Sepsis, Management & Advances in Metabolomics.

Though there have been developments in clinical care and management, early and accurate diagnosis and risk stratification are still bottlenecks in septic shock patients. Since septic shock is multifactorial with patient-specific underlying co-morbid conditions, early assessment of sepsis becomes challenging due to variable symptoms and clinical manifestations. Moreover, the treatment strategies are traditionally based on their progression and corresponding clinical symptoms, not personalized. The complex pathophysiology assures that a single biomarker cannot identify, stratify, and describe patients affected by septic shock. Traditional biomarkers like CRP, PCT, and cytokines are not sensitive and specific enough to be used entirely for a patient's diagnosis and prognosis. Thus, the need of the hour is a sensitive and specific biomarker after comprehensive analysis that may facilitate an early diagnosis, prognosis, and drug development. Integration of clinical data with metabolomics would provide means to understand the patient's condition, stratify patients better, and predict the clinical outcome.

Diagnostic and Prognostic Value of Pentraxin 3, Interleukin-6, CRP, and Procalcitonin Levels in Patients with Sepsis and Septic Shock.

INTRODUCTION AND PURPOSE: In this prospective study, we aim to evaluate the effects of antibiotherapy on pentraxin-3 (PTX3), C-reactive protein (CRP), and interleukin-6 (IL-6) levels in patients with sepsis and septic shock. MATERIALS AND METHODS: In our study, CRP, procalcitonin, IL-6, and PTX3 levels at initial and 48 hours of the antibiotherapy of patients who were admitted to the pediatric intensive care unit (PICU) with the diagnosis of sepsis and septic shock between June 2020 and March 2021 were compared. Patients were compared with the age-appropriate case-control group formed from the patients who received pre-operative routines to investigate the diagnostic value. RESULTS: CRP, IL-6, and PTX3 levels of the patients were significantly higher compared to controls (P < 0.05). After the 48th hour of treatment compared to initial CRP, lactate and PCT levels were significantly lower (P < 0.05). The IL-6 and PCT levels were significantly higher in patients with mortality than in surviving patients. Surviving patients showed a significant decrease in CRP level at the 48th hour. IL-6 levels of patients with septic shock were significantly higher than those with sepsis (P = 0.010; P < 0.05). In the diagnosis of septic shock, the area under curve was 0.785 for IL-6 and the standard deviation was 0.09 (P = 0.002, cut-off value, >32 pg/mL, 88.9% sensitivity, 65.6% specifity). CONCLUSION: The results of this study indicated that IL-6 level is an appropriate biomarker with high specificity in the diagnosis of sepsis and septic shock and in evaluating the response to treatment and determining the prognosis.

[Establishing a prognostic prediction model for patients with septic shock based on the completion time of fluid resuscitation and the negative fluid balance volumes].

OBJECTIVE: To explore the relationship between the completion time of fluid resuscitation as well as negative fluid balance volumes and the prognosis of patients with septic shock, and to try to construct a prediction model based on the completion time of fluid resuscitation and negative fluid balance volumes, and to verify the predictive efficacy of the model on the prognosis of patients with septic shock. METHODS: Patients with septic shock admitted to Wuxi People's Hospital from April 2020 to April 2023 were selected. The general data (gender, age, body mass index, infection site), pathological indicators on admission, the difference of acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) between admission and 24 hours after fluid resuscitation, the completion time of fluid resuscitation and negative fluid balance volume were recorded. Multivariate Logistic analysis was used to screen the influencing factors of the prognosis of patients with septic shock, and a nomogram model was established. Bootstrap method was used for internal validation of the model. The consistency index, calibration curve and receiver operator characteristic curve (ROC curve) were used to evaluate the accuracy and prediction efficiency of the model. RESULTS: A total of 96 patients with septic shock were enrolled, 38 patients died and 58 patients survived at 28 days. Compared with the survival group, the difference of APACHE II score, SOFA score, the proportion of fluid resuscitation completed within 1 to 3 hours, and the proportion of negative fluid balance volume -500 to -250 mL per day in the death group were lower, and the differences were statistically significant (all P < 0.05). Multivariate Logistic analysis showed that the completion time of fluid resuscitation was a risk factor for the prognosis of patients with septic shock [odds ratio (OR) = 26.285, 95% confidence interval (95%CI) was 9.984-76.902, P < 0.05]. The difference of APACHE II score (OR = 0.045, 95%CI was 0.015-0.131), SOFA score (OR = 0.056, 95%CI was 0.019-0.165) between admission and 24 hours after fluid resuscitation, and negative fluid balance volume (OR = 0.043, 95%CI was 0.015-0.127) were protective factors for the prognosis of patients with septic shock (all P < 0.05). The model validation results showed that the consistency index was 0.681 (95%CI was 0.596-0.924), indicating good discrimination. The calibration curve showed that the calibration curve fitted well with the ideal curve. The ROC curve showed that the sensitivity of the nomogram model for predicting the death of patients with septic shock was 83.7%, the specificity was 97.2%, and the area under the ROC curve (AUC) was 0.931 (95%CI was 0.846-0.985), indicating that the model had good prediction efficiency. CONCLUSIONS: The completion time of fluid resuscitation and negative fluid balance volumes are related to the prognosis of septic shock patients, and the alignment diagram model improve the identification of the risk of death in septic shock patients.

