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Usefulness of Sleep Endoscopy in Predicting Positional Obstructive Sleep Apnea Andrew J. Victores, John Hamblin, Janet Gilbert, Christi Switzer and Masayoshi Takashima Otolaryngology -- Head and Neck Surgery 2014 150: 487 originally published online 27 December 2013 DOI: 10.1177/0194599813517984 The online version of this article can be found at: http://oto.sagepub.com/content/150/3/487

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Original Research—Sleep Medicine and Surgery

Usefulness of Sleep Endoscopy in Predicting Positional Obstructive Sleep Apnea

Otolaryngology– Head and Neck Surgery 2014, Vol. 150(3) 487–493 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2013 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599813517984 http://otojournal.org

Andrew J. Victores, MD1, John Hamblin1, Janet Gilbert, MD2, Christi Switzer, CRNA2, and Masayoshi Takashima, MD1

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Abstract Objectives. The aim of the study was to (1) evaluate whether position affects drug-induced sleep endoscopy (DISE) findings in positional and nonpositional patients and (2) determine which areas of the upper airway obstruct in different body positions. Study Design. Prospective, case-controlled study. Setting. Academic tertiary care center. Subjects and Methods. Twenty-two patients with obstructive sleep apnea (OSA) were enrolled. Two groups were individually recruited to make 11 consecutive patients with positional OSA and 11 consecutive patients with nonpositional OSA. Positional OSA was defined by nonsupine 50% reduction in apnea-hypopnea index. DISE was performed with patients in both lateral and supine sleep positions. Upper airway collapse was compared between the sleep positions and between the 2 groups. Results. Most patients (77%) demonstrated multilevel obstruction on DISE. Nearly all patients with positional OSA (91%) had at least a partial improvement in collapse while in the lateral sleep position. Most of the reduction in collapse involved the tongue base and epiglottis (P \ .05). Sleep position did not significantly alter the upper airway morphology of patients with nonpositional OSA. Apneahypopnea index and body mass index were not significantly different between the 2 groups. Conclusions. Sleep position can change upper airway morphology on DISE, particularly positional OSA patients. Hypopharyngeal collapse was the primary site that improved with change in position. DISE in multiple sleep positions should be considered as part of a minimally invasive approach to surgical therapy of OSA.

Keywords obstructive sleep apnea, positional obstructive sleep apnea, drug-induced sleep endoscopy

Received September 20, 2013; revised November 18, 2013; accepted December 4, 2013.

Introduction Obstructive sleep apnea (OSA) is a common condition that falls within the spectrum of sleep-disordered breathing. Already 2% to 26% of the general population is affected by OSA, and the prevalence is only expected to rise.1,2 The disorder causes collapse of the upper airway during sleep, resulting in complete or partial cessation of airflow followed by oxygen desaturation. The impaired breathing commonly manifests as snoring, arousals, and daytime somnolence. OSA has been associated with a number of adverse outcomes, including motor vehicle accidents and cardiovascular conditions.3-6 A subset of OSA patients has more airflow obstructions, or apneas, while sleeping in a particular position, especially the supine position.7-11 Gravitational forces are thought to be the cause of these changes in upper airway collapse with body position.12 The condition is traditionally referred to as positional OSA if there is a difference of 50% or greater in the apneahypopnea index (AHI) between supine and nonsupine positions.7 Positional patients make up a substantial component of the OSA population. Several studies have shown that up to 56% of patients with OSA qualify as positional.10,11,13,14 Even more patients (30%) improve when sleeping in nonsupine positions, but not to the extent to be diagnosed with positional OSA. Numerous therapies and techniques have been developed to address OSA. Continuous positive airway pressure (CPAP) 1 Bobby R. Alford Department of Otolaryngology–Head and Neck Surgery, Baylor College of Medicine, Houston, Texas, USA 2 Department of Anesthesiology, The Methodist Hospital, Houston, Texas, USA

This article was presented at the 2013 AAO-HNSF Annual Meeting & OTO EXPO; September 29–October 2, 2013; Vancouver, British Columbia, Canada. Corresponding Author: Masayoshi Takashima, Bobby R. Alford Department of Otolaryngology– Head and Neck Surgery, Baylor College of Medicine, Smith Tower, 17th Floor, 6550 Fannin, Suite 1727, Houston, TX 77030, USA. Email: [email protected]

