Sepsis-associated delirium: the pro and con of C5a blockade

The intimate mechanisms of sepsis-induced delirium are unknown. Among the potential contributing factors, the breakdown of the blood–brain barrier is considered a key determinant of brain dysfunction. The complement activation is paramount to an appropriate activation of the central nervous system during stress. C3a and C5a have been extensively studied and may be involved in sepsis-induced delirium. Here we discuss the pro and con for inhibiting C5a to attenuate brain damage during sepsis. In particular, we discuss the hypothesis that C5a increased blood–brain barrier permeability amy ease the brain to mount an appropriate response to sepsis. Thus, blockade of C5a may be detrimental, resulting in an attenuated response of the stress system

Corticosteroids for community-acquired pneumonia: time to act!

The use of corticosteroids for the treatment of community-acquired pneumonia has been reported for almost 50 years. A recent systematic analysis of the relevant literature suggested that corticosteroids reduce the critical illness associated with community-acquired pneumonia. There is little doubt that a prolonged administration of a moderate dose of corticosteroids may alleviate the systemic inflammatory response and subsequent organ dysfunction in severe infection. Whether these favorable effects on morbidity may translate into better survival and quality of life needs to be addressed in additional adequately powered randomized controlled trials

Immune Effects of Corticosteroids in Sepsis

Sepsis, a life-threatening organ dysfunction, results from a dysregulated host response to invading pathogens that may be characterized by overwhelming systemic inflammation or some sort of immune paralysis. Sepsis remains a major cause of morbidity and mortality. Treatment is nonspecific and relies on source control and organ support. Septic shock, the most severe form of sepsis is associated with the highest rate of mortality. Two large multicentre trials, undertaken 15 years apart, found that the combination of hydrocortisone and fludrocortisone significantly reduces mortality in septic shock. The corticosteroids family is composed of several molecules that are usually characterized according to their glucocorticoid and mineralocorticoid power, relative to hydrocortisone. While the immune effects of glucocorticoids whether mediated or not by the intracellular glucocorticoid receptor have been investigated for several decades, it is only very recently that potential immune effects of mineralocorticoids via non-renal mineralocorticoid receptors have gained popularity. We reviewed the respective role of glucocorticoids and mineralocorticoids in counteracting sepsis-associated dysregulated immune systems