Transoral Robotic Surgery for Treatment of Obstructive Sleep Apnea-Hypopnea Syndrome

Transcription

1 The Laryngoscope VC 2013 The American Laryngological, Rhinological and Otological Society, Inc. Transoral Robotic Surgery for Treatment of Obstructive Sleep Apnea-Hypopnea Syndrome Ho-Sheng Lin, MD; James A. Rowley, MD; M. Safwan Badr, MD; Adam J. Folbe, MD; George H. Yoo, MD; Lyle Victor, MD; Robert H. Mathog, MD; Wei Chen, PhD Objectives/Hypothesis: To evaluate the efficacy of base of tongue (BOT) resection via transoral robotic surgery (TORS) in the treatment of obstructive sleep apnea/hypopnea syndrome (OSAHS). Study Design: Case series Methods: Between June 2010 and May 2012, BOT resection via TORS was performed on 27 patients with OSAHS. Patients were excluded from this analysis if other concomitant upper airway procedures such as uvulopalatopharyngoplasty were performed, or if postoperative polysomnograms were not available. Results: Twelve patients who underwent BOT resection alone were included in this study. The median age for these 12 patients was 48.5 (range, 19 64) and included nine females and three males. The mean apnea-hypopnea index (AHI) was preoperatively and postoperatively. This difference in AHI was statistically significant (P ¼ 0.007) and reflected an average AHI reduction of %. Statistical significant reductions in daytime somnolence level, as measured by Epworth Sleepiness Scale ( preoperatively vs postoperatively, P <0.001), and snoring intensity, as reported by a bed partner using a Visual Analogue Scale ( preoperatively vs postoperatively, P <0.001), were achieved. There was no statistical significant difference between the preoperative and postoperative body mass index ( vs , P ¼ 0.296) or minimum oxygen saturation ( % vs %, P ¼ 0.680). Conclusions: This is the first study looking at the use of TORS to address obstruction at the level of BOT only, not confounded by surgical alterations at other levels of upper airway. This preliminary result on the use of BOT resection via TORS for the treatment of patients with OSAHS is encouraging and warrants further investigations. Key Words: Obstructive sleep apnea-hypopnea syndrome, transoral robotic surgery, TORS-assisted, base of tongue resection, robotic surgery, glossectomy, sleep apnea. Level of Evidence: 4. Laryngoscope, 123: , 2013 INTRODUCTION Treatment of obstructive sleep apnea/hypopnea syndrome (OSAHS) is important since its associated repetitive arousals and nocturnal hypoxemia can lead to disruption of sleep architecture, daytime hypersomnolence, as well as a multitude of neurobehavioral and cardiopulmonary derangements 1,2 which significantly increased risk of death. 3,4 The standard treatment for patients with OSAHS is positive airway pressure (PAP). From the Department of Otolaryngology Head & Neck Surgery (H- S.L., A.J.F., G.H.Y., R.H.M.), Wayne State University and Karmanos Cancer Institute; the Biostatistics Core, Karmanos Cancer Institute, Department of Oncology (W.C.), and the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine (J.A.R., M.S.B.), Wayne State University; the Department of Surgery (H-S.L.), and the Department of Medicine (M.S.B.), John D. Dingell VA Medical Center, Detroit, Michigan; and the Department of Medical Education (L.V.), Oakwood Hospital, Dearborn, Michigan, U.S.A. Editor s Note: This Manuscript was accepted for publication November 5, H.-S. Lin has a consultant agreement as a proctor with Intuitive Surgical, Inc. The authors have no other funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Ho-Sheng Lin, MD, 4201 St. Antoine St., 5E University Health Center, Detroit, MI, hlin@med.wayne.edu DOI: /lary Although PAP is an extremely safe and effective treatment modality, it is not universally acceptable to all patients. Over the last decade, continuous improvement in PAP technology with increased focus on patient comfort has increased the compliance rate from approximately 50% 5,6 to more than 70%. 7,8 For those patients who are not compliant or cannot tolerate PAP, surgical treatment may be an important option to consider. Surgical approaches range from procedures that increase or stabilize the size of the airway by removing or repositioning tissue to procedures that completely bypass the site of airway collapse such as tracheostomy. Since the introduction of uvulopalatopharyngoplasty (UPPP) in the United States, 9 surgical treatment for OSAHS has been directed mainly at the level of soft palate which was thought to be the main area of obstruction. However, the effectiveness of this surgical procedure was brought into question in a large metaanalysis that showed UPPP to be effective in less than 50% of cases. 10 At the same time, surgeons began to realize that OSAHS is a disease entity that is much more complex than previously appreciated. Surgical procedures were developed to address obstructions at various levels of upper airway. However, reports of effectiveness of these procedures vary widely in the literature and are 1811

