Aggressive alveolar recruitment in ARDS: More shadows than lights.

Alveolar recruitment in acute respiratory distress syndrome (ARDS) is defined as the penetration of gas into previously unventilated areas or poorly ventilated areas. Alveolar recruitment during recruitment maneuvering (RM) depends on the duration of the maneuver, the recruitable lung tissue, and the balance between the recruitment of collapsed areas and over-insufflation of the ventilated areas. Alveolar recruitment is estimated using computed tomography of the lung and, at the patient bedside, through assessment of the recruited volume using pressure-volume curves and assessing lung morphology with pulmonary ultrasound and/or impedance tomography. The scientific evidence on RM in patients with ARDS remains subject to controversy. Randomized studies on ARDS have shown no benefit or have even reflected an increase in mortality. The routine use of RM is therefore not recommended.

Double and multiple cycling in mechanical ventilation: Complex events with varying clinical effects / Doble y múltiples ciclados en ventilación mecánica: eventos complejos con diferentes significado clínico

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Carbamazepine-loaded solid lipid nanoparticles and nanostructured lipid carriers: Physicochemical characterization and in vitro/in vivo evaluation.

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) represent promising alternatives for drug delivery to the central nervous system. In the present work, four different nanoformulations of the antiepileptic drug Carbamazepine (CBZ) were designed and prepared by the homogenization/ultrasonication method, with encapsulation efficiencies ranging from 82.8 to 93.8%. The formulations remained stable at 4 °C for at least 3 months. Physicochemical and microscopic characterization were performed by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), atomic force microscopy (AFM); thermal properties by differential scanning calorimetry (DSC), thermogravimetry (TGA) and X-ray diffraction analysis (XRD). The results indicated the presence of spherical shape nanoparticles with a mean particle diameter around 160 nm in a narrow size distribution; the entrapped CBZ displayed an amorphous state. The in vitro release profile of CBZ fitted into a Baker-Lonsdale model for spherical matrices and almost the 100% of the encapsulated drug was released in a controlled manner during the first 24 h. The apparent permeability of CBZ-loaded nanoparticles through a cell monolayer model was similar to that of the free drug. In vivo experiments in a mice model of seizure suggested protection by CBZ-NLC against seizures for at least 2 h after intraperitoneal administration. The developed CBZ-loaded lipid nanocarriers displayed optimal characteristics of size, shape and drug release and possibly represent a promising tool to improve the treatment of refractory epilepsy linked to efflux transporters upregulation.

Do sedation and analgesia contribute to long-term cognitive dysfunction in critical care survivors? / ¿Contribuye la sedación y la analgesia a la disfunción cognitiva en supervivientes de una enfermedad crítica?

Deep sedation during stay in the Intensive Care Unit (ICU) may have deleterious effects upon the clinical and cognitive outcomes of critically ill patients undergoing mechanical ventilation. Over the last decade a vast body of literature has been generated regarding different sedation strategies, with the aim of reducing the levels of sedation in critically ill patients. There has also been a growing interest in acute brain dysfunction, or delirium, in the ICU. However, the effect of sedation during ICU stay upon long-term cognitive deficits in ICU survivors remains unclear. Strategies for reducing sedation levels in the ICU do not seem to be associated with worse cognitive and psychological status among ICU survivors. Sedation strategy and management efforts therefore should seek to secure the best possible state in the mechanically ventilated patient and lower the prevalence of delirium, in order to prevent long-term cognitive alterations (AU)

La sedación profunda durante la estancia en una Unidad de Cuidados Intensivos (UCI) puede afectar negativamente al estado clínico y cognitivo de los pacientes críticos sometidos a ventilación mecánica. En la última década ha aparecido gran cantidad de literatura sobre diferentes estrategias dirigidas a reducir los niveles de sedación en el paciente crítico. Además, ha aumentado el interés sobre la disfunción cerebral aguda o delirium. Sin embargo, el efecto de la sedación sobre los déficits cognitivos a largo plazo continúa siendo poco conocido. Las estrategias centradas en reducir los niveles de sedación en UCI no parecen estar asociadas con un peor estado cognitivo y psicológico de los supervivientes. Por lo tanto, las estrategias de manejo de la sedación en UCI deberían focalizarse en mejorar el estado del paciente ventilado, así como en disminuir el delirium, con el fin de prevenir las alteraciones cognitivas a largo plazo (AU)

Do sedation and analgesia contribute to long-term cognitive dysfunction in critical care survivors?

