03-주은연(Positive pressure therapy).hwp

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1 종설 J Kor Sleep Soc / Volume 5 / December, 2008 주은연 성균관대학교의과대학삼성서울병원신경과수면센터 Positive Pressure Therapy; When CPAP fails, what other PAP modalities are? Eun Yeon Joo Department of Neurology, Sleep Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Positive airway pressure (PAP) is the treatment of choice for patients with moderate-to-severe obstructive sleep apnea (OSA). PAP can effectively reduce the apnea-hypopnea index and improve subjective and objective sleepiness. Also it can gives benefits in sleep quality and quality of life for both the patient and bed partner. Since continuous PAP (CPAP) treatment of OSA was described, additional modes of pressure delivery have been developed (bilevel PAP, autoadjusting PAP, flexible PAP). While none of the variants of PAP improves adherence in unselected patients compared to CPAP, individual patients may respond to a change in pressure mode. Although attended PAP titration remains the standard of practice for selecting a treatment pressure, use of autotitrating PAP devices in the unattended setting can provide an effective titration alternative with careful patient selection and review of titration results. However, despite the increase in PAP treatment options, lack of acceptance and inadequate adherence to PAP therapy remain the major causes of treatment failure. Heated humidification can improve PAP adherence, especially in patients with nasal congestion or dryness. Key Words : Positive airway pressure (PAP), Obstructive sleep apnea (OSA), Continuous PAP (CPAP), Bilevel PAP, Autoadjusting PAP, Flexible PAP 서 론 1981년호주의 Dr. Sullivan 이자체제작한 CPAP 을수면무호흡 (obstructive sleep apnea, OSA) 환자에게치료적목적으로적용한이후, 1 CPAP 은중등도이상의 OSA 환자의표준치료법으로알려져왔다. CPAP 을사용함으로써얻을수있는효과는분명하나실제임상에서는많은환자들에서 CPAP 의 adherence(=compliance, the extent to * Address of correspondence Eun Yeon Joo, MD, PhD. Department of Neurology, Sleep Center, Samsung Medical Center, Sungkyunkwan University School of Medicine 50 Irwon-dong, Gangnam-gu, Seoul, , Korea Tel: Fax: ejoo@skku.edu which a person s behavior coincides with the medical or healthy advice) 가시간이지남에따라떨어지는경우를많이본다. 임상에서적용하고있는 adequate adherence 는 PAP 사용시간이하루에 4시간이상, 전체사용일수의 70% 이상으로정하고있으며, 2,3 non-acceptance rates는 5-50% 로다양하게보고되고있으며평균 20% 정도이다. 2 PAP 의 adherence 와 tolerance 을높이기위해다양한 PAP modalities 들이계발되어소개되었으며, 현재임상에서많이사용되고있다. 여기서는 CPAP 을비롯한다른 PAP modalities 의적응증및임상효과에대해다루려고한다. 64 수면

