Shock Patients Research Articles

Effect of timing of intubation on clinical outcomes of patients with septic shock: a retrospective cohort study.

Evidence-based data regarding the timing of the application of invasive mechanical ventilation among adults with septic shock is insufficient. The guidelines fail to provide clear advice about the optimal time to initiate this support. Consequently, we aimed to investigate whether early intubation could improve survival rates in septic shock patients. We conducted a retrospective analysis of the MIMIC-IV database to evaluate the effectiveness of early intubation on mortality in a cohort of septic shock patients. Adults diagnosed with septic shock, according to the Sepsis-3 definition, were included. They were categorized into an early intubation group (first 8h after vasopressor initiation) and a non-early intubation group (unexposed). A propensity score matching (PSM) analysis was used to balance the baseline characteristics between the two groups. The primary outcomes were 30-day and 90-day all-cause mortality rates. In addition, we employed the restricted cubic spline to analyze the potential non-linear relationship between the timing of intubation and 30-day or 90-day all-cause mortality. A total of 6864 adult patients, of whom 2048 were intubated in the first 8h, were evaluated in the final cohort. Following a 1:1 PSM procedure, 2786 patients were successfully paired. At 30days, 288 of 1393 patients (20.7%) in the early intubation group and 381 of 1393 patients (27.4%) in the non-early intubation group had died (hazard ratio [HR] 0.717; 95% confidence interval [CI] 0.616-0.836; p < 0.001). Similarly, the results also showed that early intubation was associated with a lower 90day all-cause mortality rate (HR 0.761; 95% CI 0.663-0.874; p < 0.001). Furthermore, ICU and hospital lengths of stay were significantly different between the groups (3.6 [1.9, 7.1] vs. 2.3 [1.3, 4.3]; p < 0.001 and 8.9 [5.4, 15.1] vs. 7.2 [4.5, 12.0]; p < 0.001). In the subgroup analysis, we further confirmed the robustness of our findings. Additionally, we found that the timing of intubation is inversely U-shaped correlated to the 30day all-cause mortality rate. Among adult patients with septic shock, the early initiation of invasive mechanical ventilation could improve clinical outcomes. The timing of intubation demonstrated an inverse U-shaped association with the 30day all-cause mortality rate, with the peak risk of death occurring at 50.5h after septic shock.

Efficacy of methylene blue in refractory septic shock: study protocol for a multicenter, randomized, placebo-controlled trial

BackgroundSeptic shock is now the leading cause of mortality in intensive care units (ICUs). Refractory septic shock requires high doses of vasopressors. Some previous studies have revealed that methylene blue could improve hypotension status and help reduce the dosage of catecholamines. This study aims to investigate the clinical effect of methylene blue in septic shock and explore whether it can increase arterial pressure and reduce the usage of vasopressors.MethodsThis study is a multicenter, randomized, placebo-controlled trial planning to include 100 refractory septic shock patients. The protocol is to administer a bolus of 2 mg/kg methylene blue intravenously followed by a continuous infusion of 0.5 mg/kg/h for 48 h. The primary outcome is the total dose of vasopressor required in refractory septic shock in the first 48 h. Secondary outcomes include other hemodynamic parameters, oxygen metabolism indexes, tissue perfusion indexes, major organ function indexes, and certain plasma cytokines and other factors.DiscussionThis protocol aims to evaluate the safety and efficacy of methylene blue as adjuvant therapy for refractory septic shock. The main outcome measure will be vasopressor requirements and hemodynamic parameters. Additionally, bedside ultrasonography, blood gases, and cytokines will be assessed to evaluate perfusion, respiratory, and metabolic effects. The results are intended to provide evidence on the safety and efficacy of methylene blue in refractory septic shock, guiding clinical decision-making.Trial registrationThis clinical trial has been registered at ChiCTR (https://www.chictr.org.cn/) on March 16, 2023. ChiCTR registration number: ChiCTR2300069430.

Corticosteroids for Managing Pediatric Sepsis and Septic Shock: A Systematic Review and Meta-analysis.