Deep sedation during stay in the Intensive Care Unit (ICU) may have deleterious effects upon the clinical and cognitive outcomes of critically ill patients undergoing mechanical ventilation. Over the last decade a vast body of literature has been generated regarding different sedation strategies, with the aim of reducing the levels of sedation in critically ill patients. There has also been a growing interest in acute brain dysfunction, or delirium, in the ICU. However, the effect of sedation during ICU stay upon long-term cognitive deficits in ICU survivors remains unclear. Strategies for reducing sedation levels in the ICU do not seem to be associated with worse cognitive and psychological status among ICU survivors. Sedation strategy and management efforts therefore should seek to secure the best possible state in the mechanically ventilated patient and lower the prevalence of delirium, in order to prevent long-term cognitive alterations.

Hybrid inhalable microparticles for dual controlled release of levofloxacin and DNase: physicochemical characterization and in vivo targeted delivery to the lungs.

Current medical treatments against recurrent pulmonary infections caused by Pseudomonas aeruginosa, such as cystic fibrosis (CF) disorder, involve the administration of inhalable antibiotics. The main challenge is, however, the eradication of microbial biofilms immersed in dense mucus that requires high and recurrent antibiotic doses. Accordingly, the development of novel drug delivery systems capable of providing local and controlled drug release in the lungs is a key factor to improve the therapeutic outcome of such therapeutic molecules. Inhalable hybrid carriers were prepared by co-precipitation of CaCO3 in the presence of alginate and the resulting microparticles were treated with alginate lyase (AL) in order to modify their porosity and enhance the drug loading. The hybrid microparticles were loaded with DNase (mucolytic agent) and levofloxacin (LV, wide-spectrum antibiotic) in the range of 20-40% for LV and 28-67% for DNase, depending on the AL treatment. In vitro studies demonstrated that microparticles were able to control the DNase release for 24 h, while 30-50% of LV was released in 3 days. The morphological characterization was performed by optical, fluorescence and scanning electron microscopies, showing a narrow size distribution (5 µm). FTIR, XRD, DSC and nitrogen adsorption isotherm studies revealed the presence of the drugs in a non-crystalline state. A microcidal effect of microparticles was found on P. aeruginosa in agar plates and corroborated by Live/Dead kit and TEM observations. Finally, to study whether the microparticles improved the localization of LV in the lungs, in vivo studies were performed by pulmonary administration of microparticles to healthy mice via nebulization and dry powder inhalation, followed by the quantification of LV in lung tissue. The results showed that microparticles loaded with LV delivered the antibiotic at least 3 times more efficiently than free LV. The developed system opens the gateway to new drug delivery systems that may provide enhanced therapeutic solutions against bacterial infections and in particular as a potential tool in CF pathology.

A new experimental model of acid- and endotoxin-induced acute lung injury in rats.

The majority of the animal models of acute lung injury (ALI) are focused on the acute phase. This limits the studies of the mechanisms involved in later phases and the effects of long-term treatments. Thus the goal of this study was to develop an experimental ALI model of aspiration pneumonia, in which diffuse alveolar damage continues for 72 h. Rats were intratracheally instilled with one dose of HCl (0.1 mol/l) followed by another instillation of one dose of LPS (0, 10, 20, 30, or 40 µg/g body weight) 2 h later, which models aspiration of gastric contents that progresses to secondary lung injury from bacteria or bacterial products. The rats were euthanized at 24, 48, and 72 h after the last instillation. The results showed that HCl and LPS at all doses caused activation of inflammatory responses, increased protein permeability and apoptosis, and induced mild hypoxemia in rat lungs at 24 h postinstillation. However, this lung damage was present at 72 h only in rats receiving HCl and LPS at the doses of 30 and 40 µg/g body wt. Mortality (∼50%) occurred in the first 48 h and only in the rats treated with HCl and LPS at the highest dose (40 µg/g body wt). In conclusion, intratracheal instillation of HCl followed by LPS at the dose of 30 µg/g body wt results in severe diffuse alveolar damage that continues at least 72 h. This rat model of aspiration pneumonia-induced ALI will be useful for testing long-term effects of new therapeutic strategies in ALI.

Innovación y transferencia tecnológica en ciencias de la salud: Una visión transversal / Innovation and technology transfer in the health sciences: A cross-sectional perspective

Este artículo se basa en la reflexión estratégica y el debate que tuvieron lugar en las primeras jornadas de innovación y transferencia tecnológica en ciencias de la salud, organizadas por REGIC-ENS-FENIN-SEMICYUC y que se celebraron en el Instituto de Salud Carlos III en Madrid, el 7 de mayo de 2013, con el objetivo de impulsar la transferencia de la innovación tecnológica en medicina y asistencia sanitaria, más allá del programa europeo «Horizonte 2020». Las ponencias trataron de temas clave como la evaluación de la utilización de las nuevas tecnologías, la necesidad de impregnar las decisiones relacionadas con la adopción y desarrollo de innovaciones de los conceptos de valor y sostenibilidad y de la implicación de las redes de conocimiento en la necesidad de intensificar su influencia en la creación de una «cultura de la innovación» entre los profesionales de la sanidad. Pero, sobre todo, se insistió en la capacidad de innovación latente en los hospitales y en que estos, como grandes empresas que son, deben plantearse seriamente que buena parte de su sostenibilidad futura puede depender de la buena gestión de su capacidad de generar innovación, lo cual no es únicamente generar ideas, sino llegar a transformarlas en procesos o productos que generen valor y retorno económico

