Associations Between Volume of Early Intravenous Fluid and Hospital Outcomes in Septic Patients With and Without Heart Failure: A Retrospective Cohort Study.

OBJECTIVES: To evaluate the relationship between early IV fluid volume and hospital outcomes, including death in-hospital or discharge to hospice, in septic patients with and without heart failure (HF). DESIGN: A retrospective cohort study using logistic regression with restricted cubic splines to assess for nonlinear relationships between fluid volume and outcomes, stratified by HF status and adjusted for propensity to receive a given fluid volume in the first 6 hours. An ICU subgroup analysis was performed. Secondary outcomes of vasopressor use, mechanical ventilation, and length of stay in survivors were assessed. SETTING: An urban university-based hospital. PATIENTS: A total of 9613 adult patients were admitted from the emergency department from 2012 to 2021 that met electronic health record-based Sepsis-3 criteria. Preexisting HF diagnosis was identified by the International Classification of Diseases codes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 1449 admissions from patients with HF. The relationship between fluid volume and death or discharge to hospice was nonlinear in patients without HF, and approximately linear in patients with HF. Receiving 0-15 mL/kg in the first 6 hours was associated with lower likelihood of death or discharge to hospice compared with 30-45 mL/kg (odds ratio = 0.61; 95% CI, 0.41-0.90; p = 0.01) in HF patients, but no significant difference for non-HF patients. A similar pattern was identified in ICU admissions and some secondary outcomes. Volumes larger than 15-30 mL/kg for non-HF patients and 30-45 mL/kg for ICU-admitted non-HF patients were not associated with improved outcomes. CONCLUSIONS: Early fluid resuscitation showed distinct patterns of potential harm and benefit between patients with and without HF who met Sepsis-3 criteria. Restricted cubic splines analysis highlighted the importance of considering nonlinear fluid outcomes relationships and identified potential points of diminishing returns (15-30 mL/kg across all patients without HF and 30-45 mL/kg when admitted to the ICU). Receiving less than 15 mL/kg was associated with better outcomes in HF patients, suggesting small volumes may be appropriate in select patients. Future studies may benefit from investigating nonlinear fluid-outcome associations and a focus on other conditions like HF.

Timing of antibiotic treatment identifies distinct clinical presentations among patients presenting with suspected septic shock.

Objective: Recent clinical guidelines for sepsis management emphasize immediate antibiotic initiation for suspected septic shock. Though hypotension is a high-risk marker of sepsis severity, prior studies have not considered the precise timing of hypotension in relation to antibiotic initiation and how clinical characteristics and outcomes may differ. Our objective was to evaluate antibiotic initiation in relation to hypotension to characterize differences in sepsis presentation and outcomes in patients with suspected septic shock. Methods: Adults presenting to the emergency department (ED) June 2012-December 2018 diagnosed with sepsis (Sepsis-III electronic health record [EHR] criteria) and hypotension (non-resolving for ≥30 min, systolic blood pressure <90 mmHg) within 24 h. We categorized patients who received antibiotics before hypotension ("early"), 0-60 min after ("immediate"), and >60 min after ("late") treatment. Results: Among 2219 patients, 55% received early treatment, 13% immediate, and 32% late. The late subgroup often presented to the ED with hypotension (median 0 min) but received antibiotics a median of 191 min post-ED presentation. Clinical characteristics notable for this subgroup included higher prevalence of heart failure and liver disease (p < 0.05) and later onset of systemic inflammatory response syndrome (SIRS) criteria compared to early/immediate treatment subgroups (median 87 vs. 35 vs. 20 min, p < 0.0001). After adjustment, there was no difference in clinical outcomes among treatment subgroups. Conclusions: There was significant heterogeneity in presentation and timing of antibiotic initiation for suspected septic shock. Patients with later treatment commonly had hypotension on presentation, had more hypotension-associated comorbidities, and developed overt markers of infection (eg, SIRS) later. While these factors likely contribute to delays in clinician recognition of suspected septic shock, it may not impact sepsis outcomes.

