Power to mechanical power to minimize ventilator-induced lung injury?

Mechanical ventilation is a life-supportive therapy, but can also promote damage to pulmonary structures, such as epithelial and endothelial cells and the extracellular matrix, in a process referred to as ventilator-induced lung injury (VILI). Recently, the degree of VILI has been related to the amount of energy transferred from the mechanical ventilator to the respiratory system within a given timeframe, the so-called mechanical power. During controlled mechanical ventilation, mechanical power is composed of parameters set by the clinician at the bedside-such as tidal volume (VT), airway pressure (Paw), inspiratory airflow (V'), respiratory rate (RR), and positive end-expiratory pressure (PEEP) level-plus several patient-dependent variables, such as peak, plateau, and driving pressures. Different mathematical equations are available to calculate mechanical power, from pressure-volume (PV) curves to more complex formulas which consider both dynamic (kinetic) and static (potential) components; simpler methods mainly consider the dynamic component. Experimental studies have reported that, even at low levels of mechanical power, increasing VT causes lung damage. Mechanical power should be normalized to the amount of ventilated pulmonary surface; the ratio of mechanical power to the alveolar area exposed to energy delivery is called "intensity." Recognizing that mechanical power may reflect a conjunction of parameters which may predispose to VILI is an important step toward optimizing mechanical ventilation in critically ill patients. However, further studies are needed to clarify how mechanical power should be taken into account when choosing ventilator settings

Mesenchymal stromal cells in chronic respiratory diseases: What’s new?

Chronic respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD), are a major health issue worldwide due to their growing prevalence and high economic costs, which include prolonged medication use and frequent hospitalizations. Both asthma and COPD are incurable, and each is characterized by chronic inflammation, tissue remodeling, and ultrastructural alterations that might not be amenable to available therapies. Mesenchymal stromal cells (MSCs) are non-hematopoietic, immunosuppressive cells found in bone marrow, adipose tissue, placenta, and other tissues and have demonstrated anti-inflammatory actions in a number of preclinical models of asthma and COPD. Although the entire repertoire of action of MSCs has not been elucidated, there is growing interest in the potential clinical utility of MSC-based cell therapy in chronic respiratory diseases. The present review will focus on the most recent mechanisms that have been elucidated from preclinical studies in asthma and COPD. In addition, a comprehensive review of clinical trials conducted to date will be presented.Sociedad Argentina de Fisiologí

Intravenous glutamine decreases lung and distal organ injury in an experimental model of abdominal sepsis

Introduction The protective effect of glutamine, as a pharmacological agent against lung injury, has been reported in experimental sepsis; however, its efficacy at improving oxygenation and lung mechanics, attenuating diaphragm and distal organ injury has to be better elucidated. In the present study, we tested the hypothesis that a single early intravenous dose of glutamine was associated not only with the improvement of lung morpho-function, but also the reduction of the inflammatory process and epithelial cell apoptosis in kidney, liver, and intestine villi. Methods Seventy-two Wistar rats were randomly assigned into four groups. Sepsis was induced by cecal ligation and puncture surgery (CLP), while a sham operated group was used as control (C). One hour after surgery, C and CLP groups were further randomized into subgroups receiving intravenous saline (1 ml, SAL) or glutamine (0.75 g/kg, Gln). At 48 hours, animals were anesthetized, and the following parameters were measured: arterial oxygenation, pulmonary mechanics, and diaphragm, lung, kidney, liver, and small intestine villi histology. At 18 and 48 hours, Cytokine-Induced Neutrophil Chemoattractant (CINC)-1, interleukin (IL)-6 and 10 were quantified in bronchoalveolar and peritoneal lavage fluids (BALF and PLF, respectively). Results CLP induced: a) deterioration of lung mechanics and gas exchange; b) ultrastructural changes of lung parenchyma and diaphragm; and c) lung and distal organ epithelial cell apoptosis. Glutamine improved survival rate, oxygenation and lung mechanics, minimized pulmonary and diaphragmatic changes, attenuating lung and distal organ epithelial cell apoptosis. Glutamine increased IL-10 in peritoneal lavage fluid at 18 hours and bronchoalveolar lavage fluid at 48 hours, but decreased CINC-1 and IL-6 in BALF and PLF only at 18 hours. Conclusions In an experimental model of abdominal sepsis, a single intravenous dose of glutamine administered after sepsis induction may modulate the inflammatory process reducing not only the risk of lung injury, but also distal organ impairment. These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.Centres of Excellence Program (PRONEX-FAPERJ)Brazilian Council for Scientific and Technological Development (CNPq)Carlos Chagas FilhoRio de Janeiro State Research Supporting Foundation (FAPERJ)Sao Paulo State Research Supporting Foundation (FAPESP

New and personalized ventilatory strategies in patients with COVID-19

Coronavirus disease (COVID-19) is caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus and may lead to severe respiratory failure and the need for mechanical ventilation (MV). At hospital admission, patients can present with severe hypoxemia and dyspnea requiring increasingly aggressive MV strategies according to the clinical severity: noninvasive respiratory support (NRS), MV, and the use of rescue strategies such as extracorporeal membrane oxygenation (ECMO). Among NRS strategies, new tools have been adopted for critically ill patients, with advantages and disadvantages that need to be further elucidated. Advances in the field of lung imaging have allowed better understanding of the disease, not only the pathophysiology of COVID-19 but also the consequences of ventilatory strategies. In cases of refractory hypoxemia, the use of ECMO has been advocated and knowledge on handling and how to personalize strategies have increased during the pandemic. The aims of the present review are to: (1) discuss the evidence on different devices and strategies under NRS; (2) discuss new and personalized management under MV based on the pathophysiology of COVID-19; and (3) contextualize the use of rescue strategies such as ECMO in critically ill patients with COVID-19

