Timing of Initiation of Extracorporeal Membrane Oxygenation Support and Outcomes Among Patients With Cardiogenic Shock.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (ECMO) provides full hemodynamic support for patients with cardiogenic shock, but optimal timing of ECMO initiation remains uncertain. We sought to determine whether earlier initiation of ECMO is associated with improved survival in cardiogenic shock. METHODS AND RESULTS: We analyzed adult patients with cardiogenic shock who received venoarterial ECMO from the international Extracorporeal Life Support Organization (ELSO) registry from 2009 to 2019, excluding those cannulated following an operation. Multivariable logistic regression evaluated the association between time from admission to ECMO initiation and in-hospital death. Among 8619 patients (median, 56.7 [range, 44.8-65.6] years; 33.5% women), the median duration from admission to ECMO initiation was 14 (5-32) hours. Patients who had ECMO initiated within 24 hours (n=5882 [68.2%]) differed from those who had ECMO initiated after 24 hours, with younger age, more preceding cardiac arrest, and worse acidosis. After multivariable adjustment, patients with ECMO initiated >24 hours after admission had higher risk of in-hospital death (adjusted odds ratio, 1.20 [95% CI, 1.06-1.36]; P=0.004). Each 12-hour increase in the time from admission to ECMO initiation was incrementally associated with higher adjusted in-hospital mortality rate (adjusted odds ratio, 1.06 [95% CI, 1.03-1.10]; P<0.001). The association between longer time to ECMO and worse outcomes appeared stronger in patients with lower shock severity. CONCLUSIONS: Longer delays from admission to ECMO initiation were associated with higher a mortality rate in a large-scale, international registry. Our analysis supports optimization of door-to-support time and the avoidance of inappropriately delayed ECMO initiation.

Resuscitative transesophageal echocardiography in emergency departments in the United States and Canada: A cross-sectional survey.

INTRODUCTION: Over the past two decades, transesophageal echocardiography (TEE) has been used with increasing frequency to evaluate critically ill patients outside of traditional settings. The purpose of this study was to characterize the number of programs, users, practice characteristics, training and competency requirements and barriers for the current use of resuscitative transesophageal echocardiography (TEE) in Emergency Departments (EDs) in the United States and Canada. METHODS: A closed internet-based, cross-sectional, point-prevalence survey was administered via email to 120 program directors of emergency ultrasound fellowships (EUSF) and 43 physicians from EDs without EUSF from the United States and Canada. RESULTS: Ninety-eight percent of surveyed participants responded. Twenty percent of respondents reported having active resuscitative TEE programs. The majority of participating hospitals (70%) were academic centers with residency programs. A total of 33 programs reported using resuscitative TEE in their ED and of those, 82% were programs with EUSF. Most programs performing TEE (79%) had less than five attending physicians performing TEE. Evaluation of patients during resuscitation from cardiac arrest (100%) and post-arrest care (76%) are the two most frequent indications for TEE in the ED. The most common core elements of resuscitative TEE protocols used are: assessment of left ventricular (LV) systolic function (97%), assessment of right ventricular (RV) function (88%), evaluation of pericardial effusion / tamponade (52%). All programs reported using formal didactics in their training programs, 94% reported using high-fidelity simulation, and 79% live scanning of patients. Financial concerns were the most common barrier use of TEE in the ED (58%), followed by maintenance of equipment (30%), and credentialing/privileges (30%). CONCLUSIONS: This study provides a snapshot of the practice of resuscitative TEE in EDs in the United States and Canada revealing the existence of 33 programs using this emerging modality in the care of critically ill patients.

The Latest in Resuscitation Research: Highlights From the 2022 American Heart Association's Resuscitation Science Symposium.

BACKGROUND: Every year the American Heart Association's Resuscitation Science Symposium (ReSS) brings together a community of international resuscitation science researchers focused on advancing cardiac arrest care. METHODS AND RESULTS: The American Heart Association's ReSS was held in Chicago, Illinois from November 4th to 6th, 2022. This annual narrative review summarizes ReSS programming, including awards, special sessions and scientific content organized by theme and plenary session. CONCLUSIONS: By exploring both the science of resuscitation and important related topics including survivorship, disparities, and community-focused programs, this meeting provided important resuscitation updates.

