원저 Korean Circulation J 2003;33(3):227-232 혈성심낭삼출물의원인에따른심낭삼출물과혈청의생화학적분석에대한연구 부산대학교의과대학내과학교실 하재경 홍택종 전국진 이동원 김정수오준혁 송성국 이태근 김준홍 신영우 Biochemical Analysis of Serum and Pericardial Fluid in Patients with Hemorrhagic Pericardial Effusion Jae Kyung Ha, MD, Taek-Jong Hong, MD, Kook-Jin Chun, MD, Dong Won Lee, MD, Jeong Su Kim, MD, Jun Hyok Oh, MD, Sung Gook Song, MD, Tae Kun Lee, MD, June Hong Kim, MD and Yung Woo Shin, MD Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea ABSTRACT Background and Objectives:Since echocardiography became a routine diagnostic tool, pericardial effusion has become a common clinical finding. The major causes of hemorrhagic pericardial effusion are malignancy and tuberculosis. However, it was unknown to the use of biochemical analysis of pericardial fluid and serum, for differentiation of malignancy from tuberculosis. To evaluate this, we investigated the biochemical analysis of pericardial fluid and serum in relation to the causes of pericardial tamponade. Subjects and Methods:46 patients who were admitted to Pusan National University Hospital from January 1, 1995, to April 30, 2002, and underwent both a pericardiocentesis and a pericardiostomy for the relif of cardiac tamponade, were included in this study. the pericardial fluid was routinely analyzed for the following:gross appearance, cell count, glucose, total protein (TP), lactate dehydrogenase (LDH), cytology, gram stain, cultures for bacteria and mycobacterium, pericardial fluid to serum ratios of total protein and lactate dehydrogenase, (p/s TP, p/s LDH, respectively). Results:Of the 46 patients who underwent both pericardiocentesis and pericardiostomy, for the relief of cardiac tamponade, 33 patients (71.7%) had hemorrhagic pericardial effusion. The common causes of hemorrhagic pericardial effusion were malignancy (51.5%) and tuberculosis (33.3%) but, those of nonhemorrhagic pericardial effusion were idiopathic (38.5%). Cell counts were higher in hemorrhagic than nonhemorrhagic group (p=0.029). Serum LDH (sldh) was higher in malignant than tuberculous group (p=0.001) but, serum total protein (stp) was higher in tuberculous group (p=0.004). Compared malignant group with tuberculosis group in patients with hemorrhagic pericardial effusion, p/s ratio of LDH and