CASE REPORT Korean J Clin Lab Sci. 2019;51(1):119-123 https://doi.org/10.15324/kjcls.2019.51.1.119 pissn 1738-3544 eissn 2288-1662 Korean J Clin Lab Sci. Vol. 51, No. 1, March 2019 119 Case of a Change in the Polysomnograpy Results after Using Continuous Positive Airway Pressure in a Patient with Obstructive Sleep Apnea Dae Jin Kim 1, Sue Jean Mun 2, Jeong Su Choi 3, Min Woo Lee 4, Jae Wook Cho 1 1 Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, Korea 2 Department of Otorhinolaryngology-Head & Neck Surgery, Pusan National University Yangsan Hospital, Yangsan, Korea 3 Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, Seoul, Korea 4 Research Institute of Health Sciences, Korea University, Seoul, Korea 폐쇄성수면무호흡환자의지속적양압기사용후재검사시수면다원검사결과의변화 김대진 1, 문수진 2, 최정수 3, 이민우 4, 조재욱 1 1 부산대학교양산병원신경과, 2 부산대학교양산병원이비인후과, 3 고려대학교대학원의생명융합과학과, 4 고려대학교보건과학연구소 Obstructive sleep apnea (OSA) is a sleep disorder with no breathing symptoms due to repetitive upper airway resistance. OSA is a disease that can have significant effects on the cerebral cardiovascular system. Active treatment is needed to prevent these complications. The use of continuous positive airway pressure (CPAP), the standard therapy of OSA, has comparative therapeutic effects. On the other hand, there is no comparison report of the polysomnography (PSG) results before and after CPAP therapy without using a mask. This paper reports a patient who was diagnosed as OSA and used CPAP every night for more than 2 years. The patient showed a decrease in the apnea-hypopnea index from 64.7/h to 12.9/h. In addition, other sleep-related indicators improved significantly. The daily use of CPAP as a treatment for OSA for more than 2 years may improve the PSG results. Constant follow up of PSG will be needed to adjust the appropriate CPAP pressure to patients because there might be a change in the Apnea-Hypopnea Index and other sleep-related indicators for constant CPAP users for at least 2 years. Key words: Apnea-hypopnea index, Continuous positive airway pressure, Obstructive sleep apnea Corresponding author: Jae Wook Cho Department of Neurology, Pusan National University Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan 50612, Korea Tel: 82-55-360-2122 Fax: 82-55-360-2152 E-mail: sleep.cho@gmail.com ORCID: https://orcid.org/0000-0002-2742-9136 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2019 The Korean Society for Clinical Laboratory Science. All rights reserved. Received: January 4, 2019 Revised 1 st : January 23, 2019 Revised 2 nd : January 31, 2019 Revised 3 rd : February 7, 2019 Accepted: February 8, 2019 서론폐쇄성수면무호흡 (obstructive sleep apnea, OSA) 은수면중상기도저항으로인해주기적으로적절한환기가되지않는것을말하며, 성인에서 2 4% 의발병률을보이고있다 [1]. 또한숙면을방해하여수면의질을떨어뜨리며, 뇌및심장질환과의 연관성이알려짐에따라임상적으로적극적인치료가필요하다 [2-4]. 미국수면학회 (American Academy of Sleep Medicine, AASM) 에서는폐쇄성수면무호흡의치료방법으로지속적양압기 (continuous positive airway pressure, CPAP) 를권고하고있고 [5], CPAP 은주간졸음증과삶의질의개선뿐만아니라뇌심혈관계질환의치료에도효과가확인되었다 [6]. 그러나지
