Corrigendum: Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies.

[This corrects the article DOI: 10.3389/fimmu.2023.1230049.].

Short-Stay Units vs Routine Admission From the Emergency Department in Patients With Acute Heart Failure: The SSU-AHF Randomized Clinical Trial.

Importance: More than 80% of patients who present to the emergency department (ED) with acute heart failure (AHF) are hospitalized. With more than 1 million annual hospitalizations for AHF in the US, safe and effective alternatives are needed. Care for AHF in short-stay units (SSUs) may be safe and more efficient than hospitalization, especially for lower-risk patients, but randomized clinical trial data are lacking. Objective: To compare the effectiveness of SSU care vs hospitalization in lower-risk patients with AHF. Design, Setting, and Participants: This multicenter randomized clinical trial randomly assigned low-risk patients with AHF 1:1 to SSU or hospital admission from the ED. Patients received follow-up at 30 and 90 days post discharge. The study began December 6, 2017, and was completed on July 22, 2021. The data were analyzed between March 27, 2020, and November 11, 2023. Intervention: Randomized post-ED disposition to less than 24 hours of SSU care vs hospitalization. Main Outcomes and Measures: The study was designed to detect at least 1-day superiority for a primary outcome of days alive and out of hospital (DAOOH) at 30-day follow-up for 534 participants, with an allowance of 10% participant attrition. Due to the COVID-19 pandemic, enrollment was truncated at 194 participants. Before unmasking, the primary outcome was changed from DAOOH to an outcome with adequate statistical power: quality of life as measured by the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). The KCCQ-12 scores range from 0 to 100, with higher scores indicating better quality of life. Results: Of the 193 patients enrolled (1 was found ineligible after randomization), the mean (SD) age was 64.8 (14.8) years, 79 (40.9%) were women, and 114 (59.1%) were men. Baseline characteristics were balanced between arms. The mean (SD) KCCQ-12 summary score between the SSU and hospitalization arms at 30 days was 51.3 (25.7) vs 45.8 (23.8) points, respectively (P = .19). Participants in the SSU arm had 1.6 more DAOOH at 30-day follow-up than those in the hospitalization arm (median [IQR], 26.9 [24.4-28.8] vs 25.4 [22.0-27.7] days; P = .02). Adverse events were uncommon and similar in both arms. Conclusions and Relevance: The findings show that the SSU strategy was no different than hospitalization with regard to KCCQ-12 score, superior for more DAOOH, and safe for lower-risk patients with AHF. These findings of lower health care utilization with the SSU strategy need to be definitively tested in an adequately powered study. Trial Registration: ClinicalTrials.gov Identifier: NCT03302910.

Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies.

Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported. Due to the rarity of vascular air embolism and because of the many manifestations, diagnoses can be difficult and require immediate therapeutic intervention. An iatrogenic air embolism can result in both venous and arterial emboli whose anatomic locations dictate the clinical course. Most clinically significant iatrogenic air emboli are caused by arterial obstruction of small vessels because the pulmonary gas exchange filters the more frequent, smaller volume bubbles that gain access to the venous circulation. However, there is a subset of patients with venous air emboli caused by larger volumes of air who present with more protean manifestations. There have been significant gains in the understanding of the interactions of fluid dynamics, hemostasis, and inflammation caused by air emboli due to in vitro and in vivo studies on flow dynamics of bubbles in small vessels. Intensive research regarding the thromboinflammatory changes at the level of the endothelium has been described recently. The obstruction of vessels by air emboli causes immediate pathoanatomic and immunologic and thromboinflammatory responses at the level of the endothelium. In this review, we describe those immunologic and thromboinflammatory responses at the level of the endothelium as well as evaluate traditional and novel forms of therapy for this rare and often unrecognized clinical condition.

SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and non-traumatic shock.

