Drainage using urokinase for SASDH 저자들은 9명의아급성경막하혈종환자에서국소마취하에천공술후 urokinase를이용한혈종제거술결과를보고하고자한다. 재료및방법 2013년 5월 1일부터 2015년 1월 31일까지본원에서아급성경막하혈종으로수술을시행한

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1 ORIGINAL ARTICLE eissn Yeungnam Univ J Med 2015;32(1): 아급성기경막하혈종치료시천공술후 urokinase 를이용한혈종배액술 김민수, 김성호, 김오룡 영남대학교의과대학신경외과학교실 Burr hole drainage using urokinase for treatment of subacute subdural hematoma Min-Su Kim, Seong-Ho Kim, Oh-Lyong Kim Department of Neurosurgery, Yeungnam University College of Medicine, Daegu, Korea Background: Enlargement of subdural hematomas is relatively rapid in subacute stage of hematoma with clinical deterioration, which eventually necessitates surgery. The purpose of this study is to investigate the feasibility and safety of burr hole drainage using urokinase for management of patients with subacute subdural hematoma (SASDH). Methods: Nine patients with SASDH were treated by burr hole drainage using urokinase. Under local anesthesia a catheter was inserted into the hematoma through a burr hole. Burr hole drainage was followed by hematoma thrombolysis with instillation of urokinase (10,000 units) every 12 hours. Drainage was discontinued when a significant decrease of hematoma was observed on cranial computed tomography. Results: The patients median age was 70 years (range, 62-87). The median Glasgow Coma Scale score before surgery was 15 (range, 11-15). Drainage was successfully performed in all patients. All patients had Glasgow Outcome Scale scores of 5 at discharge. There was no surgery-related morbidity or mortality. Conclusion: A burr hole drainage using urokinase could be a safe, feasible and effective minimally invasive method with low morbidity in treatment of selected patients with SASDHs. Keywords: Subdural hematoma; Trephination; Drainage; Urokinase 서 론 뇌경막과지주막사이에혈종이형성되었을때경막하혈종이라고말하며, 전체두부외상환자의 5-29% 정도에서발생하는것으로알려져있다 [1-3]. 혈종은대뇌피질의동맥또는정맥의파열이나대뇌피질과정동맥사이의교정맥 (bridging vein) 의파열로인해형성되는경우가많다. 항응고제를복용하거나, 혈액질환이있는환자, 뇌수두증의단락술을시행한 Received: March 30, 2015, Revised: May 1, 2015, Accepted: May 10, 2015 Corresponding Author: Min-Su Kim, Department of Neurosurgery, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu , Korea Tel: , Fax: mogumns@daum.net 환자등에서외상이없거나아주경미한외상후에도경막하혈종이발생할수있다 [3-6]. 급성경막하혈종으로신경학적인증상이경미하여보존적인치료를시행하다가수상후아급성기에의식저하, 운동신경마비, 두통등의신경학적인증상의악화소견을보일경우천공술이나개두술과같은수술적인치료를고려해야한다 [1]. 천공술로는혈종을완전히제거하기힘든경우가많고, 개두술로는혈종을완전히제거할수는있으나, 전신마취의합병증및개두술로인한합병증을유발할가능성이있다 [7,8]. 이런아급성경막하혈종환자에서대체치료법으로국소마취하에천공술후 urokinase 를이용하여혈종을제거해보고자하였다. 자발성뇌출혈에서는 urokinase 를이용한뇌정위적혈종흡인술이많이시행되고있으나 [9,10], 아급성경막하혈종에서는현재까지문헌에서발표된예가없다. 이에 8 YUJM VOLUME 32, NUMBER 1, JUNE 2015

