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.

Quick Sequential Organ Failure Assessment Score Is a Better Predictor of Septic Shock After Percutaneous Nephrolithotomy: A Secondary Analysis of Two Multicenter Prospective Trials.

Introduction: Recent retrospective literature suggests that the quick sequential organ failure assessment (qSOFA) scoring tool is a potentially superior tool over use of the systemic inflammatory response syndrome (SIRS) criteria to predict septic shock after percutaneous nephrolithotomy (PCNL) surgery. Here we examine use of qSOFA and SIRS to predict septic shock within data series collected prospectively on PCNL patients as part of a greater study of infectious complications. Materials and Methods: We performed a secondary analysis of two prospective multicenter studies including PCNL patients across nine institutions. Clinical signs informing SIRS and qSOFA scores were collected no later than postoperative day 1. The primary outcome was sensitivity and specificity of SIRS and qSOFA (high-risk score of greater-or-equal to two points) in predicting admission to the intensive care unit (ICU) for vasopressor support. Results: A total of 218 cases at 9 institutions were analyzed. One patient required vasopressor support in the ICU. The sensitivity/specificity was 100%/72.4% (McNemar's test p < 0.001) for SIRS and was 100%/90.8% (McNemar's test p < 0.001) for qSOFA. Conclusion: Although positive predictive value for both qSOFA and SIRS in prediction of post-PCNL septic shock is low, prospectively collected data demonstrate use of qSOFA may offer greater specificity than SIRS criteria when predicting post-PCNL septic shock.

A comparison of the Sepsis-2 and Sepsis-3 definitions for assessment of mortality risk in dogs with parvovirus.

OBJECTIVE: To evaluate the use of a modified Sepsis-3 (mSepsis-3) definition compared to the currently used modified Sepsis-2 (mSepsis-2) definition to determine whether the mSepsis-2 or mSepsis-3 stratifications were able to identify populations of dogs ultimately more likely to die from canine parvovirus (CPV) infection. DESIGN: Retrospective, January 2009 to March 2020. SETTING: A private, small animal, urban, referral emergency and specialty hospital. ANIMALS: Fifty-nine client-owned dogs hospitalized for treatment of CPV. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Dogs were divided into mSepsis-2 and mSepsis-3 categories based on the highest level of illness severity reached during hospitalization. Greater illness severity based on mSepsis-2 criteria (ie, sepsis, severe sepsis, septic shock) was associated with an increase in average length of stay (P < 0.001), increase in average cost of stay (P < 0.01), and presence of leukopenia (P < 0.05). An increase in illness severity within the mSepsis-2 criteria was not associated with hyperlactatemia (P = 0.29), presence of neutropenia (P = 0.12), or mortality (P = 0.35). Greater illness severity based on mSepsis-3 criteria (ie, infection only, sepsis, septic shock) was associated with an increase in mortality (P < 0.05), increase in average length of stay (P < 0.001), increase in average cost of stay (P < 0.01), presence of leukopenia (P < 0.01), and presence of neutropenia (P < 0.05). The mSepsis-3 criteria were not associated with the presence of hyperlactatemia (P = 0.68). There was no significant difference between survivors and nonsurvivors in the presence of leukopenia (P = 0.19), neutropenia (P = 0.67), or hyperlactatemia (P = 0.58). CONCLUSIONS: The mSepsis-3 diagnostic criteria appear to better identify dogs with CPV at higher risk for mortality compared to the mSepsis-2 criteria.

SOFA Score in relation to Sepsis: Clinical Implications in Diagnosis, Treatment, and Prognostic Assessment.

