심폐바이패스시 혈액응고체계 변화의 혈전탄성검사 분석 - 단일 저용량 아프로티닌 투여 효과 분석 -

김관민,박계현 대한흉부심장혈관외과학회 1997 Journal of Chest Surgery (J Chest Surg) Vol.30 No.7

혈전탄성검사(혈전탄성검사, thomboelastography)는 혈전 생성 전 과정에 대한 신속한 정보를 제공해 주는 유용한 측정 방법 중의 하나이며, 많은 수술 과정에서 발생하는 혈액응고 장애의 진단을 용이하게 함으로써 적절한 치료를 가능케 한다. 최근, 단백질분해효소 억제제인 아프로티닌에 의해 심폐바이패스 후의 혈액응고 장애에 의한 출혈 문제가 많이 해결되었지만,그 지혈 작용 기전은 아직 정확히 알려져 있지 않다. 이 연구 는 개심술을 시행 받은 환자들에서 아프로티닌이 심폐바이패스에 의한 혈액응고 체계 변화에 미치는 효과를 혈전탄성검사로 분석하기위하여 시행하였다 20세 이상 성인 개심슬 환자 40명을 2개의 군으로 나누어 시행하였다. 대조군(남 10명, 여8명, 평균연령 53.4세)은 심폐기 충전액에 아프로티닌을 투여하지 않았고, 아프로티닌군(남 14명, 여 8명, 평균연령 50.8세) 은 심폐기 충전액에 아프로티닌 2백만 KIU(kallikrein inhibition unit)를 투여하였다. 이 들을 대상으로, 심폐바 이패스 전, 후( 프로타민에 의한 헤파린 효과 중화 30분 후)에 혈전탄성검사와, 활성응고시간, 프로트롬빈시 간, 활성부분트롬보플라스틴시간, 혈소 \ulcorner수, 섬유소원과 섬유소용해물질 농도 등 일반적인 혈액응고 검사들 을 시행하였다. 일반적인 혈액응고 검사상에서는, 두 군간에는 섬유소용해물질이 대조군에서 심폐바이패스 후 아프로티닌 군 보다 의미 있게 증가한 것(p<0.05)을 제외하고는 차이가 발견되지 않았다. 혈전탄성검사에서는 혈전형성 시간(K)과 $알파각(\alpha^{\circ})이$ 두 군 모두에서 심폐바이패스 후에 각각 증가 및 감소하였으나(p<0.05), 섬유소용해 지수(LYS60)는 차이가 없었다. 아프로티닌군에서는, 반응시간(R)은 심폐바이패스 후에 감소하였으나(p<0.09) 혈전강도최대치(h4A)는 변화가 없었다. 반면 대조군에서는, 반응시간은 변화가 없었으나 혈전강도최대치는 의미 있게 감소하였다(p<0.05). . 이상의 결과로부터, 심폐바이패스 시 혈액응고 체계의 주된 변화는 혈소판 기능 저하에 의한 혈전 강도의 저하이고, 과도한 섬유소용해의 증가는 일어나지 않으며, 아프로티닌은 심폐바이패스 후의 혈액응고 체계에 서 초기에는 항혈액응고 작용을 갖지만, 심폐바이패스에 의한 혈소판 기능의 저하를 억제하여, 일단.혈전이 형성되기 시작하면 혈전강도를 심폐바이패스 전 상태로 유지하는 효과를 갖는다고 \ulcorner각된다. Thromboelastography(TEG) is the unique measure that gives rapid information about the whole clotting process. Simplifying the diagnosis of coagulopathy during operations, TEG can provide an adequate therapy for postoperative bleeding. Remarkable improvement in hemostasis after cardiopulmonary bypass(CPB) has been achieved by the treatment with proteinase inhibitor aprotinin, but the hemostatic mechanism of aprotinin during CPB is still unclear. This study was designed to evaluate the effects of aprotinin on coagulation system during CPB by using TEG. Forty patients who underwent CPB were divided into two groups: aprotinin(2u 106 kallikrein inhibition units, as a single dose into the cardiopulmonary bypass priming solution) treatment group(male 14, female 8, mean age=50.Byears) and no aprotinin treatment(control) group(male 10, female 8, mean age=53.4 years). TEG, activated clotting time, prothrombin time, activated partial thromboplastin time, platelet counts, fibrinogen an (ibrinogen degradation product(FDP) concentrations were checked before and after CPB(30 minutes after neutralization of heparin effect by protamine sulfate). There was no significant difference in other conventional coagulation tests of two groups except postcardiopulmonary bypass FDP concentration in control group, which was significantly increased compared to that in aprotinin group(p<0.05). In TEG variables of both groups, clot formation time(K) and alpha $angle(\alpha^{\circ})$ were significantly increased and decreased, respectively, after CPB(p<0.05), but fibrinolytic index(LYS60) was not changed during CPB. In aprotinin group, reaction time(R) was decreased significantly after CPB(p<0.05) but maximum amplitude(MA) was not changed(p>0.05). On the contrary, R was not changed markedly but MA was decreased significantly in control group after CPB(p<0.05). This result shows that main change in coagulation system during CPB is not hyperfibrinolysis but cecrease in clot strength by platelet dys unction, and the main effect of aprotinin during cardiopulmonary bypass is the maintenance of clot strength to the pre-CPB level by the preservation of platelet function.