stp were higher in tuberculous group (p=0.029, p=0.017), but sldh was higher in malignant group (p=0.002). Conclusion:It is difficult to differentiate tuberculosis from malignancy only on the basis of the biochemical analysis of pericardial fluid in hemorrhagic pericardial effusion. However, the analysis of both pericardial fluid and serum may make it possible to evaluate the cause of pericardial effusion. (Korean Circulation J 2003;33 (3):227-232) KEY WORDS:Pericardial effusion;blood chemical analysis. 논문접수일 :2002 년 11 월 8 일심사완료일 :2002 년 12 월 9 일교신저자 : 홍택종, 부산광역시서구아미동 1 가 10 번지부산대학교의과대학내과학교실전화 :(051) 240-7225 전송 :(051) 254-3127 E-mail:tjhong@pusan.ac.kr 227
서 론 방법 심낭압전으로진단된환자들중에서심낭절제술또 심초음파가심장질환의기본적인진단수단으로발전한이후심낭삼출물은흔한임상적소견이되었다. 심낭삼출물의원인은다양하며심낭압전을일으킬정도의많은심낭삼출물이있는경우그원인질환에따라예후가다양하다고알려져있다. 특히, 삼출물이혈성인경우잠재적인출혈의가능성과원인질환의심각성때문에임상적으로그원인을밝히는것이중요하다. 일반적으로혈성심낭삼출물의원인은악성종양과결핵이많은것으로알려져있으나, 혈성심낭삼출물에대한검사실소견은잘알려져있지않다. 저자는심낭압전이있는환자의혈성과비혈성심낭삼출물에서육안적소견에따른원인의차이와생화학적분석의차이를알아보고자하였으며, 가장흔한원인에따른심낭 는심낭천자를시술받은환자를대상으로하여심낭삼출물을검사하였다. 검사는육안소견, 세포수, 포도당수치, 총단백질수치 (total protein, TP), 유산탈수소효소 (lactate dehydrogenase, LDH), 세포학적검사 (cytology), 세균과결핵도말과배양, 그람염색, 심낭삼출물 / 혈청단백질비율 (pericardial fluid/serum total protein;p/s TP), 심낭삼출물 / 혈청 LDH 비율 (pericardial fluid/serum LDH;p/s LDH) 을시행하였으며, 혈성과비혈성심낭삼출물군에서비교분석하였고, 혈성심낭삼출물군에서원인에따라비교분석하였다. 혈성과비혈성의구분은 Meyers 등 1) 의분류에따라적혈구 100,000/mm 3 를기준으로하였다 (Table 1). 삼출물과혈청의생화학적분석의차이도같이알아보 고자하였다. 통계 결과는 SPSS version 10.0을이용하여, t 검정과카 대상및방법 이제곱검정을시행하였고, 대상이 20명이하는비모 수검정인 Mann-Whitney 검정을시행하였으며, p는 대상환자 0.05 이하를유의수준으로하였다. 1995년 1월부터 2002년 4월까지부산대학교병원에서심낭압전으로진단된환자들중에서심낭절제술또는심낭천자를시술받은환자는 49명이었으며, 그 결 과 중 18세이상인환자 46명을대상으로하였다. 임상양상 혈성심낭삼출물군은모두 33명이었으며, 남자는 Table 1. Definitions and classification of etiologies of bloody pericardial effusion 1) Classification Bloody effusion Malignant Complication of MI* Bacterial Uremic Traumatic Anticoagulant therapy Idiopathic Postpericardiotomy Criteria Nonclotting red fluid that did not become clear after the withdrawal of the first 20 ml of the effusion with a RBC count 100,000/mm 3 A histologically confirmed cancer or finding of malignant cells in cytologic examination of the effusion LV free wall rupture, thrombolytic therapy or due to insertion of transvenous pacemaker within 3 days of MI Positive culture of the