2 Drainage using urokinase for SASDH 저자들은 9명의아급성경막하혈종환자에서국소마취하에천공술후 urokinase를이용한혈종제거술결과를보고하고자한다. 재료및방법 2013년 5월 1일부터 2015년 1월 31일까지본원에서아급성경막하혈종으로수술을시행한환자 9명을대상으로후향적조사를하였다. 본연구대상은 (1) 입원당시급성경막하혈종으로신경학적인증상이경미하여보존적인치료를시행하다가수상후아급성기 ( 수상후 4일에서 20일사이 ) 에의식저하, 운동신경마비, 두통등의신경학적인증상의악화소견을보인경우, (2) 뇌컴퓨터단층촬영 (computed tomography, CT) 상경막하혈종이고형의혈괴 ( 고밀도음영 ) 와액상 (fluid) 의혈종 ( 저밀도음영 ) 이혼합된형태를가지는경우, (3) 수술직전시행한글라스고우혼수계수 (Glasgow Coma Scale) 가 9점이상인경우를대상으로하였다. 본연구의배제대상은 (1) 뇌좌상, 경막외혈종, 뇌내출혈, 뇌실내출혈및외상성지주막하출혈이다른두부외상과동반된경우, (2) 이전에시행한개두술, 뇌실배액술, 또는뇌실복막단락등의신경외과수술로인한합병증으로경막하혈종이생긴경우, (3) 수술직전시행한글라스고우혼수계수가 8점이하인경우이다. 수술은앙와위자세로두부를약 15도거상한뒤천공부위가가장높이위치하도록두부를조정하였다. 천공의위치는혈종이가장두꺼운부위에계획하고, 두피에 1% lidocaine 으로국소마취를하고약 3cm 정도절개후전기드릴을이용하여천공을시행하였다. 경막을절개하고혈종의피막을확인한후경막하강에서나오는혈종을확인하고 9 프렌치 배액관을전두부방향으로약 5cm 정도삽입시켰다. 침상에서배액관을따라생리식염수 1mL와 urokinase 10,000 units 의혼합액을주입한후잠궈놓은뒤 2시간뒤열어배액주머니로중력에따라자연스럽게혈종이빠져나가게해주었다. 혈종내로 urokinase 주입을 12시간마다시행하였다. 수술후 2일째시행한 CT를촬영하여남아있는혈종의양을확인한후수술후 2-3일째배액관을제거하였다. 9명환자의나이, 성별, 증상, 두부외상의병력, 기저전신질환의여부, 항혈소판제제나항응고제제약물의복용여부, 혈액검사결과등을포함한임상정보를수집하였으며, 수술직전시행한글라스고우혼수계수를이용하여환자상태를평가하였다. 모든환자의치료결과는글라스고우결과계수 (Glasgow Outcome Scale) 를이용하여평가하였다. 결과 연구대상환자는남자 5명과여자 4명이었으며, 연령분포는평균 70세 (62세에서 87세 ) 로모두고령의환자였다. 사고원인으로는 8명의환자는넘어져서발생하였으며, 나머지한명은원인불명이었다. 5명에서고혈압, 3명에서당뇨가있었으며, 뇌경색환자 6명과심근경색환자 1명에서항혈소판제제를복용중이었다. 수술직전환자의임상증상으로는두통, 실어증, 편마비, 의식저하, 보행장애등이있었고, 수술직전글라스고우혼수계수는 11-15점으로나타났다. 혈액검사상혈액응고와관련이있는혈소판수치, prothrombin time 및 partial thromboplastin time 은모든환자에서정상소견을보였다. 두부외상후증상이악화된시간은평균 12.6 일 (4일에서 20일 ) 이었으며, 수술후퇴원당시글라스고우결과계수는모두 5점으로좋은결과를보여주었다 (Table 1). Table 1. Clinical data for the 9 operative cases of subacute subdural hematoma Case no. Age (year)/ sex Trauma mechanism Medical history Antiplatelet use Symptom Interval between injury GCS and deterioration (day) before surgery GOS at discharge 1 71/F Slip down HT, DM, CI Yes Hemiparesis /M Slip down No No Sensory aphasia /M Slip down CI Yes Sensory aphasia /F Slip down HT, CI Yes Drowsy mentality /M Slip down DM, CI Yes Gait disturbance /F Slip down HT, DM, CI Yes Headache /M Unknown HT, CI Yes Dysarthria Unknown /F Slip down HT, MI Yes Headache /M Slip down No No Hemiparesis GCS, Glasgow Coma Scale; GOS, Glasgow Outcome Scale; CI, cerebral infarction; HT, hypertension; DM, diabetes mellitus; MI, myocardial infarction. YUJM VOLUME 32, NUMBER 1, JUNE

