82 ISSN 1738-3544 Treatment Outcomes of Mandibular Advancement Devices in Obstructive Sleep Apnea Patients Cheon-Sik Kim, Yong-Seok Lee 1, Cheon-Ung Cho 1, and Dae-Sik Kim 2 Departments of Neurology, Asan Medical Center, Seoul 138-736, Korea 1 Department of Clinical Laboratory Science, Dongnam Health University, Suwon 440-714, Korea 2 Mandibular advancement devices (MAD) are therapeutic options for obstructive sleep apnea (OSA). The aim of study was to investigate treatment outcomes of before and after insertion of MAD in OSA patients. We retrospectively selected a total of 13 patients who were diagnosed with OSA syndrome. All sleep-related parameters including apnea-hypopnea index (AHI), oxygen desaturation index (ODI), wake after sleep onset (WASO), total arousal were measured by before and after MAD. The use of MAD proves to be efficient in reducing snoring, apnea-hypopne index (17.2±14.6 vs 20.9±14.6), WASO (27.4±28.8 vs 47.9±43.6 ), oxygen desaturation index (9.0±11.6 vs 16.4±11.7), stage N3 (54.8±45.2 vs 36.6±22.0), REM sleep times (73.3±19.4 vs 66.0±31.0) and increases sleep efficiency (92.6±6.6 vs 87.2±11.2). The decreases in apnea index based on a reduction in the overall and supine AHI values after MAD therapy were significantly greater for the positional OSA than nonpositional OSA patients. The use of MAD proves to be efficient in snoring, WASO, sleep efficiency, reduced AHI and associated with good compliance of patients. Key Words : Obstructive sleep apnea, Apnea-hypopnea index, Mandibular advancement devices 서론 폐쇄성수면무호흡 (obstructive sleep apnea, OSA) 은수면 다원검사에서상기도폐쇄로 10 초이상호흡이멈추는것을 말하며, 이러한폐쇄성수면무호흡을주증상으로하는폐쇄 성수면무호흡증후군은주간이나야간에수면무호흡과관련 된임상증상이있으면서수면다원검사에서무호흡 - 저호흡 지수 (apnea-hypopnea index, AHI) 가시간당 5 이상일때 Corresponding author: Kim, Dae-Sik. Department of Clinical Laboratory Science, Dongnam Health University, Suwon 440-714, korea. Tel: 031-249-6415, 010-7511-1886 FAX: 031-249-6410 E-mail: kdaesik@dongnam.ac.kr 본연구는 2010 년도동남보건대학연구비지원에의하여수행된것임. Received : 3 June 2011 Return for modification : 16 June 2011 Accepted : 20 June 2011 진단할수있다 (AASMTF, 1999). 야간수면중의이러한무호흡-저호흡은주간의과도한주간졸음증, 인지기능저하, 뇌졸중및허혈성심장질환등의위험을증대시키고결과적으로혈관질환으로인한사망을초래하는매우위험한질환이다 (Malhotra 과 White, 2002; Engleman 과 Douglas, 2004; Robinson 등, 2004). 폐쇄성수면무호흡증후군의치료는지속적인기도내양압장치 (continuous positive airway pressure, CPAP), 구강내하악전돌장치 (mandibular advancement devices, MAD) 및수술적방법등이사용되고있다. 폐쇄성수면무호흡증후군치료법으로지속적기도내양압장치가효능면에서가장좋은효과를보이지만불편하여사용중치료를중단하는경우가많다. 이에반해하악전돌장치는지속적인기도내양압장치보다는수면중무호홉-저호흡지수를낮추는데는효과가적지만착용이편안하다는장점으로인해환자들이하악전돌장치를선호하는경향이있다 (Clark 등, 1996). 82
