Lack of efficacy of aprotinin over tranexamic acid in type A aortic dissection repair.

BACKGROUND: The role of aprotinin in modern cardiac surgery is not well defined. While licensed for use in isolated coronary artery bypass grafting it is more commonly used for cases deemed to be at an increased risk of bleeding. The relative efficacy, and safety profile, of aprotinin as compared to other antifibrinolytics in these high-risk cases is uncertain. STUDY DESIGN AND METHODS: A retrospective observational study with propensity matching to determine whether aprotinin versus tranexamic acid reduced bleeding or transfusion requirements in patients presenting for surgical repair of type A aortic dissection (TAD). RESULTS: Between 2016 and 2022, 250 patients presented for repair of TAD. A total of 231 patients were included in the final analysis. Bleeding and transfusion were similar between both groups in both propensity matched and unmatched cohorts. Compared to tranexamic acid, aprotinin use did not reduce transfusion requirements for any product. Rates of bleeding in the first 12 h, return to theater and return to intensive care unit with an open packed chest were similar between groups. There was no difference in rates of renal failure, stroke, or death. CONCLUSION: Aprotinin did not reduce the risk of bleeding or transfusion requirements in patients undergoing repair of type A aortic dissections. Efficacy of aprotinin may vary depending on the type of surgery performed and the underlying pathology.

Pharmacological interventions for the prevention of bleeding in people undergoing elective hip or knee surgery: a systematic review and network meta-analysis.

BACKGROUND: Hip and knee replacement surgery is a well-established means of improving quality of life, but is associated with a significant risk of bleeding. One-third of people are estimated to be anaemic before hip or knee replacement surgery; coupled with the blood lost during surgery, up to 90% of individuals are anaemic postoperatively. As a result, people undergoing orthopaedic surgery receive 3.9% of all packed red blood cell transfusions in the UK. Bleeding and the need for allogeneic blood transfusions has been shown to increase the risk of surgical site infection and mortality, and is associated with an increased duration of hospital stay and costs associated with surgery. Reducing blood loss during surgery may reduce the risk of allogeneic blood transfusion, reduce costs and improve outcomes following surgery. Several pharmacological interventions are available and currently employed as part of routine clinical care. OBJECTIVES: To determine the relative efficacy of pharmacological interventions for preventing blood loss in elective primary or revision hip or knee replacement, and to identify optimal administration of interventions regarding timing, dose and route, using network meta-analysis (NMA) methodology. SEARCH METHODS: We searched the following databases for randomised controlled trials (RCTs) and systematic reviews, from inception to 18 October 2022: CENTRAL (the Cochrane Library), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), Transfusion Evidence Library (Evidentia), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: We included RCTs of people undergoing elective hip or knee surgery only. We excluded non-elective or emergency procedures, and studies published since 2010 that had not been prospectively registered (Cochrane Injuries policy). There were no restrictions on gender, ethnicity or age (adults only). We excluded studies that used standard of care as the comparator. Eligible interventions included: antifibrinolytics (tranexamic acid (TXA), aprotinin, epsilon-aminocaproic acid (EACA)), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants and non-fibrin sealants. DATA COLLECTION AND ANALYSIS: We performed the review according to standard Cochrane methodology. Two authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using CINeMA. We presented direct (pairwise) results using RevMan Web and performed the NMA using BUGSnet. We were interested in the following primary outcomes: need for allogenic blood transfusion (up to 30 days) and all-cause mortality (deaths occurring up to 30 days after the operation), and the following secondary outcomes: mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), length of hospital stay and adverse events related to the intervention received. MAIN RESULTS: We included a total of 102 studies. Twelve studies did not report the number of included participants; the other 90 studies included 8418 participants. Trials included more women (64%) than men (36%). In the NMA for allogeneic blood transfusion, we included 47 studies (4398 participants). Most studies examined TXA (58 arms, 56%). We found that TXA, given intra-articularly and orally at a total dose of greater than 3 g pre-incision, intraoperatively and postoperatively, ranked the highest, with an anticipated absolute effect of 147 fewer blood transfusions per 1000 people (150 fewer to 104 fewer) (53% chance of ranking 1st) within the NMA (risk ratio (RR) 0.02, 95% credible interval (CrI) 0 to 0.31; moderate-certainty evidence). This was followed by TXA given orally at a total dose of 3 g pre-incision and postoperatively (RR 0.06, 95% CrI 0.00 to 1.34; low-certainty evidence) and TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively (RR 0.10, 95% CrI 0.02 to 0.55; low-certainty evidence). Aprotinin (RR 0.59, 95% CrI 0.36 to 0.96; low-certainty evidence), topical fibrin (RR 0.86, CrI 0.25 to 2.93; very low-certainty evidence) and EACA (RR 0.60, 95% CrI 0.29 to 1.27; very low-certainty evidence) were not shown to be as effective compared with TXA at reducing the risk of blood transfusion. We were unable to perform an NMA for our primary outcome all-cause mortality within 30 days of surgery due to the large number of studies with zero events, or because the outcome was not reported. In the NMA for deep vein thrombosis (DVT), we included 19 studies (2395 participants). Most studies examined TXA (27 arms, 64%). No studies assessed desmopressin, EACA or topical fibrin. We found that TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively ranked the highest, with an anticipated absolute effect of 67 fewer DVTs per 1000 people (67 fewer to 34 more) (26% chance of ranking first) within the NMA (RR 0.16, 95% CrI 0.02 to 1.43; low-certainty evidence). This was followed by TXA given intravenously and intra-articularly at a total dose of 2 g pre-incision and intraoperatively (RR 0.21, 95% CrI 0.00 to 9.12; low-certainty evidence) and TXA given intravenously and intra-articularly, total dose greater than 3 g pre-incision, intraoperatively and postoperatively (RR 0.13, 95% CrI 0.01 to 3.11; low-certainty evidence). Aprotinin was not shown to be as effective compared with TXA (RR 0.67, 95% CrI 0.28 to 1.62; very low-certainty evidence). We were unable to perform an NMA for our secondary outcomes pulmonary embolism, myocardial infarction and CVA (stroke) within 30 days, mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), or length of hospital stay, due to the large number of studies with zero events, or because the outcome was not reported by enough studies to build a network. There are 30 ongoing trials planning to recruit 3776 participants, the majority examining TXA (26 trials). AUTHORS' CONCLUSIONS: We found that of all the interventions studied, TXA is probably the most effective intervention for preventing bleeding in people undergoing hip or knee replacement surgery. Aprotinin and EACA may not be as effective as TXA at preventing the need for allogeneic blood transfusion. We were not able to draw strong conclusions on the optimal dose, route and timing of administration of TXA. We found that TXA given at higher doses tended to rank higher in the treatment hierarchy, and we also found that it may be more beneficial to use a mixed route of administration (oral and intra-articular, oral and intravenous, or intravenous and intra-articular). Oral administration may be as effective as intravenous administration of TXA. We found little to no evidence of harm associated with higher doses of tranexamic acid in the risk of DVT. However, we are not able to definitively draw these conclusions based on the trials included within this review.

