Tranexamic acid compared with high-dose aprotinin in primary elective heart operations: effects on perioperative bleeding and allogeneic transfusions

OBJECTIVE: Since excessive fibrinolysis during cardiac surgery is frequently associated with abnormal perioperative bleeding, many authors have advocated prophylactic use of antifibrinolytic drugs to prevent hemorrhagic disorders. We compared the effects of tranexamic acid (a synthetic antifibrinolytic drug) with aprotinin (a natural derivative product with antifibrinolytic properties) on perioperative bleeding and the need for allogeneic transfusions. METHODS: In a single-center prospective randomized unblinded trial, 1040 consecutive patients undergoing primary, elective cardiac operations with cardiopulmonary bypass received either high-dose aprotinin or tranexamic acid. The aprotinin group (518 patients) received 280 mg in 20 minutes before the skin incision, 280 mg in the priming solution of the extracorporeal circuit, and a continuous infusion of 70 mg/h throughout the operation. The tranexamic acid group (522 patients) received 1 g in 20 minutes before the skin incision, 500 mg in the priming solution of the extracorporeal circuit, and a continuous infusion of 400 mg/h during the operation. Postoperative bleeding, perioperative transfusions, and hematologic variables were evaluated at fixed times. Postoperative thrombotic complications, intubation time, intensive care unit stay, and hospital stay were recorded. RESULTS: Postoperative bleeding was similar in the 2 groups: aprotinin 250 mL (150-400 mL) versus tranexamic acid 300 mL (200-450 mL) (median and 25th-75th quartiles), median difference of 50 mL (95% confidence intervals, 0-50 mL). The number of transfusions and the outcome did not differ. CONCLUSIONS: Tranexamic acid and aprotinin show similar clinical effects on bleeding and allogeneic transfusion in patients undergoing primary elective heart operations. Since tranexamic acid is about 100 times cheaper than aprotinin, its use is preferable in this type of patient.     

Use of antifibrinolytics in pediatric cardiac surgery: Where are we now?

Fibrinolytic activation is a major and preventable source of bleeding in neonates and children undergoing cardiac surgery with cardiopulmonary bypass. Based on the existing literature (adult and pediatric; cardiac and noncardiac), prophylactic administration of antifibrinolytic agents can help reduce fibrinolytic activation, and consequently reduces perioperative bleeding and the requirement for blood product transfusion. Due to the increased risk of renal failure and mortality reported in adults undergoing cardiac surgery, aprotinin should not be considered as a safe option in neonates and children. Further well‐designed studies would be required before the prophylactic administration of aprotinin could be considered in pediatric cardiac surgery. The lysine analogs, tranexamic acid and ?‐aminocaproic acid,, should be considered as safe and effective antifibrinolytic agents. Although no major side effects have been reported following the administration of lysine analogs in children undergoing cardiac surgery, high‐dose tranexamic acid should not be recommended in order to avoid the increased risk of clinical seizures. Despite the recent advances made in our understanding of the pharmacokinetics of tranexamic acid and ?‐aminocaproic acid,, the optimal plasmatic concentration to be targeted remains unknown. Further studies are therefore urgently needed to better define the optimal dose regimen to be used in neonates and children. In the meantime, the dose regimen published in the most recent pharmacokinetic studies can be used. Although no studies have assessed the effect of massive bleeding and transfusion on the plasmatic concentrations of the lysine analogs, additional boluses might be considered in the presence of bleeding and/or when signs of fibrinolytic activations are observed on viscoelastic hemostatic assays.     

A randomized, controlled trial of aprotinin in neonates undergoing open-heart surgery

