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Antibiotics are fundamental in sepsis management; however, the optimal empirical treatment remains debated. Despite anaerobes rarely being the causative pathogen of sepsis, antibiotics targeting them are frequently used, which might lead to unintended consequences. Multiple studies have shown that depletion of commensal anaerobic gut microbes by anti-anaerobic antibiotics influences systemic immunity and is associated with increased mortality in patients with sepsis. However, this knowledge has not yet been translated into clinical practice. When considering empirical coverage of anaerobic pathogens in sepsis, most physicians advocate for a better-safe-than-sorry approach. In this Viewpoint, we argue that anti-anaerobic antibiotics could often result in being sorry rather than safe. We provide an overview of the limited necessity of anaerobic coverage and the potential detrimental effects of anaerobic depletion in sepsis. We aim to raise anaerobic awareness to reduce the unnecessary use of anti-anaerobic antibiotics in empirical sepsis treatment and improve patient outcomes., Competing Interests: Declaration of interests HCP reported receiving grants and contracts from the National Institutes of Health/National Heart, Lung and Blood Institute, Agency for Healthcare Research and Quality, Veterans Affairs, Blue Cross Blue Shield of Michigan, and Centers for Disease Control and Prevention. HCP is a co-chair of the Surviving Sepsis Campaign Guidelines. WJW reported receiving grants from the Amsterdam University Medical Centres and European Union (H2020, Eurostars) and performing ad hoc consultancy for AstraZeneca and Shinogi related to COVID-19 (fees paid to host institution). WJW is a panel member of the Surviving Sepsis Campaign Adult Guidelines and chair of the Dutch Working Party on Antibiotic Policy's Sepsis Guidelines. All other authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: To generate consensus and provide expert clinical practice statements for the management of adult sepsis in resource-limited settings., Methods: An international multidisciplinary Steering Committee with expertise in sepsis management and including a Delphi methodologist was convened by the Asia Pacific Sepsis Alliance (APSA). The committee selected an international panel of clinicians and researchers with expertise in sepsis management. A Delphi process based on an iterative approach was used to obtain the final consensus statements., Results: A stable consensus was achieved for 30 (94%) of the statements by 41 experts after four survey rounds. These include consensus on managing patients with sepsis outside a designated critical care area, triggers for escalating clinical management and criteria for safe transfer to another facility. The experts agreed on the following: in the absence of serum lactate, clinical parameters such as altered mental status, capillary refill time and urine output may be used to guide resuscitation; special considerations regarding the volume of fluid used for resuscitation, especially in tropical infections, including the use of simple tests to assess fluid responsiveness when facilities for advanced hemodynamic monitoring are limited; use of Ringer's lactate or Hartmann's solution as balanced salt solutions; epinephrine when norepinephrine or vasopressin are unavailable; and the administration of vasopressors via a peripheral vein if central venous access is unavailable or not feasible. Similarly, where facilities for investigation are unavailable, there was consensus for empirical antimicrobial administration without delay when sepsis was strongly suspected, as was the empirical use of antiparasitic agents in patients with suspicion of parasitic infections., Conclusion: Using a Delphi method, international experts reached consensus to generate expert clinical practice statements providing guidance to clinicians worldwide on the management of sepsis in resource-limited settings. These statements complement existing guidelines where evidence is lacking and add relevant aspects of sepsis management that are not addressed by current international guidelines. Future studies are needed to assess the effects of these practice statements and address remaining uncertainties., Competing Interests: Declarations. Conflicts of interest: Massimo Antonelli: Grants from GE and Fisher & Paykel; Lecture fees from Menarini, Shionogi, Fisher & Paykel, Dimar. Jan De Waele: Consulted for Biomerieux, Menarini, MSD, Pfizer, Roche Diagnostics, ThermoFisher and Viatris (fees and honoraria paid to institution). Supported by a Sr Clinical Research Grant from the Research Foundation Flanders (FWO, Ref.1881020N). Jigeeshu Divatia: Lecture fees from Edwards India paid to my institution. Simon Finfer: Supported by an NHMRC Investigator Fellowship (Leadership Level 3 App 2017580), has received consulting fees paid to his employer from RevImmune Inc. and owns options in Sepsis Scout. Naomi E Hammond: Supported by an NHMRC Investigator Fellowship (Emerging Leader Level 1 App 1196320), has received consulting fees paid to her employer from RevImmune Inc. Arthur Kwizera: Grants from the Wellcome Trust; NIHR; Fisher & Paykel Ltd; Gradian Health Systems; Vygon Ltd; Speaker support from the ESICM; Makerere University Research and Innovation Fund. Marlies Ostermann: Institution received research funding from Baxter and Biomerieux. Ethical approval and consent: The study protocol was registered on clinicaltrials.gov [NCT05909384]. Oxford Tropical Research Ethics Committee (OxTREC) confirmed that the study was exempt from ethics review in March 2023. Consent to participate and publish: All authors and collaborators consented to participate in and publish this study., (© 2024. The Author(s).)

