Evaluation of Time-Limited Trials Among Critically Ill Patients With Advanced Medical Illnesses and Reduction of Nonbeneficial ICU Treatments.

Importance: For critically ill patients with advanced medical illnesses and poor prognoses, overuse of invasive intensive care unit (ICU) treatments may prolong suffering without benefit. Objective: To examine whether use of time-limited trials (TLTs) as the default care-planning approach for critically ill patients with advanced medical illnesses was associated with decreased duration and intensity of nonbeneficial ICU care. Design, Setting, and Participants: This prospective quality improvement study was conducted from June 1, 2017, to December 31, 2019, at the medical ICUs of 3 academic public hospitals in California. Patients at risk for nonbeneficial ICU treatments due to advanced medical illnesses were identified using categories from the Society of Critical Care Medicine guidelines for admission and triage. Interventions: Clinicians were trained to use TLTs as the default communication and care-planning approach in meetings with family and surrogate decision makers. Main Outcomes and Measures: Quality of family meetings (process measure) and ICU length of stay (clinical outcome measure). Results: A total of 209 patients were included (mean [SD] age, 63.6 [16.3] years; 127 men [60.8%]; 101 Hispanic patients [48.3%]), with 113 patients (54.1%) in the preintervention period and 96 patients (45.9%) in the postintervention period. Formal family meetings increased from 68 of 113 (60.2%) to 92 of 96 (95.8%) patients between the preintervention and postintervention periods (P < .01). Key components of family meetings, such as discussions of risks and benefits of ICU treatments (preintervention, 15 [34.9%] vs postintervention, 56 [94.9%]; P < .01), eliciting values and preferences of patients (20 [46.5%] vs 58 [98.3%]; P < .01), and identifying clinical markers of improvement (9 [20.9%] vs 52 [88.1%]; P < .01), were discussed more frequently after intervention. Median ICU length of stay was significantly reduced between preintervention and postintervention periods (8.7 [interquartile range (IQR), 5.7-18.3] days vs 7.4 [IQR, 5.2-11.5] days; P = .02). Hospital mortality was similar between the preintervention and postintervention periods (66 of 113 [58.4%] vs 56 of 96 [58.3%], respectively; P = .99). Invasive ICU procedures were used less frequently in the postintervention period (eg, mechanical ventilation preintervention, 97 [85.8%] vs postintervention, 70 [72.9%]; P = .02). Conclusions and Relevance: In this study, a quality improvement intervention that trained physicians to communicate and plan ICU care with family members of critically ill patients in the ICU using TLTs was associated with improved quality of family meetings and a reduced intensity and duration of ICU treatments. This study highlights a patient-centered approach for treating critically ill patients that may reduce nonbeneficial ICU care. Trial Registration: ClinicalTrials.gov Identifier: NCT04181294.

Correction to: Racial Differences in the Utilization of Guideline-Recommended and Life-Sustaining Procedures During Hospitalizations for Out-of-Hospital Cardiac Arrest.

There was an error in Fig. 1 as published in this article, and the Hemodialysis and Palliative Care titles in the figure are reversed.

Nonbeneficial Intensive Care: Misalignments Between Provider Assessments of Benefit and Use of Invasive Treatments.

