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1 INVITED REVIEW online ML Comm J Neurocrit Care 2008;1 Suppl 1:S25-S31 ISSN 신경 혈관집중치료에있어모니터링 울산대학교의과대학서울아산병원신경과학교실 박세미 Monitorings in NICU: What and How to Do? Sea Mi Park, MD Department of Neurology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Korea In the neurointensive care (NICU) unit, neurologic monitoring is depended upon to signal the onset of neurologic decline. Monitoring technologies assume particular importance in the Neurocritical care Unit. Beyond other intensive care unit (ICU), the NICU uses a wide array of technologies (intracranial pressure monitoring, cerebral perfusion pressure measurement, cerebral oxygen saturation, transcranial Doppler ultrasound and continuous electroencephalogram) are commonly practiced for both whole brain monitoring modalities and also considers recent advances in general ICU monitoring strategies. Most simplest and important thing is the serial neurologic examination, performed frequent intervals by staff in NICU. However, many patients in the NICU are comatose and exposed various medications (neuromuscular blocker, sedative drug etc.) so they are not easily evaluated for a detailed neurologic status. Monitoring of critically ill neurologic patients is important and requires correct interpretation of every change ahead of secondary brain damage. Many monitoring techniques are available to provide crucial, real-time information about brain performance. Monitoring of ICP changes and cerebral blood flow monitoring are the main themes of this review. We summarize neuromonitoring in the NICU and will discuss what, how and why to measure the important parameters timely. J Neurocrit Care 2008;1 Suppl 1:S25-S31 KEY WORDS: Monitoring NICU Neurocritical care. 서 론 가장중요한 NICU 모니터링의목적은손상된세포환경에적합하고신경학적회복을최대화할수있으면서도생리적상태에가장가까운최소침습적인방법으로환자의작은변화를감지해내는것이다. 기도삽관상태에서수면진정제나신경근육차단제등의사용하에의식의저하가있는환자들이대부분인 NICU에서신경학적검사만으로는환자의상태를모니터링하는것이어렵다. 또한신경학적검사는자주시행되어야하지만환자의상태변화가선행한후에시행되는성향을지니고있다. 그러나모니터링은병적현상이발생하기전에선행하여환자에게어떤 Address for correspondence: Sea Mi Park, MD Department of Neurology, College of Medicine, University of Ulsan, Asan Medical Center, Pungnap 2-dong, Songpa-gu, Seoul , Korea Tel: , Fax: 변화가일어나고있는지를감지할수있다. 물론급박한혈동학적또는대사적불균형상태에있는환자들역시임상적으로나과학적으로이상적으로환자의변화를찾아내는것이어려울수있지만타당하고효과적인모니터링을통하여우리가환자의변화를섬세하게감지해낼수만있으면뇌의이차적인손상의가능성을알수있게되어이를예방하고치료할수있게될수있다. 또한, 새로운모니터링의개념이나최근개발되어사용되고있는모니터링방식을잘알고사용한다면보다더빠른시간안에환자의섬세한변화를감지할수있고적합한 NICU 치료가가능하여환자의예후를좋게할것이다. 우리는 NICU 모니터링기술의발전의초석이되었고뇌의관류의증감과밀접한관련이있고비교적흔하게임상적으로이용되고있는뇌압, 뇌혈류, 대뇌산소포화도의모니터링을중심으로어떻게무엇을모니터링하는것인지살펴보겠다. Copyright c 2008 The Korean Neurocritical Care Society S25

