Septic Shock Patients Research Articles

Urinary Cysteinyl Leukotrienes as Biomarkers of Endothelial Activation, Inflammation and Oxidative Stress and Their Relationship with Organ Dysfunction in Human Septic Shock.

Cysteinyl leukotrienes (CysLT) are potent vascular leakage-promoting agents but have been scarcely explored in human septic shock (SS). We evaluated CysLT at admission and during hospitalization and their correlation with endothelial dysfunction, inflammation, oxidative stress, the renin-angiotensin-aldosterone system, and cardiac, renal, respiratory, and hepatic parameters in SS patients. Blood and spot-urine samples were collected at days 1-2 (admission), 3-4, and 5-8 in SS patients (n = 13) and at a single time point in controls (n = 22). Urinary CysLT (u-CysLT) and isoprostanes, plasma, and urinary angiotensinogen, serum myeloperoxidase, and IL-10 were quantified by ELISA. Serum intercellular-adhesion molecule-1, vascular cell-adhesion molecule-1, E-selectin, tumor necrosis factor-α, IL-1β, and IL-6 were measured by multiplex immunoassays. Routine markers were evaluated using automated analyzers. At admission, SS patients had increased u-CysLT, endothelial activation, inflammation, oxidative stress, and plasma and urinary angiotensinogen, as well as cardiac, respiratory, hepatic, and renal injury/dysfunction. There were no changes in u-CysLT during hospitalization. Both correlation and multivariate analyses showed positive relationships of u-CysLT with endothelial activation, inflammation, oxidative stress, proteinuria, and hepatic injury/dysfunction markers. These results suggest that u-CysLT may be potential non-invasive biomarkers for monitoring the pathophysiological mechanisms underlying SS, as well as putative therapeutic targets.

Abstract 212: The Effect Of 33 °C Vs. 36 °C Targeted Temperature Management To The Metabolism Following Out-of-hospital Cardiac Arrest.

Targeted Temperature Management (TTM) following shockable out-of-hospital cardiac arrest (OHCA) has been recommended. The effect of different targeted temperatures on the human metabolome has not been compared. Elevated levels of metabolites from the Krebs cycle have recently been associated with a poor outcome in OHCA patients. Similarly, decreased levels of the amino acids valine and leucine have been linked with a poor outcome in septic shock patients. Method: From a single center in the randomized clinical TTM trial, we analyzed blood samples from resuscitated unconscious OHCA patients at two timepoints (hospital arrival and 48 hours later) using ultra-performance liquid mass-spectrometry. Patients were randomized to either 33°C or 36°C hypothermia for the first 28 hours. Sixty-one metabolites of the ~3000 compounds detected were prespecified for quantification and analyzed in the current study. Differences (95% CI) in metabolite concentrations from a constrained linear mixed model are reported, and p-values from the interaction term timepoint x TTM arm. Results: Of the 146 patients, 70 (48 %) were randomized to TTM 33°C. The baseline characteristics (age, gender, shockable rhythm, time to return of spontaneous circulation) and outcome (180 days mortality) were similar in the TTM groups. After 48 hours, approx. 24 hours from the cessation of TTM, fourteen metabolites differed significantly between the two groups. Among these, lactate acid (190 μM (74-305 μM), p<0.001 ), pyruvic acid (26 μM (8-44 μM), p<0. 0 1 ), 2-oxoglutaric acid (2.7 μM (1.0-4.4 μM), p<0.01 ) and prostaglandin E2 (0.60 nM (0.24-1.0 nM), p<0.01 ) were increased in the TTM 33 °C arm whereas valine (25 μM (15-35 μM), p<0.001 ) and leucine (14 μM (8.3 - 20 μM), p<0.001 ) were decreased. Conclusion: TTM at 33°C for 24 hours after OHCA results in a prognostically poorer metabolome even 24 hours later compared with TTM at 36°C.

