hwp

Size: px

Start display at page:

Download "hwp"

수애 서
5 years ago
Views:

1 늑막강내 Urokinase 주입후발생된 Major Hemothorax 에기인된 Hypovolemic shock 건양대학교의과대학내과학교실 1, 건양대학교의과대학영상의학교실 2 김정규 1, 정인범 1, 손지웅 1, 최유진 1, 나문준 1, 이원영 1, 조영준 2 Major Hemothorax Induced Hypovolemic Shock Fallowing Administration of Intrapleural Urokinase Jung Kyu Kim, M.D. 1, Jung In Beom, M.D. 1, Son Ji Woong, M.D. 1, Eugene Choi, M.D. 1, Moon Jun Na, M.D. 1, Won Young Lee, M.D. 1, Cho Young Jun, M.D. 2 1 Department of Internal Medicine College of Medicine, Konyang University Taejon Korea, 2 Department of Radiology College of Medicine, Konyang University, Daejeon Korea Exudative pleural effusion can arise from pneumonia, tuberculosis, cancer, etc. Early drainage is needed for prevention of complications such as pleural fibrosis, thickening, bronchopleural fistulae and decline of lung function. Intrapleural Instillation of fibrinolytic enzymes has been used for 50years as an adjunct in the removal of fibrous material, hematoma and pus from the thoracic cavity. By the local fibrinolytic effect on fibrinous exudates within the pleural space, fibrinolytic agent has improved results of chest tube or pig tail drainage. But there were no controlled randomized studies, so significant controversy exists concerning the efficacy of this therpy, especially tuberculous pleurisy. Furthermore about complication, severe spontaneous bleeding has not been reported with intrapleural urokinase. Intrapleural fibrinolytic enzymes has shows no systemic complication. When it is administrated intravenously, not into intrpleural space, major bleeding is reported about 1-3% of patient, especially they had systemic disease, such as coagulation abnormalities. This case report presents a patient who suffered major hemothorax induced hypovolemic shock following the administration of 100,000 units of urokinase intrapleurally. He was 25-year old male with tuberculosis pleurisy without systemic illness demonstraion. (Tuberc Respir Dis 2004; 57: ) Key words : Urokinase, Hemothorax, Hypovolemic shock, Pleural effusion. 서 흉막강내염증성질환에속발되는삼출성흉막염은비중이높으며응고인자인피브리노젠 (fibrinogen) 등에의해흉막비후및섬유성막으로흉막강내에소방들을빈번히형성한다. 흉막삼출의치료가늦어지게되면흉막의섬유화, 폐기능감소, 기관지흉막루등의합병증이발생할수있어조기에적절한치료가필요하다. 더욱이결핵성흉막염은우리나라에서는비교 Address for correspondence : Eugene Choi, M.D. Department of Internal Medicine College of Medicine, Konyang University, Hospital Gasoowon-Dong, Seo- Ga, Daejeon, , Korea Phone : (042) eugene@kyuh.co.kr Received : May Accepted : Aug 론 적흔하고, 특히젊은연령층의삼출성흉막염의주종을이루고있는데, 이에대한화학요법의효과에대해서는이견이없으나, 삼출액의적절한제거와치료후의흉막유착을예방하는방법에대해서는보고가부족하다. 특히치료후흉막유착은폐기능에영향을미치기때문에예방이중요하다 1. 보통삼출성흉막염의초기치료에서흉막유착을예방하기위해흉관이나도관삽입을시행하는경우도있으며흉관은소방형성이나흉수가응고된경우에배액이잘되지않게된다. 지난수십년간이렇게흉막수의섬유화및기질화로인해배액이용이하지않을경우섬유용해제를늑막강내로주입함으로써소방용해및배액과치료기간단축을시도하여왔으며, urokinase를사용한격막용해는비교적안전한것으로생각되어져왔다 2,3. 그러나아직까지국내에서경피적도관삽입을통한 urokinase 주입의효과에대 465

JK Kim, et al.: Major hemothorax induced hypovolemic shock fallowing administration of intrapleural urokinase Figure 1. (A) Chest PA, (B) right lateral demonstra ted elevation of right diaphragm.

(A) After pigtail catheter insertion, pleural effusion was decreased yet elevated diaphragm due to loculated pleural effusion was remained.