fluid A patient on hemodialysis or serum creatinine >3.0 mg/dl Chest trauma within the preceding 24hr INR >3.5 on day of admission with no other attributable etiology of bloody pericardial effusion The etiology of the effusion could not be determined from the chart or by the attending physician:or a viral etiology was suspected but could not be confirmed by laboratory tests >1 week and <3 months after cardiac surgery Fluid total protein>3.0 g/dl;or fluid to serum total protein ratio>0.5;or fluid LDH>300 Exudative effusion U/dL;or fluid to serum LDH ratio>0.6 *MI:myocardial infarction, LV:left ventricle, INR:international normalized ratio 228 Korean Circulation J 2003;33(3):227-232
14명 (42.4%), 여자는 19명 (57.6%) 이었고, 평균나이는 57.6±14.7 세였다. 비혈성심낭삼출물군은 13명이었으며, 남자는 5명 (38.5%), 여자는 8명 (61.5%) 이었고, 평균나이는 62.4±11.7 세였다. 가장흔한증상은호흡곤란 (84.8%) 과흉통 (10.9%) 이었으며, 가장흔한진찰소견은빈맥 (52.2%) 이었고, 저혈압은 2.1% 로낮았다. 은 31명이었고여출액은 2명이었다. 비혈성심낭삼출물군에서삼출액은 9명이었고여출액은 4명이었다. 나이, 심낭삼출물의 LDH, 포도당, 단백질등은양군간에유의한차이가없었다. 그러나, 혈성심낭삼출물군에서세포수가더많았고 (p=0.029), 삼출액의빈도는혈성심낭삼출물군에서더높았다 (93.9% vs 69.2%, p=0.025)(table 3). 심낭삼출물의원인세포조직학적검사또는조직검사에서악성종양으로진단된심낭삼출물군중비혈성은 13명중에서 3 명 (23.1%), 혈성은 33명중에서 17명 (51.5%) 이었다 (p=0.017). 혈성심낭삼출물의주된원인은악성종양 (51.5%) 과결핵 (33.3%) 이었다. 악성종양중에서폐암이 33.1% 로가장많았다. 비혈성심낭삼출물의주된원인은원인불명 (38.5%), 갑상선기능저하증 (30.8%), 악성종양 (23.1%) 이었다 (Table 2). 원인에따라두군을비교해보았을때혈성심낭삼출물군은악성종양과결핵이많았고 (p<0.05), 비혈성심낭삼출물군은원인불명인경우가많았지만 (p<0.05), 그다음으로많은원인을차지하는갑상선기능저하증과악성종양은두군간에통계학적인차이가없었다. 심낭삼출물의생화학적분석혈성심낭삼출물군에서삼출액 (exudative effusion) Table 2. Etiology of hemorrhagic and nonhemorrhagic pericardial effusion Etiology Hemorrhagic Nonhemorrhagic Total n % n % n % Malignancy* 17 051.5 03 023.1 20 043.5 Lung 11 033.1 02 015.4 13 028.3 Breast 01 003.1 00 000 01 002.2 Lymphoma 01 003.1 01 007.7 02 004.33 Colon ca 02 006.1 00 000 02 004.33 Miscellaneous 02 006.1 00 000 02 004.33 Idiopathic* 03 009.1 05 038.5 08 017.4 Coagulation 01 003.05 00 000 01 002.15 Aortic dissection 01 003.05 00 000 01 002.15 Tuberculosis* 11 033.3 01 007.6 12 026.1 Hypothyroidism 00 000 04 030.8 04 008.7 Total 33 100 13 100 46 100 *:p<0.05 심낭삼출물의주된원인인악성종양과결핵의분석혈성심낭삼출물과비혈성심낭삼출물을비교했을때세포수는통계학적으로의미가있었지만, 주된원인이악성종양과결핵인두심낭삼출물군을비교했을때세포수는차이가없었다. 원인이악성종양인군에서혈청유산탈수소효소가높았고 (p=0.001), 원인이결핵인군에서혈청총단백질이높았다 (p= 0.004)(Table 4). 