Showing papers in "Asaio Journal in 2017"

Extracorporeal Life Support Organization Registry International Report 2016.

Abstract: Data on extracorporeal life support (ECLS) use and survival submitted to the Extracorporeal Life Support Organization's data registry from the inception of the registry in 1989 through July 1, 2016, are summarized in this report. The registry contained information on 78,397 ECLS patients with 58% survival to hospital discharge. Extracorporeal life support use and centers providing ECLS have increased worldwide. Extracorporeal life support use in the support of adults with respiratory and cardiac failure represented the largest growth in the recent time period. Extracorporeal life support indications are expanding, and it is increasingly being used to support cardiopulmonary resuscitation in children and adults. Adverse events during the course of ECLS are common and underscore the need for skilled ECLS management and appropriately trained ECLS personnel and teams.

Pediatric Extracorporeal Life Support Organization Registry International Report 2016.

Abstract: The purpose of this report is to describe the international growth, outcomes, complications, and technology used in pediatric extracorporeal life support (ECLS) from 2009 to 2015 as reported by participating centers in the Extracorporeal Life Support Organization (ELSO). To date, there are 59,969 children who have received ECLS in the ELSO Registry; among those, 21,907 received ECLS since 2009 with an overall survival to hospital discharge rate of 61%. In 2009, 2,409 ECLS cases were performed at 157 centers. By 2015, that number grew to 2,992 cases in 227 centers, reflecting a 24% increase in patients and 55% growth in centers. ECLS delivered to neonates (0-28 days) for respiratory support was the largest subcategory of ECLS among children <18-years old. Overall, 48% of ECLS was delivered for respiratory support and 52% was for cardiac support or extracorporeal life support to support cardiopulmonary resuscitation (ECPR). During the study period, over half of children were supported on ECLS with centrifugal pumps (51%) and polymethylpentene oxygenators (52%). Adverse events including neurologic events were common during ECLS, a fact that underscores the opportunity and need to promote quality improvement work.

Incidence and Implications of Left Ventricular Distention During Venoarterial Extracorporeal Membrane Oxygenation Support.

Abstract: Left ventricular distention (LVD) during venoarterial extracorporeal membrane oxygenation (VA-ECMO) support is increasingly recognized but seldom reported in the literature. The current study defined LVD as not present (LVD-); subclinical (LVD+, evidence of pulmonary edema on chest radiograph AND pulmonary artery diastolic blood pressure greater than 25 mm Hg within the first 2 hours of intensive care unit admission); or clinical (LVD++, need for decompression of the left ventricle immediately following VA-ECMO initiation). Among 226 VA-ECMO device runs, 121 had sufficient data to define LVD retrospectively. Nine patients (7%) developed LVD++ requiring immediate decompression, and 27 patients (22%) met the definition of LVD+. Survival to discharge was similar among groups (LVD++: 44%, LVD+: 41%, LVD-: 44%). However, myocardial recovery appeared inversely related to the degree of LVD (LVD++: 11%, LVD+: 26%, LVD-: 40%). When death or transition to device was considered as a composite outcome, event-free survival was diminished in LVD++ and LVD+ patients compared with LVD-. Multivariable analysis identified cannulation of VA-ECMO during extracorporeal cardiopulmonary resuscitation (ECPR) as a risk factor for decompression (odds ratio [OR]: 3.64, confidence interval [CI]: 1.21-10.98; p = 0.022). Using a novel definition of LVD, the severity LVD was inversely related to the likelihood of myocardial recovery. Survival did not differ between groups. Extracorporeal cardiopulmonary resuscitation was associated with need for mechanical intervention.

Left Ventricular Assist Device Infections: A Systematic Review.

Abstract: Left ventricular assist devices (LVADs) are becoming a more frequent life-support intervention. Gaining an understanding of risk factors for infection and management strategies is important for treating these patients. We conducted a systematic review and meta-analysis of studies describing infections in continuous-flow LVADs. We evaluated incidence, risk factors, associated microorganisms, and outcomes by type of device and patient characteristics. Our search identified 90 distinct studies that reported LVAD infections and outcomes. Younger age and higher body mass index were associated with higher rates of LVAD infections. Driveline infections were the most common infection reported and the easiest to treat with fewest long-term consequences. Bloodstream infections were not reported as often, but they were associated with stroke and mortality. Treatment strategies varied and did not show a consistent best approach. LVAD infections are a significant cause of morbidity and mortality in LVAD patients. Most research comes from secondary analyses of other LVAD studies. The lack of infection-oriented research leaves several areas understudied. In particular, bloodstream infections in this population merit further research. Providers need more research studies to make evidence-based decisions about the prevention and treatment of LVAD infections.

Outcomes with the Tandem Protek Duo Dual-Lumen Percutaneous Right Ventricular Assist Device.

