Lal, Amos

OBJECTIVES: Accurate identification of acute respiratory distress syndrome is essential for understanding its epidemiology, patterns of care, and outcomes. We aimed to design a computable phenotyping strategy to detect acute respiratory distress syndrome in electronic health records of critically ill patients. DESIGN: This is a retrospective cohort study. Using a near real-time copy of the electronic health record, we developed a computable phenotyping strategy to detect acute respiratory distress syndrome based on the Berlin definition. SETTING: Twenty multidisciplinary ICUs in Mayo Clinic Health System. SUBJECTS: The phenotyping strategy was applied to 196,487 consecutive admissions from year 2009 to 2019. INTERVENTIONS: The acute respiratory distress syndrome cohort generated by this novel strategy was compared with the acute respiratory distress syndrome cohort documented by clinicians during the same period. The sensitivity and specificity of the phenotyping strategy were calculated in randomly selected patient cohort (50 patients) using the results from manual medical record review as gold standard. MEASUREMENTS AND MAIN RESULTS: Among the patients who did not have acute respiratory distress syndrome documented, the computable phenotyping strategy identified 3,169 adult patients who met the Berlin definition, 676 patients (21.3%) were classified to have severe acute respiratory distress syndrome (Pao 2/Fio 2 ratio ≤ 100), 1,535 patients (48.4%) had moderate acute respiratory distress syndrome (100 < Pao 2/Fio 2 ratio ≤ 200), and 958 patients (30.2%) had mild acute respiratory distress syndrome (200 < Pao 2/Fio 2 ratio ≤ 300). The phenotyping strategy achieved a sensitivity of 94.4%, specificity of 96.9%, positive predictive value of 94.4%, and negative predictive value of 96.9% in a randomly selected patient cohort. The clinicians documented acute respiratory distress syndrome in 1,257 adult patients during the study period. The clinician documentation rate of acute respiratory distress syndrome was 28.4%. Compared with the clinicians’ documentation, the phenotyping strategy identified a cohort that had higher acuity and complexity of illness suggested by higher Sequential Organ Failure Assessment score (9 vs 7; p < 0.0001), higher Acute Physiology and Chronic Health Evaluation score (76 vs 63; p < 0.0001), higher rate of requiring invasive mechanical ventilation (99.1% vs 71.8%; p < 0.0001), higher ICU mortality (20.6% vs 16.8%; p < 0.0001), and longer ICU length of stay (5.1 vs 4.2 d; p < 0.0001). CONCLUSIONS: Our rule-based computable phenotyping strategy can accurately detect acute respiratory distress syndrome in critically ill patients in the setting of high clinical complexity. This strategy can be applied to enhance early recognition of acute respiratory distress syndrome and to facilitate best-care delivery and clinical research in acute respiratory distress syndrome.

Objectives: Our preliminary data and observational studies suggested an increasing “off label” use of oral midodrine as a vasopressor sparing agent in various groups of critically ill patients, including those with sepsis. We designed this clinical trial to evaluate the feasibility of use of midodrine hydrochloride in early sepsis to reduce the duration for IV vasopressors and decrease ICU and hospital length of stay. Design: Pilot, two-center, placebo-controlled, double blinded randomized clinical trial. Setting: Medical ICUs at Mayo Clinic Rochester and Cleveland Clinic Abu Dhabi were the study sites. Patients and Methods: Adult patients (≥ 18 yr old) were included within 24 hours of meeting the Sepsis-3 definition if the mean arterial pressure remained less than 70 mm Hg despite receiving timely antibiotics and initial IV fluid bolus of 30 cc/kg. Intervention: Three doses of 10 mg midodrine versus placebo were administered. Measurements and Main Results: Total 32 patients were randomized into midodrine (n = 17) and placebo groups (n = 15). There were no major differences in baseline variables between the groups except for higher baseline creatinine in the midodrine group (2.0 ± 0.9 mg/dL) versus placebo group (1.4 ± 0.6 mg /dL), p = 0.03. The median duration of IV vasopressor requirement was 14.5 ± 8.1 hours in midodrine group versus 18.8 ± 7.1 hours in the placebo group, p value equals to 0.19. Patients in the midodrine group needed 729 ± 963 norepinephrine equivalent compared with 983 ± 1,569 norepinephrine equivalent in the placebo group, p value equals to 0.59. ICU length of stay was 2.29 days (interquartile range, 1.65–3.9 d) in the midodrine group, compared with 2.45 days (interquartile range, 1.6–3.2 d) in the placebo group, p value equals to 0.36. No serious adverse events were observed in either group. Conclusions: Phase II clinical trial powered for clinical outcomes (duration of vasopressor use, need for central venous catheter, and ICU and hospital length of stay) is justified.

Phylogenetic analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is focused on a single isolate of bat coronaviruses (bat CoVs) which does not adequately represent genetically related coronaviruses (CoVs) [...]

OBJECTIVES: To describe the outcomes of hospitalized patients in a multicenter, international coronavirus disease 2019 registry. DESIGN: Cross-sectional observational study including coronavirus disease 2019 patients hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between February 15, 2020, and November 30, 2020, according to age and type of organ support therapies. SETTING: About 168 hospitals in 16 countries within the Society of Critical Care Medicine’s Discovery Viral Infection and Respiratory Illness University Study coronavirus disease 2019 registry. PATIENTS: Adult hospitalized coronavirus disease 2019 patients who did and did not require various types and combinations of organ support (mechanical ventilation, renal replacement therapy, vasopressors, and extracorporeal membrane oxygenation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was hospital mortality. Secondary outcomes were discharge home with or without assistance and hospital length of stay. Risk-adjusted variation in hospital mortality for patients receiving invasive mechanical ventilation was assessed by using multilevel models with hospitals as a random effect, adjusted for age, race/ethnicity, sex, and comorbidities. Among 20,608 patients with coronavirus disease 2019, the mean (± sd ) age was 60.5 (±17), 11,1887 (54.3%) were men, 8,745 (42.4%) were admitted to the ICU, and 3,906 (19%) died in the hospital. Hospital mortality was 8.2% for patients receiving no organ support ( n = 15,001). The most common organ support therapy was invasive mechanical ventilation ( n = 5,005; 24.3%), with a hospital mortality of 49.8%. Mortality ranged from 40.8% among patients receiving only invasive mechanical ventilation ( n =1,749) to 71.6% for patients receiving invasive mechanical ventilation, vasoactive drugs, and new renal replacement therapy ( n = 655). Mortality was 39% for patients receiving extracorporeal membrane oxygenation ( n = 389). Rates of discharge home ranged from 73.5% for patients who did not require organ support therapies to 29.8% for patients who only received invasive mechanical ventilation, and 8.8% for invasive mechanical ventilation, vasoactive drugs, and renal replacement; 10.8% of patients older than 74 years who received invasive mechanical ventilation were discharged home. Median hospital length of stay for patients on mechanical ventilation was 17.1 days (9.7-28 d). Adjusted interhospital variation in mortality among patients receiving invasive mechanical ventilation was large (median odds ratio 1.69). CONCLUSIONS: Coronavirus disease 2019 prognosis varies by age and level of organ support. Interhospital variation in mortality of mechanically ventilated patients was not explained by patient characteristics and requires further evaluation.