Validation of Respiratory Rate-Oxygenation Index in Patients With COVID-19-Related Respiratory Failure.

OBJECTIVES: The respiratory rate-oxygenation (ROX) index is a fraction of oxygen saturation, Fio2, and respiratory rate that has been validated to predict receipt of invasive mechanical ventilation in patients receiving high-flow nasal cannula (HFNC). This study aimed to validate ROX in a cohort of inpatients with COVID-19-related respiratory failure. DESIGN: Retrospective validation of the ROX index. We calculated sensitivity, specificity, positive predictive value, negative predictive value, and 95% CIs of ROX for invasive mechanical ventilation any time during hospitalization. SETTING: Twenty-one hospitals of Kaiser Permanente Northern California, an integrated healthcare delivery system. PATIENTS: We identified adults with positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test within 3 weeks of, or during, hospitalization between February 1, 2020, and December 31, 2020. We calculated ROX at 12 hours after HFNC initiation. We grouped patients as low (≥ 4.88), intermediate (< 4.88 and ≥ 3.85), or high (< 3.85) risk using previously published thresholds. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 1,847 patients who had no limitation of life support. Of these, 525 (31.7%) received invasive mechanical ventilation any time during hospitalization and 511 died (27.7%). The sensitivity, specificity, positive predictive value, and negative predictive value of 12-hour ROX threshold (< 3.85) predicting invasive mechanical ventilation were 32.3% (95% CI, 28.5-36.3%), 89.8% (95% CI, 88.0-91.4%), 59.4% (95% CI, 53.8-64.9%), and 74.1% (95% CI, 71.8-76.3%), respectively. CONCLUSIONS: The 12-hour ROX index has a positive predictive value (59.4%) using threshold of less than 3.85 for COVID-19 patients needing invasive mechanical ventilation. Our health system has embedded ROX into the electronic health record to prioritize rounding during periods of inpatient surge.

Association Between Peripheral Blood Oxygen Saturation (SpO2)/Fraction of Inspired Oxygen (FiO2) Ratio Time at Risk and Hospital Mortality in Mechanically Ventilated Patients.

INTRODUCTION: Acute respiratory failure requiring mechanical ventilation is a leading cause of mortality in the intensive care unit. Although single peripheral blood oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) ratios of hypoxemia have been evaluated to risk-stratify patients with acute respiratory distress syndrome, the utility of longitudinal SpO2/FiO2 ratios is unknown. OBJECTIVE: To assess time-based SpO2/FiO2 ratios ≤ 150-SpO2/FiO2 time at risk (SF-TAR)-for predicting mortality in mechanically ventilated patients. METHODS: Retrospective, observational cohort study of mechanically ventilated patients at 21 community and 2 academic hospitals. Association between the SF-TAR in the first 24 hours of ventilation and mortality was examined using multivariable logistic regression and compared with the worst recorded isolated partial pressure of arterial oxygen/fraction of inspired oxygen (P/F) ratio. RESULTS: In 28,758 derivation cohort admissions, every 10% increase in SF-TAR was associated with a 24% increase in adjusted odds of hospital mortality (adjusted odds ratio = 1.24; 95% confidence interval [CI] = 1.23-1.26); a similar association was observed in validation cohorts. Discrimination for mortality modestly improved with SF-TAR (area under the receiver operating characteristic curve [AUROC] = 0.81; 95% CI = 0.81-0.82) vs the worst P/F ratio (AUROC = 0.78; 95% CI = 0.78-0.79) and worst SpO2/FiO2 ratio (AUROC = 0.79; 95% CI = 0.79-0.80). The SF-TAR in the first 6 hours offered comparable discrimination for hospital mortality (AUROC = 0.80; 95% CI = 0.79-0.80) to the 24-hour SF-TAR. CONCLUSION: The SF-TAR can identify ventilated patients at increased risk of death, offering modest improvements compared with single SpO2/FiO2 and P/F ratios. This longitudinal, noninvasive, and broadly generalizable tool may have particular utility for early phenotyping and risk stratification using electronic health record data in ventilated patients.