Objectives: Refine the administrative data definition of sepsis in hospitalized patients, including less severe cases., Design and Setting: For each of 1928 infection and 108 organ dysfunction codes used in Canadian hospital abstracts, experts reached consensus on the likelihood that it could relate to sepsis. We developed a new algorithm, called AlgorithmL, that requires at least one infection and one organ dysfunction code adjudicated as likely or very likely to be related to sepsis. AlgorithmL was compared with four previously described algorithms, regarding included codes, population-based incidence, and hospital mortality rates-separately for ICU and non-ICU cohorts in a large Canadian city. We also compared sepsis identification from these code-based algorithms with the Centers for Disease Control's Adult Sepsis Event (ASE) definition., Subjects: Among Calgary's adult population of 1.033 million there were 61,632 eligible hospitalizations., Interventions: None., Measurements and Main Results: AlgorithmL includes 720 infection codes and 50 organ dysfunction codes. Comparison algorithms varied from 42-941 infection codes to 2-36 organ codes. There was substantial nonoverlap of codes in AlgorithmL vs. the comparators. Annual sepsis incidence rates (per 100,000 population) based on AlgorithmL were 91 in the ICU and 291 in the non-ICU cohort. Incidences based on comparators ranged from 28-77 for ICU to 11-266 for non-ICU cohorts. Hospital sepsis mortality rates based on AlgorithmL were 24% in ICU and 17% in non-ICU cohorts; based on comparators, they ranged 27-38% in the ICU cohort and 18-47% for the non-ICU cohort. Of AlgorithmL-identified cases, 41% met the ASE criteria, compared with 42-82% for the comparator algorithms., Conclusions: Compared with other code-based algorithms, AlgorithmL includes more infection and organ dysfunction codes. AlgorithmL incidence rates are higher; hospital mortality rates are lower. AlgorithmL may more fully encompass the full range of sepsis severity., Competing Interests: Drs. Garland’s and Gervais’s institutions received funding from the Canadian Institutes for Health Research (CIHR). Drs. Garland’s and Prescott’s institutions received funding from the National Institutes of Health. Drs. Garland, Li, and Gervais received support for article research from the CIHR. Dr. Li received support for article research from Sepsis Canada. Dr. Prescott’s institution received funding from the Agency for Healthcare Research and Quality and Veteran Affairs Health Systems Research and Development; she received funding from the Centers for Disease Control and Prevention and Blue Cross Blue Shield of Michigan; and she disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Importance: Traditional risk prediction and risk adjustment models have focused on clinical characteristics, but accounting for social determinants of health (SDOH) and complex health conditions could improve understanding of sepsis outcomes and our ability to predict outcomes, treat patients, and assess quality of care., Objective: To evaluate the impact of SDOH and health scales in sepsis mortality risk prediction and hospital performance assessment., Design: Observational cohort study., Setting: One hundred twenty-nine hospitals in the nationwide Veterans Affairs (VA) Healthcare System between 2017 and 2021., Participants: Veterans admitted through emergency departments with community-acquired sepsis., Exposures: Individual- and community-level SDOH (race, housing instability, marital status, Area Deprivation Index [ADI], and rural residence) and two health scales (the Care Assessment Need [CAN] score and Claims-Based Frailty Index [CFI])., Main Outcomes and Measures: The primary outcome was 90-day mortality from emergency department arrival; secondary outcomes included 30-day mortality and in-hospital mortality., Results: Among 144,889 patients admitted to the hospital with community-acquired sepsis, 139,080 were men (96.0%), median (IQR) age was 71 (64-77) years, and median (IQR) ADI was 60 (38-81). Multivariable regression models had good calibration and discrimination across models that adjusted for different sets of variables (e.g., AUROC, 0.782; Brier score, 1.33; and standardized mortality rate, 1.00). Risk-adjusted hospital performance was similar across all models. Among 129 VA hospitals, three hospitals shifted from the lowest or highest quintile of performance when comparing models that excluded SDOH to models that adjusted for all variables. Models that adjusted for ADI reported odds ratios (CI) of 1.00 (1.00-1.00), indicating that ADI does not significantly predict sepsis mortality in this cohort of patients., Conclusion and Relevance: In patients with community-acquired sepsis, adjusting for community SDOH variables such as ADI did not improve 90-day sepsis mortality predictions in mortality models and did not substantively alter hospital performance within the VA Healthcare System. Understanding the role of SDOH in risk prediction and risk adjustment models is vital because it could prevent hospitals from being negatively evaluated for treating less advantaged patients. However, we found that in VA hospitals, the potential impact of SDOH on 90-day sepsis mortality was minimal., Competing Interests: Declarations:. Conflict of Interest:: Dr. Seelye reported receiving grants from the US Agency for Healthcare Research and Quality and VA Health Services Research during the conduct of the study. Dr. Prescott reported receiving grants from the US Agency for Healthcare Research and Quality and Blue Cross Blue Shield of Michigan during the conduct of the study. Ms. Cano, Ms. Hogan, and Dr. Sussman reported no conflict of interest. Disclaimer:: This manuscript reflects the views of the authors and does not necessarily represent the position or policy of the Department of Veterans Affairs or the US government., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Medical progress is reflected in the advance from broad clinical syndromes to mechanistically coherent diagnoses. By this metric, research in sepsis is far behind other areas of medicine-the word itself conflates multiple different disease mechanisms, whilst excluding noninfectious syndromes (e.g., trauma, pancreatitis) with similar pathogenesis. New technologies, both for deep phenotyping and data analysis, offer the capability to define biological states with extreme depth. Progress is limited by a fundamental problem: observed groupings of patients lacking shared causal mechanisms are very poor predictors of response to treatment. Here, we discuss concrete steps to identify groups of patients reflecting archetypes of disease with shared underlying mechanisms of pathogenesis. Recent evidence demonstrates the role of causal inference from host genetics and randomised clinical trials to inform stratification analyses. Genetic studies can directly illuminate drug targets, but in addition they create a reservoir of statistical power that can be divided many times among potential patient subgroups to test for mechanistic coherence, accelerating discovery of modifiable mechanisms for testing in trials. Novel approaches, such as subgroup identification in-flight in clinical trials, will improve efficiency. Within the next decade, we expect ongoing large-scale collaborative projects to discover and test therapeutically relevant sepsis archetypes., Competing Interests: Conflicts of interest: The International Sepsis Forum has been generously sponsored by Cytosorbents, Genentech, GE, BD, deepull, Gentian, Inflammatix, Oxford Nanopore Technologies, Sanofi, and Baxter. JKB reports research funding from Wellcome, MRC, BBSRC, UKRI, Baillie Gifford, and NIHR. JM reports grants from the Canadian Institutes of Health Research and has served as chair of data and safety monitoring boards for AM Pharma and Adrenomed. MS-H reports funding from NIHR. TvdP has received grants from the EU's Horizon 2020 research and innovation funding programme. All other authors declare no competing interests. AG is a shareholder of and has received salaries from GSK and Novo Nordisk. AGR is the Chair of the International Sepsis Forum and has received consultancy fees from Inotrem, Thermo Fisher and Volition, and receives funding from the US National Institute of Allergy and Infectious Diseases and Centers for Disease Control. TC reports grants from the Swiss Academy of Medical Sciences, the Swiss Federal Institute of Technology Zurich and the EU's Horizon 2020 research and innovation funding programme, and consulting, speaker’s bureau, data safety monitoring boards from Basilea, Cidara, Gilead Sciences, MSD Merck Sharp & Dohme, Moderna, Novartis, Pfizer, Shionogi (payments made to his institution.) CSC reports grant funding from the NIH, Roche-Genentech, and Quantum Leap Healthcare Collaborative, and has served as a consultant or advisor to Vasomune, Gen1e Life Scienes, Arrowhead, Cellenkos, Calcimedica, EnliTISA, Novaris, Aerogen, Fisher-Paykel, and Boehringer. BPS received funds from the European Society of Intensive Care Medicine (ESICM) and Xjenza Malta Research Excellence Program (REP-2023-049). CWS reports grants from the US National Institutes of Health National Institute of General Medical Sciences, during the conduct of the study, and personal fees from Inotrem and Beckman Coulter, outside of the submitted work., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: When comparing outcomes after sepsis, it is essential to account for patient case mix to make fair comparisons. We developed a model to assess risk-adjusted 30-day mortality in the Michigan Hospital Medicine Safety sepsis initiative (HMS-Sepsis)., Research Question: Can HMS-Sepsis registry data adequately predict risk of 30-day mortality? Do performance assessments using adjusted vs unadjusted data differ?, Study Design and Methods: Retrospective cohort of community-onset sepsis hospitalizations in the HMS-Sepsis registry (April 2022-September 2023), with split derivation (70%) and validation (30%) cohorts. We fit a risk-adjustment model (HMS-Sepsis mortality model) incorporating acute physiologic, demographic, and baseline health data and assessed model performance using concordance (C) statistics, Brier scores, and comparisons of predicted vs observed mortality by deciles of risk. We compared hospital performance (first quintile, middle quintiles, fifth quintile) using observed vs adjusted mortality to understand the extent to which risk adjustment impacted hospital performance assessment., Results: Among 17,514 hospitalizations from 66 hospitals during the study period, 12,260 hospitalizations (70%) were used for model derivation and 5,254 hospitalizations (30%) were used for model validation. Thirty-day mortality for the total cohort was 19.4%. The final model included 13 physiologic variables, two physiologic interactions, and 16 demographic and chronic health variables. The most significant variables were age, metastatic solid tumor, temperature, altered mental status, and platelet count. The model C statistic was 0.82 for the derivation cohort, 0.81 for the validation cohort, and ≥ 0.78 for all subgroups assessed. Overall calibration error was 0.0%, and mean calibration error across deciles of risk was 1.5%. Standardized mortality ratios yielded different assessments than observed mortality for 33.9% of hospitals., Interpretation: The HMS-Sepsis mortality model showed strong discrimination and adequate calibration and reclassified one-third of hospitals to a different performance category from unadjusted mortality. Based on its strong performance, the HMS-Sepsis mortality model may aid in fair hospital benchmarking, assessment of temporal changes, and observational causal inference analysis., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: H. C. P., M. H., J. K. H., P. J. P., E. M., and S. A. F.) receive salary support from BCBSM for work on HMS. K. K. has salary support from BSBSM for work on the Michigan Emergency Department Improvement Collaborative, an ED-based quality network. The authors report grant funding and salary support unrelated to this study from the National Institutes of Health (H. C. P., N. J., S. P. T.), the Agency for Healthcare Research and Quality (H. C. P., S. P. T.), Department of Veterans Affairs (H. C. P.), and Centers for Disease Control and Prevention (H. C. P., J. K. H.). H. C. P. and J. N. serve on the advisory board to Sepsis Alliance (unpaid). H. C. P. serves on the Surviving Sepsis Campaign guidelines. None declared (J. B., P. B., M. Y.)., (Published by Elsevier Inc.)

Objectives: To determine the frequency of and risk factors for increased post-sepsis healthcare utilization compared with pre-sepsis healthcare utilization., Design: Retrospective observational cohort study., Setting: Years 2016-2019 MarketScan Commercial and Medicaid Database., Patients: Children (0-18 yr) with sepsis treated in a U.S. hospital., Interventions: None., Measurements and Main Results: We measured the frequency of and risk factors for increased healthcare utilization in the 90 days post- vs. pre-sepsis hospitalization. We defined increased healthcare utilization as an increase of at least 3 days in the 90 days post-hospitalization compared with the 90 days pre-hospitalization based on outpatient, emergency department, and inpatient hospitalization. We identified 2801 patients hospitalized for sepsis, of whom 865 (30.9%) had increased healthcare utilization post-sepsis, with a median (interquartile range [IQR]) of 3 days (1-6 d) total in the 90 days pre-sepsis and 10 days (IQR, 6-21 d) total in the 90 days post-sepsis ( p < 0.001). In multivariable models, the odds of increased healthcare use were higher for children with longer lengths of hospitalization (> 30 d adjusted odds ratio [aOR], 4.35; 95% CI, 2.99-6.32) and children with preexisting complex chronic conditions, specifically renal (aOR, 1.47; 95% CI, 1.02-2.12), hematologic/immunologic (aOR, 1.34; 95% CI, 1.03-1.74), metabolic (aOR, 1.39; 95% CI, 1.08-1.79), and malignancy (aOR, 1.89; 95% CI, 1.38-2.59)., Conclusions: In this nationally representative cohort of children who survived sepsis hospitalization in the United States, nearly one in three had increased healthcare utilization in the 90 days after discharge. Children with hospitalizations longer than 30 days and complex chronic conditions were more likely to experience increased healthcare utilization., Competing Interests: Dr. Carlton’s institution received funding from the National Heart, Lung, and Blood Institute (NHLBI K12 HL138039). Drs. Carlton and Prescott received support for article research from the National Institutes of Health (NIH). Dr. Maddux’s institution received funding from the National Institute of Child Health and Human Development (K23HD096018 R21HD112592). Dr. Weiss’ institution received funding from the NIH. Dr. Prescott’s institution received funding from the NHLBI, the Veterans Affairs Health Services Research and Development, and the Agency for Healthcare Research and Quality. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: To compare outcomes for 2 weeks vs. 1 week of maximal patient-intensivist continuity in the ICU., Design: Retrospective cohort study., Setting: Two U.S. urban, teaching, medical ICUs where intensivists were scheduled for 2-week service blocks: site A was in the Midwest and site B was in the Northeast., Patients: Patients 18 years old or older admitted to a study ICU between March 1, 2017, and February 28, 2020., Interventions: None., Measurements and Main Results: We applied target trial emulation to compare admission during an intensivist's first week (as a proxy for 2 wk of maximal continuity) vs. admission during their second week (as a proxy for 1 wk of maximal continuity). Outcomes included hospital mortality, ICU length of stay, and, for mechanically ventilated patients, duration of ventilation. Exploratory outcomes included imaging, echocardiogram, and consultation orders. We used inverse probability weighting to adjust for baseline differences and random-effects meta-analysis to calculate overall effect estimates. Among 2571 patients, 1254 were admitted during an intensivist's first week and 1317 were admitted during a second week. At sites A and B, hospital mortality rates were 25.8% and 24.2%, median ICU length of stay were 4 and 2 days, and median mechanical ventilation durations were 3 and 3 days, respectively. There were no differences in adjusted mortality (odds ratio [OR], 1.01 [95% CI, 0.96-1.06]) or ICU length of stay (-0.25 d [-0.82 d to +0.32 d]) for 2 weeks vs. 1 week of maximal continuity. Among mechanically ventilated patients, there were no differences in adjusted mortality (OR, 1.00 [0.87-1.16]), ICU length of stay (+0.06 d [-0.78 d to +0.91 d]), or duration of mechanical ventilation (+0.37 d [-0.46 d to +1.21 d]) for 2 weeks vs. 1 week of maximal continuity., Conclusions: Two weeks of maximal patient-intensivist continuity was not associated with differences in clinical outcomes compared with 1 week in two medical ICUs., Competing Interests: Drs. Admon’s, Gershengorn’s, and Prescott’s institutions received funding from the National Heart, Lung, and Blood Institute. Drs. Admon, Law, and Valley received support for article research from the National Institutes of Health (NIH). Dr. Admon was funded by K08HL155407. Dr. Law’s institution received funding from the NIH. Dr. Gershengorn’s institution received funding from the Canadian Institutes for Health Research; she received funding from CHEST Critical Care, Annals of the American Thoracic Society, International Symposium on Intensive Care and Emergency Medicine, and Southeastern Critical Care Summit; and she received support from the University of Miami Hospital and Clinics Data Analytics Research Team. Dr. Prescott’s institution received funding from the Agency for Healthcare Research and Quality, Veterans Affairs Health Services Research and Development, the Centers for Disease Control and Prevention, and Blue Cross Blue Shield of Michigan; she disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Critical care uses syndromic definitions to describe patient groups for clinical practice and research. There is growing recognition that a "precision medicine" approach is required and that integrated biologic and physiologic data identify reproducible subpopulations that may respond differently to treatment. This article reviews the current state of the field and considers how to successfully transition to a precision medicine approach. To impact clinical care, identification of subpopulations must do more than differentiate prognosis. It must differentiate response to treatment, ideally by defining subgroups with distinct functional or pathobiological mechanisms (endotypes). There are now multiple examples of reproducible subpopulations of sepsis, acute respiratory distress syndrome, and acute kidney or brain injury described using clinical, physiological, and/or biological data. Many of these subpopulations have demonstrated the potential to define differential treatment response, largely in retrospective studies, and that the same treatment-responsive subpopulations may cross multiple clinical syndromes (treatable traits). To bring about a change in clinical practice, a precision medicine approach must be evaluated in prospective clinical studies requiring novel adaptive trial designs. Several such studies are underway, but there are multiple challenges to be tackled. Such subpopulations must be readily identifiable and be applicable to all critically ill populations around the world. Subdividing clinical syndromes into subpopulations will require large patient numbers. Global collaboration of investigators, clinicians, industry, and patients over many years will therefore be required to transition to a precision medicine approach and ultimately realize treatment advances seen in other medical fields.

