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

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

Hemodynamic goals in sepsis and septic shock resuscitation: An umbrella review of systematic reviews and meta-analyses with trial sequential analysis.

OBJECTIVE: The objective of this study was to verify whether any parameter among those used as the target for haemodynamic optimisation (e.g., mean arterial pressure, central venous oxygen saturation, systolic or diastolic dysfunction, CO2 gap, lactates, right ventricular dysfunction, and PvaCO2/CavO2 ratio) is correlated with mortality in an undifferentiated population with sepsis or septic shock. METHODS: An umbrella review, searching MEDLINE, the Cochrane Database of Systematic Reviews, Health Technology Assessment Database, and the JBI Database of Systematic Reviews and Implementation Reports, was performed. We included systematic reviews and meta-analyses enrolling a population of unselected patients with sepsis or septic shock. The main outcome was mortality. Two authors conducted data extraction and risk-of-bias assessments independently. We used a random-effects model to pool binary and continuous data and summarised estimates of effect using equivalent odds ratios (eORs). We used the ROBIS tool to assess risk of bias and the assessment of multiple systematic reviews 2 score to assess global quality. DATA SYNTHESIS: 17 systematic reviews and meta-analyses (15 828 patients) were included in the quantitative analysis. Diastolic dysfunction (eOR: 1.42; 95% confidence interval [CI]: 1.14-1.76), PvaCO2/CavO2 ratio (eOR: 2.15; 95% CI: 1.37-3.37), and CO2 gap (eOR: 1.86; 95% CI: 1.07-3.25) showed a significant correlation with mortality. Lactates were the parameter with highest inconsistency (I2 = 92%). Central venous oxygen saturation and right ventricle dysfunction showed significant statistical excess test of significance (p-value = 0.009 and 0.005, respectively). None of the considered parameters showed statistically significant publication bias. CONCLUSIONS: According to this umbrella review, diastolic dysfunction is the haemodynamic variable that is most closely linked to the prognosis of septic patients. The PvaCO2/CavO2 ratio and the CO2gap are significantly related to the mortality of septic patients, but the poor quality of evidence or the low number of cases, studied so far, limit their clinical applicability. CLINICAL TRIAL REGISTRATION: PROSPERO: International prospective register of systematic reviews, 2023, CRD42023432813 (Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432813).

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.

Race Does Not Impact Sepsis Outcomes When Considering Socioeconomic Factors in Multilevel Modeling.

OBJECTIVES: To determine whether race is a major determinant of sepsis outcomes when controlling for socioeconomic factors. DESIGN: Retrospective cohort study. SETTING: Barnes-Jewish Hospital a 1,350 bed academic medical center. PATIENTS: Eleven-thousand four-hundred thirty-two patients hospitalized between January 2010 and April 2017 with sepsis and septic shock. INTERVENTIONS: Multilevel random effects modeling was employed whereby patients were nested within ZIP codes. Individual patient characteristics and socioeconomic variables aggregated at the ZIP code level (education, employment status, income, poverty level, access to healthcare) were included in the model. MEASUREMENTS AND MAIN RESULTS: In hospital mortality, length of stay, need for vasopressors, and mechanical ventilation were the main endpoints. Black patients had more comorbidities than White patients except for cirrhosis and malignancy. In unadjusted comparisons, White individuals were more likely to require mechanical ventilation and had higher mortality rates and longer hospital stays for both low- and high-income groups. When nesting within ZIP codes and accounting for socioeconomic variables, race did not have a significant effect on mortality. Non-White races had lower odds ratio for mechanical ventilation. CONCLUSIONS: Our study demonstrates that race is not an independent risk factor for sepsis mortality, as well as sepsis-related length of stay. We should expand our inquiry into determinants of sepsis outcomes by including socioeconomic variables.

[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.

Resource Use and Outcomes for Children Hospitalized With Severe Sepsis or Septic Shock.

