Use of Electronic Clinical Data to Track Incidence and Mortality for SARS-CoV-2-Associated Sepsis.

Importance: Efforts to quantify the burden of SARS-CoV-2-associated sepsis have been limited by inconsistent definitions and underrecognition of viral sepsis. Objective: To describe the incidence and outcomes of SARS-CoV-2-associated sepsis vs presumed bacterial sepsis using objective electronic clinical criteria. Design, Setting, and Participants: This retrospective cohort study included adults hospitalized at 5 Massachusetts hospitals between March 2020 and November 2022. Exposures: SARS-CoV-2-associated sepsis was defined as a positive SARS-CoV-2 polymerase chain reaction test and concurrent organ dysfunction (ie, oxygen support above simple nasal cannula, vasopressors, elevated lactate level, rise in creatine or bilirubin level, and/or decline in platelets). Presumed bacterial sepsis was defined by modified US Centers for Disease Control and Prevention adult sepsis event criteria (ie, blood culture order, sustained treatment with antibiotics, and organ dysfunction using identical thresholds as for SARS-CoV-2-associated sepsis). Main Outcomes and Measures: Trends in the quarterly incidence (ie, proportion of hospitalizations) and in-hospital mortality for SARS-CoV-2-associated and presumed bacterial sepsis were assessed using negative binomial and logistic regression models. Results: This study included 431 017 hospital encounters from 261 595 individuals (mean [SD] age 57.9 [19.8] years, 241 131 (55.9%) females, 286 397 [66.5%] from academic hospital site). Of these encounters, 23 276 (5.4%) were from SARS-CoV-2, 6558 (1.5%) had SARS-CoV-2-associated sepsis, and 30 604 patients (7.1%) had presumed bacterial sepsis without SARS-CoV-2 infection. Crude in-hospital mortality for SARS-CoV-2-associated sepsis declined from 490 of 1469 (33.4%) in the first quarter to 67 of 450 (14.9%) in the last (adjusted odds ratio [aOR], 0.88 [95% CI, 0.85-0.90] per quarter). Crude mortality for presumed bacterial sepsis was 4451 of 30 604 patients (14.5%) and stable across quarters (aOR, 1.00 [95% CI, 0.99-1.01]). Medical record reviews of 200 SARS-CoV-2-positive hospitalizations confirmed electronic health record (EHR)-based SARS-CoV-2-associated sepsis criteria performed well relative to sepsis-3 criteria (90.6% [95% CI, 80.7%-96.5%] sensitivity; 91.2% [95% CI, 85.1%-95.4%] specificity). Conclusions and Relevance: In this retrospective cohort study of hospitalized adults, SARS-CoV-2 accounted for approximately 1 in 6 cases of sepsis during the first 33 months of the COVID-19 pandemic. In-hospital mortality rates for SARS-CoV-2-associated sepsis were high but declined over time and ultimately were similar to presumed bacterial sepsis. These findings highlight the high burden of SARS-CoV-2-associated sepsis and demonstrate the utility of EHR-based algorithms to conduct surveillance for viral and bacterial sepsis.

Impact of changing case definitions for coronavirus disease 2019 (COVID-19) hospitalization on pandemic metrics.

