Assessment of implementation methods in sepsis: study protocol for a cluster-randomized hybrid type 2 trial.

BACKGROUND: Sepsis is the leading cause of intensive care unit (ICU) admission and ICU death. In recognition of the burden of sepsis, the Surviving Sepsis Campaign (SSC) and the Institute for Healthcare Improvement developed sepsis "bundles" (goals to accomplish over a specific time period) to facilitate SSC guideline implementation in clinical practice. Using the SSC 3-h bundle as a base, the Centers for Medicare and Medicaid Services developed a 3-h sepsis bundle that has become the national standard for early management of sepsis. Emerging observational data, from an analysis conducted for the AIMS grant application, suggest there may be additional mortality benefit from even earlier implementation of the 3-h bundle, i.e., the 1-h bundle. METHOD: The primary aims of this randomized controlled trial are to: (1) examine the effect on clinical outcomes of Emergency Department initiation of the elements of the 3-h bundle within the traditional 3 h versus initiating within 1 h of sepsis recognition and (2) examine the extent to which a rigorous implementation strategy will improve implementation and compliance with both the 1-h bundle and the 3-h bundle. This study will be entirely conducted in the Emergency Department at 18 sites. A secondary aim is to identify clinical sepsis phenotypes and their impact on treatment outcomes. DISCUSSION: This cluster-randomized trial, employing implementation science methodology, is timely and important to the field. The hybrid effectiveness-implementation design is likely to have an impact on clinical practice in sepsis management by providing a rigorous evaluation of the 1- and 3-h bundles. FUNDING: NHLBI R01HL162954. TRIAL REGISTRATION: ClinicalTrials.gov NCT05491941. Registered on August 8, 2022.

Effects of Compliance With the Early Management Bundle (SEP-1) on Mortality Changes Among Medicare Beneficiaries With Sepsis: A Propensity Score Matched Cohort Study.

BACKGROUND: US hospitals have reported compliance with the SEP-1 quality measure to Medicare since 2015. Finding an association between compliance and outcomes is essential to gauge measure effectiveness. RESEARCH QUESTION: What is the association between compliance with SEP-1 and 30-day mortality among Medicare beneficiaries? STUDY DESIGN AND METHODS: Studying patient-level data reported to Medicare by 3,241 hospitals from October 1, 2015, to March 31, 2017, we used propensity score matching and a hierarchical general linear model (HGLM) to estimate the treatment effects associated with compliance with SEP-1. Compliance was defined as completion of all qualifying SEP-1 elements including lactate measurements, blood culture collection, broad-spectrum antibiotic administration, 30 mL/kg crystalloid fluid administration, application of vasopressors, and patient reassessment. The primary outcome was a change in 30-day mortality. Secondary outcomes included changes in length of stay. RESULTS: We completed two matches to evaluate population-level treatment effects. In standard match, 122,870 patients whose care was compliant were matched with the same number whose care was noncompliant. Compliance was associated with a reduction in 30-day mortality (21.81% vs 27.48%, respectively), yielding an absolute risk reduction (ARR) of 5.67% (95% CI, 5.33-6.00; P < .001). In stringent match, 107,016 patients whose care was compliant were matched with the same number whose care was noncompliant. Compliance was associated with a reduction in 30-day mortality (22.22% vs 26.28%, respectively), yielding an ARR of 4.06% (95% CI, 3.70-4.41; P < .001). At the subject level, our HGLM found compliance associated with lower 30-day risk-adjusted mortality (adjusted conditional OR, 0.829; 95% CI, 0.812-0.846; P < .001). Multiple elements correlated with lower mortality. Median length of stay was shorter among cases whose care was compliant (5 vs 6 days; interquartile range, 3-9 vs 4-10, respectively; P < .001). INTERPRETATION: Compliance with SEP-1 was associated with lower 30-day mortality. Rendering SEP-1 compliant care may reduce the incidence of avoidable deaths.

Validation of END-of-life ScorING-system to identify the dying patient: a prospective analysis.