OBJECTIVE: To describe patient and hospital characteristics associated with in-hospital mortality, length of stay (LOS), and charges for children with severe sepsis or septic shock who often require specialized organ-supportive technology to enhance outcomes, availability of which might vary across hospitals. DESIGN: Retrospective study among children hospitalized for severe sepsis or septic shock, using the 2012 Kids' Inpatient Database. Multivariate regression methods identified factors associated with mortality, LOS, and charges. MEASUREMENTS AND MAIN RESULTS: Of an estimated 11 972 hospitalizations for pediatric severe sepsis or septic shock, most hospitalizations (85%) were to urban teaching hospitals. Hospitalizations were more frequent among neonates and older adolescents than other age groups. Mortality was 17%, average LOS was 24 days, and average hospital charges were US$314 950. Higher mortality was associated with neonates, cumulative organ dysfunction, more comorbidities, and cardiopulmonary resuscitation. Longer hospitalization and higher charges were associated with neonates, more comorbidities, higher illness severity, invasive medical technology, and urban hospitals. CONCLUSIONS: Efforts to mitigate the substantial in-hospital mortality and resource use observed in pediatric severe sepsis or septic shock should be age-specific and focused on the influence of comorbidities and organ dysfunction on outcomes. Future research should elucidate reasons for higher resource use at urban hospitals.

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.

The cost-effectiveness of adjunctive corticosteroids for patients with septic shock.

OBJECTIVE: To determine whether hydrocortisone is a cost-effective treatment for patients with septic shock. DESIGN: Data linkage-based cost-effectiveness analysis. SETTING: New South Wales and Queensland intensive care units. PARTICIPANTS AND INTERVENTION: Patients with septic shock randomly assigned to treatment with hydrocortisone or placebo in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL) trial. MAIN OUTCOME MEASURES: Health-related quality of life at 6 months using the EuroQoL 5-dimension 5-level questionnaire. Data on hospital resource use and costs were obtained by linking the ADRENAL dataset to government administrative health databases. Clinical outcomes included mortality, health-related quality of life, and quality-adjusted life-years gained; economic outcomes included hospital resource use, costs and cost-effectiveness from the health care payer perspective. We also assessed cost-effectiveness by sex. To increase the precision of cost-effectiveness estimates, we conducted unrestricted bootstrapping. RESULTS: Of 3800 patients in the ADRENAL trial, 1772 (46.6%) were eligible and 1513 (85.4% of those eligible) were included. There was no difference between hydrocortisone or placebo groups in regards to mortality (218/742 [29.4%] v 227/759 [29.9%]; HR, 0.93; 95% CI, 0.78-1.12; P = 0.47), mean number of QALYs gained (0.10 ± 0.09 v 0.10 ± 0.09; P = 0.52), or total hospital costs (A$73 515 ± 61 376 v A$69 748 ± 61 793; mean difference, A$3767; 95% CI, -A$2891 to A$10 425; P = 0.27). The incremental cost of hydrocortisone was A$1 254 078 per quality-adjusted life-year gained. In females, hydrocortisone was cost-effective in 46.2% of bootstrapped replications and in males it was cost-effective in 2.7% of bootstrapped replications. CONCLUSIONS: Adjunctive hydrocortisone did not significantly affect longer term mortality, health-related quality of life, health care resource use or costs, and is unlikely to be cost-effective.

Assessment of Health Care Exposures and Outcomes in Adult Patients With Sepsis and Septic Shock.

