Association between prehospital ROX index with 30-day mortality among septic shock.

PURPOSE: Respiratory dysfunction is one of the most frequent symptoms observed during sepsis reflecting hypoxemia and/or acidosis that may be assessed by the ROX index (ratio of oxygen saturation by pulse oximetry/fraction of inspired oxygen to respiratory rate). This study aimed to describe the relationship between the prehospital ROX index and 30-day mortality rate among septic shock patients cared for in the prehospital setting by a mobile intensive care unit (MICU). METHODS: From May 2016 to December 2021, 530 septic shock patients cared for by a prehospital MICU were retrospectively analysed. Initial ROX index value was calculated at the first contact with MICU. A Cox regression analysis after propensity score matching was performed to assess the relationship between 30-day mortality rate and a ROX index ≤ 10. RESULTS: Pulmonary, digestive and urinary sepsis were suspected among 43%, 25% and 17% patients, respectively. The 30-day overall mortality reached 31%. Cox regression analysis showed a significant association between 30-day mortality and a ROX index ≤ 10: adjusted hazard ratio of 1.54 [1.08-2.31], p < 0.05. CONCLUSIONS: During the prehospital stage of septic shock patients cared for by a MICU, ROX index is significantly associated with 30-day mortality. A prehospital ROX ≤ 10 value is associated with a 1.5-fold 30-day mortality rate increase. Prospective studies are needed to confirm the ability of prehospital ROX to predict sepsis outcome since the prehospital setting.

Diastolic/systolic blood pressure ratio for predicting febrile children with sepsis and progress to septic shock in the emergency department.

OBJECTIVE: Given the scarcity of studies analyzing the clinical predictors of pediatric septic cases that would progress to septic shock, this study aimed to determine strong predictors for pediatric emergency department (PED) patients with sepsis at risk for septic shock and mortality. METHODS: We conducted chart reviews of patients with ≥ 2 age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) criteria to recognize patients with an infectious disease in two tertiary PEDs between January 1, 2021, and April 30, 2022. The age range of included patients was 1 month to 18 years. The primary outcome was development of septic shock within 48 h of PED attendance. The secondary outcome was sepsis-related 28-day mortality. Initial important variables in the PED and hemodynamics with the highest and lowest values during the first 24 h of admission were also analyzed. RESULTS: Overall, 417 patients were admitted because of sepsis and met the eligibility criteria for the study. Forty-nine cases progressed to septic shock within 48 h after admission and 368 were discharged without progression. General demographics, laboratory data, and hemodynamics were analyzed by multivariate analysis. Only the minimum diastolic blood pressure/systolic blood pressure ratio (D/S ratio) during the first 24 h after admission remained as an independent predictor of progression to septic shock and 28-day mortality. The best cutoff values of the D/S ratio for predicting septic shock and 28-day mortality were 0.52 and 0.47, respectively. CONCLUSIONS: The D/S ratio is a practical bedside scoring system in the PED and had good discriminative ability in predicting the progression of septic shock and in-hospital mortality in PED patients. Further validation is essential in other settings.

Clinical usefulness of NT-proBNP as a prognostic factor for septic shock patients presenting to the emergency department.

Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level is primarily used as a biomarker for left ventricular (LV) dysfunction. It is influenced by various conditions, such as myocardial strain and situations affecting the clearance of NT-proBNP, including sepsis and shock. In this study, we investigated the appropriateness of NT-proBNP as a prognostic factor for septic shock. Patients with septic shock who visited the emergency department of the Ewha Womans' University Mokdong Hospital between January 1, 2018, and December 31, 2020, were classified into the survival group (those who survived in the hospital and were discharged) and the death group (those who died in the hospital). The effectiveness of NT-proBNP, lactate, and blood urea nitrogen as predictive factors of in-hospital mortality was evaluated using the area under the receiver operating characteristic (AUROC) curve. The AUROC curve was 0.678 and 0.648 for lactate and NT-proBNP, respectively, with lactate showing the highest value. However, there was no significant difference between lactate and NT-proBNP levels in the comparison of their AUROC curve (p = 0.6278). NT-proBNP could be a useful predictor of in-hospital mortality in patients with septic shock who present to the emergency department.

Restrictive calcium replacement in septic shock: a multicenter before-after intervention study. / Reposición restrictiva de calcio en pacientes con shock séptico: estudio de intervención antes-después.

