Efficacy of tranexamic acid as compared to aprotinin in open heart surgery in children.

Background: Coagulopathy is a major issue in children undergoing high‑risk pediatric cardiac surgery. Use of anti‑fibrinolytics is well documented in adults, but recently there are questions raised about safety and effectiveness of their use on routine use. Tranexamic acid is a potent anti‑fibrinolytic, but its role is not fully understood in children. This study aims to study the benefits tranexamic acid in controlling postoperative bleeding in pediatric cardiac surgical patients. Methods and Results: Fifty consecutive children who underwent cardiac surgery were randomized prospectively to receive either aprotinin (Group A; n = 24) or tranexamic acid (Group B; n = 26) from September 2009 to February 2010 were studied. Primary end points were early mortality, postoperative drainage, reoperation for bleeding and complications. Mean age and body weight was smaller in Group A (Age: 48.55 vs. 64.73 months; weight 10.75 vs. 14.80 kg) respectively. Group A had more cyanotic heart disease than Group B (87.5% vs. 76.92%). Mean cardiopulmonary bypass time (144.33 vs. 84.34 min) and aortic cross‑clamp time (78.5 vs. 41.46 min) were significantly higher in group A. While the blood and products usage was significantly higher in Group A, there was no difference in indexed postoperative drainage in first 4, 8 and 12 h and postoperative coagulation parameters. Mean C‑reactive protein was less in Group A than B and renal dysfunction was seen more in Group A (25% vs. 7.6%). Mortality in Group A was 16.66% and 7.6% in Group B. Conclusion: Anti‑fibrinolytics have a definitive role in high‑risk children who undergo open‑heart surgery. Tranexamic acid is as equally effective as aprotinin with no additional increase in morbidity or mortality. Ultramini Abstract: Coagulopathy has been a major issue in pediatric cardiac surgery, and anti‑fibrinolytics have been used fairly regularly in various settings. This study aims to evaluate the efficacy of tranexamic acid as compared against that of aprotinin in a randomized model. Tranexamic acid proves to be equally effective with less toxicity with no added mortality.

Fibrinógeno-trombina como tratamiento puente en un caso de hemoptisis masiva / Fibrinogen-thrombin as bridge therapy in massive hemoptysis

Se presenta el caso de una paciente joven con hemoptisis masiva por tuberculosis que no pudo ser controlada de forma efectiva con la inserción de un catéter Fogarty por un fibrobroncoscopio. Ante esto y el alto riesgo de asfixia o desangramiento, se decidió infundir fibrinógeno-trombina a través de un catéter, introducido por el fibrobroncoscopio; con esto se logró controlar el sangrado, intubarla con un tubo orotraqueal de doble luz y estabilizarla para remitirla a otra institución, donde fue sometida a lobectomía y se le proporcionó tratamiento antituberculoso. La infusión de fibrinógeno-trombina podría considerarse como una opción terapéutica transitoria, de tipo puente, mientras se practica el manejo definitivo.

This article presents the case of a young woman with massive hemoptysis (1,000 mL in 6 hours) due to tuberculosis, which could not be controlled by insertion of a Fogarty catheter through a fiber-optic bronchoscope. Because of asphyxia and persistent bleeding risk we instilled fibrinogen-thrombin through a fiber-optic bronchoscope inserted catheter, achieving bleeding cessation and permitting the placing of a double-lumen oro-tracheal tube. Later on, the patient underwent lobectomy and anti-tuberculosis treatment. The fibrinogen-thrombin could be considered as a bridge, transitory measure for massive hemoptysis, while definitive treatment could be established.

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

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.

Aprotinina não influencia troponina I, NTproBNP e função renal em crianças operadas com circulação extracorpórea / High-dose aprotinin does not affect troponin I, N-Terminal pro-B-type natriuretic peptid and renal function in children submitted to surgical correction with extracorporeal circulation