Abstract: Recently, a percutaneous right ventricular assist device (RVAD) called the TandemLife Protek Duo (TPD; TandemLife, Pittsburgh, PA) has been introduced. The Protek Duo (TPD) is a temporary RVAD placed via the right internal jugular vein, capable of providing up to 4.5 L of flow. We report a two-center experience using the TPD in 17 patients with right ventricular (RV) failure, 12 of whom were post-left ventricular assist device (LVAD) implantation.

FDA Benchmark Medical Device Flow Models for CFD Validation.

Abstract: Computational fluid dynamics (CFD) is increasingly being used to develop blood-contacting medical devices. However, the lack of standardized methods for validating CFD simulations and blood damage predictions limits its use in the safety evaluation of devices. Through a U.S. Food and Drug Administration (FDA) initiative, two benchmark models of typical device flow geometries (nozzle and centrifugal blood pump) were tested in multiple laboratories to provide experimental velocities, pressures, and hemolysis data to support CFD validation. In addition, computational simulations were performed by more than 20 independent groups to assess current CFD techniques. The primary goal of this article is to summarize the FDA initiative and to report recent findings from the benchmark blood pump model study. Discrepancies between CFD predicted velocities and those measured using particle image velocimetry most often occurred in regions of flow separation (e.g., downstream of the nozzle throat, and in the pump exit diffuser). For the six pump test conditions, 57% of the CFD predictions of pressure head were within one standard deviation of the mean measured values. Notably, only 37% of all CFD submissions contained hemolysis predictions. This project aided in the development of an FDA Guidance Document on factors to consider when reporting computational studies in medical device regulatory submissions. There is an accompanying podcast available for this article. Please visit the journal's Web site (www.asaiojournal.com) to listen.

Evaluation of Systemic Heparin Versus Bivalirudin in Adult Patients Supported by Extracorporeal Membrane Oxygenation.

Abstract: Systemic anticoagulation is a standard of care in adult patients supported by extracorporeal membrane oxygenation (ECMO) to prevent circuit thrombosis and subsequent thromboembolic events. Unfractionated heparin has long been considered the anticoagulant of choice, but emerging evidence reports successful ECMO runs with direct thrombin inhibitors. This retrospective study sought to determine whether bivalirudin offers distinct clinical benefits as the anticoagulant of choice in ECMO. Primary end points included thrombotic events during the initial 96 hours of anticoagulation, over the course of their entire ECMO run, and at any time during the admission, as well as in-hospital and 30-day mortality. Secondary end points included percent time within therapeutic range for each anticoagulant, neurologic events, vascular complications, and bleeding. Compared with patients receiving heparin, patients receiving bivalirudin show similar rates of thrombotic events across the three time points (17.9% vs. 9.1%; p = 0.47, 21.4% vs. 11.4%; p = 0.41, and 25% vs. 22.7%; p = 1.00, respectively). In-hospital (32.1% vs. 36.4%; p = 0.91) and 30-day mortality (32.1% vs. 36.4%; p = 0.91) were no different. Similarly, no differences were observed in percent time within therapeutic range (83.0% vs. 87.7%, p = 0.34), neurological events (7.1% vs. 11.4%, p = 0.99), vascular complications (57.1% vs. 38.6%, p = 0.20), or major (25.0% vs. 45.5%, p = 0.13) and minor (25.0% vs. 22.7%, p = 1.00) bleeding. These results suggest that bivalirudin is a viable alternative to heparin for anticoagulation in ECMO but may not offer a clinically significant advantage as the anticoagulant of choice.

Incidence of Cannula-Associated Deep Vein Thrombosis After Veno-Venous Extracorporeal Membrane Oxygenation.

Abstract: Limited literature regarding the incidence of cannula-associated deep vein thrombosis (CaDVT) after veno-venous extracorporeal membrane oxygenation (VV ECMO) exists. The purpose of this study was to identify the incidence of post decannulation CaDVT and identify any associated risk factors. Forty-eight patients were admitted between August 2014 and January 2016 to the Lung Rescue Unit were included in the study. Protocolized anticoagulation levels (partial thromboplastin time [PTT] 45-55 seconds) and routine post decannulation DVT screening were in place during the study period. Forty-one (85.4%) patients had CaDVT. Of those with CaDVT, 31 (76%) patients were treated with full anti-coagulation therapy. Thirty-four (76%) patients with right internal jugular (RIJ) cannulation had CaDVT at cannula site. Twenty-five (61%) patients had CaDVT in the lower extremity (18 associated right femoral vein cannulation and 7 left femoral vein cannulation). Eighteen (44%) patients had both upper and lower extremity CaDVT. Overall, patients with CaDVT tended to be older, have a higher body mass index (BMI), and on ECMO longer (p = NS). Mean PTT during time on ECMO between patients that did and did not have CaDVT did not differ. No clinical evidence of pulmonary embolism (PE) was seen.

The "Central Sport Model": Extracorporeal Membrane Oxygenation Using the Innominate Artery for Smaller Patients as Bridge to Lung Transplantation.

