Assessment of cardiopulmonary point-of-care ultrasound objective structured clinical examinations in graduating anesthesiology residents across multiple residency programs.

STUDY OBJECTIVE: To implement and assess a cardiopulmonary point-of-care ultrasound (POCUS) objective structured clinical examination (OSCE) in a large cohort of graduating anesthesia residents. DESIGN: Observational cohort study. SETTING: University-affiliated hospitals. SUBJECTS: 150 graduating anesthesia residents in their last nine months of training. INTERVENTIONS: A standardized cardiopulmonary OSCE was administered to each resident. MEASUREMENTS: The cardiac views evaluated were parasternal long axis (PLAX), apical 4 chamber (A4C), and parasternal short axis (PSAX). The pulmonary views evaluated were pleural effusion (PLE) and pneumothorax (PTX). In addition, a pre- and post-exam survey scored on a 5-point Likert scale was administered to each resident. MAIN RESULTS: A4C view (mean 0.7 ± 0.3) scored a lower mean, compared to PSAX (mean 0.8 ± 0.3) and PLAX (mean 0.8 ± 0.4). Residents performed well on the PTX exam (mean 0.9 ± 0.3) but more poorly on the PLE exam (mean 0.6 ± 0.4). Structural identification across cardiac and pulmonary views were mostly high (means >0.7), but advanced interpretive skills and maneuvers had lower mean scores. Pre- and post- OSCE survey results were positive with almost all questions scoring >4 on the Likert scale. CONCLUSION: Our study demonstrates that a cardiopulmonary POCUS OSCE can be successfully implemented across multiple anesthesia training programs. While most residents were able to perform basic ultrasound views and identify structures, advanced interpretive skills and maneuvers performed lower.

Graduate Medical Education Can Be an Impetus for Behavior Changes in Physicians in Practice: Point-Of-Care Ultrasound Faculty Development Intervention in Anesthesiology.

INTRODUCTION: While there is growing evidence to suggest that point-of-care ultrasound (POCUS) may aid in clinical decision-making in the perioperative setting and there are new requirements that anesthesiology residents must be trained in POCUS, few practicing anesthesiologists use POCUS in their practice. The goal of this investigation is to determine whether a multifaceted faculty development program helps a group of faculty members incorporate POCUS into their practice. METHODS: This intervention had five parts: (1) online prework, (2) 2-day workshop, (3) follow-up hands-on sessions, (4) regular communication, and (5) equipment acquisition. This is a pretest/posttest, single group, observational study where the main outcome measure is the number of POCUS examinations documented and the number of providers who performed at least one examination. In addition, presurveys and postsurveys were administered to determine whether there was a change in confidence and self-reported use of POCUS. RESULTS: The number of examinations completed and the number of providers completing examinations by month both seemed to increase over time between May 2017 and October 2018. Between August 2017 and October 2018, the number of examinations completed per month increased by a rate of approximately one examination per month (starting with one examination in May 2017) and the number of providers completing examinations increased by a rate of approximately 0.61 providers per month (staring with one provider in May 2017). DISCUSSION: This study shows that an intervention that targets interested faculty can increase the use of POCUS in practice and residents' perceptions of teaching.

Design, Development, In Vitro and Preliminary In Vivo Evaluation of a Novel Photo-Angioplasty Device: Lumi-Solve.

PURPOSE: Paclitaxel (PTX)-coated drug eluting balloon catheters (DEBc) used in the management of neointimal hyperplasia (NIH) have been associated with safety concerns. Alternative coating agents and targeted delivery systems may improve safety and DEBc efficacy. Utilizing a multi-platform approach we designed, developed and evaluated Lumi-Solve, a novel DEBc, coated with ultraviolet (UV) 365 nm-activated caged metacept-3 (c-MCT-3), an epigenetic agent from the histone deacetylase inhibitor (HDACi) class. METHODS: In vitro catheter and contrast media transmission of UV365nm was evaluated spectroscopically. UV365nm conversion of c-MCT-3 to MCT-3 was evaluated chromatographically. Cellular toxicity and HDACi activity of c-MCT-3 ∓UV365nm was evaluated in vitro. In vivo UV365nm conversion of c-MCT-3 to MCT-3 was evaluated in an ovine carotid artery model. RESULTS: Catheter material and dilute contrast media did not attenuate UV365nm transmission or c-MCT-3 activation. c-MCT-3 demonstrated less cellular toxicity than MCT-3 and PTX. UV365nm-activated c-MCT-3 demonstrated HDACi activity. In vivo activation of c-MCT-3 produced MCT-3. CONCLUSIONS: Lumi-Solve, a novel DEBc device developed utilizing a combination of chemical, fibre-optic and catheter based technology platforms, demonstrated potential for targeted delivery of bioactive HDACi to the blood vessel wall supporting direct application to the management of NIH and warranting additional in vivo studies.

