00-본문외-앞(9-2)

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1 KOR J CEREBROVASCULAR SURGERY June 2OO7 Vol. 9 No 2, page 투석을시행받는환자에서발생한자발성두개내출혈에대한임상적고찰 순천향대학교의과대학신경외과학교실구선호ㆍ박형기ㆍ김범태ㆍ장재칠ㆍ최순관 Spontaneous Intracerebral Hemorrhage in the Patients Undergoing Dialysis Therapy Sun Ho Koo, MD, Hyung Ki Park, MD, Bum Tae Kim, MD, Jae Chil Chang, MD, Sun Kwan Choi, MD Department of Neurosurgery, College of Medicine, Soonchunhyang University, Seoul, Korea ABSTRACT Objective : The management of spontaneous intracerebral hemorrhage in the patients with chronic renal failure is frequently influenced by factors such as coagulopathy, electrolyte imbalance, hemodialysis and malnutrition. This study aimed at evaluating the aggravating factors in the patients with intracerebral hemorrhage and who also underwent dialysis therapy. Methods : Eight patients with chronic renal failure and who suffered from intracerebral hemorrhage were investigated. The clinical features, the location and amount of the hematomas, the treatment methods and the hemodialysis patterns were compared. Results : The locations of hematoma were the subcortex (3 cases), putamen (2 cases), thalamus (2 csaes), and intraventricle (1 case), respectively. The types of dialysis were hemodialysis (6 cases), peritoneal dialysis (1 case), and a continuous form of renal replacement therapy (1 case). The average GCS was 8.4 (range: 5-14). All the patients underwent surgical treatment, which were EVD (3 cases), streotactic hematoma aspiration (2 cases), and decompressive craniectomy with hematoma removal (3 cases). The clinical outcomes were good recovery (1 case), moderate disability (1 case), a vegetative state (1 case) and death (5 cases). For the cases of death, the factors for aggravating the outcome were brain swelling (1 case), rebleeding (2 cases), aspiration pneumonia (1 case), and uncontrolled bleeding during the operation (1 case). The poor outcomes of intracerebral hemorrhage in the dialysis failure patients were caused by poor consciousness during bleeding, (ED note: this word ictus seems to makes no sense here.) and a high risk of rebleeding and brain edema due to anticoagulant and dialysis. Conclusion : We suggest that consideration of the patients' medical problems and an adequate environment for dialysis should be taken into account to achieve favorable patient outcomes. (Kor J Cerebrovascular Surgery 9(2):111-6, 2007) KEY WORDS : Intracerebral hemorrhage Chronic renal failure Hemodialysis 서 우리나라의만성신부전증환자의발생빈도는대한신장학회조사에따르면 1986년에등록된말기신부전환자가 2534명에서 2005년 12월말에는 4만 4333명으로 15배이상증가하 론 논문접수일 : 2007 년 5 월 16 일심사완료일 : 2007 년 6 월 18 일교신저자 : 박형기, 서울특별시용산구한남동 순천향대학교병원전화 : (02) 전송 : (02) phk007@hosp.sch.ac.kr 였으며, 이런만성신부전증의가장흔한원인은당뇨, 고혈압, 만성사구체신염순으로 14) 이중당뇨, 고혈압은신장뿐만아니라심혈관계에영향을미쳐만성신부전증환자에서뇌졸중및심혈관계질환의발생률은정상인에비해 5에서 30배에이른다고보고되어있다. 3)7)9)12) 만성신부전증환자에서발생된두개내출혈은만성빈혈, 혈액응고장애, 전해질불균형및투석시발생하는저혈압과항응고제의사용등치료시상당한제한점이있으며빈번한합병증을남길수있어그예후는또한좋지않은것으로보고되어있다. 10) 이에우리는그동안본원에내원한만성신부전증을동반한자발성두개내출혈환자에대한임상적고찰과문헌고찰 111

