Role of innate immunity in the pathogenesis of ventilation-induced lung injury / 中华危重病急救医学

For patients receiving mechanical ventilation, mechanical ventilation is also an injury factor at the same time of treatment, which can lead to or aggravate lung injury, that is, ventilator-induced lung injury (VILI). The typical feature of VILI is that the mechanical stress is transmitted to cells through the pathway, leading to uncontrollable inflammatory cascade reaction, which causes the activation of inflammatory cells in the lung and the release of a large number of cytokines and inflammatory mediators. Among them, innate immunity is also involved in the occurrence and development of VILI. A large number of studies have shown that damaged lung tissue in VILI can regulate inflammatory response by releasing a large number of damage associated molecular pattern (DAMP). Pattern recognition receptor (PRR) participates in the activation of immune response by combining with DAMP, and releases a large number of inflammatory mediators to promote the occurrence and development of VILI. Recent studies have shown that inhibition of DAMP/PRR signaling pathway can play a protective role in VILI. Therefore, this article will mainly discuss the potential role of blocking DAMP/PRR signal pathway in VILI, and provide new ideas for the treatment of VILI.

Effects of propofol on inflammatory response and activation of p38 MAPK signaling pathway in rats with ventilator-induced lung injury

ABSTRACT Purpose: To investigate the effects of propofol on inflammatory response and activation of p38 mitogen-activated protein kinase (MAPK) signaling pathway in rats with ventilator-associated lung injury (VALI). Methods: Thirty-six Sprague Dawley (SD) rats were divided into control, VALI and VALI+propofol groups. The VALI group received the mechanical ventilation for 2 h. The VALI+propofol group received the mechanical ventilation for 2 h, which was accompanied by intravenous injection of propofol with dose of 8 mg·kg-1·h-1. At the end, the mean arterial pressure (MAP) and blood gas indexes were measured, and the lung wet/dry mass ratio (W/D) and biochemical indexes of lung tissue and bronchoalveolar lavage fluid (BALF) were determined. Results: Compared with VALI group, in VALI+propofol group the blood pH, partial pressure of oxygen, partial pressure of carbon dioxide and MAP were increased, the lung W/D, lung tissue myeloperoxidase activity and total protein concentration, white blood cell count, and tumor necrosis factor α, interleukin 1β and interleukin 6 levels in BALF were decreased, and the p-p38 MAPK protein expression level and phosphorylated p38 MAPK (p-p38 MAPK)/p38 MAPK ratio were decreased. Conclusions: Propofol treatment may alleviate the VALI in rats by reducing the inflammatory response and inhibiting the activation of p38 MAPK signaling pathway.

Desafios para o desenvolvimento de ventiladores alternativos de baixo custo durante a pandemia de COVID-19 no Brasil / Challenges for the development of alternative low-cost ventilators during COVID-19 pandemic in Brazil

RESUMO A pandemia por COVID-19 tem deixado os gestores, os profissionais de saúde e a população preocupados com a potencial escassez de ventiladores pulmonares para suporte de pacientes graves. No Brasil, há diversas iniciativas com o intuito de produzir ventiladores alternativos para ajudar a suprir essa demanda. Para auxiliar as equipes que atuam nessas iniciativas, são expostos alguns conceitos básicos sobre fisiologia e mecânica respiratória, os termos comumente utilizados no contexto da ventilação mecânica, as fases do ciclo ventilatório, as diferenças entre disparo e ciclagem, os modos ventilatórios básicos e outros aspectos relevantes, como mecanismos de lesão pulmonar induzida pela ventilação mecânica, pacientes com drive respiratório, necessidade de umidificação de vias aéreas, risco de contaminação cruzada e disseminação de aerossóis. Após a fase de desenvolvimento de protótipo, são necessários testes pré-clínicos de bancada e em modelos animais, a fim de determinar a segurança e o desempenho dos equipamentos, seguindo requisitos técnicos mínimos exigidos. Então, é imprescindível passar pelo processo regulatório exigido pela Agência Nacional de Vigilância Sanitária (ANVISA). A empresa responsável pela fabricação do equipamento deve estar regularizada junto à ANVISA, que também deve ser notificada da condução dos testes clínicos em humanos, seguindo protocolo de pesquisa aprovado pelo Comitê de Ética em Pesquisa. O registro do ventilador junto à ANVISA deve ser acompanhado de um dossiê, composto por documentos e informações detalhadas neste artigo, que não tem o propósito de esgotar o assunto, mas de nortear os procedimentos necessários.

