Pharmacology of Aprotinin and Efficacy During Cardiopulmonary Bypass

Emerson, Thomas E.

doi:10.1111/j.1527-3466.1989.tb00521.x

Cited by 27 publications

(11 citation statements)

References 58 publications

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“…High doses of aprotinin inhibit fibrinolytic activity both by direct inhibition of plasmin and by inhibition of the kinin-kallikrein system. 67 Kallikrein causes conversion of plasminogen to plasmin, which can have negative effects on platelet function. Kallikrein is the contact activation protein that enhances factor XII activation.…”

Section: Aprotininmentioning

confidence: 99%

Pharmacotherapeutic Considerations in Anesthesia

Amar

2003

Heart Disease

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This article focuses on new findings leading to improved understanding of the pathophysiology and mechanisms of potential drug interactions between anesthetic drugs or techniques and cardiovascular medications in patients scheduled for surgery. Only the most frequently used drugs are reviewed. Elective surgery provides the luxury to consider these risks and alter therapy accordingly. Under urgent circumstances, however, the increased risks associated with these agents should be anticipated with the goal to minimize adverse effects while maintaining optimal cardiovascular function in the perioperative period.

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Section: Aprotininmentioning

confidence: 99%

Pharmacotherapeutic Considerations in Anesthesia

Amar

2003

Heart Disease

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“…The intraoperative use of the prot einase inhibitor aprotinin leads to a known , dose-d epend ent decreas e in intra-and postoperative blood loss and thus to a redu ction in the consumption of blood in pati ents und ergoing cardiopulmonary bypass 0 , 15). The characteristics of the enzyme inhibitor aprotinin ar e bas ed on the inhibition of trypsin, plasmin, and tissue and plasma kallikrein (6). The increase of the ACT during cardiopulmona ry bypass und er high-dose aprotinin therapy has been described in man y clinical studi es (5,8).…”

Section: 4ml Freshblood and 01ml Kaolin Activatormentioning

confidence: 99%

Celite and Kaolin Produce Differing Activated Clotting Times during Cardiopulmonary Bypass under Aprotinin Therapy

Feindt

Seyfert²,

Volkmer³

et al. 1994

Thorac cardiovasc Surg

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Since the introduction of the proteinase inhibitor aprotinin in cardiac surgery, a strong increase of the activated clotting time (ACT) during the extracorporeal circulation phase (ECC) was reported in many clinical studies, but with a lack of correlation between ACT and heparin concentration. In searching for a cause of this inconsistency we investigated different surface activators of the ACT in a clinical study. During ECC ACT was measured in parallel, using a Hemochron device and corresponding tubes (nominally 12 mg celite activator) for celite ACT, and a HemoTec device with corresponding double tubes (nominally 0.1 ml kaolin activator) for kaolin ACT. Under the conditions of ECC, the kaolin ACT values (482 +/- 145 sec) were significantly lower than the celite ACT values (985 +/- 267 sec). These results were confirmed in ex-vivo experiments using an activated partial thromboplastin time (aPTT) model. With heparin alone, aPTT activated with celite and kaolin were similar. Including aprotinin in this model, the celite aPTT showed no correlation to the heparin concentration, whereas the kaolin aPTT remained well correlated to the heparin concentration and similar to the values without aprotinin. With aprotinin alone there were no changes of the aPTT times, whereas the celite ACT times were without any correlation. Our results indicate that using kaolin instead of celite the ACT measurements under aprotinin therapy stay in the same ranges as without application of aprotinin: aprotinin has no detectable influence on kaolin-activated ACT. In our opinion, kaolin should be used as the surface activator for ACT measurements under the conditions of ECC, heparinization, and aprotinin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…[5] Aprotinin is a nonspecific serine protease inhibitor that is able to inhibit various proteases involved in the coagulation, fibrinolytic, and complement cascade. [6] Another action of aprotinin is preservation of glycoprotein IIb receptor on the platelet membrane. Aprotinin has an antiinflammatory effect similar to methylprednisolone in blunting CPB-induced systemic tumor necrosis factor release and neutrophil upregulation.…”

Section: Introductionmentioning

confidence: 99%

Comparison of three dose regimens of aprotinin in infants undergoing the arterial switch operation

et al. 2010

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To determine the most effective dose regimen of aprotinin for infants undergoing arterial switch operation for transposition of the great arteries in reducing blood loss and postoperative packed red blood cell (PRBC) requirements. A total of 24 infants scheduled for arterial switch operation for transposition of the great arteries were included in the study. The infants were randomly assigned to one of the three groups. Group I (n = 8) patients received aprotinin in a dose of 20,000 kallikrein inhibiting units (KIU)/kg after induction of anesthesia, 20,000 KIU/kg was added to the pump prime, and 20,000 KIU/kg/hour infusion for three hours after weaning from bypass; group II (n = 8) patients received aprotinin 30,000 KIU/kg after induction of anesthesia, 30,000 KIU/kg was added to the pump prime and 30,000 KIU/Kg/hour infusion for three hours after weaning from bypass; group III patients (n = 8) received aprotinin 40,000 KIU/kg after induction of anesthesia, 40,000 KIU/kg was added to the pump prime and 40,000 KIU/kg/hour infusion for three hours after weaning from bypass. Postoperatively, the cumulative hourly blood loss and PRBC requirements were noted up to 24 hours from the time of admission in the intensive care unit (ICU). Use of blood and blood products were noted. Coagulation parameters such as hematocrit, activated clotting time (ACT), fibrinogen, prothrombin time (PT), international normalized ratio (INR), platelet count, and fibrin degradation products (FDP) were investigated before cardiopulmonary bypass (CPB), after protamine administration, and at four hours postoperatively in the ICU. The number of infants reexplored for increased mediastinal drainage was recorded. Renal functions were monitored by measuring urine output (hourly) and serum urea (mg%) and serum creatinine (mg%) at 24 hours. The sternal closure time was comparable in all the three groups. Cumulative blood loss (ml/kg/24 hours) was greatest in group I (17.30 +/- 7.7), least in group III (8.14 +/- 3.17), whereas in group II, it was 16.45 +/- 6.33 (P = 0.019 group I versus group III; (P = 0.036 group II versus group III). Postoperative PRBC requirements were significantly less in high dose group III (P = 0.008, group I versus III; p = 0.116, group II versus group III) . Tests for coagulation performed at four hours postoperatively, viz. ACT, PT, INR, FDP, and platelets were comparable in the three groups. Urine output on CPB was comparable in all the groups. Serum urea and creatinine showed no significant difference between the three groups twenty four hours postoperatively. Aprotinin dosage regimen of 40,000 KIU/kg at induction, in CPB prime and postoperatively for three hours was most effective in reducing postoperative blood loss and PRBC transfusion requirements. Aprotinin does not have any adverse effect on renal function.

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Pharmacology of Aprotinin and Efficacy During Cardiopulmonary Bypass

Cited by 27 publications

References 58 publications

Pharmacotherapeutic Considerations in Anesthesia

Pharmacotherapeutic Considerations in Anesthesia

Celite and Kaolin Produce Differing Activated Clotting Times during Cardiopulmonary Bypass under Aprotinin Therapy

Comparison of three dose regimens of aprotinin in infants undergoing the arterial switch operation

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