The impact of PEEP on mechanical power and driving pressure in children with pediatric acute respiratory distress syndrome.

BACKGROUND: Positive end-expiratory pressure (PEEP) is widely used to improve oxygenation and avoid alveolar collapse in mechanically ventilated patients with pediatric acute respiratory distress syndrome (PARDS). However, its improper use can be harmful, impacting variables associated with ventilation-induced lung injury, such as mechanical power (MP) and driving pressure (∆P). Our main objective was to assess the impact of increasing PEEP on MP and ∆P in children with PARDS. INTERVENTIONS: Mechanically ventilated children on pressure-controlled volume-guaranteed mode were prospectively assessed for inclusion. PEEP was sequentially changed to 5, 12, 10, 8, and again to 5 cm H2O. After 10 min at each PEEP level, ventilatory data were collected and then variables of interest were determined. Respiratory system mechanics were measured using the least squares fitting method. RESULTS: Thirty-one patients were included, with median age and weight of 6 months and 6.3 kg. Most subjects were admitted for acute viral bronchiolitis (45%) or community-acquired pneumonia (32%) and were diagnosed with mild (45%) or moderate (42%) PARDS. There was a significant increase in MP and ∆P at PEEP levels of 10 and 12 cm H2O. When PEEP was increased from 5 to 12 cm H2O, there was a relative increase in MP of 60.7% (IQR 49.3-82.9) and in ΔP of 33.3% (IQR 17.8-65.8). A positive correlation was observed between MP and ΔP (ρ = 0.59). CONCLUSIONS: Children with mild or moderate PARDS may experience a significant increase in MP and ∆P with increased PEEP. Therefore, respiratory system mechanics and lung recruitability must be carefully evaluated during PEEP titration.

A machine-learning regional clustering approach to understand ventilator-induced lung injury: a proof-of-concept experimental study.

BACKGROUND: The spatiotemporal progression and patterns of tissue deformation in ventilator-induced lung injury (VILI) remain understudied. Our aim was to identify lung clusters based on their regional mechanical behavior over space and time in lungs subjected to VILI using machine-learning techniques. RESULTS: Ten anesthetized pigs (27 ± 2 kg) were studied. Eight subjects were analyzed. End-inspiratory and end-expiratory lung computed tomography scans were performed at the beginning and after 12 h of one-hit VILI model. Regional image-based biomechanical analysis was used to determine end-expiratory aeration, tidal recruitment, and volumetric strain for both early and late stages. Clustering analysis was performed using principal component analysis and K-Means algorithms. We identified three different clusters of lung tissue: Stable, Recruitable Unstable, and Non-Recruitable Unstable. End-expiratory aeration, tidal recruitment, and volumetric strain were significantly different between clusters at early stage. At late stage, we found a step loss of end-expiratory aeration among clusters, lowest in Stable, followed by Unstable Recruitable, and highest in the Unstable Non-Recruitable cluster. Volumetric strain remaining unchanged in the Stable cluster, with slight increases in the Recruitable cluster, and strong reduction in the Unstable Non-Recruitable cluster. CONCLUSIONS: VILI is a regional and dynamic phenomenon. Using unbiased machine-learning techniques we can identify the coexistence of three functional lung tissue compartments with different spatiotemporal regional biomechanical behavior.

Prospective, randomized, controlled trial assessing the effects of a driving pressure-limiting strategy for patients with acute respiratory distress syndrome due to community-acquired pneumonia (STAMINA trial): protocol and statistical analysis plan / Estudo randomizado prospectivo e controlado de avaliação dos efeitos de uma estratégia de limitação da driving pressure em pacientes com síndrome do desconforto respiratório agudo devido à pneumonia adquirida na comunidade (estudo STAMINA): protocolo e plano de análise estatística

ABSTRACT Background: Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress syndrome. Whether a driving pressure-limiting strategy can improve clinical outcomes is unclear. Objective: To describe the protocol and statistical analysis plan that will be used to test whether a driving pressure-limiting strategy including positive end-expiratory pressure titration according to the best respiratory compliance and reduction in tidal volume is superior to a standard strategy involving the use of the ARDSNet low-positive end-expiratory pressure table in terms of increasing the number of ventilator-free days in patients with acute respiratory distress syndrome due to community-acquired pneumonia. Methods: The ventilator STrAtegy for coMmunIty acquired pNeumoniA (STAMINA) study is a randomized, multicenter, open-label trial that compares a driving pressure-limiting strategy to the ARDSnet low-positive end-expiratory pressure table in patients with moderate-to-severe acute respiratory distress syndrome due to community-acquired pneumonia admitted to intensive care units. We expect to recruit 500 patients from 20 Brazilian and 2 Colombian intensive care units. They will be randomized to a driving pressure-limiting strategy group or to a standard strategy using the ARDSNet low-positive end-expiratory pressure table. In the driving pressure-limiting strategy group, positive end-expiratory pressure will be titrated according to the best respiratory system compliance. Outcomes: The primary outcome is the number of ventilator-free days within 28 days. The secondary outcomes are in-hospital and intensive care unit mortality and the need for rescue therapies such as extracorporeal life support, recruitment maneuvers and inhaled nitric oxide. Conclusion: STAMINA is designed to provide evidence on whether a driving pressure-limiting strategy is superior to the ARDSNet low-positive end-expiratory pressure table strategy for increasing the number of ventilator-free days within 28 days in patients with moderate-to-severe acute respiratory distress syndrome. Here, we describe the rationale, design and status of the trial.