Abstract: Venoarterial extracorporeal membrane oxygenation (VA ECMO) may be used in patients with advanced cardiac or pulmonary failure. Arterial cannulation via the femoral arteries is suboptimal in many clinical scenarios because of associated complications and the potential for differential hypoxemia between the upper and lower body. To address these concerns, we typically use an upper body configuration (sport model) with right internal jugular and axillary or subclavian artery cannulation to allow a safe and durable means of providing VA ECMO support without differential hypoxemia. Unfortunately, this approach may not be feasible in smaller patients, whose vessels may preclude optimal use of the axillary or subclavian arteries and in those with systemic vasculopathy associated with connective tissue disorders. We describe a new approach for patients of small stature using the innominate artery through a mini-upper sternotomy in seven patients.

Del Nido Cardioplegia for Myocardial Protection in Adult Cardiac Surgery: A Systematic Review and Meta-Analysis.

Abstract: Cardioplegia is an important strategy for myocardial protection during cardiac surgery. This meta-analysis was to compare the effects of del Nido and conventional cardioplegia in adult patients. Systematic searches were performed to identify studies using PubMed, Embase, the Cochrane Library, and the International Clinical Trials Registry Platform. A total of nine studies were included. Cardiopulmonary bypass and cross-clamp time were significantly shorter in the del Nido than conventional cardioplegia (mean difference [MD]: -7.52, 95% confidence interval [95% CI]: -14.76 to -0.29, p = 0.04; MD: -5.74, 95% CI: -10.14 to -1.34, p = 0.01). During the operation, cardioplegia volume and blood glucose level were lower in the del Nido group (MD: -522.53, 95% CI: -926.68 to -118.37, p = 0.01; standardized mean difference [SMD]: -1.11, 95% CI: -1.74 to -0.48, p = 0.0006). Ventilation time and length of intensive care unit were decreased significantly with del Nido cardioplegia (MD: -1.05, 95% CI: -1.79 to -0.31, p = 0.006; MD: -0.65, 95% CI: -0.92 to -0.38, p < 0.00001). There were no differences in myocardial enzyme, postoperative inotropic support, atrial fibrillation, hospital, and mortality between the two groups. In adult cardiac surgery, myocardial protection used with the del Nido or conventional cardioplegia solution yield similar short-term clinical outcomes.

Left lateral thoracotomy for centrifugal continuous-flow left ventricular assist device placement: An analysis from the mechanical circulatory support research network

Abstract: Continuous-flow left ventricular assist devices (CF-LVADs) have revolutionized the management of patients with advanced heart failure. Alternative implant strategies are increasingly used for device placement. We reviewed our experience from the Mechanical Circulatory Support Research Network registry with the HeartWare centrifugal CF-LVAD (HVAD). From May 2004 to August 2015, 1,150 patients underwent primary CF-LVAD implantation at our institutions. Within this group, a total of 283 patients (25%) were implanted with the HVAD. A minimally invasive left lateral thoracotomy (MILT) implant strategy was used in 53 patients (20%), of which 22 (42%) were implanted off-pump. Median age at implant was 59 years and 183 patients (65%) were implanted as bridge-to-transplantation. Follow-up was 100% complete for a total of 302 patient-years of support. In-hospital mortality was 4.9% (14 patients), and was comparable between the conventional sternotomy (CS) and MILT cohorts (p = 0.15). Patients in the MILT cohort had a shorter median length of stay (p < 0.01) and had a lower incidence of postimplant pump thrombus (p = 0.02). Cumulative survival at the end of follow-up reached 84%, and was comparable between the two groups (p = 0.298). Multivariate analysis identified preoperative bilirubin level as the only independent predictor of survival. Surgical technique had no impact on survival. In this large, multicenter experience, data demonstrate excellent survival and adverse event profiles for patients supported with the HVAD technology, regardless of surgical implant technique. With constant advancements in device technology along with our increasing clinical experience with the newer techniques, minimally invasive LVAD implantation continues to evolve as a valuable alternative to CS in selected patients.

LVAD Outflow Graft Angle and Thrombosis Risk.

Abstract: This study quantifies thrombogenic potential (TP) of a wide range of left ventricular assist device (LVAD) outflow graft anastomosis angles through state-of-the-art techniques: 3D imaged-based patient-specific models created via virtual surgery and unsteady computational fluid dynamics with Lagrangian particle tracking. This study aims at clarifying the influence of a single parameter (outflow graft angle) on the thrombogenesis associated with flow patterns in the aortic root after LVAD implantation. This is an important and poorly-understood aspect of LVAD therapy, because several studies have shown strong inter and intrapatient thrombogenic variability and current LVAD implantation strategies do not incorporate outflow graft angle optimization. Accurate platelet-level investigation, enabled by statistical treatment of outliers in Lagrangian particle tracking, demonstrates a strong influence of outflow graft anastomoses angle on thrombogenicity (platelet residence times and activation state characterized by shear stress accumulation) with significantly reduced TP for acutely-angled anastomosed outflow grafts. The methodology presented in this study provides a device-neutral platform for conducting comprehensive thrombogenicity evaluation of LVAD surgical configurations, empowering optimal patient-focused surgical strategies for long-term treatment and care for advanced heart failure patients.

