Assessment of Aprotinin Loaded Microemulsion Formulations for Parenteral Drug Delivery: Preparation, Characterization, in vitro Release and Cytotoxicity Studies.

The object of the current study was to prepare novel microemulsion formulations of aprotinin for parenteral delivery and to compare in vitro characteristics and release behaviour of different Technetium-99m ((99m)Tc)-Aprotinin loaded microemulsion formulations. In addition, cytotoxicity of microemulsion formulation was evaluated with cell culture studies on human immortalized pancreatic duct epithelial-like cells. For this aim, firstly, pseudo-ternary phase diagrams were plotted to detect the formulation region and optimal microemulsions were characterized for their thermodynamic stability, conductivity, particle size, zeta potential, viscosity, pH and in vitro release properties. For in vitro release studies aprotinin was labelled with (99m)Tc and labelling efficiency, radiochemical purity and stability of the radiolabeled complex were determined by several chromatography techniques. Radiolabeling efficiency of (99m)Tc-Aprotinin was found over than 90% without any significant changes up to 6 hours after labelling at room temperature. After that, in vitro release studies of (99m)Tc-Aprotinin loaded microemulsions were performed with two different methods; dissolution from diffusion cells and dialysis bags. Both methods showed that release rate of (99m)Tc- Aprotinin from microemulsion could be controlled by microemulsion formulations. Drug release from the optimized microemulsion formulations was found lower compared to drug solution at the end of six hours. According to stability studies, the optimized formulation was found to be stable over a period of 12 months. Also, human immortalized pancreatic duct epithelial-like cells were used to evaluate the cytotoxicity of optimum formulation. Developed microemulsion did not reveal cytotoxicity. In conclusion the present study indicated that the M1-APT microemulsion is appropriate for intravenous application of aprotinin.

Differential effects of aprotinin and tranexamic acid on outcomes and cytokine profiles in neonates undergoing cardiac surgery.

OBJECTIVE: Factors contributing to postoperative complications include blood loss and a heightened inflammatory response. The objective of this study was to test the hypothesis that aprotinin would decrease perioperative blood product use, reduce biomarkers of inflammation, and result in improved clinical outcome parameters in neonates undergoing cardiac operations. METHODS: This was a secondary retrospective analysis of a clinical trial whereby neonates undergoing cardiac surgery received either aprotinin (n = 34; before May 2008) or tranexamic acid (n = 42; after May 2008). Perioperative blood product use, clinical course, and measurements of cytokines were compared. RESULTS: Use of perioperative red blood cells, cryoprecipitate, and platelets was reduced in neonates receiving aprotinin compared with tranexamic acid (P < .05). Recombinant activated factor VII use (2/34 [6%] vs 18/42 [43%]; P < .001), delayed sternal closure (12/34 [35%] vs 26/42 [62%]; P = .02), and inotropic requirements at 24 and 36 hours (P < .05) were also reduced in the aprotinin group. Median duration of mechanical ventilation was reduced compared with tranexamic acid: 2.9 days (interquartile range: 1.7-5.1 days) versus 4.2 days (2.9-5.2 days), P = .04. Production of tumor necrosis factor and interleukin-2 activation were attenuated in the aprotinin group at 24 hours postoperatively. No differential effects on renal function were seen between agents. CONCLUSIONS: Aprotinin, compared with tranexamic acid, was associated with reduced perioperative blood product use, improved early indices of postoperative recovery, and attenuated indices of cytokine activation, without early adverse effects. These findings suggest that aprotinin may have unique effects in the context of neonatal cardiac surgery and challenge contentions that antifibrinolytics are equivalent with respect to early postoperative outcomes.

Population pharmacokinetic analysis and dosing regimen optimization of aprotinin in neonates and young infants undergoing cardiopulmonary bypass.