Background:  Neonates undergoing open-heart surgery are especially at risk for massive bleeding and pronounced inflammation. The efficacy of aprotinin, a serine protease inhibitor, at ameliorating these adverse effects of cardiopulmonary bypass has not been clearly demonstrated in neonates.
Methods:  Term neonates were enrolled and randomly assigned in a blinded fashion to receive saline (group P, placebo) or high-dose aprotinin (group A). Intraoperative management was standardized: surgeon, anesthesia, cardiopulmonary bypass and hemostasis therapy. Patients were admitted postoperatively to a pediatric cardiac intensive care unit. Primary outcome measure of efficacy was duration of the postoperative mechanical ventilation. Secondary outcome measures were total volume and units of blood products transfused intraoperatively and for 24 h after surgery, duration of chest tube in situ , and intensive care and hospital stays after surgery.
Results:  Twenty-six neonates were enrolled; 13 received aprotinin and 13 received placebo. The study was halted prematurely because of US Food and Drug Administation's concerns about aprotinin's safety. Baseline patient, surgery and cardiopulmonary bypass characteristics were similar between groups. No outcome variables differed between groups ( P  > 0.05). Duration of postoperative ventilation was 115 ± 139 h (group A); 126 ± 82 h (group P); P  = 0.29, and total blood product exposure was 8.2 ± 2.6 U (group A); 8.8 ± 1.4 U (group P); P  = 0.1. Postoperative blood creatinine values did not differ between groups. In-hospital mortality rate was 4%.
Conclusions:  Aprotinin was not shown to be efficacious in neonates undergoing open-heart surgery. It is unclear whether adult aprotinin safety data are relevant to neonates undergoing open-heart surgery.     

Aprotinin and nafamostat mesilate in liver surgery: effect on blood loss

The origin of blood loss during liver surgery is multifactorial. Surgical skill, technique, anesthesiological care, but also hyperfibrinolysis have been shown to play a role in the origin of bleeding during partial hepatectomy and liver transplantation. The latter has provided the scientific basis for the prophylactic use of antifibrinolytic drugs, such as aprotinin and nafamostat mesilate in liver surgery. Recently however, concern has been voiced about potential risks associated with aprotinin, including renal failure and thromboembolic events. In this review we discuss the efficacy and safety issues of aprotinin and nafamostat mesilate in liver surgery. We identified a total of 19 studies on the use of either aprotinin or nafamostat mesilate in liver surgery reported in the time period between 1966 and July 2006. The use of aprotinin or nafamostat mesilate in partial hepatectomies was studied in three studies. In 16 studies the use of aprotinin in liver transplantation was investigated. With respect to partial hepatectomy, improvements in surgical technique and anesthesiological care seem to be more important in reducing blood loss than the use of the antifibrinolytic drugs. Aprotinin may be indicated in a selected group of patients with cirrhosis undergoing liver resection, but further studies in this specific group of patients will be needed. In liver transplantation, the use of aprotinin is associated with a significant reduction in blood loss and transfusion requirements of around 30-40%. Results of prospective studies do not provide support for safety concerns as no increased risk for thromboembolic events or renal dysfunction has been observed in liver transplant patients treated with aprotinin. In conclusion, there is currently no scientific support for the routine use of aprotinin or nafamostat mesilate in patients undergoing partial hepatectomy, whereas the efficacy of aprotinin in liver transplantation is well established. More studies will be needed to address the safety aspects of aprotinin in patients undergoing liver surgery in more detail.     

Zero‐Balance Ultrafiltration of Priming Blood Attenuates Procalcitonin and Improves the Respiratory Function in Infants After Cardiopulmonary Bypass: A Randomized Controlled Trial

Blood priming is needed for cardiopulmonary bypass (CPB) in neonates and infants to avoid exceeding hemodilution; however, transfusion‐related inflammation affects post‐CPB outcomes in infant open‐heart surgery. Procalcitonin, a newly detected inflammatory moderator and a sensitive parameter for predicting pulmonary dysfunction secondary to CPB, rises after CPB. We hypothesized that the hemofiltration of priming blood before CPB might decrease inflammatory mediators in the blood and post‐CPB inflammatory replications, thereby improving the respiratory function after CPB in infants. Sixty infants with a weight below 10 kg were divided randomly into two equal groups of CPB with the zero‐balance ultrafiltration (Z‐BUF) of priming blood and CPB without it. The procalcitonin level was measured before anesthesia, after admission to the intensive care unit (ICU), and 24 h afterward. The respiratory index and pulmonary compliance were measured after anesthesia, at the end of CPB, and 2 h after admission to the ICU. Additionally, time to extubation was recorded. The Z‐BUF of priming blood maintained electrolytes within a physiologic level, and procalcitonin had a slighter rise in the Z‐BUF Group at 24 h after admission to the ICU (P = 0.05). The respiratory index was decreased in the Z‐BUF Group, but the difference with the control group did not reach statistical significance (P > 0.05). The change in pulmonary compliance was significantly increased in the cyanotic patients in the intervention group, but there was no significant difference between the two groups. The time to extubation and the ICU stay were shorter in the Z‐BUF Group (P < 0.05). A positive correlation was found between the peak procalcitonin concentration and the time to extubation directly and pulmonary compliance reversely. These results suggest that the Z‐BUF of priming blood may have some beneficial clinical effects such as improved respiratory function and attenuated procalcitonin.     