Purpose: To analyze the clinical significance of the sequential organ failure assessment (SOFA) score in the diagnosis, treatment, and prognostic assessment of sepsis. Methods: 140 patients with sepsis from January 2020 to January 2021 were selected as the observation group, and 40 healthy people were selected as the control group. The observation group was divided into mild group, severe group, and septic shock group by single blind grouping according to the condition of the disease, and they were also divided into survival group and death group according to the prognosis. Collect the fasting venous blood of the subjects in each group in the morning, compare the levels of total bilirubin (TBIL), blood creatinine (CR), and platelet count (PLT) in each group, and record and compare the patients' respiratory system oxygen partial pressure/inhaled oxygen concentration (po2/fio2), acute physiology and chronic health scoring system II (APACHE II), sequential organ failure assessment (sofa) score, q-SOFA score, and △SOFA score; Pearson analysis was used to analyze the correlation between SOFA score and other indicators; multivariate logistic regression was used to analyze the prognostic risk factors of patients with sepsis; receiver-operating characteristic curve (ROC) was used to analyze the value of SOFA score alone and in combination in the diagnosis, condition, and prognosis of sepsis. Results: There were significant differences in Apache II score, SOFA score, q-SOFA score map, po2/fio2, PLT, GCS, TBIL, and serum creatinine (SCR) between the control group and the observation group (P < 0.05). There were significant differences in Apache II score, SOFA score, q-SOFA score, mean arterial pressure (map) po2/fio2, PLT, Glasgow Coma Score (GCS), TBIL, SCR, and △SOFA score among patients in mild, severe, and septic shock groups (P < 0.05). There were significant differences in age, Apache II score, SOFA score, q-SOFA score, map, po2/fio2, PLT, GCS, TBIL, SCR, and △SOFA score between survival group and death group (P < 0.05). SOFA score and q-SOFA score were significantly positively correlated with TBIL and SCR and significantly negatively correlated with po2/fio2 and PLT; △SOFA score was significantly negatively correlated with TBIL and SCR and significantly positively correlated with map, po2/fio2, PLT, and GCS. Apache II score, SOFA score, and q-SOFA score were independent risk factors for sepsis patients, and △SOFA score, po2/fio2, and GCS score were protective factors (P < 0.05). ROC curve analysis showed that the AUC of sepsis combined with SOFA score and q-SOFA score was 0.880; the AUC of sepsis assessed by SOFA score, q-SOFA score, and △SOFA score was 0.929; the AUC of sepsis prognosis assessed by SOFA score, q-SOFA score, and △SOFA score was 0.900. Conclusion: SOFA score, q-SOFA score, and △SOFA score were abnormally expressed in patients with sepsis and were risk factors for the severity of the patient's condition and prognosis. The SOFA score, q-SOFA score, and △SOFA score were risk factors for the severity and prognosis of patients with sepsis and had some value in diagnosing sepsis and assessing the condition and prognosis, of which the combined value of the three was higher.

Antibiotics: it is all about timing, isn't it?

PURPOSE OF REVIEW: Sepsis guidelines and quality measures set aggressive deadlines for administering antibiotics to patients with possible sepsis or septic shock. However, the diagnosis of sepsis is often uncertain, particularly upon initial presentation, and pressure to treat more rapidly may harm some patients by exposing them to unnecessary or inappropriate broad-spectrum antibiotics. RECENT FINDINGS: Observational studies that report that each hour until antibiotics increases mortality often fail to adequately adjust for comorbidities and severity of illness, fail to account for antibiotics given to uninfected patients, and inappropriately blend the effects of long delays with short delays. Accounting for these factors weakens or eliminates the association between time-to-antibiotics and mortality, especially for patients without shock. These findings are underscored by analyses of the Centers for Medicaid and Medicare Services SEP-1 measure: it has increased sepsis diagnoses and broad-spectrum antibiotic use but has not improved outcomes. SUMMARY: Clinicians are advised to tailor the urgency of antibiotics to their certainty of infection and patients' severity of illness. Immediate antibiotics are warranted for patients with possible septic shock or high likelihood of infection. Antibiotics can safely be withheld to allow for more investigation, however, in most patients with less severe illnesses if the diagnosis of infection is uncertain.

Validation of the Pediatric Sequential Organ Failure Assessment Score and Evaluation of Third International Consensus Definitions for Sepsis and Septic Shock Definitions in the Pediatric Emergency Department.