2 J Neurocrit Care 2008;1 Suppl 1:S25-S31 각론 뇌압의모니터링뇌압의증가는뇌실질의압력의증가나뇌혈류와뇌척수액의순환의이상등의다양한질병들에서발생할수있으며역동적으로변하기때문에잘알려져있듯이지속적인뇌압의확인이필요하다. 뇌실또는뇌의실질내에위치한모니터링기구로주로는침습적인방법으로모니터링하게되는데종류에는뇌실카테터 (EVD), 카미오 1 등이있다. 경막하또는경막외에위치하는기구 ( 코드맨마이크로센서등 ) 는상대적으로흔하게사용하고있지않다. 2 뇌실질내부의마이크로센서도감염이나국소출혈의위험이상대적으로낮지만시간이지남에따라뇌실질내에서잘움직이는경향이있어부정확하게측정되는경향이있다. 이러한경향은 EVD 카테터에서는잘나타나지않아뇌압모니터링에있어 EVD가가장많이사용되고있다. 3 나아가 EVD 카테터는뇌척수액의배액을가능하게하여치료적인효과도함께있다. EVD 모니터링시에관찰할수있는뇌압의파형은뇌의순응도를측정함에있어중요한진단적인가치를갖는다. 뇌의순응도는이러한뇌압에대한뇌의보상능력은뇌압과뇌의내부공간의부피의변화와관계를갖는데가장단순하게뇌압변화에따른순응도를그래프로나타내면 3가지구역 (RAP=0; flat zone, RAP=1; poor compensatory reserve, RAP<0; exponential zone) 으로나누어진 다 (Fig. 1). 4 실제환자의모니터에서관찰되는뇌압의개개의파형자체도역시뇌의순응도를반영하는데이를해석하는데있어뇌압의파형이진단적으로이용될수있다. 파형내에서두번째피크가첫번째피크보다더많이상승된경우에뇌압의증가와뇌의순응도의감소가있는것으로해석된다. 5 오랜시간모니터링중에 Plateau 파형 은갑작스런뇌압의증가가 50~100 mmhg 정도까지 5분에서 20분간지속되는경우로정의되는데이현상은뇌혈류량의항상성으로다시갑작스런뇌압의감소가뒤따르게된다 (Fig. 2). 6 이러한현상의모니터링팁의잘못된위치에의해유발되기도하므로그러한기술적오류를고려하여해석에주의하여야하고전신적으로도뇌압과그의파형을해석에있어혈압과뇌혈관의반응이주요한요인으로작용하기때문에 ICP Critical ICP RAP=0 Good compensatory reserve RAP=1 Poor compensatory reserve Pulsatile cerebral blood volume FIGURE 1. Pressure-Volume curve of ICP. RAP<0 Deranged Cerebrovascular reactivity Pressure response-icp pulse amplitude ICP (mmhg) 60 a) ICP recording b) ABP recording 160 Termination ABP (mmhg) c) Serial Mean ICP d) Serial Mean ABP 100 ICP (mmhg) 20 ABP (mmhg) 80 Termination Onset 80 e) Serial Mean CPP f) Serial HMF 5 CCP (mmhg) Time (min) HMF (Hz) Time (min) FIGURE 2. Plateau wave. ICP: intracranial pressure, ABP: arterial blood pressure, CPP: cerebral perfusion pressure. S26

3 Monitorings in NICU SM Park 혈관의확장이있는신체적상황이라든지갑작스런혈압의변화가있는상황에서의 Plateau 파형 에대하여해석에있어주의해야한다. 6 뇌압의모니터링기구의원리와삽입되는해부학적위치는 Fig. 3-5에서알수있다. 대뇌산소포화도및대사량에대한모니터링 NICU 의치료의가장중요한부분이뇌의허혈성손상에대한이차적인손상을예방하는일이다. 흔하게세가지의뇌의산소포화도를모니터링하는방법이이용되고있는데정맥산소포화도측정법, Near-infrared spectroscopy 방법, 뇌조직산소장력측정법이다. 5-cm mark 정맥산소포화도측정법은 jugular venous bulb에산소포화도측정기를삽입하여그팁이 bulb 에정확하게위치하는지 x-ray 로확인을 (Fig. 6) 하고혈액이순환후에돌아오는양 (SjvO 2 ) 을지속적으로모니터링한다. 7-9 이산소포화도측정기는자기공명영상의시행이가능하다. 정상적인 SjvO 2 는 55~69% 로 7 이것은뇌의산소도달양에서뇌의대사를위한산소요구량을빼주면나오는수치이다. 그래서이수치는정해진적혈구의농도에서뇌관류량의직접적인정보를제공하여주며뇌의산소도달양의저하와뇌의대사증가로인한산소의요구량증가를동시에반영하므로 {CMRO2=CBF (arterial O2 content-sjvo 2 )} 만약이수치가높다면 CMRO2 의증가상태에서관류 (CBF) 가보상적으로증가되고있지않는상황이다. 그러나절대적인값보다는수치의경향이중요하다 (Fig. 7). 10,11 임상 Fiberoptic catheter FIGURE 3. Intraparenchymal monitoring. Drip chamber fixed at desired level (typically 15 cm H2O) Stopcock leveled at ear FIGURE 6. Lateral neck radiography demonstrating catheter tip position (black arrow). FIGURE 4. Intraventricular monitoring. FIGURE 5. Epidural monitoring. FIGURE 7. Clinical guidelines for jugular bulb saturation monitoring. From J Clin Neurophysiol 2005;22(2) April: S27

