DOI QR코드

DOI QR Code

심장수술시 심폐기 충전액에 첨가된 저용량 aprotinin의 효과

Effect of Low Dose Administration of Aprotinin in Pump Priming Solution on Cardiac Surgery

  • 문성민 (동아대학교 의과대학 흉부외과학교실 체외순환연구실) ;
  • 최석철 (부산가톨릭대학교 보건과학대학 임상병리학과)
  • Moon, Seong-Min (Laboratory of Extracorporeal Circulation, Department of Thoracic and Cardiovascular Surgery, Dong-A University Medical Center, College of Medicine, Dong-A University) ;
  • Choi, Seok-Cheol (Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan)
  • 발행 : 2007.04.25

초록

Serine protease 억제약물인 aprotinin은 체외순환을 동반한 심장수술 후 필연적으로 발생하는 혈액성분 손상을 포함한 유해한 합병증을 감소시키기 위해 사용한다. 그러나 이 약물의 용량이나 사용법에 대해 여전히 논란의 여지가 있다. 본 연구자들은 심장수술 동안 심폐기 충전액에 저 용량의 aprotinin을 투여하여 그 효과를 연구하였다. 30명의 성인 심장수술 환자들을 대상으로 aprotinin 투여군(n=15)과 대조군(n=15)으로 나눈 뒤 수술 전, 동안, 후의 시기에 혈액학적 및 생화학적 변수들, 사이토카인 및 심장 표지자, 수술 후 각종 임상결과들을 비교분석 하였다. 혈소판수와 activated partial thromboplastin time은 수술 후 24시간 때 아프로티닌군이 대조군 보다 유의하게 높았다. Troponin-I 농도와 수술 후 출혈량은 아프로티닌군이 대조군보다 유의하게 낮았다. 이러한 결과들을 볼 때 심장수술시 저 용량의 aprotinin을 심폐기 충전액에 첨가하는 방법은 혈소판의 파괴를 줄여줘 수술 후 출혈량의 감소를 제공해주며 심근보호 효과가 있는 것으로 판단된다. 향후 더 많은 성인 환자군과 소아환자에 대한 다양한 연구가 더 많이 수행되어야 할 것으로 사료된다.

Aprotinin, a serine protease inhibitor, has been used to ameliorate the inevitable consequences, including blood component injury after cardiac surgery with cardiopulmonary bypass (CPB). However, there are many arguments on its dosage or usage. We assessed whether administration of low dose of aprotinin in only priming solution has any beneficial effect or reduces its side effects on cardiac surgery. Thirty patients scheduled for elective cardiac surgery were randomly assigned to aprotinin group (n=15) which received aprotinin in priming solution (two million kallikrein inhibitory unit, KIU) and added one million KIU at 1 hour after the beginning of CPB or control group (n=15) which did not receive it. Hematological and biochemical variables, cytokines and cardiac marker levels, and postoperative outcomes were compared between two groups at before, during or after operation. Platelet count in aprotinin group was higher than that of control group at postoperative 24 hr. Activated partial thromboplastin time in aprotinin group was longer than that of control group at intensive care unit (ICU). Troponin-I level and postoperative blood loss volumes in aprotinin group were lower than those of control group at ICU. There were no significant differences between the two groups on the others. These results showed that low dosage of only priming solution during cardiac surgery with CPB reduced platelet destruction and postoperative bleeding, and attenuates myocardial damage. However, further studies need to be carried out with more population or pediatric patients for evaluating various aprotinin usage.

