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Venoarterial extracorporeal membrane oxygenation (VA-ECMO) shunts venous blood to the systemic arterial circulation to provide end-organ perfusion while increasing afterload that may impede left ventricle (LV) ejection and impair cardiac recovery. To maintain flow across the aortic valve and reduce risk of lethal clot formation, secondary mechanical circulatory support (MCS) devices are increasingly used despite limited understanding of their effects on cardiac function. This study sought to quantify the effects of VA-ECMO and combined with either intraaortic balloon pump (IABP) or percutaneous ventricular assist device (pVAD) on LV physiologic state and perfusion metrics in a porcine model of acute cardiogenic shock. Shock was induced through serial left anterior descending artery microbead embolization followed by initiation of VA-ECMO support and then placement of either IABP or pVAD. Hemodynamic measurements, LV pressure-volume loops, and carotid artery blood flow were evaluated before and after institution of combined MCS. The IABP decreased LV end-diastolic pressure by a peak of 15% while slightly increasing LV stroke work compared with decreases of more than 60% and 50% with the pVAD, respectively. The pVAD also demonstrated increased coronary perfusion and systemic pressure gradients in comparison to the IABP. Combined support with VA-ECMO and pVAD improves cardiovascular state in comparison to IABP., (Copyright © ASAIO 2024.)