BACKGROUND: The purpose of this study was to examine how frequently invasive intensive care unit (ICU) treatments are delivered to critically ill patients despite clinicians' impressions that ICU care may be nonbeneficial. METHODS: Patients admitted to the medical ICU of an academic public hospital were prospectively categorized according to guidelines from the Society of Critical Care Medicine which classifies patients based on severity of illness and likelihood of recovery (categories 1-4). Clinical data and use of ICU treatments in patients with high (category 1) and low (category 3) likelihoods of benefit were collected by chart review. Multivariable regression analyses examined associations between use of invasive treatments and patient categories, and clinical factors associated with receiving invasive ICU treatments despite low likelihood of benefit. RESULTS: There were 533 patients (369 in category 1 and 164 in category 3) in the study. A total of 19.8%, 29.9%, and 28.9% of patient-days on mechanical ventilation, vasopressors, and renal replacement therapy, respectively, were delivered to patients who were considered unlikely to benefit from ICU treatments (category 3) and ultimately did not survive hospitalization. These patients also received 35.2% of cardiopulmonary resuscitation attempts and 22.6% of central venous catheter placements. Clinicians' impressions of likelihood of benefit (category 1 vs 3) were not associated with odds of receiving invasive ICU treatments. Clinical characteristics associated with greater odds of receiving potentially nonbeneficial treatments included older age, presence of dementia or malignancy, and higher Acute Physiologic Assessment and Chronic Health Evaluation score. CONCLUSIONS: Invasive ICU treatments are frequently delivered to patients who are not expected to benefit from ICU care and die during hospitalization. These findings highlight the need to improve utilization of ICU services among patients with advanced medical illnesses.

Racial Differences in the Utilization of Guideline-Recommended and Life-Sustaining Procedures During Hospitalizations for Out-of-Hospital Cardiac Arrest.

BACKGROUND: Racial and ethnic minorities are at risk for disparities in quality of care after out-of-hospital cardiopulmonary arrest (OHCA). As such, we examined associations between race and ethnicity and use of guideline-recommended and life-sustaining procedures during hospitalizations for OHCA. METHODS: This was a retrospective study of hospitalizations for OHCA in all acute-care, non-federal California hospitals from 2009 to 2011. Associations between the use of (1) guideline-recommended procedures (cardiac catheterization for ventricular fibrillation/tachycardia, therapeutic hypothermia), (2) life-sustaining procedures (percutaneous endoscopic gastrostomy (PEG)/tracheostomy, renal replacement therapy (RRT)), and (3) palliative care and race/ethnicity were examined using hierarchical logistic regression analysis. RESULTS: Among 51,198 hospitalizations for OHCA, unadjusted rates of cardiac catheterization were 34.9% in Whites, 19.8% in Blacks, 27.2% in Hispanics, and 30.9% in Asians (P < 0.01). Rates of therapeutic hypothermia were 2.3% in Whites, 1.1% in Blacks, 1.3% in Hispanics, and 1.9% in Asians (P < 0.01). Rates of PEG/tracheostomy and RRT were 2.2% and 9.8% in Whites, 5.7% and 19.9% in Blacks, 4.2% and 19.9% in Hispanics, and 3.4% and 18.2% in Asians, respectively (P < 0.01). Rates of palliative care were 14.8% in Whites, 9.6% in Blacks, 10.1% in Hispanics, and 14.3% in Asians (P < 0.01). Differences in utilization of procedures persisted after adjustment for patient and hospital-related factors. CONCLUSION: Racial and ethnic minorities are less likely to receive guideline-recommended interventions and palliative care, and more likely to receive life-sustaining treatments following OHCA. These findings suggest that significant disparities exist in medical care after OHCA.

Patient- and Hospital-Level Factors Associated With Readmission for Malignant Pleural Effusion.

PURPOSE: Readmission after hospitalization for malignant pleural effusion (MPE) may represent gaps in the quality of health care delivery. The goal of this study was to determine the frequency of 30-day readmission for MPE and identify clinical factors associated with rehospitalization. PATIENTS AND METHODS: A retrospective cohort of adults hospitalized for MPE from 2009 to 2011 was analyzed using an administrative database. The primary outcome was all-cause 30-day readmission rate. Hierarchic mixed-effects logistic regression models were used to examine associations between patient- and hospital-level factors and 30-day readmission and assess variation in readmission rates across hospitals. RESULTS: The 7-, 14-, 30-, 60-, and 90-day readmission rates for MPE were 16.1%, 25.9%, 38.3%, 52.5%, and 63.8%, respectively. The most common primary diagnoses for 30-day readmission were MPE (69.5%) and other clinical issues related to malignancy (21.1%). Clinical factors associated with 30-day readmission were female sex (odds ratio [OR], 0.78; 95% CI, 0.63 to 0.95), greater number of medical comorbidities (OR, 1.51; 95% CI, 1.15 to 1.99), and having a do-not-resuscitate order (OR, 1.37; 95% CI, 1.03 to 1.84). Hospitals in the 90th percentile were only 1.1 times more likely to have a 30-day readmission for MPE than those in the lowest 10th percentile (40.9% v 37%). CONCLUSION: Readmission for MPE is common and frequently results from progression of malignancy. Readmission rates were similar across all hospitals, suggesting they are unlikely to be mutable using conventional approaches to reduce rehospitalizations. Instead, interventions may need to focus on addressing care planning at the end of life.