Ventricular tachycardia and in-hospital mortality in the intensive care unit.

Background: Continuous electrocardiographic (ECG) monitoring is used to identify ventricular tachycardia (VT), but false alarms occur frequently. Objective: The purpose of this study was to assess the rate of 30-day in-hospital mortality associated with VT alerts generated from bedside ECG monitors to those from a new algorithm among intensive care unit (ICU) patients. Methods: We conducted a retrospective cohort study in consecutive adult ICU patients at an urban academic medical center and compared current bedside monitor VT alerts, VT alerts from a new-unannotated algorithm, and true-annotated VT. We used survival analysis to explore the association between VT alerts and mortality. Results: We included 5679 ICU admissions (mean age 58 ± 17 years; 48% women), 503 (8.9%) experienced 30-day in-hospital mortality. A total of 30.1% had at least 1 current bedside monitor VT alert, 14.3% had a new-unannotated algorithm VT alert, and 11.6% had true-annotated VT. Bedside monitor VT alert was not associated with increased rate of 30-day mortality (adjusted hazard ratio [aHR] 1.06; 95% confidence interval [CI] 0.88-1.27), but there was an association for VT alerts from our new-unannotated algorithm (aHR 1.38; 95% CI 1.12-1.69) and true-annotated VT(aHR 1.39; 95% CI 1.12-1.73). Conclusion: Unannotated and annotated-true VT were associated with increased rate of 30-day in-hospital mortality, whereas current bedside monitor VT was not. Our new algorithm may accurately identify high-risk VT; however, prospective validation is needed.

Increased rates of secondary bacterial infections, including Enterococcus bacteremia, in patients hospitalized with coronavirus disease 2019 (COVID-19).

OBJECTIVE: We compared the rates of hospital-onset secondary bacterial infections in patients with coronavirus disease 2019 (COVID-19) with rates in patients with influenza and controls, and we investigated reports of increased incidence of Enterococcus infections in patients with COVID-19. DESIGN: Retrospective cohort study. SETTING: An academic quaternary-care hospital in San Francisco, California. PATIENTS: Patients admitted between October 1, 2019, and October 1, 2020, with a positive SARS-CoV-2 PCR (N = 314) or influenza PCR (N = 82) within 2 weeks of admission were compared with inpatients without positive SARS-CoV-2 or influenza tests during the study period (N = 14,332). METHODS: National Healthcare Safety Network definitions were used to identify infection-related ventilator-associated complications (IVACs), probable ventilator-associated pneumonia (PVAP), bloodstream infections (BSIs), and catheter-associated urinary tract infections (CAUTIs). A multiple logistic regression model was used to control for likely confounders. RESULTS: COVID-19 patients had significantly higher rates of IVAC and PVAP compared to controls, with adjusted odds ratios of 4.7 (95% confidence interval [CI], 1.7-13.9) and 10.4 (95 % CI, 2.1-52.1), respectively. COVID-19 patients had higher incidence of BSI due to Enterococcus but not BSI generally, and whole-genome sequencing of Enterococcus isolates demonstrated that nosocomial transmission did not explain the increased rate. Subanalyses of patients admitted to the intensive care unit and patients who required mechanical ventilation revealed similar findings. CONCLUSIONS: COVID-19 is associated with an increased risk of IVAC, PVAP, and Enterococcus BSI compared with hospitalized controls, which is not fully explained by factors such as immunosuppressive treatments and duration of mechanical ventilation. The mechanism underlying increased rates of Enterococcus BSI in COVID-19 patients requires further investigation.

Racial Disparities in 7-Day Readmissions from an Adult Hospital Medicine Service.