Background: This study seeks to quantify the effects of upper body veno-arterial extracorporeal membrane oxygenation (VA ECMO) on the anatomical distribution of oxygen delivery in the setting of hypoxic respiratory failure and provide new insights that will guide clinical use of this support strategy to bridge patients to lung transplant., Methods: Employing a patient-specific vascular geometry and a quantitative model of oxygen transport, computational simulations were performed to determine hemodynamics and oxygen delivery in the ascending and descending aorta, left and right coronary arteries, and great vessels during upper body VA ECMO support. Oxygen content in ECMO circuit blood flow was varied while considering different degrees of lung failure severity. Using lumped parameter models to dynamically apply perfusion boundary conditions, hemodynamic parameters and oxygen content were analyzed to assess the effect of ECMO supply titration., Results: The results emphasize the importance of anatomical distribution for tissue oxygen delivery in severe lung failure, with ECMO-derived flow primarily augmenting oxygen content in specific vascular beds. They also demonstrate that although cannulating the subclavian artery can enhance cerebral oxygen delivery, its ability to ensure sufficient oxygen delivery to the coronary circulation seems to be comparatively restricted., Conclusions: The oxygen delivery to a specific vascular area is primarily determined by the oxygen content in the source of perfusion. Caution is advised with upper body VA ECMO for patients with hypoxic respiratory failure and right ventricle dysfunction, due to potential coronary ischemia. Management of these patients is challenging due to disease progression and organ availability uncertainties., Competing Interests: Declaration of competing interest Hamed Moradi denies any competing interests. Raghu Seethala denies any competing interests. Elazer Edelman is the primary investigator of an educational grant to the Massachusetts Institute of Technology (MIT) from Abiomed, Inc. that investigates use of mechanical circulatory support devices. He has developed intellectual property that is licensed to Abiomed, Inc. through MIT. This work is in the related field of mechanical support but is not directly related to the submitted work. Farhad Nezami denies any competing interests. Steven Keller is a co-inventor of intellectual property with Dr. Edelman that is licensed to Abiomed, Inc. through MIT. This work is not directly related to the submitted work., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Percutaneous ventricular assist devices are increasingly relied on to maintain perfusion for cardiogenic shock patients. Optimal medical management strategies however remain uncertain from limited understanding of interventricular effects. This study analyzed the effects of pharmacologic and left-sided mechanical support on right ventricular function., Methods: A porcine model was developed to assess biventricular function during bolus pharmacologic administration before and after left-sided percutaneous ventricular assist and in cardiogenic shock., Results: The presence of mechanical support increased right ventricular load and stress with respect to the left ventricle. This shifted and exaggerated the relative effects of commonly used vasoactive agents. Furthermore, induction of cardiogenic shock led to differential pulmonary vascular and right ventricular responses., Conclusions: Left ventricular ischemia and mechanical support altered interventricular coupling. Resulting impacts of pharmacologic agents indicate differential right heart responses and sensitivity to treatments and the need for further study to optimize biventricular function in shock patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Postcardiotomy shock in the cardiac surgical patient is a highly morbid condition characterized by profound myocardial impairment and decreased systemic perfusion inadequate to meet end-organ metabolic demand. Postcardiotomy shock is associated with significant morbidity and mortality. Poor outcomes motivate the increased use of mechanical circulatory support (MCS) to restore perfusion in an effort to prevent multiorgan injury and improve patient survival. Despite growing acceptance and adoption of MCS for postcardiotomy shock, criteria for initiation, clinical management, and future areas of clinical investigation remain a topic of ongoing debate. This article seeks to (1) define critical cardiac dysfunction in the patient after cardiotomy, (2) provide an overview of commonly used MCS devices, and (3) summarize the relevant clinical experience for various MCS devices available in the literature, with additional recognition for the role of MCS as a part of a modified approach to the cardiac arrest algorithm in the cardiac surgical patient., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: Glenn JR Whitman reports a relationship with Avania that includes: consulting or advisory. Glenn JR Whitman reports a relationship with GWBN LLC that includes: equity or stocks. Michael C Grant reports a relationship with ERAS Cardiac Society that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Skin pigmentation influences peripheral oxygen saturation (SpO 2 ) compared to arterial saturation of oxygen (SaO 2 ). Occult hypoxemia (SaO 2  ≤ 88% with SpO 2  ≥ 92%) is associated with increased in-hospital mortality in venovenous-extracorporeal membrane oxygenation (VV-ECMO) patients. We hypothesized VV-ECMO cannulation, in addition to race/ethnicity, accentuates the SpO 2 -SaO 2 discrepancy due to significant hemolysis., Methods: Adults (≥ 18 years) supported with VV-ECMO with concurrently measured SpO 2 and SaO 2 measurements from over 500 centers in the Extracorporeal Life Support Organization Registry (1/2018-5/2023) were included. Multivariable logistic regressions were performed to examine whether race/ethnicity was associated with occult hypoxemia in pre-ECMO and on-ECMO SpO 2 -SaO 2 calculations., Results: Of 13,171 VV-ECMO patients, there were 7772 (59%) White, 2114 (16%) Hispanic, 1777 (14%) Black, and 1508 (11%) Asian patients. The frequency of on-ECMO occult hypoxemia was 2.0% (N = 233). Occult hypoxemia was more common in Black and Hispanic patients versus White patients (3.1% versus 1.7%, P < 0.001 and 2.5% versus 1.7%, P = 0.025, respectively). In multivariable logistic regression, Black patients were at higher risk of pre-ECMO occult hypoxemia versus White patients (adjusted odds ratio [aOR] = 1.55, 95% confidence interval [CI] = 1.18-2.02, P = 0.001). For on-ECMO occult hypoxemia, Black patients (aOR = 1.79, 95% CI = 1.16-2.75, P = 0.008) and Hispanic patients (aOR = 1.71, 95% CI = 1.15-2.55, P = 0.008) had higher risk versus White patients. Higher pump flow rates (aOR = 1.29, 95% CI = 1.08-1.55, P = 0.005) and on-ECMO 24-h lactate (aOR = 1.06, 95% CI = 1.03-1.10, P < 0.001) significantly increased the risk of on-ECMO occult hypoxemia., Conclusion: SaO 2 should be carefully monitored if using SpO 2 during ECMO support for Black and Hispanic patients especially for those with high pump flow and lactate values at risk for occult hypoxemia., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: We sought to characterize the association between venovenous extracorporeal membrane oxygenation (VV-ECMO) bridging duration and outcomes in patients listed for lung transplantation., Methods: A retrospective observational study was conducted using the Organ Procurement and Transplantation Network (OPTN) database to identify adults (aged ≥18 years) who were listed for lung transplantation between 2016 and 2020 and were bridged with VV-ECMO. Patients were then stratified into groups, determined by risk inflection points, depending on the amount of time spent on pretransplant ECMO: group 1 (≤5 days), group 2 (6-10 days), group 3 (11-20 days), and group 4 (>20 days). Waiting list survival between groups was analyzed using Fine-Gray competing risk models. Posttransplant survival was compared using Cox regression., Results: Of 566 eligible VV-ECMO bridge-to-lung-transplant patients (median age, 54 years, 49% men), 174 (31%), 124 (22%), 130 (23%), and 138 (24%) were categorized as groups 1, 2, 3, and 4, respectively. Overall, median duration of VV-ECMO was 10 days (interquartile range, 1-211 days), and 178 patients (31%) died on the waiting list. In the Fine-Gray model, compared with group 1, patients bridged with longer ECMO durations in group 2 (subdistribution hazard ratio [SHR], 2.95; 95% CI, 1.63-5.35), group 3 (SHR, 3.96; 95% CI, 2.36-6.63), and group 4 (SHR, 4.33; 95% CI, 2.59-7.22, all P < .001) were more likely to die on the waiting list. Of 388 patients receiving a transplant, pretransplant ECMO duration was not associated with 1-year survival in Cox regression., Conclusions: Prolonged duration of ECMO bridging was associated with worse waiting list mortality but did not impact survival after lung transplant. Prioritization of very early transplantation may improve waiting list outcomes in this population., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Cannulation strategy, vasopressors, and hemolysis are important physiological factors that influence hemodynamics in extracorporeal membrane oxygenation (ECMO). We hypothesized these factors influence the discrepancy between oxygen saturation measured by pulse oximetry (Spo 2 ) and arterial blood gas (Sao 2 ) in patients on ECMO., Methods: We retrospectively analyzed adults (aged ≥18 years) on venoarterial or venovenous ECMO at a tertiary academic ECMO center. Spo 2 -Sao 2 pairs with oxygen saturation ≥70% and measured within 10 minutes were included. Occult hypoxemia was defined as Sao 2 ≤88% with a time-matched Spo 2 ≥92%. Adjusted linear mixed-effects modeling was used to assess the Spo 2 -Sao 2 discrepancy with preselected demographics and time-matched laboratory variables. Vasopressor use was quantified by vasopressor dose equivalences., Results: Of 139 venoarterial-ECMO and 88 venovenous-ECMO patients, we examined 20,053 Spo 2 -Sao 2 pairs. The Spo 2 -Sao 2 discrepancy was greater in venovenous-ECMO (1.15%) vs venoarterial-ECMO (-0.35%, P < .001). Overall, 81 patients (35%) experienced occult hypoxemia during ECMO. Occult hypoxemia was more common in venovenous-ECMO (65%) than in venoarterial-ECMO (17%, P < .001). In linear mixed-effects modeling, Spo 2 underestimated Sao 2 by 9.48% in central vs peripheral venoarterial-ECMO (95% CI, -17.1% to -1.79%; P = .02). Higher vasopressor dose equivalences significantly worsened the Spo 2 -Sao 2 discrepancy (P < .001). In linear mixed-effects modeling, Spo 2 overestimated Sao 2 by 25.43% in single lumen-cannulated vs double lumen-cannulated venovenous-ECMO (95% CI, 5.27%-45.6%; P = .03). Higher vasopressor dose equivalences and lactate dehydrogenase levels significantly worsened the Spo 2 -Sao 2 discrepancy (P < .001)., Conclusions: Venovenous-ECMO patients are at higher risk for occult hypoxemia compared with venoarterial-ECMO. A higher vasopressor requirement and different cannulation strategies (central venoarterial-ECMO; single-lumen venovenous-ECMO) were significant factors for clinically significant Spo 2 -Sao 2 discrepancy in both ECMO modes., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Ventricular assist devices (VADs) offer mechanical support for patients with cardiogenic shock by unloading the impaired ventricle and increasing cardiac outflow and subsequent tissue perfusion. Their ability to adjust ventricular assistance allows for rapid and safe dynamic changes in cardiac load, which can be used with direct measures of chamber pressures to quantify cardiac pathophysiologic state, predict response to interventions, and unmask vulnerabilities such as limitations of left-sided support efficacy due to intolerance of the right heart. We defined hemodynamic metrics in five pigs with dynamic peripheral transvalvular VAD (pVAD) support to the left ventricle. Metrics were obtained across a spectrum of disease states, including left ventricular ischemia induced by titrated microembolization of a coronary artery and right ventricular strain induced by titrated microembolization of the pulmonary arteries. A sweep of different pVAD speeds confirmed mechanisms of right heart decompensation after left-sided support and revealed intolerance. In contrast to the systemic circulation, pulmonary vascular compliance dominated in the right heart and defined the ability of the right heart to adapt to left-sided pVAD unloading. We developed a clinically accessible metric to measure pulmonary vascular compliance at different pVAD speeds that could predict right heart efficiency and tolerance to left-sided pVAD support. Findings in swine were validated with retrospective hemodynamic data from eight patients on pVAD support. This methodology and metric could be used to track right heart tolerance, predict decompensation before right heart failure, and guide titration of device speed and the need for biventricular support.