Irrespective of the reason for hypoperfusion, hypocoagulable and/or hyperfibrinolytic hemostatic aberrancies afflict up to one-quarter of critically ill patients in shock. Intensivists and traumatologists have embraced the concept of SHock-INduced Endotheliopathy (SHINE) as a foundational derangement in progressive shock wherein sympatho-adrenal activation may cause systemic endothelial injury. The pro-thrombotic endothelium lends to micro-thrombosis, enacting a cycle of worsening perfusion and increasing catecholamines, endothelial injury, de-endothelialization, and multiple organ failure. The hypocoagulable/hyperfibrinolytic hemostatic phenotype is thought to be driven by endothelial release of anti-thrombogenic mediators to the bloodstream and perivascular sympathetic nerve release of tissue plasminogen activator directly into the microvasculature. In the shock state, this hemostatic phenotype may be a counterbalancing, yet maladaptive, attempt to restore blood flow against a systemically pro-thrombotic endothelium and increased blood viscosity. We therefore review endothelial physiology with emphasis on glycocalyx function, unique biomarkers, and coagulofibrinolytic mediators, setting the stage for understanding the pathophysiology and hemostatic phenotypes of SHINE in various etiologies of shock. We propose that the hyperfibrinolytic phenotype is exemplified in progressive shock whether related to trauma-induced coagulopathy, sepsis-induced coagulopathy, or post-cardiac arrest syndrome-associated coagulopathy. Regardless of the initial insult, SHINE appears to be a catecholamine-driven entity which early in the disease course may manifest as hyper- or hypocoagulopathic and hyper- or hypofibrinolytic hemostatic imbalance. Moreover, these hemostatic derangements may rapidly evolve along the thrombohemorrhagic spectrum depending on the etiology, timing, and methods of resuscitation. Given the intricate hemochemical makeup and changes during these shock states, macroscopic whole blood tests of coagulative kinetics and clot strength serve as clinically useful and simple means for hemostasis phenotyping. We suggest that viscoelastic hemostatic assays such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are currently the most applicable clinical tools for assaying global hemostatic function-including fibrinolysis-to enable dynamic resuscitation with blood products and hemostatic adjuncts for those patients with thrombotic and/or hemorrhagic complications in shock states.

Resonant Acoustic Rheometry to Measure Coagulation Kinetics in Hemophilia A and Healthy Plasma: A Novel Viscoelastic Method.

Compared with conventional coagulation tests and factor-specific assays, viscoelastic hemostatic assays (VHAs) can provide a more thorough evaluation of clot formation and lysis but have several limitations including clot deformation. In this proof-of-concept study, we test a noncontact technique, termed resonant acoustic rheometry (RAR), for measuring the kinetics of human plasma coagulation. Specifically, RAR utilizes a dual-mode ultrasound technique to induce and detect surface oscillation of blood samples without direct physical contact and measures the resonant frequency of the surface oscillation over time, which is reflective of the viscoelasticity of the sample. Analysis of RAR results of normal plasma allowed defining a set of parameters for quantifying coagulation. RAR detected a flat-line tracing of resonant frequency in hemophilia A plasma that was corrected with the addition of tissue factor. Our RAR results captured the kinetics of plasma coagulation and the newly defined RAR parameters correlated with increasing tissue factor concentration in both healthy and hemophilia A plasma. These findings demonstrate the feasibility of RAR as a novel approach for VHA, providing the foundation for future studies to compare RAR parameters to conventional coagulation tests, factor-specific assays, and VHA parameters.

The Choice between Plasma-Based Common Coagulation Tests and Cell-Based Viscoelastic Tests in Monitoring Hemostatic Competence: Not an either-or Proposition.

There has been a significant interest in the last decade in the use of viscoelastic tests (VETs) to determine the hemostatic competence of bleeding patients. Previously, common coagulation tests (CCTs) such as the prothrombin time (PT) and partial thromboplastin time (PTT) were used to assist in the guidance of blood component and hemostatic adjunctive therapy for these patients. However, the experience of decades of VET use in liver failure with transplantation, cardiac surgery, and trauma has now spread to obstetrical hemorrhage and congenital and acquired coagulopathies. Since CCTs measure only 5 to 10% of the lifespan of a clot, these assays have been found to be of limited use for acute surgical and medical conditions, whereby rapid results are required. However, there are medical indications for the PT/PTT that cannot be supplanted by VETs. Therefore, the choice of whether to use a CCT or a VET to guide blood component therapy or hemostatic adjunctive therapy may often require consideration of both methodologies. In this review, we provide examples of the relative indications for CCTs and VETs in monitoring hemostatic competence of bleeding patients.

Relative Hypercoagulopathy of the SARS-CoV-2 Beta and Delta Variants when Compared to the Less Severe Omicron Variants Is Related to TEG Parameters, the Extent of Fibrin Amyloid Microclots, and the Severity of Clinical Illness.