Reduction of blood transfusion need with aprotinin in orthopedic surgery. Spanish Study Group on the Use of Aprotinin in Hip Arthroplasty (GEEEAAC)

Aprotinin is a protease inhibitor of interest for its antifibrinolytic effect of reducing perioperative bleeding in certain types of surgery, with wide use in heart surgery, liver transplantation and vascular surgery. The application of aprotinin during orthopedic surgery has recently been suggested. Such use is controversial, as there is lack of consensus as to the type of patient for whom aprotinin administration would be indicated, the surgical procedure during which it would be most effective (hip or knee arthroplasty, spinal arthrodesis, major tumor or septic surgery), the doses to administer, its safety and its real efficacy for conserving homologous blood. That is to say, there is no agreement as to the cost/benefit relation of aprotinin for the various types of orthopedic surgery. This critical review of the literature leads to the conclusion that aprotinin is a promising drug for use in orthopedic surgery, given that published studies have established the benefit in blood product savings and decreased blood loss during surgery.     

Heparin-level-based anticoagulation management during cardiopulmonary bypass: a pilot investigation on the effects of a half-dose aprotinin protocol on postoperative blood loss and hemostatic activation and inflammatory response

Cardiac surgery involving cardiopulmonary bypass (CPB) leads to activation of the hemostatic/inflammatory system. We compared the influence of a half-dose aprotinin regimen on postoperative blood loss and the activation of the hemostatic/inflammatory system during CPB, when used during a heparin-level-based heparin management for cardiac surgery. Two-hundred patients (n = 100 in each group) were enrolled in this randomized prospective study. In Group I only heparin was given according to the results of the Hepcon HMS Plus. In Group II aprotinin was added with a bolus of 1 x 10(6) kallikrein inhibiting units (KIU) for the patient immediately before initiation of CPB, 1 x 10(6) KIU in the priming solution of the CPB, and a continuous infusion of 250,000 KIU/h during CPB. Postoperative blood loss was determined after 12 h. Heparin and antithrombin activity were evaluated by an anti-Xa assay and measurement of antithrombin III activity. Hemostatic activation was evaluated by adenosine diphosphate-stimulated platelet aggregometry and by measurements of the generation/release of beta-thromboglobulin (beta-TG), soluble P-selectin (sPS), thrombin (TAT), prothrombin 1 and 2 fragments (PTF1+2), factor XIIa (FXIIa), plasmin (PAP), and D-dimers. Inflammatory response was evaluated by measuring complement factors 5b-9 (C5b-9), interleukin (IL)-6, and neutrophil elastase (NE). There were no differences in the pre-CPB values or duration of CPB between the two groups. There were no differences in the post-CPB values for platelet count, platelet aggregation, beta-TG, sPS, TAT, PTF1+2, C5b-9, NE, or IL-6. The additional use of aprotinin resulted in a significant decrease of PAP, D-dimers, and 12 h postoperative blood loss, whereas generation of the contact factor XIIa was increased. The administration of aprotinin significantly reduced postoperative blood loss after cardiac surgery and CPB. This most likely has to be attributed to the antifibrinolytic effects of aprotinin. No effects on thrombin generation, platelet activation, inflammatory response, or clinical outcome were noted. IMPLICATIONS: The use of half-dose aprotinin and heparin-level-based anticoagulation management during cardiopulmonary bypass leads to a significant reduction of postoperative blood loss after cardiac surgery. This effect can most likely be attributed to the antifibrinolytic effects of aprotinin, as we did not observe effects on other variables of activation of the hemostatic/inflammatory system.     