Objetivo: Avaliar se o uso de aprotinina em altas doses hemostáticas pode influenciar as funções miocárdicas, renais e metabólicas em crianças operadas com circulação extracorpórea (CEC). Métodos: Estudo prospectivo randomizado em crianças de 30 dias a 4 anos de idade, submetidas à correção de cardiopatia congênita acianogênica, com CEC e divididas em dois grupos, um denominado Controle (n=9) e o outro, Aprotinina (n=10). Neste, a droga foi administrada antes e durante a CEC. As disfunções miocárdicas e multiorgânicas foram analisadas por marcadores clínicos e bioquímicos. Foram consideradas significantes as diferenças com P<0,05. Resultados: Os grupos foram semelhantes quanto às variáveis demográficas e intra-operatórias, exceto por maior hemodiluição no Grupo Aprotinina. Não houve benefício quanto aos tempos de ventilação pulmonar mecânica, permanência no Centro de Terapia Intensiva Pediátrica (CTIP) e hospitalar, nem quanto ao uso de inotrópicos e função renal. A relação PaO2/FiO2 (pressão parcial de oxigênio arterial/fração inspirada de oxigênio) apresentou queda significativa com 24h PO, no Grupo Controle. As perdas sanguíneas foram semelhantes nos dois grupos. Os marcadores troponina I cardíaca (cTnI), fração MB da creatinofosfoquinase (CKMB), transaminase glutâmico-oxalacética (TGO) e fração amino-terminal do peptídio natriurético tipo B (NT-proBNP) não apresentaram diferenças marcantes inter-grupos. A lactatemia e acidose metabólica pós-CEC foi maior no Grupo Aprotinina. Não houve complicações tromboembólicas, neurológicas ou de hipersensibilidade com o uso da aprotinina. Conclusão: A aprotinina em altas doses não influenciou significativamente nos marcadores séricos troponina I e NTproBNP e de função renal, porém foi associado com maior hemodiluição, lactatemia e acidose metabólica.

Objective: To evaluate if the use of hemostatic high-dose aprotinin seems influence to myocardial, renal and metabolic functions in children submitted to surgical correction with extracorporeal circulation (ECC). Material and Methods A prospective randomized study was conducted on children aged 30 days to 4 years submitted to correction of acyanogenic congenital heart disease with ECC and divided into two groups: Control (n=9) and Aprotinin (n=10). In the Aprotinin Group the drug was administered before and during ECC and the myocardial and multiorgan dysfunctions were analyzed on the basis of clinical and biochemical markers. Differences were considered to be significant when P<0.05. Results: The groups were similar regarding demographic and intraoperative variables, except for a greater hemodilution in the Aprotinin Group. The drug had no benefit regarding time of mechanical pulmonary ventilation, permanence in the pediatric postoperative intensive care unit (ICU) and length of hospitalization, or regarding the use of inotropic drugs and renal function. The partial arterial oxygen pressure/inspired oxygen fraction ratio (PaO2/FiO2) was significantly reduced 24h after surgery in the Control Group. Blood loss was similar for both groups. Cardiac troponin I (cTnI), creatine kinase MB fraction (CKMB), serum glutamic-oxaloacetic transaminase (SGOT) and the aminoterminal fraction of natriuretic peptide type B (NT-proBNP) did not differ significantly between groups. Post-ECC blood lactate concentration and metabolic acidosis was more intense in the Aprotinin Group. There were no complications with the use of aprotinin. Conclusion: High-dose aprotinin did not significant influence in serum markers troponin I, NT-proBNP and renal function, but did associated with hemodilution, blood lactate concentration and metabolic acidosis more intense.

Aprotinin reverses ECG abnormalities induced by Mesobuthus tamulus concanesis, Pocock venom in adult rats.

The kinins are implicated in the pathogenesis of scorpion envenomation. Therefore, this study was carried out to examine the involvement of kinins for the ECG abnormalities induced by M. tamulus concanesis, (BT) venom in anaesthetized rats. ECG was recorded using needle electrodes with limb lead II configuration. The PR interval, QRS wave pattern, QRS duration, ST segment and heart rate were examined in saline only, venom alone, and venom after aprotinin groups. BT venom (5 mg/kg) produced heart block of varying degree and ischemia-like changes in ECG wave pattern and the animals died within 30 min after exposure to venom. In aprotinin pretreated animals, the initial ECG changes produced by venom persisted, but after 15 min the ECG pattern improved and the animals survived for the entire period of observation (120 min). The results indicate that aprotinin protected the rats against the cardiotoxicity induced by BT venom.