RESUMO Contexto: Em estudos observacionais sobre a síndrome do desconforto respiratório agudo, sugeriu-se que a driving pressure é o principal fator de lesão pulmonar induzida por ventilador e de mortalidade. Não está claro se uma estratégia de limitação da driving pressure pode melhorar os desfechos clínicos. Objetivo: Descrever o protocolo e o plano de análise estatística que serão usados para testar se uma estratégia de limitação da driving pressure envolvendo a titulação da pressão positiva expiratória final de acordo com a melhor complacência respiratória e a redução do volume corrente é superior a uma estratégia padrão envolvendo o uso da tabela de pressão positiva expiratória final baixa do protocolo ARDSNet, em termos de aumento do número de dias sem ventilador em pacientes com síndrome do desconforto respiratório agudo devido à pneumonia adquirida na comunidade. Métodos: O estudo STAMINA (ventilator STrAtegy for coMmunIty acquired pNeumoniA) é randomizado, multicêntrico e aberto e compara uma estratégia de limitação da driving pressure com a tabela de pressão positiva expiratória final baixa do protocolo ARDSnet em pacientes com síndrome do desconforto respiratório agudo moderada a grave devido à pneumonia adquirida na comunidade internados em unidades de terapia intensiva. Esperamos recrutar 500 pacientes de 20 unidades de terapia intensiva brasileiras e duas colombianas. Eles serão randomizados para um grupo da estratégia de limitação da driving pressure ou para um grupo de estratégia padrão usando a tabela de pressão positiva expiratória final baixa do protocolo ARDSnet. No grupo da estratégia de limitação da driving pressure, a pressão positiva expiratória final será titulada de acordo com a melhor complacência do sistema respiratório. Desfechos: O desfecho primário é o número de dias sem ventilador em 28 dias. Os desfechos secundários são a mortalidade hospitalar e na unidade de terapia intensiva e a necessidade de terapias de resgate, como suporte de vida extracorpóreo, manobras de recrutamento e óxido nítrico inalado. Conclusão: O STAMINA foi projetado para fornecer evidências sobre se uma estratégia de limitação da driving pressure é superior à estratégia da tabela de pressão positiva expiratória final baixa do protocolo ARDSnet para aumentar o número de dias sem ventilador em 28 dias em pacientes com síndrome do desconforto respiratório agudo moderada a grave. Aqui, descrevemos a justificativa, o desenho e o status do estudo.

Respiratory system parameters in children with low severity cystic fibrosis: is there early involvement in relation to healthy peers? / Parâmetros do sistema respiratório em crianças com fibrose cística de baixa gravidade: há acometimento precoce em relação a pares saudáveis?

ABSTRACT Objective: To compare and analyze pulmonary function and respiratory mechanics parameters between healthy children and children with cystic fibrosis. Methods: This cross-sectional analytical study included healthy children (HSG) and children with cystic fibrosis (CFG), aged 6-13 years, from teaching institutions and a reference center for cystic fibrosis in Florianópolis/SC, Brazil. The patients were paired by age and sex. Initially, an anthropometric evaluation was undertaken to pair the sample characteristics in both groups; the medical records of CFG were consulted for bacterial colonization, genotype, and disease severity (Schwachman-Doershuk Score — SDS) data. Spirometry and impulse oscillometry were used to assess pulmonary function. Results: In total, 110 children were included, 55 in each group. In the CFG group, 58.2% were classified as excellent by SDS, 49.1% showed the ΔF508 heterozygotic genotype, and 67.3% were colonized by some pathogens. Statistical analysis revealed significant differences between both groups (p<0.05) in most pulmonary function parameters and respiratory mechanics. Conclusions: Children with cystic fibrosis showed obstructive ventilatory disorders and compromised peripheral airways compared with healthy children. These findings reinforce the early changes in pulmonary function and mechanics associated with this disease.

RESUMO Objetivo: Comparar e analisar parâmetros de função pulmonar e de mecânica respiratória entre escolares saudáveis e com fibrose cística (FC). Métodos: Estudo transversal que incluiu escolares saudáveis (GES) e com FC (GFC), com idades entre seis e 13 anos, provenientes de instituições de ensino e de um centro de referência da FC em Florianópolis/SC, Brasil, pareados por idade e sexo, respectivamente. Inicialmente, conduziu-se avaliação antropométrica para pareamento e caracterização de ambos os grupos e, no GFC, consultou-se prontuário médico para registro dos dados de colonização bacteriana, genótipo e gravidade da doença (Escore de Schwachman-Doershuk — ESD). Para a avaliação da função pulmonar, realizou-se espirometria e a avaliação da mecânica respiratória foi conduzida por meio do sistema de oscilometria de impulso. Resultados: Participaram 110 escolares, 55 em cada grupo. No GFC, 58,2% foram classificados pelo ESD como excelentes, 49,1% apresentaram genótipo ∆F508 heterozigoto e 67,3% eram colonizados por alguma patógeno. Houve diferença significativa (p<0,05) na maioria dos parâmetros de função pulmonar e de mecânica respiratória entre os grupos. Conclusões: Escolares com FC apresentaram distúrbio ventilatório obstrutivo e com comprometimento de vias aéreas periféricas, em comparação aos escolares hígidos. Esse evento reforça o início precoce da alteração de função pulmonar e de mecânica respiratória nessa enfermidade, evidenciados pelos achados desta investigação.

Effects of atelectatic areas on the surrounding lung tissue during mechanical ventilation in an experimental model of acute lung injury induced by lipopolysaccharide / Efeitos das áreas atelectásicas no tecido pulmonar circundante durante a ventilação mecânica em um modelo experimental de lesão pulmonar aguda induzida por lipopolissacarídeo

ABSTRACT Objective: To assess the effect of atelectasis during mechanical ventilation on the periatelectatic and normal lung regions in a model of atelectasis in rats with acute lung injury induced by lipopolysaccharide. Methods: Twenty-four rats were randomized into the following four groups, each with 6 animals: the Saline-Control Group, Lipopolysaccharide Control Group, Saline-Atelectasis Group, and Lipopolysaccharide Atelectasis Group. Acute lung injury was induced by intraperitoneal injection of lipopolysaccharide. After 24 hours, atelectasis was induced by bronchial blocking. The animals underwent mechanical ventilation for two hours with protective parameters, and respiratory mechanics were monitored during this period. Thereafter, histologic analyses of two regions of interest, periatelectatic areas and the normally-aerated lung contralateral to the atelectatic areas, were performed. Results: The lung injury score was significantly higher in the Lipopolysaccharide Control Group (0.41 ± 0.13) than in the Saline Control Group (0.15 ± 0.51), p < 0.05. Periatelectatic regions showed higher lung injury scores than normally-aerated regions in both the Saline-Atelectasis (0.44 ± 0.06 x 0.27 ± 0.74 p < 0.05) and Lipopolysaccharide Atelectasis (0.56 ± 0.09 x 0.35 ± 0.04 p < 0.05) Groups. The lung injury score in the periatelectatic regions was higher in the Lipopolysaccharide Atelectasis Group (0.56 ± 0.09) than in the periatelectatic region of the Saline-Atelectasis Group (0.44 ± 0.06), p < 0.05. Conclusion: Atelectasis may cause injury to the surrounding tissue after a period of mechanical ventilation with protective parameters. Its effect was more significant in previously injured lungs.

