SARS-CoV-2 infection and persistence in the human body and brain at autopsy.

Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction1-3 during acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients experiencing prolonged symptoms, termed post-acute sequelae of SARS-CoV-2 (refs. 4,5). However, the burden of infection outside the respiratory tract and time to viral clearance are not well characterized, particularly in the brain3,6-14. Here we carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients, to map and quantify the distribution, replication and cell-type specificity of SARS-CoV-2 across the human body, including the brain, from acute infection to more than seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite extensive distribution of SARS-CoV-2 RNA throughout the body, we observed little evidence of inflammation or direct viral cytopathology outside the respiratory tract. Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.

Anticoagulation and Bleeding during Veno-Venous Extracorporeal Membrane Oxygenation: Insights from the PROTECMO Study.

Rationale: Definitive guidelines for anticoagulation management during veno-venous extracorporeal membrane oxygenation (VV ECMO) are lacking, whereas bleeding complications continue to pose major challenges. Objectives: To describe anticoagulation modalities and bleeding events in adults receiving VV ECMO. Methods: This was an international prospective observational study in 41 centers, from December 2018 to February 2021. Anticoagulation was recorded daily in terms of type, dosage, and monitoring strategy. Bleeding events were reported according to site, severity, and impact on mortality. Measurements and Main Results: The study cohort included 652 patients, and 8,471 days on ECMO were analyzed. Unfractionated heparin was the initial anticoagulant in 77% of patients, and the most frequently used anticoagulant during the ECMO course (6,221 d; 73%). Activated partial thromboplastin time (aPTT) was the most common test for monitoring coagulation (86% of days): the median value was 52 seconds (interquartile range, 39 to 61 s) but dropped by 5.3 seconds after the first bleeding event (95% confidence interval, -7.4 to -3.2; P < 0.01). Bleeding occurred on 1,202 days (16.5%). Overall, 342 patients (52.5%) experienced at least one bleeding event (one episode every 215 h on ECMO), of which 10 (1.6%) were fatal. In a multiple penalized Cox proportional hazard model, higher aPTT was a potentially modifiable risk factor for the first episode of bleeding (for 20-s increase; hazard ratio, 1.07). Conclusions: Anticoagulation during VV ECMO was a dynamic process, with frequent stopping in cases of bleeding and restart according to the clinical picture. Future studies might explore lower aPTT targets to reduce the risk of bleeding.

Triage of V-V ECMO referrals for COVID-19 respiratory failure.

BACKGROUND: As the pandemic progressed, the use of extracorporeal membrane oxygenation (ECMO) for COVID-19-related acute respiratory distress syndrome increased, and patient triage and transfer to ECMO centers became important to optimize patient outcomes. Our objectives are to identify predictors of patient transfer for veno-venous extracorporeal membrane oxygenation (V-V ECMO) evaluation as well as to describe the outcomes of accepted patients. METHODS: This is a single-center, retrospective analysis of V-V ECMO transfer requests for adult patients with known or suspected COVID-19 and respiratory failure from March 2020 until March 2021. Data were collected prospectively during the triage process for transfer requests as part of clinical patient care at our institution. RESULTS: Of 341 referred patients, 112 (33%) were accepted for transfer to our facility, whereas 229 (67%) patients were declined for transfer. The Classification and Regression Tree analysis showed that patients' high pressure during airway pressure release ventilation (APRV) and age were the variables most significantly associated with the decision to accept or decline patients for transfer. CONCLUSIONS: Our triage process enabled one-third of referred patients to be transferred for evaluation, with nearly 70% of those patients ultimately receiving ECMO support. High ventilator settings on APRV and young age were associated with acceptance for transfer. Accepted patients also had a higher incidence of adjunctive therapies (proning and paralysis) prior to transfer request, less cardiac or renal dysfunction, and a shorter duration of mechanical ventilation. Further research is warranted to investigate the outcomes of nontransferred patients.

Functional recovery in a cohort of ECMO and non-ECMO acute respiratory distress syndrome survivors.

