Trajectories of State-Level Sepsis-Related Mortality by Race and Ethnicity Group in the United States.

Background: Recent reports on the national temporal trends of sepsis-related mortality in the United States (US) suggested improvement of outcomes in several race and ethnicity groups. However, it is unknown whether national data reflect state-level trajectories. Methods: We used the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death data set to identify all decedents with sepsis in the US during 2010-2019. Negative binomial regression models were fit to estimate national and state-level trends of age-adjusted sepsis-related mortality rates within race and ethnicity groups. Results: There were 1,852,610 sepsis-related deaths in the US during 2010-2019. Nationally, sepsis-related mortality rates decreased among Blacks and Asians, were unchanged among Hispanics and Native Americans, and rose among Whites. The percent of states with similar trends were 30.0% among Blacks, 32.1% among Asians, 74.3% among Hispanics, 75.0% among Native Americans, and 66.7%% among Whites, while trending in opposite direction from 3.6% among Asians to 15.0% among Blacks. Conclusions: National trends in sepsis-related mortality in the US did not represent state-level trajectories in race ethnicity groups. Gains in sepsis outcomes among race and ethnicity groups at the national level were not shared equitably at the state level.

Epidemiology and outcomes of previously healthy critically ill patients with COVID-19: A population-based cohort.

Comorbid conditions represent a major risk for severe illness among persons with COVID-19. Previously healthy people with COVID-19 can also develop severe illness, but are expected to have better outcomes than those with comorbid conditions. Nevertheless, recent data suggest that the former may have, counterintuitively, higher risk of death among those with non-COVID sepsis. However, the epidemiology and outcomes of previously healthy people among critically ill patients with COVID-19 are unknown. We used statewide data to identify intensive care unit (ICU) admissions aged ≥18 years in Texas with COVID-19 in 2020. Multilevel logistic regression was used to estimate the association of comorbid state with short-term mortality (defined as in-hospital mortality or discharge to hospice) overall and with higher illness severity among ICU admissions. Among 52,776 ICU admissions with COVID-19, 6373 (12.1%) were previously healthy. Short-term mortality among previously healthy ICU admissions and those with comorbidities was 16.9% versus 34.6%. On adjusted analyses, the odds of short-term mortality were lower among the previously healthy compared to those with comorbidities overall (adjusted odds ratio (aOR) 0.84 (95% CI: 0.73-0.98)), but did not differ among those with ≥3 organ dysfunctions (aOR 1.11 (95% CI: 0.84-1.46)) and the mechanically ventilated (aOR 0.87 (95% CI: 0.68-1.12)), while being higher among those with do-not-resuscitate status (aOR 1.40 (95% CI: 1.04-1.89)). Over one in eight ICU admissions with COVID-19 were previously healthy. Although being previously healthy was associated with lower risk of death compared to those with comorbidities overall, it had no prognostic advantage among the more severely ill.

Previously healthy adults among septic patients: Population-level epidemiology and outcomes.

PURPOSE: Previously healthy adults with community-onset sepsis were recently reported to have, counterintuitively, higher short-term mortality than those with comorbid conditions. However, the population-level generalizability of this finding and its applicability to all hospitalized septic patients are unclear. METHODS: We used a statewide dataset to identify hospitalizations aged ≥18 years with a diagnosis of sepsis in Texas during 2018-2019. Comorbidities were defined as those included in the Charlson Comorbidity Index and other prevalent conditions associated with mortality. Hierarchical models were used to estimate the association of comorbid state with short-term mortality (defined as in-hospital mortality or discharge to hospice), overall and in community-onset and hospital-onset sepsis. RESULTS: Among 120,371 sepsis hospitalizations, 6611 (5.5%) were previously healthy and 105,455 (87.6%) had community-onset sepsis. Short-term mortality among the previously healthy and those with comorbidities was 11.7% vs 28.2% overall, 11.0% vs 25.2% in community-onset sepsis, and 22.0% vs 48.7% in hospital-onset sepsis, respectively. On adjusted analysis, being previously healthy remained associated with lower short-term mortality overall (adjusted odds ratio 0.62 [95% CI 0.57-0.69]), with findings consistent with the primary analysis in community-onset sepsis, hospital-onset sepsis. CONCLUSIONS: Previously healthy septic patients had lower short-term mortality compared to those with comorbid conditions.

The Impact of COVID-19 on Sepsis-Related Mortality in the United States.