RESUMO Objetivo: Avaliar o efeito da atelectasia durante a ventilação mecânica nas regiões periatelectáticas e pulmonares normais em um modelo de atelectasia em ratos com lesão pulmonar aguda induzida por lipopolissacarídeo. Métodos: Foram distribuídos aleatoriamente 24 ratos em quatro grupos, cada um com 6 animais: Grupo Salina-Controle, Grupo Lipopolissacarídeo-Controle, Grupo Salina-Atelectasia e Grupo Lipopolissacarídeo-Atelectasia. A lesão pulmonar aguda foi induzida por injeção intraperitoneal de lipopolissacarídeo. Após 24 horas, a atelectasia foi induzida por bloqueio brônquico. Os animais foram submetidos à ventilação mecânica por 2 horas com parâmetros ventilatórios protetores, e a mecânica respiratória foi monitorada durante esse período. Em seguida, foram realizadas análises histológicas de duas regiões de interesse: as áreas periatelectásicas e o pulmão normalmente aerado contralateral às áreas atelectásicas. Resultados: O escore de lesão pulmonar foi significativamente maior no Grupo Controle-Lipopolissacarídeo (0,41 ± 0,13) do que no Grupo Controle-Solução Salina (0,15 ± 0,51), com p < 0,05. As regiões periatelectásicas apresentaram escores maiores de lesão pulmonar do que as regiões normalmente aeradas nos Grupos Atelectasia-Solução Salina (0,44 ± 0,06 versus 0,27 ± 0,74, p < 0,05) e Atelectasia-Lipopolissacarídeo (0,56 ± 0,09 versus 0,35 ± 0,04, p < 0,05). O escore de lesão pulmonar nas regiões periatelectásicas foi maior no Grupo Atelectasia-Lipopolissacarídeo (0,56 ± 0,09) do que na região periatelectásica do Grupo Atelectasia-Solução Salina (0,44 ± 0,06), p < 0,05. Conclusão: A atelectasia pode causar lesão no tecido circundante após um período de ventilação mecânica com parâmetros ventilatórios protetores. Seu efeito foi mais significativo em pulmões previamente lesionados.

Mechanical Power Correlates With Stress, Strain, and Atelectrauma Only When Normalized to Aerated Lung Size in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: First, to investigate whether the severity of acute respiratory distress syndrome (ARDS) influences ventilator-induced lung injury (VILI) risk in ventilated patients with similar mechanical power of respiratory system (MPRS). Second, to determine whether, under these circumstances, there is a relationship between transpulmonary mechanical power (MPTp) normalized to the aerated lung (specific lung mechanical power or SLMP) and VILI risk, and third, to determine whether normalizing MPRS to compliance of respiratory system (CRS) can replace SLMP to bedside. DESIGN: Prospective cohort study. SETTING: The study was conducted in a tertiary academic ICU. PATIENTS: The study included 18 patients with ARDS. INTERVENTIONS: Ventilatory settings were adjusted to achieve a similar MPRS. MEASUREMENTS AND MAIN RESULTS: Mechanical power was normalized to CRS (specific mechanical power or SMP = MPRS/CRS), and SLMP was calculated as the ratio between MPTp and end-expiratory lung volume (SLMP = MPTp/EELV). The strain was defined as the ratio between tidal volume and EELV (strain = Vt/EELV), stress as transpulmonary pressure at the end of inspiration, and atelectrauma as the difference between expiration and inspiration in the nonaerated lung. Although patients had been ventilated with similar MPRS = 23.75 (23-24) J/min and MPTp = 11.6 (10.8-12.8) J/min, SLMP increased linearly with the fall in Pao2/Fio2 (R = -0.83, p = 0.0001). MPRS only correlated positively with VILI-associated mechanisms when normalized to aerated lung size: correlations between SLMP and stress (R = 0.9, R2 = 0.84, p = 0.00004), strain (R = 0.97, R2 = 0.94, p < 0.00001) and atelectrauma (R = 0.82, R2 = 0.70, p = 0.00002), and correlations between SMP and stress (R = 0.86, R2 = 0.75, p = 0.00001), strain (R = 0.68, R2 = 0.47, p = 0.001) and atelectrauma (R = 0.67, R2 = 0.46, p = 0.002). CONCLUSIONS: The results suggest that normalizing mechanical power to lung-aerated size or CRS may correlate positively with stress, strain, and atelectrauma.

Airway and Transpulmonary Driving Pressure by End-Inspiratory Holds During Pressure Support Ventilation.

BACKGROUND: The precision of quasi-static airway driving pressure (ΔP) assessed in pressure support ventilation (PSV) as a surrogate of tidal lung stress is debatable because persistent muscular activity frequently alters the readability of end-inspiratory holds. In this study, we used strict criteria to discard excessive muscular activity during holds and assessed the accuracy of ΔP in predicting global lung stress in PSV. Additionally, we explored whether the physiological effects of high PEEP differed according to the response of respiratory system compliance (CRS). METHODS: Adults with ARDS undergoing PSV were enrolled. An esophageal catheter was inserted to calculate lung stress through transpulmonary driving pressure (ΔPL). ΔP and ΔPL were assessed in PSV at PEEP 5, 10, and 15 cm H2O by end-inspiratory holds. CRS was calculated as tidal volume (VT)/ΔP. We analyzed the effects of high PEEP on pressure-time product per minute (PTPmin), airway pressure at 100 ms (P0.1), and VT over PTP per breath (VT/PTPbr) in subjects with increased versus decreased CRS at high PEEP. RESULTS: Eighteen subjects and 162 end-inspiratory holds were analyzed; 51/162 (31.5%) of the holds had ΔPL ≥ 12 cm H2O. Significant association between ΔP and ΔPL was found at all PEEP levels (P < .001). ΔP had excellent precision to predict ΔPL, with 15 cm H2O being identified as the best threshold for detecting ΔPL ≥ 12 cm H2O (area under the receiver operating characteristics 0.99 [95% CI 0.98-1.00]). CRS changes from low to high PEEP corresponded well with lung compliance changes (R2 0.91, P < .001) When CRS increased, a significant improvement of PTPmin and VT/PTPbr was found, without changes in P0.1. No benefits were observed when CRS decreased. CONCLUSIONS: In subjects with ARDS undergoing PSV, high ΔP assessed by readable end-inspiratory holds accurately detected potentially dangerous thresholds of ΔPL. Using ΔP to assess changes in CRS induced by PEEP during assisted ventilation may inform whether higher PEEP could be beneficial.

Worsening of lung perfusion to tissue density distributions during early acute lung injury.

