Kaur, Nirmaljot

IMPORTANCE: Initial Society of Critical Care Medicine Discovery Viral Infection and Respiratory illness Universal Study (VIRUS) Registry analysis suggested that improvements in critical care processes offered the greatest modifiable opportunity to improve critically ill COVID-19 patient outcomes. OBJECTIVES: The Structured Team-based Optimal Patient-Centered Care for Virus COVID-19 ICU Collaborative was created to identify and speed implementation of best evidence based COVID-19 practices. DESIGN, SETTING, AND PARTICIPANTS: This 6-month project included volunteer interprofessional teams from VIRUS Registry sites, who received online training on the Checklist for Early Recognition and Treatment of Acute Illness and iNjury approach, a structured and systematic method for delivering evidence based critical care. Collaborators participated in weekly 1-hour videoconference sessions on high impact topics, monthly quality improvement (QI) coaching sessions, and received extensive additional resources for asynchronous learning. MAIN OUTCOMES AND MEASURES: Outcomes included learner engagement, satisfaction, and number of QI projects initiated by participating teams. RESULTS: Eleven of 13 initial sites participated in the Collaborative from March 2, 2021, to September 29, 2021. A total of 67 learners participated in the Collaborative, including 23 nurses, 22 physicians, 10 pharmacists, nine respiratory therapists, and three nonclinicians. Site attendance among the 11 sites in the 25 videoconference sessions ranged between 82% and 100%, with three sites providing at least one team member for 100% of sessions. The majority reported that topics matched their scope of practice (69%) and would highly recommend the program to colleagues (77%). A total of nine QI projects were initiated across three clinical domains and focused on improving adherence to established critical care practice bundles, reducing nosocomial complications, and strengthening patient- and family-centered care in the ICU. Major factors impacting successful Collaborative engagement included an engaged interprofessional team; an established culture of engagement; opportunities to benchmark performance and accelerate institutional innovation, networking, and acclaim; and ready access to data that could be leveraged for QI purposes. CONCLUSIONS AND RELEVANCE: Use of a virtual platform to establish a learning collaborative to accelerate the identification, dissemination, and implementation of critical care best practices for COVID-19 is feasible. Our experience offers important lessons for future collaborative efforts focused on improving ICU processes of care.

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.

OBJECTIVES: 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.

Background: Ketamine, a dissociative anesthetic, induces improvement in depressive symptoms by antagonizing glutaminergic NMDA receptors. Ketamine has been used previously in outpatient setting for treatment-resistant depression, but we showcase its utility in depression management at the Intensive Care Unit (ICU). Research Question: Can ketamine be used for depression treatment in ICU patients? Study Design and Methods: A retrospective chart review of ICU patients was done at a tertiary center from 2018 to 2021, to assess the ketamine usage. Among the patients reviewed, ketamine was used for depression in 12, and for analgesia & sedation in 2322 patients. Ketamine was administered in doses of 0.5mg/kg & 0.75mg/kg for depression. Each course consisted of 3 doses of ketamine administered over 3 days, and 7 in 12 patients received a single course of ketamine. The rest received 3–4 courses 1 week apart. Results: Ketamine was found to improve mood and affect in most of the patients with depression. 11 in 12 patients had a positive response with better sleep. It has a major advantage over conventional anti-depressants since it takes only a few hours to induce clinical improvement. Patients who were observably withdrawn from care team and family, were administered ketamine. Conclusion: A major drawback of ketamine is that the duration of clinical improvement is short, with the response lasting only up to seven days after a single dose. Hence, all the patients in our study were weaned off ketamine with a supporting antidepressant. Ketamine has been documented to cause cardio-neurotoxicity; however, only one patient had worsening lethargy in our study. To conclude, ketamine has a marked benefit in treating depression in the ICU. Although our study was associated with positive outcomes, there is a need for prospective studies with long-term follow-up assessments.

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 Pao 2/Fio 2 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.

IMPORTANCE: At the start of the coronavirus disease 2019 pandemic, medications repurposed for management of coronavirus disease 2019 were used in the absence of clinical trial evidence. OBJECTIVES: To describe the variation and evolution in use of repurposed medications for coronavirus disease 2019. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of adults hospitalized with coronavirus disease 2019 between February 15, 2020, and April 12, 2021, across 76 United States and international hospitals within the Society of Critical Care Medicine’s Discovery Viral Infection and Respiratory Illness Universal Study coronavirus disease 2019 registry. MAIN OUTCOMES AND MEASURES: Hospital variation was quantified using multivariable adjusted random effects logistic regression models and unsupervised clustering. Repurposed medications included antivirals, corticosteroids, hydroxychloroquine, immunomodulators, and therapeutic dose anticoagulants. RESULTS: Among 7,069 adults hospitalized with coronavirus disease 2019, 1,979 (28%) received antivirals, 2,876 (41%) received corticosteroids, 1,779 (25%) received hydroxychloroquine, 620 (9%) received immunomodulators, and 2,154 (31%) received therapeutic dose anticoagulants. Contribution of hospital site to risk-adjusted variation was 46% for antivirals, 30% for corticosteroids, 48% for hydroxychloroquine, 46% for immunomodulators, and 52% for therapeutic dose anticoagulants. Compared with the early pandemic, the later pandemic practice phenotypes converged with increased use of antivirals (odds ratio, 3.14; 95% CI, 2.40–4.10) and corticosteroids (odds ratio, 5.43; 95% CI, 4.23–6.97), with decreased use of hydroxychloroquine (odds ratio, 0.02; 95% CI, 0.01–0.04) and immunomodulators (odds ratio, 0.49; 95% CI, 0.34–0.70). There was no clinically significant change in the use of therapeutic dose anticoagulants (odds ratio, 1.01; 95% CI, 1.01–1.02). There were no differences in risk-adjusted mortality between hospitals with high rates of repurposed medication use compared with hospitals with low rates of use. CONCLUSIONS AND RELEVANCE: Hospital variation in the use of repurposed medications varied widely across hospitals early in the pandemic and later converged with the emergence of randomized clinical trials. Platforms developed for rapid activation and enrollment in clinical trials of repurposed medications are needed prior to the next pandemic to expedite effective, evidence-based practice.