To assess the efficacy and safety of corticosteroids for the management of pediatric sepsis and septic shock. Ovid MEDLINE, Ovid Embase, CENTRAL, Web of Science (Core Collection) and China National Knowledge Infrastructure were systematically searched up to September 2023. Preprint servers, clinical trial registries and the reference sections of previous reviews were hand-searched. Randomized controlled trials that enrolled pediatric sepsis, septic shock or systemic inflammatory response syndrome patients, compared the use of corticosteroid regimens against standard sepsis care and reported eligible outcomes were included. Title/abstract and full-text screening were conducted in-duplicate. Eligible articles were extracted using a standardized form in-duplicate. Outcomes extracted include mortality incidence, hospital and pediatric intensive care unit length of stay, duration of shock, incidence of adverse events and serious adverse events and incidence of corticosteroid-related adverse events. The risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Assessing Randomized Trials. Random-effects meta-analyses were conducted, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. Sixteen randomized controlled trials (N = 973) were included. Corticosteroid use may be associated with reduced mortality risks (risk ratio: 0.65, 95% CI: 0.50-0.85), shorter length of hospital stay (MD: -3.76 days, 95% CI: -6.66 to -0.86), and shorter pediatric intensive care unit length of stay (MD -2.34 days, 95% CI: -3.14 to -1.53 days). Corticosteroid use may be associated with gastrointestinal bleeding but not a higher risk of secondary infection. No studies reported on serious adverse events. All findings were based on low to very low quality of evidence. While corticosteroids show promise for managing pediatric sepsis and septic shock, the question of how to select the best candidate and the most optimal regimen remains unanswered. Future trials need to focus on assessing corticosteroid-related adverse events and stratifying patient inclusion by sepsis subphenotypes.

Biomarkers as Predictors of Mortality in Sepsis and Septic Shock for Patients Admitted to Emergency Department: Who Is the Winner? A Prospective Study

Background/Objectives: Sepsis and septic shock remain significant contributors to high early mortality rates among patients admitted to the emergency department (ED). The objective of this study was to identify among newer biomarkers those with the highest sensitivity in early mortality prediction. Methods: This prospective, unicentric, observational study enrolled 47 adult patients admitted to the ED between November 2020 and December 2022. This study monitored the kinetics of the older and newer biomarkers, including azurocidin (AZU1), soluble triggering receptor expressed on myeloid cells (sTREM), soluble urokinase-type plasminogen activator receptor (suPAR), high-sensitivity C-reactive protein (hsCRP), procalcitonin (PCT), and interleukin-6 (IL-6), and their capacity in predicting mortality. Results: SuPAR showed the most significant predictive utility for early prognosis of mortality in the ED, with an area under the curve (AUC) of 0.813 (95% CI: 0.672 to 0.912), a cutoff value &gt; 8168 ng/mL, sensitivity of 75%, and specificity of 81.48% (p &lt; 0.001). IL-6 and PCT showed comparable prognostic accuracy, whereas hsCRP and AZU1 demonstrated lower predictive performance. Conclusions: In our study, suPAR, IL-6, and PCT showed good predictive value for short-term mortality in sepsis and septic shock patients.

Visualizing the assumptions of network meta-analysis.

Network meta-analysis (NMA) incorporates all available evidence into a general statistical framework for comparing multiple treatments. Standard NMAs make three major assumptions, namely homogeneity, similarity, and consistency, and violating these assumptions threatens an NMA's validity. In this article, we suggest a graphical approach to assessing these assumptions and distinguishing between qualitative and quantitative versions of these assumptions. In our plot, the absolute effect of each treatment arm is plotted against the level of effect modifiers, and the three assumptions of NMA can then be visually evaluated. We use four hypothetical scenarios to show how violating these assumptions can lead to different consequences and difficulties in interpreting an NMA. We present an example of an NMA evaluating steroid use to treat septic shock patients to demonstrate how to use our graphical approach to assess an NMA's assumptions and how this approach can help with interpreting the results. We also show that all three assumptions of NMA can be summarized as an exchangeability assumption. Finally, we discuss how reporting of NMAs can be improved to increase transparency of the analysis and interpretability of the results.

Cardiogenic shock in general intensive care unit: a nationwide prospective analysis of epidemiology and outcome