Evaluating the predictive value of initial lactate/albumin ratios in determining prognosis of sepsis patients.

Sepsis remains a significant clinical challenge owing to its complex pathophysiology and variable prognosis. The early identification of patients at a higher risk of poor outcomes can be crucial for improving treatment strategies. This study aimed to evaluate the predictive value of early serum lactate and albumin levels and the lactate/albumin (L/A) ratio for 28-day prognosis in patients with sepsis. Patients diagnosed with sepsis between January 2021 and December 2022 were evaluated using a retrospective cohort methodology. Inclusion followed the International Consensus on sepsis and septic shock (Sepsis-3) guidelines and patients were selected based on well-defined criteria. Variables such as lactate, albumin, and the L/A ratio were documented within the first 24 hours of admission. Statistical analyses were performed using various tools, including the nonparametric Mann-Whitney U test and receiver operating characteristic curves. A total of 301 patients were divided into the survival (n = 167) and death (n = 134) groups. Notable differences were detected in the incidence of pulmonary infection, shock, lactate, albumin, and the L/A ratio. The L/A ratio was identified as a key predictor with an area under the curve of 0.868, an optimal cutoff value of >0.17, a sensitivity of 56.21%, and a specificity of 94.18%. Significant disparities in mortality rates and survival times were observed for the lactate, albumin, and L/A levels. This study underscores the predictive value of early serum lactate and albumin levels and the L/A ratio for 28-day prognosis in patients with sepsis, with the L/A ratio showing a superior predictive capability. These findings highlight the importance of L/A ratio as a robust and precise marker for evaluating the future clinical course of patients with sepsis, potentially aiding early detection and management.

Alterations of the Adipo-Myokine Irisin in Sepsis and Septic Shock: Diagnostic and Prognostic Implications.

Irisin, a novel adipo-myokine with metabolic regulatory functions, exerts anti-inflammatory, antioxidant, and anti-apoptotic actions that may confer protection against sepsis-induced organ injury in experimental studies. Until now, only one human study has explored circulating irisin at sepsis onset. We aimed to examine serum irisin and its kinetics in critically ill patients with sepsis and septic shock with regard to sepsis severity and outcome. We enrolled 102 critically ill patients with sepsis or septic shock within 48 h of diagnosis and 102 age- and gender-matched healthy controls. Irisin was determined in serum upon enrollment in all participants and one week later in patients using an immunoenzymatic method. The outcome of sepsis was recorded 28 days after enrollment. At enrollment, circulating irisin was significantly lower in patients than controls (22.3 ± 6.8 µg/L vs. 28.1 ± 6.7 µg/L, p < 0.001), and increased significantly one week later (22.3 ± 6.8 µg/L vs. 26.6 ± 9.5 µg/L, p < 0.001). Irisin was significantly lower in patients who presented with septic shock than those with sepsis, and in non-survivors than survivors both at enrollment and one week later. However, kinetics of irisin did not differ between the groups (p > 0.05). Patients with higher circulating irisin during the first week of sepsis had a better outcome (p < 0.001). Lower irisin was independently associated with 28-day mortality (sepsis onset: HR 0.44, 95% C.I. 0.26-0.77, p = 0.004 and one week after: HR 0.37, 95% C.I. 0.23-0.58, p < 0.001). Irisin was negatively correlated with severity scores, metabolic, and inflammatory biomarkers. Circulating irisin decreases early in sepsis and is an independent predictor of 28-day mortality. Irisin may be a promising diagnostic and prognostic sepsis biomarker; nevertheless, larger studies are needed to explore its role in sepsis.