2 difficult to interpret due to the wide variety of diagostic and surgical procedures employed. 10,11 Although there have been significant progress in both diagnostic as well as therapeutic modalities, surgical treatment of OSAHS patients remains challenging and even controversial. 12 Thus, there exists a critical need to improve surgical treatment of OSAHS patients through either a shift in treatment paradigm or technological advances. Transoral robotic surgery (TORS) for resection of oropharyngeal and supraglottic neoplasm was pioneered by Weinstein and O Malley As safety and tolerability of this procedure were established in cancer patients, 13,16 the use of this technology for treatment of OSAHS has been investigated. 17,18 However, these reports described the use of TORS-assisted based of tongue (BOT) resection with other concomitant upper airway procedures, making interpretation of the efficacy of BOT procedure itself difficult. In this study, we analyzed the clinical and polysomnographic data on 12 patients who underwent TORS-assisted BOT resection without any other concomitant surgical alterations at other levels of upper airway in order to assess the efficacy of this new procedure alone. MATERIALS AND METHODS A retrospective analysis of our initial surgical experience with TORS-assisted BOT resection was performed after receiving an institutional review board approval. A total of 27 patients who underwent TORS-assisted BOT resection between June 2010 and May 2012 for treatment of OSAHS were identified. A single surgeon (H.S.L.) performed all of the cases. Patient demographics were recorded to include age, race, and gender. Other clinical characteristics recorded included preoperative and postoperative height, weight, body mass index (BMI), neck circumference (NC), Friedman tongue position, tonsil size, Friedman stage, sleep endoscopy findings, Epworth Sleepiness Scale (ESS), snoring intensity based on a Visual Analog Scale (VAS) from 0 (no noise) to 10 (extreme noise causing bed partner to leave the room) as reported by bed partner, apnea-hypopnea index (AHI), and lowest oxygen saturation (LO 2 sat). Finally, indications for surgery, prior history of upper airway surgery, operative time, blood loss, total volume of tongue tissue removed, duration of hospital stay, and intraoperative as well as postoperative complications were recorded. Patient Selection In order to keep the focus of the study on the efficacy of TORS-assisted BOT resection only, we excluded patients from this analysis if other upper airway procedures such as UPPP, modified Z-palatoplasty (ZPP), 19 other nonrobotic BOT procedures, or epiglottopexy were performed concomitantly with TORS-assisted BOT resection. Further, only patients with complete clinical information, including both preoperative and postoperative polysomnograms (PSGs), were included. A total of 12 patients satisfied the above selection criteria and were included in this analysis. The other 15 patients were excluded on the basis of unavailability of postoperative PSG (n ¼ 2), having concomitant surgery (n ¼ 3), or both (n ¼ 10). Surgical Technique The technique for TORS of the BOT neoplasm has been previously described. 13,16 Here, we will briefly describe our slightly modified version tailored for OSAHS. Prior to surgery, 1812 all patients undergo sleep endoscopy to evaluate the site of obstruction. The amount and pattern of BOT collapse are carefully analyzed to determine subjectively the extent of tissue resection necessary for each individual patient. The final amount of tissue resected is measured right after the resection by immersing the tissue in saline and measuring the amount of saline displaced inside a 120-ml sterile specimen cup. All patients receive perioperative antibiotics and steroid. In order to avoid distortion of anatomy at the BOT, nasotracheal intubation is routinely performed. To minimize risk of inadvertent airway fire, a wire-reinforced endotracheal