Breast Cancer and Anaesthesia: Genetic Influence.

Breast cancer is the leading cause of mortality in women. It is a heterogeneous disease with a high degree of inter-subject variability even in patients with the same type of tumor, with individualized medicine having acquired significant relevance in this field. The clinical and morphological heterogeneity of the different types of breast tumors has led to a diversity of staging and classification systems. Thus, these tumors show wide variability in genetic expression and prognostic biomarkers. Surgical treatment is essential in the management of these patients. However, the perioperative period has been found to significantly influence survival and cancer recurrence. There is growing interest in the pro-tumoral effect of different anaesthetic and analgesic agents used intraoperatively and their relationship with metastatic progression. There is cumulative evidence of the influence of anaesthetic techniques on the physiopathological mechanisms of survival and growth of the residual neoplastic cells released during surgery. Prospective randomized clinical trials are needed to obtain quality evidence on the relationship between cancer and anaesthesia. This document summarizes the evidence currently available about the effects of the anaesthetic agents and techniques used in primary cancer surgery and long-term oncologic outcomes, and the biomolecular mechanisms involved in their interaction.

Renal and Neurologic Benefit of Levosimendan vs Dobutamine in Patients With Low Cardiac Output Syndrome After Cardiac Surgery: Clinical Trial FIM-BGC-2014-01.

BACKGROUND: Low-cardiac output syndrome (LCOS) after cardiac surgery secondary to systemic hypoperfusion is associated with a higher incidence of renal and neurological damage. A range of effective therapies are available for LCOS. The beneficial systemic effects of levosimendan persist even after cardiac output is restored, which suggests an independent cardioprotective effect. METHODS: A double-blind clinical trial was conducted in patients with a confirmed diagnosis of LCOS randomized into two treatment groups (levosimendan vs. dobutamine). Monitoring of hemodynamic (cardiac index, systolic volume index, heart rate, mean arterial pressure, central venous pressure, central venous saturation); biochemical (e.g. creatinine, S100B protein, NT-proBNP, troponin I); and renal parameters was performed using acute kidney injury scale (AKI scale) and renal and brain ultrasound measurements [vascular resistance index (VRI)] at diagnosis and during the first 48 h. RESULTS: Significant differences were observed between groups in terms of cardiac index, systolic volume index, NT-proBNP, and kidney injury stage at diagnosis. In the levosimendan group, there were significant variations in AKI stage after 24 and 48 h. No significant differences were observed in the other parameters studied. CONCLUSION: Levosimendan showed a beneficial effect on renal function in LCOS patients after cardiac surgery that was independent from cardiac output and vascular tone. This effect is probably achieved by pharmacological postconditioning. CLINICAL TRIAL REGISTRATION: EUDRA CT, identifier 2014-001461-27. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001461-27.

Periprocedural Direct Oral Anticoagulant Management: The RA-ACOD Prospective, Multicenter Real-World Registry.

Introduction There is scarce real-world experience regarding direct oral anticoagulants (DOACs) perioperative management. No study before has linked bridging therapy or DOAC-free time (pre-plus postoperative time without DOAC) with outcome. The aim of this study was to investigate real-world management and outcomes. Methods RA-ACOD is a prospective, observational, multicenter registry of adult patients on DOAC treatment requiring surgery. Primary outcomes were thrombotic and hemorrhagic complications. Follow-up was immediate postoperative (24-48 hours) and 30 days. Statistics were performed using a univariate and multivariate analysis. Data are presented as odds ratios (ORs [95% confidence interval]). Results From 26 Spanish hospitals, 901 patients were analyzed (53.5% major surgeries): 322 on apixaban, 304 on rivaroxaban, 267 on dabigatran, 8 on edoxaban. Fourteen (1.6%) patients suffered a thrombotic event, related to preoperative DOAC withdrawal (OR: 1.57 [1.03-2.4]) and DOAC-free time longer than 6 days (OR: 5.42 [1.18-26]). Minor bleeding events were described in 76 (8.4%) patients, with higher incidence for dabigatran (12.7%) versus other DOACs (6.6%). Major bleeding events occurred in 17 (1.9%) patients. Bridging therapy was used in 315 (35%) patients. It was associated with minor (OR: 2.57 [1.3-5.07]) and major (OR: 4.2 [1.4-12.3]) bleeding events, without decreasing thrombotic events. Conclusion This study offers real-world data on perioperative DOAC management and outcomes in a large prospective sample size to date with a high percentage of major surgery. Short-term preprocedural DOAC interruption depending on the drug, hemorrhagic risk, and renal function, without bridging therapy and a reduced DOAC-free time, seems the safest practice.