Avoiding transfusions in children undergoing cardiac surgery: a meta-analysis of randomized trials of aprotinin

Aprotinin, a potent antifibrinolytic drug, reduces the proportion of adults who receive blood transfusions during cardiac surgery, although the effect in children remains unclear. We performed a systematic review of the literature to identify all English language, randomized controlled trials of aprotinin involving children undergoing corrective or palliative cardiac surgery with cardiopulmonary bypass. All studies were assessed for methodological quality, and sources of heterogeneity were examined. We measured the effect of aprotinin on the proportion of children transfused, the volume of blood transfused, and the volume of chest tube drainage. Twelve trials enrolling 626 eligible children met the inclusion criteria. Aprotinin reduced the proportion of children who received red blood cell or whole blood transfusions during cardiac surgery by 33% (relative risk = 0.67; 95% confidence interval, 0.51 to 0.89). Aprotinin did not have a significant effect on the volume of blood transfused or on the amount of postoperative chest tube drainage. Most of the studies were of poor methodological quality and predefined transfusion triggers were infrequently used. Overall, aprotinin reduced the proportion of children who received blood transfusion during cardiac surgery with cardiopulmonary bypass. Further high-quality trials with clinically important outcomes may be warranted before aprotinin can be routinely recommended in this population.     

Use of aprotinin in patients undergoing deep hypothermic circulatory arrest: a review

Hemostatic derangements continue to be a major clinical challenge during thoracic aortic surgery using deep hypothermic circulatory arrest despite advances in surgical and pharmacologic therapy. Aprotinin, a broad-based, nonspecific serine protease inhibitor has been advocated for prophylactic use in cardiac surgery to decrease perioperative blood loss and blood transfusions. Its efficacy has been documented in several studies throughout the United States and Europe. Currently, aprotinin is advocated for use in patients undergoing cardiopulmonary bypass in the course of coronary artery bypass graft surgery. A review of current studies is provided that examines aprotinin usage under deep hypothermic circulatory arrest.     

Comparison of the effects of epsilon-aminocaproic acid and aprotinin on intra- and postoperative bleeding in heart surgery]

Excessive bleeding during and after cardiac surgery with cardiopulmonary bypass is a real problem in this kind of surgery. The use of prophylactic high doses of aprotinin (APROT) reduces blood loss in this context but this treatment is expensive. Some investigators have advocated that epsilon-aminocaproic acid (EACA), a cheaper antifibrinolytic drug, could reduce blood loss in cardiac surgery. The goal of this prospective study was to determine if EACA is as effective as APROT for this clinical condition. Sixty patients undergoing elective surgery for cardiac disease were randomly allocated to one of the two groups. Drugs were administered after induction of anesthesia at a dose of 2.10(6) UIK in the APROT group or 5 g in the EACA group. The same dose was added to the priming of the cardiopulmonary bypass circuit. Until the skin closure the patients received 5.10(5) UIK/h of APROT or 2 g/h of EACA. Bleeding during and after surgery was not different between the two groups. No complication, directly due to the treatment administered, was observed. EACA seems to be as effective as APROT to reduce intra and post cardiac surgery blood loss. EACA has the advantage of being cheaper (treatment is approximately 200 times cheaper), therefore allowing a wider use.     

Mechanisms and attenuation of hemostatic activation during extracorporeal circulation.

Patients undergoing cardiac surgery with cardiopulmonary bypass are at risk for excessive microvascular bleeding, which often leads to transfusion of allogeneic blood and blood components as well as reexploration in a smaller subset of patients. Excessive bleeding after cardiac surgery is generally related to a combination of several alterations in the hemostatic system pertaining to hemodilution, excessive activation of the hemostatic system, and potentially the use of newer, longer-acting antiplatelet or antithrombotic agents. Although several nonpharmacologic strategies have been proposed, this review summarizes the role of pharmacologic interventions as means to attenuate the alterations in the hemostatic system during CPB in an attempt to reduce excessive bleeding, transfusion, and reexploration. Specifically, agents that inhibit platelets, fibrinolysis, factor Xa and thrombin, as well as broad-spectrum agents, have been investigated with respect to their role in reducing consumption of clotting factors and better preservation of platelet function. Prophylactic administration of agents with antifibrinolytic, anticoagulant, and possibly antiinflammatory properties can decrease blood loss and transfusion. Although aprotinin seems to be the most effective blood conservation agent (which is most likely related to its broad-spectrum nature), agents with isolated antifibrinolytic properties may be as effective in low-risk patients. The ability to reduce blood product transfusions and to decrease operative times and reexploration rates favorably affects patient outcomes, availability of blood products, and overall health care costs.     

