REVIEW online ML Comm J Neurocrit Care 2010;3:7-12 ISSN 중환자실에서지속뇌파검사의유용성 연세대학교의과대학강남세브란스병원신경과학교실 김원주 Usefulness of Continuous Electroencepha

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1 REVIEW online ML Comm J Neurocrit Care 2010;3:7-12 ISSN 중환자실에서지속뇌파검사의유용성 연세대학교의과대학강남세브란스병원신경과학교실 김원주 Usefulness of Continuous Electroencephalography Monitoring in Intensive Care Unit Won-Joo Kim, MD Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea When we care critically ill patient in intensive care unit (ICU), many kinds of monitoring such as pulse oximetry, electrocardiogram, respiration, arterial blood pressure and etc. are needed. But for brain, continuous monitoring has been unavailable until recently. By mechanical development, continuous EEG monitoring (ceeg) is possible to use and provides functional information about brain function. Those ICUs caring for patients with status epilepticus should have access to ceeg monitoring for treatment and recognizing non-convulsive seizures. ceeg should be integrated into the multimodality brain monitoring approach of acutely brain-injured patients. Various kinds of quantitative EEG parameters can now be analyzed in combination with other neuromonitoring measures to detect early pathological changes preceding clinical detection of these events. Further studies show the impact on outcome and making ceeg monitoring out of the subspecialized ICU setting into the general ICU environment. J Neurocrit Care 2010;3:7-12 KEY WORDS: Electroencephalography Intensive care unit Monitoring. 서 중환자실에환자가입원하게되면심전도, 동맥산소분압, 호흡수측정장치등여러종류의감시장치를사용하여 24 시간관찰하게된다. 대부분의감시장치로심폐기능의지속적감시는가능하였지만신경계를지속적으로감시하는장치는드물기때문에, 신경계중환자를치료하기위해서는일정한간격으로의료진이신경학적검사를시행하는방법이주로사용되었다. 그러나이러한방법은검사를실시하는일정시각의신경학적상태만을평가하기때문에, 언제부터환자의증상변화가발생하였는지를정확하게감지할수없는단점이있다. 이외에도대뇌를검사하는방사선방법들도뇌의기능적인변화보다는형태학적인변화만을관찰하는한계가있었다. Address for correspondence: Won-Joo Kim, MD Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, 712 Eonju-ro, Gangnam-gu, Seoul , Korea Tel: , Fax: kzoo@yuhs.ac 론 뇌파검사는비침습적인방법으로대뇌기능의전기학적상태를평가하는검사로, 근래에컴퓨터과학발달로뇌파결과들이디지털화가이루어지고모니터를통하여지속적인뇌파의관찰이가능하며, 장기간시행되는뇌파기록의저장도간편하게이루어져지속뇌파검사가가능해졌다. 중환자실에서지속뇌파검사로환자대뇌의기능적변화를실시간으로관찰할수있기때문에이전에감지해내지못하였던대뇌의기능적변화를알아낼수있게되어중환자치료에많은도움을얻을수있게되었다. 본종설에서는이러한지속뇌파검사가도움이되는신경계질환들에서의유용성에대하여기술하고자한다. 발작 뇌파검사가유용하게사용되는신경계의대표적인질환은발작이다. 특히간질지속상태환자에서지속뇌파검사는매우중요하다. 경련성간질지속상태환자에서경련성발작이멈춘이후에도뇌파에서전기적발작이지속되는경우가종종있다. 1,2 또한의식이저하된환자에서비경련성간질지 Copyright 2010 The Korean Neurocritical Care Society 7

2 이와같이중환자실에서의식혼수상태의환자들중에 NCSz를나타 내는비율이여러연구를통하여약 8~48% 까지보고되었다 (Table 1). 2-10 이환자들에서나타나는증상은단순한의식저하이기때문에진단을위해서는지속뇌파검사가반드시필요하다. NCSE와 NCSz는원인질환에따라영향을받기때문에연구마다발생률의차이가있으며아직대단위역학연구는이루어지지않고있다.