Lung perfusion magnitude and distribution are essential for oxygenation and, potentially, lung inflammation and protection during acute respiratory distress syndrome (ARDS). Yet, perfusion patterns and their relationship to inflammation are unknown pre-ARDS. We aimed to assess perfusion/density ratios and spatial perfusion-density distributions and associate these to lung inflammation, during early lung injury in large animals at different physiological conditions caused by different systemic inflammation and positive end-expiratory pressure (PEEP) levels. Sheep were protectively ventilated (16-24 h) and imaged for lung density, pulmonary capillary perfusion (13Nitrogen-saline), and inflammation (18F-fluorodeoxyglucose) using positron emission and computed tomography. We studied four conditions: permissive atelectasis (PEEP = 0 cmH2O); and ARDSNet low-stretch PEEP-setting strategy with supine moderate or mild endotoxemia, and prone mild endotoxemia. Perfusion/density heterogeneity increased pre-ARDS in all groups. Perfusion redistribution to density depended on ventilation strategy and endotoxemia level, producing more atelectasis in mild than moderate endotoxemia (P = 0.010) with the oxygenation-based PEEP-setting strategy. The spatial distribution of 18F-fluorodeoxyglucose uptake was related to local Q/D (P < 0.001 for Q/D group interaction). Moderate endotoxemia yielded markedly low/zero perfusion in normal-low density lung, with 13Nitrogen-saline perfusion indicating nondependent capillary obliteration. Prone animals' perfusion was remarkably homogeneously distributed with density. Lung perfusion redistributes heterogeneously to density during pre-ARDS protective ventilation in animals. This is associated with increased inflammation, nondependent capillary obliteration, and lung derecruitment susceptibility depending on endotoxemia level and ventilation strategy.NEW & NOTEWORTHY Perfusion redistribution does not follow lung density redistribution in the first 16-24 h of systemic endotoxemia and protective tidal volume mechanical ventilation. The same oxygenation-based positive end-expiratory pressure (PEEP)-setting strategy can lead at different endotoxemia levels to different perfusion redistributions, PEEP values, and lung aerations, worsening lung biomechanical conditions. During early acute lung injury, regional perfusion-to-tissue density ratio is associated with increased neutrophilic inflammation, and susceptibility to nondependent capillary occlusion and lung derecruitment, potentially marking and/or driving lung injury.

Exogenous surfactant reduces inflammation and redox imbalance in rats under prone or supine mechanical ventilation.

Mechanical ventilation (MV) is a lifesaving therapy for patients with acute or chronic respiratory failure. Despite, it can also cause lung injury by inducing or worsening inflammatory responses and oxidative stress. Several clinical approaches have protective effects on the lungs, including the prone position and exogenous surfactant; however, few studies have evaluated the association between the two strategies, especially in individuals without previous lung injury. We tested the hypothesis that the effects of the homogenization in lung aeration caused by the prone position in association with the anti-inflammatory properties of exogenous surfactant pre-treatment could have a cumulative protective effect against ventilator-induced lung injury. Therefore, Wistar rats were divided into four experimental groups: Mechanical Ventilation in Supine Position (MVSP), Mechanical Ventilation in Prone position (MVPP), Mechanical Ventilation in Supine Position + surfactant (MVSPS), and Mechanical Ventilation in Prone Position + Surfactant (MVPPS). The intranasal instillation of a porcine surfactant (Curosurf®) was performed in the animals of MVSPS and MVPPS 1 h before the MV, all the rats were subjected to MV for 1 h. The prone position in association with surfactant decreased mRNA expression levels of pro-inflammatory cytokines in ventilated animals compared to the supine position; in addition, the NfκB was lower in MVPP, MVSPS and MVPPS when compared to MVSP. However, it had no effects on oxidative stress caused by MV. Pre-treatment with exogenous surfactant was more efficient in promoting lung protection than the prone position, as it also reduced oxidative damage in the lung parenchyma. Nevertheless, the surfactant did not cause additional improvements in most parameters that were also improved by the prone position. Our results indicate that the pre-treatment with exogenous surfactant, regardless of the position adopted in mechanical ventilation, preserves the original lung histoarchitecture, reduces redox imbalance, and reduces acute inflammatory responses caused by mechanical ventilation in healthy adult Wistar rats.

Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries.

Acute and chronic lung injuries are among the leading causes of mortality worldwide. Lung injury can affect several components of the respiratory system, including the airways, parenchyma, and pulmonary vasculature. Although acute and chronic lung injuries represent an enormous economic and clinical burden, currently available therapies primarily focus on alleviating disease symptoms rather than reversing and/or preventing lung pathology. Moreover, some supportive interventions, such as oxygen and mechanical ventilation, can lead to (further) deterioration of lung function and even the development of permanent injuries. Lastly, sepsis, which can originate extrapulmonary or in the respiratory system itself, contributes to many cases of lung-associated deaths. Considering these challenges, we aim to summarize molecular and cellular mechanisms, with a particular focus on airway inflammation and oxidative stress that lead to the characteristic pathophysiology of acute and chronic lung injuries. In addition, we will highlight the limitations of current therapeutic strategies and explore new antioxidant-based drug options that could potentially be effective in managing acute and chronic lung injuries.

Remoción extracorpórea de CO2 en un paciente con estatus asmático que evoluciona con barotrauma / Extracorporeal CO2 Removal in a Patient with Status Asthmaticus who Evolved with Barotrauma

RESUMEN Paciente varón de 20 años, con diagnóstico de asma conocida, llegó al departamento de emergencias de un hospital de su localidad con historia de disnea 1 d antes de la admisión. Posteriormente, se torna taquicárdico, taquipneico y cianótico, por lo que fue intubado de emergencia. En la UCI del hospital general de tercer nivel, presentó bron coespasmo grave, presiones de vía aérea elevadas durante la ventilación mecánica e hipoperfusión grave. Recibió cristaloides y norepinefrina como resucitación. Al tercer día, presentó enfisema subcutáneo, neumotórax e hipercapnia con acidosis mixta. Se decidió utilizar ventilación mecánica ultraprotectora asociada con Novalung®. Con esta estrategia, logramos reducir las presiones de la vía aérea, la PEEPi, la potencia mecánica (PM) resistiva y mejorar la hipercapnia y la acidosis. El paciente permaneció 10 d en Novalung® y mostró buena evolución posterior. Finalmente, es extubado, dado de alta de la UCI y salió del hospital en buenas condiciones.

ABSTRACT A 20-year-old male with known asthma arrived at the emergency department in the first hospital with story of shortness of breath 1 day before admission. He suddenly became tachycardic, tachypneic and cyanotic, for which he was intubated. In the tertiary care general hospital ICU, he showed severe bronchospasm, high airway pressures during mechanical ventilation (MV) and severe hypoperfusion. He received crystalloids and norepinephrine. On the third day, he developed subcutaneous emphysema, pneumo thorax and hypercapnia with mixed acidosis. We decided to use ultra-protective me chanical ventilation concomitant with Novalung®. With this strategy, we could reduce airway pressures, PEEPi, resistive mechanical power and improve hypercapnia and acidosis. The patient stayed for 10 days in Novalung® and showed good evolution. He was later extubated and discharged of ICU, leaving the hospital in good conditions.

