Moderate Hyperkalemia Regulates Autophagy to Reduce Cerebral Ischemia-Reperfusion Injury in a CA/CPR Rat Model.

BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) can cause irreversible brain damage and autophagy has been implicated in the pathophysiology. Increasing serum potassium (K+) levels reduces CIRI, but the relationship between its protective mechanism and autophagy is unclear. In this study, we aimed to find the optimal degree of raising serum (K+) and to investigate the relationship between high (K+) and autophagy and the underlying mechanisms in a cardiac arrest/cardiopulmonary resuscitation (CA/CPR) rat model. METHODS: Sprague Dawley (SD) rats were divided into four groups: S group, N group, P group, and Q group. The rats S group and N group were administered saline. The rats P group and Q group were administered 640 mg/kg of potassium chloride (KCl) continuously pumped at 4 mL/h (21.3 mg/(kg·min) and divided according to the electrocardiogram (ECG) changes during the administration of KCl. After 24-h of resuscitation, neural damage was assessed by measuring neurological deficit score (NDS), oxidative stress markers, and pathological staining of the cerebral cortex. The level of autophagy and the expression of mTOR-ULK1-Beclin1 pathway-related proteins were evaluated using transmission electron microscopy (TEM), immunostaining, and western blotting. RESULTS: Our results revealed that high (K+) improved NDS and decreased the oxidative stress markers. The autophagosomes, autolysosomes, and lysosomes were decreased following treatment KCl. Furthermore, the levels of micro-tubule-associated protein 1 light chain 3 (LC3) Ⅱ/Ⅰ, Unc-51-like kinase 1 (ULK1), and Beclin1 were decreased, whereas mTOR expression was increased in the cortex. CONCLUSION: The results demonstrated that moderate hyperkalemia could alleviate autophagy after CIRI via regulating the mTOR-ULK1-Beclin1 pathway.

A Nanotherapy of Octanoic Acid Ameliorates Cardiac Arrest/Cardiopulmonary Resuscitation-Induced Brain Injury via RVG29- and Neutrophil Membrane-Mediated Injury Relay Targeting.

Treatment of cardiac arrest/cardiopulmonary resuscitation (CA/CPR)-induced brain injury remains a challenging issue without viable therapeutic options. Octanoic acid (OA), a lipid oil that is mainly metabolized in the astrocytes of the brain, is a promising treatment for this type of injury owing to its potential functions against oxidative stress, apoptosis, inflammation, and ability to stabilize mitochondria. However, the application of OA is strictly limited by its short half-life and low available concentration in the target organ. Herein, based on our previous research, an OA-based nanotherapy coated with a neutrophil membrane highly expressing RVG29, RVG29-H-NPOA, was successfully constructed by computer simulation-guided supramolecular assembly of polyethylenimine and OA. The in vitro and in vivo experiments showed that RVG29-H-NPOA could target and be distributed in the injured brain focus via the relay-targeted delivery mediated by RVG29-induced blood-brain barrier (BBB) penetration and neutrophil membrane protein-induced BBB binding and injury targeting. This results in enhancements of the antioxidant, antiapoptotic, mitochondrial stability-promoting and anti-inflammatory effects of OA and exhibited systematic alleviation of astrocyte injury, neuronal damage, and inflammatory response in the brain. Due to their systematic intervention in multiple pathological processes, RVG29-H-NPOA significantly increased the 24 h survival rate of CA/CPR model rats from 40% to 100% and significantly improved their neurological functions. Thus, RVG29-H-NPOA are expected to be a promising therapeutic for the treatment of CA/CPR-induced brain injury.

Glibenclamide Directly Prevents Neuroinflammation by Targeting SUR1-TRPM4-Mediated NLRP3 Inflammasome Activation In Microglia.