The objective of this study was to determine an optimal dosing regimen for maintaining the therapeutic target range of aprotinin in neonates and young infants during cardiopulmonary bypass (CPB). A total of 27 patients scheduled for open heart surgery were enrolled. Aprotinin was administered a 25 000 KIU (kallikrein inhibition unit)/kg bolus before operation, a 35 000 KIU/kg for CPB circuit priming, and a 12 500 KIU/kg/hour continuous infusion intra- and immediate postoperative period. Blood samples were obtained at 12 time points per patient. Population pharmacokinetic modeling and Monte-Carlo simulations were used to optimize the aprotinin dosing regimen. No mortality or aprotinin-related complication was encountered. A CPB adjusted 2-compartment model best fit the data. Clearance was 687 mL/hour during CPB and 350 mL/hour pre- and post-CPB, and corresponding volumes of distribution were 1577 mL and 1352 mL, respectively. The simulations conducted showed that more than twice the dose administered in this study is required to maintain the target concentration of aprotinin. The pharmacokinetics of aprotinin appears to be affected more sensitively by CPB in neonates and young infants than in adults. Therefore, dosage adjustment considering these pharmacokinetic differences and the influence of CPB is needed in neonates and young infants.

Aprotinin in pediatric neuromuscular scoliosis surgery.

Reduction of blood transfusions in patients with neuromuscular scoliosis can decrease potential complications such as immune suppression, infection, hemolytic reaction and viral transmission. Aprotinin (Trasylol), Bayer), an antifibrinolytic, has proven to be effective in reducing blood loss in cardiac and liver surgery, but little data exists in patients undergoing spinal fusion for neuromuscular scoliosis. The purpose of this study was to evaluate the safety and efficacy of aprotinin in pediatric neuromuscular scoliosis patients undergoing spinal fusion. The medical records of all patients undergoing initial spinal fusions for neuromuscular scoliosis between January 1999 and March 2003 were reviewed to determine demographic data, perioperative data, wound drainage and number of transfusion required. Cases were compared to a matched group of historical controls. We had 14 patients in the aprotinin group and 17 in the control group. Total blood loss in the aprotinin group was significantly lower compared to the control group (715 vs. 2,110 ml; P = 0.007). Significantly less blood loss occurred in the aprotinin group when blood loss per kilogram was evaluated as well (23 vs. 60 ml/kg, respectively; P = 0.002). Intra-operative packed red blood cell (PRBC) transfusions were also significantly lower in the aprotinin group (1.25 vs. 3.16 units; P = 0.001). No clinical evidence of anaphylaxis, deep vein thrombosis (DVT) or renal failure was observed in the aprotinin group. After considering the price of drug therapy, operating room time, and the cost of blood products, the use of aprotinin saved an average of $8,577 per patient. In our series, the use of aprotinin resulted in decreased blood loss and a decreased rate of transfusions in children with neuromuscular scoliosis undergoing extensive spinal fusion. At out institution, the use of aprotinin is safe and cost effective for patients with neuromuscular scoliosis.

Cost analysis of aprotinin for coronary artery bypass patients: analysis of the randomized trials.

BACKGROUND: The full kallikrein-inhibiting dose of aprotinin has been shown to reduce blood loss, transfusion requirements, and the systemic inflammatory response associated with cardiopulmonary bypass graft surgery (CABG). A half-dose regimen, although having a reduced delivery cost, inhibits plasmin and fibrinolysis without substantially effecting kallikrein-mediated inflammation associated with bypass surgery. The differing pharmacologic effects of the two regimens impact the decision-making process. The current study assessed the medical cost offset of full-dose and half-dose aprotinin from short- and long-term perspectives to provide a rational decision-making framework for clinicians. METHODS: To estimate CABG admission costs, resource utilization and clinical data from aprotinin clinical trials were combined with unit costs estimated from a Duke University-based cost model. Lifetime medical costs of stroke and acute myocardial infarction were based on previous research. RESULTS: Relative to placebo, the differences in total perioperative cost for primary CABG patients receiving full-dose or half-dose aprotinin were not significant. When lifetime medical costs of complications were considered, total costs in full-dose and half-dose aprotinin-treated patients were not different relative to that of placebo. Total perioperative cost was significantly lower for repeat CABG patients treated with aprotinin, with savings of $2,058 for full-dose and $2,122 for half-dose patients when compared with placebo. Taking lifetime costs of stroke and acute myocardial infarction into consideration, the cost savings estimates were $6,044 for full-dose patients and $4,483 for half-dose patients, due to substantially higher lifetime stroke costs incurred by the placebo patients. CONCLUSIONS: Using this cost model, use of full-dose and half-dose aprotinin in primary CABG patients was cost neutral during hospital admission, whereas both dosing regimens were significantly cost saving in reoperative CABG patients. Additional lifetime cost savings were realized relative to placebo due to reduced complication costs, particularly with the full-dose regimen. As the full kallikrein-inhibiting dose of aprotinin has been shown to be safe and effective, the current results support its use in both primary and repeat CABG surgery. No demonstrable economic advantage was observed with the half-dose aprotinin regimen.