Sources of Circuit Thrombosis in Pediatric Extracorporeal Membrane Oxygenation.

Abstract: Extracorporeal membrane oxygenation (ECMO) for cardiopulmonary support of critically ill patients is used frequently in the pediatric population. ECMO is burdened by complications, including thrombosis and hemorrhage. Here we demonstrate the focused location of clots, their histologic composition, and the relationship of in situ thrombus to local hemodynamics in ECMO circuits. Pediatric ECMO circuits from Children's Healthcare of Atlanta, Emory University (Atlanta, GA) were obtained after removal from extracorporeal support over a 2.5 year period (n = 50). All clots and material deposited within the circuit were recorded. Location of clot was compared with local hemodynamics. Most clots were adherent to the junctions made by the tubing and connectors, as opposed to being randomly disturbed throughout the circuit tubing (p << 0.05). Loose, nonadherent clots were also found at the entry side of oxygenators. The clots colocated directly with zones of low shear rate. Histology revealed a fibrinous composition, consistent with coagulation potentiated by low shear. Centrifugal pump circuits (n = 16) had more clots than roller pump (n = 34) circuits (p << 0.05). In addition, all centrifugal pumps had clots that formed at the top of the pump shaft. The ECMO circuits from our single-center study demonstrate the concentrated location of fibrin clots at low shear zones created by tubing-connector junctions. Type of pump also influences the frequency of clot formation. Since the mechanism of the majority of ECMO circuit thrombosis is low shear and fibrin driven, optimization of hemodynamics and anticoagulation regimen may reduce clot formation and bleeding.

Percutaneous Transcatheter Interventions for Aortic Insufficiency in Continuous-Flow Left Ventricular Assist Device Patients: A Systematic Review and Meta-Analysis.

Abstract: De novo progressive aortic insufficiency (AI) is a side effect frequently related to prolonged support with continuous-flow left ventricular assist devices (CF-LVAD). Its progression can result in recurrent clinical heart failure symptoms and significantly increased mortality. Recently, percutaneous intervention methods, such as transcatheter aortic valve replacement (TAVR) and percutaneous occluder devices, have emerged. However, given the very scarce global experience with these approaches, evidence in the literature is lacking. We sought to assess the outcomes of CF-LVAD patients who had undergone percutaneous intervention for AI. A systematic search of six databases from inception to April 2016 was performed by two independent reviewers. Eligible studies were those that included series or cases where patients had percutaneous transcatheter interventions for AI in CF-LVAD patients. Data were extracted and meta-analyzed from the identified studies. A total of 29 patients from 15 published studies and 3 unpublished records were included in the analysis. Mean patient age was 56.6 ± 13.7 years, and 72.4% were male. The etiology of heart failure resulting in LVAD placement was ischemic cardiomyopathy in 17.2%. The two intervention groups were TAVR (27.6%) and occluder devices (72.4%). A transfemoral approach (69%), apical approach (10%), brachial approach (7%), subclavian approach (3%), and mini-sternotomy (3%) were used. The preintervention AI grade was severe with a median grade of 4 (interquartile range, 4-4). Postoperatively, the AI grade improved significantly to a median grade of 0 (0-2). At long-term follow-up AI grade was still trivial with a median AI grade of 1 (0-1). Subgrouping the treatments into the occluder device and TAVR, it was found that both interventional techniques were similarly effective in reducing the AI grade from severe to trivial. In terms of complications, from the occluder group, two patients were complicated with device migration and another two with transient hemolysis. In the TAVR cohort, two patients experienced device migration and another had significant postimplant perivalvular leakage. Our results indicate that percutaneous interventions for AI in CF-LVAD patients with TAVR, and closure devices demonstrate similar efficacy in significantly reducing severe AI. Current results are encouraging, potentiating viability as a treatment option, particularly in nonsurgical candidates. Future research with larger patient cohorts and comparative controls is required to sufficiently evaluate the efficacy of this technique and promote its widespread acceptance as a mainstay treatment.

Medical Management of Pump-Related Thrombosis in Patients with Continuous-Flow Left Ventricular Assist Devices: A Systematic Review and Meta-Analysis.

Abstract: Pump thrombosis is a dreaded complication of left ventricular assist devices (LVADs). We completed a systematic review to evaluate the efficacy and complications associated with medical management of LVAD thrombosis. Databases were searched using the terms "vad*" or "ventricular assist device" or "heart assist device" and "thrombus" or "thrombosis" or "thromboembolism." Of 2,383 manuscripts, 49 articles met the inclusion criteria. The risk of partial or no resolution of LVAD thrombosis did not significantly differ between thrombolytic and nonthrombolytic regimens (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.20-1.16). When response to therapy was evaluated based on pump type, there were no significant differences in how patients with a HeartMate II or HeartWare ventricular assist device responded to thrombolytic or nonthrombolytic treatment. Pooled risk of major bleeding in the thrombolytic group was 29% (95% CI, 0.17-0.44) and 12% (95% CI, 0.01-0.57) in the nonthrombolytic group. Odds of death did not differ between thrombolytic and nonthrombolytic regimens (OR, 1.28; 95% CI, 0.42-3.89). Although thrombolytic and nonthrombolytic treatment similarly resolved LVAD thrombosis, major hemorrhage may be increased with the use of thrombolysis. Randomized clinical trials comparing thrombolytic and nonthrombolytic treatment of LVAD thrombosis are needed to establish the most effective and safe option for patients who are not surgical candidates.