Aprotinin (I): Understanding the Role of Host Proteases in COVID-19 and the Importance of Pharmacologically Regulating Their Function.

Proteases are produced and released in the mucosal cells of the respiratory tract and have important physiological functions, for example, maintaining airway humidification to allow proper gas exchange. The infectious mechanism of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), takes advantage of host proteases in two ways: to change the spatial conformation of the spike (S) protein via endoproteolysis (e.g., transmembrane serine protease type 2 (TMPRSS2)) and as a target to anchor to epithelial cells (e.g., angiotensin-converting enzyme 2 (ACE2)). This infectious process leads to an imbalance in the mucosa between the release and action of proteases versus regulation by anti-proteases, which contributes to the exacerbation of the inflammatory and prothrombotic response in COVID-19. In this article, we describe the most important proteases that are affected in COVID-19, and how their overactivation affects the three main physiological systems in which they participate: the complement system and the kinin-kallikrein system (KKS), which both form part of the contact system of innate immunity, and the renin-angiotensin-aldosterone system (RAAS). We aim to elucidate the pathophysiological bases of COVID-19 in the context of the imbalance between the action of proteases and anti-proteases to understand the mechanism of aprotinin action (a panprotease inhibitor). In a second-part review, titled "Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions", we explain in depth the pharmacodynamics, pharmacokinetics, toxicity, and use of aprotinin as an antiviral drug.

Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions.

Aprotinin is a broad-spectrum inhibitor of human proteases that has been approved for the treatment of bleeding in single coronary artery bypass surgery because of its potent antifibrinolytic actions. Following the outbreak of the COVID-19 pandemic, there was an urgent need to find new antiviral drugs. Aprotinin is a good candidate for therapeutic repositioning as a broad-spectrum antiviral drug and for treating the symptomatic processes that characterise viral respiratory diseases, including COVID-19. This is due to its strong pharmacological ability to inhibit a plethora of host proteases used by respiratory viruses in their infective mechanisms. The proteases allow the cleavage and conformational change of proteins that make up their viral capsid, and thus enable them to anchor themselves by recognition of their target in the epithelial cell. In addition, the activation of these proteases initiates the inflammatory process that triggers the infection. The attraction of the drug is not only its pharmacodynamic characteristics but also the possibility of administration by the inhalation route, avoiding unwanted systemic effects. This, together with the low cost of treatment (≈2 Euro/dose), makes it a good candidate to reach countries with lower economic means. In this article, we will discuss the pharmacodynamic, pharmacokinetic, and toxicological characteristics of aprotinin administered by the inhalation route; analyse the main advances in our knowledge of this medication; and the future directions that should be taken in research in order to reposition this medication in therapeutics.

Aprotinin in high-risk isolated coronary artery bypass graft patients: a 3-year propensity matched study.

