risk of persistent facial paresthesias

at 1 year of 14.2%, and a post-treatment mal-occlusion rate of 44%.140 The two large meta-analyses by Caples, et al. and Holty and Guil-leminault emphasize that despite multiple surgeries (Phase I and Phase II) both patient groups still had OSA, with a mean endpoint AHI of 7.7 and 9.5, respectively.133,140 This re-emphasizes the complexity of the disor-der, our meager understanding of its genesis, and the conundrum of determining the most appropriate treatment regime for individuals that cannot tolerate CPAP.

Long-term results of MMA were recent-ly reviewed by Jaspers et al.142 A minimum 8 mm of advancement was performed on six patients. In all cases AHI decreased to less than 5 at 6 months following surgery. Their values on the Epworth Sleepiness Scale also decreased accordingly. At 8 years follow-up one patient had a significant relapse, with AHI worsening from 2 to 41, although this was still better than the pre-op AHI of 81. Despite this relapse, his daytime somnolence did not increase significantly.143 (Fig. 6 on P. 16) Additionally, two other patients had small increases in post-op AHI at 8 years, which put them at an AHI greater than 5. Although this study is small, it demonstrates the long-term stability of MMA as an effec-tive therapy for OSA.

Li, et al. also found long-term results of MMA to be stable.143 They reported that aging and mild weight gain do not appear to adversely affect long-term results. However, major weight gain did lead to relapse.

One possible aid in predicting which patients may or may not benefit from MMA is improvement seen with the use of a man-


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Figure 6: Clinical changes in OSA following maxil-lomandibular advancement. A. Changes in Apnea/Hypopnea Index,145 B. Changes in Epworth Sleepiness Scale.138

____________________________________

A.

B.

dibular repositioning appliance (MRA). Although a limited study, Hoekema, et al. found that patients with moderate to severe OSA (AHI from 26 to 81) who experience a more than 50% reduction in AHI with use of an MRA benefitted significantly from MMA, with complete elimination of OSA (i.e., AHI less than 5).144 (Fig. 7)

CONCLUSION

Obstructive sleep apnea remains a complex enigma confronting physicians of multiple specialties. Surgical solutions remain elusive. Targeted surgical therapy appears to be the best approach to clear obstructions at different regions in the naso-, velo-, and oro-hypopharynx. Many surgical therapies that

have been tried and extensively studied con-tinue to yield unsatisfactory results, including UPPP, LAUP, RFA, and soft palate implants. Surgeries that appear to have some benefit when targeted appropriately are genioglossal advancement with hyoid myotomy and sur-geries to correct nasal obstruction. Although the latter do not cure OSA they do lead to increased quality of life with decreased EDS. The two surgeries which undoubtedly have the highest success rate are tonsillectomies when clearly indicated and maxillo-man-dibular advancement. However, the surgical literature, especially regarding MMA and tonsillectomies in adults, lacks randomized controlled studies that would lend credence to what appear to be promising solutions to a difficult problem.


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Dr. Richard A. Finn received his DDS degree from the University of Illinois Col-lege of Dentistry in 1976. He completed his oral and maxillofacial surgery training from Parkland Memorial Hospital in 1981. His academic career began at the Univer-sity of Texas Southwestern Medical Center in 1981 and continues at UTSWMC to date as a Professor in the Departments of Sur-gery and Cell Biology as well as the Chief of Oral & Maxillofacial Surgery at the Vet-erans Administration North Texas Health Care Center. Dr. Finn has a long history of involvement in clinical and laboratory based anatomical issues and studies. He has been actively engaged in treating sleep-disordered breathing problems since 1990.

Dr. David Yates received his DMD from the University of Florida School of Dental Medicine (2008) and his MD from Univer-sity of Texas Southwestern Medical School (2011). He is currently a chief resident at Parkland/UTSW hospitals and will finish his training in June of 2014. He has been accepted for a Cleft/Craniofacial fellowship at Lousiana State University, Shreveport with Dr. Ghali and hopes to pursue career in aca-demics following fellowship training.

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RELATED ARTICLES FROM SELECT-ED READINGS IN ORAL AND MAXILLO-FACIAL SURGERY.

Surgical Correction of the Incompetent Nasal Valve for Sleep Disordered Breathing. Joseph E. Cillo, Jr, DMD; Richard A. Finn, DDS, Selected Readings in Oral and Maxillofacial Surgery, Vol. 12, #1, 2004.

Functional Rhinoplasty―Assessment and Management of Nasal Obstruction. Ron Caloss, DDS, MD and Douglas P. Sinn, DDS, Selected Readings in Oral and Maxillofacial Surgery, Vol. 14, # 4, 2006.

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