Importance: Pediatric sepsis definitions have evolved, and some have proposed using the measure used in adults to quantify organ dysfunction, a Sequential Organ Failure Assessment (SOFA) score of 2 or more in the setting of suspected infection. A pediatric adaptation of SOFA (pSOFA) showed excellent discrimination for mortality in critically ill children but has not been evaluated in an emergency department (ED) population. Objective: To delineate test characteristics of the pSOFA score for predicting in-hospital mortality among (1) all patients and (2) patients with suspected infection treated in pediatric EDs. Design, Setting, and Participants: This retrospective cohort study took place from January 1, 2012, to January 31, 2020 in 9 US children's hospitals included in the Pediatric Emergency Care Applied Research Network (PECARN) Registry. The data was analyzed from February 1, 2020, to April 18, 2022. All ED visits for patients younger than 18 years were included. Exposures: ED pSOFA score was assigned by summing maximum pSOFA organ dysfunction components during ED stay (each 0-4 points). In the subset with suspected infection, visit meeting criteria for sepsis (suspected infection with a pSOFA score of 2 or more) and septic shock (suspected infection with vasoactive infusion and serum lactate level >18.0 mg/dL) were identified. Main Outcomes and Measures: Test characteristics of pSOFA scores of 2 or more during the ED stay for hospital mortality. Results: A total of 3 999 528 (female, 47.3%) ED visits were included. pSOFA scores ranged from 0 to 16, with 126 250 visits (3.2%) having a pSOFA score of 2 or more. pSOFA scores of 2 or more had sensitivity of 0.65 (95% CI, 0.62-0.67) and specificity of 0.97 (95% CI, 0.97-0.97), with negative predictive value of 1.0 (95% CI, 1.00-1.00) in predicting hospital mortality. Of 642 868 patients with suspected infection (16.1%), 42 992 (6.7%) met criteria for sepsis, and 374 (0.1%) met criteria for septic shock. Hospital mortality rates for suspected infection (599 502), sepsis (42 992), and septic shock (374) were 0.0%, 0.9%, and 8.0%, respectively. The pSOFA score had similar discrimination for hospital mortality in all ED visits (area under receiver operating characteristic curve, 0.81; 95% CI, 0.79-0.82) and the subset with suspected infection (area under receiver operating characteristic curve, 0.82; 95% CI, 0.80-0.84). Conclusions and Relevance: In a large, multicenter study of pediatric ED visits, a pSOFA score of 2 or more was uncommon and associated with increased hospital mortality yet had poor sensitivity as a screening tool for hospital mortality. Conversely, children with a pSOFA score of 2 or less were at very low risk of death, with high specificity and negative predictive value. Among patients with suspected infection, patients with pSOFA-defined septic shock demonstrated the highest mortality.

High Inter-Patient Variability in Sepsis Evolution: A Hidden Markov Model Analysis.

BACKGROUND: Severe sepsis and septic shock are common in the intensive care unit (ICU) and contribute significantly to cost and mortality. Early treatment is critical but is confounded by the difficulty of real-time diagnosis. This study uses hidden Markov models (HMMs) to examine whether the time evolution of sepsis can add diagnostic accuracy or value using a proven set of bio-signals. METHODS: Clinical data (N=36 patients; 6071 hours), including an hourly personalised insulin sensitivity metric. A two hidden state HMM is created to discriminate diagnosed cases (Severe Sepsis, Septic Shock) from controls (SIRS, Sepsis) states. Diagnostic performance is measured by ROC curves, likelihood ratios (LHRs), sensitivity/specificity, and diagnostic odds-ratios (DOR), for a best-case resubstitution estimate and a worst-case 80/20% repeated holdout analysis. RESULTS: The HMM delivered near perfect results (95% Sensitivity; 96% Specificity) for best-case resubstitution estimates, but was comparatively poor (59% Sensitivity; 61% Specificity) for worst-case repeated holdout estimations. Adding the time evolution of sepsis did not add to the accuracy of diagnosis from using the signals alone without time history. CONCLUSIONS: These potentially surprising results indicate significant inter-patient variability in the time evolution of sepsis, preventing effective diagnosis in the context of the bio-signals, data, and HMM topology used. Efforts for improved real-time, early sepsis diagnosis should concentrate on the robustness and efficacy of the bio-signals and data used, as well as the level of model complexity, to create more effective real-time classifiers.

[Comparative assessment of prognostic systems for secondary peritonitis outcome]. / Sravnitel'naya otsenka sistem prognoza iskhoda vtorichnogo peritonita.