Background: Extracorporeal membrane oxygenation (ECMO) is increasingly relied on to bridge patients with respiratory failure to lung transplantation despite limited evidence for its use in this setting. This study evaluated longitudinal trends in practice patterns, patient characteristics, and outcomes in patients bridged with ECMO to lung transplant., Methods: A retrospective review of all adult isolated lung transplant patients in the United Network for Organ Sharing database between 2000 and 2019 was performed. Patients were classified as "ECMO" if supported with ECMO at the time of listing or transplantation and "non-ECMO" otherwise. Linear regression was used to evaluate trends in patient demographics during the study period. Trends in mortality were evaluated using Cox proportional hazards modeling, with time period as the primary covariate (2000-2004, 2005-2009, 2010-2014, or 2015-2019) and age, time on the waitlist, and underlying diagnosis as covariates., Results: The number of patients included were 40,866, of whom 1,387 (3.4%) were classified as ECMO and 39,479 (96.6%) as no ECMO. Average age and initial Lung Allocation Score increased significantly during the study period in both cohorts, but occurred at a slower rate in the ECMO population. The hazard of death was significantly lower in more recent years (2015-2019) for both the ECMO and non-ECMO cohorts (aHR (adjusted hazards ratio) 0.59, 95% confidence interval (CI) 0.37-0.96 and aHR 0.74, 95% CI 0.70-0.79) when compared to the early years (2000-2004) of the study period., Conclusions: Post-transplantation survival for patients bridged to transplantation with ECMO demonstrates ongoing improvement despite cannulation of progressively older and sicker patients., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Importance: Skin pigmentation influences peripheral oxygen saturation (SpO 2 ) measured by pulse oximetry compared to the arterial saturation of oxygen (SaO 2 ) measured via arterial blood gas analysis. However, data on SpO 2 -SaO 2 discrepancy are limited in venovenous-extracorporeal membrane oxygenation (VV-ECMO) patients., Objective: To determine whether there is racial/ethnical discrepancy between SpO 2 and SaO 2 in patients receiving VV-ECMO. We hypothesized VV-ECMO cannulation, in addition to race/ethnicity, accentuates the SpO 2 -SaO 2 discrepancy due to significant hemolysis., Design: Retrospective cohort study of the Extracorporeal Life Support Organization Registry from 1/2018-5/2023., Setting: International, multicenter registry study including over 500 ECMO centers., Participants: Adults (≥ 18 years) supported with VV-ECMO with concurrently measured SpO 2 and SaO 2 measurements., Exposure: Race/ethnicity and ECMO cannulation., Main Outcomes and Measures: Occult hypoxemia (SaO 2 ≤ 88% with SpO 2 ≥ 92%) was our primary outcome. Multivariable logistic regressions were performed to examine whether race/ethnicity was associated with occult hypoxemia in pre-ECMO and on-ECMO SpO 2 -SaO 2 calculations. Covariates included age, sex, temporary mechanical circulatory support, pre-vasopressors, and pre-inotropes for pre-ECMO analysis, plus single-lumen versus double-lumen cannulation, hemolysis, hyperbilirubinemia, ECMO pump flow rate, and on-ECMO 24h lactate for on-ECMO analysis., Results: Of 13,171 VV-ECMO patients (median age = 48.6 years, 66% male), there were 7,772 (59%) White, 2,114 (16%) Hispanic, 1,777 (14%) Black, and 1,508 (11%) Asian patients. The frequency of on-ECMO occult hypoxemia was 2.0% ( N = 233). Occult hypoxemia was more common in Black and Hispanic versus White patients (3.1% versus 1.7%, P < 0.001 and 2.5% versus 1.7%, P = 0.025, respectively).In multivariable logistic regression, Black patients were at higher risk of pre-ECMO occult hypoxemia versus White patients (adjusted odds ratio [aOR] = 1.55, 95% confidence interval [CI] = 1.18-2.02, P = 0.001). For on-ECMO occult hypoxemia, Black patients (aOR = 1.79, 95%CI = 1.16-2.75, P = 0.008) and Hispanic patients (aOR = 1.71, 95%CI = 1.15-2.55, P = 0.008) had higher risk versus White patients. Furthermore, higher pump flow rate (aOR = 1.29, 95%CI = 1.08-1.55, P = 0.005) and higher on-ECMO 24h lactate (aOR = 1.06, 95%CI = 1.03-1.10, P < 0.001) significantly increased the risk of on-ECMO occult hypoxemia., Conclusions and Relevance: Hispanic and Black VV-ECMO patients experienced occult hypoxemia more than White patients. SaO 2 should be carefully monitored during ECMO support for Black and Hispanic patients especially for those with high pump flow and lactate values at risk for occult hypoxemia., Competing Interests: Dr. Tonna is supported by a Career Development Award from the National Institutes of Health/National Heart, Lung, And Blood Institute (K23 HL141596). Dr. Tonna is the Chair of the Registry Committee of the Extracorporeal Life Support Organization (ELSO). Dr. Brodie receives research support from and consults for LivaNova. He has been on the medical advisory boards for Abiomed, Xenios, Medtronic, Inspira and Cellenkos. He is the President-elect of the Extracorporeal Life Support Organization (ELSO) and the Chair of the Executive Committee of the International ECMO Network (ECMONet), and he writes for UpToDate. Dr. Lorusso is a consultant for Medtronic, LivaNova, Getinge and ASbiomed, and Member of the Medical Advisory Board of Eurosets and Xenios. He is the ELSO Research Committee Chair, and Honorary Secretary of EuroELSO. The authors do not have any additional conflicts of interest to declare. SPK is supported by NHLBI (5K08HL14332). SMC is supported by NHLBI (1K23HL157610).Disclosures: The authors have nothing to disclose

Background: Lung transplantation (LTx) is the definitive treatment for end-stage lung failure. However, there have been no large, long-term studies on the impact of acute in-hospital stroke in this population., Research Question: What are the trends, risk factors, and outcomes of acute stroke in patients undergoing LTx in the United States?, Study Design and Methods: We identified adult first-time isolated LTx recipients from the United Network for Organ Sharing database, which comprehensively captures every transplant in the United States, between May 2005 and December 2020. Stroke was defined as occurring at any time after LTx but prior to discharge. Multivariable logistic regression with stepwise feature elimination was used to identify risk factors for stroke. Freedom from death in patients with a stroke vs those without a stroke was evaluated with Kaplan-Meier analysis. Cox proportional hazards analysis was used to identify predictors of death at 24 months., Results: Of 28,564 patients (median age, 60 years; 60% male), 653 (2.3%) experienced an acute in-hospital stroke after LTx. Median follow-up was 1.2 (stroke) and 3.0 (non-stroke) years. Annual incidence of stroke increased (1.5% in 2005 to 2.4% in 2020; P for trend = .007), as did lung allocation score and utilization of post-LTx extracorporeal membrane oxygenation (P = .01 and P < .001, respectively). Compared with those without stroke, patients with stroke had lower survival at 1 month (84% vs 98%), 12 months (61% vs 88%), and 24 months (52% vs 80%) (log-rank test, P < .001 for all). In Cox analysis, acute stroke conferred a high hazard of mortality (hazard ratio, 3.01; 95% CI, 2.67-3.41). Post-LTx extracorporeal membrane oxygenation was the strongest risk factor for stroke (adjusted OR, 2.98; 95% CI, 2.19-4.06)., Interpretation: Acute in-hospital stroke post-LTx has been increasing over time and is associated with markedly worse short- and long-term survival. As increasingly sicker patients undergo LTx as well as experience stroke, further research on stroke characteristics, prevention, and management strategies is warranted., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Despite the high prevalence of neurological complications and mortality associated with extracorporeal cardiopulmonary resuscitation (ECPR), neurologically-focused animal models are scarce. Our objective is to review current ECPR models investigating neurological outcomes and identify key elements for a recommended model., Methods: We searched PubMed and four other engines for animal ECPR studies examining neurological outcomes. Inclusion criteria were: animals experiencing cardiac arrest, ECPR/ECMO interventions, comparisons of short versus long cardiac arrest times, and neurological outcomes., Results: Among 20 identified ECPR animal studies ( n  = 442), 13 pigs, 4 dogs, and 3 rats were used. Only 10% (2/20) included both sexes. Significant heterogeneity was observed in experimental protocols. 90% (18/20) employed peripheral VA-ECMO cannulation and 55% (11/20) were survival models (median survival = 168 hours; ECMO duration = 60 minutes). Ventricular fibrillation (18/20, 90%) was the most common method for inducing cardiac arrest with a median duration of 15 minutes (IQR = 6-20). In two studies, cardiac arrests exceeding 15 minutes led to considerable mortality and neurological impairment. Among seven studies utilizing neuromonitoring tools, only four employed multimodal devices to evaluate cerebral blood flow using Transcranial Doppler ultrasound and near-infrared spectroscopy, brain tissue oxygenation, and intracranial pressure. None examined cerebral autoregulation or neurovascular coupling., Conclusions: The substantial heterogeneity in ECPR preclinical model protocols leads to limited reproducibility and multiple challenges. The recommended model includes large animals with both sexes, standardized pre-operative protocols, a cardiac arrest time between 10-15 minutes, use of multimodal methods to evaluate neurological outcomes, and the ability to survive animals after conducting experiments., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

