A long-lasting porcine model of ARDS caused by pneumonia and ventilator-induced lung injury.

BACKGROUND: Animal models of acute respiratory distress syndrome (ARDS) do not completely resemble human ARDS, struggling translational research. We aimed to characterize a porcine model of ARDS induced by pneumonia-the most common risk factor in humans-and analyze the additional effect of ventilator-induced lung injury (VILI). METHODS: Bronchoscopy-guided instillation of a multidrug-resistant Pseudomonas aeruginosa strain was performed in ten healthy pigs. In six animals (pneumonia-with-VILI group), pulmonary damage was further increased by VILI applied 3 h before instillation and until ARDS was diagnosed by PaO2/FiO2 < 150 mmHg. Four animals (pneumonia-without-VILI group) were protectively ventilated 3 h before inoculum and thereafter. Gas exchange, respiratory mechanics, hemodynamics, microbiological studies and inflammatory markers were analyzed during the 96-h experiment. During necropsy, lobar samples were also analyzed. RESULTS: All animals from pneumonia-with-VILI group reached Berlin criteria for ARDS diagnosis until the end of experiment. The mean duration under ARDS diagnosis was 46.8 ± 7.7 h; the lowest PaO2/FiO2 was 83 ± 5.45 mmHg. The group of pigs that were not subjected to VILI did not meet ARDS criteria, even when presenting with bilateral pneumonia. Animals developing ARDS presented hemodynamic instability as well as severe hypercapnia despite high-minute ventilation. Unlike the pneumonia-without-VILI group, the ARDS animals presented lower static compliance (p = 0.011) and increased pulmonary permeability (p = 0.013). The highest burden of P. aeruginosa was found at pneumonia diagnosis in all animals, as well as a high inflammatory response shown by a release of interleukin (IL)-6 and IL-8. At histological examination, only animals comprising the pneumonia-with-VILI group presented signs consistent with diffuse alveolar damage. CONCLUSIONS: In conclusion, we established an accurate pulmonary sepsis-induced ARDS model.

Optimal approaches to preventing severe community-acquired pneumonia.

Introduction: Community-acquired pneumonia (CAP) has the highest rate of mortality of all infectious diseases, especially among the elderly. Severe CAP (sCAP) is defined as a CAP in which intensive care management is required and is associated with an unfavorable clinical course. Areas covered: This review aims to identify prevention strategies for reducing the incidence of CAP and optimized management of sCAP. We highlight the main prevention approaches for CAP, focusing on the latest vaccination plans and on the influence of health-risk behaviors. Lastly, we report the latest recommendations about the optimal approach for sCAP when CAP has already been diagnosed, including prompt admission to ICU, early empirical antibiotic therapy, and optimization of antibiotic use. Expert opinion: Despite improvements in the diagnosis and treatment of sCAP, more efforts are needed to combat preventable causes, including the implementation and improvement of vaccine coverage, anti-tobacco campaigns and correct oral hygiene. Moreover, future research should aim to assess the benefits of early antimicrobial therapy in primary care. Pharmacokinetic studies in the target population may help clinicians to adjust dosage regimens in critically ill patients with CAP and thus reduce rates of treatment failure.