혈성심낭삼출물의주된원인인악성종양과결핵의분석혈성심낭삼출물군과비혈성심낭삼출물군을비교했을때악성종양과결핵이혈성심낭삼출물군에서많았다. 혈성심낭삼출물군에서악성종양과결핵을비교했을때혈청유산탈수소효소가악성종양군에서높았으며, 심낭삼출물 / 혈청유산탈수소효소비율 (p/s LDH) 과혈청총단백질은결핵군에서높았다. 혈성심낭삼출물인경우심낭삼출물의생화학적분석 Table 3. Comparison of data in patients with hemorrhagic and nonhemorrhagic pericardial effusion Hemorrhagic (n=33) Nonhemorrhagic (n=13) Age, yr 57.6 (±14.7) 62.4 (±11.7) - Cell count (/dl) 1634.9 430.5 0.029 Neutrophil (%) 0048.9 054.6 - Lymphocyte (%) 0051.3 045.4 - *pldh (U/dl) 1747.9 897.46 - sldh (U/dL) 0828.2 504.2 - p/s LDH 0003.1 001.43 0.057 *ptp (g/dl) 0004.2 002.96 0.062 stp (g/dl) 0006.4 005.9 - p/s TP 0000.68 000.49 - Glucose (mg/dl) 0076.3 111.54 - Exudative effusion (n/%) 31/93.9 9/69.2 0.025 *p:pericardial fluid, p/s:pericardial fluid/serum, s:serum p 229
Table 4. Comparison of data in patients with malignant or tuberculous pericardial effusion Malignancy (n=20) Tuberculosis (n=12) Others (n=14) P Age, yr 59.4±11.8 60.8±16.4 56.9±13.6 - Cell count (/dl) 1546.5 1126.1 1226.8 - Neutrophil (%) 0048.9 0032.2 0068.5 - Lymphocyte (%) 0051.1 0068.3 0031.5 - *pldh (U/dL) 2054.1 1945.8 0342.4 - sldh (U/dL) 1075.2 0447.5 0532.3 0.001 p/s LDH 0002.4 0005.1 0000.7 - *ptp (g/dl) 0004.2 0004.7 0002.7 - stp (g/dl) 0005.9 0007.0 0006.1 0.004 p/s TP 0000.7 0000.7 0000.4 - Glucose (mg/dl) 0066.1 0075.4 123 - *p:pericardial fluid, s:serum, p/s=pericardial fluid/serum Table 5. Comparison of data in patients with malignancy and tuberculosis in hemorrhagic pericardial effusion Malignancy (n=17) Tuberculosis (n=11) Others (n=5) p Age, yr 58±12.1 60.6±17.1 0049.8 - Cell count (/dl) 1788.5 1200.9 2481.8 - Neutrophil (%) 0053.1 0032.4 0070.8 - Lymphocyte (%) 0046.9 0068.2 0029.2 - *pldh (U/dL) 2113.6 1936.5 0297.6 - sldh (U/dL) 11320 0467.5 0677.4 0.002 p/s LDH 0002.2 0005.5 0000.5 0.029 *ptp (g/dl) 0004.2 00004.67 0003.8 - stp (g/dl) 00005.97 0007.0 0006.2 0.017 p/s TP 0000.7 0000.7 0000.6 - Glucose (mg/dl) 0064.9 0072.6 121 - *p:pericardial fluid, s:serum, p/s:pericardial fluid/serum 만으로는악성종양과결핵을감별하기힘들다. 하지만심낭삼출물과혈청의생화학적검사를비교분석함으로써감별이가능하였다 (Table 5). 고찰 심초음파가심장질환의기본적인진단수단으로발전한이후심낭삼출물은흔한임상적소견이되었다. 그원인 2) 은관통성외상, 흉부외상, 악성질환, 대동맥박리및혈종, 혈전용해술, 심막염, 괴혈병, 응고장애, 요독성심막염, 혈관염등이있다. 혈성심낭삼출물의경우, 외상과같은원인은출혈의원인으로쉽게알수있지만, 그렇지않은경우에는서서히나타나서원인을잘알수없기도하고, 다양한정도의출혈이있기때문에진단에어려움이있다. 