BACKGROUND: The mortality benefit of VV-ECMO in ARDS has been extensively studied, but the impact on long-term functional outcomes of survivors is poorly defined. We aimed to assess the association between ECMO and functional outcomes in a contemporaneous cohort of survivors of ARDS. METHODS: Multicenter retrospective cohort study of ARDS survivors who presented to follow-up clinic. The primary outcome was FVC% predicted. Univariate and multivariate regression models were used to evaluate the impact of ECMO on the primary outcome. RESULTS: This study enrolled 110 survivors of ARDS, 34 of whom were managed using ECMO. The ECMO cohort was younger (35 [28, 50] vs. 51 [44, 61] years old, p < 0.01), less likely to have COVID-19 (58% vs. 96%, p < 0.01), more severely ill based on the Sequential Organ Failure Assessment (SOFA) score (7 [5, 9] vs. 4 [3, 6], p < 0.01), dynamic lung compliance (15 mL/cmH20 [11, 20] vs. 27 mL/cmH20 [23, 35], p < 0.01), oxygenation index (26 [22, 33] vs. 9 [6, 11], p < 0.01), and their need for rescue modes of ventilation. ECMO patients had significantly longer lengths of hospitalization (46 [27, 62] vs. 16 [12, 31] days, p < 0.01) ICU stay (29 [19, 43] vs. 10 [5, 17] days, p < 0.01), and duration of mechanical ventilation (24 [14, 42] vs. 10 [7, 17] days, p < 0.01). Functional outcomes were similar in ECMO and non-ECMO patients. ECMO did not predict changes in lung function when adjusting for age, SOFA, COVID-19 status, or length of hospitalization. CONCLUSIONS: There were no significant differences in the FVC% predicted, or other markers of pulmonary, neurocognitive, or psychiatric functional recovery outcomes, when comparing a contemporaneous clinic-based cohort of survivors of ARDS managed with ECMO to those without ECMO.

Pneumothorax in acute respiratory distress syndrome on extracorporeal membrane oxygenation support.

INTRODUCTION: Pneumothorax is associated with poor prognosis in patients with acute respiratory distress syndrome (ARDS). We sought to examine the outcomes of patients who are supported on veno-venous extracorporeal membrane oxygenation (VV ECMO) and develop a pneumothorax. METHODS: We retrospectively reviewed all adult VV ECMO patients supported for ARDS between 8/2014-7/2020 at our institution, excluding patients with recent lung resection and trauma. Clinical outcomes were compared between patients with a pneumothorax to those without a pneumothorax. RESULTS: Two hundred eighty patients with ARDS on VV ECMO were analyzed. Of those, 213 did not have a pneumothorax and 67 did. Patients with a pneumothorax had a longer duration of ECMO support (30 days [16-55] versus 12 [7-22], p < 0.001) and hospital length of stay (51 days [27-93] versus 29 [18-49], p < 0.001), and lower survival-to-discharge (58.2% versus 77.5%, p = 0.002) compared to patients without a pneumothorax. Controlling for age, BMI, sex, RESP score and pre-ECMO ventilator days, the odds ratio of survival-to-discharge was 0.41 (95% CI 0.22-0.78) in patients with a pneumothorax compared to those without. There was a lower incidence of significant bleeding when chest tubes were placed by proceduralist services (2.4% versus 16.2%, p = 0.03). Removal of the chest tube prior to ECMO decannulation compared to removal after decannulation was associated with need for replacement (14.3% versus 0%, p = 0.01). CONCLUSION: Patients who develop a pneumothorax and are supported with VV ECMO for ARDS have longer duration on ECMO and decreased survival. Further studies are needed to assess risk factors for development of pneumothorax in this patient population.

