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BACKGROUND: Mechanical insufflation-exsufflation (MI-E) has been proposed as a potential strategy to generate high expiratory flows and simulate cough in the critically ill. However, efficacy and safety of MI-E during invasive mechanical ventilation are still to be fully elucidated. This study in intubated and mechanically ventilated pigs aimed to evaluate the effects of 8 combinations of insufflation-exsufflation pressures during MI-E on mucus displacement, respiratory flows, as well as respiratory mechanics and hemodynamics. METHODS: Six healthy Landrace-Large White female pigs were orotracheally intubated, anesthetized, and invasively ventilated for up to 72 h. Eight combinations of insufflation-exsufflation pressures (+40/-40, +40/-50, +40/-60, +40/-70, +50/-40, +50/-50, +50/-60, +50/-70 cm H2O) were applied in a randomized order. The MI-E device was set to automatic mode, medium inspiratory flow, and an inspiratory-expiratory time 3 and 2 s, respectively, with a 1-s pause between cycles. We performed 4 series of 5 insufflation-exsufflation cycles for each combination of pressures. Velocity and direction of movement of a mucus simulant containing radio-opaque markers were assessed through sequential lateral fluoroscopic images of the trachea. We also evaluated respiratory flows, respiratory mechanics, and hemodynamics before, during, and after each combination of pressures. RESULTS: In 3 of the animals, experiments were conducted twice; and for the remaining 3, they were conducted once. In comparison to baseline mucus movement (2.85 ± 2.06 mm/min), all insufflation-exsufflation pressure combinations significantly increased mucus velocity (P = .01). Particularly, +40/-70 cm H2O was the most effective combination, increasing mucus movement velocity by up to 4.8-fold (P < .001). Insufflation pressure of +50 cm H2O resulted in higher peak inspiratory flows (P = .004) and inspiratory transpulmonary pressure (P < .001) than +40 cm H2O. CONCLUSIONS: MI-E appeared to be an efficient strategy to improve mucus displacement during invasive ventilation, particularly when set at +40/-70 cm H2O. No safety concerns were identified although a transient significant increase of transpulmonary pressure was observed. [ABSTRACT FROM AUTHOR]

Objectives: Latest trials failed to confirm merits of nebulized amikacin for critically ill patients with nosocomial pneumonia. We studied various nebulized and IV antibiotic regimens in a porcine model of severe Pseudomonas aeruginosa pneumonia, resistant to amikacin, fosfomycin, and susceptible to meropenem.Design: Prospective randomized animal study.Setting: Animal Research, University of Barcelona, Spain.Subjects: Thirty female pigs.Interventions: The animals were randomized to receive nebulized saline solution (CONTROL); nebulized amikacin every 6 hours; nebulized fosfomycin every 6 hours; IV meropenem alone every 8 hours; nebulized amikacin and fosfomycin every 6 hours; amikacin and fosfomycin every 6 hours, with IV meropenem every 8 hours. Nebulization was performed through a vibrating mesh nebulizer. The primary outcome was lung tissue bacterial concentration. Secondary outcomes were tracheal secretions P. aeruginosa concentration, clinical variables, lung histology, and development of meropenem resistance.Measurements and Main Results: We included five animals into each group. Lung P. aeruginosa burden varied among groups (p < 0.001). In particular, IV meropenem and amikacin and fosfomycin + IV meropenem groups presented lower P. aeruginosa concentrations versus amikacin and fosfomycin, amikacin, CONTROL, and fosfomycin groups (p < 0.05), without significant difference between these two groups undergoing IV meropenem treatment. The sole use of nebulized antibiotics resulted in dense P. aeruginosa accumulation at the edges of the interlobular septa. Amikacin, amikacin and fosfomycin, and amikacin and fosfomycin + IV meropenem effectively reduced P. aeruginosa in tracheal secretions (p < 0.001). Pathognomonic clinical variables of respiratory infection did not differ among groups. Resistance to meropenem increased in IV meropenem group versus amikacin and fosfomycin + meropenem (p = 0.004).Conclusions: Our findings corroborate that amikacin and fosfomycin alone efficiently reduced P. aeruginosa in tracheal secretions, with negligible effects in pulmonary tissue. Combination of amikacin and fosfomycin with IV meropenem does not increase antipseudomonal pulmonary tissue activity, but it does reduce development of meropenem-resistant P. aeruginosa, in comparison with the sole use of IV meropenem. Our findings imply potential merits for preemptive use of nebulized antibiotics in order to reduce resistance to IV meropenem. [ABSTRACT FROM AUTHOR]

Rationale: The Sepsis-3 Task Force updated the clinical criteria for sepsis, excluding the need for systemic inflammatory response syndrome (SIRS) criteria. The clinical implications of the proposed flowchart including the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) and SOFA scores are unknown.Objectives: To perform a clinical decision-making analysis of Sepsis-3 in patients with community-acquired pneumonia.Methods: This was a cohort study including adult patients with community-acquired pneumonia from two Spanish university hospitals. SIRS, qSOFA, the Confusion, Respiratory Rate and Blood Pressure (CRB) score, modified SOFA (mSOFA), the Confusion, Urea, Respiratory Rate, Blood Pressure and Age (CURB-65) score, and Pneumonia Severity Index (PSI) were calculated with data from the emergency department. We used decision-curve analysis to evaluate the clinical usefulness of each score and the primary outcome was in-hospital mortality.Measurements and Main Results: Of 6,874 patients, 442 (6.4%) died in-hospital. SIRS presented the worst discrimination, followed by qSOFA, CRB, mSOFA, CURB-65, and PSI. Overall, overestimation of in-hospital mortality and miscalibration was more evident for qSOFA and mSOFA. SIRS had lower net benefit than qSOFA and CRB, significantly increasing the risk of over-treatment and being comparable with the "treat-all" strategy. PSI had higher net benefit than mSOFA and CURB-65 for mortality, whereas mSOFA seemed more applicable when considering mortality/intensive care unit admission. Sepsis-3 flowchart resulted in better identification of patients at high risk of mortality.Conclusions: qSOFA and CRB outperformed SIRS and presented better clinical usefulness as prompt tools for patients with community-acquired pneumonia in the emergency department. Among the tools for a comprehensive patient assessment, PSI had the best decision-aid tool profile. [ABSTRACT FROM AUTHOR]