ABSTRACT The COVID-19 pandemic has brought concerns to managers, healthcare professionals, and the general population related to the potential mechanical ventilators' shortage for severely ill patients. In Brazil, there are several initiatives aimed at producing alternative ventilators to cover this gap. To assist the teams that work in these initiatives, we provide a discussion of some basic concepts on physiology and respiratory mechanics, commonly used mechanical ventilation terms, the differences between triggering and cycling, the basic ventilation modes and other relevant aspects, such as mechanisms of ventilator-induced lung injury, respiratory drive, airway heating and humidification, cross-contamination risks, and aerosol dissemination. After the prototype development phase, preclinical bench-tests and animal model trials are needed to determine the safety and performance of the ventilator, following the minimum technical requirements. Next, it is mandatory going through the regulatory procedures as required by the Brazilian Health Regulatory Agency (Agência Nacional de Vigilância Sanitária - ANVISA). The manufacturing company should be appropriately registered by ANVISA, which also must be notified about the conduction of clinical trials, following the research protocol approval by the Research Ethics Committee. The registration requisition of the ventilator with ANVISA should include a dossier containing the information described in this paper, which is not intended to cover all related matters but to provide guidance on the required procedures.

Tratamento prévio com adalimumabe reduz lesão pulmonar induzida por ventilação mecânica em um modelo experimental / Pretreatment with adalimumab reduces ventilator-induced lung injury in an experimental model

RESUMO Objetivo: Determinar se a administração de adalimumabe previamente à ventilação mecânica reduz a lesão pulmonar induzida por ventilação mecânica. Métodos: Randomizaram-se 18 ratos em três grupos submetidos à ventilação mecânica por 3 horas com uma fração inspirada de oxigênio de 0,40%. Os três grupos foram assim caracterizados: um grupo com baixo volume corrente (n = 6), no qual se utilizaram volume corrente de 8mL/kg e pressão expiratória final positiva de 5cmH2O; um grupo com alto volume corrente (n = 6), no qual se utilizaram volume corrente de 35mL/kg e pressão expiratória final positiva de zero; e um grupo pré-tratado com alto volume corrente (n = 6), no qual se administraram adalimumabe (100µg/kg) por via intraperitoneal 24 horas antes do início da ventilação mecânica, volume corrente de 35mL/kg e pressão expiratória final positiva de zero. Realizou-se ANOVA para comparação de dano histológico (com utilização de escores segundo o ATS 2010 Lung Injury Scoring System), edema pulmonar, complacência pulmonar, pressão parcial de oxigênio arterial e pressão arterial média entre os grupos. Resultados: Após 3 horas de ventilação, o escore médio de lesão histológica pulmonar foi mais elevado no grupo com alto volume corrente do que no grupo com baixo volume corrente (0,030 versus 0,0051; p = 0,003). O grupo com alto volume corrente demonstrou complacência pulmonar diminuída após 3 horas (p = 0,04) e hipoxemia (p = 0,018 versus controle). O grupo alto volume corrente tratado previamente teve melhora do escore histológico, principalmente devido à redução significante da infiltração leucocitária (p = 0,003). Conclusão: O exame histológico após 3 horas de ventilação lesiva revelou lesão pulmonar induzida por ventilação mecânica na ausência de modificações mensuráveis na mecânica pulmonar e na oxigenação; a administração de adalimumabe antes da ventilação mecânica diminuiu o edema pulmonar e o dano histológico.

ABSTRACT Objective: To determine whether adalimumab administration before mechanical ventilation reduces ventilator-induced lung injury (VILI). Methods: Eighteen rats randomized into 3 groups underwent mechanical ventilation for 3 hours with a fraction of inspired oxygen = 0.40% including a low tidal volume group (n = 6), where tidal volume = 8mL/kg and positive end-expiratory pressure = 5cmH2O; a high tidal volume group (n = 6), where tidal volume = 35mL/kg and positive end-expiratory pressure = 0; and a pretreated + high tidal volume group (n = 6) where adalimumab (100ug/kg) was administered intraperitoneally 24 hours before mechanical ventilation + tidal volume = 35mL/kg and positive end-expiratory pressure = 0. ANOVA was used to compare histological damage (ATS 2010 Lung Injury Scoring System), pulmonary edema, lung compliance, arterial partial pressure of oxygen, and mean arterial pressure among the groups. Results: After 3 hours of ventilation, the mean histological lung injury score was higher in the high tidal volume group than in the low tidal volume group (0.030 versus 0.0051, respectively, p = 0.003). The high tidal volume group showed diminished lung compliance at 3 hours (p = 0.04) and hypoxemia (p = 0,018 versus control). Pretreated HVt group had an improved histological score, mainly due to a significant reduction in leukocyte infiltration (p = 0.003). Conclusion: Histological examination after 3 hours of injurious ventilation revealed ventilator-induced lung injury in the absence of measurable changes in lung mechanics or oxygenation; administering adalimumab before mechanical ventilation reduced lung edema and histological damage.

