Effects of Aprotinin on Acute Lung Injury by Endotoxin in Rabbits / 대한마취과학회지

BACKGROUND: Aprotinin, a serine protease inhibitor, has an anti-inflammatory and hemostatic effect and has been used to reduce perioperative blood loss and lung injury after cardiopulmonary bypass in cardiac surgery. Acute respiratory distress syndrome (ARDS), which results in clinical manifestations due to non-cardiogenic permeability edema is a fatal condition associated with a mortality rate of 50 to 80%. The purpose of this study was to evaluate the effects of aprotinin on acute lung injury induced by bacterial endotoxin in rabbits. METHODS: Nineteen rabbits were anesthetized with intravenous xylazine, Ketamine and vecuronium and ventilated with a Harvard apparatus maintaining normocapnea. In 7 rabbits, 2 mg/Kg of lipopolysaccharide from E. coli was infused intravenously for 30 min (Toxin group) and in another 7 rabbits aprotonin loading with 200,000 KIU/Kg followed by a continuous infusion of 50,000 KIU/Kg/hr was performed 30 min before the endotoxin infusion throughout the experiment (Aprotinin group). At 1, 2, 3, and 4 hours after endotoxin infusion, arterial blood gas, blood cell count, prothrombin time, activated partial thromboplastin time, fibrinogen, and hemodynamic profiles were checKed. At four hours, the animals were dissected at which time the lungs were divided into three regions for wet/dry weight ratio (WW/DW), myeloperoxidase activity and microscopic examination. RESULTS: In the Aprotinin group, pulmonary vascular resistance, arterial oxygen partial pressure and coagulation function were well preserved compared with the Toxin group. Furthermore, lung WW/DW, myeloperoxidase activity, and inflammatory responses also increased less in the Aprotinin group. CONCLUSIONS: The results of the current data showed that aprotinin has prophylactic effects against acute lung injury and coagulation impairment induced by bacterial endotoxin in rabbits.

The Influence of High- and Low-Dose Aprotinin on Thromboelastography in Coronary Artery Bypass Grafting Surgery / 대한마취과학회지

BACKGROUND: The protease inhibitor aprotinin reduces blood loss and homologous blood usage after a cardiac operation. The aim of the present study was to investigate the effect of low- and high-dose aprotinin on thromboelastography (TEG) variables and to examine the relationship between the clinical effect of aprotinin and the TEG variables in coronary artery bypass grafting surgery (CABG). METHODS: Twenty-three patients scheduled for an elective CABG were randomly assigned to receive either high does (group H, n = 12) or low does (group L, n = 11) aprotinin. TEG variables, and a coagulation profile test at baseline and arrival in ICU were performed. Amount of blood loss, homologous blood transfusion and heparin requirements were measured. RESULTS: In group L, there were significant increases in r time and k time and significant decreases in MA and alpha angle after aprotinin administration. In group H, just k time after aprotinin administration was significantly increased compared with baseline data. There were no significant differences in amount of blood loss and allogenic blood transfusions between the two groups. There was not a significant correlation between TEG variables and amount of blood loss in both groups. Interestingly a siginificant negative correlation between the length of cardiopulmonary bypass and MA was noted in group H (r = -0.63; P < 0.05). CONCLUSIONS: In CABG patients, aprotinin preserves platelet function more significantly in the high-dose aprotinin group. In addition, TEG variables indicated a later clot formation in the low dose aprotinin group.

Thromboelastography and Activated Clotting Time as Guides to Prediction of Postoperative Bleeding in Cardiac Patients with Administration of Aprotinin / 대한마취과학회지

BACKGROUND: Activated clotting time (ACT) and thromboelastography (TEG) are generally accepted as adequate measures of the coagulation system for monitoring of the cardiac system. Aprotinin is alleged to affect ACT and TEG. We performed this study to see if the determination of ACT and TEG can provide a basis for the assessment of coagulation and the prediction of postoperative hemorrhage in cardiac surgical patients treated with aprotinin. METHODS: Twenty patients undergoing cardiac operation were studied. The values (control) of ACT and TEG were obtained just after induction of anesthesia. Each patient was fully heparinized and received aprotinin, 2,000,000 KIU added to the prime solution. At the end of the procedure, protamine, 3 mg/kg was given for the neutralization of heparin. Measurement of ACT and TEG were made 20 minutes after the administration of protamine, at the end of surgery, and 1 hour after transfer to ICU. The values were compared with the amount of hemorrage collected by chest tubes 1 hour, 2 hours and 8 hours after transferred to ICU. RESULTS: The values of ACT at 20 minutes after protamine administration and at the end of surgery significantly (P < 0.05) increased compared with the values of control, but the values in ICU did not show significant change. All values of TEG significantly (P < 0.05) changed compared with the values of control. No single variable of ACT and TEG showed correlation with the amount of hemorrhage through chest tubing postoperatively. CONCLUSIONS: The results indicate that neither ACT nor TEG predict the amount of postperative hemorrhage in aprotinin-treated patients having cardiac surgery. Therefore the TEG results should be interpreted cautiously because of the high rate of unreliable results.

Intraoperative Anaphylactoid Reaction Due to Aprotinin during Pediatric Open Heart Surgery / 대한마취과학회지

Aprotinin is a serine protease inhibitor that improves the hemostatic function and modulates the anti-inflammatory responses. Recently, aprotinin has been widely used in various surgical procedures including open heart surgery. One of the complications of aprotinin is anaphylactic reaction and the incidence increases with re-exposure. We experienced a case of anaphylactic reaction in a 5-year-old female during open heart surgery. After cardiopulmonary bypass weaning, during aprotinin i.v. infusion for reducing blood loss, sudden hypotension and bradycardia occurred. After re-institution of CPB, the patient recovered. In the post-operative review of the chart and patient, we found that this patient had been exposed to aprotinin 20 days ago. In conclusion, we recommend some preventable methods for anaphylaxis of aprotinin; aprotinin should be used after a skin test or i.v. infusion test and used by mixing with CPB priming solution.