OBJECTIVE: To compare the most common prognostic systems in patients with peritonitis. MATERIAL AND METHODS: The study included 352 patients with secondary peritonitis. At admission, sepsis was diagnosed in 15 (4.3%) patients, septic shock - in 4 (1.1%) cases. Mortality was associated with the following main causes: purulent intoxication and/or sepsis - 51 cases (87.9%), cancer-induced intoxication - 4 (6.9%) cases, acute cardiovascular failure - 3 cases (5.2%). We analyzed the efficacy of Manheim Peritoneal Index (MPI), WSES prognostic score, APACHE-II scale, gSOFA score and Peritonitis Prediction System (PPS) developed by the authors. RESULTS: Age of a patient, malignant tumor, exudate nature, sepsis (septic shock) and organ failure not associated with peritonitis are the most important criteria in predicting fatal outcome. ROC analysis was used to assess prognostic value of various prediction systems. Standard error was less than 0.05 for all scales. Therefore, all prediction systems can be considered accurate for prediction of mortality in patients with peritonitis. CONCLUSION: PPS (AUC 0.942) has the greatest accuracy in predicting fatal outcome in patients with advanced secondary peritonitis, APACHE II (AUC 0.840) - minimum accuracy. MPI had predictive accuracy > 90% too.

Gender-related differences in the performance of sequential organ failure assessment (SOFA) to predict septic shock after percutaneous nephrolithotomy.

The study aims to identify whether gender differences exist in the sequential organ failure assessment (SOFA) score to the extent of affecting its predictive accuracy for septic shock after percutaneous nephrolithotomy (PCNL). A retrospective study of 612 patients undergoing PCNL was performed. The SOFA scores of male and female groups were compared to identify any gender differences. The ROC curve was used to find differences between the original and adjusted SOFA scores. Postoperative septic shock developed in 21 (3.43%) cases. A marginally significant discrepancy in median SOFA scores between genders was discovered in a subgroup of patients < 40 years old (p = 0.048). A gender difference existed in the SOFA score after PCNL, with greater proportion of high scores in female patients (p = 0.011). Male patients had a higher proportion of ≥ 2 sub-score in hepatic and renal systems than female patients, caused by their higher preoperative bilirubin and creatinine (p < 0.05). An adjusted SOFA score was created to replace the original postoperative SOFA score with the perioperative changed values of bilirubin and creatinine. Performance of the adjusted SOFA score for predicting septic shock was comparable with the original SOFA score (AUC 0.987 vs. 0.985, p = 0.932). Under the premise of ensuring 100% sensitivity, the adjusted SOFA score reduced the 43.7% (31/71) false-positive rate for predicting septic shock compared with the original SOFA score. In conclusion, the gender should not be neglected when applying SOFA score for patients after PCNL. The adjusted SOFA score eliminates negative effects caused by gender differences in predicting septic shock.

Infectious Diseases Society of America Position Paper: Recommended Revisions to the National Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) Sepsis Quality Measure.

The Centers for Medicare & Medicaid Services' Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1's potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. IDSA is also concerned that SEP-1's complex "time zero" definition is not evidence-based and is prone to inter-observer variation. In this position paper, IDSA outlines several recommendations aimed at reducing the risk of unintended consequences of SEP-1 while maintaining focus on its evidence-based elements. IDSA's core recommendation is to limit SEP-1 to septic shock, for which the evidence supporting the benefit of immediate antibiotics is greatest. Prompt empiric antibiotics are often appropriate for suspected sepsis without shock, but IDSA believes there is too much heterogeneity and difficulty defining this population, uncertainty about the presence of infection, and insufficient data on the necessity of immediate antibiotics to support a mandatory treatment standard for all patients in this category. IDSA believes guidance on managing possible sepsis without shock is more appropriate for guidelines that can delineate the strengths and limitations of supporting evidence and allow clinicians discretion in applying specific recommendations to individual patients. Removing sepsis without shock from SEP-1 will mitigate the risk of unnecessary antibiotic prescribing for noninfectious syndromes, simplify data abstraction, increase measure reliability, and focus attention on the population most likely to benefit from immediate empiric broad-spectrum antibiotics.

Assessment of Machine Learning to Estimate the Individual Treatment Effect of Corticosteroids in Septic Shock.