3 Min-Su Kim et al. 모든환자에서감염, 두개강내출혈등의수술과관련된합병증은없었으며, urokinase 사용으로인한다른장기의출혈이나혈액검사상이상소견도없었다. 증례 1 71세여자환자로넘어진후두부외상을입고두통을호소하여응급실로내원하였다. 신경학적으로의식저하, 언어장애, 사지마비및뇌신경장애등의이상소견은없었다. 뇌 CT 상우측전두부및측두부에급성경막하혈종이발견되었으며, 이로인해우측뇌실이약간압박되고있는소견을보였다 (Fig. 1A). 환자가고령으로증상이비교적경미하여우선입원후보존적인치료를시행하였다. 입원 17일째환자의좌측상하지에마비증상이생겨뇌 CT를촬영한결과경막하혈종이증가하면서우측뇌실이더압박되고, 뇌의중심선이좌측으로이동되는뇌압증가소견을보였다 (Fig. 1B). 뇌 CT상경막하혈종이고형의혈괴와액상의혈종이혼합된형태를가지고있었다. 수술은국소마취하에천공술을시행하였고, 경막을절개하고혈종의피막을확인한후경막하강 에서나오는혈종을확인하고 9 프렌치배액관을전두부방향으로약 5cm정도삽입시켰다 (Fig. 1C). 침상에서배액관을따라생리식염수 1mL와 urokinase 10,000 units 의혼합액을혈종내로 12시간마다주입하였고, 수술후 2일째시행한 CT에서혈종의제거가충분하여배액관을제거하였다. 수술후 7일째 CT상혈종의재발소견은없었으며 (Fig. 1D), 퇴원시글라스고우결과계수는 5점으로증상은완전히호전되었다. 증례 2 79세남자환자로넘어진후두부외상을입고감각성언어장애및인지력저하를호소하여응급실로내원하였다. 입원당시뇌 CT상좌측전두부및측두부에급성경막하혈종이발견되었으며, 이로인해좌측뇌실이약간압박되고있는소견을보였다 (Fig. 2A). 환자가고령으로입원후보존적인치료를시행하였다. 입원 12일째환자가언어장애및인지력저하가심해지고, 뇌 CT상경막하혈종이증가하면서좌측뇌실이더압박되고뇌의중심선이우측으로이동되는뇌압증가소견을보였다. 뇌 CT상경막하혈종이고형의혈괴와 Fig. 1. Case 1 was a 71-year-old patient who presented with headache after traumatic head injury by slip down. (A) At admission, computed tomography (CT) scan shows a hyperdense hematoma at the subdural space in the right frontotemporal convexity. (B) Sudden onset left-sided hemiparesis occurred at 17 days after admission. The follow-up CT shows a mixed hypodense and hyperdense subdural hematoma and progression of midline shifting. (C) An immediate postoperative CT scan shows a catheter in the subdural space and a significant amount of residual hematoma with mass effect. (D) CT scan at postoperative 7 days shows marked decrease of the subdural hematoma and resolution of the mass effect. Fig. 2. Case 2 was a 79-year-old patient who presented with sensory aphasia and poor cognitive function after traumatic head injury by slip down. (A) At admission, computed tomography (CT) scan shows a hyperdense hematoma at the subdural space in the left frontotemporal convexity. (B) Aggravation of symptoms occurred at 12 days after admission. The follow-up CT scan shows a mixed hypodense and hyperdense subdural hematoma and progression of midline shifting. (C) An immediate postoperative CT scan shows a catheter in the subdural space and partial removal of hematoma. (D) CT scan at postoperative 7 days shows marked decrease of the subdural hematoma and resolution of the mass effect. 10 YUJM VOLUME 32, NUMBER 1, JUNE 2015

4 Drainage using urokinase for SASDH 액상의혈종이혼합된형태를가지고있었다 (Fig. 2B). 응급으로국소마취하에천공술및 urokinase 를이용한혈종배액술을시행하였다 (Fig. 2C). 침상에서배액관을따라생리식염수 1mL와 urokinase 10,000 units 혼합액을혈종내로 12 시간마다주입하였고, 수술후 2일째시행한 CT에서혈종의제거가충분히되어배액관을제거하였다. 수술후 7일째 CT상혈종의재발소견없었으며 (Fig. 2D), 퇴원시글라스고우결과계수는 5점으로증상은많이호전되었다. 고찰 고령인구의증가로가벼운두부외상으로인해발생한급성경막하혈종을가진노인환자들이많아지고있다. 특히, 항혈소판제제나항응고제복용으로출혈성경향을가진노인환자들에서급성경막하혈종의발생이높다고알려져있다 [3-6,11]. 경막하혈종은급상, 아급성및만성의 3단계로분류하며, 뇌 CT 소견상혈종이고형의혈괴 (blood clot) 형태인경우급성, 고형의혈괴와액상의혈종이혼합된형태의경우아급성, 그리고액상의혈종형태를보일경우만성으로분류한다 [12,13]. 시기적으로분류하면급성경막하혈종은수상후 72 시간이내, 아급성경막하혈종은수상후 4일에서 20일사이에, 만성경막하혈종은수상후 3주이상경과한혈종이다 [1]. 