Impact of tranexamic acid vs. aprotinin on blood loss and transfusion requirements after cardiopulmonary bypass: a prospective, randomised, double-blind trial.

INTRODUCTION: Aprotinin (AP) reduces blood loss and transfusions after cardiopulmonary bypass (CPB), but may sensitise patients and is expensive. Tranexamic acid (TA) has less side-effects, but data regarding its efficacy are controversial. The aim of our prospective, randomised, double-blind study was to compare the impact of AP vs. TA on drainage blood loss and transfusion requirements in patients undergoing first time CABG on CPB. MATERIALS AND METHODS: One hundred and twenty adult patients were randomised to receive either high-dose AP according to Hammersmith or a total of 2 g TA. Perioperative blood products were transfused in a standardised fashion. Blood loss was measured up to 24 h. Demographic and clinical patient data were collected until hospital discharge. RESULTS: The data from 118 patients (TA: n = 58, AP: n = 60) who completed the study according to protocol were analysed. Blood loss at 24 h postoperation in TA patients was significantly higher (896 +/- 354 ml) as compared to AP patients (756 +/- 347 ml; p = 0.03). TA patients received 1.5 +/- 1.5 units of red blood cells (AP: 1.5 +/- 1.7, p = 1.0), 1.3 +/- 2.0 units of fresh frozen plasma (AP: 1.0 +/- 2.0, p = 0.38) and 0.5 +/- 1.4 units of platelets (AP: 0.2 +/- 0.7, p = 0.15). Clinical data, including perioperative myocardial infarction rate, acute renal failure, mechanical ventilation, hospital stay and mortality, were not significantly different between either group. CONCLUSION: Our data show a difference in blood loss between TA and high-dose AP. Although statistically significant, it has little clinical relevance, because perioperative transfusion requirements were similar for both groups. Thus, TA appears to be a cost-effective alternative to AP in primary CABG patients.

Aprotinin: antifibrinolytic and anti-inflammatory mechanisms of action in cardiac surgery with cardiopulmonary bypass.

Cardiopulmonary bypass results in activation of the coagulation, fibrinolytic, inflammatory, and complement cascades. These activated cascades result in a decrease in the number of circulating coagulation factors, hyperfibrinolysis, thrombocytopenia, platelet defects, coagulopathies, and an acute inflammatory response. Patients experiencing cardiac surgery with cardiopulmonary bypass are at risk for many potential problems. The use of aprotinin, an antifibrinolytic agent, has multiple effects that tend to reduce hematological defects and blunts the inflammatory response that is associated with cardiac surgery. The pathophysiological consequences of cellular activation associated with cardiopulmonary bypass, basic mechanisms of action of aprotinin, pharmacodynamic and pharmacokinetic properties, dosing, adverse reactions, and cost/benefit ratio are discussed in this article. Critical care nurses need to know about aprotinin to understand its role in reducing blood loss and transfusions during and after cardiac surgery.

Leukodepletion and aprotinin improve clinical outcome after extracorporeal circulation.

