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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Study hypothesis : Implementation of a new pathway dedicated to septic patients within the emergency department (ED) would improve early management, organ dysfunction, and outcome. Methods: During phase 1, all consecutive adult patients with infection and qualifying quick Sequential Organ Failure Assessment (qSOFA) score upon ED admission were managed according to standards of care. A multifaceted intervention was then performed (implementation phase): educational program, creation of a sepsis alert upon ED admission incorporated in the professional software, together with severity scores and Surviving Sepsis Campaign (SSC) bundle reminders, and dedication of two rooms to the management of septic patients (sepsis unit). ⋯ Mortality significantly decreased during the second phase, on day 3 (28% vs. 15%, P = 0.008) and on day 28 (40% vs. 28%, P = 0.013). Conclusion: Systematic detection, education, and per protocol organization with a sepsis unit dedicated to the early management of septic patients appear to improve compliance with SSC bundles, organ dysfunction, and short-term mortality. These results warrant to be confirmed by prospective studies.
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Thrombomodulin alfa (TM alfa) has been shown effective for treatment of disseminated intravascular coagulation (DIC) associated with sepsis, although the optimal therapeutic plasma concentration has not been clarified. In the present study, the plasma trough concentration of TM alfa in septic patients with DIC was determined, then the cutoff value for that concentration showing influence on treatment outcome was calculated using a receiver operating characteristic curve. With a cutoff value of 1,010, the area under the curve of the receiver operating characteristic was 0.669 (95% confidence interval, 0.530-0.808), with sensitivity of 0.458 and specificity of 0.882. ⋯ The above-cutoff group showed a significantly higher 90-day survival rate (91.7%) as compared with the below-cutoff group (63.4%) ( P = 0.017), with a hazard ratio of 0.199 (95% confidence interval, 0.045-0.871). Interestingly, the incidence of hemorrhagic adverse effects was not significantly different between the groups. Based on these results, the recommended plasma trough concentration of TM alfa for treatment of septic DIC is 1,010 ng/mL, which should minimize the risk of severe bleeding while maximizing the therapeutic effect.
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Randomized Controlled Trial
Chronic ethanol use worsens gut permeability and alters tight junction expression in a murine sepsis model.
Alcohol use disorder is associated with increased mortality in septic patients. Murine studies demonstrate that ethanol/sepsis is associated with changes in gut integrity. This study examined intestinal permeability after ethanol/sepsis and investigated mechanisms responsible for alterations in barrier function. ⋯ The frequency of CD4 + cells expressing TNF and IL-17A and the frequency of CD8 + cells expressing IFN-γ in Peyer's Patches were also increased in ethanol/CLP. Thus, there is an ethanol-specific worsening of gut barrier function after CLP that impacts all pathways of intestinal permeability, mediated, in part, via changes to the tight junction. Differences in the host response in the setting of chronic alcohol use may play a role in future precision medicine approaches toward the treatment of sepsis.
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Background: As an immune marker, serum soluble programmed cell death ligand-1 (sPD-L1) is significantly increased in sepsis and is predictive of mortality. We investigated the prognostic value of sPD-L1 in postseptic immunosuppression and progression to chronic critical illness (CCI). Methods: Adults with sepsis in intensive care units (ICUs) for the first time were screened and assigned to either a CCI group (ICU stay ≥14 days with persistent organ dysfunction) or a rapid recovery (RAP) group based on clinical outcome. ⋯ D 7 -sPD-L1 remained higher in the CCI group, and the area under the curve that predicted the occurrence of CCI was equivalent to the APACHE II score, with areas under the curve of 0.782 and 0.708, respectively. Conclusions: The severity of infection and immunosuppression in sepsis may be linked to serum sPD-L1. D 7 -sPD-L1 is valuable in predicting the progression of CCI in patients.
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Key underlying pathological mechanisms contributing to sepsis are hemostatic dysfunction and overwhelming inflammation. Platelet aggregation is required for hemostasis, and platelets are also separately involved in inflammatory responses that require different functional attributes. Nevertheless, P2Y receptor activation of platelets is required for this dichotomy of function. ⋯ However, platelets isolated from patients with sepsis lost the ability to undergo chemotaxis toward N -formylmethionyl-leucyl-phenylalanine, and this suppression was evident at admission through to and including discharge from hospital. Our results suggest that P2Y 1 -dependent inflammatory function in platelets is lost in patients with sepsis resulting from community-acquired pneumonia. Further studies will need to be undertaken to determine whether this is due to localized recruitment to the lungs of a platelet responsive population or loss of function as a result of dysregulation of the immune response.