BACKGROUND: Health systems have targeted hospital readmissions to promote health equity as there may be racial and ethnic disparities across different patient groups. However, 7-day readmissions have been understudied in adult hospital medicine. DESIGN: This is a retrospective study. We performed multivariable logistic regression between patient race/ethnicity and 7-day readmission. Mediation analysis was performed for limited English proficiency (LEP) status. Subgroup analyses were performed for patients with initial admissions for congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and cancer. PATIENTS: We identified all adults discharged from the adult hospital medicine service at UCSF Medical Center between July 2016 and June 2019. MAIN MEASURES: The primary outcome was 7-day all-cause readmission back to the discharging hospital. RESULTS: There were 18,808 patients in our dataset who were discharged between July 2016 and June 2019. A total of 1,297 (6.9%) patients were readmitted within 7 days. Following multivariable regression, patients who identified as Black (OR 1.35, 95% CI 1.15-1.58, p <0.001) and patients who identified as Asian (OR 1.26, 95% CI 1.06-1.50, p = 0.008) had higher odds of readmission compared to white patients. Multivariable regression at the subgroup level for CHF, COPD, and cancer readmissions did not demonstrate significant differences between the racial and ethnic groups. CONCLUSIONS: Black patients and Asian patients experienced higher rates of 7-day readmission than patients who identified as white, confirmed on adjusted analysis.

Ask About What Matters: An Intervention to Improve Accessible Advance Care Planning Documentation.

CONTEXT: Advance care planning (ACP) informs future medical decision-making, especially for patients with advanced age or serious illness. For clinicians to act on these preferences, or continue the ACP conversation as illness progresses, documentation of ACP discussions must be readily accessible within the electronic health record (EHR). OBJECTIVES: Develop an intervention to improve accessible ACP documentation for hospitalized patients and assess its impact on viewing and documentation of ACP conversations within a specific EHR location. METHODS: Adult patients age 75 or older or with serious illness discharged during a two-year period were included. The EHR's ACP Navigator was targeted as the intended location for documenting ACP-related activities. We implemented a hospital-wide, multipronged intervention that included increased ACP Navigator visibility and a process for workflow-congruent ACP documentation. Accessible ACP documentation was measured by documentation within the ACP Navigator and was analyzed by interrupted time-series analysis. ACP Navigator access was measured by user audit logs. RESULTS: After the intervention, 6703 of 16,117 (41.6%) patient encounters had accessible ACP documentation, compared to 3689 of 13,143 (28.1%) preintervention (P < .001). In the intervention's first month, accessible ACP documentation increased 5.3% (P < .001, CI 2.9%-7.6%), followed by a 1.3% monthly increase relative to the preintervention period (P < .001, CI 1.0%-1.6%). ACP Navigator access for patients with ACP documentation increased in the intervention period (52.2% vs. 39.8%, P < .001). CONCLUSION: An institution-wide intervention significantly increased accessible ACP documentation within a centralized location of the EHR. EHR usability changes improved rates of accessible ACP documentation and subsequent views of this documentation.

Applying Machine Learning Across Sites: External Validation of a Surgical Site Infection Detection Algorithm.

BACKGROUND: Surgical complications have tremendous consequences and costs. Complication detection is important for quality improvement, but traditional manual chart review is burdensome. Automated mechanisms are needed to make this more efficient. To understand the generalizability of a machine learning algorithm between sites, automated surgical site infection (SSI) detection algorithms developed at one center were tested at another distinct center. STUDY DESIGN: NSQIP patients had electronic health record (EHR) data extracted at one center (University of Minnesota Medical Center, Site A) over a 4-year period for model development and internal validation, and at a second center (University of California San Francisco, Site B) over a subsequent 2-year period for external validation. Models for automated NSQIP SSI detection of superficial, organ space, and total SSI within 30 days postoperatively were validated using area under the curve (AUC) scores and corresponding 95% confidence intervals. RESULTS: For the 8,883 patients (Site A) and 1,473 patients (Site B), AUC scores were not statistically different for any outcome including superficial (external 0.804, internal [0.784, 0.874] AUC); organ/space (external 0.905, internal [0.867, 0.941] AUC); and total (external 0.855, internal [0.854, 0.908] AUC) SSI. False negative rates decreased with increasing case review volume and would be amenable to a strategy in which cases with low predicted probabilities of SSI could be excluded from chart review. CONCLUSIONS: Our findings demonstrated that SSI detection machine learning algorithms developed at 1 site were generalizable to another institution. SSI detection models are practically applicable to accelerate and focus chart review.