When COVID-19 ARDS abolishes pulmonary function, VV-ECMO can provide gas exchange. If oxygenation remains insufficient despite maximal VV-ECMO support, the addition of esmolol has been proposed. Conflict exists, however, as to the oxygenation level which should trigger beta-blocker initiation. We evaluated the effect of esmolol therapy on oxygenation and oxygen delivery in patients with negligible native lung function and various degrees of hypoxemia despite maximal VV-ECMO support. We found that, in COVID-19 patients with negligible pulmonary gas exchange, the generalized use of esmolol administration to raise arterial oxygenation by slowing heart rate and thereby match native cardiac output to maximal attainable VV ECMO flows actually reduces systemic oxygen delivery in many cases.

Background: Pulse pressure is a dynamic marker of cardiovascular function and is often impaired in patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Pulsatile blood flow also serves as a regulator of vascular endothelium, and continuous-flow mechanical circulatory support can lead to endothelial dysfunction. We explored the impact of early low pulse pressure on occurrence of acute brain injury (ABI) in VA-ECMO., Methods: We conducted a retrospective analysis of adults with VA-ECMO at a tertiary care center between July 2016 and January 2021. Patients underwent standardized multimodal neuromonitoring throughout ECMO support. ABI included intracranial hemorrhage, ischemic stroke, hypoxic ischemic brain injury, cerebral edema, seizure, and brain death. Blood pressures were recorded every 15 min. Low pulse pressure was defined as a median pulse pressure < 20 mm Hg in the first 12 h of ECMO. Multivariable logistic regression was performed to investigate the association between pulse pressure and ABI., Results: We analyzed 5138 blood pressure measurements from 123 (median age 63; 63% male) VA-ECMO patients (54% peripheral; 46% central cannulation), of whom 41 (33%) experienced ABI. Individual ABIs were as follows: ischemic stroke (n = 18, 15%), hypoxic ischemic brain injury (n = 14, 11%), seizure (n = 8, 7%), intracranial hemorrhage (n = 7, 6%), cerebral edema (n = 7, 6%), and brain death (n = 2, 2%). Fifty-eight (47%) patients had low pulse pressure. In a multivariable model adjusting for preselected covariates, including cannulation strategy (central vs. peripheral), lactate on ECMO day 1, and left ventricle venting strategy, low pulse pressure was independently associated with ABI (adjusted odds ratio 2.57, 95% confidence interval 1.05-6.24). In a model with the same covariates, every 10-mm Hg decrease in pulse pressure was associated with 31% increased odds of ABI (95% confidence interval 1.01-1.68). In a sensitivity analysis model adjusting for systolic pressure, pulse pressure remained significantly associated with ABI., Conclusions: Early low pulse pressure (< 20 mm Hg) was associated with ABI in VA-ECMO patients. Low pulse pressure may serve as a marker of ABI risk, which necessitates close neuromonitoring for early detection., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Acute brain injury (ABI) remains common after extracorporeal cardiopulmonary resuscitation (ECPR). Using a large international multicenter cohort, we investigated the impact of peri-cannulation arterial oxygen (PaO 2 ) and carbon dioxide (PaCO 2 ) on ABI occurrence., Methods: We retrospectively analyzed adult (≥18 years old) ECPR patients in the Extracorporeal Life Support Organization registry from 1/2009 through 12/2020. Composite ABI included ischemic stroke, intracranial hemorrhage (ICH), seizures, and brain death. The registry collects 2 blood gas data pre- (6 hours) and post- (24 hours) cannulation. Blood gas parameters were classified as: hypoxia (<60mm Hg), normoxia (60-119mm Hg), and mild (120-199mm Hg), moderate (200-299mm Hg), and severe hyperoxia (≥300mm Hg); hypocarbia (<35mm Hg), normocarbia (35-44mm Hg), mild (45-54mm Hg) and severe hypercarbia (≥55mm Hg). Missing values were handled using multiple imputation. Multivariable logistic regression analysis was used to assess the relationship of PaO 2 and PaCO 2 with ABI., Results: Of 3,125 patients with ECPR intervention (median age=58, 69% male), 488 (16%) experienced ABI (7% ischemic stroke; 3% ICH). In multivariable analysis, on-ECMO moderate (aOR=1.42, 95%CI: 1.02-1.97) and severe hyperoxia (aOR=1.59, 95%CI: 1.20-2.10) were associated with composite ABI. Additionally, severe hyperoxia was associated with ischemic stroke (aOR=1.63, 95%CI: 1.11-2.40), ICH (aOR=1.92, 95%CI: 1.08-3.40), and in-hospital mortality (aOR=1.58, 95%CI: 1.21-2.06). Mild hypercarbia pre-ECMO was protective of composite ABI (aOR=0.61, 95%CI: 0.44-0.84) and ischemic stroke (aOR=0.56, 95%CI: 0.35-0.89)., Conclusions: Early severe hyperoxia (≥300mm Hg) on ECMO was a significant risk factor for ABI and mortality. Careful consideration should be given in early oxygen delivery in ECPR patients who are at risk of reperfusion injury., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether there is racial/ethnical discrepancy between pulse oximetry (SpO 2 ) and oxygen saturation (SaO 2 ) in patients receiving extracorporeal membrane oxygenation (ECMO)., Methods: This was a retrospective observational study at a tertiary academic ECMO center with adults (>18 years) on venoarterial (VA) or venovenous (VV) ECMO. Datapoints were excluded if oxygen saturation ≤70% or SpO 2 -SaO 2 pairs were not measured within 10 minutes. The primary outcome was the presence of a SpO 2 -SaO 2 discrepancy between different races/ethnicities. Bland-Altman analyses and linear mixed-effects modeling, adjusting for prespecified covariates, were used to assess the SpO 2 -SaO 2 discrepancy between races/ethnicities. Occult hypoxemia was defined as SaO 2 <88% with a time-matched SpO 2 ≥92%., Results: Of 139 patients receiving VA-ECMO and 57 patients receiving VV-ECMO, we examined 16,252 SpO 2 -SaO 2 pairs. The SpO 2 -SaO 2 discrepancy was greater in VV-ECMO (1.4%) versus VA-ECMO (0.15%). In VA-ECMO, SpO 2 overestimated SaO 2 in Asian (0.2%), Black (0.94%), and Hispanic (0.03%) patients and underestimated SaO 2 in White (-0.06%) and nonspecified race (-0.80%) patients. The proportion of SpO 2 -SaO 2 measurements considered occult hypoxemia was 70% from Black compared to 27% from White patients ( P  < .0001). In VV-ECMO, SpO 2 overestimated SaO 2 in Asian (1.0%), Black (2.9%), Hispanic (1.1%), and White (0.50%) patients and underestimated SaO 2 in nonspecified race patients (-0.53%). In linear mixed-effects modeling, SpO 2 overestimated SaO 2 by 0.19% in Black patients (95% confidence interval, 0.045%-0.33%, P  = .023). The proportion of SpO 2 -SaO 2 measurements considered occult hypoxemia was 66% from Black compared with 16% from White patients ( P  < .0001)., Conclusions: SpO 2 overestimates SaO 2 in Asian, Black, and Hispanic versus White patients, and this discrepancy was greater in VV-ECMO versus VA-ECMO, suggesting the need for physiological studies., (© 2023 The Author(s).)