Identification of a hyperinflammatory sepsis phenotype using protein biomarker and clinical data in the ProCESS randomized trial.

Sepsis is a heterogeneous syndrome and phenotypes have been proposed using clinical data. Less is known about the contribution of protein biomarkers to clinical sepsis phenotypes and their importance for treatment effects in randomized trials of resuscitation. The objective is to use both clinical and biomarker data in the Protocol-Based Care for Early Septic Shock (ProCESS) randomized trial to determine sepsis phenotypes and to test for heterogeneity of treatment effect by phenotype comparing usual care to protocolized early, goal-directed therapy(EGDT). In this secondary analysis of a subset of patients with biomarker sampling in the ProCESS trial (n = 543), we identified sepsis phenotypes prior to randomization using latent class analysis of 20 clinical and biomarker variables. Logistic regression was used to test for interaction between phenotype and treatment arm for 60-day inpatient mortality. Among 543 patients with severe sepsis or septic shock in the ProCESS trial, a 2-class model best fit the data (p = 0.01). Phenotype 1 (n = 66, 12%) had increased IL-6, ICAM, and total bilirubin and decreased platelets compared to phenotype 2 (n = 477, 88%, p < 0.01 for all). Phenotype 1 had greater 60-day inpatient mortality compared to Phenotype 2 (41% vs 16%; p < 0.01). Treatment with EGDT was associated with worse 60-day inpatient mortality compared to usual care (58% vs. 23%) in Phenotype 1 only (p-value for interaction = 0.05). The 60-day inpatient mortality was similar comparing EGDT to usual care in Phenotype 2 (16% vs. 17%). We identified 2 sepsis phenotypes using latent class analysis of clinical and protein biomarker data at randomization in the ProCESS trial. Phenotype 1 had increased inflammation, organ dysfunction and worse clinical outcomes compared to phenotype 2. Response to EGDT versus usual care differed by phenotype.

Case report: Metagenomics next-generation sequencing in the diagnosis of septic shock due to Fusobacterium necrophorum in a 6-year-old child.

Fusobacterium necrophorum (F. necrophorum) infection is rare in pediatrics. In addition, the detection time of F. necrophorum by blood culture is long, and the positive rate is low. Infection with F. necrophorum bacilli usually follows rapid disease progression, resulting in high mortality. In previous reports of F. necrophorum-related cases, the most dangerous moment of the disease occurred after the appearance of Lemierre's syndrome. We report an atypical case of a 6-year-old female patient who developed septic shock within 24 h of admission due to F. necrophorum infection in the absence of Lemierre's syndrome. F. necrophorum was identified in a blood sample by metagenomics next-generation sequencing (mNGS) but not by standard blood culture. The patient was finally cured and discharged after receiving timely and effective targeted anti-infection treatment. In the present case study, it was observed that the heightened virulence and invasiveness of F. necrophorum contribute significantly to its role as a primary pathogen in pediatric septic shock. This can precipitate hemodynamic instability and multiple organ failure, even in the absence of Lemierre's syndrome. The use of mNGS can deeply and rapidly identify infectious pathogens, guide the use of targeted antibiotics, and greatly improve the survival rate of patients.

Easy method to determine fluid responsiveness in septic shock patients: end-tidal CO2 - a prospective observational study.