Características de la ventilación mecánica invasiva en COVID-19 para médicos no especialistas / Characteristics of invasive mechanical ventilation in COVID-19 for non-specialist medical

SARS-CoV-2 is the agent responsible for COVID-19, the current pandemic, which is characterized by developing respiratory disturbances that are associated with severe hypoxemia associated with symptoms of non-bacterial pneumonia, ARDS up to multi-organ failure. It has been characterized by presenting 2 different phenotypes (phenotype L and phenotype H), with phenotype H being a stage of progressive deterioration of phenotype L, which depends on the earliness with which ventilatory management begins and the degree of inflammatory compromise. However, since VMI can generate VILI, the use of protective ventilation has been recommended as a ventilatory strategy for COVID-19. This review aims to comment on the available evidence of the essential aspects of protective IMV in the context of ARDS associated with COVID-19, in addition to the use of neuromuscular blockade and prone strategies.

El SARS-CoV-2 es el agente responsable del COVID-19, actual pandemia, que se caracteriza por desarrollar alteraciones respiratorias que cursan con hipoxemia severa asociada a cuadros de neumonía no bacteriana, SDRA hasta la falla multiorgánica. Se ha caracterizado por presentar 2 fenotipos distintos (fenotipo L y fenotipo H), siendo el fenotipo H un estadío de deterioro progresivo del fenotipo L, que depende de la precocidad con la que se inicia el manejo ventilatorio y del grado de compromiso inflamatorio. Sin embargo, dado que la VMI puede generar VILI, se ha recomendado el uso de una ventilación protectora como estrategia ventilatoria para COVID-19. La presente revisión tiene como objetivo comentar la evidencia disponible de los aspectos esenciales de la VMI protectora en el contexto del SDRA asociado a COVID-19, además del uso de bloqueo neuromuscular y las estrategias de prono.

Modelo predictivo del riesgo de muerte por neumonía asociada a la ventilación mecánica / Predictive model of the risk of death due to pneumonia associated with mechanical ventilation

Introducción: En la unidad de terapia intensiva del Hospital Dr. Agostinho Neto, Guantánamo, Cuba, no hay disponible un instrumento para valorar el riesgo de muerte del paciente con neumonía asociada a la ventilación mecánica. Objetivo: Diseñar un instrumento para la predicción del riesgo de muerte por neumonía asociada a la ventilación mecánica. Método: Estudio observacional, prospectivo y longitudinal de 144 pacientes, de los que se consideró la edad, sexo, diagnóstico, estadía, tipo y etiología de la neumonía, tiempo y duración de la ventilación, y complicaciones. Se elaboró y validó un modelo predictivo de la muerte por esta neumonía. Resultados: La aplicación del modelo mostró su nivel de precisión, pues sobre todo fue muy específico para predecir este riesgo. Conclusiones: Se diseñó un modelo de probabilidad de muerte del paciente con neumonía asociada a la ventilación mecánica, que contribuyó a la valoración más objetiva de su pronóstico(AU)

Introduction: In the intensive care unit of the Hospital Dr. Agostinho Neto, Guantanamo, Cuba, there is no instrument available to assess the risk of death of patients with pneumonia associated with mechanical ventilation. Objective: Design an instrument for predicting the risk of death from pneumonia associated with mechanical ventilation. Method: Observational, prospective and longitudinal study of 144 patients. Age, sex, diagnosis, stay, type and etiology of pneumonia, time and duration of ventilation, as well as complications were considered. A predictive model of death from this pneumonia was developed and validated. Results: The application of the model showed its level of precision, since above all it was very specific to predict this risk. Conclusions: A model of the probability of death of the patient with pneumonia associated with mechanical ventilation was designed, which contributed to the more objective assessment of the prognosis(AU)

Hypercapnia attenuates ventilator-induced lung injury through vagus nerve activation

Abstract Purpose: To investigate the role of vagus nerve activation in the protective effects of hypercapnia in ventilator-induced lung injury (VILI) rats. Methods: Male Sprague-Dawley rats were randomized to either high-tidal volume or low-tidal volume ventilation (control) and monitored for 4h. The high-tidal volume group was further divided into either a vagotomy or sham-operated group and each surgery group was further divided into two subgroups: normocapnia and hypercapnia. Injuries were assessed hourly through hemodynamics, respiratory mechanics and gas exchange. Protein concentration, cell count and cytokines (TNF-α and IL-8) in bronchoalveolar lavage fluid (BALF), lung wet-to-dry weight and pathological changes were examined. Vagus nerve activity was recorded for 1h. Results: Compared to the control group, injurious ventilation resulted in a decrease in PaO2/FiO2 and greater lung static compliance, MPO activity, enhanced BALF cytokines, protein concentration, cell count, and histology injury score. Conversely, hypercapnia significantly improved VILI by decreasing the above injury parameters. However, vagotomy abolished the protective effect of hypercapnia on VILI. In addition, hypercapnia enhanced efferent vagus nerve activity compared to normocapnia. Conclusion: These results indicate that the vagus nerve plays an important role in mediating the anti-inflammatory effect of hypercapnia on VILI.