This article is based on the strategic reflection and discussion that took place on occasion of the first conference on innovation and technology transfer in the health sciences organized by the REGIC - ENS- FENIN - SEMICYUC and held in Madrid in the Instituto de Salud Carlos III on May 7th, 2013, with the aim of promoting the transfer of technological innovation in medicine and health care beyond the European program «Horizon 2020». The presentations dealt with key issues such as evaluation of the use of new technologies, the need to impregnate the decisions related to adoption and innovation with the concepts of value and sustainability, and the implication of knowledge networks in the need to strengthen their influence upon the creation of a «culture of innovation» among health professionals. But above all, emphasis was placed on the latent innovation potential of hospitals, and the fact that these, being the large companies that they are, should seriously consider that much of their future sustainability may depend on proper management of their ability to generate innovation, which is not only the generation of ideas but also their transformation into products or processes that create value and economic returns

Innovation and technology transfer in the health sciences: a cross-sectional perspective.

This article is based on the strategic reflection and discussion that took place on occasion of the first conference on innovation and technology transfer in the health sciences organized by the REGIC-ENS-FENIN-SEMICYUC and held in Madrid in the Instituto de Salud Carlos III on May 7th, 2013, with the aim of promoting the transfer of technological innovation in medicine and health care beyond the European program "Horizon 2020". The presentations dealt with key issues such as evaluation of the use of new technologies, the need to impregnate the decisions related to adoption and innovation with the concepts of value and sustainability, and the implication of knowledge networks in the need to strengthen their influence upon the creation of a "culture of innovation" among health professionals. But above all, emphasis was placed on the latent innovation potential of hospitals, and the fact that these, being the large companies that they are, should seriously consider that much of their future sustainability may depend on proper management of their ability to generate innovation, which is not only the generation of ideas but also their transformation into products or processes that create value and economic returns.

The future of intensive care medicine / El futuro de la medicina intensiva

Intensive care medical training, whether as a primary specialty or as secondary add-on training, should include key competences to ensure a uniform standard of care, and the number of intensive care physicians needs to increase to keep pace with the growing and anticipated need. The organisation of intensive care in multiple specialty or central units is heterogeneous and evolving, but appropriate early treatment and access to a trained intensivist should be assured at all times, and intensivists should play a pivotal role in ensuring communication and high-quality care across hospital departments. Structures now exist to support clinical research in intensive care medicine, which should become part of routine patient management. However, more translational research is urgently needed to identify areas that show clinical promise and to apply research principles to the real-life clinical setting. Likewise, electronic networks can be used to share expertise and support research. Individuals, physicians and policy makers need to allow for individual choices and priorities in the management of critically ill patients while remaining within the limits of economic reality. Professional scientific societies play a pivotal role in supporting the establishment of a defined minimum level of intensive health care and in ensuring standardised levels of training and patient care by promoting interaction between physicians and policy makers. The perception of intensive care medicine among the general public could be improved by concerted efforts to increase awareness of the services provided and of the successes achieved (AU)

La formación en medicina intensiva, ya sea como especialidad primaria o a partir de una troncalidad común para después convertirse en supra-especialidad, debería incluir competencias clave que garanticen un cuidado estándar y homogéneo del paciente crítico, así como proveer al sistema sanitario del número de especialistas en medicina intensiva (intensivistas) de forma ajustada y anticipada al ritmo de crecimiento de la necesidad asistencial. La organización de los cuidados intensivos desde la visión de las distintas especialidades o en unidades centralizadas y jerarquizadas, es heterogénea y está en constante evolución. No obstante el acceso y tratamiento precoz del enfermo crítico por parte de un intensivista, debería estar siempre garantizado, no únicamente en los servicios de medicina intensiva, sino en todos los departamentos de un hospital, actuando el intensivista como elemento central en la comunicación y coordinación entre los diferentes servicios y especialistas, a fin de lograr la más alta calidad y eficacia en la asistencia. La investigación clínica en medicina intensiva está sustentada por la excelencia de conocimiento de sus profesionales, pero son necesarias estructuras de apoyo: la integración de la investigación e innovación en la rutina diaria y un incremento de la investigación traslacional, a fin de identificar áreas que muestren elementos potenciales de avance en el aspecto clínico y la aplicación de los principios de la investigación básica y fisiológica en el entorno de la medicina intensiva. Las tecnologías de la comunicación y la información ofrecen un marco idóneo para compartir y poner en común el conocimiento y apoyar (..) (AU)

The future of intensive care medicine.

