Effect of invasive mechanical ventilation on the diversity of the pulmonary microbiota.

Pulmonary microbial diversity may be influenced by biotic or abiotic conditions (e.g., disease, smoking, invasive mechanical ventilation (MV), etc.). Specially, invasive MV may trigger structural and physiological changes in both tissue and microbiota of lung, due to gastric and oral microaspiration, altered body posture, high O2 inhalation-induced O2 toxicity in hypoxemic patients, impaired airway clearance and ventilator-induced lung injury (VILI), which in turn reduce the diversity of the pulmonary microbiota and may ultimately lead to poor prognosis. Furthermore, changes in (local) O2 concentration can reduce the diversity of the pulmonary microbiota by affecting the local immune microenvironment of lung. In conclusion, systematic literature studies have found that invasive MV reduces pulmonary microbiota diversity, and future rational regulation of pulmonary microbiota diversity by existing or novel clinical tools (e.g., lung probiotics, drugs) may improve the prognosis of invasive MV treatment and lead to more effective treatment of lung diseases with precision.

Adoption of Lung Protective ventilation IN patients undergoing Emergency laparotomy: the ALPINE study. A prospective multicentre observational study.

BACKGROUND: Emergency abdominal surgery is associated with a high risk of postoperative pulmonary complications (PPCs). The primary aim of this study was to determine whether patients undergoing emergency laparotomy are ventilated using a lung-protective ventilation strategy employing tidal volume ≤8 ml kg-1 ideal body weight-1, PEEP >5 cm H2O, and recruitment manoeuvres. The secondary aim was to investigate the association between ventilation factors (lung-protective ventilation strategy, intraoperative FiO2, and peak inspiratory pressure) and the occurrence of PPCs. METHODS: Data were collected prospectively in 28 hospitals across London as part of routine National Emergency Laparotomy Audit (NELA). Patients were followed for 7 days. Complications were defined according to the European Perioperative Clinical Outcome definition. RESULTS: Data were collected from 568 patients. The median [inter-quartile range (IQR)] tidal volume observed was 500 ml (450-540 ml), corresponding to a median tidal volume of 8 ml kg-1 ideal body weight-1 (IQR: 7.2-9.1 ml). A lung-protective ventilation strategy was employed in 4.9% (28/568) of patients, and was not protective against the occurrence of PPCs in the multivariable analysis (hazard ratio=1.06; P=0.69). Peak inspiratory pressure of <30 cm H2O was protective against development of PPCs (hazard ratio=0.46; confidence interval: 0.30-0.72; P=0.001). Median FiO2 was 0.5 (IQR: 0.44-0.53), and an increase in FiO2 by 5% increased the risk of developing a PPC by 8% (2.6-14.1%; P=0.008). CONCLUSIONS: Both intraoperative peak inspiratory pressure and FiO2 are independent factors significantly associated with development of a postoperative pulmonary complication in emergency laparotomy patients. Further studies are required to identify causality and to demonstrate if their manipulation could lead to better clinical outcomes.

High-Fat Feeding Protects Mice From Ventilator-Induced Lung Injury, Via Neutrophil-Independent Mechanisms.

OBJECTIVE: Obesity has a complex impact on acute respiratory distress syndrome patients, being associated with increased likelihood of developing the syndrome but reduced likelihood of dying. We propose that such observations are potentially explained by a model in which obesity influences the iatrogenic injury that occurs subsequent to intensive care admission. This study therefore investigated whether fat feeding protected mice from ventilator-induced lung injury. DESIGN: In vivo study. SETTING: University research laboratory. SUBJECTS: Wild-type C57Bl/6 mice or tumor necrosis factor receptor 2 knockout mice, either fed a high-fat diet for 12-14 weeks, or age-matched lean controls. INTERVENTIONS: Anesthetized mice were ventilated with injurious high tidal volume ventilation for periods up to 180 minutes. MEASUREMENTS AND MAIN RESULTS: Fat-fed mice showed clear attenuation of ventilator-induced lung injury in terms of respiratory mechanics, blood gases, and pulmonary edema. Leukocyte recruitment and activation within the lungs were not significantly attenuated nor were a host of circulating or intra-alveolar inflammatory cytokines. However, intra-alveolar matrix metalloproteinase activity and levels of the matrix metalloproteinase cleavage product soluble receptor for advanced glycation end products were significantly attenuated in fat-fed mice. This was associated with reduced stretch-induced CD147 expression on lung epithelial cells. CONCLUSIONS: Consumption of a high-fat diet protects mice from ventilator-induced lung injury in a manner independent of neutrophil recruitment, which we postulate instead arises through blunted up-regulation of CD147 expression and subsequent activation of intra-alveolar matrix metalloproteinases. These findings may open avenues for therapeutic manipulation in acute respiratory distress syndrome and could have implications for understanding the pathogenesis of lung disease in obese patients.