Most cardiac operations involve the use of extracorporeal circulation with its attendant systemic inflammatory response syndrome. Many anti-inflammatory strategies hold promise for reducing the associated morbidity of cardiopulmonary bypass. The application of pharmacological and mechanical strategies to control this inflammatory response now has demonstrable clinical benefit. The additional costs of these successful strategies are offset by the economic savings and improved quality of care.

Comparison of epsilon aminocaproic acid and low-dose aprotinin in cardiopulmonary bypass: efficiency, safety and cost.

BACKGROUND: In this study we compared the clinical efficiency, safety, and economic benefit of low-dose aprotinin with epsilon aminocaproic acid (EACA) in reducing bleeding after cardiopulmonary bypass operation. METHODS: In a double-blind, randomized study, 100 patients received low-dose aprotinin (2 x 10(6) kallikrein inhibitor units) or EACA (20 g). The surgical procedure was single- or double-valve replacement with or without coronary artery bypass grafts. RESULTS: Mediastinal chest drainage and transfusion requirements with both therapies were similar. There were no urgent reoperations to secure hemostasis in either group. Similar levels of D-dimer with both therapies indicate a similar inhibition of fibrinolysis. Release of troponin I was less in the low-dose aprotinin group 1 and 4 hours after bypass, although electrocardiographic measurements did not reflect this difference. Levels of S-100beta and neuron-specific enolase were similar with both therapies, confirming that there was no difference in the occurrence of any adverse neurologic events in either group. CONCLUSIONS: Low-dose aprotinin and EACA showed similar effects on the reduction of intraoperative and postoperative bleeding. The lower cost of EACA with no change in safety outcome suggests it is the preferred treatment.

Ultra-low dose aprotinin decreases transfusion requirements and is cost effective in coronary operations.

BACKGROUND: The recommended dose of aprotinin has been shown to reduce blood loss and need for blood transfusions, but the cost precludes its routine use. This study was designed to determine whether a less expensive, ultra-low dose of aprotinin is effective when used in coronary artery bypass grafting with left internal mammary artery. METHODS: Patients (n = 202) were randomized to receive either placebo or aprotinin, 0.5 million KIU before incision and 0.5 million KIU during initiation of cardiopulmonary bypass. Differences in quantity of blood transfused were analyzed. Further groups were analyzed to account for the effect of aspirin. Multivariable analysis was performed to determine risk factors for transfusion. Direct costs of blood products and aprotinin were tabulated for each group. RESULTS: There was an important reduction in the proportion of patients transfused, and number of blood units transfused when aprotinin was given before coronary artery bypass grafting. These differences were even more important in patients on aspirin preoperatively. Independent predictors for increased number of transfusions were aspirin continued before operation, smaller body surface area, and the use of placebo instead of ultra-low dose aprotinin. There was no difference in morbidity between treatment groups. There was a reduction in direct costs associated with the use of aprotinin. CONCLUSIONS: These data support the routine use of aprotinin 1 million KIU in coronary artery bypass grafting with left internal mammary artery to reduce cost and transfusion requirements.

Role of aprotinin in the management of patients during and after cardiac surgery.

Management of patients undergoing cardiac surgery has evolved in recent years as more is understood about the physiological changes and responses that occur during and after cardiopulmonary bypass (CPB). In particular, our understanding of the mechanisms involved in haemostasis and in the inflammatory response to bypass surgery, has allowed significant refinements in patient management. Improvements in the pharmacological conservation of blood loss have been striking, particularly with the development of the serine protease inhibitor, aprotinin (Trasylol, Bayer). Aprotinin represents a significant improvement, especially for patients at high risk, since it reduces the need for allogeneic and (sometimes scarce) blood products. However, in view of its cost, making an appropriate selection of patients most at risk of serious blood loss is a major consideration in the use of aprotinin. While its mechanisms of action are not well understood, the use of aprotinin also appears to reduce inflammatory response to CPB.

Economic evaluation of high-dose and low-dose aprotinin therapy during cardiopulmonary bypass.

