Association of Renin Angiotensin Aldosterone System Inhibitors and Outcomes of Hospitalized Patients With COVID-19.

OBJECTIVES: To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19. DESIGN: Retrospective observational study. SETTING: Multicenter, international COVID-19 registry. SUBJECTS: Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19-1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03-1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81-0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20-1.56]; p < 0.0001). CONCLUSIONS: Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with significantly higher mortality in hospitalized COVID-19 patients.

Post-thrombolytic coagulopathy and complications in patients with pulmonary embolism treated with fixed-dose systemic alteplase.

BACKGROUND: Alteplase treatment can cause a systemic coagulopathy although the incidence and contributory factors are unknown in pulmonary embolism (PE). Fixed-dosing of alteplase for PE may lead to interpatient variability in drug exposure and influence post-thrombolytic coagulopathy (PTC). While changes in fibrinogen and INR have been used to describe PTC, no universal PTC definition is available. OBJECTIVES: Evaluate the incidence of PTC after alteplase treatment for PE, the effect of patient weight and blood/plasma volume and the association with bleeding complications. METHODS: We conducted a retrospective cohort study of patients treated with alteplase for massive or high-risk submassive PE. Demographics, alteplase dosing, laboratory assessment of coagulopathy, and bleeding events were collected. The primary endpoint was incidence of PTC defined as an international normalized ratio (INR) > 1.5 or fibrinogen < 170 mg/dL. Secondary outcomes included correlation between coagulopathies and alteplase dose normalized to actual body weight (ABW), ideal body weight (IBW), plasma volume (PV), and estimated blood volume (EBV). Bleeding events in patients with and without PTC were compared. RESULTS: 125 patients met criteria for inclusion in the study. PTC occurred in 35.3% of patients, with INR >1.5 in 21.8% and fibrinogen <170 mg/dL in 26%. Alteplase dose >50 mg was associated with increased odds of PTC (OR 6.5, CI 2.1-19.9). Dose normalized to ABW and EBV correlated weakly with absolute increase in post-alteplase INR (r =0.20, p =0.06 and r =0.21, p =0.057 respectively) and to percent change in INR (r =0.20, p = 0.058 and r =0.21, p =0.048 respectively). Dose/ABW, dose/PV, and dose/EBV each correlated moderately with absolute decrease in fibrinogen (r =-0.53, -0.49, and -0.47 respectively, p <0.001 for each) and percent change in fibrinogen (r = -0.55, -0.49, and -0.49 respectively, p < 0.001 for each). Dose/IBW correlated weakly with absolute and percent decrease in fibrinogen (r = -0.32, p =0.013 and r =-0.33, p =0.011). Patients with bleeding were more likely to have PTC (58.3% vs. 28.6%, p= 0.05) and a bleeding event was predictive of PTC (OR 5.33, 1.32-23.99). CONCLUSIONS: PTC is prevalent in patients with PE. PTC is influenced by alteplase dose and exposure parameters (ABW, IBW, PV, EBV) and may contribute to the bleeding risk.

Comparative Performance of Pulmonary Ultrasound, Chest Radiograph, and CT Among Patients With Acute Respiratory Failure.