American Society of Regional Anesthesia and Pain Medicine expert panel recommendations on point-of-care ultrasound education and training for regional anesthesiologists and pain physicians-part II: recommendations.

Point-of-care ultrasound (POCUS) is a critical skill for all regional anesthesiologists and pain physicians to help diagnose relevant complications related to routine practice and guide perioperative management. In an effort to inform the regional anesthesia and pain community as well as address a need for structured education and training, the American Society of Regional Anesthesia and Pain Medicine Society (ASRA) commissioned this narrative review to provide recommendations for POCUS. The recommendations were written by content and educational experts and were approved by the guidelines committee and the Board of Directors of the ASRA. In part II of this two-part series, learning goals and objectives were identified and outlined for achieving competency in the use of POCUS, specifically, airway ultrasound, lung ultrasound, gastric ultrasound, the focus assessment with sonography for trauma exam, and focused cardiac ultrasound, in the perioperative and chronic pain setting. It also discusses barriers to POCUS education and training and proposes a list of educational resources. For each POCUS section, learning goals and specific skills were presented in the Indication, Acquisition, Interpretation, and Medical decision-making framework.

American Society of Regional Anesthesia and Pain Medicine expert panel recommendations on point-of-care ultrasound education and training for regional anesthesiologists and pain physicians-part I: clinical indications.

Point-of-care ultrasound (POCUS) is a critical skill for all regional anesthesiologists and pain physicians to help diagnose relevant complications related to routine practice and guide perioperative management. In an effort to inform the regional anesthesia and pain community as well as address a need for structured education and training, the American Society of Regional Anesthesia and Pain Medicine (ASRA) commissioned this narrative review to provide recommendations for POCUS. The guidelines were written by content and educational experts and approved by the Guidelines Committee and the Board of Directors of the ASRA. In part I of this two-part series, clinical indications for POCUS in the perioperative and chronic pain setting are described. The clinical review addresses airway ultrasound, lung ultrasound, gastric ultrasound, the focus assessment with sonography for trauma examination and focused cardiac ultrasound for the regional anesthesiologist and pain physician. It also provides foundational knowledge regarding ultrasound physics, discusses the impact of handheld devices and finally, offers insight into the role of POCUS in the pediatric population.

Identification of physiologic treatment targets with favourable haemodynamic consequences in heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is characterized by complex pathophysiology including an impaired diastolic reserve. We recently showed that milrinone favourably modifies filling pressures at rest and during exertion in HFpEF patients; however, the responsible mechanism is uncertain. The objective of this study was to develop a clearer understanding of the acutely modifiable physiologic parameters that may be targeted in HFpEF. METHODS AND RESULTS: We conducted computer modelling simulations based on invasive haemodynamic assessments, by right heart catheterization, in HFpEF patients at baseline and in response to milrinone. Our aim was to develop a detailed understanding of the physiologic mechanisms, which accounted for the observed actions. The resultant circulatory model of HFpEF encompassed the left ventricular (LV) end-systolic and end-diastolic pressure-volume relations, together with stressed blood volume, heart rate, and arterial mechanics. To support the modelled action of milrinone, we conducted complementary LV conductance catheter and echocardiography studies in sheep to evaluate LV end-systolic and end-diastolic pressure-volume relations. In HFpEF patients, the acute haemodynamic effects of intravenous milrinone (n = 10) administration compared with placebo (n = 10) included significant reductions in right atrial pressure (7 ± 1 to 3 ± 1 mmHg, P < 0.001) and pulmonary capillary wedge pressure (13 ± 1 to 8 ± 1 mmHg, P < 0.001), while cardiac index increased (2.77 ± 0.19 to 3.15 ± 0.14 L/min/m2 , P < 0.05), and mean arterial pressure remained unchanged (95 ± 2 to 93 ± 3 mmHg, P = not significant). Computer simulations showed that these haemodynamic effects were explained by a concomitant 31% reduction in stressed blood volume together with 44% increase in LV end-systolic elastance (LV Ees ). Individually, changes in these parameters were not sufficient to explain the haemodynamic effects of milrinone. In vivo studies conducted in sheep (n = 5) showed that milrinone reduced LV filling pressure (8.0 ± 0.8 to 2.7 ± 0.6 mmHg, P < 0.01) and increased LV Ees (0.96 ± 0.07 to 2.07 ± 0.49, P < 0.05), while no significant effect on LV stiffness was observed (0.038 ± 0.003 to 0.034 ± 0.008, P = not significant). CONCLUSIONS: These data demonstrate that stressed blood volume in HFpEF represents a relevant physiologic target in HFpEF; however, concomitant modulation of other cardiovascular parameters including LV contractility may be required to achieve desirable haemodynamic effects.

