Effects of Radiofrequency Versus Sham Surgery of the Soft Palate on Daytime Sleepiness

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1 The Laryngoscope VC 2014 The American Laryngological, Rhinological and Otological Society, Inc. Effects of Radiofrequency Versus Sham Surgery of the Soft Palate on Daytime Sleepiness Thorbjorn Holmlund, MD; Eva Levring-J aghagen, DDS, PhD; Karl A. Franklin, MD, PhD; Marie Lindkvist, PhD; Diana Berggren, MD, PhD Objectives/Hypothesis: To evaluate the effect of radiofrequency surgery of the soft palate on daytime sleepiness in snoring men with mild or no sleep apnea. Study Design: Randomized controlled trial. Methods: Thirty-five men were recruited from consecutive patients referred to the Ear, Nose, and Throat Clinic due to snoring and complaints of daytime sleepiness. The inclusion criteria were an apnea-hypopnea index (AHI) of 15, male gender, and age 18 to 65 years. Patients were randomized to either radiofrequency or sham surgery of the soft palate. All but one chose and received the option of three treatments. All patients participated in a follow-up, including an overnight sleep apnea recording and questionnaires 12 months after the last treatment. The primary outcome was daytime sleepiness measured with the Epworth Sleepiness Scale (ESS) and other questionnaires. Secondary outcomes were effects on the AHI and subjective snoring. Results: Thirty-two of 35 patients 19 of 20 patients in the radiofrequency surgery group and 13 of 15 patients in the sham surgery group completed the study. No differences between the two groups in relation to the ESS or AHI were found at follow-up. Conclusion: Radiofrequency surgery of the soft palate has no effect on daytime sleepiness, snoring, or apnea frequency in snoring men with mild or no sleep apnea 1 year after surgery. Key Words: Radiofrequency, sham surgery, randomized controlled trial, daytime sleepiness, snoring, sleep apnea syndrome. Level of Evidence: 1b. Laryngoscope, 124: , 2014 INTRODUCTION Snoring occurs in 15% to 47% of men. 1 3 Snoring is associated with a number of negative health effects, including daytime sleepiness, hypertension, cardiovascular disease, and impairment of cognitive functions. 4 6 Continuous positive airway pressure and oral appliances are effective treatments for sleep apnea and snoring, but compliance with treatment is lower among snorers and patients with mild obstructive sleep apnea. 7,8 Different surgical techniques have been suggested. Uvulopalatopharyngoplasty with removal of the tonsils and parts of the soft palate has been used worldwide for decades to treat snoring and sleep apnea. 9 From the Department of Otorhinolaryngology (T.H., D.B.); the Department of Oral and Maxillofacial Radiology (E.L-J.); the Department of Surgery (K.A.F.); and the Department of Statistics (M.L.), Umeå School of Business and Economics; the Department of Epidemiology and Global Health (M.L.), Umeå University. Umeå, Sweden Editor s Note: This Manuscript was accepted for publication December 30, The preliminary results of this trial were presented at the World Congress on Sleep Apnea 2012 in Rome, Italy, August 27 September 1, The study was supported by the Acta Otolaryngologica Foundation. The authors have no other funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Thorbj orn Holmlund, MD, Department of Otorhinolaryngology/ Clinical Sciences, SE Umeå, Sweden. thorbjorn.holmlund@vll.se DOI: /lary Radiofrequency surgery of the soft palate was introduced by Powel et al. in 1998 with the aim of reducing snoring and mild sleep apnea. 10 The method became popular because of its simplicity as an outpatient procedure with a low risk of adverse postoperative effects. 11 The technique uses temperatures from 85 to 100 C in a controlled way to deliver scaring lesions, designed to shrink and stiffen the tissue in the applied area. 12 To date, only two placebo-controlled studies have been published on the radiofrequency treatment of snoring. 13,14 In 2005, Stuck et al. reported that radiofrequency surgery was better than placebo when it came to reducing snoring, according to a bedroom partner at follow-up 6 to 8 weeks after treatment, but there was no difference in daytime sleepiness, measured with the Epworth Sleepiness Scale (ESS). 