The risks associated with aprotinin use: a retrospective study of cardiac cases in Nova Scotia

Purpose

In light of the concerns about the safety of aprotinin, we wanted to determine if aprotinin use during cardiac surgery was associated with an increased risk of mortality and morbidity compared with the use of tranexamic acid (TXA). We hypothesized that use of aprotinin is associated with a higher risk of adverse outcomes than use of TXA in our patient population.

Methods

In this retrospective study at a single surgical centre, we examined primary in-hospital outcomes of postoperative mortality, new acute renal failure, and perioperative blood transfusion, and we also investigated secondary outcomes of stroke, infection, and prolonged stay in the intensive care unit (ICU). The effect of the type of antifibrinolytic on outcome was evaluated for aprotinin cases matched 1:1 with TXA cases using propensity score.

Results

This study included 3,340 patients who received antifibrinolytics during cardiac surgery (376 patients received aprotinin and 2,964 patients received TXA). Patients who received aprotinin were more often elderly and female; they were more commonly presented with congestive heart failure, atrial fibrillation, renal failure, and lower hemoglobin, and they underwent complex and/or urgent surgery. In the matched sample, in-hospital mortality was significantly higher in the aprotinin group (10.9%) compared with the TXA group (5.9%), and ICU stay >72 hr was significantly increased in the aprotinin group (30.0%) compared with the TXA group (21.7%). There was no significant difference in blood product administration between the two groups.

Conclusions

Aprotinin was associated with an increased risk of in-hospital mortality and morbidity following cardiac surgery, and aprotinin was not associated with a decrease in blood product requirements. Continued use of aprotinin in cardiac surgery should follow careful consideration, weighing the demonstrated risks and potential advantages compared with other TXA.     

Aprotinin application has no negative effect on osseous implant integration: a biomechanical and histomorphometric investigation in a rat model

Intraoperative blood loss requiring allogenic blood transfusion (ABT) is a common problem in major orthopedic surgery. Since transfusion related side effects up to fatal consequences due to blood type incompatibility cannot be excluded completely, it is desirable to reduce the amount of blood loss and transfusions to a minimum. Encouraging results in the application of aprotinin, a natural protease-inhibitor with antifibrinolytic, bleeding-reducing properties, in thoracic-, heart- and abdominal surgery led to the use of aprotinin also in orthopedic surgery. One important safety issue in the use of aprotinin in orthopedic surgery is a possible negative effect on the osseous integration of an implant due to the multiple interactions of aprotinin with several enzymatic systems. In this study, we therefore investigated the influence of aprotinin on the osseous ingrowth of a titanium-implant in a rat model. Forty female Sprague–Dawley rats underwent unilateral retrograde nailing of the femur. Animals were divided in two groups, one receiving i.v. aprotinin intraoperatively, the other group receiving the same amount as saline solution. After 56 days animals were killed and from each group half of the femora were prepared for biomechanical testing, the other half for histological examination. The push-out experiment revealed no significant difference between the aprotinin-group and the control-group, both showing comparable shear stresses. In addition, the histomorphometrical analysis showed comparable implant integration between both groups. The results demonstrate that perioperative aprotinin application has no negative effect on osseous implant integration in a rat model. An erratum to this article can be found at     

Aminocaproic Acid (Amicar) as an Alternative to Aprotinin (Trasylol) in Liver Transplantation

Introduction

This study compared clinical outcomes for a large number of liver transplant patients receiving intraoperative epsilon-aminocaproic acid (EACA), aprotinin, or no antifibrinolytic agent over an 8-year period.

Patients and Methods

Records for deceased donor liver transplants were reviewed. Data included antifibrinolytic agent, blood loss, early graft function, and postoperative complications. Study groups included low-dose aprotinin, high-dose aprotinin, EACA (25 mg/kg, 1-hour infusion), or no antifibrinolytic agent.

