Sepsis-associated encephalopathy is a severe neurologic syndrome characterized by a diffuse dysfunction of the brain caused by sepsis. This review provides a concise overview of diagnostic tools and management strategies for SAE at the acute phase and in the long term. Early recognition and diagnosis of SAE are crucial for effective management. Because neurologic evaluation can be confounded by several factors in the intensive care unit setting, a multimodal approach is warranted for diagnosis and management. Diagnostic tools commonly employed include clinical evaluation, metabolic tests, electroencephalography, and neuroimaging in selected cases. The usefulness of blood biomarkers of brain injury for diagnosis remains limited. Clinical evaluation involves assessing the patient’s mental status, motor responses, brainstem reflexes, and presence of abnormal movements. Electroencephalography can rule out non-convulsive seizures and help detect several patterns of various severity such as generalized slowing, epileptiform discharges, and triphasic waves. In patients with acute encephalopathy, the diagnostic value of non-contrast computed tomography is limited. In septic patients with persistent encephalopathy, seizures, and/or focal signs, magnetic resonance imaging detects brain injury in more than 50% of cases, mainly cerebrovascular complications, and white matter changes. Timely identification and treatment of the underlying infection are paramount, along with effective control of systemic factors that may contribute to secondary brain injury. Upon admission to the ICU, maintaining appropriate levels of oxygenation, blood pressure, and metabolic balance is crucial. Throughout the ICU stay, it is important to be mindful of the potential neurotoxic effects associated with specific medications like midazolam and cefepime, and to closely monitor patients for non-convulsive seizures. The potential efficacy of targeted neurocritical care during the acute phase in optimizing patient outcomes deserves to be further investigated. Sepsis-associated encephalopathy may lead to permanent neurologic sequelae. Seizures occurring in the acute phase increase the susceptibility to long-term epilepsy. Extended ICU stays and the presence of sepsis-associated encephalopathy are linked to functional disability and neuropsychological sequelae, underscoring the necessity for long-term surveillance in the comprehensive care of septic patients. Weniger anzeigen

Background: Appropriate antibiotic (AB) therapy remains a challenge in the intensive care unit (ICU). Procalcitonin (PCT)-guided AB stewardship could help optimize AB treatment and decrease AB-related adverse effects, but firm evidence is still lacking. Our aim was to compare the effects of PCT-guided AB therapy with standard of care (SOC) in critically ill patients. Methods: We searched databases CENTRAL, Embase and Medline. We included randomized controlled trials (RCTs) comparing PCT-guided AB therapy (PCT group) with SOC reporting on length of AB therapy, mortality, recurrent and secondary infection, ICU length of stay (LOS), hospital LOS or healthcare costs. Due to recent changes in sepsis definitions, subgroup analyses were performed in studies applying the Sepsis-3 definition. In the statistical analysis, a random-effects model was used to pool effect sizes. Results: We included 26 RCTs (n = 9048 patients) in the quantitative analysis. In comparison with SOC, length of AB therapy was significantly shorter in the PCT group (MD – 1.79 days, 95% CI: -2.65, – 0.92) and was associated with a significantly lower 28-day mortality (OR 0.84, 95% CI: 0.74, 0.95). In Sepsis-3 patients, mortality benefit was more pronounced (OR 0.46 95% CI: 0.27, 0.79). Odds of recurrent infection were significantly higher in the PCT group (OR 1.36, 95% CI: 1.10, 1.68), but there was no significant difference in the odds of secondary infection (OR 0.81, 95% CI: 0.54, 1.21), ICU and hospital length of stay (MD – 0.67 days 95% CI: – 1.76, 0.41 and MD – 1.23 days, 95% CI: – 3.13, 0.67, respectively). Conclusions: PCT-guided AB therapy may be associated with reduced AB use, lower 28-day mortality but higher infection recurrence, with similar ICU and hospital length of stay. Our results render the need for better designed studies investigating the role of PCT-guided AB stewardship in critically ill patients. Weniger anzeigen