2 PAP의적응증 PAP 은중등도이상의 OSA 환자 (AHI 15/ 시간 ) 들에게가장적절한치료방법이다. 4,5 Medicare Services에서는 CPAP 치료기준을임상증상유무와상관없이 AHI가시간당 15 이상인환자들에게적용하기로결정했다. 6 AHI가시간당 5 이상이며 15 이하인환자들에서는임상증상 ( 주간졸림증, 불면증, 인지기능저하, 감정장애 ) 이나다른질환 ( 고혈압, 뇌혈관계질환의기왕력, 허혈성심장질환 ) 이동반되어야한다. PAP은중등도이상의 OSA 환자들에서효과적으로 AHI 를시간당 5-10 이하로줄인다. 4,5 경구위약또는 sham CPAP 을대상으로한무작위조정연구들을보면, PAP 치료후주관적인주간졸림증 (Epworth sleepiness scale) 과객관적인졸림증 (multiple sleep latency test의평균수면잠복기 ) 이유의하게호전되었다. 7-9 임상증상을동반하는중등도미만의 OSA 환자 (AHI < 15-30/hr) 에서는 PAP 치료로임상증상은호전되었으나, adherence 가낮은경향을보였다. 10 반면, 경한 OSA 환자들을대상으로한무작위조정연구에서는 PAP에대한방법적인문제 ( 경구위약군이대조군이거나, 주간졸림증이거의없거나약간높은환자들을대상으로함 ) 로인해결과의일관성을갖지못했다 중등도이하의 OSA 환자들에서 CPAP 과다른치료법인구강내장치, 16,17 체위치료, 18 상기도수술 19 효과를직접비교한연구는많지않다. 대체적으로 CPAP 이구강내장치나, 체위치료보다 AHI 를줄이는데더효과적이었으나, 16,18 체위치료나상기도수술 (temperature-controlled radiofrequency tissue ablation on palate and tongue) 보다주간졸림증을더호전시키지는못했다. 18,19 CPAP과수술은주간졸림증은유사하게호전시켰지만, 24명의 CPAP 사용자중 9명만이야간사용시간이 4시간이상이었다. 19 PAP Modalities CPAP 은이미결정된일정한압력을호기 (expiration) 와흡기 (Inspiration) 시모두불어넣어주는장비이다. 물론 conventional, fixed-pressure CPAP 치료가대부분의 OSA 환자들에게효과적이라는것은주지의사실이지만, 상기도의허탈성 (collapsibility) 은하룻밤동안 ( 예를들어, 체위의변화, 음주여부 ) 뿐만아니라, 장기적으로도 ( 체질량지수의변화 ) 가변적일수있기때문에고정압력한가지만매일사용한다는것은문제점을내포할수있다. Bilevel PAP 은흡기시에는낮은압력 (expiratory positive airway pressure, EPAP) 호기시에는좀더높은압력 (inspiratory positive airway pressure, IPAP) 을전달한다. 20,21 호기호흡을더힘들어하는일부의환자들은 CPAP 보다 Bilevel PAP을더잘견딘다 환기주기 (ventilatory cycle) 내내같은압력이부과되는 CPAP 과달리 bilevel PAP 은흡기시와호기시의부하압력을조절한다. 호기 PAP은호기의끝부분에발생하는정적인상기도폐색 (static upper airway occlusion) 을막는반면, 흡기 PAP은흡기시발생하는동적인상기도폐쇄 (dynamic upper airway obstruction) 을예방한다. Bilevel PAP도 fixed-pressure CPAP 보다더낮은호기압력으로도 fixedpressure CPAP에비견되게 AHI를호전시킨다고보고되었다. 23 그러나, 전체 OSA 환자들에서초기 PAP 처방으로 Bilevel PAP이적절할지에대한증거자료는충분치않다. 24,25 몇몇의증례연구에서 bilevel PAP이비만-저환기증후군 (obesity hypoventilation syndrome) 과고탄산만성폐쇄성호흡기질환환자 (hypercapnic patients with chronic obstructive pulmonary disease) 들에게효과적이라고보고했지만대상자가많지않았고장기관찰결과가아니라는제한점이있다. 26,27 Autoadjusting PAP(APAP) 은상기도의개방 (patency) 을유지하기위한압력을실시간으로제공하도록고안되었다. 이론적으로는주어진시간동안가장낮고도효과적인압력을공급하게된다. Fixed-pressure CPAP은가장허탈성이큰상황에서상기도의개방을유지할수있는압력이밤새지속되지만, A-PAP 은평균이하의압력을유지하여, 부작용을줄이고안락함을증진시켜, 치료의 adherence 를높인다고알려져있다. APAP 은다음의 2가지목적을갖는다. (1) autotitrating PAP; attended titration하지않고도효과적인 CPAP 압력을결정하기위하여, (2) autoadjusting PAP; 장기간동안어떠한상황에서도가장낮고도효과적인압력을전달하기위하여 APAP은 CPAP titration 의수고를덜어줄수있다. APAP 알고리즘은장 Vol.5, No.2 / December,