Using a multiomics approach to unravel a septic shock specific signature in skeletal muscle

Sepsis is defined as a dysregulated host response to infection leading to organs failure. Among them, sepsis induces skeletal muscle (SM) alterations that contribute to acquired-weakness in critically ill patients. Proteomics and metabolomics could unravel biological mechanisms in sepsis-related organ dysfunction. Our objective was to characterize a distinctive signature of septic shock in human SM by using an integrative multi-omics approach. Muscle biopsies were obtained as part of a multicenter non-interventional prospective study. Study population included patients in septic shock (S group, with intra-abdominal source of sepsis) and two critically ill control populations: cardiogenic shock (C group) and brain dead (BD group). The proteins and metabolites were extracted and analyzed by High-Performance Liquid Chromatography-coupled to tandem Mass Spectrometry, respectively. Fifty patients were included, 19 for the S group (53% male, 64 ± 17 years, SAPS II 45 ± 14), 12 for the C group (75% male, 63 ± 4 years, SAPS II 43 ± 15), 19 for the BD group (63% male, 58 ± 10 years, SAPS II 58 ± 9). Biopsies were performed in median 3 days [interquartile range 1–4]) after intensive care unit admission. Respectively 31 patients and 40 patients were included in the proteomics and metabolomics analyses of 2264 proteins and 259 annotated metabolites. Enrichment analysis revealed that mitochondrial pathways were significantly decreased in the S group at protein level: oxidative phosphorylation (adjusted p = 0.008); branched chained amino acids degradation (adjusted p = 0.005); citrate cycle (adjusted p = 0.005); ketone body metabolism (adjusted p = 0.003) or fatty acid degradation (adjusted p = 0.008). Metabolic reprogramming was also suggested (i) by the differential abundance of the peroxisome proliferator-activated receptors signaling pathway (adjusted p = 0.007), and (ii) by the accumulation of fatty acids like octanedioic acid dimethyl or hydroxydecanoic. Increased polyamines and depletion of mitochondrial thioredoxin or mitochondrial peroxiredoxin indicated a high level of oxidative stress in the S group. Coordinated alterations in the proteomic and metabolomic profiles reveal a septic shock signature in SM, highlighting a global impairment of mitochondria-related metabolic pathways, the depletion of antioxidant capacities, and a metabolic shift towards lipid accumulation.ClinicalTrial registration: NCT02789995. Date of first registration 03/06/2016.

Anti-endotoxin antibodies consumption in cardiovascular collapse: Pathophysiological concerns

ObjectiveAbnormal endotoxin activity in critically ill patients has been described in the absence of Gram-negative bacterial (GNB) infection. As disease severity seems to be crucial in the detection of this phenomenon, we decided to assess and compare endotoxin exposure in those patients representing the critical situation: septic shock and cardiogenic shock. DesignProspective, observational non intervention study. SettingCritical Care Department of a University tertiary hospital. PatientsCardiogenic shock (CS) and septic shock (SS) patients. InterventionsNone. Measurements and main resultsFollow-up was performed for the first three days. Inflammatory biomarkers (C-reactive protein, procalcitonin and interleuquin-6) and IgM antiendotoxin-core antibodies titter (IgM EndoCAb) were daily analyzed. Sixty-two patients were included; twenty-five patients with SS and thirty-seven with CS. Microbial etiology was established in 23 SS patients (92%) and GNB were present in 13 cases (52%). Although infection was suspected and even treated in 30 CS patients (81%), any episode could be finally confirmed.EndoCAb consumption was more intense in SS patients, although twenty-two CS patients (59.5%) had IgM anti-endotoxin value below 10th percentile range for healthy people. No statistically significant difference in endotoxin exposure was detected between Gram-positive and Gram-negative infections in the SS group. Endotoxin exposure ability to distinguish between SS and CS was moderate (AUC 0.7892, 95% IC: 0.6564–0.9218). ConclusionsIn the severely ill patient some mechanisms take place allowing endotoxin incursion and therefore blurring the limits of diseases pathophysiology. Our work representatively shows how exposure to endotoxin was not fully capable of distinguishing between CS and SS.

