• Journal of Chest Surgery
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• v.32 no.4
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• pp.358-363
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• 1999

Background: Recently, many cardiac centers have been using aprotinin to reduce operative bleeding in cardiac operations using cardiopulmonary bypass. A variety of reports have confirmed the effectiveness of the drug in cardiac operations. In addition to the operations which could be considered to cause severe operative bleeding such as redo operation, long cardiopulmonary bypass operation and etc, the use of aprotinin is increasing in the field of primary cardiac operations. Varying doses of regimen have been introduced since the first report by Royston et al, and also various opinions on the effectiveness and safeness of the each regimen have been reported. We reviewed our own experience of the full dose aprotinin regimen(Hammersmith regimen) retrospectively. Material and Method: From October 1994 to February 1998, 40 cases of cardiac operative patients were randomized into two groups: aprotinin group(20 patients) which received a full dose aprotinin regimen and control group(20 patients) which did not receive aprotinin. To evaluate the degree of bleeding decrease, we analysed and compared the amount of postoperative 6 hours and 24 hours bleeding in the each group. To confirm the renal dysfunction, we measured the postoperative creatinine level. Result: In the amount of postoperative 6 hours bleeding, a statistically significant bleeding decrease was demonstrated in the aprotinin group compared to the control group(aprotinin group: 186${\pm}$40cc, control group:409${\pm}$69cc, P=0.010). Similar result was observed in the postoperative 24 hours(aprotinin group:317${\pm}$53cc, control group: 671${\pm}$133cc, P=0.024). Conclusion: We concluded that full dose regimen of aprotinin can remarkably reduce postoperative bleeding in cardiac operations without significant renal dysfunctions.

• Journal of Chest Surgery
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• v.30 no.7
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• pp.677-685
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• 1997

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.

• Journal of Chest Surgery
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• v.29 no.3
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• pp.303-310
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• 1996

From December of 1994 to April of 1995, we, SHUH Department of Pediatric Thoracic and Cardiovascular Surgery, studied effects of aprotinin. 95 patients were randomly divided into two groups : group I (n=47) with aprotinin and group ll (n=48) without aprotinin. Aprotinin was given as one shot injection to cardiopulmonary bypass perfusion solution with dose of 50,000 KIUikg. Laboratory data such as hemoglobin, hematocrit, BUH, creatinine, fibrinogen, electrolyte concentration, aPTT, PT, and AT R was checked preoperatively, 5 minutes after anesthesia, 5 minutes and 35 minutes after CPB circulation, and 5 minutes, 3 hours, and 24 hours after reperfusion. Also, chest-tube drainage, transfused amount of RBC, platelet concentrate, and fresh frozen plasma within first 24 hours postoperatively were checked and analyzed after transition nn body weight demension. Only RBC transfused postoperatively had statistical significance with P value of less than 0.001. Others had no difference statistical wise. Postoperative side effects of aprotinin was not detected weeks after the surgery and there was no reoperated patient due to postoperative bleeding.

• Journal of Chest Surgery
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• v.33 no.7
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• pp.560-564
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• 2000

Background; Aprotinin, which is a nonspecific serine protease inhibitor, has an antiinflammatory and thrombogenic effect. However, it has an antithrombogenic effect during the cardiopulmonary bypass. This study was performed to evaluated the effects of aprotinin on the activated clotting time(ACT) and the total amount of the heparin used during the cardiopulmonary bypass. Marterial and Method; From December 1998 to November 1999, 82 consecutive patients electively underwent open heart surgery at Gachon medical school. The patients were older than 18 years. Eighty two patients were classified into a control group(group C, n=36) and a aprotinin-treated group(group A, n=46). Body weight, height, body surface area(BSA), pump time(PT), aortic cross clamping time(ACCT), and body temperature(BT) were determined. Total amount of heparin and protamine during the CPB were also measured. ACT was determined before heparin administration, at 20, 40 and 60 minutes after heparin administration, and after protamine administration. Result; No significant differences were noted in either group in body weight, height, BSA, BT, and the total amoun of heparin and protamine. Group A demonstrated a significant(p <0.05) increase in age, PT, ACCT, and ACT at 20, 40, and 60 minutes after heparin administration. Conclusion; In summary, the use of aprotinin prime resulted in an increase in ACT. The total amount of heparin in aproinin-treated patient was similar to that of the control group in spite of having the prolonged pump time. Therefore aprotinin may reduce the requirement of heparin.