Durable Biventricular Support Using Right Atrial Placement of the HeartWare HVAD.

Abstract: Patients with Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) levels 1-2 who either have or are at risk for right ventricular failure face significant morbidity and mortality after continuous flow left ventricular assist device (CF-LVAD) implantation. Currently, the options for biventricular support are limited the Total Artificial Heart (TAH; CardioWest, Syncardia, Tuscon, AZ) or biventricular assist device (BiVAD), which uses bulky extracorporeal or implantable displacement pumps. We describe a successful series based on an innovative approach for biventricular support in consecutive INTERMACS levels 1-2 patients utilizing a HeartWare Ventricular Assist Device (HVAD; HeartWare, Framingham, MA) in a left ventricular (LV-HVAD) and a right atrial (RA-HVAD) configuration. From June 2014 through May 2016, 11 consecutive INTERMACS levels 1-2 patients with evidence of biventricular failure underwent implantation of a CF LVAD (10 LV-HVAD and 1 HeartMate II LVAD, Thoratec, Pleasanton, CA) and RA-HVAD pumps. A total of 4,314 BiVAD support days were accumulated in our case series. Seven patients have undergone orthotopic heart transplant, whereas 3 are ambulatory and are either waiting transplant or reconsideration for transplantation. There is one mortality in this case series, which was due to an intracranial bleed from supratherapeutic anticoagulation. Two other patients experienced hemorrhagic strokes, but without neurologic sequelae, whereas no patients have experienced ischemic strokes. There were two episodes of gastrointestinal bleeding. This is the largest series to date involving this approach with outcomes superior to those previously described in patients receiving biventricular support. We conclude this novel therapy is a viable alternative to current practices in the management of biventricular failure.

HVAD Flow Waveform Morphologies: Theoretical Foundation and Implications for Clinical Practice.

Abstract: Continuous-flow ventricular assist device (cfVAD) performance and patient hemodynamic conditions are intimately interrelated and dynamic, changing frequently with alterations in physiologic conditions, particularly pre- and afterloading conditions. The Heartware cfVAD (HVAD) provides a unique feature among currently approved VADs of providing an estimated instantaneous flow waveform, the characteristics of which can provide significant insights into patient and device properties. Despite being readily available, HVAD waveforms are poorly understood, underutilized, and insufficiently leveraged, even by clinicians who regularly manage HVAD patients. The purpose of this review is to provide the theoretical foundation for understanding the determinants of HVAD waveform characteristics and to provide practical examples illustrating how to interpret and integrate changes of HVAD waveforms into clinical practice. Heartware cfVAD waveforms should be considered a complimentary tool for the optimization of medical therapies and device speed in HVAD patients.

Is Stopping Heparin Safe in Patients on Extracorporeal Membrane Oxygenation Treatment

Abstract: Anticoagulation treatment during extracorporeal membrane oxygenation (ECMO) treatment is unavoidable. However, discontinuation of heparin infusion is necessary when challenges associated with the use of heparin, such as bleeding and thrombocytopenia, are encountered. The medical records of 94 adult (age ≥ 18 years) patients treated with ECMO from January 2011 to March 2015, at Chung-Ang University Hospital, Seoul, Korea, were reviewed. Among the 94 patients, 55 patients underwent ECMO treatment for three or more days. In 52.7% of these patients (n = 29, group A), heparin was stopped for three or more days because of thrombocytopenic events ( 230 seconds) activated clotting time (ACT), bleeding complications, or the need for other surgical procedures. In 43.6% of patients (n = 24, group B), heparin was continuously infused during the entire ECMO process. The mean length of ECMO support after the initiation of heparin discontinuation in patients in group A was 10.2 ± 14.7 days. There were no intracardiac, intravascular, or intracircuit thrombotic complications in group A. There was no difference in the ECMO weaning success rate between the two groups (41.4% in group A vs. 54.2% in group B, p = 0.353). Heparin discontinuation can be considered in a select group of patients with coagulation abnormalities or bleeding.

