Abstract
Currently, aprotinin is the unique clinically applicable serine-protease inhibitor of protein group which actively
regulates many biological processes. Depending on the dose it can influence the activity of coagulation and
cellular hemostasis, fibrinolysis, systemic inflammatory reaction, organ injury associated with ischemiareperfusion
and apoptosis. However the results of aprotinin application in pediatric cardiosurgery and the
dose administration remain controversial. Safety of its application is also uncertain. All these factors predetermined
the rationale and aims of the study - to evaluate the influence of aprotinin on perioperative hemorrhage
and safety of its application in infants after correction of congenital heart defects under cardiopulmonary
bypass.
Retrospective non-randomized study cohort study included 1261 patients aged from 0 to 14 years. 1285 corrections
of congenital heart defects under cardiopulmonary bypass were performed consecutively, during one
year. Influence of aprotinin on hemostasis was estimated according to incidence of intra- and postoperative
hemorrhage, volume of intra- and postoperative hemorrhage, intraoperative hemostasis time, requirements in
blood product transfusion, necessity in surgical arrest of postoperative bleeding. Efficiency of prophylactic and
therapeutic application of aprotinin was studied. Evaluation of aprotinin safe application supposed analysis
of heart failure incidence, respiratory and cerebral complications, hospital mortality depending on its use.
After follow-up standardization of initial severity of congenital heart defect it was noted reliable reduction of
postoperative blood loss associated with aprotinin use. Among the patients receiving aprotinin heart failure
incidence was more (71.9%) than in control group (19.0%) (p=0.002), however we are prone to associate this
fact with more often application of the drug in more severe cases. In the patients receiving aprotinin and free
from its use incidence of respiratory (27.2% vs 20.7%, p=0.39) and renal (7.9% vs 7.4%, p=0.915) insufficiency,
peritoneal dialysis use (4.6% vs 3.7%, p=0.787), cerebral dysf unction (21.3% vs 22.3%, p=0.887) as well as hospital
lethality (7.4% vs 7.4%, p=0.99) did not differ.
Aprotinin use in pediatric cardiosurgery for hemorrhagic complications is reasonable both with preventive
and therapeutic purpose. The drug does not affect the development of cerebral, renal, respiratory dysfunction
and hospital lethality rate.
References
Дементьева, И. И. Система гемостаза при операциях на сердце и магистральных сосудах. Нарушения, профилактика, коррекция / И. И. Дементьева, М. А. Чарная, Ю. А. Морозов. - М.: ГЭОТАР-Медиа, 2009. - 432 с.
Arnold, D. M. Avoiding transfusions in children undergoing cardiac surgery: a meta-analysis of randomized trials of aprotinin. / D. M. Arnold, D. A. Fergusson, A. K. Chan et al. // Anesth. Analg. - 2006. -Vol. 102. - P. 731-737.
Beuchelt, H. Trasylol, ein Proteinasen-Inhibitor in Experiment und klinischer Anwendung / H. Beuchelt // Med. Chem. - 1963. - Vol. 7. - P. 763-768.
Boldt, J. Aprotinin in pediatric cardiac operations: platelet function, blood loss, and use of homologous blood / J. Boldt, C. Knothe, B. Zickmann et al. // Ann. Thorac. Surg. - 1993. - Vol. 55. - P. 1460-1466.
Boldt, J. Comparison of two aprotinin dosage regiments in pediatric patients having cardiac operations / J. Boldt, C. Knothe, B. Zickmann et al. // J. Thorac. Cardiovasc. Surg. - 1993. - Vol. 105. - P. 705-711.
Boldt, J. Influence of aprotinin on the thrombomodulin/protein c system in pediatric cardiac operations / J. Boldt, B. Zickmann, E. Schindler et al. // J. Thorac. Cardiovasc. Surg. - 1994. - Vol. 107. - P. 1215-1221.
Bulutcu, F. S. Which may be effective to reduce blood loss after cardiac operations in cyanotic children: tranexamic acid, aprotinin or a combination? / F. S. Bulutcu, U. Ozbek, B. Polat et al. // Paediatr. Anaesth. - 2005. - Vol. 15. - P. 41-46.
Chauhan, S. Efficacy of aprotinin, epsilon aminocaproic acid, or combination in cyanotic heart disease / S. Chauhan, B. A. Kumar, B. H. Rao et al. // Ann. Thorac. Surg. - 2000. - Vol. 70. - P. 1308-1312.