BACKGROUND: Aprotinin, a serine protease inhibitor, has been used variably in cardiac surgery amidst ongoing debates about its safety following several previous studies. This study assesses the outcomes of aprotinin in high-risk isolated Coronary Artery Bypass Graft (iCABG) patients. METHODS: The study retrospectively analysed a cohort of 1026 iCABG patients, including 51 patients who underwent aprotinin treatment. Logistic regression powered score matching was employed to compare aprotinin patients with a control group, in a propensity-matched cohort of 96 patients. The primary outcome measured was in-hospital death, with secondary outcomes including renal dysfunction, stroke, myocardial infarction, re-exploration for bleeding or tamponade, and postoperative stay durations. RESULTS: The aprotinin cohort had high-risk preoperative patients with significantly higher EUROSCORE II values, 7.5 (± 4.2), compared to 3.9 (± 2.5) in control group. However, aprotinin group showed no statistically significant increase (p-value: 0.44) in hospital mortality with OR 2.5 [95% CI 0.51, 12.3]. Major secondary outcome rates of renal replacement therapy and postoperative stroke compared to the control group were also statistically insignificant between the two groups. CONCLUSION: This study suggests that aprotinin may be safely used in a select group of high-risk iCABG patients. The reintroduction of aprotinin under specific conditions reflects its potential benefits in managing bleeding in high-risk surgeries, but also underscores the complexity of its risk-benefit profile in such critical care settings. Nonetheless, it highlights the importance of carefully selecting patients and conducting additional research, including larger and more controlled studies to fully comprehend the potential risks and benefits of aprotinin.

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.

Actualización en anemia y terapia transfusional / Anemia and transfusion therapy: an update

La anemia representa una de las patologías más prevalentes en la población general y constituye una entidad extremadamente frecuente en pacientes médicos y quirúrgicos de todas las especialidades. Una correcta valoración de su impacto y de las posibilidades terapéuticas resulta crucial. La transfusión de sangre alogénica representa una medida eficaz en el manejo de la anemia, pero no está exenta de importantes complicaciones. Es responsabilidad del clínico conocer y sopesar todas las alternativas disponibles para el manejo global de la anemia. Transfusiones sanguíneas, agentes estimuladores de la eritropoyesis, ferroterapia (oral y endovenosa) y otras alternativas terapéuticas han de ser empleadas de forma racional y ajustándonos a la evidencia clínica disponible hasta la fecha. El presente artículo de revisión resume algunas características epidemiológicas de la anemia, su valoración clínica y las principales alternativas terapéuticas a la luz de los conocimientos actuales, con especial énfasis en el paciente crítico (AU)

Anemia is one of the most prevalent diseases in the general population and is a very frequently found condition in medical and surgical patients in all medical specialties. A good evaluation of its clinical impact and its therapeutic possibilities is essential. Allogenic blood transfusion is a useful procedure in anemia management, although it has important adverse effects. It is the responsibility of the clinician to know and to take into account all the available alternatives for the treatment of anemia. Blood transfusions, erythropoiesis-stimulating agents, iron therapy (oral and endovenous) and other therapeutic alternatives must be rationally used, in accordance with the currently available clinical evidence. This review article summarizes some epidemiological characteristics of anemia, its clinical evaluation and the main therapeutic possibilities based on the present knowledge, placing special emphasis on the critically ill patient (AU)

Aprotinina preserva plaquetas em crianças com cardiopatia congênita acianogênica operadas com circulação extracorpórea? / Does aprotinin preserve platelets in children with acyanogenic congenital heart disease undergone surgery with cardiopulmonary bypass?

OBJETIVO: Avaliação dos efeitos hemostáticos e plaquetários em crianças submetidas a correção de cardiopatias congênitas acianogênicas com circulação extracorpórea que receberam aprotinina. MÉTODOS: Estudo prospectivo randomizado em crianças de 30 dias a 4 anos de idade, submetidas a correção de cardiopatia congênita acianogênica, com circulação extracorpórea (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. A disfunção hemostática foi analisada 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 e hospitalar, nem quanto ao uso de inotrópicos e função renal. Ocorreu preservação da concentração plaquetária com a Aprotinina, enquanto no grupo Controle houve plaquetopenia desde o início da CEC. As perdas sanguíneas foram semelhantes nos dois grupos. Não houve complicações com o uso da Aprotinina. CONCLUSÃO: A Aprotinina preservou quantitativamente as plaquetas em crianças com cardiopatia congênita acianogênica

OBJECTIVE: Evaluation of the hemostatic and platelets effects in children with acyanogenic congenital heart disease undergone on-pump surgery who received aprotinin. METHODS: A prospective randomized study was performed on children aged 30 days to 4 years who had undergone correction of acyanogenic congenital heart disease using cardiopulmonary bypass (CPB) and were divided into two groups: Control (n=9) and Aprotinin (n=10). In the Aprotinin Group the drug was administered before and during CPB and the hemostatic dysfunction was analyzed by 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 presented no benefit regarding time of mechanical pulmonary ventilation, stay in the postoperative intensive care unit and hospital, or regarding the use of inotropic drugs and renal function. Platelet concentration was preserved with the use of Aprotinin, whereas thrombocytopenia occurred in the Control Group since the initiation of CPB. Blood loss was similar for both groups. There were no complications with the use of Aprotinin. CONCLUSION: Aprotinin quantitatively preserved the blood platelets in children with acyanogenic congenital heart disease

Anestesia para tratamento de aspergilose cardíaca em paciente com trombocitopenia: o uso criterioso da aprotinina / Anesthesia for treatment of cardiac aspergillosis in a patient with thrombocytopenia and the judicious use of aprotinin