Extracorporeal Circulation During Lung Transplantation Procedures: a Meta-Analysis

Abstract: Extracorporeal circulation (ECC) is an invaluable tool in lung transplantation (lutx). More than the past years, an increasing number of centers changed their standard for intraoperative ECC from cardiopulmonary bypass (CPB) to extracorporeal membrane oxygenation (ECMO) - with differing results. This meta-analysis reviews the existing evidence. An online literature research on Medline, Embase, and PubMed has been performed. Two persons independently judged the papers using the ACROBAT-NRSI tool of the Cochrane collaboration. Meta-analyses and meta-regressions were used to determine whether veno-arterial ECMO (VA-ECMO) resulted in better outcomes compared with CPB. Six papers - all observational studies without randomization - were included in the analysis. All were considered to have serious bias caused by heparinization as co-intervention. Forest plots showed a beneficial trend of ECMO regarding blood transfusions (packed red blood cells (RBCs) with an average mean difference of -0.46 units [95% CI = -3.72, 2.80], fresh-frozen plasma with an average mean difference of -0.65 units [95% CI = -1.56, 0.25], platelets with an average mean difference of -1.72 units [95% CI = -3.67, 0.23]). Duration of ventilator support with an average mean difference of -2.86 days [95% CI = -11.43, 5.71] and intensive care unit (ICU) length of stay with an average mean difference of -4.79 days [95% CI = -8.17, -1.41] were shorter in ECMO patients. Extracorporeal membrane oxygenation treatment tended to be superior regarding 3 month mortality (odds ratio = 0.46, 95% CI = 0.21-1.02) and 1 year mortality (odds ratio = 0.65, 95% CI = 0.37-1.13). However, only the ICU length of stay reached statistical significance. Meta-regression analyses showed that heterogeneity across studies (sex, year of ECMO implementation, and underlying disease) influenced differences. These data indicate a benefit of the intraoperative use of ECMO as compared with CPB during lung transplant procedures regarding short-term outcome (ICU stay). There was no statistically significant effect regarding blood transfusion needs or long-term outcome. The superiority of ECMO in lutx patients remains to be determined in larger multi-center randomized trials.

Sedation Practice in Extracorporeal Membrane Oxygenation-Treated Patients with Acute Respiratory Distress Syndrome: A Retrospective Study.

Abstract: Our objective was to characterize sedation management in adult patients with severe respiratory distress syndrome (ARDS) treated with venovenous extracorporeal membrane oxygenation (VV-ECMO). We conducted a retrospective chart review of these patients treated at Toronto General Hospital between January 2012 and October 2015. Medications administered (sedative, analgesic, paralytic, and antipsychotic), sedation depth (Sedation Agitation Scale [SAS] score) delirium assessments, and mobilization were recorded daily. Forty-five adults (33 males, median age 47 years; interquartile range [IQR], 35-56]) with ARDS (median PaO2/FiO2 71; IQR 59-83) because of respiratory infection (91%) were treated with VV-ECMO for a median of 11 days (IQR, 7-17). After ECMO initiation, 96% patients were deeply sedated (SAS score < 3) with continuous infusions of midazolam (49%), propofol (18%), or both (29%) and 98% were receiving opioid infusions (93% fentanyl). Patients were deeply sedated for a median of 6 days (IQR, 3-10) after cannulation before transitioning to intermediate or light sedation (SAS score ≥ 3). Before ECMO discontinuation, 77% of surviving patients were intermediately or lightly sedated, 20% were receiving no sedatives, and 9% were receiving no opioids. During ECMO, 58% had positive delirium assessment and 24% experienced agitation (SAS ≥ 6). During ECMO support, 71% received physical therapy that occurred after a median of 7 days (IQR, 4-12) after cannulation. In conclusion, we found that although patients were deeply sedated for a prolonged duration after VV-ECMO initiation, many were able to safely achieve light sedation and active mobilization.

Clinical Implications of Physiologic Flow Adjustment in Continuous-Flow Left Ventricular Assist Devices.

Abstract: There is increasing evidence for successful management of end-stage heart failure with continuous-flow left ventricular assist device (CF-LVAD) technology. However, passive flow adjustment at fixed CF-LVAD speed is susceptible to flow balancing issues as well as adverse hemodynamic effects relating to the diminished arterial pulse pressure and flow. With current therapy, flow cannot be adjusted with changes in venous return, which can vary significantly with volume status. This limits the performance and safety of CF-LVAD. Active flow adjustment strategies have been proposed to improve the synchrony between the pump and the native cardiovascular system, mimicking the Frank-Starling mechanism of the heart. These flow adjustment strategies include modulation by CF-LVAD pump speed by synchrony and maintenance of constant flow or constant pressure head, or a combination of these variables. However, none of these adjustment strategies have evolved sufficiently to gain widespread attention. Herein we review the current challenges and future directions of CF-LVAD therapy and sensor technology focusing on the development of a physiologic, long-term active flow adjustment strategy for CF-LVADs.

Esperanza: The First Neonatal ECMO Patient.

Abstract: The first successful neonatal extracorporeal membrane oxygenation case (1975) is important in the development of extracorporeal life support, but the case report was never published. This is the report of that case with commentary on the evolution of extracorporeal membrane oxygenation since 1975.