Manejo perioperatorio y periprocedimiento del tratamiento antitrombótico: documento de consenso de SEC, SEDAR, SEACV, SECTCV, AEC, SECPRE, SEPD, SEGO, SEHH, SETH, SEMERGEN, SEMFYC, SEMG, SEMICYUC, SEMI, SEMES, SEPAR, SENEC, SEO, SEPA, SERVEI, SECOT y AEU / Perioperative and periprocedural management of antithrombotic therapy: consensus document of SEC, SEDAR, SEACV, SECTCV, AEC, SECPRE, SEPD, SEGO, SEHH, SETH, SEMERGEN, SEMFYC, SEMG, SEMICYUC, SEMI, SEMES, SEPAR, SENEC, SEO, SEPA, SERVEI, SECOT and AEU

En los últimos años, el número de pacientes anticoagulados y antiagregados está aumentando significativamente. Al ser un tratamiento crónico, es de esperar que a lo largo de su vida necesiten un procedimiento quirúrgico o intervencionista que pueda requerir la interrupción del fármaco antitrombótico. La decisión de retirar o mantener dicho tratamiento estará determinada, por un lado, por el riesgo trombótico y, por otro, por el hemorrágico. De la interacción entre estos 2 factores dependerá la actitud ante la anticoagulación y la antiagregación. El objetivo de este documento de consenso, coordinado desde el Grupo de Trabajo de Trombosis Cardiovascular de la Sociedad Española de Cardiología y certificado por un amplio número de sociedades científicas que participan en el proceso asistencial del paciente durante el periodo perioperatorio o periprocedimiento, consiste en proponer una serie de recomendaciones prácticas y sencillas con el fin de homogeneizar la práctica clínica diaria

During the last few years, the number of patients receiving anticoagulant and antiplatelet therapy has increased worldwide. Since this is a chronic treatment, patients receiving it can be expected to need some kind of surgery or intervention during their lifetime that may require treatment discontinuation. The decision to withdraw antithrombotic therapy depends on the patient's thrombotic risk versus hemorrhagic risk. Assessment of both factors will show the precise management of anticoagulant and antiplatelet therapy in these scenarios. The aim of this consensus document, coordinated by the Cardiovascular Thrombosis Working Group of the Spanish Society of Cardiology, and endorsed by most of the Spanish scientific societies of clinical specialities that may play a role in the patient-health care process during the perioperative or periprocedural period, is to recommend some simple and practical guidelines with a view to homogenizing daily clinical practice

'Patient blood management' en cirugía ortopédica / 'Patient blood management' in orthopaedic surgery

Los procedimientos de cirugía ortopédica y traumatológica (COT) pueden ocasionar pérdidas significativas de sangre y anemia postoperatoria aguda, que en muchos casos requiere transfusión de sangre alogénica (TSA). Las desventajas clínicas, económicas y logísticas de la TSA han promovido el desarrollo de programas multidisciplinares y multimodales, genéricamente conocidos como programas de Patient Blood Management (PBM), cuyo objetivo es el de reducir o eliminar la necesidad de TSA y mejorar el resultado clínico. Estos programas se apoyan en la aplicación de cuatro grupos de medidas perioperatorias: 1) uso de criterios restrictivos de transfusión; 2) estimulación de la eritropoyesis; 3) reducción del sangrado; y 4) transfusión de sangre autóloga. En este artículo, revisamos la eficacia, seguridad y recomendaciones de las estrategias aplicables en COT, así como los condicionantes para el desarrollo e implementación de los programas de PBM en esta especialidad (AU)