tube is used and fraction of inspired oxygen (FiO 2 ) is kept at less than 30% if possible. A Leivers mouth gag (Bausch & Lomb Surgical, Rochester, NY) with Davis-Meyer tongue blade (Storz, El Segundo, CA) is used, and the foramen cecum is positioned in the middle of the surgical field to help with orientation. The da Vinci robot (Intuitive Surgical, Sunnyvale, CA) is docked to the right of patient at a 30 angle, and a 5-mm monopolar spatula, an 8-mm fenestrated bipolar forceps, and an 8.5-mm 0 scope (Intuitive Surgical, Sunnyvale, CA) are then introduced. Placement of the three robotic arms and instruments is carefully optimized to avoid collision and interference during the surgery. Resection then begins in the midline starting from foramen cecum down toward the vallecula posteriorly. The lateral extent of resection is based on the sleep endoscopy findings. In order to gain improved visualization of BOT tissue posteriorly, the Leivers mouth gag and 0 scope are replaced with Feyh-Kastenbauer-Weinstein-O Malley (FK-WO) retractor (Gyrus Medical, Germany) and 30 scope. Further resection of BOT down to the vallecula and lingual surface of the epiglottis is then carried out. Statistical Analysis The primary efficacy endpoint is changes in AHI. The secondary efficacy endpoints are changes in LO 2 sat, ESS, BMI, and snoring intensity. Surgical responseis achieved when postoperative PSG shows > 50% reduction in AHI with a final AHI <20.The baseline predictors are gender, race, age, history of prior upper airway surgery, Friedman tongue position, tonsil size, Friedman stage, sleep endoscopy findings, NC, volume of tissue removed, andpreoperativebmi,ahi,andlo 2 sat.the2-tailedpairedstudent s t test is used to compare preoperative and postoperative differences in the endpoints. Independent two-sample Student s t test or Fisher s Exact test, when categorical is used to compare demographic and clinical characteristics between surgical responders and nonresponders. Univariate and multivariate regression analyses are used to identify statistically significant correlation between baseline predictors and the endpoints in terms of absolute change and % change. Statistical significance is accepted when P <0.05. Multiple testing is not adjusted because of the exploratory nature of this current study. R is used for statistical analysis. 20 RESULTS Patient Demographics and Clinical Characteristics The median age was 48.5 (range, 19 64) and included nine females and three males. The median BMI was 33.5 (range, ). The majority of patients in this study had previously undergone other types of upper airway procedures, including a combination of UPPP/ZPP, coblation-assisted lingual tonsillectomy, hyoid advancement, and tracheostomy. Prior to undergoing TORS-assisted BOT resection, all patients had a baseline preoperative PSG. They also had a postoperative

3 Clinical Characteristics TABLE I. Patient Demographics and Clinical Characteristics. Number (%) Mean (SD) Gender 9 (75%) Female 3 (25%) Male Race 5 (41.7%) Caucasian 2 (16.7%) Hispanic 5 (41.6%) African American Age 46.5 (13.3) Body mass index Neck circumference Friedman tongue position 34.5 (7.3) 15.4 (1.0) 3.6 (0.5) Tonsil size 0.6 (0.5) Friedman stage 3.3 (0.5) Sleep endoscopy findings % Velopharyngeal collapse (AP) % Velopharyngeal collapse (L) % Base of tongue collapse (AP) % Base of tongue collapse (L) % Epiglottic collapse (AP) 100.0% (0.0%) 54.2% (36.7%) 91.7% (16.3%) 60.4% (34.5%) 85.4% (31.0%) Median (Range) 48.5 ( ) 33.5 ( ) 15.0 ( ) 4.0 ( ) 1.0 ( ) 3.0 ( ) 100% (100% 100%) 50% (0% 100%) 100% (50% 100%) 50% (0% 100%) 100% (0% 100%) AP ¼ anterior-posterior; L ¼ lateral; SD ¼ standard deviation. PSG4 to 6 months following the surgery. TORS-assisted BOT resection was the only upper airway intervention performed between these two PSGs (Table I). Clinical Characteristics of 12 TORS-Assisted BOT Resection No intraoperative difficulty or complication was encountered. Median total operative time was 75 minutes (range, ) with median setup time of 25 minutes (range, 20 45) and median console time of 45 minutes (range, 20 90). The median blood loss was 20 ml (range, 5 30) and the median total volume of BOT tissue removed was 22.1 ml (range, ). Patients were kept in the hospital until they can take adequate fluid. None of the patient required feeding tube. Median hospital stay was 3 days (range, 1 4) (Table II). Outcome Following TORS-Assisted BOT Resection Ten patients were kept intubated