BACKGROUND: The "END-of-Life ScorING-System" (ENDING-S) was previously developed to identify patients at high-risk of dying in the ICU and to facilitate a practical integration between palliative and intensive care. The aim of this study is to prospectively validate ENDING-S in a cohort of long-term critical care patients. MATERIALS AND METHODS: Adult long-term ICU patients (with a length-of-stay> 4 days) were considered for this prospective multicenter observational study. ENDING-S and SOFA score were calculated daily and evaluated against the patient's ICU outcome. The predictive properties were evaluated through a receiver operating characteristic (ROC) analysis. RESULTS: Two hundred twenty patients were enrolled for this study. Among these, 21.46% died during the ICU stay. ENDING-S correctly predicted the ICU outcome in 71.4% of patients. Sensitivity, specificity, positive and negative predictive values associated with the previously identified ENDING-S cut-off of 11.5 were 68.1, 72.3, 60 and 89.3%, respectively. ROC-AUC for outcome prediction was 0.79 for ENDING-S and 0.88 for SOFA in this cohort. CONCLUSIONS: ENDING-S, while not as accurately as in the pilot study, demonstrated acceptable discrimination properties in identifying long-term ICU patients at very high-risk of dying. ENDING-S may be a useful tool aimed at facilitating a practical integration between palliative, end-of-life and intensive care. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02875912; First registration August 4, 2016.

Fluctuations of consciousness after stroke: Associations with the confusion assessment method for the intensive care unit (CAM-ICU) and potential undetected delirium.

PURPOSE: To examine associations between fluctuating consciousness and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) assessments in stroke patients compared to non-neurological patients. MATERIALS AND METHODS: We linked all recorded CAM-ICU assessments with corresponding Richmond Agitation Sedation Scale (RASS) measurements in patients with stroke or sepsis from a single-center ICU database. Fluctuating consciousness was defined by RASS variability using standard deviations (SD) over 24-h periods; regression analyses were performed to determine associations with RASS variability and CAM-ICU rating. RESULTS: We identified 16,509 paired daily summaries of CAM-ICU and RASS measurements in 546 stroke patients and 1586 sepsis patients. Stroke patients had higher odds of positive (OR 4.2, 95% CI 3.3-5.5) and "unable to assess" (UTA; OR 5.2, 95% CI 4.0-6.8) CAM-ICU ratings compared to sepsis patients, and CAM-ICU-positive and UTA assessment-days had higher RASS variability than CAM-ICU-negative assessment-days, especially in stroke patients. Based on model-implied associations of RASS variability (OR 2.0 per semi-IQR-difference in RASS-SD, 95% CI 1.7-2.2) and stroke diagnosis (OR 2.7, 95% CI 2.0-3.7) with CAM-ICU-positive assessments, over one-third of probable delirium cases among stroke patients were potentially missed by the CAM-ICU. CONCLUSIONS: Post-stroke delirium may frequently go undetected by the CAM-ICU, even in the setting of fluctuating consciousness.

The SOFA score-development, utility and challenges of accurate assessment in clinical trials.

The Sequential Organ Failure Assessment or SOFA score was developed to assess the acute morbidity of critical illness at a population level and has been widely validated as a tool for this purpose across a range of healthcare settings and environments.In recent years, the SOFA score has become extensively used in a range of other applications. A change in the SOFA score of 2 or more is now a defining characteristic of the sepsis syndrome, and the European Medicines Agency has accepted that a change in the SOFA score is an acceptable surrogate marker of efficacy in exploratory trials of novel therapeutic agents in sepsis. The requirement to detect modest serial changes in a patients' SOFA score therefore means that increased clarity on how the score should be assessed in different circumstances is required.This review explores the development of the SOFA score, its applications and the challenges associated with measurement. In addition, it proposes guidance designed to facilitate the consistent and valid assessment of the score in multicentre sepsis trials involving novel therapeutic agents or interventions.ConclusionThe SOFA score is an increasingly important tool in defining both the clinical condition of the individual patient and the response to therapies in the context of clinical trials. Standardisation between different assessors in widespread centres is key to detecting response to treatment if the SOFA score is to be used as an outcome in sepsis clinical trials.