BACKGROUND: In critically ill patients, especially those with septic shock, fluid management can be a challenging aspect of clinical care. One of the primary steps in treating patients with hemodynamic instability is optimizing intravascular volume. The Passive Leg Raising (PLR) maneuver is a reliable test for assessing fluid responsiveness, as demonstrated by numerous studies and meta-analyses. However, its use requires the measurement of cardiac output, which is often complex and may necessitate clinician experience and specialized equipment. End-Tidal Carbon Dioxide (ETCO2) measurement is relatively easy and is generally stable under steady metabolic conditions. It depends on the body's CO2 production, diffusion of CO2 from the lungs into the bloodstream, and cardiac output. If the other two parameters (metabolic conditions and minute ventilation) are constant, ETCO2 can provide information about cardiac output. The aim of the present study is to investigate the sensitivity of ETCO2 measurement in demonstrating fluid responsiveness. METHODS: All patients diagnosed with septic shock and meeting the inclusion criteria were subjected to a passive leg raising test, and cardiac outputs were measured by echocardiography. An increase in cardiac output of 15% or more was considered indicative of the fluid responder group, while patients with an increase below 15% or no increase were classified as the non-responder group. Patients' intensive care unit admission diagnoses, initial laboratory parameters, tidal volume, minute volume before and after the PLR maneuver, mean and systolic blood pressure, heart rate, Pulse Pressure Variation (PPV) values, and ETCO2 values were recorded. RESULTS: Before and after the ETCO2 test, there was no statistically significant difference between the two groups. However, the change in ETCO2 (ΔETCO2) was significantly higher in the responder group. In the non-responder group, ΔETCO2 was 2.57% (0.81), whereas it was 5.71% (2.83) in the responder group (p<0.001). Receiver Operating Characteristic (ROC) analysis was performed for ΔETCO2, baseline Stroke Volume Variation (SVV), ΔSVV, baseline Heart Rate (HR), ΔHR, baseline PPV, and ΔPPV to predict fluid responsiveness. ΔETCO2 predicted fluid responsiveness with a sensitivity of 85% and a specificity of 86% when it was 4% or higher. When ΔETCO2 was 5% or higher, it predicted fluid responsiveness with a specificity of 99.3% and a sensitivity of 75.5%, with an Area Under the Curve (AUC) of 0.89 (95% confidence interval, 0.828-0.961). CONCLUSION: This study demonstrates that in septic patients, ETCO2 during the PLR test can indicate fluid responsiveness with high sensitivity and specificity and can be used as an alternative to cardiac output measurement.

Predicting septic shock in patients with sepsis at emergency department triage using systolic and diastolic shock index.

INTRODUCTION: Identifying patients with at a high risk of progressing to septic shock is essential. Due to systemic vasodilation in the pathophysiology of septic shock, the use of diastolic blood pressure (DBP) has emerged. We hypothesized that the initial shock index (SI) and diastolic SI (DSI) at the emergency department (ED) triage can predict septic shock. METHOD: This observational study used the prospectively collected sepsis registry. The primary outcome was progression to septic shock. Secondary outcomes were the time to vasopressor requirement, vasopressor dose, and severity according to SI and DSI. Patients were classified by tertiles according to the first principal component of shock index and diastolic shock index. RESULTS: A total of 1267 patients were included in the analysis. The area under the receiver operating characteristic curve (AUC) for predicting progression to septic shock for DSI was 0.717, while that for SI was 0.707. The AUC for predicting progression to septic shock for DSI and SI were significantly higher than those for conventional early warning scores. Middle tertile showed adjusted Odd ratio (aOR) of 1.448 (95% CI 1.074-1.953), and that of upper tertile showed 3.704 (95% CI 2.299-4.111). CONCLUSION: The SI and DSI were significant predictors of progression to septic shock. Our findings suggest an association between DSI and vasopressor requirement. We propose stratifying lower tertile as being at low risk, middle tertile as being at intermediate risk, and upper tertile as being at high risk of progression to septic shock. This system can be applied simply at the ED triage.

The prehospital NEW score to assess septic shock in-hospital, 30-day and 90-day mortality.