BACKGROUND: Aprotinin therapy is now widely used during cardiac surgery. This study examined the clinical and economic effectiveness of high-dose or low-dose aprotinin in comparison to placebo. METHODS: In a double blind, randomized study, three groups of 50 patients received high-dose aprotinin costing AUS$614 per patient (AUS$ = Australian dollars), low-dose aprotinin costing AUS$220 per patient or placebo. Resource use influenced by aprotinin therapy was measured. RESULTS: Both doses were effective in reducing chest drainage and postoperative transfusion requirements, high-dose being more effective than low-dose. Both doses reduced the rate of reoperations for hemostasis. A base case of statistically significant differences associated with the high-dose and low-dose aprotinin showed cost savings of AUS$77 and AUS$348 per patient, respectively. If the demonstrated less significant reductions in operating room and ward stay are included, these savings become AUS$463 and AUS$715, respectively. Alternately, if cross-matches are replaced by group-and-hold and cell savers are not used, the savings per patient would be AUS$196 and AUS$467, respectively. CONCLUSIONS: While high-dose aprotinin is clinically more effective than low-dose aprotinin, low-dose therapy demonstrates greater cost savings.

The efficacy and safety of aprotinin use in cardiac surgery.

BACKGROUND: The serine protease inhibitor aprotinin has received much attention in cardiac surgical practice as a pharmacologic intervention to improve the hemostatic derangement associated with cardiopulmonary bypass. This review highlights the major studies undertaken to investigate the efficacy and safety of aprotinin use in both primary and repeat coronary artery bypass graft surgical procedures. METHODS: There have been at least 45 controlled studies in more than 7,000 patients in a variety of patient populations. These have ranged from primary coronary artery bypass graft and valve operations to complex reoperation procedures, including aortic arch reconstructions and thoracic organ transplantation. The recently completed International Multicenter Graft Patency Experience trial, the largest study to date, involved 870 patients at 13 international sites. The study examined the effects of aprotinin on graft patency, incidence of myocardial infarction, and blood loss in patients undergoing primary coronary artery bypass graft operations with cardiopulmonary bypass. RESULTS: Twenty-one studies in approximately 5,000 patients undergoing primary coronary artery bypass graft or valve operations reported 33% to 66% reduction in blood loss with full-dose aprotinin therapy; 15 of the same studies reported significant reductions in transfusion requirements, ranging from 31% to 85%. The recently completed International Multicenter Graft Patency Experience study observed a significant reduction in thoracic-drainage volume of 43% (p < 0.0001) and a 49% (p < 0.001) reduction in the requirement for allogeneic blood transfusions. Aprotinin did not affect the occurrence of definite myocardial infarction (aprotinin, 2.9% versus placebo, 3.8%) or mortality (aprotinin, 1.4% versus placebo, 1.6%). There was no observed difference in the patency of internal mammary artery bypass grafts from all study sites in aprotinin- versus placebo-treated patients (aprotinin, 98.2% versus placebo, 98.0%). CONCLUSIONS: Given the risks and costs associated with excessive bleeding and transfusions and the limited supply of banked blood, aprotinin represents an important and safe approach to blood conservation.

Hematologic and economic impact of aprotinin in reoperative pediatric cardiac operations.

BACKGROUND: Aprotinin consistently reduces blood loss and transfusion requirements in adults during and after cardiac surgical procedures, but its effectiveness in children is debated. We evaluated the hemostatic and economic effects of aprotinin in children undergoing reoperative cardiac procedures with cardiopulmonary bypass. METHODS: Control, low-dose aprotinin, and high-dose aprotinin groups were established with 15 children per group. Platelet counts, fibrinogen levels, and thromboelastographic values at baseline and after protamine sulfate administration, number of blood product transfusions, and 6-hour and 24-hour chest tube drainage were used to evaluate the effects of aprotinin on postbypass coagulopathies. Time needed for skin closure after protamine administration and lengths of stay in the intensive care unit and the hospital were recorded prospectively to determine the economic impact of aprotinin. RESULTS: Coagulation tests performed after protamine administration rarely demonstrated fibrinolysis but did show significant decreases in platelet and fibrinogen levels and function. The thromboelastographic variables indicated a preservation of platelet function by aprotinin. Decreased blood product transfusions, shortened skin closure times, and shortened durations of intensive care unit and hospital stays were found in the aprotinin groups, most significantly in the high-dose group with a subsequent average reduction of nearly $3,000 in patient charges. CONCLUSIONS: In children undergoing reoperative cardiac surgical procedures, aprotinin is effective in attenuating postbypass coagulopathies, decreasing blood product exposure, improving clinical outcome, and reducing patient charges.