Body mass index does not impact survival in COVID-19 patients requiring veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: With the increased demand for veno-venous extracorporeal membrane oxygenation (VV ECMO) during the COVID-19 pandemic, guidelines for patient candidacy have often limited this modality for patients with a body mass index (BMI) less than 40 kg/m2. We hypothesize that COVID-19 VV ECMO patients with at least class III obesity (BMI ≥ 40) have decreased in-hospital mortality when compared to non-COVID-19 and non-class III obese COVID-19 VV ECMO populations. METHODS: This is a single-center retrospective study of COVID-19 VV ECMO patients from January 1, 2014, to November 30, 2021. Our institution used BMI ≥ 40 as part of a multi-disciplinary VV ECMO candidate screening process in COVID-19 patients. BMI criteria were not considered for exclusion criteria in non-COVID-19 patients. Univariate and multivariable analyses were performed to assess in-hospital mortality differences. RESULTS: A total of 380 patients were included in our analysis: The COVID-19 group had a lower survival rate that was not statistically significant (65.7% vs.74.9%, p = .07). The median BMI between BMI ≥ 40 COVID-19 and non-COVID-19 patients was not different (44.5 vs 45.5, p = .2). There was no difference in survival between the groups (73.3% vs. 78.5%, p = .58), nor was there a difference in survival between the COVID-19 BMI ≥ 40 and BMI < 40 patients (73.3, 62.7, p= .29). Multivariable logistic regression with the outcome of in-hospital mortality was performed and BMI was not found to be significant (OR 0.99, 95% CI 0.89, 1.01; p = .92). CONCLUSION: BMI ≥ 40 was not an independent risk factor for decreased in-hospital survival in this cohort of VV ECMO patients at a high-volume center. BMI should not be the sole factor when deciding VV ECMO candidacy in patients with COVID-19.

COVID-19 outcomes of venovenous extracorporeal membrane oxygenation for acute respiratory failure vs historical cohort of non-COVID-19 viral infections.

INTRODUCTION: Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become a support modality for patients with acute respiratory failure refractory to standard therapies. VV ECMO has been increasingly used during the current COVID-19 pandemic for patients with refractory respiratory failure. The object of this study was to evaluate the outcomes of VV ECMO in patients with COVID-19 compared to patients with non-COVID-19 viral infections. METHODS: We retrospectively reviewed all patients supported with VV ECMO between 8/2014 and 8/2020 whose etiology of illness was a viral pulmonary infection. The primary outcome of this study was to evaluate in-hospital mortality. The secondary outcomes included length of ECMO course, ventilator duration, hospital length of stay, incidence of adverse events through ECMO course. RESULTS: Eighty-nine patients were included (35 COVID-19 vs 54 non-COVID-19). Forty (74%) of the non-COVID-19 patients had influenza virus. Prior to cannulation, COVID-19 patients had longer ventilator duration (3 vs 1 day, p = .003), higher PaCO2 (64 vs 53 mmHg, p = .012), and white blood cell count (14 vs 9 ×103/µL, p = .004). Overall in-hospital mortality was 33.7% (n = 30). COVID-19 patients had a higher mortality (49% vs. 24%, p = .017) when compared to non-COVID-19 patients. COVID-19 survivors had longer median time on ECMO than non-COVID-19 survivors (24.4 vs 16.5 days p = .03) but had a similar hospital length of stay (HLOS) (41 vs 48 Extracorporeal Membrane Oxygenationdays p = .33). CONCLUSION: COVID-19 patients supported with VV ECMO have a higher mortality than non-COVID-19 patients. While COVID-19 survivors had significantly longer VV ECMO runs than non-COVID-19 survivors, HLOS was similar. This data add to a growing body of literature supporting the use of ECMO for potentially reversible causes of respiratory failure.

A descriptive evaluation of causes of death in venovenous extracorporeal membrane oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become an important support modality for patients with acute respiratory failure refractory to optimal medical therapy, such as low tidal volume mechanical ventilator support, early paralytic infusion, and early prone positioning. The objective of this cohort study was to investigate the causes and timing of in-hospital mortality in patients on VV ECMO. All patients, excluding trauma and bridge to lung transplant, admitted 8/2014-6/2019 to a specialty ICU for VV ECMO were reviewed. Two hundred twenty-five patients were included. In-hospital mortality was 24.4% (n = 55). Most non-survivors (46/55, 84%) died prior to lung recovery and decannulation from VV ECMO. Most common cause of death (COD) for patients who died on VV ECMO was removal of life sustaining therapy (LST) in setting of multisystem organ failure (MSOF) (n = 24). Nine patients died a median of 9 days [6, 11] after decannulation. Most common COD in these patients was palliative withdrawal of LST due to poor prognosis (n = 3). Non-survivors were older and had worse predictive mortality scores than survivors. We found that death in patients supported with VV ECMO in our study most often occurs prior to decannulation and lung recovery. This study demonstrated that the most common cause of death in patients supported with VV ECMO was removal of LST due MSOF. Acute hemorrhage (systemic or intracranial) was not found to be a common cause of death in our patient population.