Extended-Release Oral Milrinone for the Treatment of Heart Failure With Preserved Ejection Fraction.

Background Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent form of heart failure, representing half of the total burden of heart failure. We hypothesised that modulation of the phosphodiesterase type 3/cyclic AMP using a novel oral formulation of milrinone might exert favorable effects HFpEF via pulmonary and systemic vasodilation and enhancement of ventricular relaxation. We assessed the safety and efficacy of oral milrinone on quality of life and functional outcomes in patients with HFpEF. Methods and Results The MilHFPEF (Extended Release Oral Milrinone for the Treatment of Heart Failure With Preserved Ejection Fraction) study was a randomized, double-blind, placebo-controlled pilot study in 23 patients with symptomatic HFpEF. Efficacy end points included changes from baseline in Kansas City Cardiomyopathy Questionnaire summary score and 6-minute walk distance. The primary safety end point was the development of clinically significant arrhythmia. The Kansas City Cardiomyopathy Questionnaire score improved significantly in milrinone-treated patients compared with placebo (+10±13 versus -3±15; P=0.046). Six-minute walk distance also tended to improve in the treatment group compared with placebo (+22 [-8 to 49] versus -47 [-97 to 12]; P=0.092). Heart rate (-1±5 versus -2±9 bpm; P=0.9) and systolic blood pressure (-3±18 versus +1±12 mm Hg; P=0.57) were unchanged. Early filling velocity/early mitral annular velocity (-0.3±3.0 versus -1.9±4.8; P=0.38) was unchanged. One patient in the placebo arm was hospitalized for heart failure. Holter monitoring did not demonstrate evidence of a proarrhythmic effect of milrinone. Conclusions In this novel pilot study, extended release oral milrinone was well tolerated and associated with improved quality of life in patients with HFpEF. Further longer-term studies are warranted to establish the role of this therapeutic approach in HFpEF. Registration URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12616000619448.

A Novel Epigenetic Drug-Eluting Balloon Angioplasty Device: Evaluation in a Large Animal Model of Neointimal Hyperplasia.

PURPOSE: Drug-eluting balloon catheters (DEBc) coated with paclitaxel (PTX) have been associated with potential safety concerns. An efficacious but less toxic balloon coating may reduce these outcomes. We evaluated a novel DEBc, Epi-Solve, coated with metacept-3 (MCT-3), a member of the histone deacetylase inhibitor (HDACi) class of epigenetic agents, in a large animal model of neointimal hyperplasia (NIH). METHODS: Plain balloon angioplasty (PABA) catheters were ultrasonically coated with MCT-3 to generate Epi-Solve DEBc. An ovine model of NIH formation was established utilising partial left common carotid artery (LCA) ligation. Twenty-eight days post neointima (NI) induction, PABA, Epi-Solve or PTX-coated DEBc were deployed at the site of induced NI formation. Twenty-eight days post-intervention, ligated vessels were evaluated for attenuation of NI formation, gene expression profiles and immunohistochemical analysis. RESULTS: Epi-Solve DEBc demonstrated attenuation of NIH over no intervention and a trend to inhibition of NIH over PABA. Gene expression analysis and immunohistochemical studies identified significant anti-proliferative and anti-inflammatory signatures and reduced vascular endothelial cell activation compared to PABA. CONCLUSIONS: Epi-Solve is a novel HDACi-coated DEBc which demonstrates significant anti-proliferative and anti-inflammatory signatures and reduced vascular endothelial cell activation compared to PABA in an ovine model and may afford endothelial protection.