OBJECTIVE: To examine the impact of commonly used case definitions for coronavirus disease 2019 (COVID-19) hospitalizations on case counts and outcomes. DESIGN, PATIENTS, AND SETTING: Retrospective analysis of all adults hospitalized between March 1, 2020, and March 1, 2022, at 5 Massachusetts acute-care hospitals. INTERVENTIONS: We applied 6 commonly used definitions of COVID-19 hospitalization: positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) assay within 14 days of admission, PCR plus dexamethasone administration, PCR plus remdesivir, PCR plus hypoxemia, institutional COVID-19 flag, or COVID-19 International Classification of Disease, Tenth Revision (ICD-10) codes. Outcomes included case counts and in-hospital mortality. Overall, 100 PCR-positive cases were reviewed to determine each definition's accuracy for distinguishing primary or contributing versus incidental COVID-19 hospitalizations. RESULTS: Of 306,387 hospital encounters, 15,436 (5.0%) met the PCR-based definition. COVID-19 hospitalization counts varied substantially between definitions: 4,628 (1.5% of all encounters) for PCR plus dexamethasone, 5,757 (1.9%) for PCR plus remdesivir, 11,801 (3.9%) for PCR plus hypoxemia, 15,673 (5.1%) for institutional flags, and 15,868 (5.2%) for ICD-10 codes. Definitions requiring dexamethasone, hypoxemia, or remdesivir selected sicker patients compared to PCR alone (mortality rates 12.2%, 10.7%, and 8.8% vs 8.3%, respectively). Definitions requiring PCR plus remdesivir or dexamethasone did not detect a reduction in in-hospital mortality associated with the SARS-CoV-2 Omicron variant. ICD-10 codes had the highest sensitivity (98.4%) but low specificity (39.5%) for distinguishing primary or contributing versus incidental COVID-19 hospitalizations. PCR plus dexamethasone had the highest specificity (92.1%) but low sensitivity (35.5%). CONCLUSIONS: Commonly used definitions for COVID-19 hospitalizations generate variable case counts and outcomes and differentiate poorly between primary or contributing versus incidental COVID-19 hospitalizations. Surveillance definitions that better capture and delineate COVID-19-associated hospitalizations are needed.

Update on Sepsis Epidemiology in the Era of COVID-19.

Timely and accurate data on the epidemiology of sepsis is essential to inform public policy, clinical practice, and research priorities. Recent studies have illuminated several ongoing questions about sepsis epidemiology, including the incidence and outcomes of sepsis in non-Western countries and in specialized populations such as surgical patients, patients with cancer, and the elderly. There have also been new insights into the limitations of current surveillance methods using administrative data and increasing experience tracking sepsis incidence and outcomes using "big data" approaches that take advantage of detailed electronic health record data. The COVID-19 pandemic, however, has fundamentally changed the landscape of sepsis epidemiology. It has increased sepsis rates, helped highlight ongoing controversies about how to define sepsis, and intensified debate about the possible unintended consequences of overly rigid sepsis care bundles. Despite these controversies, there is a growing consensus that severe COVID-19 causing organ dysfunction is appropriate to label as sepsis, even though it is treated very differently from bacterial sepsis, and that surveillance strategies need to be modified to reliably identify these cases to fully capture and delineate the current burden of sepsis. This review will summarize recent insights into the epidemiology of sepsis and highlight several urgent questions and priorities catalyzed by COVID-19.

Prevalence, Clinical Characteristics, and Outcomes of Sepsis Caused by Severe Acute Respiratory Syndrome Coronavirus 2 Versus Other Pathogens in Hospitalized Patients With COVID-19.

The prevalence and causes of sepsis in patients hospitalized with COVID-19 are poorly characterized. OBJECTIVES: To investigate the prevalence, clinical characteristics, and outcomes of sepsis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) versus other pathogens in patients hospitalized with COVID-19. DESIGN SETTING AND PARTICIPANTS: Cross-sectional, retrospective chart review of 200 randomly selected patients hospitalized with COVID-19 at four Massachusetts hospitals between March 2020 and March 2021. MAIN OUTCOMES AND MEASURES: The presence or absence of sepsis was determined per Sepsis-3 criteria (infection leading to an increase in Sequential Organ Failure Assessment score by ≥ 2 points above baseline). Sepsis episodes were assessed as caused by SARS-CoV-2, other pathogens, or both. Rates of organ dysfunction and in-hospital death were also assessed. RESULTS: Sepsis was present in 65 of 200 COVID-19 hospitalizations (32.5%), of which 46 of 65 sepsis episodes (70.8%) were due to SARS-CoV-2 alone, 17 of 65 (26.2%) were due to both SARS-CoV-2 and non-SARS-CoV-2 infections, and two of 65 (3.1%) were due to bacterial infection alone. SARS-CoV-2-related organ dysfunction in patients with sepsis occurred a median of 1 day after admission (interquartile range, 0-2 d) and most often presented as respiratory (93.7%), neurologic (46.0%), and/or renal (39.7%) dysfunctions. In-hospital death occurred in 28 of 200 COVID-19 hospitalizations (14.0%), including two of 135 patients without sepsis (1.5%), 16 of 46 patients with sepsis (34.8%) due to SARS-CoV-2 alone, and 10 of 17 patients with sepsis (58.8%) due to both SARS-CoV-2 and bacterial pathogens. CONCLUSIONS: Sepsis occurred in one in three patients hospitalized with COVID-19 and was primarily caused by SARS-CoV-2 itself, although bacterial infection also contributed in a quarter of sepsis cases. Mortality in COVID-19 patients with sepsis was high, especially in patients with mixed SARS-CoV-2 and bacterial sepsis. These findings affirm SARS-CoV-2 as an important cause of sepsis and highlight the need to improve surveillance, recognition, prevention, and treatment of both viral and bacterial sepsis in hospitalized patients with COVID-19.