Association Between Intensive Care Unit Utilization During Hospitalization and Costs, Use of Invasive Procedures, and Mortality.

IMPORTANCE: Maximizing the value of critical care services requires understanding the relationship between intensive care unit (ICU) utilization, clinical outcomes, and costs. OBJECTIVE: To examine whether hospitals had consistent patterns of ICU utilization across 4 common medical conditions and the association between higher use of the ICU and hospital costs, use of invasive procedures, and mortality. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 156 842 hospitalizations in 94 acute-care nonfederal hospitals for diabetic ketoacidosis (DKA), pulmonary embolism (PE), upper gastrointestinal bleeding (UGIB), and congestive heart failure (CHF) in Washington state and Maryland from 2010 to 2012. Hospitalizations for DKA, PE, UGIB, and CHF were identified from the presence of compatible International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Multilevel logistic regression models were used to determine the predicted hospital-level ICU utilization during hospitalizations for the 4 study conditions. For each condition, hospitals were ranked based on the predicted ICU utilization rate to examine the variability in ICU utilization across institutions. MAIN OUTCOMES AND MEASURES: The primary outcomes were associations between hospital-level ICU utilization rates and risk-adjusted hospital mortality, use of invasive procedures, and hospital costs. RESULTS: The 94 hospitals and 156 842 hospitalizations included in the study represented 4.7% of total hospitalizations in this study. ICU admission rates ranged from 16.3% to 81.2% for DKA, 5.0% to 44.2% for PE, 11.5% to 51.2% for UGIB, and 3.9% to 48.8% for CHF. Spearman rank coefficients between DKA, PE, UGIB, and CHF showed significant correlations in ICU utilization for these 4 medical conditions among hospitals (ρ ≥ 0.90 for all comparisons; P < .01 for all). For each condition, hospital-level ICU utilization rate was not associated with hospital mortality. Use of invasive procedures and costs of hospitalization were greater in institutions with higher ICU utilization for all 4 conditions. CONCLUSIONS AND RELEVANCE: For medical conditions where ICU care is frequently provided, but may not always be necessary, institutions that utilize ICUs more frequently are more likely to perform invasive procedures and have higher costs but have no improvement in hospital mortality. Hospitals had similar ICU utilization patterns across the 4 medical conditions, suggesting that systematic institutional factors may influence decisions to potentially overutilize ICU care. Interventions that seek to improve the value of critical care services will need to address these factors that lead clinicians to admit patients to higher levels of care when equivalent care can be delivered elsewhere in the hospital.

Association Between Race and Case Fatality Rate in Hospitalizations for Sepsis.