120 Dae Jin Kim, et al. Change in PSG Results Using CPAP in OSA Patient 금까지연구에서는수면무호흡환자의 CPAP 마스크착용유무에따른수면다원검사결과차이를비교한단면적연구는있었으나 [7] 장기간 CPAP 치료에따른수면다원검사결과차이를비교한증례보고는없었다. 이에저자들은, 최초내원시수면다원검사를통해중증 (severe) 폐쇄성수면무호흡으로진단된환자가 2년이상 CPAP 치료후, CPAP 마스크를착용하지않은수면다원검사에서경도 (mild) 폐쇄성수면무호흡으로호전된결과를보고하고자한다. 증례 Table 1. The comparison of pre-cpap and post-cpap for questionnaires and PSG characteristics Questionnaires pre-cpap post-cpap ESS 6 6 BDI 1 2 PSQI-K 14 14 SF36 71 83 Physical health 79 82 Mental health 61 80 PSG pre-cpap post-cpap TST, min 350 162.5 Sleep latency, min 6.5 5.8 AI, N/hr 70.3 48 Sleep Efficiency, % 79 85.2 WASO (%) 82.8 (19.8) 28.3 (12.2) Non-REM, % 80.3 92.3 N1, % 37.1 29.8 N2, % 42.3 46.2 N3, % 0.9 16.3 REM, % 19.7 7.7 AHI, N/hr 64.7 12.9 Spine index, N/hr 70.2 22.3 Lateral index, N/hr 16.7 0.8 Apnea max length, sec 52.8 26.7 Hypopnea max length, sec 77.3 38.4 Lowest SaO2, % 75 83 Abbreviations: ESS, Epworth sleepiness scale; BDI, Beck depressive inventory; PSQI-K, Pittsburgh sleep quality index Korea; SF-36, short form-36; PSG, polysomnography; TST, total sleep time; AI, arousal index; WASO, wakefulness after sleep onset; REM, rapid eye movement; AHI, apnea-hypopnea index; Min O 2, minimum O 2; CPAP, continuous positive airway pressure. 36세남자가코골이와보호자에게서관찰된수면무호흡을주소로내원하였다. 코골이는 10년전부터시작되었으며, 동반된내과질환은없었으나중학교때비염수술을하였다. 수면과관련된증상으로는주간졸림증과피로감을호소하였고, 구강호흡과기상시구강내건조감, 간헐적인이갈이 (bruxism) 가있었다. 그러나수면발작 (sleep attack), 수면마비 (sleep paralysis), 탈력발작 (cataplexy), 입면환각 (hypnagogic hallucination), 불면증 (insomnia) 은동반되지않았다. 수면다원검사전설문지를통해주간졸림증척도 (Epworth sleepiness scale, ESS) 는 6점, 우울증척도 (Beck depression inventory, BDI) 는 1점, 한국판피츠버그수면의질지수 (Pittsburgh sleep quality index Korea, PSQI-K) 는총 14점, Short-form 36 건강조사는 71점으로확인되었다 (Table 1). 환자는신장 177 cm, 체중 87.2 kg으로체질량지수 27.9로과체중에해당했다. 이비인후과에서시행한내시경검사에서는비강과후두는정상이지만, 구강은 Friedman 의분류 [8] 에근거하여편도크기 grade II ( 편도가기둥까지커진경우 ), 구개위치 grade II ( 구개수는보이나편도는보이지않는경우 ) 로관찰되었으며 (Table 2), 부정교합이있었다. 또한약물유도수면내시경검사 (drug-induced sedation endoscopy, DISE) 상연구개의환상형폐쇄및설기저부의부분폐색이확인되었으며, 최저산소포화도가 81% 였다. 측면 (lateral) 수면에서는연구개의환상형폐쇄만확인할수있었다. 야간수면다원검사결과는총수면시간 350.0분중수면잠복기가 6.5분으로짧아져있었고, 입면후각성은 81.8분으로전체수면중 19.8% 로증가하였으며, 수면효율은 79.0% 로감소하였다. 각성지수도 70.3/h로상당히증가되었는데대부분이코골이 (3.6/h) 및무호흡 (66.7/h) 과관련되었다. 수면구조는비급속안구운동 (non-rapid eye movement, non-rem) 80.3% 중수면 1단계 37.1%, 2단계 42.3% 로증가되어선잠 (light sleep) 이많았고, 3단계는 0.9% 로감소되었다. 무호흡-저호흡지수는 64.7/h로상당한중증상태이고, 중추성수면무호흡은없었다. 똑바로누웠을때는 70.2/h, 옆으로누웠을때는 16.7/h로자세변화에따른차이가있었으며, 최저산소포화도는 75% 였다 (Table 1). 수면다원검사결과폐쇄성수면무호흡의치료로 Auto-CPAP 을사용하였다. 