Ventilação mecânica protetora: revisão de ensaios clínicos randomizados / Protective mechanical ventilation: revision of randomized clinical trials

Introdução: A ventilação mecânica pode ser uma estratégia salvadora de vidas em pacientes com insuficiência respiratória. Porém, ela é potencialmente perigosa e pode causar a chamada lesão pulmonar induzida pela ventilação mecânica (VILI). Esta revisão objetivou analisar os resultados de ensaios clínicos randomizados (ECR) que avaliaram o impacto de ajustes ventilatórios sobre a mortalidade. Material e Métodos: Nós Buscou-se, na base PubMed ECR, artigos publicados entre 1980 e 2019, usando os seguintes termos MeSH: "respiratory distress syndrome, adult" and "respiration, artificial". Selecionou-se os ECR que compararam diferentes parâmetros ventilatórios e que tiveram a mortalidade como desfecho. Resultados: Em pacientes com síndrome do desconforto respiratório agudo (SDRA), demonstrou-se que a limitações do volume corrente, da pressão de platô e da pressão de distensão reduzem a mortalidade. Na SDRA grave, o uso de pressão expiratória final positiva (PEEP) mais alta e a posição prona também reduzem a mortalidade. Entre pacientes sem SDRA, ainda é incerto se alguma dessas estratégias associa-se a melhor sobrevida. Conclusão: Em pacientes com SDRA, deve-se estar atento para o ajuste da ventilação mecânica, pois parâmetros protetores podem aumentar a sobrevida.

Introduction: Mechanical ventilation can be a life-saving strategy in patients with respiratory failure. However, it is potentially dangerous and can induce a so-called ventilator-induced lung injury (VILI). This revision aimed to analyze the results of randomized clinical trials (RCT) that evaluated the impact of ventilatory settings on mortality. Material and Methods: We search in PubMed for RCT, published from 1980 to 2019, using the following MeSH terms: "respiratory distress syndrome, adult" and "respiration, artificial". We selected the RCT that compared different ventilatory settings and had mortality as an outcome. Results: In patients with acute respiratory distress syndrome (ARDS), it has been demonstrated that limiting tidal volume, plateau pressure, and driving pressure reduced mortality. In severe ARDS, the use of higher PEEP and prone position also reduced mortality. Among non-ARDS patients, it is still uncertain if any strategy is associated with better survival rates. Conclusion: In ARDS patients, one has to be aware of setting the ventilatory parameters because protective settings can improve survival.

Non-invasive continuous positive airway pressure ventilation and high-flow nasal cannula oxygen therapy use in children without primary lung pathology: A prospective observational study

Background. Non-invasive nasal continuous positive airway pressure (nCPAP) and high-flow nasal cannula oxygen therapy (HFNC) are non-invasive ventilation (NIV) modalities appropriate for children in developing countries. There is minimal literature describing nCPAP and HFNC use in children with respiratory compromise secondary to non-pulmonary disease. Objectives. Th present study aimed to describe the characteristics and outcomes of children without primary lung pathology, who received nCPAP and HFNC during their admission to Red Cross War Memorial Children's Hospital, Cape Town, South Africa. Methods. This was a prospective observational study of routinely collected data, between August 2015 and January 2016. Primary and secondary outcome measures were NIV failure (progression to intubation and invasive ventilation) and paediatric intensive care unit (PICU) admission, respectively. Comparative statistics were conducted using Mann-Whitney U or t-tests. Data significantly associated with the primary and secondary outcomes on univariate analysis were entered into backward stepwise logistic regression models to determine independent predictive factors. Results. There were 31 cases of nCPAP and 1 case of HFNC use in 31 patients (median age 3.5 (interquartile range (IQR) 1.8 - 7.6) months). The majority (n=23; 71.9%) presented with primary diarrhoeal disease. There were 2 deaths (6.5%), 17 (53.1%) PICU admissions, and 5 (15.6%) cases received invasive ventilation (NIV failure). The median duration of hospital stay was 11.5 (IQR 6.0 - 17.5) days. Patients who failed NIV had lower admission SaO2 levels than those without treatment failure (95% (IQR 95 - 99) v. 100% (IQR 100 - 100); p=0.03). On multiple logistic regression, lower temperature (adjusted OR (aOR) 0.19; 95% confidence interval (CI) 0.05 - 0.78; p=0.02) and receiving inotropes in the emergency setting (aOR 23.05; 95% CI 1.64 - 325.06; p=0.02) were independently associated with PICU admission. Conclusion. nCPAP was used clinically for the management of children with respiratory compromise secondary to non-pulmonary illnesses, particularly diarrhoeal disease. Larger controlled clinical studies are needed to determine the effectiveness and utility of nCPAP in this population. HFNC was not commonly used, and this modality requires further investigation in this population