Background: According to past studies, recovery and survival following severe vascular events such as acute myocardial infarction and stroke are negatively impacted by vitamin D deficiency. However, the national estimate on disability-related burden is unclear. We intend to evaluate the prevalence and outcomes of vitamin D deficiency (VDD) among patients with cardiovascular disease (CVD) and cerebrovascular disorder (CeVD). Methods: We performed a cross-sectional study on the Nationwide Inpatient Sample data (2016–2017) of adult (≥18 years) hospitalizations. We identified patients with a secondary diagnosis of VDD and a primary diagnosis of CVD and CeVD using the 9th revision of the International Classification of Diseases, clinical modification code (ICD-10-CM) codes. A univariate and mixed-effect multivariable survey logistic regression analysis was performed to evaluate the prevalence, disability, and discharge disposition of patients with CVD and CeVD in the presence of VDD. Results: Among 58,259,589 USA hospitalizations, 3.44%, 2.15%, 0.06%, 1.28%, 11.49%, 1.71%, 0.38%, 0.23%, and 0.08% had primary admission of IHD, acute MI, angina, AFib, CHF, AIS, TIA, ICeH, and SAH, respectively and 1.82% had VDD. The prevalence of hospitalizations due to CHF (14.66% vs. 11.43%), AIS (1.87% vs. 1.71%), and TIA (0.4% vs. 0.38%) was higher among VDD patients as compared with non-VDD patients (p < 0.0001). In a regression analysis, as compare with non-VDD patients, the VDD patients were associated with higher odds of discharge to non-home facilities with an admission diagnosis of CHF (aOR 1.08, 95% CI 1.07–1.09), IHD (aOR 1.24, 95% CI 1.21–1.28), acute MI (aOR 1.23, 95% CI 1.19–1.28), AFib (aOR 1.21, 95% CI 1.16–1.27), and TIA (aOR 1.19, 95% CI 1.11–1.28). VDD was associated with higher odds of severe or extreme disability among patients hospitalized with AIS (aOR 1.1, 95% CI 1.06–1.14), ICeH (aOR 1.22, 95% CI 1.08–1.38), TIA (aOR 1.36, 95% CI 1.25–1.47), IHD (aOR 1.37, 95% CI 1.33–1.41), acute MI (aOR 1.44, 95% CI 1.38–1.49), AFib (aOR 1.10, 95% CI 1.06–1.15), and CHF (aOR 1.03, 95% CI 1.02–1.05) as compared with non-VDD. Conclusions: CVD and CeVD in the presence of VDD increase the disability and discharge to non-home facilities among USA hospitalizations. Future studies should be planned to evaluate the effect of VDD replacement for improving outcomes.

Introduction: Previous studies had provided evidence that vitamin D deficiency is a strong negative predictor for survival and recovery after severe vascular events but national estimate on disability related burden is not clear. Hypothesis: We evaluate the prevalence of vitamin D deficiency (VDD) amongst patients with cardiovascular disease (CVD) and cerebrovascular disorders (CeVD) and to find out whether or not CVD and CeVD in the presence of VDD increases the disability. Methods: We performed a retrospective analysis of the Nationwide Inpatient Sample data (years 2016-2017) in adults (≥18 years) hospitalizations. We identified patients with secondary diagnosis of VDD and primary diagnosis of CVD (AFib, CHF, IHD, acute MI, and angina) and CeVD (AIS, TIA, ICeH and SAH) using ICD-10-CM codes. We performed a chi-square test and multivariable survey logistic regression to analyze disability of patients with CVD and CeVD in presence of VDD. Disability/loss of function was investigated by APRDRGs severity using 3M Health Information Systems software. (Score 1-4 indicates minor to extreme loss of function) Results: Among 58,259,589 US hospitalizations, 3.44%, 2.15%, 0.06%, 1.28%, 11.49%, 1.71%, 0.38%, 0.23% and 0.08% had primary admission of IHD, acute MI, angina, AFib, CHF, AIS, TIA, ICeH and SAH, respectively and 1.82% had VDD. Prevalence of hospitalizations due to CHF (14.66% vs 11.43%), AIS (1.87% vs 1.71%) and TIA (0.4% vs 0.38%) was higher; and IHD (2.62% vs 3.45%), acute MI (1.58% vs 2.16), angina (0.05% vs 0.06%), AFib (1.14% vs 1.28%), ICeH (0.17% vs 0.23%) and SAH (0.05% vs 0.08%) was lower among VDD patients in compare to non-VDD. (p<0.0001) In regression analysis, VDD was associated with higher odds of severe or extreme disability amongst patients hospitalized with AIS (OR:1.1; 95%CI:1.06-1.14), ICeH (1.22; 1.08-1.39), TIA (1.36; 1.25-1.47), IHD (1.37; 1.33-1.41), acute MI (1.44; 1.38-1.49), Afib (1.10; 1.06-1.15), and CHF (1.03; 1.02-1.05) in comparison to without VDD. Conclusions: CVD and CeVD in presence of VDD increase the disability amongst US hospitalizations. Future studies should be planned to evaluate the discharge outcomes as well as the effect of identification and in-hospital management of VDD on improvement of the outcomes.