Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalization Among Immunocompetent Adults Aged ≥18 Years - VISION and IVY Networks, September 2023-January 2024.

In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. However, few estimates of updated vaccine effectiveness (VE) against medically attended illness are available. This analysis evaluated VE of an updated COVID-19 vaccine dose against COVID-19-associated emergency department (ED) or urgent care (UC) encounters and hospitalization among immunocompetent adults aged ≥18 years during September 2023-January 2024 using a test-negative, case-control design with data from two CDC VE networks. VE against COVID-19-associated ED/UC encounters was 51% (95% CI = 47%-54%) during the first 7-59 days after an updated dose and 39% (95% CI = 33%-45%) during the 60-119 days after an updated dose. VE estimates against COVID-19-associated hospitalization from two CDC VE networks were 52% (95% CI = 47%-57%) and 43% (95% CI = 27%-56%), with a median interval from updated dose of 42 and 47 days, respectively. Updated COVID-19 vaccine provided increased protection against COVID-19-associated ED/UC encounters and hospitalization among immunocompetent adults. These results support CDC recommendations for updated 2023-2024 COVID-19 vaccination. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccine.

Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients With COVID-19: COVID-PACT.

BACKGROUND: The efficacy and safety of prophylactic full-dose anticoagulation and antiplatelet therapy in critically ill COVID-19 patients remain uncertain. METHODS: COVID-PACT (Prevention of Arteriovenous Thrombotic Events in Critically-ill COVID-19 Patients Trial) was a multicenter, 2×2 factorial, open-label, randomized-controlled trial with blinded end point adjudication in intensive care unit-level patients with COVID-19. Patients were randomly assigned to a strategy of full-dose anticoagulation or standard-dose prophylactic anticoagulation. Absent an indication for antiplatelet therapy, patients were additionally randomly assigned to either clopidogrel or no antiplatelet therapy. The primary efficacy outcome was the hierarchical composite of death attributable to venous or arterial thrombosis, pulmonary embolism, clinically evident deep venous thrombosis, type 1 myocardial infarction, ischemic stroke, systemic embolic event or acute limb ischemia, or clinically silent deep venous thrombosis, through hospital discharge or 28 days. The primary efficacy analyses included an unmatched win ratio and time-to-first event analysis while patients were on treatment. The primary safety outcome was fatal or life-threatening bleeding. The secondary safety outcome was moderate to severe bleeding. Recruitment was stopped early in March 2022 (≈50% planned recruitment) because of waning intensive care unit-level COVID-19 rates. RESULTS: At 34 centers in the United States, 390 patients were randomly assigned between anticoagulation strategies and 292 between antiplatelet strategies (382 and 290 in the on-treatment analyses). At randomization, 99% of patients required advanced respiratory therapy, including 15% requiring invasive mechanical ventilation; 40% required invasive ventilation during hospitalization. Comparing anticoagulation strategies, a greater proportion of wins occurred with full-dose anticoagulation (12.3%) versus standard-dose prophylactic anticoagulation (6.4%; win ratio, 1.95 [95% CI, 1.08-3.55]; P=0.028). Results were consistent in time-to-event analysis for the primary efficacy end point (full-dose versus standard-dose incidence 19/191 [9.9%] versus 29/191 [15.2%]; hazard ratio, 0.56 [95% CI, 0.32-0.99]; P=0.046). The primary safety end point occurred in 4 (2.1%) on full dose and in 1 (0.5%) on standard dose (P=0.19); the secondary safety end point occurred in 15 (7.9%) versus 1 (0.5%; P=0.002). There was no difference in all-cause mortality (hazard ratio, 0.91 [95% CI, 0.56-1.48]; P=0.70). There were no differences in the primary efficacy or safety end points with clopidogrel versus no antiplatelet therapy. CONCLUSIONS: In critically ill patients with COVID-19, full-dose anticoagulation, but not clopidogrel, reduced thrombotic complications with an increase in bleeding, driven primarily by transfusions in hemodynamically stable patients, and no apparent excess in mortality. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04409834.

Society of Critical Care Medicine Clinical Practice Guidelines for Rapid Sequence Intubation in the Critically Ill Adult Patient.

