Conferences and Reviews

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1 Obstructive Sleep Apnea Trends in Therapy 143 Conferences and Reviews ROBERT W. RILEY, DDS, MD; NELSON B. POWELL, MD; CHRISTIAN GUILLEMINAULT, MD; ALEX CLERK, MD; and ROBERT TROELL, MD, Palo Alto, California The National Commission on Sleep Disorders Research, in its report to Congress, concluded that the primary care community generally does not understand sleep disorders. Obstructive sleep apnea carries a risk of substantial morbidity and mortality. Excessive daytime sleepiness results from fragmented sleep and microarousals associated with apneic events. It causes poor work performance and increases the incidence of automobile accidents due to driving while drowsy. The commission estimates that the loss of productivity in the United States from excessive daytime sleepiness is more than $20 billion per year. Obstructive sleep apnea is strongly associated with hypertension, myocardial infarction, and stroke. Risk factors for obstructive sleep apnea include male sex, obesity, older age, craniofacial anomalies, and familial risk. Treatment is based on documenting the disorder by polysomnography. Medical management of the syndrome includes weight loss and nasal continuous positive airway pressure. A network of follow-up and support is necessary to maintain compliance. Surgical treatment is reserved for those for whom nasal airway pressure treatment fails. A surgical protocol is presented that demonstrates efficacy equal to nasal airway pressure treatment. Primary care physicians should assume the responsibility of identifying patients at risk for obstructive sleep apnea and refer them appropriately. (Riley RW, Powell NB, Guilleminault C, Clerk A, Troell R: Obstructive sleep apnea-trends in therapy. West j Med 1995; 162: ) Obstructive sleep apnea syndrome (OSAS) continues to be little more than a medical curiosity to primary care physicians. Thought to be of little importance, the hallmark symptom of snoring is more a subject of humor than of serious scientific investigation. In 1988 the United States Congress established the National Commission on Sleep Disorders Research "to conduct a comprehensive study of sleep disorders and to develop a long-range plan for the use and organization of national resources to deal effectively with sleep disorders research and medicine."'t10 The commission found that the primary care community generally did not understand sleep disorders. In one survey, the commission conducted searches of computerized clinical databases in 50 primary care settings throughout the United States, accumulating data on more than 10 million patients. Even though ICD-9 [International Classification of Diseases, 9th revision] codes for sleep disorders have been part of the international classification system for nearly 20 years, only 73 specific cases of sleep disorders were identified in this sample. Considering currently accepted prevalence estimates, more than a million cases should have been seen. To further confirm these results, the raw records of more than 10,000 patients in primary care clinics were carefully examined by commission investigators. Every physician-patient interaction from a patient's first visit to the time of the study was examined, adding up to more than 50,000 physician-patient interactions. In this huge mass of data, not a single appropriate response to a patient with a sleep-related complaint was found. The most serious sleep disorder in terms of morbidity and mortality is OSAS, which represents greater than 80% of the diagnoses made by the Stanford (California) Sleep Disorders Center.'* The syndrome is characterized by recurrent episodes of obstructed breathing during sleep, caused by the collapse of the upper airway. The trachea and bronchi maintain patency by cartilaginous support. Upper airway patency is critically dependent on the dilator muscles of the pharynx. Sleep results in the loss of tone of the upper airway muscles and, specifically, the dilator muscles. Patients with "disproportionate" anatomy of the upper airways are therefore susceptible *See also the editorial by A. E. Sher, MD, "Treating Obstructive Sleep Apnea Syndrome-A Complex Task," on pages of this issue. From the Stanford University Sleep Disorders and Research Center, Palo Alto, Califomia. Reprint requests to Robert W. Riley, DDS, MD, Stanford University Sleep Disorders and Research Center, 750 Welch Rd, Ste 317, Palo Alto, CA