Importance: Experimental and observational studies have suggested that empirical treatment for bacterial sepsis with antianaerobic antibiotics (eg, piperacillin-tazobactam) is associated with adverse outcomes compared with anaerobe-sparing antibiotics (eg, cefepime). However, a recent pragmatic clinical trial of piperacillin-tazobactam and cefepime showed no difference in short-term outcomes at 14 days. Further studies are needed to help clarify the empirical use of these agents., Objective: To examine the use of piperacillin-tazobactam compared with cefepime in 90-day mortality in patients treated empirically for sepsis, using instrumental variable analysis of a 15-month piperacillin-tazobactam shortage., Design, Setting, and Participants: In a retrospective cohort study, hospital admissions at the University of Michigan from July 1, 2014, to December 31, 2018, including a piperacillin-tazobactam shortage period from June 12, 2015, to September 18, 2016, were examined. Adult patients with suspected sepsis treated with vancomycin and either piperacillin-tazobactam or cefepime for conditions with presumed equipoise between piperacillin-tazobactam and cefepime were included in the study. Data analysis was conducted from December 17, 2022, to April 11, 2023., Main Outcomes and Measures: The primary outcome was 90-day mortality. Secondary outcomes included organ failure-free, ventilator-free, and vasopressor-free days. The 15-month piperacillin-tazobactam shortage period was used as an instrumental variable for unmeasured confounding in antibiotic selection., Results: Among 7569 patients (4174 men [55%]; median age, 63 [IQR 52-73] years) with sepsis meeting study eligibility, 4523 were treated with vancomycin and piperacillin-tazobactam and 3046 were treated with vancomycin and cefepime. Of patients who received piperacillin-tazobactam, only 152 (3%) received it during the shortage. Treatment groups did not differ significantly in age, Charlson Comorbidity Index score, Sequential Organ Failure Assessment score, or time to antibiotic administration. In an instrumental variable analysis, piperacillin-tazobactam was associated with an absolute mortality increase of 5.0% at 90 days (95% CI, 1.9%-8.1%) and 2.1 (95% CI, 1.4-2.7) fewer organ failure-free days, 1.1 (95% CI, 0.57-1.62) fewer ventilator-free days, and 1.5 (95% CI, 1.01-2.01) fewer vasopressor-free days., Conclusions and Relevance: Among patients with suspected sepsis and no clear indication for antianaerobic coverage, administration of piperacillin-tazobactam was associated with higher mortality and increased duration of organ dysfunction compared with cefepime. These findings suggest that the widespread use of empirical antianaerobic antibiotics in sepsis may be harmful.