RATIONALE: Controversies and practice variations exist related to the pharmacologic and nonpharmacologic management of the airway during rapid sequence intubation (RSI). OBJECTIVES: To develop evidence-based recommendations on pharmacologic and nonpharmacologic topics related to RSI. DESIGN: A guideline panel of 20 Society of Critical Care Medicine members with experience with RSI and emergency airway management met virtually at least monthly from the panel's inception in 2018 through 2020 and face-to-face at the 2020 Critical Care Congress. The guideline panel included pharmacists, physicians, a nurse practitioner, and a respiratory therapist with experience in emergency medicine, critical care medicine, anesthesiology, and prehospital medicine; consultation with a methodologist and librarian was available. A formal conflict of interest policy was followed and enforced throughout the guidelines-development process. METHODS: Panelists created Population, Intervention, Comparison, and Outcome (PICO) questions and voted to select the most clinically relevant questions for inclusion in the guideline. Each question was assigned to a pair of panelists, who refined the PICO wording and reviewed the best available evidence using predetermined search terms. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used throughout and recommendations of "strong" or "conditional" were made for each PICO question based on quality of evidence and panel consensus. Recommendations were provided when evidence was actionable; suggestions, when evidence was equivocal; and best practice statements, when the benefits of the intervention outweighed the risks, but direct evidence to support the intervention did not exist. RESULTS: From the original 35 proposed PICO questions, 10 were selected. The RSI guideline panel issued one recommendation (strong, low-quality evidence), seven suggestions (all conditional recommendations with moderate-, low-, or very low-quality evidence), and two best practice statements. The panel made two suggestions for a single PICO question and did not make any suggestions for one PICO question due to lack of evidence. CONCLUSIONS: Using GRADE principles, the interdisciplinary panel found substantial agreement with respect to the evidence supporting recommendations for RSI. The panel also identified literature gaps that might be addressed by future research.

Perceived Hospital Stress, Severe Acute Respiratory Syndrome Coronavirus 2 Activity, and Care Process Temporal Variance During the COVID-19 Pandemic.

OBJECTIVES: The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity. DESIGN: Prospective weekly hospital stress survey, November 2020-June 2022. SETTING: Society of Critical Care Medicine's Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study. SUBJECTS: Thirteen hospitals across seven U.S. health systems. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% ( sd , 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82; p < 0.0001) but only moderately correlated with ED stress (ρ = 0.52; p < 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5-12%), 7% (3-10%), and 4% (2-6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9-14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk [6-14 wk] after local case peak; p = 0.59) while the resolution of ED stress (median 6 wk [5-6 wk] after local case peak; p = 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge. CONCLUSIONS: During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked.

SARS-CoV-2 infection increases risk of acute kidney injury in a bimodal age distribution.

BACKGROUND: Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern. METHODS: Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, and clustering within centers. Sensitivity analyses assessed different baseline creatinine estimators. RESULTS: Overall, among 6874 hospitalized patients, 39.6% (n = 2719) developed AKI. There was a bimodal distribution of AKI by age with peaks in older age (≥60 years) and middle childhood (5-15 years), which persisted despite controlling for illness severity, pre-existing comorbidities, or different baseline creatinine estimators. For example, the adjusted OR of developing AKI among hospitalized patients with SARS-CoV2 was 2.74 (95% CI 1.66-4.56) for 10-15-year-olds compared to 30-35-year-olds and similarly was 2.31 (95% CI 1.71-3.12) for 70-75-year-olds, while adjusted OR dropped to 1.39 (95% CI 0.97-2.00) for 40-45-year-olds compared to 30-35-year-olds. CONCLUSIONS: SARS-CoV2-related AKI is common with a bimodal age distribution that is not fully explained by known risk factors or confounders. As the pandemic turns to disproportionately impacting younger individuals, this deserves further investigation as the presence of AKI and SARS-CoV2 infection increases hospital mortality risk.

Comparison of a Novel Rapid Lateral Flow Assay to Enzyme Immunoassay Results for Early Diagnosis of Coccidioidomycosis.

