ABSTRACT
Purpose of Review: To highlight the challenges associated with providing sedation and analgesia to critically ill patients with coronavirus disease 2019 (COVID-19) and also understand the pathophysiological alterations induced by the disease process as well as the logistical difficulties encountered by providers caring for these patients. We also discuss the rationale and risks associated with the use of common sedative agents specifically within the context of COVID-19 and provide evidence-based management strategies to help manage sedation and analgesia in such patients. Recent Findings: A significant proportion of patients with COVID-19 require intensive care and mechanical ventilation, thus requiring sedation and analgesia. These patients tend to require higher doses of sedative medications and often for long periods of time. Most of the commonly used sedative and analgesic agents carry unique risks that should be considered within the context of the unique pathophysiology of COVID-19, the logistical issues the disease poses, and the ongoing drug shortages. Summary: With little attention being paid to sedation practices specific to patients with COVID-19 in critical care literature and minimal mention in national guidelines, there is a significant gap in knowledge. We review the existing literature to discuss the unique challenges that providers face while providing sedation and analgesia to critically ill patients with COVID-19 and propose evidence-based management strategies.
ABSTRACT
Acute myocardial infarction (MI) provokes an inflammatory response in the heart that removes damaged tissues to facilitate tissue repair/regeneration. However, overactive and prolonged inflammation compromises healing, which may be counteracted by antiinflammatory mechanisms. A key regulatory factor in an inflammatory response is the antiinflammatory cytokine IL-10, which can be produced by a number of immune cells, including subsets of B lymphocytes. Here, we investigated IL-10-producing B cells in pericardial adipose tissues (PATs) and their role in the healing process following acute MI in mice. We found that IL-10-producing B cells were enriched in PATs compared to other adipose depots throughout the body, with the majority of them bearing a surface phenotype consistent with CD5+ B-1a cells (CD5+ B cells). These cells were detected early in life, maintained a steady presence during adulthood, and resided in fat-associated lymphoid clusters. The cytokine IL-33 and the chemokine CXCL13 were preferentially expressed in PATs and contributed to the enrichment of IL-10-producing CD5+ B cells. Following acute MI, the pool of CD5+ B cells was expanded in PATs. These cells accumulated in the infarcted heart during the resolution of MI-induced inflammation. B cell-specific deletion of IL-10 worsened cardiac function, exacerbated myocardial injury, and delayed resolution of inflammation following acute MI. These results revealed enrichment of IL-10-producing B cells in PATs and a significant contribution of these cells to the antiinflammatory processes that terminate MI-induced inflammation. Together, these findings have identified IL-10-producing B cells as therapeutic targets to improve the outcome of MI.