BACKGROUND: The early identification of sepsis presenting a high risk of deterioration is a daily challenge to optimise patient pathway. This is all the most crucial in the prehospital setting to optimize triage and admission into the appropriate unit: emergency department (ED) or intensive care unit (ICU). We report the association between the prehospital National Early Warning Score 2 (NEWS-2) and in-hospital, 30 and 90-day mortality of SS patients cared for in the pre-hospital setting by a mobile ICU (MICU). METHODS: Septic shock (SS) patients cared for by a MICU between 2016, April 6th and 2021 December 31st were included in this retrospective cohort study. The NEWS-2 is based on 6 physiological variables (blood pressure, heart rate, respiratory rate, temperature, oxygen saturation prior oxygen supplementation, and level of consciousness) and ranges from 0 to 20. The Inverse Probability Treatment Weighting (IPTW) propensity method was applied to assess the association with in-hospital, 30 and 90-day mortality. A NEWS-2 ≥ 7 threshold was chosen for increased clinical deterioration risk definition and usefulness in clinical practice based on previous reports. RESULTS: Data from 530 SS patients requiring MICU intervention in the pre-hospital setting were analysed. The mean age was 69 ± 15 years and presumed origin of sepsis was pulmonary (43%), digestive (25%) or urinary (17%) infection. In-hospital mortality rate was 33%, 30 and 90-day mortality were respectively 31% and 35%. A prehospital NEWS-2 ≥ 7 is associated with an increase in-hospital, 30 and 90-day mortality with respective RRa = 2.34 [1.39-3.95], 2.08 [1.33-3.25] and 2.22 [1.38-3.59]. Calibration statistic values for in-hospital mortality, 30-day and 90-day mortality were 0.54; 0.55 and 0.53 respectively. CONCLUSION: A prehospital NEWS-2 ≥ 7 is associated with an increase in in-hospital, 30 and 90-day mortality of septic shock patients cared for by a MICU in the prehospital setting. Prospective studies are needed to confirm the usefulness of NEWS-2 to improve the prehospital triage and orientation to the adequate facility of sepsis.

Big data insights into the diagnostic values of CBC parameters for sepsis and septic shock in burn patients: a retrospective study.

Sepsis and septic shock are prevalent and life-threatening complications in burn patients. Despite their severity, existing diagnostic methods are limited. This study aims to evaluate the efficacy of Complete Blood Count (CBC) and CBC ratio markers in diagnosing sepsis and septic shock, and in predicting mortality among burn patients. A cohort of 2757 burn patients was examined to ascertain the correlation between various CBC parameters, their ratios, and the incidence of sepsis and related mortality. Key markers analyzed included Red Cell Distribution Width (RDW), Mean Platelet Volume (MPV), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Mean Platelet Volume-to-Platelet Ratio (MPVPR). Our findings indicate that 65.5% of the patients developed sepsis, and 24.3% succumbed to their conditions. The CBC parameters RDW, MPV, NLR, MPVPR, and MPV-to-Lymphocyte Ratio (MPVLR) were significantly associated with sepsis and mortality. These markers showed considerable temporal variation and yielded an Area Under the Curve (AUC) of over 0.65 in an unadjusted Generalized Estimating Equations (GEE) model. This study underscores the potential of RDW, MPV, NLR, MPVPR, and MPVLR as vital prognostic tools for diagnosing sepsis, septic shock, and predicting mortality in burn patients. Although based on a single-center dataset, our results contribute to the enhancement of sepsis management by facilitating earlier, more precise diagnosis and treatment strategies. Further multi-center research is necessary to confirm these findings and broaden their applicability, establishing a solid base for future explorations in this crucial field.

Serum lactate and mean arterial pressure thresholds in patients with cirrhosis and septic shock.