2 투석을시행받는환자에서발생한자발성두개내출혈에대한임상적고찰 을통하여악화요인의분석을통하여효과적인치료방법을찾고자본연구를시행하였다. 대상및방법 본연구는 2001년 5월부터 2006년 5월까지본원에내원하여전산화단층촬영에서두개내출혈로진단된환자중혈액또는복막투석을시행받는만성신부전증환자를대상으로하였다. 이중외상에의한뇌출혈이나의식저하가다른전신적원인에기인한다고판단된경우를제외한자발성두개내출혈환자 8명을대상으로후향적분석을시행하였다. 임상양상으로연령및성별분포, 내원시임상증상및상태, 과거력, 투약력그리고뇌전산화단층촬영에서혈종의위치, 크기, 수두증여부등과예후와의관계를조사하였다. 수술적요소로는수술 방법및출혈량, 그리고만성신부전증의내과적문제와혈액투석과예후와의관계등에대한임상분석을시행하였다 (Table 1). 결과 1. 임상양상 8명의환자중남자가 5명여자가 3명이었고평균연령은 60세 (46~67) 였다. 내원시의식이혼미상태이하, 글라스고우혼수척도상 5점이하인경우가 8례중 4례 (50%) 로비교적발생초기에중증의상태를보였으며, 평균은 8.4점이었다. 고혈압은 7례 (86%), 당뇨는 6례 (75%) 에서확인되었고, 5례 (63%) 에서는고혈압과당뇨가함께동반되어있었다. 항혈소판제를복용하는사람이 2명 (25%) 이었다. 치료기간내에투 Table 1. Clinical and radiological features of patients with spontaneous intracerebral hemorrhage, undergoing dialysis therapy No Sex Age GCS Past hitory Site of hemorrhage Amount of hemorrhage Treatment GOS 1 F DM, HTN IVH 56cc EVD D 2 F 65 5 DM, HTN Subcortex & IVH 41cc EVD D 3 M 46 5 HTN Lt putamen & IVH 56cc decomp & removal of hematoma VS 4 M HTN Subcortex 40cc streotactic aspiration MD 5 F DM Rt putamen 34cc streotactic decomp D 6 M 54 5 DM, HTN Rt thalamus & IVH 50cc EVD D 7 M 67 5 DM, HTN Lt thalamus & IVH 86cc decomp & removal of hematoma D 8 M 54 9 DM, HTN Subcortex & IVH 60cc craniotomy & removal of hematoma GD GCS: Glasgow coma scale, DM: diabetus mellitus, HTN: hypertension, GOS: Glasgow outcome scale, IVH: intraventricular hemorrhage, EVD: extraventricular drainage, decomp: decompressive craniectomy, D: death, VS: vegetative state, MD: moderate disability, GD: good recovery Table 2. Characteristics of past medical history and cause of deterioration No GCS GOS Amount of bleeding Dialysis Time of Cause of Drug Hx in operation type deterioration deterioration 1 10 D below 50cc HD after dialysis aspirin rebleeding 2 5 D below 50cc HD - - aspiration pneumonia 3 5 VS 400cc HD - - brain edema 4 14 MD below 50cc CRRT D below 50cc HD after dialysis - rebleeding 6 5 D below 50cc PD gradually aggravate - brain edema 7 5 D 1500cc HD after operation aspirin massive bleeding during operation 8 9 GD 400cc HD GCS: Glasgow coma scale, GOS: Glasgow outcome scale, D: death, VS: vegetative state, MD: moderate disability, GD: good recovery, HD: hemodialysis, CRRT: continuous renal replacement therapy, PD: peritoneal dialysis 112 Kor J Cerebrovascular Surgery 9(2):111-6, 2007

이중뇌실질내출혈중뇌실내출혈이함께발생한경우가 5례 (63%) 이며초기출혈량이 50cc 이상인중증인경우가 5례 (63%) 로조사되었다 (Table 1). 3. 수술방법수술의시기및방법의선택은비만성신부전환자와동일하게적용된것으로조사되었다.