Evaluation of a novel metric for personalized opioid prescribing after hospitalization.

BACKGROUND: The duration of an opioid prescribed at hospital discharge does not intrinsically account for opioid needs during a hospitalization. This discrepancy may lead to patients receiving much larger supplies of opioids on discharge than they truly require. OBJECTIVE: Assess a novel discharge opioid supply metric that adjusts for opioid use during hospitalization, compared to the conventional discharge prescription signature. DESIGN, SETTING, & PARTICIPANTS: Retrospective study using electronic health record data from June 2012 to November 2018 of adults who received opioids while hospitalized and after discharge from a single academic medical center. MEASURES & ANALYSIS: We ascertained inpatient opioids received and milligrams of opioids supplied after discharge, then determined days of opioids supplied after discharge by the conventional prescription signature opioid-days ("conventional days") and novel hospital-adjusted opioid-days ("adjusted days") metrics. We calculated descriptive statistics, within-subject difference between measurements, and fold difference between measures. We used multiple linear regression to determine patient-level predictors associated with high difference in days prescribed between measures. RESULTS: The adjusted days metric demonstrates a 2.4 day median increase in prescription duration as compared to the conventional days metric (9.4 vs. 7.0 days; P<0.001). 95% of all adjusted days measurements fall within a 0.19 to 6.90-fold difference as compared to conventional days measurements, with a maximum absolute difference of 640 days. Receiving a liquid opioid prescription accounted for an increased prescription duration of 135.6% by the adjusted days metric (95% CI 39.1-299.0%; P = 0.001). Of patients who were not on opioids prior to admission and required opioids during hospitalization but not in the last 24 hours, 325 (8.6%) were discharged with an opioid prescription. CONCLUSIONS: The adjusted days metric, based on inpatient opioid use, demonstrates that patients are often prescribed a supply lasting longer than the prescription signature suggests, though with marked variability for some patients that suggests potential under-prescribing as well. Adjusted days is more patient-centered, reflecting the reality of how patients will take their prescription rather than providers' intended prescription duration.

Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: A retrospective cohort study of patients with and without COVID-19.

BACKGROUND: Most data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have been presented as case series without comparison to patients with other acute respiratory illnesses. METHODS: We examined emergency department patients between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared clinical presentation, diagnostics, treatment, and outcomes. FINDINGS: Among 316 patients, 33 tested positive for SARS-CoV-2; 31 without COVID-19 tested positive for another respiratory virus. Among patients with additional viral testing (27/33), no SARS-CoV-2 co-infections were identified. Compared to those who tested negative, patients with COVID-19 reported longer symptoms duration (median 7d vs. 3d, p < 0.001). Patients with COVID-19 were more often hospitalized (79% vs. 56%, p = 0.014). When hospitalized, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, p < 0.001) and more often developed ARDS (23% vs. 3%, p < 0.001). Most comorbidities, medications, symptoms, vital signs, laboratories, treatments, and outcomes did not differ by COVID-19 status. INTERPRETATION: While we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. FUNDING: National Center for Advancing Translational Sciences, National Heart Lung Blood Institute, National Institute of Allergy and Infectious Diseases, Chan Zuckerberg Biohub, Chan Zuckerberg Initiative.

Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: a comparison of patients with and without COVID-19.