Multicenter Implementation of a Treatment Bundle for Patients with Sepsis and Intermediate Lactate Values.

RATIONALE: Treatments for patients with sepsis with intermediate lactate values (≥2 and <4 mmol/L) are poorly defined. OBJECTIVES: To evaluate multicenter implementation of a treatment bundle (including timed intervals for antibiotics, repeat lactate testing, and intravenous fluids) for hemodynamically stable patients with sepsis and intermediate lactate values in the emergency department. METHODS: We evaluated patients in annual intervals before and after bundle implementation in March 2013. We evaluated bundle compliance and compared outcome measures across groups with multivariable logistic regression. Because of their perceived risk for iatrogenic fluid overload, we also evaluated patients with a history of heart failure and/or chronic kidney disease. MEASUREMENTS AND MAIN RESULTS: We identified 18,122 patients with sepsis and intermediate lactate values, including 36.1% treated after implementation. Full bundle compliance increased from 32.2% in 2011 to 44.9% after bundle implementation (P < 0.01). Hospital mortality was 8.8% in 2011, 9.3% in 2012, and 7.9% in 2013 (P = 0.02). Treatment after bundle implementation was associated with an adjusted hospital mortality odds ratio of 0.81 (95% confidence interval, 0.66-0.99; P = 0.04). Decreased hospital mortality was observed primarily in patients with a heart failure and/or kidney disease history (P < 0.01) compared with patients without this history (P > 0.40). This corresponded to notable changes in the volume of fluid resuscitation in patients with heart failure and/or kidney disease after implementation. CONCLUSIONS: Multicenter implementation of a treatment bundle for patients with sepsis and intermediate lactate values improved bundle compliance and was associated with decreased hospital mortality. These decreases were mediated by improved mortality and increased fluid administration among patients with a history of heart failure and/or chronic kidney disease.

Evaluation Following Staggered Implementation of the "Rethinking Critical Care" ICU Care Bundle in a Multicenter Community Setting.

OBJECTIVES: To evaluate process metrics and outcomes after implementation of the "Rethinking Critical Care" ICU care bundle in a community setting. DESIGN: Retrospective interrupted time-series analysis. SETTING: Three hospitals in the Kaiser Permanente Northern California integrated healthcare delivery system. PATIENTS: ICU patients admitted between January 1, 2009, and August 30, 2013. INTERVENTIONS: Implementation of the Rethinking Critical Care ICU care bundle which is designed to reduce potentially preventable complications by focusing on the management of delirium, sedation, mechanical ventilation, mobility, ambulation, and coordinated care. Rethinking Critical Care implementation occurred in a staggered fashion between October 2011 and November 2012. MEASUREMENTS AND MAIN RESULTS: We measured implementation metrics based on electronic medical record data and evaluated the impact of implementation on mortality with multivariable regression models for 24,886 first ICU episodes in 19,872 patients. After implementation, some process metrics (e.g., ventilation start and stop times) were achieved at high rates, whereas others (e.g., ambulation distance), available late in the study period, showed steep increases in compliance. Unadjusted mortality decreased from 12.3% to 10.9% (p < 0.01) before and after implementation, respectively. The adjusted odds ratio for hospital mortality after implementation was 0.85 (95% CI, 0.73-0.99) and for 30-day mortality was 0.88 (95% CI, 0.80-0.97) compared with before implementation. However, the mortality rate trends were not significantly different before and after Rethinking Critical Care implementation. The mean duration of mechanical ventilation and hospital stay also did not demonstrate incrementally greater declines after implementation. CONCLUSIONS: Rethinking Critical Care implementation was associated with changes in practice and a 12-15% reduction in the odds of short-term mortality. However, these findings may represent an evaluation of changes in practices and outcomes still in the midimplementation phase and cannot be directly attributed to the elements of bundle implementation.