Circulatory Support with Extracorporeal Membrane Oxygenation and/or Impella for Cardiogenic Shock During Myocardial Infarction

Abstract: Temporary mechanical circulatory support (TCS) is recommended for patients with profound cardiogenic shock (CS). Extracorporeal membrane oxygenation (ECMO) and Impella are possible TCS devices, but the device choice and the implantation timing are not definitely established, specifically during acute myocardial infarction. We have analyzed the respective use of ECMO or Impella (2.5, CP, or 5.0) for CS following acute myocardial infarction, from a cohort of patients who underwent TCS within 72 hours after admission for emergency percutaneous coronary intervention (PCI) from January 2009 to April 2015. Among 88 TCS-treated patients, 42 had early TCS: 23 ECMO and 19 Impella. Cardiac management, including PCI, was similar between the two groups, but ECMO patients were sicker than Impella patients (higher blood lactate level at ICU admission, higher vasoactive-inotroic and ENCOURAGE scores before TCS implantation, p ≤ 0.02). Three patients (7%) have had TCS implantation before admission, but TCS was implanted mostly in cathlab (43%, 1 during PCI, 13 just after PCI) or soon after ICU admission (50%, n = 21). Modification of the initial TCS choice was required in 10 cases (24%) for assistance upgrading in case of Impella (n = 4) or for left ventricle unloading in case of ECMO (n = 6). Extracorporeal membrane oxygenation is the technique of choice in case of profound CS, whereas Impella devices seem more appropriate for less severe hemodynamic compromise. Interestingly, the combination of both techniques may help to overcome the limits inherent to each device.

An International Survey on Ventilator Practices Among Extracorporeal Membrane Oxygenation Centers

Abstract: Although the optimal ventilation strategy is unknown for patients placed on extracorporeal support, there are increasing reports of extubation being used Our objective was to describe the change in ventilation strategies and use of tracheostomy and bronchoscopy practices among extracorporeal membrane oxygenation (ECMO) centers across the world A descriptive, cross-sectional 22 item survey of neonatal, pediatric, and adult ECMO centers was used to evaluate ventilator strategies, extubation, bronchoscopy, and tracheostomy practices Extubation practices are increasing among all types of ECMO centers, representing 27% of all patients in pediatric centers, 41% of all patients in mixed centers, and 52% of all patients in adult centers The most common mode of ventilation during ECMO is pressure control There is a trend toward increased use of bilevel ventilation particularly for lung recruitment Additionally, there is a trend toward increase in performance of bronchoscopy (pediatrics: 69%, mixed centers: 81%, adults: 76%) and tracheostomy Among the centers performing tracheostomies, 45% reported the percutaneous method (pediatric: 31%, mixed: 46%, adult: 57%), 19% reported the open method (pediatric: 9%, mixed: 27%, adult: 24%), and 10% reported using both types of tracheostomies (pediatric: 2%, mixed: 8%, adult: 16%) Our study shows that ECMO centers are extubating their patients, performing tracheostomies and bronchoscopies on their patients more than in the previous years There remains significant variation in ECMO ventilator strategies and management internationally Future studies are needed to correlate these changes in practices to outcome benefits

Assessing Frailty in Patients Undergoing Destination Therapy Left Ventricular Assist Device: Observations from Interagency Registry for Mechanically Assisted Circulatory Support.

Abstract: Frailty and heart failure share common pathways with symptoms that often coexist Assessment of frailty may inform patient selection for left ventricular assist device (LVAD) therapy Using Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data of destination therapy (DT) LVAD patients from January 1, 2012, to March 31, 2014, we examined preimplantation provider-assessed frailty and gait speed testing and the association with 1 year postimplantation outcomes Of 2,469 patients, 227 (92%) had provider-assessed frailty Only 320 (130%) completed gait speed testing, whereas 1,047 (424%) were "too sick" to perform the test Provider-assessed frail and nonfrail patients had similar distributions of INTERMACS profiles and similar median gait speeds One year mortality was higher for patients with provider-assessed frailty versus nonfrail (246% vs 189%; p = 001) and for those too sick to complete gait speed testing versus completed testing (220% vs 159%) There was an association between provider-assessed frailty and mortality, although it was not clinically significant after adjustment (hazard ratio [HR]: 138 [95% confidence interval {CI}: 097-195]) Useful information regarding frailty on postimplant mortality is gained from provider assessment of frailty or knowing gait speed could not be performed Development of frailty measures better suited for DT LVAD candidates may help in distinguishing between a frailty phenotype and a more reversible from heart failure-related vulnerability

Therapeutic Interventions and Risk Factors of Bleeding During Extracorporeal Membrane Oxygenation.

Abstract: Bleeding is the most common complication during extracorporeal membrane oxygenation (ECMO). It is associated with an increased mortality and represents the most frequent cause of preliminary ECMO termination. We performed a retrospective analysis in a single ECMO referral center delineating the risk factors and therapeutic interventions of bleeding during adult ECMO in a total of 59 patients. The median length of ECMO support was 158 hours, with an all-cause mortality of 41%. Bleeding occurred on 40% of the days. On multivariate analysis, fungal pneumonia was the only significant factor associated with the occurrence of a bleeding event. The most common bleeding locations were the ECMO cannulation sites. Termination of ECMO support was the most successful therapeutic intervention, followed by the administration of tranexamic acid, replacement of the membrane oxygenator or the ECMO system, administration of factor VIIa, and repositioning of at least one ECMO cannula. Moreover, the transfusion of platelets was a successful mean, as well as the utilization of desmopressin to enhance platelet function. As such, further delineation of the coagulation disorders during ECMO support to provide a sophisticated pharmacotherapy may stop this serious adverse event.