3 구선호ㆍ박형기ㆍ김범태ㆍ장재칠ㆍ최순관 석의형태는혈액투석이 6례, 복막투석이 1례, 지속적신대치요법이 1례에서시행되었다. 모두혈액응고검사는정상이었고혈중전해질도정상범위를유지하고있었다. 치료결과는경쾌 1례, 중등도장애 1례, 식물상태가 1례이었고나머지 5명은모두사망하였으며항혈소판제를복용하였던 2례모두재출혈및과다출혈로사망하였고지속적신대치요법 (Continuous Renal Replacement Therapy:CRRT) 을시행하였던경우는중등도장애의결과가관찰되었다 (Table 1). 2. 방사선학적소견출혈부위는피질하 3례, 피각부 2례, 시상부 2례, 그리고뇌실내출혈이 1례이었다. 이중뇌실질내출혈중뇌실내출혈이함께발생한경우가 5례 (63%) 이며초기출혈량이 50cc 이상인중증인경우가 5례 (63%) 로조사되었다 (Table 1). 3. 수술방법수술의시기및방법의선택은비만성신부전환자와동일하게적용된것으로조사되었다. 수술방법은뇌실액배액술 3 례, 감압술및혈종제거술 2례, 뇌정위혈종배액술 2례, 두개골절개술및혈종제거술 1례이었으며, 수술기록지고찰상출혈전항혈소판제사용으로수술시과다출혈 (1500cc) 을보인 1례를제외하고지혈이상소견은없었다 (Table 1, 2). 4. 악화요인분석치료결과가좋지않은요인들로는첫출혈시글라스고우혼수척도상 5점이하로중증이 8례중 4례로이중 3례는사망하였으며 1례는식물상태의치료결과를보였다. 그외의요인으로는재출혈 2례, 뇌부종 2례, 수술중과다출혈 1례그리고흡입성폐렴 1례가있었다. 재출혈 1례는항혈소판제 재를복용의과거력을가지고있었고 1례는투석중재출혈이발생하였다. 뇌부종 2례는모두투석후뇌부종이악화된것으로조사되었으며투석형태는혈액투석과복막투석각각 1 례이었다. 수술시과다출혈 (1500cc) 를보인 1례는출혈전항혈소판제를복용한병력을가지고있었다. 종합하면치료시악화요인들은투석과연관된뇌부종과재출혈그리고항혈소판제복용과연관된재출혈및수술중과다출혈로조사되었다 (Table 2). 증례 5 67세여자환자로기면상태에좌측편마비로내원하였다. 글라스고우혼수척도상 13점 (E3V4M6) 이었고, 과거력상당뇨가약 20년간있었으며당뇨합병증에의한만성신부전으로 10년전부터혈액투석을받고있었다. 혈액검사상빈혈은관찰되지않았으며크레아티닌은 8.4mg/dL, 칼륨은 5.7mmol/L로증가되었고혈액응고검사상정상소견이었다. 단층촬영을시행하였으며우측기저부에 34cc 정도의뇌실질내출혈이관찰되었다. 내원 2일째뇌정위혈종배액술을시행하였으며수술시 30cc 흡입하였다. 수술후혈압은정상으로유지되었고, 수술 2일째투석중갑작스런의식저하소견이보여컴퓨터단층촬영을시행하였으며뇌출혈이 65cc로재출혈소견이보였다 (Fig. 1). 응급으로갑압적개두술및혈종제거술을하였고수술후에도반혼수상태로지속되다가호흡마비로수술 3일째사망하였다. 증례 8 54세남자환자로혼미한의식상태로내원하였다. 글라스고우혼수척도상 9점 (E2V2M5) 이었고, 과거력상당뇨와고혈압이있었으며 1년전부터만성신부전으로혈액투석중이었다. 혈액검사상혈색소는 9.6g/dL로빈혈소견및크레아티닌 Fig. 1. Case 5. Preoperative computed tomography (A) shows right putaminal hemorrhage. Postoperative computed tomography (B) shows increased amount of putaminal hemorrhage after stereotactic hematoma aspiration. Kor J Cerebrovascular Surgery 9(2):111-6,

투석을시행받는환자에서발생한자발성두개내출혈에대한임상적고찰 은 12.5mg/dL 칼륨은 5.7mmol/L로증가되었고혈액응고검사상정상소견이었다. 단층촬영을시행하였으며우측두정부-후두부에약 60cc 정도의뇌실질내출혈및뇌실내출혈이관찰되었다 (Fig. 2). 응급수술을시행하였으며두개골절제술과혈종제거술을시행하였다. 수술후다음날부터혈액투석을하였으며헤파린은사용하지않았다.