Importance: The survival benefit of corticosteroids in septic shock remains uncertain. Objective: To estimate the individual treatment effect (ITE) of corticosteroids in adults with septic shock in intensive care units using machine learning and to evaluate the net benefit of corticosteroids when the decision to treat is based on the individual estimated absolute treatment effect. Design, Setting, and Participants: This cohort study used individual patient data from 4 trials on steroid supplementation in adults with septic shock as a training cohort to model the ITE using an ensemble machine learning approach. Data from a double-blinded, placebo-controlled randomized clinical trial comparing hydrocortisone with placebo were used for external validation. Data analysis was conducted from September 2019 to February 2020. Exposures: Intravenous hydrocortisone 50 mg dose every 6 hours for 5 to 7 days with or without enteral 50 µg of fludrocortisone daily for 7 days. The control was either the placebo or usual care. Main Outcomes and Measures: All-cause 90-day mortality. Results: A total of 2548 participants were included in the development cohort, with median (interquartile range [IQR]) age of 66 (55-76) years and 1656 (65.0%) men. The median (IQR) Simplified Acute Physiology Score (SAPS II) was 55 [42-69], and median (IQR) Sepsis-related Organ Failure Assessment score on day 1 was 11 (9-13). The crude pooled relative risk (RR) of death at 90 days was 0.89 (95% CI, 0.83 to 0.96) in favor of corticosteroids. According to the optimal individual model, the estimated median absolute risk reduction was of 2.90% (95% CI, 2.79% to 3.01%). In the external validation cohort of 75 patients, the area under the curve of the optimal individual model was 0.77 (95% CI, 0.59 to 0.92). For any number willing to treat (NWT; defined as the acceptable number of people to treat to avoid 1 additional outcome considering the risk of harm associated with the treatment) less than 25, the net benefit of treating all patients vs treating nobody was negative. When the NWT was 25, the net benefit was 0.01 for the treat all with hydrocortisone strategy, -0.01 for treat all with hydrocortisone and fludrocortisone strategy, 0.06 for the treat by SAPS II strategy, and 0.31 for the treat by optimal individual model strategy. The net benefit of the SAPS II and the optimal individual model treatment strategies converged to zero for a smaller number willing to treat, but the individual model was consistently superior than model based on the SAPS II score. Conclusions and Relevance: These findings suggest that an individualized treatment strategy to decide which patient with septic shock to treat with corticosteroids yielded positive net benefit regardless of potential corticosteroid-associated side effects.

Quantitative Assessment of Blood Lactate in Shock: Measure of Hypoxia or Beneficial Energy Source.

Blood lactate concentration predicts mortality in critically ill patients and is clinically used in the diagnosis, grading of severity, and monitoring response to therapy of septic shock. This paper summarizes available quantitative data to provide the first comprehensive description and critique of the accepted concepts of the physiology of lactate in health and shock, with particular emphasis on the controversy of whether lactate release is simply a manifestation of tissue hypoxia versus a purposeful transfer ("shuttle") of lactate between tissues. Basic issues discussed include (1) effect of nonproductive lactate-pyruvate exchange that artifactually enhances flux measurements obtained with labeled lactate, (2) heterogeneous tissue oxygen partial pressure (Krogh model) and potential for unrecognized hypoxia that exists in all tissues, and (3) pathophysiology that distinguishes septic from other forms of shock. Our analysis suggests that due to exchange artifacts, the turnover rate of lactate and the lactate clearance are only about 60% of the values of 1.05 mmol/min/70 kg and 1.5 L/min/70 kg, respectively, determined from the standard tracer kinetics. Lactate turnover reflects lactate release primarily from muscle, gut, adipose, and erythrocytes and uptake by the liver and kidney, primarily for the purpose of energy production (TCA cycle) while the remainder is used for gluconeogenesis (Cori cycle). The well-studied physiology of exercise-induced hyperlactatemia demonstrates massive release from the contracting muscle accompanied by an increased lactate clearance that may occur in recovering nonexercising muscle as well as the liver. The very limited data on lactate kinetics in shock patients suggests that hyperlactatemia reflects both decreased clearance and increased production, possibly primarily in the gut. Our analysis of available data in health and shock suggests that the conventional concept of tissue hypoxia can account for most blood lactate findings and there is no need to implicate a purposeful production of lactate for export to other organs.

