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.

Prediction of ventilator-associated pneumonia outcomes according to the early microbiological response: a retrospective observational study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a leading infectious cause of morbidity in critically ill patients, yet current guidelines offer no indications for follow-up cultures. We aimed to evaluate the role of follow-up cultures and microbiological response 3 days after diagnosing VAP as predictors of short- and long-term outcomes. METHODS: We performed a retrospective analysis of a cohort prospectively collected from 2004 to 2017. VAP was diagnosed based on clinical, radiographical and microbiological criteria. For microbiological identification, a tracheobronchial aspirate was performed at diagnosis and repeated after 72 h. We defined three groups when comparing the two tracheobronchial aspirate results: persistence, superinfection and eradication of causative pathogens. RESULTS: 157 patients were enrolled in the study, among whom microbiological persistence, superinfection or eradication was present in 67 (48%), 25 (16%) and 65 (41%), respectively, after 72 h. Those with superinfection had the highest mortalities in the intensive care unit (p=0.015) and at 90 days (p=0.036), while also having the fewest ventilator-free days (p=0.019). Multivariable analysis revealed shock at VAP diagnosis (OR 3.43, 95% CI 1.25-9.40), Staphylococcus aureus isolation at VAP diagnosis (OR 2.87, 95% CI 1.06-7.75) and hypothermia at VAP diagnosis (OR 0.67, 95% CI 0.48-0.95, per +1°C) to be associated with superinfection. CONCLUSIONS: Our retrospective analysis suggests that VAP short- and long-term outcomes may be associated with superinfection in follow-up cultures. Follow-up cultures may help guide antibiotic therapy and its duration. Further prospective studies are necessary to verify our findings.

Safety considerations of current drug treatment strategies for nosocomial pneumonia.

Introduction: Nosocomial pneumonia unfortunately remains a frequent event for which appropriate antibiotic treatment is central to improving outcomes. Physicians must choose an early and appropriate empirical treatment, basing their decision on the safety profile and possible side effects. Areas covered: In this review, we analyzed the safety profiles of the most common antimicrobials for treating nosocomial pneumonia. Beta-lactams are used most often for these infections, with a high percentage (6% to 25%) of patients reporting allergy or hypersensitivity reactions; however, exhaustive evaluation is key because it seems possible to de-label as many as 90% by proper assessment. Combinations including a beta-lactam are recommended in patients with risk factors for drug-resistant microorganisms and septic shock. Although aminoglycosides are safe for 3-5 days of therapy, renal function should be monitored. Fluoroquinolones must also be used with care given the risk of collagen degradation and cardiovascular events, mainly aneurysm or aortic dissection. Linezolid or vancomycin are both viable for the treatment of methicillin-resistant Staphylococcus aureus, but linezolid seems to be the superior option. Antibiotic stewardships programs must be developed for each center. Expert opinion: Choosing the most appropriate antimicrobial based on information from national and international guidelines, local microbiology data, and stewardship programs may reduce the use of broad-spectrum antibiotics. Daily assessment for the emergence of adverse events related to antimicrobial use is essential.

Neuromonitoring during general anesthesia in non-neurologic surgery.

Cerebral complications are common in perioperative settings even in non-neurosurgical procedures. These include postoperative cognitive dysfunction or delirium as well as cerebrovascular accidents. During surgery, it is essential to ensure an adequate degree of sedation and analgesia, and at the same time, to provide hemodynamic and respiratory stability in order to minimize neurological complications. In this context, the role of neuromonitoring in the operating room is gaining interest, even in the non-neurolosurgical population. The use of multimodal neuromonitoring can potentially reduce the occurrence of adverse effects during and after surgery, and optimize the administration of anesthetic drugs. In addition to the traditional focus on monitoring hemodynamic and respiratory systems during general anesthesia, the ability to constantly monitor the activity and maintenance of brain homeostasis, creating evidence-based protocols, should also become part of the standard of care: in this challenge, neuromonitoring comes to our aid. In this review, we aim to describe the role of the main types of noninvasive neuromonitoring such as those based on electroencephalography (EEG) waves (EEG, Entropy module, Bispectral Index, Narcotrend Monitor), near-infrared spectroscopy (NIRS) based on noninvasive measurement of cerebral regional oxygenation, and Transcranial Doppler used in the perioperative settings in non-neurosurgical intervention. We also describe the advantages, disadvantage, and limitation of each monitoring technique.