JUSTIFICATIVA E OBJETIVOS: A aprotinina tem sido muito utilizada em intervenções cirúrgicas cardíacas como recurso terapêutico para redução dos efeitos da circulação extracorpórea (CEC) sobre a coagulação e fibrinólise. A recuperação da hemostasia adequada ao final do procedimento é um dos objetivos do anestesiologista. Porém, o uso da aprotinina tem indicação específica. O objetivo deste trabalho foi apresentar o caso de um paciente com plaquetopenia intensa submetido à intervenção cirúrgica cardíaca no qual a interconsulta com a Hematologia e o planejamento adequado permitiram o sucesso do procedimento. RELATO DO CASO: Paciente do sexo masculino, 18 anos, 64 kg, estado físico ASA IV, portador de aplasia de medula, em investigação para ser submetido a transplante de medula. Apresentava febre persistente, de um mês de evolução, sem melhora com antibioticoterapia. Na investigação com métodos de imagem, diagnosticou-se massa intra-atrial esquerda. Ao exame laboratorial apresentava hemoglobina de 9 g.dL-1 e trombocitopenia - 6.000 plaquetas.mm-3. Foi submetido à esternotomia com CEC para retirada de trombo intracavitário. Com objetivo de controlar o sangramento intra-operatório foram administrados: plaquetaférese, hidrocortisona e aprotinina. Durante a intervenção cirúrgica não houve aumento do sangramento nem instabilidade hemodinâmica e o paciente foi encaminhado à Unidade de Terapia Intensiva (UTI) sem intercorrências. O exame anatomopatológico revelou trombo repleto de Aspergillus (massa fúngica). No sétimo dia de pós-operatório o paciente evoluiu com insuficiência respiratória e parada cardiorrespiratória sem resposta às manobras de reanimação. CONCLUSÕES: Apesar do grande risco de sangramento no paciente descrito, conseguiu-se realizar intervenção cirúrgica cardíaca com CEC sem intercorrências graças ao uso de aprotinina e plaquetoaférese.

BACKGROUND AND OBJECTIVES: Aprotinin has been widely used in cardiac surgeries as a therapeutic resource for reducing the effects of cardiopulmonary bypass (CPB) on coagulation and fibrinolysis. Recovery of adequate hemostasia at the end of the procedure is one of the objectives of the anesthesiologist. However, aprotinin has specific indications. The objective of this report was to present the case of a patient with severe thrombocytopenia undergoing cardiac surgery in which consultation with Hematology and adequate planning were responsible for the success of the procedure. CASE REPORT: An 18-year old male patient, weighing 64 kg, physical status ASA IV, with a diagnosis of bone marrow aplasia, was being investigated to undergo bone marrow transplantation. He had persistent fever for a month, which did not improve with antibiotics. During the investigation with imaging exams, a left atrial mass was discovered. Laboratory exams revealed hemoglobin 9 g.dL-1 and thrombocytopenia with 6,000 platelets.mm³. He underwent a sternotomy with CPB to remove the intracavitary thrombus. In order to control intraoperative bleeding, the following was administered: plateletpheresis, hydrocortisone, and aprotinin. Increased bleeding and hemodynamic instability did not develop during the surgery, and the patient was transferred to the Intensive Care Unit (ICU) without intercurrences. The anatomo-pathologic exam revealed the thrombus to be filled with Aspergillus (fungal mass). On the seventh postoperative day the patient developed respiratory failure and cardiorespiratory arrest that did not respond to resuscitation maneuvers. CONCLUSIONS: Despite the increased risk of bleeding in this patient, cardiac surgery with CPB was performed without intercurrences due to the use of aprotinin and plateletpheresis.

JUSTIFICATIVA Y OBJETIVOS: La aprotinina ha sido muy utilizada en intervenciones quirúrgicas cardiacas como recurso terapéutico para la reducción de los efectos de la circulación extracorpórea (CEC) sobre la coagulación y la fibrinólisis. La recuperación de la hemostasia adecuada al final del procedimiento es uno de los objetivos del anestesiólogo. Sin embargo, el uso de la aprotinina tiene una indicación específica. El objetivo de este trabajo fue presentar el caso de un paciente con plaquetopenia intensa sometido a la intervención quirúrgica cardiaca en el cual la interconsulta con hematología y la planificación adecuada permitieron el éxito del procedimiento. RELATO DEL CASO: Paciente del sexo masculino, 18 años, 64 kg, estado físico ASA IV, portador de aplasia de medula, en investigación para ser sometido al transplante de médula. Presentaba fiebre persistente, de un mes de evolución, sin mejoría con antibioticoterapia. En la investigación con métodos de imagen, se diagnosticó masa intra atrial izquierda. En el examen de laboratorio presentaba hemoglobina de 9 g.dL-1 y trombocitopenia - 6.000 plaquetas mm-3. Se sometió a la esternotomía con CEC para retirada de trombo intracavitario. Con el objetivo de controlar el sangramiento intraoperatorio fueron administrados: plaqueto-aferesis, hidrocortisona y aprotinina. Durante la intervención quirúrgica no hubo aumento del sangramiento ni inestabilidad hemodinámica y el paciente fue llevado a la Unidad de Terapia Intensiva (UTI) sin intercurrencias. El examen anátomo patológico reveló trombo repleto de Aspergilus (masa fúngica). Al sétimo día del postoperatorio el paciente evolucionó con insuficiencia respiratoria y parada cardiorrespiratoria sin respuesta a las maniobras de reanimación. CONCLUSIONES: A pesar del gran riesgo de sangramiento en el paciente descrito, se logró realizar la intervención quirúrgica cardiaca con CEC sin intercurrencias gracias al uso de aprotinina y plaquetoaféresis.