Abstract Aims Cardiogenic shock (CS) is a life-threatening disease burdened by a mortality up to 50%. The epidemiology has changed with non-ischaemic aetiologies being predominant, although data were mainly derived from patients admitted to dedicated acute cardiac care. We report the epidemiology and outcome of patients with CS admitted to general intensive care unit (ICU). Methods and results Prospective multicentric epidemiological study including 314 general ICU adhering to the GiViTI nationwide registry from 2011 to 2018, excluding cardiac arrest. The primary endpoint of the study was mortality. The association between clinical factors and mortality was evaluated using a logistic regression model. The odds ratios (ORs) of the covariates quantify their association with mortality during hospitalization. A total of 11 052 patients admitted to general ICU {incidence 2.17%; median age 72 [interquartile range (66–81)], 38.7% were women} with CS were included. Forty-seven per cent of patients had more than three organ insufficiency at the time of admission. The most common CS aetiologies were left heart failure (LHF, 5247—47.5%); acute myocardial infarction (3612—32.6%); right heart failure (RHF, 515—4.6%); and biventricular failure (532—4.8%). A total of 85.5% were mechanically ventilated during the ICU hospitalization. The overall ICU mortality was 44.8%, increasing to 53.4% during the hospitalization in the index hospital and to 54.3% at the latest hospital. Right heart failure–cardiogenic shock patients exhibited the highest mortality risk [OR: 1.19, 95% confidence interval (CI) (0.94–1.50); P &amp;lt; 0.001], followed by biventricular CS [OR 1.04, 95% CI (0.82–1.32)]. Respiratory failure [OR 1.13 (95% CI 1.08–1.19)], coagulation disorder [1.17 (95% CI 1.1–1.24)], renal dysfunction [OR 1.55 (95% CI 1.50–1.61)], and neurological alteration [OR 1.45 (95% CI 1.39–1.50)] were associated with worsen outcome along with severe hypotension [systolic blood pressure &amp;lt; 70 mmHg—OR 2.35, 95% CI (2.06–2.67)], increasing age [OR 2.21 95% CI (2.01–2.42)], and longer ICU stay prior to admission (two-fold increase for each 4.7 days). Conclusion In the general ICU, the aetiology of CS, excluding cardiac arrest, remains characterized mostly by LHF with RHF–CS burdened by higher mortality. Multiorgan failure at admission and longer hospital stay before ICU admission predispose to worsen outcome.

The polymyxin-B direct hemoperfusion OPTimal Initiation timing with Catecholamine PMX-OPTIC study: A multicenter retrospective observational study.

Polymyxin-B direct hemoperfusion (PMX-DHP) is an endotoxin adsorption column-based blood purification therapy. Since one of the most potent effects of PMX-DHP is blood pressure elevations, it may be the most effective when it is introduced at the time when the need for vasopressors is the greatest, which, in turn, may reduce mortality. A multicenter retrospective study was conducted at 24 ICUs in Japan. In each ICU, the 20 most recent consecutive cases of septic shock treated with PMX-DHP were analyzed. The duration between the time of the peak vasopressive agent dose, expressed as the noradrenaline equivalent dose (NEq), and the time of PMX initiation was evaluated. The primary outcome was 28-day mortality, and a multivariable analysis was performed to investigate factors associated with mortality. A total of 480 septic shock patients were included in the analysis. Among all patients, the 28-day mortality group was older, more severely ill, and had a higher body mass index. The NEq peak and NEq on PMX-DHP initiation were both higher in deceased patients. Regarding the timing of PMX-DHP initiation from the NEq peak, -4 << 4 h had more survivors (229/304, 75.3%) than ≤-4 h (50/75, 66.7%) and ≥4 h (66/101, 65.4%) (p = 0.085). When -4 << 4 h was assigned as a reference, the timing of PMX-DHP initiation from the NEq peak of ≤-4 h had an odds ratio of 1.96 (1.07-3.58), p = 0.029, while ≥4 h had an odds ratio of 1.64 (0.94-2.87), p = 0.082 for 28-day mortality, in the multivariable regression analysis. A spline curve of the relationship between the probability of death and the timing of PMX-DHP initiation from the NEq peak showed a downward convex curve with a nadir at timing = 0. The odds ratios of the timing of PMX-DHP initiation other than -4 << 4 h were significantly higher in an older age, male sex, lower BMI, more severe illness, and higher oxygenation. The induction of PMX-DHP at the time of the peak vasopressor dose correlated with lower mortality. PMX-DHP is one of the options available for elevating blood pressure in septic shock, and its initiation either too early or late for shock peak may not improve the outcome.

Assessment of Racial, Ethnic, and Sex-Based Disparities in Time-to-Antibiotics and Sepsis Outcomes in a Large Multihospital Cohort.

