INVITED REVIEW J Neurocrit Care 2009;2 Suppl 2:S80-S85 ISSN 2005-0348 실 신 - 진단과치료 - 성균관대학교의과대학내과학교실 김준수 Syncope - Evaluation & Management - June Soo Kim, MD Division of Cardiology, Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Syncope is very common in the general population. The evaluation of syncope is sometimes difficult because the occurrence of syncope is unpredictable and diverse factors and diseases may involve in the occurrence of syncope. Therefore, a detailed history taking is a very important step of initial evaluation of syncope. Initial evaluation of syncope consists of careful history taking, physical examination, including orthostatic BP measurements, and 12 lead electrocardiogram. After initial evaluation of syncope, further diagnostic tests are performed based on the risk stratification. Risk stratification is important in managing syncope. Syncope from cardiac disease could cause sudden cardiac death if proper treatment was not made for underlying heart disease. The management of syncope depends on the cause of syncope. Therefore, the treatment modalities in all causes of syncope could not be described in this paper. Neurally mediated syncope is the most common cause of syncope. Therefore, the management of neurally mediated syncope is mentioned as follows: In the past, several drugs such as beta-blockers, disopyramide, theophylline, etilefrine, midodrine, serotonine reuptake inhibitors were used to prevent the recurrence of syncope in neutrally mediated syncope. While the effects of drugs have been satisfactory in uncontrolled studies or shortterm controlled trials, placebo-controlled prospective trials did not show a benefit of trial drug over placebo. Currently, beta-blocker is not recommended in the treatment of neurally mediated syncope. But, midodrine may indicate in patients refractory to lifestyle measures. The role of pacing therapy for neurally mediated syncope has been also controversial. Several multicenter, randomized controlled trials showed contradicting results. Therefore, pacing should not consider as the treatment for neurally mediated syncope without severe spontaneous bradycardia. Tilt training was introduced to prevent the recurrence of symptoms in patients with recurrent neurally mediated syncope. Previous several non-randomized studies showed the dramatic significant benefit of tilt training. However, this treatment was difficult to continue because of the low compliance of patients. Recently, small-scaled, randomized controlled trials failed to