다한증-땀을 많이 흘린다

김관민 인구보건복지협회 2000 가정의벗 Vol.33 No.7

전통의 맥-해동검도

김관민 충남대학교 아시아지역연구소 1998 아시아지역연구 Vol.2 No.-

Video-Assisted Thoracic Surgery Mediastinal Lymph Node Dissection in Lung Cancer Surgery

김관민 대한흉부외과학회 2021 Journal of Chest Surgery (J Chest Surg) Vol.54 No.4

Mediastinal lymph node dissection is an important part of lung cancer surgery that pro- vides accurate nodal staging and may improve survival outcomes. The minimally invasive approach, such as video-assisted thoracic surgery (VATS) lobectomy for patients with non-small cell lung cancer, has become a standard operation worldwide. VATS mediastinal lymph node dissection should be thorough and accurate to ensure the completeness of lung cancer surgery. Herein, the author describes techniques for VATS mediastinal lymph node dissection.

인공 심장판막의 재치환술 -수술 위험인자와 수술 결과의 분석-

김관민 대한흉부심장혈관외과학회 1995 Journal of Chest Surgery (J Chest Surg) Vol.28 No.1

From January 1985 to December 1992, of 1257 patients who underwent a heart valve replacement 210 [16.8% underwent reoperation on prosthetic heart valves, and 6 of them had a second valve reoperation. The indications for reoperation were structural deterioration [176 cases, 81.5% , prosthetic valve endocarditis [25 cases, 11.6% , paravalvular leak [12 cases, 5.6% , valve thrombosis [2 cases, 0.9% and ascending aortic aneurysm [1 case, 0.4% . Prosthetic valve failure developed most frequently in mitral position [57.9% and prosthetic valve endocarditis and paravalvular leak developed significantly in the aortic valve [40%, 75% [P<0.02 . Mean intervals between the primary valve operation and reoperation were 105.3$\pm$28.4 months in the case of prosthetic valve failure, 61.5$\pm$38.5 months in prosthetic valve endocarditis, 26.8$\pm$31.2 months in paravalvualr leak, and 25.0$\pm$7.0 months in valve thrombosis. In bioprostheses, the intervals were in 102.0$\pm$23.9 months in the aortic valve, and 103.6$\pm$30.8 months in the mitral valve. The overall hospital mortality rate was 7.9% [17/26 : 15% in aortic valve reoperation [6/40 , 6.5% in reoperation on the mitral prostheses [9/135 and 5.7% in multiple valve replacement [2.35 . Low cardiac output syndrome was the most common cause of death [70.6% . Advanced New York Heart Association class [P=0.00298 , explant period [P=0.0031 , aortic cross-clamp time [P=0.0070 , prosthetic valve endocarditis [P=0.0101 , paravalvularr leak [P=0.0096 , and second reoperation [P=0.00036 were the independent risk factors, but age, sex, valve position and multiple valve replacement did not have any influence on operative mortality. Mean follow up period was 38.6$\pm$24.5 months and total patient follow up period was 633.3 patient year. Actuarial survival at 8 year was 97.3$\pm$3.0% and 5 year event-free survival was 80.0$\pm$13.7%. The surgical risk of reoperation on heart valve prostheses in the advanced NYHA class patients is higher, so reoperation before severe hemodynamic impairment occurs is recommended.