Earlier variants of SARS-CoV-2 have been associated with hypercoagulability and an extensive formation of fibrin amyloid microclots, which are considered to contribute to the pathology of the coronavirus 2019 disease (COVID-19). The newer omicron variants appear to be far more transmissible, but less virulent, even when taking immunity acquired from previous infections or vaccination into account. We here show that while the clotting parameters associated with omicron variants are significantly raised over those of healthy, matched controls, they are raised to levels significantly lower than those seen with more severe variants such as beta and delta. We also observed that individuals infected with omicron variants manifested less extensive microclot formation in platelet-poor plasma compared with those harboring the more virulent variants. The measurement of clotting effects between the different variants acts as a kind of "internal control" that demonstrates the relationship between the extent of coagulopathies and the virulence of the variant of interest. This adds to the evidence that microclots may play an important role in reflecting the severity of symptoms observed in COVID-19.

Acute coronary syndrome prediction in emergency care: A machine learning approach.

BACKGROUND AND OBJECTIVE: Clinical concern for acute coronary syndrome (ACS) is one of emergency medicine's most common patient encounters. This study aims to develop an ensemble learning-driven framework as a diagnostic support tool to prevent misdiagnosis. METHODS: We obtained extensive clinical electronic health data on patient encounters with clinical concerns for ACS from a large urban emergency department (ED) between January 2017 and August 2020. We applied an analytical framework equipped with many well-developed algorithms to improve the data quality by addressing missing values, dimensionality reduction, and data imbalance. We trained ensemble learning algorithms to classify patients with ACS or non-ACS etiologies of their symptoms. We used performance evaluation metrics such as accuracy, sensitivity, precision, F1-score, and the area under the receiver operating characteristic (AUROC) to measure the model's performance. RESULTS: The analysis included 31,228 patients, of whom 563 (1.8%) had ACS and 30,665 (98.2%) had alternative diagnoses. Eleven features, including systolic blood pressure, brain natriuretic peptide, chronic heart disease, coronary artery disease, creatinine, glucose, heart attack, heart rate, nephrotic syndrome, red cell distribution width, and troponin level, are reported as significantly contributing risk factors. The proposed framework successfully classifies these cohorts with sensitivity and AUROC as high as 86.3% and 93.3%. Our proposed model's accuracy, precision, specificity, Matthew's correlation coefficient, and F1-score were 85.7%, 86.3%, 93%, 80%, and 86.3%, respectively. CONCLUSION: Our proposed framework can identify early patients with ACS through further refinement and validation.

A Comparison of Univariate and Multivariate Forecasting Models Predicting Emergency Department Patient Arrivals during the COVID-19 Pandemic.

The COVID-19 pandemic has heightened the existing concern about the uncertainty surrounding patient arrival and the overutilization of resources in emergency departments (EDs). The prediction of variations in patient arrivals is vital for managing limited healthcare resources and facilitating data-driven resource planning. The objective of this study was to forecast ED patient arrivals during a pandemic over different time horizons. A secondary objective was to compare the performance of different forecasting models in predicting ED patient arrivals. We included all ED patient encounters at an urban teaching hospital between January 2019 and December 2020. We divided the data into training and testing datasets and applied univariate and multivariable forecasting models to predict daily ED visits. The influence of COVID-19 lockdown and climatic factors were included in the multivariable models. The model evaluation consisted of the root mean square error (RMSE) and mean absolute error (MAE) over different forecasting horizons. Our exploratory analysis illustrated that monthly and weekly patterns impact daily demand for care. The Holt-Winters approach outperformed all other univariate and multivariable forecasting models for short-term predictions, while the Long Short-Term Memory approach performed best in extended predictions. The developed forecasting models are able to accurately predict ED patient arrivals and peaks during a surge when tested on two years of data from a high-volume urban ED. These short- and long-term prediction models can potentially enhance ED and hospital resource planning.

Vaginal Swabs Are Non-inferior to Endocervical Swabs for Sexually Transmitted Infection testing in the Emergency Department.