Extracorporeal membrane oxygenation for cardiac arrest: what, when, why, and how.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) facilitated resuscitation was first described in the 1960s, but only recently garnered increased attention with large observational studies and randomized trials evaluating its use. AREAS COVERED: In this comprehensive review of extracorporeal cardiopulmonary resuscitation (ECPR), we report the history of resuscitative ECMO, terminology, circuit configuration and cannulation considerations, complications, selection criteria, implementation and management, and important considerations for the provider. We review the relevant guidelines, different approaches to cannulation, postresuscitation management, and expected outcomes, including neurologic, cardiac, and hospital survival. Finally, we advocate for the participation in national/international Registries in order to facilitate continuous quality improvement and support scientific discovery in this evolving area. EXPERT OPINION: ECPR is the most disruptive technology in cardiac arrest resuscitation since high-quality CPR itself. ECPR has demonstrated that it can provide up to 30% increased odds of survival for refractory cardiac arrest, in tightly restricted systems and for select patients. It is also clear, though, from recent trials that ECPR will not confer this high survival when implemented in less tightly protocoled settings and within lower volume environments. Over the next 10 years, ECPR research will explore the optimal initiation thresholds, best practices for implementation, and postresuscitation care.

Pulmonary Artery Pressures and Mortality during VA ECMO: An ELSO Registry Analysis.

Background: Systemic hemodynamics and specific ventilator settings have been shown to predict survival during venoarterial extracorporeal membrane oxygenation (VA ECMO). While these factors are intertwined with right ventricular (RV) function, the independent relationship between RV function and survival during VA ECMO is unknown. Objectives: To identify the relationship between RV function with mortality and duration of ECMO support. Methods: Cardiac ECMO runs in adults from the Extracorporeal Life Support Organization (ELSO) Registry between 2010 and 2022 were queried. RV function was quantified via pulmonary artery pulse pressure (PAPP) for pre-ECMO and on-ECMO periods. A multivariable model was adjusted for Society for Cardiovascular Angiography and Interventions (SCAI) stage, age, gender, and concurrent clinical data (i.e., pulmonary vasodilators and systemic pulse pressure). The primary outcome was in-hospital mortality. Results: A total of 4,442 ECMO runs met inclusion criteria and had documentation of hemodynamic and illness severity variables. The mortality rate was 55%; non-survivors were more likely to be older, have a worse SCAI stage, and have longer pre-ECMO endotracheal intubation times (P < 0.05 for all) than survivors. Improving PAPP from pre-ECMO to on-ECMO time (Δ PAPP) was associated with reduced mortality per 10 mm Hg increase (OR: 0.91 [95% CI: 0.86-0.96]; P=0.002). Increasing on-ECMO PAPP was associated with longer time on ECMO per 10 mm Hg (Beta: 15 [95% CI: 7.7-21]; P<0.001). Conclusions: Early improvements in RV function from pre-ECMO values were associated with mortality reduction during cardiac ECMO. Incorporation of Δ PAPP into risk prediction models should be considered.

The safety and tolerability of pirfenidone for bronchiolitis obliterans syndrome after hematopoietic cell transplant (STOP-BOS) trial.

Bronchiolitis obliterans syndrome (BOS) is the most morbid form of chronic graft-versus-host disease (cGVHD) after hematopoietic cell transplantation (HCT). Progressive airway fibrosis leads to a 5-year survival of 40%. Treatment options for BOS are limited. A single arm, 52-week, Phase I study of pirfenidone was conducted. The primary outcome was tolerability defined as maintaining the recommended dose of pirfenidone (2403 mg/day) without a dose reduction totaling more than 21 days, due to adverse events (AEs) or severe AEs (SAEs). Secondary outcomes included pulmonary function tests (PFTs) and patient reported outcomes (PROs). Among 22 participants treated for 1 year, 13 (59%) tolerated the recommended dose, with an average daily tolerated dose of 2325.6 mg/day. Twenty-two SAEs were observed, with 90.9% related to infections, none were attributed to pirfenidone. There was an increase in the average percent predicted forced expiratory volume in 1 s (FEV1%) of 7 percentage points annually and improvements in PROs related to symptoms of cGVHD. In this Phase I study, treatment with pirfenidone was safe. The stabilization in PFTs and improvements in PROs suggest the potential of pirfenidone for BOS treatment and support the value of a randomized controlled trial to evaluate the efficacy of pirfenidone in BOS after HCT. The study is registered in ClinicalTrials.gov (NCT03315741).