Glibenclamide (GLB) reduces brain edema and improves neurological outcome in animal experiments and preliminary clinical studies. Recent studies also suggested a strong anti-inflammatory effect of GLB, via inhibiting nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation. However, it remains unknown whether the anti-inflammatory effect of GLB is independent of its role in preventing brain edema, and how GLB inhibits the NLRP3 inflammasome is not fully understood. Sprague-Dawley male rats underwent 10-min asphyxial cardiac arrest and cardiopulmonary resuscitation or sham-operation. The Trpm4 siRNA and GLB were injected to block sulfonylurea receptor 1-transient receptor potential M4 (SUR1-TRPM4) channel in rats. Western blotting, quantitative real-time polymerase chain reaction, behavioral analysis, and histological examination were used to evaluate the role of GLB in preventing NLRP3-mediated neuroinflammation through inhibiting SUR1-TRPM4, and corresponding neuroprotective effect. To further explore the underlying mechanism, BV2 cells were subjected to lipopolysaccharides, or oxygen-glucose deprivation/reperfusion. Here, in rat model of cardiac arrest with brain edema combined with neuroinflammation, GLB significantly alleviated neurocognitive deficit and neuropathological damage, via the inhibition of microglial NLRP3 inflammasome activation by blocking SUR1-TRPM4. Of note, the above effects of GLB could be achieved by knockdown of Trpm4. In vitro under circumstance of eliminating distractions from brain edema, SUR1-TRPM4 and NLRP3 inflammasome were also activated in BV2 cells subjected to lipopolysaccharides, or oxygen-glucose deprivation/reperfusion, which could be blocked by GLB or 9-phenanthrol, a TRPM4 inhibitor. Importantly, activation of SUR1-TRPM4 in BV2 cells required the P2X7 receptor-mediated Ca2+ influx, which in turn magnified the K+ efflux via the Na+ influx-driven opening of K+ channels, leading to the NLRP3 inflammasome activation. These findings suggest that GLB has a direct anti-inflammatory neuroprotective effect independent of its role in preventing brain edema, through inhibition of SUR1-TRPM4 which amplifies K+ efflux and promotes NLRP3 inflammasome activation.

Profile and outcomes of in-hospital cardiac arrest in a paediatric emergency department.

A retrospective study was conducted to determine the profile and outcome of patients who experienced in-hospital cardiac arrest (IHCA) in an emergency department (ED), from January to December 2017. Newborns of day one till children 14 years of age who suffered cardiac arrest during their stay in the ED of National Institute of Child Health, Karachi, Pakistan, were included in the study. The outcome variables were the return of spontaneous circulation and survival before final discharge from the ED. IHCA was observed in 935 (4.82%) out of the 19,385 children studied, while in 568 (61%) children spontaneous circulation was restored. Most of the patients who suffered IHCA were infants, i.e. 719 (77%). A significant association of return of spontaneous circulation and survival till final discharge from the ED was observed with age (p-value <0.001) and mode of arrival at the hospital (p-value <0.001). Thus, IHCA was reported in approximately five percent of patients and return of spontaneous circulation was reported in 61 percent.

Recommendations for Cardiopulmonary Resuscitation (CPR) of patients with suspected or confirmed COVID-19.

The care for patients suffering from cardiopulmonary arrest in a context of a COVID-19 pandemic has particularities that should be highlighted. The following recommendations from the Brazilian Association of Emergency Medicine (ABRAMEDE), the Brazilian Society of Cardiology (SBC) and the Brazilian Association of Intensive Medicine (AMIB) and the Brazilian Society of Anesthesiology (SBA), associations and societies official representatives of specialties affiliated to the Brazilian Medical Association (AMB), aim to guide the various assistant teams, in a context of little solid evidence, maximizing the protection of teams and patients. It is essential to wear full Personal Protective Equipment (PPE) for aerosols during the care of Cardiopulmonary Resuscitation (CPR) and it is imperative to consider and treat the potential causes in these patients, especially hypoxia and arrhythmias caused by changes in the QT interval or myocarditis. The installation of an advanced invasive airway must be obtained early and the use of High Efficiency Particulate Arrestance (HEPA) filters at the interface with the valve bag is mandatory; situations of occurrence of CPR during mechanical ventilation and in a prone position demand peculiarities that are different from the conventional CPR pattern. Faced with the care of a patient diagnosed or suspected of COVID-19, the care follows the national and international protocols and guidelines 2015 ILCOR (International Alliance of Resuscitation Committees), AHA 2019 Guidelines (American Heart Association) and the Update of the Cardiopulmonary Resuscitation and Emergency Care Directive of the Brazilian Society of Cardiology 2019.