STUDY OBJECTIVE: Emergency department (ED) testing for sexually transmitted infections (STI) in women is typically performed with a pelvic examination and an endocervical swab. However, vaginal swabs are effective for STI testing and the preferred specimen type according to the US Centers for Disease Control and Prevention. The utility of using vaginal swabs in the ED for STI screening has not been thoroughly investigated. Our objective was to assess detection rates for two bacterial STIs before and after implementing a screening protocol using vaginal swabs. METHODS: We conducted a quasi-experimental, pre-post study using standardized data from electronic health records across nine metropolitan Detroit hospital EDs. Patients included women who were tested for Chlamydia trachomatis or Neisseria gonorrhoeae in the ED between April 2018-December 2019. Pre-implementation tests from April 2018-February 2019 were done using endo-cervical swabs, and post-implementation tests from February 2019-December 2019 were done with vaginal swabs. We used non-inferiority testing for proportion with a non-inferiority margin of one percentage point absolute difference in detection rates of STI. RESULTS: The study included 22,291 encounters with 11,732 in the pre-implementation and 10,559 in the post-implementation phases. The C. trachomatis detection rates were 7.5% pre-implementation and 7.6% post-implementation (between-group difference, 0.1 percentage points; 95% confidence interval [CI]: -0.7, 0.4; p<.01 for non-inferiority). The N. gonorrhoeae detection rates were 3.1% pre-implementation and 3.6% post-implementation (between-group difference, 0.5 percentage points; 95% CI: -0.8, 0.04; p<.01 for non-inferiority). CONCLUSION: Using vaginal swabs for STI testing in the ED may be a non-inferior alternative to using endocervical swabs.

Hepatitis C Virus Reflex Testing Protocol in an Emergency Department.

INTRODUCTION: Our aim was to measure hepatitis C virus (HCV) screening and linkage-to-care rates in an urban emergency department (ED) before and after implementing an HCV viral RNA (vRNA) reflex testing protocol within a HCV screening program for at-risk patients. Our hypothesis was that using a reflex testing protocol would increase HCV testing rates of at-risk patients in the ED, which would increase the linkage-to-care rate. METHODS: In August 2018, our institution implemented an automated, electronic health record-based HCV screening protocol in the ED for at-risk patients. In January 2019, we implemented an HCV vRNA reflex testing protocol (reflex testing) for all positive HCV antibody (Ab) tests that were initiated through the screening protocol. We compared completion rates of HCV vRNA testing and the rate of linkage to care for patients with positive HCV Ab test results before and after implementation of reflex testing (five months per study period). RESULTS: Prior to reflex testing implementation, 233/425 (55%) patients with a positive HCV Ab test had an HCV vRNA test performed, whereas 270/323 (84%) patients with a positive HCV Ab test result had vRNA testing after reflex testing implementation (odds ratio [OR], 4.2; 95% confidence interval (CI): 3.0-6.0; P < 0.001). Of the eligible patients with positive HCV Ab test results who could be linked to care, 45 (10.6%) were linked to care before HCV reflex implementation and 46 (14.2%) were linked to care with reflex testing (OR, 1.4; 95% CI: 0.9-2.2; P = 0.13). CONCLUSION: Implementing a reflex testing initiative into an HCV screening program in the ED can result in an increase of the percentage of patients who receive an HCV vRNA test after having had a positive HCV Ab. Hepatitis C virus vRNA reflex testing was not associated with a statistically significant increase in linkage-to-care rates for HCV Ab-positive patients; however, further studies are required.

COVID-associated non-vasculitic thrombotic retiform purpura of the face and extremities: A case report.

SARS-CoV-2 infection can manifest many rashes. However, thrombotic retiform purpura rarely occurs during COVID-19 illness. Aggressive anti-COVID-19 therapy with a high-dose steroid regimen led to rapid recovery. This immunothrombotic phenomenon likely represents a poor type 1 interferon response and complement activation on the endothelial surface in response to acute infection.

Unaffected ex vivo clotting cascade by experimental hemostatic nanoparticles when introduced in the presence of recombinant tissue plasminogen activator.