13 In 2009, B ack et al. found no improvement in daytime sleepiness or snoring. 14 The primary aim of this study was to evaluate the effect of radiofrequency surgery of the soft palate on daytime sleepiness in snoring men with mild or no sleep apnea. A secondary objective was to investigate the effect on snoring and apnea frequency. MATERIALS AND METHODS Participants Thirty-five men were randomized to either radiofrequency surgery of the soft palate or sham surgery. The inclusion criteria were male gender, age 18 to 65 years, an apnea-hypopnea

2 Fig. 1. Progress of participants in the trial. index (AHI) of 15, and a body mass index (BMI) of 31. The exclusion criteria were smoking, prior palatal surgery, or severe systemic disease (American Society of Anesthesiologists class 3). The eligible group comprised 68 consecutive patients referred to the Ear, Nose, and Throat Clinic because of habitual snoring and daytime sleepiness. Eighteen patients declined participation, and 15 patients were excluded due to smoking or cardiovascular disease. Twenty patients were randomized to surgery and 15 to sham surgery (Fig 1). The baseline characteristics are given in Table I. According to questions drawn from the Short Form-36 Health Survey questionnaire regarding general health, the participants evaluated their health level to be on a par with that found for the general population in Sweden. 15 The study was approved by the regional ethical review board in Umeå (Dnr ). All the patients gave their informed written consent to participate. Outcomes The primary outcome was daytime sleepiness using the ESS measured at follow-up, 1 year after treatment (Table II). The ESS is a questionnaire on the probability of falling asleep in different situations in daily life. 16 The secondary outcomes were the AHI, and subjective snoring according to a bedroom partner with questions relating to the frequency and level of snoring (Table II and Table III). The Basic Nordic Sleep Questionnaire (BNSQ), with five possible answers to each question, were used to evaluate snoring frequency, snoring intensity, daytime sleepiness, and the probability of falling asleep at work. 17 Sleep Apnea Recordings Overnight ambulatory sleep apnea recordings (Embletta, Embla systems, Kanata, Canada) included continuous recordings of airflow using nasal cannula pressure, thoracic,and abdominal respiratory effort Xact Trace Belts (Embla Systems, Kanata, Canada), finger pulsoximetry (Nonin Oximeter XPOD, Nonin Medical, Inc. Plymouth, USA), and a body position sensor. All the recordings were scored manually and the duration of sleep was estimated from the recordings. The scorer was blinded to treatment and the scoring was not performed by any of the authors. An apnea was defined as a cessation of airflow lasting at least 10 seconds, while a hypopnea was defined as a TABLE I. Baseline Patient Demographics and Clinical Characteristics. Surgery (n 5 20) Mean (SD) Sham Surgery (n 5 15) Mean (SD) P* Age 47.6 (7.5) 49.9 (7.9) Weight 85.0 (9.8) 84.4 (9.1) BMI 26.5 (2.2) 26.2 (1.7) ESS 9.8 (3.5) 10.0 (5.0) AHI 4.6 (3.6) 4.6 (2.6) Self-rated health n (%) n (%) excellent 4 (20) 1 (7) very good 7 (35) 8 (53) good 7 (35) 4 (27) fairly good 2 (10) 2 (13) poor 0 (0) 0 (0) Self-rated health: Questions drawn from the Short Form-36 Health Survey questionnaire. *Independent samples t test. AHI 5 apnea hypopnea index; ESS 5 Epworth Sleepiness Scale; SD 5 standard deviation; SF-36 5 The Short Form-36 Health Survey. 2423