Extracorporeal membrane oxygenation (ECMO) is a vital mechanical circulatory support modality capable of restoring perfusion for the patient in circulatory failure. Despite increasing adoption of ECMO, there is incomplete understanding of its effects on systemic hemodynamics and how the vasculature responds to varying levels of continuous retrograde perfusion. To gain further insight into the complex ECMO:failing heart circulation, computational fluid dynamics simulations focused on perfusion distribution and hemodynamic flow patterns were conducted using a patient-derived aorta geometry. Three case scenarios were simulated: (1) healthy control; (2) 90% ECMO-derived perfusion to model profound heart failure; and, (3) 50% ECMO-derived perfusion to model the recovering heart. Fluid-structure interface simulations were performed to quantify systemic pressure and vascular deformation throughout the aorta over the cardiac cycle. ECMO support alters pressure distribution while decreasing shear stress. Insights derived from computational modeling may lead to better understanding of ECMO support and improved patient outcomes., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Extracorporeal membrane oxygenation (ECMO) via femoral cannulation is a vital intervention capable of rapidly restoring perfusion for patients in shock. Despite increasing use to provide circulatory support, its hemodynamic effects are poorly understood and the impact of patient-specific anatomical variation on perfusion is unknown. This study investigates the complex failing heart-mechanical circulatory support circulation and analyzes the effect of patient-specific vascular anatomical variations on hemodynamics and end-organ perfusion., Methods: Patient-specific vascular geometries were constructed from segmenting clinical computerized tomography angiography images and quantitatively compared using tortuosity, curvature, torsion, and lumen diameter. Computational fluid dynamic simulations were performed on a subset of geometries selected to represent a range of anatomical variation. Heart failure severity was modeled by varying the relative fraction of total flow provided by the heart and the extracorporeal circuit. A 3-element lumped parameter model was applied to accurately and dynamically model distal perfusion boundary conditions. Hemodynamic parameters and end-organ perfusion were analyzed and compared to assess the effect of anatomical variation., Results: Pulsatile antegrade cardiac perfusion and ECMO retrograde perfusion collide in the aorta to form a dynamic watershed region. The size, position, and variation of this region over the cardiac cycle is substantially altered by patient anatomical region. Increased vascular tortuosity reduces the proximal extent of flow from circulatory support and decreases the size of the watershed region., Conclusions: Patient vascular anatomy is a key determinant of the ECMO-failing heart circulation that alters the location and extent of the watershed region and affects the tissues at risk for differential hypoxia and circuit-derived thromboemboli for a given level of support., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Acute heart failure and cardiogenic shock remain highly morbid conditions despite prompt medical therapy in critical care settings. Mechanical circulatory support (MCS) is a promising therapy for these patients, yet remains managed with open-loop control. Continuous measure of cardiac function would support and optimize MCS deployment and weaning. The nature of indwelling MCS provides a platform for attaining this information. This study investigates how hysteresis modeling derived from MCS device signals can be used to assess contractility changes to provide continuous indication of changing cardiac state. Load-dependent MCS devices vary their operation with cardiac state to yield a device-heart hysteretic interaction. Predicting and examining this hysteric relation provides insight into cardiac state and can be separated by cardiac cycle phases. Here, we demonstrate this by predicting hysteresis and using the systolic portion of the hysteresis loop to estimate changes in native contractility. This study quantified this measurement as the enclosed area of the systolic portion of the hysteresis loop and correlated it with other widely accepted contractility metrics in animal studies (n = 4) using acute interventions that alter inotropy, including a heart failure model. Clinical validation was performed in patients (n = 8) undergoing Impella support., Results: Hysteresis is well estimated from device signals alone (r = 0.92, limits of agreement: - 0.18 to 0.18). Quantified systolic area was well correlated in animal studies with end-systolic pressure-volume relationship (r = 0.84), preload recruitable stroke work index (r = 0.77), and maximum slope of left ventricular pressure (dP/dt max ) (r = 0.95) across a range of inotropic conditions. Comparable results were seen in patients with dP/dt max (r = 0.88). Diagnostic capability from ROC analysis yielded AUC measurements of 0.92 and 0.90 in animal and patients, respectively., Conclusions: Mechanical circulatory support hysteretic behavior can be well modeled using device signals and used to estimate contractility changes. Contractility estimate is correlated with other accepted metrics, captures temporal trends that elucidate changing cardiac state, and is able to accurately indicate changes in inotropy. Inherently available during MCS deployment, this measure will guide titration and inform need for further intervention., (© 2021. The Author(s).)

Objective: Effective mechanical circulatory support (MCS) relies on cardiac function measures to guide titration. Left ventricular end diastolic pressure (LVEDP) is a useful measure that is indirectly estimated using pulmonary artery catheters (PACs). PACs require additional intervention and provide intermittent and unreliable estimations. MCS device signals can estimate LVEDP but are prone to inter-device variability and require rigorous specialized characterization. We present a scalable and implementable approach to calculate LVEDP continuously using device signals., Methods: LVEDP was calculated from MCS device measured aortic pressure and motor current, which approximates the pressure head between the aorta and left ventricle. This motor current-pressure head relationship is device-specific but approximated using existing flow calibration and assumed physiologic relationships. Performance was evaluated with comparison from direct measurement of LVEDP in a series of acute animal models., Results: LVEDP measures (n = 178,279) from 18 animals had good correlation (r = 0.84) and calibration (Bland-Altman limits of agreement -7.77 to 7.63 mmHg; mean bias -0.07 ± 0.02 mmHg). The total mean error prediction interval was -3.42 to 3.32 mmHg and RMS error was 3.85 mmHg., Conclusion: LVEDP can be continuously calculated using device signals without specialized characterization. Calculated LVEDP values improved upon PAC estimations and were found using a scalable and manufacturer-accessible method., Significance: This method improves upon existing LVEDP measures without the need for rigorous characterization, external calibration, or additional intervention; this allows widescale deployment of continuous LVEDP measurement for patients on MCS and demonstrates key considerations necessary to translate research-grade technologies.