To characterize associations between race/ethnicity/sex, time-to-antibiotics, and mortality in patients with suspected sepsis or septic shock. Retrospective cohort study, with race/ethnicity/sex as the exposure, and time-to-antibiotics (relative to emergency department arrival) and in-hospital mortality as the outcome. Five Massachusetts hospitals. Forty-nine thousand six hundred nine adults admitted 2015-2022 with suspected sepsis or septic shock (blood cultures drawn and IV antibiotics administered within 24 hr of arrival, plus evidence of organ dysfunction for sepsis, and hypotension or lactate ≥ 4.0 mmol/L for septic shock). None. Among included patients, 22,598 (46%) were women, 36,626 (75%) were White, and 4,483 (9.2%) were Black. Women had longer median time-to-antibiotics than men when presenting with either suspected sepsis (203 vs. 190 min) or septic shock (160 vs. 142 min). Differences in time-to-antibiotics for women vs. men persisted after adjusting for age, race, comorbidities, source of infection, and severity of illness (adjusted odds ratio [aOR] for 3-6 vs. < 3 hr; 1.16 [95% CI, 1.07-1.25] for sepsis and aOR, 1.09 [95% CI, 1.01-1.18] for septic shock). Median time-to-antibiotics was also longer for Black vs. White patients for both sepsis (215 vs. 194 min; aOR for 3-6 vs. < 3 hr; 1.24 [95% CI, 1.06-1.45]) and septic shock (median 159 vs. 148 min; aOR, 1.32 [95% CI, 1.12-1.55]). There was no association between race/ethnicity/sex and in-hospital mortality for sepsis without shock; however, women with septic shock had higher mortality (aOR, 1.16; 95% CI, 1.04-1.29) vs. men. Higher mortality for women with septic shock persisted when also adjusting for time-to-antibiotics (aOR, 1.16; 95% CI, 1.03-1.32). In a large cohort of patients with sepsis, time-to-antibiotics was longer for both women and Black patients even after detailed risk-adjustment. Women with septic shock had higher adjusted in-hospital mortality than men, but this association was not moderated by time-to-antibiotics.

Impella 5.5: A Systematic Review of the Current Literature.

Impella 5.5 (Abiomed, Danvers, MA, USA) is a temporary mechanical circulatory support device used for patients in cardiogenic shock. This review provides a comprehensive overview of the device's clinical effectiveness, safety profile, patient outcomes, and relevant procedural considerations. We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed/MEDLINE database. The search query included articles available from October 6, 2022, through January 13, 2023. Our initial search identified 75 studies. All records were screened by 2 independent reviewers using the Covidence software for adherence to our inclusion criteria, and 8 retrospective cohort studies were identified as appropriate for inclusion. Across the included studies, the sample size ranged from 4 to 275, with predominantly male cohorts. Indications for Impella support varied, and the duration of support ranged from 9.8 to 70 days. Overall, Impella support appeared to be associated with favorable survival rates and manageable complications in various patient populations. Complications associated with Impella use included bleeding, stroke, and device malfunctions. Two studies compared prolonged and Food and Drug Administration-approved Impella support, showing similar outcomes and adverse events. Impella 5.5 continues to be an attractive option for bridging patients to definitive therapy. Survival during and after Impella 5.5 was favorable for patients regardless of initial indication. However, device use was associated with several important complications, which calls for judicious use and a precontemplated exit strategy. Limitations of this literature review include biases inherent to the retrospective studies included, such as selection and publication bias.

Exploration of different statistical approaches in the comparison of dopamine and norepinephrine in the treatment of shock: SOAP II

BackgroundExploring clinical trial data using alternative methods may enhance original study’s findings and provide new insights. The SOAP II trial has been published more than 10 years ago; but there is still some speculation that some patients may benefit from dopamine administration for shock management. We aimed to reanalyse the trial under different approaches and evaluate for heterogeneity in treatment effect (HTE).MethodsAll patients enrolled in SOAP II were eligible for reanalysis. We used a variety of methods including the win-ratio (WR), a Bayesian reanalysis stratified according to shock type, and both a risk-based and effect-based explorations for HTE. The methods were applied to different endpoints, including a hierarchy of death, new use of renal-replacement therapy (RRT), and new-onset arrhythmia; 28-day mortality; a composite endpoint (mortality, new use of RRT, and new-onset arrhythmia), and days alive and free of ICU at 28-days (DAFICU28).ResultsA total of 1679 patients were included (average age was 64.9 years, 57% male, 62% with septic and 17% with cardiogenic shock). All analysis favoured norepinephrine over dopamine. Under the WR approach, dopamine had fewer wins compared to norepinephrine (WR 0.79; 95% confidence intervals [CI] 0.68–0.92; p = 0.003), evident in both cardiogenic and septic shock subgroups. The Bayesian reanalysis for type of shock showed, for dopamine, a probability of harm of 0.95 for mortality, > 0.99 probability of harm for composite endpoint, and 0.91 probability of harm for DAFICU28. The fewer DAFICU28 with dopamine was more apparent in those with cardiogenic shock (0.92). Under the risk-based HTE, there was a high probability that dopamine resulted fewer DAFICU28 in the highest quartile of predicted mortality risk. The effect-based HTE assessment model did not recommended dopamine over norepinephrine for any combination of possible modifiers including age, type of shock, presence of cardiomyopathy, and SOFA score. Receiving dopamine when the effect-based model recommended norepinephrine was associated with an absolute increase in composite endpoint of 6%.ConclusionThe harm associated with the use of dopamine for the management of shock appears to be present in both septic and cardiogenic shock patients. There was no suggestion of any subgroup in which dopamine was found to be favourable over norepinephrine.