Biological impact of restrictive and liberal fluid strategies at low and high PEEP levels on lung and distal organs in experimental acute respiratory distress syndrome.

Background: Fluid regimens in acute respiratory distress syndrome (ARDS) are conflicting. The amount of fluid and positive end-expiratory pressure (PEEP) level may interact leading to ventilator-induced lung injury (VILI). We therefore evaluated restrictive and liberal fluid strategies associated with low and high PEEP levels with regard to lung and kidney damage, as well as cardiorespiratory function in endotoxin-induced ARDS. Methods: Thirty male Wistar rats received an intratracheal instillation of Escherichia coli lipopolysaccharide. After 24 h, the animals were anesthetized, protectively ventilated (VT = 6 ml/kg), and randomized to restrictive (5 ml/kg/h) or liberal (40 ml/kg/h) fluid strategies (Ringer lactate). Both groups were then ventilated with PEEP = 3 cmH2O (PEEP3) and PEEP = 9 cmH2O (PEEP9) for 1 h (n = 6/group). Echocardiography, arterial blood gases, and lung mechanics were evaluated throughout the experiments. Histologic analyses were done on the lungs, and molecular biology was assessed in lungs and kidneys using six non-ventilated animals with no fluid therapy. Results: In lungs, the liberal group showed increased transpulmonary plateau pressure compared with the restrictive group (liberal, 23.5 ± 2.9 cmH2O; restrictive, 18.8 ± 2.3 cmH2O, p = 0.046) under PEEP = 9 cmH2O. Gene expression associated with inflammation (interleukin [IL]-6) was higher in the liberal-PEEP9 group than the liberal-PEEP3 group (p = 0.006) and restrictive-PEEP9 (p = 0.012), Regardless of the fluid strategy, lung mechanical power and the heterogeneity index were higher, whereas birefringence for claudin-4 and zonula-ocludens-1 gene expression were lower in the PEEP9 groups. Perivascular edema was higher in liberal groups, regardless of PEEP levels. Markers related to damage to epithelial cells [club cell secreted protein (CC16)] and the extracellular matrix (syndecan) were higher in the liberal-PEEP9 group than the liberal-PEEP3 group (p = 0.010 and p = 0.024, respectively). In kidneys, the expression of IL-6 and neutrophil gelatinase-associated lipocalin was higher in PEEP9 groups, regardless of the fluid strategy. For the liberal strategy, PEEP = 9 cmH2O compared with PEEP = 3 cmH2O reduced the right ventricle systolic volume (37%) and inferior vena cava collapsibility index (45%). Conclusion: The combination of a liberal fluid strategy and high PEEP led to more lung damage. The application of high PEEP, regardless of the fluid strategy, may also be deleterious to kidneys.

Poder mecánico como predictor de mortalidad en los pacientes con diagnóstico de neumonía por SARS-CoV-2 que recibieron ventilación mecánica invasiva / Mechanical power as a predictor of mortality in patients diagnosed with SARS-CoV-2 pneumonia who received invasive mechanical ventilation / Potência mecânica como preditor de mortalidade em pacientes diagnosticados com pneumonia por SARS-CoV-2 que receberam ventilação mecânica invasiva

Resumen: Introducción: Las fuerzas mecánicas generadas durante la ventilación mecánica por la interacción entre el ventilador y el sistema respiratorio pueden dañar al pulmón en un proceso que se ha denominado lesión inducida por el ventilador. El grado de lesión se ha relacionado con la cantidad de energía transferida desde el ventilador mecánico al sistema respiratorio dentro de un periodo de tiempo determinado, denominado poder mecánico; datos experimentales basados en tomografías sugieren que el poder mecánico mayor de 12 J/min podría generar lesión. Se proyecta como otra de las variables a controlar dentro de las estrategias de protección pulmonar, determinado en estudios experimentales como un umbral de energía a partir del cual inician los cambios mecánicos en el pulmón que pueden conducir a lesión inducida por el ventilador. Material y métodos: Se realizó un estudio retrospectivo, analítico, comparativo, se incluyeron todos los pacientes con diagnóstico de neumonía por SARS-CoV-2 que requieren ventilación mecánica invasiva; en un periodo de tiempo comprendido de marzo-agosto de 2021 que ingresaron a la Unidad de Cuidados Intensivos y utilizaron el poder mecánico como variable para predecir la mortalidad. Resultados: La población estudiada se compuso de 67 pacientes; se evaluó la asociación entre el poder mecánico alto a las 48 horas y la mortalidad, se documentó que 49.25% (n = 33) de los casos que mantuvieron el poder mecánico alto en 48 horas murieron, 28.35% (n = 19) con poder mecánico alto no se asoció con mortalidad, 8.95% (n = 6) que no mantuvieron cálculo de poder mecánico alto murieron y 13.43% (n = 9) de los pacientes con poder mecánico menor a 12 J/min no murieron. Se realizó una prueba de asociación con χ2 de Pearson en la que se obtiene un valor de p = 0.105, por lo que no existe diferencia estadísticamente significativa y no se corrobora la asociación entre la mortalidad de los pacientes con poder mecánico alto (> 12 J/min) a las 48 horas. Conclusión: El poder mecánico puede considerarse como otra variable a controlar como estrategia de protección pulmonar del paciente con infección por SARS-CoV-2, basado en que la energía transmitida al pulmón tiene mayor impacto en los pacientes que reciben ventilación mecánica por un intervalo de tiempo mayor de siete días, con un promedio de estancia en la Unidad de Cuidados Intensivos 12.3 + 6.2 días y el promedio de días de ventilación mecánica invasiva 9.2 + 5.6.

Abstract: Introduction: The mechanical forces generated during mechanical ventilation by the interaction between the ventilator and the respiratory system can damage the lung in a process that has been called ventilator induced injury. The degree of injury has been related to the amount of energy transferred from the mechanical ventilator to the respiratory system within a given period of time, called mechanical power, experimental data based on tomographies suggest that mechanical power greater than 12 J/min could generate injury. It is projected as another variables to control within lung protection strategies, determining in experimental studies as an energy threshold from which mechanical changes in the lung begin that can lead to ventilator induced injury. Material and methods: A retrospective, analytical, comparative study was carried out. All patients with a diagnosis of SARS-CoV-2 pneumonia who required invasive mechanical ventilation were admitted; In a period of time between March-August 2021, they were admitted to the intensive care unit and used mechanical power as a variable to predict mortality. Results: The studied population consisted of 67 patients; the association between high mechanical power at 48 hours and mortality was evaluated, it was documented that 49.25% (n = 33) of the patients who maintained high mechanical power in 48 hours died, 28.35% (n = 19) with power high mechanical was not associated with mortality, 8.95% (n = 6) who did not have high mechanical power calculation died and 13.43% (n = 9) of patients with mechanical power less than 12 J/min survived. An association test was performed with Pearson's χ2 in which a p value of 0.105 was obtained, so there is no statistically significant difference and the association between the mortality of the patients is not corroborated. with high mechanical power (> 12 J/min) at 48 hours. Conclusion: Mechanical power can be considered as another variable to control as a lung protection strategy for patients with SARS-CoV-2 infection, based on the fact that the energy transmitted to the lung has a greater impact on patients who receive mechanical ventilation for an interval time greater than seven days, with an average stay in the intensive care unit 12.3 + 6.2 days and the average days of invasive mechanical ventilation 9.2 + 5.6.