OBJECTIVES: The study goal was to concurrently evaluate agreement of a 9-point pulmonary ultrasound protocol and portable chest radiograph with chest CT for localization of pathology to the correct lung and also to specific anatomic lobes among a diverse group of intubated patients with acute respiratory failure. DESIGN: Prospective cohort study. SETTING: Medical, surgical, and neurologic ICUs at a 670-bed urban teaching hospital. PATIENTS: Intubated adults with acute respiratory failure having chest CT and portable chest radiograph performed within 24 hours of intubation. INTERVENTIONS: A 9-point pulmonary ultrasound examination performed at the time of intubation. MEASUREMENTS AND MAIN RESULTS: Sixty-seven patients had pulmonary ultrasound, portable chest radiograph, and chest CT performed within 24 hours of intubation. Overall agreement of pulmonary ultrasound and portable chest radiograph findings with correlating lobe ("lobe-specific" agreement) on CT was 87% versus 62% (p < 0.001), respectively. Relaxing the agreement definition to a matching CT finding being present anywhere within the correct lung ("lung-specific" agreement), not necessarily the specific mapped lobe, showed improved agreement for both pulmonary ultrasound and portable chest radiograph respectively (right lung: 92.5% vs 65.7%; p < 0.001 and left lung: 83.6% vs 71.6%; p = 0.097). The highest lobe-specific agreement was for the finding of atelectasis/consolidation for both pulmonary ultrasound and portable chest radiograph (96% and 73%, respectively). The lowest lobe-specific agreement for pulmonary ultrasound was normal lung (79%) and interstitial process for portable chest radiograph (29%). Lobe-specific agreement differed most between pulmonary ultrasound and portable chest radiograph for interstitial findings (86% vs 29%, respectively). Pulmonary ultrasound had the lowest agreement with CT for findings in the left lower lobe (82.1%). Pleural effusion agreement also differed between pulmonary ultrasound and portable chest radiograph (right: 99% vs 87%; p = 0.009 and left: 99% vs 85%; p = 0.004). CONCLUSIONS: A clinical, 9-point pulmonary ultrasound protocol strongly agreed with specific CT findings when analyzed by both lung- and lobe-specific location among a diverse population of mechanically ventilated patients with acute respiratory failure; in this regard, pulmonary ultrasound significantly outperformed portable chest radiograph.

Pulmonary ultrasound scoring system for intubated critically ill patients and its association with clinical metrics and mortality: A prospective cohort study.

PURPOSE: Pulmonary ultrasound (PU) examination at the point-of-care can rapidly identify the etiology of acute respiratory failure (ARF) and assess treatment response. The often-subjective classification of PU abnormalities makes it difficult to document change over time and communicate findings across providers. The study goal was to develop a simple, PU scoring system that would allow for standardized documentation, have high interprovider agreement, and correlate with clinical metrics. METHODS: In this prospective study of 250 adults intubated for ARF, a PU examination was performed at intubation, 48-hours later, and at extubation. A total lung score (TLS) was calculated. Clinical metrics and final diagnosis were extracted from the medical record. RESULTS: TLS correlated positively with mortality (P = .03), ventilator hours (P = .003), intensive care unit, and hospital length of stay (P = .003, P = .008), and decreasing PaO2 /FiO2 (P < .001). Agreement of PU findings was very good (kappa = 0.83). Baseline TLS and subscores differed significantly between ARF categories (nonpulmonary, obstructive, and parenchymal disease). CONCLUSIONS: A quick, scored, PU examination was associated with clinical metrics, including mortality among a diverse population of patients intubated for ARF. In addition to diagnostic and prognostic information at the bedside, a standardized and quantifiable approach to PU provides objectivity in serial assessment and may enhance communication of findings between providers.

Validation of automated data abstraction for SCCM discovery VIRUS COVID-19 registry: practical EHR export pathways (VIRUS-PEEP).

Background: The gold standard for gathering data from electronic health records (EHR) has been manual data extraction; however, this requires vast resources and personnel. Automation of this process reduces resource burdens and expands research opportunities. Objective: This study aimed to determine the feasibility and reliability of automated data extraction in a large registry of adult COVID-19 patients. Materials and methods: This observational study included data from sites participating in the SCCM Discovery VIRUS COVID-19 registry. Important demographic, comorbidity, and outcome variables were chosen for manual and automated extraction for the feasibility dataset. We quantified the degree of agreement with Cohen's kappa statistics for categorical variables. The sensitivity and specificity were also assessed. Correlations for continuous variables were assessed with Pearson's correlation coefficient and Bland-Altman plots. The strength of agreement was defined as almost perfect (0.81-1.00), substantial (0.61-0.80), and moderate (0.41-0.60) based on kappa statistics. Pearson correlations were classified as trivial (0.00-0.30), low (0.30-0.50), moderate (0.50-0.70), high (0.70-0.90), and extremely high (0.90-1.00). Measurements and main results: The cohort included 652 patients from 11 sites. The agreement between manual and automated extraction for categorical variables was almost perfect in 13 (72.2%) variables (Race, Ethnicity, Sex, Coronary Artery Disease, Hypertension, Congestive Heart Failure, Asthma, Diabetes Mellitus, ICU admission rate, IMV rate, HFNC rate, ICU and Hospital Discharge Status), and substantial in five (27.8%) (COPD, CKD, Dyslipidemia/Hyperlipidemia, NIMV, and ECMO rate). The correlations were extremely high in three (42.9%) variables (age, weight, and hospital LOS) and high in four (57.1%) of the continuous variables (Height, Days to ICU admission, ICU LOS, and IMV days). The average sensitivity and specificity for the categorical data were 90.7 and 96.9%. Conclusion and relevance: Our study confirms the feasibility and validity of an automated process to gather data from the EHR.