급성경막하혈종과만성경막하혈종의경우구분이잘되지만, 아급성경막하혈종과만성경막하혈종의경우명확히구분하기어렵다. 급성경막하혈종의경우혈종량이적고두개강내압의상승징후가없을때에는보존적인치료를시행하며, 혈종의양이많고두개강내압의증가로신경학적상태가나쁘다면즉각적인개두술 (craniotomy) 을시행하여혈종을제거하여야한다 [2]. 만성경막하혈종의경우혈종의양이많고혈종의두께가 1cm 이상인경우수술적인치료가필요하며, 고형의급성기혈종과달리만성혈종은액상이므로개두술없이천공배액술 (burr hole drainage) 로혈종을제거하여치료할수있다 [8,14]. 급성기경막하혈종으로보존적인치료중아급성기에갑자기증가하여수술적인치료가필요한경우가있다 [2]. 아급성경막하혈종의경우고형의혈괴와액상이혼합된형태로천공배액술로액상의혈종은제거할수있으나, 고형의혈괴를제거하기는힘들다 [13,14]. 특히, 두껍고넓게분포하고있는고형의혈종이있는경우개두술을고려해야하지만, 이는혈종을완전히제거할수는있으나전신 마취의위험성및개두술로인한합병증이있을수있다. 특히, 고령의환자로심장질환및호흡기질환등의내과적인질환이있어전신마취의위험성이높은환자나항혈소판제제나항응고제를복용하는경우지혈이잘안되어과량의혈액소실의위험성이높은개두술을시행하기가힘들수있다 [15,16]. 천공술및 urokinase 를이용한혈종배액술은자발성급성기뇌실내출혈에서뇌척수액배액으로뇌압을낮춰주고, 고형의혈종을제거하는데보편적으로시행되고있다 [9,10,17] 항응고제와연관된뇌출혈의경우수술중대량의혈액소실이있을수있고, 재출혈의위험성이높고, 항응고제의중단으로인한지병의악화등이올수있다 [18]. 이런환자들에서천공술및 urokinase를이용한혈종배액술이개두술에비해사망률및합병증의가능성이더낮아좋은미세침습적인치료법으로보고하고있다 [16]. 신경학적이상소견이경미하고, 응급개두술로내압을낮춰줄필요가없는외상성경막외혈종에서도천공술및 urokinase 를이용한혈종배액술로좋은결과를보고하고있다 [19]. 본연구에서비록 9예의적은수의환자에서시행되었으나, 천공술및 urokinase 를이용한혈종배액술이고형의혈종이많은아급성기경막하혈종을가진환자에서국소마취하에안전하게시행할수있는좋은미세침습적인치료법으로생각된다. 특히, 이시술은심장질환및호흡기질환등의내과적인질환이있는고령환자로, 전신마취의위험성이높거나항혈소판제제나항응고제의복용으로지혈이잘안되어과량의혈액소실의위험성이높은환자에서개두술을대체할좋은수술법으로생각된다. 하지만추후더많은예에서임상경험을축적하여안정성및결과에대한분석이필요할것으로생각된다. ETHICS STATEMENT This study was approved by the institutional review board of the Yeungnam University Hospital (IRB No. YUMC ). ACKNOWLEDGEMENT This work was supported by a grant from the Chunma Medical Research Foundation, Korea, YUJM VOLUME 32, NUMBER 1, JUNE

5 Min-Su Kim et al. REFERENCES 1. Izumihara A, Yamashita K, Murakami T. Acute subdural hematoma requiring surgery in the subacute or chronic stage. Neurol Med Chir (Tokyo) 2013;53: Bullock MR, Chesnut R, Ghajar J, Gordon D, Hartl R, Newell DW, et al. Surgical management of acute subdural hematomas. Neurosurgery 2006;58(3 Suppl):S Son S, Yoo CJ, Lee SG, Kim EY, Park CW, Kim WK. Natural course of initially non-operated cases of acute subdural hematoma: the risk factors of hematoma progression. J Korean Neurosurg Soc 2013;54: Patel NY, Hoyt DB, Nakaji P, Marshall L, Holbrook T, Coimbra R, et al. Traumatic brain injury: patterns of failure of nonoperative management. J Trauma 2000;48: Kawamata T, Takeshita M, Kubo O, Izawa M, Kagawa M, Takakura K. Management of intracranial hemorrhage associated with anticoagulant therapy. Surg Neurol 1995;44: Oertel M, Kelly DF, McArthur D, Boscardin WJ, Glenn TC, Lee JH, et al. Progressive hemorrhage after head trauma: predictors and consequences of the evolving injury. J Neurosurg 2002;96: Lind CR, Lind CJ, Mee EW. Reduction in the number of repeated operations for the treatment of subacute and chronic subdural