Extracorporeal membrane oxygenation (ECMO) is increasingly deployed to provide percutaneous mechanical circulatory support despite incomplete understanding of its complex interactions with the failing heart and its effects on hemodynamics and perfusion. Using an idealized geometry of the aorta and its major branches and a peripherally inserted return cannula terminating in the iliac artery, computational fluid dynamic simulations were performed to (1) quantify perfusion as function of relative ECMO flow and (2) describe the watershed region produced by the collision of antegrade flow from the heart and retrograde ECMO flow. To simulate varying degrees of cardiac failure, ECMO flow as a fraction of systemic perfusion was evaluated at 100%, 90%, 75%, and 50% of total flow with the remainder supplied by the heart calculated from a patient-derived flow waveform. Dynamic boundary conditions were generated with a three-element lumped parameter model to accurately simulate distal perfusion. In profound failure (ECMO providing 90% or more of flow), the watershed region was positioned in the aortic arch with minimal pulsatility observed in the flow to the visceral organs. Modest increases in cardiac flow advanced the watershed region into the thoracic aorta with arch perfusion entirely supplied by the heart., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2020.)

The 1918 influenza killed approximately 50 million people in a few short years, and now, the world is facing another pandemic. In December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an international outbreak of a respiratory illness termed coronavirus disease 2019 (COVID-19) and rapidly spread to cause the worst pandemic since 1918. Recent clinical reports highlight an atypical presentation of acute respiratory distress syndrome (ARDS) in COVID-19 patients characterized by severe hypoxemia, an imbalance of the renin-angiotensin system, an increase in thrombogenic processes, and a cytokine release storm. These processes not only exacerbate lung injury but can also promote pulmonary vascular remodeling and vasoconstriction, which are hallmarks of pulmonary hypertension (PH). PH is a complication of ARDS that has received little attention; thus, we hypothesize that PH in COVID-19-induced ARDS represents an important target for disease amelioration. The mechanisms that can promote PH following SARS-CoV-2 infection are described. In this review article, we outline emerging mechanisms of pulmonary vascular dysfunction and outline potential treatment options that have been clinically tested.

Clinical adoption of mechanical circulatory support for shock is rapidly expanding. Achieving optimal therapeutic benefit requires metrics of state to guide titration and weaning of support. Using the transvalvular positioning of a percutaneous ventricular assist device (pVAD), device:heart interactions are leveraged to determine cardiac output (CO) and systemic vascular resistance (SVR) near-continuously without disrupting therapeutic function. An automated algorithm rapidly alternates between device support levels to dynamically modulate physiological response. Employing a two-element lumped parameter model of the vasculature, SVR and CO are quantified directly from measurements obtained by the pVAD without external calibration or invasive catheters. The approach was validated in an acute porcine model across a range of cardiac (CO = 3-10.6 L/min) and vascular (SVR = 501-1897 dyn s/cm 5 ) states. Cardiac output calculations closely correlated (r = 0.82) to measurements obtained by the pulmonary artery catheter-based thermodilution method with a mean bias of 0.109 L/min and limits of agreement from - 1.67 to 1.89 L/min. SVR was also closely correlated (r = 0.86) to traditional catheter-based measurements with a mean bias of 62.1 dyn s/cm 5 and limits of agreement from - 260 to 384 dyn s/cm 5 . Use of diagnostics integrated into therapeutic device function enables the potential for optimizing support to improve outcomes for cardiogenic shock.

Introduction: Extracorporeal membrane oxygenation (ECMO) is a life-saving technology capable of restoring perfusion but is not without significant complications that limit its realizable therapeutic benefit. ECMO-induced hemodynamics increase cardiac afterload risking left ventricular distention and impaired cardiac recovery. To mitigate potentially harmful effects, multiple strategies to unload the left ventricle (LV) are used in clinical practice but data supporting the optimal approach is presently lacking., Materials & Methods: We reviewed outcomes of our ECMO population from September 2015 through January 2019 to determine if our LV unloading strategies were associated with patient outcomes. We compared reactive (Group 1, n = 30) versus immediate (Group 2, n = 33) LV unloading and then compared patients unloaded with an Impella CP (n = 19) versus an intra-aortic balloon pump (IABP, n = 16), analyzing survival and ECMO-related complications., Results: Survival was similar between Groups 1 and 2 (33 vs 42%, P = .426) with Group 2 experiencing more clinically-significant hemorrhage (40 vs. 67%, P = .034). Survival and ECMO-related complications were similar between patients unloaded with an Impella versus an IABP. However, the Impella group exhibited a higher rate of survival (37%) than predicted by their median SAVE score (18%)., Discussion: Based on this analysis, reactive unloading appears to be a viable strategy while venting with the Impella CP provides better than anticipated survival. Our findings correlate with recent large cohort studies and motivate further work to design clinical guidelines and future trial design., (© 2020 Wiley Periodicals LLC.)

The severe acute respiratory syndrome (SARS)-CoV-2 is an emerging viral pathogen responsible for the global coronavirus disease 2019 (COVID)-19 pandemic resulting in significant human morbidity and mortality. Based on preliminary clinical reports, hypoxic respiratory failure complicated by acute respiratory distress syndrome is the leading cause of death. Further, septic shock, late-onset cardiac dysfunction, and multiorgan system failure are also described as contributors to overall mortality. Although extracorporeal membrane oxygenation and other modalities of mechanical cardiopulmonary support are increasingly being utilized in the treatment of respiratory and circulatory failure refractory to conventional management, their role and efficacy as support modalities in the present pandemic are unclear. We review the rapidly changing epidemiology, pathophysiology, emerging therapy, and clinical outcomes of COVID-19; and based on these data and previous experience with artificial cardiopulmonary support strategies, particularly in the setting of infectious diseases, provide consensus recommendations from ASAIO. Of note, this is a "living document," which will be updated periodically, as additional information and understanding emerges.

Extracorporeal CO 2 removal is a highly promising support therapy for patients with hypercapnic respiratory failure but whose clinical implementation and patient benefit is hampered by high cost and highly specialized expertise required for safe use. Current approaches target removal of the gaseous CO 2 dissolved in blood which limits their ease of clinical use as high blood flow rates are required to achieve physiologically significant CO 2 clearance. Here, a novel hybrid approach in which a zero-bicarbonate dialysis is used to target removal of bicarbonate ion coupled to a gas exchange device to clear dissolved CO 2 , achieves highly efficiently total CO 2 capture while maintaining systemic acid-base balance. In a porcine model of acute hypercapnic respiratory failure, a CO 2 -reduction of 61.4 ± 14.4 mL/min was achieved at a blood flow rate of 248 mL/min using pediatric-scale priming volumes. The dialyzer accounted for 81% of total CO 2 capture with an efficiency of 33% with a minimal pH change across the entire circuit. This study demonstrates the feasibility of a novel hybrid CO 2 capture approach capable of achieving physiologically significant CO 2 removal at ultralow blood flow rates with low priming volumes while leveraging widely available dialysis platforms to enable clinical adoption.