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remains the gold standard for treatment. Although CPAP is effective when used appropriately, more than half of OSA patients fail to comply with the treatment, often finding it intolerable.15-17 In these patients, conservative measures such as weight loss and positional therapy can serve an important role. Several positional devices have been developed that share the common goal of preventing the individual from assuming his or her worst sleep position, usually being the supine position. Most research suggests that positional therapy has better compliance than CPAP but is less effective at reducing the AHI, defined as the mean number of apneas and hypopneas per hour of sleep.18,19 However, select patient populations may benefit just as much from these therapies. One recent study found that positional therapy with a wedgeshaped pillow was equivalent to CPAP in improving the AHI of patients with mild to moderate positional OSA.20 It is important to acknowledge that most current positional therapies also have poor long-term compliance. This is in part due to patient discomfort with the device or to lack of improvement in their quality of life.21-23 An alternative approach to managing OSA is surgical modification of the upper airway. One of the major criticisms of upper airway surgery is the relatively low success rate.24-27 One recent study found that the most common sleep procedure, uvulopalatopharyngoplasty, cured OSA for 44% of patients.24 The difficulty lies in identifying the relevant mechanism of pharyngeal collapse and determining the appropriate surgery for the individual. Clinical examination and techniques have been devised to aid in this process with varied success. In 1991, Croft and Pringle described druginduced sleep endoscopy (DISE), a methodology that artificially induces sleep apnea with a pharmacologic agent while visualizing the upper airway using a flexible endoscope.28 DISE findings can be classified based on level, configuration, degree, and sustainability of collapse.29-31 The results of DISE are valid, reliable, and have been shown to affect surgical planning and decision making.32-34 To our knowledge, no previous study has reported DISE findings in both the lateral and supine positions or in patients with positional OSA. This study will determine whether position affects the findings of drug-induced sleep endoscopy and compare upper airway collapse in positional and nonpositional OSA patients in each of these positions.

Methods Patient Selection This study was conducted in accordance with the Declaration of Helsinki at an academic tertiary care center. The study subjects were 22 patients (age .18 years) who had OSA between September 2011 and February 2012. Patients with prior surgery for OSA or allergy to propofol were excluded from the study. Formal laboratory polysomnography (PSG) was conducted prior to DISE. Obstructive apneas were defined by 90% oronasal airflow reduction for more than 10 seconds. Obstructive hypopneas were defined by a 30% or more decrease in airflow for more than 10 seconds

accompanied by a 4% decrease in oxygenation. OSA was classified based on the AHI as mild (5 to 14 events/h), moderate (15 to 29 events/h), or severe (30 events/h). Oxygen desaturation was defined as a 4% decrease in oxygenation. Positional OSA was defined as a difference of 50% or more in the AHI between supine and nonsupine positions.7 Eleven consecutive patients were selected with positional OSA, and 11 consecutive patients were selected with nonpositional OSA, as defined by the PSG. An author (M.T.) obtained physical and historical assessments. Eligibility for the study and determination of the presence or the absence of positional OSA was made by a different author (A.J.V.). The Institutional Review Board at Baylor College of Medicine approved this study.

Positional DISE and Classification of Morphological Features DISE was performed in an operating room and digitally recorded by the same endoscopist (M.T.), who was blinded as to whether or not the patient had positional OSA. Patients were initially positioned laterally on the operating room table with standard anesthetic monitoring, including pulse oximetry and electrocardiography. Unconscious sedation was induced with an intravenous bolus administration of the sedative propofol. Adequate sedation for DISE was defined as the absence of a response to verbal stimulation in a normal voice.33,35 Propofol infusion was slowly titrated and rate adjusted to avoid oversedation. Only propofol was used for the sedation protocol. Once the patient was sedated, a flexible video endoscope was introduced, and the upper airway was observed for obstruction in the lateral position. All DISEs were recorded in a consistent manner, keeping the orientation of the base of tongue at the bottom of the screen and posterior pharyngeal wall at the top of the screen. A recording device was used to store the video from the lateral DISE. The flexible endoscope was removed, and the patient was placed into a supine position. The propofol sedation was adjusted to achieve adequate sedation. DISE was again performed, the endoscope was again introduced, and the upper airway was observed in the supine position. Video recordings of the supine DISE were also collected. The senior author (M.T.) was then blinded as to the patient name or patient position, and the digital recordings were then evaluated for sites of collapse, as described in Table 1.29,31,36 Briefly, the potential sites of upper airway collapse included the palate, the lateral oropharyngeal walls, the base of tongue, and the epiglottis. Each area was further characterized by the degree of collapse, either as partial (\75%) or as complete (.75%). The location and degree of collapse were recorded by listing the first letter of the site of collapse in either lower case, for partial obstruction, or upper case, for complete obstruction. No obstruction at a particular level would receive no letter designation and be left blank. A single letter could thereby convey both the site and degree of obstruction. Obstruction at the base of tongue and epiglottic levels were further classified by the sustainability