The Pathophysiology of Nitrogen Dioxide During Inhaled Nitric Oxide Therapy.

Abstract: Administration of inhaled nitric oxide (NO) with the existing compressed gas delivery systems is associated with unavoidable codelivery of nitrogen dioxide (NO2), an unwanted toxic contaminant that forms when mixed with oxygen. The NO2 is generated when NO is diluted with O2-enriched air before delivery to the patient. When NO2 is inhaled by the patient, it oxidizes protective antioxidants within the epithelial lining fluid (ELF) and triggers extracellular damage in the airways. The reaction of NO2 within the ELF triggers oxidative stress (OS), possibly leading to edema, bronchoconstriction, and a reduced forced expiratory volume in 1 second. Nitrogen dioxide has been shown to have deleterious effects on the airways of high-risk patients including neonates, patients with respiratory and heart failure, and the elderly. Minimizing co-delivery of NO2 for the next generation delivery systems will be a necessity to fully optimize the pulmonary perfusion of NO because of vasodilation, whereas minimizing the negative ventilatory and histopathological effects of NO2 exposure during inhaled NO therapy.

The Starling Relationship and Veno-Arterial ECMO: Ventricular Distension Explained.

Abstract: The use of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) to support patients with acute heart failure has been associated with ventricular distension and pulmonary edema, the mechanism of which is not fully understood. This study examined the impact of VA ECMO on left ventricular (LV) Starling curves to elaborate a framework for anticipating and treating LV distension. A previously developed and validated model of the cardiovascular system was used to generate pressure-volume (PV) loops and Starling curves while holding mean arterial pressure (mABP) constant at a range of values either by adjusting systemic resistance or by adding VA ECMO support. It was found that under all conditions of similar mAPB, the Starling curve was unchanged; therefore, the degree of LV distension is obligated by the mAPB (irrespective of whether controlled pharmacologically with or without ECMO support and independent of heart rate), LV contractility, and target stroke volume. The Starling relationship provides a conceptual framework for understanding the risk and treatment of LV distension during VA ECMO support.

Investigation of Key Circuit Constituents Affecting Drug Sequestration During Extracorporeal Membrane Oxygenation Treatment.

Abstract: We quantified the influence of the elements of the extracorporeal oxygenation (ECMO) circuit on drug sequestration by focusing on the interactions between materials and drugs. Tubing of three different brands (Tygon/Maquet/Terumo) and oxygenators of two different brands (Maquet/Terumo) were used. Drugs included dexmedetomidine, meropenem, and heparin, which were dissolved in deionized water. Tubing was cut into approximately 7 cm sections and allowed drug solutions enclosed inside by clamping both ends. The oxygenator housing, gas membrane, and heat exchanger were dissected into approximately 1 g pieces and submerged into drug solutions. The experimental samples were then immersed in a water bath at 37°C for 1, 6, 12, and 24 h. After 24 h, the dexmedetomidine concentration was significantly reduced in all three types of tubing (<30.1%), the oxygenator heat exchanger from Maquet Inc. (41.8%), and the gas exchanger from Terumo Inc. (8.6%), while no significant losses were found for meropenem and heparin compared with the control group. The heparin concentration within the Maquet gas exchanger, on the contrary, increased significantly compared with the control group at 1 and 12 h (p < 0.05). Our in vitro study reveals that material selection is a vital part of ECMO development.

Time in Therapeutic Range for Left Ventricular Assist Device Patients Anticoagulated With Warfarin: A Correlation to Clinical Outcomes.

Abstract: Left ventricular assist devices (LVADs) require anticoagulation therapy with vitamin K antagonists to reduce the risk of thrombotic events. The quality of anticoagulation may be assessed by the time in therapeutic range (TTR). We analyzed a retrospective cohort of LVAD patients at a single institution from January 2012 to September 2014. Primary outcomes included TTR during the study time period and TTR 30 days preceding a bleeding or thrombotic event. Fifty-one patients (mean age 57.0 ± 14.6 years; 78% male) had an overall TTR of 52%. Median international normalized ratio (INR) preceding a bleeding and thrombotic event was 2.7 and 2.2, respectively (p = 0.049). In the 30 days before an event, patients with a bleeding event were more likely to be on low-dose aspirin (37% vs. 12%; p = 0.018) and spend a higher proportion of time above therapeutic range (41% vs. 17%; p = 0.007) compared with those with thrombotic events. The association between a greater percentage of time above therapeutic range in the 30 days before a bleeding event demonstrates the importance of avoiding a supratherapeutic INR in the LVAD patient population and the usefulness of TTR as a measure of the overall quality of anticoagulation and monitoring in an LVAD cohort.