Mechanical Ventilation in Patients with Acute Brain Injuries: A Pathophysiology-based Approach.

Applying mechanical ventilation and selecting ventilatory strategies in patients with acute brain injuries, especially those with lung damage, is challenging. Static (positive end-expiratory pressure) and dynamic (intratidal) changes in ventilator pressure, via complex pathways, influence cerebral arterial inflow and cerebral venous pressure and thus cerebral blood volume and intracranial pressure. In this process, the relationship between airway pressure and pleural and transalveolar pressures, heavily affected by elastance of the chest wall and lung, respectively, plays a central role.

Respiratory drive: a journey from health to disease.

Respiratory drive is defined as the intensity of respiratory centers output during the breath and is primarily affected by cortical and chemical feedback mechanisms. During the involuntary act of breathing, chemical feedback, primarily mediated through CO, is the main determinant of respiratory drive. Respiratory drive travels through neural pathways to respiratory muscles, which execute the breathing process and generate inspiratory flow (inspiratory flow-generation pathway).

Lung- and diaphragm-protective strategies in acute respiratory failure: an in silico trial.

Background: Lung- and diaphragm-protective (LDP) ventilation may prevent diaphragm atrophy and patient self-inflicted lung injury in acute respiratory failure, but feasibility is uncertain. The objectives of this study were to estimate the proportion of patients achieving LDP targets in different modes of ventilation, and to identify predictors of need for extracorporeal carbon dioxide removal (ECCOR) to achieve LDP targets.

Methods: An in silico clinical trial was conducted using a previously published mathematical model of patient-ventilator interaction in a simulated patient population (n = 5000) with clinically relevant physiological characteristics.

Driving pressure of respiratory system and lung stress in mechanically ventilated patients with active breathing.

Background: During control mechanical ventilation (CMV), the driving pressure of the respiratory system (ΔP) serves as a surrogate of transpulmonary driving pressure (ΔP). Expiratory muscle activity that decreases end-expiratory lung volume may impair the validity of ΔP to reflect ΔP. This prospective observational study in patients with acute respiratory distress syndrome (ARDS) ventilated with proportional assist ventilation (PAV+), aimed to investigate: (1) the prevalence of elevated ΔP, (2) the ΔP-ΔP relationship, and (3) whether dynamic transpulmonary pressure (Plung) and effort indices (transdiaphragmatic and respiratory muscle pressure swings) remain within safe limits.

Evaluation of the Acid-Base Status in Patients Admitted to the ICU Due to Severe COVID-19: Physicochemical versus Traditional Approaches.

Background: Stewart's approach is known to have better diagnostic accuracy for the identification of metabolic acid-base disturbances compared to traditional methods based either on plasma bicarbonate concentration ([HCO]) and anion gap (AG) or on base excess/deficit (BE). This study aimed to identify metabolic acid-base disorders using either Stewart's or traditional approaches in critically ill COVID-19 patients admitted to the ICU, to recognize potential hidden acid-base metabolic abnormalities and to assess the prognostic value of these abnormalities for patient outcome.

Methods: This was a single-center retrospective study, in which we collected data from patients with severe COVID-19 admitted to the ICU.

Hiccup-like Contractions in Mechanically Ventilated Patients: Individualized Treatment Guided by Transpulmonary Pressure.

Hiccups-like contractions, including hiccups, respiratory myoclonus, and diaphragmatic tremor, refer to involuntary, spasmodic, and inspiratory muscle contractions. They have been repeatedly described in mechanically ventilated patients, especially those with central nervous damage. Nevertheless, their effects on patient-ventilator interaction are largely unknown, and even more overlooked is their contribution to lung and diaphragm injury.

Neural Network-Enabled Identification of Weak Inspiratory Efforts during Pressure Support Ventilation Using Ventilator Waveforms.

During pressure support ventilation (PSV), excessive assist results in weak inspiratory efforts and promotes diaphragm atrophy and delayed weaning. The aim of this study was to develop a classifier using a neural network to identify weak inspiratory efforts during PSV, based on the ventilator waveforms. Recordings of flow, airway, esophageal and gastric pressures from critically ill patients were used to create an annotated dataset, using data from 37 patients at 2-5 different levels of support, computing the inspiratory time and effort for every breath.

Impact of Molecular Syndromic Diagnosis of Severe Pneumonia in the Management of Critically Ill Patients.

The impact of syndromic molecular diagnosis in the management of nosocomial infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens has been incompletely characterized. We evaluated the performance of a molecular syndromic platform (BioFire FilmArray-Pneumonia plus Panel) in patients with pneumonia in the intensive care unit (ICU) of a University Hospital in Greece over a 2-year period. We evaluated 79 consecutive patients diagnosed with pneumonia in the ICU (2018-2020), including 55 patients with ventilator associated pneumonia (VAP).

Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations.

Oxidative stress is considered pivotal in the pathophysiology of sepsis. Oxidants modulate heat shock proteins (Hsp), interleukins (IL), and cell death pathways, including apoptosis. This multicenter prospective observational study was designed to ascertain whether an oxidant/antioxidant imbalance is an independent sepsis discriminator and mortality predictor in intensive care unit (ICU) patients with sepsis ( = 145), compared to non-infectious critically ill patients ( = 112) and healthy individuals ( = 89).

COVID-19 ARDS: Points to Be Considered in Mechanical Ventilation and Weaning.