overnight on high dose steroid and extubated the next morning without any airway issues. Two patients had prior tracheostomy were taken off the ventilator prior to leaving OR. One patient is currently decannulated, and the other is currently capping her tracheostomy tube 24 hours a day. There was one (8%) case of oropharyngeal scarring causing dysphagia that required another surgery to lyse the scar tissue. Three patients (25%) complained of taste disturbance following the surgery. This taste disturbance resolved within a few months in two patients, but persisted for more than 1 year in the third patient. No complication related to bleeding, airway, tongue mobility, swallowing, or speech was observed in this series. The mean AHI was preoperatively and postoperatively. This difference in AHI was statistically significant (P ¼ 0.007) and reflected an average AHI reduction of %. Statistical significant reduction in daytime somnolence level (ESS), as well as snoring intensity was achieved. There was no statistical significant difference between preoperative and postoperative BMI or LO 2 sat (Table III). Comparison of Patient Demographics and Clinical Characteristics Between Surgical Responder and Nonresponder Groups Surgical response was achieved in six of 12 patients (50%). Using Fisher s Exact test and independent twosample Student s t test, none of the demographic and clinical characteristics was statistically significantly associated to surgical response (Table IV). The preoperative and postoperative AHI for patients in the responder and nonresponder group are shown in Figure 1. Association Between Clinical Variables and Clinical Outcomes No predictor was identified for % change of AHI in univariate or multivariate regression model. However, preoperative AHI (P < 0.001) and preoperative LO 2 sat (P ¼ 0.034) in the univariate model were predictive for AHI reduction. The preoperative LO 2 sat was no longer significant for AHI reduction when adjusted for preoperative AHI. Friedman tonsil position was predictive (P ¼ 0.033) for % change of ESS (P ¼ 0.033), % change of VAS (P ¼ 0.04), and VAS reduction (P ¼ 0.043). DISCUSSION BOT resection for treatment of OSAHS is not a new concept. Recognizing the important contribution of BOT TABLE II. Clinical Characteristics of 12 Robotic-Assisted Base of Tongue Resection. Mean (SD) Median (Range) Total operative time (min) 76.3 (20.0) 75.0 ( ) Robot setup time (min) 27.9 (9.2) 25.0 ( ) Robotic surgical time (min) 48.3 (20.4) 45.0 ( ) Total blood loss (ml) 14.6 (8.9) 20.0 ( ) Total volume removed (ml) 27.6 (16.9) 22.1 ( ) Hospital stay (days) 2.7 (0.8) 3.0 ( ) min ¼ minutes; ml ¼ milliliter; SD ¼ standard deviation. 1813

4 TABLE III. Comparison of Preoperative and Postoperative BMI, AHI, LO 2 sat, ESS, and Snoring Intensity. Preoperative Mean (SD) Postoperative Mean (SD) P value (Paired Student s t test) Body mass index 34.5(7.3) 33.5(6.7) Apnea hypopnea index 43.9 (41.1) 17.6 (16.2) Lowest oxygen saturation 83.3% (5.5%) 84.0% (6.4%) Epworth sleepiness scale 13.7 (5.2) 6.4 (4.5) <0.001 Snoring intensity (VAS, 0 10) 8.6 (1.2) 4.2 (1.9) <0.001 AHI ¼ apnea hypopnea index; BMI ¼ body mass index; ESS ¼ Epworth sleepiness scale; LO 2 sat ¼ lowest oxygen saturation, SD ¼ standard deviation; VAS ¼ visual analog scale. obstruction in OSAHS, Fujita first reported on the use of carbon dioxide laser for midline glossectomy in 12 patients. 21 Perhaps due to the complexity of the surgery and the potential for major complications, this procedure never became popular. Submucosal minimally invasive lingual excision (SMILE) 22 and coblation-assisted lingual tonsillectomy 23,24 were recently described to address large tongue base in children with obstructive macroglossia and were found to be promising in the treatment of BOT obstruction in OSAHS patients. 