Importance: Current information on the characteristics of patients who develop sepsis may help in identifying opportunities to improve outcomes. Most recent studies of sepsis epidemiology have focused on changes in incidence or have used administrative data sets that provided limited patient-level data. Objective: To describe sepsis epidemiology in adults. Design, Setting, and Participants: This retrospective cohort study reviewed the medical records, death certificates, and hospital discharge data of adult patients with sepsis or septic shock who were discharged from the hospital between October 1, 2014, and September 30, 2015. The convenience sample was obtained from hospitals in the Centers for Disease Control and Prevention Emerging Infections Program in 10 states (California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee). Patients 18 years and older with discharge diagnosis codes for severe sepsis or septic shock were randomly selected. Data were analyzed between May 1, 2018, and January 31, 2019. Main Outcomes and Measures: The population's demographic characteristics, health care exposures, and sepsis-associated infections and pathogens were described, and risk factors for death within 30 days after sepsis diagnosis were assessed. Results: Among 1078 adult patients with sepsis (569 men [52.8%]; median age, 64 years [interquartile range, 53-75 years]), 973 patients (90.3%) were classified as having community-onset sepsis (ie, sepsis diagnosed within 3 days of hospital admission). In total, 654 patients (60.7%) had health care exposures before their hospital admission for sepsis; 260 patients (24.1%) had outpatient encounters in the 7 days before admission, and 447 patients (41.5%) received medical treatment, including antimicrobial drugs, chemotherapy, wound care, dialysis, or surgery, in the 30 days before admission. A pathogen associated with sepsis was found in 613 patients (56.9%); the most common pathogens identified were Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Clostridioides difficile. After controlling for other factors, an association was found between underlying comorbidities, such as cirrhosis (odds ratio, 3.59; 95% CI, 2.03-6.32), immunosuppression (odds ratio, 2.52; 95% CI, 1.81-3.52), vascular disease (odds ratio, 1.54; 95% CI, 1.10-2.15), and 30-day mortality. Conclusions and Relevance: Most adults experienced sepsis onset outside of the hospital and had recent encounters with the health care system. A sepsis-associated pathogen was identified in more than half of patients. Future efforts to improve sepsis outcomes may benefit from examination of health maintenance practices and recent health care exposures as potential opportunities among high-risk patients.

Quality assessment of meta-analyses evaluating randomized clinical trials to improve the prognosis of septic shock: an overview of systematic reviews.

Objective: Clinical guidelines for the treatment of septic shock are based on the studies with the best scientific evidence, which are meta-analyses of clinical trials. However, these meta-analyses may have methodological limitations that prevent their conclusions from being extrapolated to routine clinical practice. Therefore, the objective of this study is to determine the quality of these meta-analyses through a systematic review.Methods: In this systematic review, we searched MEDLINE, Scopus and EMBASE from inception to May 2019. We selected meta-analyses from clinical trials that determined the effectiveness of an intervention in reducing the incidence of mortality in patients with septic shock. All items were extracted from the Overview Quality Assessment Questionnaire (OQAQ), which collects information from both systematic reviews and meta-analyses.Results: A total of 34 studies were included. Most elements of the OQAQ were conducted satisfactorily, although 35.3% of meta-analyses did not use a quality assessment of the studies included in other analyses. In 52.9% of meta-analyses, the quality of the studies was high or very high.Conclusions: The methods used to obtain the results should be taken into account when recommending an intervention to treat septic shock if the evidence comes from a meta-analysis of the analyzed characteristics.

Implementation of the Affordable Care Act: A Comparison of Outcomes in Patients With Severe Sepsis and Septic Shock Using the National Inpatient Sample.