또한만성신부전증으로인한에리스로포이에틴감소는만성적인빈혈과혈소판기능장애및활성인자 Ⅲ 감소로인한과다출혈을유발할수있다. 14) 이러한출혈성성향으로인하여두개내출혈빈도증가와출혈정도가일반환자에비해악화될수있으며본연구에서도 50% 에서초기출혈이중증으로발생된것으로조사되었다. 투석치료를받고있는환자들은치료에도제한이많이따르게된다.

4 투석을시행받는환자에서발생한자발성두개내출혈에대한임상적고찰 은 12.5mg/dL 칼륨은 5.7mmol/L로증가되었고혈액응고검사상정상소견이었다. 단층촬영을시행하였으며우측두정부-후두부에약 60cc 정도의뇌실질내출혈및뇌실내출혈이관찰되었다 (Fig. 2). 응급수술을시행하였으며두개골절제술과혈종제거술을시행하였다. 수술후다음날부터혈액투석을하였으며헤파린은사용하지않았다. 혈압은정상혈압내에서유지되었고환자는차츰의식을회복하여명료한상태 ( 글라스고우혼수척도 14점 ) 로퇴원하였다. 토론 만성신부전증은여러가지요인에의해발생하는데그중가장흔한원인은당뇨, 고혈압이며이는심장및뇌혈관의동맥경화증형성에기여하여뇌졸중의발생률을일반환자에비해 5~30배증가시키는것으로알려져있다. 또한만성신부전증으로인한에리스로포이에틴감소는만성적인빈혈과혈소판기능장애및활성인자 Ⅲ 감소로인한과다출혈을유발할수있다. 14) 이러한출혈성성향으로인하여두개내출혈빈도증가와출혈정도가일반환자에비해악화될수있으며본연구에서도 50% 에서초기출혈이중증으로발생된것으로조사되었다. 투석치료를받고있는환자들은치료에도제한이많이따르게된다. 특히두개내압력조절을위해가장먼저선택되는만니톨및이뇨제등은만성신부전증환자에있어가장큰제약의요소중하나로이뇨제는만성신부전증환자에게는효과가없을뿐아니라만니톨투약후에는잦은투석이필수적이기때문이다. 또한수술을요한경우에도빈혈및출혈성경향으로수술결정이어렵고장기간투병으로인한환자및보호자입장에서도수술치료의동의가쉽지않아중요한수술적시기를놓쳐버리는경우도있다. 이러한예후를불량하게하 는요인들로인해보고된사망률은전신질환없이뇌출혈만있는경우 (7~58%) 에비해 53~79% 로상당히높다. 4)6)13) 수술적치료에대한적응증은아직논란의여지가많다. 본원에서경험한 8례에서는모두일반환자와같은적응증을가지고수술을하였으며그중5명이사망하였다. 이에비해 Murakami 등 10) 은만성신부전증환자 36명을치료하였으며그중 3례만뇌정위혈종흡입술을시행하였고뇌실외배액술를 2례시행하였으며나머지는모두보전적치료를하여전체사망률은 61.1% 로보고하였다. 이는본연구와큰차이는보이지않았으며이는환자의치료결과의악화요인이수술적방법보다는초기출혈이중증인점, 출혈경향이높은점그리고투석의문제점이큰것으로추측된다. 수술적적응증에대해서는아직명확하지는않으나출혈량이많고뇌부종이동반되어있는경우에는감압적개두술이필요하지만가능한수술부위를적게하여수술시간및수술중발생하는실혈량을최소화하는방법은환자에게나수술자에게있어보다부담이적은하나의방법으로생각할수있다. 투석을시행받는만성신부전증환자에서신경외과적으로고려해야할내과적인문제점이몇가지있다. 첫째는뇌압조절을위한보전적치료다. 당뇨및고혈압이동반된경우가많으므로이차적손상을예방하기위해혈당조절및혈압조절이필요하며심폐기관에대한검사도필요하다. 적당한과호흡및혈중나트륨농도유지는삼투압차에의한뇌부종방지에도움이된다. 만성신부전증환자에대한만니톨용량은문헌상정확하게보고된바는없으나삼투성이뇨제로써두개내부종을혈액내로이동시키고이를다시체외로배출하기위해서지속적인투석과병행되어할것으로생각된다. 본원에입원한환자에서도심한전해질불균형이있던 1례를제외하고선일반인과같은용량을사용, 혈액투석이나지속적신대치요법 (CRRT) 과병행하였으며주기적인투입 / 배출량평형및 Fig. 2. Case 8. Preoperative computed tomography (A) shows subcortical intracerebral hemorrhage on right patrieto-occitipal lobes with intraventricular hemorrhage. Postoperative computed tomography (B) shows successful removal of intracerebral hemorrhage and improved midline shift. 114 Kor J Cerebrovascular Surgery 9(2):111-6, 2007