A atenção ao paciente vítima de parada cardiorrespiratória em um contexto de pandemia de COVID-19 possui particularidades que devem ser ressaltadas. As seguintes recomendações da Associação Brasileira de Medicina de Emergência (ABRAMEDE), Sociedade Brasileira de Cardiologia (SBC), Associação de Medicina Intensiva Brasileira (AMIB) e Sociedade Brasileira de Anestesiologia (SBA), associações e sociedades representantes oficiais de especialidades afiliadas a Associação Medica Brasileira (AMB), têm por objetivo orientar as diversas equipes assistentes, em um contexto de poucas evidências sólidas, maximizando a proteção das equipes e dos pacientes.É fundamental a paramentação completa com Equipamentos de Proteção Individual (EPIs) para aerossóis durante o atendimento de Parada Cardiorrespiratória (PCR), e imperativo que se considerem e tratem os potenciais causas nesses pacientes, principalmente hipóxia e arritmias causadas por alterações no intervalo QT ou miocardites. A instalação de via aérea invasiva avançada deve ser obtida precocemente e o uso de filtros High Efficiency Particulate Arrestance (HEPA) na interface com a bolsa-válvula é obrigatório; situações de ocorrência de PCR durante a ventilação mecânica e em posição pronada demandam peculiaridades distintas do padrão convencional de PCR. Frente ao atendimento de um paciente com diagnóstico ou suspeito de COVID-19, o atendimento segue em acordo com os protocolos e diretrizes nacionais e internacionais 2015 ILCOR (Aliança Internacional dos Comitês de Ressuscitação), Diretrizes AHA 2019 (American Heart Association) e a Atualização da Diretriz de Ressuscitação Cardiopulmonar e Cuidados de Emergência da Sociedade Brasileira de Cardiologia 2019.

Critical incidents as perceived by rapid response teams in emergency services / Incidentes críticos percibidos por los equipos de respuesta rápida en atención de emergência / Incidentes críticos percebidos pelos times de resposta rápida nos atendimentos de emergência

Abstract Objective: To analyze two hospital emergency services, one in a public institution and another in a philanthropic one, from the perspective of rapid response team professionals in the face of positive and negative critical incidents. Method: Descriptive, exploratory, qualitative study carried with 62 health professionals. Critical Incident Technique was employed as the theoretical-methodological framework, along with Content Analysis for analyzing data. Results: Sixty-two health professionals - including 23 nurses, 20 physiotherapists and 19 doctors - took part in this study. Clusters for 89 critical incidents were obtained; 66 of them were considered positive, whereas 23 were negative. The situations associated to the provided services were discriminated in three categories: recognition of patient clinical deterioration; rapid response team activation in the unit; and time until rapid response team arrival at the ward. Conclusion: In spite of the difficulties faced by such professionals while providing care to patients who become severely ill in non-critical wards, positive reports were predominant in all categories, what legitimized this service's importance as a contribution to quality and safety of hospitalized patients.

Resumen Objetivo: Analizar las atenciones de emergencia en la perspectiva de los profesionales de los equipos de respuesta rápida en dos hospitales, siendo uno público y otro filantrópico, ante incidentes críticos positivos y negativos. Método: Estudio descriptivo, exploratorio, con abordaje cualitativo, realizado con 62 profesionales de salud. Se utilizó la Técnica del Incidente Crítico como propuesta teórico-metodológica y, para el análisis de los datos, el análisis de contenido. Resultados: Participaran 62 profesionales de salud, siendo 23 enfermeros, 20 fisioterapeutas y 19 médicos. Se obtuvo el agrupamiento de 89 incidentes críticos, siendo 66 considerados positivos y 23 negativos. Las situaciones relacionadas a las atenciones realizadas por los servicios fueron clasificadas en tres categorías, a saber: el reconocimiento del deterioro clínico del paciente; la activación del equipo de respuesta rápida en la unidad; y el tiempo de llegada del equipo de respuesta rápida al pabellón. Conclusión: Se destaca que, a pesar de las dificultades que enfrentan los profesionales durante la atención a pacientes que sufren deterioro en las unidades de cuidados no críticos, predominaran informes positivos en las tres categorías, que muestran la importancia del servicio como una contribución a la cualidad y seguridad de los pacientes hospitalizados.