Objective: To evaluate inter-hospital variation in 90-day total episode spending for sepsis, estimate the relative contributions of each component of spending, and identify drivers of spending across the distribution of episode spending on sepsis care., Data Sources/study Setting: Medicare fee-for-service claims for beneficiaries (n=324,694) discharged from acute care hospitals for sepsis, defined by MS-DRG, between October 2014 and September 2018., Research Design: Multiple linear regression with hospital-level fixed effects was used to identify average hospital differences in 90-day episode spending. Separate multiple linear regression and quantile regression models were used to evaluate drivers of spending across the episode spending distribution., Results: The mean total episode spending among hospitals in the most expensive quartile was $30,500 compared with $23,150 for the least expensive hospitals ( P <0.001). Postacute care spending among the most expensive hospitals was almost double that of least expensive hospitals ($7,045 vs. $3,742), accounting for 51% of the total difference in episode spending between the most expensive and least expensive hospitals. Female patients, patients with more comorbidities, urban hospitals, and BPCI-A-participating hospitals were associated with significantly increased episode spending, with the effect increasing at the right tail of the spending distribution., Conclusion: Inter-hospital variation in 90-day episode spending on sepsis care is driven primarily by differences in post-acute care spending., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Patients presenting to the emergency department (ED) with hypoxemia often have mixed or uncertain causes of respiratory failure. The optimal treatment for such patients is unclear. Both high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) are used., Objectives: We sought to compare the effectiveness of initial treatment with HFNC versus NIV for acute hypoxemic respiratory failure., Design Setting and Participants: We conducted a retrospective cohort study of patients with acute hypoxemic respiratory failure treated with HFNC or NIV within 24 hours of arrival to the University of Michigan adult ED from January 2018 to December 2022. We matched patients 1:1 using a propensity score for odds of receiving NIV., Main Outcomes and Measures: The primary outcome was major adverse pulmonary events (28-d mortality, ventilator-free days, noninvasive respiratory support hours) calculated using a win ratio., Results: A total of 1154 patients were included. Seven hundred twenty-six (62.9%) received HFNC and 428 (37.1%) received NIV. We propensity score matched 668 of 1154 (57.9%) patients. Patients on NIV versus HFNC had lower 28-day mortality (16.5% vs. 23.4%, p = 0.033) and required noninvasive treatment for fewer hours (median 7.5 vs. 13.5, p < 0.001), but had no difference in ventilator-free days (median [interquartile range]: 28 [26, 28] vs. 28 [10.5, 28], p = 0.199). Win ratio for composite major adverse pulmonary events favored NIV (1.38; 95% CI, 1.15-1.65; p < 0.001)., Conclusions and Relevance: In this observational study of patients with acute hypoxemic respiratory failure, initial treatment with NIV compared with HFNC was associated with lower mortality and fewer composite major pulmonary adverse events calculated using a win ratio. These findings underscore the need for randomized controlled trials to further understand the impact of noninvasive respiratory support strategies., Competing Interests: Dr. Munroe was supported by grant number T32 HL 007749 (Multidisciplinary Training Program in Lung Disease), grant number F32 HL 172463 and grant number L30 HL 170379 (Loan Repayment Award) from the National Institutes of Health (NIH) and the National Heart, Lung, and Blood Institute (NHLBI). This work was also supported in part by a grant from NIH (NINDS and NHLBI) for infrastructure for the Clinical Coordinating Center for the Strategies to Innovate EmeRgENcy Care Clinical Trials Network—2U24NS100659. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This article does not represent the views of the Department of Veterans Affairs or the U.S. government. Dr. Mosier has received travel support from Fisher & Paykel. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Objective: Pulmonary function test (PFT) results are recorded variably across hospitals in the Department of Veterans Affairs (VA) electronic health record (EHR), using both unstructured and semi-structured notes. We developed and validated a hospital-specific code to extract pre-bronchodilator measures of obstruction (ratio of forced expiratory volume in one second [FEV 1 ] to forced vital capacity [FVC]) and severity of obstruction (percent predicted of FEV 1 )., Results: Among 36 VA facilities with the most PFTs completed between 2018 and 2022 from a parent cohort of veterans receiving long-acting controller inhalers, 12 had a consistent syntactical convention or template for reporting PFT data in the EHR. Of the 42,718 PFTs identified from these 12 facilities, the hospital-specific text processing pipeline yielded 24,860 values for the FEV 1 :FVC ratio and 23,729 values for FEV 1 . A ratio of FEV 1 :FVC less than 0.7 was identified in 17,615 of 24,922 studies (70.7%); 8864 of 24,922 (35.6%) had a severe or very severe reduction in FEV 1 (< 50% of the predicted value). Among 100 randomly selected PFT reports reviewed by two pulmonary physicians, the coding solution correctly identified the presence of obstruction in 99 out of 100 studies and the degree of obstruction in 96 out of 100 studies., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Sepsis is a common and deadly condition. Within the current model of sepsis immunobiology, the framing of dysregulated host immune responses into proinflammatory and immunosuppressive responses for the testing of novel treatments has not resulted in successful immunomodulatory therapies. Thus, the recent focus has been to parse observable heterogeneity into subtypes of sepsis to enable personalised immunomodulation. In this Personal View, we highlight that many fundamental immunological concepts such as resistance, disease tolerance, resilience, resolution, and repair are not incorporated into the current sepsis immunobiology model. The focus for addressing heterogeneity in sepsis should be broadened beyond subtyping to encompass the identification of deterministic molecular networks or dominant mechanisms. We explicitly reframe the dysregulated host immune responses in sepsis as altered homoeostasis with pathological disruption of immune-driven resistance, disease tolerance, resilience, and resolution mechanisms. Our proposal highlights opportunities to identify novel treatment targets and could enable successful immunomodulation in the future., Competing Interests: Declaration of interests MS-H is supported by the UK National Institute for Health and Care Research (NIHR) Clinician Scientist Award (CS-2016-16-011; 2017–2023). MPS's laboratory is supported by the Calouste Gulbenkian Foundation, La Caixa Foundation (HR18-00502), Fundação para a Ciência e a Tecnologia (GlucoInfect, 5723/2014; FEDER029411, FEDER/29411/2017; Infectenergy, PTDC/MED-FSL/4681/2020; MalBil, 2022.02426.PTDC), the Oeiras–European Research Council Frontier Research Incentive Awards, SymbNET Research Grants (H2020-WIDESPREAD-2020-5-952537), and Congento (LISBOA-01-0145-FEDER-022170). MPS is an associate member of the Deutsche Forschungsgemeinschaft (DFG) Balance of the Microverse initiative (EXC 2051; 390713860). MB is principal investigator of the DFG Balance of the Microverse initiative (EXC 2051; 390713860). JCK is supported by the Medical Research Council (MR/V002503/1), a Wellcome Trust Investigator Award (204969/Z/16/Z), and Wellcome Trust grants (090532/Z/09/Z and 203141/Z/16/Z) to the Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, and the NIHR Oxford Biomedical Research Centre. JM reports grants from the Canadian Institutes of Health Research and has served as chair of data and safety monitoring boards for AM Pharma and Adrenomed. CWS reports grants from the US National Institutes of Health National Institute of General Medical Sciences, during the conduct of the study, and personal fees from Inotrem and Beckman Coulter, outside of the submitted work. IBM has received funding or consultancy fees from Abbvie, Amgen, Bristol Myers Squibb, Cabaletta, Causeway, Eli Lilly, Evelo, GSK, Janssen, Moonlake, Novartis, Pfizer, and UCB. TvdP has received grants from the EU's Horizon 2020 research and innovation funding programme (grant agreements: Flagellin Aerosol Therapy in Treatment of Drug-resistant Bacterial Pneumonia, 847786; ImmunoSEP, 847422). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Rationale: Shorter time-to-antibiotics improves survival from sepsis, particularly among patients in shock. There may be other subgroups for whom faster antibiotics are particularly beneficial. Objectives: Identify patient characteristics associated with greater benefit from shorter time-to-antibiotics. Methods: Observational cohort study of patients hospitalized with community-onset sepsis at 173 hospitals and treated with antimicrobials within 12 hours. We used three approaches to evaluate heterogeneity of benefit from shorter time-to-antibiotics: 1 ) conditional average treatment effects of shorter (⩽3 h) versus longer (>3-12 h) time-to-antibiotics on 30-day mortality using multivariable Poisson regression; 2 ) causal forest to identify characteristics associated with greatest benefit from shorter time-to-antibiotics; and 3 ) logistic regression with time-to-antibiotics modeled as a spline. Measurements and Main Results: Among 273,255 patients with community-onset sepsis, 131,094 (48.0%) received antibiotics within 3 hours. In Poisson models, shorter time-to-antibiotics was associated with greater absolute mortality reduction among patients with metastatic cancer (5.0% [95% confidence interval; CI: 4.3-5.7] vs. 0.4% [95% CI: 0.2-0.6] for patients without cancer, P < 0.001); patients with shock (7.0% [95% CI: 5.8-8.2%] vs. 2.8% [95% CI: 2.7-3.5%] for patients without shock, P = 0.005); and patients with more acute organ dysfunctions (4.8% [95% CI: 3.9-5.6%] for three or more dysfunctions vs. 0.5% [95% CI: 0.3-0.8] for one dysfunction, P  < 0.001). In causal forest, metastatic cancer and shock were associated with greatest benefit from shorter time-to-antibiotics. Spline analysis confirmed differential nonlinear associations of time-to-antibiotics with mortality in patients with metastatic cancer and shock. Conclusions: In patients with community-onset sepsis, the mortality benefit of shorter time-to-antibiotics varied by patient characteristics. These findings suggest that shorter time-to-antibiotics for sepsis is particularly important among patients with cancer and/or shock.

Importance: Recent sepsis trials suggest that fluid-liberal vs fluid-restrictive resuscitation has similar outcomes. These trials used generalized approaches to resuscitation, and little is known about how clinicians personalize fluid and vasopressor administration in practice., Objective: To understand how clinicians personalize decisions about resuscitation in practice., Design, Setting, and Participants: This survey study of US clinicians in the Society of Critical Care Medicine membership roster was conducted from November 2022 to January 2023. Surveys contained 10 vignettes of patients with sepsis where pertinent clinical factors (eg, fluid received and volume status) were randomized. Respondents selected the next steps in management. Data analysis was conducted from February to September 2023., Exposure: Online Qualtrics clinical vignette survey., Main Outcomes and Measures: Using multivariable logistic regression, the associations of clinical factors with decisions about fluid administration, vasopressor initiation, and vasopressor route were tested. Results are presented as adjusted proportions with 95% CIs., Results: Among 11 203 invited clinicians, 550 (4.9%; 261 men [47.5%] and 192 women [34.9%]; 173 with >15 years of practice [31.5%]) completed at least 1 vignette and were included. A majority were physicians (337 respondents [61.3%]) and critical care trained (369 respondents [67.1%]). Fluid volume already received by a patient was associated with resuscitation decisions. After 1 L of fluid, an adjusted 82.5% (95% CI, 80.2%-84.8%) of respondents prescribed additional fluid and an adjusted 55.0% (95% CI, 51.9%-58.1%) initiated vasopressors. After 5 L of fluid, an adjusted 17.5% (95% CI, 15.1%-19.9%) of respondents prescribed more fluid while an adjusted 92.7% (95% CI, 91.1%-94.3%) initiated vasopressors. More respondents prescribed fluid when the patient examination found dry vs wet (ie, overloaded) volume status (adjusted proportion, 66.9% [95% CI, 62.5%-71.2%] vs adjusted proportion, 26.5% [95% CI, 22.3%-30.6%]). Medical history, respiratory status, lactate trend, and acute kidney injury had small associations with fluid and vasopressor decisions. In 1023 of 1127 vignettes (90.8%) where the patient did not have central access, respondents were willing to start vasopressors through a peripheral intravenous catheter. In cases where patients were already receiving peripheral norepinephrine, respondents were more likely to place a central line at higher norepinephrine doses of 0.5 µg/kg/min (adjusted proportion, 78.0%; 95% CI, 74.7%-81.2%) vs 0.08 µg/kg/min (adjusted proportion, 25.2%; 95% CI, 21.8%-28.5%) and after 24 hours (adjusted proportion, 59.5%; 95% CI, 56.6%-62.5%) vs 8 hours (adjusted proportion, 47.1%; 95% CI, 44.0%-50.1%)., Conclusions and Relevance: These findings suggest that fluid volume received is the predominant factor associated with ongoing fluid and vasopressor decisions, outweighing many other clinical factors. Peripheral vasopressor use is common. Future studies aimed at personalizing resuscitation must account for fluid volumes and should incorporate specific tools to help clinicians personalize resuscitation.