Evaluation of SI, MSI and DSI for very early (3-day) mortality in patients with septic shock

BackgroundSeptic shock is associated with increased mortality. Predicting mortality, including early prediction for septic shock patients in intensive care units (ICUs), remains an important challenge.MethodWe searched the Medical Information Mart for Intensive Care IV database. Odds ratios (ORs) with 95% confidence intervals (CIs) of the relationships between shock index (SI), modified SI (MSI), and diastolic SI (DSI) of patients with septic shock requiring vasopressors and 3-day/in-hospital mortality were calculated using logistic regression models. The time-course changes of these parameters were compared between survivors and non-survivors. The performance of the different parameters was described by the area under the receiver operating characteristic (ROC) curve (AUC) and compared with DeLong analysis.ResultsA total of 1266 patients with septic shock requiring vasopressors were identified. The 3-day mortality rate and in-hospital mortality rate were 8.7% and 23.5%, respectively. Multivariable logistic regression analysis showed significant associations between pre-vasopressor SI/MSI/DSI and 3-day mortality in patients with septic shock requiring vasopressors in fully adjusted models (Ps for trend < 0.01). The AUCs of pre-vasopressor SI, MSI, and DSI were 0.746, 0.710, and 0.732 for 3-day mortality, respectively. There were significant differences in the time-course of SI, MSI, and DSI between survivors and non-survivors at 3-day/in-hospital mortality among patients with septic shock requiring vasopressors (repeated-measures ANOVA, inter-subjects difference P < 0.001).ConclusionPre-vasopressor SI, MSI, and DSI values identified patients with septic shock requiring vasopressors who are at increased risk of early death. Of these easy-to-acquire values, SI and MSI show a comparatively better performance.

A cohort study of developing a death risk prediction model in patients with septic shock based on MIMIC-III database

To develop and validate a model for predicting death risk in septic shock patients using LASSO-Logistic methods. A retrospective cohort study was conducted. Based on the open-source database Medical Information Mart for Intensive Care-III v1.4 (MIMIC-III v1.4), the septic shock patients meeting the Sepsis-3 criteria were included, and the data on demographic characteristics, major signs, laboratory examinations, hospitalization, and outcomes were extracted. Predictive variables were selected by LASSO regression and predictive models were derived using Logistic regression. The calibration of the model was evaluated using the Hosmer-Lemeshow test and discrimination was evaluated using the receiver operator characteristic curve (ROC curve). A total of 693 patients with septic shock were enrolled, in which 445 patients survived and 248 patients dead within 30 days and the mortality was 35.8%. Logistic regression model was constructed according to nine predictive variables and outcome variables screened by LASSO regression method, which showed that advanced age, Elixhauser index, blood lactic acid (Lac), K+ level and mechanical ventilation were associated with increased 30-day mortality [odds ratio (OR) and 95% confidence interval (95%CI) was 1.023 (1.010-1.037), 1.047 (1.022-1.074), 1.213 (1.133-1.305), 2.241 (1.664-3.057), 2.165 (1.433-3.301), respectively, all P < 0.01], and reduced systolic blood pressure (SBP), diastolic blood pressure (DBP), body temperature, and pulse oxygen saturation (SpO2) were also associated with increased 30-day mortality [OR (95%CI) was 0.974 (0.957-0.990), 0.972 (0.950-0.994), 0.693 (0.556-0.857), 0.971 (0.949-0.992), respectively, all P < 0.05]. The calibration curve showed that the predicted risk of septic shock death risk prediction model had good agreement with the real situation. ROC curve analysis showed that the area under the ROC curve (AUC) of the prediction model was 0.839 (95%CI was 0.803-0.876), which could distinguish patients at risk of death from those at risk of survival. The septic shock death risk prediction model has a good ability to identify the 30-day mortality risk of septic shock patients, including nine hospital readily variables (age, Elixhauser index, mechanical ventilation, Lac, K+, SBP, DBP, body temperature and SpO2). The model could be used by clinicians to calculate the risk of death in septic shock individuals.

Prognostic Value of PCO2 Gap in Adult Septic Shock Patients: A Systematic Review and Meta-Analysis.

Sepsis cases caused substantial mortality and a significant burden on healthcare costs and resources. To tackle this problem, there has been discussion surrounding O2 parameters as it has a distinct outcome in septic patients. This review aimed to evaluate the prognostic value of the central venous-arterial carbon dioxide difference (PCO2) gap in patients with septic shock. A comprehensive systematic search was performed through electronic databases including Pubmed, Scopus, and Embase for studies focusing on the use of PCO2 gap as a mortality predictor in septic shock patients. Other secondary outcomes such as mean arterial pressure, lactate clearance, the acute physiology and chronic health evaluation II score, and intensive care unit length of stay were also measured. The Newcastle-Ottawa Scale tool was used to assess the risk of bias. A total of 8 studies were analysed. The mortality rate (odds ratio=0.50, 95% CI=0.28-0.87, P < .01) and lactate levels (mean difference [MD] = -0.98; 95% CI=-1.62 to -0.35; P=.001) of the low PCO2 gap group were significantly lower than the high gap group. The low gap group had a significantly higher mean arterial pressure compared to the high gap group (MD=4.54; 95% CI=2.14 to 6.95; P=.001). There were no pronounced outcomes in acute physiology and chronic health evaluation score and intensive care unit length of stay. PCO2 gap can potentially be used as a marker for mortality rate in septic shock patients. It is also significantly associated with other predictors, such as mean arterial pressure and lactate clearance.