Sepsis and septic shock - an observational study of the incidence, management, and mortality predictors in a medical intensive care unit.

AIM: To prospectively determine the number of patients with sepsis and septic shock in a medical intensive care unit (ICU) using the Sepsis-3 definition; to analyze patients' characteristics, clinical signs, diagnostic test results, treatment and outcomes; and to define independent risk factors for ICU mortality. METHODS: This prospective observational study enrolled all patients with the diagnosis of sepsis treated in the medical ICU of "Sestre Milosrdnice" University Hospital Center, Zagreb, between April 2017 and May 2018. RESULTS: Out of 116 patients with sepsis, 54.3% were female. The median age was 73.5 years (IQR 63-82). The leading source of infection was the genitourinary tract (56.9%), followed by the lower respiratory tract (22.4%). A total of 35.3% of the patients experienced septic shock. Total ICU mortality for sepsis was 37.9%: 63.4% in patients with septic shock and 24.0% in patients without shock. Independent risk factors for ICU mortality were reduced mobility level (odds ratio [OR] 11.16, 95% confidence interval [CI] 2.45-50.91), failure to early recognize sepsis in the emergency department (OR 6.59, 95% CI 1.09-39.75), higher Sequential Organ Failure Assessment score at admission (OR 2.37, 95% CI 1.59-3.52), and inappropriate antimicrobial treatment (OR 9.99, 95% CI 2.57-38.87). CONCLUSION: While reduced mobility level and SOFA score are predetermined characteristics, early recognition of sepsis and the choice of appropriate antimicrobial treatment could be subject to change. Raising awareness of sepsis among emergency department physicians could improve its early recognition and increase the number of timely obtained specimens for microbial cultures.

Assessment of tissue oxygenation to personalize mean arterial pressure target in patients with septic shock.

OBJECTIVE: To investigate whether assessment of tissue oxygenation could help personalizing the mean arterial pressure (MAP) target in patients with septic shock. METHODS: We prospectively measured near-infrared spectroscopy variables in 22 patients with septic shock receiving norepinephrine with a MAP>75 mmHg within the first six hours of intensive care unit (ICU) stay for patients with community-acquired septic shock and within the first six hours of resuscitation for patients with ICU-acquired septic shock. All measurements were performed at MAP>75 mmHg ("high-MAP") and at MAP 65-70 mmHg ("low-MAP") after decreasing the norepinephrine dose. Relative changes in StO2 recovery slope (RS) >8% were considered clinically relevant. RESULTS: After decreasing the norepinephrine dose by 45 ± 24%, MAP significantly decreased from 81[78;84] to 68[67;69]mmHg, whereas cardiac index did not change. On average, the StO2-RS significantly decreased between high and low-MAP from 2.86[1.87;4.32] to 2.41[1.14;3.72]%/sec with a large interindividual variability: the StO2-RS decreased by >8% in 14 patients, increased by >8% in 4 patients and changes were < 8% in 4 patients. These changes in StO2-RS were correlated with the StO2-RS at low-MAP (r = 0.57,p = 0.006). At high-MAP, there was no difference between patients exhibiting a relevant decrease or increase in StO2-RS. CONCLUSIONS: A unique MAP target may not be suitable for all patients with septic shock as its impact on peripheral oxygenation may widely differ among patients. It could make sense to personalize MAP target through a multimodal assessment including peripheral oxygenation.

[Assessment of outcomes of implementing the Sepsis Code in the emergency department of a tertiary hospital]. / Evaluación de los resultados de la implantación del Código Sepsis en el servicio de urgencias de un hospital terciario.