Resumo Objetivo: Analisar os atendimentos de emergência na perspectiva dos profissionais dos times de resposta rápida em dois hospitais, sendo um público e um filantrópico, diante de incidentes críticos positivos e negativos. Método: Estudo descritivo, exploratório, de abordagem qualitativa, realizado com 62 profissionais de saúde. Utilizou-se a Técnica do Incidente Crítico como referencial teórico-metodológico e, para análise dos dados, a análise de conteúdo. Resultados: Participaram 62 profissionais de saúde, sendo 23 enfermeiros, 20 fisioterapeutas e 19 médicos. Obteve-se o agrupamento de 89 incidentes críticos, sendo 66 considerados positivos e 23 negativos. As situações relacionadas aos atendimentos realizados pelos serviços foram classificadas em três categorias, a saber: o reconhecimento da deterioração clínica do paciente; o acionamento do time de resposta rápida na unidade; e o tempo de chegada do time de resposta rápida à enfermaria. Conclusão: Destaca-se que, apesar das dificuldades enfrentadas por esses profissionais durante os atendimentos aos pacientes que se tornam graves nas unidades de internação não críticas, predominaram relatos positivos nas três categorias, que legitimaram a importância do serviço como contribuição à qualidade e segurança dos pacientes hospitalizados.

Conhecimento da equipe de enfermagem sobre ressuscitação cardiopulmonar / Nursing team knowledge on cardiopulmonary resuscitation

Objetivou-se identificar o conhecimento teórico da equipe de enfermagem sobre as manobras de ressuscitação cardiopulmonar em suporte básico de vida, associando tal conhecimento às variáveis sociodemográficas, econômicas e de formação profissional. Trata-se de estudo transversal, descritivo e quantitativo, cujos dados foram obtidos de questionários aplicados a 351 funcionários de uma equipe de enfermagem de um serviço de emergência e de unidades de terapia intensiva. Houve declínio do conhecimento dos sujeitos sobre ressuscitação e parada cardiopulmonar com o passar do tempo. Fatores socioeconômicos e profissionais estiveram associados ao conhecimento dos profissionais de enfermagem. Sugere-se que treinamentos com menores intervalos aumentem o grau de retenção e o conhecimento da equipe de enfermagem.

The objective of this study was to identify the theoretical knowledge of the nursing team on the cardiopulmonary resuscitation manoeuvres in basic life support, associating such knowledge to sociodemographic, economic and professional training variables. This is a cross-sectional, descriptive and quantitative study, in which the data were obtained from questionnaires applied to 351 employees of a nursing team of an emergency service and intensive care units. There was a decline in the subjects' knowledge about resuscitation and cardiopulmonary arrest over time. Socio-economic and professional factors were associated with the knowledge of nursing professionals. It is suggested that training with shorter intervals would increase the degree of retention and knowledge of the nursing team.

An Experience of Video Based Training on Basic Life Support.

INTRODUCTION: Basic life support is foundation to save lives. In contrast to the developed countries, there is still no national standard BLS training module in Nepal. Basic life support training is being provided by various institutions but lack in consistency and coordination. The Nepal basic life support Course is the video based training in Nepali language with reference to recent advances which was intended for all health care personnel of Nepal in urban as well as rural setting. We aimed to describe the features of this video based training module in local language, to analyse the differences of knowledge before and after the training and to find out the participants perception and satisfaction with this course. METHODS: This is a descriptive cross-sectional study based on data of trainings conducted over the study period. Ethical approval was taken. The post-test score was recorded and compared with the occupational using ANOVA. On the spot and delayed feedbacks from the participants were collected voluntarily and summarized. RESULTS: Total of 576 participants (435 clinical doctors, 92 nurses/paramedics, 18 non-clinical doctors and 41 intern doctors) successfully completed the training. The difference in post test scores (mean = 12.9±1.8) among the different occupational background was not significant (P=0.159). The feedbacks from the participants were mostly positive and encouraging. CONCLUSIONS: The knowledge of basic life support improved significantly irrespective of the occupation of the participants. A universal, nationwide video based training module in Nepali language should be developed focusing all health care personnel of urban as well rural Nepal.

