Implementation of Lung-Protective Ventilation in Patients With Acute Respiratory Failure.

OBJECTIVES: We implemented a computerized protocol for low tidal volume ventilation (LTVV) to improve management and outcomes of mechanically ventilated patients with, and without, the acute respiratory distress syndrome (ARDS). DESIGN: Pragmatic, nonrandomized stepped wedge type II hybrid implementation/effectiveness trial. SETTING: Twelve hospitals in an integrated healthcare system over a 2-year period. PATIENTS: Patients greater than or equal to 18 years old who had initiation of mechanical ventilation in the emergency department or ICU. We excluded patients who died or transitioned to comfort care on the day of admission to the ICU. We defined a subgroup of patients with ARDS for analysis. INTERVENTIONS: Implementation of ventilator protocols for LTVV in the ICU. MEASUREMENTS AND MAIN RESULTS: Our primary clinical outcome was ventilator-free days (VFDs) to day 28. Our primary process outcome was median initial set tidal volume. We included 8,692 mechanically ventilated patients, 3,282 (38%) of whom had ARDS. After implementation, set tidal volume reported as mL/kg predicted body weight decreased from median 6.1 mL/kg (interquartile range [IQR], 6.0-6.8 mL/kg) to 6.0 mL/kg (IQR, 6.0-6.6 mL/kg) ( p = 0.009). The percent of patients receiving LTVV (tidal volume ≤ 6.5 mL/kg) increased from 69.8% ( n = 1,721) to 72.5% ( n = 1,846) ( p = 0.036) after implementation. The percent of patients receiving greater than 8 mL/kg initial set tidal volume was reduced from 9.0% ( n = 222) to 6.7% ( n = 174) ( p = 0.005) after implementation. Among patients with ARDS, day 1 positive end-expiratory pressure increased from 6.7 to 8.0 cm H 2 O ( p < 0.001). We observed no difference in VFD (adjusted odds ratio, 1.06; 95% CI, 0.91-1.24; p = 0.44), or in secondary outcomes of length of stay or mortality, either within the main cohort or the subgroup of patients with ARDS. CONCLUSIONS: We observed improved adherence to optimal ventilator management with implementation of a computerized protocol and reduction in the number of patients receiving tidal volumes greater than 8 mL/kg. We did not observe improvement in clinical outcomes.

D-dimer Thresholds to Exclude Pulmonary Embolism among COVID-19 Patients in the Emergency Department: Derivation with Independent Validation.

OBJECTIVE: To derive and validate a D-dimer cutoff for ruling out pulmonary embolism (PE) in COVID-19 patients presenting to the emergency department (ED). METHODS: A retrospective cohort study was performed in an integrated healthcare system including 22 adult ED's between March 1, 2020, and January 31, 2021. Results were validated among patients enrolled in the RECOVER Registry, representing data from 154 ED's from 26 US states. Consecutive ED patients with laboratory confirmed COVID-19, a D-dimer performed within 48 h of ED arrival, and with objectively confirmed PE were compared to those without PE. After identifying a D-dimer threshold at which the 95% confidence lower bound of the negative predictive value for PE was higher than 98% in the derivation cohort, it was validated using RECOVER registry data. RESULTS: Among 3978 patients with a D-dimer result, 3583 with confirmed COVID-19 infection were included in the derivation cohort. Overall, PE incidence was 4.1% and a D-dimer cutoff of <2 µ/mL (2000 ng/mL) was associated with a NPV of 98.5% (95% CI = 98.0%-98.9%). In the validation cohort of 13,091 patients with a D-dimer, 7748 had confirmed COVID-19 infection, and the PE incidence was 1.14%. A D-dimer cutoff of <2 µ/mL was associated with a NPV of 99.5% (95% CI = 99.3%-99.7%). CONCLUSION: A D-dimer cutoff of <2 µ/ml was associated with a high negative predictive value for PE among patients with COVID-19. However, the resultant sensitivity for PE result at that threshold without pre-test probability assessment would be considered clinically unsafe.

An alert tool to promote lung protective ventilation for possible acute respiratory distress syndrome.