Clinician Ethical Perspectives on Extracorporeal Membrane Oxygenation in Practice.

PURPOSE: Extracorporeal membrane oxygenation (ECMO) is an expensive and scarce life sustaining treatment provided to certain critically ill patients. Little is known about the informed consent process for ECMO or clinician viewpoints on ethical complexities related to ECMO in practice. METHODS: We sent a cross-sectional survey to all departments providing ECMO within 7 United States hospitals in January 2021. One clinician from each department completed the 42-item survey representing their department. RESULTS: Fourteen departments within 7 hospitals responded (response rate 78%, N = 14/18). The mean time spent consenting patients or surrogate decision-makers for ECMO varied, from 7.5 minutes (95% CI 5-10) for unstable patients to 20 minutes (95% CI 15-30) for stable patients (p = 0.0001). Few clinician respondents (29%) report patients or surrogate decision-makers always possess informed consent for ECMO. Most departments (92%) have absolute exclusion criteria for ECMO such as older age (43%, cutoffs ranging from 60-75 years), active malignancy (36%), and elevated body mass index (29%). A significant minority of departments (29%) do not always offer the option to withdraw ECMO to patients or surrogate decision-makers. For patients who cannot be liberated from ECMO and are ineligible for heart or lung transplant, 36% of departments would recommend the patient be removed from ECMO and 64% would continue ECMO support. CONCLUSION: Adequate informed consent for ECMO is a major ethical challenge, and the content of these discussions varies. Use of categorical exclusion criteria and withdrawal of ECMO if a patient cannot be liberated from it differ among departments and institutions.

Likelihood of Bacterial Infection in Patients Treated With Broad-Spectrum IV Antibiotics in the Emergency Department.

OBJECTIVES: Best practice guidelines and quality metrics recommend immediate antibiotic treatment for all patients with suspected sepsis. However, little is known about how many patients given IV antibiotics in the emergency department are ultimately confirmed to have bacterial infection. DESIGN, SETTING, AND PATIENTS: We performed a retrospective study of adult patients who presented to four Massachusetts emergency departments between June 2015 and June 2018 with suspected serious bacterial infection, defined as blood cultures drawn and broad-spectrum IV antibiotics administered. Structured medical record reviews were performed on a random sample of 300 cases to determine the post hoc likelihood of bacterial infection, categorized as definite, likely, unlikely, or definitely none. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 300 patients with suspected serious bacterial infections, mean age was 68 years (sd 18), median hospital length of stay was 5 days (interquartile range, 3-8 d), 45 (15%) were admitted directly to ICU, and 14 (5%) died in hospital. Overall, 196 (65%) had definite (n = 115; 38%) or likely (n = 81; 27%) bacterial infection, whereas 104 (35%) were unlikely (n = 55; 18%) or definitely not infected (n = 49; 16%). Antibiotic treatment durations differed by likelihood of infection (median 15 days for definite, 9 for likely, 7 for unlikely, and 3 for definitely not infected). The most frequent post hoc diagnoses in patients with unlikely or definitely no bacterial infection included viral infections (28%), volume overload or cardiac disease (9%), drug effects (9%), and hypovolemia (7%). The likelihoods of infection were similar in the subset of 96 cases in whom emergency department providers explicitly documented possible or suspected sepsis and in the 45 patients admitted from the emergency department to the ICU. CONCLUSIONS: One third of patients empirically treated with broad-spectrum antibiotics in the emergency department are ultimately diagnosed with noninfectious or viral conditions. These findings underscore the difficulty diagnosing serious infections in the emergency department and have important implications for guidelines and quality measures that compel immediate empiric antibiotics for all patients with possible sepsis.