Efficacy of Adjunct Hemoperfusion Compared to Standard Medical Therapy on 28-Day Mortality in Leptospirosis Patients with Renal Failure and Shock: A Single-Center Randomized Controlled Trial.

Hemoperfusion is a novel adjunct therapy that targets the dysregulated inflammatory events in severe sepsis. Previous studies have reported conflicting results on its efficacy and safety. This study was designed to assess the efficacy and safety of hemoperfusion among leptospirosis patients in septic shock and renal failure in terms of improvement in 28-day mortality, SOFA score, level of inflammatory markers, hemodynamics, and renal and pulmonary function. A total of 37 severe leptospirosis patients were enrolled and randomized into either standard medical therapy (SMT) alone, n = 20, or with hemoperfusion (HP), n = 17. Vital signs, urine output, vasopressor dose, PaO2/FiO2 (P/F) ratio, and biochemical parameters of patients from each treatment arm were compared. The hemoperfusion group showed a 36.84% (p = 0.017) risk reduction in 28-day mortality. Levels of procalcitonin, IL6, and lactate significantly decreased from baseline to day 7 in both groups. Statistically significant improvements in serum creatinine (p = 0.04) and PF ratio (p = 0.045) were observed in the hemoperfusion cohort. Intention-to-treat and per-protocol approaches showed that hemoperfusion increased the survival rate and decreased the mortality risk. This benefit for survival persisted even when patients were also receiving extracorporeal membrane oxygenation (ECMO), showing that hemoperfusion's benefits are independent of ECMO use. Hemoperfusion is a safe and effective adjunct therapy for managing severe sepsis. It promotes earlier renal and pulmonary function recovery and improves the survival of septic shock patients.

Low T3 vs low T3T4 euthyroid sick syndrome in septic shock patients: A prospective observational cohort study.

Both phases of euthyroid sick syndrome (ESS) are associated with worse prognosis in septic shock patients. Although there are still no indications for supplementation therapy, there is no evidence that both phases (initial and prolonged) are adaptive or that only prolonged is maladaptive and requires supplementation. To analyze clinical, hemodynamic and laboratory differences in two groups of septic shock patients with ESS. A total of 47 septic shock patients with ESS were divided according to values of their thyroid hormones into low T3 and low T3T4 groups. The analysis included demographic data, mortality scores, intensive care unit stay, mechanical ventilation length and 28-day survival and laboratory with hemodynamics. The Simplified Acute Physiology Score II score (P = 0.029), dobutamine (P = 0.003) and epinephrine requirement (P = 0.000) and the incidence of renal failure and multiple organ failure (MOF) (P = 0.000) were significantly higher for the low T3T4. Hypoalbuminemia (P = 0.047), neutrophilia (P = 0.038), lymphopenia (P = 0.013) and lactatemia (P = 0.013) were more pronounced on T2 for the low T3T4 group compared to the low T3 group. Diastolic blood pressure at T0 (P = 0.017) and T1 (P = 0.007), as well as mean arterial pressure at T0 (P = 0.037) and T2 (P = 0.033) was higher for the low T3 group. The low T3T4 population is associated with higher frequency of renal insufficiency and MOF, with worse laboratory and hemodynamic parameters. These findings suggest potentially maladaptive changes in the chronic phase of septic shock.

Hyperoxia in Sepsis and Septic Shock: A Comprehensive Review of Clinical Evidence and Therapeutic Implications.