5 구선호ㆍ박형기ㆍ김범태ㆍ장재칠ㆍ최순관 전해질검사를통하여즉각적인교정을시도함으로써만니톨의사용은치료결과의악화요인으로조사되지는않았다. 둘째는투석과연관된문제점들로투석방법에는혈액투석및복막투석, 지속적신대치요법등이있으며각각의장단점이존재한다. 혈액투석은만성신부전증환자에게널리시행되는방법이나혈액투석중또는후에발생하는뇌압상승은갑작스런신경학적이상을초래할수있다. 이는요소농도및삼투압에의한뇌척수액과혈액간의차이로발생하며뇌척수액의양적증가및뇌부종을초래하면서뇌압이상승되어나타나게된다. 16) 또한혈액투석시함께주입되는항응고제는출혈부위나수술부위또는두개내압감시부위등에출혈을유발할수있어신중한사용이고려되어야한다. 이와다르게복막투석은상대적으로심혈관계에부담이적으며항응고제의사용도필요없어추가적인출혈에대한위험성도적다. 17) 또한혈액투석후에따르는뇌부종의위험도복막투석에는적은편이다. 8) 그러나몇가지단점이존재하는데혈액투석에비해투석의효과가상대적으로미비하고체내수분배출에있어도비효과적이다. 보통효과적인수분배출은투석시작후 2~3일부터나타나므로급성기환자에게있어적합한방법은아니다. 1)5)10) 지속적신대치요법은중환자실에서신경외과환자에게이용하기에앞서설명한두가지방법보다는효과적으로뇌부종의위험성도적고효과적인수분배출및조절이가능하나항응고제의사용이필요하므로신중한사용이고려되어야한다. 2)11)15) 본연구에서도투석과연관된뇌부종과재출혈이 3례에서관찰되었으며이는중요한치료결과의악화요인으로분석되어투석치료가필요한만성심부전증환자에서발생한두개내출혈의치료시투석방법, 투석시헤파린의사용및혈압조절이매우중요한것으로생각되었다. 이러한내용을종합해볼때투석받은환자가일반환자에비해좋지않은경과를가지는요인을열거해보면첫째, 출혈성경향으로인한대량출혈이빈번하여초기의식상태가좋지않고둘째, 전신상태가좋지못하여다른내과적문제를동반하는경우가많아수술및약물치료시제한이많으며셋째, 투석과연관된재출혈및뇌부종의발생가능성이높다는것이다. 따라서본연구를통하여치료에있어고려하여야할사항으로는동반된내과적문제파악을통하여치료방법을선택하고투석시재출혈과뇌부종을예방하기위해투석시기및약물사용그리고투석방법선택에신중을기하며, 수술적치료시최소한의출혈및시간단축등이좋은예후를이끌어내는데도움이될것으로생각된다. 결론 본연구를통하여투석을시행받는환자에서발생한두개 내출혈에대해치료결과의향상을위해서는적절한투석환경과동반된내과질환에대한충분한인식이중요하며이후추가적인연구가필요할것으로생각된다. 중심단어 : 두개내출혈 만성신부전 투석. REFERENCES 01) Caruso DM, Vishteh AG, Greene KA, Matthews MR, Carrion CA: Continuous hemodialysis for the management of acute renal failure in the presence of cerebellar hemorrhage. Case report. J Neurosurg 89:649-52, ) Davenport A: Is there a role for continuous renal replacement therapies in patients with liver and renal failure? Kidney Int Suppl 72:S62-6, ) Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D: Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 342: , ) Iseki K, Kinjo K, Kimura Y, Osawa A, Fukiyama K: Evidence for high risk of cerebral hemorrhage in chronic dialysis patients. Kidney Int 44: , ) Kanaya H: Result of conservative and surgical treatment in hypertensive intracerebral hemorrhage: Cooperative study in Japan. Jpn J Stroke 12:509-24, ) Kawamuara M, Fukimoto S, Hisanaga S, Yamamoto Y, Eto T: Incidence, outcome, and risk factors of cerebrovascular events in patients undergoing maintenance hemodialysis. Am J Kidney Dis 31: 991-6, ) Kennedy R, Case C, Fathi R, Johnson D, Isbel N, Marwick TH: Does renal