BACKGROUND: Coccidioidomycosis (CM) is a common cause of community-acquired pneumonia where CM is endemic. Manifestations include self-limited pulmonary infection, chronic fibrocavitary pulmonary disease, and disseminated coccidioidomycosis. Most infections are identified by serological assays including enzyme-linked immunoassay (EIA), complement fixation, and immunodiffusion. These are time-consuming and take days to result, impeding early diagnosis. A new lateral flow assay (LFA; Sona; IMMY, Norman, OK) improves time-to-result to 1 hour. METHODS: We prospectively enrolled 392 patients with suspected CM, compared the LFA with standard EIA and included procalcitonin evaluation. RESULTS: Compared with standard EIA, LFA demonstrates 31% sensitivity (95% confidence interval [CI], 20-44%) and 92% specificity (95% CI, 88-95%). Acute pulmonary disease (74%) was the most common clinical syndrome. Hospitalized patients constituted 75% of subjects, and compared with outpatients, they more frequently had ≥3 previous healthcare facility visits (P = .05), received antibacterials (P < .01), and had >3 antibacterial courses (P < .01). Procalcitonin (PCT) was <0.25 ng/mL in 52 (83%) EIA-positive patients, suggesting infection was not bacterial. CONCLUSIONS: When CM is a possible diagnosis, LFA identified nearly one-third of EIA-positive infections. Combined with PCT <0.25 ng/mL, LFA could reduce unnecessary antibacterial use by 77%.

Healthcare disparities among anticoagulation therapies for severe COVID-19 patients in the multi-site VIRUS registry.

Here we analyze hospitalized andintensive care unit coronavirus disease 2019 (COVID-19) patient outcomes from the international VIRUS registry (https://clinicaltrials.gov/ct2/show/NCT04323787). We find that COVID-19 patients administered unfractionated heparin but not enoxaparin have a higher mortality-rate (390 of 1012 = 39%) compared to patients administered enoxaparin but not unfractionated heparin (270 of 1939 = 14%), presenting a risk ratio of 2.79 (95% confidence interval [CI]: [2.42, 3.16]; p = 4.45e-52). This difference persists even after balancing on a number of covariates including demographics, comorbidities, admission diagnoses, and method of oxygenation, with an increased mortality rate on discharge from the hospital of 37% (268 of 733) for unfractionated heparin versus 22% (154 of 711) for enoxaparin, presenting a risk ratio of 1.69 (95% CI: [1.42, 2.00]; p = 1.5e-8). In these balanced cohorts, a number of complications occurred at an elevated rate for patients administered unfractionated heparin compared to patients administered enoxaparin, including acute kidney injury, acute cardiac injury, septic shock, and anemia. Furthermore, a higher percentage of Black/African American COVID patients (414 of 1294 [32%]) were noted to receive unfractionated heparin compared to White/Caucasian COVID patients (671 of 2644 [25%]), risk ratio 1.26 (95% CI: [1.14, 1.40]; p = 7.5e-5). After balancing upon available clinical covariates, this difference in anticoagulant use remained statistically significant (311 of 1047 [30%] for Black/African American vs. 263 of 1047 [25%] for White/Caucasian, p = .02, risk ratio 1.18; 95% CI: [1.03, 1.36]). While retrospective studies cannot suggest any causality, these findings motivate the need for follow-up prospective research into the observed racial disparity in anticoagulant use and outcomes for severe COVID-19 patients.

Evaluation and Management of the Physiologically Difficult Airway: Consensus Recommendations From Society for Airway Management.

Multiple international airway societies have created guidelines for the management of the difficult airway. In critically ill patients, there are physiologic derangements beyond inadequate airway protection or hypoxemia. These risk factors contribute to the "physiologically difficult airway" and are associated with complications including cardiac arrest and death. Importantly, they are largely absent from international guidelines. Thus, we created management recommendations for the physiologically difficult airway to provide practical guidance for intubation in the critically ill. Through multiple rounds of in-person and telephone conferences, a multidisciplinary working group of 12 airway specialists (Society for Airway Management's Special Projects Committee) over a time period of 3 years (2016-2019) reviewed airway physiology topics in a modified Delphi fashion. Consensus agreement with the following recommendations among working group members was generally high with 80% of statements showing agreement within a 10% range on a sliding scale from 0% to 100%. We limited the scope of this analysis to reflect the resources and systems of care available to out-of-operating room adult airway providers. These recommendations reflect the practical application of physiologic principles to airway management available during the analysis time period.