Background: Mega-dose sodium ascorbate (NaAscorbate) appears beneficial in experimental sepsis. However, its physiological effects in patients with septic shock are unknown. Methods: We conducted a pilot, single-dose, double-blind, randomized controlled trial. We enrolled patients with septic shock within 24 h of diagnosis. We randomly assigned them to receive a single mega-dose of NaAscorbate (30 g over 1 h followed by 30 g over 5 h) or placebo (vehicle). The primary outcome was the total 24 h urine output (UO) from the beginning of the study treatment. Secondary outcomes included the time course of the progressive cumulative UO, vasopressor dose, and sequential organ failure assessment (SOFA) score. Results: We enrolled 30 patients (15 patients in each arm). The mean (95% confidence interval) total 24-h UO was 2056 (1520-2593) ml with placebo and 2948 (2181-3715) ml with NaAscorbate (mean difference 891.5, 95% confidence interval [- 2.1 to 1785.2], P = 0.051). Moreover, the progressive cumulative UO was greater over time on linear mixed modelling with NaAscorbate (P < 0.001). Vasopressor dose and SOFA score changes over time showed faster reductions with NaAscorbate (P < 0.001 and P = 0.042). The sodium level, however, increased more over time with NaAscorbate (P < 0.001). There was no statistical difference in other clinical outcomes. Conclusion: In patients with septic shock, mega-dose NaAscorbate did not significantly increase cumulative 24-h UO. However, it induced a significantly greater increase in UO and a greater reduction in vasopressor dose and SOFA score over time. One episode of hypernatremia and one of hemolysis were observed in the NaAscorbate group. These findings support further cautious investigation of this novel intervention. Trial registration Australian New Zealand Clinical Trial Registry (ACTRN12620000651987), Date registered June/5/2020. Weniger anzeigen

Sepsis and septic shock are life-threatening conditions which are associated with high mortality and considerable healthcare costs. The association between prior angiotensin converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) use and outcomes following sepsis is elusive. The aim of this study is to evaluate the role of the prior use of ACEi and ARBs and outcomes post sepsis and septic shock. A relevant literature review was performed in four databases from inception until July 2022. Independent reviewers first screened the title, abstract and full text, then data extraction and analysis were performed. One post-hoc analysis of a trial and six retrospective cohort studies were included in this review. There were 22% lower odds of in-hospital/30-day mortality among patients who have used ACEi/ARBs in the past, (23.83% vs. 37.20%; OR 0.78, 95% CI 0.64-0.96) as well as reduced 90-day mortality (OR 0.80, 95% CI 0.69-0.92). ACEi/ARBs users were found to have 31% lesser odds of developing acute kidney injury (AKI) as compared to non-users (OR 0.69, 95% CI 0.63-0.76). There was no significant difference in the length of hospital stay (MD 1.26, 95% CI -7.89 to 10.42), need for renal replacement therapy (OR 0.71, 95% CI 0.13- 3.92), mechanical ventilation (OR 1.10, 95% CI 0.88-1.37) or use of vasopressors (OR 1.21, 95% CI 0.91-1.61). Based on this analysis, prior use of ACEi/ARBs lowers the risk of mortality and adverse renal events in patients with sepsis and septic shock. Weniger anzeigen

Purpose: Previously healthy adults with community-onset sepsis were recently reported to have, counterintuitively, higher short-term mortality than those with comorbid conditions. However, the population-level generalizability of this finding and its applicability to all hospitalized septic patients are unclear. Methods: We used a statewide dataset to identify hospitalizations aged ≥18 years with a diagnosis of sepsis in Texas during 2018-2019. Comorbidities were defined as those included in the Charlson Comorbidity Index and other prevalent conditions associated with mortality. Hierarchical models were used to estimate the association of comorbid state with short-term mortality (defined as in-hospital mortality or discharge to hospice), overall and in community-onset and hospital-onset sepsis. Results: Among 120,371 sepsis hospitalizations, 6611 (5.5%) were previously healthy and 105,455 (87.6%) had community-onset sepsis. Short-term mortality among the previously healthy and those with comorbidities was 11.7% vs 28.2% overall, 11.0% vs 25.2% in community-onset sepsis, and 22.0% vs 48.7% in hospital-onset sepsis, respectively. On adjusted analysis, being previously healthy remained associated with lower short-term mortality overall (adjusted odds ratio 0.62 [95% CI 0.57-0.69]), with findings consistent with the primary analysis in community-onset sepsis, hospital-onset sepsis. Conclusions: Previously healthy septic patients had lower short-term mortality compared to those with comorbid conditions. Weniger anzeigen