2 144 WIM, WIM. --JI. February 1995-Vol 162, No. 2 Obstructive ti-vi Sleep Apnea-Riley et al ABBREVIATIONS USED IN TEXT CPAP = continuous positive airway pressure NS = not significant OSAS = obstructive sleep apnea syndrome RDI = respiratory disturbance index Sao, = arterial oxygen saturation SD = standard deviation to complete airway collapse during sleep. This is usually preceded by many years of loud, heroic snoring that is the result of muscle relaxation and partial airway obstruction. With complete obstruction, snoring is interrupted by periods of silence lasting ten seconds to more than a minute. The apneic periods are characterized by paradoxical respiratory efforts and often severe arterial hypoxemia. The apneic periods are terminated by sleep reversals or microarousals that produce increased muscle tone and airway patency, which correspond to a generalized startle response or gasping that is usually noted by a spouse. After a brief period of normal breathing, this cycle of events is repeated. This sequence of events can occur several hundred times during a normal night of sleep. The primary symptom of obstructive sleep apnea is excessive daytime sleepiness or hypersomnolence due to the fragmented sleep and microarousals associated with the apneic events.3 Excessive daytime sleepiness may result in impaired cognition and memory loss that in turn can result in poor performance at work and emotional disturbance. A major concern with excessive daytime sleepiness is driving while drowsy, which increases the risk of automobile and truck accidents. The risk of such accidents has been reported to be as much as seven times greater in patients with OSAS than in the general population.4 The national commission estimates the loss of productivity in the United States from daytime hypersomnolence to be greater than $20 billion per year. In addition to the effects of excessive daytime sleepiness on productivity, several studies have demonstrated strong associations between snoring and hypertension, myocardial infarction, and stroke.56 One study determined existing morbidity and incident mortality over a seven-year period among patients with sleep apnea who had had tracheotomies and been conservatively treated (for example, weight loss).7 Compared with the general population, patients with sleep apnea have twice the prevalence of hypertension, three times as much coronary artery disease, and four times as much cerebrovascular disease. A recent case-control study from Italy found that the risk of myocardial infarction was about four times higher in patients who reported snoring every night than in those without this history.8 Patients who undergo treatment of their obstructive sleep apnea show improvement in their morbidity-mortality risks. Prevalence estimates have shown some discrepancy because of the diversity of study groups and sizes. Employed men in Israel had a 5% incidence of OSAS,9 whereas employed men in Germany aged 19 to 61 had a 10% incidence of the syndrome."0 Both of these studies involved relatively small groups (< 100). In contrast, a recent study examined sleep studies from more than 600 patients in a population-based sampling of working men and women aged 30 to 60 years. In all, 9% of women and 24% of men showed OSAS above the minimum cutoff level, and 4% of women and 9% of men in this age group have substantial OSAS that could increase cardiovascular risk and produce debilitating daytime hypersomnolence.'" The risk factors for OSAS include male sex, obesity, older age, craniofacial anomalies, and familial risks."2 About 85% of patients diagnosed with the syndrome are male. The male sex predisposition to a greater number of obstructive respiratory events has been noted even among "healthy" volunteers. Preliminary data from the study of such patients between the ages of 7 and 75 years in Cleveland suggest that men are six times more likely than women to have the syndrome.'3 Sleep apnea is most commonly diagnosed in persons between the fifth and seventh decades of life. Symptoms of loud snoring and hypersomnolence may precede the diagnosis by many years. It is not uncommon, however, for symptoms to develop as early as the first or second decade of life. This suggests that mechanisms that lead to the development of sleep apnea may operate over many years. Studies of the general population have shown a clear age-related increase in the number of respiratory pauses during sleep.'4 About two thirds of the patients with OSAS diagnosed at the Stanford Sleep Disorders Center are obese (>20% ideal body weight). Obesity has been