심낭압전의진단기준으 로는첫째, 심초음파상혈류학적이상을동반한심낭삼출물이있을때, 둘째, 경정맥압이증가되어있거나, 셋째, 심낭삼출물이있으면서수축기혈압이 90 mmhg 이하일때, 넷째, 심낭절제술과심낭천자를시행후기이적동맥압이소실되거나경정맥압이감소되는경우심낭압전으로진단했다. 심낭압전을일으킬정도의심낭삼출물이있는경우그원인에따라예후가다양하지만심낭삼출물에대한검사실소견은잘알려져있지않다. 그에비해흉수에대한검사실소견은잘정립되어있다. 3-5) 예를들면, 삼출액흉수는단백질농도가 3.0 g/dl 이상, 비중이 1.015 이상, 흉수 / 혈청단백질비율이 0.5 이상또는흉수 / 혈청 LDH 비율이 0.6 이상일때이며, 여출액은그외의경우이다. 육안적혈성흉수삼출물은적혈구 100,000/mm 3 이상으로정의되며, 그원인으로는외상, 악성종양, 폐색전증 230 Korean Circulation J 2003;33(3):227-232
등이있으며, 흉수세포수가 10,000/mm 3 이상인경우는농흉, 부폐렴삼출액, 췌장염, 폐경색, 결체조직질환, 결핵, 악성종양등이다. 흉수단백질이 6.0 g/dl 이상인경우는종종결핵이나부폐렴삼출액인경우이며, 흉수의단백질수치는정상이면서 LDH 수치가증가된경우가장흔한것은악성종양이고, 흉수포도당농도가 60~80 mg/dl 이하로감소된경우는부폐렴삼출액, 류마티스, 결핵, 악성종양등이다. 1) Guberman 등 6) 에의하면심낭압전의원인으로는악성종양과원인불명인경우가많았다. 국내에서발표된논문을보면, 김등 7) 은심낭삼출물총 28예중 23 예에서혈성심낭삼출물이있었지만, 원인및그에따른차이를보고하지않았으며, 최등 8) 은총 37예중악성종양이 7예, 결핵이 10예를보고하였고, 윤등 9) 도역시중등도이상의심낭삼출물의원인으로총 49 예중악성종양 20예 (40.8%), 결핵 9예 (18.4%) 를보고하였지만, 혈성과비혈성에따라원인을분석한논문은없었다. 본논문은혈성과비혈성심낭삼출물에따른원인과생화학적분석의차이를알아보려했으며, 원인이결핵과악성종양일때심낭삼출물의생화학적차이도같이알아보았다. 혈성심낭삼출물인경우육안적소견은원인에대한실마리를제공하고예후는대부분나쁜것으로알려져있으며, 또한삼출액인경우일반적으로악성종양과감염때문인것으로알려져있다. 10) 심낭천자는심낭압전으로위급한상황인경우에명확히적응증이되며, 심낭절제술은심근손상으로인한수술시또는진단적심막조직검사가필요할경우, 심낭천자로심낭압전이호전되지않을때에적응이된다. 6) 심낭압전이있는환자들중에서대부분 (72%) 이혈성심낭삼출물로서 Meyers 등 1) (73%), Colombo 등 11) (80%), Zayas 등 12) (89%) 의보고와비교했을때차이가없었다. Meyers 등 1) 은적혈구수가 100,000/ mm 3 이상일때혈성심낭삼출물로분류하였지만혈성과비혈성심낭삼출물의원인에따른비교를하지않았다. Colombo 등 11) 과 Zayas 등 12) 은혈성심낭삼출물의가장많은원인은악성종양이라고발표했으며, Colombo 등 11) 은장액성심낭삼출물의가장많은원인은원인불명이며, 예후는양성이라고하였다. 본연구에서혈성심낭삼출물의주된원인은악성종양 (51.5%) 과결핵 (33.3%) 이었다. 비혈성심낭삼출물의주된원인은원인불명 (38.5%) 이었다. 본연구결 과에서도비혈성심낭삼출물군에비해혈성심낭삼출물군에서악성종양과결핵이많았다. 혈성심낭삼출물이비혈성심낭삼출물보다심낭삼출물내세포수 (p=0.029) 가많았다. 악성종양과결핵의두군을비교했을때 sldh 는악성종양군에서높았고 (p= 0.001), stp는결핵군에서높았다 (p=0.004). 혈성심낭삼출물군에서원인이악성종양과결핵인두군을비교했을때악성종양군이 sldh, stp 가높았고, p/s LDH 는낮았다 (p=0.029). 결론적으로혈성심낭삼출물인경우심낭삼출물의생화학적분석만으로는악성종양과결핵을감별하기힘들고심낭삼출물과혈청을같이생화학적검사를하여비교분석함으로써감별이가능할것으로사료된다. 요약 배경및목적 : 심초음파가기본적인진단수단으로발전한이후심낭삼출물은흔한임상적소견이되었다. 혈성인경우에는질환의특징과잠재적인출혈의가능성및심각성때문에임상적으로중요하다. 국외발표에서혈성심낭삼출물의주된원인은악성종양과결핵으로알려져있다. 심낭압전으로진단된환자에서혈성과비혈성심낭삼출물의원인과생화학적분석및차이, 그리고원인이악성종양과결핵인경우, 심낭삼출물과혈청의생화학적분석및차이에대해알아보고자하였다. 방법 : 1995년 1월부터 2002년 4월까지부산대학교병원에서심낭압전으로진단되어심낭절제술과심낭천자를시술받은 46명을대상으로육안소견, 세포수, 포도당수치, 총단백질수치 (TP), 유산탈수소효소 (lactate dehydrogenase, LDH), 세포학적검사 (cytology), 세균과결핵도말과배양, 그람염색, 심낭삼출물 / 혈청단백질비율 (p/s TP), 심낭삼출물 / 혈청 LDH 비율 (p/s LDH) 을시행하고분석하였다. 결과 : 심낭압전으로심낭절제술또는심낭천자를시술받은 46명의환자에서 33명 (71.7%) 이혈성심낭삼출물이었고, 그원인은악성종양 (51.5%) 과결핵 (33.3%) 이가장많았고, 비혈성심낭삼출물은원인불명 (38.5%) 이많았다. 심낭삼출물의세포수는비혈 231