An Analysis of the Top-cited Articles in Anesthesiology Education Literature.

BACKGROUND: In the same way that impact factor is calculated for journals, the number of citations an article receives can indicate its influence or value to a particular field. This study was designed to identify the most frequently cited articles in anesthesiology education to yield insight into which articles have been most useful for researchers in ongoing research and publication. METHODS: The Web of Science database was searched to capture the top-cited articles in anesthesiology education both in anesthesiology and nonanesthesiology journals. Results were sorted by the most frequently cited. The top 40 cited articles were identified. Articles were included if they (1) related to anesthesiology or included anesthesiologists as subjects and (2) were related to the education of current or future anesthesiologists. The full text was analyzed, and themes were identified. RESULTS: There was a total of 2923 citations of articles in anesthesiology journals and 924 citations of articles in nonanesthesiology journals. Thirty-two of 40 articles (80%) were research studies. Twenty-four of 40 (60%) were about teaching methods. Twenty-five of 40 (63%) focused on simulation, and 31 of 40 (78%) had residents as the subjects. Twenty-eight of 40 (70%) articles were about either case management (15) or learning procedures (13). CONCLUSIONS: This study identifies the most widely cited articles in anesthesiology education. Common themes included procedural learning, interventional research study designs, simulation, and studies involving residents as subjects. This article may be a resource to anesthesiology education researchers to identify what articles are widely cited by other researchers.

Extended Release Oral Milrinone, CRD-102, for Advanced Heart Failure.

Although heart transplantation and mechanical circulatory support are effective therapies for patients with advanced heart failure (HF), many patients are ineligible due to co-morbidities. Continuous home intravenous with positive inotropes such as milrinone are used in these patients to improve quality of life. We hypothesized that, unlike previous studies with oral milrinone, a slow-release formulation that provides stable lower plasma levels may be better tolerated and provide symptomatic benefit. Accordingly, we developed an extended release milrinone formulation (CRD-102) and evaluated its effects in 26 patients with no-option Stage D HF. One month after open-label therapy there were significant improvements in NYHA class, Minnesota Living with Heart Failure score and 6-minute walk distance. There was no evidence of hypotension or increased arrhythmic burden. In conclusion, the present study demonstrates evidence of beneficial actions of extended release milrinone in advanced HF. Longer-term randomized clinical trial data are required.

Cardiac Gene Delivery Using Recirculating Devices.

Cardiac gene delivery has become an important issue following the emergence of gene therapy for the possible treatment of heart failure. Despite many advances in the management of heart failure (HF), treatment options for many patients with advanced HF remain limited. At a cellular and molecular level, many of the fundamental alterations that contribute to the pathogenesis of HF are becoming better understood and this has resulted in the discovery of new therapeutic targets in animal models of HF, in particular in the area of gene therapy.Numerous small animal and preclinical studies have examined the efficacy of delivering genes targeting various signaling pathways that are affected as the heart fails. However, the translation of this work into the clinic has been difficult due to the requirement for large scale targeted delivery of the gene. This methods chapter describes a percutaneous method of recirculation that we have employed to successfully deliver potential therapeutic agents, including genes, to the heart.

The use of the AVERT system to limit contrast volume administration during peripheral angiography and intervention.