이에본연구에서는수면다원검사를통하여하악전돌장치착용전후환자의수면구조의변화, 무호흡-저호흡지수및코골이변화등하악전돌장치의효과에대해서알아보고자한다. 대상과방법 1. 대상 2008년 7월부터 2010년 10월까지코골이및수면무호흡으로내원하여수면다원검사를시행한환자중무호흡-저호흡지수가시간당 5 이상이면서지속적기도내양압장치나수술적방법을거부하고하악전돌장치를시행한환자를대상으로하였다. 전체환자는 15명중여자가 4명이였으며, 연령은 21세에서 68세까지다양하였다. 하악전돌장치는시행하였으나하악전돌장치착용후수면다원검사를재시행한환자를대상으로하였고, 검사를시행하지않은 2명의환자는연구에서제외하였다. 2. 수면다원검사수면단계측정을위해 6개채널의뇌파, 2개채널의안전도, 3개채널의턱밑근전도를시행하였다. 무호흡과저호흡측정을위한호흡센서로는온도감지센서와비강공기압센서를동시에사용하였고, 호흡에따른흉복부의움직임을관찰하기위해흉부및복부에호흡벨트를착용하였다. 심전도, 하지근전도, 산소포화도, 코골이및수면중체위변동을분석하기위해체위감지센서등을동시에기록하였다. 3. 무호흡및저호흡판독무호흡및저호흡의판독은미국수면학회수면다원검사자격증을가지고있는숙련된 2명의임상병리사가담당하였다. 무호흡, 저호흡을판독한기준은개정된 2007년미국의학회권장기준을사용하였다. 무호흡은온도감지센서에서최소 10초이상, 공기의흐름이 90% 이상감소된경우로정의하였다. 저호흡은비강공기압센서에서최소 10초이상, 호흡량이 30% 이상감소하고동시에 4% 이상혈중산소포화도가감소된경우로정의하였다 (Iber 등, 1997). 4. 하악전돌장치 (mandibular advancement device) 하악전돌장치는상악과하악치아에각각부착하고, 하악을전방으로돌출시켜주는장치이다. 하악전돌장치가폐쇄성수면무호흡환자에서작용을나타내는원리는하악의전방위치를통해기도의직경이증가되며, 이로인해흡기시의음압에대한기도의협착저항성이증가한다는이론과하악의전방이동으로인하여인두의신장이발생하며, 이로인한인두운동체계 (pharyngeal motor system) 가활성화된다는이론이다 (Yoon과 Kim, 2006). 본연구에사용되어진하악전돌장치는 13명모두에게동일한종류의변형된 Herbst 장치를사용하였다 (Fig. 1). 5. 통계분석환자의일반적특징및수면다원검사에서의수면관련변수, 그리고각판독기준에따른무호흡-저호흡지수등의기술통계를사용하여분석하였다. 하악전돌장치착용전후의무호흡-저호흡지수비교와앙와위자세와비앙와위자 Fig 1. Modified herbst appliance. Treatment Outcomes of MAD in OSA Patients 83
세에서의폐쇄성수면무호흡환자에서의하악전돌장치착용 전후의호흡지수비교는윌콕슨의결합 - 조기호 - 순위검정 (Wilcoxon matched-pairs signed-ranks test) 을사용하여 분석하였다. 무호흡환자에서무호흡 - 저호흡지수가앙와 위자세와비앙와위자세에서 2 배이상차이가나는경우 를체위성무호흡환자로정의하였다 (Cartwright, 1984). 통 계처리는 SPSS version 13.0(SPSS Inc., Chicago, IL, USA) 을사용하였다. 1. 대상자의일반적특징 결과 대상자의연령범위는 21 세에서 68 세로평균연령은 49.4±14.0 세였고, 체질량지수는 26.0±23.2 이었다. 하악 전돌장치착용전전체환자의평균무호흡 - 저호흡지수 는 20.9±14.6 이였고, 이중앙와위무호흡 - 저호흡지수는 31.0±25.9, 비앙와위무호흡 - 저호흡지수는 11.2±23.8 로 자세에따른무호흡 - 저호흡지수의차이가 2 배이상이었다 (Table 1). Table 1. Characteristics of study population at baseline Variables Mean ± SD Age (y) 49.4 ± 14.0 Gender, % male 69.2 BMI (kg/m 2 ) 26.0 ± 23.2 Neck circumference (cm) 42.0 ± 37.0 Overall AHI 20.9 ± 14.6 Supine AHI 31.0 ± 25.9 Nonsupine AHI 11.2 ± 23.8 Snoring time (min) 51.9 ± 53.8 ESS 7.8 ± 2.8 Abbreviations: SD, standard deviation; BMI, body mass index; AHI, apnea hypopnea index; ESS, epworth sleepiness scale 2. 