Sangre y Cirugía. EStrategia de Ahorro en cirugía cardiaca / Blood and Surgery. Strategic saving in cardiac surgery

El incremento de intervenciones quirúrgicas y su mayor complejidad y agresividad, especialmente en cirugía cardiovascular y trasplantes, junto con el envejecimiento de la población ha supuesto un considerable aumento de la demanda de transfusión sanguínea y derivados hemáticos. Los riesgos médicos inherentes al uso de sangre homóloga, el rechazo por motivaciones personales, éticas o creencias religiosas y una insuficiente disponibilidad de hemoderivados consecuencia de la escasezde donaciones, ha condicionado la necesidad del desarrollo de procesos de ahorro de sangre en cirugía y la búsqueda de técnicas alternativas a la transfusión. Problemática que alcanza su máxima expresión en cirugía cardiaca bajo circulación extracorpórea, como consecuencia del alto consumo de sangre de los enfermos cardiológicos intervenidos. Con la experiencia que aporta un promedio de quinientas cirugías anuales de corazón se realiza una revisión sobre las diferentes medidas y procedimientos asociados al ahorro de sangre en cirugía, especialmente en cirugía cardiovascular (AU)

The increase in the number of operations and their greater complexity and aggressiveness, especially in cardiovascular surgery and transplants, together with the aging of the population, has entailed an increase in the demand for transfusion and haematological derivates. The inherent medical risks of homolog blood usage, rejection for personal motivations, ethical and religious beliefs and insufficient availability of haematological derivates as a consequence of the shortage of donations, have conditioned the necessity for the development of processes for saving blood during surgery and the search for alternative techniques to transfusion. This is a problem which has its highest repercussions in cardiac surgery with cardio-pulmonary by-pass because of the high consumption of blood of patients undergoing cardiac surgery. With the experience of approximately 500 operations per year a review of the different measures and procedures associated with saving blood in surgery has been carried out, especially with regard to cardiovascular surgery (AU)

Métodos de puntuación de propensión para crear una distribución equilibrada de las covariables en los estudios observacionales / Propensity score methods for creating covariate balance in observational studies

La asignación aleatoria del tratamiento en los experimentos divide a los pacientes en grupos de tratamiento que están aproximadamente equilibrados en cuanto a las covariables basales. Sin embargo, en los estudios observacionales, en los que la asignación del tratamiento no es aleatoria, los pacientes de los grupos de tratamiento activo y de control difieren a menudo en covariables cruciales que están relacionadas con las variables de respuesta. Estos desequilibrios en las covariables pueden conducir a estimaciones sesgadas del efecto del tratamiento. La puntuación de propensión (propensity score) es la probabilidad de que a un paciente con unas características basales específicas se le asigne el tratamiento activo, y no el control. Aunque las puntuaciones de propensión son desconocidas en los estudios observacionales, al parear o subclasificar a los pacientes según las puntuaciones de propensión estimadas, podemos diseñar estudios observacionales que sean análogos a los experimentos aleatorios, con un equilibrio aproximado entre pacientes en cuanto a las covariables observadas. Los diseños de estudios observacionales basados en puntuaciones de propensión estimadas pueden producir estimaciones aproximadamente insesgadas del efecto del tratamiento. Una cuestión crucial es que los diseños de puntuación de propensión deben crearse sin tener acceso a las respuestas, imitando la separación entre el diseño del estudio y el análisis de las respuestas que es propia de los experimentos aleatorios. En este artículo se describen el marco conceptual de las respuestas potenciales para la inferencia causal y las mejores prácticas para el diseño de estudios observacionales con puntuaciones de propensión. Comentamos el uso de puntuaciones de propensión en dos estudios en los que se evaluaron la efectividad y los riesgos de los fármacos antifibrinolíticos durante las cirugías cardiacas (AU)

Randomization of treatment assignment in experiments generates treatment groups with approximately balanced baseline covariates. However, in observational studies, where treatment assignment is not random, patients in the active treatment and control groups often differ on crucial covariates that are related to outcomes. These covariate imbalances can lead to biased treatment effect estimates. The propensity score is the probability that a patient with particular baseline characteristics is assigned to active treatment rather than control. Though propensity scores are unknown in observational studies, by matching or subclassifying patients on estimated propensity scores, we can design observational studies that parallel randomized experiments, with approximate balance on observed covariates. Observational study designs based on estimated propensity scores can generate approximately unbiased treatment effect estimates. Critically, propensity score designs should be created without access to outcomes, mirroring the separation of study design and outcome analysis in randomized experiments. This paper describes the potential outcomes framework for causal inference and best practices for designing observational studies with propensity scores. We discuss the use of propensity scores in two studies assessing the effectiveness and risks of antifibrinolytic drugs during cardiac surgery (AU)