3 TABLE II. Values at Baseline and Follow-up for the ESS and AHI. Surgery (n 5 19) Placebo (n 5 13) mean (SD) mean (SD) Baseline Follow-up Baseline Follow-up Adjusted Difference* (95% CI) at Follow-up ESS 9.84 (3.6) 8.05 (4.2) (5.3) 8.31 (5.1) 0.10 (21.87 to 2.07) AHI 4.15 (3.1) 5.91 (4.8) 4.65 (2.8) 5.95 (4.8) 0.20 (23.29 to 3.69) *Function score adjusted for baseline and BMI (baseline). AHI 5 apnea hypopnea index; CI 5 confidence interval; ESS 5 Epworth Sleepiness Scale; SD 5 standard deviation. TABLE III. Results of the BNSQ (The Basic Nordic Sleep Questionnarie) Questionnarie. Radiofrequency Sham Surgery Baseline Follow-up Baseline Follow-up Difference at Follow-up Median Median Median Median P Value Q1 Snoring frequency (1 5) Q2 Snoring intensity (1 5) Q3 Daytime sleepiness (1 5) Q4 Probability of falling asleep at work (1 5) Values represent the degree of experienced disturbances. Q1: 1 5 never or less than once a month, 2 5 less than once a week, 3 5 on 1 2 nights a week, 4 5 on 3 5 nights a week, 5 5 every night or almost every night; Q2: 1 5 I don t snore, 2 5 my snoring sounds regular and it is of low volume, 3 5 it sounds regular but fairly loud, 4 5 it sounds regular, but it is very loud (other people hear my snoring in the next room), 5 5 I snore very loudly and intermittently (there are silent breathing pauses when snoring is not heard and at times very loud snorts with gasping); Q3 Q4: 1 5 never or less than once a month, 2 5 less than once a week, 3 5 on 1 2 days a week, 4 5 on 3 5 days a week, 5 5 daily or almost daily. 50% reduction in airflow compared with baseline, in combination with an oxygen desaturation of 3%. 18 Randomization The participants were randomly assigned to either radiofrequency or sham surgery by means of prefilled closed envelopes. Initially there were 50 envelopes containing one of 25 radiofrequency surgery notes or 25 sham surgery notes. Reception personnel not involved in the study randomly selected one envelope and wrote the patient s name and date of birth on it before it was handed over to the surgeon, who was sitting in a separate room. The surgeon opened the envelope and the patient was given treatment according to the note in the randomly received envelope. The patients were blinded to their treatment alternative. The patients were offered a nonsteroidal antiinflammatory drug as a postoperative painkiller. No antibiotics or corticosteroids were prescribed. The patients were given the option of receiving up to three treatments. All of the patients chose to receive three treatments, with the exception of one patient in the radiofrequency group who chose only one treatment. The treatment sessions were given at 4- to 6-week intervals. All the surgical procedures were performed by two of the authors (TH, DB). Changes in voice or swallowing function were evaluated with questionnaires at baseline and follow-up. Statistical Analysis The data were analyzed using PASW statistics version 20 (IBM, Armonk, NY). The descriptive results are presented as Surgical Procedures The radiofrequency and sham surgery procedures were performed in an outpatient setting. All patients were given a topical lidocaine spray, 10 mg/dose on the soft palate, followed by an injection of approximately 4 ml Carbocain 1%. In the radiofrequency group, the Coblator surgery system 1 (Arthrocare Corp, Sunnyvale, CA) was used to administer highfrequency energy via the ReFlex Ultra 55 Plasma Wand to the soft palate. The machine settings were set at level 6. The wand was inserted into the muscular layer of the soft palate and held in place for 10 seconds at each of the three sites in the soft palate, in the midline 1 cm below the border of the hard and soft palate, and 1 cm laterally on both sides as illustrated in Figure 2. The same setting for local anesthesia, wand, and machine was used in the sham surgery group, with the exception that no energy was supplied to the wand. Fig. 2. The three treatment locations in the soft palate. 2424

4 TABLE IV. Comparison Between Randomized Controlled Studies of Radiofrequency Surgery. Holmlund et al (present study) B ack et al Stuck et el No. of patients Gender male male not reported Inclusion age Mean age (years) 49 not reported 43 Inclusion BMI 31 < 35 < 35 Inclusion AHI < 15 Sleep recording polygraphic polygraphic * Generator type coblation Celon Lab ENT somnoplasty No. of treatments Follow-up period 13 months 4 months 6 8 weeks Primary outcome ESS/daytime sleepiness, ESS/AHI/quality of life ESS/snoring (VAS) snoring (questionnaire) (SF-36) ESS difference pre/post ns ns ns AHI difference pre/post ns ns Not reported Effect on snoring ns ns Significant improvement (P < 0.05) *Sleep recordings with polygraphy or polysomnography were only performed before inclusion in the study. AHI 5 apnea hyponea index; BMI 5 