OBJECTIVES: To study the impact of a restrictive calcium replacement protocol in comparison with a liberal one in patients with septic shock. MATERIAL AND METHODS: Multicenter retrospective before-after study that estimated the impact of implementing a restrictive calcium replacement protocol in patients with septic shock. Patients admitted to an intensive care unit between May 2019 and April 2021 were assigned to liberal calcium replacement, and those admitted between May 2021 and April 2022 were assigned to a restrictive protocol. The primary outcome measure was 28-day mortality. Patients were matched with propensity scores. RESULTS: A total of 644 patients were included; liberal replacement was used in 453 patients and the restrictive replacement in 191. We paired 553 patients according to propensity scores, 386 in the liberal group and 167 in the restrictive group. Mortality did not differ significantly between the groups at 28 days (35.3% vs 32.3%, respectively; hazard ratio, 0.97; 95% CI, 0.72-1.29) or after resolution of septic shock (81.5% vs 83.8%; hazard ratio, 0.89; 95% CI, 0.73-1.09). Nor did scores on the Sepsis-related Organ Failure Assessment scale differ (2.1 vs 2.6; P = 0.20). CONCLUSION: The implementation of a restrictive calcium replacement protocol in patients with septic shock was not associated with a decrease in 28-day mortality in comparison with use of a liberal protocol. However, we were able to reduce calcium replacement without adverse effects.

OBJETIVO: Investigar el efecto de un protocolo de reposición restrictiva de calcio frente a una estrategia liberal en pacientes con shock séptico. METODO: Estudio multicéntrico, antes-después y retrospectivo que evaluó el efecto de la implementación de un protocolo de reposición restrictiva de calcio en pacientes con shock séptico. Los pacientes que ingresaron en unidades de cuidados intensivos (UCI) entre mayo de 2019 y abril de 2021 se asignaron al grupo con administración liberal, y los que se presentaron entre mayo de 2021 y abril de 2022 ­tras la implementación del protocolo­ al grupo con administración restrictiva. La variable de resultado principal fue la mortalidad a 28 días. Se realizó un emparejamiento por puntuación de propensión. RESULTADOS: Se incluyeron 644 pacientes, 453 en el grupo liberal y 191 en el grupo restrictivo. De los que 553 se emparejaron (386 en el grupo liberal, y 167 en el grupo restrictivo). No hubo diferencias entre los dos grupos en la mortalidad a los 28 días (35,3% vs 32,3%; HR: 0,97; IC 95%: 0,72-1,29), en la finalización del shock (81,5% vs a 83,8%; HR: 0,89; IC 95%: 0,73-1,09) ni en la puntuación de la escala SOFA (2,1 vs 2,6; p = 0,20). CONCLUSIONES: La implementación de un protocolo de administración restrictiva de calcio, en pacientes con shock séptico, no se asoció a una disminución de la mortalidad a los 28 días en comparación con una administración liberal. No obstante, la reposición de calcio podría reducirse sin efectos adversos.

Protocolized reduction of non-resuscitation fluids versus usual care in septic shock patients (REDUSE): a randomized multicentre feasibility trial.

BACKGROUND/PURPOSE: Non-resuscitation fluids constitute the majority of fluid administered for septic shock patients in the intensive care unit (ICU). This multicentre, randomized, feasibility trial was conducted to test the hypothesis that a restrictive protocol targeting non-resuscitation fluids reduces the overall volume administered compared with usual care. METHODS: Adults with septic shock in six Swedish ICUs were randomized within 12 h of ICU admission to receive either protocolized reduction of non-resuscitation fluids or usual care. The primary outcome was the total volume of fluid administered within three days of inclusion. RESULTS: Median (IQR) total volume of fluid in the first three days, was 6008 ml (interquartile range [IQR] 3960-8123) in the restrictive fluid group (n = 44), and 9765 ml (IQR 6804-12,401) in the control group (n = 48); corresponding to a Hodges-Lehmann median difference of 3560 ml [95% confidence interval 1614-5302]; p < 0.001). Outcome data on all-cause mortality, days alive and free of mechanical ventilation and acute kidney injury or ischemic events in the ICU within 90 days of inclusion were recorded in 98/98 (100%), 95/98 (98%) and 95/98 (98%) of participants respectively. Cognition and health-related quality of life at six months were recorded in 39/52 (75%) and 41/52 (79%) of surviving participants, respectively. Ninety out of 134 patients (67%) of eligible patients were randomized, and 15/98 (15%) of the participants experienced at least one protocol violation. CONCLUSION: Protocolized reduction of non-resuscitation fluids in patients with septic shock resulted in a large decrease in fluid administration compared with usual care. A trial using this design to test if reducing non-resuscitation fluids improves outcomes is feasible. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05249088, 18 February 2022. https://clinicaltrials.gov/ct2/show/NCT05249088.

Survival benefit of resin cartridge extracorporeal blood purification therapy in patients with septic shock.