BACKGROUND: Differentiating whether disparities in outcomes for sepsis among racial groups are due to differences in hospital care versus pre-hospitalization factors is an important step in developing effective strategies to reduce these disparities. As such, we examined the association between race and case fatality rates among hospitalizations for sepsis. METHODS: This was a case-control study of hospitalizations for sepsis in all acute-care, non-federal California hospitals during 2011. The association between hospital mortality and race was examined using hierarchical logistic regression analysis. RESULTS: Among 131,831 hospitalizations for sepsis, the unadjusted case fatality rates were 15.1 % in whites, 14.0 % in blacks, 13.8 % in Hispanics, and 16.2 % in Asians (P < 0.001). Compared to whites, the odds of hospital mortality was 0.84 (95 % CI 0.79-0.89) for blacks, 0.88 (95 % CI 0.84-0.92) for Hispanics, and 0.93 (95 % CI 0.87-0.98) for Asians after controlling for patient, healthcare systems, and hospital-level factors. There was no difference in the variability of sepsis mortality across hospitals between racial groups. The range of case fatality rates for sepsis among hospitals was 8.3-22.9 % for whites, 9.1-20.5 % for blacks, 7.0-19.1 % for Hispanics, and 10.0-23.0 % for Asians. CONCLUSION: Case fatality rates for sepsis hospitalizations are lower in minority racial groups in California. Future studies and interventions that seek to reduce racial disparities in sepsis need to focus on pre-hospitalization factors that contribute to population-level racial differences in sepsis outcomes.

Rehospitalizations Following Sepsis: Common and Costly.

OBJECTIVE: Although recent studies have shown that 30-day readmissions following sepsis are common, the overall fiscal impact of these rehospitalizations and their variability between hospitals relative to other high-risk conditions, such as congestive heart failure and acute myocardial infarction, are unknown. The objectives of this study were to characterize the frequency, cost, patient-level risk factors, and hospital-level variation in 30-day readmissions following sepsis compared with congestive heart failure and acute myocardial infarction. DESIGN: A retrospective cohort analysis of hospitalizations from 2009 to 2011. SETTING: All acute care, nonfederal hospitals in California. PATIENTS: Hospitalizations for sepsis (n = 240,198), congestive heart failure (n = 193,153), and acute myocardial infarction (n = 105,684) identified by administrative discharge codes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were the frequency and cost of all-cause 30-day readmissions following hospitalization for sepsis compared with congestive heart failure and acute myocardial infarction. Variability in predicted readmission rates between hospitals was calculated using mixed-effects logistic regression analysis. The all-cause 30-day readmission rates were 20.4%, 23.6%, and 17.7% for sepsis, congestive heart failure, and acute myocardial infarction, respectively. The estimated annual costs of 30-day readmissions in the state of California during the study period were $500 million/yr for sepsis, $229 million/yr for congestive heart failure, and $142 million/yr for acute myocardial infarction. The risk- and reliability-adjusted readmission rates across hospitals ranged from 11.0% to 39.8% (median, 19.9%; interquartile range, 16.1-26.0%) for sepsis, 11.3% to 38.4% (median, 22.9%; interquartile range, 19.2-26.6%) for congestive heart failure, and 3.6% to 40.8% (median, 17.0%; interquartile range, 12.2-20.0%) for acute myocardial infarction. Patient-level factors associated with higher odds of 30-day readmission following sepsis included younger age, male gender, Black or Native American race, a higher burden of medical comorbidities, urban residence, and lower income. CONCLUSION: Sepsis is a leading contributor to excess healthcare costs due to hospital readmissions. Interventions at clinical and policy levels should prioritize identifying effective strategies to reduce sepsis readmissions.

Volume of fluids administered during resuscitation for severe sepsis and septic shock and the development of the acute respiratory distress syndrome.

PURPOSE: The purpose of this study was to examine the association between the volume of intravenous (IV) fluids administered in the resuscitative phase of severe sepsis and septic shock and the development of the acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: This was a retrospective cohort study of adult patients admitted with severe sepsis and septic shock at a large academic public hospital. The relationship between the volume of IV fluids administered and the development of ARDS was examined using multivariable logistic regression analysis. RESULTS: Among 296 patients hospitalized for severe sepsis and septic shock, 75 (25.3%) developed ARDS. After controlling for confounding variables, there was no significant association between the volume of IV fluids administered in the first 24 hours of hospitalization and the development of ARDS (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.95-1.18). Serum albumin (OR, 0.52; 95% CI, 0.31-0.87) and Acute Physiology and Chronic Health Evaluation II score (OR, 1.08; 95% CI, 1.04-1.13) on admission were the most informative covariates for the development of ARDS in the regression model. CONCLUSIONS: For patients hospitalized for severe sepsis and septic shock, fluid administration to improve end-organ perfusion should remain the top priority in early resuscitation despite the potential risk of inducing ARDS.

