Effect Of High-dose Aprotinin Research Articles

Platelet dysfunction after normothermic cardiopulmonary bypass in children: Effect of high-dose aprotinin

Platelet dysfunction after cardiopulmonary bypass (CPB) can contribute to excessive post-operative bleeding. Most trials of the protective effect of aprotinin in this setting have involved hypothermic CPB, which is more deleterious for platelets than normothermic CPB. Here we investigated the effect of aprotinin on platelet function during normothermic CPB in pediatric patients. Twenty patients (9 newborns [<1 month old] and 11 infants [<36 month old]), weighting less than 15 kg and undergoing normothermic CPB (35-36 degrees C) were randomly assigned to two equal groups, one of which received high-dose aprotinin. Platelet function was assessed by flow cytometry just before CPB and 5 minutes after heparin neutralization. F1 + 2 fragments were measured by ELISA before and 5 minutes after CPB. Platelet activation marker expression (CD62P and activated alphaIIbbeta3) induced by ADP or TRAP was lower after CPB than before CPB, suggesting a deleterious effect of normothermic CPB on platelet function. Prothrombin fragment F1 + 2 levels increased after CPB. Aprotinin administration did not influence the level of prothrombin fragments or platelet marker expression measured in basal condition. However, after CPB, the capacity for platelet activation was higher in the aprotinin group, as shown by measuring CD62P expression after TRAP activation (p = 0.05). This study suggests that pediatric normothermic CPB causes platelet dysfunction, and that high-dose aprotinin has a protective effect.

High-dose aprotinin modulates the balance between proinflammatory and anti-inflammatory responses during coronary artery bypass graft surgery

Objective: To rule out the effect of high-dose aprotinin in respect to the balance of proinflammatory and anti-inflammatory mediators induced by cardiopulmonary bypass (CPB). Design: Randomized, double-blind, placebo-controlled study. Setting: University-affiliated cardiac center. Participants: Twenty patients scheduled for coronary artery bypass graft surgery. Interventions: In group A patients (n = 10), high-dose aprotinin was administered (2 × 106 KIU pre-CPB, 2 × 106 KIU in prime, 500,000 KIU/hr during CPB). In group C patients (n = 10), placebo was used instead. Proinflammatory interleukin (IL)-6, anti-inflammatory IL-1-receptor antagonist, and clinical parameters were measured 8 times perioperatively. The values are presented as mean ± SEM. Measurements and Main Results: Four hours after CPB, IL-6 concentration reached the maximum value, being significantly lower in group A patients as compared with group C patients (615 ± 62 pg/mL v 1409 ± 253 pg/mL; p = 0.019). On the first postoperative day, the concentration of IL-6 in group A patients remained lower (219 ± 24 pg/mL v 526 ± 123 pg/mL; p = 0.015). In contrast, IL-1-receptor antagonist concentration was higher in group A patients as compared with group C patients after CPB (13,857 ± 4264 pg/mL v 5675 ± 1832 pg/mL; p = 0.03). Total postoperative blood loss was lower in group A patients as compared with group C patients (648 ± 64 mL v 1284 ± 183 mL; p = 0.002). Conclusions: High-dose aprotinin treatment reduced the inflammatory reaction and postoperative blood loss. The anti-inflammatory reaction was significantly enhanced in these patients, which suggests that the physiologic reaction of the organism to reduce the deleterious effects from CPB is more pronounced by using high-dose aprotinin. Copyright © 2000 by W.B. Saunders Company

Effect of High-Dose Aprotinin on Plasma Levels During Cardiopulmonary Bypass

In this study, 30 patients who were to undergo open heart surgery were examined in two separate groups. A high dosage of aprotinin (5 mg/kg) was given before and during cardiopulmonary bypass (CPB) to 20 of the patients. Blood samples were taken from the radial artery at the following times: (1) before anesthesia, (2) 30 minutes into the CPB, (3) at the end of the CPB, (4) 30 minutes after a protamine infusion, (5) 24 hours after surgery. The plasma elastase levels in the aprotonin group were much lower than those in the control group at the 30-minute mark of the CPB (p0.01, for all). Serum fibrinogen levels in the aprotinin group were higher than in the control group at the 30 minute mark of the CPB, at the end of the CPB, and 30 minutes after the protamine infusion (p

Effect of High-dose Aprotinin on Postoperative Homologous Blood Requirement in Adult Cardiac Surgery

Effect of High-dose Aprotinin on Postoperative Homologous Blood Requirement in Adult Cardiac Surgery

Effects of high-dose aprotinin on renal function in aortocoronary bypass grafting