Background/aim: Extracorporeal blood purification (EBP) therapies have shown promise as potential rescue treatments for patients with septic shock. However, precise evidence regarding their effectiveness is lacking. This case-control study aimed to evaluate the 28-day survival benefit of a resin cartridge-based EBP therapy compared to conventional therapies in patients with septic shock. Materials and methods: The study sample was collected retrospectively from the medical records of patients admitted to the intensive care unit (ICU) between 2015 and 2020. The study included patients with septic shock aged ≥18 years who had ICU stays >96 h and excluded those lost to follow-up by 28 days or readmitted. First, 28-day survival was compared between EBP patients and 1:1 matched conventionally treated controls. Second, the EBP patients were evaluated for clinical and laboratory improvements within 72 h of EBP therapy. Results: Of 3742 patients, 391 were included in this study, of whom 129 received EBP therapy and had a 28-day survival rate of 44%, compared to 262 matched controls who received conventional therapy alone and had a survival rate of 33% (p = 0.001, log-rank = 0.05, number needed to treat = 8, and odds ratio = 1.7). After receiving EBP therapy for 72 h, improvements were observed in the Sequential Organ Failure Assessment scores (p < 0.05), shock indices (p < 0.05), partial pressure of oxygen in the arterial blood to the fraction of inspiratory oxygen concentration ratios (p < 0.001), vasopressor requirements (p < 0.001), pH (p < 0.05), lactate levels (p < 0.001), and C-reactive protein levels (p < 0.05). Conclusion: The findings suggest that administering resin cartridge-based EBP therapy to patients with septic shock may improve their survival compared to conventional therapies.

The Role of Soluble Urokinase Plasminogen Activator Receptor (suPAR) as an Early Indicator of Mortality in Pediatric Septic Shock.

BACKGROUND: Despite advancements in antibiotic therapy and resuscitation protocols, sepsis and septic shock remain major contributors to morbidity and mortality in children. We aimed to investigate the utility of soluble urokinase plasminogen activator receptor (suPAR) for the early detection of septic shock and to evaluate its accuracy in predicting mortality. METHODS: A prospective study was conducted in a tertiary pediatric emergency department (ED), enrolling patients diagnosed with the sepsis, severe sepsis, or septic shock. In addition to assessing infection biomarkers such as C-reactive protein and procalcitonin, suPAR levels were quantified upon admission using enzyme-linked immunosorbent assay. The primary outcome measure was 30-day mortality. RESULTS: Overall 72 patients and 80 healthy children included. Plasma suPAR levels demonstrated a statistically significant elevation in the sepsis, severe sepsis, and septic shock groups compared with the control group (p < 0.001 for all). The septic shock group exhibited the highest suPAR levels upon admission, surpassing both the sepsis and severe sepsis groups (p = 0.009 and 0.042). ROC analysis underscored the promising potential of suPAR with an AUC of 0.832 for septic shock. Analysis of mortality prediction revealed significantly higher suPAR levels in nonsurvivors than survivors (9.7 ng/mL vs. 4.2 ng/mL; p < 0.001). Employing plasma suPAR levels to discriminate between mortality and survival, a threshold of ≥7.0 ng/mL demonstrated a sensitivity of 90.9% and specificity of 71.0%. CONCLUSION: Plasma suPAR levels have the potential as a biomarker for predicting mortality in children with septic shock. In pediatric septic shock, the presence of plasma suPAR ≥7 ng/mL along with an underlying disease significantly increases the risk of mortality.

Assessment of Outcomes in Patients with Heart Failure and End-Stage Kidney Disease after Fluid Resuscitation for Sepsis and Septic Shock.

BACKGROUND: Sepsis fluid resuscitation is controversial, especially for patients with volume overload risk. The Surviving Sepsis Campaign recommends a 30-mL/kg crystalloid fluid bolus for patients with sepsis-induced hypoperfusion. Criticism of this approach includes excessive fluid resuscitation in certain patients. OBJECTIVE: The aim of this study was to assess the efficacy and safety of guideline-concordant fluid resuscitation in patients with sepsis and heart failure (HF) or end-stage kidney disease (ESKD). METHODS: A retrospective cohort study was conducted in patients with sepsis who qualified for guideline-directed fluid resuscitation and concomitant HF or ESKD. Those receiving crystalloid fluid boluses of at least 30 mL/kg within 3 h of sepsis diagnosis were placed in the concordant group and all others in the nonconcordant group. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) and hospital length of stay (LOS); vasoactive medications and net volume over 24 h; new mechanical ventilation, new or increased volume removal, and acute kidney injury within 48 h; and shock-free survival at 7 days. RESULTS: One hundred twenty-five patients were included in each group. In-hospital mortality was 34.4% in the concordant group and 44.8% in the nonconcordant group (p = 0.1205). The concordant group had a shorter ICU LOS (7.6 vs. 10.5 days; p = 0.0214) and hospital LOS (12.9 vs. 18.3 days; p = 0.0163), but increased new mechanical ventilation (37.6 vs. 20.8%; p = 0.0052). No differences in other outcomes were observed. CONCLUSIONS: Receipt of a 30-mL/kg fluid bolus did not affect outcomes in a cohort of patients with mixed types of HF and sepsis-induced hypoperfusion.

Lactate dynamics in paediatric patients with severe sepsis: insights from a prospective cohort study.

