The Surviving Sepsis Campaign: Basic/Translational Science Research Priorities.

OBJECTIVES: Expound upon priorities for basic/translational science identified in a recent paper by a group of experts assigned by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. DATA SOURCES: Original paper, search of the literature. STUDY SELECTION: By several members of the original task force with specific expertise in basic/translational science. DATA EXTRACTION: None. DATA SYNTHESIS: None. CONCLUSIONS: In the first of a series of follow-up reports to the original paper, several members of the original task force with specific expertise provided a more in-depth analysis of the five identified priorities directly related to basic/translational science. This analysis expounds on what is known about the question and what was identified as priorities for ongoing research. It is hoped that this analysis will aid the development of future research initiatives.

Efficacy and safety of early target-controlled plasma volume replacement with a balanced gelatine solution versus a balanced electrolyte solution in patients with severe sepsis/septic shock: study protocol, design, and rationale of a prospective, randomized, controlled, double-blind, multicentric, international clinical trial : GENIUS-Gelatine use in ICU and sepsis.

BACKGROUND: Sepsis is associated with capillary leakage and vasodilatation and leads to hypotension and tissue hypoperfusion. Early plasma volume replacement is required to achieve haemodynamic stability (HDS) and maintain adequate tissue oxygenation. The right choice of fluids to be used for plasma volume replacement (colloid or crystalloid solutions) is still a matter of debate, and large trials investigating the use of colloid solutions containing gelatine are missing. This study aims to investigate the efficacy and safety of plasma volume replacement using either a combined gelatine-crystalloid regime (1:1 ratio) or a pure crystalloid regime. METHODS: This is a prospective, controlled, randomized, double-blind, international, multicentric phase IV study with two parallel groups that is planned to be conducted at European intensive care units (ICUs) in a population of patients with hypovolaemia in severe sepsis/septic shock. A total of 608 eligible patients will be randomly assigned to receive either a gelatine-crystalloid regime (Gelaspan® 4% and Sterofundin® ISO, B. Braun Melsungen AG, in a 1:1 ratio) or a pure crystalloid regime (Sterofundin® ISO) for plasma volume replacement. The primary outcome is defined as the time needed to achieve HDS. Plasma volume replacement will be target-controlled, i.e. fluids will only be administered to volume-responsive patients. Volume responsiveness will be assessed through passive leg raising or fluid challenges. The safety and efficacy of both regimens will be assessed daily for 28 days or until ICU discharge (whichever occurs first) as the secondary outcomes of this study. Follow-up visits/calls will be scheduled on day 28 and day 90. DISCUSSION: This study aims to generate evidence regarding which regimen-a gelatine-crystalloid regimen or a pure crystalloid regimen-is more effective in achieving HDS in critically ill patients with hypovolaemia. Study participants in both groups will benefit from the increased safety of target-controlled plasma volume replacement, which prevents fluid administration to already haemodynamically stable patients and reduces the risk of harmful fluid overload. TRIAL REGISTRATION: The European clinical trial database EudraCT 2015-000057-20 and the ClinicalTrials.gov Protocol Registration and Results System ClinicalTrials.gov NCT02715466 . Registered on 17 March 2016.

[Clinical Consensus Recommendations Regarding Non-Invasive Respiratory Support in the Adult Patient with Acute Respiratory Failure Secondary to SARS-CoV-2 infection]. / Recomendaciones de consenso respecto al soporte respiratorio no invasivo en el paciente adulto con insuficiencia respiratoria aguda secundaria a infección por SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Currently, the World Health Organization (WHO) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. While most people with COVID-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure. This consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four Spanish scientific societies (Spanish Society of Intensive Care Medicine [SEMICYUC], Spanish Society of Pulmonologists [SEPAR], Spanish Society of Emergency [SEMES], Spanish Society of Anesthesiology, Reanimation, and Pain [SEDAR]) with experience in the clinical management of patients with COVID-19 and other viral infections, including SARS, as well as sepsis and ARDS. The document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of COVID-19 with acute respiratory failure.This consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials.

[Clinical consensus recommendations regarding non-invasive respiratory support in the adult patient with acute respiratory failure secondary to SARS-CoV-2 infection]. / Recomendaciones de consenso respecto al soporte respiratorio no invasivo en el paciente adulto con insuficiencia respiratoria aguda secundaria a infección por SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Currently, the World Health Organization (WHO) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. While most people with COVID-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure. This consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four Spanish scientific societies (Spanish Society of Intensive Care Medicine [SEMICYUC], Spanish Society of Pulmonologists [SEPAR], Spanish Society of Emergency [SEMES], Spanish Society of Anesthesiology, Reanimation, and Pain [SEDAR]) with experience in the clinical management of patients with COVID-19 and other viral infections, including SARS, as well as sepsis and ARDS. The document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of COVID-19 with acute respiratory failure. This consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials.