CONTEXT: Hemostatic nanoparticles (hNPs) have shown efficacy in decreasing intracerebral hemorrhage (ICH) in animal models and are suggested to be of use to counter tissue plasminogen activator (tPA)-induced acute ICH. AIMS: The objective of this study was to test the ability of an hNP preparation to alter the clotting properties of blood exposed to tPA ex vivo. MATERIALS AND METHODS: Fresh blood samples were obtained from normal male Sprague-Dawley rats (~300 g; n = 6) and prepared for coagulation assays by thromboelastography (TEG) methods. Samples were untreated, exposed to tPA, or exposed to tPA and then to hNP. TEG parameters included reaction time (R, time in minutes elapsed from test initiation to initial fibrin formation), coagulation time (K, time in minutes from R until initial clot formation), angle (α, a measure in degrees of the rate of clot formation), maximum amplitude (MA, the point when the clot reaches its MA in mm), lysis at 30 min after MA (LY30, %), and clot strength (G, dynes/cm2), an index of clot strength. STATISTICAL ANALYSIS USED: Kruskal-Wallis test was employed to compare TEG parameters measured for untreated control samples versus those exposed to tPA and to compare tPA-exposed samples to samples treated with tPA + hNPs. Significances were inferred at P ≤ 0.05. RESULTS: Compared to untreated samples, tPA-treated samples showed a trend toward decreased angle and G suggesting potentially clot formation rate and clot strength. The addition of hNP did not affect any of these or other measured indices. CONCLUSIONS: The data demonstrated no hemostatic effects when the hNP was used in the presence of tPA. The lack of change in any of the TEG parameters measured in the present study may indicate limitations of the hNPs to reverse the thrombolytic cascade initiated by tPA.

Prehospital Tibial Intraosseous Drug Administration is Associated with Reduced Survival Following Out of Hospital Cardiac Arrest: A study for the CARES Surveillance Group.

BACKGROUND: Recent reports have questioned the efficacy of intraosseous (IO) drug administration for out-of-hospital cardiac arrest (OHCA) resuscitation. Our aim was to determine whether prehospital administration of resuscitative medications via the IO route was associated with lower rates of return of spontaneous circulation (ROSC) and survival to hospital discharge than peripheral intravenous (IV) infusion in the setting of OHCA. METHODS: We obtained data on all OHCA patients receiving prehospital IV or IO drug administration from the three most populous counties in Michigan over three years. Data was from the Michigan Cardiac Arrest Registry to Enhance Survival (CARES) database. The association between route of drug administration and outcomes was tested using a matched propensity score analysis. RESULTS: From a total of 10,626 OHCA patients, 6869 received parenteral drugs during their prehospital resuscitation (37.8% by IO) and were included in analysis. Unadjusted outcomes were lower in patients with IO vs. IV access: 18.3% vs. 23.8% for ROSC (p < 0.001), 3.2% vs. 7.6% for survival to hospital discharge (p < 0.001), and 2.0% vs. 5.8% for favorable neurological function (p < 0.001). After adjustment, IO route remained associated with lower odds of sustained ROSC (OR 0.72, 95% CI 0.63-0.81, p < 0.001), hospital survival (OR 0.48, 95% CI 0.37-0.62, p < 0.001), and favorable neurological outcomes (OR 0.42, 95% CI 0.30-0.57, p < 0.001). CONCLUSION: In this cohort of OHCA patients, the use of prehospital IO drug administration was associated with unfavorable clinical outcomes.

Hospital-Initiated Care Bundle, Posthospitalization Care, and Outcomes in Adults with Asthma Exacerbation.

BACKGROUND: Hospitalization for asthma exacerbation is an opportune setting for initiating preventive efforts. However, hospital-initiated preventive asthma care remains underdeveloped and its effectiveness is uncertain. OBJECTIVE: To examine the effectiveness of a hospital-initiated asthma care bundle on posthospitalization asthma care and clinical outcomes. METHODS: Prospective multicenter study of adults (18-54 years) hospitalized for asthma exacerbation in 2017 to 2019. During the hospitalization, we implemented an asthma-care bundle (inpatient laboratory testing, asthma education, and discharge care), and prospectively measured chronic asthma care (eg, immunoglobulin E testing, specialist care) and asthma exacerbation (ie, systemic corticosteroid use, emergency department [ED] visit, hospitalizations) outcomes. By applying a self-controlled case series method, we examined within-person changes in these outcomes before (2-year period) and after (1-year period) the bundle implementation. RESULTS: Of 103 adults hospitalized for asthma exacerbation, the median age was 40 years and 72% were female. Compared with the preimplementation period, the postimplementation period had improved posthospitalized asthma care, including serum specific immunoglobulin E testing (rate ratio [RR] 2.18; 95% confidence interval [95% CI] 0.99-4.84; P = .051) and evaluation by asthma specialist (RR 2.66; 95% CI 1.77-4.04; P < .001). Likewise, after care bundle implementation, patients had significantly lower annual rates of systemic corticosteroid use (4.2 vs 2.9 per person-year; RR 0.70; 95% CI 0.61-0.80; P < .001), ED visits (3.2 vs 2.7 per person-year; RR 0.83; 95% CI 0.72-0.95; P = .008), and hospitalizations (2.1 vs 1.8 per person-year; RR 0.82; 95% CI 0.69-0.97; P = .02). Stratified analyses by sex, race and ethnicity, and health insurance yielded consistent results. CONCLUSIONS: After hospital-initiated care bundle implementation, patients had improved posthospitalization care and reduced rates of asthma exacerbation.