2 JK Kim, et al.: Major hemothorax induced hypovolemic shock fallowing administration of intrapleural urokinase Figure 1. (A) Chest PA, (B) right lateral demonstra ted elevation of right diaphragm. (C) Large amount of fluid shifts on right decubitus position. Figure 2. (A) After pigtail catheter insertion, pleural effusion was decreased yet elevated diaphragm due to loculated pleural effusion was remained. (B) After second intrapleural injection of urokinase, haziness on right anterior chest was developed, suddenly. 한연구가부족하며, 더욱이이로인한문제점에대한보고도드물다. 본저자들은소방이형성되어배액이제한적이었던흉막염환자에서흉막강내 urokinase 주입후심각한정도의혈흉이발생한예를경험하였기에이를여러문헌고찰과함께보고하는바이다. 증례 환자 : 석, 남자, 25세주소 : 기침, 흉통현병력 : 내원한달전부터기침, 흉통과전신통이있어오다가지속되는기침으로내원하였다. 내원당시기침은있지만객담은심하지않았고열감을호소하였다. 과거력 : 환자는 5갑년의흡연력이외에특이한과거력은없었다. 가족력 : 특이사항없음신체검사소견 : 생체활력징후에서혈압은 120/80 mmhg, 분당맥박수는 68회, 호흡수는 16회, 체온은 36.7도씨로안정적이었다. 청진상우하폐야에서호흡음이감소되어있었다. 타진상우하폐야에서둔탁음이들렸고, 진동촉감, 양명음등이양성소견보였다. 검사소견 : 내원당시시행한말초혈액검사, 소변검사등은이상소견보이지않았고 PT/aPTT는각각 13.9/36.4초 ( 정상 PT 12초~15 초, aptt 25초~40초 ) 이었다. 흉부 X-선사진상우하폐야에서음영이증가되고음영과갈비가로막각의둔화와우측측와위에서변위 (shifting) 가확인되었다 (Fig. 1A, B, C). 흉막천자 : 우측흉수에대한진단적흉막천자검사상흉수의색상은담황색이였으며, 비중 1.015, ph 7.5, 적혈구 210개, 백혈구 400개 ( 다형핵호중구 21%, 단핵구 73%, 호산구 6%), 단백질 4,315mg/dl, 당 98mg/dl, 아밀라제 31IU/L, LDH 690IU/L, adenosine deaminase 91.9IU/L 로삼출성흉수의소견을보였다. 임상경과 : 입원 3일째삼출성흉수의제거를위해우측흉강내에 pig-tail insertion을시행하여배액시켰으나, 9일째흉부 X-선사진상소방이형성되어배액되지않는상당량의삼출이남아있어 (Fig. 2A), 섬유소용해및격막제거를통한용이한배액을위해 urokinase 100,000unit 을생리식염수 100cc에혼합하여주사후 2시간후 450cc 배액하였다. 11일째두번째로 urokinase 100,000unit 늑막강내주입을시행하였다. 30분후갑자기환자는우측흉통과함께, 호흡곤란을호소하였다. 생체활력징후상혈압은 100/60mmHg 으로저하되었고, 맥박수는분당 120회로빈맥을보이는등 hypovolumic shock 양태를나타냈으며, 즉시시행된흉부방사선사진상우상폐야에새롭게발생된증가된음영이관찰되었다 (Fig. 2B). 환자는 38.1 의발열과검사실소견상백혈구 9,880(10 3 /ul), 혈색소 8.6g/dL 적혈구용적율은 29.1% 로전일에비해각각 3.5g/dL, 8.6% 감소된소견을보였다. 우상폐야의병변을확인하기위해시행된진단적흉수천자상혈흉 466

Tuberculosis and Respiratory Diseases Vol. 57. No. 5, Nov, 2004 Figure 3. (A) After hematoma removal and decortica tion, lung was expanded fully and there was no blunting of costophrenic angle.