The COVID-19 disease can cause hypoxemic respiratory failure due to ARDS, requiring invasive mechanical ventilation. Although early studies reported that COVID-19-associated ARDS has distinctive features from ARDS of other causes, recent observational studies have demonstrated that ARDS related to COVID-19 shares common clinical characteristics and respiratory system mechanics with ARDS of other origins. Therefore, mechanical ventilation in these patients should be based on strategies aiming to mitigate ventilator-induced lung injury.

Ventilatory Ratio Threshold for Unassisted Breathing: A Retrospective Exploratory Analysis.

Background: The ventilatory ratio (VR) is a simple index of ventilatory efficiency and dead space. Because increased dead space and high ventilatory demands impose a limitation to unassisted ventilation, and may predispose patients to injurious strong efforts during assisted ventilation, evaluation of the VR could provide helpful information during weaning. We hypothesize that there is a threshold of VR associated with tolerance of unassisted breathing.

Performance of Lung Ultrasound for Monitoring Interstitial Lung Disease.

Objectives: In this study, we sought to assess the validity of lung ultrasound (LUS) during the follow-up of patients with a wide spectrum of interstitial lung diseases (ILDs).

Methods: Twenty-four patients (13 males, 11 females; mean age ± SD, 65.4 ± 14.

Uncoupling of IL-6 signaling and LC3-associated phagocytosis drives immunoparalysis during sepsis.

Immune deactivation of phagocytes is a central event in the pathogenesis of sepsis. Herein, we identify a master regulatory role of IL-6 signaling on LC3-associated phagocytosis (LAP) and reveal that uncoupling of these two processes during sepsis induces immunoparalysis in monocytes/macrophages. In particular, we demonstrate that activation of LAP by the human fungal pathogen Aspergillus fumigatus depends on ERK1/2-mediated phosphorylation of p47phox subunit of NADPH oxidase.

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis.

Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin.

Inspiratory effort and breathing pattern change in response to varying the assist level: A physiological study.

Aim: To describe the response of breathing pattern and inspiratory effort upon changes in assist level and to assesss if changes in respiratory rate may indicate changes in respiratory muscle effort.

Methods: Prospective study of 82 patients ventilated on proportional assist ventilation (PAV+). At three levels of assist (20 %-50 %-80 %), patients' inspiratory effort and breathing pattern were evaluated using a validated prototype monitor.

Lung- and Diaphragm-Protective Ventilation.

Mechanical ventilation can cause acute diaphragm atrophy and injury, and this is associated with poor clinical outcomes. Although the importance and impact of lung-protective ventilation is widely appreciated and well established, the concept of diaphragm-protective ventilation has recently emerged as a potential complementary therapeutic strategy. This Perspective, developed from discussions at a meeting of international experts convened by PLUG (the Pleural Pressure Working Group) of the European Society of Intensive Care Medicine, outlines a conceptual framework for an integrated lung- and diaphragm-protective approach to mechanical ventilation on the basis of growing evidence about mechanisms of injury.

A physiology-based mathematical model for the selection of appropriate ventilator controls for lung and diaphragm protection.

Mechanical ventilation is used to sustain respiratory function in patients with acute respiratory failure. To aid clinicians in consistently selecting lung- and diaphragm-protective ventilation settings, a physiology-based decision support system is needed. To form the foundation of such a system, a comprehensive physiological model which captures the dynamics of ventilation has been developed.

Validation of a Proposed Algorithm for Assistance Titration During Proportional Assist Ventilation With Load-Adjustable Gain Factors.

Background: The present study aimed to validate a recently proposed algorithm for assistance titration during proportional assist ventilation with load-adjustable gain factors, based on a noninvasive estimation of maximum inspiratory pressure (peak P) and inspiratory effort (pressure-time product [PTP] peak P).

Methods: Retrospective analysis of the recordings obtained from 26 subjects ventilated on proportional assist ventilation with load-adjustable gain factors under different conditions, each considered as an experimental case. The estimated inspiratory output (peak P) and effort (PTP-peak P) were compared with the actual-determined by the measurement of transdiaphragmatic pressure- and the derived PTP.

Akt2 deficiency protects from acute lung injury via alternative macrophage activation and miR-146a induction in mice.

Acute respiratory distress syndrome (ARDS) is a major cause of respiratory failure, with limited effective treatments available. Alveolar macrophages participate in the pathogenesis of ARDS. To investigate the role of macrophage activation in aseptic lung injury and identify molecular mediators with therapeutic potential, lung injury was induced in wild-type (WT) and Akt2(-/-) mice by hydrochloric acid aspiration.

Impact of lung ultrasound on clinical decision making in critically ill patients.

Purpose: To assess the impact of lung ultrasound (LU) on clinical decision making in mechanically ventilated critically ill patients.

Methods: One hundred and eighty-nine patients took part in this prospective study. The patients were enrolled in the study when LU was requested by the primary physician for (1) unexplained deterioration of arterial blood gases and (2) a suspected pathologic entity [pneumothorax, significant pleural effusion (including parapneumonic effusion, empyema, or hemothorax), unilateral atelectasis (lobar or total), pneumonia and diffuse interstitial syndrome (pulmonary edema)].

Pulmonary microRNA profiling in a mouse model of ventilator-induced lung injury.

The aim of this study was to investigate the changes induced by high tidal volume ventilation (HVTV) in pulmonary expression of micro-RNAs (miRNAs) and identify potential target genes and corresponding miRNA-gene networks. Using a real-time RT-PCR-based array in RNA samples from lungs of mice subjected to HVTV for 1 or 4 h and control mice, we identified 65 miRNAs whose expression changed more than twofold upon HVTV. An inflammatory and a TGF-β-signaling miRNA-gene network were identified by in silico pathway analysis being at highest statistical significance (P = 10(-43) and P = 10(-28), respectively).