Preventing Thrombohemorrhagic Complications of Heparinized COVID-19 Patients Using Adjunctive Thromboelastography: A Retrospective Study.

BACKGROUND: The treatment of COVID-19 patients with heparin is not always effective in preventing thrombotic complications, but can also be associated with bleeding complications, suggesting a balanced approach to anticoagulation is needed. A prior pilot study supported that thromboelastography and conventional coagulation tests could predict hemorrhage in COVID-19 in patients treated with unfractionated heparin or enoxaparin, but did not evaluate the risk of thrombosis. METHODS: This single-center, retrospective study included 79 severely ill COVID-19 patients anticoagulated with intermediate or therapeutic dose unfractionated heparin. Two stepwise logistic regression models were performed with bleeding or thrombosis as the dependent variable, and thromboelastography parameters and conventional coagulation tests as the independent variables. RESULTS: Among all 79 patients, 12 (15.2%) had bleeding events, and 20 (25.3%) had thrombosis. Multivariate logistic regression analysis identified a prediction model for bleeding (adjusted R2 = 0.787, p < 0.001) comprised of increased reaction time (p = 0.016), decreased fibrinogen (p = 0.006), decreased D-dimer (p = 0.063), and increased activated partial thromboplastin time (p = 0.084). Multivariate analysis of thrombosis identified a weak prediction model (adjusted R2 = 0.348, p < 0.001) comprised of increased D-dimer (p < 0.001), decreased reaction time (p = 0.002), increased maximum amplitude (p < 0.001), and decreased alpha angle (p = 0.014). Adjunctive thromboelastography decreased the use of packed red cells (p = 0.031) and fresh frozen plasma (p < 0.001). CONCLUSIONS: Significantly, this study demonstrates the need for a precision-based titration strategy of anticoagulation for hospitalized COVID-19 patients. Since severely ill COVID-19 patients may switch between thrombotic or hemorrhagic phenotypes or express both simultaneously, institutions may reduce these complications by developing their own titration strategy using daily conventional coagulation tests with adjunctive thromboelastography.

Hospital length of stay, do not resuscitate orders, and survival for post-cardiac arrest patients in Michigan: A study for the CARES Surveillance Group.

OBJECTIVE: Current guidelines recommend deferring prognostic decisions for at least 72 h following admission after Out of Hospital cardiac arrest (OHCA). Most non-survivors experience withdrawal of life sustaining therapy (WLST), and early WLST may adversely impact survival. We sought to characterize the hospital length of stay (LOS) and timing of Do Not Resuscitate (DNR) orders (as surrogates for WLST), to assess their relationship to survival following cardiac arrest. DESIGN: We performed a retrospective cohort study of probabilistically linked cardiac arrest registries (Cardiac Arrest Registry to Enhance Survival (CARES) and Michigan Inpatient Database (MIDB) from 2014 to 2017. PATIENTS: Adult (≥18 years) patients admitted following OHCA were included. We considered LOS ≤ 3 days (short LOS) and written DNR order with LOS ≤ 3 days (Early DNR) as indicators of early WLST. Our primary outcome was survival to hospital discharge. We utilized multilevel logistic regression clustered by hospital to examine associations of these variables, patient characteristics and survival to hospital discharge. MEASUREMENT AND MAIN RESULTS: We included 3644 patients from 38 hospitals with >30 patients. Patients mean age was 62.4 years and were predominately male (59.3%). LOS ≤ 3 days (ORadj = 0.11) and early DNR (ORadj = 0.02) were inversely associated with survival to discharge. There was a non-significant inverse association between hospital rates of LOS ≤ 3 days and survival (p = 0.11), and Early DNR and survival (p = 0.83). In the multilevel model, using median odd ratios to assess variation in LOS ≤ 3 days and survival, patient characteristics contributed more to variability in surviival than between-hospital variation. However, between-hospital variation contributed more to variability than patient characteristics in the provision of early DNR orders. CONCLUSIONS: We observed that LOS ≤ 3 days for post-arrest patients was negatively-associated with survival, with both patient characteristics and between-hospital variation associated with outcomes. However, between-hospital variation appears to be more highly-associated with provision of early DNR orders than patient characteristics. Further work is needed to assess variation in early DNR orders and their impact on patient survival.