BACKGROUND: Emerging data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have largely been presented as case series. Few studies have compared these clinical features and outcomes of COVID-19 to other acute respiratory illnesses. METHODS: We examined all patients presenting to an emergency department in San Francisco, California between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared demographics, comorbidities, symptoms, vital signs, and laboratory results including viral diagnostics using PCR and mNGS. Among those hospitalized, we determined differences in treatment (antibiotics, antivirals, respiratory support) and outcomes (ICU admission, ICU interventions, acute respiratory distress syndrome, cardiac injury). FINDINGS: In a cohort of 316 patients, 33 (10%) tested positive for SARS-CoV-2; 31 patients, all without COVID-19, tested positive for another respiratory virus (16%). Among patients with additional viral testing, no co-infections with SARS-CoV-2 were identified by PCR or mNGS. Patients with COVID-19 reported longer symptoms duration (median 7 vs. 3 days), and were more likely to report fever (82% vs. 44%), fatigue (85% vs. 50%), and myalgias (61% vs 27%); p<0.001 for all comparisons. Lymphopenia (55% vs 34%, p=0.018) and bilateral opacities on initial chest radiograph (55% vs. 24%, p=0.001) were more common in patients with COVID-19. Patients with COVID-19 were more often hospitalized (79% vs. 56%, p=0.014). Of 186 hospitalized patients, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, p<0.001) and were more likely to develop ARDS (23% vs. 3%, p<0.001). Most comorbidities, home medications, signs and symptoms, vital signs, laboratory results, treatment, and outcomes did not differ by COVID-19 status. INTERPRETATION: While we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. These findings enhance understanding of the clinical characteristics of COVID-19 in comparison to other acute respiratory illnesses. .

The Association between Limited English Proficiency and Sepsis Mortality.

BACKGROUND: Limited English proficiency (LEP) has been implicated in poor health outcomes. Sepsis is a frequently fatal syndrome that is commonly encountered in hospital medicine. The impact of LEP on sepsis mortality is not currently known. OBJECTIVE: To determine the association between LEP and sepsis mortality. DESIGN: Retrospective cohort study. SETTING: 800-bed, tertiary care, academic medical center. PATIENTS: Electronic health record data were obtained for adults admitted to the hospital with sepsis between June 1, 2012 and December 31, 2016. MEASUREMENTS: The primary predictor was LEP. Patients were defined as having LEP if their self-reported primary language was anything other than English and interpreter services were required during hospitalization. The primary outcome was inpatient mortality. Mortality was compared across races stratified by LEP using chi-squared tests of significance. Bivariable and multivariable logistic regressions were performed to investigate the association between mortality, race, and LEP, adjusting for baseline characteristics, comorbidities, and illness severity. RESULTS: Among 8,974 patients with sepsis, we found that 1 in 5 had LEP, 62% of whom were Asian. LEP was highly associated with death across all races except those identifying as Black and Latino. LEP was associated with a 31% increased odds of mortality after adjusting for illness severity, comorbidities, and other baseline characteristics, including race (OR 1.31, 95% CI 1.06-1.63, P = .02). CONCLUSIONS: In a single-center study of patients hospitalized with sepsis, LEP was associated with mortality across nearly all races. This is a novel finding that will require further exploration into the causal nature of this association.

Time to Recognition of Sepsis in the Emergency Department Using Electronic Health Record Data: A Comparative Analysis of Systemic Inflammatory Response Syndrome, Sequential Organ Failure Assessment, and Quick Sequential Organ Failure Assessment.