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Table 1. Upper airway obstruction classification system.a Degree Level Palate (velum) Lateral wall/tonsillar pillars Tongue base Epiglottis

Sustainability

Partial

Complete

Intermittent

Sustained

p l t e

P L T E

— — 1 1

— — 2 2

Abbreviation: —, not visualized. a Partial = \75% obstruction; complete = .75% obstruction; intermittent = obstruction only during inspiration in an apneic episode; sustained = obstruction throughout an apneic episode.

Table 2. Study demographics. Nonpositional

Positional

Patient characteristics

Mean 6 SD

Mean 6 SD

Range

P valuea

Age, y Gender, M/F BMI, kg/m2 Tonsil size, grade 0-4 AHI total, events/h AHI REM, events/h AHI supine, events/h Minimum SaO2, %

44.6 6 13.8 9/2 29.7 6 4.8 1.6 6 0.9 26.7 6 14.4 30.1 6 17.3 31.9 6 20.1 78.2 6 10.8

39.1 6 12.5 8/3 27.5 6 6.4 2.2 6 1.3 21.7 6 11.1 28.5 6 13.1 37.9 6 18.9 82.7 6 8.4

19-73 — 14-41 0-4 7-62 9-77 9-89 68-92

.36 1.0 .42 .26 .43 .38 .49 .20

Abbreviations: AHI, apnea-hypopnea index; BMI, body mass index; REM, rapid eye movement; SaO2, oxygen saturation; SD, standard deviation. a P \.05 is significant.

of collapse, with intermittent obstruction occurring only during inspiratory effort and with sustained obstruction occurring throughout the respiratory cycle. Lateral wall and palatal obstruction did not clearly and consistently demonstrate this relationship to respiratory effort. The sustainability of collapse for the tongue base and the epiglottis was recorded by listing a 1, for intermittent obstruction, or 2, for sustained obstruction. This number would follow the letter designation as described above.

Statistical Analysis The primary comparison was between DISE in the supine and lateral positions. The McNemar test was used to analyze changes to the pattern of upper airway obstruction visualized by DISE in each of these positions. The Fisher exact test was used to analyze changes to the pattern of upper airway obstruction visualized by DISE in positional and nonpositional patients as well as categorical variables. Correlation between tonsil size and body mass index (BMI) with other variables was carried out by the Spearman correlation test. The paired t test was used to compare DISE findings with AHI and BMI. A P value of \.05 was considered statistically significant. Continuous variables were summarized using means and standard deviations. Categorical variables were summarized using percentages. Statistical analysis was performed with the STATA System (version 13.0, College Station, TX).

Results Twenty-two patients, 17 male and 5 female, were enrolled in the study. Three patients were not enrolled during the study period because of the presence of prior surgery for OSA. Demographic data for participants are summarized in Table 2. All patients had OSA with the severity, as defined by AHI, distributed as follows: mild (32%), moderate (41%), and severe (27%). The mean Epworth Sleepiness Scale (ESS) was 14.2 6 7.5. The mean total sleep time during PSG was 378.3 minutes. Both positional and nonpositional OSA patients spent most of their time in the supine position (61% and 55%, respectively). The worst sleep position, based on AHI, was supine for all positional OSA patients. These patients had a mean supine AHI of 39.1 6 20.4 events/h and lateral AHI of 8.1 6 5.7 events/h (P \ .05). Body position did not significantly change the AHI of nonpositional OSA patients (P . .05). The overall AHI of positional OSA patients was lower than that of nonpositional patients, but this difference was not significant (mean of 21.7 to 26.7 events/h, respectively, P . .05). There was no significant correlation between tonsil size or BMI and change in the pattern of upper airway obstruction with lateral body position (P . .05). Propofol-induced sleep endoscopy was administered to all patients in the supine and lateral positions. No complications were incurred during or following sleep endoscopy.