3 주은연 비마다다르며, 대부분 airflow magnitude, airflow limitation, snoring(vibration), airway impedance에따라압력이변화하도록설계되었다 압력의변화는각성을유도하지않도록미리정해놓은가장낮은압력과높은압력사이에서점진적으로변하도록고안된다. 별다른호흡의변화가없으면, 서서히압력이줄어들어가장낮게설정된압력까지내려간다. 단, 많은다른업체의장비들은 airflow 변화에대한반응이서로다를수있다. 31 마스크나입에서바람이새는것 (air leaks) 을수면호흡장애로오인할수있으며, 중추성과폐쇄성수면무호흡증을구분할수없다는점은 APAP 의가장큰제한점이다. 29 APAP 과 fixed-pressure CPAP 를비교한연구에서는, A-PAP 에서마스크나입으로바람이새서불필요하게압력이높게책정되지만않는다면 AHI 의호전은거의비슷하다고보고했다. APAP 과 fixed-pressure CPAP 를비교한보고에서는 APAP 사용군의평균 PAP 압력이현저히낮고 AHI 도낮지만, 두군간의주간졸림증이나, adherence 간에는차이는없다고했다. 32 그러나 APAP 이 fixed-pressure CPAP 에비해더우월하지는않아서여전히 PAP 치료의근간은 fixed-pressure CPAP 라고결론지었다. 다른유사임상연구들에서는위와동일한결론에도달하지는못했다 향후전향적인무작위연구를통해 APAP 에효과적이고도높은 adherence 를보일수있는 OSA 세부환자군을결정하는것이매우필요하다. 역설적으로이연구는 A-PAP 이효과적이지않은환자군을규명해줄수있을것이다. 또한 APAP 유용성연구는 fixed-pressure CPAP 에적응하지못하거나, 임상효과가적은 OSA 환자들에게큰도움이줄것이다. 최근소개된 autobilevel PAP 은 minimum EPAP, maximum IPAP-EPAP difference(minimum, 3 cm H2O) 과 maximum IPAP 을미리결정한상태에서상황에따라 EPAP 과 IPAP 를조절하게되는장비이다. Auto-bilevel PAP이다른 PAP들에비해어떠한점이유용한지에대한연구결과는아직충분치않지만, bilevel PAP으로적정압력을찾지못했거나, 높은압력을견디지못하는환자들에게도움이될수있다. Expiratory pressure relief(flexible CPAP) 은 Pressurerelief PAP는 fixed-pressure CPAP의일종으로호기동 안가해지는 PAP 의압력을약간낮춰서환자의호기시부담을줄이고 adherence 를향상시키고자계발되었다. 29 환자의호기량에비례하여압력이낮춰지다가호기가끝나는시점에서다시이전압력으로올라간다. C-flex(Respironics; Murrysville, PA) 와 EPR(ResMed Corporation; Poway, CA) 의두종류가시판되고있다. C-flex 는 settings 1, 2, 3의순서로점차호기시압력감소폭을증가시키는데, 감소폭은호기량에따라결정되며, 이는장비고유의특허알고리즘이다. EPR 장비의 setting 1, 2, 3의순서로 1, 2, 3 cm H2O씩압력이감소한다고한다. Flexible PAP은 APAP, bilevel PAP, autobilevel PAP(Respironics) 모두에서가능하며, flexible bilevel PAP 은흡기끝-호기시작시점에서압력을일시적으로낮춰준다. 전향적무작위연구를보면, pressure-relief CPAP 사용군의 AHI 와수면효율의호전성과각성지수의감소는 fixed pressure CPAP 사용군과차이가없었지만, pressure-relief CPAP 의 adherence 가더우월하다고할수는없었다. 39,40 향후 bilevel PAP이특히도움이될수있는 OSA 세부환자군을찾기위한전향적인무작위연구가필요하다. Adaptive servoventilation(asv) 는가장최근에소개된장비로본래울혈성심부전을갖고있는환자들의 Cheyne-Stokes central apnea를치료할목적으로계발되었다. 41 Backup rate가포함된 ASV와 bilevel PAP 장비는 complex sleep apnea(central apnea that persists or appears during a PAP titration) 치료에도승인되었다. ASV 에서는상기도개방을유지하기위한 EPAP 을미리결정하며, IPAP-EPAP difference 로최근환기량평균치의 90% 를제공하기위해, 최저와최고압력간의차이를조정하게된다. 환기량이작으면 IPAP-EPAP difference 가증가하고, 환기량이크면 IPAP-EPAP difference 은감소한다. Backup rate은중추성무호흡이발생할경우 IPAP/ EPAP cycle 을유발시킨다. ASV는저환기환자들에게는처방하지않으며, EPAP 이매우높아야하는환자에게도도움이되지않는다. PAP Humidification 대부분의 PAP 장비에는 heated humidification system 66 수면