Monitoring NLRP3 Inflammasome Activation and Exhaustion in Clinical Samples: A Refined Flow Cytometry Protocol for ASC Speck Formation Measurement Directly in Whole Blood after Ex Vivo Stimulation.

Alteration of NLRP3 inflammasome pathway including hyper-activation or exhaustion has been implicated in the pathophysiology of many diseases. Following cell stimulation, aggregation of the ASC protein into a multiprotein complex, the ASC speck, has been proposed as a specific read-out for monitoring NLRP3 inflammasome activation by flow cytometry in clinical samples. So far, only a few papers have described a technique to detect ASC speck formation directly in whole blood without any cell purification, and none included an ex vivo stimulation. The objective of this study was thus to develop a simple and shortened flow cytometry protocol to detect ASC speck formation directly in whole blood including an ex vivo stimulation step. We showed that after red blood cells lysis and removal of the LPS stimulation step, ASC speck formation can be detected in both monocytes and neutrophils from healthy donors directly in nigericin-stimulated whole blood samples. Using samples from four septic shock patients, we showed that this technique allows for the detection of NLRP3 inflammasome exhaustion in clinical samples. This novel shortened and simple whole blood protocol should facilitate day-to-day monitoring of NLRP3 inflammasome activation and exhaustion in both monocytes and neutrophils in clinical studies.

Comparison of APACHE II and APACHE IV score as predictors of mortality in patients with septic shock in intensive care unit: A prospective observational study.

Prediction of outcome in intensive care unit (ICU) patients is of imperative importance. Our aim was to assess and compare the performance of Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE IV scores in predicting mortality in adult patients suffering from septic shock admitted to our ICU. This was a prospective observational study conducted in a 14-bedded medical ICU of a tertiary care center from January 2019 to March 2020; 128 patients suffering from septic shock were included and APACHE II and IV scores were calculated. We also calculated the predicted and actual mortality rates and standardized mortality ratios. The receiver operating characteristic curves were used to assess discrimination. Out of the 128 patients, 63 patients (49.21%) died. The mean (± standard deviation) admission APACHE II score was 16.7 ± 5.53, while the mean APACHE IV score was 67.25 ± 25.99. The non-survivors had significantly higher APACHE II and IV scores when compared to those who survived (P < 0.001). APACHE II had a slightly better discriminative power (with the area under the Receiver operating characteristic (ROC) curve of 0.78) than APACHE IV (with the area under the ROC curve of 0.74). The mean predicted mortality rate (PMR) of the patient population calculated on the basis of the APACHE II scoring system was 22.46 ± 15.76, and the mean PMR calculated as per the APACHE IV scoring system was 11.64 ± 15.59. Both APACHE II and APACHE IV underestimated mortality in septic shock patients. Both APACHE II and APACHE IV were comparable in differentiating survivors from non-survivors. However, there was a good correlation between the two models.

CIITA promoter polymorphism impairs monocytes HLA-DR expression in patients with septic shock

SummaryLow monocyte (m)HLA-DR expression is associated with mortality in sepsis. G-286A∗rs3087456 polymorphism in promoter III of HLA class II transactivator (CIITA), the master regulator of HLA, has been associated with autoimmune diseases but its role in sepsis has never been demonstrated. In 203 patients in septic shock, GG genotype was associated with 28-day mortality and mHLA-DR remained low whereas it increased in patients with AA or AG genotype. In ex vivo cells, mHLA-DR failed to augment in GG in comparison with AG or AA genotype on exposure to IFN-γ. Promoter III transcript levels were similar in control monocytes regardless of genotype and exposure to IFN-γ. Promoter III activity was decreased in GG genotype in monocyte cell line but restored after stimulation with IFN-γ. Hereby, we demonstrated that G-286A∗rs3087456 significantly impact mHLA-DR expression in patients with septic shock in part through CIITA promoter III activity, that can be rescued using IFN-γ.