Similarities in extracorporeal membrane oxygenation management across intensive care unit types in the United States: An analysis of the Extracorporeal Life Support Organization Registry.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) use in the United States occurs often in cardiothoracic ICUs (CTICU). It is unknown how it varies across ICU types. METHODS: We identified 10 893 ECMO runs from the Extracorporeal Life Support Organization (ELSO) Registry across 2018 and 2019. Primary outcome was ECMO case volume by ICU type (CTICU vs. non-CTICU). Adjusting for pre-ECMO characteristics and case mix, secondary outcomes were on-ECMO physiologic variables by ICU location stratified by support type. RESULTS: CTICU ECMO occurred in 65.1% and 55.1% (2018 and 2019) of total runs. A minority of total runs related to cardiac surgery procedures (CTICU: 21.7% [2018], 18% [2019]; non-CTICU: 11.2% [2018], 13% [2019]). After multivariate adjustment, non-CTICU ECMO for cardiac support associated with lower 4- and 24-h circuit flow (3.9 liters per minute [LPM] vs. 4.1 LPM, p < 0.0001; 4.1 LPM vs. 4.3 LPM, p < 0.0001); for respiratory support, lower on-ECMO mean fraction of inspired oxygen ([Fi O2 ], 67% vs. 69%, p = 0.02) and lower respiratory rate (14 vs. 15, p < 0.0001); and, for extracorporeal cardiopulmonary resuscitation (ECPR), lower ECMO flow rates at 24 h (3.5 LPM vs. 3.7 LPM, p = 0.01). CONCLUSIONS: ECMO mostly remains in CTICUs though a minority is associated with cardiac surgery. Statistically significant but clinically minor differences in on-ECMO metrics were observed across ICU types.

Unexpected Interruptions in the Inhaled Epoprostenol Delivery System: Incidence of Adverse Sequelae and Therapeutic Consequences in Critically Ill Patients.

OBJECTIVES: Inhaled epoprostenol is a continuously delivered selective pulmonary vasodilator that is used in patients with refractory hypoxemia, right heart failure, and postcardiac surgery pulmonary hypertension. Published data suggest that inhaled epoprostenol administration via vibrating mesh nebulizer systems may lead to unexpected interruptions in drug delivery. The frequency of these events is unknown. The objective of this study was to describe the incidence and clinical consequences of unexpected interruption in critically ill patients. DESIGN: Retrospective review and analysis. SETTING: Stanford University Hospital, a 605-bed tertiary care center. PATIENTS: Patients receiving inhaled epoprostenol in 2019. INTERVENTIONS: No interventions. MEASUREMENTS AND MAIN RESULTS: Clinical indication, duration of inhaled epoprostenol delivery, mode of respiratory support, and documented unexpected interruption. In 2019, there were 493 administrations of inhaled epoprostenol in 433 unique patients. Primary indications for inhaled epoprostenol were right heart dysfunction (n = 394; 79.9%) and hypoxemia (n = 92; 18.7%). Unexpected delivery interruptions occurred in 31 administrations (6.3%). Median duration of therapy prior to unexpected interruption was 2 days (interquartile range, 2-5 d). Respiratory support at the time of unexpected interruption was mechanical ventilation (61.3%), high-flow nasal cannula (35.5%), and noninvasive positive pressure ventilation (3.2%). Adverse sequelae of unexpected interruption included elevated pulmonary artery pressures (n = 12), systemic hypotension (n = 8), hypoxemia (n = 8), elevated central venous pressure (n = 4), and cardiac arrest (n = 1). Therapeutic interventions following unexpected interruption included initiation of inhaled nitric oxide (n = 21), increase in vasoactive medication (n = 2), and increase in respiratory support (n = 2). Most of the adverse events were Common Terminology Criteria for Adverse Events grade 3 and 4 (93.5%). CONCLUSIONS: A retrospective review of patients receiving inhaled epoprostenol via vibrating mesh nebulizer in 2019 revealed interruptions in 6.3% of administrations with most of these interruptions requiring therapeutic intervention. The true incidence of unexpected interruption and subsequent rate of unexpected interruption's requiring intervention is unknown due to the reliance on unexpected interruption identification and subsequent documentation in the electronic medical record. Sudden interruption in inhaled epoprostenol delivery can result in severe cardiopulmonary compromise, and on rare occasion, death.