[Consensus document of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC), the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) and the Spanish Society of Anesthesiology and Resuscitation (SEDAR) on tracheotomy in patients with COVID-19 infection]. / Documento de consenso de la Sociedad Española de Medicina Intensiva, Crítica, y Unidades Coronarias (SEMICYUC), la Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello (SEORL-CCC) y la Sociedad Española de Anestesiología y Reanimación (SEDAR) sobre la traqueotomía en pacientes con COVID-19.

The current COVID-19 pandemic has rendered up to 15% of patients under mechanical ventilation. Because the subsequent tracheotomy is a frequent procedure, the three societies mostly involved (SEMICYUC, SEDAR and SEORL-CCC) have setup a consensus paper that offers an overview about indications and contraindications of tracheotomy, be it by puncture or open, clarifying its respective advantages and enumerating the ideal conditions under which they should be performed, as well as the necessary steps. Regular and emergency situations are displayed together with the postoperative measures.

Cytokine release syndrome. Reviewing a new entity in the intensive care unit.

Immunotherapy seeks to harness the power of the immune system to eradicate malignant tissues. Despite impressive therapeutic success, however, it can be accompanied by severe adverse effects such as cytokine release syndrome (CRS). These therapies cause the release of a great amount of cytokines, with IL-6 playing a central role, that can potentially lead to multiple organ dysfunction. The diagnosis is based on the presence of compatible clinical symptoms, elevated biomarkers and recent treatment with a biological agent. Mild cases can be managed through symptomatic treatment and fluids, while more severe episodes may need supportive therapy and specific care with the anti-IL-6 receptor monoclonal antibody tocilizumab. Although corticosteroids are also effective, they suppress T-cell activity, and so should only be considered as second line therapy or in cases of severe neurological involvement, since tocilizumab does not cross the blood-brain barrier. Cytokine release syndrome generally has a good prognosis, often being reversible and with a good response to specific treatment. Despite possible concerns about the admission of such patients (mainly with advanced oncological disease), we consider that the Intensive Care Unit should remain an option, since these individuals present a potentially reversible drug-related adverse event and are being treated with a new drug that could change the prognosis of the disorder. Intensive care medicine will become a key component in the management of the complications of modern cancer therapies, dealing with patients presenting an overactive immune system producing organ dysfunction while also trying to maintain treatment efficacy. This is the new paradigm.

Inflammatory cytokines and organ dysfunction associate with the aberrant DNA methylome of monocytes in sepsis.

BACKGROUND: Sepsis, a life-threatening organ dysfunction caused by a dysregulated systemic immune response to infection, associates with reduced responsiveness to subsequent infections. How such tolerance is acquired is not well understood but is known to involve epigenetic and transcriptional dysregulation. METHODS: Bead arrays were used to compare global DNA methylation changes in patients with sepsis, non-infectious systemic inflammatory response syndrome, and healthy controls. Bioinformatic analyses were performed to dissect functional reprogramming and signaling pathways related to the acquisition of these specific DNA methylation alterations. Finally, in vitro experiments using human monocytes were performed to test the induction of similar DNA methylation reprogramming. RESULTS: Here, we focused on DNA methylation changes associated with sepsis, given their potential role in stabilizing altered phenotypes. Tolerized monocytes from patients with sepsis display changes in their DNA methylomes with respect to those from healthy controls, affecting critical monocyte-related genes. DNA methylation profiles correlate with IL-10 and IL-6 levels, significantly increased in monocytes in sepsis, as well as with the Sequential Organ Failure Assessment score; the observed changes associate with TFs and pathways downstream to toll-like receptors and inflammatory cytokines. In fact, in vitro stimulation of toll-like receptors in monocytes results in similar gains and losses of methylation together with the acquisition of tolerance. CONCLUSION: We have identified a DNA methylation signature associated with sepsis that is downstream to the response of monocytes to inflammatory signals associated with the acquisition of a tolerized phenotype and organic dysfunction.