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Table 3. Pattern of upper airway obstruction: supine and lateral. Nonpositional Level of obstruction Palate (velum) Partial/flutter (p) Complete (P) Single level Lateral wall (tonsillar pillars) Partial (l) Complete (L) Single level Tongue base Partial intermittent (t1) Partial sustained (t2) Complete intermittent (T1) Complete sustained (T2) Single level Epiglottis Partial intermittent (e1) Partial sustained (e2) Complete intermittent (E1) Complete sustained (E2) Single level Multilevel

Positional

Supine, %

Lateral, %

P valuea

Supine, %

Lateral, %

P valuea

91 36 55 27 18 18 0 0 36 18 9 9 0 9 36 27 9 0 0 0 64

91 46 46 36 18 18 0 0 36 18 18 0 0 9 27 27 0 0 0 0 55

NS NS NS NS NS NS — — NS NS NS —b — NS NS NS —b — — — NS

82 46 36 9 18 9 9 0 73 18 18 27 9 0 64 27 9 27 0 0 91

73 55 18 46 27 18 9 9 18 9 9 0 0 9 9 9 0 0 0 0 58

NS NS NS NS NS NS NS —b .03 NS NS NS —b —b .03 NS —b NS — — NS

Abbreviation: NS, not significant. a McNemar test for paired data. P \.05 is significant. b Insufficient subject number for statistical analysis.

DISE findings in the supine and lateral positions are shown in Table 3. Most patients demonstrated multilevel obstruction in the supine position (77%). The most common site of collapse was the palate for both positional and nonpositional patients in both supine (91% and 82%, respectively) and nonsupine (91% and 73%, respectively) positions. Both tongue base and epiglottic obstruction in the supine position were twice as frequent in the positional (73% and 64%, respectively) as compared with the nonpositional (36% and 36%, respectively) OSA group. Most positional OSA patients demonstrated combined palatal and tongue base obstruction (64%). Body position did not significantly alter the pattern of upper airway obstruction for nonpositional OSA patients (P . .05). In contrast, nearly all patients with positional OSA showed at least a partial improvement in obstruction from supine to lateral positioning (91%). Lateral positioning significantly improved tongue base and epiglottic collapse of positional OSA patients (P \ .05). Nearly half of these patients had single-level palatal collapse in the lateral position (46%), and 1 patient had complete resolution of multilevel collapse (9%).

Discussion To our knowledge, this is the first study to evaluate the effect of positional OSA on upper airway collapse using

DISE. For most patients with positional OSA, DISE findings improved in the lateral sleep position. In contrast, the pattern of obstruction in nonpositional OSA patients did not significantly change in the lateral position. Our study suggests that changing body position can elicit positional OSA findings during DISE. The first-line treatment for OSA is CPAP. Unfortunately, this therapy often has poor compliance, leaving patients to seek alternatives. Surgical interventions have been advanced as a means to address sleep apnea in some of these patients. Sleep surgery has traditionally faced problems in achieving high success rates, and results are often inconsistent.25 Some surgical failures are thought to be a product of the multilevel nature of upper airway collapse. Patients often demonstrate obstruction at the palate, tongue base, epiglottis, or, less commonly, lateral oropharyngeal walls.37 One solution is to improve the process of stratifying patients for specific surgical interventions.38 Techniques such as DISE can help to enhance the response to treatment by localizing the site of obstruction.39 One of the criticisms of DISE is its reliance on the evaluation of sleep in the supine position.40-42 Some argue that snoring and obstruction vary with sleep position, and therefore, DISE is not representative of a normal night of sleep. This study demonstrates that DISE can be performed in both supine and lateral sleep positions. Moreover, different anatomic sites of obstruction were observed in