Pharmacoeconomics analysis in a pediatric population.

BACKGROUND: Pharmacoeconomics is becoming increasingly important in the health-care environment, but pharmacoeconomic studies are fraught with problems. Pharmacoeconomics can be applied to analysis of the benefits of pharmacologic hemostasis. METHODS: This article reviews the available methods of pharmacoeconomic analysis and their inherent methodologic concerns. It reviews pharmacoeconomic studies of pharmacologic hemostasis, with particular focus on the Pediatric Reoperative Open Heart Surgery study. In this study, patients were randomized to receive either high-dose aprotinin, low-dose aprotinin, or placebo. Results were analyzed from the viewpoint of cost-benefit, cost-effectiveness calculated with use of a roll-back decision tree, and cost-effective ratios. RESULTS: Cost-benefit analysis showed low-dose aprotinin to have a greater cost-benefit than high-dose aprotinin, cost-effectiveness analysis and analysis of cost-effective ratios showed high-dose aprotinin to be more cost-effective than low-dose aprotinin, and all analyses showed aprotinin to be preferable to placebo. CONCLUSIONS: Aprotinin in pediatric repeat open heart operations not only has a cost-benefit but is cost-effective as well.

The effect on costs of the use of half-dose aprotinin for first-time reoperative coronary artery bypass patients.

Half-dose aprotinin previously has been shown to reduce bleeding and the need for blood transfusions, but the results of cost-reduction studies have been variable. The purpose of the present retrospective study was to compare, from the perspective of the acute care hospital as health care provider, the costs associated with first-time reoperative coronary artery bypass graft (CABG) surgery in patients who received half-dose aprotinin with the costs in those who did not. Medical records from 46 historical controls (first-time reoperative CABG patients receiving no aprotinin) and 51 half-dose aprotinin-treated patients were reviewed. A total of 36 variables were abstracted from the medical records for analysis. It was found that more aprotinin-treated patients did not require transfusion compared with nontreated patients (47% vs 26%). Twenty-one percent fewer aprotinin-treated patients received red blood cell transfusions, 21% fewer received plateletpheresis packs, and 19% fewer received fresh frozen plasma. Cost savings per patient receiving half-dose aprotinin compared with no aprotinin were approximately $878 in blood products and $1088 in total length of stay (including critical care), for total savings of $1966. When the cost of aprotinin ($450) was subtracted, the approximate net mean savings per patient were $1516. This did not include additional cost savings with aprotinin resulting from a median 19.5-minute shorter pump time. The authors conclude that the use of half-dose aprotinin results in reductions in surgical and associated hospitalization costs because of decreases in the length of hospital stay, including length of stay in critical care, and in the use of blood products.

Reduction in costs, blood products, and operating time in patients undergoing open heart surgery.

OBJECTIVE: To test the hypothesis that use of aprotinin at hall dose would be more cost-effective or as efficacious as full-dose aprotinin or no aprotinin during open heart surgery. DESIGN: Cost-effective analysis, unmasked prospective comparison. SETTING: Community hospital. PATIENTS: One hundred thirty-three patients undergoing open heart surgery. INTERVENTIONS: Patients in 3 consecutive groups undergoing open heart surgery were allocated to receive no aprotinin, full-dose aprotinin, or half-dose aprotinin. MAIN OUTCOME MEASURES: Total cost (in dollars) of blood products administered plus cost of aprotinin at various dosages, comparison of total blood products administered during hospitalization, and closure time required in the operating room. RESULTS: Full-dose and half-dose aprotinin significantly (P < .05) reduced the total blood products administered during hospitalization and the operating room closure time. However, use of half-dose aprotinin resulted in a significant cost savings (P < .05) when compared with either the cost of blood products required in the nodose aprotinin group or the cost of blood products plus aprotinin in the full-dose aprotinin group. CONCLUSION: Use of aprotinin at half dose in a community hospital resulted in a significant reduction in costs, blood product use, and operating room closure time in patients undergoing open heart surgery.