Kaiser Permanente's performance improvement system, part 3: multisite improvements in care for patients with sepsis.

BACKGROUND: In 2008, Kaiser Permanente Northern California implemented an initiative to improve sepsis care. Early detection and expedited implementation of sepsis treatment bundles that include early goal-directed therapy (EGDT) for patients with severe sepsis were implemented. METHODS: In a top-down, bottom-up approach to performance improvement, teams at 21 medical centers independently decided how to implement treatment bundles, using a "playbook" developed by rapid cycle pilot testing at two sites and endorsed by a sepsis steering committee of regional and medical center clinical leaders. The playbook contained treatment algorithms, standardized order sets and flow charts, best practice alerts, and chart abstraction tools. Regional mentors and improvement advisers within the medical centers supported team-building and rapid implementation. Timely and actionable data allowed ongoing identification of improvement opportunities. A consistent approach to performance improvement propelled local rapid improvement cycles and joint problem solving across facilities. RESULTS: The number of sepsis diagnoses per 1,000 admissions increased from a baseline value of 35.7 in July 2009 to 119.4 in May 2011. The percent of admitted patients who have blood cultures drawn who also have a serum lactate level drawn increased from a baseline of 27% to 97% in May 2011. The percent of patients receiving EGDT who had a second and lower lactate level within six hours increased from 52% at baseline to 92% in May 2011. CONCLUSION: Twenty-one cross-functional frontline teams redesigned processes of care to provide regionally standardized, evidence-based treatment algorithms for sepsis, substantially increasing the identification and risk stratification of patients with suspected sepsis and the provision of a sepsis care bundle that included EGDT.

Intra-hospital transfers to a higher level of care: contribution to total hospital and intensive care unit (ICU) mortality and length of stay (LOS).

BACKGROUND: Patients who experience intra-hospital transfers to a higher level of care (eg, ward to intensive care unit [ICU]) are known to have high mortality. However, these findings have been based on single-center studies or studies that employ ICU admissions as the denominator. OBJECTIVE: To employ automated bed history data to examine outcomes of intra-hospital transfers using all hospital admissions as the denominator. DESIGN: Retrospective cohort study. SETTING: A total of 19 acute care hospitals. PATIENTS: A total of 150,495 patients, who experienced 210,470 hospitalizations, admitted to these hospitals between November 1st, 2006 and January 31st, 2008. MEASUREMENTS: Predictors were age, sex, admission type, admission diagnosis, physiologic derangement on admission, and pre-existing illness burden; outcomes were: 1) occurrence of intra-hospital transfer, 2) death following admission to the hospital, 3) death following transfer, and 4) total hospital length of stay (LOS). RESULTS: A total of 7,868 hospitalizations that began with admission to either a general medical surgical ward or to a transitional care unit (TCU) had at least one transfer to a higher level of care. These hospitalizations constituted only 3.7% of all admissions, but accounted for 24.2% of all ICU admissions, 21.7% of all hospital deaths, and 13.2% of all hospital days. Models based on age, sex, preadmission laboratory test results, and comorbidities did not predict the occurrence of these transfers. CONCLUSIONS: Patients transferred to higher level of care following admission to the hospital have excess mortality and LOS.

Cystic fibrosis in adults: current and future management strategies.

Over 30,000 individuals in the United States of America are living with cystic fibrosis (CF). Despite incremental advances in care and understanding of its pathophysiology, CF remains a significantly life-limiting disease. Readily accessible newborn screening, genetic testing, and an improved awareness have increased the early recognition of CF, atypical presentations of CF, and the CF-related diseases. Improvements in medical management have led to continually improving life expectancy for patients with CF. Despite improved management strategies, severe lung disease remains the commonly life-limiting pathology. We review the pathophysiology, diagnosis, and management of the respiratory-tract manifestations of CF that represent the life-limiting aspects of the condition and summarize upcoming and possible future therapies for patients with CF.