Orthopaedic and trauma surgical procedures (OTS) can lead to significant blood losses and acute postoperative anaemia, which in many cases requires allogeneic blood transfusions (ABT). The clinical, economic and logistical disadvantages of ABT have promoted the development of multidisciplinary and multimodal programs generically known as Patient Blood Management (PBM) programs, which have as their objective to reduce or eliminate the need for ABT and improve clinical outcomes. These programs are supported by the implementation of four groups of perioperative measures: (1) use of restrictive transfusion criteria; (2) stimulation of erythropoiesis; (3) reduction of bleeding; and (4) autologous blood transfusion. In this article, a review is presented of the effectiveness, safety and recommendations of applicable strategies in OTS, as well as the barriers and requirements to the development and implementation of PBM programs in this surgical specialty (AU)

"Patient blood management" in orthopaedic surgery.

Orthopaedic and trauma surgical procedures (OTS) can lead to significant blood losses and acute postoperative anaemia, which in many cases requires allogeneic blood transfusions (ABT). The clinical, economic and logistical disadvantages of ABT have promoted the development of multidisciplinary and multimodal programs generically known as Patient Blood Management (PBM) programs, which have as their objective to reduce or eliminate the need for ABT and improve clinical outcomes. These programs are supported by the implementation of four groups of perioperative measures: (1) use of restrictive transfusion criteria; (2) stimulation of erythropoiesis; (3) reduction of bleeding; and (4) autologous blood transfusion. In this article, a review is presented of the effectiveness, safety and recommendations of applicable strategies in OTS, as well as the barriers and requirements to the development and implementation of PBM programs in this surgical specialty.

Recomendaciones de uso de los anticoagulantes orales directos en el período perioperatorio / Recommendations on use of direct oral anticoagulants in the perioperative period

Las características de los anticoagulantes orales de acción directa (ACOD), la ausencia de antídoto para revertir completamente sus efectos anticoagulantes, la falta de sistematización en la monitorización de sus efectos y la experiencia limitada de su empleo, hacen necesarias unas recomendaciones específicas para su uso en el periodo perioperatorio o ante situaciones de urgencia. En cirugía programada, en pacientes con función renal normal y riesgos hemorrágico/trombótico bajos, se recomienda suspender el ACOD 2 días antes de la cirugía; en situaciones de mayor riesgo hemorrágico/trombótico se propone como alternativa una terapia puente con una heparina de bajo peso molecular desde 5 días antes de la cirugía. Ante cirugía urgente no se recomienda la administración sistemática de hemostáticos de forma profiláctica. En caso de hemorragia aguda relacionada con la toma de un ACOD, se debe valorar la administración de concentrados de complejo protrombínico, plasma fresco o factor VIIa, implementando las medidas generales de control de la hemorragia (AU)

Because of the characteristics of direct oral anticoagulants (DOA), the lack of an antidote to completely reverse their anticoagulant effects, the absence of standardization in monitoring of their effects, and limited experience of their use, specific recommendations for their management in the perioperative period or in emergencies are required. In elective surgery, in patients with normal renal function and low hemorrhagic/ thrombotic risk, DOA should be withdrawn 2 days before the intervention; when the hemorrhagic/ thrombotic risk is higher, bridge therapy with a low molecular weight hepatin beginning 5 days before the intervention is proposed as an alternative. In emergency surgery, systematic administration of hemostatic drugs as prophylaxis is not recommended. In DOA-related acute hemorrhage, administration of prothrombin complex concentrate, fresh plasma or factor VIIa should be evaluated, and general measures to control bleeding should be implemented (AU)

[Recommendations on use of direct oral anticoagulants in the perioperative period]. / Recomendaciones de uso de los anticoagulantes orales directos en el período perioperatorio.