Background: Data on the methods used for microbiological diagnosis of hospital-acquired pneumonia (HAP) are mainly extrapolated from ventilator-associated pneumonia. HAP poses additional challenges for respiratory sampling, and the utility of sputum or distal sampling in HAP has not been comprehensively evaluated, particularly in HAP admitted to the ICU., Methods: We analyzed 200 patients with HAP from six ICUs in a teaching hospital in Barcelona, Spain. The respiratory sampling methods used were divided into non-invasive [sputum and endotracheal aspirate (EAT)] and invasive [fiberoptic-bronchoscopy aspirate (FBAS), and bronchoalveolar lavage (BAL)]., Results: A median of three diagnostic methods were applied [range 2-4]. At least one respiratory sampling method was applied in 93% of patients, and two or more were applied in 40%. Microbiological diagnosis was achieved in 99 (50%) patients, 69 (70%) by only one method (42% FBAS, 23% EAT, 15% sputum, 9% BAL, 7% blood culture, and 4% urinary antigen). Seventy-eight (39%) patients underwent a fiberoptic-bronchoscopy when not receiving mechanical ventilation. Higher rates of microbiological diagnosis were observed in the invasive group (56 vs. 39%, p = 0.018). Patients with microbiological diagnosis more frequently presented changes in their empirical antibiotic scheme, mainly de-escalation., Conclusions: A comprehensive approach might be undertaken for microbiological diagnosis in critically ill nonventilated HAP. Sputum sampling determined one third of microbiological diagnosis in HAP patients who were not subsequently intubated. Invasive methods were associated with higher rates of microbiological diagnosis.

Objectives: We investigated the effects of two different types of manual rib cage compression on expiratory flow and mucus clearance during prolonged mechanical ventilation in pigs., Design: Prospective randomized animal study., Setting: Animal research facility, University of Barcelona, Spain., Subjects: Nine healthy pigs., Measurement and Main Results: Pigs were tracheally intubated, sedated, paralyzed, and mechanically ventilated. The animals were prone on a surgical bed in the anti-Trendelenburg position. The experiments were carried out at approximately 60 and 80 hrs from the beginning of mechanical ventilation. Two types of manual rib cage compressions were tested: Hard and brief rib cage compressions synchronized with early expiratory phase (hard manual rib cage compression) and soft and gradual rib cage compressions applied during the late expiratory phase (soft manual rib cage compression). The interventions were randomly applied for 15min with a 15-min interval between treatments. Respiratory flow and mucus movement were assessed during the interventions. Respiratory mechanics and hemodynamics were assessed prior to and after the interventions. Peak expiratory flow increased to 60.1±7.1L/min in comparison to 51.2±4.6L/min without treatment (p < 0.0015) and 48.7±4.3L/min with soft manual rib cage compression (p = 0.0002). Similarly, mean expiratory flow increased to 28.4±5.2L/min during hard manual rib cage compression vs. 15.9±2.2 and 16.6±2.8L/min without treatment and soft manual rib cage compression, respectively (p = 0.0006). During hard manual rib cage compression, mucus moved toward the glottis (1.01 ± 2.37mm/min); conversely, mucus moved toward the lungs during no treatment and soft manual rib cage compression, -0.28 ± 0.61 and -0.15±0.95mm/min, respectively (p = 0.0283). Soft manual rib cage compression slightly worsened static lung elastance and cardiac output (p = 0.0391)., Conclusions: Hard manual rib cage compression improved mucus clearance in animals positioned in the anti-Trendelenburg position. The technique appeared to be safe. Conversely, soft manual rib cage compression was not effective and potentially unsafe. These findings corroborate the predominant role of peak expiratory flow on mucus clearance.

Confocal laser scanning microscopy (CLSM) helps to observe the biofilms formed in the endotracheal tube (ETT) of ventilated subjects and to determine its structure and bacterial viability using specific dyes. We compared the effect of three different treatments (placebo, linezolid, and vancomycin) on the bacterial biofilm viability captured by CLSM. Eight pigs with pneumonia induced by methicillin-resistant Staphylococcus aureus (MRSA) were ventilated up to 96 h and treated with linezolid, vancomycin, or placebo (controls). ETT images were microscopically examined after staining with the live/dead(®) BacLight(™) Kit (Invitrogen, Barcelona, Spain) with a confocal laser scanning microscope. We analyzed 127 images obtained by CLSM. The median ratio of live/dead bacteria was 0.51, 0.74, and 1 for the linezolid, vancomycin, and control groups, respectively (P = 0.002 for the three groups); this ratio was significantly lower for the linezolid group, compared with the control group (P = 0.001). Images showed bacterial biofilm attached and non-attached to the ETT surface but growing within secretions accumulated inside ETT. Systemic treatment with linezolid is associated with a higher proportion of dead bacteria in the ETT biofilm of animals with MRSA pneumonia. Biofilm clusters not necessarily attach to the ETT surface., (© 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.)