Hospital Variation in Management and Outcomes of Acute Respiratory Distress Syndrome Due to COVID-19.

OBJECTIVES: To describe hospital variation in use of "guideline-based care" for acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN: Retrospective, observational study. SETTING: The Society of Critical Care Medicine's Discovery Viral Infection and RESPIRATORY ILLNESS UNIVERSAL STUDY COVID-19 REGISTRY. PATIENTS: Adult patients with ARDS due to COVID-19 between February 15, 2020, and April 12, 2021. INTERVENTIONS: Hospital-level use of "guideline-based care" for ARDS including low-tidal-volume ventilation, plateau pressure less than 30 cm H2O, and prone ventilation for a Pao2/Fio2 ratio less than 100. MEASUREMENTS AND MAIN RESULTS: Among 1,495 adults with COVID-19 ARDS receiving care across 42 hospitals, 50.4% ever received care consistent with ARDS clinical practice guidelines. After adjusting for patient demographics and severity of illness, hospital characteristics, and pandemic timing, hospital of admission contributed to 14% of the risk-adjusted variation in "guideline-based care." A patient treated at a randomly selected hospital with higher use of guideline-based care had a median odds ratio of 2.0 (95% CI, 1.1-3.4) for receipt of "guideline-based care" compared with a patient receiving treatment at a randomly selected hospital with low use of recommended therapies. Median-adjusted inhospital mortality was 53% (interquartile range, 47-62%), with a nonsignificantly decreased risk of mortality for patients admitted to hospitals in the highest use "guideline-based care" quartile (49%) compared with the lowest use quartile (60%) (odds ratio, 0.7; 95% CI, 0.3-1.9; p = 0.49). CONCLUSIONS: During the first year of the COVID-19 pandemic, only half of patients received "guideline-based care" for ARDS management, with wide practice variation across hospitals. Strategies that improve adherence to recommended ARDS management strategies are needed.

Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Patients During the First Year of the COVID-19 Pandemic.

To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: Prospective observational study. SETTING: One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry. PATIENTS: Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. INTERVENTIONS: None. RESULTS: Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0-81.0 yr) versus 61 years (48.0-72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, -0.84, -1.34, and -0.84; p < 0.001). CONCLUSIONS: Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.

Improved Outcomes With Integrated Intensivist Consultation for Cardiac Surgery Patients.

This study examined the impact of integrated intensivist consultation in the immediate postoperative period on outcomes for cardiac surgery patients. A retrospective cohort study was conducted in 1711 adult cardiac surgery patients from a single quaternary care center in Minnesota. Outcomes were compared across 2 consecutive 2-year time periods reflecting an elective intensivist model (n = 801) and an integrated intensivist model (n = 910). Patients under the 2 models were comparable with respect to demographics, comorbidities, procedure types, and Society for Thoracic Surgery predicted risk of mortality score; however, patients in the earlier cohort were slightly older and more likely to have chronic kidney disease ( P = .003). Integrated intensivist involvement was associated with reduced postoperative ventilator time, length of stay (LOS), stroke, encephalopathy, and reoperations for bleeding (all P < .01) but was not associated with mortality. Intensivist integration into the postoperative care of cardiac surgery patients may reduce ventilator time, LOS, and complications but may not improve survival.