Requerimientos transfusionales y morbimortalidad en cirugía cardiaca en relación al empleo de antifibrinolíticos: aprotinina comparada con ácido tranexámico / Transfusion requirements, morbidity and mortality in cardiac surgery and the use of antifibrinolytic agents: a comparison of aprotinin and tranexamic acid

Objetivo: Evaluar los requerimientos transfusionales y morbimortalidad en relación con los antifibrinolíticos empleados (aprotinina o ácido tranexámico) en pacientes sometidos a cirugía cardiaca. Pacientes y método: Estudio comparativo, retrospectivo, de 243 pacientes sometidos a cirugía cardiaca, en relación al antifibrinolítico empleado, entre diciembre 2006 y junio 2008. Se registraron procedimientos quirúrgicos, necesidades transfusionales de hemoderivados, morbimortalidad –especialmente renal– y estancia hospitalaria. Resultados: Distribuidos en dos grupos, ácido tranexámico (TX, n = 144) y aprotinina (AP, n = 99), se objetivó una incidencia de transfusión de sangre alogénica inferior en el grupo TX (31,94% frente a 38,38%; p = 0,31), pero sin diferencia estadística. El grupo TX recibió una media de 0,67 ± 1,18 U de concentrado de hematíes totales, frente a 1,01 ± 1,54 U del grupo AP (p = 0,07). El valor medio de la hemoglobina preoperatoria del grupo TX resultó inferior (11,79 ± 1,71 mg/dL) respecto al grupo AP (12,35 ± 1,70 mg/dL) de modo significativo (p < 0,01). La disfunción renal postoperatoria debutante se presentó en mayor frecuencia en el grupo AP (19,6% frente a 16%, p = 0,47). La mortalidad <= 1 año fue inferior en el grupo TX (9,02% frente a 14,14%, p = 0,21), persistiendo esta diferencia al relacionar la mortalidad con la disfunción renal postoperatoria (7,6% frente a 12,4%, p = 0,22). No evidenciamos diferencias significativas en relación a complicaciones postoperatorias, ni estancia hospitalaria. Sin embargo, la ausencia de randomización y la limitada muestra del estudio, restringen las conclusiones definitivas. Conclusiones: El presente trabajo demuestra con las limitaciones mencionadas, que en nuestro medio, el ácido tranexámico empleado en cirugía cardiaca es tan efectivo como la aprotinina a la hora de disminuir los requerimientos transfusionales(AU)

Objective: To evaluate transfusion requirements, morbidity and mortality when 2 antifibrinolytic agents (aprotinin and tranexamic acid) were used in patients undergoing cardiac surgery. Patients and methods: Comparison of the effects of 2 antifibrinolytic agents in 243 patients undergoing cardiac surgery between December 2006 and June 2008. We recorded the surgical procedures used, blood product transfusions required, complications (particularly renal), mortality, and length of hospital stay. Results: The patients were distributed into 2 groups to receive tranexamic acid (n=144) or aprotinin (n=99). The incidence of transfusion in the tranexamic acid group (31.94%) was nonsignificantly lower than in the aprotinin group (38.38%) (P=.31). The mean (SD) number of units of packed red blood cells transfused was 0.67 (1.18) in the tranexamic acid group and 1.01 (1.54) in the aprotinin group (P=.07). The mean preoperative hemoglobin concentration in the tranexamic acid group (11.79 [1.71] mg/dL) was significantly lower than in the aprotinin group (12.35 [1.70] mg/dL) (P<.01). Incipient postoperative renal failure tended to occur more frequently in the aprotinin group (19.6% compared to 16%; P=.47). Mortality at 1 year was 9.02% in the tranexamic acid group (compared to 14.14% in the aprotinin group; P=.21); the trend for mortality related to postoperative renal failure was similar (7.6% in the tranexamic acid group compared to 12.4% in the aprotinin group; P=.22). No significant differences were observed in postoperative complications or length of hospital stay. However, the lack of randomization and the small sample size do not allow for definitive conclusions. Conclusions: This study, subject to the aforementioned limitations, shows that tranexamic acid is as effective as aprotinin for reducing transfusion requirements in cardiac surgery in Spain(AU)

Utilización de aprotinina como agente hemostático en la prótesis total de cadera / Aprotinin used as a hemostatic agent in THR