Resumo: Introdução: As forças mecânicas geradas durante a ventilação mecânica pela interação entre o ventilador e o sistema respiratório podem lesar o pulmão em um processo que tem sido chamado de lesão induzida pelo ventilador. O grau de lesão tem sido relacionado à quantidade de energia transferida do ventilador mecânico para o sistema respiratório em um determinado período de tempo, denominado potência mecânica. Dados experimentais baseados em tomografia sugerem que potência mecânica superior a 12 J/min pode gerar lesão. Ele é projetado como mais uma das variáveis a serem controladas dentro das estratégias de proteção pulmonar, determinando em estudos experimentais como um limiar de energia a partir do qual se iniciam as alterações mecânicas no pulmão que podem levar à lesão induzida pelo ventilador. Material e métodos: Realizou-se um estudo retrospectivo, analítico e comparativo, foram admitidos todos os pacientes com diagnóstico de pneumonia por SARS-CoV-2 que necessitaram de ventilação mecânica invasiva; em um período de março a agosto de 2021 que foram internados na unidade de terapia intensiva e utilizaram a potência mecânica como variável para predizer mortalidade. Resultados: A população do estudo foi composta por 67 pacientes; Foi avaliada a associação entre alta potência mecânica em 48 horas e mortalidade, foi documentado que 49.25% (n = 33) dos pacientes que mantiveram potência mecânica alta em 48 horas morreram, 28.35% (n = 19) com potência mecânica alta não foi associado à mortalidade, 8.95% (n = 6) que ñao mantiveran o calculo de alta potencia mecanoca morreram e 13.4% (n = 9) dos pacientes com potencia mecanica menor que 12 J/min nao morreram. Realizou-se um teste de associação com o χ2 de Pearson, no qual se obtém um valor de p de 0.105, portanto não há diferença estatisticamente significante e a associação entre mortalidade do paciente não é corroborada com alta potência mecânica (> 12 Joul/min) em 48 horas. Conclusão: A potência mecânica pode ser considerada mais uma variável a ser controlada como estratégia de proteção pulmonar para pacientes com infecção por SARS-CoV-2, tendo em vista que a energia transmitida ao pulmão tem maior impacto em pacientes que recebem ventilação mecânica por um intervalo de tempo superior a 7 dias, com média de permanência na unidade de terapia intensiva 12.3 + 6.2 dias e média de dias de ventilação mecânica invasiva 9.2 + 5.6.

Respuesta inmune e inmunosupresión en pacientes con ventilación mecánica por infección por SARS-CoV-2 / Immune response and immune suppression in patients with mechanical ventilation secondary to SARS-CoV-2 infection / Resposta imune e imunossupressão em pacientes com ventilação mecânica devido à infecção por SARS-CoV-2

Resumen Introducción: La pandemia por SARS-CoV-2 ha inspirado intriga sobre la respuesta inmune a dicho virus, especialmente en pacientes graves con síndrome de dificultad respiratoria aguda (SDRA). Este estudio describe el comportamiento de la respuesta inmune, la inmunosupresión y sus desenlaces en los pacientes con ventilación mecánica (VM). Material y métodos: Cohorte prospectiva. Del 23 de marzo al 31 de diciembre de 2020 se recolectó información basal, parámetros ventilatorios, gasométricos y estudios de laboratorio de todos los pacientes mayores de 18 años que recibieron VM por COVID-19 con registros hasta el día 15 de VM. Se dividieron los grupos en pacientes vivos a los 90 días y defunciones. Resultados: Registramos 218 pacientes, con mortalidad de 23%. En el día 1 de VM, los pacientes no presentaron diferencias en conteos celulares o reactantes de fase aguda, excepto dímero D de 1,020 (705-1,711) vs 1,328 (940-2,340) ng/dL p = 0.035. En el análisis de regresión lineal de efectos mixtos se observaron diferencias cronológicas estadísticamente significativas en leucocitos y proteína C reactiva (PCR) concordante con la elevación de la presión de distensión alveolar (PDalv). No se encontró asociación con mortalidad en el uso de tocilizumab 2.20 (0.279-17.358) y corticosteroides 0.54 (0.229-1.273) en riesgos proporcionales de Cox al día 1 de VM. Durante los 15 días de VM los pacientes que fallecieron recibieron dosis más altas de corticosteroides, dosis mayores de 150 mg/día equivalente a prednisona se asocian a mortalidad. Conclusiones: Existe evolución cronológica similar en elevación de PCR, leucocitos y elevación de la PDalv, las cuales se explican por la disminución de la distensibilidad pulmonar estática (Cstat) y la presión positiva al final de la espiración total (PEEP total). El uso de tocilizumab no tuvo asociación con la mortalidad y dosis equivalentes a prednisona entre 100-150 mg/día se asocian a mejores resultados.

Abstract Introduction: The SARS-CoV-2 pandemic has inspired interest in the immune response to the virus, especially in severe patients with acute respiratory distress syndrome (ARDS). The study describes the behaviour of the immune response, immune suppression, and their results in patients under mechanical ventilation (MV). Material and methods: Prospective cohort. From March 23rd to December 31st, 2020, we recollected basal information, MV parameters, blood gas analysis and laboratory studies of all the patients over 18 years who received MV secondary to COVID-19. We registered 15 continuous days of MV. We divided the groups in patients alive at day 60 and deaths. Results: We included 218 patients with a mortality of 23%. In day 1 of MV, the patients didn't have any differences in cell counts or acute phase reactants, except for D Dimer (705-1,711) vs 1,328 (940-2,340) ng/dL p = 0.035. In mixed effects linear regressions, we found statistically significant chronological differences in C reactive protein (CPR) and leucocyte count, concordant with the elevation of the driving pressure (DP). In the Cox regression we found no association with tocilizumab and corticosteroids with mortality on day 1 of MV. Patients who died received higher doses of corticosteroids throughout the 15 days of MV, with doses equivalent to prednisone over 150 mg/day are associated with mortality. Conclusions: There is a similar chronological behaviour in the elevation of acute phase reactants and the elevation con DP with no elevation of Vt, which can be explained by the drop of total PEEP and Cstat. There was no association with the use of tocilizumab and mortality, and a dose of 100-150 mg/día of equivalent of prednisone was associated with better results.