Because of the characteristics of direct oral anticoagulants (DOA), the lack of an antidote to completely reverse their anticoagulant effects, the absence of standardization in monitoring of their effects, and limited experience of their use, specific recommendations for their management in the perioperative period or in emergencies are required. In elective surgery, in patients with normal renal function and low hemorrhagic/ thrombotic risk, DOA should be withdrawn 2 days before the intervention; when the hemorrhagic/ thrombotic risk is higher, bridge therapy with a low molecular weight hepatin beginning 5 days before the intervention is proposed as an alternative. In emergency surgery, systematic administration of hemostatic drugs as prophylaxis is not recommended. In DOA-related acute hemorrhage, administration of prothrombin complex concentrate, fresh plasma or factor VIIa should be evaluated, and general measures to control bleeding should be implemented.

Prevention of the renarrowing of coronary arteries using drug-eluting stents in the perioperative period: an update.

The management of patients scheduled for surgery with a coronary stent, and receiving 1 or more antiplatelet drugs, has many controversies. The premature discontinuation of antiplatelet drugs substantially increases the risk of stent thrombosis (ST), myocardial infarction, and cardiac death, and surgery under an altered platelet function could also lead to an increased risk of bleeding in the perioperative period. Because of the conflict in the recommendations, this article reviews the current antiplatelet protocols after positioning a coronary stent, the evidence of increased risk of ST associated with the withdrawal of antiplatelet drugs and increased bleeding risk associated with its maintenance, the different perioperative antiplatelet protocols when patients are scheduled for surgery or need an urgent operation, and the therapeutic options if excessive bleeding occurs.

The platelet of the patients with ischemic cardiopathy and cardiac valve disease showed a reduction of 8OH-DPAT binding sites.

Depression is prospectively associated with increased risk of coronary artery disease in individuals initially free of clinical cardiovascular disease probably by an increased platelet activity. The serotonergic receptors mainly implied in depression are 5-HT1A and 5-HT2 receptors. Activation of 5HT2 receptor induces platelet aggregation. Drugs with 5-HT1A receptor agonist and 5-HT2A receptor antagonist effects reduced the receptor-mediated platelet aggregation. There are only indirect data about 5-HT1A receptors presence in platelet membranes, thus our aims were to study the characteristics of the platelet membranes 5-HT1A binding sites of both healthy volunteers and patients with cardiac valve disease and ischemic cardiopathy. The bound of the 5-HT1A selective agonist 3H-8OH-DPAT to the platelet membranes 5-HT1A binding sites of patients with cardiac valve disease and ischemic cardiopathy were compared with a control group of healthy voluntaries using radioligand binding methods. The patients with cardiovascular disease showed a reduction (-50.40%) (p<0.01) of the 3H-8OH-DPAT bound to the platelet membranes 5-HT1A receptors (1.652+/-0.79 fmol/mg protein) with respect to the control group (3.331+/-0.16 fmol/mg protein). 3H-8OH-DPAT binding to human platelet membranes is saturable, of high affinity, and seems selective for 5-HT1A receptors, and similar to that described in animal brain and in other human cells. Patients with ischemic cardiopathy and cardiac valve disease showed a reduction of the 8OH-DPAT bound to the platelet membranes. Taken together, these findings suggest that the 8OH-DPAT bound to the human platelet membranes is modulated by modifications produced by cardiovascular disease conditions.

Corticosterone strongly increases the affinity of dorsal raphe 5-HT1A receptors.

The effects of corticosterone (10 mg/kg, s.c., 6 h) on dorsal raphe 5-HT1A autoreceptors have been studied in adrenalectomized rats with or without porcine galanin modulation. Adrenalectomy diminishes 5-HT1A autoreceptors affinity. Corticosterone increases 5-HT1A autoreceptor agonist affinity (+90%, p<0.001) in adrenalectomized rats. Galanin (10 nM) increases dorsal raphe 5-HT1A autoreceptor density (+65%, p<0.05) and its Kd value (+248%, p<0.05) only in adrenalectomized rats treated with corticosterone. Dorsal raphe glucocorticoid receptors activation by corticosterone may therefore lead to an increased signalling of 5-HT1A autoreceptors that may become counteracted by galanin receptor activation. Glucocorticoids, by enhancing dorsal raphe 5-HT1A autoreceptor function, may therefore cause reduced 5-HT neuronal activity and thus lead to a depressive state.