BACKGROUND: The Sepsis-3 guidelines have incorporated serum lactate levels of >2 mmol/L in septic shock definition to account for higher observed mortality. Further evidence is needed to support this threshold in cirrhosis, as well as target mean arterial pressure (MAP) during resuscitation. METHODS: This observational cohort study investigated the association between initial serum lactate and resuscitation MAP levels on in-hospital mortality in patients with and without cirrhosis. Patients admitted to the intensive care unit for the treatment of septic shock between 2006 and 2021 in a quaternary academic center were included. Patients with cirrhosis documented on imaging and International Classification of Disease codes (n=595) were compared to patients without cirrhosis (n=575). The association of intensive care unit admission lactate levels and median 2-hour MAP with in-hospital mortality and the need for continuous renal replacement therapy was assessed. The association between median 24-hour MAP and in-hospital mortality was analyzed post hoc. RESULTS: Within the cirrhosis group, admission lactate levels of 2-4 and >4 mmol/L were associated with increased in-hospital mortality compared to lactate <2 mmol/L [adjusted odds ratio (aOR): 1.69, CI: 1.03-2.81, aOR: 4.02, CI: 2.53-6.52]. Median 24-hour MAP 60-65 and <60 mm Hg were also associated with increased in-hospital mortality compared with MAP >65 mm Hg (aOR: 2.84, CI: 1.64-4.92 and aOR: 7.34, CI: 3.17-18.76). In the noncirrhosis group, associations with in-hospital mortality were weaker for lactate 2-4 and >4 mmol/L (aOR: 1.32, CI: 0.77-2.27 and aOR: 2.25, CI: 1.40-3.67) and median 24-hour MAP 60-65 and <60 mm Hg (aOR: 1.70, CI: 0.65-4.14 and aOR: 4.41, CI: 0.79-29.38). CONCLUSIONS: These findings support utilizing lactate >2 mmol/L in the definition of septic shock, as well as a target MAP of >65 mm Hg during resuscitation in patients with cirrhosis.

Surviving Sepsis Campaign Research Priorities 2023.

OBJECTIVES: To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock. DESIGN: Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities. METHODS: Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article. RESULTS: A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis? CONCLUSIONS: Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock.

Hemodynamic Management Strategies in Pediatric Septic Shock: Ten Concepts for the Bedside Practitioner.

The three pathophysiologic contributors to septic shock include varying combinations of hypovolemia (relative > absolute), decreased vascular tone or vasoplegia, and myocardial dysfunction. The three pillars of hemodynamic support include fluid boluses, vasopressors with or without inotrope infusions. The three end-points of hemodynamic resuscitation include an adequate cardiac output (CO), adequate mean arterial pressure (MAP) and diastolic blood pressure (DBP) for organ perfusion, and avoiding congestion (worse filling) parameters. Only 33-50% of septic patients show post-fluid bolus CO improvements; this may be sustained in ≥10% on account of sepsis-mediated glycocalyx injury. A pragmatic approach is to administer a small bolus (10 mL/kg over 20-30 min) and judge the response based on clinical perfusion markers, pressure elements, and congestive features. Vasoplegia marked by low DBP is a major contributor to hypotension in septic shock. Hence, a strategy of restricted fluid bolus with early low-dose norepinephrine (NE) (0.05-0.1 µg/kg/min) can be helpful. NE may also be useful in septic myocardial dysfunction (SMD) as an initial agent to maintain adequate coronary perfusion and DBP while minimizing tachycardia and providing inotropy. Severe SMD may benefit from additional inotropy (epinephrine/dobutamine). Except vasopressin, most vasoactive drugs may safely be administered via a peripheral route. The lowest MAP (5th centile for age) may be an acceptable target, provided end-organ perfusion is satisfactory. A clinical individualized approach combining the history, serial physical examination, laboratory analyses, available monitoring tools, and repeated assessment to individualize circulatory support may to lead to better outcomes than one-size-fits-all algorithms.

Prior Use of Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers and Clinical Outcomes of Sepsis and Septic Shock: A Systematic Review and Meta-analysis.

ABSTRACT: Sepsis and septic shock are life-threatening conditions that are associated with high mortality and considerable health care costs. The association between prior angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) use and outcomes after sepsis is elusive. The aim of this study was to evaluate the role of the prior use of ACEi or ARBs and outcomes after sepsis and septic shock. A relevant literature review was performed in 4 databases from inception until July 2022. Independent reviewers first screened the title, abstract, and full text, and then, data extraction and analysis were performed. One post hoc analysis of a trial and 6 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%; odds ratio (OR), 0.78, 95% confidence interval (CI), 0.64-0.96], and 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 as compared with nonusers (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.