Resumo Introdução: A pandemia de SARS-CoV-2 inspirou intrigas sobre a resposta imune ao referido vírus, especialmente em pacientes gravemente doentes com síndrome do desconforto respiratório do adulto (SDRA). Este estudo descreve o comportamento da resposta imune, imunossupressão e seus desfechos em pacientes em ventilação mecânica (VM). Material e métodos: Coorte prospectiva. De 23 de março a 31 de dezembro de 2020, foram coletadas informações basais, parâmetros ventilatórios e gasométricos e estudos laboratoriais de todos os pacientes maiores de 18 anos que receberam VM para COVID-19 com registros até o dia 15 de VM. Os grupos foram divididos em pacientes vivos em 90 dias e óbitos. Resultados: Registramos 218 pacientes, com mortalidade de 23%. No dia 1 de VM, os pacientes não apresentaram diferenças na contagem de células ou reagentes de fase aguda, exceto dimero D 1020 (705-1711) vs 1328 (940-2340) ng/dL p = 0.035. Na análise de regressão linear dos efeitos mistos, observam-se diferenças cronológicas estatisticamente significativas nos leucócitos e na proteína C reativa (PCR), consistentes com o aumento da pressão de distensão alveolar (PDalv). Não foi encontrada associação com mortalidade no uso de tocilizumab 2.20 (0.279-17.358) e corticoide 0.54 (0.229-1.273) nos riscos proporcionais de COX no 1o dia de VM. Durante os 15 dias de VM, os pacientes que foram a óbito receberam doses maiores de corticosteróides, doses a partir de 150 mg/dia equivalentes a prednisona estão associadas à mortalidade. Conclusões: Há evolução cronológica semelhante em PCR e leucócitos elevados e PDalv elevados, explicados pela diminuição da complacência pulmonar estática (Cstat) e da pressão positiva ao final da expiração total (PEEPtotal). O uso de tocilizumab não foi associado à mortalidade e doses equivalentes à prednisona entre 100-150 mg/dia estão associadas a melhores resultados.

Computed Tomography Assessment of Tidal Lung Overinflation in Domestic Cats Undergoing Pressure-Controlled Mechanical Ventilation During General Anesthesia.

Objective: This study aimed to evaluate lung overinflation at different airway inspiratory pressure levels using computed tomography in cats undergoing general anesthesia. Study Design: Prospective laboratory study. Animals: A group of 17 healthy male cats, aged 1.9-4.5 years and weighing 3.5 ± 0.5 kg. Methods: Seventeen adult male cats were ventilated in pressure-controlled mode with airway pressure stepwise increased from 5 to 15 cmH2O in 2 cmH2O steps every 5 min and then stepwise decreased. The respiratory rate was set at 15 movements per min and end-expiratory pressure at zero (ZEEP). After 5 min in each inspiratory pressure step, a 4 s inspiratory pause was performed to obtain a thoracic juxta-diaphragmatic single slice helical CT image and to collect respiratory mechanics data and an arterial blood sample. Lung parenchyma aeration was defined as overinflated, normally-aerated, poorly-aerated, and non-aerated according to the CT attenuation number (-1,000 to -900 HU, -900 to -500 HU, -500 to -100 HU, and -100 to +100 HU, respectively). Result: At 5 cmH2O airway pressure, tidal volume was 6.7± 2.2 ml kg-1, 2.1% (0.3-6.3%) of the pulmonary parenchyma was overinflated and 84.9% (77.6%-87.6%) was normally inflated. Increases in airway pressure were associated with progressive distention of the lung parenchyma. At 15 cmH2O airway pressure, tidal volume increased to 31.5± 9.9 ml kg-1 (p < 0.001), overinflated pulmonary parenchyma increased to 28.4% (21.2-30.6%) (p < 0.001), while normally inflated parenchyma decreased 57.9% (53.4-62.8%) (p < 0.001). Tidal volume and overinflated lung fraction returned to baseline when airway pressure was decreased. A progressive decrease was observed in arterial carbon dioxide partial pressure (PaCO2) and end-tidal carbon dioxide (ETCO2) when the airway pressures were increased above 9 cmH2O (p < 0.001). The increase in airway pressure promoted an elevation in pH (p < 0.001). Conclusions and Clinical Relevance: Ventilation with 5 and 7 cmH2O of airway pressure prevents overinflation in healthy cats with highly compliant chest walls, despite presenting acidemia by respiratory acidosis. This fact can be controlled by increasing or decreasing respiratory rate and inspiratory time.

The exogenous surfactant pre-treatment attenuates ventilator-induced lung injury in adult rats.

Mechanical ventilation is an essential supportive therapy in the treatment of critical patients, and it aims to maintain adequate gas exchange; however, it can also contribute to inflammation and oxidative stress, thus leading to lung injury. We tested the hypothesis that exogenous surfactant administration will be protective against ventilator-induced lung injury in adult healthy Wistar rats both because of its anti-inflammatory properties as well as its role in preventing alveolar collapse at end-expiration. Thus, the effect of intranasal instillation of a bovine exogenous surfactant was tested in Wistar rats submitted to mechanical ventilation. The animals were divided into four groups: (1) CONTROL; (2) SURFACTANT; (3) Mechanical ventilation (MV); (4) MV with pre-treatment with surfactant (MVSURFACTANT). The MV and MVSURFACTANT were submitted to MV with high tidal volume (12 mL/kg) for 1 h. After the experimental protocol, all animals were euthanized and the arterial blood, bronchoalveolar lavage fluid and lungs were collected for biochemical, immunoenzymatic assay, arterial blood gases, and morphometric analyzes. The Wistar rats that received exogenous surfactant (Survanta®) by intranasal instillation before MV demonstrated reduced levels of leukocytes, inflammatory biomarkers such as CCL2, IL-1, IL-6 and TNF-α. Furthermore, it prevented oxidative damage by reducing lipid peroxidation and protein carbonylation as well as histological pattern changes of pulmonary parenchyma. Our data indicate that exogenous surfactant attenuated lung inflammation and redox imbalance induced by mechanical ventilation in healthy adult rats suggesting a preventive effect on ventilator-induced lung injury.

Brain-lung interaction: a vicious cycle in traumatic brain injury.