BACKGROUND: Sepsis is an infection-related systemic inflammatory response that often leads to elevated lactate levels. Monitoring lactate levels during severe sepsis is vital for influencing clinical outcomes. The aim of this study was to assess the association between plasma lactate levels and mortality in children with severe sepsis or septic shock. METHODS: The current prospective study was conducted in the PICU of University Children's Hospital. The International Paediatric Sepsis Consensus Conference criteria for Definitions of Sepsis and Organ Failure in 2005 were used to diagnose patients with sepsis. We measured plasma lactate levels upon admission (Lac H0) and 6 h later (Lac H6). The static indices included the absolute lactate values (Lac H0 and Lac H6), while the dynamic indices included the delta-lactate level (ΔLac) and the 6-hour lactate clearance. The 6-hour lactate clearance was calculated using the following formula: [(Lac H0-Lac H6)100/Lac H0]. ΔLac was calculated as the difference between the Lac H0 and Lac H6 levels. Patient survival or death after a PICU stay was the primary outcome. RESULTS: A total of 46 patients were included in this study: 25 had septic shock, and 21 had severe sepsis. The mortality rate was 54.3%. The Lac H0 did not significantly differ between survivors and nonsurvivors. In contrast, the survivors had significantly lower Lac H6 levels, higher ΔLac levels, and higher 6-hour lactate clearance rates than nonsurvivors. Lactate clearance rates below 10%, 20%, and 30% were significantly associated with mortality. The best cut-off values for the lactate clearance rate and Lac H6 for the prediction of mortality in the PICU were < 10% and ≥ 4 mmol/L, respectively. Patients with higher Lac H6 levels and lower lactate clearance rates had significantly higher PICU mortality based on Kaplan-Meier survival curve analysis. CONCLUSIONS: This study highlights the significance of lactate level trends over time for the prediction of mortality in the PICU in patients with severe sepsis or septic shock. Elevated lactate levels and decreased lactate clearance six hours after hospitalisation are associated with a higher mortality rate.

[Constructing a predictive model for the death risk of patients with septic shock based on supervised machine learning algorithms].

OBJECTIVE: To construct and validate the best predictive model for 28-day death risk in patients with septic shock based on different supervised machine learning algorithms. METHODS: The patients with septic shock meeting the Sepsis-3 criteria were selected from Medical Information Mart for Intensive Care-IV v2.0 (MIMIC-IV v2.0). According to the principle of random allocation, 70% of these patients were used as the training set, and 30% as the validation set. Relevant predictive variables were extracted from three aspects: demographic characteristics and basic vital signs, serum indicators within 24 hours of intensive care unit (ICU) admission and complications possibly affecting indicators, functional scoring and advanced life support. The predictive efficacy of models constructed using five mainstream machine learning algorithms including decision tree classification and regression tree (CART), random forest (RF), support vector machine (SVM), linear regression (LR), and super learner [SL; combined CART, RF and extreme gradient boosting (XGBoost)] for 28-day death in patients with septic shock was compared, and the best algorithm model was selected. The optimal predictive variables were determined by intersecting the results from LASSO regression, RF, and XGBoost algorithms, and a predictive model was constructed. The predictive efficacy of the model was validated by drawing receiver operator characteristic curve (ROC curve), the accuracy of the model was assessed using calibration curves, and the practicality of the model was verified through decision curve analysis (DCA). RESULTS: A total of 3 295 patients with septic shock were included, with 2 164 surviving and 1 131 dying within 28 days, resulting in a mortality of 34.32%. Of these, 2 307 were in the training set (with 792 deaths within 28 days, a mortality of 34.33%), and 988 in the validation set (with 339 deaths within 28 days, a mortality of 34.31%). Five machine learning models were established based on the training set data. After including variables at three aspects, the area under the ROC curve (AUC) of RF, SVM, and LR machine learning algorithm models for predicting 28-day death in septic shock patients in the validation set was 0.823 [95% confidence interval (95%CI) was 0.795-0.849], 0.823 (95%CI was 0.796-0.849), and 0.810 (95%CI was 0.782-0.838), respectively, which were higher than that of the CART algorithm model (AUC = 0.750, 95%CI was 0.717-0.782) and SL algorithm model (AUC = 0.756, 95%CI was 0.724-0.789). Thus above three algorithm models were determined to be the best algorithm models. After integrating variables from three aspects, 16 optimal predictive variables were identified through intersection by LASSO regression, RF, and XGBoost algorithms, including the highest pH value, the highest albumin (Alb), the highest body temperature, the lowest lactic acid (Lac), the highest Lac, the highest serum creatinine (SCr), the highest Ca2+, the lowest hemoglobin (Hb), the lowest white blood cell count (WBC), age, simplified acute physiology score III (SAPS III), the highest WBC, acute physiology score III (APS III), the lowest Na+, body mass index (BMI), and the shortest activated partial thromboplastin time (APTT) within 24 hours of ICU admission. ROC curve analysis showed that the Logistic regression model constructed with above 16 optimal predictive variables was the best predictive model, with an AUC of 0.806 (95%CI was 0.778-0.835) in the validation set. The calibration curve and DCA curve showed that this model had high accuracy and the highest net benefit could reach 0.3, which was significantly outperforming traditional models based on single functional score [APS III score, SAPS III score, and sequential organ failure assessment (SOFA) score] with AUC (95%CI) of 0.746 (0.715-0.778), 0.765 (0.734-0.796), and 0.625 (0.589-0.661), respectively. CONCLUSIONS: The Logistic regression model, constructed using 16 optimal predictive variables including pH value, Alb, body temperature, Lac, SCr, Ca2+, Hb, WBC, SAPS III score, APS III score, Na+, BMI, and APTT, is identified as the best predictive model for the 28-day death risk in patients with septic shock. Its performance is stable, with high discriminative ability and accuracy.