Background: Coronavirus disease 2019 (COVID-19)-related organ dysfunction is increasingly considered as sepsis of viral origin. In recent clinical and autopsy studies, sepsis has been present in the majority of decedents with COVID-19. Given the high mortality toll of COVID-19, sepsis epidemiology would be expected to be substantially transformed. However, the impact of COVID-19 on sepsis-related mortality at the national level has not been quantified. We aimed to estimate the contribution of COVID-19 to sepsis-related mortality in the USA during the first year of the pandemic. Methods: We used the Centers for Disease Control Wide-Ranging Online Data for Epidemiological Research (CDC WONDER) Multiple Cause of Death dataset to identify decedents with sepsis during 2015 - 2019, and those with a diagnosis of sepsis, COVID-19, or both in 2020. Negative binomial regression was used on the 2015 - 2019 data to forecast the number of sepsis-related deaths in 2020. We then compared the observed vs. predicted number of sepsis-related deaths in 2020. In addition, we examined the frequency of a diagnosis of COVID-19 among decedents with sepsis and the proportion of a diagnosis of sepsis among decedents with COVID-19. The latter analysis was repeated within each of the Department of Health and Human Services (HHS) regions. Results: In 2020, there were 242,630 sepsis-related deaths, 384,536 COVID-19-related deaths, and 35,807 deaths with both in the USA. The predicted number of sepsis-related deaths for 2020 was 206,549 (95% confidence interval (CI): 201,550 - 211,671). COVID-19 was reported in 14.7% of decedents with sepsis, while a diagnosis of sepsis was reported in 9.3% of all COVID-19-related deaths, ranging from 6.7% to 12.8% across HHS regions. Conclusions: A diagnosis of COVID-19 was reported in less than one in six of decedents with sepsis in 2020, with corresponding less than one in 10 diagnoses of sepsis among decedents with COVID-19. These findings suggest that death certificate-based data may have substantially underestimated the toll of sepsis-related deaths in the USA during the first year of the pandemic.

The association of systemic lupus erythematosus with short-term mortality in sepsis: a population-level analysis.

Systemic lupus erythematosus (SLE) is associated with higher risks of sepsis and sepsis-related mortality compared to the general population. However, the prognostic impact of SLE in sepsis is uncertain. We used statewide data to identify hospitalizations aged ≥18 years in Texas with sepsis, with and without SLE during 2014-2017. Multilevel logistic regression with propensity adjustment (primary model), propensity score matching, and multivariable logistic regression without propensity adjustment were used to estimate the association of SLE with short-term mortality (defined as in-hospital mortality or discharge to hospice) among sepsis hospitalizations. Among 283,025 sepsis hospitalizations, 2933 (1.0%) had SLE. Compared to sepsis hospitalizations without SLE, those with SLE were younger (aged ≥65 years, 25.0% vs 57.0%) and had higher burden of comorbidities (mean Deyo comorbidity index 3.0 vs 2.6). Short-term mortality of sepsis hospitalizations with and without SLE was 22.9% vs 31.3%. SLE remained associated with lower short-term mortality on the secondary models, but not on the primary one (adjusted odds ratio: 0.905; 95% confidence interval: 0.817-1.001). When in-hospital mortality was used as secondary outcome, SLE was associated with mortality only on propensity score matching. The increased sepsis-related mortality in SLE is driven by higher risk of sepsis, but not by higher case fatality among septic patients. SLE may be associated with lower risk of mortality among septic patients, but further studies are needed due to heterogeneity of the prognostic associations across models.

Disparities in Palliative Care Among Critically Ill Patients With and Without COVID-19 at the End of Life: A Population-Based Analysis.

Background: The surge in critical illness and associated mortality brought by the coronavirus virus disease 2019 (COVID-19) pandemic, coupled with staff shortages and restrictions of family visitation, may have adversely affected delivery of palliative measures, including at the end of life of affected patients. However, the population-level patterns of palliative care (PC) utilization among septic critically ill patients with and without COVID-19 during end-of-life hospitalizations are unknown. Methods: A statewide dataset was used to identify patients aged ≥ 18 years with intensive care unit (ICU) admission and a diagnosis of sepsis in Texas, who died during hospital stay during April 1 to December 31, 2020. COVID-19 was defined by the International Classification of Diseases, 10th Revision (ICD-10) code U07.1, and PC was identified by ICD-10 code Z51.5. Multivariable logistic models were fitted to estimate the association of COVID-19 with use of PC among ICU admissions. A similar approach was used for sensitivity analyses of strata with previously reported lower and higher than reference use of PC. Results: There were 20,244 patients with sepsis admitted to ICU during terminal hospitalization, and 9,206 (45.5%) had COVID-19. The frequency of PC among patients with and without COVID-19 was 32.0% vs. 37.1%, respectively. On adjusted analysis, the odds of PC use remained lower among patients with COVID-19 (adjusted odds ratio (aOR): 0.84, 95% confidence interval (CI): 0.78 - 0.90), with similar findings on sensitivity analyses. Conclusions: PC was markedly less common among critically ill septic patients with COVID-19 during terminal hospitalization, compared to those without COVID-19. Further studies are needed to determine the factors underlying these findings in order to reduce disparities in use of PC.