OBJECTIVES: Sepsis is the most common and costly diagnosis in U.S.' hospitals. Despite quality improvement programs and heightened awareness, sepsis accounts for greater than 50% of all hospital deaths. A key modifier of outcomes is access to healthcare. The Affordable Care Act, passed in 2010, expanded access to health insurance coverage. The purpose of this study was to evaluate changes in insurance coverage and outcomes in patients with severe sepsis and septic shock as a result of the full implementation of the Affordable Care Act. DESIGN: This retrospective study uses data from the Healthcare Cost and Utilization Project National Inpatient Sample during 2011-2016. Data were divided into two groups: 2011-2013 (pre Affordable Care Act) and 2014-2016 (post Affordable Care Act). Outcomes were in-hospital mortality, mortality rates based on insurance type, and hospital length of stay. PATIENTS: Hospitalized adults between the ages 18 and 64. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 361,323 severe sepsis or septic shock hospital discharges were included. Comparing pre-Affordable Care Act with post-Affordable Care Act, there was a 4.75% increase in medicaid coverage and a 1.91% decrease in the uninsured. Overall in-hospital mortality decreased from 22.90% pre-Affordable Care Act to 18.59% post-Affordable Care Act. Pre-Affordable Care Act uninsured patients had the highest mortality (25.68%). Patients with medicaid had the greatest reduction in mortality (5.71%) and length of stay (2.45 d). The mean (SD) length of stay pre Affordable Care Act was 13.92 (17.42) days, compared with 12.35 (15.76) days post Affordable Care Act. All results were statistically significant (p < 0.0001). CONCLUSIONS: In this cohort, there was an increase in insured patients with severe sepsis and septic shock post Affordable Care Act. Mortality and length of stay decreased in the post-Affordable Care Act period with the greatest reduction identified in the medicaid population. The improvement in outcomes could be attributed to advances in management, earlier presentation, patients being less severely ill and receiving treatment sooner.

Sepsis Among Medicare Beneficiaries: 1. The Burdens of Sepsis, 2012-2018.

OBJECTIVES: To provide contemporary estimates of the burdens (costs and mortality) associated with acute inpatient Medicare beneficiary admissions for sepsis. DESIGN: Analysis of paid Medicare claims via the Centers for Medicare & Medicaid Services DataLink Project. SETTING: All U.S. acute care hospitals, excluding federally operated hospitals (Veterans Administration and Defense Health Agency). PATIENTS: All Medicare beneficiaries, 2012-2018, with an inpatient admission including one or more explicit sepsis codes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total inpatient hospital and skilled nursing facility admission counts, costs, and mortality over time. From calendar year (CY)2012-CY2018, the total number of Medicare Part A/B (fee-for-service) beneficiaries with an inpatient hospital admission associated with an explicit sepsis code rose from 811,644 to 1,136,889. The total cost of inpatient hospital admission including an explicit sepsis code for those beneficiaries in those calendar years rose from $17,792,657,303 to $22,439,794,212. The total cost of skilled nursing facility care in the 90 days subsequent to an inpatient hospital discharge that included an explicit sepsis code for Medicare Part A/B rose from $3,931,616,160 to $5,623,862,486 over that same interval. Precise costs are not available for Medicare Part C (Medicare Advantage) patients. Using available federal data sources, we estimated the aggregate cost of inpatient admissions and skilled nursing facility admissions for Medicare Advantage patients to have risen from $6.0 to $13.4 billion over the CY2012-CY2018 interval. Combining data for fee-for-service beneficiaries and estimates for Medicare Advantage beneficiaries, we estimate the total inpatient admission sepsis cost and any subsequent skilled nursing facility admission for all (fee-for-service and Medicare Advantage) Medicare patients to have risen from $27.7 to $41.5 billion. Contemporary 6-month mortality rates for Medicare fee-for-service beneficiaries with a sepsis inpatient admission remain high: for septic shock, approximately 60%; for severe sepsis, approximately 36%; for sepsis attributed to a specific organism, approximately 31%; and for unspecified sepsis, approximately 27%. CONCLUSION: Sepsis remains common, costly to treat, and presages significant mortality for Medicare beneficiaries.

Sepsis Among Medicare Beneficiaries: 2. The Trajectories of Sepsis, 2012-2018.