Results

Data were included for 1170 consecutive transplants. Groups included low-dose aprotinin (n = 324 [28%]), high-dose aprotinin (n = 308 [26%]), EACA (n = 216 [18%]), or no antifibrinolytic (n = 322 [28%]). EACA had the lowest intraoperative blood loss and required the fewest transfusions of plasma. Patients receiving no agent required the most blood transfusions. Early graft loss was lowest in the EACA group, and 90-day and 1-year patient survival rates were significantly higher for the low-dose aprotinin and EACA groups according to Cox regression. Complications were similar, but there were more episodes of deep vein thrombosis in patients receiving EACA.

Conclusions

These results suggest that transitioning from aprotinin to EACA did not result in worse outcomes. In addition to decreased intraoperative blood loss, a trend toward improved graft and patient survival was seen in patients receiving EACA.     

Efficacy of aprotinin, epsilon aminocaproic acid, or combination in cyanotic heart disease

BACKGROUND: Aprotinin and epsilon aminocaproic acid are antifibrinolytic agents used to reduce postoperative blood loss after cardiopulmonary bypass. We compared low dose aprotinin with epsilon aminocaproic acid and a combination of the two agents to reduce postoperative blood loss in infants with congenital cyanotic heart disease undergoing corrective surgical procedures. METHODS: This prospective study was conducted randomly on 300 children. Group I (n = 80) acted as the control and did not receive either of the study drugs. Group II (n = 100) received low dose aprotinin, group III (n = 60) received epsilon aminocaproic acid, and group IV (n = 60) received a combination of the two antifibrinolytic agents. RESULTS: The control group had the longest time for sternal closure, maximum blood loss at 24 hours, and greatest requirements for packed red blood cells and platelets. Fibrinogen levels were significantly lower, and levels of fibrin breakdown products were significantly higher compared with the groups given either or both of the antifibrinolytics. CONCLUSIONS: Epsilon aminocaproic acid is as efficacious as low dose aprotinin in reducing postoperative blood loss and packed red blood cell and platelet requirements in children with congenital cyanotic heart disease. The combination of the two was slightly more effective.     

Cardiac surgery with cardiopulmonary bypass: does aprotinin affect outcome?

BACKGROUND: Aprotinin, a non-specific serine protease inhibitor, has been used for two decades to reduce perioperative blood loss and the risk for allogeneic transfusion in cardiac surgery. This study evaluated the effects of aprotinin on outcome (mortality, cardiac events, renal failure, and cerebrovascular events) in such patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Data were obtained in patients who received a strict blood conservation protocol: no antifibrinolytic therapy when at low risk (n = 854) and aprotinin (n = 1210) when at high risk for blood transfusion. Relative risk of different pre- and intra-operative variables was calculated for the different outcome variables. Backward stepwise logistic regression analysis was used to identify the independent risk factors associated with the different outcome variables. Statistical significance was accepted at P < 0.01. RESULTS: Postoperative mortality and morbidity were higher in the aprotinin group but this was related to an increased incidence of perioperative risk factors. Mortality was similar to that predicted by the Euroscore. Complex surgery was the only independent variable associated with postoperative cardiac events. Preoperative heart failure, preoperative creatinine > 1.5 mg dl(-1), urgent, and redo surgery were the independent variables associated with postoperative haemodialysis. Age > 70 yr was identified as the only independent variable associated with neurologic dysfunction. CONCLUSIONS: In the present study, patients receiving aprotinin as part of a strict blood conservation strategy represent a population at high risk for postoperative complications. For the outcome variables studied, aprotinin administration was not identified as an independent risk factor.     

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.     

A review of aprotinin in orthotopic liver transplantation: can its harmful effects offset its beneficial effects?

