Triage and Ongoing Care for Critically Ill Patients in the Emergency Department: Results from a National Survey of Emergency Physicians

Introduction: We conducted a cross-sectional study at the Icahn School of Medicine at Mount Sinai to elicit emergency physician (EP) perceptions regarding intensive care unit (ICU) triage decisions and ongoing management for boarding of ICU patients in the emergency department (ED). We assessed factors influencing the disposition decision for critically ill patients in the ED to characterize EPs’ perceptions about ongoing critical care delivery in the ED while awaiting ICU admission.Methods: Through content expert review and pilot testing, we iteratively developed a 25-item written survey targeted to EPs, eliciting current ICU triage structure, opinions on factors influencing ICU admission decisions, and views on caring for critically ill patients “boarding” in the ED for >4-6 hours.Results: We approached 732 EPs at a large, national emergency medicine conference, achieving 93.6% response and completion rate, with 54% academic and 46% community participants. One-fifth reported having formal ICU admission criteria, although only 36.6% reported adherence. Common factors influencing EPs’ ICU triage decisions were illness severity (91.1%), ICU interventions needed (87.6%), and diagnosis (68.2%), while ICU bed availability (13.5%) and presence of other critically ill patients in ED (10.2%) were less or not important. While 72.1% reported frequently caring for ICU boarders, respondents identified high patient volume (61.3%) and inadequate support staffing (48.6%) as the most common challenges in caring for boarding ICU patients.Conclusion: Patient factors (eg, diagnosis, illness severity) were seen as more important than system factors (eg, bed availability) in triaging ED patients to the ICU. Boarding ICU patients is a common challenge for more than two-thirds of EPs, exacerbated by ED volume and staffing constraints

Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US

Importance: The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19. Objectives: To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19. Design, Setting, and Participants: This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020. Exposures: Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds. Main Outcomes and Measures: The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes. Results: A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (≥80 vs <40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (≥40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (Pao2:Fio2<100 vs ≥300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2 vs 0: OR, 2.61; 95% CI, 1.30–5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46–4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs ≥100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies. Conclusions and Relevance: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.Dr. Gupta reported receiving grants from the National Institutes of Health (NIH) and is a scientific coordinator for GlaxoSmithKline’s ASCEND (Anemia Studies in Chronic Kidney Disease: Erythropoiesis via a Novel Prolyl Hydroxylase Inhibitor Daprodustat) trial. Dr. Chan reported receiving grants from the Renal Research Institute outside the submitted work. Dr. Mathews reported receiving grants from the NIH/National Heart, Lung, and Blood Institute (NHLBI) during the conduct of the study and serves on the steering committee for the BREATHE trial (Breathing Retraining for Asthma–Trial of Home Exercises), funded by Roivant/Kinevant Sciences. Dr. Melamed reported receiving honoraria from the American Board of Internal Medicine and Icon Medical Consulting. Dr. Reiser reported receiving personal fees from Biomarin, TRISAQ, Thermo BCT, Astellas, Massachusetts General Hospital, Genentech, UptoDate, Merck, Inceptionsci, GLG, and Clearview and grants from the NIH and Nephcure outside the submitted work. Dr. Srivastava reported receiving personal fees from Horizon Pharma PLC, AstraZeneca, and CVS Caremark outside the submitted work. Dr. Vijayan reported receiving personal fees from NxStage, Boeringer Ingelheim, and Sanofi outside the submitted work. Dr. Velez reported receiving personal fees from Mallinckrodt Pharmaceuticals, Retrophin, and Otsuka Pharmaceuticals outside the submitted work. Dr. Shaefi reported receiving grants from the NIH/National Institute on Aging and NIH/National Institute of General Medical Sciences outside the submitted work. Dr. Admon reported receiving grants from the NIH/NHLBI during the conduct of the study. Dr. Donnelly reported receiving grants from the NIH/NHLBI during the conduct of the study and personal fees from the American College of Emergency Physicians/Annals of Emergency Medicine outside the submitted work. Dr. Hernán reported receiving grants from the NIH during the conduct of the study. Dr. Semler reported receiving grants from the NIH/NHLBI during the conduct of the study. No other disclosures were reported