found to be the strongest predictor of OSAS. In one study of elderly patients, obesity was estimated to be about fourfold stronger than the influence of age and twice as strong as the influence of sex in predicting the presence of OSAS. 3 Several families have been described that have multiple members with sleep apnea. The transmission of OSAS in families is unclear, although the occurrence of the disorder in nonobese male and female family members suggests the importance of genetic factors.'" Included in the genetic predisposition to OSAS are craniofacial anomalies. Anomalies associated with mandibular maldevelopment (for example, the Pierre Robin syndrome or the Treacher Collins syndrome [mandibulofacial dysostosis]) often lead to OSAS. Preliminary data from an ongoing geneticepidemiologic study suggest that subjects with a family member with OSAS are 1.5 times more likely to have the disorder.'6 Diagnosis Given the high prevalence of symptomatic OSAS in the general population, its serious consequences, and the fact that it is readily treatable, primary care physicians have the responsibility to identify patients at risk for the disorder and to make appropriate referrals. Clinical

3 IM 195Vl12 No btutv le e-ie ta 4 WIM, February 1995-Vol 162, No. 2 Obstructive Sleep Apnea-Riley et al 145 features that are helpful in identifying such patients include habitual snoring, nocturnal gasping, episodes of apnea, and daytime somnolence.'7 Any combination of these symptoms is strongly indicative of substantial obstructive sleep apnea. As previously stated, most patients with this syndrome are obese. When seen in combination with habitual snoring, obesity becomes a significant risk factor for the disorder in men, though this is less the case in women." Polysomnography is the primary method of determining the presence of OSAS. This procedure is usually done in a sleep laboratory; more recently, however, ambulatory monitoring has also become available. The polysomnogram systematically monitors the electroencephalogram, electro-oculogram, chin and leg electromyograms, electrocardiogram (modified V2 lead), air flow, thoracic and abdominal efforts, and pulse oximetry. The measurements with the greatest clinical importance are the respiratory disturbance index (RDI), which is the number of respiratory events per hour of sleep, and oximetry. Respiratory events include apneas, which are defined as the cessation of breathing for greater than ten seconds, and hypopneas, which are defined as a decrease in tidal volume by at least 50% from baseline. The RDI represents the total number of apneic and hypopneic episodes per hour of sleep (RDI = apnea + hypopnea + total sleep time X 60). An RDI of more than 5 is considered the upper limits of normal. An RDI of 20 or higher is considered substantial enough to produce daytime hypersomnolence and increased cardiovascular risk, although patients with an RDI of less than 20 can also experience microarousals and daytime hypersomnolence requiring treatment. Another important measurement is the oxygen desaturation level (Sao2), which is the lowest blood oxygen level observed in a recording period. An Sao2 of less than 85% is relevant. Treatment Medical Management We have reviewed the positive correlation between obesity and obstructive sleep apnea. It would therefore follow that weight loss would be an important consideration in the management of OSAS. In fact, several studies have documented that weight loss will, indeed, improve sleep-disordered breathing.'8 In a review of 415 patients at the Stanford Sleep Disorders Center who underwent surgical correction of their problem, almost all the patients lost a considerable amount of weight postoperatively (7 to 18 kg [15 to 40 lb]). Despite aggressive dietary counseling and reinforcement, essentially all patients had regained their weight to their preoperative level after 6 to 12 months. Although it remains an integral part of treatment, weight loss as the sole or even primary treatment modality for OSAS is inadequate. Nasal continuous positive airway pressure (CPAP) is the primary form of treatment of OSAS. More than 85% of the patients seen at the Stanford Sleep Disorders Center are treated by this method. Nasal CPAP was originally described in 1982.'1 The concept is to deliver positive pressure through a nasal mask to the pharynx, thereby creating a pneumatic stent. Excessive daytime sleepiness is reversed, and the cardiopulmonary sequelae are eliminated with nasal CPAP.20 One problem with nasal