Background: Vasopressors traditionally are administered via central access, but newer data suggest that peripheral administration may be safe and may avoid delays and complications associated with central line placement., Research Question: How commonly are vasopressors initiated through peripheral IV lines in routine practice? Is vasopressor initiation route associated with in-hospital mortality?, Study Design and Methods: This retrospective cohort study included adults hospitalized with sepsis (November 2020-September 2022) at 29 hospitals in the Michigan Hospital Medicine Safety Consortium, a Collaborative Quality Initiative sponsored by Blue Cross Blue Shield of Michigan. We assessed route of early vasopressor initiation, factors and outcomes associated with peripheral initiation, and timing of central line placement., Results: Five hundred ninety-four patients received vasopressors within 6 h of hospital arrival and were included in this study. Peripheral vasopressor initiation was common (400/594 [67.3%]). Patients with peripheral vs central initiation were similar; BMI was the only patient factor associated independently with initiation route (adjusted OR [aOR] of peripheral initiation [per 1-kg/m 2 increase], 0.98; 95% CI, 0.97-1.00; P = .015). The specific hospital showed a large impact on initiation route (median OR, 2.19; 95% CI, 1.31-3.07). Compared with central initiation, peripheral initiation was faster (median, 2.5 h vs 2.7 h from hospital arrival; P = .002), but was associated with less initial norepinephrine use (84.3% vs 96.8%; P = .001). We found no independent association between initiation route and in-hospital mortality (32.3% vs 42.2%; aOR, 0.66; 95% CI, 0.39-1.12). No tissue injury from peripheral vasopressors was documented. Of patients with peripheral initiation, 135 of 400 patients (33.8%) never received a central line., Interpretation: Peripheral vasopressor initiation was common across Michigan hospitals and had practical benefits, including expedited vasopressor administration and avoidance of central line placement in one-third of patients. However, the findings of wide practice variation that was not explained by patient case mix and lower use of first-line norepinephrine with peripheral administration suggest that additional standardization may be needed., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: H. B. G. is the editor of CHEST Critical Care and served on an advisory panel for COVID therapeutics for Gilead Sciences, Inc. None declared (E. S. M., M. E. H., M. E., J. K. H., J. J., S. K., M. T. K., E. M., S. A F., H. C. P.)., (Copyright © 2023 American College of Chest Physicians. All rights reserved.)

The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM-RPG) was to provide evidence-based clinical guidance about the use of higher versus lower oxygenation targets for adult patients in the intensive care unit (ICU). The guideline panel comprised 27 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. We adhered to the methodology for trustworthy clinical practice guidelines, including the use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and used the Evidence-to-Decision framework to generate recommendations. A recently published updated systematic review and meta-analysis constituted the evidence base. Through teleconferences and web-based discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients' values and preferences, costs and resources, equity, feasibility, acceptability, and research priorities. The updated systematic review and meta-analysis included data from 17 randomized clinical trials with 10,248 participants. There was little to no difference between the use of higher versus lower oxygenation targets for all outcomes with available data, including all-cause mortality, serious adverse events, stroke, functional outcomes, cognition, and health-related quality of life (very low certainty of evidence). The panel felt that values and preferences, costs and resources, and equity favored the use of lower oxygenation targets. The ICM-RPG panel issued one conditional recommendation against the use of higher oxygenation targets: "We suggest against the routine use of higher oxygenation targets in adult ICU patients (conditional recommendation, very low certainty of evidence). Remark: an oxygenation target of SpO 2 88%-92% or PaO 2 8 kPa/60 mmHg is relevant and safe for most adult ICU patients.", (© 2023 Acta Anaesthesiologica Scandinavica Foundation.)

Rationale: Sepsis is a frequent cause of ICU admission and mortality. Objectives: To evaluate temporal trends in the presentation and outcomes of patients admitted to the ICU with sepsis and to assess the contribution of changing case mix to outcomes. Methods: We conducted a retrospective cohort study of patients admitted to 261 ICUs in the United Kingdom during 1988-1990 and 1996-2019 with nonsurgical sepsis. Measurements and Main Results: A total of 426,812 patients met study inclusion criteria. The patients had a median (interquartile range) age of 66 (53-75) years, and 55.6% were male. The most common sites of infection were respiratory (60.9%), genitourinary (11.5%), and gastrointestinal (10.3%). Compared with patients in 1988-1990, patients in 2017-2019 were older (median age, 66 vs. 63 yr), were less acutely ill (median Acute Physiology and Chronic Health Evaluation II acute physiology score, 14 vs. 20), and more often had genitourinary sepsis (13.4% vs. 2.0%). Hospital mortality decreased from 54.6% (95% confidence interval [CI], 51.0-58.1%) in 1988-1990 to 32.4% (95% CI, 32.1-32.7%) in 2017-2019, with an adjusted odds ratio of 0.64 (95% CI, 0.54-0.75). The adjusted absolute hospital mortality reduction from 1988-1990 to 2017-2019 was 8.8% (95% CI, 5.6-12.1). Thus, of the observed 22.2-percentage point reduction in hospital mortality, 13.4 percentage points (60% of total reduction) were explained by case mix changes, whereas 8.8 percentage points (40% of total reduction) were not explained by measured factors and may be a result of improvements in ICU management. Conclusions: Over a 30-year period, mortality for ICU admissions with sepsis decreased substantially. Although changes in case mix accounted for the majority of observed mortality reduction, there was an 8.8-percentage point reduction in mortality not explained by case mix.

Objective: Patients who survive critical illness endure complex physical and mental health conditions, referred to as post-intensive care syndrome (PICS). The University of Michigan's post-intensive cardiac care outpatient long-term outreach (PICCOLO) clinic is designed for patients recently admitted to the coronary care unit (CCU). The long-term goal of this clinic is to understand post-CCU patients' needs and design targeted interventions to reduce their morbidity and mortality post-discharge. As a first step toward this goal, we aimed to define the post-discharge needs of CCU survivors., Design Setting Particpants: We retrospectively reviewed case-mix data (including rates of depression, PTSD, disability, and cognitive abnormalities) and health outcomes for patients referred to the PICCOLO clinic from July 1, 2018, through June 30, 2021 at Michigan Medicine., Results: Of the 134 referred patients meeting inclusion criteria, 74 (55 %) patients were seen in the PICCOLO clinic within 30 days of discharge. Patients seen in the clinic frequently screened positive for depression (PHQ-2 score ≥3, 21.4 %) and cognitive impairment (MOCA < 26, 38.8 %). Further, patients also reported high rates of physical difficulty (mean WHODAS 2.0 score 28.4 %, consistent with moderate physical difficulty). Consistent with medical intensive care unit (ICU) patients, CCU survivors experience PICS., Conclusion: This work highlights the feasibility of an outpatient care model and the need to leverage information gathered from this care model to develop treatment strategies and pathways to address symptoms of PICS in CCU survivors, including depression, cognitive impairment, and physical disability., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andrea D. Thompson reports financial support was provided by National Heart Lung and Blood Institute. Andrea D. Thompson reports financial support was provided by University of Michigan - Protein Folding Disease Initiative and Michigan Biology of Cardiovascular Aging (M-BoCA). This material is the result of work supported with resources and use of facilities at the Ann Arbor VA Medical Center. Dr. Thompson receives compensation as editor for Merck Manuals. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Objectives: To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock., Design: Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities., Methods: Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article., Results: A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis?, Conclusions: Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock., Competing Interests: Drs. De Backer, Pontes Azevedo, and Tissieres received funding from Baxter. Dr. De Backer received funding from Edwards Lifesciences, Phillips, and Viatris Pharmazz. Dr. Deutschman received funding from Elsevier, Siemens Healthcare Diagnostics (Tarrytown, NY), Enliven (Jerusalem, Israel), The Society of Critical Care Medicine, the National Institute of General Medical Sciences, and La Jolla Pharmaceuticals; he received support for article research form the National Institutes of Health (NIH); he received Giapreza (angiotensin II infusion) for experimental use from La Jolla Pharmaceuticals (La Jolla, CA); and he received honorarium for serving as Scientific Editor of the journal Critical Care Medicine. Dr. Ostermann received research funding from Baxter, Fresenius Medical, bioMerieux, and La Jolla Pharma. Dr. Talmor received funding from NIH, Clew Medical, Mindray, and STIMIT. Dr. Prescott’s institution received funding from the NIH, U.S. Department of Veterans Affairs, the Agency for Healthcare and Research and Quality, the U.S. Centers for Disease Control and Prevention, and Blue Cross Blue Shield Michigan; she disclosed government work. Dr. Antonelli received funding from General Electrics, Fisher & Paykel, Menarini, and Pfizer. Dr. Pontes Azevedo received funding from Merck Sharp Dohme (MSD) and Nestle. Dr. Loeches received funding from ThermoFisher, Polyphor, MSD, Fresenius Kabi, Gilead, Clinigen, Biotest, Accelerate, and bioMérieux. Dr. Tissieres received funding from Sanofi, bioMerieux, Abionic, Sedana, and ThermoFisher. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Rationale: Shorter time-to-antibiotics is lifesaving in sepsis, but programs to hasten antibiotic delivery may increase unnecessary antibiotic use and adverse events. Objectives: We sought to estimate both the benefits and harms of shortening time-to-antibiotics for sepsis. Methods: We conducted a simulation study using a cohort of 1,559,523 hospitalized patients admitted through the emergency department with meeting two or more systemic inflammatory response syndrome criteria (2013-2018). Reasons for hospitalization were classified as septic shock, sepsis, infection, antibiotics stopped early, and never treated (no antibiotics within 48 h). We simulated the impact of a 50% reduction in time-to-antibiotics for sepsis across 12 hospital scenarios defined by sepsis prevalence (low, medium, or high) and magnitude of "spillover" antibiotic prescribing to patients without infection (low, medium, high, or very high). Outcomes included mortality and adverse events potentially attributable to antibiotics (e.g., allergy, organ dysfunction, Clostridiodes difficile infection, and culture with multidrug-resistant organism). Results: A total of 933,458 (59.9%) hospitalized patients received antimicrobial therapy within 48 hours of presentation, including 38,572 (2.5%) with septic shock, 276,082 (17.7%) with sepsis, 370,705 (23.8%) with infection, and 248,099 (15.9%) with antibiotics stopped early. A total of 199,937 (12.8%) hospitalized patients experienced an adverse event; most commonly, acute liver injury (5.6%), new MDRO (3.5%), and Clostridiodes difficile infection (1.7%). Across the scenarios, a 50% reduction in time-to-antibiotics for sepsis was associated with a median of 1 to 180 additional antibiotic-treated patients and zero to seven additional adverse events per death averted from sepsis. Conclusions: The impacts of faster time-to-antibiotics for sepsis vary markedly across simulated hospital types. However, even in the worst-case scenario, new antibiotic-associated adverse events were rare.