하악전돌장치착용전후의수면구조의변화 하악전돌장치착용후수면의구조는 1 단계수면 (stage N1) 은줄고, 3 단계수면 (stage N3) 과 REM 수면시간은증가 하는것을볼수있었으며, 1 단계수면은통계상유의한차 이를보였다 (p<0.039)(table 2). 수면잠복기 (sleep latency), 수면중각성시간 (wake after sleep onset), 최소산소포화도 (minium saturation), 산소포화 도지수, 전체각성수 (total arousal number) 는하악전돌장 치착용후전반적으로감소하였으나, 수면효율성 (sleep efficiency) 은증가하였으며, 통계적으로유의한차이를보였 다 (Table 2). 하악전돌장치착용전후의무호흡 - 저호흡지수는 ( 착용 전 vs 착용후 ; 20.9±14.6 vs 17.2±14.6: p = 0.345) 통계적 으로유의한차이는보이지는않았지만착용후무호흡 - 저 호흡지수가줄어드는것을볼수있었다 (Table 2). Table 2. Changes in sleep event pre-post MAD therapy in OSA patents (n=13) Variables With MAD Mean ± SD Without MAD Mean ± SD Stage N1 (min) 79.4 ± 31.4 93.9 ± 29.9 0.039 Stage N2 (min) 159.8 ± 43.3 165.8 ± 55.6 0.65 Stage N3 (min) 54.8 ± 45.2 36.6 ± 22.0 0.249 REM (min) 73.3 ± 19.4 66.0 ± 31.0 0.507 TST (min) 367.3 ± 20.3 362.5 ± 58.5 0.861 SL (min) 3.0 ± 2.8 4.6 ± 4.2 0.05 WASO (min) 27.4 ± 28.8 47.9 ± 43.6 0.039 MinSaO2 85.3 ± 3.7 84.2 ± 5.0 0.5 ODI 9.0 ± 11.6 16.4 ± 11.7 0.006 AHI 17.2 ± 14.6 20.9 ± 14.6 0.345 Seff (%) 92.6 ± 6.6 87.2 ± 11.2 0.028 Snoring time (min) 33.0 ± 25.8 51.9 ± 53.8 0.422 Total arousal (number) 136.0 ± 59.3 158.7 ± 49.8 0.043 Abbreviations: MAD, mandibular advancement devices; OSA, obstructive sleep apnea; SD, standard deviation; REM, rapid eye movement; TST, total sleep time; SL, sleep latency; WASO, wake after sleep onset; MinSaO 2, minium saturation; ODI, oxygen desaturation index; AHI, apnea hypopnea index; Seff, sleep efficiency. p 84 Treatment Outcomes of MAD in OSA Patients
3. 수면자세에따른하악전돌장치착용전과후의호흡지수비교하악전돌장치를착용한 13명의폐쇄성수면무호흡환자중 10명은앙와위폐쇄성수면무호흡환자였고, 3명은비앙와위폐쇄성수면무호흡환자였다. 앙와위폐쇄성수면무호흡환자의경우하악전돌장치착용후산소포화도지수, 무호흡-저호흡지수, 앙와위자세에서의무호흡-저호흡지수및전체각성수가전반적으로감소하였고, 이는통계적으로유의한차이를보였지만 (Table 3), 비앙와위폐쇄성수면무호흡환자의경우하악돌장치착용후 3단계수면과 REM 수면시간의증가, 산소포화도지수, 무호흡-저호흡지수, 앙와위자세에서의무호흡-저호흡지수및전체각성수는전반적으로감소하였으나, 통계적으로유의한차이는보이지않았다 (Table 4). 고찰 폐쇄성수면무호흡환자의치료법으로지속적기도내양압장치가가장많이사용되고있지만, 지속적기도내양압장치를사용하는 5~50% 의환자들은사용시의불편감으로인해치료를중단하는것으로보고되었고 (Kushida 등, 2006), 최근에는이에대한대안으로하악전돌장치가폐쇄성수면무호흡치료도구로사용되고있다. 폐쇄성수면무호흡을가진 24명의환자를대상으로하악전돌장치착용전과후의호흡장애지수 (respiratory disturbance index) 를비교한결과장치착용전호흡장애지수 48±34에서장치착용후 12±21로약 58% 의환자에서호흡장애지수가감소한결과를보였고, 이는통계적으로유의한차이를보였다 (Clark 등, 1993). Clark 등 (1996) 에의하면폐쇄성수면무호흡을가진환자를대상으로하악전돌장치착용전후의무호흡-저호흡지 Table 3. Changes in sleep event pre-post MAD in positional OSA patients (n=10) With MAD Without MAD Variables Mean ± SD Mean ± SD Number 10 10 Stage