Endothelial cells line the inner portion of the heart, blood vessels, and lymphatic vessels; a basal membrane of extracellular matrix lines the extraluminal side of endothelial cells. The apical side of endothelial cells is the site for the glycocalyx, which is a complex network of macromolecules, including cell-bound proteoglycans and sialoproteins. Sepsis-associated alterations of this structure may compromise endothelial permeability with associated interstitial fluid shift and generalized edema. Indeed, in sepsis, the glycocalyx acts as a target for inflammatory mediators and leukocytes, and its ubiquitous nature explains the damage of tissues that occurs distant from the original site of infection. Inflammatory-mediated injury to glycocalyx can be responsible for a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and hepatic dysfunction. Moreover, some markers of glycocalyx degradation, such as circulating levels of syndecan or selectins, may be used as markers of endothelial dysfunction and sepsis severity. Although a great deal of experimental evidence shows that alteration of glycocalyx is widely involved in endothelial damage caused by sepsis, therapeutic strategies aiming at preserving its integrity did not significantly improve the outcome of these patients.
Postoperative atrial fibrillation (POAF) is common among surgical patients and associated with a worse outcome. Pathophysiology of POAF is not fully disclosed, and several perioperative factors could be involved. Direct cardiac stimulation from perioperative use of catecholamines or increased sympathetic outflow from volume loss/anaemia/pain may play a role. Metabolic alterations, such as hypo-/hyperglycaemia and electrolyte disturbances, may also contribute to POAF. Moreover, inflammation, both systemic and local, may play a role in its pathogenesis. Strategies to prevent POAF aim at reducing its incidence and ameliorate global outcome of surgical patients. Nonpharmacological prophylaxis includes an adequate control of postoperative pain, the use of thoracic epidural analgesia, optimization of perioperative oxygen delivery, and, possibly, modulation of surgery-associated inflammatory response with immunonutrition and antioxidants. Perioperative potassium and magnesium depletion should be corrected. The impact of those interventions on patients outcome needs to be further investigated.
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.
Continuous veno-venous hemodialysis with high cut-off membranes (HCO-CVVHD) removes inflammatory mediators involved in organ dysfunction during sepsis. The aim of the present study was to assess the variations in SOFA score and identify early predictors of short-term mortality in a cohort of patients with septic shock, treated with HCO-CVVHD for acute kidney injury (AKI). An observational prospective multicenter cohort study was conducted in four mixed medical-surgical ICUs. Thirty-eight patients with septic shock and AKI (KDIGO stage≥1) treated with HCO-CVVHD have been included in this study. Patients were divided into Survivors and non-Survivors according to mortality observed at 72nd hr of treatment. The variation of SOFA scores and clinical/biochemical parameters were described over time for the entire population and specifically for Survivors and non-Survivors. Similarly, circulating inflammatory mediators (as IL-6, TNF-a and IL-10) were described over time. A logistic regression analysis was used to identify the baseline clinical and biochemical parameters associated with 72 hrs-ICU mortality. Overall, the mean SOFA score was 12±3 at baseline, 10.9±3 at 6hrs, 9.8±3 at 12hrs, 8.9±3.3 at 24 hrs, and 8±3.5 at 48 hrs after HCO-CVVHD initiation; and 6.5±2.7 at 24 hrs and 6.6±3 at 48 hrs after HCO-CVVHD discontinuation. In the multivariate regression analysis, baseline serum lactate levels and AKI stage independently correlated with short-term mortality during HCO-CVVHD. A significant reduction was observed in circulating levels of TNFα and IL-6 among Survivors. SOFA score significantly decreased early after initiation of HCO-CVVHD in patients with septic AKI. Baseline lactate levels and the AKI stage resulted to be associated to 72 hrs-ICU-mortality.
12 January 2023 in Journal of Anesthesia, Analgesia and Critical Care
Adult and pediatric palliative care (PC) share common aims and ethical principles but differ in many organizational and practical aspects. The aim of this narrative review is to analyze these differences and focus on which key aspects of pediatric palliative care could integrate adult services for a better care of suffering patients.Interventions which are peculiar of pediatric PC respect to adult PC include: an earlier referral to the PC service to identify the needs and plan the interventions at an earlier stage of the disease; consequently, a more systematic cooperation with the disease-specific physicians to reduce the burden of treatments; a better integration with the community and the social surroundings of the patients, to prevent social isolation and preserve their social role; a more dynamic organization of the PC services, to give patients the chance of being stabilized at in-hospital or residential settings and subsequently discharged and cared at home whenever possible and desired; the implementation of respite care for adults, to help the families coping with the burden of the disease of their beloved and promote the home-based PC.This review underlines the relevance of some key-aspects of pediatric PC that can be beneficial also within PC of adults. Its findings give the chance for a more dynamic and modern organization of adult PC services and may serve as a basis of future research for new interventions.