confirm shortterm effectiveness of tilt training in reducing the positive response of head-up tilt testing. Therefore, tilt training may be used in the younger, very symptomatic, well-motivated patients. Considering no established pharmacological and non-pharmacological treatment, education to avoid triggering factor and specific situation and reassurance are very important in managing patient with neurally mediated syncope. Physical counter-pressure maneuvers such as leg crossing or hand grip and arm tensing are emerging as a new non-pharmacological physical treatment of neurally mediated syncope. J Neurocrit Care 2009;2 Suppl 2:S80-S85 KEY WORDS: Syncope Diagnosis Treatment. 서 론 실신은모든연령층에서발생하는흔한증상이다. 실신은 그원인이매우다양하고평소증상이없어그원인을진단하기가쉽지않다. 조기에적절한진단적검사로진단하지못하면부적절한검사와잦은입원으로의료비용이증가하 Address for correspondence: June Soo Kim, MD Division of Cardiology, Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710, Korea Tel: +82-2-3410-3849, Fax: +82-2-3410-3414, E-mail: juneskim@skku.edu S80 Copyright c 2009 The Korean Neurocritical Care Society
Syncope - Evaluation&Management JS Kim 고, 심장질환환자에서는심장돌연사의위험성도있다. 따라서실신환자에대한적절한진단적방법과치료에대하여알아보는것이임상의에게중요하다. 실신의정의 실신은 일시적인뇌혈류저하로발생하는일시적인의식소실로특별한조치없이짧은시간내후유증없이의식을완전히회복하는경우 로정의하고있다. 따라서실신은그정의상대사장애나약물중독에의한의식혼돈, 간질, 정신성유사실신 (psychogenic pseudo-syncope), 두부외상에의한일시적인의식소실, 어지럼증, 현훈과는구별되어야한다. 실신의분류 실신의원인은신경매개성실신 (neurally-mediated syncope), 기립성저혈압에의한실신, 심혈관계질환에의한실신, 원인불명의실신으로구분할수있다. 신경매개성실신은실신의원인중에서가장흔하며심장신경성실신 (neurocardiogenic syncope), 반사매개성실신 (reflex-mediated syncope) 용어로도사용되고있다. 신경매개성실신에는혈관미주신경성실신 (vasovagal syncope), 특정상황에서발생하는상황성실신 (situational syncope), 목동맥굴실신 (carotid sinus syncope), 비전형적형태의실신 (atypical syncope) 이속하며이중혈관미주신경성실신이가장흔하다. 기립성저혈압에의한실신은체내자율신경계의기능부전, 약물, 출혈, 설사등으로인한체액부족으로발생하는실신을포함한다. 심혈관계질환에의한실신은부정맥, 심혈관계질환에의한실신을포함한다. 원인불명의실신은여러가지진단적검사에도불구하고그원인이밝혀지지않은경우를말한다. 실신의발생기전 실신은여러가지원인에의하여뇌혈류가 6초내지 8초정도일시적으로정지시발생하게된다. 기립경사검사를이용한연구에서는수축기혈압이 60 mmhg 또는그이하로내려갈때실신이초래된다. 1 수축기혈압은심박출량과전체말초혈관저항에의해결정된다. 뇌혈류저하를초래하는심박출량의저하와말초혈관혈관저항감소의정도는 실신의원인에따라다르다. 신경매개성실신신경매개성실신의발생기전은단순하지않다. 그러나신경매개성실신은대부분장시간서있는상태에서하지정맥내혈액정체로인하여심실내혈액유입이감소하고심실용적이감소하는상태에서잘발생한다. 이러한상황에서증가된교감신경계에의해심실의과도한수축이일어나면심실내기계수용체가자극된다. 자극된수용체로부터구심성신경신호가뇌간의연수에도달하면, 연수로부터원심성신경신호가심장과말초혈관으로전달된다. 따라서항진되었던교감신경계가급격히떨어져말초혈관이확장되면혈압이갑자기내려가고, 항진된부교감신경이심장내동결절이나방실결절에작용하면동정지나방실차단이발생하여일시적인뇌혈류중단으로실신이발생한다. 이러한체내자율신경계의부적절한반응으로발생하는혈역학적변화를 Bezold-Jarisch 반사라고한다. 2,3 이러한체내자율신경계의부적절한반응에의해발생하는심박출량의저하와말초혈관저항감소정도에따라 3가지형태로구분하기도한다. 말초혈관의저항이주로감소되는경우는혈관운동억제형 (vasodepressor type), 일시적인심정지로인한심박출량이감소되는경우는심장기능억제형 (cardioinhibitory type), 말초혈관저항감소및심박출량이감소되는경우는혼합형 (mixed type) 으로구분하기도한다. 