Research progress in perioperative ventilator-induced lung injury / 中南大学学报(医学版)

Lung-protective ventilation (such as low tidal volume and application of positive end-expiratory pressure) is beneficial for patients with acute lung injury or acute respiratory distress syndrome (ARDS) and has become the standard treatment in intensive care unit (ICU). However, some experts now question whether the protective ventilation strategy for ARDS patients in the ICU is equally beneficial for patients after surgery, especially for most patients without any pre-existing lung lesions. This review will discuss preoperative, intraoperative, and postoperative lung protection strategies to reduce the risk of complications associated with anesthesia.

Tidal volume in mechanically ventilated dogs: can human strategies be extrapolated to veterinary patients?

This paper compares and describes the tidal volume (Vt) used in mechanically ventilated dogs under a range of clinical conditions. Twenty-eight dogs requiring mechanical ventilation (MV) were classified into 3 groups: healthy dogs mechanically ventilated during surgery (group I, n = 10), dogs requiring MV due to extra-pulmonary reasons (group II, n = 7), and dogs that required MV due to pulmonary pathologies (group III, n = 11). The median Vt used in each group was 16 mL/kg (interquartile range [IQR], 15.14–21) for group I, 12.59 mL/kg (IQR, 9–14.25) for group II, and 12.59 mL/kg (IQR, 10.15–14.96) for group III. The Vt used was significantly lower in group III than in group I (p = 0.016). The thoraco-pulmonary compliance was significantly higher in group I than in groups II and III (p = 0.011 and p = 0.006, respectively). The median driving pressure was similar among the groups with a median of 9, 11, and 10 cmH2O in groups I, II, and III, respectively (p = 0.260). Critically-ill dogs requiring MV due to the primary pulmonary pathology received a significantly lower Vt than healthy dogs but with a range of values that were markedly higher than those recommended by human guidelines.

Molecular Mechanisms of Ventilator-Induced Lung Injury / 中华医学杂志(英文版)

<p><b>Objective</b>Mechanical ventilation (MV) has long been used as a life-sustaining approach for several decades. However, researchers realized that MV not only brings benefits to patients but also cause lung injury if used improperly, which is termed as ventilator-induced lung injury (VILI). This review aimed to discuss the pathogenesis of VILI and the underlying molecular mechanisms.</p><p><b>Data Sources</b>This review was based on articles in the PubMed database up to December 2017 using the following keywords: "ventilator-induced lung injury", "pathogenesis", "mechanism", and "biotrauma".</p><p><b>Study Selection</b>Original articles and reviews pertaining to mechanisms of VILI were included and reviewed.</p><p><b>Results</b>The pathogenesis of VILI was defined gradually, from traditional pathological mechanisms (barotrauma, volutrauma, and atelectrauma) to biotrauma. High airway pressure and transpulmonary pressure or cyclic opening and collapse of alveoli were thought to be the mechanisms of barotraumas, volutrauma, and atelectrauma. In the past two decades, accumulating evidence have addressed the importance of biotrauma during VILI, the molecular mechanism underlying biotrauma included but not limited to proinflammatory cytokines release, reactive oxygen species production, complement activation as well as mechanotransduction.</p><p><b>Conclusions</b>Barotrauma, volutrauma, atelectrauma, and biotrauma contribute to VILI, and the molecular mechanisms are being clarified gradually. More studies are warranted to figure out how to minimize lung injury induced by MV.</p>

Role of glutamine in the mediation of E-cadherin, p120-catenin and inflammation in ventilator-induced lung injury / 中华医学杂志(英文版)