body mass index; ENT 5ears, nose, and throat; ESS 5 Epworth Sleepiness Scale; ns 5 not significant; SF-36 5 The Short Form-36 Health Survey; VAS 5 visual analog scale. means, standard deviations, numbers, and percentages. The normality assumptions for the quantitative variables were checked with histograms and skewness. When it came to quantitative variables, linear regression was used to estimate adjusted differences between groups adjusting for baseline values. The Mann-Whitney U test was used to investigate differences in ordinal variables between groups. The follow-up time is presented as the mean (Table IV). Statistical significance was defined as P < RESULTS Thirty-five patients were included and given treatment according to the protocol, 20 patients in the radiofrequency group and 15 patients in the sham surgery group. There were no differences in patient characteristics at baseline (Table I). Three patients one patient in the radiofrequency surgery group and two patients in the sham surgery group failed to attend the 12-month follow-up. The mean follow-up time was months. About two-thirds of the participants in both the radiofrequency surgery and the sham surgery groups guessed that they had received a sham treatment, 11 of 19 of the participants in the radiofrequency group and 8 of 13 of the participants in the sham surgery group (Fig 1). The power to detect a difference of three units in ESS (SD 5 4) in the surgery group (n 5 19) was 87%, and the power to detect a difference of two units was 53%. The ESS, AHI, and subjective snoring did not differ at follow-up between patients in the radiofrequency and sham surgery groups (Tables II and III). The ESS was lower at follow-up compared with baseline both in the radiofrequency group (P < 0.001) and in the sham surgery group (P < 0.05) (Fig 3). The mean BMI did not differ between baseline and follow-up. Complications No serious complications were reported in either of the study groups. There were no differences in reported problems with swallowing or voice between the two treatment groups. DISCUSSION This randomized, placebo-controlled trial was feasible because the patients were unable to distinguish Fig. 3. Effect on the Epworth Sleepiness Scale (mean, 95% confidence interval) in the radiofrequency group (RF) and sham surgery group. 2425

5 between radiofrequency surgery of the soft palate and sham surgery. Radiofrequency treatment of the soft palate was also well tolerated, and there were no reports of adverse effects. Radiofrequency surgery of the soft palate had no effect on daytime sleepiness measured with the ESS and other questionnaires, either on snoring or on the AHI at follow-up after 1 year (Tables II and III). Instead, our results showed a classical placebo effect because the ESS declined in both the radiofrequency surgery and the sham surgery groups (Fig. 3). Earlier studies and reviews have reported a reduction in snoring among radiofrequency-treated patients, but the follow-up period was often short and most studies were observational. 12 To the best of our knowledge, only two randomized controlled studies have been published on the effect of radiofrequency on snorers and patients with mild sleep apnea. Stuck et al. reported that radiofrequency was better than placebo at reducing snoring, according to a bedroom partner at follow-up after 6 to 8 weeks, but there was no difference in daytime sleepiness measured using the ESS. 13 B ack et al. did not find any improvement in snoring or daytime sleepiness measured with the ESS and other questionnaires 4 months after treatment. 14 In the present study, there was no effect on daytime sleepiness or snoring 1 year after treatment. The study sample was fairly small, with only 32 patients included. The power was still 87% to detect a difference three units in ESS, but it was lower to detect smaller effects in ESS. Therefore, we are unable to rule out a small effect on daytime sleepiness from the present study. However, the results of our study, together with the above-mentioned studies by B ack et al. 14 and Stuck et al., 13 support the conclusion that radiofrequency has no effect on daytime sleepiness (Table IV). We had a somewhat uneven distribution of patients in the two groups: 13 in the placebo group and 19 in the surgery group. This was due to the randomization procedure with 35 patients and 50 envelopes. We used the ESS, the most commonly used questionnaire for measuring daytime sleepiness, to measure daytime sleepiness. The ESS is also validated against the multiple sleep latency test. 16 The included patients had an ESS score of about 10, which is regarded as the lower limit for pathological daytime sleepiness. 