The prognostic impact of rheumatoid arthritis in sepsis: a population-based analysis.

BACKGROUND: Rheumatoid arthritis (RA) is associated with increased risk of sepsis and higher infection-related mortality compared to the general population. However, the evidence on the prognostic impact of RA in sepsis has been inconclusive. We aimed to estimate the population-level association of RA with short-term mortality in sepsis. METHODS: We used statewide data to identify hospitalizations aged ≥18 years in Texas with sepsis, with and without RA during 2014-2017. Hierarchical logistic models with propensity adjustment (primary model), propensity score matching, and multivariable logistic regression without propensity adjustment were used to estimate the association of RA with short-term mortality among sepsis hospitalizations. RESULTS: Among 283,025 sepsis hospitalizations, 7,689 (2.7%) had RA. Compared to sepsis hospitalizations without RA, those with RA were older (aged ≥65 years, 63.9% vs. 56.4%) and had higher burden of comorbidities (mean Deyo comorbidity index, 3.2 vs. 2.7). Short-term mortality of sepsis hospitalizations with and without RA was 26.8% vs. 31.4%. Following adjustment for confounders, short-term mortality was lower among RA patients (adjusted odds ratio [aOR], 0.910; 95% confidence interval [CI], 0.856-0.967), with similar findings on alternative models. On sensitivity analyses, short-term mortality was lower in RA patients among sepsis hospitalizations aged ≥65 years and those with septic shock, but not among those admitted to intensive care unit (ICU; aOR, 0.990; 95% CI, 0.909-1.079). CONCLUSIONS: RA was associated, unexpectedly, with lower short-term mortality in septic patients. However, this "protective" association was driven by those patients without ICU admission. Further studies are warranted to confirm these findings and to examine the underlying mechanisms.

Association of multiple sclerosis with mortality in sepsis: a population-level analysis.

BACKGROUND: Multiple sclerosis (MS) is associated with increased risk of sepsis and higher sepsis-related mortality, compared to the general population. However, the evidence on the prognostic impact of MS in sepsis has been scarce. We aimed to evaluate the population-level association of MS with short-term mortality in sepsis. METHODS: We performed a retrospective population-based cohort study using a statewide data set to identify hospitalizations aged ≥ 18 years in Texas with sepsis, with and without MS during 2010-2017. Multilevel logistic models were fit to estimate the association of MS with short-term mortality among all sepsis hospitalizations, and for sensitivity analyses among hospitalizations with septic shock and those admitted to ICU. RESULTS: Among 283,025 sepsis hospitalizations, 1687 (0.6%) had MS. Compared to sepsis hospitalizations without MS, those with MS were younger (aged ≥ 65 years 35.0% vs 56.8%), less commonly racial/ethnic minority (36.2% vs 48.1%), and had lower mean Deyo comorbidity index (1.6 vs 2.7). The rates of septic shock and ICU admission were similar for sepsis hospitalizations with and without MS (58.7% vs 59.6% and 46.7% vs 46.0%, respectively). The unadjusted short-term mortality among sepsis hospitalizations with and without MS for the whole cohort, among those with septic shock, and among ICU admissions were 20.2% vs 31.3%, 25.6% vs 40.0%, and 24.0% vs 34.8%, respectively. On adjusted analyses, MS was associated with 17% lower odds of short-term mortality (adjusted odds ratio [aOR] 0.828 [95% CI 0.723-0.947]). Similar findings were observed on sensitivity analyses of patients with septic shock (aOR 0.764 [95% CI 0.651-0.896]), but MS was not associated with mortality among sepsis hospitalizations admitted to ICU (aOR 0.914 [95% CI 0.759-1.101]). CONCLUSIONS: MS was associated with lower short-term mortality among septic patients, with findings consistent among the subset with septic shock. Among septic patients admitted to ICU, MS was not associated with mortality.

Impact of history of mental disorders on short-term mortality among hospitalized patients with sepsis: A population-based cohort study.