Dynamic changes of platelet count in first week and their predictive value for prognosis in septic shock patients

To observe the dynamic changes of platelet counts in septic shock patients within first week, and to explore their predictive value for prognosis. Retrospective analysis of clinical data of patients with septic shock admitted to the department of intensive care unit (ICU) of the First Affiliated Hospital of University of Science and Technology of China from January 2020 to December 2021 was conducted. The baseline data on gender, age and primary diseases, clinical indicators on infection site, pathogenic microbial type, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA), laboratory indicators and the trend of platelet count (PLT) on day 1, 3, 5 and 7 admitting ICU and patients prognosis of in-hospital were collected. Binary Logistic regression was used to assess the independent risk factors of in-hospital death in septic shock patients. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive power of each index for in-hospital mortality. A total of 193 patients with sepsis were enrolled. Among them, 73 patients died and 120 patients survived. Univariate analysis showed that the age, proportion of hypertension and respiratory system infection, APACHE II score, SOFA score and blood lactic acid (Lac) in the death group were significantly higher than those in the survival group, while the proportion of urinary system infection, white blood cell (WBC) and neutrophil (NEU) were significantly lower in the death group. Within 7 days after admitting ICU, the platelet (PLT) firstly decreased and then rebounded in the survival group, whereas it's showed a continuous downward trend in the death group. And the PLT count in both day 5 and 7 were significantly higher in the survival group compared with the dead group [×109/L: 94.5 (54.0, 182.0) vs. 50.0 (30.5, 87.5), 135.0 (86.8, 205.8) vs. 46.0 (23.5, 71.5), all P < 0.05]. Multivariate binary Logistic regression analysis showed that age [odds ratio (OR) = 1.059, 95% confidence interval (95%CI) was 1.002-1.118], hypertension (OR = 6.108, 95%CI was 1.340-27.851), respiratory system infection (OR = 5.300, 95%CI was 1.116-25.118), APACHE II score (OR = 1.158, 95%CI was 1.054-1.273), SOFA score (OR = 1.494, 95%CI was 1.060-2.107) and PLT on day 7 after admitting ICU (OR = 0.926, 95%CI was 0.894-0.958) were independent risk factors for in-hospital prognosis in septic shock patients (all P < 0.05). ROC analysis showed that APACHE II score, SOFA score and PLT on day 7 after admitting ICU all had good predictive value for in-hospital prognosis in septic shock patients, and the area under the ROC curve (AUC) of PLT on day 7 (AUC = 0.899, 95%CI was 0.857-0.941) was significantly higher than that of APACHE II score (AUC = 0.748, 95%CI was 0.680-0.816), SOFA score (AUC = 0.767, 95%CI was 0.702-0.833). Clinicians should pay close attention to the dynamic changes of platelet counts in septic shock patients, especially the platelet counts on day 7 after admitting ICU. And active intervention should be provided to improve the prognosis.

Establishment of SEP-1 national practice guidelines does not impact fluid administration for septic shock patients

BackgroundThe Centers for Medicare and Medicaid Services introduced the Early Management Bundle, Severe Sepsis/Septic Shock (SEP-1) as a national quality measure in October 2015. The purpose of SEP-1 is to facilitate the efficient, effective, and timely delivery of high-quality care to patients presenting along the spectrum of sepsis severity.Objectives: The primary aim of this study was to investigate whether provider practice surrounding emergency department (ED) fluid management of suspected septic shock patients was impacted by SEP-1. MethodsThe study was a retrospective observational analysis of 470,558 patient encounters at an urban academic center over a five-year period. The sample of suspected septic shock patients was defined by the following: blood cultures collected, antibiotics administered, and vasopressors initiated. Participants were divided into two cohorts based on date of presentation (Pre-SEP-1: May 1, 2013, − August 30, 2015, and Post-SEP-1: November 1, 2015, − February 28, 2018). The primary outcome was classified as a dichotomous variable based on whether the total volume of fluids administered equaled or exceeded the calculated weight-based (≥30 cc/kg) goal. Segmented logistic regression analyses were used to assess the immediate impact of SEP-1 as well as to compare the long-term trend of fluid volume administered between Pre-SEP-1 and Post-SEP-1 cohorts. ResultsA total of 413 and 482 septic shock patients were included in the Pre-SEP-1 and Post-SEP-1 cohorts, respectively. There was no statistically significant change in weight-based fluid management between the cohorts. The odds of compliance with the weight-based goal decreased 22% immediately following dissemination of SEP-1, however, this was not statistically significant (log-odds = −0.25, p = 0.41). A positive trend in compliance was observed during both the Pre-SEP-1 and Post-SEP-1 periods with odds ratios increasing 0.005 and 0.018 each month, respectively, however, these findings were not statistically significant (log-odds = 0.005, p = 0.736, and log-odds = 0.018, p = 0.10, respectively). ConclusionsOverall, there were no clinically or statistically meaningful changes in fluid volume resuscitation strategies for suspected septic shock patients following SEP-1. Broad mandates may not be effective tools for promoting practice change in the ED setting. Further research investigating barrier to changes in practice patterns surrounding fluid administration and other SEP-1 bundle elements is warranted.