Septic shock and biliary sepsis: 90-day mortality and associated risk factors.

BACKGROUND: Biliary sepsis is common in patients with digestive cancer. Recommendations call for antibiotic de-escalation (ADE) as a strategy for antibiotic treatment of sepsis or septic shock. The aim of this study was to identify factors influencing 90-day mortality and to evaluate the impact of ADE. METHODS: This retrospective study was conducted between November 2008 and December 2019 in a referral cancer center. Adults with biliary sepsis or septic shock admitted to the ICU were included. Variables associated with 90-day mortality were identified using univariate and multivariate Cox proportional hazards models. RESULTS: 122 patients were included. The 90-day mortality was 30.3% (n = 37). After multivariate analysis, the factors independently associated 90-day mortality were metastatic stage (p = 0.004), biliary tract tumour compression (p = 0.001), multi drug resistant (MDR) bacteria carriage on intensive care unit (ICU)admission (p = 0.048), serum lactate on ICU admission (p < 0.001), the use of extra-renal replacement (p = 0.008), factor V < 50% (p = 0.009) and performance status (ECOG-PS) > 2 (p < 0.001). ADE of the pivotal antibiotic (p = 0.041) and recent cancer surgery (p < 0.001) appeared to be associated with survival. CONCLUSION: The 90-day mortality of biliary sepsis seems to be favourable. The 90-day mortality is associated with organ dysfunctions, but also with ECOG-PS, cancer stage, MDR bacteria colonisation. ADE seems to be safe.

Importance of lactate/albumin ratio in pediatric nosocomial infection and mortality at different times.

Aim: To evaluate the lactate/albumin ratio and its relation to mortality in children with nosocomial infections. Materials & methods: One hundred six children were included in this study. Blood gas and albumin levels were analyzed at the first, 24th and 48th h. Results: The types of detected microbial agents, signs of sepsis, development of septic shock and mortality rates were different. The first-, 24th- and 48th h lactate levels of the children who died were higher than those of the living children, but the albumin levels were lower. The highest area under the curve value for the lactate/albumin ratio was detected at the 24th h. Conclusion: Lactate/albumin ratio can be used to predict mortality in children with nosocomial infections.

[Guideline-conform treatment of sepsis]. / Leitliniengerechte Therapie der Sepsis.

The time to administration of broad-spectrum antibiotics and (secondarily) to the initiation of hemodynamic stabilization are the most important factors influencing survival of patients with sepsis and septic shock; however, the basic prerequisite for the initiation of an adequate treatment is that a suspected diagnosis of sepsis is made first. Therefore, the treatment of sepsis, even before it has begun, is an interdisciplinary and interprofessional task. This article provides an overview of the current state of the art in sepsis treatment and points towards new evidence that has the potential to change guideline recommendations in the coming years. In summary, the following points are critical: (1) sepsis must be diagnosed as soon as possible and the implementation of a source control intervention (in case of a controllable source) has to be implemented as soon as (logistically) possible. (2) In general, intravenous broad-spectrum antibiotics should be given within the first hour after diagnosis if sepsis or septic shock is suspected. In organ dysfunction without shock, where sepsis is a possible but unlikely cause, the results of focused advanced diagnostics should be awaited before a decision to give broad-spectrum antibiotics is made. If it is not clear within 3 h whether sepsis is the cause, broad-spectrum antibiotics should be given when in doubt. Administer beta-lactam antibiotics as a prolonged (or if therapeutic drug monitoring is available, continuous) infusion after an initial loading dose. (3) Combination treatment with two agents for one pathogen group should remain the exception (e.g. multidrug-resistant gram-negative pathogens). (4) In the case of doubt, the duration of anti-infective treatment should rather be shorter than longer. Procalcitonin can support the clinical decision to stop (not to start!) antibiotic treatment! (5) For fluid treatment, if hypoperfusion is present, the first (approximately) 2L (30 ml/kg BW) of crystalloid solution is usually safe and indicated. After that, the rule is: less is more! Any further fluid administration should be carefully weighed up with the help of dynamic parameters, the patient's clinical condition and echo(cardio)graphy.