3 Tuberculosis and Respiratory Diseases Vol. 57. No. 5, Nov, 2004 Figure 3. (A) After hematoma removal and decortica tion, lung was expanded fully and there was no blunting of costophrenic angle. (B) A few months later, he visited out patient department. We could find only pleural thickening on right mid-lung field. 이발생되었음을확인할수있었다. 즉시환자에게수액요법과함께수혈을시행하였으며, 우측늑막강내흉관을삽입하여혈흉을배액시켰다. 이후증상은호전되었으나방사선사진상전측흉막강내에소방이형성되어, 남아있는병변의제거를위해혈종제거술 (hematoma removal) 과박피술 (decortication) 을시행하였다. 수술후폐는완전히확장되었으며, 결핵에대한화학요법을시행하고외래에서추적관찰중이다 (Fig. 3 A,B). 고찰 정상인에있어서흉막액은벽측흉막의모세혈관에서생성되어흉막강을거쳐장측흉막의모세혈관과림프관으로흡수되어하루평균 1-2L 정도의교환이일어나게되며, 정상적으로 ml/kg 가존재한다. 생리적인흉막의여출액의성분중에는 g% 의단백질이함유되어있고그중피브리노겐이 2~7% 를구성하고있다. 흉막의염증성변화는흉막에분포하는모세혈관과임파관의투과성을증가시켜흉막강내로유입되는혈청단백질의양과종류는증가하게된다. 이때유입된피브리노겐을비롯한응고인자들이흉막강내에서응고될때흉막의비후가초래되거나소방이형성되며, 흉막강내에는트롬빈 (thrombin) 합성이촉진되고 4,5, 섬유용해능이감소하는것으로알려져있다 6-8. 염증의진행에따른흉막삼출액의구성성분과흉막 의구조적변화는 3단계로구분된다. 제 1단계는삼출기로흉막주위의감염원에서진행되어삼출액이되는시기로소수의세포성분과정상적인 ph와당을보여준다. 제 2 단계는섬유화농성기로초기에는육안으로농이보이지않으나백혈구수가많아지고 ph가 , 당은 40mg/dl 이하이다. 제3단계는조직화기로피브린 (fibrin) 이침착되어비탄력막인흉막피를형성하여폐기능을저하시키게된다. urokinase는섬유용해제의하나로직접적인섬유용해능을가지지는않으나국한성흉막삼출을치료할수있는기전은플라스미노겐 (plasminogen) 을플라스민 (plasmin) 으로전환시켜섬유소또는혈전등을녹이는것이다 12,13. 세균단백의일종인 streptokinase가 urokinase를사용하기전에이용되어왔으나이는항체반응을일으켜발열같은부작용이나타나항체반응이없는 urokinase로대치되어졌다 12,13. 이와같은기전을통해소방이형성된농흉이나흉막삼출액에 urokinase를주입하면소방을형성하는격막의용해를볼수있다. 그러나흉막에염증반응이시작된후 6 주가지나면섬유화가진행하여 urokinase의효과가감소하거나없어진다. 소방을형성하는흉막염의치료는적절한항생제치료와병행한반복적인흉막천자, 폐쇄식흉관삽입술또는늑골박리를통한개방성배농과흉막박피술등의수술적처치를하여왔다. 흉막내로혈전용해제를투여하기시작한것은 1949년 Tillet 등 9 이 strepto kinase를사용하였으며, 이후 1989년 Moulton 등 10 이국한적흉막삼출의치료에 urokinase를사용하여효과가우수함을보고하였다. Robinson 등 11 은 13명의환자를대상으로 77% 의완치를보인다고보고하고있다. Temes 등 3 은 62% 의완치율을보였고, strepto kinase보다 urokinase에서완치율이더높다고보고하는등국내외에서흉막강내 urokinase에대한좋은성적이보고되고있으나아직장기추적조사는되어있지못한상태이다. 특히결핵성흉막염의배액이소방의형성으로인해잘안되는경우에는더욱그러하다. 아직삼출액의제거및이것으로인한흉막의유착등에대한예방적방법에는정설이없다. 흉막의유착은폐기능을저하시켜임상적으로문제가 467