Effects of restrictive fluid therapy on the time to resolution of hyperlactatemia in ICU patients with septic shock. A secondary post hoc analysis of the CLASSIC randomized trial.

PURPOSE: The aim of this study was to examine the effects of intravenous (IV) fluid restriction on time to resolution of hyperlactatemia in septic shock. Hyperlactatemia in sepsis is associated with worse outcome. Sepsis guidelines suggest targeting lactate clearance to guide fluid therapy despite the complexity of hyperlactatemia and the potential harm of fluid overload. METHODS: We conducted a post hoc analysis of serial plasma lactate concentrations in a sub-cohort of 777 patients from the international multicenter clinical CLASSIC trial (restriction of intravenous fluids in intensive care unit (ICU) patients with septic shock). Adult ICU patients with septic shock had been randomized to restrictive (n = 385) or standard (n = 392) intravenous fluid therapy. The primary outcome, time to resolution of hyperlactatemia, was analyzed with a competing-risks regression model. Death and discharge were competing outcomes, and administrative censoring was imposed 72 h after randomization if hyperlactatemia persisted. The regression analysis was adjusted for the same stratification variables and covariates as in the original CLASSIC trial analysis. RESULTS: The hazard ratios (HRs) for the cumulative probability of resolution of hyperlactatemia, in the restrictive vs the standard group, in the unadjusted analysis, with time split, were 0.94 (confidence interval (CI) 0.78-1.14) at day 1 and 1.21 (0.89-1.65) at day 2-3. The adjusted analyses were consistent with the unadjusted results. CONCLUSION: In this post hoc retrospective analysis of a multicenter randomized controlled trial (RCT), a restrictive intravenous fluid strategy did not seem to affect the time to resolution of hyperlactatemia in adult ICU patients with septic shock.

Identifying predictors and determining mortality rates of septic cardiomyopathy and sepsis-related cardiogenic shock: A retrospective, observational study.

INTRODUCTION: Septic shock is a severe form of sepsis that has a high mortality rate, and a substantial proportion of these patients will develop cardiac dysfunction, often termed septic cardiomyopathy (SCM). Some SCM patients may develop frank cardiac failure, termed sepsis-related cardiogenic shock (SeRCS). Little is known of SeRCS. This study describes baseline characteristics of patients with SCM and SeRCS compared to patients with septic shock without cardiac dysfunction. We compare clinical outcomes among SCM, SeRCS, and septic shock, and identify risk factors for the development of SCM and SeRCS. METHODS: Septic patients admitted to the ICU with an echocardiogram obtained within 72 hours were included. Left ventricular ejection fraction of ≤55% was used to define SCM, and cardiac index ≤2.1 L/min/m2 among patients with SCM defined SeRCS. Machine learning was used to identify risk factors for development of SCM and SeRCS. Logistic regression was used to compare mortality among groups. RESULTS: Among 1229 patients, 977 patients had septic shock without cardiac dysfunction, 207 had SCM, and 45 had SeRCS. In patients with septic shock, the strongest predictor for developing SCM and SeRCs was a prior history of cardiac dysfunction. Mortality did not significantly differ among the three groups. CONCLUSIONS: SCM and SeRCS affect a minority of patients with septic shock, disproportionately affecting individuals with a history of cardiac disease. We did not identify a mortality difference associated with SCM or SeRCS. Additional work is needed to define further subtypes and treatment options for this patient population.

Efficacy of dietary supplements on mortality and clinical outcomes in adults with sepsis and septic shock: A systematic review and network meta-analysis.