Maintenance of therapeutic plasma aprotinin levels during prolonged cardiopulmonary bypass using a large-dose regimen.

Aprotinin concentrations in the range of 127-191 kallikrein inactivator units (KIU)/mL at the end of cardiopulmonary bypass (CPB) (< 2 h duration) reduce transfusion requirements. It has been suggested that prolonged CPB may require higher infusion rates which significantly increase cost. We tested the hypothesis that large-dose aprotinin maintains therapeutic plasma levels during prolonged periods of CPB (< 2 h). Aprotinin was administered as follows: 2 x 10(6) KIU upon skin incision; 0.5 x 10(6) KIU/h x 4-h infusion on initiation of CPB; and 2 x 10(6) KIU added to the CPB prime solution. Aprotinin activity was measured 1) 30 min after initiation of drug administration (Pre-CPB); 2) 30 min after initiation of CPB (CPB + 30); 3) 90 min after initiation of CPB (CPB + 90); and 4) at CPB termination (End CPB). CPB duration (mean +/- SD) was 158 +/- 51 min. Plasma aprotinin concentrations (KIU/mL, mean +/- SD) were: 234 +/- 30 at Pre-CPB; 229 +/- 35 at CPB + 30; 184 +/- 27 at CPB + 90; and 179 +/- 22 at End CPB. In all patients, aprotinin levels at the completion of CPB were in the range previously reported to be effective. The authors conclude that large-dose regimen limited to 6 x 10(6) KIU maintained therapeutic plasma aprotinin concentrations during prolonged CPB.

The efficacy and cost of aprotinin in children undergoing reoperative open heart surgery.

We performed a prospective, randomized, placebo-controlled, double-blind trial to assess the efficacy of aprotinin in 61 children (median age 3.7 yr) undergoing reoperative open heart surgery (OHS). Three demographically similar groups were studied: large-dose aprotinin (ALD), small-dose aprotinin (ASD), and placebo (P). Over the first 24 postoperative hours fewer patients in the aprotinin groups received packed red cells (ALD, 53%; ASD, 89%; and P, 95%; P = 0.001), platelets (ALD, 32%; ASD, 50%; and P, 65%; P = 0.04), and fresh frozen plasma (ALD, 16%; ASD, 17%; and P, 60%; P = 0.003) than placebo patients. Most importantly, aprotinin patients had fewer exposures to banked blood components (ALD, median 1 U; and ASD, median 2 U) than P (median 6 U; P = 0.001), with no difference in overall complication rate. Use of aprotinin was associated with a savings in the patient charges for blood components, operating room time, and duration of hospitalization. In conclusion, aprotinin decreased the number of units of banked blood components used during the first 24 postoperative hours in reoperative pediatric OHS. Aprotinin thus decreases the risks associated with exposure to banked blood components and reduces hospital charges.

[Blood transfusion in surgery: can it still be reduced by human recombinant erythropoietin?]. / Transfusions en chirurgie: peuvent-elles encore être réduites par l'érythropoïétine humaine recombinante?

New agents such as recombinant human erythropoietin (rHu EPO) modify conventional transfusionnal strategies. For accurate indications, such as, anaemia associated with chronic renal failure, cancer or cardiac disease, the preoperative prescription of rHu EPO may reduce transfusion requirements. rHu EPO may also be associated with pre-deposit transfusion in patients with anaemia before blood donation, when the transfusion needs are high, or the period for blood pre-deposit donation shortened. Postoperatively rHu EPO is only efficient if it is administered for a prolonged period; this condition limits its indications and value because of its high cost.