CPAP, however, is the issue of long-term patient compliance. In one study, long-term home nasal CPAP therapy was analyzed, and a compliance rate of 75% was found.2' This finding was later reconfirmed.22 These reports had inherent flaws because compliance was based on subjective patient reporting. In a recent review, objective data of nasal CPAP compliance were obtained by placing covert monitors on the nasal CPAP machines of a select group." The results indicate that self-reporting of estimated CPAP use during the night and over a long period of time is exaggerated. In fact, objective data suggest that nasal CPAP compliance is less than 50%. At the Stanford Sleep Disorders Center, nasal CPAP continues to be the primary modality because the clinic provides a network of follow-up and support to maintain an acceptable level of compliance. A follow-up report further demonstrated that limited or part-time use of CPAP is not a satisfactory method of controlling obstructive sleep apnea.m Surgical Management Surgical treatment of obstructive sleep apnea is limited to about 15% of the patients seen at the Stanford Sleep Disorders Center. It is usually reserved for those persons in whom a trial of nasal CPAP fails. The most common problems cited are nasal irritation, rhinorrhea, claustrophobia, and inconvenience. The first surgical procedure for the treatment of obstructive sleep apnea was a tracheostomy, which conceptually bypassed the upper airway obstruction.-' It was initially described in 1969 and was the treatment of choice during the 1970s. The procedure is now rarely done at Stanford, partly because it is poorly tolerated and there are other surgical procedures that better correct the problem. In 1979 the initial use of uvulopalatopharyngoplasty as a primary treatment of OSAS was reported.2' This procedure removes redundant tissue from the palate and tonsil area. It was the treatment of choice in the early 1980s and proved to be an excellent method of controlling snoring; however, several retrospective reviews reported improvement in only 50% of the patients and complete control of the syndrome in only about 30%.27,11 This relative lack of success has led to misunderstanding and confusion about the surgical treatment of obstructive sleep apnea. The Stanford surgical group subsequently reviewed cases in which uvulopalatopharyngoplasties were unsuccessful and concluded that although the procedure eliminated the obstruction at the level of the soft palate, persistent obstruction was present at the base of the tongue.2' It is now generally accepted that there are many sites in the upper airway, including the soft palate,

4 146 WJM, February 1995-Vol 162, No. 2 Obstructive Sleep Apnea-Riley et al pharyngeal walls, and base of tongue, that possibly contribute to obstruction. Based on this concept of the potential for multiple obstructive sites, a Stanford surgical protocol was designed in These surgical procedures represent a modification of techniques previously reported in the maxillofacial and reconstructive surgical literature.3t The protocol represents improved surgical treatment of the disorder and offers an alternative to patients intolerant of nasal CPAP. Surgical Protocol The surgical protocol begins with a polysomnogram and presurgical evaluation, including physical examination, cephalometric roentgenograms, and fiberoptic pharyngoscopy. The goal of this evaluation is to determine the site or sites of obstruction and then to direct treatment to the appropriate areas. The physical examination emphasizes evaluation of the head and neck. It includes a close examination of the nasal cavity to identify obstructing deformities of the septum and turbinates; oropharyngeal obstruction from a long, redundant soft palate or hypertrophic tonsils; and hypopharyngeal obstruction from a prominent base of tongue. The fiberoptic pharyngoscopy, which is positioned transnasally, allows close examination of the oropharyngeal and hypopharyngeal areas and supplements the physical examination. Particular attention is given to the area of the soft palate and the base of the tongue, using the modified Mueller technique.32 Cephalometric analysis is used to confirm the findings of the physical and fiberoptic examinations. Figure 1 shows a cephalometric tracing and its anatomic land- SNA 82 SNB 80 PAS 11 PNS-P35 MP-H 15 Figure 1.