Decreased PRESET-Score corresponds with improved survival in COVID-19 veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: The PREdiction of Survival on ECMO Therapy Score (PRESET-Score) predicts mortality while on veno-venous extracorporeal membrane oxygenation (VV ECMO) for acute respiratory distress syndrome. The aim of our study was to assess the association between PRESET-Score and survival in a large COVID-19 VV ECMO cohort. METHODS: This was a single-center retrospective study of COVID-19 VV ECMO patients from 15 March 2020, to 30 November 2021. Univariable and Multivariable analyses were performed to assess patient survival and score differences. RESULTS: A total of 105 patients were included in our analysis with a mean PRESET-Score of 6.74. Overall survival was 65.71%. The mean PRESET-Score was significantly lower in the survivor group (6.03 vs 8.11, p < 0.001). Patients with a PRESET-Score less than or equal to six had improved survival compared to those with a PRESET-Score greater than or equal to 8 (97.7% vs. 32.5%, p < 0.001). In a multivariable logistic regression, a lower PRESET-Score was also predictive of survival (OR 2.84, 95% CI 1.75, 4.63, p < 0.001). CONCLUSION: We demonstrate that lower PRESET scores are associated with improved survival. The utilization of this validated, quantifiable, and objective scoring system to help identify COVID-19 patients with the greatest potential to benefit from VV-ECMO appears feasible. The incorporation of the PRESET-Score into institutional ECMO candidacy guidelines can help insure and improve access of this limited healthcare resource to all critically ill patients.

Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months.

We report orthotopic (life-supporting) survival of genetically engineered porcine cardiac xenografts (with six gene modifications) for almost 9 months in baboon recipients. This work builds on our previously reported heterotopic cardiac xenograft (three gene modifications) survival up to 945 days with an anti-CD40 monoclonal antibody-based immunosuppression. In this current study, life-supporting xenografts containing multiple human complement regulatory, thromboregulatory, and anti-inflammatory proteins, in addition to growth hormone receptor knockout (KO) and carbohydrate antigen KOs, were transplanted in the baboons. Selective "multi-gene" xenografts demonstrate survival greater than 8 months without the requirement of adjunctive medications and without evidence of abnormal xenograft thickness or rejection. These data demonstrate that selective "multi-gene" modifications improve cardiac xenograft survival significantly and may be foundational for paving the way to bridge transplantation in humans.

New-Onset Atrial Arrhythmias Are Independently Associated With In-Hospital Mortality in Veno-Venous Extracorporeal Membrane Oxygenation.

OBJECTIVE: To explore if atrial arrhythmias are associated with in-hospital mortality in veno-venous extracorporeal membrane oxygenation (VV-ECMO) patients. DESIGN: Retrospective observational cohort study. SETTING: Quaternary care academic medical center. PARTICIPANTS: Patients with respiratory failure requiring VV-ECMO for >24 hours between January 1, 2016, and January 1, 2019. INTERVENTIONS: None, observational study. MEASUREMENTS AND MAIN RESULTS: Two hundred nineteen VV-ECMO patients were included. Patients were stratified by absence or presence of clinically significant atrial arrhythmias during the VV-ECMO run. Atrial arrhythmias were defined as either atrial fibrillation or atrial flutter that occurred during VV-ECMO and required pharmacologic or electrical intervention. The primary outcome was in-hospital mortality. Secondary outcomes included a composite of thrombotic events, which included ischemic stroke and on-pump arterial thrombosis. Other objectives of this analysis included characterization of atrial arrhythmia incidence, risk factors, and management. A total of 67 patients (30.5%) experienced new-onset atrial arrhythmias post-ECMO cannulation. Age, male sex, and norepinephrine use were independently associated with atrial arrhythmia development. In-hospital mortality was significantly higher in the atrial arrhythmia group (38.8% v 19.1%; p = 0.003). In the multivariate logistic regression analysis, atrial arrhythmias during VV-ECMO were independently associated with increased odds of in-hospital mortality (odds ratio, 2.21; 95% confidence interval, 1.08-4.55; p = 0.03), after controlling for Respiratory Extracorporeal Membrane Oxygenation Survival Prediction score, acute renal failure, total norepinephrine dose, and total cannulation time. CONCLUSIONS: New-onset atrial arrhythmias are a frequent complication during VV-ECMO and are independently associated with excessive in-hospital mortality. Thus, their presence may serve as an important prognostic tool in this patient population.