Rationale: There have been advances in both cancer and sepsis treatment over the past several decades, yet little is known about trends in sepsis-associated mortality in patients with versus without cancer. Objectives: To assess trends in sepsis-associated mortality in hospitalized patients with and without cancer using objective clinical criteria to identify sepsis and detailed clinical data to adjust for severity of illness. Methods: This was a retrospective cohort study at a tertiary referral hospital and cancer center. Adult in-patients with clinical indicators of sepsis (U.S. Centers for Disease Control and Prevention Adult Sepsis Event criteria) were identified between 2003 and 2014. Patients with cancer were identified using diagnosis codes from their hospitalization or the preceding 90 days. Sepsis-associated in-hospital mortality rates were assessed in 3-year intervals. Multivariable logistic regression models were used to adjust for case mix and severity of illness and to test for subgroup interactions in trends. Results: The cohort included 20,975 patients with sepsis, of whom 7,489 (35.7%) had cancer (61.7% solid and 38.3% hematologic). Sepsis-associated mortality rates in patients with cancer decreased from 31.3% in 2003-2005 to 26.0% in 2012-2014 (absolute decrease, 5.2% [95% confidence interval (CI), 2.3-8.2%]). This mortality reduction persisted after risk adjustment (adjusted odds ratio, 0.53 [95% CI, 0.45-0.63] in 2012-2014 relative to 2003-2005). In contrast, sepsis-associated mortality rates increased in patients without cancer from 20.9% in 2003-2005 to 23.9% in 2012-2014 (absolute increase, 2.1% [95% CI, 0.1-4.1%]), but were stable after risk-adjustment (adjusted odds ratio, 0.90 [95% CI, 0.79-1.03]) ( P  < 0.001 for comparison of trends between patients with vs. without cancer on both crude and adjusted analysis). Among patients with cancer, declines in risk-adjusted sepsis-associated mortality were observed in both solid and hematologic cancer subgroups, with both community-onset and hospital-onset sepsis, in patients receiving active cancer treatments, and in patients requiring mechanical ventilation at sepsis onset. Conclusions: Sepsis-associated mortality rates declined significantly over a 12-year period in patients with cancer, but not in patients without cancer. Potential explanations include advances in the management of cancer and/or better sepsis treatments specifically in patients with cancer. Further research is needed to elucidate the reasons for our findings and to assess their generalizability to other hospitals.

The introduction of the lung allocation score in 2005 prioritized patients with decreased transplant-free survival as the recipients of donor organs and effectively increased the number of critically-ill patients with end-stage lung disease waiting for transplantation. This change presented transplant programs with the challenge of how to both extend the lives of critically-ill, end-stage lung disease patients waiting for donor organs and maintain patient vitality to survival through the rigors of surgery and post-transplant recovery. Motivated by the dismal outcomes of patients maintained on mechanical ventilation pre-transplant, transplant centers increasingly deploy extracorporeal membrane oxygenation (ECMO) as a means of supporting patients with advanced disease as a bridge to successful lung transplantation. ECMO is an extracorporeal gas exchange device providing delivery of oxygen and removal of carbon dioxide from blood passed through the circuit. The specific cannulation strategy determines whether ECMO provides primarily respiratory or circulatory support. The cannulation approach is tailored to the specific physiological manifestations of the pre-lung transplant candidate's disease process. For patients with profound hypoxic respiratory failure, a cannulation strategy that captures a large fraction of the venous return is required to maintain adequate support whereas lower circuit flows are sufficient for patients with predominantly hypercapnic respiratory failure. Improving outcomes and increasing experience with ECMO is motivating transplant centers to initiate support before patients require mechanical ventilation. Awake cannulation is increasingly common and is used to avoid the complications associated with intubation in advanced lung failure. Determining criteria for initiation of support and identifying the optimal approach to support patients with right heart failure in need of circulatory support are avenues of active investigation. Use of ECMO and other forms of extracorporeal support are rapidly becoming a mainstay in the care of the pre-lung transplant patient with advanced disease., Competing Interests: Conflicts of Interest: SP Keller serves on the Critical Care Advisory Board of Abiomed, Inc., the Scientific Advisory Board of Paragonix Technologies, and consults for X-COR Therapuetics, Inc. He is also a co-founder and serves on the Board of Directors of X-COR Therapeutics, Inc., (2020 Annals of Cardiothoracic Surgery. All rights reserved.)

Objective: Limitations in available diagnostic metrics restrict the efficacy of managing therapies for cardiogenic shock. In current clinical practice, cardiovascular state is inferred through measurement of pulmonary capillary wedge pressure and reliance on linear approximations between pressure and flow to estimate peripheral vascular resistance. Mechanical circulatory support devices residing within the left ventricle and aorta provide an opportunity for both determining cardiac and vascular state and offering therapeutic benefit. We leverage the controllable mode of operation and transvalvular position of an indwelling percutaneous ventricular assist device to assess vascular and, in turn, cardiac state through the effects of device-arterial coupling across different levels of device support., Methods: Vascular state is determined by measuring changes in the pressure waveforms induced through intentional variation in the device generated blood flow. We evaluate this impact by applying a lumped parameter model to quantify state-specific vascular resistance and compliance and calculate beat-to-beat stroke volume and cardiac output in both animal models and retrospective patient data without external calibration., Results: Vascular state was accurately predicted in patients and animals in both baseline and experimental conditions. In the animal, stroke volume was predicted within a total root mean square error of 3.71 mL (n = 482)., Conclusion: We demonstrate that device-arterial coupling is a powerful tool for evaluating patient and state specific parameters of cardiovascular function., Significance: These insights may yield improved clinical care and support the development of next generation mechanical circulatory support devices that determine and operate in tandem with the supported organ.

Objectives: Cardiogenic shock is a highly morbid condition in which inadequate end-organ perfusion leads to death if untreated. Peripheral venoarterial extracorporeal membrane oxygenation is increasingly used to restore systemic perfusion despite limited understanding of how to optimally titrate support. This review provides insights into the physiologic basis of extracorporeal membrane oxygenation support and presents an approach to extracorporeal membrane oxygenation management in the cardiogenic shock patient., Data Sources, Study Selection, and Data Extraction: Data were obtained from a PubMed search of the most recent medical literature identified from MeSH terms: extracorporeal membrane oxygenation, cardiogenic shock, percutaneous mechanical circulatory support, and heart failure. Articles included original articles, case reports, and review articles., Data Synthesis: Current evidence detailing the use of extracorporeal membrane oxygenation to support patients in cardiogenic shock is limited to isolated case reports and single institution case series focused on patient outcomes but lacking in detailed approaches to extracorporeal membrane oxygenation management. Unlike medical therapy, in which dosages are either prescribed or carefully titrated to specific variables, extracorporeal membrane oxygenation is a mechanical support therapy requiring ongoing titration but without widely accepted variables to guide treatment. Similar to mechanical ventilation, extracorporeal membrane oxygenation can provide substantial benefit or induce significant harm. The widespread use and present lack of data to guide extracorporeal membrane oxygenation support demands that intensivists adopt a physiologically-based approach to management of the cardiogenic shock patient on extracorporeal membrane oxygenation., Conclusions: Extracorporeal membrane oxygenation is a powerful mechanical circulatory support modality capable of rapidly restoring systemic perfusion yet lacking in defined approaches to management. Adopting a management approach based physiologic principles provides a basis for care.