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.

Specific Considerations for Venovenous Extracorporeal Membrane Oxygenation During Coronavirus Disease 2019 Pandemic.

Extracorporeal membrane oxygenation (ECMO) is recognized as organ support for potentially reversible acute respiratory distress syndrome (ARDS). However, limited resource during the outbreak and the coagulopathy associated with coronavirus disease 2019 (COVID-19) make the utilization of venovenous (VV) ECMO highly challenging. We herein report specific considerations for cannulation configurations and ECMO management during the pandemic. High blood flow and anticoagulation at higher levels than usual practice for VV ECMO may be required because of thrombotic hematologic profile of COVID-19. Among our first 24 cases (48.8 ± 8.9 years), 17 patients were weaned from ECMO after a mean duration of 19.0 ± 10.1 days and 16 of them have been discharged from ICU.

Physiology of the Assisted Circulation in Cardiogenic Shock: A State-of-the-Art Perspective.

Mechanical circulatory support (MCS) has made rapid progress over the last 3 decades. This was driven by the need to develop acute and chronic circulatory support as well as by the limited organ availability for heart transplantation. The growth of MCS was also driven by the use of extracorporeal membrane oxygenation (ECMO) after the worldwide H1N1 influenza outbreak of 2009. The majority of mechanical pumps (ECMO and left ventricular assist devices) are currently based on continuous flow pump design. It is interesting to note that in the current era, we have reverted from the mammalian pulsatile heart back to the continuous flow pumps seen in our simple multicellular ancestors. This review will highlight key physiological concepts of the assisted circulation from its effects on cardiac dynamic to principles of cardiopulmonary fitness. We will also examine the physiological principles of the ECMO-assisted circulation, anticoagulation, and the haemocompatibility challenges that arise when the blood is exposed to a foreign mechanical circuit. Finally, we conclude with a perspective on smart design for future development of devices used for MCS.

End-of-Life Care, Palliative Care Consultation, and Palliative Care Referral in the Emergency Department: A Systematic Review.

CONTEXT: There is growing interest in providing palliative care (PC) in the emergency department (ED), but relatively little is known about the efficacy of ED-based PC interventions. A 2016 systematic review on this topic found no evidence that ED-based PC interventions affect patient outcomes or health care utilization, but new research has emerged since the publication of that review. OBJECTIVES: This systematic review provides a concise summary of current literature addressing the impact of ED-based PC interventions on patient-reported or family reported outcomes, health care utilization, and survival. METHODS: We searched PubMed, Embase, Web of Science, Scopus, and the Cumulative Index to Nursing and Allied Health Literature from inception until September 1, 2018 and reviewed references. Eligible articles evaluated the effects of PC interventions in the ED on patient-reported or family reported outcomes, health care utilization, or survival. RESULTS: We screened 3091 abstracts and 98 full-text articles with 13 articles selected for final inclusion. Two articles reported the results of a single randomized controlled trial, whereas the remaining 11 studies were descriptive or quasi-experimental cohort studies. More than half of the included articles were published after the previous systematic review on this topic. Populations studied included older adults, patients with advanced malignancy, and ED patients screening positive for unmet PC needs. Most interventions involved referral to hospice or PC or PC provided directly in the ED. Compared with usual care, ED-PC interventions improved quality of life, although this improvement was not observed when comparing ED-PC to inpatient PC. ED-PC interventions expedited PC consultation; most studies reported a concomitant reduction in hospital length of stay and increase in hospice utilization, but some data were conflicting. Short-term mortality rates were high across all studies, but ED-PC interventions did not decrease survival time compared with usual care. CONCLUSION: Existing data support that PC in the ED is feasible, may improve quality of life, and does not appear to affect survival.