Entanglement of sepsis, chronic kidney disease, and other comorbidities in patients who develop acute kidney injury.

Acute kidney injury (AKI) is a common and severe complication for patients in the intensive care setting, often occurring in the setting of sepsis. Both sepsis and AKI are complex and heterogeneous syndromes with overlapping risk factors. Comorbidities - such as chronic kidney disease, diabetes mellitus, liver disease, cardiac disease and cancer - may contribute to the development of these syndromes and complicate their management. Recognition of the complex interplay between comorbid conditions, sepsis, and AKI is key to the successful management of these syndromes.

Lesao pulmonar induzida pela ventilacao em recem-nascidos prematuros / Ventilator-induced lung injury in preterm infants

A necessidade de intubação e do uso de ventilação mecânica na prematuridade está relacionada à chamada lesão pulmonar induzida pela ventilação e à consequente displasia broncopulmonar. Busca-se a melhor compreensão dos mecanismos de lesão envolvendo resposta inflamatória mediada pelas citocinas para o desenvolvimento de novas estratégias protetoras. Pesquisou-se na base de dados PubMed, incluindo artigos relevantes, os unitermos "ventilator induced lung injury preterm", "continuous positive airway pressure", "preterm" e "bronchopulmonary dysplasia". Dados e informações significativas foram compilados em tópicos, com o objetivo de formar uma visão crítica e plena acerca da lesão induzida pela ventilação e de suas consequências ao prematuro. Foi revisado o papel das citocinas pró-inflamatórias como mediadores da lesão, especialmente interleucinas 6 e 8, e fator de necrose tumoral alfa. Foram apresentadas evidências em estudos com animais e também em humanos, mostrando que breves períodos de ventilação mecânica são suficientes para a liberação dessas interleucinas inflamatórias. Também foram revisadas outras formas de ventilação mecânica e de ventilação não invasiva, como alternativas protetoras aos modos convencionais. Concluiu-se que o uso de ventilação não invasiva, a intubação com administração precoce de surfactante e a extubação rápida para CPAP nasal, além de estratégias que regulam o volume corrente evitando o volutrauma (como a ventilação com volume garantido), são medidas protetoras da lesão pulmonar induzida pela ventilação mecânica no prematuro.

In preterm infants, the need for intubation and mechanical ventilation is associated with ventilator-induced lung injuries and subsequent bronchopulmonary dysplasia. The aim of the present review was to improve the understanding of the mechanisms of injury that involve cytokine-mediated inflammation to contribute to the development of new preventive strategies. Relevant articles were retrieved from the PubMed database using the search terms "ventilator-induced lung injury preterm", "continuous positive airway pressure", "preterm", and "bronchopulmonary dysplasia". The resulting data and other relevant information were divided into several topics to ensure a thorough, critical view of ventilation-induced lung injury and its consequences in preterm infants. The role of pro-inflammatory cytokines (particularly interleukins 6 and 8 and tumor necrosis factor alpha) as mediators of lung injury was assessed. Evidence from studies conducted with animals and human newborns is described. This evidence shows that brief periods of mechanical ventilation is sufficient to induce the release of pro-inflammatory cytokines. Other forms of mechanical and non-invasive ventilation were also analyzed as protective alternatives to conventional mechanical ventilation. It was concluded that non-invasive ventilation, intubation followed by early surfactant administration and quick extubation for nasal continuous positive airway pressure, and strategies that regulate tidal volume and avoid volutrauma (such as volume guarantee ventilation) protect against ventilator-induced lung injury in preterm infants.

Ventilator-induced lung injury in preterm infants.