The brain-lung interaction can seriously affect patients with traumatic brain injury, triggering a vicious cycle that worsens patient prognosis. Although the mechanisms of the interaction are not fully elucidated, several hypotheses, notably the "blast injury" theory or "double hit" model, have been proposed and constitute the basis of its development and progression. The brain and lungs strongly interact via complex pathways from the brain to the lungs but also from the lungs to the brain. The main pulmonary disorders that occur after brain injuries are neurogenic pulmonary edema, acute respiratory distress syndrome, and ventilator-associated pneumonia, and the principal brain disorders after lung injuries include brain hypoxia and intracranial hypertension. All of these conditions are key considerations for management therapies after traumatic brain injury and need exceptional case-by-case monitoring to avoid neurological or pulmonary complications. This review aims to describe the history, pathophysiology, risk factors, characteristics, and complications of brain-lung and lung-brain interactions and the impact of different old and recent modalities of treatment in the context of traumatic brain injury.

A more gradual positive end-expiratory pressure increase reduces lung damage and improves cardiac function in experimental acute respiratory distress syndrome.

Increases in positive end-expiratory pressure (PEEP) or recruitment maneuvers may increase stress in lung parenchyma, extracellular matrix, and lung vessels; however, adaptative responses may occur. We evaluated the effects of PEEP on lung damage and cardiac function when increased abruptly, gradually, or more gradually in experimental mild/moderate acute respiratory distress syndrome (ARDS) induced by Escherichia coli lipopolysaccharide intratracheally. After 24 h, Wistar rats (n = 48) were randomly assigned to four mechanical ventilation strategies according to PEEP levels: 1) 3 cmH2O for 2 h (control); 2) 3 cmH2O for 1 h followed by an abrupt increase to 9 cmH2O for 1 h (no adaptation time); 3) 3 cmH2O for 30 min followed by a gradual increase to 9 cmH2O over 30 min then kept constant for 1 h (shorter adaptation time); and 4) more gradual increase in PEEP from 3 cmH2O to 9 cmH2O over 1 h and kept constant thereafter (longer adaptation time). At the end of the experiment, oxygenation improved in the shorter and longer adaptation time groups compared with the no-adaptation and control groups. Diffuse alveolar damage and expressions of interleukin-6, club cell protein-16, vascular cell adhesion molecule-1, amphiregulin, decorin, and syndecan were higher in no adaptation time compared with other groups. Pulmonary arterial pressure was lower in longer adaptation time than in no adaptation (P = 0.002) and shorter adaptation time (P = 0.025) groups. In this model, gradually increasing PEEP limited lung damage and release of biomarkers associated with lung epithelial/endothelial cell and extracellular matrix damage, as well as the PEEP-associated increase in pulmonary arterial pressure.NEW & NOTEWORTHY In a rat model of Escherichia coli lipopolysaccharide-induced mild/moderate acute respiratory distress syndrome, a gradual PEEP increase (shorter adaptation time) effectively mitigated histological lung injury and biomarker release associated with lung inflammation, damage to epithelial cells, endothelial cells, and the extracellular matrix compared with an abrupt increase in PEEP. A more gradual PEEP increase (longer adaptation time) decreased lung damage, pulmonary vessel compression, and pulmonary arterial pressure.

Annexin A1 peptide Ac2-26 mitigates ventilator-induced lung injury in acute respiratory distress syndrome rats and partly depended on the endothelial nitric oxide synthase pathway

Purpose: Although mechanical ventilation is an essential support for acute respiratory distress syndrome (ARDS), ventilation also leads to ventilator-induced lung injury (VILI). This study aimed to estimate the effect and mechanism of Annexin A1 peptide (Ac2-26) on VILI in ARDS rats. Methods: Thirty-two rats were randomized into the sham (S), mechanical ventilation (V), mechanical ventilation/Ac2-26 (VA), and mechanical ventilation/Ac2-26/L-NIO (VAL) groups. The S group only received anesthesia, and the other three groups received endotoxin and then ventilation for 4 h. Rats in the V, VA and VAL groups received saline, Ac2-26, and A c2-26/N5-(1-iminoethyl)-l-ornithine (L-NIO), respectively. Results: All indexes deteriorated in the V, VA and VAL groups compared with the S group. Compared with V group, the PaO2/FiO2 ratio was increased, but the wet-to-dry weight ratio and protein levels in bronchoalveolar lavage fluid were decreased in the VA group. The inflammatory cells and proinflammatory factors were reduced by Ac2-26. The oxidative stress response, lung injury and apoptosis were also decreased by Ac2-26 compared to V group. All improvements of Ac2-26 were partly reversed by L-NIO. Conclusions: Ac2-26 mitigates VILI in ARDS rats and partly depended on the endothelial nitric oxide synthase pathway.

Síndrome de Hamman - rich: Reporte de caso / Hamman-Rich Syndrome: case report

Resumen La neumonía intersticial aguda, también conocida como síndrome de Hamman-Rich, se caracteriza por la presencia de insuficiencia respiratoria aguda, hallazgo imagenológico de infiltrados difusos bilaterales del parénquima pulmonar y daño alveolar difuso en histopatología pulmonar. Es una patología con una mortalidad mayor al 50% debido a la falta de una terapia específica más allá del manejo sintomático y soporte ventilatorio. Se expone el caso de un paciente masculino de 56 años quien se presenta con síntomas respiratorios inespecíficos, deterioro progresivo de la oxigenación y hallazgo de opacidades en vidrio esmerilado difusas bilaterales. Además, biopsia pulmonar en la que se evidencia daño alveolar difuso en fase fibroproliferativa en quien se descarta proceso infeccioso, enfermedades autoinmunes y toxicidad medicamentosa, por lo que se hace el diagnóstico. Recibió manejo con pulsos de metilprednisolona con recuperación completa del cuadro. MÉD.UIS.2021;34(3): 103-8.

Abstract Acute interstitial pneumonitis, also known as Hamman Rich syndrome, characterised by acute respiratory failure, bilateral lung infiltrates on radiographs and diffuse alveolar damage (DAD) on lung histopathology, is an exclusion diagnosis which requires a complete study of other possible etiologies of DAD. It is a pathology with a mortality greater than 50% due to not having a specific therapy beyond symptomatic management and ventilatory support. We present a case of a 56 year old male with respiratory symptoms, who has progressive worsening oxygen levels and bilateral ground glass opacities on chest images. Lung biopsy with diffuse alveolar damage, infection, autoimmune diseases, and drug adverse reaction were ruled out. Managed with mechanical ventilation and high dose systemic corticoids with complete recovery. MÉD.UIS.2021;34(3): 103-8.