4 J Neurocrit Care 2008;1 Suppl 1:S25-S31 적인이용은환자의예후예측에도움을주고뇌압의조절을위한과호흡을유발하는경우그정도를알수있도록도와주며수술후또는수술중관류저하의모니터링에이용될수있어 실제로동맥혈전제거술과같은모니터링이필요한수술에효과적으로적용될수있다 (Fig. 8). 11 Near-infrared spectroscopy 는헤모글로빈, 데옥시헤모글로빈의농도를측정함으로써뇌의산소포화도와혈액의부피의변화를모니터링할수있게한다 (Fig. 9). 15,16 적외선은조직에따라다른파장의투과력을보인다. 뇌의산소측정기는그림과같이두개골에직접닿아있고탐식자를통하여헤모글로빈의산도포화도를정맥에흡수되는파장정도에의하여측정한다. 정상치는 60~80% 17 정도로보고되어있다. 그러나이장치의단점으로는경막외혈종과같은질환에서는측정이부정확하다는점을들수있다. 18 그외에도마이크로카테터를뇌실질에넣어뇌실질의직접적인산소의포화량을측정하는뇌조직산소장력측정법이이용되고있지만제현성과신뢰도에대한검증이필요하다. 19,20 뇌의대사량을모니터링하는방법으로는대뇌미세투석법이있다 (Fig. 9). 이것은세포외분획에생화학적인환경을모니터링하는방법 21 으로투석막이달린모세혈관만 Light source Scalp Bone FIGURE 8. Near-infrared spectroscopy. Detectors 큼가는탐식자를관심이있는뇌의영역에삽입하여탐식자안으로신체의전해질등의환경과비슷한조성을갖는링거액을주입하고세포외공간과링거액사이에있는투석막에서는확산현상이일어나게된다. 22 그이동을탐식자가감지하여세포외액의혈당, 아미노산, 싸이토카인, 약물농도, 신경전달물질등다양한물질에대한정보를간접적으로알수있게된다 뇌혈류의모니터링생리학적으로신경세포는일정수준이하의혈류공급이이루어지지않으면산소를사용하는대사에서산소를사용하지않는대사로전환하게되는데 27 이러한조심스러운신경세포의적응현상은손상되어대사적요구가많은뇌조직에서이차적인손상을유발할가능성이높아진다. 그외에서경막하출혈과같은혈관연축의위험성으로인한합병증의예방이나신경외과의혈관수술과정이나수술후에생길수있는변화를알기위하여뇌혈류의모니터링이중요하다. 최근까지도지속적인실시간뇌혈류의측정은이루어지지않고있다. 가장흔하게는제논조영 CT가비침습적으로뇌혈류측정을가능하게하는모니터링수단으로이용되고있지만그효용성과해석에대하여는여러가지논쟁이있어왔다 경두개초음파가지속적인혈류의속도의측정을가능하게하지만초음파를보낸특정한혈관에만국한된정보를얻을수있기때문에제한점이있다. 최근들어경두개초음파와같은원리로써레이저를사용한레이저도플러속도측정기는두개골의 burr hole 을통하여뇌의실질내부로직접적으로탐식자가삽입되어레이저로적혈구의속도와농도를동시에모니터링할수있는기구로역시적은샘플볼륨의한계점을갖고있다 또한가지새로운모니터링방식으로써미스터법은열의확산을이용하여국소적인뇌혈류의양을측정하는방식으로작은탐식자로최소침습적인방식으로섭씨 39도이상의열을발생시기는작은탐식자를이용하여열의확산 FIGURE 9. Photograph of a triplelumen transcranial bolt for fixation of the microdialysis probe (top panel), along with an oxygen sensor (bottom panel). From J Neurosurg 1998;89: S28

5 Monitorings in NICU SM Park 의정도를측정하여뇌혈류양을모니터링을한다 이새로운방식의뇌혈류의측정은뇌경막하출혈환자와신경외과수술과정중에서모니터링을위하여잘적용될수있다고보고된바가있다. 43,44 경두개초음파경두개초음파는뇌혈류의간접적인측정으로혈류와파형으로뇌혈류를추론하는방법이다. 혈류의측정은시간별평균치를구하고입사각을조정하여각단면의정보를종합하여혈류의부피에대한간접적인정보를얻을수있다. 또한경동맥과척추동맥의혈류양을더하여전체적인뇌혈류의부피를예측할수있다. 45 환자들에게모니터링을위한헤드셋을계속유지하기에어려움이있기때문에대부분의 NICU에서는모니터링보다는경막하출혈환자에서반복적인측정을선호한다. 46 가장큰단점으로는검사자의경험이매우중요하며이에따라검사자간의일치도가떨어진다는점이다. 47 지속뇌파모니터링 NICU에서뇌파검사의장점은비침습적인검사로경련, 의식의수준결정, 뇌손상의범위를결정하는데있어필수적인진단법이며지속뇌파모니터링은다른모니터링 방법과함께사용될수있는가장바람직한수단이다. 컴퓨터에서다량의정보가자동모니터링과자동저장이가능해지면서종이도없이다량의정보를얻게되었지만검사의시행과해석에있어서여전히노동집약적인검사로잘훈련된인력과팀체제가필요하다. 