Noninvasive Ventilation for Critically Ill Subjects With Acute Respiratory Failure in the Emergency Department.

BACKGROUND: We aimed to investigate the association between noninvasive ventilation (NIV) initiated in the emergency department and patient outcomes for those requiring invasive mechanical ventilation so that we could understand the effect of extended NIV use (ie, > 4 h) prior to invasive mechanical ventilation on patient outcomes. METHODS: We conducted a retrospective single-center cohort study at an academic tertiary care hospital center. All emergency department patients with acute respiratory failure requiring invasive mechanical ventilation and admission to the ICU within 48 h of initial presentation over a 24-month period were included. RESULTS: Subject characteristics, ventilator parameters, and clinical course were captured via electronic query, respiratory billing data, and standardized chart abstraction. A total of 431 subjects with acute respiratory failure requiring invasive mechanical ventilation within 48 h of arrival were identified, of whom 115 (26.7%) were exposed to NIV prior to invasive mechanical ventilation, with a median duration of 4 h (interquartile range 1.9-9.3). Based on a multivariable model controlling for covariates, any NIV exposure prior to invasive mechanical ventilation was not associated with an increased odds of persistent organ dysfunction or death. However, in the subset of subjects exposed to NIV, extended NIV use (ie, > 4 h) prior to invasive mechanical ventilation was associated with increased odds of persistent organ dysfunction or death (odds ratio 4.11, 95% CI 1.51-11.19). Extended NIV use was also associated with increased odds of in-hospital mortality (odds ratio 4.02, 95% CI 1.51-10.74). CONCLUSIONS: Although any exposure to NIV prior to invasive mechanical ventilation did not appear to affect morbidity and mortality, extended NIV use prior to invasive mechanical ventilation was associated with worse patient outcomes, suggesting a need for additional study to better understand the ramifications of duration of NIV use prior to failure on outcomes. Given this early timeframe for intervention, future studies should be collaborations between the emergency department and ICU.

The effect of emergency department crowding on lung-protective ventilation utilization for critically ill patients.

OBJECTIVE: To measure effects of ED crowding on lung-protective ventilation (LPV) utilization in critically ill ED patients. METHODS: This is a retrospective cohort study of adult mechanically ventilated ED patients admitted to the medical intensive care unit (MICU), over a 3.5-year period at a single academic tertiary care hospital. Clinical data, including reason for intubation, severity of illness (MPM0-III), acute respiratory distress syndrome (ARDS) risk score (EDLIPS), and ventilator settings were extracted via electronic query of electronic health record and standardized chart abstraction. Crowding metrics were obtained at 5-min intervals and averaged over the ED stay, stratified by acuity and disposition. Multivariate logistic regression was used to predict likelihood of LPV prior to ED departure. RESULTS: Mechanical ventilation was used in 446 patients for a median ED duration of 3.7 h (interquartile ratio, IQR, 2.3, 5.6). Mean MPM0-III score was 32.5 ±â€¯22.7, with high risk for ARDS (EDLIPS ≥5) seen in 373 (82%) patients. Initial and final ED ventilator settings differed in 134 (30.0%) patients, of which only 47 (35.1%) involved tidal volume changes. Higher percentages of active ED patients (workup in-progress) and those requiring eventual admission were associated with lower odds of LPV utilization by ED departure (OR 0.97, 95%CI 0.94-1.00; OR 0.97, 95%CI 0.94-1.00, respectively). In periods of high volume, ventilator adjustments to settings other than the tidal volume were associated with higher odds of LPV utilization. Reason for intubation, MPM0-III, and EDLIPS were not associated with LPV utilization, with no interactions detected in times of crowding. CONCLUSIONS: ED patients remain on suboptimal tidal volume settings with infrequent ventilator adjustments during the ED stay. Hospitals should focus on both systemic factors and bedside physician and/or respiratory therapist interventions to increase LPV utilization in times of ED boarding and crowding for all patients.