Surveillance Strategies for Tracking Sepsis Incidence and Outcomes.

Sepsis is a leading cause of death and the target of intense efforts to improve recognition, management and outcomes. Accurate sepsis surveillance is essential to properly interpreting the impact of quality improvement initiatives, making meaningful comparisons across hospitals and geographic regions, and guiding future research and resource investments. However, it is challenging to reliably track sepsis incidence and outcomes because sepsis is a heterogeneous clinical syndrome without a pathologic reference standard, allowing for subjectivity and broad discretion in assigning diagnoses. Most epidemiologic studies of sepsis to date have used hospital discharge codes and have suggested dramatic increases in sepsis incidence and decreases in mortality rates over time. However, diagnosis and coding practices vary widely between hospitals and are changing over time, complicating the interpretation of absolute rates and trends. Other surveillance approaches include death records, prospective clinical registries, retrospective medical record reviews, and analyses of the usual care arms of randomized controlled trials. Each of these strategies, however, has substantial limitations. Recently, the US Centers for Disease Control and Prevention released an "Adult Sepsis Event" definition that uses objective clinical indicators of infection and organ dysfunction that can be extracted from most hospitals' electronic health record systems. Emerging data suggest that electronic health record-based clinical surveillance, such as surveillance of Adult Sepsis Event, is accurate, can be applied uniformly across diverse hospitals, and generates more credible estimates of sepsis trends than administrative data. In this review, we discuss the advantages and limitations of different sepsis surveillance strategies and consider future directions.

A Tight Squeeze: Focal Tamponade and Obstructive Shock From Esophageal Stenting.

Cardiac tamponade is a rare cause of shock in the medical intensive care unit. This paper describes the case of a focal cardiac tamponade caused by compression of the left atrium due to an esophageal stent. Echocardiography yielded a diagnosis when other diagnostic methods did not. (Level of Difficulty: Advanced.).

Predictors of In-Hospital Mortality After Rapid Response Team Calls in a 274 Hospital Nationwide Sample.

OBJECTIVES: Despite wide adoption of rapid response teams across the United States, predictors of in-hospital mortality for patients receiving rapid response team calls are poorly characterized. Identification of patients at high risk of death during hospitalization could improve triage to intensive care units and prompt timely reevaluations of goals of care. We sought to identify predictors of in-hospital mortality in patients who are subjects of rapid response team calls and to develop and validate a predictive model for death after rapid response team call. DESIGN: Analysis of data from the national Get with the Guidelines-Medical Emergency Team event registry. SETTING: Two-hundred seventy four hospitals participating in Get with the Guidelines-Medical Emergency Team from June 2005 to February 2015. PATIENTS: 282,710 hospitalized adults on surgical or medical wards who were subjects of a rapid response team call. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was death during hospitalization; candidate predictors included patient demographic- and event-level characteristics. Patients who died after rapid response team were older (median age 72 vs 66 yr), were more likely to be admitted for noncardiac medical illness (70% vs 58%), and had greater median length of stay prior to rapid response team (81 vs 47 hr) (p < 0.001 for all comparisons). The prediction model had an area under the receiver operating characteristic curve of 0.78 (95% CI, 0.78-0.79), with systolic blood pressure, time since admission, and respiratory rate being the most important variables. CONCLUSIONS: Patients who die following rapid response team calls differ significantly from surviving peers. Recognition of these factors could improve postrapid response team triage decisions and prompt timely goals of care discussions.

Nipple Aspirate Fluid Hormone Concentrations and Breast Cancer Risk.