24,25 However, these procedures are limited by poor visualization and access to the BOT region. The combination of highresolution 3-dimensional magnification and surgical precision afforded by the da Vinci robot may finally provide the technological advances necessary to overcome difficulties in accessing the BOT area. Vicini 17,26 reported on their experience with 20 patients who underwent TORS-assisted tongue base reduction concomitantly with multiple other procedures such as septoplasty, supraglottoplasty, UPPP, turbinate reduction, and ethmoidectomy. In this group, the mean AHI dropped from to (P ¼ TABLE IV. Comparison of Patient Demographics and Clinical Characteristics Between Surgical Responders (n 5 6) and Nonresponders (n 5 6). Demographics and Clinical Characteristics Number of Responders Number of Nonresponders P value (Fisher s Exact Test) Gender Female Male 0 3 Race Caucasian African-American 2 3 Hispanics 1 1 Prior surgery Yes No 4 1 Friedman tongue position III IV 3 4 Tonsil size 0 þ þ 5 2 Friedman stage III IV 1 3 Mean (SD) Mean (SD) P value (independent two sample t test) Age 47.3 (11.8) 45.7(15.8) Body mass index 31.9(6.5) 37.0 (7.7) Apnea Hypopnea Index 24.2 (11.3) 63.5 (51.6) Lowest oxygen saturation 86.3% (3.9%) 80.0% (5.5%) Neck circumference 15.0 in (0.9) 15.7 in (1.0) Tongue tissue removed 30.4 ml (17.9) 24.8 ml (17.0) in ¼ inches; ml ¼ milliliters; SD ¼ standard deviation. 1814

5 Fig. 1. Preoperative and postoperative AHI of the six patients in the responder group and the six patients in the nonresponder group. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] ), and mean ESS dropped from to postoperatively (P ¼ ). 17 Recently, Friedman reported on 27 patients who underwent robotic-assisted midline glossectomy in conjunction with ZPP. The mean AHI dropped from to (P < 0.001) and mean ESS dropped from to postoperatively (P < 0.001). 18 The results from these two studies are promising. However, these reports described the use of TORS-assisted BOT resection in conjunction with other concomitant upper airway procedures, making interpretation of the true efficacy of TORS-assisted BOT procedure itself difficult. In this study, we report on the clinical and polysomnographic outcome of 12 patients who underwent TORSassisted BOT resection alone without any other concomitant surgical interventions. To our knowledge, this is the first study looking at the efficacy of TORS to address obstruction at the level of BOT only, not confounded by surgical alterations at other levels of airway. We showed significant reduction in AHI, ESS, and snoring intensity following TORS-assisted BOT resection. Six of 12 patients (50%) achieved surgical response, and all have postoperative AHI of less than 10 (range, ). Despite undergoing only the BOT procedure, our patients surgical outcomes (AHI and ESS) appeared to be similar to those patients who underwent BOT procedure, in addition to other upper airway surgeries reported by the two other groups. Several similarities and differences exist between our study and those of Vicini s 17 and Friedman s. 18 Our surgical technique appeared to be more similar to that reported by Vicini and differed significantly to that reported by Friedman. Although Vicini did not report on the amount of tongue tissue removed, our mean volume of tissue removed was ml, while the mean weight of tissue removed by Friedman was grams (g). Here we can assume the density of the removed tissue to be about 1 g/ml since density of muscle is 1.06 g/ml 27 and density of fat is 0.9 g/ml. 28 Further, our practice of keeping the patient intubated overnight in the intensive care unit (ICU) appeared to be a compromise between routine tracheostomy by Vicini 17 and extubation at the end of the procedure by Friedman. 18 Our mean hospital stay of days falls within the range reported by Vicini ( days) and Friedman ( days). The mean BMI in our group ( ) is similar to that of Friedman s ( ) but is much higher than that from Vicini s series ( ). Finally, our operative and setup time is similar to that reported by Vicini. Proper patient selection is perhaps one of the most important factors to take into account when evaluating the applicability of a novel surgical approach. Unfortunately, given the retrospective nature of this study as well as the small sample size, we were not able to identify any clinical or demographic factors that may be predictive of surgical response. In this current series, three patients complained of taste disturbance that lasted for a few months after surgery. Taste disturbance is a well-known complication following any oral procedure, even tonsillectomy. 