4 JK Kim, et al.: Major hemothorax induced hypovolemic shock fallowing administration of intrapleural urokinase 될수있는데, 이는혈액에의노출, 마찰, 이물질또는부분허혈등에의하여중피세포 (mesothelial cell) 가손상되어섬유소용해능 (fibrinolytic activity) 이감소되어발생한다. 삼출환자에서경피적도관의삽입및 urokinase 주입의적응증은확실히정해진바는없으나삼출액의증가된점성과응고성, 다발성소방의형성, 흉막피의존재등으로단순경피적늑막배액술이실패한경우고려되고있다 12,13. 늑막강내유로키나제주입을이용한격막용해는비교적안전한것으로생각되어져왔으나 2,3 아직까지국내에서경피적도관삽입을통한 urokinase 주입의효과에대해연구가부족하며, 더욱이이에대한문제점또는합병증에대한연구는없다. 현재까지이러한혈전용해제의늑막강내주입은전신적인반응을일으키지는않는것으로알려져있다. 단지 Godley 등 14 은박피술후지속되는기흉과소방이형성된흉막삼출을제거하기위해 500,000 단위의 streptokinase를주입후 9시간째부터전신출혈증상의발생을보고하였고, 이러한결과에서이들은 (1) 혈액응고장애 ; (2) 최근의기관지수술 ; (3) 간, 비장, 또는두개강내의병변을동반할수있는심한외상등경우에는 streptokinase의상대적금기로제시하였었다. 또한 Porter 등 15 은심장판막수술후흉막삼출을동반한폐렴을보인 2 명의환자에서 streptokinase를흉막강내로주입후발생한혈흉을보고하였다. 이들은심장판막수술후항응고제의사용과상대적인섬유소결핍및응고장애등의전신적인출혈의위험인자가존재하였던경우로써, 이러한제반사항에서혈전용해제의사용이혈흉을유발하였을것으로추정하고있다. 본증례에서는이전의보고와는달리주입전검사에서특이한혈액응고장애나패혈증등의전신적인출혈의위험인자가없었던환자에서, 흉막강내 urokinase 투여후 hypovolumic shock이발생할정도의심각한출혈성합병증이발생할수있음을보여준예로, 앞으로소방이형성된삼출성늑막수의치료를위해섬유소용해제의투여에있어그효과적인측면과함께적응증및위험성에대한평가가이루어져야 할필요성이있음을시사한다고사료된다. 요약 저자들은패혈증이나혈액응고장애가이상이없는소방이형성된흉막삼출환자에서비교적안전한것으로알려진 urokinase의주입후에발생한혈흉과이로인한 hypovolemic shock 을경험하였기에문헌고찰과함께보고하는바이다. 참고문헌 1. Light RW. Pleural disease. 2nd ed. Philadelphia. Lea & Febiger, 1990: Sohn DH, Yoon SM, Kim CM, Park IS, Sohn JW, Yang SC, ea al. Effects of Intracavitary Urokinase Instillation in Complicated Pleural Effusion. Tubercs Respi Dis. 2000;48: Temes RT, Follis F, Kessler RM, Pett SB Jr, Wernly JA. Intrapleural fibrinolytics in management of empyema thoracis. Chest 1996;110: Landay MJ, Christensen EE, Bynum LJ, Goodman C. Anaerobic pleural and pulmonary infections. AJR 1980;134: Widstrom O, Chmielewska J, Blomback M. Measu rements of enzymatic activities in pleural exudates with chromogenic substrates. Thromb Res. 1986;42: Agrenius V, Chmielewska J, Widstrom O, Blomback M. Pleural fibrinolytic activity is decreased in infl ammation as demonstrated in quinacrine pleurodesis treatment of malignant pleural effusion. Am Rev Respir Dis 1989;140: Glauser FL, Otis PT, Levine RI, Smith WR. In vitro pleural fluid clottability and fibrinogen content. Chest 1975;68: Widstrom O, Egberg N, Chmielewska J, Blomback M. Fibrinolytic and coagulation mechanisms in stages of inflammation; a study of BCG-induced pleural exudate in guinea pig. Thromb Res 1983;29: Tillet WS, Sherry S. The effect in patients of stre ptococcal fibrinolysis (streptokinase) and streptoco ccal deoxyribonuclease on fibrinous purulent, and sanguinous pleural exudations. J. Clin. Inverst 1949; 28: Moulton JS, Moore PT, Mencini RA. Treatment of loculated pleural effusions with transcatheter intra 468

5 Tuberculosis and Respiratory Diseases Vol. 57. No. 5, Nov, 2004 cavitary urokinase. AJR 1989;153: Robinson LA, Moulton AL, Fleming WH, Alonso A, Galbraith TA. Intrapleural fibrinolytic treatment of multiloculated thoracic empyemas. Ann Thorac Surg 1994;57: Jung TG, Han YM, Jang SK, Jung KH, Son MH, Kim JS, Choi KC. Acute and Long-term effect of intraluminal urokinase in Korean empyema patients. J Korean Radiol Soc. 1989;32: Lee KS, Im JG, Jim YH, Hwang SH, Bae WK, Lee BH. Treatment of thoracic multiloculated empyemas with intracavitary urokinase: A prospective study. J Korean Radiol Soc. 1991;179: Godley PJ, Bell RC. Major hemorrhage following administration of intrapleural streptokinase. Chest 1984;86: Porter J, Banning AP. Intrapleural streptokinase. Thorax 1998;53:

<C1A4C0E7C8A331302E687770>

<C1A4C0E7C8A331302E687770> Tuberculosis and Respiratory Diseases 원저 결핵및호흡기질환,Vol.55,No.4,Oct,2003 심한흉막비후로진행하여흉막박피술을시행받은결핵성흉막염환자들의흉막액분석 연세대학교의과대학내과학교실 1, 흉부외과학교실 2, 폐질환연구소 3, BK21 의과학사업단 4 정재호 1, 박무석 1, 김세규 1,3,4, 장준 1,3, 정경영 2,3,