Intravenous Aviptadil and Remdesivir for Treatment of COVID-19-Associated Hypoxaemic Respiratory Failure in the USA (Tesico): A Randomised, Placebo-Controlled Trial

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure. METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly assigned to both study treatments in a 2 × 2 factorial design or to just one of the agents. Participants were randomly assigned with a web-based application. For each site, randomisation was stratified by disease severity (high-flow nasal oxygen or non-invasive ventilation vs invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and four strata were defined by remdesivir and aviptadil eligibility, as follows: (1) eligible for randomisation to aviptadil and remdesivir in the 2 × 2 factorial design; participants were equally randomly assigned (1:1:1:1) to intravenous aviptadil plus remdesivir, aviptadil plus remdesivir matched placebo, aviptadil matched placebo plus remdesvir, or aviptadil placebo plus remdesivir placebo; (2) eligible for randomisation to aviptadil only because remdesivir was started before randomisation; (3) eligible for randomisation to aviptadil only because remdesivir was contraindicated; and (4) eligible for randomisation to remdesivir only because aviptadil was contraindicated. For participants in strata 2-4, randomisation was 1:1 to the active agent or matched placebo. Aviptadil was administered as a daily 12-h infusion for 3 days, targeting 600 pmol/kg on infusion day 1, 1200 pmol/kg on day 2, and 1800 pmol/kg on day 3. Remdesivir was administered as a 200 mg loading dose, followed by 100 mg daily maintenance doses for up to a 10-day total course. For participants assigned to placebo for either agent, matched saline placebo was administered in identical volumes. For both treatment comparisons, the primary outcome, assessed at day 90, was a six-category ordinal outcome: (1) at home (defined as the type of residence before hospitalisation) and off oxygen (recovered) for at least 77 days, (2) at home and off oxygen for 49-76 days, (3) at home and off oxygen for 1-48 days, (4) not hospitalised but either on supplemental oxygen or not at home, (5) hospitalised or in hospice care, or (6) dead. Mortality up to day 90 was a key secondary outcome. The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility. On June 9, 2022, the sponsor stopped the trial of remdesivir due to slow enrolment. The trial is registered with ClinicalTrials.gov, NCT04843761. FINDINGS: Between April 21, 2021, and May 24, 2022, we enrolled 473 participants in the study. For the aviptadil comparison, 471 participants were randomly assigned to aviptadil or matched placebo. The modified intention-to-treat population comprised 461 participants who received at least a partial infusion of aviptadil (231 participants) or aviptadil matched placebo (230 participants). For the remdesivir comparison, 87 participants were randomly assigned to remdesivir or matched placebo and all received some infusion of remdesivir (44 participants) or remdesivir matched placebo (43 participants). 85 participants were included in the modified intention-to-treat analyses for both agents (ie, those enrolled in the 2 x 2 factorial). For the aviptadil versus placebo comparison, the median age was 57 years (IQR 46-66), 178 (39%) of 461 participants were female, and 246 (53%) were Black, Hispanic, Asian or other (vs 215 [47%] White participants). 431 (94%) of 461 participants were in an intensive care unit at baseline, with 271 (59%) receiving high-flow nasal oxygen or non-invasive ventiliation, 185 (40%) receiving invasive mechanical ventilation, and five (1%) receiving ECMO. The odds ratio (OR) for being in a better category of the primary efficacy endpoint for aviptadil versus placebo at day 90, from a model stratified by baseline disease severity, was 1·11 (95% CI 0·80-1·55; p=0·54). Up to day 90, 86 participants in the aviptadil group and 83 in the placebo group died. The cumulative percentage who died up to day 90 was 38% in the aviptadil group and 36% in the placebo group (hazard ratio 1·04, 95% CI 0·77-1·41; p=0·78). The primary safety outcome of death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group (OR 1·40, 95% CI 0·94-2·08; p=0·10). INTERPRETATION: Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo. The smaller than planned sample size for the remdesivir trial did not permit definitive conclusions regarding safety or efficacy. FUNDING: National Institutes of Health

Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19

Importance: Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness. Objective: To test whether tocilizumab decreases mortality in this population. Design, Setting, and Participants: The data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding. Exposures: Treatment with tocilizumab in the first 2 days of ICU admission. Main Outcomes and Measures: Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences. Results: Among the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of <200 mm Hg) than patients not treated with tocilizumab. After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups. A total of 1544 patients (39.3%) died, including 125 (28.9%) treated with tocilizumab and 1419 (40.6%) not treated with tocilizumab. In the primary analysis, during a median follow-up of 27 (IQR, 14-37) days, patients treated with tocilizumab had a lower risk of death compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56-0.92). The estimated 30-day mortality was 27.5% (95% CI, 21.2%-33.8%) in the tocilizumab-treated patients and 37.1% (95% CI, 35.5%-38.7%) in the non-tocilizumab–treated patients (risk difference, 9.6%; 95% CI, 3.1%-16.0%). Conclusions and Relevance: Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.The writing committee was supported by grants F32HL149337 (Dr. Admon), K23DK120811 (Dr. Srivastava), R01HL085757 (Dr. Parikh), R01HL144566 and R01DK125786 (Dr. Leaf), K12HL138039 (Dr. Donnelly), K23HL130648 (Dr. Mathews), R37AI102634 (Dr. Hernán), F32DC017342 (Dr. Gupta), K08GM134220 and R03AG060179 (Dr. Shaefi), K23HL143053 (Dr. Semler), and R01HL153384 (Dr. Hayek) from the NIH and grant U-M G024231 from the Frankel Cardiovascular Center COVID-19: Impact Research Ignitor (Dr. Hayek)

Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Background: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). Objective: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. Design: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. Setting: 67 hospitals in the United States. Participants: Adults with COVID-19 admitted to a participating ICU. Measurements: Time to death, censored at hospital discharge, or date of last follow-up. Results: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). Limitation: Observational design. Conclusion: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation

The Boarding Patient: Effects of ICU and Hospital Occupancy Surges on Patient Flow

Patients admitted to a hospital's intensive care unit (ICU) often endure prolonged boarding within the ICU following receipt of care, unnecessarily occupying a critical care bed, and thereby delaying admission for other incoming patients due to bed shortage. Using patient-level data over two years at two major academic medical centers, we estimate the impact of ICU and ward occupancy levels on ICU length of stay (LOS), and test whether simultaneous "surge occupancy" in both areas impacts overall ICU length of stay. In contrast to prior studies that only measure total LOS, we split LOS into two individual periods based on physician requests for bed transfers. We find that "service time" (when critically ill patients are stabilized and treated) is unaffected by occupancy levels. However, the less essential "boarding time" (when patients wait to exit the ICU) is accelerated during periods of high ICU occupancy and, conversely, prolonged when hospital ward occupancy levels are high. When the ICU and wards simultaneously encounter bed occupancies in the top quartile of historical levels-which occurs 5% of the time-ICU boarding increases by 22% compared to when both areas experience their lowest utilization, suggesting that ward bed availability dominates efforts to accelerate ICU discharges to free up ICU beds. We find no adverse effects of high occupancy levels on ICU bouncebacks, in-hospital deaths, or 30-day hospital readmissions, which supports our finding that the largely discretionary boarding period fluctuates with changing bed occupancy levels

A Conceptual Framework for Improving Critical Care Patient Flow and Bed Use.