Background: Few studies have reported on mortality beyond one year after sepsis. We aim to describe trends in short- and long-term mortality among patients admitted with sepsis, and to describe the association between clinical characteristics and mortality for improved monitoring, treatment and prognosis., Methods: Patients ≥ 18 years admitted to all Norwegian hospitals (2008-2021) with a first sepsis episode were identified using Norwegian Patient Registry and International Classification of Diseases 10th Revision codes. Sepsis was classified as implicit (known infection site plus organ dysfunction), explicit (unknown infection site), or COVID-19-related sepsis. The outcome was all-cause mortality. We describe age-standardized 30-day, 90-day, 1-, 5- and 10-year mortality for each admission year and estimated the annual percentage change with 95% confidence interval (CI). The association between clinical characteristics and all-cause mortality is reported as hazard ratios (HRs) adjusted for age, sex and calendar year in Cox regression., Results: The study included 222,832 patients, of whom 127,059 (57.1%) had implicit, 92,928 (41.7%) had explicit, and 2,845 (1.3%) had COVID-19-related sepsis (data from 2020 and 2021). Trends in overall age-standardized 30-day, 90-day, 1- and 5-year mortality decreased by 0.29 (95% CI - 0.39 to - 0.19), 0.43 (95% CI - 0.56 to - 0.29), 0.61 (95% CI - 0.73 to - 0.49) and 0.66 (95% CI - 0.84 to - 0.48) percent per year, respectively. The decrease was observed for all infections sites but was largest among patients with respiratory tract infections. Implicit, explicit and COVID-19-related sepsis had largely similar overall mortality, with explicit sepsis having an adjusted HR of 0.980 (95% CI 0.969 to 0.991) and COVID-19-related sepsis an adjusted HR of 0.916 (95% CI 0.836 to 1.003) compared to implicit sepsis. Patients with respiratory tract infections have somewhat higher mortality than those with other infection sites. Number of comorbidities was positively associated with mortality, but mortality varied considerably between different comorbidities. Similarly, number of acute organ dysfunctions was strongly associated with mortality, whereas the risk varied for each type of organ dysfunction., Conclusion: Overall mortality has declined over the past 14 years among patients with a first sepsis admission. Comorbidity, site of infection, and acute organ dysfunction are patient characteristics that are associated with mortality. This could inform health care workers and raise the awareness toward subgroups of patients that needs particular attention to improve long-term mortality., (© 2023. The Author(s).)

The Surviving Sepsis Campaign (SSC) International Guidelines for the Management of Sepsis and Septic Shock provide recommendations on the care of hospitalized adult patients with (or at risk for) sepsis. This review discusses what is new or different in the 2021 SSC adult sepsis guidelines compared to 2016. The guidelines include new weak recommendations for use of balanced fluid over saline 0.9%, use of intravenous corticosteroids for septic shock when there is ongoing vasopressor requirement, and peripheral initiation of intravenous vasopressors over delaying initiation in order to obtain central venous access. As before, there is a strong recommendation to initiate antimicrobials within 1 h of sepsis and septic shock, but there are now additional recommendations when the diagnosis is uncertain. The recommendation for initial fluid resuscitation in septic shock of 30 mL/kg crystalloid has been downgraded from strong to weak. Finally, there are 12 new recommendations addressing long-term outcomes from sepsis, including strong recommendations to screen for economic and social support and to make referrals for follow-up where available; use shared decision-making in post-intensive care unit (ICU) and hospital discharge planning; reconcile medications at both ICU and hospital discharge; provide information about sepsis and its sequelae in written and verbal hospital discharge summary; and to provide assessment and follow-up for physical, cognitive, and emotional problems after hospital discharge., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Sepsis survivors commonly experience functional impairment, which may limit return to work. We investigated return to work (RTW) of patients hospitalized with sepsis and the associations with patient and clinical characteristics., Methods: Working-age patients (18-60 years) admitted to a Norwegian hospital with sepsis between 2010 and 2021 were identified using the Norwegian Patient Registry and linked to sick-leave data from the Norwegian National Social Security System Registry. The main outcome was proportion of RTW in patients hospitalized with sepsis at 6 months, 1 year, and 2 years after discharge. Secondary outcomes were time trends in age-standardized proportions of RTW and probability of sustainable RTW (31 days of consecutive work). The time trends were calculated for each admission year, reported as percentage change with 95% confidence interval (CI). Time-to-event analysis, including crude and adjusted hazard risk (HRs), was used to explore the association between sustainable RTW, characteristics and subgroups of sepsis patients (intensive care unit (ICU) vs. non-ICU and COVID-19 vs. non-COVID-19)., Results: Among 35.839 hospitalizations for sepsis among patients aged 18-60 years, 12.260 (34.2%) were working prior to hospitalization and included in this study. The mean age was 43.7 years. At 6 months, 1 year, and 2 years post-discharge, overall estimates showed that 58.6%, 67.5%, and 63.4%, respectively, were working. The time trends in age-standardized RTW for ICU and non-ICU sepsis patients remained stable over the study period, except the 2-year age-standardized RTW for non-ICU patients that declined by 1.51% (95% CI - 2.22 to - 0.79) per year, from 70.01% (95% CI 67.21 to 74.80) in 2010 to 57.04% (95% CI 53.81-60.28) in 2019. Characteristics associated with sustainable RTW were younger age, fewer comorbidities, and fewer acute organ dysfunctions. The probability of sustainable RTW was lower in ICU patients compared to non-ICU patients (HR 0.56; 95% CI 0.52-0.61) and higher in patients with COVID-19-related sepsis than in sepsis patients (HR 1.31; 95% CI 1.15-1.49)., Conclusion: Absence of improvement in RTW proportions over time and the low probability of sustainable RTW in sepsis patients need attention, and further research to enhance outcomes for sepsis patients is required., (© 2023. The Author(s).)

Objectives: To identify opportunities for improving hospital-based sepsis care and to inform an ongoing statewide quality improvement initiative in Michigan., Design: Surveys on hospital sepsis processes, including a self-assessment of practices using a 3-point Likert scale, were administered to 51 hospitals participating in the Michigan Hospital Medicine Safety Consortium, a Collaborative Quality Initiative sponsored by Blue Cross Blue Shield of Michigan, at two time points (2020, 2022). Forty-eight hospitals also submitted sepsis protocols for structured review., Setting: Multicenter quality improvement consortium., Subjects: Fifty-one hospitals in Michigan., Interventions: None., Measurements and Main Results: Of the included hospitals, 92.2% ( n = 47/51) were nonprofit, 88.2% ( n = 45/51) urban, 11.8% ( n = 6/51) rural, and 80.4% ( n = 41/51) teaching hospitals. One hundred percent ( n = 51/51) responded to the survey, and 94.1% ( n = 48/51) provided a sepsis policy/protocol. All surveyed hospitals used at least one quality improvement approach, including audit/feedback (98.0%, n = 50/51) and/or clinician education (68.6%, n = 35/51). Protocols included the Sepsis-1 (18.8%, n = 9/48) or Sepsis-2 (31.3%, n = 15/48) definitions; none ( n = 0/48) used Sepsis-3. All hospitals ( n = 51/51) used at least one process to facilitate rapid sepsis treatment, including order sets (96.1%, n = 49/51) and/or stocking of commonly used antibiotics in at least one clinical setting (92.2%, n = 47/51). Treatment protocols included guidance on antimicrobial therapy (68.8%, n = 33/48), fluid resuscitation (70.8%, n = 34/48), and vasopressor administration (62.5%, n = 30/48). On self-assessment, hospitals reported the lowest scores for peridischarge practices, including screening for cognitive impairment (2.0%, n = 1/51 responded "we are good at this") and providing anticipatory guidance (3.9%, n = 2/51). There were no meaningful associations of the Centers for Medicare and Medicaid Services' Severe Sepsis and Septic Shock: Management Bundle performance with differences in hospital characteristics or sepsis policy document characteristics., Conclusions: Most hospitals used audit/feedback, order sets, and clinician education to facilitate sepsis care. Hospitals did not consistently incorporate organ dysfunction criteria into sepsis definitions. Existing processes focused on early recognition and treatment rather than recovery-based practices., Competing Interests: Dr. Prescott receives salary support from the Blue Cross Blue Shield of Michigan (BCBSM) for leadership of sepsis work. Dr. Flanders receives salary support from the BCBSM for oversight of sepsis work. Dr. Heath receives salary support from the BCBSM. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Background: In 2020, many family members were thrust into the role of caregiving for a relative with COVID-19 with little preparation, training, or understanding of the disease and its symptoms., Objectives: To explore the barriers to and facilitators of caregiving experienced by family caregivers of patients with COVID-19 who had been in intensive care in the pandemic's earliest months., Methods: In-depth qualitative interviews were conducted by web conference with 16 adults recovering at home after intubation for COVID-19 in an intensive care unit at a major academic medical center and their primary caregivers from March to August 2020 (N = 32). Thematic qualitative analysis was done using Watkins' rigorous and accelerated data reduction technique with MAXQDA software., Results: Seven themes emerged regarding factors that facilitated or posed barriers to care: other health conditions that increased complexity of care, interactions and experiences in the health care system, COVID-19's proliferation into other areas of life, the psychological well-being of the patient-caregiver dyad, experience of support from the dyad's network, the role of caregiving in the dyad, and contextual circumstances of the dyad. The themes often included both barriers and facilitators, depending on the experience of the dyad (eg, feeling encouraged vs fatigued by their support network)., Conclusions: Understanding how patients with COVID-19 and their caregivers experience illness management across the recovery journey can help clarify the COVID-19 care-giving process and identify intervention targets to improve overall health and well-being of the care dyad., (©2023 American Association of Critical-Care Nurses.)