2 J Neurocrit Care 2010;3:7-12 속상태 (nonconvulsive status epilepticus: NCSE) 나비경련성발작 (nonconvulsive seizure: NCSz) 여부를확인하는데지속뇌파검사가필수적이다. 경련성간질지속상태환자에서경련성발작이소실되고 24 시간동안지속뇌파검사를시행한결과에서 48% 의환자에서 NCSz가있었고, 14% 에서는 NCSE가있었으며이들은단순히의식혼수만이나타나는임상적증상이었다고보고하여지속뇌파검사의필요성을보여주었다 (Fig. 1). 2 이와같이중환자실에서의식혼수상태의환자들중에 NCSz를나타 내는비율이여러연구를통하여약 8~48% 까지보고되었다 (Table 1) 이환자들에서나타나는증상은단순한의식저하이기때문에진단을위해서는지속뇌파검사가반드시필요하다. NCSE와 NCSz는원인질환에따라영향을받기때문에연구마다발생률의차이가있으며아직대단위역학연구는이루어지지않고있다. 그러나원인질환에따라 NCSz 등의발생률이차이가있다. 외상성뇌손상의경우에는예방적인항경련제치료에의하여대규모연구에서임상적발작의발생률이 1% 이하로감소되었다고하지만, 11 A B FIGURE 1. Continuous electroencephalogram (ceeg) recording in a 68-yr-old woman who had altered mental status after generalized tonicclonic seizure. A: Initial EEG reveals nonconvulsive seizure evolving from left temporal region without clinical convulsive activity. B: The epileptiform discharges were abolished after 3 days. 8

3 Continuous EEG in ICU WJ Kim TABLE 1. Studies using continuous electroencephalography monitoring for nonconvulsive seizures Privitera 3 Study patients Patients with altered level of consciousness or suspected subclinical seizures Percentage Percentage N of patients of NCSz (%) with seizures (%) Jordan 4 Patients admitted to NCU DeLorenzo 2 All patients with prior convulsive SE and altered level of consciousness without clinical seizure activity Vespa 6 All patients with moderate to severe traumatic brain injury Vespa 5 Patients admitted to NCU with stroke or intracerebral hemorrhage Claassen 7 Jette 8 Claassen 9 Oddo 10 Patients with unexplained decreased level of consciousness or suspected subclinical seizures Patients <18 yr old admitted to ICU with unexplained decreased level of consciousness or suspected subclinical seizures Patients with intracerebral hemorrhage with unexplained decreased level of consciousness or suspected subclinical seizures Medical ICU patients without known brain injury undergoing ceeg with unexplained decreased level of consciousness or suspected subclinical seizures ICU: intensive care unit, NCU: Neuro ICU, ceeg: continuous EEG, NCSz: nonconvulsive seizure ~33% 에서 NCSz가발생하며 8% 정도에서 NCSE가발생한다는연구들에서예방적인치료가일부환자에서는부족하다는가능성이제시되었다. 7,12,13 뇌수술후의발작발생률은천막위 (supratentorial) 부위이면약 4~17% 이지만, NCSz나 NCSE의발생률은아직밝혀지지는않았다. 