Sepsis and septic shock are leading causes of mortality in intensive care units, characterized by a dysregulated immune response to infection, leading to severe organ dysfunction. Oxygen therapy is a cornerstone of supportive care in sepsis management, aimed at correcting hypoxemia and improving tissue oxygenation. However, the administration of supplemental oxygen must be carefully managed to avoid hyperoxia, which can lead to oxidative stress and additional tissue damage. This review aims to comprehensively analyze the clinical evidence regarding hyperoxia in the context of sepsis and septic shock, evaluating its potential therapeutic benefits and risks and discussing the implications for clinical practice. A thorough literature review included observational studies, randomized controlled trials (RCTs), meta-analyses, and clinical guidelines. The review focuses on the pathophysiology of sepsis, the mechanisms of hyperoxia-induced injury, and the clinical outcomes associated with different oxygenation strategies. The evidence suggests that while oxygen is crucial in managing sepsis, the risk of hyperoxia-related complications is significant. Hyperoxia has been associated with increased mortality and adverse outcomes in septic patients due to mechanisms such as oxidative stress, impaired microcirculation, and potential worsening of organ dysfunction. RCTs and meta-analyses indicate that conservative oxygen therapy may be beneficial in reducing these risks, though optimal oxygenation targets remain under investigation. This review highlights the importance of careful oxygen management in sepsis and septic shock, emphasizing the need for individualized oxygen therapy to avoid the dangers of hyperoxia. Further research is required to refine oxygenation strategies, establish clear clinical guidelines, and optimize outcomes for sepsis and septic shock patients. Balancing adequate oxygenation with the prevention of hyperoxia-induced injury is crucial in improving the prognosis of these critically ill patients.

Effectiveness of β-blockers in improving 28-day mortality in septic shock: insights from subgroup analysis and retrospective observational study.

In recent years, septic shock remains a common fatal disease in the intensive care unit (ICU). After sufficient fluid resuscitation, some patients still experience tachycardia, which may lead to adverse effects on cardiac function. However, the use of β-blockers in the treatment of septic shock remains controversial. Thus, the purpose of this study is to evaluate the efficacy of β-blockers in the treatment of patients with septic shock and explore the most appropriate patient subgroups for this treatment. This retrospective observational study enrolled septic shock patients from the Medical Information Mart for Intensive Care (MIMIC)-IV and used propensity score matching (PSM) to balance some baseline differences between patients with and without β-blockers treatment. The primary outcome was the 28-day mortality. Length of stay (LOS) in the ICU and hospital, and the degree of support for organs such as circulatory, respiratory and renal systems were also assessed. Subgroup analysis and multivariate logistic regression were performed to determine the relationship between β-blockers therapy and 28-day mortality in different patient groups. A total of 4,860 septic shock patients were enrolled in this study and 619 pairs were finally matched after PSM. Our analysis revealed that β-blocker therapy was associated with a significant improvement in 28-day mortality (21.5% vs. 27.1%; P = 0.020) and led to a prolonged LOS in both the ICU and hospital. Subgroup analysis indicated that there was an interaction between cardiovascular diseases and β-blocker therapy in patients with septic shock. Patients with pre-existing heart disease or atrial arrhythmias were more likely to derive benefits from β-blocker treatment. We found β-blockers therapy was effective to improve 28-day mortality in patients with septic shock. Patients in the subgroup with cardiovascular diseases were more likely to benefit from β-blockers in mortality.

Role of arterial blood glucose and interstitial fluid glucose difference in evaluating microcirculation and clinical prognosis of patients with septic shock: a prospective observational study