처음압력값은최소압력 : 4.0 cmh 2 O, 최고압력 : 15 cmh 2 O로하여치료를시작하였고, 1달후데이터확인결과평균압력 : 5.9 cmh 2O, Table 2. The definition of tonsils and Mallampati by Friedman Classification Definition (Tonsil) Definition (Mallampati) Grade 0 No tonsils seen - Grade I In the tonsillar fossa, barely seen behind the anterior pillars Complete visualization of the soft palate, uvula, and pillars Grade II Visible behind the anterior pillars Complete visualization of the uvula Grade III Extended 3/4 of the way to midline Visualization of the base of the uvula Grade IV Completely obstructing the airway Soft palate is not visible at all
Korean J Clin Lab Sci. Vol. 51, No. 1, March 2019 121 Figure 1. The comparison of pre- and post-cpap on hypnogram. 95th Percentile: 7.7 cmh 2O, 최대압력 : 8.8cmH 2O이었고, 무호흡-저호흡지수는 0.8로관찰되었다. 이에압력을최소압력 : 4.0 cmh 2 O, 최대압력 : 9 cmh 2 O로조절하여사용하기시작하였다. CPAP 을사용한지 2년 6개월후환자가재검을원하여병원에내원하였으며, 체중이 88.0 kg으로증가하여체질량지수 28.1로약간증가한상태였다. 야간수면다원검사결과는총수면시간 162.5분중수면잠복기가 5.8분으로여전히짧아져있었지만, 입면후각성은 28.3분으로전체수면중 12.2% (7.6% 감소 ), 수면효율은 85.2% (6.2% 증가 ), 각성지수는 48.0/h (22.3/h 감소 ) 로 CPAP 사용전보다호전되었다 (Figure 1). 수면구조도 non-rem 92.3% (12% 증가 ) 중수면 1단계 29.8% (7.3% 감소 ), 2단계 46.2% (3.9% 증가 ), 3단계 16.3% (15.4% 증가 ) 로깊은잠 (deep sleep) 이이전결과보다증가하였다. 무호흡-저호흡지수는 12.9/h로경도상태로관찰되어 CPAP 사용전보다 51.8/h 감소되었다. 똑바로누웠을때는 22.3/h, 옆으로누웠을때는 0.8/h로여전히자세변화에따른차이가있었으며, 최저산소포화도는 83% (8% 증가 ) 였다 (Table 1). 또한 CPAP 사용이후조사된 SF-36 건강조사에서는 83점 (12점증가 ) 으로좋아졌지만, 나머지주간졸음증척도 6 점, 우울증척도 2점, 한국판피츠버그수면의질지수는 14점으 로큰변화없었다 (Table 1). 고찰본증례에서나타난 CPAP 을꾸준히사용한환자의수면다원검사결과는 CPAP 을사용하기전결과와비교했을때, 무호흡- 저호흡지수뿐만아니라, 수면관련지표들이호전되었다. 폐쇄성수면무호흡은임상적인증상, 병력, 수면다원검사, DISE등을통해서미국수면학회의권고에따라치료방법을결정한다 [5]. 대표적으로 CPAP 은중등도내지중증폐쇄성수면무호흡의경우, 주간졸림증을동반한경증폐쇄성수면무호흡의경우등에서권고되며 [6], 수술적치료와구강내장치는 CPAP 의이차적인치료법으로권고한다 [9, 10]. 본증례의환자는야간수면다원검사에서상당히짧은수면잠복기를보였고, 수면효율은낮아져있었으며, 얕은잠이증가된것은주간졸음증이원인이라고생각할수있다. 또한무호흡-저호흡지수가 64.7/h로나타났고, 이로인하여수면각성이증가되었다. 이와같은결과로중증폐쇄성수면무호흡이진단되어 AASM의권고에따라 CPAP 을사용하기시작하였다. 환자는 CPAP 을사용할수없는경우를제외하고 2년 6개월동안 CPAP 의사용권장기준인하
122 Dae Jin Kim, et al. Change in PSG Results Using CPAP in OSA Patient 루 4시간이상씩꾸준히사용하였다고했다. CPAP 의사용후의수면다원검사결과는여전히수면잠복기는짧아져있었지만, 수면효율은좋아지고깊은잠이증가하였다. 또한무호흡-저호흡지수는 64.7/h에서 12.9/h로상당히감소된것을확인할수있었다. 이전까지의보고에서 CPAP 의사용전과후의마스크를착용하지않은상태에서수면다원검사를직접비교한것은없어무호흡 저호흡지수의감소이유는정확히확인할방법은없다. 그러나환자는체중이오히려증가되었기때문에, 체중에의한무호흡-저호흡지수의호전효과는배제할수있었다 [11]. 따라서그밖의가능한기전으로첫째, CPAP 의장기적사용으로인한상기도의일시적해부학적개방정도의변화, 둘째, 호흡조절안정성기전의변화를생각할수있겠다. 첫째가설을확인해보면폐쇄성수면무호흡의해부학적원인은연구개 (Soft palate) 의위치, 편도 (tonsil) 및주변조직의크기, 혀의크기, 아래턱의위치, 후두의협착유무등으로인한상기도의폐쇄이다 [12, 13]. 본증례의환자는 CPAP 을사용하기전과후의내시경검사에서비강과후두는모두정상소견이었지만, 구강내시경에서는편도크기가기둥까지커져있었고 (Grade II), 연구개위치는전체구개수는보이나편도는보이지않는 (Grade II) 동일한소견을보여차이점은없었다. 그러나각성상태일때진행한내시경검사는폐쇄성수면무호흡의원인이되는실제폐쇄부위를확인하기는어렵고, 상기도가폐쇄되었더라도반드시일치하지않을수있는가능성이있다 [14]. 즉환자의각성상태일때내시경검사결과는동일하나실제수면상태일때차이가발생하였을가능성이있어, CPAP 사용전과후의변화가있었을것이라예측되며, 이로인하여무호흡 저호흡지수가감소되었다고사료된다. 