In preterm infants, the need for intubation and mechanical ventilation is associated with ventilator-induced lung injuries and subsequent bronchopulmonary dysplasia. The aim of the present review was to improve the understanding of the mechanisms of injury that involve cytokine-mediated inflammation to contribute to the development of new preventive strategies. Relevant articles were retrieved from the PubMed database using the search terms "ventilator-induced lung injury preterm", "continuous positive airway pressure", "preterm", and "bronchopulmonary dysplasia". The resulting data and other relevant information were divided into several topics to ensure a thorough, critical view of ventilation-induced lung injury and its consequences in preterm infants. The role of pro-inflammatory cytokines (particularly interleukins 6 and 8 and tumor necrosis factor alpha) as mediators of lung injury was assessed. Evidence from studies conducted with animals and human newborns is described. This evidence shows that brief periods of mechanical ventilation is sufficient to induce the release of pro-inflammatory cytokines. Other forms of mechanical and non-invasive ventilation were also analyzed as protective alternatives to conventional mechanical ventilation. It was concluded that non-invasive ventilation, intubation followed by early surfactant administration and quick extubation for nasal continuous positive airway pressure, and strategies that regulate tidal volume and avoid volutrauma (such as volume guarantee ventilation) protect against ventilator-induced lung injury in preterm infants.

Changes in respiratory support of preterm infants in the last decade: are we improving?

BACKGROUND: Ventilator-induced lung injury has been recognized as a major contributing factor for bronchopulmonary dysplasia (BPD) in preterm infants. In the last decade, focus has shifted towards a more gentle respiratory approach. AIM: To evaluate whether guideline changes in respiratory management in the delivery room and the unit improved the incidence of BPD in very preterm infants. METHODS: Three cohorts of infants <30 weeks of gestation, born at the Leiden University Medical Center in the Netherlands in 1996-1997 (cohort '96), 2003-2004 (cohort '03) and 2008-2009 (cohort '08), were compared retrospectively. The major change was increasing use of continuous positive airway pressure in time, and monitoring the tidal volume during mechanical ventilation in cohort '08. The primary outcome was BPD at 36 weeks. RESULTS: The incidence of BPD did not change from 47% in cohort '96 to 55% in cohort '03 (n.s.), but decreased significantly to 37% in cohort '08 (cohort '96 vs. '08 and cohort '03 vs. '08: p < 0.01). We observed the same effect when only moderate and severe BPD were counted with 27% in cohort '96, 31% in cohort '03 and 14% in '08 (cohort '96 vs. '03: p = n.s., cohort '96 vs. '08: p < 0.01, cohort '03 vs. '08: p < 0.05). The mortality rate was not significantly different between the three cohorts. CONCLUSION: The incidence of BPD in our cohort of preterm infants has decreased during the last decade and could be due to the changes in respiratory management.

Pneumatoceles in preterm infants-incidence and outcome in the post-surfactant era.

OBJECTIVE: Pneumatoceles are gas-filled cysts within the lung parenchyma resulting mostly from ventilator-induced lung injury and air-leak in premature infants with respiratory distress syndrome. The use of surfactant in the treatment of respiratory distress syndrome has resulted in a decrease in the incidence of air-leak disease. Our aim was to study the incidence and clinical course of pneumatoceles in the surfactant era. STUDY DESIGN: A retrospective study of infants born at < or =30 weeks gestational age was admitted to the University of Connecticut Health Center NICU from 1998 to 2007. Pneumatoceles and other intrathoracic air-leaks were identified and comparisons were made with infants without these conditions. RESULT: Pneumatoceles were identified in 19 preterm infants, born at gestational age < or =30 weeks, needing positive pressure ventilation for respiratory distress syndrome between the years 1998 to 2007. Pneumatoceles appeared early (median, 7th day of life; range, 1st to 28th day of life) and usually resolved with decrease in mean airway pressure (median, 4 days; range, 3 to 125 days). The majority of pneumatoceles were located in the right parahilar region (18/19). Associated intrathoracic air-leaks were pulmonary interstitial emphysema (5/19), pneumothorax (10/19), and pneumomediastinum (1/19). None of the infants required any invasive procedures to alleviate the pneumatoceles. In infants who survived, most pneumatoceles resolved with a decrease in mean airway pressure or extubation (14/15). One infant had a persistent pneumatocele for 125 days without any cardiopulmonary compromise and five infants died as a result air-leaks along with other complications of prematurity. CONCLUSION: Pneumatoceles are a manifestation of intrathoracic air-leaks of prematurity. They are markers for ventilator-induced lung injury and are associated with significant mortality similar to other intrathoracic air-leaks. However, conservative management with reduction in mean airway pressure is effective in the resolution of this condition and interventional decompression of the pneumatocele is generally not necessary.