Objetivo. Estudiar el efecto de la administración de aprotinina sobre el sangrado postoperatorio de la prótesis total de cadera. Material y método. Estudio retrospectivo sobre 88 pacientes divididos en un grupo de casos (44 pacientes) que recibió una dosis de aprotinina de 2 × 10 unidades inhibidoras de kalicreína (KIU), y un grupo de control (44 pacientes) que no recibió ninguna dosis del fármaco. Se estudiaron la hemoglobina, el hematocrito y el número de plaquetas en hemogramas preoperatorio y postoperatorio (sala de reanimación, a las 6-12 y a las 24 horas de la intervención). Se registró el volumen recogido por los drenajes de Redón. Se contabilizó el número de concentrados de hematíes transfundido en cada caso. Resultados. Los hemogramas de control obtenidos en el postoperatorio mostraron valores semejantes de hemoglobina y hematocrito en ambos grupos. Hubo menor pérdida de sangre y exudados en los drenajes del grupo de casos. Se transfundieron menor número de pacientes del grupo de casos y globalmente menor número de concentrados de hematíes al grupo de casos que al de controles. Las diferencias halladas entre los valores estudiados de ambos grupos, resultaron estadísticamente significativas. Conclusión. La administración de aprotinina contribuye a reducir la cantidad de hemoderivados que es preciso administrar en el postoperatorio de la prótesis total de cadera, así como las pérdidas en los drenajes. La administración de menor número de concentrados al grupo de casos no implicó diferencias en los valores de hemoglobina y hematocrito frente al grupo control

Purpose. To study the effect of the administration of aprotinin on postoperative bleeding in total hip replacement. Materials and methods. Retrospective study of 88 patients divided into two groups: the first group contained 44 patients that received a dose of aprotinin of 2 × 10 kallicrein inhibiting units (KIUs) and the other, also containing 44 patients, was the control group, which was not given any aprotonin at all. Pre- and postoperative blood counts were carried out to study hemoglobin, hematocrit and platelet count (shock room at 6-12 hours and 24 hours post-op). The amount of blood collected during Redon drainage was recorded. The number of red blood cells concentrates transfused was also noted. Results. Control blood counts make during the postoperative period showed similar hemoglobin and hematocrit values in both groups. Less blood loss and fewer exudates were recorded in the treated group. Fewer patients were transfused in the treated group and, on the whole, fewer red blood cell concentrates were transfused in the treated group than in the control group. The differences found between the values studied in both groups turned out to be statistically significant. Conclusion. The administration of aprotinin contributes to reducing the amount of hemoderivatives administered further to THR and the volume of blood loss in drainage. The administration of fewer concentrates to the treated group did not lead to differences vis-à-vis the control group in terms of the values for hemoglobin and hematocrit

Documento «Sevilla» de Consenso sobre Alternativas a la Transfusión de Sangre Alogénica / The «Seville» Consensus Document on Alternatives to Allogenic Blood Transfusion

El Documento de Consenso sobre Alternativas a la Transfusión de Sangre Alogénica (ATSA) ha sido elaborado por un panel de expertos pertenecientes a 5 sociedades científicas. Han participado y patrocinado las sociedades españolas de Anestesiología (SEDAR), Medicina Intensiva (SEMICYUC), Hematología y Hemoterapia (AEHH), Transfusión sanguínea (SETS) y Trombosis y Hemostasia (SETH). Las alternativas a la transfusión se han clasificado en farmacológicas y no farmacológicas, con un total de 4 módulos y 12 tópicos. La disminución de las transfusiones de sangre alogénica y/o el número de pacientes transfundidos fue la principal variable objetivo. El grado de cumplimiento de este objetivo, para cada ATSA, se llevó a cabo siguiendo la metodología Delphi, que clasifica el grado de recomendación desde «A» (apoyado por estudios controlados) hasta «E» (estudios no controlados y opinión de expertos). Los expertos concluyeron que la mayor parte de las indicaciones de las ATSA se sustentan en grados de recomendación medios y bajos, «C», «D» o «E», precisándose nuevos estudios controlados (AU)

The Consensus Document on Alternatives to Allogenic Blood Transfusion (AABT) has been drawn up by a panel of experts from 5 scientific societies. The Spanish Societies of Anesthesiology (SEDAR), Critical Care Medicine and Coronary Units (SEMICYUC), Hematology and Hemotherapy (AEHH), Blood Transfusion (SETS) and Thrombosis and Hemostasis (SETH) have sponsored and participated in this Consensus Document. Alternatives to blood transfusion have been divided into pharmacological and non-pharmacological, with 4 modules and 12 topics. The main objective variable was the reduction of allogenic blood transfusions and/or the number of transfused patients. The extent to which this objective was achieved by each AABT was evaluated using the Delphi method, which classifies the grade of recommendation from A (supported by controlled studies) to E (non-controlled studies and expert opinion). The experts concluded that most of the indications for AABT were based on middle or low grades of recommendation, «C», «D», or «E», thus indicating the need for further controlled studies (AU)

Influencia de la aprotinina en el sangrado postoperatorio de la artroplastia total de rodilla / Effect of aprotinin on postoperative bleeding in total knee replacement