해동검도의 가치와 그 발전 방향

김관민,이범렬 충남대학교 아시아지역연구소 2005 아시아지역연구 Vol.7 No.-

전 흉부 대동맥 동시 치환술 -1례 보고-

김관민,김성철,박표원 대한흉부심장혈관외과학회 1999 Journal of Chest Surgery (J Chest Surg) Vol.32 No.6

원위부 대동맥궁류가 과도하게 커서 elephant trunk 술식을 적용하기 어려운 경우나 하행 대동맥류가 파열된 경우와 같은 합병증이 동반된, 전 흉부 대동맥을 침범하는 광범위 대동맥류에 있어서는 단계적 수술이 불가능하다. 저자들은 상행 대동맥에서부터 하행 대동맥까지의 대동맥을 동시에 치환하는 수술을 성공적으로 시행하였다. 환자는 65세 남자로서 하행 대동맥류의 파열을 동반한 전 흉부 대동맥류를 갖고 있었다. 수술은 횡행 개흉 흉골 절개술을 통하여 접근하여 초 저체온 완전 체외순환 정지 및 역행성 뇌관류하에 시행하였다. 환자는 순조롭게 회복하였으며 신경학적 합병증 없이 퇴원하였다. Some extensive thoracic aortic aneurysms are not amenable to staged repair, such as extremely large distal aortic aneurysms that are unsuitable for an elephant trunk anastomosis, or aneurysms that are accompanied by complications such as ruptured descending thoracic aneurysm. We report here a case of successful replacement of the aorta from the ascending to the descending aorta in one operation. The patient was 65-year-old man who had an aneurysm which involved the entire thoracic aorta and ruptured in the descending aorta. The operation was performed via transverse thoracosternotomy, and under the deep hypothermic circulatory arrest with retrograde cerebral perfusion. The patient recovered uneventfully and was discharged without any neurologic complications.

가토에서 Cisplatin을 사용한 분리 폐 관류 -약리학적 변화 및 폐의 장기적 병리학적 변화에 관한 연구-

김관민,김진국,한정호 대한흉부심장혈관외과학회 1999 Journal of Chest Surgery (J Chest Surg) Vol.32 No.7