Impact of colonization with multidrug-resistant bacteria on the risk of ventilator-associated pneumonia in septic shock

The objective is to identify the risk markers of multi-drug resistant bacteria (MDRB) related ventilator-associated pneumonia (VAP) in septic shock patients with previous MDRB carriage. This retrospective study was conducted in a medical ICU from 2010 to 2020. Consecutive patients with septic shock and still in the ICU after 48 h, were eligible. The following microorganisms were defined as MDRB: extended-spectrum beta-lactamase producing enterobacteriaceae, methicillin-resistant Staphylococcus aureus, multi-drug resistant Pseudomonas aeruginosa, imipenem-resistant Acinetobacter baumanii and Stenotrophomonas maltophilia. Screening for MDRB colonization was performed at ICU admission and during ICU stay. The determinants of MDRB-related VAP were assessed using a time-dependent cause-specific Cox model. 643 patients were analyzed and 122 (18.9%) had at least one episode of VAP. The overall ICU mortality was 32.5%. The incidence of MDRB carriage was 31%, distributed into MDRB carriage at admission (14.3%) and MDRB acquired during ICU stay (16.7%). In multivariate analysis, MDRB colonization in ICU was independently associated with an increased risk of VAP (CSH: 1.85; 95% CI: 1.05-3.23; p = 0.03) whereas carriage prior to admission was not. Imported and acquired MDRB carriage harbor different risks of subsequent MDRB-related VAP in patients with septic shock.

P(v-a)CO2/C(a-v)O2 as a red blood cell transfusion trigger and prognostic indicator for sepsis-related anaemia: protocol for a prospective cohort study

IntroductionRed blood cell (RBC) transfusion primarily aims to improve oxygen transport and tissue oxygenation. The transfusion strategy based on haemoglobin concentration could not accurately reflect cellular metabolism. The ratio of...

406EMF Early Fluid Delivery by Emergency Medical Services for Sepsis Using a Novel Rapid Infusion Device

406EMF Early Fluid Delivery by Emergency Medical Services for Sepsis Using a Novel Rapid Infusion Device

212 Wait, What? Oral Midodrine Instead of Pressors for Septic Shock?

212 Wait, What? Oral Midodrine Instead of Pressors for Septic Shock?

80 Identifying Positive Deviant Nurses in the Speed of Administering Antibiotics for Sepsis and Discovering Their Tactics

Positive deviance (PD) is an application of complexity leadership theory that fosters organizational learning of difficult tasks. PD may also be able to avoid the increased burnout associated with the top-down management tactics of traditional quality improvement (QI). We assessed whether PD may be an appropriate strategy to improve sepsis care by testing for the presence of heterogeneity in nursing antibiotic administration time (AAT) for severe sepsis or septic shock patients and identifying the positive deviant nurses.

Venous-arterial CO2 to arterial-venous O2 content ratio in different shock types and correlation with hypoxia indicators.