BACKGROUND: Mental disorders are associated with markedly reduced life expectancy, in part due to an increased risk of death due to infection, likely reflecting sepsis-associated mortality. Patients with mental disorders are at an increased risk of sepsis, but data on the prognostic impact of mental disorders in sepsis are sparse, showing conflicting findings. METHODS: We used statewide data to identify hospitalizations aged ≥18 years with sepsis in Texas during 2014-2017. Mental disorders, including mood, anxiety, psychosis, and personality disorders were identified using Clinical Classification Software codes. Multilevel, multivariable logistic regression with propensity adjustment (primary model), with propensity score matching, and multivariable logistic regression as alternative models, were used to estimate the association between mental disorders and short-term mortality (defined as in-hospital mortality or discharge to hospice). Additional models were fitted for sensitivity analyses and to estimate the prognostic associations of individual categories of mental disorders. RESULTS: Among 283,025 hospitalizations with sepsis, 56,904 (20.1%) had mental disorders. Hospitalizations with vs without mental disorders were younger (age 18-44 years 12.2% vs 10.6%), more commonly white (61.0% vs 49.8%), with lower burden of comorbidities (mean [SD] Deyo comorbidity index 2.53 [2.27] vs 2.73 [2.47]), and with lower need for organ support (mechanical ventilation 32.8% vs 36.0%); p<0.0001 for all comparisons. Crude short-term mortality among sepsis hospitalizations with and without mental disorders was 25.0% vs 32.8%, respectively. On adjusted analyses, mental disorders remained associated with lower odds of short-term mortality (adjusted odds ratio 0.792 [95% CI 0.772-0.812]). This finding was consistent on the alternative modeling approaches, sensitivity analyses, and examination of individual categories of mental disorders. CONCLUSIONS: Mental disorders were associated, unexpectedly, with markedly lower risk of short-term mortality in sepsis. Further studies to examine the mechanisms underlying these findings may inform future efforts to improve sepsis outcomes.

The burden of sepsis in critically ill patients with multiple sclerosis: A population-based cohort study.

PURPOSE: Multiple sclerosis (MS) is associated with increased risk of critical illness, sepsis, and sepsis-related death, compared to the general population. The epidemiology of sepsis and its impact on the outcomes of critically ill patients with MS are unknown. METHODS: A statewide dataset was used to identify retrospectively ICU admissions in Texas aged ≥18 years with a diagnosis of MS during 2010-2017. The prevalence of sepsis and its impact on inpatient resource utilization and short-term mortality (a combination of in-hospital death or discharge to hospice) were examined. RESULTS: Among 19,837 ICU admissions with MS, 6244 (31.5%) had sepsis. Compared to ICU admissions without sepsis, those with sepsis were older (aged ≥65 years 34.1% vs 24.1%), less commonly racial/ethnic minority (32.6% vs 35.2%), and had higher mean [SD] Deyo comorbidity index (1.7 [1.8] vs 1.2 [1.7]). On adjusted analyses, sepsis was associated with 42.7% longer hospital length of stay and 26.2% higher total hospital charges. Risk-adjusted short-term mortality among ICU admissions with and without sepsis was 13.4% vs 3.3%, respectively. CONCLUSIONS: Sepsis was present in nearly 1 in 3 ICU admissions with MS, had substantial adverse impact on hospital resource utilization, and was associated with over 4-times higher short-term mortality.

Critical illness in patients with metastatic cancer: a population-based cohort study of epidemiology and outcomes.

The appropriateness of intensive care unit (ICU) admission of patients with metastatic cancer remains debated. We aimed to examine the short-term outcomes and their temporal pattern in critically ill patients with metastatic disease. We used state-wide data to identify hospitalizations aged ≥18 years with metastatic cancer admitted to ICU in Texas during 2010-2014. Multivariable logistic regression modeling was used to examine the factors associated with short-term mortality and its temporal trends among all ICU admissions and those undergoing mechanical ventilation. Among 136,644 ICU admissions with metastatic cancer, 50.8% were aged ≥65 years, with one or more organ failures present in 53.3% and mechanical ventilation was used in 11.1%. The crude short-term mortality among all ICU admissions and those mechanically ventilated was 28.1% and 62.0%, respectively. Discharge to home occurred in 57.1% of all ICU admissions. On adjusted analyses, short-term mortality increased with rising number of organ failures (adjusted OR (aOR) 1.399, 95% CI 1.374 to 1.425), while being lower with chemotherapy (aOR 0.467, 95% CI 0.432 to 0.506) and radiation therapy (aOR 0.832, 95% CI 0.749 to 0.924), and decreased over time (aOR 0.934 per year, 95% CI 0.924 to 0.945). Predictors of short-term mortality were largely similar among those undergoing mechanical ventilation. Most ICU admissions with metastatic cancer survived hospitalization, although short-term mortality was very high among those undergoing mechanical ventilation. Short-term mortality decreased over time and was lower among those receiving chemotherapy and radiation therapy. These findings support consideration of critical care in patients with metastatic cancer, but underscore the need to address patient-centered goals of care ahead of ICU admission.