배경: 최근 항암제의 전신성 독성을 최소화 하면서 고농도의 항암제를 투여할 수 있는 방법으로서 항암제의 국소 관류 혹은 장기의 분리 관류 방법이 다시 연구되고 있다. 폐암의 항암제로 널리 사용되고 있는 cisplatin 을 사용하여 분리 폐 관류를 시행하였을 때 폐에 미치는 약물학적 및 병리학적 변화를 관찰하고자 하였다. 연구방법: 25마리의 가토를 I군 10마리, II군 15마리로 나눈다음, 각 군을 다시 5마리씩 2, 3개의 소 군으로 나누어 I군에서는 cisplatin 5 mg/kg을 정맥주사와 분리 폐 관류한 후 30분 경과하였을 때의 폐, 신장 및 혈장 에서의 platinum 농도를 비교하였고, II군의 첫번째 5마리에서는 10% pentastarch 용액만으로 분리 폐 관류 후 30분, 1주일째의 병리학적 변화를 관찰하였으며, II군의 두 번째 5마리에서는 cisplatin 5 mg/kg으로 분리 폐 관류 후 30분, 1주일째, II군의 나머지 5마리에서는 cisplatin분리 폐 관류 후 4주일째의 병리학적 소견을 비교 관찰 하였다. 결과: Cisplatin 5 mg/Kg을 정맥 주입한 군에서 폐와 신장 조직, 혈장에서의 평균 platinum 농도 는 각각 1.50$\pm$0.43 $\mu\textrm{g}$/g, 7.65$\pm$2.49 $\mu\textrm{g}$/g, 1.19$\pm$0.03 $\mu\textrm{g}$/ml로서 신장 조직에서 platinum 농도가 가장 높았으며 (p< 0.05), 폐 조직과 혈장에서는 비슷하였다. 그러나 Cisplatin 5 mg/Kg을 분리 폐 관류한 군에서의 platinum 농도는 폐, 신장, 혈장에서 각각 75.43$\pm$11.47 $\mu\textrm{g}$/g, 1.30$\pm$0.35 $\mu\textrm{g}$/g, 0.13$\pm$0.02 $\mu\textrm{g}$/ml로서 분리 폐 관류 군의 폐 조직에서의 platinum 농도는 정맥주입 군에서 보다 약 50배 가량 높게 측정되었으며, 신장 조직 및 혈장에 서는 현저히 낮게 측정되었다(p< 0.05). 분리 폐 관류 후의 폐 조직의 병리학적 변화는 pentastarch 용액과 cisplatin을 사용한 군 모두에서 비슷한 소견을 나타냈다. 즉, 관류 직후인 30분에는 경미한 간질성 부종 외에 는 비교적 정상적인 소견을 보였으며, 1주일 이상 4주까지에서는 비교적 폐포는 정상적 구조를 유지하면서 부분적으로 소폐동맥 중막의 비후와 간질에 호산구 침윤의 소견이 특징적으로 관찰되었다. 결론: 분리 폐 관류는 정맥주입 방법에 비해 고농도의 cisplatin 투여로 인한 다른 장기에서의 농도 증가 없이 폐 조직에 약 50배 정도의 고농도 cisplatin을 투여할 수 있었으며, 또한 분리 폐 관류 시 cisplatin에 의한 직접적 폐 독성은 발견되지 않았다 Background: Recently, regional or isolated organ perfusion is being studied again as a drug administration modality which is able to reduce systemic toxicity while delivering high-dose chemotherapeutic agents. This research was planned to evaluate the pharmacokinetics and long-term pathologic changes of the lung in isolated lung perfusion (ILP) with cisplatin. Material and Method: Twenty-five New Zealand white rabbits were divided into 2 groups (Group I: 10, Group II: 15). The groups were then subdivided into 2 and 3 subgroups of 5 rabbits. In group I, tissue samples of the lung and kidney, and systemic blood for platinum concentration measurement were taken 30 minutes after systemic intravenous infusion of cisplatin (5 mg/kg) and isolated lung perfusion in each 5 rabbits. In 2 subgroups of group II, lung tissues for pathologic exams were taken 30 minutes and 1 week after ILP in each 5 rabbits, which received 10% pentastarch solution only and cisplatin, respectively. In the other subgroups, lung biopsy was undertaken 4 weeks after ILP with cisplatin. Result: When cisplatin was infused via systemic vein, the platinum concentration in the lung, kidney and plasma were 1.50${\pm}$0.43 $\mu\textrm{g}$/g, 7.65${\pm}$2.49 $\mu\textrm{g}$/g, 1.19${\pm}$0.03 $\mu\textrm{g}$/ml, respectively. However, the platinum concentration in the lung was about 50 times higher (75.43${\pm}$11.47 $\mu\textrm{g}$/g) than that of intravenous infusion group, and those in the kidney and plasma were decreased (1.30${\pm}$ 0.35 $\mu\textrm{g}$/g, 0.13${\pm}$0.02 $\mu\textrm{g}$/ml) when cisplatin was introduced through ILP. Pathologic change in the treated lung with ILP was characterized by the medial hypertrophy of the pulmonary arterioles and interstitial eosinophilic infiltration, which was not dependent on cisplatin