• Proceedings of the KTCVS Conference
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• 1995.10a
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• pp.16-16
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• 1995

• Proceedings of the KTCVS Conference
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• 1998.10a
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• pp.16-16
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• 1998

• Journal of Life Science
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• v.17 no.4 s.84
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• pp.515-521
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• 2007

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.

• Journal of Chest Surgery
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• v.31 no.9
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• pp.867-872
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• 1998

Background: The fixed dose regimen with activated coagulation time(ACT) is the most commonly employed method for determining the required dosage of heparin and protamine during cardiopulmonary bypass(CPB). Material and Method: We performed a prospective study on a fixed dose regimen for analyzing adequate dosages of heparin and protamine, the incidence of heparin resistance and heparin-induced thrombocyt openia, factors affecting ACT during CPB, and changes of ACT during aprotinin usage. 300 units/kg of heparin were administered to patients, and ACTs were measured after 5 mins. ACTs were checked at 10 mins and 30 mins after the onset of CPB, and then at 30 min intervals thereafter. If the measured ACT was under 400 secs, we added 100 units/kg of heparin. The heparin was reversed with 1 mg of protamine for each 100 units administered. If the measured ACT was longer than 130 secs 30 mins after protamine administration or if there was definitive evidence of a coagulation defect, we administered a further 0.5 mg/kg of protamine. Result: We studied 80 patients(50 adults and 30 children) who underwent open heart surgery(OHS) at Seoul National University Hospital. Preoperative ACT was 114.3${\pm}$19.3 secs in adults, and 119.5${\pm}$18.2 secs in children. There were no differences in preoperative ACT due to age, body weight, body surface area, or sex. The preoperative ACT was not influenced by a positive past history of OHS. Ten adults(20%) and 3 pediatric patients(10%) needed additional doses of heparin to maintain the ACT above 400 secs. Additional protamine administration was needed in 9 adults(18%) and 10 children(33%). Heparin resistance was found in only two adults. Heparin-induced thrombocytopenia was detected in 2 adults and 1 child. During CPB, ACT was prolonged. 12 adult patients received a low dose of aprotinin and showed longer celite activated ACT compared to the control group.The kaolin activated ACT showed a lower tendency than the celite activated ACT in aprotinin users. Conclusion: In conclusion, fixed dose regimen of heparin and protamine can be used without significant problems, but the incidence of need of additional dosage remains unsatisfactory.

• Journal of Chest Surgery
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• v.28 no.6
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• pp.549-556
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• 1995

We investigated the effects of aprotinin, a protease inhibitor, on isolated rat heart subjected to cardioplegia and global ischemia for 4 hours and then reperfused for 40 minutes. Before ischemia, hearts were perfused with either aprotinin 1x105KIU/L[Aprotinin group,n=8 or no aprotinin[control group,n=8 added to Krebs-Henseleite solution for 30 minutes. Hemodynamic and biochemical parameters such as heart rate, LVP, dP/dt, coronary flow and creatine kinase were measured before cardioplegia and after reperfusion 10,20,30,40 minutes. After completion of experiment, wet and dry heart weight were measured for tissue water and water content evaluation. On reperfusion, recovery of LVP of aprotinin group at each time point was significantly better than that of control group[p<0.05 , and of dP/dt at reperfusion 40 minutes[p=0.034 . No statistically significant differences in heart rate, coronary flow and CK were observed between the two groups, but aprotinin group seemed to have better recovery. No significant differences in tissue water and water content were observed between the two group.These results suggest that pretreatment of aprotinin is effective in myocardial preservation in prolonged hypothermic ischemia and reperfusion.