Objective: Computer-aided decision tools may speed recognition of acute respiratory distress syndrome (ARDS) and promote consistent, timely treatment using lung-protective ventilation (LPV). This study evaluated implementation and service (process) outcomes with deployment and use of a clinical decision support (CDS) synchronous alert tool associated with existing computerized ventilator protocols and targeted patients with possible ARDS not receiving LPV. Materials and Methods: We performed an explanatory mixed methods study from December 2019 to November 2020 to evaluate CDS alert implementation outcomes across 13 intensive care units (ICU) in an integrated healthcare system with >4000 mechanically ventilated patients annually. We utilized quantitative methods to measure service outcomes including CDS alert tool utilization, accuracy, and implementation effectiveness. Attitudes regarding the appropriateness and acceptability of the CDS tool were assessed via an electronic field survey of physicians and advanced practice providers. Results: Thirty-eight percent of study encounters had at least one episode of LPV nonadherence. Addition of LPV treatment detection logic prevented an estimated 1812 alert messages (41%) over use of disease detection logic alone. Forty-eight percent of alert recommendations were implemented within 2 h. Alert accuracy was estimated at 63% when compared to gold standard ARDS adjudication, with sensitivity of 85% and positive predictive value of 62%. Fifty-seven percent of survey respondents observed one or more benefits associated with the alert. Conclusion: Introduction of a CDS alert tool based upon ARDS risk factors and integrated with computerized ventilator protocol instructions increased visibility to gaps in LPV use and promoted increased adherence to LPV.

Order Substitutions and Education for Balanced Crystalloid Solution Use in an Integrated Health Care System and Association With Major Adverse Kidney Events.

Importance: Trials comparing balanced crystalloids with normal saline have yielded mixed results regarding reductions in kidney complications and mortality for hospitalized patients receiving intravenous fluids. Objective: To evaluate the association of a multifaceted implementation program encouraging the preferential use of lactated Ringer solution with patient outcomes and intravenous fluid-prescribing practices in a large, multilevel health care system. Design, Setting, and Participants: This type 2 hybrid implementation and comparative effectiveness study enrolled all patients 18 years or older who received 1 L or more of intravenous fluids while admitted to an emergency department and/or inpatient unit at 1 of 22 hospitals in Idaho and Utah between November 1, 2018, and February 29, 2020. An interrupted time series analysis was used to assess study outcomes before and after interventions to encourage use of lactated Ringer solution. Exposures: Implementation program combining order set modification, electronic order entry alerts, and sequential clinician-targeted education to encourage prescribing of lactated Ringer solution instead of normal saline. Main Outcomes and Measures: The primary implementation outcome was the patient-level proportion of intravenous fluids that was balanced crystalloids. The primary effectiveness outcome was the incidence of major adverse kidney events (MAKE30)-a composite of new persistent kidney dysfunction, new initiation of dialysis, and death-at 30 days. Results: Among 148 423 patients (median [IQR] age, 47 [30-67] years; 91 302 women [61%]), the proportion of total fluids received that was lactated Ringer solution increased from 28% to 75% in the first week vs the last week of the study (immediate implementation effect odds ratio [OR], 3.44; 95% CI, 2.79-4.24). The estimated MAKE30 absolute risk reduction was 2.2% (95% CI, 1.3%-3.3%) based on interrupted time series analysis showing a decrease in the week-on-week trend for MAKE30 (OR difference, 0.03; 95% CI, 0.03-0.03, P < .001). The immediate postimplementation OR for MAKE30 was 0.88 (95% CI, 0.76-1.01), with a decrease in persistent kidney dysfunction (OR, 0.80; 95% CI, 0.69-0.93) and mortality (OR, 0.78; 95% CI, 0.65-0.93) but not dialysis (OR, 1.00; 95% CI, 0.76-1.32). Conclusions and Relevance: In this comparative effectiveness study, an implementation program was associated with an increase in the proportion of fluids administered as lactated Ringer solution compared with normal saline and was associated with a reduction in MAKE30 events among patients treated in a large integrated health care system.

Evaluation of potential COVID-19 recurrence in patients with late repeat positive SARS-CoV-2 testing.