BackgroundMicrocirculation abnormality in septic shock is closely associated with organ dysfunction and mortality rate. It was hypothesized that the arterial blood glucose and interstitial fluid (ISF) glucose difference (GA−I) as a marker for assessing the microcirculation status can effectively evaluate the severity of microcirculation disturbance in patients with septic shock.MethodsThe present observational study enrolled patients with septic shock admitted to and treated in the intensive care unit (ICU) of a tertiary teaching hospital. The parameters reflecting organ and tissue perfusion, including lactic acid (Lac), skin mottling score, capillary refill time (CRT), venous-to-arterial carbon dioxide difference (Pv-aCO2), urine volume, central venous oxygen saturation (ScvO2) and GA−I of each enrolled patient were recorded at the time of enrollment (H0), H2, H4, H6, and H8. With ICU mortality as the primary outcome measure, the ICU mortality rate at any GA−I interval was analyzed.ResultsA total of 43 septic shock patients were included, with median sequential organ failure assessment (SOFA) scores of 10.5 (6–16), and median Acute Physiology and Chronic Health Evaluation (APACHAE) II scores of 25.7 (9–40), of whom 18 died during ICU stay. The GA−I levels were negative correlation with CRT (r = 0.369, P < 0.001), Lac (r = -0.269, P < 0.001), skin mottling score (r=-0.223, P < 0.001), and were positively associated with urine volume (r = 0.135, P < 0.05). The ICU mortality rate of patients with septic shock presenting GA−I ≤ 0.30 mmol/L and ≥ 2.14 mmol/L was significantly higher than that of patients with GA−I at 0.30–2.14 mmol/L [65.2% vs. 15.0%, odds ratio (OR) = 10.625, 95% confidence interval (CI): 2.355–47.503].ConclusionGA−I was correlated with microcirculation parameters, and with differences in survival. Future studies are needed to further explore the potential impact of GA−I on microcirculation and clinical prognosis of septic shock, and the bedside monitoring of GA−I may be beneficial for clinicians to identify high-risk patients.

Impact of adequate empirical combination therapy on mortality in septic shock due to Pseudomonas aeruginosa bloodstream infections: a multicentre retrospective cohort study.

To determine the association of adequate empirical combination therapy (AECT) with 30-day all-cause mortality in patients with septic shock due to Pseudomonas aeruginosa bloodstream infections (BSI). This multicentre, retrospective cohort study analysed data from 14 public hospitals in Italy, including all consecutive adult patients admitted during 2021-2022 with septic shock due to P. aeruginosa BSI. We compared the outcomes of patients receiving AECT to those on adequate empirical monotherapy (AEMT) using Cox regression analyses. Of the 98 patients who received adequate empirical antibiotic treatment for septic shock due to P. aeruginosa BSI, 24 underwent AECT and 74 were given AEMT. AECT was associated with a lower 30-day all-cause mortality (25%, six out of 24) compared to AEMT (56.8%, 42 out of 74; P = 0.007). Multivariate Cox regression analysis indicated AECT as the only factor significantly associated with improved survival (aHR 0.30; 95% CI 0.12-0.71; P = 0.006). By contrast, the use of monotherapy or combination therapy in the definitive regimen did not influence mortality (aHR 0.73; 95% CI 0.25-2.14; P = 0.568). AECT may be associated with reduced mortality compared to monotherapy in septic shock patients due to P. aeruginosa BSI. However, the administration of definitive adequate monotherapy or combination therapy yields similar outcomes, suggesting that once susceptibility is documented, switching to a single active in vitro drug is safe and feasible. Further studies are recommended to validate these findings.

Evaluation of Amiodarone Administration in Patients with New-Onset Atrial Fibrillation in Septic Shock.

Background and Objective: New-onset atrial fibrillation (NOAF) is a common cardiac condition often observed in intensive care units. When amiodarone is used to treat this condition, either to maintain sinus rhythm after electrical cardioversion or to control heart rate, complications can arise when a systemic pathology is present. Systemic pathology can result in a decrease in cardiac output and blood pressure, making the management of NOAF and septic shock challenging. Limited international research exists on the coexistence of NOAF and septic shock, making it difficult to determine the optimal course of treatment. While amiodarone is not the primary choice of antiarrhythmic drug for patients in septic shock, it may be considered for those with underlying cardiac issues. This paper aims to investigate the safety of administering amiodarone to patients with septic shock and explore whether another antiarrhythmic drug may be more effective, especially considering the cardiac conditions that patients may have. Materials and Methods: To write this article, we searched electronic databases for studies where authors used amiodarone and other medications for heart rate control or sinus rhythm restoration. Results: The studies reviewed in this work have shown that for the patients with septic shock and NOAF along with a pre-existing cardiac condition like a dilated left atrium, the use of amiodarone may provide greater benefits compared to other antiarrhythmic drugs. For patients with NOAF and septic shock without underlying heart disease, the initial use of propafenone has been found to be advantageous. However, a challenge arises when deciding between rhythm or heart rate control using various drug classes. Unfortunately, there is limited literature available on this specific scenario. Conclusions: NOAF is a frequent and potentially life-threatening complication occurring in one out of seven patients with sepsis, and its incidence is rising among patients with septic shock.

