Pathophysiology of Sepsis in the Elderly: Clinical Impact and Therapeutic Considerations

Abstract

The aging world population will increase the incidence and mortality of severe sepsis. The aim of the present article is to review the pathophysiological differences in sepsis and its clinical impact on the elderly. The impact of immunosenescence on innate and acquired immunity is associated with relative immunologic depression that may favor the spreading of inflammation. Elderly patients also have enhanced apoptotic pathways that may contribute to the incidence of mortality due to sepsis. The inflammation-coagulation network is activated by age, explaining the success of some specific therapies. The initial clinical picture of sepsis in the elderly may be ambiguous but the specific pathopysiological changes of aging increase the risk of a sudden deterioration to severe sepsis with the development of a serious cardiovascular dysfunction. The reduced stress tolerance characteristic of aged tissues explains the high incidence of multi-organ failure in such patients. The specific pathophysiological and clinical picture of sepsis underlies the increased mortality in such patients and prompts research on therapeutic strategies with particular benefits to elderly septic patients.

Contribution of host, bacterial factors and antibiotic treatment to mortality in adult patients with bacteraemic pneumococcal pneumonia

“…Interestingly, age was a very strong contributor to mortality even in patients without recorded comorbidities. This could be due to unmeasured or misclassified comorbidities, but another plausible explanation is immunosenescence 30 31. Ageing is associated with changes in both the innate and adaptive immune response, such as an increase in functionally impaired macrophages and a shift from Th1 to Th2 cytokine response 30.…”

“…This could be due to unmeasured or misclassified comorbidities, but another plausible explanation is immunosenescence 30 31. Ageing is associated with changes in both the innate and adaptive immune response, such as an increase in functionally impaired macrophages and a shift from Th1 to Th2 cytokine response 30. Interestingly, a recent study reported age-related impairment of alveolar macrophages and Toll-like receptor levels during pneumonia caused by S pneumoniae in mice 32.…”

Combination of Acute Physiology and Chronic Health Evaluation II score, early lactate area, and N-terminal prohormone of brain natriuretic peptide levels as a predictor of mortality in geriatric patients with septic shock

“…In elderly patients, metabolic disorders and cardiac dysfunction are important components of multiorgan failure after sepsis [13][14][15] and are poor prognostic factors for patients with severe sepsis [16]. In septic patients, lactate is recognized as an important metabolic biomarker, as it is produced following cellular conversion from normal aerobic oxidative phosphorylation to abnormal anaerobic metabolism or abnormal aerobic glycolysis following tissue perfusion-induced cellular hypoxia or sepsis-induced immune cell activation [17,18].…”

Molecular Mechanism Responsible for the Priming of Macrophage Activation

“…Recently, super low levels of LPS have been detected in circulation of humans and experimental animals with adverse health conditions, including obesity, chronic smoking, infection, and aging (8 -12). Humans with these adverse conditions tend to have elevated mortality associated with septic shock (13,14). Endotoxin priming and exacerbated mortality are also observed in experimental animals (15,16).…”