Tracheal Intubation in the Critically Ill. Where We Came from and Where We Should Go.

Tracheal intubation is commonly performed in critically ill patients. Unfortunately, this procedure also carries a high risk of complications; half of critically ill patients with difficult airways experience life-threatening complications. The high complication rates stem from difficulty with laryngoscopy and tube placement, consequences of physiologic derangement, and human factors, including failure to recognize and reluctance to manage the failed airway. The last 10 years have seen a rapid expansion in devices available that help overcome anatomic difficulties with laryngoscopy and provide rescue oxygenation in the setting of failed attempts. Recent research in critically ill patients has highlighted other important considerations for critically ill patients and evaluated interventions to reduce the risks with repeated attempts, desaturation, and cardiovascular collapse during emergency airway management. There are three actions that should be implemented to reduce the risk of danger: 1) preintubation assessment for potential difficulty (e.g., MACOCHA score); 2) preparation and optimization of the patient and team for difficulty-including using a checklist, acquiring necessary equipment, maximizing preoxygenation, and hemodynamic optimization; and 3) recognition and management of failure to restore oxygenation and reduce the risk of cardiopulmonary arrest. This review describes the history of emergency airway management and explores the challenges with modern emergency airway management in critically ill patients. We offer clinically relevant recommendations on the basis of current evidence, guidelines, and expert opinion.

High-Flow Oxygen Therapy Concepts: Time to Standardize Nomenclature and Avoid Confusion.

High-flow nasal oxygen systems are rapidly being adopted as an initial noninvasive treatment for acute respiratory failure. However, the term "high-flow nasal cannula" is nonspecific and leads to imprecise communication between physicians, respiratory therapists, and nurses with the potential for patient harm. In this viewpoint and a brief review of the technology, we argue for a change in nomenclature in order to reduce the chance for future clinical, administrative, and research misunderstanding surrounding high-flow nasal oxygen systems.

Management of Patients with Predicted Difficult Airways in an Academic Emergency Department.

BACKGROUND: Patients with difficult airways are sometimes encountered in the emergency department (ED), however, there is a little data available regarding their management. OBJECTIVES: To determine the incidence, management, and outcomes of patients with predicted difficult airways in the ED. METHODS: Over the 1-year period from July 1, 2015 to June 30, 2016, data were prospectively collected on all patients intubated in an academic ED. After each intubation, the operator completed an airway management data form. Operators performed a pre-intubation difficult airway assessment and classified patients into routine, challenging, or difficult airways. All non-arrest patients were included in the study. RESULTS: There were 456 patients that met inclusion criteria. Fifty (11%) had predicted difficult airways. In these 50 patients, neuromuscular blocking agents (NMBAs) were used in 40 (80%), an awake intubation technique with light sedation was used in 7 (14%), and no medications were used in 3 (6%). In the 40 difficult airway patients who underwent NMBA facilitated intubation, a video laryngoscope (GlideScope 21, Verathon, Bothell, WA and C-MAC 19, Karl Storz, Tuttlingen, Germany) was used in each of these, with a first-pass success of 90%. In the 7 patients who underwent awake intubation, a video laryngoscope was used in 5, and a flexible fiberoptic scope was used in 2. Ketamine was used in 6 of the awake intubations. None of these difficult airway patients required rescue with a surgical airway. CONCLUSIONS: Difficult airways were predicted in 11% of non-arrest patients requiring intubation in the ED, the majority of which were managed using an NMBA and a video laryngoscope with a high first-pass success.

The Utility of the C-MAC as a Direct Laryngoscope for Intubation in the Emergency Department.