-A cephalometric tracing is shown. The numbers represent a normal tracing and measurements. A = subspinale (deepest point of maxilla), ANS = anterior nasal spine, B = supramentale (deepest point of mandible), Gn = gnathion (inferior point of chin), Go = gonion (angle of mandible), H = hyoid bone, MP = mandibular plane (line Go to Gn), MP-H = distance (mm) of mandibular plane to hyoid, N = nasion, P = palate (tip), PAS = distance (mm) of tongue base to posterior pharyngeal wall, PNS = posterior nasal spine, PNS-P = distance (mm) of posterior nasal spine to palate, s = sella turcica, SNA = angle (degrees) of sella nasion point A, SNB = angle (degrees) of sella nasion point B Presurgical Evaluation (Physical Examination, Cephalometric Analysis, Fiberoptic Pharyngoscopy) Phase I (Site of Obstruction) UPPP UPPP+GAHM GAHM (Type 1 Oropharynx) (Type 2 Oropharynx - Hypopharynx) (lype 3 Hypopharynx) Postoperative Polysomnogram (6 mo) (Failure) Phase II MMO Figure 2.-The diagram is of the Stanford Sleep Disorders Center surgical protocol for the treatment of the obstructive sleep apnea syndrome. GAHM = genioglossus advancement with hyoid myotomy, MMO = maxillary and mandibular advancement osteotomy, UPPP = uvulopalatopharyngoplasty marks. The techniques and norms have been described previously.33 The usefulness of the cephalometric analysis has been confirmed elsewhere.' The presurgical evaluation allows for a classification according to the site of obstruction: type 1, oropharynx; type 2, oropharynx/hypopharynx; and type 3, hypopharynx. Patients are considered to have oropharyngeal obstruction when a redundant soft palate or hypertrophic tonsils are noted on the physical examination, the soft palate collapses against the posterior pharyngeal wall with the modified Mueller maneuver on fiberoptic examination, and the cephalometric analysis shows a long, soft palate. Hypopharyngeal obstruction is considered to be present when the base of the tongue collapses against the posterior pharyngeal wall and restricts visualization of the larynx on the physical and fiberoptic examinations, or the cephalometric analysis demonstrates a narrow posterior airway space. Patients with OSAS who have mandibular skeletal deficiency documented by cephalometric analysis (sella-nasion B point < 76 degrees) almost uniformly have a narrow posterior airway space and base of tongue obstruction. Once the diagnosis of OSAS has been made by polygraphic monitoring and the sites of obstruction are identified, the reconstruction of the upper airway according to the surgical protocol is undertaken (Figure 2). There are possibly two phases to upper airway reconstruction. Phase I therapy is considered a conservative approach. Persons with isolated obstruction at the level of the soft palate receive uvulopalatopharyngoplasty, and patients with obstruction at the base of the tongue undergo a conservative tongue advancement that consists of anterior repositioning of the genioglossus muscle and hyoid bone. If the patient has both palatal and base of tongue obstruction, they receive both procedures. The time required to do the operation is about an hour. The morbidity associated with this procedure is low, and the mean hospital stay is about two days. Six months after the operation, patients undergo a second polysomnogram to determine surgical success. Success is defined as postoperative polysomnographic

5 WJM, February 1995-Vol 162, No. 2 Obstructive Sleep Apnea-Riley et al 147 TABLE 1.-Stanford Sleep Disorders Center Surgical Protocol Results (239 Patients) Patient Success! Total Patients Success Surgery Groups No./No. Rate, % Phase I Genioglossus advancement with hyoid myotomy plus uvulopalatopharyngoplasty / Genioglossus advancement with hyoid myotomy... 4/6 66 Uvulopalatopharyngoplasty... 8/10 80 Total / Phase II Maxillary and mandibular osteotomy... 24/ findings equivalent to those of the nasal-cpap study or a postoperative RDI of less than 20 with at least a 50% reduction over the preoperative study and Sao2 levels equivalent to those seen with nasal CPAP. In addition to objective polygraphic data, patients must also experience improvement in their snoring and sleep hygiene. The elimination of daytime hypersomnolence must correspond to reports of better quality sleep, improved ability to concentrate, elimination of the need for naps, and improved work performance. Patients with residual sleep apnea will be offered phase II therapy. Phase II therapy consists of maxillary and mandibular advancement osteotomies. The surgical time for phase II is about three hours. Although conceptually this would seem to be an aggressive therapy, the morbidity is low and the mean hospital stay is only 2.4 