Effects of Positive End-Expiratory Pressure on Lung Recruitment, Respiratory Mechanics, and Intracranial Pressure in Mechanically Ventilated Brain-Injured Patients.

Background: The pathophysiological effects of positive end-expiratory pressure (PEEP) on respiratory mechanics, lung recruitment, and intracranial pressure (ICP) in acute brain-injured patients have not been completely elucidated. The primary aim of this study was to assess the effects of PEEP augmentation on respiratory mechanics, quantitative computed lung tomography (qCT) findings, and its relationship with ICP modifications. Secondary aims included the assessment of the correlations between different factors (respiratory mechanics and qCT features) with the changes of ICP and how these factors at baseline may predict ICP response after greater PEEP levels. Methods: A prospective, observational study included mechanically ventilated patients with acute brain injury requiring invasive ICP and who underwent two-PEEP levels lung CT scan. Respiratory system compliance (Crs), arterial partial pressure of carbon dioxide (PaCO2), mean arterial pressure (MAP), data from qCT and ICP were obtained at PEEP 5 and 15 cmH2O. Results: Sixteen examinations (double PEEP lung CT and neuromonitoring) in 15 patients were analyzed. The median age of the patients was 54 years (interquartile range, IQR = 39-65) and 53% were men. The median Glasgow Coma Scale (GCS) at intensive care unit (ICU) admission was 8 (IQR = 3-12). Median alveolar recruitment was 2.5% of total lung weight (-1.5 to 4.7). PEEP from 5 to 15 cmH2O increased ICP [median values from 14.0 (11.2-17.5) to 23.5 (19.5-26.8) mmHg, p < 0.001, respectively]. The amount of recruited lung tissue on CT was inversely correlated with the change (Δ) in ICP (rho = -0.78; p = 0.0006). Additionally, ΔCrs (rho = -0.77, p = 0.008), ΔPaCO2 (rho = 0.81, p = 0.0003), and ΔMAP (rho = -0.64, p = 0.009) were correlated with ΔICP. Baseline Crs was not predictive of ICP response to PEEP. Conclusions: The main factors associated with increased ICP after PEEP augmentation included reduced Crs, lower MAP and lung recruitment, and increased PaCO2, but none of these factors was able to predict, at baseline, ICP response to PEEP. To assess the potential benefits of increased PEEP in patients with acute brain injury, hemodynamic status, respiratory mechanics, and lung morphology should be taken into account.

Impact of Cardiovascular Failure in Intensive CareUnit-Acquired Pneumonia: A Single-Center, Prospective Study.

BACKGROUND: Cardiovascular failure (CVF) may complicate intensive care unit-acquired pneumonia (ICUAP) and radically alters the empirical treatment of this condition. The aim of this study was to determine the impact of CVF on outcome in patients with ICUAP. METHODS: A prospective, single-center, observational study was conducted in six medical and surgical ICUs at a University Hospital. CVS was defined as a score of 3 or more on the cardiovascular component of the Sequential Organ Failure Assessment (SOFA) score. At the onset of ICUAP, CVF was reported as absent, transient (if lasting ≤ 3 days) or persistent (>3 days). The primary outcome was 90-day mortality modelled through a Cox regression analysis. Secondary outcomes were 28-day mortality, hospital mortality, ICU length of stay (LOS) and hospital LOS. RESULTS: 358 patients were enrolled: 203 (57%) without CVF, 82 (23%) with transient CVF, and 73 (20%) with persistent CVF. Patients with transient and persistent CVF were more severely ill and presented higher inflammatory response than those without CVF. Despite having similar severity and aetiology, the persistent CVF group more frequently received inadequate initial antibiotic treatment and presented more treatment failures than the transient CVF group. In the persistent CVF group, at day 3, a bacterial superinfection was more frequently detected. The 90-day mortality was significantly higher in the persistent CVF group (62%). The 28-day mortality rates for patients without CVF, with transient and with persistent CVF were 19, 35 and 41% respectively and ICU mortality was 60, 38 and 19% respectively. In the multivariate analysis chronic pulmonary conditions, lack of Pa02/FiO2 improvement at day 3, pulmonary superinfection at day 3 and persistent CVF were independently associated with 90-day mortality in ICUAP patients. Conclusions: Persistent CVF has a significant impact on the outcome of patients with ICUAP. Patients at risk from persistent CVF should be promptly recognized to optimize treatment and outcomes.