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patients with and without positional OSA during DISE, consistent with the findings on PSG. Another criticism of sedative-induced sleep is alteration of sleep architecture. Sedatives seem to reduce or abolish rapid eye movement (REM) sleep.40,43 This may be particularly problematic for the population of patients who have sleep apnea only during REM sleep.44 Despite these concerns, propofol infusion does not seem to alter the respiratory parameter of AHI significantly.40 Taken together, these results give further support for drug-induced sleep as a surrogate for natural sleep in the evaluation of upper airway collapse. Many clinicians and researchers judge the success of a sleep surgery by the reduction of total AHI. One commonly referenced metric of surgical success is a postoperative AHI \15 events-h–1 and a 50% decrease from the preoperative AHI.45 This benchmark of success may need to be reconsidered given the impact of body position on AHI.46-48 Body position during sleep is variable, which could alter the total AHI of a repeat PSG, independent of any intervention. The perceived success or failure of a procedure would thereby be skewed by body position and the percentage of sleep time spent in each position. Some studies have already found that sleep position can affect surgical success. A small study by Katsantonis et al49 compared PSGs for patients before and after uvulopalatopharyngoplasty (UPPP).49 They found that improvement in respiratory indices following UPPP was significantly greater in the lateral as opposed to the supine position. A more recent study demonstrated that this effect seemed to be particularly prominent in nonpositional patients.50 Interestingly, body position did not appear to affect surgical success for positional patients. Our results suggest that positional OSA patients nearly all have some residual collapse in the lateral position, although this obstruction is often at a single site and tends to be less severe. Consideration should be given to adjunct therapies, such as positional therapies, which could augment the success rates of surgical intervention. Although the sleep surgeon should still address the obstruction in the least favorable position, a better understanding of the effect of body position on the success of individual surgical techniques will help to direct a minimally invasive approach to sleep surgery. Tongue base and epiglottic collapse have been shown to be more frequent in positional OSA patients.11,37 Our findings were consistent with these studies. We also identified the tongue base and the epiglottis as the primary sites to improve in the lateral position. This suggests that base of tongue and epiglottic obstruction is at least in part responsible for position-dependent OSA (Figure 1). One explanation for positional dependency may be the susceptibility of the hypopharyngeal structures to gravitational-induced collapse. This could be a function of both anatomic structure and dilator muscle activity. The genioglossus muscle has been recognized as a major dilator of the upper airway, and its function is augmented in OSA patients.51 Subsets of patients with particularly poor genioglossus function have been identified.52,53 It remains unclear whether patients with positional OSA could represent one of these subsets.

Figure 1. Nasopharyngoscopic view during drug-induced sleep endoscopy comparing tongue base and epiglottic collapse in supine and lateral body positions for patients with positional (A and B, respectively) and nonpositional (C and D, respectively) OSA.

The higher rate of tongue base obstruction in positional OSA patients led some to believe that interventions directed to the tongue base would improve the response rate. One recent study contradicts this theory, as the response rate to tongue base surgery was comparable for positional and nonpositional OSA patients.54 Another intervention that can be focused at the tongue base level includes neurostimulators. These devices act to promote dilator function by simulating the hypoglossal nerve, causing tongue protrusion and anterior pharyngeal wall stiffening.55 Future studies should evaluate the role of these devices in positional OSA patients. Some weaknesses of the present study should be acknowledged. Our study was underpowered, and a larger study could provide a more detailed representation of the effects of body position on upper airway morphology during sleep. We also did not assess the effects of head position, sleep surgery, or positional therapy on upper airway collapse. A limitation of DISE is the reliance on a qualitative characterization of upper airway obstruction. Some methods such as the VOTE classification system have attempted to standardize this qualitative process.29 However, we did not use the VOTE classification in the present study, as it does not account for the sustainability of upper airway obstruction. Our study could also be biased by the use of a single reviewer who performed and reviewed the drug-induced sleep endoscopies. However, the reviewer was blinded as to whether or not patients had positional OSA.

Conclusion This study suggests that sleep position changes the DISE findings for positional OSA patients. Hypopharyngeal collapse

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was the primary site that improved with change in position. DISE in multiple sleep positions should be considered as part of a minimally invasive approach to surgical therapy of OSA. Author Contributions Andrew J. Victores, main author of the manuscript, substantial contribution in the sense of study information acquisition and interpretation, final approval of the version to be published; John Hamblin, substantial contribution in the sense of study information acquisition and interpretation, critical revision of the article, final approval of the version to be published; Janet Gilbert, substantial contribution in the sense of study information acquisition and interpretation, critical revision of the article, final approval of the version to be published; Christi Switzer, substantial contribution in the sense of study information acquisition and interpretation, critical revision of the article, final approval of the version to be published; Masayoshi Takashima, initial conception of the study concerning the clinical problem, substantial contribution in the sense of study information acquisition and interpretation, critical revision of the article, final approval of the version to be published.

Disclosures Competing interests: Masayoshi Takashima, Consultant and Speaker’s Bureau for Medtronic; Speaker’s Bureau, Meda Pharmaceuticals. Sponsorships: None. Funding source: None.

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Usefulness of sleep endoscopy in predicting positional obstructive sleep apnea.

The aim of the study was to (1) evaluate whether position affects drug-induced sleep endoscopy (DISE) findings in positional and nonpositional patient...
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