Importance: Despite growing evidence of persistent problems after acute COVID-19, how long the excess mortality risk associated with COVID-19 persists is unknown., Objective: To measure the time course of differential mortality among Veterans who had a first-documented COVID-19 infection by separately assessing acute mortality from later mortality among matched groups with infected and uninfected individuals who survived and were uncensored at the start of each period., Design, Settings, and Participants: This retrospective cohort study used prospectively collected health record data from Veterans Affairs hospitals across the US on Veterans who had COVID-19 between March 2020 and April 2021. Each individual was matched with up to 5 comparators who had not been infected with COVID-19 at the time of matching. This match balanced, on a month-by-month basis, the risk of developing COVID-19 using 37 variables measured in the 24 months before the date of the infection or match. A primary analysis censored comparators when they developed COVID-19 with inverse probability of censoring weighting in Cox regression. A secondary analysis did not censor. Data analyses were performed from April 2021 through June 2023., Exposure: First-documented case of COVID-19 (SARS-CoV-2) infection., Main Outcome Measures: Hazard ratios for all-cause mortality at clinically meaningful intervals after infection: 0 to 90, 91 to 180, 181 to 365, and 366 to 730 days., Results: The study sample comprised 208 061 Veterans with first-documented COVID-19 infection (mean [SD] age, 60.5 (16.2) years; 21 936 (10.5) women; 47 645 [22.9] Black and 139 604 [67.1] White individuals) and 1 037 423 matched uninfected comparators with similar characteristics. Veterans with COVID-19 had an unadjusted mortality rate of 8.7% during the 2-year period after the initial infection compared with 4.1% among uninfected comparators, with censoring if the comparator later developed COVID-19-an adjusted hazard ratio (aHR) of 2.01 (95% CI, 1.98-2.04). The risk of excess death varied, being highest during days 0 to 90 after infection (aHR, 6.36; 95% CI, 6.20-6.51) and still elevated during days 91 to 180 (aHR, 1.18; 95% CI, 1.12-1.23). Those who survived COVID-19 had decreased mortality on days 181 to 365 (aHR, 0.92; 95% CI, 0.89-0.95) and 366 to 730 (aHR, 0.89; 95% CI, 0.85-0.92). These patterns were consistent across sensitivity analyses., Conclusion and Relevance: The findings of this retrospective cohort study indicate that although overall 2-year mortality risk was worse among those infected with COVID-19, by day 180 after infection they had no excess mortality during the next 1.5 years.

Rationale: The optimal treatment for early hypoxemic respiratory failure is unclear, and both high-flow nasal cannula and non-invasive ventilation are used. Determining clinically relevant outcomes for evaluating non-invasive respiratory support modalities remains a challenge., Objectives: To compare the effectiveness of initial treatment with high-flow nasal cannula versus non-invasive ventilation for acute hypoxemic respiratory failure., Methods: We conducted a retrospective cohort study of patients with acute hypoxemic respiratory failure treated with high-flow nasal cannula or non-invasive ventilation within 24 hours of Emergency Department arrival (1/2018-12/2022). We matched patients 1:1 using a propensity score for odds of receiving non-invasive ventilation. The primary outcome was major adverse pulmonary events (28-day mortality, ventilator-free days, non-invasive respiratory support hours) calculated using a Win Ratio., Measurements and Main Results: 1,265 patients met inclusion criteria. 795 (62.8%) received high-flow oxygen and 470 (37.2%) received non-invasive ventilation. We propensity score matched 736/1,265 (58.2%) patients. There was no difference between non-invasive ventilation vs high-flow nasal cannula in 28-day mortality (17.7% vs 23.1%, p=0.08) or ventilator-free days (median [Interquartile Range]: 28 [25, 28] vs 28 [13, 28], p=0.50), but patients on non-invasive ventilation required treatment for fewer hours (median 7 vs 13, p< 0.001). Win Ratio for composite major adverse pulmonary events favored non-invasive ventilation (1.26, 95%CI 1.06-1.49, p< 0.001)., Conclusions: In this observational study of patients with acute hypoxemic respiratory failure, initial treatment with non-invasive ventilation was superior to high-flow nasal cannula for major pulmonary adverse events. Evaluation of composite outcomes is important in the assessment of respiratory support modalities., Competing Interests: Conflicts of Interest: JMM has received travel support from Fisher & Paykel.

Rationale: Despite the importance of sepsis surveillance, no optimal approach for identifying sepsis hospitalizations exists. The Centers for Disease Control and Prevention Adult Sepsis Event Definition (CDC-ASE) is an electronic medical record-based algorithm that yields more stable estimates over time than diagnostic coding-based approaches but may still result in misclassification. Objectives: We sought to assess three approaches to identifying sepsis hospitalizations, including a modified CDC-ASE. Methods: This cross-sectional study included patients in the Veterans Affairs Ann Arbor Healthcare System admitted via the emergency department (February 2021 to February 2022) with at least one episode of acute organ dysfunction within 48 hours of emergency department presentation. Patients were assessed for community-onset sepsis using three methods: 1 ) explicit diagnosis codes, 2 ) the CDC-ASE, and 3 ) a modified CDC-ASE. The modified CDC-ASE required at least two systemic inflammatory response syndrome criteria instead of blood culture collection and had a more sensitive definition of respiratory dysfunction. Each method was compared with a reference standard of physician adjudication via medical record review. Patients were considered to have sepsis if they had at least one episode of acute organ dysfunction graded as "definitely" or "probably" infection related on physician review. Results: Of 821 eligible hospitalizations, 449 were selected for physician review. Of these, 98 (21.8%) were classified as sepsis by medical record review, 103 (22.9%) by the CDC-ASE, 132 (29.4%) by the modified CDC-ASE, and 37 (8.2%) by diagnostic codes. Accuracy was similar across the three methods of interest (80.6% for the CDC-ASE, 79.6% for the modified CDC-ADE, and 84.2% for diagnostic codes), but sensitivity and specificity varied. The CDC-ASE algorithm had sensitivity of 58.2% (95% confidence interval [CI], 47.2-68.1%) and specificity of 86.9% (95% CI, 82.9-90.2%). The modified CDC-ASE algorithm had greater sensitivity (69.4% [95% CI, 59.3-78.3%]) but lower specificity (81.8% [95% CI, 77.3-85.7%]). Diagnostic codes had lower sensitivity (32.7% [95% CI, 23.5-42.9%]) but greater specificity (98.6% [95% CI, 96.7-99.55%]). Conclusions: There are several approaches to identifying sepsis hospitalizations for surveillance that have acceptable accuracy. These approaches yield varying sensitivity and specificity, so investigators should carefully consider the test characteristics of each method before determining an appropriate method for their intended use.

Sepsis, life-threatening organ dysfunction secondary to infection, contributes to at least 1.7 million adult hospitalizations and at least 350,000 deaths annually in the United States. Sepsis care is complex, requiring the coordination of multiple hospital departments and disciplines. Sepsis programs can coordinate these efforts to optimize patient outcomes. The 2022 National Healthcare Safety Network (NHSN) annual survey evaluated the prevalence and characteristics of sepsis programs in acute care hospitals. Among 5,221 hospitals, 3,787 (73%) reported having a committee that monitors and reviews sepsis care. Prevalence of these committees varied by hospital size, ranging from 53% among hospitals with 0-25 beds to 95% among hospitals with >500 beds. Fifty-five percent of all hospitals provided dedicated time (including assigned protected time or job description requirements) for leaders of these committees to manage a program and conduct daily activities, and 55% of committees reported involvement with antibiotic stewardship programs. These data highlight opportunities, particularly in smaller hospitals, to improve the care and outcomes of patients with sepsis in the United States by ensuring that all hospitals have sepsis programs with protected time for program leaders, engagement of medical specialists, and integration with antimicrobial stewardship programs. CDC's Hospital Sepsis Program Core Elements provides a guide to assist hospitals in developing and implementing effective sepsis programs that complement and facilitate the implementation of existing clinical guidelines and improve patient care. Future NHSN annual surveys will monitor uptake of these sepsis core elements., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Mary Whitaker reported being secretary and board member of the Certification Board for Infection Control Test committee, Georgia Infection Prevention Network; Elizabeth S. McLaughlin reported participation in Blue Cross Blue Shield of Michigan Value Partnership Program and funding support for program management with the Michigan Hospital Medicine Safety Consortium. Patricia J. Posa reported receiving support to attend the American Association of Critical Nurses’ National Teaching Institute during 2022 and 2023; Hallie C. Prescott reported receiving honoraria for grand rounds or talks at academic medical centers, conference travel funds to International Sepsis Forum and International Symposium of Intensive Care and Emergency Medicine conferences, serving on data safety monitoring boards unrelated to this manuscript, and serving as co-chair of the Surviving Sepsis Campaign 2021 Adult Guidelines.