N1 (min) 74.2 ± 32.8 87.7 ± 27.6 0.074 Stage N2 (min) 153.0 ± 44.6 176.3 ± 56.8 0.241 Stage N3 (min) 63.8 ± 47.6 32.8 ± 23.6 0.074 REM (min) 76.5 ± 17.0 70.1 ± 28.4 0.721 TST (min) 367.5 ± 22.6 367.1 ± 53.2 0.799 SL (min) 3.1 ± 3.0 4.9 ± 4.6 0.059 WASO (min) 28.8 ± 32.5 36.8 ± 35.8 0.241 MinSaO2 84.6 ± 3.9 82.9 ± 4.8 0.386 ODI 9.0 ± 11.8 16.9 ± 10.4 0.017 AHI 15.2 ± 11.8 21.6 ± 12.9 0.047 Supine AHI 12.6 ± 15.2 33.5 ± 26.2 0.005 Nonsupine AHI 3.1 ± 6.9 5.0 ± 9.9 0.214 Seff (%) 92.3 ± 7.4 89.7 ± 9.4 0.169 Snoring time (min) 32.6 ± 23.9 51.6 ± 60.2 0.646 Total arousal (number) 117.3 ± 50.3 150.7 ± 47.3 0.022 See Tabel 2. p Table 4. Changes in sleep event pre-post MAD in nonpositional OSA patients with MAD without MAD Variables mean ± SD mean ± SD Number 3 3 Stage N1 (min) 96.6 ± 21.6 114.5 ±33.2 0.285 Stage N2 (min) 182.5 ± 35.9 130.8 ± 40.6 0.285 Stage N3 (min) 24.6 ± 17.5 49.5 ± 9.9 0.109 REM (min) 62.8 ± 27.4 52.3 ± 42.1 0.285 TST (min) 366.7 ± 12.9 347.2 ± 85.7 1 SL (min) 2.9 ± 2.0 3.5 ± 2.7 0.655 WASO (min) 22.9 ± 14.1 85.1 ± 54.1 0.109 MinSaO2 87.8 ± 1.2 88.2 ± 3.9 1 ODI 8.9 ± 13.3 15.1 ± 18.1 0.109 AHI 23.7 ± 23.9 18.7 ± 23.0 0.109 Supine AHI 19.0 ± 23.1 22.8 ± 28.4 0.285 Nonsupine AHI 13.3 ± 17.9 32.0 ± 46.2 0.109 Seff (%) 93.5 ± 3.8 79.0 ± 14.7 0.109 Snoring time (min) 34.1 ± 37.9 52.6 ± 32.5 0.593 Total arousal (number) 198.6 ± 46.0 185.6 ± 58.5 0.593 See Tabel 2. p Treatment Outcomes of MAD in OSA Patients 85
Fig. 2. Theses 6 graphs show the pre-post MAD changes for positional subjects and nonpositional subjects. The 2 top figures (a and b) show the overall AHI data, the middle 2 figures (c and d) show the supine-only AHI data, and the bottom 2 figures (e and f) show the nonpositional AHI data. 수를비교한결과하악전돌장치를착용한후무호흡 - 저호 흡지수가착용전보다 38.9% 감소하였다고보고하였다. 본연구결과모든환자의하악전돌장치착용후무호흡 - 저호흡지수가 15% 감소하는것을볼수있었고, 이는 Clark 등 (1996) 이보고한수치보다는감소율이낮았지만, 앙와위 폐쇄성수면무호흡환자의경우무호흡 - 저호흡지수가하악 86 Treatment Outcomes of MAD in OSA Patients
전돌장치착용후 62.3% 나감소하는것을볼수있었고, 이는곧앙와위폐쇄성수면무호흡환자에서하악전돌장치의효능이훨씬좋은것으로나타났다 (Table 3). Sjoholm 등 (1994) 은하악을전방으로이동할수있게조절된하악전돌장치를사용한 12명의수면무호흡환자와하악전돌장치를착용하지않은수면무호흡환자를대상으로수면중산소포화도를측정하였고, 이결과하악전돌장치를착용한 12명의환자에서는산소포화도지수가 44.7에서 29.6으로감소하였고이는통계적으로유의한차이를보였으나, 하악전돌장치를착용하지않은환자의경우 44.7에서 40.9로통계적으로유의한차이를보이지않았다. 본연구결과하악전돌장치착용후수면중산소포화도지수 ( 착용전 vs 착용후 ; 16.4±11.7 vs 9.0±11.6: p=0.006) 가통계적으로유의한차이를보이는것으로나타났으며 (Fig. 2), 이는하악전돌장치가아래턱을전방으로잡아당겨상대적으로상기도의통로를넓혀주기때문에수면중산소의유입이용이해짐으로인해산소포화도저하가감소한것으로생각되어지며, 이는 Sjoholm 등 (1994) 이보고한것과비슷한결과를보였다. 