Intensive care medical training, whether as a primary specialty or as secondary add-on training, should include key competences to ensure a uniform standard of care, and the number of intensive care physicians needs to increase to keep pace with the growing and anticipated need. The organisation of intensive care in multiple specialty or central units is heterogeneous and evolving, but appropriate early treatment and access to a trained intensivist should be assured at all times, and intensivists should play a pivotal role in ensuring communication and high-quality care across hospital departments. Structures now exist to support clinical research in intensive care medicine, which should become part of routine patient management. However, more translational research is urgently needed to identify areas that show clinical promise and to apply research principles to the real-life clinical setting. Likewise, electronic networks can be used to share expertise and support research. Individuals, physicians and policy makers need to allow for individual choices and priorities in the management of critically ill patients while remaining within the limits of economic reality. Professional scientific societies play a pivotal role in supporting the establishment of a defined minimum level of intensive health care and in ensuring standardised levels of training and patient care by promoting interaction between physicians and policy makers. The perception of intensive care medicine among the general public could be improved by concerted efforts to increase awareness of the services provided and of the successes achieved.

Patient-ventilator dyssynchrony during assisted invasive mechanical ventilation.

Patient-ventilator dyssynchrony is common during mechanical ventilation. Dyssynchrony decreases comfort, prolongs mechanical ventilation and intensive care unit stays, and might lead to worse outcome. Dyssynchrony can occur during the triggering of the ventilator, the inspiration period after triggering, the transition from inspiration to expiration, and the expiratory phase. The most common dyssynchronies are delayed triggering, autotriggering, ineffective inspiratory efforts (which can occur at any point in the respiratory cycle), mismatch between the patient's and ventilator's inspiratory times, and double triggering. At present, the detection of dyssynchronies usually depends on healthcare staff observing ventilator waveforms; however, performance is suboptimal and many events go undetected. To date, technological complexity has made it impossible to evaluate patient-ventilator synchrony throughout the course of mechanical ventilation. Studies have shown that a high index of dyssynchrony may increase the duration of mechanical ventilation. Better training, better ventilatory modes, and/or computerized systems that permit better synchronization of patients' demands and ventilator outputs are necessary to improve patient-ventilator synchrony.

[Lung-brain interaction in the mechanically ventilated patient]. / Interacción pulmón-cerebro en el paciente ventilado mecánicamente.

Patients with acute lung injury or acute respiratory distress syndrome (ARDS) admitted to the ICU present neuropsychological alterations, which in most cases extend beyond the acute phase and have an important adverse effect upon quality of life. The aim of this review is to deepen in the analysis of the complex interaction between lung and brain in critically ill patients subjected to mechanical ventilation. This update first describes the neuropsychological alterations occurring both during the acute phase of ICU stay and at discharge, followed by an analysis of lung-brain interactions during mechanical ventilation, and finally explores the etiology and mechanisms leading to the neurological disorders observed in these patients. The management of critical patients requires an integral approach focused on minimizing the deleterious effects over the short, middle or long term.

Interpretación de las curvas del respirador en pacientes con insuficiencia respiratoria aguda / Interpretation of ventilator curves in patients with acute respiratory failure

La ventilación mecánica es una intervención terapéutica de sustitución temporal de la función ventilatoria enfocada a mejorar los síntomas en los pacientes que sufren insuficiencia respiratoria aguda. Los avances tecnológicos han facilitado el desarrollo de ventiladores sofisticados que permiten visualizar y registrar las ondas respiratorias, lo que constituye una fuente de información muy valiosa para el clínico. La correcta interpretación de los trazados es de vital importancia tanto para el correcto diagnóstico como para la detección precoz de anomalías y para comprender aspectos de la fisiología relacionados con la ventilación mecánica y con la interacción paciente-ventilador. El presente trabajo da una orientación de cómo interpretar las curvas del ventilador mediante el análisis de trazados de presión en la vía aérea, flujo aéreo y volumen en distintas situaciones clínicas (AU)

Mechanical ventilation is a therapeutic intervention involving the temporary replacement of ventilatory function with the purpose of improving symptoms inpatients with acute respiratory failure. Technological advances have facilitated the development of sophisticated ventilators for viewing and recording the respiratory waveforms, which are a valuable source of information for the clinician. The correct interpretation of these curves is crucial for the correct diagnosis and early detection of anomalies, and for understanding physiological aspects related to mechanical ventilation and patient-ventilator interaction. The present study offers a guide for the interpretation of the airway pressure and flow and volume curves of the ventilator, through the analysis of different clinical scenarios (AU)