Nitroglycerin challenge identifies microcirculatory target for improved resuscitation in patients with circulatory shock

BackgroundCirculatory shock and multi-organ failure remain major contributors to morbidity and mortality in critically ill patients and are associated with insufficient oxygen availability in the tissue. Intrinsic mechanisms to improve tissue perfusion, such as up-regulation of functional capillary density (FCD) and red blood cell velocity (RBCv), have been identified as maneuvers to improve oxygen extraction by the tissues; however, their role in circulatory shock and potential use as resuscitation targets remains unknown. To fill this gap, we examined the baseline and maximum recruitable FCD and RBCv in response to a topical nitroglycerin stimulus (FCDNG, RBCvNG) in patients with and without circulatory shock to test whether this may be a method to identify the presence and magnitude of a microcirculatory reserve capacity important for identifying a resuscitation target.MethodsSublingual handheld vital microscopy was performed after initial resuscitation in mechanically ventilated patients consecutively admitted to a tertiary medical ICU. FCD and RBCv were quantified using an automated computer vision algorithm (MicroTools). Patients with circulatory shock were retrospectively identified via standardized hemodynamic and clinical criteria and compared to patients without circulatory shock.Results54 patients (57 ± 14y, BMI 26.3 ± 4.9 kg/m2, SAPS 56 ± 19, 65% male) were included, 13 of whom presented with circulatory shock. Both groups had similar cardiac index, mean arterial pressure, RBCv, and RBCvNG. Heart rate (p < 0.001), central venous pressure (p = 0.02), lactate (p < 0.001), capillary refill time (p < 0.01), and Mottling score (p < 0.001) were higher in circulatory shock after initial resuscitation, while FCD and FCDNG were 10% lower (16.9 ± 4.2 and 18.9 ± 3.2, p < 0.01; 19.3 ± 3.1 and 21.3 ± 2.9, p = 0.03). Nitroglycerin response was similar in both groups, and circulatory shock patients reached FCDNG similar to baseline FCD found in patients without shock.ConclusionCritically ill patients suffering from circulatory shock were found to present with a lower sublingual FCD. The preserved nitroglycerin response suggests a dysfunction of intrinsic regulation mechanisms to increase the microcirculatory oxygen extraction capacity associated with circulatory shock and identifies a potential resuscitation target. These differences in microcirculatory hemodynamic function between patients with and without circulatory shock were not reflected in blood pressure or cardiac index.

2: Awake insertion of transplant-bridging veno-arterial extracorporeal membrane oxygenation in a shocked patient with severe thrombocytopenia: a case report.

2: Awake insertion of transplant-bridging veno-arterial extracorporeal membrane oxygenation in a shocked patient with severe thrombocytopenia: a case report.

Noncoding Vault RNA1-1 Impairs Intestinal Epithelial Renewal and Barrier Function by Interacting With CUG-binding Protein 1

Small noncoding vault RNAs (vtRNAs) are involved in many cell processes important for health and disease, but their pathobiological functions in the intestinal epithelium are underexplored. Here, we investigated the role of human vtRNA1-1 in regulating intestinal epithelial renewal and barrier function. Studies were conducted in vtRNA1-1 transgenic (vtRNA1-1Tg) mice, primary enterocytes, and Caco-2 cells. Extracellular vesicles (EVs) were isolated from the serum of shock patients and septic mice. Intestinal organoids (enteroids) were prepared from vtRNA1-1Tg and littermate mice. Mucosal growth was measured by Ki67 immunostaining or BrdU incorporation, and gut permeability assessed using the FITC-dextran assay. Intestinal tissues recovered from shock patients and septic mice evidenced mucosal injury and gut barrier dysfunction; vtRNA levels were elevated in EVs isolated from their sera. In mice, intestinal epithelial-specific transgenic expression of vtRNA1-1 inhibited mucosal growth, reduced Paneth cell numbers and intercellular junction (IJ) protein expression, and increased gut barrier vulnerability to lipopolysaccharide exposure. Conversely, in vitro silencing of vtRNA1-1 increased IJ protein levels and enhanced epithelial barrier function. Exposing enteroids to vtRNA1-1-rich EVs augmented paracellular permeability. Mechanistically, vtRNA1-1 interacted with CUG-binding protein 1 (CUGBP1) and increased CUGBP1 association with claudin-1 and occludin mRNAs, thereby inhibiting their expression. These findings indicate that elevated levels of vtRNA1-1 in EVs and mucosal tissues repress intestinal epithelial renewal and barrier function. Notably, this work reveals a novel role for dysregulation of the vtRNA1-1/CUGBP1 axis in the pathogenesis of gut mucosal disruption in critical illness.