AIM: The aim of this network meta-analysis (NMA) was to investigate the effects of different dietary supplements on the mortality and clinical status of adults with sepsis. METHODS: We searched PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials until February 2023. The inclusion criteria were: 1) randomized controlled trials (RCT)s; 2) adults suffering sepsis or septic shock; 3) evaluation of short- or long-mortality; and 4) publications between 1994 and 2023. The general information of studies and details of interventions were extracted. The primary outcome was short-term mortality (<90 days), and the secondary outcomes were long-term mortality (≥90 days), length of ICU and hospital stays, and duration of mechanical ventilation (MV). The risk of bias of RCTs was assessed using the Cochrane risk of bias tool 2 (ROB2). A random effect NMA was performed to rank the effect of each intervention using a frequentist approach. RESULTS: Finally, 56 RCTs with 5957 participants met the criteria. Approximately, one-third of RCTs were low risk of bias. NMA analysis revealed that there was no treatment more effective in short- or long-term mortality than control or other interventions, except for magnesium (RR: 0.33, 95% CI: 0.14, 0.79; GRADE = low) and vitamin C (RR: 0.81, 95% CI: 0.67, 0.99; low certainty evidence), which had beneficial effects on short-term mortality. Moreover, eicosapentaenoic acid, gamma-linolenic acid, and antioxidants (EPA + GLA + AOs) combination was the most effective, and magnesium, vitamin D and vitamin C were the other effective approaches in terms of duration of MV, and ICU length of stay. There was no beneficial dietary supplement for hospital stay in these patients. CONCLUSIONS: In septic patients, none of the dietary supplements had a substantial effect on mortality except for magnesium and vitamin C, which were linked to lower short-term mortality with low certainty of evidence. Further investigation into high-quality studies with the use of dietary supplements for sepsis should be highly discouraged.

CytoSorb® in burn patients with septic shock and Acute Kidney Injury on Continuous Kidney Replacement Therapy is associated with improved clinical outcome and survival.

BACKGROUND: In burn patients, septic shock and acute kidney injury (AKI) with use of continuous renal replacement therapy (CRRT) severely increase morbidity and mortality. Sorbent therapies could be an adjunctive therapy to address the underlying metabolic changes in inflammatory and anti-inflammatory cytokines dysregulated production. METHODS: A retrospectively observational study of 35 severe burn patients admitted to the Burn Center (Turin, Italy, from January 2017 to December 2022), who underwent CRRT for AKI-associated septic shock. Out of 35 patients, 11 were treated with CytoSorb® as adjunctive therapy to CRRT (Sorbent group) and 24 patients only with CRRT (Control group). RESULTS: The application of CytoSorb® took place in a very dispersed way. Out of 11 patients, 7 started the CRRT together with the sorbent application. The patients of the sorbent group exhibited a significant reduction in norepinephrine use compared to that of the control group. A clinical improvement over the first 4 days of Cytosorb® was observed in both survivors and no survivors of the sorbent group, with significant norepinephrine decreased use on day 4 compared to day 1. In-hospital mortality was 45.4% and 70.8% in the sorbent and control group, respectively, and significantly better at Kaplan-Meier survival analysis at 270 days (p = 0.0445). In both groups, all survivor patients recovered renal function at discharge, whereas no survivors did not. CONCLUSIONS: Adjunctive treatment with CytoSorb® for burn patients with AKI-CRRT and septic shock poorly responsive to standard therapy led to a significant clinical improvement, and was associated with a lower mortality rate compared to CRRT alone.

Dysfunction of the renin-angiotensin-aldosterone system in human septic shock.

Sepsis and septic shock are global healthcare problems associated with mortality rates of up to 40% despite optimal standard-of-care therapy and constitute the primary cause of death in intensive care units worldwide. Circulating biomarkers of septic shock severity may represent a clinically relevant approach to individualize those patients at risk for worse outcomes early in the course of the disease, which may facilitate early and more precise interventions to improve the clinical course. However, currently used septic shock biomarkers, including lactate, may be non-specific and have variable impact on prognosis and/or disease management. Activation of the renin-angiotensin-aldosterone system (RAAS) is likely an early event in septic shock, and studies suggest that an elevated level of renin, the early and committed step in the RAAS cascade, is a better predictor of worse outcomes in septic shock, including mortality, than the current standard-of-care measure of lactate. Despite a robust increase in renin, other elements of the RAAS, including endogenous levels of Ang II, may fail to sufficiently increase to maintain blood pressure, tissue perfusion, and protective immune responses in septic shock patients. We review the current clinical literature regarding the dysfunction of the RAAS in septic shock and potential therapeutic approaches to improve clinical outcomes.

Association of medical care capacity and the patient mortality of septic shock: a cross-sectional study.

BACKGROUND: Hospitals with higher septic shock case volume demonstrated lower hospital mortality. We conducted this study to investigate whether this phenomenon was only caused by the increase in the number of admissions or the need to improve the medical care capacity in septic shock at the same time. METHODS: Seven-hundred and eighty-seven hospitals from China collected in a survey from January 1, 2021 to December 31, 2021. Medical care capacity for septic shock was explored by patients with septic shock in intensive care units (ICU) divided into beds, intensivists, and nurses respectively. MAIN RESULTS: The proportion of ICU patients with septic shock was negatively associated with the patient mortality of septic shock (Estimate [95%CI], -0.2532 [-0.5038, -0.0026]) (p-value 0.048). The ratios of patients with septic shock to beds, intensivists, and nurses were negatively associated with mortality of septic shock (Estimate [95%CI], -0.370 [-0.591, -0.150], -0.136 [-0.241, -0.031], and -0.774 [-1.158, -0.389]) (p-value 0.001, 0.011 and < 0.001). Severe pneumonia, the most common infection that caused a septic shock, correlated positively with its mortality (Estimate [95%CI], 0.1002 [0.0617, 0.1387]) (p-value < 0.001). CONCLUSIONS: Hospitals with higher medical care capacity for septic shock were associated with lower hospital mortality.