결론 모니터링의활용은몇가지기본개념에서출발하여야한다. 첫째로가능한뇌손상의범위내에서최소침습적인방법이이루어져야한다. 예를들어급성전뇌반구뇌경색의뇌압모니터링의경우손상된뇌의범위내에서이루어지는것이바람직하다. 손상된뇌의주변은정확하게조직의상태를반영한다고말하기어려우며회복가능한조직의손상을가져올수있다. 두번째로, 모니터링의해석에주의해야하는데기술적인문제가항상고려되어야하며보고되어있는절대적인정상치 (Table 1) 48 보다는지속적인모니터링과정중에나타나는상대적인경향에관심을두어야한다. 세번째로, 특정원인이있는뇌손상이있는경우원인에대한특정기능의모니터링이필요할수있다. 그예로는급성수두증으로인하여뇌압이증가하게되어전두엽기능손상이급속히악화된뇌압을정상화하는되 TABLE 1. Multimodal monitoring reference Values for cerebral Health and pathologic condition From J Clin Neurophysiol 2995;22(2) April:124-7 S29

6 J Neurocrit Care 2008;1 Suppl 1:S25-S31 는경우는급성기일지라도전두엽기능같은뇌의기능적인평가가조직의손상과회복의정도를반영하는데있어중요한정보를줄수있다. 넷째로발생할수있는이차적뇌손상의예측을기반으로모니터링의방법의타당성과효용성에대한연구결과들을고려하여한가지또는여러가지조합의모니터링방법이결정되어야한다. 그예로는급성전뇌반구뇌경색으로아직뇌부종이일어나지는않았지만부종또는출혈이발생할위험성이있는경우예방적으로뇌압의모니터링을일찍시작하는것에대한유용성과타당성은현재잘알려져있지만뇌경막하출혈의경우에는뇌압의모니터링을일찍시작하는것의효과에대한입증된결과는없다. 혈관연축을모니터링하기위한초음파혈류검사나손상된조직의뇌파의모니터링이더효과적인것으로알려져있다. 다섯째로모니터링을통하여얻은정보를잘못해석하는것을주의하여야한다. 증상이없는환자에서갑작스런뇌압의증가는뇌실질내에위치한모니터링기구의위치가변하면서발생할수있다. 이러한경우에는뇌압의파형과환자의다른신체적상태를함께고려하는것이판단에중요하다. 미래 최근뇌손상을최소화하면서보다생리적인상태의모니터링을가능하게할수있는비침습형모니터링도구의필요성이강조되면서다양한원리의대뇌정맥산소포화도측정, 정맥혈류측정장치의계발과함께뇌압측정의경우에는고막의압력측정장치, 중심망막정맥압측정장치, 동공의수축속도를측정하는장치들이계발되어사용되고있다. 48 이러한배경에서다양한모니터링도구의조합으로단점을극복하여활용도를높이는것이는것이바람직하다. 그러나다양한모니터링장비의유지는경제적으로나시간적으로소모가많으며장비의유지를위하여많은인력과교육이필요하다. 또한수많은기계의알람시스템으로인한소음문제와환자의스트레스또한간과할수는없다. 따라서모니터링의다양성이개별환자에모두적용되기는힘들지만이러한접근이한가지모니터링으로부터발생할수있는오류와단점의극복에있어상호보완적인역할을할수있을것이다. 국내에서장비의보급이어렵고충분한경험이축적되지않았지만이러한다양한기구들의특성을이해하고열정을가지고활용한다면 NICU 모니터링의새로운발전을기대할수있을것이다. REFERENCES 1. Weinstabl C, Richling B, Plainer B, Czech T, Spiss CK. Comparative analysis between epidural (gaeltec) and subdural (camino) intracranial pressure probes. J Clin Monit 1992;8: Eide PK. Comparison of simultaneous continuous intracranial pressure (icp) signals from icp sensors placed within the brain parenchyma and the epidural space. Med Eng Phys 2008;30: Hong WC, Tu YK, Chen YS, Lien LM, Huang SJ. Subdural intracranial pressure monitoring in severe head injury: clinical experience with the codman microsensor. Surg Neurol 2006;66 Suppl 2:S8-S Balestreri M, Czosnyka M, Steiner LA, Schmidt E, Smielewski P, Matta B, et al. Intracranial hypertension: what additional information can be derived from icp waveform after head injury? Acta Neurochir (Wien) 2004;146: Czosnyka M, Pickard JD. Monitoring and interpretation of intracranial pressure. J Neurol Neurosurg Psychiatry 2004;75: Hamer J, Alberti E, Hoyer S, Wiedemann K. Influence of systemic and cerebral vascular factors on the cerebrospinal fluid pulse waves. J Neurosurg 1977;46: Algotsson L, Messeter