중등도의폐쇄성수면무호흡증후군환자를대상으로조절된하악전돌장치와지속적기도내양압장치를비교한연구에서, 지속적기도내양압장치의경우 70% 에서치료효과를보였으며, 환자의협조를얻지못하는경우는 30% 였다. 조절된하악전돌장치를사용한경우치료효과를나타낸환자가 55% 였고이중협조를얻지못한경우는 5% 에불과하였다 (Ferguson 등, 1997). 본연구대상환자모두가지속적기도내양압장치를시행하였으나불편하다는이유로지속적으로사용을하지못하였으며, 이의대안으로하악전돌장치를시행하였고, 대상자 13명중 3명 (23%) 은하악전돌장치가턱관절통증과입벌림으로인해사용을포기하였으나 10명은지속적기도내양압장치보다착용이간편하고, 폐쇄공포증이나입마름증상이없어협조도 (78%) 가매우높은것을볼수있었다. 본연구의제한점으로는하악전돌장치착용전과후의수면다원검사를통해서객관적으로검증된대상환자의숫자가적음에기인하여통계적으로모든폐쇄성수면무호흡- 저호흡증후군을가진환자의치료결과를대변하기는어렵 겠지만국내에서처음으로폐쇄성수면무호흡 - 저호흡환 자를대상으로하악전돌장치에대한연구를시행하였다는 것에의의를가질수있겠다. 결론적으로하악전돌장치는지속적기도내양압장치보다 는폐쇄성수면무호흡을치료하는데효능은떨어지지만환 자의불편감및협조정도를고려할때지속적기도내양압 장치를대신할수있는매우유용한장치로사료된다. 참고문헌 1. American Academy of Sleep Medicine Task Force (AASMTF). 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, 22:667-689. 2. Cartwright RD. Effect of sleep position on sleep apnea severity. Sleep. 1984, 7:110-114. 3. Clark GT, Arand D, Chung E, Tong D. Effect of anterior mandibular positioning on obstructive sleep apnea. Am Rev Respir Dis. 1993, 147:624-629. 4. Clark GT, Blumenfeld I, Yoffe N, Peled E, Lavie P. A crossover study comparing the efficacy of continuous positive airway pressure with anterior mandibular positioning devices on patients with obstructive sleep apnea. Chest. 1996, 109:1477-1483. 5. Engleman HM, Douglas NJ. Sleep. 4: Sleepiness, cognitive function, and quality of life in obstructive sleep apnoea/hypopnea syndrome. Thorax. 2004, 59:618-622. 6. Ferguson KA, Ono T, Lowe AA, al-majed S, Love LL, Fleetham JA. A short-term controlled trial of an adjustable oral appliance for the treatment of mild to moderate obstructive sleep apnoea. Thorax. 1997, 52:362-368. 7. Iber C, Ancoil-Israel S, Chesson AL, Quan SF. The AASM manual for the scoring of sleep and associated event: rules, terminology and technical specifications. American Academy of Sleep Medicine, 2007. Westchester, IL. 8. Kushida CA, Littner MR, Hirshkowitz M, Morgenthaler TI, Alessi CA, Bailey D et al. Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders. Sleep. 2006, 29:375-380. 9. Malhotra A, White DP. Obstructive sleep apnea. Lancet. 2002, 360(9328):237-245. 10. Robinson GV, Stradling JR, Davies RJO. Sleep. 6: Obstructive Treatment Outcomes of MAD in OSA Patients 87
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