다른원인질환들로중추신경감염환자의 33% 에서 NCSz가발생하며 17% 에서 NCSE가발생하고, 7,17 지주막하출혈에서는 18% 와 13%, 7 뇌출혈에서는 18~23% 와 7%, 5,9 급성뇌경색증환자에서는 9% 와 7% 의비율로 7 NCSz와 NCSE가발생한다고보고되고있다. 저산소뇌증환자에서도 NCSz의발생률은높은편이어서약 20% 에서발생한다. 7 특히심정지이후에저온치료법을사용하는경우에는체온저하에따른떨림과발작을감별하기위하여반드시지속뇌파검사를시행하여야한다. 18 내과질환환자에서도여러독성물질이나대사성, 전해질이상이의식저하와발작을일으킬수있다. 신경계질환이뚜렷하지않으며설명되지않는의식저하가있지만임상적으로발작증상이없는환자의 8% 에서 NCSE가관찰되었으며, 중추신경계질환의과거력이없는패혈증환자의약 19% 에서 NCSz가발생하였다는연구를통하여패혈증이독립적인 NCSz의원인이되며, 발작자체가패혈뇌병 (septic encephalopathy) 의발생에영향을준다고본다. 10 아직도 NCSz나 NCSE의치료가환자의예후에어떠한영향을주는지에대한전향적무작위연구는없다. 경련성간질지속상태에서는 lorazepam 투여, phenobarbital 투여, diazepam 을투여하고 phenytoin 투여와 phenytoin 단독투여의네가지치료법을무작위이중눈가림방법으로비교 하였으나치료의성공률과 30일이후의예후에서차이가없었다. 1 이연구에서 NCSE나 NCSz의치료결과를보여주지는않았지만노인환자에서 NCSE가있는경우가나쁜예후를보이고, 19 노인연령층에서 NCSz의적극적인치료가좋지않은결과를보여주었지만, NCSE가노인환자의예후에나쁜영향을미치는지아니면단순하게질병의중증여부를나타내는것인지는확실하지않다. 20 NSCE의사망률에는원인이되는질환과합병증의영향이가장크다. 21 간질지속상태로치료받은후에뇌파에서도특이한소견이발견되지않았던환자에서사망률이 13% 였으나임상적으로간질지속상태가중단되어도뇌파상에서 NCSz가보이는환자의사망률은 32%, NCSE가나타난환자는 52% 의사망률을보여, 지속되는 NCSE가환자에게더많은손상을준다고추정된다. 2 이러한결과는대뇌손상이없는내과중환자에서도유사하여 NCSz나뇌파에서 periodic epileptiform discharge(ped) 가나타나는경우에도나쁜예후를보였다. 10 NCSz나 NCSE가신경계에손상을주는증거로는 neuron-specific enolase(nse) 라는신경손상의생화학적지표를나타내는물질이 NCSz 때에증가한다는결과가보고되었으며, 22 이러한손상은발작에의한대뇌혈류변화나흥분독소, 산화작용에의한다고추정한다. NCSE의초기치료가실패하여불응성인경우에는지속적인항경련효과의약물의정맥내투여가필요하다. 이때널리사용되는약제는 midazolam, propofol, pentobarbital 등이있는데이러한약물을효과적으로사용하기위해서는지속뇌파검사를시행하여야한다. 23 즉약물의적정량을결정하기위하여지속적으로뇌파의변화를관찰하며조절하 9

4 J Neurocrit Care 2010;3:7-12 는것이저용량사용에의한치료실패나과다한약물투여에의한심각한부작용을예방할수있게된다. 또한일시적인뇌파검사만시행하는경우에위음성이 50% 까지증가하기때문에지속뇌파검사가필수적이다. 7,24 을사용한다. 대표적인방법으로는 alpha variability 와 poststimulation alpha to delta 비율로써 alpha variability 는임상증상이나타나기최대 2일전초기혈관수축을감지하기도한다고보고되었다. 28,34 뇌경색증 기 타 발작이외에도지속뇌파검사는지주막하출혈이후의혈관수축일때나재발되는뇌경색증, 경동맥내막절제술동안클램프연결시에뇌혈류감소를감지하는검사로사용된다. 뇌혈류가감소하여신경세포의기능이저하되지만아직가역적인상태인약 25~30 ml/100 g/min 정도에서도뇌파의변화가관찰된다. 이때에뇌파에나타나는소견은속파 (fast activity) 의소실, 서파의증가와배경파의감소등이있다. 25 이러한변화가미약하여표준뇌파에서간과하기쉬우나정량뇌파 (quantitative EEG: qeeg) 분석을통하여쉽게판별할수있다. qeeg는디지털화된뇌파의진폭이나빈도를정량적으로분석하는방법으로, 뇌경색증에는속파와서파의비율을비교하여나타내는방법이많이사용된다 이밖에도압축스펙트럼배열 (compressed spectral array), suppression-burst 비율, 비대칭지수 (asymmetry index), 진폭-통합뇌파 (amplitude-integrated EEG) 등의방법을사용하며, 정상면과비교하여비대칭적소견을감지하여편측의뇌경색증발생여부를평가한다. 뇌파를사용한뇌경색의감지는동맥내막절제술이나내경동맥일시폐쇄검사 (temporary balloon test) 에서처음으로사용되었다. 29,30 근래에는초기에나타나는미약한차이를감지하기위하여 spatial brain symmetry index(sbsi) 나뇌파의 temporal distributions(tbsi) 를통한비대칭성을비교하는방법을사용한다. 