Sepsis syndromes have been recognized since antiquity yet still pose significant challenges to modern medicine. One of the biggest challenges lies in the heterogeneity of triggers and its protean clinical manifestations, as well as its rapidly progressive and lethal nature. Thus, there is a critical need for biomarkers that can quickly and accurately detect sepsis onset and predict treatment response. In this review, we will briefly describe the current consensus definitions of sepsis and the ideal features of a biomarker. We will then delve into currently available and in-development markers of pathogens, hosts, and their interactions that together comprise the sepsis syndrome. Keywords: critical care, decision-making, infections, intensive care unit, sepsis, shock Weniger anzeigen

Atrial fibrillation (AF) is associated with increased risk of mortality in various clinical conditions. However, the prognostic role of preexisting and new-onset AF in critically ill patients, such as patients with septic or cardiogenic shock remains unclear. This study investigates the prognostic impact of preexisting and new-onset AF on 30-day all-cause mortality in patients with septic or cardiogenic shock. Consecutive patients with sepsis, or septic or cardiogenic shock were enrolled in 2 prospective, monocentric registries from 2019 to 2021. Statistical analyses included Kaplan-Meier, multivariable logistic, and Cox proportional regression analyses. In total, 644 patients were included (cardiogenic shock: n = 273; sepsis/septic shock: n = 361). The prevalence of AF was 41% (29% with preexisting AF, 12% with new-onset AF). Within the entire study cohort, neither preexisting AF (log-rank p = 0.542; hazard ratio [HR] 1.075, 95% confidence interval [CI] 0.848 to 1.363, p = 0.551) nor new-onset AF (log-rank p = 0.782, HR = 0.957, 95% CI 0.683 to 1.340, p = 0.797) were associated with 30-day all-cause mortality compared with non-AF. In patients with AF, ventricular rates >120 beats/min compared with ≤120 beats/min were shown to increase the risk of reaching the primary end point in AF patients with cardiogenic shock (log-rank p = 0.006, HR 1.886, 95% CI 1.164 to 3.057, p = 0.010). Furthermore, logistic regression analyses suggested increased age was the only predictor of new-onset AF (odds ratio 1.042, 95% CI 1.018 to 1.066, p = 0.001). In conclusion, neither the presence of preexisting AF nor the occurrence of new-onset AF was associated with the risk of 30-day all-cause mortality in consecutive patients admitted with cardiogenic shock. Weniger anzeigen