Prior reports identify higher serum concentrations of estrogens and androgens as risk factors for breast cancer, but steroids in nipple aspirate fluid (NAF) may be more related to risk. Incident breast cancer cases and mammography controls were recruited. Sex steroids were measured in NAF from the unaffected breasts of cases and one breast of controls. Menopausal status and menstrual cycle phase were determined. NAF steroids were purified by HPLC and quantified by immunoassays. Conditional logistic regression models were used to examine associations between NAF hormones and case-control status. NAF samples from 160 cases and 157 controls were evaluable for hormones. Except for progesterone and dehydroepiandrosterone (DHEA), the NAF and serum concentrations were not significantly correlated. NAF estradiol and estrone were not different between cases and controls. Higher NAF (but not serum) DHEA concentrations were associated with cases, particularly among estrogen receptor (ER)-positive cases (NAF odds ratio (OR) = 1.18, 95 % confidence interval (CI) 1.02, 1.36). NAF DHEA was highly correlated with NAF estradiol and estrone but not with androstenedione or testosterone. Higher progesterone concentrations in both NAF and serum were associated with a lower risk of ER-negative cancer (NAF OR = 0.69, 95 % CI 0.51, 0.92). However, this finding may be explained by case-control imbalance in the number of luteal phase subjects (2 cases and 19 controls). The significantly higher concentration of DHEA in NAF of cases and its correlation with NAF estradiol indicates a potentially important role of this steroid in breast cancer risk; however, the negative association of progesterone with risk is tentative.

Practice variability in brain death determination: a call to action.

OBJECTIVE: To characterize the present state of brain death (BD) determination in actual practice relative to contemporary American Academy of Neurology (AAN) guidelines. METHODS: We reviewed the charts of all adult (16 years and older) BD organ donors during 2011 from 68 heterogeneous hospitals in the Midwest United States. Data were collected across 5 categories: guideline performance, preclinical testing, clinical examination, apnea testing, and use of ancillary tests. Practice within categories and overall adherence to AAN guidelines were assessed. RESULTS: Two hundred twenty-six BD organ donors were included. Practice exceeded recommendations in guideline performance but varied widely and deviated from AAN guidelines in all other categories. One hundred two (45.1%) had complete documentation of brainstem areflexia and absent motor response. One hundred sixty-six (73.5%) had completed apnea testing. Of the 60 without completed apnea testing, 56 (93.3%) had ancillary tests consistent with BD. Overall, 101 (44.7%) strictly and 84 (37.2%) loosely adhered to contemporary AAN guidelines. CONCLUSIONS: There is wide variability in the documentation of BD determination, likely reflecting similar variability in practice. This is a call for improved documentation, better uniformity of policies, and comprehensive and strategically targeted educational initiatives to ensure consistently contemporary approaches to BD determination in every patient.

Effect of MRI on the management of ductal carcinoma in situ of the breast.

INTRODUCTION: The accuracy of breast magnetic resonance imaging (MRI) for detection of ductal carcinoma in situ (DCIS) has prompted recommendations for its routine preoperative use, but its clinical benefit is debated. We reviewed our experience with MRI in DCIS patients to assess the utility of MRI for surgical planning. METHODS: DCIS patients (2008-2010) were identified through a prospectively maintained database and grouped into MRI and no-MRI groups. The rates of additional biopsies, altered surgical management, and reoperation were compared. Additionally, DCIS size ascertained by mammography, MRI, and final pathology was compared. RESULTS: Of 352 DCIS patients, 217 received MRI and 135 did not. The type of initial operation and number of reoperations were similar between the two groups, but successful breast conservation was more frequent in the no-MRI group (p = 0.06). The additional biopsy rate was 38 % in the MRI group versus 7 % in the no-MRI group; ≥2 additional biopsies were performed in 18 % of the MRI group and 2 % of the no-MRI group (p < 0.0001). These yielded a cancer diagnosis in 26 % of MRI and 33 % of no-MRI patients (p = 0.73). MRI was not superior to mammogram in detecting size of DCIS lesions preoperatively; 52 % of mammograms were accurate (within 1 cm) compared with 41 % of MRIs. CONCLUSIONS: DCIS patients who undergo preoperative breast MRI are far more likely to undergo additional biopsies. Unless these can be demonstrated to lead to improved long-term outcomes, the utility of routine preoperative MRI in DCIS patients remains questionable.