Anaphylactic Reaction after Aprotinin Reexposure: A case report / 대한마취과학회지

Aprotinin, a proteinase inhibitor, is known to significantly reduce blood loss during cardiac, thoracic and vascular surgery. Despite the wide use of this medication, there are only a few reports of anaphylactic reactions. We experienced a case of severe intraoperative anaphylactic reaction due to reexposure of aprotinin used to reduce intraoperative bleeding. During anesthesia for brain tumor removal, systemic hypotension and generalized rash were developed following the administration of aprotinin in a 34-year-old woman. We suggest that it is necessary, in patients known to have had previous aprotinin therapy, to perform skin test with diluted aprotinin before infusion.

Comparison of Hemostatic Effects between Aprotinin and Tranexamic Acid during Open Heart Surgery in Adults / 대한마취과학회지

BACKGROUND: Antifibrinolytics such as aprotinin and tranexamic acid have been administered to reduce blood loss of cardiac surgery, but opinions differ regarding the efficacy of each drug. This study was performed to compare the hemostatic effects between aprotinin and tranexamic acid on adult open heart anesthesia and to evaluate their additive effects. METHODS: We randomly allocated 73 patients undergoing coronary artery bypass grafting or double valve surgery to 4 groups. Group I was non-medicated control(n=15), group II(n=21)patients were recipients of a high dose of aprotinin, group III(n=16) patients were recipients of a conventional dose of tranexamic acid, and group IV(n=21) were recipient of both drugs. Cardiopulmonary bypass time, total operation time, hematocrit, platelet count, transfusion amount and 6 hours of postoperative chest tube drainage were measured. RESULTS: The medicated three groups significantly demonstrated less amounts of blood transfusion and blood loss over the first 6 hours at ICU compared to the nonmedicated control group. Total operation times were shorter in group II, III, and IV compared to group I. Use of both agents together was more effective in reducing the total operation time and blood loss compared to tranexamic alone. CONCLUSIONS: We conclude that the use of aprotinin and tranexamic acid result in significant positive hemostatic effects but superiority of one agent vs. the others is not proved. Use of two agents together yield a more positive effective in reducing the operation time and the blood loss compared to single agent alone but further study would be needed to fully confirm.

In Vitro Aprotinin Enhanced Anticoagulation Synergistically to Heparinized Blood on Thromboelastography / 대한마취과학회지

BACKGROUND: Aprotinin is a potent, nonspecific broad serine protease inhibitor. It's inhibitory effects on intrinsic pathway of coagulation cascade can augment anticoagulation by heparin. This study designed to demonstrate augmented anticoagulation of aprotinin to heparin contaminated blood on thromboelastography(TEG). METHODS: This study designed into two phases for 21 healthy volunteers undergoing elective opeation. The first phase study, it was for looking at TEG differences between blood treated with aprotinin 200 KIU and blood treated with heparin 0.05 unit and 0.1 unit per blood 1 ml. The second phase study was for looking at anticoagulation of aprotinin added by heparin 0.05 unit and 0.1 unit per blood 1 ml and their reversal added by optimal dose of protamine sulfate. RESULTS: The aprotinin treated blood showed only a prolonged reaction time. Blood treated with incremental dose of heparin showed longer reaction time and smaller alpha angle than TEGs of native blood. Aprotinin added to the heparin contaminated blood showed much longer reaction time and much less alpha angle when compared with TEGs of aprotinin or heparin treated blood. Depressed TEG pattern by the heparin and aprotinin mixture reversed back to the TEGs of blood treated with aprotinin when optimal dose of protamine added. CONCLUSIONS: Those results suggest that aprotinin administered in open cardiac surgery can augment the remained anticoagulation effect due to heparin even after first dose fo protamine after weaning of cardiopulmonary bypass. This is of clinically improtance to distinguish heparin related coagulopathy from heparin non related coagulopathy by thromboelastography.

Effects of Three Different Regimens of Aprotinin Dosage on Blood Loss During Open Heart Surgery / 대한마취과학회지

BACKGROUND: High dose of aprotinin has been known to reduce the requirement for homologous transfusion and the loss of blood during cardiac operation. The aim of this study was to investigate an effective minimal dose of aprotinin. METHODS: With IRB approval 61 patients undergoing cardiac operation were divided into four groups. Group I was control (n=15). Group II(high dose aprotinin, n=16) received an infusion of 24,000 KIU/kg of aprotinin followed by continous infusion of 6,000 KIU/kg per hour until the end of operation. A bolus of 24,000 KIU/kg was added to pump prime solution. Group III(low dose aprotinin, n=16) received a bolus of 24,000 KIU/kg to prime solution. Group IV(minimal dose aprotinin, n=14) received a bolus of 12,000 KIU/kg to prime solution. Coagulation profiles were analysed and blood loss through chest tubes & amount of homologous transfusion was measured. Statistical analysis was performed using one-way variance analysis. RESULTS: Group II demonstrated less amount of blood loss than group I with statistical significance. Blood loss in group III was reduced about 20% but the reduction was not statistically significant. Group IV could not reduce the blood loss. CONCLUSION: This study shows the efficacy of high and low dose(not statistically significant) aprotinin infusion during cardiac surgery in postoperative blood loss. Use of aprotinin less than low dose regimen may not be effective in reducing the blood loss and amount of homologous transfusion in cardiac operation.