Early Neurologic Recovery, Practice Pattern Variation, and the Risk of Endotracheal Intubation Following Established Status Epilepticus.

OBJECTIVE: To quantify the association between early neurologic recovery, practice pattern variation, and endotracheal intubation during established status epilepticus, we performed a secondary analysis within the cohort of patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT). METHODS: We evaluated factors associated with the endpoint of endotracheal intubation occurring within 120 minutes of ESETT study drug initiation. We defined a blocked, stepwise multivariate regression, examining 4 phases during status epilepticus management: (1) baseline characteristics, (2) acute treatment, (3) 20-minute neurologic recovery, and (4) 60-minute recovery, including seizure cessation and improving responsiveness. RESULTS: Of 478 patients, 117 (24.5%) were intubated within 120 minutes. Among high-enrolling sites, intubation rates ranged from 4% to 32% at pediatric sites and 19% to 39% at adult sites. Baseline characteristics, including seizure precipitant, benzodiazepine dosing, and admission vital signs, provided limited discrimination for predicting intubation (area under the curve [AUC] 0.63). However, treatment at sites with an intubation rate in the highest (vs lowest) quartile strongly predicted endotracheal intubation independently of other treatment variables (adjusted odds ratio [aOR] 8.12, 95% confidence interval [CI] 3.08-21.4, model AUC 0.70). Site-specific variation was the factor most strongly associated with endotracheal intubation after adjustment for 20-minute (aOR 23.4, 95% CI 6.99-78.3, model AUC 0.88) and 60-minute (aOR 14.7, 95% CI 3.20-67.5, model AUC 0.98) neurologic recovery. CONCLUSIONS: Endotracheal intubation after established status epilepticus is strongly associated with site-specific practice pattern variation, independently of baseline characteristics, and early neurologic recovery and should not alone serve as a clinical trial endpoint in established status epilepticus. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT01960075.

Substantial variation exists in post-cardiac arrest outcomes across Michigan hospitals.

AIM: Resuscitation from out of hospital cardiac arrest (OHCA) requires success across the entire chain of survival. Using a large state-wide registry, we characterized variation in clinical outcomes at hospital discharge in Michigan hospitals. METHODS: We utilized the Michigan Cardiac Arrest Registry to Enhance Survival (CARES) and included adult OHCA subjects with return of spontaneous circulation (ROSC) from 2014 - 2017 that survived to hospital admission. 39 Michigan hospitals were included which managed >30 cases during the study period. Multilevel logistic regression, controlling for both subject characteristics and clustering of subjects within hospitals, assessed variation across hospitals in survival to hospital discharge and survival with cerebral performance category (CPC 1-2). RESULTS: There were 5,486 CARES subjects that survived to hospital admission, and 4,690 met inclusion for analysis. Of 39 included hospitals, median survival to discharge was 31.3% (range 12.5%-46.7%) and median survival to discharge with CPC 1-2 was 25.0% (range 5.2%-42.2%). We identified 12-fold variation in the utilization of TTM by hospital (median 47.9%, range 6.7%-80.0%) for all admitted subjects. Similarly, there was nearly an eight-fold variation in LHC for all post-arrest subjects (median 22.1%, range 5.4%-42.2%). In multivariable analyses, median adjusted survival to discharge was 26.9% (range 18.1%-42.1%) and median adjusted survival to discharge with CPC 1-2 was 21.3% (range 9.6%-32.1%). CONCLUSION: We observed substantial variation in clinical outcomes at discharge between Michigan hospitals, including a four-fold range of survival and eight-fold range of survival with CPC 1-2. This variation was ameliorated but still persisted in adjusted modeling. Variation in post arrest survival by hospital was not fully explained by available covariates, which suggests the possibility of improving post-arrest clinical outcomes at some hospitals via quality improvement activities.