BACKGROUND: Although the C-MAC (Karl Storz, Tuttlingen, Germany) is a video laryngoscope (VL), it can also be used as a direct laryngoscope (DL). OBJECTIVE: The goal of this study was to evaluate the utility of the C-MAC as a DL for intubations in the emergency department (ED). METHODS: This was an analysis of prospectively collected continuous quality-improvement data during the 6-year period from February 1, 2009 to January 31, 2015, when both the C-MAC and Macintosh DL (Mac DL) were clinically available in our ED. This analysis included adult patients who underwent rapid sequence intubation by an emergency medicine resident in the ED with a C-MAC initially used as a DL or a Mac DL. The primary outcome measure was the first pass success (FPS). RESULTS: When the C-MAC was used as a DL, the initial DL attempt was successful in 199 of 346 (57.6%) cases. When the attempt could not be completed using the C-MAC as a DL, the operator utilized the video monitor and successfully completed the intubation using VL in 104 of 134 (77.6%) cases, thus achieving an overall FPS of 303 of 346 (87.6%). When the Mac DL was used, the FPS was 505 of 671 (75.3%). CONCLUSIONS: The C-MAC is a useful device for DL because in the event of a failed DL attempt, operators have the option of switching to the video monitor to successfully complete the intubation using VL without having to make a second attempt.

Ventilator Strategies and Rescue Therapies for Management of Acute Respiratory Failure in the Emergency Department.

Acute respiratory failure is commonly encountered in the emergency department (ED), and early treatment can have effects on long-term outcome. Noninvasive ventilation is commonly used for patients with respiratory failure and has been demonstrated to improve outcomes in acute exacerbations of chronic obstructive lung disease and congestive heart failure, but should be used carefully, if at all, in the management of asthma, pneumonia, and acute respiratory distress syndrome. Lung-protective tidal volumes should be used for all patients receiving mechanical ventilation, and FiO2 should be reduced after intubation to achieve a goal of less than 60%. For refractory hypoxemia, new rescue therapies have emerged to help improve the oxygenation, and in some cases mortality, and should be considered in ED patients when necessary, as deferring until ICU admission may be deleterious. This review article summarizes the pathophysiology of acute respiratory failure, management options, and rescue therapies including airway pressure release ventilation, continuous neuromuscular blockade, inhaled nitric oxide, and extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) for critically ill adults in the emergency department: history, current applications, and future directions.

Extracorporeal membrane oxygenation (ECMO) is a mode of extracorporeal life support that augments oxygenation, ventilation and/or cardiac output via cannulae connected to a circuit that pumps blood through an oxygenator and back into the patient. ECMO has been used for decades to support cardiopulmonary disease refractory to conventional therapy. While not robust, there are promising data for the use of ECMO in acute hypoxemic respiratory failure, cardiac arrest, and cardiogenic shock and the potential indications for ECMO continue to increase. This review discusses the existing literature on the potential use of ECMO in critically ill patients within the emergency department.

A comparison of video laryngoscopy to direct laryngoscopy for the emergency intubation of trauma patients.

BACKGROUND: Direct laryngoscopy (DL) has long been the gold standard for tracheal intubation in emergency and trauma patients. Video laryngoscopy (VL) is increasingly used in many settings and the purpose of this study was to compare its effectiveness to direct laryngoscopy in trauma patients. Our hypothesis was that the success rate of VL would be higher than that of DL. METHODS: Data were collected prospectively on all trauma patients, from January 2008 to June 2011, who were intubated emergently in an academic level I trauma center. After intubation, the physician that performed the intubation completed a structured data collection form that included demographics, complications, and the presence of difficult airway predictors. Our primary outcome measure was overall successful tracheal intubation, which was defined as successful intubation with the first device used. RESULTS: During the study period, 709 trauma patients were intubated by either VL or DL. VL was performed in 55% of cases. The overall success rate of VL was 88% compared to 83% with DL (P = 0.05). Cervical (C-Spine) immobilization was predictive of higher initial success with VL (87%) than with DL (80%) (P < 0.05). In multivariate regression analysis DL was associated with higher risk of intubation failure compared to VL (OR 1.82, CI: 1.15-2.86). CONCLUSIONS: In trauma patients intubated emergently, VL had a significantly higher success rate than DL. These data suggest that, in select circumstances, VL is superior to DL for the intubation of trauma patients with difficult airways.