29 Although the etiology for this complication following TORS-assisted BOT resection is largely unknown, possible causes include direct surgical injury to the taste buds in the BOT, as well as compression and stretching injury to the branches of lingual nerve from the prolonged retraction during surgery. It is therefore important that the surgeon periodically relaxes the retractor during surgery. Patients should also be informed of this possible complication prior to surgery. Due to the absence of a reliable and constant anatomic landmark, surgical intervention in the BOT can be burdened with the potential devastating complication of injuring the critical hypoglossal/lingual artery neurovascular bundle (HLNVB). In this current series, the mean intraoperative blood loss was ml, and no significant postoperative bleeding was observed. However, major catastrophic postoperative bleeding can and will occur with surgical manipulation in the BOT. Thus, familiarity with anatomy of the HLNVB is critically important. The average distance from the foramen cecum to the HLNVB was found to be cm in a cadaver study, 30 and cm in a study using computed tomographic angiography. 31 Thus, functional surgery performed within approximately 1.5 cm of the foramen cecum should be safe. Our current practice is to keep the lateral extent of BOT resection to about 1.5 cm from the midline bilaterally if there is minimal lingual tonsil tissue and minimal contribution to airway collapse from lateral BOT, as noted on sleep endoscopy. However, in patients with large amount of lingual tonsils and 1815

6 large contribution to collapse from the lateral BOT tissue, resection of the lateral BOT tissue down to the inferior tonsillar fossa is necessary in order for the surgery to be effective. When operating beyond the 1.5 cm boundary from the midline, it is extremely important to increase the magnification to allow the clear visualization of the layer-by-layer cutting of the muscle fibers. Slow and careful dissection should be carried out over the lateral BOT to identify the dorsal branch of the lingual artery, which will need to be carefully ligated multiple times with clips before dividing. Finally, we like to point out that, although we demonstrated the effectiveness of TORS-assisted BOT resection as a stand-alone surgical modality in the treatment of OSAHS in this small series, we do not necessarily advocate the use of this surgical technique alone for treatment of OSAHS. This study was not done to prove that a single site (BOT) surgery works. Rather, it was a retrospective review of a small group of patients who happen to undergo only BOT resection in order to assess the effectiveness of this procedure alone. No single surgical procedure is perfect, and it is incumbent upon the surgeon to identify and select the most optimal procedure or combination of procedures to treat the anatomic obstruction unique to each OSAHS patients. Currently, most of our patients undergo a combination of TORS-assisted BOT resection, epiglottopexy, and UPPP/ ZPP depending on preoperative sleep endoscopy findings. In patients who required extensive lateral BOT resection to involve the inferior tonsillar fossa, we would be sufficiently worried about the possibility of circumferential oropharyngeal scarring/stenosis if the BOT resection was performed at the same time as the UPPP/ ZPP. Thus, we would recommend a two-stage approach in which the first stage comprised of TORS-assisted BOT resection to be followed, if necessary, by a second stage consisting of other upper airway surgeries such as UPPP/ZPP. CONCLUSION This preliminary result on the use of TORS-assisted BOT resection for treatment of OSAHS is encouraging. We showed a 50% surgical response rate and a statistically significant improvement in ESS, AHI, and snoring intensity. This is the first study looking at the use of TORS to address obstruction at the level of BOT only, not confounded by surgical alterations at other levels of upper airway. However, BOT surgery can be fraught with serious complications, and a surgeon must be knowledgeable about the anatomy of HLNVB. Since the use of this procedure is in its early infancy, there remain many unanswered questions. Currently there are no standardized criteria to identify which patients would most benefit from this procedure. Further investigations are warranted to further evaluate the benefits and limitations of this new technique. BIBLIOGRAPHY 1. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005;365: Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA 2003;290: Young T, Finn L, Peppard PE, et al. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep 2008; 31: Punjabi NM, Caffo BS, Goodwin JL, et al. Sleep-disordered breathing and mortality: a prospective cohort study. PLoS Med 2009;6:e American Thoracic Society. Indications and standards for use of nasal continuous positive airway pressure (CPAP) in sleep apnea syndromes. 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