본환자의경우, CPAP 사용전에는 DISE를시행하였으나, CPAP 사용후에는 DISE를시행하지않아, 실제수면시상기도폐쇄정도가변화한정도를확인할수는없어, 추적이불가능하였다. 둘째가설로호흡을조절하는기전중불안정한호흡에대한반응성을나타내는루프이득 (loop gain) 은수면무호흡을가진환자에게서증가되어있고, 이로인해해부학적으로폐쇄되어있는상기도와함께무호흡을악화시킬수있는요인으로작용된다 [15, 16]. 앞선연구에따르면루프이득에영향을끼치는주된요소인컨트롤러이득 (controller gain) 이 CPAP 의사용으로인해감소된것을확인할수있다 [17]. 이는호흡장애에대해과하게조정하려는경향을낮춘것을의미하여적절한호흡조절기전을통해무호흡이완화될수있다는것을시사한다. 위와같은맥락으로이번증례의경우 CPAP 의꾸준한사용이수면무호흡의원인중컨트롤러이득의완화로인하여적절한호흡조절기전을통해무호흡 저 호흡지수가감소되었다고가정할수있다. 기존의 CPAP 치료는환자의최초내원시수면다원검사결과를기초로하여적정양압을설정하고장기간지속적인치료를권장하였다. 하지만 CPAP 치료로인한환자의무호흡-저호흡지수와수면관련지표들이개선된위증례에따라 CPAP 치료중인환자들은주기적인수면다원검사를통해수면지표를추적할필요성이있고, 수면지표의객관적인변화가발생하면그결과에맞춘적정양압을재설정할필요가있을것으로사료된다. 또한수면지표의개선에따른 CPAP 사용횟수의조절도가능하여환자들의 CPAP 적응증을높일수있을것으로기대한다. 그러나본증례의제한점은다음과같다. 첫째는 1회의수면다원검사로수면지표가호전되었다는것이매우주관적일수있다. 그러나수면다원검사의정확성과신뢰성에대한의문이없다는점은이번증례의결과를뒷받침할수있는근거가된다 [18]. 하지만좀더객관적인결과를확인하기위해서는추가적인검사결과가필요할것이다. 둘째로각성상태일때만상기도를확인하였으며, 추적 DISE를시행하지않았기때문에무호흡이발생하는정확한해부학적인변화정도를관찰하기어렵다. 이는수면다원검사중무호흡레벨검사 (apnea level test) 를통해상기도폐쇄위치와정도를파악하면 CPAP 사용으로인한해부학적변화를확인할수있을것이다. 또한무호흡과관련된호흡조절기전을확인하면 CPAP 사용으로인한무호흡 저호흡지수의변화를좀더정확하게설명할수있으리라사료된다. 요약폐쇄성수면무호흡은반복적인상기도저항으로인해호흡이없는상태를말하며, 뇌심혈관계질환과의연관성이있어적극적인치료가필요하다. 대표적인방법인지속적양압기의치료효과는많은연구로입증되었다. 그러나지속적양압기사용전과후의마스크를착용하지않은상태에서의수면다원검사결과를비교한것은없다. 본증례에서폐쇄성수면무호흡으로진단된환자가 2년이상꾸준히지속적양압기를사용한후재검사를통해무호흡 저호흡지수의감소 (64.7/h에서 12.9/h) 및그외수면관련지표들도호전된결과를보였다. CPAP 의장기적사용은상기도저항이감소할수있는기전을제공하는것으로사료되며, 이로인한무호흡 저호흡지수가변화가능성이있으므로꾸준한수면다원검사의추적관찰이필요하겠다. Acknowledgements: None Conflict of interest: None
Korean J Clin Lab Sci. Vol. 51, No. 1, March 2019 123 Author s information (Position): Kim DJ 1, M.T.; Mun SJ 2, M.D.; Choi JS 3, Graduate student; Lee MW 4, Adjunct professor; Cho JW 1, M.D. REFERENCES 1. Yun CH. A diagnosis and treatment of obstructive sleep apnea syndrome. J Kor Sleep Research Soc. 2004;1:34-40. http://doi.org/10.13078/jksrs.04006. 2. Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Nieto FJ, et al. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the sleep heart health study. Am J Respir Crit Care Med. 2001:163:19-25. http://doi.org/ 10.1164/ajrccm.163.1.2001008. 3. Li J, Li MX, Liu SN, Wang JH, Huang M, Wang M, et al. Is brain damage really involved in the pathogenesis of obstructive sleep apnea? Neuroreport. 2014;25:593-595. http://doi.org/10. 1097/WNR.0000000000000143. 4. Kim CS. The association between blood pressure and obstructive sleep apnea-hypopnea syndrome. Korean J Clin Lab Sci. 2014;46:106-110. http://doi.org/10.15324/kjcls.2014.46.3.1063. 5. Kapur VK, Auckley DH, Chowdhuri S, Kuhlmann DC, Mehra R, Ramar K, et al. Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13:479-504. http://doi.org/10.5664/jcsm.6506. 6. Gay P, Weaver T, Loube D, Iber C, Positive airway pressure task force, Standards of practice committee, et al. Evaluation of positive airway pressure treatment for sleep related breathing disorders in adults. Sleep. 