RESUMO
Mechanical ventilation serves as crucial life support for critically ill patients. Although it is life-saving prolonged ventilation carries risks and complications like barotrauma, Ventilator-associated pneumonia, sepsis, and many others. Optimizing patient-ventilator interactions and facilitating early weaning is necessary for improved intensive care unit (ICU) outcomes. Traditionally Pressure support ventilation (PSV) mode is widely used for weaning patients who are intubated and mechanically ventilated. Neurally adjusted ventilatory assist (NAVA) mode of the ventilator is an emerging ventilator mode that delivers pressure depending on the patient's respiratory drive, which in turn prevents over-inflation and improves the patient's ventilator interactions. Our article revises and compares the effectiveness of NAVA compared to PSV ventilation under different contexts. Overall we conclude that NAVA level of ventilation can be safely administered in a patient with acute respiratory failure, provided diaphragmatic paralysis is not considered. NAVA improves asynchrony index, wean-off time, and sleep quality and is associated with increased ventilator-free days. These results are based on small-scale studies with low power, and further studies are warranted in large-scale cohorts with more diverse populations to confirm these results.
RESUMO
Psychiatric use of lithium has been associated with hypoglycemic effects, but its effect on type 1 diabetes mellitus (T1D) is unknown. In streptozotocin (STZ) induced murine models of T1D, microdose lithium therapy improved hyperglycemia, attenuated body weight loss and prevented early signs of diabetic kidney injury. This beneficial effect was associated with preservation of pancreatic islet histology and ß-cell production of insulin as well as mitigated oxidative damage of islets. Mechanistically, lithium in islets cells induced inhibitory phosphorylation of glycogen synthase kinase 3ß (GSK3ß), the major molecular target of lithium that has been recently implicated in non-canonical regulation of Nrf2 activity. In turn, Nrf2 antioxidant response was potentiated in islets, marked by nuclear translocation of Nrf2 and augmented expression of its target antioxidant enzyme heme oxygenase 1 (HO-1). Conversely, cotreatment with trigonelline, a selective blockade of Nrf2, offset the lithium enhanced Nrf2 antioxidant response in islets, blunted the protective effect of lithium on pancreatic islets and ß-cells, and abolished the hypoglycemic activity of lithium in STZ-injured mice. Collectively, our findings suggest that microdose lithium confers a protective effect on islet ß-cells via targeting the GSK3ß-regulated Nrf2 antioxidant response and thereby ameliorates T1D and its related kidney impairment.