RationaleHigh demand for intensive care unit (ICU) services and limited bed availability have prompted hospitals to address capacity planning challenges. Simulation modeling can examine ICU bed assignment policies, accounting for patient acuity, to reduce ICU admission delays.ObjectivesTo provide a framework for data-driven modeling of ICU patient flow, identify key measurable outcomes, and present illustrative analysis demonstrating the impact of various bed allocation scenarios on outcomes.MethodsA description of key inputs for constructing a queuing model was outlined, and an illustrative simulation model was developed to reflect current triage protocol within the medical ICU and step-down unit (SDU) at a single tertiary-care hospital. Patient acuity, arrival rate, and unit length of stay, consisting of a "service time" and "time to transfer," were estimated from 12 months of retrospective data (n = 2,710 adult patients) for 36 ICU and 15 SDU staffed beds. Patient priority was based on acuity and whether the patient originated in the emergency department. The model simulated the following hypothetical scenarios: (1) varied ICU/SDU sizes, (2) reserved ICU beds as a triage strategy, (3) lower targets for time to transfer out of the ICU, and (4) ICU expansion by up to four beds. Outcomes included ICU admission wait times and unit occupancy.Measurements and main resultsWith current bed allocation, simulated wait time averaged 1.13 (SD, 1.39) hours. Reallocating all SDU beds as ICU decreased overall wait times by 7.2% to 1.06 (SD, 1.39) hours and increased bed occupancy from 80 to 84%. Reserving the last available bed for acute patients reduced wait times for acute patients from 0.84 (SD, 1.12) to 0.31 (SD, 0.30) hours, but tripled subacute patients' wait times from 1.39 (SD, 1.81) to 4.27 (SD, 5.44) hours. Setting transfer times to wards for all ICU/SDU patients to 1 hour decreased wait times for incoming ICU patients, comparable to building one to two additional ICU beds.ConclusionsHospital queuing and simulation modeling with empiric data inputs can evaluate how changes in ICU bed assignment could impact unit occupancy levels and patient wait times. Trade-offs associated with dedicating resources for acute patients versus expanding capacity for all patients can be examined

A Conceptual Framework for Improving Critical Care Patient Flow and Bed Use.

RationaleHigh demand for intensive care unit (ICU) services and limited bed availability have prompted hospitals to address capacity planning challenges. Simulation modeling can examine ICU bed assignment policies, accounting for patient acuity, to reduce ICU admission delays.ObjectivesTo provide a framework for data-driven modeling of ICU patient flow, identify key measurable outcomes, and present illustrative analysis demonstrating the impact of various bed allocation scenarios on outcomes.MethodsA description of key inputs for constructing a queuing model was outlined, and an illustrative simulation model was developed to reflect current triage protocol within the medical ICU and step-down unit (SDU) at a single tertiary-care hospital. Patient acuity, arrival rate, and unit length of stay, consisting of a "service time" and "time to transfer," were estimated from 12 months of retrospective data (n = 2,710 adult patients) for 36 ICU and 15 SDU staffed beds. Patient priority was based on acuity and whether the patient originated in the emergency department. The model simulated the following hypothetical scenarios: (1) varied ICU/SDU sizes, (2) reserved ICU beds as a triage strategy, (3) lower targets for time to transfer out of the ICU, and (4) ICU expansion by up to four beds. Outcomes included ICU admission wait times and unit occupancy.Measurements and main resultsWith current bed allocation, simulated wait time averaged 1.13 (SD, 1.39) hours. Reallocating all SDU beds as ICU decreased overall wait times by 7.2% to 1.06 (SD, 1.39) hours and increased bed occupancy from 80 to 84%. Reserving the last available bed for acute patients reduced wait times for acute patients from 0.84 (SD, 1.12) to 0.31 (SD, 0.30) hours, but tripled subacute patients' wait times from 1.39 (SD, 1.81) to 4.27 (SD, 5.44) hours. Setting transfer times to wards for all ICU/SDU patients to 1 hour decreased wait times for incoming ICU patients, comparable to building one to two additional ICU beds.ConclusionsHospital queuing and simulation modeling with empiric data inputs can evaluate how changes in ICU bed assignment could impact unit occupancy levels and patient wait times. Trade-offs associated with dedicating resources for acute patients versus expanding capacity for all patients can be examined