<p><b>Background</b>Ventilator-induced lung injury (VILI) is commonly associated with barrier dysfunction and inflammation reaction. Glutamine could ameliorate VILI, but its role has not been fully elucidated. This study examined the relationship between inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, and IL-10) and adherens junctions (E-cadherin, p120-catenin), which were ameliorated by glutamine in VILI, both in vitro and in vivo.</p><p><b>Methods</b>For the in vivo study, 30 healthy C57BL/6 mice weighing 25-30 g were randomly divided into five groups with random number table (n = 6 in each group): control (Group C); low tidal volume (Group L); low tidal volume + glutamine (Group L + G); high tidal volume (Group H); and high tidal volume + glutamine (Group H + G). Mice in all groups, except Group C, underwent mechanical ventilation for 4 h. For the in vitro study, mouse lung epithelial 12 (MLE-12) cells pretreated with glutamine underwent cyclic stretching at 20% for 4 h. Cell lysate and lung tissue were obtained to detect the junction proteins, inflammatory cytokines, and lung pathological changes by the Western blotting, cytokine assay, hematoxylin and eosin staining, and immunofluorescence.</p><p><b>Results</b>In vivo, compared with Group C, total cell counts (t = -28.182, P < 0.01), the percentage of neutrophils (t = -28.095, P < 0.01), IL-6 (t = -28.296, P < 0.01), and TNF-α (t = -19.812, P < 0.01) in bronchoalveolar lavage (BAL) fluid, lung injury scores (t = -6.708, P < 0.01), and the wet-to-dry ratio (t = -15.595, P < 0.01) were increased in Group H; IL-10 in BAL fluid (t = 9.093, P < 0.01) and the expression of E-cadherin (t = 10.044, P < 0.01) and p120-catenin (t = 13.218, P < 0.01) were decreased in Group H. Compared with Group H, total cell counts (t = 14.844, P < 0.01), the percentage of neutrophils (t = 18.077, P < 0.01), IL-6 (t = 18.007, P < 0.01), and TNF-α (t = 10.171, P < 0.01) in BAL fluid were decreased in Group H + G; IL-10 in BAL fluid (t = -7.531, P < 0.01) and the expression of E-cadherin (t = -14.814, P < 0.01) and p120-catenin (t = -9.114, P < 0.01) were increased in Group H + G. In vitro, compared with the nonstretching group, the levels of IL-6 (t = -21.111, P < 0.01) and TNF-α (t = -15.270, P < 0.01) were increased in the 20% cyclic stretching group; the levels of IL-10 (t = 5.450, P < 0.01) and the expression of E-cadherin (t = 17.736, P < 0.01) and p120-catenin (t = 16.136, P < 0.01) were decreased in the 20% cyclic stretching group. Compared with the stretching group, the levels of IL-6 (t = 11.818, P < 0.01) and TNF-α (t = 8.631, P < 0.01) decreased in the glutamine group; the levels of IL-10 (t = -3.203, P < 0.05) and the expression of E-cadherin (t = -13.567, P < 0.01) and p120-catenin (t = -10.013, P < 0.01) were increased in the glutamine group.</p><p><b>Conclusions</b>High tidal volume mechanical ventilation and 20% cyclic stretching could cause VILI. Glutamine regulates VILI by improving cytokines and increasing the adherens junctions, protein E-cadherin and p120-catenin, to enhance the epithelial barrier function.</p>

Monitoring and Interpretation of Mechanical Ventilator Waveform in the Neuro-Intensive Care Unit

Management of mechanical ventilation is essential for patients with neuro-critical illnesses who may also have impairment of airways, lungs, respiratory muscles, and respiratory drive. However, balancing the approach to mechanical ventilation in the intensive care unit (ICU) with the need to prevent additional lung and brain injury, is challenging to intensivists. Lung protective ventilation strategies should be modified and applied to neuro-critically ill patients to maintain normocapnia and proper positive end expiratory pressure in the setting of neurological closed monitoring. Understanding the various parameters and graphic waveforms of the mechanical ventilator can provide information about the respiratory target, including appropriate tidal volume, airway pressure, and synchrony between patient and ventilator, especially in patients with neurological dysfunction due to irregularity of spontaneous respiration. Several types of asynchrony occur during mechanical ventilation, including trigger, flow, and termination asynchrony. This review aims to present the basic interpretation of mechanical ventilator waveforms and utilization of waveforms in various clinical situations in the neuro-ICU.

O uso de níveis altos de PEEP previne a lesão pulmonar induzida pelo ventilador? / Does the use of high PEEP levels prevent ventilator-induced lung injury?

RESUMO A distensão excessiva e o recrutamento alveolar pelo volume corrente foram defendidos como os principais mecanismos físicos responsáveis pela lesão pulmonar induzida pelo ventilador. A limitação do volume corrente demonstrou benefícios quanto à sobrevivência em pacientes com síndrome da angústia respiratória aguda e é reconhecida como a pedra fundamental da ventilação protetora. Em contraste, o uso de elevados níveis de pressão positiva expiratória final em estudos clínicos gerou resultados conflitantes e ainda é um assunto controvertido. Nesta revisão, discutimos os benefícios e as limitações da abordagem de pulmão aberto, e debatemos alguns recentes estudos experimentais e clínicos, referentes ao uso de níveis baixos e moderados de pressão positiva expiratória final. Também distinguimos o estiramento dinâmico (volume corrente) do estático (pressão expiratória final positiva e pressão média nas vias aéreas) e discutimos seus papéis na indução da lesão pulmonar induzida pela ventilação. As estratégias com elevada pressão positiva expiratória final claramente diminuem a hipoxemia refratária em pacientes com síndrome da angústia respiratória aguda, porém também aumentam o estiramento estático, que, por sua vez, pode ser lesiva aos pacientes, especialmente para aqueles com nível mais baixo de recrutabilidade pulmonar. Em pacientes com insuficiência respiratória grave, recomenda-se a titulação da pressão positiva expiratória final contra a gravidade da hipoxemia, ou sua aplicação de uma forma decrescente após manobra de recrutamento. Caso sejam observadas elevadas pressões de platô, driving pressure ou pressão média nas vias aéreas, a posição prona ou ventilação ultraprotetora podem ser indicadas para melhora da oxigenação, sem estresse adicional e estiramento dos pulmões.