Ethical decision-making climate, moral distress, and intention to leave among ICU professionals in a tertiary academic hospital center.

BACKGROUND: Commentators believe that the ethical decision-making climate is instrumental in enhancing interprofessional collaboration in intensive care units (ICUs). Our aim was twofold: (1) to determine the perception of the ethical climate, levels of moral distress, and intention to leave one's job among nurses and physicians, and between the different ICU types and (2) determine the association between the ethical climate, moral distress, and intention to leave. METHODS: We performed a cross-sectional questionnaire study between May 2021 and August 2021 involving 206 nurses and physicians in a large urban academic hospital. We used the validated Ethical Decision-Making Climate Questionnaire (EDMCQ) and the Measure of Moral Distress for Healthcare Professionals (MMD-HP) tools and asked respondents their intention to leave their jobs. We also made comparisons between the different ICU types. We used Pearson's correlation coefficient to identify statistically significant associations between the Ethical Climate, Moral Distress, and Intention to Leave. RESULTS: Nurses perceived the ethical climate for decision-making as less favorable than physicians (p < 0.05). They also had significantly greater levels of moral distress and higher intention to leave their job rates than physicians. Regarding the ICU types, the Neonatal/Pediatric unit had a significantly higher overall ethical climate score than the Medical and Surgical units (3.54 ± 0.66 vs. 3.43 ± 0.81 vs. 3.30 ± 0.69; respectively; both p ≤ 0.05) and also demonstrated lower moral distress scores (both p < 0.05) and lower "intention to leave" scores compared with both the Medical and Surgical units. The ethical climate and moral distress scores were negatively correlated (r = -0.58, p < 0.001); moral distress and "intention to leave" was positively correlated (r = 0.52, p < 0.001); and ethical climate and "intention to leave" were negatively correlated (r = -0.50, p < 0.001). CONCLUSIONS: Significant differences exist in the perception of the ethical climate, levels of moral distress, and intention to leave between nurses and physicians and between the different ICU types. Inspecting the individual factors of the ethical climate and moral distress tools can help hospital leadership target organizational factors that improve interprofessional collaboration, lessening moral distress, decreasing turnover, and improved patient care.

Aspirin Use Is Associated With Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients With Coronavirus Disease 2019.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is associated with hypercoagulability and increased thrombotic risk in critically ill patients. To our knowledge, no studies have evaluated whether aspirin use is associated with reduced risk of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality. METHODS: A retrospective, observational cohort study of adult patients admitted with COVID-19 to multiple hospitals in the United States between March 2020 and July 2020 was performed. The primary outcome was the need for mechanical ventilation. Secondary outcomes were ICU admission and in-hospital mortality. Adjusted hazard ratios (HRs) for study outcomes were calculated using Cox-proportional hazards models after adjustment for the effects of demographics and comorbid conditions. RESULTS: Four hundred twelve patients were included in the study. Three hundred fourteen patients (76.3%) did not receive aspirin, while 98 patients (23.7%) received aspirin within 24 hours of admission or 7 days before admission. Aspirin use had a crude association with less mechanical ventilation (35.7% aspirin versus 48.4% nonaspirin, P = .03) and ICU admission (38.8% aspirin versus 51.0% nonaspirin, P = .04), but no crude association with in-hospital mortality (26.5% aspirin versus 23.2% nonaspirin, P = .51). After adjusting for 8 confounding variables, aspirin use was independently associated with decreased risk of mechanical ventilation (adjusted HR, 0.56, 95% confidence interval [CI], 0.37-0.85, P = .007), ICU admission (adjusted HR, 0.57, 95% CI, 0.38-0.85, P = .005), and in-hospital mortality (adjusted HR, 0.53, 95% CI, 0.31-0.90, P = .02). There were no differences in major bleeding (P = .69) or overt thrombosis (P = .82) between aspirin users and nonaspirin users. CONCLUSIONS: Aspirin use may be associated with improved outcomes in hospitalized COVID-19 patients. However, a sufficiently powered randomized controlled trial is needed to assess whether a causal relationship exists between aspirin use and reduced lung injury and mortality in COVID-19 patients.