OBJECTIVES: To distinguish characteristics of Medicare beneficiaries who will have an acute inpatient admission for sepsis from those who have an inpatient admission without sepsis, and to describe their further trajectories during and subsequent to those inpatient admissions. DESIGN: Analysis of paid Medicare claims via the Centers for Medicare and Medicaid Services DataLink Project. SETTING: All U.S. acute care hospitals, excepting federal hospitals (Veterans Administration and Defense Health Agency). PATIENTS: Medicare beneficiaries, 2012-2018, with an inpatient hospital admission including one or more explicit sepsis codes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Prevalent diagnoses in the year prior to the inpatient admission; healthcare contacts in the week prior to the inpatient admission; discharges, transfers, readmissions, and deaths (trajectories) for 6 months following discharge from the inpatient admission. Beneficiaries with no sepsis inpatient hospital admission for a year prior to an index hospital admission for sepsis were nearly indistinguishable by accumulated diagnostic codes from beneficiaries who had an index hospital admission without sepsis. Although the timing of healthcare services in the week prior to inpatient hospital admission was similar among beneficiaries who would be admitted for sepsis versus those whose inpatient admission did not include a sepsis code, the setting differed: beneficiaries destined for a sepsis admission were more likely to have received skilled nursing or unskilled nursing (e.g., nursing aide for activities of daily living) care. In contrast, comparing beneficiaries who had been free of any inpatient admission for an entire year and then required an inpatient admission, acute inpatient stays that included a sepsis code led to more than three times as many deaths within 1 week of discharge, with more admissions to skilled nursing facilities and fewer discharges to home. Comparing all beneficiaries who were admitted to a skilled nursing facility after an inpatient hospital admission, those who had sepsis coded during the index admission were more likely to die in the skilled nursing facility; more likely to be readmitted to an acute inpatient hospital and subsequently die in that setting; or if they survive to discharge from the skilled nursing facility, they are more likely to go next to a custodial nursing home. CONCLUSIONS: Although Medicare beneficiaries destined for an inpatient hospital admission with a sepsis code are nearly indistinguishable by other diagnostic codes from those whose admissions will not have a sepsis code, their healthcare trajectories following the admission are worse. This suggests that an inpatient stay that included a sepsis code not only identifies beneficiaries who were less resilient to infection but also signals increased risk for worsening health, for mortality, and for increased use of advanced healthcare services during and postdischarge along with an increased likelihood of an inpatient hospital readmission.

Sepsis Among Medicare Beneficiaries: 3. The Methods, Models, and Forecasts of Sepsis, 2012-2018.

OBJECTIVE: To evaluate the impact of sepsis, age, and comorbidities on death following an acute inpatient admission and to model and forecast inpatient and skilled nursing facility costs for Medicare beneficiaries during and subsequent to an acute inpatient sepsis admission. DESIGN: Analysis of paid Medicare claims via the Centers for Medicare & Medicaid Services DataLink Project (CMS) and leveraging the CMS-Hierarchical Condition Category risk adjustment model. SETTING: All U.S. acute care hospitals, excepting federal hospitals (Veterans Administration and Defense Health Agency). PATIENTS: All Part A/B (fee-for-service) Medicare beneficiaries with an acute inpatient admission in 2017 and who had no inpatient sepsis admission in the prior year. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Logistic regression models to determine covariate risk contribution to death following an acute inpatient admission; conventional regression to predict Medicare beneficiary sepsis costs. Using the Hierarchical Condition Category risk adjustment model to illuminate influence of illness on outcome of inpatient admissions, representative odds ratios (with 95% CIs) for death within 6 months of an admission (referenced to beneficiaries admitted but without the characteristic) are as follows: septic shock, 7.27 (7.19-7.35); metastatic cancer and acute leukemia (Hierarchical Condition Category 8), 6.76 (6.71-6.82); all sepsis, 2.63 (2.62-2.65); respiratory arrest (Hierarchical Condition Category 83), 2.55 (2.35-2.77); end-stage liver disease (Hierarchical Condition Category 27), 2.53 (2.49-2.56); and severe sepsis without shock, 2.48 (2.45-2.51). Models of the cost of sepsis care for Medicare beneficiaries forecast arise approximately 13% over 2 years owing the rising enrollments in Medicare offset by the cost of care per admission. CONCLUSIONS: A sepsis inpatient admission is associated with marked increase in risk of death that is comparable to the risks associated with inpatient admissions for other common and serious chronic illnesses. The aggregate costs of sepsis care for Medicare beneficiaries will continue to increase.