Patient and hospital-level characteristics associated with the use of do-not-resuscitate orders in patients hospitalized for sepsis.

BACKGROUND: Identifying factors associated with do-not-resuscitate (DNR) orders is an informative step in developing strategies to improve their use. As such, a descriptive analysis of the factors associated with the use of DNR orders in the early and late phases of hospitalizations for sepsis was performed. METHODS: A retrospective cohort of adult patients hospitalized for sepsis was identified using a statewide administrative database. DNR orders placed within 24 h of hospitalization (early DNR) and after 24 h of hospitalization (late DNR) were the primary outcome variables. Multivariable logistic regression analysis was used to identify patient, hospital, and healthcare system-related factors associated with the use of early and late DNR orders. RESULTS: Among 77,329 patients hospitalized for sepsis, 27.5 % had a DNR order during their hospitalization. Among the cases with a DNR order, 75.5 % had the order within 24 h of hospitalization. Smaller hospital size and the absence of a teaching program increased the likelihood of an early DNR order being written. Additionally, greater patient age, female gender, White race, more medical comorbidities, Medicare payer status and admission from a skilled nursing facility were all significantly associated with the likelihood of having an early DNR. The strength of association between these factors and the use of late DNR orders was weaker. In contrast, the greater the burden of medical comorbidities, the more likely a patient was to receive a late DNR order. CONCLUSION: Multiple patient, hospital, and healthcare system-related factors are associated with the use of DNR orders in sepsis, many of which appear to be independent of a patient's clinical status. Over the course of the hospitalization, the burden of medical illness shows a stronger association relative to other variables. The influence of these multi-level factors needs to be recognized in strategies to improve the use of DNR orders. .

Proteomic and computational analysis of bronchoalveolar proteins during the course of the acute respiratory distress syndrome.

RATIONALE: Acute lung injury causes complex changes in protein expression in the lungs. Whereas most prior studies focused on single proteins, newer methods allowing the simultaneous study of many proteins could lead to a better understanding of pathogenesis and new targets for treatment. OBJECTIVES: The purpose of this study was to examine the changes in protein expression in the bronchoalveolar lavage fluid (BALF) of patients during the course of the acute respiratory distress syndrome (ARDS). METHODS: Using two-dimensional difference gel electrophoresis (DIGE), the expression of proteins in the BALF from patients on Days 1 (n = 7), 3 (n = 8), and 7 (n = 5) of ARDS were compared with findings in normal volunteers (n = 9). The patterns of protein expression were analyzed using principal component analysis (PCA). Biological processes that were enriched in the BALF proteins of patients with ARDS were identified using Gene Ontology (GO) analysis. Protein networks that model the protein interactions in the BALF were generated using Ingenuity Pathway Analysis. MEASUREMENTS AND MAIN RESULTS: An average of 991 protein spots were detected using DIGE. Of these, 80 protein spots, representing 37 unique proteins in all of the fluids, were identified using mass spectrometry. PCA confirmed important differences between the proteins in the ARDS and normal samples. GO analysis showed that these differences are due to the enrichment of proteins involved in inflammation, infection, and injury. The protein network analysis showed that the protein interactions in ARDS are complex and redundant, and revealed unexpected central components in the protein networks. CONCLUSIONS: Proteomics and protein network analysis reveals the complex nature of lung protein interactions in ARDS. The results provide new insights about protein networks in injured lungs, and identify novel mediators that are likely to be involved in the pathogenesis and progression of acute lung injury.