Nivel de conocimiento sobre soporte vital básico del personal no médico de una institución de salud, Pasto- Colombia, 2017 / Level of knowledge about basic life support of non-medical workers of a health institution at Pasto city- Colombia, 2017

Objetivo: el objetivo de la presente investigación es describir el nivel de conocimiento acerca de soporte vital básico, del personal asistencial no médico del servicio de urgencias de una institución de salud, en la ciudad de Pasto-Colombia,en el año 2017. La parada cardiorrespiratoria corresponde a la interrupción brusca, inesperada y potencialmente reversible de la respiración y la actividad mecánica cardíaca; que requiere de la implementación de medidas de reanimación,cuyo éxito depende del nivel conocimiento y habilidades del personal que la lleva a cabo Materiales y métodos: se realizó un estudio descriptivo de corte transversal. El nivel de conocimiento se determinó mediante un cuestionario diseñado para tal fin. Resultados: se reclutaron en total 58 participantes. En 39,65% de los casos el nivel de conocimiento fue aceptable, mientas que se consideró adecuado en un 41,37% de los casos. Los puntajes fueron más altos en el grupo con capacitación en soporte vital básico o avanzado en los dos años previos. Conclusiones: la capacitación continua en soporte vital, representa una estrategia que conlleva a la obtención de mejores niveles de conocimiento en reanimación cardiopulmonar que, posiblemente impacten, en los desenlaces del paro cardíaco intrahospitalario..(AU)

Objective: the aim of the present investigation is to describe the level of knowledge of non-medical workers of the emergency service of a health institution at city of Pasto-Colombia in 2017. Cardiorespiratory arrest is the abrupt, unexpected and potentially reversible interruption of respiration and the mechanical activity of the heart; which requires the implementation of resuscitation measures, whose success depends on the level of knowledge and skill level of the staff that carries it out. Materials and methods: a cross-sectional study was permormed. The level of knowledge was determined through a questionnaire designed for that purpose. Results: a total of 58 participants were recruited. In 39.65% of cases, the level of knowledge was acceptable, while it was considered adequate in 41.37% of the cases. Scores were higher in the group with basic or advanced life support training in the previous two years. Conclusions: continuous training in life support represents a strategy that leads to obtaining better levels of knowledge in cardiopulmonary resuscitation that, possibly, impacts the outcomes of in-hospital cardiac arrest..(AU)

Social influences on microglial reactivity and neuronal damage after cardiac arrest/cardiopulmonary resuscitation.

Social isolation presents a risk factor and worsens outcome to cerebrovascular diseases; however, the underlying mechanisms remain underspecified. This study examines the effect of social environment on microglial reactivity after global cerebral ischemia, to test the hypothesis that social isolation leads to greater microglial responses. Adult female and male mice were pair-housed or socially isolated for one week prior to cardiac arrest/cardiopulmonary resuscitation (CA/CPR) or the sham procedure, and following either 2 or 24 h of reperfusion, microglia samples were enriched and analyzed for gene expression. At the 2-hour time point, microglia from both females and males exhibited ischemia-induced inflammation, characterized by the gene expression increase of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß) and interleukin 6 (IL-6), regardless of the housing conditions. However, at 24 h post-ischemia, social housing attenuated microglial pro-inflammatory gene expression in a sex-specific manner. At this time point, the ischemia-induced increased expression of IL-1ß and IL-6 was attenuated by social interaction in microglia from male mice, while among female mice social attenuation of the inflammatory response was observed in the microglial expression of cell surface protein major histocompatibility complex II (MHC II). A second study examined behavioral and physiological measures 96 h after ischemic injury. At this time point, female and male mice displayed increased locomotion and exploratory behavior following CA/CPR relative to controls. Regardless of sex, ischemia also elicited neuroinflammation and neurodegeneration, both of which were modulated by the social environment. Hippocampal nitric oxide (iNOS), cortical TNF-α, and counts of Fluoro-Jade C positive stained cells in the CA1 region of the hippocampus, were increased in the isolated CA/CPR group relative to sham controls and the pair-housed CA/CPR groups. Together, these data indicate that female and male mice exhibit similar outcome measures and social modulation at 96 h post-ischemic injury, nonetheless, that social environment influences microglial reactivity to global cerebral ischemia in a sex-specific manner.