Background: As critical care practice evolves, the sepsis survivor population continues to expand, often with lingering inflammation in many organs, including the liver. Given the concurrently increasing population of patients with NAFLD, in this study, we aimed to understand the long-term effect of sepsis on pre-existing NAFLD and hyperglycemia., Methods: Male mice were randomized to a high-fat diet or a control diet (CD). After 24 weeks on diet, mice were inoculated with Klebsiella pneumoniae (Kpa). Serial glucose tolerance tests, and insulin and pyruvate challenge tests were performed 1 week before infection and at 2 and 6 weeks after infection. Whole tissue RNA sequencing and histological evaluation of the liver were performed. To test whether persistent inflammation could be reproduced in other abnormal liver environments, mice were also challenged with Kpa after exposure to a methionine-choline-deficient high-fat diet. Finally, a retrospective cohort of 65,139 patients was analyzed to evaluate whether obesity was associated with liver injury after sepsis., Results: After Kpa inoculation, high-fat diet mice had normalized fasting blood glucose without a change in insulin sensitivity but with a notable decrease in pyruvate utilization. Liver examination revealed focal macrophage collections and a unique inflammatory gene signature on RNA analysis. In the clinical cohort, preobesity, and class 1 and class 2 obesity were associated with increased odds of elevated aminotransferase levels 1-2 years after sepsis., Conclusions: The combination of diet-induced obesity and pneumosepsis survival in a murine model resulted in unique changes in gluconeogenesis and liver inflammation, consistent with the progression of benign steatosis to steatohepatitis. In a cohort study, obese patients had an increased risk of elevated aminotransferase levels 1-2 years following sepsis., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Rationale: Little is known about the safety of infusing vasopressors through a midline catheter. Objectives: To evaluate safety outcomes after vasopressor administration through a midline. Methods: We conducted a cohort study of adults admitted to 39 hospitals in Michigan (December 2017-March 2022) who received vasopressors while either a midline or peripherally inserted central catheter (PICC) was in place. Patients receiving vasopressors through a midline were compared with those receiving vasopressors through a PICC and, separately, to those with midlines in place but who received vasopressors through a different catheter. We used descriptive statistics to characterize and compare cohort characteristics. Multivariable mixed effects logistic regression models were fit to determine the association between vasopressor administration through a midline with outcomes, primarily catheter-related complications (bloodstream infection, superficial thrombophlebitis, exit site infection, or catheter occlusion). Results: Our cohort included 287 patients with midlines through which vasopressors were administered, 1,660 with PICCs through which vasopressors were administered, and 884 patients with midlines who received vasopressors through a separate catheter. Age (median [interquartile range]: 68.7 [58.6-75.7], 66.6 [57.1-75.0], and 67.6 [58.7-75.8] yr) and gender (percentage female: 50.5%, 47.3%, and 43.8%) were similar in all groups. The frequency of catheter-related complications was lower in patients with midlines used for vasopressors than PICCs used for vasopressors (5.2% vs. 13.4%; P  < 0.001) but similar to midlines with vasopressor administration through a different device (5.2% vs. 6.3%; P  = 0.49). After adjustment, administration of vasopressors through a midline was not associated with catheter-related complications compared with PICCs with vasopressors (adjusted odds ratios [aOR], 0.65 [95% confidence interval, 0.31-1.33]; P  = 0.23) or midlines with vasopressors elsewhere (aOR, 0.85 [0.46-1.58]; P  = 0.59). Midlines used for vasopressors were associated with greater risk of systemic thromboembolism (vs. PICCs with vasopressors: aOR, 2.69 [1.31-5.49]; P  = 0.008; vs. midlines with vasopressors elsewhere: aOR, 2.42 [1.29-4.54]; P  = 0.008) but not thromboses restricted to the ipsilateral upper extremity (vs. PICCs with vasopressors: aOR, 2.35 [0.83-6.63]; P  = 0.10; model did not converge for vs. midlines with vasopressors elsewhere). Conclusions: We found no significant association of vasopressor administration through a midline with catheter-related complications. However, we identified increased odds of systemic (but not ipsilateral upper extremity) venous thromboembolism warranting further evaluation.

Critical illness results in subjective financial distress for families, but little is known about objective caregiver finances after a child's pediatric intensive care unit (PICU) hospitalization. Using statewide commercial insurance claims linked to cross-sectional commercial credit data, we identified caregivers of children with PICU hospitalizations in January-June 2020 and January-June 2021. Credit data included delinquent debt, debt in collections (medical and non-medical), low credit score (< 660), and a composite of any debt or poor credit and were measured in January 2021 for all caregivers. For the 2020 cohort ("post-PICU"), credit outcomes in January 2021 were measured at least 6 months following PICU hospitalization and reflect financial status after the hospitalization. For the 2021 cohort (comparison), financial outcomes were measured prior to their child's PICU hospitalization and therefore reflect pre-hospitalization financial status. We identified 2032 caregivers, 1017 post-PICU caregivers and 1015 comparison cohort caregivers, of which 1016 and 1014 were matched to credit data, respectively. Post-PICU caregivers had higher adjusted odds of having any delinquent debt [aOR 1.25; 95%CI 1.02-1.53; p = 0.03] and having a low credit score [aOR 1.29; 95%CI 1.06-1.58; p = 0.01]. However, there was no difference in the amount of delinquent debt or debt in collections among those with nonzero debt. Overall, 39.5% and 36.5% of post-PICU and comparator caregivers, respectively, had delinquent debt, debt in collections or poor credit. Many caregivers of critically ill children have financial debt or poor credit during hospitalization and post-discharge. However, caregivers may be at higher risk for poor financial status following their child's critical illness., (© 2023. The Author(s).)

Sepsis survivors are at increased risk for morbidity and functional impairment. There are recommended practices to support recovery after sepsis, but it is unclear how often they are implemented. We sought to assess the current use of recovery-based practices across hospitals., Design: Electronic survey assessing the use of best practices for recovery from COVID-related and non-COVID-related sepsis. Questions included four-point Likert responses of "never" to "always/nearly always.", Setting: Twenty-six veterans affairs hospitals with the highest ( n = 13) and lowest ( n = 13) risk-adjusted 90-day sepsis survival., Subjects: Inpatient and outpatient clinician leaders., Interventions: None., Measurements and Main Results: For each domain, we calculated the proportion of "always/nearly always" responses and mean Likert scores. We assessed for differences by hospital survival, COVID versus non-COVID sepsis, and sepsis case volume. Across eight domains of care, the proportion "always/nearly always" responses ranged from: 80.7% (social support) and 69.8% (medication management) to 22.5% (physical recovery and adaptation) and 0.0% (emotional support). Higher-survival hospitals more often performed screening for new symptoms/limitations (49.2% vs 35.1% "always/nearly always," p = 0.02) compared with lower-survival hospitals. There was no difference in "always/nearly always" responses for COVID-related versus non-COVID-related sepsis, but small differences in mean Likert score in four domains: care coordination (3.34 vs 3.48, p = 0.01), medication management (3.59 vs 3.65, p = 0.04), screening for new symptoms/limitations (3.13 vs 3.20, p = 0.02), and anticipatory guidance and education (2.97 vs 2.84, p < 0.001). Lower case volume hospitals more often performed care coordination (72.7% vs 43.8% "always/nearly always," p = 0.02), screening for new symptoms/limitations (60.6% vs 35.8%, p < 0.001), and social support (100% vs 74.2%, p = 0.01)., Conclusions: Our findings show variable adoption of practices for sepsis recovery. Future work is needed to understand why some practice domains are employed more frequently than others, and how to facilitate practice implementation, particularly within rarely adopted domains such as emotional support., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Although respiratory manifestations are the most common driver of hospitalization, SARS-CoV-2 infection has a wide range of manifestations, including multisystem organ failure in severe cases. This review discusses the prevalence, pathophysiology, clinical manifestations, treatment, and outcomes of nonpulmonary organ dysfunction from SARS-CoV2, including renal, liver, cardiac, neurologic, and coagulation system dysfunction. At this time, management largely focuses on supportive care practices that are applicable regardless of the cause of organ injury., (Published by Elsevier Inc.)

Sepsis causes significant morbidity and mortality worldwide. Resuscitation is a cornerstone of management. This review covers five areas of evolving practice in the management of early sepsis-induced hypoperfusion: fluid resuscitation volume, timing of vasopressor initiation, resuscitation targets, route of vasopressor administration, and use of invasive blood pressure monitoring. For each topic, we review the seminal evidence, discuss the evolution of practice over time, and highlight questions for additional research. Intravenous fluids are a core component of early sepsis resuscitation. However, with growing concerns about the harms of fluid, practice is evolving toward smaller-volume resuscitation, which is often paired with earlier vasopressor initiation. Large trials of fluid-restrictive, vasopressor-early strategies are providing more information about the safety and potential benefit of these approaches. Lowering blood pressure targets is a means to prevent fluid overload and reduce exposure to vasopressors; mean arterial pressure targets of 60-65 mm Hg appear to be safe, at least in older patients. With the trend toward earlier vasopressor initiation, the need for central administration of vasopressors has been questioned, and peripheral vasopressor use is increasing, although it is not universally accepted. Similarly, although guidelines suggest the use of invasive blood pressure monitoring with arterial catheters in patients receiving vasopressors, blood pressure cuffs are less invasive and often sufficient. Overall, the management of early sepsis-induced hypoperfusion is evolving toward fluid-sparing and less-invasive strategies. However, many questions remain, and additional data are needed to further optimize our approach to resuscitation.