hematomas by placement of subdural drains. J Neurosurg 2003;99: Singla A, Jacobsen WP, Yusupov IR, Carter DA. Subdural evacuating port system (SEPS)--minimally invasive approach to the management of chronic/subacute subdural hematomas. Clin Neurol Neurosurg 2013;115: Chen X, Chen W, Ma A, Wu X, Zheng J, Yu X, et al. Frameless stereotactic aspiration and subsequent fibrinolytic therapy for the treatment of spontaneous intracerebral haemorrhage. Br J Neurosurg 2011;25: Liu L, Shen H, Zhang F, Wang JH, Sun T, Lin ZG. Stereotactic aspiration and thrombolysis of spontaneous intracerebellar hemorrhage. Chin Med J (Engl) 2011;124: Rosand J, Eckman MH, Knudsen KA, Singer DE, Greenberg SM. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med 2004;164: Izumihara A, Orita T, Tsurutani T, Kajiwara K. [Natural course of non-operative cases of acute subdural hematoma: sequential computed tomographic study in the acute and subacute stages]. No Shinkei Geka 1997;25: Takeuchi S, Takasato Y, Otani N, Miyawaki H, Masaoka H, Hayakawa T, et al. Subacute subdural hematoma. Acta Neurochir Suppl 2013;118: Kenning TJ, Dalfino JC, German JW, Drazin D, Adamo MA. Analysis of the subdural evacuating port system for the treatment of subacute and chronic subdural hematomas. J Neurosurg 2010;113: Vigue B, Ract C, Tremey B, Engrand N, Leblanc PE, Decaux A, et al. Ultra-rapid management of oral anticoagulant therapy-related surgical intracranial hemorrhage. Intensive Care Med 2007;33: Rohde V, Uzma N, Rohde I, St Clair E, Samadani U. Fibrinolytic therapy versus craniotomy for anticoagulant-associated intracerebral hemorrhage. Clin Neurol Neurosurg 2009;111: Gaberel T, Montagne A, Lesept F, Gauberti M, Lemarchand E, Orset C, et al. Urokinase versus Alteplase for intraventricular hemorrhage fibrinolysis. Neuropharmacology 2014;85: Mendelow AD, Gregson BA, Fernandes HM, Murray GD, Teasdale GM, Hope DT, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 2005;365(9457): Liu W, Ma L, Wen L, Shen F, Sheng H, Zhou B, et al. Drilling skull plus injection of urokinase in the treatment of epidural haematoma: a preliminary study. Brain Inj 2008;22: YUJM VOLUME 32, NUMBER 1, JUNE 2015

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KISEP Clinical Research J Korean Neurosurg Soc , 2000 급성경막하혈종에서응급두개골천공의위치 문수현 김근회 권택현 박윤관 정흥섭 서중근 = Abstract = Emergency Trephination Site o KISEP Clinical Research J Korean Neurosurg Soc 29659-663, 2000 급성경막하혈종에서응급두개골천공의위치 = bstract = Emergency Trephination Site of cute Subdural Hematoma Soo-Hyeon Moon, M.D., Geun-Hoe Kim, M.D., Taek-Hyun

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