days Ṫhe results of the surgical protocol are shown in Table 1. In all, 239 patients entered phase I therapy, with most requiring genioglossal advancement with hyoid myotomy plus uvulopalatopharyngoplasty. Treatment was successful for 61 % of the patients. The results were based on the six-month polysomnogram and included analysis of changes in sleep architecture and sleepdisordered breathing. The results indicate that successful surgical treatment is as effective as nasal CPAP (Table 2). More than half of the patients were using nasal CPAP, but they elected surgical treatment because nasal CPAP was an unacceptable long-term treatment modality. Despite rejecting nasal CPAP, they were required to continue its use until the postoperative polysomnogram indicated surgical success. The mean pretreatment RDI was The nasal CPAP and postoperative mean RDI were 7.2 and 9.5, respectively (P = not significant [NS]). The mean follow-up period was nine months, but 44 patients have had long-term follow-up (1 to 4 years) with polysomnographic recordings. Only two patients have had recurrence of OSAS. Most of the patients who underwent unsuccessful phase I therapy had severe OSAS (mean RDI, 61.9) and morbid obesity (mean body mass index, 32.3 kg/m2, with normal being < 27.8 kg/m2). Patients treated with phase I surgery were further evaluated by comparing the measurements of surgical success with those of OSAS severity (Table 3). Patients with mildly to moderately severe OSAS had the highest frequency of success (70% to 80%). Surgical success declined to 42% when patients had severe OSAS. Of the 94 patients for whom phase I therapy failed, 24 elected to have phase II treatment. Most of the patients who declined phase II treatment (and were dropped from the surgical protocol) were older, with a mean age of 51.8 years (standard deviation [SD] = 9.8). The mean age of the patients entering phase II treatment was 43.5 years (SD = 11.5). The 24 patients who underwent unsuccessful phase I surgical treatment showed an improvement, however, in their OSAS phase I postoperative polysomnogram. The mean RDI improved from 75.1 to 56.3, and the mean Sao2 level improved from 64.0% to 71.9%. All the patients who elected to have phase II therapy had a successful outcome (Table 2). The mean RDI improved from 75.1 (SD = 26.7) to 9.6 (SD = 2.9), and the mean Sao2 levels improved from 64.0% (SD = 15.9) to 86.4% (SD = 7.0). The nasal CPAP mean RDI and mean Sao2 was 8.2 (SD = 2.9; P = NS) and 87.5% (SD = 6.7; P = NS), respectively. Conclusion The National Commission on Sleep Disorders Research reported that each year the lives of millions of TABLE 2.-Phase I and Phase 11 Surgical Results Phase I Treatment Phase II Treatment n= 145 n =24 Before Operation, After Operation, Before Operation, After Operation, Sleep Before Treatment CPAP After Treatment Before Treatment CPAP After Treatment Meosurements (SD) (SD) (SD) (SD) (SD) (SD) RDI (25.8) 7.2 (4.9) 9.5 (9.5) 75.1 (26.7) 8.2 (2.9) 9.6 (2.9) Lowest Sao2, % (12.9) 86.4 (11.0) 86.6 (4.5) 64.0 (15.9) 87.5 (6.9) 86.7 (7.0) Total sleep time, minutes (72.0) 363 (67.0) 379 (63.0) 379 (58.0) 376 (69.0) 388 (56.0) Stages 3-4sleep,% (5.6) 11.1 (10.8) 8.5 (7.7) 2.7 (4.3) 11.0 (13.3) 8.2 (6.7) REM sleep, % (5.8) 18.3 (7.0) 17.7 (5.6) 8.1 (3.1) 21.2 (8.4) 21.5 (6.1) Body mass index (5.2) (4.9) 31.4 (6.5) (6.0) CPAP = continuous positive airway pressure, RDI = respiratory disturbance index, REM = rapid eye movement, Sao, = arterial oxygen saturation, SD = standard deviation

6 IWJM, WJM, February 1995-Vol 162, No. 2 Obstructive Sleep Apnea-Riley et al- al TABLE 3.-Results of Phase I Stanford Surgical Protocol by Severity of Obstructive Sleep Apnea Syndrome (OSAS) Patient Success! OSAS Lowest Total Patients, Success Severity RDI Sao2, % No/No. Rate, % Mild... < 20 > 85 20/26 77 Moderate > 80 45/58 78 Moderate to severe > 70 36/51 71 Severe... > 60 < 70 44/ RDI = respiratory disturbance index, Sao, = arterial oxygen saturation Americans are disturbed, disrupted, or destroyed by the consequences of sleep disorders. Obstructive sleep apnea syndrome is easily diagnosed and treated with nasal CPAP. The Stanford surgical protocol puts to rest the controversy surrounding the surgical treatment of OSAS and demonstrates that it is a viable option for persons intolerant of nasal CPAP. Primary care physicians are in a unique position to alter the staggering effects of sleep disorders on the health and welfare of the nation. REFERENCES 1. 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