Shock is a generalized form of acute circulatory failure characterized by low tissue perfusion. If not recognized early, it highly increases patient morbidity and mortality. Central venous-arterial CO2 (Carbon dioxide) to arterial-central venous O2 (Oxygen) content ratio (Pcv-aCO2/Ca-cvO2) has been used for the early prediction of anaerobic metabolism in septic shock patients. However, knowledge about the usability of this ratio in cardiogenic shock is scarce. We retrospectively collected the data of patients admitted to our 18-bed intensive care unit (Haga Hospital, Department of Intensive Care, The Hague, The Netherlands) with a diagnosis of septic shock or cardiogenic shock in 2018. All patients who had undergone Swan-Ganz or Pulse index Continuous Cardiac Output device insertion were included in the study. The hemodynamic variables were recorded both at ICU admission and during catheterization. Forty-six (n= 46) patients with a mean age of 62 ± 13 years and 52% female gender were enrolled in the study. The Acute Physiology and Chronic Health Evaluation IV (APACHE IV) score was 96 ± 39. Twenty-four patients had septic shock, and twenty-two were diagnosed with cardiogenic shock. Although Pcv-aCO2 (Central venous-arterial CO2) and ScvO2 (Central venous oxygen) were not found different between the cardiogenic and septic shock groups, the Pcv-aCO2/Ca-cvO2 ratio was significantly lower in patients with cardiogenic shock (p= 0.035). The Pcv-aCO2/Ca-cvO2 ratio had a weak correlation with ScvO2 (r= 0.21, p= 0.040). Pcv-aCO2 and ScvO2 showed negative lower moderate correlation (r= -0.40, p= 0.030). Twenty patients [nine (19%) with cardiogenic shock, and eleven (23%) with septic shock] died during their ICU or hospital stay. Although Ca-cvO2, Pcv-aCO2, and ScvO2 were not associated with mortality, a higher Pcv-aCO2/Ca-cvO2 ratio was associated with increased mortality (p= 0.035). The Pcv-aCO2/Ca-cvO2 ratio is a valuable hypoxia indicator in states of shock. However, cutoff levels should be identified for different shock types.

Sepsis associated acute kidney injury in pediatric intensive care unit.

We aimed to compare the acute kidney injury (AKI) incidence in pediatric septic shock patients according to the three different classifications. We analyzed retrospectively 52 patients with severe sepsis between January 2019 and December 2019. While 21 patients have been diagnosed with SA-AKI according to the pRIFLE criteria, 20 children have been diagnosed according to the AKIN criteria, and 21 children have been diagnosed according to the KDIGO criteria. Older age, lower platelet count were determined as independently risk factor for SA-AKI. Older age and higher PRISM score were associated with mortality. According to Canonical correlation coefficients, pRIFLE is the most successful classification to distinguish AKI state. The canonical correlation coefficients for pRIFLE, KDIGO, and AKIN were 0.817, 0.648, and 0.615, respectively. Although AKI incidence was similar between the three classifications, pRIFLE was the most successful classification to distinguish AKI state.

Optimal target blood pressure in elderly with septic shock (OPTPRESS) trial: study protocol for a randomized controlled trial

BackgroundHemodynamic stabilization is a core component in the resuscitation of septic shock. However, the optimal target blood pressure remains debatable. Previous randomized controlled trials suggested that uniformly adopting a target mean arterial pressure (MAP) higher than 65 mmHg for all adult septic shock patients would not be beneficial; however, it has also been proposed that higher target MAP may be beneficial for elderly patients, especially those with arteriosclerosis.MethodsA multicenter, pragmatic single-blind randomized controlled trial will be conducted to compare target MAP of 80–85 mmHg (high-target) and 65–70 mmHg (control) in the resuscitation of septic shock patients admitted to 28 hospitals in Japan. Patients with septic shock aged ≥65 years are randomly assigned to the high-target or control groups. The target MAP shall be maintained for 72 h after randomization or until vasopressors are no longer needed to improve patients’ condition. To minimize the adverse effects related to catecholamines, if norepinephrine dose of ≥ 0.1 μg/kg/min is needed to maintain the target MAP, vasopressin will be initiated. Other therapeutic approaches, including fluid administration, hydrocortisone use, and antibiotic choice, will be determined by the physician in charge based on the latest clinical guidelines. The primary outcome is all-cause mortality at 90 days after randomization.DiscussionThe result of this trial will provide great insight on the resuscitation strategy for septic shock in the era of global aged society. Also, it will provide the better understanding on the importance of individualized treatment strategy in hemodynamic management in critically ill patients.Trial registrationUMIN Clinical Trials Registry; UMIN000041775. Registered 13 September 2020.