BACKGROUND: The AVERT(TM) Contrast Modulation System (AVERT) (Osprey Medical, MN) is designed to reduce contrast volume administration during angiography. The AVERT provides an adjustable resistance circuit which decreases the pressure head delivering contrast towards the patient. The AVERT has not been previously studied in patients undergoing peripheral digital subtraction angiography (DSA). The purpose of this study was (1) to evaluate contrast savings with the AVERT and (2) to evaluate the ability to generate clinically acceptable DSA images in the process. To better define the mechanism of action in the peripheral circulation, we also developed a bench model to study the effects of the AVERT on the hydrodynamics of contrast delivery. METHODS: Patients undergoing lower extremity DSA (diagnostic or intervention, sheath or catheter) were studied. The following variables were recorded for each injection: starting control syringe contrast volume, contrast volume injected towards patient, contrast volume returned to AVERT reservoir, net contrast administered to the patient and % savings. The AVERT resistance was adjusted manually based on operator's discretion--balancing image quality and contrast savings. RESULTS: About 408 DSA angiographic sequences were obtained in 22 patients undergoing 29 procedures. Almost 68% of the patients had chronic kidney disease. An 82% presented with critical limb ischemia, 18% had claudication. There was an overall 37% ± 14% savings of contrast (31% for diagnostic DSA, 40% for interventional procedures). Overall 91% of all images were acceptable for clinical decision making. Specifically, 94% of diagnostic and 87% of interventional images were acceptable. Injection through a 4 Fr catheter (77% acceptable) resulted in poorer image quality as compared to a 5 Fr catheter (96% acceptable). Image quality for 5, 6, and 7 Fr sheath injections was 86%, 91%, 98%, respectively. The bench model of peripheral angiography demonstrated a significant reduction in reflux of contrast proximal to the end of the catheter without loss of antegrade image quality - confirming the in vivo findings. CONCLUSIONS: We demonstrate that the use of the AVERT device during peripheral angiography results in significant contrast savings without compromising image quality.

CXCR4 Antagonism Attenuates the Development of Diabetic Cardiac Fibrosis.

Heart failure (HF) is an increasingly recognized complication of diabetes. Cardiac fibrosis is an important causative mechanism of HF associated with diabetes. Recent data indicate that inflammation may be particularly important in the pathogenesis of cardiovascular fibrosis. We sought to determine the mechanism by which cardiac fibrosis develops and to specifically investigate the role of the CXCR4 axis in this process. Animals with type I diabetes (streptozotocin treated mice) or type II diabetes (Israeli Sand-rats) and controls were randomized to treatment with a CXCR4 antagonist, candesartan or vehicle control. Additional groups of mice also underwent bone marrow transplantation (GFP+ donor marrow) to investigate the potential role of bone marrow derived cell mobilization in the pathogenesis of cardiac fibrosis. Both type I and II models of diabetes were accompanied by the development of significant cardiac fibrosis. CXCR4 antagonism markedly reduced cardiac fibrosis in both models of diabetes, similar in magnitude to that seen with candesartan. In contrast to candesartan, the anti-fibrotic actions of CXCR4 antagonism occurred in a blood pressure independent manner. Whilst the induction of diabetes did not increase the overall myocardial burden of GFP+ cells, it was accompanied by an increase in GFP+ cells expressing the fibroblast marker alpha-smooth muscle actin and this was attenuated by CXCR4 antagonism. CXCR4 antagonism was also accompanied by increased levels of circulating regulatory T cells. Taken together the current data indicate that pharmacological inhibition of CXCR4 significantly reduces diabetes induced cardiac fibrosis, providing a potentially important therapeutic approach.

Abnormal mitochondrial L-arginine transport contributes to the pathogenesis of heart failure and rexoygenation injury.

BACKGROUND: Impaired mitochondrial function is fundamental feature of heart failure (HF) and myocardial ischemia. In addition to the effects of heightened oxidative stress, altered nitric oxide (NO) metabolism, generated by a mitochondrial NO synthase, has also been proposed to impact upon mitochondrial function. However, the mechanism responsible for arginine transport into mitochondria and the effect of HF on such a process is unknown. We therefore aimed to characterize mitochondrial L-arginine transport and to investigate the hypothesis that impaired mitochondrial L-arginine transport plays a key role in the pathogenesis of heart failure and myocardial injury. METHODS AND RESULTS: In mitochondria isolated from failing hearts (sheep rapid pacing model and mouse Mst1 transgenic model) we demonstrated a marked reduction in L-arginine uptake (p<0.05 and p<0.01 respectively) and expression of the principal L-arginine transporter, CAT-1 (p<0.001, p<0.01) compared to controls. This was accompanied by significantly lower NO production and higher 3-nitrotyrosine levels (both p<0.05). The role of mitochondrial L-arginine transport in modulating cardiac stress responses was examined in cardiomyocytes with mitochondrial specific overexpression of CAT-1 (mtCAT1) exposed to hypoxia-reoxygenation stress. mtCAT1 cardiomyocytes had significantly improved mitochondrial membrane potential, respiration and ATP turnover together with significantly decreased reactive oxygen species production and cell death following mitochondrial stress. CONCLUSION: These data provide new insights into the role of L-arginine transport in mitochondrial biology and cardiovascular disease. Augmentation of mitochondrial L-arginine availability may be a novel therapeutic strategy for myocardial disorders involving mitochondrial stress such as heart failure and reperfusion injury.