Davies, M. J. Prospective, randomized, double-blind study of high-dose aprotinin in pediatric cardiac operations / M. J. Davies, A. Allen, H. Kort et al. // Ann. Thorac. Surg. - 1997. - Vol. 63. - P. 497-503.
DErrico, C. C. The efficacy and cost of aprotinin in children undergoing reoperative open heart surgery / C. C. DErrico, J. R. Shayevitz, S. J. Martindale et al. // Anesth. Analg. - 1996. - Vol. 83. - P. 1193-1199.
Dietrich, W. Hemostatic activation during cardiopulmonary bypass with different aprotinin dosages in pediatric patients having cardiac operations / W. Dietrich, H. Mossinger, M. Spannagl et al. // J. Thorac. Cardiovasc. Surg. - 1993. - Vol. 105. - P. 712-720.
Herynkopf, F. Aprotinin in children undergoing correction of congenital heart defects. A double-blind pilot study / F. Herynkopf, F. Lucchese, E. Pereira et al. // J. Thorac. Cardiovasc. Surg. - 1994. - Vol. 108. - P. 517-521.
Huang, H. Mechanism of the preserving effect of aprotinin on platelet function and its use in cardiac surgery / H. Huang, W. Ding, Z. Su, W. Zhang // J. Thorac. Cardiovasc. Surg. - 1993. - Vol. 106. - P. 11-18.
Kraut, E. ЖberdieInaktivierung des Kallikreins (VI. Mitteilungьber dieses Kreislaufhormon) / E. Kraut, K. Frey, E. Werle // Hoppe. Seylers. Z. Physiol. Chem. - 1930. - Bd. 192. - S. 1-21.
Kunitz, M. Isolation from beef pancreas of crystalline trypsinogen, trypsin, a trypsin inhibitor, and an inhibitor-trypsin compound / M. Kunitz, J. H. Northrop // J. Gen. Physiol. - 1936. - Vol. 19. - P. 991-1007.
Mangano, D. T. Multicenter study of perioperative ischemia research group, ischemia research and education foundation. The risk associated with aprotinin in cardiac surgery / D. T. Mangano, I. C. Tudor, C. Dietzel // N. Engl. J. Med. - 2006. - Vol. 354. - P. 353-365.
Mangano, D. T. Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery / D. T. Mangano, Y. Miao, A. Vuylstekc et al. // JAMA. - 2007. - Vol. 297. - P. 471-479.
McEvoy, M. D. Aprotinin in cardiac surgery: a review of conventional and novel mechanisms of action / M. D. McEvoy, S. T. Reeves, J. G. Reves, F. G. Spinale // Anesth. Analg. - 2007. Vol. 105. - P. 949-962.
McEvoy, M. D. Aprotinin exerts differential and dose-dependent effects on myocardial contractility, oxidative stress, and cytokine release after ischemia-reperfusion / M. D. McEvoy, A.-G. Taylor, J. A. Zavadzkas et al. // Ann. Thorac. Surg. - 2008. - Vol. 86. - P. 568-575.
Miller, B. E. Hematologic and economic impact of aprotinin in reoperative pediatric cardiac operations / B. E. Miller, S. R. Tosone, V. K. Tam et al. // Ann. Thorac. Surg. - 1998. - Vol. 66. - P. 535-541.
Mossinger, H. High-dose aprotinin reduces activation of hemostasis, allogeneic blood requirement, and duration of postoperative ventilation in pediatric cardiac surgery / H. Mossinger, W. Dietrich, S. L. Braun et al. // Ann. Thorac. Surg. - 2003. - Vol. 75. - P. 430-437.
Primack, C. Aprotinin modulation of platelet activation in patients undergoing cardiopulmonary bypass operations / C. Primack, J. M. Walenga, M. J. Koza et al. // Ann. Thorac. Surg. - 1996. - Vol. 61. - P. 1188-1193.
Seghaye, C. M. Influence of low-dose aprotinin on the inflammatory reaction due to cardiopulmonary bypass in children / C. M. Seghaye, J. Duchateau, G. R. Grabitz et al. // Ann. Thorac. Surg. - 1996. - Vol. 61. - P. 1205-1211.
Verstraete, M. Clinical application of inhibitors of fibrinolysis // Drugs. - 1985. - Vol. 29. - P. 236-261.
Wippermann C. F. Reduced inotropic support after aprotinin therapy during pediatric cardiac operations / C. F. Wippermann, F. X. Schmid, B. Eberle et al. // Ann. Thorac. Surg. - 1999. - Vol. 67. - P. 173-176.