Estudio de la protección plaquetaria de la aprotinina evaluada por tromboelastograma / Tromboelastograph's study of the platelet protection by aprotinin

Introducción: Con frecuencia la transfusión intraoperatoria se basa en criterios individuales y subjetivos. En cirugía cardiovascular se transfunden plaquetas y otros componentes de banco, asumiendo que la circulación extracorpórea produce el deterioro de los mismos. A su vez, con el propósito de disminuir el sangrado intraoperatorio, se indican drogas antifibrinolíticas como la aprotinina o el ácido-aminocaproico. Es controvertido el efecto adicional de la aprotinina como "protector plaquetario", así como la transfusión rutinaria de hemoderivados y drogas antifibrinolíticas en ausencia de criterios objetivos. En la búsqueda de los mismos, empleamos el tromboelastograma con técnicas nuevas para comprobar las siguientes hipótesis: 1.- evaluar el impacto de la circulación extracorpórea sobre las plaquetas y 2.- establecer si la aprotinina ejerce efecto protector sobre las últimas. Materiales y métodos: Se estudiaron prospectivamente 52 pacientes de cirugía cardiovascular divididos en 2 grupos: aprotinina (A) y control (C), empleando una técnica anestésica estándar, monitoreo invasivo, laboratorio de medio interno, coagulograma básico y tromboelastograma. Del último se midió la variable máxima amplitud, lo que con modificaciones técnicas (celite, heparinasa, reopro), permitió evaluar con precisión la función plaquetaria durante las distintas etapas de la cirugía (MA1 = basal, MA2 = en circulación extracorpórea). Los grupos se randomizaron por cuadros, recibiendo el A: 2 millones de UKIU postinducción en infusión endovenosa, 2 millones en la circulación extracorpórea y 500 mil por hora hasta la terminación de la cirugía. Resultados: 1.- La diferencia entre MA1 y MA2 en el grupo A estableció una P = 0.0006 y en el grupo C una P = 0.0001. 2.- Función plaquetaria de A vs C = NS. Conclusiones: 1.- En ambos grupos se demuestra que la circulación extracorpórea produciría un significativo deterioro de la función plaquetaria. 2.- La aprotinina no produce ningún efecto protector sobre la plaqueta.

Single dose aprotinin in routine cardiac surgery

Evidence exists that the serine protease inhibitor, aprotinin, when used in high dosage, can reduce the bleeding associated with cardiopulmonary bypass. This high dosage is particularly effective in patients at increased risk for bleeding. Less convincing information is available for regimes that use a lower dose and its place in routine cardiac surgery has not been fully resolved. Some studies have shown significant benefit from a single dose added to the cardio-pulmonary bypass prime and we re-examined this alternative. In a randomized, prospective, double-blinded study, we compared this single dose method with placebo in low risk adults undergoing a first procedure. Benefit was considered established if a significant reduction in blood loss or the use of transfused blood products were seen. We found a significant reduction in red cell transfusion but no improvement in blood loss or blood component transfusion in the treated group. This included patients maintained on aspirin as well as those not receiving aspirin. Aspirin significantly increased blood loss in both control and treatment groups and the usage of blood products in the treatment group. Aprotinin in this low, single dosage was not confirmed as an effective means of improving hemostasis following CPB in routine cardiac surgery

Effect of Long-Term Administration of Secretory Suppressives on Rat Pancreas (1)

Atropine (2.5 mg/kg), hexamethonium (1 mg/kg), Trasylol (1,000 u/kg), acetazolamide (100 mg/kg), cortisone (5 mg /kg) or procaine (5 mg/kg) were injected intraperitoneally once a day for 21 days into rats (both sexes) fed a low protein diet. The rats were fasted and sacrificed 24 hr after the last injection. Atropine and cortisone, but not the other agents, cause a significant increase in both pancreatic weight and enzymes. Serum amylase increased markedly in the cortisone group and serum GOT and GPT increased but slightly in the atropine group. Enlargement of the pancreatic acini, cellular hypertrophy and increases of zymogen granules were observed in all the groups except the procaine and normal control group. The hypertrophy of acini was more prominent in the atropine and cortisone groups. None of drugs used could induce decrease or depress the enzyme formation and weight of pancreas. This data indicates that long-term administration of these drugs, particularly atropine, cortisone or even other Ragents may induce preferential formation of pancreatic enzymes to exocrine secretions and consequently may cause enlargement of the pancreatic acini.