Daily Ards Research Analysis

BACKGROUND: Mechanical power (MP) estimates the energy delivered to the lungs during ventilation. This study reviews pediatric research on MP and its association with ventilation duration and mortality. METHODS: According to the PRISMA guidelines, a systematic search was conducted in the databases Pubmed, Embase, Scopus, Web of Science, Lilacs, and Cochrane. A manual search was performed in the bibliography of the included studies and in the grey literature. All articles on mechanical power were included, and then studies focusing on the pediatric population were selected. The risk of bias was assessed using the Newcastle-Ottawa scale. RESULTS: Nine articles were included. No randomized controlled trials were found. A total of 1769 children were included, of whom 1417 were diagnosed with acute respiratory distress syndrome (ARDS), while 148 had no evidence of lung injury. The median age ranged from 5.7 to 114 months, and 275 children died. MP values were found to be associated with increased mortality. Most studies utilized adaptations of the Gattinoni or Becher formulas. In children without lung pathology, average MP values were 3.93 ± 1.1 J/min. For children with ARDS, median MP values were 10 J/min in survivors and 15 J/min in non-survivors. Elevated MP values, particularly when assessed dynamically within the first 24 h of ventilation and adjusted for body weight, were consistently associated with increased mortality and, in some studies, prolonged ventilation duration. CONCLUSION: Mechanical power can be measured in children on pressure-controlled ventilation, preferably adjusted for body weight. Further research is needed to define risk thresholds.

Over the past decade, global investigations have rigorously assessed the safety and therapeutic potential of mesenchymal stem cells (MSCs) in managing acute respiratory distress syndrome (ARDS). MSCs, obtained from sources like bone marrow, adipose tissue, and umbilical cord, exert therapeutic effects in ARDS primarily through complex paracrine mechanisms, including anti-inflammatory, immunoregulatory, pro-reparative, antioxidant, antimicrobial, and mitochondrial transfer functions. Preclinical studies have consistently demonstrated significant therapeutic benefits. Clinical trials have further confirmed a favorable safety profile, with no significant infusion-related toxicity or serious adverse events observed even at higher doses (up to 10 × 10⁶ cells/kg) or following multiple administrations. Yet, while some early-phase clinical trials have not conclusively demonstrated a significant reduction in mortality among ARDS patients, multiple studies note diminished inflammatory biomarkers, enhanced markers of endothelial and epithelial repair (e.g., angiopoietin-2), and suggestive benefits in subgroups like younger patients or those receiving higher doses of viable cells. MSC-derived therapies, particularly extracellular vesicles and conditioned medium, represent promising "cell-free" strategies that may overcome limitations associated with live-cell therapy. Despite encouraging progress, clinical translation faces challenges, including optimizing cell sources, preparation, dosing, delivery, and developing robust potency assays. Future research should prioritize large, high-quality randomized trials to confirm efficacy across various ARDS etiologies and clinical phenotypes, evaluate repeat dosing, and explore innovative strategies such as gene modification, cellular preconditioning, and combination therapies. Collectively, MSCs and their derivatives hold substantial potential for ARDS treatment, though their widespread application requires further validation and a deeper understanding of their interactions with the complex ARDS microenvironment.

Acute respiratory distress syndrome (ARDS) is a life-threatening form of acute lung injury (ALI), which is a common cause of respiratory failure and high mortality in critically ill patients. Long-term mortality and cognitive impairment have been documented in ARDS patients after hospital discharge. Inflammation plays a key role in ALI/ARDS pathogenesis. Neural cholinergic signaling regulates cytokine responses and inflammation. Here, we studied the effects of galantamine, an approved cholinergic drug (for Alzheimer's disease) on ALI/ARDS severity and inflammation in mice, using a clinically relevant mouse model induced by intratracheal administration of hydrochloric acid and lipopolysaccharide. Mice were treated 30 min prior to each insult with vehicle or galantamine (4 mg/kg, i.p.). Galantamine treatment significantly decreased bronchoalveolar lavage (BAL) and serum TNF, IL-1b, and IL-6 levels, as well as BAL total protein and myeloperoxidase (MPO) and lung histopathology in ALI/ARDS mice. In addition, galantamine improved the functional state of mice with ALI/ARDS during a 10-day monitoring and attenuated lung injury and indices of brain inflammation at 10 days. These findings support further studies utilizing this approved cholinergic drug in therapeutic strategies for ALI/ARDS and its subacute sequelae.