failure cause an atherosclerotic milieu in patients with end-stage renal disease? Am J Med 110: , ) Krane NK: Intracranial pressure measurement in a patient undergoing hemodialysis and peritoneal dialysis. Am J Kidney Dis 13:336-9, ) Longenecker JC, Coresh J, Powe NR, Levey AS, Fink NE, Martin A: Traditional cardiovascular disease risk factors in dialysis patients compared with general population: The CHOICE study. J Am Soc Nephrol 13: , ) Murakami M, Hamasaki T, Kimura S, Maruyama D, Kakita K: Clinical features and management of intracranial hemorrhage in patients undergoing maintenance dialysis therapy. Neurol Med Chir(Tokyo) 44:225-32, ) Ronco C, Bellomo R, Brendolan A, Pinna V, La Greca G: Brain density change renal replacement in critically ill patients with acute renal failure. Continuous hemofiltration versus intermittent hemodialysis. J Nephrol 12:173-8, ) Seliger SL, Gillen DL, Tirschwell D, Wasse H, Kestenbaum BR, Stehman-Breen CO: Risk factors for incident stroke among patients with end-stage renal disease. J Am Soc Nephrol 14: , ) Singh R. Prusmack C, Morcos J: Spontaneous intracerebral hemorrhage: Non-Arteriovenous Malformation, Nonaneurysm, in Winn HR: Youmans Neurological Surgery. ed 5, Saunders Co., 2003, pp ) Skerecki K, Green J, Barry M: Chronic renal failure, in Harrison TR: Principles of internal Medicine. ed 16, vol2. McGraw Hill Co., 2005, pp ) Ward DM: The approach to anticoagulation in patients treated Kor J Cerebrovascular Surgery 9(2):111-6,

6 투석을시행받는환자에서발생한자발성두개내출혈에대한임상적고찰 with extracorporeal therapy in the intensive care unit. Adv Ren Replace Ther 4:160-73, ) Winney RJ, Kean DM, Best JJK, Smith MA: Changes in brain water with hemodialysis. Lancet 2:1107-8, ) Yorioka N, Oda H, Ogawa T, Taniguchi Y, Kushihata S, Takemasa A, Usui K, Shigemoto K: Continuous ambulatory peritoneal dialysis is superior to hemodialysis in chronic dialysis patients with cerebral hemorrhage. Nephron 67:365-6, Kor J Cerebrovascular Surgery 9(2):111-6, 2007

노영남

노영남 Purpose: Delayed massive hemorrhages from pseudoaneurysm rupture of the peripancreatic large arteries, after pancreaticoduodenectomy, are fatal. We reviewed the clinical course and outcome of bleeding