Mortality Changes Associated with Mandated Public Reporting for Sepsis. The Results of the New York State Initiative.

RATIONALE: In 2013, the New York State Department of Health (NYSDOH) began a mandatory state-wide initiative to improve early recognition and treatment of severe sepsis and septic shock. OBJECTIVES: This study examines protocol initiation, 3-hour and 6-hour sepsis bundle completion, and risk-adjusted hospital mortality among adult patients with severe sepsis and septic shock. METHODS: Cohort analysis included all patients from all 185 hospitals in New York State reported to the NYSDOH from April 1, 2014, to June 30, 2016. A total of 113,380 cases were submitted to NYSDOH, of which 91,357 hospitalizations from 183 hospitals met study inclusion criteria. NYSDOH required all hospitals to submit and follow evidence-informed protocols (including elements of 3-h and 6-h sepsis bundles: lactate measurement, early blood cultures and antibiotic administration, fluids, and vasopressors) for early identification and treatment of severe sepsis or septic shock. MEASUREMENTS AND MAIN RESULTS: Compliance with elements of the sepsis bundles and risk-adjusted mortality were studied. Of 91,357 patients, 74,293 (81.3%) had the sepsis protocol initiated. Among these individuals, 3-hour bundle compliance increased from 53.4% to 64.7% during the study period (P < 0.001), whereas among those eligible for the 6-hour bundle (n = 35,307) compliance increased from 23.9% to 30.8% (P < 0.001). Risk-adjusted mortality decreased from 28.8% to 24.4% (P < 0.001) in patients among whom a sepsis protocol was initiated. Greater hospital compliance with 3-hour and 6-hour bundles was associated with shorter length of stay and lower risk and reliability-adjusted mortality. CONCLUSIONS: New York's statewide initiative increased compliance with sepsis-performance measures. Risk-adjusted sepsis mortality decreased during the initiative and was associated with increased hospital-level compliance.

Reporting of Sepsis Cases for Performance Measurement Versus for Reimbursement in New York State.

OBJECTIVES: Under "Rory's Regulations," New York State Article 28 acute care hospitals were mandated to implement sepsis protocols and report patient-level data. This study sought to determine how well cases reported under state mandate align with discharge records in a statewide administrative database. DESIGN: Observational cohort study. SETTING: First 27 months of mandated sepsis reporting (April 1, 2014, to June 30, 2016). PATIENTS: Hospitalizations with sepsis at New York State Article 28 acute care hospitals. INTERVENTION: Sepsis regulations with mandated reporting. MEASUREMENTS AND MAIN RESULTS: We compared cases reported to the New York State Department of Health Sepsis Clinical Database with discharge records in the Statewide Planning and Research Cooperative System database. We classified discharges as 1) "coded sepsis discharges"-a diagnosis code for severe sepsis or septic shock and 2) "possible sepsis discharges," using Dombrovskiy and Angus criteria. Of 111,816 sepsis cases reported to the New York State Department of Health Sepsis Clinical Database, 105,722 (94.5%) were matched to discharge records in Statewide Planning and Research Cooperative System. The percentage of coded sepsis discharges reported increased from 67.5% in the first quarter to 81.3% in the final quarter of the study period (mean, 77.7%). Accounting for unmatched cases, as many as 82.7% of coded sepsis discharges were potentially reported, whereas at least 17.3% were unreported. Compared with unreported discharges, reported discharges had higher rates of acute organ dysfunction (e.g., cardiovascular dysfunction 63.0% vs 51.8%; p < 0.001) and higher in-hospital mortality (30.2% vs 26.1%; p < 0.001). Hospital characteristics (e.g., number of beds, teaching status, volume of sepsis cases) were similar between hospitals with a higher versus lower percent of discharges reported, p values greater than 0.05 for all. Hospitals' percent of discharges reported was not correlated with risk-adjusted mortality of their submitted cases (Pearson correlation coefficient 0.11; p = 0.17). CONCLUSIONS: Approximately four of five discharges with a diagnosis code of severe sepsis or septic shock in the Statewide Planning and Research Cooperative System data were reported in the New York State Department of Health Sepsis Clinical Database. Incomplete reporting appears to be driven more by underrecognition than attempts to game the system, with minimal bias to risk-adjusted hospital performance measurement.

