Critical care clinics
-
It is now recognized that sepsis is not a uniformly proinflammatory state. There is a well-recognized counter anti-inflammatory response that occurs in many patients. ⋯ Studies in animals and humans have now identified a small number of biologic responses that characterize this immunosuppressed state, such as lymphocyte death, HLA receptor downregulation, and monocyte exhaustion. Researchers are now trying to use these as markers of individual immunosuppression to predict outcomes and identify patients who would and would not benefit from new immune stimulatory therapies.
-
Numerous compounds have been tested as potential biomarkers for multiple possible applications within intensive care medicine but none is or will ever be sufficiently specific or sensitive for the heterogeneous syndromes of critical illness. New technology and access to huge patient databases are providing new biomarker options and the focus is shifting to combinations of several or multiple biomarkers rather than the single markers that research has concentrated on in the past. Biomarkers will increasingly be used as part of routine clinical practice in the future, complementing clinical examination and physician expertise to provide accurate disease diagnosis, prediction of complications, personalized treatment guidance, and prognosis.
-
There is a tight relationship between lactate levels (and its changes over time) with morbidity and mortality and the presence of tissue hypoxia/hypoperfusion in both models of shock and clinical studies. These findings have placed lactate in the center of guiding resuscitation in patients with increased lactate levels. However, given the complex metabolism and clearance of lactate, especially in sepsis, the actual use of lactate is more complex than suggested by some guidelines. By using other markers of tissue hypoperfusion together with lactate levels provides a more solid framework to guide the initial hours of resuscitation.
-
Critical care clinics · Jan 2020
Review Historical ArticleThe History of Biomarkers: How Far Have We Come?
Sepsis is one of the oldest and most elusive syndromes in medicine that is still incompletely understood. Biomarkers may help to transform sepsis from a physiologic syndrome to a group of distinct biochemical disorders. This will help to differentiate between systemic inflammation of infectious and noninfectious origin and aid therapeutic decision making, hence improve the prognosis for patients, guide antimicrobial therapy, and foster the development of novel adjunctive sepsis therapies. To reach this goal requires increased systematic investigation that includes twenty-first century scientific approaches and technologies and appropriate clinical evaluation.
-
Critical care clinics · Jan 2020
ReviewCheck Point Inhibitors and Their Role in Immunosuppression in Sepsis.
Checkpoint regulators are a group of membrane-bound receptors or ligands expressed on immune cells to regulate the immune cell response to antigen presentation and other immune stimuli, such as cytokines, chemokines, and complement. In the context of profound immune activation, such as sepsis, the immune system can be rendered anergic by these receptors to prevent excessive inflammation and tissue damage. If this septic immunosuppression is prolonged, the host is unable to mount the appropriate immune response to a secondary insult or infection. This article describes the manner in which major regulators in the B7-CD28 family and their ligands mediate immunosuppression in sepsis.