Documento de consenso de la Sociedad Española de Medicina Intensiva, Crítica, y Unidades Coronarias (SEMICYUC), la Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello (SEORL-CCC) y la Sociedad Española de Anestesiología y Reanimación (SEDAR) sobre la traqueotomía en pacientes con COVID-19 / Consensus document of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC), the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) and the Spanish Society of Anesthesiology and Resuscitation (SEDAR) on tracheotomy in patients with COVID-19 infection

La alta incidencia de insuficiencia respiratoria aguda en el contexto de la pandemia por COVID-19 ha conllevado el uso de ventilación mecánica hasta en un 15%. Dado que la traqueotomía es un procedimiento quirúrgico frecuente, este documento de consenso, elaborado por tres Sociedades Científicas, la SEMICYUC, la SEDAR y la SEORL-CCC, tiene como objetivo ofrecer una revisión de las indicaciones y contraindicaciones de traqueotomía, ya sea por punción o abierta, esclarecer las posibles ventajas y exponer las condiciones ideales en que deben realizarse y los pasos que considerar en su ejecución. Se abordan situaciones regladas y urgentes, así como los cuidados posoperatorios

The current COVID-19 pandemic has rendered up to 15% of patients under mechanical ventilation. Because the subsequent tracheotomy is a frequent procedure,the three societies mostly involved (SEMICYUC, SEDAR and SEORL-CCC) have setup a consensus paper that offers an overview about indications and contraindications of tracheotomy, be it by puncture or open, clarifying its respective advantages and enumerating the ideal conditions under which they should be performed, as well as the necessary steps. Regularand emergency situations are displayed together with the postoperative measures

Documento de consenso de la Sociedad Española de Medicina Intensiva, Crítica, y Unidades Coronarias (SEMICYUC), la Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello (SEORL-CCC) y la Sociedad Española de Anestesiología y Reanimación (SEDAR) sobre la traqueotomía en pacientes con COVID-19 / Consensus documentof the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC), the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) and the Spanish Society of Anesthesiology and Resuscitation (SEDAR) on tracheotomy in patients with COVID-19 infection

La alta incidencia de insuficiencia respiratoria aguda en el contexto de la pandemia por COVID-19 ha conllevado el uso de ventilación mecánica hasta en un 15%. Dado que la traqueotomía es un procedimiento quirúrgico frecuente, este documento de consenso, elaborado por tres Sociedades Científicas, la SEMICYUC, la SEDAR y la SEORL-CCC, tiene como objetivo ofrecer una revisión de las indicaciones y contraindicaciones de traqueotomía, ya sea por punción o abierta, esclarecer las posibles ventajas y exponer las condiciones ideales en que deben realizarse y los pasos que considerar en su ejecución. Se abordan situaciones regladas y urgentes, así como los cuidados posoperatorios

The current COVID-19 pandemic has rendered up to 15% of patients under mechanical ventilation. Because the subsequent tracheotomy is a frequent procedure,the three societies mostly involved (SEMICYUC, SEDAR and SEORL-CCC) have setup a consensus paper that offers an overview about indications and contraindications of tracheotomy, be it by puncture or open, clarifying its respective advantages and enumerating the ideal conditions under which they should be performed, as well as the necessary steps. Regular and emergency situations are displayed together with the postoperative measures

Recomendaciones de consenso respecto al soporte respiratorio no invasivo en el paciente adulto con insuficiencia respiratoria aguda secundaria a infección por SARS-CoV-2 / Clinical consensus recommendations regarding non-invasive respiratory support in the adult patient with acute respiratory failure secondary to SARS-CoV-2 infection

La enfermedad por coronavirus 2019 (COVID-19) es una infección del tracto respiratorio causada por un nuevo coronavirus emergente, que se reconoció por primera vez en Wuhan, China, en diciembre de 2019. Actualmente, la Organización Mundial de la Salud (OMS) ha definido la infección como pandemia y existe una situación de emergencia sanitaria y social para el manejo de esta nueva infección. Mientras que la mayoría de las personas con COVID-19 desarrollan solo una enfermedad leve o no complicada, aproximadamente el 14% desarrolla una enfermedad grave que requiere hospitalización y oxígeno, y el 5% puede requerir ingreso en una Unidad de Cuidados Intensivos (1). En casos severos, COVID-19 puede complicarse por el síndrome de dificultad respiratoria aguda (SDRA), sepsis y shock séptico y fracaso multiorgánico. Este documento de consenso se ha preparado sobre directrices basadas en evidencia desarrolladas por un panel multidisciplinario de profesionales médicos de cuatro sociedades científicas españolas (Sociedad Española de Medicina Intensiva y Unidades Coronarias [SEMICYUC], Sociedad Española de Neumología y Cirugía Torácica [SEPAR], Sociedad Española de Urgencias y Emergencias [SEMES], Sociedad Española de Anestesiología, Reanimación y Terapéutica delDolor [SEDAR]) con experiencia en el manejo clínico de pacientes con COVID-19 y otras infecciones virales, incluido el SARS, así como en sepsis y SDRA. El documento proporciona recomendaciones clínicas para el soporte respiratorio no invasivo (ventilación no invasiva, oxigenoterapia de alto flujo con cánula nasal) en cualquier paciente con presentación sospechada o confirmada de COVID-19 con insuficiencia respiratoria aguda. Esta guía de consenso debe servir como base para una atención optimizada y garantizar la mejor posibilidad de supervivencia, así como permitir una comparación fiable de las futuras intervenciones terapéuticas de investigación que formen parte de futuros estudios observacionales o de ensayos clínicos. Palabras clave: Ventilación mecánica no invasiva, terapia nasal de alto flujo, procedimientos generadores de aerosoles, control de infección. Esta guía de consenso debe servir como base para una atención optimizada y garantizar la mejor posibilidad de supervivencia, así como permitir una comparación fiable de las futuras intervenciones terapéuticas de investigación que formen parte de futuros estudios observacionales o de ensayos clínicos