ABSTRACT Overdistention and intratidal alveolar recruitment have been advocated as the main physical mechanisms responsible for ventilator-induced lung injury. Limiting tidal volume has a demonstrated survival benefit in patients with acute respiratory distress syndrome and is recognized as the cornerstone of protective ventilation. In contrast, the use of high positive end-expiratory pressure levels in clinical trials has yielded conflicting results and remains controversial. In the present review, we will discuss the benefits and limitations of the open lung approach and will discuss some recent experimental and clinical trials on the use of high versus low/moderate positive end-expiratory pressure levels. We will also distinguish dynamic (tidal volume) from static strain (positive end-expiratory pressure and mean airway pressure) and will discuss their roles in inducing ventilator-induced lung injury. High positive end-expiratory pressure strategies clearly decrease refractory hypoxemia in patients with acute respiratory distress syndrome, but they also increase static strain, which in turn may harm patients, especially those with lower levels of lung recruitability. In patients with severe respiratory failure, titrating positive end-expiratory pressure against the severity of hypoxemia, or providing it in a decremental fashion after a recruitment maneuver, is recommended. If high plateau, driving or mean airway pressures are observed, prone positioning or ultraprotective ventilation may be indicated to improve oxygenation without additional stress and strain in the lung.

Ventilación de alta frecuencia oscilatoria en pediatría / High frequency oscillatory ventilation in pediatrics

Mechanical ventilation (MV) is a usual therapy for the management of critically ill children. However its inappropriate use can produce lung injury. Today, the evidence recommends protective ventilation such as strategie low tidal volumes (VT) that minimize injury and thus, high frequency oscillatory ventilation (HFOV) would have a theoretical role. HFOV allows gas exchange using low tidal volumes (1 – 2 ml/kg) and supraphysiologic respiratory frequencies. In pediatrics it comprises 3 – 30 percent of mechanically ventilated patients, most of the time as a rescue therapy in refractory respiratory failure cases where conventional mechanical ventilation fails. Many aspects of HFVO in children remain unclear, theoretical benefits has no solid clinical basis, when is the best time to initiate (early vs rescue mode), which are the optimal settings, and how to monitor lung mechanics. This review examines HFVO theoretical bases, suggest recommendations for its use and considers the available evidence to understand the aspects that are still unclear.

La ventilación mecánica (VM) constituye un apoyo frecuente en el manejo de niños críticamente enfermos, quienes pueden requerirla por diferentes etiologías, entre ellas el síndrome de dificultad respiratoria aguda (SDRA). Sabemos que a pesar de ser un soporte vital, su uso inapropiado puede producir daño inducido por ventilación mecánica (DIVM). En la actualidad, la evidencia recomienda las estrategias de “ventilación protectora”, bajos volúmenes corrientes, que minimicen este daño y es ahí donde la ventilación de alta frecuencia oscilatoria (VAFO) tendría un rol teórico. La VAFO permite el intercambio gaseoso usando pequeños volúmenes corrientes (VT) 1-2 ml /kg y frecuencias respiratorias supra fisiológicas, con la consiguiente disminución del riesgo de atelectrauma, manteniendo el “pulmón abierto” y en la zona de seguridad de la curva presión-volumen. Su uso en pediatría oscila entre el 3 y el 30 por ciento de los pacientes ventilados, la mayoría de las veces como terapia de rescate frente a la falla de la ventilación convencional (VMC) en insuficiencia respiratoria refractaria. Muchos aspectos de la VAFO en pediatría no han sido totalmente esclarecidos; su efecto protector teórico permanece aún sin bases sólidas en el escenario clínico, quienes se benefician de su uso, cuál es el mejor momento para iniciarla (temprana o rescate), cuales son los valores óptimos del oscilador y como monitorear la mecánica pulmonar en VAFO. La presente revisión pretende repasar los conceptos teóricos de la VAFO, formular recomendaciones para su uso y considerar la evidencia disponible que nos permitan dilucidar las interrogantes antes mencionadas.