Barriers to end-of-life care in the intensive care unit: perceptions vary by level of training, discipline, and institution.

PURPOSE: Barriers to providing quality end-of-life (EOL) care in the intensive care unit (ICU) are common, but little is known about how these barriers vary by level of training or discipline. METHODS: Medical residents and ICU fellows, attendings, and nurses at two teaching hospitals were surveyed about barriers to EOL care in the ICU. The survey consisted of questions about possible barriers in four domains: patient-family factors, clinician factors, institutional factors, and education-training factors. RESULTS: There were significant differences in reported barriers to EOL care by level of training, discipline, and institution, particularly in the education-training domain. Insufficient resident training in EOL care was reported as a large or huge barrier by a smaller proportion of residents (20%) than attendings (62%), fellows (55%) or nurses (36%) (p=0.001). Nurses' perceptions of barriers to EOL care varied between institutions. Barriers that varied significantly between nurses included difficulty communicating due to language (p=0.008), and inadequate training in recognition of pain and anxiety (p=0.001). CONCLUSIONS: We found that perceived barriers to EOL care differed significantly by level of training, discipline and institution, suggesting the interventions to improve EOL care may need to be locally targeted and specific to level of training and discipline.

Rule of rescue or the good of the many? An analysis of physicians' and nurses' preferences for allocating ICU beds.

PURPOSE: To examine intensive care unit (ICU) clinicians' willingness to trade off societal benefits in favor of a small chance of rescuing an identifiable critically ill patient. METHODS: We sent mixed-methods questionnaires to national samples of US ICU clinicians, soliciting their preferences for allocating their last bed to a gravely ill patient with little chance to survive, versus a deceased or dying patient for whom aggressive management could help others through organ donation. RESULTS: Complete responses were obtained from 684 of 2,206 physicians (31.0%) and 438 of 988 nurses (44.3%); there was no evidence of non-response bias. Physicians were more likely than nurses to adhere to the "rule of rescue" by allocating the last bed to the gravely ill patient (45.9 vs. 32.6%, difference = 13.2%; 95% CI 9.1-17.3%). The magnitude of the social benefit to be obtained through organ donor management (5 or 30 life-years added for transplant recipients) had small and inconsistent effects on clinicians' willingness to prioritize the donor. In qualitative analyses, the most common reason for allocating the last bed to an identifiable patient (identified by 65% of physicians and 75% of nurses) was that clinicians perceived strong obligations to identifiable living patients. CONCLUSIONS: More than one-third of ICU clinicians forewent substantial social benefits so as to devote resources to an individual patient unlikely to benefit from them. Such allegiance to the rule of rescue suggests challenges for efforts to reform ICU triage practices.

Cost-effectiveness of the Surviving Sepsis Campaign protocol for severe sepsis: a prospective nation-wide study in Spain.