31 이러한방법은뇌경색증환자의관찰에도사용된다. 관류강조영상 MRI에서측정된뇌혈류량과 BSI가연관성이있으며, 급성델타파변화지수 (delta change index) 도연관이있다는연구가있다. 32 이외에도몇가지뇌파지표가뇌경색증환자의변화를감지하는데유용하다고하지만아직방사선검사나임상적양상보다우월하지는않다. 33 지주막하출혈에서는혈관수축이발생하는시기를감지하여빠른치료를시작하는것이중요하다. 지속뇌파검사도이러한목적으로연구되어초기혈관수축을감지하면다른검사를통하여확인하고치료를시작할수있다. 혈관수축에의하여국소뇌경색증이오는경우에는위에서기술된 qeeg 방법을사용하여비대칭성을초기에감지하기도하지만, 28 전반적인뇌허혈증상이생기는경우에는 qeeg의다른방법 두개강내압이뇌파에미치는영향은압력이매우증가하거나뇌혈류량이변하는경우이다. 두개강내압력이증가하며뇌혈류량의감소와뇌관류압 (cerebral perfusion pressure) 이변하는데뇌파검사는민감한반응을보인다. 대뇌피질확산억제 (cortical spreading depression: CSD) 현상이뇌압상승초기에관찰된다고한다. 35 이밖에지속뇌파검사를이용하는경우가마취와관련되어있다. 수술실에서마취정도를평가하기위해서나, 중환자실에서안정된정도를평가하기위하여또는신경근육차단제를사용하였을때진정의정도를파악하기위하여뇌파검사를이용한다 여기에서도 qeeg에서 bispectral index 등의방법을사용한다. 그러나근육잡파나수술실의전기적영향에의하여나오는뇌파파형이진정단계를오판하거나간질파형으로착각할수있기때문에숙련자가시행하여야한다. 다른연구에서외상성뇌손상환자의경과관찰을위하여지속뇌파검사를사용했으며특히침습적감시를하는환자에서 intracortical EEG를시행하여두피뇌파와비교한결과발작이나이차적신경학적손상에의한뇌파변화감지비율이더높았다고보고하였다. 39 이와같이신경학적이나내과적중환자에서지속뇌파검사의유용성은입증되었으나아직도해결해야하는문제점이있다. 즉, 중환자실에서지속뇌파검사기기를다수설치하는데필요로하는비용적인문제가있으며, 다음으로는뇌파검사를유지하는데필요로하는인력의문제가따르게된다. 중환자실에서는전기적차폐가어려운상황이므로뇌파검사를시행하는데여러잡파가영향을주며, 40 환자의자세를일정시간간격으로변동시켜야하고, 여러검사를진행하기위하여환자의움직임이많기때문에숙련된뇌파기사가뇌파검사를점검, 유지시켜야하므로 24시간기사가대기상태로근무하는것이바람직하다. 또한방대한양의뇌파결과를빠르게분석하기위하여뇌파판독의숙련의가필요하며치료에참여하는전공의, 간호사들도기본적으로뇌파에대한지식을가지고있어야한다. 지속뇌파검사가환자의상태변화를빠르게감지하여치료기간을단축시켜경제적이득이있다고하지만, 41 이러한문제점이해결되어야만효과적인검사가이루어질수있다. 10

5 Continuous EEG in ICU WJ Kim 결 론 지속뇌파검사는실시간으로우리에게대뇌기능의변화를 보여주는검사방법이다. 지금까지간질지속상태의치료와 재발을관찰하거나, 뇌경색증의변화를보는데유용한검사 로입증되었다. 앞으로도많은연구를통하여다양한중증 신경계질환에서유용한 qeeg 지표와이것을해석하기쉬 운방법, 그리고치료자들이쉽게접근하는방법들이개발 되면중환자실에서기본적으로시행되어야하는검사로자 리를잡을것이다. REFERENCES 1. Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ, et al. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med 1998;339: DeLorenzo RJ, Waterhouse EJ, Towne AR, Boggs JG, Ko D, DeLorenzo GA, et al. Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus. Epilepsia 1998;39: Privitera M, Hoffman M, Moore JL, Jester D. EEG detection of nontonic-clonic status epilepticus in patients with altered consciousness. Epilepsy Res 1994;18: Jordan KG. Neurophysiologic monitoring in the neuroscience intensive care unit. 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untitled 294 Cheon-Sik Kim. Analysis of Continuous Monitored EEG Patterns ORIGINAL ARTICLE Korean J Clin Lab Sci. 2017;49(3):294-299 https://doi.org/10.15324/kjcls.2017.49.3.294 pissn 1738-3544 eissn 2288-1662