4 이내장되어있다. Heated humidity 은 cool humidification 보다더많은양의습기를전달하여특히 mouth leak 나 nasal congestion 이있는환자들에게유용하다. 구호흡을하게되면장비내의습기가입밖으로유출이되어비강과구강의점막이말라서비강저항을증가시킨다. 42 마스크내의습기량이높이며 mouth leak가줄어든다고한다. 43 가습의정도는사용중인환자가반정량적으로조절할수있다. 가습기통과호스를깨끗하게유지하는일이매우중요하다. 하지만, 한연구에서는가습이상기도감염의증가와연관이있을수있음을보고했다. 44 PAP 사용평가시고려할점 Fixed-pressure CPAP 에서발생한압력이마스크를통해상기도로효과적으로전달되기위해서는장비내부의저항성을올릴수있는요인들 ( 긴호스와호스내액체응결 ) 들을제거해야하며, 호흡횟수및일회호흡량 (tidal volume) 과같은역학적요인들도고려되어야한다. 45 PAP을사용중인환자가지속적이거나반복적으로증상으로호소하거나치료를불편해할경우다시한번위의요인들을점검해보아야한다. APAP 은실제임상에서적용시키기용이하지않은장비이다. 우선자동적으로이상호흡패턴을발견하여구분할수있는소프웨어와센서가장비내에장착되어야한다. 또한 A-CPAP 은압력조절이필요한코골이, 수면무호흡, 저호흡, 호흡량제한 (airflow limitation) 과같은수면관련호흡장애사건들 (sleep-disordered breathing events) 과압력조절이되면안되는기침, 한숨, 삼킴, 말, 구호흡, leaks 와수면중각성을유발할만한사건들을구분할수있어야하기때문이다. 또다른어려움은감지해낸다양한사건들에따라적정압력을맞추는알고리즘의문제이다. 아직까지 PAP 치료의적정목표가결정되지못했다. 많은 APAP 장비회사들간의알고리즘계발은특허사항이어서공개되지않아정확한프로세스를알수없다는점도 APAP 의제한점이된다. 46 결론아직까지 OSA 의가장대표적이고도근간이되는치료는 PAP이다. OSA 환자들은 CPAP 치료로도움을받을수있으며, 그외 A-PAP 치료가도움이되는경우도있다. 그러나, 호흡계질환을갖고있는경우, bilevel PAP이효과적일수있다. PAP 치료는 OSA의임상증상을호전시킴과동시에, 삶의질을높일수있다. 그러나무엇보다성공적인 PAP 치료는 adherence 를올리는데있으며, 이는철저한사전환자교육, 사용중객관적인 adherence 모니터링, 부작용의초기제거, 전화상담및정기적인외래방문을통해 adherence 을높일수있다. REFERENCES 1. Sullivan CE, Issa FG, Berthon-Jones M, Eves L. Reversal of obstrcutive sleep apneas by continuous positive airway pressure applied through the nares. Lancet 1981;1: Engleman HM, Wild MR. Improving CPAP use by patients with the sleep apnea/hypopnea syndrome. Sleep Med Rev 2003;7: Pépin JL, Krieger J, Rodenstein D, et al. Effective compliance during the first 3 months of continuous positive airway pressure: a European prospective study of 121 patients. Am J Respir Crit Care Med 1999;160: Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N EnglJ Med 2000;342: Tobin MJ. The role of a journal in a scientific controversy. Am J Respir Crit Care Med 2003;168: Pepperell JCT, Ramdassingh-Dow S, Crosthwaite N, Mullins R, Jenkinson C, Stradling JR, Davies RJO. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet 2002;359: Robinson GV, Smith DM, Langford BA, Davies RJO, Stradling JR. Continuous positive airway pressure does not reduce blood pressure in nonsleepy hypertensive OSA patients. Eur Respir J 2006;27: Norman D, Loredo JS, Nelesen RA, Ancoli-Israel S, Mills PJ, Ziegler MG, Dimsdale JE. Effects of continuous positive airway pressure versus supplemental oxygen on 24-hour ambulatory blood pressure. Hypertension 2006;47: Arias MA, García-Río F, Alonso-Fernández A, Martínez I, Villamor Vol.5, No.2 / December,

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A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R