Early impact of abdominal compartment syndrome on liver, kidney and lung damage in a rodent model

Background: Abdominal compartment syndrome (ACS) sometimes occurs in critically ill patients following damage control surgery. The purpose of the present study was to develop a model of ACS and to evaluate its pathologic impact on liver, kidney, and lung morphology. Methods: Twenty Wistar rats (mass 300\u2013350 g) were randomly divided into four groups: 1) intra-abdominal hypertension (IAH): a laparotomy was performed and the abdomen packed with cotton until an intra-abdominal pressure (IAP) of 15 mm Hg was reached; 2) hypovolemia (HYPO): blood was withdrawn until a mean arterial pressure ~60 mm Hg was reached; 3) IAH + HYPO (to resemble clinical ACS); and 4) sham surgery. After 3 hours of protective mechanical ventilation, the animals were euthanized and the liver, kidney and lungs removed to examine the degree of tissue damage. Results: IAH resulted in the following: oedema and neutrophil infiltration in the kidney; necrosis, congestion, and microsteatosis in the liver; and alveolar collapse, haemorrhage, interstitial oedema, and neutrophil infiltration in the lungs. Furthermore, IAH was associated with greater cell apoptosis in the kidney, liver and lungs compared to sham surgery. HYPO led to oedema and neutrophil infiltration in the kidney. The combination of IAH and HYPO resulted in all the aforementioned changes in lung, kidney and liver tissue, as well as exacerbation of the inflammatory process in the kidney and liver and kidney cell necrosis and apoptosis. Conclusions: Intra-abdominal hypertension by itself is associated with kidney, liver and lung damage; when combined with hypovolemia, it leads to further impairment and organ damage

DNA nanoparticle-mediated thymulin gene therapy prevents airway remodeling in experimental allergic asthma

Thymulin has been shown to present anti-inflammatory and anti-fibrotic properties in experimental lung diseases. We hypothesized that a biologically active thymulin analog gene, methionine serum thymus factor, delivered by highly compacted DNA nanoparticles may prevent lung inflammation and remodeling in a mouse model of allergic asthma. The DNA nanoparticles are composed of a single molecule of plasmid DNA compacted with block copolymers of poly-L-lysine and polyethylene glycol (CK30PEG), which have been found safe in a human phase I/II clinical trial. Thymulin plasmids were detected in the lungs of ovalbumin-challenged asthmatic mice up to 27days after administration of DNA nanoparticles carrying thymulin plasmids. A single dose of DNA nanoparticles carrying thymulin plasmids prevented lung inflammation, collagen deposition and smooth muscle hypertrophy in the lungs of a murine model of ovalbumin-challenged allergic asthma, leading to improved lung mechanics. In the present model of chronic allergic asthma, highly compacted DNA nanoparticles using thymulin analog gene modulated the inflammatory and remodeling processes improving lung mechanics.Instituto de Investigaciones Bioquímicas de La Plat

Distribution of transpulmonary pressure during one-lung ventilation in pigs at different body positions

Background. Global and regional transpulmonary pressure (PL) during one-lung ventilation (OLV) is poorly characterized. We hypothesized that global and regional PL and driving PL (ΔPL) increase during protective low tidal volume OLV compared to two-lung ventilation (TLV), and vary with body position.Methods. In sixteen anesthetized juvenile pigs, intra-pleural pressure sensors were placed in ventral, dorsal, and caudal zones of the left hemithorax by video-assisted thoracoscopy. A right thoracotomy was performed and lipopolysaccharide administered intravenously to mimic the inflammatory response due to thoracic surgery. Animals were ventilated in a volume-controlled mode with a tidal volume (VT) of 6 mL kg−1 during TLV and of 5 mL kg−1 during OLV and a positive end-expiratory pressure (PEEP) of 5 cmH2O. Global and local transpulmonary pressures were calculated. Lung instability was defined as end-expiratory PL<2.9 cmH2O according to previous investigations. Variables were acquired during TLV (TLVsupine), left lung ventilation in supine (OLVsupine), semilateral (OLVsemilateral), lateral (OLVlateral) and prone (OLVprone) positions randomized according to Latin-square sequence. Effects of position were tested using repeated measures ANOVA.Results. End-expiratory PL and ΔPL were higher during OLVsupine than TLVsupine. During OLV, regional end-inspiratory PL and ΔPL did not differ significantly among body positions. Yet, end-expiratory PL was lower in semilateral (ventral: 4.8 ± 2.9 cmH2O; caudal: 3.1 ± 2.6 cmH2O) and lateral (ventral: 1.9 ± 3.3 cmH2O; caudal: 2.7 ± 1.7 cmH2O) compared to supine (ventral: 4.8 ± 2.9 cmH2O; caudal: 3.1 ± 2.6 cmH2O) and prone position (ventral: 1.7 ± 2.5 cmH2O; caudal: 3.3 ± 1.6 cmH2O), mainly in ventral (p ≤ 0.001) and caudal (p = 0.007) regions. Lung instability was detected more often in semilateral (26 out of 48 measurements; p = 0.012) and lateral (29 out of 48 measurements, p < 0.001) as compared to supine position (15 out of 48 measurements), and more often in lateral as compared to prone position (19 out of 48 measurements, p = 0.027).Conclusion. Compared to TLV, OLV increased lung stress. Body position did not affect stress of the ventilated lung during OLV, but lung stability was lowest in semilateral and lateral decubitus position