Trajectory of Mortality and Health-Related Quality of Life Morbidity Following Community-Acquired Pediatric Septic Shock.

OBJECTIVES: In-hospital pediatric sepsis mortality has decreased substantially, but long-term mortality and morbidity among children initially surviving sepsis, is unknown. Accordingly, the Life After Pediatric Sepsis Evaluation investigation was conducted to describe the trajectory of mortality and health-related quality of life morbidity for children encountering community-acquired septic shock. DESIGN: Prospective, cohort-outcome study, conducted 2013-2017. SETTING: Twelve academic PICUs in the United States. PATIENTS: Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support. INTERVENTIONS: Demographic, infection, illness severity, organ dysfunction, and resource utilization data were collected daily during PICU admission. Serial parent proxy-report health-related quality of life assessments were obtained at baseline, 7 days, and 1, 3, 6, and 12 months following PICU admission utilizing the Pediatric Quality of Life Inventory or Stein-Jessop Functional Status Scale. MEASUREMENTS AND MAIN RESULTS: Among 389 children enrolled, mean age was 7.4 ± 5.8 years; 46% were female; 18% were immunocompromised; and 51% demonstrated chronic comorbidities. Baseline Pediatric Overall Performance Category was normal in 38%. Median (Q1-Q3) Pediatric Risk of Mortality and Pediatric Logistic Organ Dysfunction scores at PICU admission were 11.0 (6.0-17.0) and 9.0 (6.0-11.0); durations of vasoactive-inotropic and mechanical ventilation support were 3.0 days (2.0-6.0 d) and 8.0 days (5.0-14.0 d); and durations of PICU and hospital stay were 9.4 days (5.6-15.4 d) and 15.7 days (9.2-26.0 d). At 1, 3, 6, and 12 months following PICU admission for the septic shock event, 8%, 11%, 12%, and 13% of patients had died, while 50%, 37%, 30%, and 35% of surviving patients had not regained their baseline health-related quality of life. CONCLUSIONS: This investigation provides the first longitudinal description of long-term mortality and clinically relevant, health-related quality of life morbidity among children encountering community-acquired septic shock. Although in-hospital mortality was 9%, 35% of survivors demonstrated significant, health-related quality of life deterioration from baseline that persisted at least 1 year following hospitalization for septic shock.

Mortality, Morbidity, and Costs After Implementation of a Vasopressin Guideline in Medical Intensive Care Patients With Septic Shock: An Interrupted Time Series Analysis.

Background: Vasopressin decreases vasopressor requirements in patients with septic shock. However, the optimal norepinephrine dose for initiation or cessation of vasopressin is unclear. Objective: Analyze monthly intensive care unit (ICU) mortality rates 1 year preimplementation and postimplementation of a guideline suggesting a norepinephrine dose of 50 µg/min or more for initiation of vasopressin and early cessation of vasopressin. Methods: This retrospective quasi-experimental study included adult patients with septic shock admitted to the medical ICU of a tertiary care medical center over 2 years. Time periods were evaluated with interrupted time series analysis. Results: A total of 1148 patients were included: 573 patients preguideline and 575 patients postguideline. Group characteristics were well balanced at baseline, except patients postguideline had higher sequential organ failure assessment scores. Postguideline, fewer patients were initiated on vasopressin (305 [53.2%] vs 217 [37.7%], absolute difference -15.5% [95% CI -21.2% to -9.8%]), and the norepinephrine dose at vasopressin initiation was higher (median 25 [interquartile range 18, 40] µg/min vs 40 [22, 52] µg/min; median difference 15 [95% CI 11 to 19] µg/min; P < 0.01). After guideline implementation, there was no evidence for a difference in ICU mortality rate slope (slope change 0.07% [95% CI -0.8% to 1.0%] per month; P 0.87), but the vasoactive cost level decreased by US$183 (95% CI -US$327 to -US$39) per patient immediately after implementation. Conclusion and Relevance: Implementation of a guideline suggesting a high norepinephrine dose threshold for vasopressin initiation and early vasopressin cessation in patients with septic shock appears to be safe and may decrease vasoactive costs.