성심낭삼출물보다혈성심낭삼출물에서많았다 (p= 0.029). 악성종양과결핵의두군을비교했을때악성종양군에서 sldh 가높았고 (p=0.001), 결핵군에서혈청단백질 (p=0.004) 이높았다. 혈성심낭삼출물군에서주된원인인악성종양과결핵인두군을비교했을때, 악성종양군에서 sldh 가높았고 (p=0.002), stp와 p/s LDH는결핵군에서높았다 (p=0.017, p= 0.029). 결론 : 혈성심낭삼출물인경우심낭삼출물의생화학적분석만으로는악성종양과결핵을감별하기힘들고심낭삼출물과혈청을같이생화학적검사를하여비교분석함으로써감별이가능할것으로사료된다. 중심단어 : 심낭삼출 ; 혈청화학분석. 감사문본논문을작성하는데있어서부족한부분에대한많은지도와도움을주신교수님께감사드립니다. REFERENCES 1) Meyers DG, Meyers RE, Prendergast TW. The usefulness of diagnostic tests on pericardial fluid. Chest 1997;111: 1213-21. 2) Spodick HD. Hemopericardium. In: The pericardium: a comprehensive textbook. New York: Marcel Dekker;1997. p.82-4. 3) Light RW. Pleural effusions. Med Clin North Am 1977; 61:1339-52. 4) Jay SJ. Pleural effusions: preliminary evaluation recognition of the transudate. Postgrad Med 1986;80:164-77. 5) Jay SJ. Pleural effusions: definitive evaluation of the exudate. Postgrad Med 1986;80:181-8. 6) Guberman BA, Fowler NO, Engel PJ, Gueron M, Allen JM. Cardiac tamponade in medical patients. Circulation 1981; 64:633-40. 7) Kim TS, Lee SK, Shin KY, Choi WK, Kim JS. The clinical study on 28 patients with the pericardial effusion. Korean Circ J 1981;11:131-42. 8) Choi DY, Kim YD, Won KJ, Ko YH, Sohn DS, Cho DY, Yang KM. Clinical experience of pericardial effusion. Korean J Thorac Cardiovasc Surg 1995;28:487-90. 9) Yoon KM, Kim TR, Chung WS, Lee MY, Baek SH, Jun SS, Choi KB, Hong SJ. Clinical study in patients were performed pericardiocentesis and percutaneous pericardial biopy. Korean Cir J 1990;20:697-702. 10) Jouriles NJ. Pericardial and myocardial disease. In: Mark JA, Barkin RM, editor. Rosen s Emergency Medicine: concepts and clinical practice. 5th ed. St. Louis: Mosby;2002. p.1131-9. 11) Colombo A, Olson HG, Egan J, Gardin JM. Etiology and prognostic implications of a large pericardial effusion in men. Clin Cardiol 1988;11:389-94. 12) Zayas R, Anguita M, Torres F, Gimenez D, Bergillos F, Ruiz M, Ciudad M, Gallardo A, Valles F. Incidence of specific etiology and role of methods for specific etiologic diagnosis of primary acute pericarditis. Am J Cardiol 1995;75:378-82. 232 Korean Circulation J 2003;33(3):227-232