INTRODUCTION: A Sepsis Code (CS) is a comprehensive multidisciplinary system which has the aim of optimising the identification and intervention times of patients with sepsis, as well as improving their monitoring and treatment adjustments in order to reduce their mortality. OBJECTIVES: To present the outcomes of the first year of introducing the CS in the emergency department of a tertiary hospital. MATERIAL AND METHODS: A single-centre retrospective descriptive observational study was conducted on all patients in whom the CS was activated in the emergency department of a tertiary hospital during the first year of implementation. The variables included: demographics, CS activation, comorbidities, focus of infection, microbiology, antibiotic treatment, and mortality. RESULTS: CS was activated in 555 patients, of which 302 (54.4%) had a definitive diagnosis of sepsis or septic shock on discharge from the emergency department. The degree of completion of the protocol variables was variable (41.8-95%).The large majority (86.1%) of the patients received antibiotics in the first hour, and in 76.2% blood cultures were collected prior to the antibiotic. Of the blood cultures performed, 13.3% of the isolated germs were multi-resistant and the level of contamination of blood cultures was 9.1%. All patients received empirical treatment and recommendations were followed in patients with septic shock in 28.3%. During follow-up, 64.4% the antibiotic treatment was targeted, and 39.5% received sequential therapy. In-hospital mortality was 32.2%. CONCLUSIONS: Areas of improvement in the completion of the variables, contamination of blood cultures, and empirical treatment received were detected, with the strong points being the early administration of the antibiotic and the collection of blood cultures.

Impact of SEP-1 on broad-spectrum combination antibiotic therapy in the emergency department.

BACKGROUND: The SEP-1 measures have tied financial reimbursement to the treatment of patients with severe sepsis and septic shock. The purpose of this study was to assess the impact of a SEP-1 initiative on the utilization of broad-spectrum combination therapy (BSCT) in the emergency department (ED). METHODS: This was an IRB-approved, retrospective evaluation of adult patients who received vancomycin plus an antipseudomonal beta-lactam for a urinary tract infection (UTI) or skin or soft tissue infection (SSTI) in the ED. The primary outcome was the proportion of patients in which use of BSCT was considered appropriate based on clinical criteria. Secondary outcomes included door to antibiotic order time, door to administration time, proportion of patients continued on BSCT upon admission, duration of BSCT, and in-hospital mortality. RESULTS: A total of 400 patients were included in the analysis. Following SEP-1 implementation, appropriate use of BSCT decreased by 12%, with 54% of patients in the pre-SEP-1 group meeting clinical criteria compared to 42% in the post-SEP-1 group (p = 0.028). In the subgroup of patients with a suspected UTI the appropriate use of BSCT declined by 25% (40% vs 15%, p = 0.005). The median door to first antibiotic administration time was not significantly different between groups (63 min vs 61 min, p = 0.091). CONCLUSIONS: The implementation of the SEP-1 mandated measures was associated with an increase in the unnecessary use of BSCT. Additionally, no difference was seen in time to antibiotic administration. The results of this study demonstrate the negative impact that the SEP-1 mandate may have on antimicrobial utilization within the ED.

Impact of the Addition of Examples to the American Society of Anesthesiologists Physical Status Classification System.

Examples of comorbidities for the widely used American Society of Anesthesiologists physical status (ASA-PS) classification system were developed and approved in 2014. We conducted a retrospective cohort study of patients with 4 comorbidities included in the examples as warranting a specific minimum ASA-PS class. For each comorbidity subgroup, we used interrupted time-series models to compare ASA-PS underclassification for the periods before (2011-2014) and after (2015-2017) the introduction of examples. Rates of underclassification ranged from 4.8% to 38.7%. We observed no evidence of a significant impact on ASA-PS classification with the introduction of examples in 2014.

Rapid Diagnostics for Blood Cultures: Supporting Decisions for Antimicrobial Therapy and Value-Based Care.

Bacteremia and sepsis are critically important syndromes with high mortality, morbidity, and associated costs. Bloodstream infections and sepsis are among the top causes of mortality in the US, with >600 deaths each day. Most septic patients can be found in emergency medicine departments or critical care units, settings in which rapid administration of targeted antibiotic therapy can reduce mortality. Unfortunately, routine blood cultures are not rapid enough to aid in the decision of therapeutic intervention at the onset of bacteremia. As a result, empiric, broad-spectrum treatment is common-a costly approach that may fail to target the correct microbe effectively, may inadvertently harm patients via antimicrobial toxicity, and may contribute to the evolution of drug-resistant microbes. To overcome these challenges, laboratorians must understand the complexity of diagnosing and treating septic patients, focus on creating algorithms that rapidly support decisions for targeted antibiotic therapy, and synergize with existing emergency department and critical care clinical practices put forth in the Surviving Sepsis Guidelines.