Background: Vasopressin is a second-line vasoactive agent for refractory septic shock. Vasopressin loading is not generally performed because of the lack of evidence for its effects and safety. However, based on our previous findings, we hypothesized it can predict the responsibility to vasopressin infusion with safety, and prospectively examined it in the present study. Methods: Vasopressin loading was performed via the intravenous administration of a bolus of 1 U, followed by its continuous infusion at 1U/h in patients with septic shock treated with ≥ 0.2 μg/kg/min noradrenaline. An arterial pressure wave analysis was conducted, and endocrinological tests were performed immediately prior to vasopressin loading. We classified patients into responders/non-responders based on mean arterial pressure (MAP) changes after vasopressin loading. Based on our previous findings, the lower tertile of MAP changes was selected as the cut-off. The change in the catecholamine index (CAI) after 6 h was assigned as the primary outcome. Digital ischemia, mesenteric ischemia, and myocardial ischemia during the admission period were prospectively and systematically recorded as adverse events. Results: Ninety-two patients were registered during the study period and examined. Sixty-two patients with a MAP change > 22 mmHg were assigned as responders and the others as non-responders. Blood adrenocorticotropic hormone levels were significantly higher in non-responders. Stroke volume variations were higher in responders before loading, while stroke volume and dP/dtmax were higher in responders after loading. Median CAI changes were – 10 in responders and 0 in non-responders, which was significantly lower in the former (p < 0.0001). AUROC of MAP change with vasopressin loading to predict CAI change < 0 after continuous infusion was 0.843 with sensitivity of 0.92 and specificity of 0.77. Ischemia events were observed in 5 cases (5.4%). Conclusions: Vasopressin loading may be safely introduced for septic shock. Vasopressin loading may be used to predict responses to its continuous infusion and select appropriate strategies to increase blood pressure. Weniger anzeigen

Purpose of review: In the current review, we highlight developing strategies taken by healthcare systems to improve posthospital outcomes for sepsis and critical illness. Recent findings: Multiple studies conducted in the adult population over the last 18 months have advanced current knowledge on postdischarge care after sepsis and critical illness. Effective interventions are complex and multicomponent, targeting the multilevel challenges that survivors face. Health systems can leverage existing care models such as primary care or invest in specialty programs to deliver postdischarge care. Qualitative and implementation science studies provide insights into important contextual factors for program success. Several studies demonstrate successful application of telehealth to improve reach of postdischarge support. Research is beginning to identify subtypes of survivors that may respond to tailored intervention strategies. Summary: Several successful critical illness survivor models of care have been implemented and knowledge about effectiveness, cost, and implementation factors of these strategies is growing. Further innovation is needed in intervention development and evaluation to advance the field. Weniger anzeigen

Objectives: Clinical sepsis phenotypes may be defined by a wide range of characteristics such as site of infection, organ dysfunction patterns, laboratory values, and demographics. There is a paucity of literature regarding the impact of site of infection on the timing and pattern of clinical sepsis markers. This study hypothesizes that important phenotypic variation in clinical markers and outcomes of sepsis exists when stratified by infection site. Design: Retrospective cohort study. Setting: Five hospitals within the Wake Forest Health System from June 2019 to December 2019. Patients: Six thousand seven hundred fifty-three hospitalized adults with a discharge International Classification of Diseases, 10th Revision code for acute infection who met systemic inflammatory response syndrome (SIRS), quick Sepsis-related Organ Failure Assessment (qSOFA), or Sequential Organ Failure Assessment (SOFA) criteria during the index hospitalization. Interventions: None. Measurements and main results: The primary outcome of interest was a composite of 30-day mortality or shock. Infection site was determined by a two-reviewer process. Significant demographic, vital sign, and laboratory result differences were seen across all infection sites. For the composite outcome of shock or 30-day mortality, unknown or unspecified infections had the highest proportion (21.34%) and CNS infections had the lowest proportion (8.11%). Respiratory, vascular, and unknown or unspecified infection sites showed a significantly increased adjusted and unadjusted odds of the composite outcome as compared with the other infection sites except CNS. Hospital time prior to SIRS positivity was shortest in unknown or unspecified infections at a median of 0.88 hours (interquartile range [IQR], 0.22-5.05 hr), and hospital time prior to qSOFA and SOFA positivity was shortest in respiratory infections at a median of 54.83 hours (IQR, 9.55-104.67 hr) and 1.88 hours (IQR, 0.47-17.40 hr), respectively. Conclusions: Phenotypic variation in illness severity and mortality exists when stratified by infection site. There is a significantly higher adjusted and unadjusted odds of the composite outcome of 30-day mortality or shock in respiratory, vascular, and unknown or unspecified infections as compared with other sites. Keywords: biological variation, phenotypic variability, sepsis, septic shock, systemic inflammatory response syndrome Weniger anzeigen