A pilot study of electronic directly observed therapy to improve hydroxyurea adherence in pediatric patients with sickle-cell disease.

BACKGROUND: Poor hydroxyurea (HU) adherence limits effective HU use in patients with sickle cell disease (SCD). Electronic directly observed therapy (DOT) may limit costs and achieve high HU adherence in children with SCD. This study aimed to determine if electronic DOT was feasible, acceptable, and could achieve ≥ 90% HU adherence. PROCEDURE: Children with SCD were recruited for this single institution, 6-month pilot study if they had been prescribed HU for ≥ 6 months and had daily access to a smartphone or computer. Participants submitted HU administration videos daily and received electronic reminder alerts, personalized feedback, and incentives to encourage adherence as part of electronic DOT. Primary outcomes were feasibility, participant satisfaction with electronic DOT, and HU adherence. Secondary outcomes included mean corpuscular volume (MCV), hemoglobin F percentage (HbF), and overall participant satisfaction with HU therapy. RESULTS: Of 15 enrolled participants, 14 completed the study. Satisfaction surveys showed electronic DOT reminded participants to take HU and could be completed in fewer than 5 minutes daily. Participants' median medication possession ratio at study entry improved from 0.75 (0.59-0.82) to 0.91 (0.85-1.00) (P = 0.02) at the end of the study. Overall median observed HU adherence with electronic DOT was 93.3%. Median MCV and HbF increased from 96.0 to 107.2 (P = 0.009) and 10.5 to 11.4 (P = 0.03), respectively. CONCLUSIONS: This study demonstrates electronic DOT is feasible, acceptable, and can achieve high HU adherence. Further study is needed to confirm that electronic DOT can improve HU adherence and impact clinical outcomes in children with SCD.

Extracorporeal membrane oxygenation to support cardiopulmonary resuscitation in a sheep model of refractory ischaemic cardiac arrest.

BACKGROUND: Survival after out-of-hospital cardiac arrest remains limited. It is therefore imperative to develop new resuscitation techniques. We aimed to determine the potential role of extracorporeal membrane oxygenation assisted CPR (ECPR) in an animal model of refractory ischaemic cardiac arrest. METHODS: Twelve sheep were assigned to either ECPR (n=6) or 'conventional' (n=6) resuscitation. All sheep had coronary occlusion, followed by induction of ventricular fibrillation (VF). CPR was than commenced for 10 min in both groups, followed by randomisation to ECPR or CPR for a further 10 min. At 23 min post induction of VF, advanced life support measures were commenced with direct cardioversion, adrenaline and amiodarone. Outcomes measures included rates of return of spontaneous circulation (ROSC), and analysis of VF wave form. RESULTS: Baseline haemodynamics were similar between the two groups. CPR consistently produced coronary perfusion pressures (CPP) greater than 15 mmHg in both groups, with significantly increased CPP post commencement of ECMO in the ECPR group (17.84±2 mmHg vs 22.94±3 mmHg, p=0.04). Number of shocks, pH, lactate and oxygenation were also comparable. Significantly greater rates of ROSC were seen in the ECPR sheep, 3/6 (50%) vs 0/6 (0%) (p=0.032), which was also associated with significantly increased VF amplitude measures (0.51±0.08 mV vs 0.42±0.06 mV, p=0.04). CONCLUSIONS: This study indicates that ECPR increases return of circulation and coronary perfusion pressure in a sheep model of ischaemic VF arrest. Our findings have supported the development of a pilot trial into the effectiveness and feasibility of ECPR in the clinical setting.