Blood transfusion can adversely affect patient outcome and graft survival in orthotopic liver transplantation (OLT). With this respect, prophylactic aprotinin administration decreases blood loss, transfusion requirements, and the hemodynamic changes associated with graft reperfusion in patients undergoing OLT. However, data indicate limiting the use of aprotinin in OLT: (a) clinical, biological, echocardiographic, and postmortem findings recorded in patients with chronic liver disease or undergoing OLT suggest that a continuous prothrombotic state exists in these patients. Whether the inhibition of fibrinolysis associated with aprotinin therapy will expose some patients to untoward thrombosis is questionable; (b) aprotinin does not appear to alter postoperative outcome in patients undergoing OLT; (c) aprotinin decreases blood transfusion requirements only when surgery is associated with significant blood loss. However, at the present time, median transfusion requirements of 2 to 5 red blood cell units are required in OLT.     

Increased recombinant activated factor VII use and need for surgical reexploration following a switch from aprotinin to epsilon-aminocaproic acid in infant cardiac surgery

Study ObjectiveTo evaluate whether conversion from aprotinin to epsilon-aminocaproic acid (EACA) during infant cardiac surgery was associated with increased perioperative bleeding.DesignStructured retrospective chart review.SettingUniversity-affiliated large congenital cardiac surgery program.MeasurementsRecords from 145 infants (age < 1 yr) receiving aprotinin as antifibrinolytic therapy for cardiac surgery between 6/1/2006 and 12/31/2006 were compared with a cohort of infants receiving EACA for cardiac surgery between 6/1/2008 and 12/31/2008. Sixty-eight infants received aprotinin and 77 infants received EACA. Measured indicators of perioperative bleeding included transfusion volumes, recombinant activated clotting factor VIIa (rFVIIa) administration, need for reexploration, and perioperative chest tube output.Main ResultsEACA treated patients received significantly more rFVIIa for uncontrolled bleeding (19/77 [25%] vs 3/68 [4%]; P < 0.001) and required surgical reexploration more frequently (21/77 [27%] vs 7/68 [10%]; P = 0.01]. Median (25th-75th percentiles) intraoperative platelet transfusion requirements were also increased after the switch to EACA (28 mL [0-58 mL] vs 0 mL [0 mL - 34.5 mL]), but this difference did not reach statistical significance (P = 0.06).ConclusionsBleeding in infant cardiac surgery increased following the change in antifibrinolytic therapy from aprotinin to EACA. Given the potential for major harm, especially thrombotic complications, from rFVIIa use, prospective studies examining the safety of postcardiopulmonary bypass rFVIIa administration in infants are necessary before the routine off-label use may be recommended.     

Pediatric patients requiring extracorporeal membrane oxygenation in heart failure: 30‐day outcomes; mid‐ and long‐term survival. A single center experience

Nowadays, an increasing number of neonatal and pediatric patients with severe heart failure benefits from extracorporeal membrane oxygenation (ECMO) support. A total of 39 pediatric patients needed venoarterial ECMO (vaECMO) support in our department between January 2008 and December 2016. Patients were retrospectively divided in two groups: 30‐day survivor group (17 patients) and 30‐day nonsurvivor group (22 patients). Outcome and factors predictive for 30‐day mortality and mid‐ as well as long‐term survival up to 7‐year follow‐up were analyzed by univariate analysis and Kaplan‐Meier survival estimation. Basic demographics and preoperative characteristics did not differ between groups (P > 0.05). 67% of patients were successfully weaned off ECMO and 44% survived 30‐day after ECMO application. After 7‐year follow‐up 28% of pediatric patients were alive. Thirty‐day survivors were significantly more likely to undergo elective cardiac surgery (P = 0.001), whereas significantly more 30‐day nonsurvivors underwent urgent surgery (P = 0.004). Odds of incidence of catecholamine refractory circulatory failure, failed myocardial recovery, and cerebral edema was significantly higher in 30‐day nonsurvivor group (41.6‐fold, 16‐fold, and 2.5‐fold, respectively). Kaplan‐Meier survival estimation analysis revealed significant differences in terms of mid‐ and long‐term survival among neonates, infants, toddlers, and preadolescents (Breslow P = 0.037 and Log‐Rank P = 0.028, respectively). vaECMO provides an efficient therapy option for life‐threatening heart disorders in neonates and pediatric patients being at high risk for myocardial failure leading to circulatory arrest. Urgency of surgery effected on higher mortality, but there was no difference in terms of mortality in 30‐day survivor group in comparison to 30‐day nonsurvivor group among neonates, infants, toddlers, and preadolescents.