그러나신경매개성실신발생기전은단순하지가않아전형적인 Bezold-Jarisch 반사외에상위대뇌중추가직접관여할수도있으며, 4 그외에대뇌의세로토닌, 5 아편유사물질과같은매개물질이나, 6 뇌혈관의비정상적인수축 7,8 도관여하는것으로알려져있다. 기립성저혈압에의한실신정상인에서는누웠다가갑자기일어나는경우교감신경계의활성도가증가하고부교감신경계의활성도가억제되어심박동수가빨라지고말초혈관저항이증가되어혈압이유지된다. 그러나자율신경계의기능부전, 약물영향으로체위변화에따른교감신경계활성도가적절하게증가하지못하는경우에는말초혈관저항이증가하지못하여혈압이급격히내려가실신이초래된다. 또한말초혈관확장과중력작용으로횡경막아래의정맥내에혈액이정체되고, 출혈, 설사로인한체액부족하면이로인한심박출량감소로기립성저혈압이발생할수도있다. S81
J Neurocrit Care 2009;2 Suppl 2:S80-S85 심혈관계질환에의한실신부정맥으로인한느린심박동, 빠른심박동으로심박출량의감소와과도한심실수축에의한심장내기계수용체자극으로실신이발생할수있다. 심실빈맥혹은심실세동이발생하는경우에는적절한조치를하지않으면심장돌연사도초래될수있다. 좌심실이나우심실의심박출장애를초래하는심혈관계질환의경우에는심박출량감소로실신이발생할수있다. 급성하벽부심근경색의경우에는허혈성변화로좌심실기계수용체가자극되어 Bezold-Jarisch 반사가일어나실신이발생한다. 심각한심혈관계질환에서는심장돌연사도초래될수있다. 실신원인진단 일차평가실신환자에서실신의원인진단을위해서는병력조사, 신체검사및체위변화에따른혈압측정, 12 유도심전도검사를일차평가로반드시시행하여야한다. 이러한실신에대한적절한일차평가과정에서실신환자의 23~50% 에서실신의원인이진단될수있다. 9,10 그러나이러한일차평가과정을생략하고부적절한여러가지진단적검사를시행하면조기에실신원인을진단하지못하고의료비용만증가시킬수있다. 병력조사환자의병력조사는실신환자의진단적접근에서가장중요하다. 그러므로환자실신병력에대하여환자및실신당시목격자로부터자세하게조사해야한다. 환자가진짜의식소실이있었고특별한조치없이저절로완전히의식을회복하였는지, 실신이아닌다른증상 ( 예를들면장애물에발이걸려넘어짐, 대사장애나약물중독에의한의식혼돈, 간질, 정신성유사실신, 두부외상에의한일시적인의식소실, 어지럼증, 현훈 ) 이었는지를구별해야한다. 실신발생하기전상황도자세하게알아보아야한다. 신경매개성실신은충격적인장면을목격하거나, 역한냄새를맡거나, 심한통증발생시, 장시간부동자세로서있거나, 혼잡한환경, 더운실내환경에노출될시, 식사도중혹은식사후상황, 운동직후에잘발생한다. 그리고기침, 배뇨, 배변, 연하, 기도자극, 경동맥동부위자극과같은특정한상황에서도발생한다. 기립성저혈압에의한실신은자다가갑자기일어날때, 고혈압치료약을시작할때, 약용량을 변경할때, 심한운동직후에잘발생한다. 실신발생전오심, 구토, 복부통증, 식은땀, 하품, 무력감, 어지럼증등의전구증상이있었다면신경매개성실신을의심할수있고, 심한심계항진증상이있었다면빈맥성부정맥에의한실신을의심할수가있다. 실신당시목격자로부터실신당시환자가넘어지는양상, 실신당시환자의얼굴및피부색깔, 의식소실기간, 호흡양상, 사지의경직이나움직임양상, 혀를깨물었는지, 요실금이있었는지에대하여알아보아야한다. 실신이후의식혼돈이나다른증상이있었는지, 신체적외상을입었는지에관하여서도알아보아야한다. 환자가족력상실신, 심장돌연사, 심장질환이있었는지알아보아야한다. 환자가과거심장질환을앓았거나현재앓고있는지, 다른질환이있었는지, 복용중인약물이있는지도알아보아야한다. 실신이자주재발하는경우에는첫실신발생시기와재발시기, 실신발생시의상황, 과거실신에대한진단적검사및치료여부에대한정보도알아보아야한다. 신체검사및체위변화에따른혈압측정흉부촉지및청진시심비대, 심잡음, 심박동수의규칙성, 경동맥부위에서청진시잡음유무를확인하고, 실신당시넘어지면서신체적외상이있다면이에대한평가도해야한다. 체위변화에따른혈압을측정하여, 기립시 3분이내에수축기혈압이 20 mmhg 이상, 이완기혈압이 10 mmhg 이상내려가는경우기립성저혈압이있다고할수있다. 11 12 유도심전도검사 12 유도심전도검사그자체로실신의원인을직접진단하는경우는드물다. 그러나 12 유도심전도소견상 Q파, 심실내전도장애, 동서맥, 방실차단, 연장된 QT 간격, 조기흥분 QRS complex, 특이한우각차단소견이관찰되면관동맥질환이나부정맥에의한실신을의심할수가있어일차평가이후적절한심장관련진단적검사를시행할때도움을줄수있다. 심혈관계합병증이나심장돌연사의위험도평가병력조사, 체위변화에따른혈압측정, 신체검사, 12 유도심전도검사를통한실신원인에대한일차평가에서그원인이확실하지않을때에는심혈관계합병증이나심장돌연사의위험도에따라진단적검사여부를결정하여야한다. S82