잡견에서 분리폐관류 방법으로 투여된 고농도 cisplatin의 페독성에 관한 연구

김관민,한정호,김주현 대한흉부심장혈관외과학회 2000 Journal of Chest Surgery (J Chest Surg) Vol.33 No.9

Background: Isolated lung perfusion(ILP) was developed as a new treatment approach to non-resectable primary or metastatic lung cancer, because of its ability to reduce systemic toxicity while delivering high-dose chemotherapeutic agents to the target organs. This research was planned to evaluate the direct toxic effect of high-dose cisplatin to the lung tissue during isolated lung perfusion. Material and Method: Fifteen mongrel dogs were divided in the perfusate for 40 minutes. The second group was composed of 5 mongrel dogs which underwent ILP with cisplatin 2.5 mg/Kg added to the perfusate for 30 minutes and 10 minutes with washing solution without cisplatin. The third group underwent the same procedure as the second group except cisplatin 5.0 mg/Kg in the perfusate. Activities of serum angiotensin converting enzyme(ACE), tumor necrosis factor-$\alpha$(TNF-$\alpha$), and concentration of serum lactate dehydrogenase(LDH) and blood urea nitrogen/creatinine (BUN/Cr) were analyzed in each groups at the time of pre-perfusion, 1 hour, 1 day, 1 week, and 2 weeks after ILP. Result: Serum ACE activities before and 1 hour, 1 day, 1 week, and 2 weeks after ILP in control group were 45.1$\pm$6.3, 44.6$\pm$9.3, 46.7$\pm$9.5, 50.8$\pm$9.1, 46.1$\pm$4.3 U/L. Those in cisplatin 2.5 and 5.0 mg/Kg groups were 49.4$\pm$12.6, 39.0$\pm$8.6, 42.3$\pm$15.9, 50.0$\pm$2.6, 53.8$\pm$8.3 and 55.5$\pm$12.3, 47.0$\pm$6.3, 45.1$\pm$6.9, 74.8$\pm$19.5, 60.2$\pm$12.0 U/L, respectively. Serum TNF-$\alpha$ activities in each group before and after ILP were 5.0$\pm$1.5 / 7.7$\pm$2.2 / 6.6$\pm$2.5 / 4.3$\pm$1.3 / 5.2$\pm$1.1(control), 8.7$\pm$1.6 / 9.9$\pm$2.2 / 7.9$\pm$1.5 / 6.3$\pm$2.2 / 7.4$\pm$2.4 (cisplatin 2.5 mg/Kg), and 6.9$\pm$0.7 / 8.9$\pm$3.4 / 7.9$\pm$4.0 / 3.3$\pm$0.9 / 5.8$\pm$1.3 pg/ml(cisplatin 5.0 mg/Kg). Mean LDH levels of each group were 225.7 / 271.3 / 328.9 / 350.8 / 255.7(control), 235.7 / 265.7 / 336.0 / 379.5 / 299.2 (cisplatin 2.5 mg/Kg), and 259.6 / 285.2 / 340.6 / 433.4 / 292.4 IU/L(cisplatin 5.0 mg/Kg). So there was no significant difference in serum ACE, TNF-$\alpha$, and LDH activity changes after ILP between the 3 groups. And, there was no significant changes in BUN/Cr in each groups, which was independent of ILP and perfused concentration of cisplatin. In addition, all dogs survived the ILP and there was no significant evidence of pulmonary vascular injury after 2 weeks of ILP with cisplatin. Conclusion: There was no harmful effect of cisplatin to the lund tissue of the mongrel dog up to 5.0 mg/Kg in perfusate. Therefore, it is perceived to be safe and effective to deliver high-dose cisplatin to the lung without pulmonary toxicity and renal damage with ILP.

가토에서 cisplatin을 사용한 일측성 분리 폐관류

김관민,김진국,심영목,이종헌,한용철,한정호 대한결핵 및 호흡기학회 1997 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.85 No.0