This Review Article provides a multi-stakeholder view on the current status of neoadjuvant therapy in lung cancer. Given the success of oncogene-targeted therapy and immunotherapy for patients with advanced lung cancer, there is a renewed interest in studying these agents in earlier disease settings with the opportunity to have an even greater impact on patient outcomes. There are unique opportunities and challenges with the neoadjuvant approach to drug development. To achieve more rapid knowledge turns, study designs, endpoints, and definitions of pathologic response should be standardized and harmonized. Continued dialogue with all stakeholders will be critical to design and test novel induction strategies, which could expedite drug development for patients with early lung cancer who are at high risk for metastatic recurrence., (Published by Elsevier Inc.)

The full potential of mechanical circulatory systems in the treatment of cardiogenic shock is impeded by the lack of accurate measures of cardiac function to guide clinicians in determining when to initiate and how to optimally titrate support. The left ventricular end diastolic pressure (LVEDP) is an established metric of cardiac function that refers to the pressure in the left ventricle at the end of ventricular filling and immediately before ventricular contraction. In clinical practice, LVEDP is typically only inferred from, and poorly correlates with, the pulmonary capillary wedge pressure (PCWP). We leveraged the position of an indwelling percutaneous ventricular assist device and advanced data analysis methods to obtain LVEDP from the hysteretic operating metrics of the device. We validated our hysteresis-derived LVEDP measurement using mock flow loops, an animal model of cardiac dysfunction, and data from a patient in cardiogenic shock to show greater measurement precision and correlation with actual pressures than traditional inferences via PCWP. Delineation of the nonlinear relationship between device and heart adds insight into the interaction between ventricular support devices and the native heart, paving the way for continuous assessment of underlying cardiac state, metrics of cardiac function, potential closed-loop automated control, and rational design of future innovations in mechanical circulatory support systems., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objectives: Cardiac involvement in the course of acute kidney injury is described in humans as cardiorenal syndrome type 3 but has received only limited attention in dogs. This study was designed to evaluate cardiac injury and dysfunction in acute kidney injury in dogs and its association with outcome., Methods: This prospective cohort study enrolled 24 client-owned dogs with acute kidney injury. Cardiac disorders were evaluated with thoracic radiographs, echocardiography, 24-hour Holter monitoring and cardiac troponin I concentrations within 2 days of admission and 7 to 10 days later., Results: Most dogs were diagnosed with leptospirosis (n=18, 75%) and presented with moderate-to-severe acute kidney injury, International Renal Interest Society grades III to V. Dogs with ê100 ventricular premature complexes per 24 hour in the first examination (n=8) had significantly higher initial cTnI concentrations (P=0·007) compared to dogs with fewer than 100. In receiver operating characteristic curve analysis, the number of ventricular premature complexes was predictive of outcome (AUC 0·83, P<0·001)., Clinical Significance: Acute kidney injury seems to be associated with cardiac injury and arrhythmias in dogs. The data do not indicate a cardiac cause of poor outcome in dogs with increased number of ventricular premature complexes but the association may reflect the severity of disease., (© 2016 British Small Animal Veterinary Association.)

Opinion Statement: There are more than 300,000 out-of-hospital cardiac arrests (OHCA) in the USA annually, which can be grouped into those presenting with tachyarrhythmic (shockable) rhythms and those presenting with non-tachyarrhythmic rhythms. The incidence of tachyarrhythmic rhythms, which include ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT), has been noted to be progressively decreasing in multiple studies of OHCA. Improved medical and surgical therapies for ischemic heart disease, and the widespread use of implantable cardiac defibrillators (ICDs), have likely contributed to a declining incidence of VF arrest and may result in conversion of an otherwise VF event into a pulseless electrical activity (PEA) arrest. As the incidence of VF has declined, it is unclear if the absolute incidence of non-tachyarrhythmic rhythms has increased or remained largely unchanged. This article discusses the changing rates of presenting rhythms in sudden cardiac arrest, the underlying cellular mechanisms of PEA, the factors contributing to the relative increase in the rate of PEA arrests, and current treatment options.

Purpose of Review: Studies in patients with acute respiratory distress syndrome (ARDS) have been unable to demonstrate a survival advantage with higher levels of positive end-expiratory pressure (PEEP) to open atelectatic lung regions or prevent their cyclic collapse. This review will discuss the challenges of accurately measuring pleural pressure with balloon-tipped catheters in the oesophagus, and the utility of such pressure monitoring to set PEEP and assess lung mechanics, focusing on patients with ARDS., Recent Findings: Recent investigations have suggested that the monitoring of oesophageal pressure in ARDS patients may help individualize PEEP settings to optimize lung recruitment based on transpulmonary pressure., Summary: Changes in oesophageal pressure likely accurately reflect global changes in pleural pressure in supine patients with ARDS. However, absolute oesophageal pressure values in such patients may be subject to local artefacts and may substantially overestimate pleural pressure in other lung regions. Setting PEEP high enough to achieve a targeted end-expiratory transpulmonary pressure in the region of the oesophageal balloon catheter could overdistend other lung regions. Measurement of oesophageal pressure is feasible, but its clinical utility to titrate PEEP, compared with routine assessment, awaits experimental confirmation.

The presence of spontaneous muscle activity was determined by analysis of the power spectra of computer-model-generated sequences of spontaneous activity and additive noise. The modeling results identified the frequency band of 100-300 Hz as the band of peak signal-to-noise ratio for the detection of fibrillation potentials. Animal experiments were conducted in which the left sciatic nerves of three rats were transected. Measurements were taken 14 days following surgery with Ag/AgCl gel electrodes on the skin surface. Data was recorded from the gastrocnemius muscle on both the normal and denervated side for all three rats. The normal data and the denervated data yielded no discernible difference in the time-domain. Spectral analysis, however, demonstrated a clear and quantifiable difference between denervated and normal muscle signals. The average difference between the denervated and normal power spectral densities for the frequency band from 100 Hz to 300 Hz was 3.43, 1.90, and 3.02 dB for the three rats. The additional energy observed in the signals recorded from denervated muscles suggests that the single fiber spontaneous muscle activity that occurs in denervated muscle can be noninvasively detected. The potential diagnostic utility of noninvasive fibrillation potential detection is discussed and suggestions for future experiments are made.