Syncope - Evaluation&Management JS Kim 일차평가에서심혈관계합병증이나심장돌연사의위험도가낮고처음발생하였거나, 매우드물게발생한경우에는더이상의진단적검사를시행하지않고경과관찰하는것이좋다. 일차평가에서심혈관계합병증이나심장돌연사의위험도가낮으나실신이자주발생하는경우에는심장관련검사나신경매개성실신의확진을위하여기립경사검사 (headup tilt test) 를시행할수있다. 12-15 일차평가에서심혈관계합병증이나심장돌연사의위험도가높은경우에는조기에심장관련검사를철저히시행하여실신원인을찾아서치료하여야심혈관계합병증이나심장돌연사를예방할수가있다. 원인불명의실신일차평가, 진단적검사에도불구하고실신의원인이밝혀지지않고실신은계속간헐적으로발생하며부정맥에의한실신이의심되는경우에는장기간환자의심율동을관찰하여실신의원인이되는부정맥을진단할수있는삽입형루프기록기를환자의흉부피하조직에시술하여장기간환자의심율동을관찰하여실신의원인이되는부정맥을진단할수가있다. 16,17 실신에대한치료 실신의원인은매우다양하여각질환이나원인에대한치료를모두다설명할수는없다. 따라서실신의원인중에서가장흔한신경매개성실신의예방및치료에대해서만설명하기로한다. 신경매개성실신에대한예방및치료 환자교육환자에게실신이발생하는기전에대하여설명을해주고, 심혈관계질환에의한실신과는달리신경매개성실신은자주발생하더라도심장돌연사의위험성은매우낮다고설명을하여환자의지나친불안감을해소시켜주는것이중요하다. 환자에게과격한운동이나실신이잘유발될수있는상황은피하도록교육을하고, 과거차운전도중실신이발생하였다면운전을계속할지여부에관해서조언을해주는것이좋다. 대부분의환자에서신경매개성실신이발생하기전힘이빠지거나, 속이메스껍거나, 가슴이답답하거나, 하품이나거나, 어지럽거나하는전구증상이있기때문에환자에게 이러한전구증상을느낄시에는환자스스로즉각적으로눕도록하여실신까지진행되지않도록교육을하여야한다. 환자중실신전에비교적전구증상을느끼는경우에는, 전구증상이발생시즉시주먹을꽉쥐고팔에힘을주는방법이나, 서있는상태에서다리를서로교차하여압박을주면서, 다리, 복부, 엉덩이근육에힘을주는방법을통하여혈압을상승시켜실신발생을방지할수도있다. 18-20 그러나이러한방법은전구증상이없거나있어도매우짧거나, 전구증상발생시신속하게이러한방법을시행하기어려운환자의경우에는사용할수가없다. 환자가실신후의식을회복한뒤에는가능하면바로일어나지않고수분이상휴식을취한뒤에서서히일어나도록해야한다. 간혹환자가의식을잃고쓰러진것을목격한보호자들이환자를다른장소로이동시키기위해바로일으켜세우면서다시의식을잃는경우가있다. 젊은청소년의경우에는매일충분한물과염분을섭취함으로써실신재발방지에도움을받을수있다. 약물치료자주재발하는실신환자에서실신재발방지를위해서과거여러가지약물들이임상에서사용되었다. 베타- 차단제는교감신경계의활성도를억제하고심근수축력을감소시켜심실내기계수용체의활성화를억제하는효과로, 디소피라마이드는베타- 차단제와유사한기전인심근수축력감소와항콜린성효과로, 스코폴라민은미주신경을억제하는효과로, 프루드로코티존은체액이나체내염분을축적시키는효과로, 테오필린은혈관확장에관여하는내인성아데노신의작용을차단하는효과로, 세로토닌재흡수억제제인파로섹틴, 플루옥세틴, 세르트라린은대뇌신경전달물질인세로토닌에영향을주는효과로, 에틸에프린과미도드린은자율신경계의말초알파-수용체에작용하여말초혈관을수축시켜혈압을상승시켜효과로신경매개성실신환자에서실신재발방지를위하여사용되어왔다. 그러나이들약물의실신재발방지효과에관한전향적무작위연구가없거나, 전향적무작위연구가있어도소규모환자를대상으로한일부약물 ( 미도드린, 파로섹틴 ) 을제외하고는그효과가입증되지않았다. 21-24 따라서현재는재발성신경매개성실신환자에서약물치료는권장되지않으며미도드린만일부환자에서사용할수있다 (2009년유럽심장학회기준 Class IIb). 25 인공심박조율기시술경동맥동실신환자중에서경동맥동자극시심장기능억 S83
J Neurocrit Care 2009;2 Suppl 2:S80-S85 제형형태를보이는경우에는인공심박조율기의시술적응증이된다 (2009 년유럽심장학회기준 Class IIa). 25 기립경사검사시심장기능억제형의형태를보이는신경매개성실신환자에서는과거인공심박조율기의시술이실신재발방지에효과가있다고하였으나, 26 전향적무작위연구에서는그효과가입증되지않았다. 27 따라서신경매개성실신환자에서는인공심박조율기시술이실신재발방지를위한일차치료로시행해서는안된다 (2009년유럽심장학회기준 Class IIa, IIb, III). 25 기립경사훈련 (Tilt training) 신체내부혹은외부자극에대한체내자율신경계의과도한반응에의해신경매개성실신이발생함으로, 신경매개성실신환자에서기립경사자극을반복시행하면탈감작효과에의하여실신재발효과가나타난다. 국내외연구들에서신경매개성실신환자에서기립경사훈련의치료효과가있는것으로보고되었다. 28,29 그러나최근발표된전향적무작위연구에서는기립경사훈련치료군에서치료순응도가매우낮아집에서시행하는기립경사훈련의치료로는대조군과비교시치료효과의차이를보이지않았다. 30,31 따라서기립경사훈련치료는신경매개성실신환자중증상이자주발생하고, 약물치료에반응이없고, 기립경사훈련치료를받을의지가확실한환자를대상으로선별적으로시행해야한다 (2009년유럽심장학회기준 Class IIb). 25 REFERENCES 1. Stephenson J. Fits and Faints. Oxford: Blackwell Scientific Publications. 1990;41-57. 2. von Bezold A, Hirt L. Über die physiologischen Wirkungen des Essigsauren Veratrins. Untersuch Physiol Lab Wuerzburg 1867;1:73. 3. Waller A. Experimental researches on the functions of the vagus and the cervical sympathetic nerves in man. 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