CONTEXT: Severe sepsis is associated with high mortality and increased costs. The 'Surviving Sepsis Campaign' (SSC) protocol was developed as an international initiative to reduce mortality. However, its cost-effectiveness is unknown. OBJECTIVE: To determine the cost-effectiveness of the SSC protocol for the treatment of severe sepsis in Spain after the implementation of an educational program compared with the conventional care of severe sepsis. DESIGN: Observational prospective before-and-after study. SETTING: 59 medical-surgical intensive care units located throughout Spain. PATIENTS: A total of 854 patients were enrolled in the pre-educational program cohort (usual or standard care of severe sepsis) and 1,465 patients in the post-educational program cohort (SSC protocol care of severe sepsis). INTERVENTIONS: The educational program aimed to increase adherence to the SSC protocol. The SSC protocol included pharmacological and medical interventions. MAIN OUTCOME MEASURES: Clinical (hospital mortality) and economic (health-care resource and treatment costs) outcomes were recorded. A health-care system perspective was used for costs. The primary outcome was incremental cost-effectiveness ratio (ICER). RESULTS: Patients in the SSC protocol care cohort had a lower risk of hospital mortality (44.0% vs. 39.7%, P = 0.04). However, mean costs per patient were 1,736 euros higher in the SSC protocol care cohort (95% CI 114-3,358 euros), largely as a result of increased length of stay. Mean life years gained (LYG) were higher in the SSC protocol care cohort: 0.54 years (95% CI 0.02-1.05 years). The adjusted ICER of the SSC protocol was 4,435 euros per LYG. Nearly all (96.5%) the bootstrap replications were below the threshold of 30,000 euros per LYG. CONCLUSION: The SSC protocol seems to be a cost-effective option for treating severe sepsis in Spain.

Biomarkers: diagnosis and risk assessment in sepsis.

Prompt diagnosis, intervention, and risk assessment are critical in caring for septic patient but remain difficult with currently available methods. Biomarkers may become useful adjuncts to clinicians and ultimately serve as targets for future therapeutic trials in sepsis. The most relevant markers are reviewed in this article, including interleukin-6, C-reactive protein, procalcitonin, triggering receptor expressed on myeloid cells-1, and biomarker panels.

Perceptions of cost constraints, resource limitations, and rationing in United States intensive care units: results of a national survey.

OBJECTIVE: To examine cost constraints, resource limitations, and rationing within U.S. intensive care units (ICUs) as perceived by ICU clinicians and the roles of ICU physician and nurse directors in resource allocation decisions. DESIGN: A national survey of hospitals with ICUs. SETTING: The study included 447 U.S. hospitals with ICUs. SUBJECTS: ICU nurse and physician directors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We randomly selected 447 U.S. hospitals stratified for location and ICU size and contacted them for this survey. The institutional response rate was 63%. When asked to characterize their involvement in budgetary decisions, 55% of nurse directors vs. 3% (p < .001) of physician directors answered "heavy" involvement. Additionally, 91% of nurse vs. 38% of physician directors were given feedback on expenditures (p < .001). Responses to questions about specific situations or practices that may be associated with rationing showed that a substantial minority respondents perceived these practices "sometimes" (occurring 25% to 74% of the time) but the majority perceived it "rarely" (occurring <25% of the time) or not at all. Few perceived rationing as occurring "frequently" (occurring >75% of the time) because of costs or availability. When asked if any rationing occurs in their ICUs (using a prestated definition), only 11% of physician and 6% of nurse directors responded yes. Only 6% of nurses and 5% of physicians said that cost constraints have a significant effect on care. In contrast, when asked how often patients receive "too much" care, 46% of respondents said "sometimes or frequently." CONCLUSIONS: Nurse managers have a larger role in managing ICU costs than physicians. Furthermore, both groups perceive that rationing and other cost-related practices sometimes occur in their ICU, but they more commonly perceived excessive care in ICUs. These data may be helpful for policy makers and administrators and may serve as a benchmark for future studies in critical care or other realms of health care.

Rationing and critical care medicine.

As healthcare expenditures have continued to grow in the United States and elsewhere, the demand for cost-cutting measures has increased. This has led many to wonder if we are, in fact, rationing health care. Critical care is characterized by very high expenditures on a relatively few number of patients, many of whom do not survive, and it is therefore a likely place where rationing could occur. Although much has been written about the concept of rationing, there are few data about the practice, with the exception of studies that examined triaging in the intensive care unit. Research in this area is greatly hampered by the fact that identifying rationing can be very subjective given the relatively inconsistent methods by which critical care is actually practiced and the lack of a clear definition of rationing. This article reviews the concept of healthcare rationing by exploring the many different definitions and methods by which it could occur and the ethical principles underlying these methods. In addition, we review the pertinent literature on resource allocation and rationing in intensive care units.