Von Willebrand Factor Concentrate Administration for Acquired Von Willebrand Syndrome- Related Bleeding During Adult Extracorporeal Membrane Oxygenation.

OBJECTIVE: To review the use of Von Willebrand Factor (VWF) concentrate for treatment of acquired Von Willebrand syndrome (VWS)-related bleeding in adult extracorporeal membrane oxygenation (ECMO) patients and determine if it was associated with improved VWF laboratory parameters. DESIGN: Retrospective observational cohort study. SETTING: Tertiary care academic medical center. PARTICIPANTS: Adult ECMO patients who received VWF concentrate for treatment of acquired VWS- related bleeding. INTERVENTIONS: None, observational study. MEASUREMENTS AND MAIN RESULTS: Ten adult ECMO patients received VWF concentrate for treatment of bleeding with evidence of acquired VWS over a 15-month period. Six patients were on veno-arterial ECMO and 4 were on veno-venous ECMO. The most common site of bleeding was airway or tracheal bleeding. The mean dose of VWF concentrate was 41 IU/kg. Mean VWF antigen was 263 ± 93 IU/dL before treatment and 394 ± 54 after treatment. Mean ristocetin cofactor activity was 127 ± 47 IU/dL before treatment and 240 ± 33 after treatment. The mean VWF ristocetin cofactor activity antigen ratio increased from 0.52 ± 0.14 before treatment to 0.62 ± 0.04 after treatment. Four of 10 patients had complete resolution of their bleeding within 24 hours, and 6 of 10 had complete resolution of their bleeding within 2- to- 4 days. There were 3 patients who had thrombotic events potentially related to VWF concentrate administration. No patient had an arterial thrombosis, stroke, or myocardial infarction. CONCLUSIONS: VWF concentrate administration increases VWF function in adult ECMO patients, but also may be associated with increased thrombotic risk. Larger studies are needed to determine VWF concentrate's safety, efficacy, and optimal dosing in adult ECMO patients.

Development of Neurological Emergency Simulations for Assessment: Content Evidence and Response Process.

OBJECTIVE: To document two sources of validity evidence for simulation-based assessment in neurological emergencies. BACKGROUND: A critical aspect of education is development of evaluation techniques that assess learner's performance in settings that reflect actual clinical practice. Simulation-based evaluation affords the opportunity to standardize evaluations but requires validation. METHODS: We identified topics from the Neurocritical Care Society's Emergency Neurological Life Support (ENLS) training, cross-referenced with the American Academy of Neurology's core clerkship curriculum. We used a modified Delphi method to develop simulations for assessment in neurocritical care. We constructed checklists of action items and communication skills, merging ENLS checklists with relevant clinical guidelines. We also utilized global rating scales, rated one (novice) through five (expert) for each case. Participants included neurology sub-interns, neurology residents, neurosurgery interns, non-neurology critical care fellows, neurocritical care fellows, and neurology attending physicians. RESULTS: Ten evaluative simulation cases were developed. To date, 64 participants have taken part in 274 evaluative simulation scenarios. The participants were very satisfied with the cases (Likert scale 1-7, not at all satisfied-very satisfied, median 7, interquartile range (IQR) 7-7), found them to be very realistic (Likert scale 1-7, not at all realistic-very realistic, median 6, IQR 6-7), and appropriately difficult (Likert scale 1-7, much too easy-much too difficult, median 4, IQR 4-5). Interrater reliability was acceptable for both checklist action items (kappa = 0.64) and global rating scales (Pearson correlation r = .70). CONCLUSIONS: We demonstrated two sources of validity in ten simulation cases for assessment in neurological emergencies.