BACKGROUND: SARS-CoV-2 reinfection and reactivation has mostly been described in case reports. We therefore investigated the epidemiology of recurrent COVID-19 SARS-CoV-2. METHODS: Among patients testing positive for SARS-CoV-2 between March 11 and July 31, 2020 within an integrated healthcare system, we identified patients with a recurrent positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) assay ≥60 days after an initial positive test. To assign an overall likelihood of COVID-19 recurrence, we combined quantitative data from initial and recurrent positive RT-PCR cycle thresholds-a value inversely correlated with viral RNA burden- with a clinical recurrence likelihood assigned based on independent, standardized case review by two physicians. "Probable" or "possible" recurrence by clinical assessment was confirmed as the final recurrence likelihood only if a cycle threshold value obtained ≥60 days after initial testing was lower than its preceding cycle threshold or if the patient had an interval negative RT-PCR. RESULTS: Among 23,176 patients testing positive for SARS-CoV-2, 1,301 (5.6%) had at least one additional SARS-CoV-2 RT-PCRs assay ≥60 days later. Of 122 testing positive, 114 had sufficient data for evaluation. The median interval to the recurrent positive RT-PCR was 85.5 (IQR 74-107) days. After combining clinical and RT-PCR cycle threshold data, four patients (3.5%) met criteria for probable COVID-19 recurrence. All four exhibited symptoms at recurrence and three required a higher level of medical care compared to their initial diagnosis. After including six additional patients (5.3%) with possible recurrence, recurrence incidence was 4.3 (95% CI 2.1-7.9) cases per 10,000 COVID-19 patients. CONCLUSIONS: Only 0.04% of all COVID-19 patients in our health system experienced probable or possible recurrence; 90% of repeat positive SARS-CoV-2 RT-PCRs were not consistent with true recurrence. Our pragmatic approach combining clinical and quantitative RT-PCR data could aid assessment of COVID-19 reinfection or reactivation by clinicians and public health personnel.

Multi-factorial barriers and facilitators to high adherence to lung-protective ventilation using a computerized protocol: a mixed methods study.

BACKGROUND: Lung-protective ventilation (LPV) improves outcomes for patients with acute respiratory distress syndrome (ARDS) through the administration of low tidal volumes (≤ 6.5 ml/kg predicted body weight [PBW]) with co-titration of positive end-expiratory pressure and fraction of inspired oxygen. Many patients with ARDS, however, are not managed with LPV. The purpose of this study was to understand the implementation barriers and facilitators to the use of LPV and a computerized LPV clinical decision support (CDS) tool in intensive care units (ICUs) in preparation for a pilot hybrid implementation-effectiveness clinical trial. METHODS: We performed an explanatory sequential mixed methods study from June 2018 to March 2019 to evaluate the variation in LPV adherence across 17 ICUs in an integrated healthcare system with > 4000 mechanically ventilated patients annually. We analyzed 47 key informant interviews of ICU physicians, respiratory therapists (RTs), and nurses in 3 of the ICUs using a qualitative content analysis paradigm to investigate site variation as defined by adherence level (low, medium, high) and to identify barriers and facilitators to LPV and LPV CDS tool use. RESULTS: Forty-two percent of patients had an initial set tidal volume of ≤ 6.5 ml/kg PBW during the measurement period (site range 21-80%). LPV CDS tool use was 28% (site range 6-91%). This study's main findings revealed multi-factorial facilitators and barriers to use that varied by ICU site adherence level. The primary facilitator was that LPV and the LPV CDS tool could be used on all mechanically ventilated patients. Barriers included a persistent gap between clinician attitudes regarding the use of LPV and actual use, the perceived loss of autonomy associated with using a computerized protocol, the nature of physician-RT interaction in ventilation management, and the lack of clear organization measures of success. CONCLUSIONS: Variation in adherence to LPV persists in ICUs within a healthcare delivery system that was an early adopter of LPV. Potentially promising strategies to increase adherence to LPV and the LPV CDS tool for ARDS patients include initiating low tidal ventilation on all mechanically ventilated patients, establishing and measuring adherence measures, and focused education addressing the physician-RT interaction. These strategies represent a blueprint for a future hybrid implementation-effectiveness trial.