Objetivo. Estudiar el efecto de la administración de aprotinina sobre el sangrado postoperatorio de la artroplastia total de rodilla. Material y método. Estudio retrospectivo sobre 64 pacientes divididos en un grupo de casos (30 pacientes) que recibió una dosis de aprotinina de 2 x 106 unidades inhibidoras de kalicreína (KIU), y un grupo de control (34 pacientes) que no recibió ninguna dosis del fármaco. Se estudiaron la hemoglobina, el hematocrito y el número de plaquetas en hemogramas preoperatorio y postoperatorio (entre las 6 y 12 horas y a las 24 horas de la intervención). Se registró el volumen de sangre obtenido por los drenajes de Redon. Se contabilizó el número de concentrado de hematíes transfundidos en cada caso. Resultados. Los pacientes a los que se administró aprotinina tuvieron un menor descenso de los valores de hemoglobina y hematocrito y un menor volumen de sangre recogido en los drenajes de Redon que el grupo control. Durante el postoperatorio se transfundió a menos pacientes del grupo de casos que del grupo de control. Las diferencias entre los valores estudiados de ambos grupos resultaron estadísticamente significativas. Conclusión. La administración de aprotinina contribuye a reducir el descenso de hemoglobina y hematocrito, así como las pérdidas en los drenajes y la administración de hemoderivados en el postoperatorio de la artroplastia total de rodilla

Aim. To study the effect of the administration of aprotinin on postoperative bleeding in total knee replacement (TKR). Materials and methods. A retrospective study was performed on 64 patients divided into a treatment group (30 patients) that received a dose of aprotinin of 2x106 inhibitory units of kalicrein and a control group (34 patients) that did not receive any drug. Different variables were studied: hemoglobin, hematocrit, and platelets in preoperative and postoperative (6-12 hs and 24 hs) hemograms. The volume of blood in Redon high-vacuum drainage was registered. The number of packed red blood cell concentrate (pRBC) units transfused were also registered. Results. The patients that received aprotinin had a smaller decrease of hemoglobin and hematocrit than the patients in the control group. The volume of blood collected in the Redon drainage for these patients was also smaller than in the control group. During the postoperative period fewer patients in the treated group received transfusions than in the control group. The differences in the variables studied in both groups were statistically significant. Conclusion. The administration of aprotinin helps reduce the fall in hemoglobin and hematocrit, the blood losses into drainage and the administration of transfusions during the postoperative period in TKR

El síndrome de defibrinación aguda en tocoginecología: nuestra experiencia / Acute defibrination syndrome in tocogynecology: our experience

En 10 casos de hipo y afibrinogenemias secundarias relacionadas a la tocoginecología, se usó aprontinina, 200.000 a 400.000 unidades em bolo lento endovenoso seguido de un goteo de 1 a 2 millones de unidades por día. La respuesta rápida uniforme y sin efectos colaterales permite afirmar que justifica su uso en la emergencia de la desfibrinación. Esta puede diagnosticarse con aproximación, si no se cuenta con un laboratorio de hemostasia reconociendo el defecto por observación del coágulo (AU)

El síndrome de defibrinación aguda en tocoginecología: nuestra experiencia / Acute defibrination syndrome in tocogynecology: our experience

En 10 casos de hipo y afibrinogenemias secundarias relacionadas a la tocoginecología, se usó aprontinina, 200.000 a 400.000 unidades em bolo lento endovenoso seguido de un goteo de 1 a 2 millones de unidades por día. La respuesta rápida uniforme y sin efectos colaterales permite afirmar que justifica su uso en la emergencia de la desfibrinación. Esta puede diagnosticarse con aproximación, si no se cuenta con un laboratorio de hemostasia reconociendo el defecto por observación del coágulo

Pancreatitis aguda necrohemorrágica experimental: mecanismo de la acción terápeutica del bloqueo ductal / Experimental necrohemorrhagic acute pancreatitis: mechanism of the therapeutic effect of the ductal block

Con el objetivo de profundizar las investigaciones originales con Ethibloc, se decidió emplear otra sustancia para el bloqueo ductal, con iguales propiedades físicas y distinta fórmula química. La pancreatitis aguda necrohemorrágica se desencadenó con cloruro de calcio al 20%, y una vez producida la hemorragia a los 20 a 30 minutos, se inyectaron 5 a 7 cm del adhesivo tisular biológico (Tissucol). La evolución clínica y de laboratorio fue satisfactoria. Murió un sólo perro de los 10 que componían el grupo, al 9º día del postoperatorio por una peritonitis difusa de posible origen pancreático. Los otros animales fueron sacrificados a los 15 y 35 días mientras evolucionaban favorablemente. La anatomía patológica demostró progresiva disminución de la hemorragia y necrosis, y muy escasa fibrosis residual (AU)

Pancreatitis aguda necrohemorrágica experimental: mecanismo de la acción terápeutica del bloqueo ductal / Experimental necrohemorrhagic acute pancreatitis: mechanism of the therapeutic effect of the ductal block

Con el objetivo de profundizar las investigaciones originales con Ethibloc, se decidió emplear otra sustancia para el bloqueo ductal, con iguales propiedades físicas y distinta fórmula química. La pancreatitis aguda necrohemorrágica se desencadenó con cloruro de calcio al 20%, y una vez producida la hemorragia a los 20 a 30 minutos, se inyectaron 5 a 7 cm del adhesivo tisular biológico (Tissucol). La evolución clínica y de laboratorio fue satisfactoria. Murió un sólo perro de los 10 que componían el grupo, al 9§ día del postoperatorio por una peritonitis difusa de posible origen pancreático. Los otros animales fueron sacrificados a los 15 y 35 días mientras evolucionaban favorablemente. La anatomía patológica demostró progresiva disminución de la hemorragia y necrosis, y muy escasa fibrosis residual