K, Nordstrom CH, Ryding E. Cerebral blood flow and oxygen consumption during isoflurane and halothane anesthesia in man. Acta Anaesthesiol Scand 1988;32: Alten J, Mariscalco MM. Critical appraisal of perez et al: Jugular venous oxygen saturation or arteriovenous difference of lactate content and outcome in children with severe traumatic brain injury. Pediatr Crit Care Med 2005;6: Heran NS, Hentschel SJ, Toyota BD. Jugular bulb oximetry for prediction of vasospasm following subarachnoid hemorrhage. Can J Neurol Sci 2004;31: Kadoi Y, Saito S, Takahashi K, Fujita N, Goto F. Jugular venous oxygen saturation during mild hypothermic versus normothermic cardiopulmonary bypass in elderly patients. Surg Today 2004;34: Kubo T, Nakagawa I, Hidaka S, Uesugi F, Hamaguchi K, Kato T. Relationship between regional cerebrovascular oxygen saturation and jugular bulb oxygen saturation during carotid endarterectomy. Masui 2005;54: Nagdyman N, Fleck T, Schubert S, Ewert P, Peters B, Lange PE, et al. Comparison between cerebral tissue oxygenation index measured by near-infrared spectroscopy and venous jugular bulb saturation in children. Intensive Care Med 2005;31: Paino R, Milazzo F. Jugular bulb oxygen saturation in hypothermic circulatory arrest procedures: a possible role of continuous monitoring. J Cardiothorac Vasc Anesth 2008;22: Uesugi F, Nakagawa I, Hidaka S, Kubo T, Okamura K, Kato T. Evaluation of cerebral oxygen balance during normothermic cardiopulmonary bypass using jugular oxygen saturation. Masui 2005;54: Abdul-Khaliq H, Schubert S, Troitzsch D, Huebler M, Boettcher W, Baur MO, Lange PE. Dynamic changes in cerebral oxygenation related to deep hypothermia and circulatory arrest evaluated by nearinfrared spectroscopy. Acta Anaesthesiol Scand 2001;45: Adelson PD, Nemoto E, Scheuer M, Painter M, Morgan J, Yonas H. Noninvasive continuous monitoring of cerebral oxygenation periictally using near-infrared spectroscopy: a preliminary report. Epilepsia 1999;40: Misra M, Stark J, Dujovny M, Widman R, Ausman JI. Transcranial cerebral oximetry in random normal subjects. Neurol Res 1998;20: Wahr JA, Tremper KK, Samra S, Delpy DT. Near-infrared spectroscopy: theory and applications. J Cardiothorac Vasc Anesth 1996;10: Perez-de-Sa V, Cunha-Goncalves D, Nordh A, Hansson S, Larsson A, Ley D, et al. High brain tissue oxygen tension during ventilation with 100% oxygen after fetal asphyxia in newborn sheep. Pediatr Res In press S30

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