Intervenção educativa sobre parada cardiorrespiratória intra-hospitalar: conhecimento dos profissionais de enfermagem de unidades médico-cirúrgicas / Educational intervention about in-hospital cardiorespiratory arrest: knowledge of nursing professionals from medical-surgical units*

Esta pesquisa objetivou avaliar o efeito de uma intervenção educativa sobre parada cardiorrespiratória no conhecimento teórico de profissionais de enfermagem em unidades de internação médico-cirúrgica. Estudo quase experimental, desenvolvido com profissionais atuantes em duas unidades de internação, de um hospital universitário público do Paraná. Como intervenções educativas, realizaram-se treinamentos teórico-práticos. Aplicaram-se um questionário antes e, imediatamente após os treinamentos. Consideraram-se valores de p <0,05, como significativos. Dos 47 profissionais presentes nas unidades, 37 (78,72%) participaram do pré-teste e 32 (68,09%) do pós-teste. Identificou-se prevalência de mulheres, com idade entre 31 e 45 anos, que trabalhavam em sua unidade laboral e apresentavam tempo de formação profissional maior que cinco anos. Os escores obtidos após as intervenções educativas (pós-teste) apresentaram aumento estatisticamente significativo (p<0,0001), em relação ao pré-teste. A intervenção educativa colaborou, positivamente, no conhecimento teórico dos profissionais de enfermagem sobre parada cardiorrespiratória.

The present study aimed to assess the effect of an educational intervention about cardiorespiratory arrest in the theoretical knowledge of nursing professionals in medical-surgical hospitalization units. This is a quasi-experimental study, developed with professionals working in two admission units from a public university hospital in Paraná state. As an educational intervention, we conducted theoretical-practical training. We applied a questionnaire before and after training. We considered p values <0.05 as significant. Of the 47 professionals who worked in these units, 37 (78.72%) participated in the pre-test and, 32 (68.09%) in the post-test. We identified a female prevalence, aged between 31 and 45 years, who worked in their unit and had more than five years of professional training. The scores obtained after the educational intervention (post-test) was statistically significant (p<0.0001), in comparison to the pre-test. The educational intervention positively collaborated with the theoretical knowledge of nursing professionals about cardiorespiratory arrest.

Effect of pre-hospital advanced airway management for out-of-hospital cardiac arrest caused by respiratory disease: a propensity score-matched study.

Optimal pre-hospital care for out-of-hospital cardiac arrest (OHCA) caused by respiratory disease may differ from that for OHCA associated with other aetiologies, especially with respect to respiratory management. We aimed to investigate whether pre-hospital advanced airway management (AAM) was associated with favourable outcomes after OHCA caused by intrinsic respiratory disease. This nationwide, population-based, propensity score-matched study of adult patients in Japan with OHCA due to respiratory disease from 1 January 2005 to 31 December 2012 compared patients with and without pre-hospital AAM. The primary outcome was neurologically favourable survival at one month after the OHCA. Of 49,534 eligible patients, 20,458 received pre-hospital AAM and 29,076 did not. In a propensity score-matched cohort (18,483 versus 18,483 patients), the odds of neurologically favourable survival were significantly lower for patients receiving pre-hospital AAM (0.6% versus 1.5%; odds ratio [OR] 0.42 [95% confidence interval {CI} 0.34 to 0.52]). The results from multivariable logistic regression analysis also showed that pre-hospital AAM was significantly associated with a decreased chance of neurologically favourable survival (adjusted OR 0.43 [95% CI 0.35 to 0.52]). Similar findings were observed for one-month survival and pre-hospital return of spontaneous circulation. In subgroup analyses, pre-hospital AAM was associated with poor neurological outcomes, regardless of the type of airway device used (laryngeal mask airway, adjusted OR 0.35 [95% CI 0.19 to 0.57]; oesophageal obturator airway, adjusted OR 0.44 [95% CI 0.35 to 0.55]; and endotracheal tube, adjusted OR 0.47 [95% CI 0.30 to 0.69]). In conclusion, pre-hospital AAM was associated with poor neurological outcome among patients with OHCA caused by intrinsic respiratory disease.