Síndrome de distrés respiratorio agudo en pediatría / Pediatric acute respiratory distress syndrome

The Acute Respiratory Distress Syndrome (ARDS) is a life-threatening disease with a high mortality rate. In children it represents a diagnostic and therapeutic challenge. The primary feature in the development of ARDS is the non-cardiogenic pulmonary edema resulting from a disproportionate inflammatory response that increases the blood-gas barrier permeability. There is strong evidence that aninappropriate ventilatory support may induce lung injury, organ dysfunction and increasing mortality.The aim of this article is to review current concepts related to the diagnostic of pediatric ARDS, its pathophysiologic mechanisms, ventilator induced lung injury and a brief description of rescue therapies.

El Síndrome de Distrés Respiratorio Agudo (SDRA) es una entidad grave de elevada mortalidad, siendo en pediatría un desafío diagnóstico y terapéutico. La característica primaria del SDRA es el desarrollo de edema pulmonar no cardiogénico debido a una respuesta inflamatoria excesiva que aumenta la permeabilidad de la barrera sangre-gas. Existe una fuerte evidencia de que una estrategia inadecuada de soporte ventilatorio puede aumentar el daño pulmonar, inducir disfunciones de َrganos a distancia y aumentar la mortalidad.El presente artيculo pretende revisar conceptos actuales relacionados al diagnóstico de SDRA pediátrico, mecanismos fisiopatológicos, daño pulmonar inducido por la ventilación mecánica y una breve revisión de las terapias de rescate.

Pre-treatment with dexamethasone attenuates experimental ventilator-induced lung injury / Pré-tratamento com dexametasona atenua a lesão pulmonar induzida por ventilação mecânica em modelo experimental

ABSTRACT Objective: To evaluate the effects that administering dexamethasone before the induction of ventilator-induced lung injury (VILI) has on the temporal evolution of that injury. Methods: Wistar rats were allocated to one of three groups: pre-VILI administration of dexamethasone (dexamethasone group); pre-VILI administration of saline (control group); or ventilation only (sham group). The VILI was induced by ventilation at a high tidal volume. Animals in the dexamethasone and control groups were euthanized at 0, 4, 24, and 168 h after VILI induction. We analyzed arterial blood gases, lung edema, cell counts (total and differential) in the BAL fluid, and lung histology. Results: At 0, 4, and 24 h after VILI induction, acute lung injury (ALI) scores were higher in the control group than in the sham group (p < 0.05). Administration of dexamethasone prior to VILI induction decreased the severity of the lung injury. At 4 h and 24 h after induction, the ALI score in the dexamethasone group was not significantly different from that observed for the sham group and was lower than that observed for the control group (p < 0.05). Neutrophil counts in BAL fluid were increased in the control and dexamethasone groups, peaking at 4 h after VILI induction (p < 0.05). However, the neutrophil counts were lower in the dexamethasone group than in the control group at 4 h and 24 h after induction (p < 0.05). Pre-treatment with dexamethasone also prevented the post-induction oxygenation impairment seen in the control group. Conclusions: Administration of dexamethasone prior to VILI induction attenuates the effects of the injury in Wistar rats. The molecular mechanisms of such injury and the possible clinical role of corticosteroids in VILI have yet to be elucidated.

RESUMO Objetivo: Avaliar os efeitos da administração de dexametasona antes da indução de lesão pulmonar induzida por ventilação mecânica (LPIVM) na evolução temporal dessa lesão. Métodos: Ratos Wistar foram alocados em um dos três grupos: administração de dexametasona pré-LPIVM (grupo dexametasona); administração de salina pré-LPIVM (grupo controle); e somente ventilação (grupo sham). A LPIVM foi realizada por ventilação com volume corrente alto. Os animais dos grupos dexametasona e controle foram sacrificados em 0, 4, 24 e 168 h após LPIVM. Analisamos gasometria arterial, edema pulmonar, contagens de células (totais e diferenciais) no lavado broncoalveolar e histologia de tecido pulmonar. Resultados: Em 0, 4 e 24 h após LPIVM, os escores de lesão pulmonar aguda (LPA) foram maiores no grupo controle que no grupo sham (p < 0,05). A administração de dexametasona antes da LPIVM reduziu a gravidade da lesão pulmonar. Em 4 e 24 h após a indução, o escore de LPA no grupo dexametasona não foi significativamente diferente daquele observado no grupo sham e foi menor que o observado no grupo controle (p < 0,05). As contagens de neutrófilos no lavado broncoalveolar estavam aumentadas nos grupos controle e dexametasona, com pico em 4 h após LPIVM (p < 0,05). Entretanto, as contagens de neutrófilos foram menores no grupo dexametasona que no grupo controle em 4 e 24 h após LPIVM (p < 0,05). O pré-tratamento com dexametasona também impediu o comprometimento da oxigenação após a indução visto no grupo controle. Conclusões: A administração de dexametasona antes de LPIVM atenua os efeitos da lesão em ratos Wistar. Os mecanismos moleculares dessa lesão e o possível papel clínico dos corticosteroides na LPIVM ainda precisam ser elucidados.