Intoxication and overdose should not preclude veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: Acute intoxication (AI) related morbidity and mortality are increasing in the United States. For patients with severe respiratory failure in the setting of an acute ingestion, veno-venous extracorporeal membrane oxygenation (VV ECMO) can provide salvage therapy. The purpose of this study was to evaluate outcomes in patients with overdose-related need for VV ECMO. METHODS: We performed a retrospective review of all patients admitted to a specialty VV ECMO unit between August 2014 and August 2018. Patients were stratified by those whose indication for VV ECMO was directly related to an acute ingestion (alcohol, illicit drug, or prescription drug overdose) and those with unrelated diagnoses. Demographics, pre-cannulation clinical characteristics, ECMO parameters, and outcomes data was collected and analyzed with parametric and non-parametric statistics as indicated. RESULTS: 189 patients were enrolled with 27 (14%) diagnosed with AI. Patients requiring VV ECMO for an AI were younger, had lower median BMI and PaO2/FiO2, and higher RESP scores than non-AI patients (p = 0.002, 0.01, 0.03 and 0.01). There was no difference in pre-cannulation pH, lactate, or SOFA scores between the two groups (p = 0.24, 0.5, 0.6). There was no difference in survival to discharge (p = 0.95). Among survivors, there was no difference in ECMO time or hospital stay (p = 0.24, 0.07). CONCLUSION: We demonstrate no survival difference for patients with and without an AI-related need for VV ECMO. AI patients should be supported with VV ECMO when traditional therapies fail despite potential stigma against acceptance on referral.

Methylprednisolone may be associated with improved lung compliance in acute respiratory distress syndrome patients on veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: Methylprednisolone has been used for acute respiratory distress syndrome with variable results. Veno-venous extracorporeal membrane oxygenation use in acute respiratory distress syndrome has increased. Occasionally, both are used. We hypothesized that methylprednisolone could improve lung compliance and ease weaning from extracorporeal membrane oxygenation in acute respiratory distress syndrome patients. METHODS: We retrospectively reviewed all patients in our veno-venous extracorporeal membrane oxygenation unit treated with methylprednisolone over a 20 month period. Methylprednisolone was initiated for inability to wean off veno-venous extracorporeal membrane oxygenation. Dynamic compliance (Cdyn) was calculated at cannulation, methylprednisolone initiation, and decannulation. Demographics, extracorporeal membrane oxygenation-specific data, and ventilator data were collected. Wilcoxon rank-sum test was used to test for differences in dynamic compliance. RESULTS: A total of 12 veno-venous extracorporeal membrane oxygenation patients received methylprednisolone. Mean age was 50 (±15) years. Seven had influenza. Methylprednisolone was started on median Day 16 (interquartile range: 11-22) of veno-venous extracorporeal membrane oxygenation. In total, 10 patients had veno-venous extracorporeal membrane oxygenation decannulation on median Day 12 (7-22) after methylprednisolone initiation. Two patients died before decannulation. The 10 decannulated patients had initial median dynamic compliance (mL × cm H2O-1) of 12 (7-23), then 16 (10-24) at methylprednisolone initiation, and then 44 (34-60) at decannulation. Dynamic compliance was higher at decannulation than methylprednisolone initiation (p = 0.002), and unchanged from cannulation to methylprednisolone initiation for all patients (p = 0.97). A total of 10 patients had significant infections. None had significant gastrointestinal bleed or wound healing issues. CONCLUSION: Methylprednisolone may be associated with improved compliance in acute respiratory distress syndrome allowing for decannulation from veno-venous extracorporeal membrane oxygenation. High rates of infection are associated with methylprednisolone use in veno-venous extracorporeal membrane oxygenation. Further studies are required to identify appropriate patient selection for methylprednisolone use in patients on veno-venous extracorporeal membrane oxygenation.