Biomarker Assessment of a High-Risk, Data-Driven Pediatric Sepsis Phenotype Characterized by Persistent Hypoxemia, Encephalopathy, and Shock.

OBJECTIVES: Identification of children with sepsis-associated multiple organ dysfunction syndrome (MODS) at risk for poor outcomes remains a challenge. We sought to the determine reproducibility of the data-driven "persistent hypoxemia, encephalopathy, and shock" (PHES) phenotype and determine its association with inflammatory and endothelial biomarkers, as well as biomarker-based pediatric risk strata. DESIGN: We retrained and validated a random forest classifier using organ dysfunction subscores in the 2012-2018 electronic health record (EHR) dataset used to derive the PHES phenotype. We used this classifier to assign phenotype membership in a test set consisting of prospectively (2003-2023) enrolled pediatric septic shock patients. We compared profiles of the PERSEVERE family of biomarkers among those with and without the PHES phenotype and determined the association with established biomarker-based mortality and MODS risk strata. SETTING: Twenty-five PICUs across the United States. PATIENTS: EHR data from 15,246 critically ill patients with sepsis-associated MODS split into derivation and validation sets and 1,270 pediatric septic shock patients in the test set of whom 615 had complete biomarker data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The area under the receiver operator characteristic curve of the modified classifier to predict PHES phenotype membership was 0.91 (95% CI, 0.90-0.92) in the EHR validation set. In the test set, PHES phenotype membership was associated with both increased adjusted odds of complicated course (adjusted odds ratio [aOR] 4.1; 95% CI, 3.2-5.4) and 28-day mortality (aOR of 4.8; 95% CI, 3.11-7.25) after controlling for age, severity of illness, and immunocompromised status. Patients belonging to the PHES phenotype were characterized by greater degree of systemic inflammation and endothelial activation, and were more likely to be stratified as high risk based on PERSEVERE biomarkers predictive of death and persistent MODS. CONCLUSIONS: The PHES trajectory-based phenotype is reproducible, independently associated with poor clinical outcomes, and overlapped with higher risk strata based on prospectively validated biomarker approaches.

Removal of inflammatory factors and prognosis of patients with septic shock complicated with acute kidney injury by hemodiafiltration combined with HA330-II hemoperfusion.

INTRODUCTION: To explore the effect of CRRT using CVVHDF + HP on the removal of inflammatory mediators in patients with septic shock complicated with AKI. METHODS: A total of 20 patients between January 1, 2018, and December 31, 2021, were included. The patients were randomly divided into the treatment group (CVVHDF + HP) and the control group (CVVHDF). Changes in inflammatory factors, including IL-1ß, IL-6, IL-8, TNF-α, PCT, and CRP were compared. Other observed measures were also analyzed, for example, Lac, Scr, BUN, SOFA, and norepinephrine (NE) dosage. The clinical outcomes of both groups were followed up for 28 days. RESULTS: The IL-6 and PCT levels in the treatment group were significantly lower (p = 0.005, 0.007). Although the IL-1ß, TNFα, and CRP levels in the treatment group decreased, there were no statistical differences (p > 0.05). There were significant differences in Lac, SOFA, and NE dosage levels between both groups (p = 0.023, 0.01, 0.023). Survival analysis showed that the 28-day survival rate was significantly higher in the treatment group. CONCLUSION: CRRT using CVVHDF+HP can effectively remove inflammatory factors and improve the prognosis of patients.

Hydrocortisone plus fludrocortisone for community acquired pneumonia-related septic shock: a subgroup analysis of the APROCCHSS phase 3 randomised trial.