2006;3:381-401. http://doi.org/10.1093/sleep/29.3.381. 7. Weaver TE, Chasens ER. Continuous positive airway pressure treatment for sleep apnea in older adults. Sleep Med Rev. 2007;11:99-111. https://doi.org/10.1016/j.smrv.2006.08.001. 8. Frideman M, Ibrahim H, Joseph NJ. Staging of obstructive sleep apnea/hypopnea syndrome: A guide to appropriate treatment. Laryngoscope. 2004;114:454-459. https://doi.org/10.1097/ 00005537-200403000-00013. 9. Kushida CA, Morgenthaler TI, Littner MR, Alessi CA, Bailey D, Coleman J Jr, et al. Practice parameters for the treatment of snoring and obstructive sleep apnea with oral appliances: an update for 2005. Sleep. 2006;29:240-243. http://doi.org/ 10.1093/sleep/29.2.240. 10. Aurora RN, Casey KR, Kristo D, Auerbach S, Bista SR, Chowdhuri S, et al. Practice parameters for the surgical modifications of the upper airway for obstructive sleep apnea in adults. Sleep. 2010;33:1408-1413. http://doi.org/10.1093/ sleep/33.10.1408. 11.Peppard PE, Toung T, Palta M, Dempsey J, Skatrud J. Longitudinal study of moderate weight change and sleep-disordered breathing. JAMA. 2000;284:3015-3021. http://doi.org/10.1001/jama.284.23.3015. 12. Caples SM, Rowley Ja, Prinsell JR, Pallanch JF, Elamin MB, Katz SG, et al. Surgical modifications of the upper airway for obstructive sleep apnea in adults: a systematic review and meta-analysis. Sleep. 2010;33:1396-1407. http://doi.org/ 10.1093/sleep/33.10.1396. 13. Lee CH, Hong SL, Rhee CS, Kim SW, Kim JW. Analysis of upper airway obstruction by sleep videofluoroscopy in obstructive sleep apnea: a large population-based study. Laryngoscope. 2012;122:237-241. http://doi.org/10.1002/lary.22344. 14. Moos DD. Obstructive sleep apnea and sedation in the endoscopy suite. Gastroenterol Nurs. 2006;29:456-463. 15. Deacon NL, Sande SA, McEvoy DR, Catcheside PG. Daytime loop gain is elevated in obstructive sleep apnea but not reduced by CPAP treatment. J Appl Physiol. 2018;125:1490-1497. http://doi.org/10.1152/japplphysiol.00175.2018. 16. Younes M, Ostrowski M, Thompson W, Leslie C, Shewchuk W. Chemical control stability in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2001;163:1181-1190. http://doi.org/10.1164/ajrccm163.5.2007013. 17. Salloum A, Rowley JA, Mateika JH, Chowdhuri S, Omran Q, Badr MS. Increased propensity for central apnea in patients with obstructive sleep apnea: effect of nasal continuous positive airway pressure. Am J Respire Crit Care Med. 2010;181:189-193. http://doi.org/10.1164/rccm.200810-1658oc. 18. Kusida CA, Littner MR, Morgenthaler T, Alessi CA, Bailey D, Coleman J Jr, et al. Practice parameters for the indications for polysomnography and related procedures: an update for 2005. Sleep. 2005;28:499-521. https://doi.org/10.1093/sleep/28.4.499.