키워드

참고문헌

  1. Ashraf, S., Y. Tian and D. Cowan. 1997. 'Low-dose' aprotinin modifies hemostasis but not proinfIammatory cytokine release. Ann. Thorae. Surg. 63, 68-73 https://doi.org/10.1016/S0003-4975(96)00812-0
  2. Baufreton, C., H. Velthuis, P. G. M. Jansen, P. Lebesnerais, C. H. R. Wildevuur and D. Y. Loisance. 1996. Reduction of blood activation in patients requiring aprotinin during cardiopulmonary bypass for coronary artery surgery. ASAlO. J. 42:M, 417-423 https://doi.org/10.1097/00002480-199609000-00023
  3. Boher, H., A. Bach, F. Fleicher and J. Lang. 1990. Adverse haemodynamic effects of high-dose aprotinin in a paediatric cardiac surgical patients. Anaesthesia 45, 853-854 https://doi.org/10.1111/j.1365-2044.1990.tb14571.x
  4. Covino, E., D. Pepino, D. Iorio, L. Marino, P. Ferrara and N. Spampinalo. 1991. Low dose aprotinin as blood saver in open heart surgery. Eur. J. Cardiothorac. Surg. 5, 619-624
  5. Defraigne, J. O., J. Pincemail, R. Larbuisson, F. Blaffart and R. Limet. 2000. Cytokine release and neutrophil activation are not prevented by heparin-coated circuits and aprotinin administration. Ann. Thorac. Surg. 69, 1084-1091 https://doi.org/10.1016/S0003-4975(00)01093-6
  6. Gurevith, J., J. Barak, E. Hochhauser, Y. Paz and V. Yakirevich. 1994. Aprotinin improves myocardial recovery after ischemia and reperfusion: Effects of the drug on isolated rat hearts. J. Thorac. Cardiovasc. Surg. 108, 109-118
  7. Harder, M. P., L. Eijsman, K. J. Roozendal, W. van Oevern and C. R. Wildevuur. 1991. Aprotinin reduces intraoperative and postoperative blood loss in membrane oxygenator cardiopulmonary bypass. Ann. Thorac. Surg. 51, 936-941 https://doi.org/10.1016/0003-4975(91)91009-K
  8. Kawasuji, M., K. Ueyama and S. Naoki. 1993. Effect of low-dose aprotinin on coagulation and fibrinolysis in cardiopulmonary bypass. Ann. Thorac. Surg. 55, 1205-1209 https://doi.org/10.1016/0003-4975(93)90035-G
  9. Liu, B., L. Tengborn and G. Larson. 1995. Half-dose aprotinin preserve hemostatic function in patient undergoing bypass operations. Ann. Thorac. Surg. 59, 1534-1540 https://doi.org/10.1016/0003-4975(95)00240-L
  10. McMahon, M. J. and A. T. R. Axon. 1984. Anaphylactic reaction to aprotinin. Br. J. Med. 289, 1696
  11. Royston, D., B. P. Bidstrup, K. M. Taylor and R. N. Sapsford. 1987. Effect of aprotinin on need for blood transfusion after repeat open heart surgery. Lancet 2, 1289-1291
  12. Shin, Y. C., T. K. Cheon, Y. S. Won, Y. J Kim and J. R. Rho. 1996. Effect of aprotinin on postoperative bleeding and blood coagulation system in pediatric open heart surgery. Kor. J. Thorac. Cardiovasc. Surg. 29, 303-310
  13. Sunamori, M., I. Sultan and A. Suzuki. 1991. Effect of aprotinin to improve myocardial viability in myocardial preservation followed by reperfusion. Ann. Thorac. Surg. 52, 971-9 https://doi.org/10.1016/0003-4975(91)91263-U
  14. Sundt, T. M., N. T. Kouchoukos and J. E. Saffitz. 1993. Renal dysfunction and intravascular coagulation with aprotinin and hypothermic circulatory arrest. Ann. Thorac. Surg. 55, 1418-1424 https://doi.org/10.1016/0003-4975(93)91082-X
  15. Ulker, S., P. P. Mckeown and U. Bayraktutan. 2002. Aprotinin impairs coronary endothelial function and down-regulates endothelial NOs in rat coronary microvascular endothelial cells. Cardiovascular Research 55, 830-837 https://doi.org/10.1016/S0008-6363(02)00489-3
  16. van Oeveren, W., M. P. Harder, K. J. Roozendaal, L. Eijsman and C. R. Wildevuur. 1990. Aprotinin products platelet against the initial effect of cardiopulmonary bypass. J. Thorac. Cardiovasc. Surg. 99, 788-797
  17. Wachtfogel, Y. T., U. Kucich and C. E. Hack. 1993. Aprotinin inhibits the contact, neutrophil and platelet activation systems, during simulated extracorporeal perfusion. J. Thorac. Cardiovasc. Surg. 106, 1-10
  18. Westaby, S. 1993. Aprotinin in perspective. Ann. Thorac. Surg. 55, 1033-1041 https://doi.org/10.1016/0003-4975(93)90149-C
  19. Wippermann, C. F., F. X. Schmid and B. Eberle. 1999. Reduced inotrpic support after aprotinin therapy during pediatric cardiac operations. Ann. Thorac. Surg. 67, 173-176 https://doi.org/10.1016/S0003-4975(98)00974-6