Assessment of clinical features and determinants of mortality among cancer patients with septic shock of pulmonary origin: a prospective analysis.

BACKGROUND: Pneumonia-associated septic shock (PASS) in patients with cancer inflicts healthcare burden attributed to high morbidity and mortality. Current study was aimed to evaluate the clinical outcomes, microbiological characteristics, risk factors and impact of life-support interventions on 28-day mortality among cancer patients with PASS. METHODS: A prospective observational study was conducted among cancer patients with PASS admitted to intensive care unit (ICU) of 'Shaukat Khanum Memorial Cancer Hospital'. Data were analysed using appropriate statistical methods. RESULTS: Out of 100 patients who sought medical care during the study period, 59 (59%) were male and majority had solid tumour than haematological malignancies (68% vs 32%). Nosocomial pneumonia was most frequent (90%) followed by healthcare-associated pneumonia (HCAP) (9%) and community-acquired pneumonia (CAP) (1%). The most common causative pathogen was Pseudomonas aeruginosa, 21 (32%). Overall mortality rate was 76% including 15% hospital and 61% ICU mortality. Sequential Organ Failure Assessment (SOFA) score at first day (HR 3.8; 95% CI 1.7 to 8.9; p=0.002), SOFA score at seventh day (HR 8.9; 95% CI 3.6 to 22.7; p=<0.001), invasive mechanical ventilation (HR 8.0; 95% CI 3.2 to 20; p<0.001) and performance status (HR 5.4; 95% CI 2.5 to 11.3; p<0.001) were found to be independently associated with 28-day mortality. Receiver operating characteristic curve analysis accentuates the excellent predictive accuracy of Cox regression model for mortality indicated by area under the curve of 0.892 (95% CI 0.801 to 0.983, p<0.001). CONCLUSION: Our analysis demonstrates substantial mortality associated with PASS among patients with cancer. Timely recognition of patients with high predilection of increased mortality could be of value in improving the disease burden.

Delayed vasopressor initiation is associated with increased mortality in patients with septic shock.

PURPOSE: Mortality rate for septic shock, despite advancements in knowledge and treatment, remains high. Treatment includes administration of broad-spectrum antibiotics and stabilization of the mean arterial pressure (MAP) with intravenous fluid resuscitation. Fluid-refractory shock warrants vasopressor initiation. There is a paucity of evidence regarding the timing of vasopressor initiation and its effect on patient outcomes. MATERIALS AND METHODS: This retrospective, single-centered, cohort study included patients with septic shock from January 2017 to July 2017. Time from initial hypotension to vasopressor initiation was measured for each patient. The primary outcome was 30-day mortality. RESULTS: Of 530 patients screened,119 patients were included. There were no differences in baseline patient characteristics. Thirty-day mortality was higher in patients who received vasopressors after 6 h (51.1% vs 25%, p < .01). Patients who received vasopressors within the first 6 h had more vasopressor-free hours at 72 h (34.5 h vs 13.1, p = .03) and shorter time to MAP of 65 mmHg (1.5 h vs 3.0, p < .01). CONCLUSION: Vasopressor initiation after 6 h from shock recognition is associated with a significant increase in 30-day mortality. Vasopressor administration within 6 h was associated with shorter time to achievement of MAP goals and higher vasopressor-free hours within the first 72 h.