Anestesia locorregional y fármacos que alteran la hemostasia. Sugerencias de la reunión de expertos en el Congreso de la ESRA de Barcelona / Regional anesthesia and hemostasis-altering agents: suggestions from the ESRA meeting of experts in Barcelona

El creciente interés mostrado en las implicaciones de los fármacos que alteran la hemostasia en el empleo de técnicas de anestesia locorregional, se plasmó recientemente en un artículo de revisión que proponía determinadas sugerencias de seguridad (Llau JV et al, Rev Esp Anestesiol Reanim 2001;48:270-278). Sin embargo, surgió la necesidad de completar y ampliar algunos aspectos clínicos, redactándose este artículo como continuación del previo, a partir de una reunión celebrada en el VIII ESRA Local Meeting en Barcelona en mayo de 2002, donde se revisaron los asuntos más controvertidos y con mayor implicación práctica (tiempos de seguridad, actitud ante determinados antiagregantes plaquetarios, fibrinolíticos o ciertas combinaciones de fármacos, etc.). El presente documento aúna así las sugerencias y propuestas de los asistentes a la citada reunión, de forma fiel a cómo se plantearon. Además, ante la necesidad mostrada por la mayoría de anestesiólogos de encontrar recomendaciones en relación con los fármacos fibrinolíticos, se recogen las cuestiones más importantes referentes a la implicación de los mismos en la práctica de la anestesia locorregional (AU)

S-adenosyl-L-methionine prevents 5-HT(1A) receptors up-regulation induced by acute imipramine in the frontal cortex of the rat.

S-adenosyl-L-methionine (SAM) has shown efficacy in speeding the onset of the antidepressant effect of imipramine in depressed patients. This effect may be related to their interactions at the serotonin(1A) (5-HT(1A)) receptors. Acute imipramine up-regulated the frontal cortex 5-HT(1A) receptors (B(max), 51.5 +/- 8.4 fmol/mg protein) vs. saline (B(max), 27.5 +/- 5.9 fmol/mg protein), and did not show antidepressant effect. Acute SAM and imipramine+SAM did not modify frontal cortex 5-HT(1A) receptors, and showed antidepressant effects (decrease of the immobility response of 26%, P<0.01; and 47%, P<0.001) vs. saline. All the chronic treatments showed antidepressant effects and up-regulated the hippocampus 5-HT(1A) receptors. SAM prevents the 5-HT(1A) receptor up-regulation induced by acute imipramine in the frontal cortex. This mechanism may contribute to imipramine's antidepressant effect.

[Locoregional anesthesia and drugs that affect hemostasis. Suggestions of the expert meeting in the ESRA Congress in Barcelona]. / Anestesia locorregional y fármacos que alteran la hemostasia. Sugerencias de la reunión de expertos en el Congreso de la ESRA de Barcelona.

Growing interest in the effect of hemostasis-altering medications on regional anesthetic techniques was analyzed recently in a review article suggesting certain safety measures, by Llau and colleages in Revista Española de Anestesiología y Reanimación. Since that review, however, it has become necessary to extend the discussion of clinical issues, based on information presented at the Eighth Local Meeting of the European Society for Regional Anesthesia (ESRA) of May 2002. There, participants debated the most controversial aspects, with attention to practical questions such as temporal safety margins and approaches to take given certain platelet antiaggregants, fibrinolytics or drug combinations. This paper faithfully presents the suggestions made by participants at the meeting. As most anesthesiologists expressed the need to set guidelines for fibrinolytics, the main issues related to those drugs in regional anesthesia are reviewed.