Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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We sought to review the pharmacology of vasoactive therapy and fluid administration in sepsis and septic shock, with specific insight into the physiologic interplay of these agents. A PubMed/MEDLINE search was conducted using the following terms (vasopressor OR vasoactive OR inotrope) AND (crystalloid OR colloid OR fluid) AND (sepsis) AND (shock OR septic shock) from 1965 to October 2020. ⋯ Current guidelines are not in alignment with the data available, which suggests a potential benefit from low-dose fluid administration and early vasopressor exposure. Future data must account for the impact of both of these pharmacotherapies when assessing clinical outcomes and should assess personalization of therapy based on the possible interaction.
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Studies have shown nonlinear relationships between systolic blood pressure (SBP) and outcomes, with increased risk observed at both low and high blood pressure levels. However, the relationships between cumulative times at different SBP levels and outcomes in critically ill patients remain unclear. We hypothesized that an appropriate SBP level is associated with a decrease in adverse outcomes after intensive care unit (ICU) admission. ⋯ SBP at 120 mm Hg to 140 mm Hg was associated with decreased adverse outcomes. Randomized trials are required to determine whether the outcomes in critically ill patients improve with early maintenance of a SBP level at 120 mm Hg to 140 mm Hg.
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Levels of the apoptosis regulator Fas ligand (FasL) are associated with severity of sepsis, but its association with the mortality of sepsis and necroptosis, a regulated cell death mechanism, is not yet clear. We aimed to assess the association of FasL level with outcomes of sepsis and receptor interacting protein kinase-3 (RIPK3), an essential necroptosis mediator, for determining the relationship between FasL and necroptosis. ⋯ The plasma level of FasL was associated with severity of sepsis and was predictive of mortality. However, it was not correlated with RIPK3 level.
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Vascular hypo-reactivity plays a critical role inducing organ injury during hemorrhagic shock. 17β-estradiol (E2) can induce vasodilation to increase blood flow in various vascular beds. This study observed whether E2 can restore vascular hypo-reactivity induced by hemorrhagic shock, and whether E2 effects are associated with RhoA-Rho kinase (ROCK)-myosin light chain kinase phosphatase (MLCP) pathway. The hemorrhagic shock model (40 ± 2 mm Hg for 1 h, resuscitation for 4 h) was established in ovary intact sham operation (OVI), ovariectomized (OVX), and OVX plus E2 supplement female mice. ⋯ In OVX plus E2 supplement mice with hemorrhagic shock, Y-27632 inhibited microvascular reactivity, which was abolished by concomitant U-46619 application. Lastly, hemorrhagic shock remarkably decreased intestinal loop blood flow, RhoA and ROCK mRNA expressions in vascular tissues in OVX females, but not in OVI females, which were reversed by E2 supplement. These results indicate that estrogen improves microvascular reactivity during hemorrhagic shock, and RhoA-ROCK signaling pathway may mediate E2 effects.
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Polymyxin B hemoperfusion (PMX-HP) may improve the clinical outcomes of patients with sepsis and gram-negative bacteremia by reducing endotoxin levels. However, the recent studies with the variable degree of renal support have shown that the improvement of survival rate by PMX-HP remains unclear in such patients. Therefore, we investigated whether the addition of PMX-HP to continuous renal replacement therapy (CRRT) could improve the survival rate than CRRT alone. ⋯ To correct for disease severity, propensity score (PS) matching was performed with acute respiratory distress syndrome, mechanical ventilation support, extracorporeal membrane oxygenation, infection source (abdomen), age, inotropic score, SOFA score, C-reactive protein, and procalcitonin levels. Sixty-six PS-matched pairs revealed significantly higher 28-day and 90-day mortality rates in the PMX-HP with CRRT group than in the CRRT-alone group. Considering the mortality rates after PS matching, the additional use of PMX-HP does not improve the clinical outcomes of patients with sepsis and acute kidney injury requiring CRRT.