To reduce blood consumption in cardiac surgery, aprotinin has been widely used for years. Because aprotinin is metabolized in the kidney, damage of the renal system has been discussed. To study these possibly unfavorable effects of aprotinin, a prospective, randomized, placebo-controlled study of 20 patients undergoing aortocoronary bypass operations was performed. A placebo group P was compared with group A, in which patients received high-dose aprotinin according to the "Hammersmith" regimen. Renal function was assessed for 5 postoperative days using sodium dodecyl sulfate gel electrophoresis and quantitative protein analysis of the urine. During and after the operation, temporary renal dysfunction was found in all patients, with a substantial increase of all investigated indices. The alpha 1-microglobulin level in the urine was significantly increased in the aprotinin group for 5 days in comparison with the placebo group, with a maximum on the third postoperative day (64.8 +/- 13.7 versus 21.0 +/- 6.5 mg/L; p < 0.05). Similarly, after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the bands of proteins filtrated in the renal tubular system were almost tripled in the aprotinin group 5 days postoperatively (5.0 +/- 0.8 versus 2.1 +/- 0.2; p < 0.05). Although urine production was significantly increased in group A (4789 +/- 580 versus 3653 +/- 492 mL/24 h postoperatively; p < 0.05), no relevant changes in serum or urine creatinine levels could be observed in either group. Patients undergoing aortocoronary bypass operations demonstrate a temporary renal dysfunction. Aprotinin impairs renal function in addition by overloading the tubular reabsorption mechanisms. Patients with normal renal function preoperatively--as were included in this study--are able to compensate for both the perioperative renal dysfunction caused by the extracorporeal circulation and the additional tubular damage due to aprotinin.

Effect of high-dose aprotinin on blood loss and need for blood transfusion after repeat open heart surgery

Effect of high-dose aprotinin on blood loss and need for blood transfusion after repeat open heart surgery

Hemostatic Effects of High-Dose Aprotinin in Open Heart Operations

Hemostatic Effects of High-Dose Aprotinin in Open Heart Operations

Effects of high-dose aprotinin on blood loss, platelet function, fibrinolysis, complement, and renal function after cardiopulmonary bypass

The use of aprotinin to reduce blood loss after cardiopulmonary bypass is under debate. Concern has been raised about the renal effects of aprotinin. We administered a mean aprotinin dose of 4.2 x 10(6) kallikrein-inhibiting units to 13 patients with coronary disease undergoing cardiopulmonary bypass for 74 +/- 5 minutes (mean +/- standard error of the mean); 13 comparable patients having cardiopulmonary bypass served as control subjects, and all were studied postoperatively for 24 hours. Aprotinin reduced postoperative blood loss by 50% (p = 0.0082). Two of the 13 patients who received aprotinin needed one red cell unit each versus a total of 18 units in eight of 13 control patients (p = 0.0096). Blood pressure, hemoglobin value and serum protein concentration were higher after operation in the aprotinin group (p less than 0.05 to p less than 0.01). Platelet counts did not differ, but plasma thromboxane was lower in aprotinin recipients (p less than 0.001). In control patients fibrinogen degradation products (D dimer) doubled, and alpha 2-antiplasmin activity was halved during and after cardiopulmonary bypass (p less than 0.01 to p less than 0.001), whereas aprotinin patients showed no changes. The complement breakdown products C4a, C3a, and C3dg as well as C9 neoantigen increased from prebypass baseline in both groups (p less than 0.001); the increment of C3a and C3dg was greater in the aprotinin than in the control patients (p less than 0.001). Serum electrolytes, osmolality, and creatinine remained normal in both groups of patients. Creatinine clearance was normal or above normal and virtually identical in both groups. Osmolar clearance and fractional sodium excretion were higher in the aprotinin group than in the control group shortly after cardiopulmonary bypass (p less than 0.05 to p less than 0.01); renal function was unremarkable the next morning. No adverse clinical effects attributable to aprotinin were seen. In summary, aprotinin offers advantages for cardiopulmonary bypass.

Reduction in blood loss and blood use after cardiopulmonary bypass with high dose aprotinin (Trasylol)

The effect of high dose aprotinin (Trasylol) was evaluated in three groups of patients undergoing cardiopulmonary bypass. In a prospective, placebo-controlled, double-blind study, 80 patients having primary aorta-coronary bypass grafting received aprotinin (700 mg approximately) or saline placebo from the beginning of the procedure until skin closure. Standardized anesthetic, perfusion, and surgical techniques were used. The total loss from the thoracic drains was significantly reduced in the aprotinin group as compared with the loss in the placebo group (309 +/- 133 ml versus 573 +/- 166 ml, p less than 0.01; mean +/- standard deviation). There was a threefold difference in the total hemoglobin loss into the chest drains (aprotinin 12.0 +/- 12.6 gm versus placebo 37.7 +/- 18.3 gm). Patients of the aprotinin group received remarkably less bank blood postoperatively: 13 units total compared with 75 units. Of the 40 patients in the aprotinin group, 32 received no bank blood compared with 2 of 37 patients in the placebo group. Venous hemoglobin levels preoperatively, on day 1, and on day 7 postoperatively did not differ between the groups. At day 7 the values were 13.1 +/- 1.4 gm/dl versus 12.5 +/- 1.2 gm/dl in the aprotinin group and the placebo group, respectively. Platelet counts determined at fixed times perioperatively did not differ between the two groups. In contrast, template bleeding time measured in 32 study patients was distinctly different between groups, with a postoperative rise of 6.2 +/- 2.1 minutes in the placebo group opposed to only 1.5 +/- 1.1 minutes in the aprotinin group.(ABSTRACT TRUNCATED AT 250 WORDS)