BACKGROUND: Glucocorticoids probably improve outcomes in patients hospitalised for community acquired pneumonia (CAP). In this a priori planned exploratory subgroup analysis of the phase 3 randomised controlled Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trial, we aimed to investigate responses to hydrocortisone plus fludrocortisone between CAP and non-CAP related septic shock. METHODS: APROCCHSS was a randomised controlled trial that investigated the effects of hydrocortisone plus fludrocortisone, drotrecogin-alfa (activated), or both on mortality in septic shock in a two-by-two factorial design; after drotrecogin-alfa was withdrawn on October 2011, from the market, the trial continued on two parallel groups. It was conducted in 34 centres in France. In this subgroup study, patients with CAP were a preselected subgroup for an exploratory secondary analysis of the APROCCHSS trial of hydrocortisone plus fludrocortisone in septic shock. Adults with septic shock were randomised 1:1 to receive, in a double-blind manner, a 7-day treatment with daily administration of intravenous hydrocortisone 50 mg bolus every 6h and a tablet of 50 µg of fludrocortisone via the nasogastric tube, or their placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included all-cause mortality at intensive care unit (ICU) and hospital discharge, 28-day and 180-day mortality, the number of days alive and free of vasopressors, mechanical ventilation, or organ failure, and ICU and hospital free-days to 90-days. Analysis was done in the intention-to-treat population. The trial was registered at ClinicalTrials.gov (NCT00625209). FINDINGS: Of 1241 patients included in the APROCCHSS trial, CAP could not be ruled in or out in 31 patients, 562 had a diagnosis of CAP (279 in the placebo group and 283 in the corticosteroid group), and 648 patients did not have CAP (329 in the placebo group and 319 in the corticosteroid group). In patients with CAP, there were 109 (39%) deaths of 283 patients at day 90 with hydrocortisone plus fludrocortisone and 143 (51%) of 279 patients receiving placebo (odds ratio [OR] 0·60, 95% CI 0·43-0·83). In patients without CAP, there were 148 (46%) deaths of 319 patients at day 90 in the hydrocortisone and fludrocortisone group and 157 (48%) of 329 patients in the placebo group (OR 0·95, 95% CI 0·70-1·29). There was significant heterogeneity in corticosteroid effects on 90-day mortality across subgroups with CAP and without CAP (p=0·046 for both multiplicative and additive interaction tests; moderate credibility). Of 1241 patients included in the APROCCHSS trial, 648 (52%) had ARDS (328 in the placebo group and 320 in the corticosteroid group). There were 155 (48%) deaths of 320 patients at day 90 in the corticosteroid group and 186 (57%) of 328 patients in the placebo group. The OR for death at day 90 was 0·72 (95% CI 0·53-0·98) in patients with ARDS and 0·85 (0·61-1·20) in patients without ARDS (p=0·45 for multiplicative interaction and p=0·42 for additive interaction). The OR for observing at least one serious adverse event (corticosteroid group vs placebo) within 180 days post randomisation was 0·64 (95% CI 0·46-0·89) in the CAP subgroup and 1·02 (0·75-1·39) in the non-CAP subgroup (p=0·044 for multiplicative interaction and p=0·042 for additive interaction). INTERPRETATION: In a pre-specified subgroup analysis of the APROCCHSS trial of patients with CAP and septic shock, hydrocortisone plus fludrocortisone reduced mortality as compared with placebo. Although a large proportion of patients with CAP also met criteria for ARDS, the subgroup analysis was underpowered to fully discriminate between ARDS and CAP modifying effects on mortality reduction with corticosteroids. There was no evidence of a significant treatment effect of corticosteroids in the non-CAP subgroup. FUNDING: Programme Hospitalier de Recherche Clinique of the French Ministry of Health, by Programme d'Investissements d'Avenir, France 2030, and IAHU-ANR-0004.

Association of an In-Hospital Desirability of Outcomes Ranking Scale With Postdischarge Health-Related Quality of Life: A Secondary Analysis of the Life After Pediatric Sepsis Evaluation.

OBJECTIVES: To develop a desirability of outcome ranking (DOOR) scale for use in children with septic shock and determine its correlation with a decrease in 3-month postadmission health-related quality of life (HRQL) or death. DESIGN: Secondary analysis of the Life After Pediatric Sepsis Evaluation prospective study. SETTING: Twelve U.S. PICUs, 2013-2017. PATIENTS: Children (1 mo-18 yr) with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We applied a 7-point pediatric critical care (PCC) DOOR scale: 7: death; 6: extracorporeal life support; 5: supported by life-sustaining therapies (continuous renal replacement therapy, vasoactive, or invasive ventilation); 4: hospitalized with or 3: without organ dysfunction; 2: discharged with or 1: without new morbidity to patients by assigning the highest applicable score on specific days post-PICU admission. We analyzed Spearman rank-order correlations (95% CIs) between proximal outcomes (PCC-DOOR scale on days 7, 14, and 21, ventilator-free days, cumulative 28-day Pediatric Logistic Organ Dysfunction-2 (PELOD-2) scores, and PICU-free days) and 3-month decrease in HRQL or death. HRQL was measured by Pediatric Quality of Life Inventory 4.0 or Functional Status II-R for patients with developmental delay. Patients who died were assigned the worst possible HRQL score. PCC-DOOR scores were applied to 385 patients, median age 6 years (interquartile range 2, 13) and 177 (46%) with a complex chronic condition(s). Three-month outcomes were available for 245 patients (64%) and 42 patients (17%) died. PCC-DOOR scale on days 7, 14, and 21 demonstrated fair correlation with the primary outcome (-0.42 [-0.52, -0.31], -0.47 [-0.56, -0.36], and -0.52 [-0.61, -0.42]), similar to the correlations for cumulative 28-day PELOD-2 scores (-0.51 [-0.59, -0.41]), ventilator-free days (0.43 [0.32, 0.53]), and PICU-free days (0.46 [0.35, 0.55]). CONCLUSIONS: The PCC-DOOR scale is a feasible, practical outcome for pediatric sepsis trials and demonstrates fair correlation with decrease in HRQL or death at 3 months.