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus , that was first recognized in Wuhan, China, in December 2019. Currently, the World Health Organization (WHO) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. While most people with COVID-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit (1). In severe cases, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure. This consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four spanish scientific societies (Spanish Society of Intensive Care Medicine [SEMICYUC], Spanish Society of Pulmonologists [SEPAR], Spanish Society of Emergency [SEMES], Spanish Society of Anesthesiology, Reanimation, and Pain [SEDAR]) with experience in the clinical management of patients with COVID-19 and other viral infections, including SARS, as well as sepsis and ARDS. The document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of COVID-19 with acute respiratory failure. This consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials

Cytokine release syndrome. Reviewing a new entity in the intensive care unit / Síndrome de liberación de citocinas. Revisando una nueva enfermedad en la unidad de cuidados intensivos

Immunotherapy seeks to harness the power of the immune system to eradicate malignant tissues. Despite impressive therapeutic success, however, it can be accompanied by severe adverse effects such as cytokine release syndrome (CRS). These therapies cause the release of a great amount of cytokines, with IL-6 playing a central role, that can potentially lead to multiple organ dysfunction. The diagnosis is based on the presence of compatible clinical symptoms, elevated biomarkers and recent treatment with a biological agent. Mild cases can be managed through symptomatic treatment and fluids, while more severe episodes may need supportive therapy and specific care with the anti-IL-6 receptor monoclonal antibody tocilizumab. Although corticosteroids are also effective, they suppress T-cell activity, and so should only be considered as second line therapy or in cases of severe neurological involvement, since tocilizumab does not cross the blood-brain barrier. Cytokine release syndrome generally has a good prognosis, often being reversible and with a good response to specific treatment. Despite possible concerns about the admission of such patients (mainly with advanced oncological disease), we consider that the Intensive Care Unit should remain an option, since these individuals present a potentially reversible drug-related adverse event and are being treated with a new drug that could change the prognosis of the disorder. Intensive care medicine will become a key component in the management of the complications of modern cancer therapies, dealing with patients presenting an overactive immune system producing organ dysfunction while also trying to maintain treatment efficacy. This is the new paradigm

La inmunoterapia potencia el sistema inmunitario para erradicar las células malignas. A pesar de mostrar un importante éxito terapéutico, puede ir acompañada de efectos adversos graves, como el síndrome de liberación de citocinas. Dichas terapias pueden causar la liberación de importantes cantidades de citocinas, siendo IL-6 el mediador principal, e inducir un cuadro de disfunción multiorgánica. El diagnóstico se basa en la presencia de síntomas clínicos compatibles, elevación de biomarcadores y tratamiento reciente con un agente biológico. Los casos leves se pueden manejar con tratamiento sintomático y fluidoterapia, mientras que los episodios graves necesitarán tratamiento de soporte y específico con tocilizumab, un anticuerpo monoclonal anti-receptor de IL-6. Los corticoides, aunque efectivos, suprimen la actividad de las células T, por lo que su uso se considera de segunda línea o en afectación neurológica grave, ya que tocilizumab no cruza la barrera hematoencefálica. A pesar de que puedan existir dudas sobre el ingreso en unidades de críticos de estos pacientes, principalmente con enfermedad avanzada, consideramos que podrían beneficiarse del ingreso en las UCI, ya que se trata de pacientes con un evento adverso potencialmente reversible, recibiendo un nuevo fármaco que podría cambiar el pronóstico de su enfermedad. La medicina intensiva es clave en el manejo de las complicaciones de las nuevas terapias oncológicas, tratando pacientes con un sistema inmunitario excesivamente activado mientras se intenta preservar la eficacia del tratamiento. Este es el nuevo paradigma

Prevención de la neumonía asociada a la ventilación mecánica. Evaluación del coste-beneficio de las estrategias actuales / Prevention of ventilator associated pneumonia. Evaluation of the cost-benefit of the current strategies

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