OBJECTIVES: Early identification of sepsis is critical to improving patient outcomes. Impact of the new sepsis definition (Sepsis-3) on timing of recognition in the emergency department has not been evaluated. Our study objective was to compare time to meeting systemic inflammatory response syndrome (Sepsis-2) criteria, Sequential Organ Failure Assessment (Sepsis-3) criteria, and quick Sequential Organ Failure Assessment criteria using electronic health record data. DESIGN: Retrospective, observational study. SETTING: The emergency department at the University of California, San Francisco. PATIENTS: Emergency department encounters between June 2012 and December 2016 for patients greater than or equal to 18 years old with blood cultures ordered, IV antibiotic receipt, and identification with sepsis via systemic inflammatory response syndrome or Sequential Organ Failure Assessment within 72 hours of emergency department presentation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed timestamped electronic health record data from 16,612 encounters identified as sepsis by greater than or equal to 2 systemic inflammatory response syndrome criteria or a Sequential Organ Failure Assessment score greater than or equal to 2. The primary outcome was time from emergency department presentation to meeting greater than or equal to 2 systemic inflammatory response syndrome criteria, Sequential Organ Failure Assessment greater than or equal to 2, and/or greater than or equal to 2 quick Sequential Organ Failure Assessment criteria. There were 9,087 patients (54.7%) that met systemic inflammatory response syndrome-first a median of 26 minutes post-emergency department presentation (interquartile range, 0-109 min), with 83.1% meeting Sequential Organ Failure Assessment criteria a median of 118 minutes later (interquartile range, 44-401 min). There were 7,037 patients (42.3%) that met Sequential Organ Failure Assessment-first, a median of 113 minutes post-emergency department presentation (interquartile range, 60-251 min). Quick Sequential Organ Failure Assessment was met in 46.4% of patients a median of 351 minutes post-emergency department presentation (interquartile range, 67-1,165 min). Adjusted odds of in-hospital mortality were 39% greater in patients who met systemic inflammatory response syndrome-first compared with those who met Sequential Organ Failure Assessment-first (odds ratio, 1.39; 95% CI, 1.20-1.61). CONCLUSIONS: Systemic inflammatory response syndrome and Sequential Organ Failure Assessment initially identified distinct populations. Using systemic inflammatory response syndrome resulted in earlier electronic health record sepsis identification in greater than 50% of patients. Using Sequential Organ Failure Assessment alone may delay identification. Using systemic inflammatory response syndrome alone may lead to missed sepsis presenting as acute organ dysfunction. Thus, a combination of inflammatory (systemic inflammatory response syndrome) and organ dysfunction (Sequential Organ Failure Assessment) criteria may enhance timely electronic health record-based sepsis identification.

Reducing Unnecessary Treatment of Asymptomatic Elevated Blood Pressure with Intravenous Medications on the General Internal Medicine Wards: A Quality Improvement Initiative.

BACKGROUND: Asymptomatic elevated blood pressure (BP) is common in the hospital. There is no evidence supporting the use of intravenous (IV) antihypertensives in this setting. OBJECTIVE: To determine the prevalence and effects of treating asymptomatic elevated BP with IV antihypertensives and to investigate the efficacy of a quality improvement (QI) initiative aimed at reducing utilization of these medications. DESIGN: Retrospective cohort study. SETTING: Urban academic hospital. PATIENTS: Patients admitted to the general medicine service, including the intensive care unit (ICU), with ≥1 episode of asymptomatic elevated BP (>160/90 mm Hg) during hospitalization. INTERVENTION: A two-tiered, QI initiative. MEASUREMENTS: The primary outcome was the monthly proportion of patients with asymptomatic elevated BP treated with IV labetalol or hydralazine. We also analyzed median BP and rates of balancing outcomes (ICU transfers, rapid responses, cardiopulmonary arrests). RESULTS: We identified 2,306 patients with ≥1 episode of asymptomatic elevated BP during the 10-month preintervention period, of which 251 (11%) received IV antihypertensives. In the four-month postintervention period, 70 of 934 (7%) were treated. The odds of being treated were 38% lower in the postintervention period after adjustment for baseline characteristics, including length of stay and illness severity (OR = 0.62; 95% CI 0.47-0.83; P = .001). Median SBP was similar between pre- and postintervention (167 vs 168 mm Hg; P = .78), as were the adjusted proportions of balancing outcomes. CONCLUSIONS: Hospitalized patients with asymptomatic elevated BP are commonly treated with IV antihypertensives, despite the lack of evidence. A QI initiative was successful at reducing utilization of these medications.