Safety and Feasibility of Early Physical Therapy for Patients on Extracorporeal Membrane Oxygenator: University of Maryland Medical Center Experience.

OBJECTIVES: To examine the feasibility and safety of mobilizing patients while on extracorporeal membranous oxygenation support. DESIGN: Retrospective cohort study. SETTING: Medical and Surgical ICUs in a large tertiary care hospital in the United States. PATIENTS: Adults supported on extracorporeal membranous oxygenation from January 2014 to December 2015. MEASUREMENTS AND MAIN RESULTS: We reviewed the medical records from physical therapy, perfusion, and intensivists to obtain the number and type of physical therapy interventions and discharge status; extracorporeal membranous oxygenation type and description of support, cannulation sites; and risk management details of adverse effects, if any. Of 254 patients supported on extracorporeal membranous oxygenation, 167 patients (66.7%) received a total of 607 physical therapy sessions while on extracorporeal membranous oxygenation support. In this cohort, 134 patients (80.2%) had at least one femoral cannula during physical therapy intervention. Sixty-six of the 167 patients (39.5%) were supported on extracorporeal membranous oxygenation with bifemoral cannulas, and 44 (26.3%) were on veno-arterial extracorporeal membranous oxygenation. A dual lumen catheter was only used in five cases. Twenty-five patients (15%) (13 bifemoral cases) participated in standing or ambulation activities. Seventy-five patients (68.8%) who were successfully weaned from extracorporeal membranous oxygenation were discharged to a rehabilitation facility; 26 patients (23.8%) went home. Three minor events (< 0.5%) involving two episodes of arrhythmias and a hypotension event interrupted the therapy sessions, but mobility activities and exercises resumed that day. No major events were reported. CONCLUSIONS: With a highly trained multidisciplinary team and a focus on restoring function, it is feasible and safe to deliver early rehabilitation including standing and ambulation to patients on extracorporeal membranous oxygenation support even those with femoral cannulation sites with veno-arterial extracorporeal membranous oxygenation and veno-venous extracorporeal membranous oxygenation.

Veno-Venous Extracorporeal Membrane Oxygenation (VV ECMO) for Acute Respiratory Failure Following Injury: Outcomes in a High-Volume Adult Trauma Center with a Dedicated Unit for VV ECMO.

INTRODUCTION: The use of veno-venous extracorporeal membrane oxygenation (VV ECMO) has increased over the past decade. The purpose of this study was to evaluate outcomes in adult trauma patients requiring VV ECMO. METHODS: Data were collected on adult trauma patients admitted between January 1, 2015, and November 1, 2016. Demographics, injury-specific data, ECMO data, and survival to discharge were recorded. Medians [interquartile range (IQR)] were reported. A p value ≤0.05 was considered statistically significant. RESULTS: Eighteen patients required VV ECMO during the study period. Median age was 28.5 years (IQR 24-43). Median injury severity score (ISS) was 27 (IQR 21-41); median PaO2/FiO2 (P/F) prior to ECMO cannulation was 61 (IQR 50-70). Median time from injury to cannulation was 3 (IQR 0-6) days. Median duration of ECMO was 266 (IQR 177-379) hours. Survival to discharge was 78%. Survivors had a significantly higher ISS (p = 0.03), longer intensive care unit length of stay (ICU LOS) (p < 0.0004), hospital LOS (p < 0.000004), and time on the ventilator (p < 0.0003). Median time of injury to cannulation was significantly longer in patients who survived to discharge (p = 0.01). There was no difference in P/F ratio prior to cannulation (p = ns). CONCLUSION: We have demonstrated improved outcome of patients requiring VV ECMO following injury compared to historical data. Although shorter time from injury to cannulation for VV ECMO was associated with death, select patients who meet criteria for VV ECMO early following injury should be referred/transferred to a tertiary care facility that specializes in trauma and ECMO care.