16 In the present study, radiofrequency surgery of the palate had no effect on snoring when it came to the perception of a bedroom partner. However, it is difficult to evaluate the presence and severity of snoring and there is no generally accepted gold standard. We used the basic BSNQ. 17 The BSNQ focuses on the bedroom partner s perception of snoring, which is a common method of evaluation, albeit with obvious shortcomings when using subjective measurements. The BNSQ contains a basic scale of five answers, which is less than if we had chosen a visual analogue scale and this is a limitation because we could have missed some effects on snoring. 17 CONCLUSION Radiofrequency surgery of the soft palate has no effect on daytime sleepiness, snoring, or apnea frequency in snoring men with mild or no sleep apnea 1 year after surgery. BIBLIOGRAPHY 1. Enright PL, Newman AB, Wahl PW, Manolio TA, Haponik EF, Boyle PJ. Prevalence and correlates of snoring and observed apneas in 5,201 older adults. Sleep 1996;19: Lindberg E, Taube A, Janson C, Gislason T, Svardsudd K, Boman G. A 10- year follow-up of snoring in men. Chest 1998;114: Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993;328: Shin C, Joo S, Kim JK, Kim T. Prevalence and correlates of habitual snoring in high school students. Chest 2003;124: Janszky I, Ljung R, Rohani M, Hallqvist J. Heavy snoring is a risk factor for case fatality and poor short-term prognosis after a first acute myocardial infarction. Sleep 2008;31: Telakivi T, Kajaste S, Partinen M, et al. Cognitive function in middle-aged snorers and controls: role of excessive daytime somnolence and sleeprelated hypoxic events. Sleep 1988;11: Lim J, Lasserson TJ, Fleetham J, Wright JJ. Oral appliances for obstructive sleep apnoea. Editorial Group: Cochrane Airways Group. Published Online: 8 JUL Giles TL, Lasserson TJ, Smith BH, White J, Wright J, Cates CJ. Continuous positive airways pressure for obstructive sleep apnoea in adults. Editorial Group: Cochrane Airways Group. Published Online: 8 OCT Fujita S, Conway W, Zorick F, Roth T. Surgical correction of anatomic abnormalities in obstructive sleep apnea syndrome: uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg 1981;89: Powel NB, Riley RW, Troell RJ, Li K, Blumen MB, Guilleminault C. Radiofrequency volumetric tissue reduction of the palate in subjects with sleep-disordered breathing. Chest 1998;113: Kezirian EJ, Powell NB, Riley RW, Hester JE. Incidence of complications in radiofrequency treatment of the upper airway. Laryngoscope 2005; 115: Back LJ, Hytonen ML, Roine RP, Malmivaara AO. Radiofrequency ablation treatment of soft palate for patients with snoring: a systematic review of effectiveness and adverse effects. Laryngoscope 2009;119: Review. 13. Stuck BA, Sauter A, Horman K, Verse T, Maurer JT. Radiofrequency surgery of the soft palate in the treatment of snoring. A placebo-controlled trial. Sleep 2005;28: Back LJ, Liukko T, Rantanen I, et al. Radiofrequency surgery of the soft palate in the treatment of mild obstructive sleep apnea is not effective as a single-stage procedure: a randomized single blinded placebocontrolled trial. Laryngoscope 2009;119: Sullivan M, Karlsson J, Ware J. The Swedish SF-36 Health Survey-I. Evaluation of data quality, scaling assumptions, reliability, and construct validity across general populations in Sweden. Soc Sci Med 1995; 41: Johns MW. Daytime sleepiness, snoring, and obstructive sleep apnea. The Epworth sleepiness scale. Chest 1993;103: Partinen M, Gislason T. Basic Nordic Sleep Questionnaire (BNSQ): a quantitated measure of subjective sleep complaints. J Sleep Res 1995; 4(suppl 1): Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 1999;22: