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Objectives: Following a user‐centred redesign and refinement process of an electronic delirium screening tool (eDIS‐MED), further accuracy assessment was performed prior to anticipated testing in the clinical setting. Methods: Content validity of each of the existing questions was evaluated by an expert group in the domains of clarity, relevance and importance. Questions with a Content Validity Index (CVI) <0.80 were reviewed by the development group for potential revision. Items with CVI <0.70 were discarded. Next, face validity of the entirety of the tests was conducted and readability measured. Results: A panel of five clinical experts evaluated the test battery comprising eDIS‐MED. The content validity process endorsed 61 items. The overall scale CVI was 0.92. Eighty‐eight per cent of the responses with regard to question relevancy, usefulness and appropriateness were positive. The questions were deemed fifth grade level and very easy to read. Conclusions: A revised electronic screening tool was shown to be accurate according to an expert group. A clinical validation study is planned. [ABSTRACT FROM AUTHOR]

Background: Left ventricular stroke work index (LVSWI) and afterload‐related cardiac performance (ACP) consider left ventricular (LV) afterload and could be better prognosticators in septic cardiomyopathy. However, their invasive nature prevents their routine clinical applications. This study aimed to investigate (1) whether a proposed speckle‐tracking echocardiography parameter, Pressure‐Strain Product (PSP), can non‐invasively predict catheter‐based LVSWI, ACP and serum lactate in an ovine model of septic cardiomyopathy; and (2) whether PSP can distinguish the sub‐phenotypes of acute respiratory distress syndrome (ARDS) with or without sepsis‐like conditions. Methods: Sixteen sheep with ARDS were randomly assigned to either (1) sepsis‐like (n = 8) or (2) non‐sepsis‐like (n = 8) group. Each ARDS and sepsis‐like condition was induced by intravenous infusion of oleic acid and lipopolysaccharide, respectively. Pulmonary artery catheter‐based LVSWI (the product of stroke work index, mean arterial pressure and.0136), ACP (the percentage of cardiac output measured to cardiac output predicted as normal) and serum lactate were measured simultaneously with transthoracic echocardiography. Two PSP indices were calculated by multiplying the mean arterial blood pressure and either global circumferential strain (PSPcirc) or radial strain (PSPrad). Results: PSPcirc showed a significant correlation with LVSWI (r2 =.66, p <.001) and ACP (r2 =.82, p <.001) in the sepsis‐like group. Although PSP could not distinguish subphenotypes, PSPcirc predicted LVSWI (AUC.86) and ACP (AUC.88), and PSPrad predicted serum lactate (AUC.75) better than LV ejection fraction, global circumferential and radial strain. Conclusions: A novel PSP has the potential to non‐invasively predict catheter‐based LVSWI and ACP, and was associated with serum lactate in septic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal life support (ECLS) has extensive applications in managing patients with acute cardiac and pulmonary failure. Two primary modalities of ECLS, cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO), include several similarities in their composition, complications, and patient outcomes. Both CPB and ECMO pose a high risk of thrombus formation and platelet activation due to the large surface area of the devices and bleeding due to system anticoagulation. Therefore, novel methods of anticoagulation are needed to reduce the morbidity and mortality associated with extracorporeal support. Nitric oxide (NO) has potent antiplatelet properties and presents a promising alternative or addition to anticoagulation with heparin during extracorporeal support. Methods: We developed two ex vivo models of CPB and ECMO to investigate NO effects on anticoagulation and inflammation in these systems. Results: Sole addition of NO as an anticoagulant was not successful in preventing thrombus formation in the ex vivo setups, therefore a combination of low‐level heparin with NO was used. Antiplatelet effects were observed in the ex vivo ECMO model when NO was delivered at 80 ppm. Platelet count was preserved after 480 min when NO was delivered at 30 ppm. Conclusion: Combined delivery of NO and heparin did not improve haemocompatibility in either ex vivo model of CPB and ECMO. Anti‐inflammatory effects of NO in ECMO systems have to be evaluated further. [ABSTRACT FROM AUTHOR]

Objective: Pulsatile‐flow veno‐arterial extracorporeal membrane oxygenation (V‐A ECMO) has shown encouraging results for microcirculation resuscitation and left ventricle unloading in patients with refractory cardiogenic shock. We aimed to comprehensively assess different V‐A ECMO parameters and their contribution to hemodynamic energy production and transfer through the device circuit. Methods: We used the i‐cor® ECMO circuit, which composed of Deltastream DP3 diagonal pump and i‐cor® console (Xenios AG), the Hilite 7000 membrane oxygenator (Xenios AG), venous and arterial tubing and a 1 L soft venous pseudo‐patient reservoir. Four different arterial cannulae (Biomedicus 15 and 17 Fr, Maquet 15 and 17 Fr) were used. For each cannula, 192 different pulsatile modes were investigated by adjusting flow rate, systole/diastole ratio, pulsatile amplitudes and frequency, yielding 784 unique conditions. A dSpace data acquisition system was used to collect flow and pressure data. Results: Increasing flow rates and pulsatile amplitudes were associated with significantly higher hemodynamic energy production (both p < 0.001), while no significant associations were seen while adjusting systole‐to‐diastole ratio (p = 0.73) or pulsing frequency (p = 0.99). Arterial cannula represents the highest resistance to hemodynamic energy transfer with 32%–59% of total hemodynamic energy generated being lost within, depending on pulsatile flow settings used. Conclusions: Herein, we presented the first study to compare hemodynamic energy production with all pulsatile ECLS pump settings and their combinations and widely used yet previously unexamined four different arterial ECMO cannula. Only increased flow rate and amplitude increase hemodynamic energy production as single factors, whilst other factors are relevant when combined. [ABSTRACT FROM AUTHOR]

Background: Various strategies of weaning V‐A ECMO have been described. PCRTO is a weaning technique which involves serial decremental pump revolutions until a retrograde flow from the arterial to venous ECMO cannula is achieved. It has been reported as a feasible weaning strategy in the pediatric population, but its application in adults has not been widely reported. Methods: This was a case series including all adult patients who underwent PCRTO during weaning from V‐A ECMO at a tertiary ECMO center between January 2019 and July 2021. The primary end point was the successful weaning from V‐A ECMO support. Results: A total of 57 runs of PCRTO in 36 patients were analyzed—45 (78.9%) of the trials were concluded successfully. The median retrograde blood flow rate during PCRTO was 0.6 ± 0.2 L/min, and the median duration of each PCRTO was 180 (120–240) min. Of the 35 patients who had at least one session of successful PCRTO, 31 (88.6%) were ultimately weaned from ECMO. There were no major complications from PCRTO including systemic or circuit thrombosis. Conclusions: PCRTO is a feasible strategy for assessing readiness for weaning from V‐A ECMO with a low risk of adverse events and high rate of predicting eventual successful ECMO decannulation. Further investigation including comparison with alternative weaning strategies in prospective studies is required to confirm the approach. [ABSTRACT FROM AUTHOR]

Due to the poor tribological properties of titanium (Ti) and its alloy Ti6Al4V (commonly used for ventricular assist devices manufacturing), diamond‐like carbon (DLC) films with excellent anti‐wear properties are pursued to improve the wear resistance of Ti and its alloys. Considering the effect of temperature on magnets inside pump impellers and workpiece deformation, DLC films are preferred to be prepared under low temperature. In this study, DLC films were prepared on Ti6Al4V alloys by periodic and continuous processes, and the corresponding maximum deposition temperature was 85 and 154°C, respectively. The periodic DLC films exhibited the feature of columnar structure, and the surface hillocks were less uniform than that of continuous DLC films. The periodic DLC films possessed more sp3‐bonded structures, and the accessorial sp3‐bonding mainly existed in the form of CH. Compared to continuous DLC films, the periodic DLC films had lower residual stress and better adhesion with Ti6Al4V substrates. Both DLC films could effectively reduce the friction coefficient and wear rate of Ti6Al4V alloys both in air and fetal bovine serum (FBS), and the periodic DLC films exhibited superior anti‐wear properties to that of continuous DLC films in FBS. Haemocompatibility evaluation revealed that both DLC films presented similar levels of more human platelet adhesion and activation as compared with that of bare Ti6Al4V. However, both DLC films significantly prolonged plasma clotting time in comparison to bare Ti6Al4V. This study demonstrates the potential of low‐temperature DLC films as wear‐resistant surface modification for VADs. [ABSTRACT FROM AUTHOR]

Aims: To identify clinical and biochemical markers associated with nutrition adequacy and gastrointestinal and liver dysfunction in adults on extracorporeal membrane oxygenation (ECMO). Methods: A retrospective, observational, study was conducted at 2 centres in Australia. Adult patients who received ECMO from July 2011 to June 2015 were included. Mode of ECMO used, fluid balance, number of systemic inflammatory response syndrome (SIRS) criteria present, vasoactive‐inotropic scores (VIS) and liver function tests (LFTs) were collected for the duration of ECMO until 7 days after ECMO cessation. Multiple regression models were used to determine if the collected variables were associated with nutrition adequacy. The mean LFTs during ECMO were also compared to mean LFTs post ECMO cessation. Results: During the first 5 days of ECMO commencement, mean nutrition adequacy was 10% higher in the veno‐venous (VV) ECMO group than in the veno‐arterial (VA) group (95% confidence interval [CI], 2% to 17%). For every 5000 ml increase of fluid balance, an associated decrease in nutrition adequacy was observed (−8%, 95% CI: −15% to −2%). A doubling of bilirubin and VIS were associated with a mean reduction in nutrition adequacy of −5% (95% CI –8% to −2%) and − 2% (95% CI: −3% to −1%), respectively. Conclusions: In the first 5 days of ECMO commencement, higher nutrition adequacy was associated with the VV mode of ECMO and reduced nutrition adequacy with increased fluid balance, more vasopressor and inotropic support and raised bilirubin. Prospective investigation is required to confirm whether these associations have a causal relationship. [ABSTRACT FROM AUTHOR]

The acute respiratory distress syndrome (ARDS) describes a heterogenous population of patients with acute severe respiratory failure. However, contemporary advances have begun to identify distinct sub‐phenotypes that exist within its broader envelope. These sub‐phenotypes have varied outcomes and respond differently to several previously studied interventions. A more precise understanding of their pathobiology and an ability to prospectively identify them, may allow for the development of precision therapies in ARDS. Historically, animal models have played a key role in translational research, although few studies have so far assessed either the ability of animal models to replicate these sub‐phenotypes or investigated the presence of sub‐phenotypes within animal models. Here, in three ovine models of ARDS, using combinations of oleic acid and intravenous, or intratracheal lipopolysaccharide, we investigated the presence of sub‐phenotypes which qualitatively resemble those found in clinical cohorts. Principal Component Analysis and partitional clustering identified two clusters, differentiated by markers of shock, inflammation, and lung injury. This study provides a first exploration of ARDS phenotypes in preclinical models and suggests a methodology for investigating this phenomenon in future studies. [ABSTRACT FROM AUTHOR]

Pre‐existing cardiovascular disease (CVD) increases the morbidity and mortality of COVID‐19 and is strongly associated with poor disease outcomes. However, SARS‐CoV‐2 infection can also trigger de novo acute and chronic cardiovascular disease. Acute cardiac complications include arrhythmia, myocarditis and heart failure, which are significantly associated with higher in‐hospital mortality. The possible mechanisms by which SARS‐CoV‐2 causes this acute cardiac disease include direct damage caused by viral invasion of cardiomyocytes as well as indirect damage through systemic inflammation. The long‐term cardiac complications associated with COVID‐19 are incompletely characterised and thought to include hypertension, arrhythmia, coronary atherosclerosis and heart failure. Although some cardiac‐related symptoms can last over 6 months, the effect of these complications on long‐term patient health remains unclear. The risk factors associated with long‐term cardiovascular disease remain poorly defined. Determining which patients are most at‐risk of long‐term cardiovascular disease is vital so that targeted follow‐up and patient care can be provided. The aim of this review was to summarise the current evidence of the acute and long‐term cardiovascular consequences of SARS‐CoV‐2 infection and the mechanisms by which SARS‐CoV‐2 may cause cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background and objectives: Sheep are increasingly being used as a large in vivo animal model of blood transfusion because they provide several advantages over small animals. Understanding the effects of storage duration on ovine (ov) red cell concentrates (RCCs) and how these changes compare with stored human (hu) RCCs is necessary to facilitate clinical translation of research findings. Materials and methods: OvRCCs (n = 5) collected and processed in standard human blood collection packs, and equivalent huRCCs provided by Australian Red Cross Lifeblood (n = 5), were stored at 2–6°C for 42 days, with samples collected weekly. Haemolysis index was determined by measuring supernatant haemoglobin concentration. Biochemical parameters were evaluated using a blood gas analyser. Energy metabolites and biologically active lipids were measured using commercial assays. Osmotic fragility was determined by lysis in various saline concentrations. Extracellular vesicles were characterized by nanoparticle tracking analysis. Results: Ovine red blood cells (RBCs) are double in number, smaller in size and more fragile than human RBCs. Haematological values were unchanged throughout storage. In contrast, biochemical and metabolic values, and haemolysis index in three of the five ovRCCs exceeded huRCCs licensing criteria by day 42. Accumulation of extracellular vesicles and biologically active lipids was comparable between huRCCs and ovRCCs. Conclusion: This study documents similarities and differences in the storage lesion of ovRCCs and huRCCs. This new information will guide the design of ovine transfusion models to enhance translation of findings to human transfusion settings. [ABSTRACT FROM AUTHOR]

Limb ischemia is a major complication associated with peripheral venoarterial extracorporeal membrane oxygenation (VA‐ECMO). The high velocity jet from arterial cannulae can cause "sandblasting" injuries to the arterial endothelium, with the potential risk of distal embolization and end organ damage. The aim of this study was to identify, for a range of clinically relevant VA‐ECMO cannulae and flow rates, any regions of peak flow velocity on the aortic wall which may predispose to vascular injury, and any regions of low‐velocity flow which may predispose to thrombus formation. A silicone model of the aortic and iliac vessels was sourced and the right external iliac artery was cannulated. Cannulae ranged from 15 to 21 Fr in size. Simulated steady state ECMO flow rates were instituted using a magnetically levitated pump (CentriMag pump). Adaptive particle image velocimetry was performed for each cannula at 3, 3.5, 4, and 4.5 L/min. For all cannulae, in both horizontal and vertical side hole orientations, the peak velocity on the aortic wall ranged from 0.3 to 0.45 m/s, and the regions of lowest velocity flow were 0.05 m/s. The magnitude of peak velocity flow on the aortic wall was not different between a single pair versus multiple pairs of side holes. Maximum velocity flow on the aortic wall occurred earlier at a lower pump flow rate in the vertical orientation of distal side holes compared to a horizontal position. The presence of multiple paired side holes was associated with fewer low‐velocity flow regions, and some retrograde flow, in the distal abdominal aorta compared to cannulae with a single pair of side holes. From this in vitro visualization study, the selection of a cannula design with multiple versus single pairs of side holes did not change the magnitude of peak velocity flow delivered to the vessel wall. Cannulae with multiple side holes were associated with fewer regions of low‐velocity flow in the distal abdominal aorta. Further in vivo studies, and ideally clinical data would be required to assess any correlation of peak velocity flows with incidence of vascular injury, and any low‐velocity flow regions with incidence of thrombosis. [ABSTRACT FROM AUTHOR]

Nonsurgical bleeding is the most frequent complication of left ventricular assist device (LVAD) support. Supraphysiologic shear rates generated in LVAD causes impaired platelet aggregation, which increases the risk of bleeding. The effect of shear rate on the formation size of platelet aggregates has never been reported experimentally, although platelet aggregation size can be considered to be directly relevant to bleeding complications. Therefore, this study investigated the impact of shear rate and exposure time on the formation size of platelet aggregates, which is vital in predicting bleeding in patients with an LVAD. Human platelet‐poor plasma (containing von Willebrand factor, vWF) and fluorochrome‐labeled platelets were subjected to a range of shear rates (0‐10 000 s−1) for 0, 5, 10, and 15 minutes using a custom‐built blood‐shearing device. Formed sizes of platelet aggregates under a range of shear‐controlled environment were visualized and measured using microscopy. The loss of high molecular weight (HMW) vWF multimers was quantified using gel electrophoresis and immunoblotting. An inhibition study was also performed to investigate the reduction in platelet aggregation size and HMW vWF multimers caused by either mechanical shear or enzymatic (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13—ADAMTS13, the von Willebrand factor protease) mechanism under low and high shear conditions (360 and 10 000 s−1). We found that the average size of platelet aggregates formed under physiological shear rates of 360‐3000 s−1 (200‐300 μm2) was significantly larger compared to those sheared at >6000 s−1 (50‐100 μm2). Furthermore, HMW vWF multimers were reduced with increased shear rates. The inhibition study revealed that the reduction in platelet aggregation size and HWM vWF multimers were mainly associated with ADAMTS13. In conclusion, the threshold of shear rate must not exceed >6000 s−1 in order to maintain the optimal size of platelet aggregates to "plug off" the injury site and stop bleeding. [ABSTRACT FROM AUTHOR]

Use of extracorporeal membrane oxygenation (ECMO) is expanding, however, it is still associated with significant morbidity and mortality. Activation of inflammatory and innate immune responses and hemostatic alterations contribute to complications. Hyperoxia may play a role in exacerbating these responses. Nine ex vivo ECMO circuits were tested using fresh healthy human whole blood, with two oxygen levels: 21% inspired fraction of oxygen (FiO2; mild hyperoxia; n = 5) and 100% FiO2 (severe hyperoxia; n = 4). Serial blood samples were taken for analysis of platelet aggregometry, leukocyte activation, inflammatory, and oxidative stress markers. ECMO resulted in reduced adenosine diphosphate‐ (P <.05) and thrombin receptor activating peptide‐induced (P <.05) platelet aggregation, as well as increasing levels of the neutrophil activation marker, neutrophil elastase (P =.013). Additionally, levels of the inflammatory chemokine interleukin‐8 were elevated (P <.05) and the activity of superoxide dismutase, a marker of oxidative stress, was increased (P =.002). Hyperoxia did not augment these responses, with no significant differences detected between mild and severe hyperoxia. Our ex vivo model of ECMO revealed that the circuit itself triggers a pro‐inflammatory and oxidative stress response, however, exposure to supra‐physiologic oxygen does not amplify that response. Extended‐duration studies and inclusion of an endothelial component could be beneficial in characterizing longer term changes. [ABSTRACT FROM AUTHOR]

Similarly, ECMO for COVID-19 related ARDS was discussed from the French perspective by Dr. Matthieu Schmidt from Piié Salpetrière Hospital and Dr. Keiki Shimizu the Japanese experience, Dr. Xiaotong Hou the Chinese experience, Dr. Urvi Shukla the Indian experience and Dr. Eva Marwali the Indonesian experience. Dr. Chiao-Feng Cheng from National Taiwan University received the second-place award for his abstract on ECMO in immunocompromised patients with ARDS. The Asia-Pacific Extracorporeal Life Support Organization (APELSO) is the Asia-Pacific Chapter of the Extracorporeal Life Support Organization (ELSO), which had its first meeting in Melbourne, July 2012, hosted by Dr. Vin Pellegrino from the Alfred Hospital, Melbourne, and Dr. Steve Conrad, then the Chair of the Global ELSO Steering Committee. [Extracted from the article]

Objectives: To describe haemodynamic resuscitation practices in ED patients with suspected sepsis and hypotension. Methods: This was a prospective, multicentre, observational study conducted in 70 hospitals in Australia and New Zealand between September 2018 and January 2019. Consecutive adults presenting to the ED during a 30‐day period at each site, with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation, were eligible. Data included baseline demographics, clinical and laboratory variables and intravenous fluid volume administered, vasopressor administration at baseline and 6‐ and 24‐h post‐enrolment, time to antimicrobial administration, intensive care admission, organ support and in‐hospital mortality. Results: A total of 4477 patients were screened and 591 were included with a mean (standard deviation) age of 62 (19) years, Acute Physiology and Chronic Health Evaluation II score 15.2 (6.6) and a median (interquartile range) systolic blood pressure of 94 mmHg (87–100). Median time to first intravenous antimicrobials was 77 min (42–148). A vasopressor infusion was commenced within 24 h in 177 (30.2%) patients, with noradrenaline the most frequently used (n = 138, 78%). A median of 2000 mL (1500–3000) of intravenous fluids was administered prior to commencing vasopressors. The total volume of fluid administered from pre‐enrolment to 24 h was 4200 mL (3000–5661), with a range from 1000 to 12 200 mL. Two hundred and eighteen patients (37.1%) were admitted to an intensive care unit. Overall in‐hospital mortality was 6.2% (95% confidence interval 4.4–8.5%). Conclusion: Current resuscitation practice in patients with sepsis and hypotension varies widely and occupies the spectrum between a restricted volume/earlier vasopressor and liberal fluid/later vasopressor strategy. [ABSTRACT FROM AUTHOR]

Controlled and repeatable in vitro evaluation of cardiovascular devices using a mock circulation loop (MCL) is essential prior to in vivo or clinical trials. MCLs often consist of only a systemic circulation with no autoregulatory responses and limited validation. This study aimed to develop, and validate against human data, an advanced MCL with systemic, pulmonary, cerebral, and coronary circulations with autoregulatory responses. The biventricular MCL was constructed with pneumatically controlled hydraulic circulations with Starling responsive ventricles and autoregulatory cerebral and coronary circulations. Hemodynamic repeatability was assessed and complemented by validation using impedance cardiography data from 50 healthy humans. The MCL successfully simulated patient scenarios including rest, exercise, and left heart failure with and without cardiovascular device support. End‐systolic pressure‐volume relationships for respective healthy and heart failure conditions had slopes of 1.27 and 0.54 mm Hg mL−1 (left ventricle), and 0.18 and 0.10 mm Hg mL−1 (right ventricle), aligning with the literature. Coronary and cerebral autoregulation showed a strong correlation (R2:.99) between theoretical and experimentally derived circuit flow. MCL repeatability was demonstrated with correlation coefficients being statistically significant (P <.05) for all simulated conditions while MCL hemodynamics aligned well with human data. This advanced MCL is a valuable tool for inexpensive and controlled evaluation of cardiovascular devices. [ABSTRACT FROM AUTHOR]

Aim: Nasal high-flow oxygen therapy is increasingly used in infants for supportive respiratory therapy in bronchiolitis. It is unclear whether enteral hydration is safe in children receiving high-flow.Methods: We performed a planned secondary analysis of a multi-centre, randomised controlled trial of infants aged <12 months with bronchiolitis and an oxygen requirement. Children were assigned to treatment with either high-flow or standard-oxygen therapy with optional rescue high-flow. We assessed adverse events based on how children on high-flow were hydrated: intravenously (IV), via bolus or continuous nasogastric tube (NGT) or orally.Results: A total of 505 patients on high-flow via primary study assignment (n = 408), primary treatment (n = 10) or as rescue therapy (n = 87) were assessed. While on high flow, 15 of 505 (3.0%) received only IV fluids, 360 (71.3%) received only enteral fluids and 93 (18.4%) received both IV and enteral fluids. The route was unknown in 37 (7.3%). Of the 453 high-flow infants hydrated enterally patients could receive one or more methods of hydration; 80 (15.8%) received NGT bolus, 217 (43.0%) NGT continuous, 118 (23.4%) both bolus and continuous, 32 (6.3%) received only oral hydration and 171 (33.9%) a mix of NGT and oral hydration. None of the patients receiving oral or NGT hydration on high-flow sustained pulmonary aspiration (0%; 95% confidence interval N/A); one patient had a pneumothorax (0.2%; 95% confidence interval 0.0-0.7%).Conclusions: The vast majority of children with hypoxic respiratory failure in bronchiolitis can be safely hydrated enterally during the period when they receive high-flow. [ABSTRACT FROM AUTHOR]

Coronary artery bypass grafting (CABG) triggers a systemic inflammatory response that may contribute to adverse outcomes. Dendritic cells (DC) and monocytes are immunoregulatory cells potentially affected by CABG, contributing to an altered immune state. This study investigated changes in DC and monocyte responses in CABG patients at 5 time‐points: admission, peri‐operative, ICU, day 3 and day 5. Whole blood from 49 CABG patients was used in an ex vivo whole blood culture model to prospectively assess DC and monocyte responses. Lipopolysaccharide (LPS) was added in parallel to model responses to an infectious complication. Co‐stimulatory and adhesion molecule expression and intracellular mediator production was measured by flow cytometry. CABG modulated monocyte and DC responses. In addition, DC and monocytes were immunoparalysed, evidenced by failure of co‐stimulatory and adhesion molecules (eg HLA‐DR), and intracellular mediators (eg IL‐6) to respond to LPS stimulation. DC and monocyte modulation was associated with prolonged ICU length of stay and post‐operative atrial fibrillation. DC and monocyte cytokine production did not recover by day 5 post‐surgery. This study provides evidence that CABG modulates DC and monocyte responses. Using an ex vivo model to assess immune competency of CABG patients may help identify biomarkers to predict adverse outcomes. [ABSTRACT FROM AUTHOR]

The interface between synthetic percutaneous devices and skin is a common area for bacterial infection, which may ultimately result in failure of the device. Better integration of percutaneous devices with skin may help reduce infection rates due to the creation of a dermal seal. However, the mismatch in material and chemical properties of devices and skin presents a challenge for closing the dermal gap at the skin–device interface. Here, we have used a tissue engineering approach to tissue integration by creating a highly fibrous poly(ε‐caprolactone) scaffold using melt electrowriting and seeding this with dermal fibroblasts, followed by maturation and insertion into a full‐thickness defect made in an ex vivo skin model. The integration of seeded scaffolds was compared with controls including a non‐seeded scaffold and a polymer tube with a smooth surface. Dermal fibroblast inclusion in the scaffold and epidermal upgrowth versus downgrowth/marsupialization around the device were used as measures of integration. Based on these measures, almost all pre‐seeded scaffolds performed better than both the non‐seeded scaffolds and smooth tubes. The hypothesis is that the fibroblasts act as a barrier to epithelial downward migration, and provide healthy tissue for nascent epidermal development. [ABSTRACT FROM AUTHOR]

Due to improved durability and survival rates, rotary blood pumps (RBPs) are the preferred left ventricular assist device when compared to volume displacement pumps. However, when operated at constant speed, RBPs lack a volume balancing mechanism which may result in left ventricular suction and suboptimal ventricular unloading. Starling‐like controllers have previously been developed to balance circulatory volumes; however, they do not consider ventricular workload as a feedback and may have limited sensitivity to adjust RBP workload when ventricular function deteriorates or improves. To address this, we aimed to develop a Starling‐like total work controller (SL‐TWC) that matched the energy output of a healthy heart by adjusting RBP hydraulic work based on measured left ventricular stroke work and ventricular preload. In a mock circulatory loop, the SL‐TWC was evaluated using a HeartWare HVAD in a range of simulated patient conditions. These conditions included changes in systemic hypertension and hypotension, pulmonary hypertension, blood circulatory volume, exercise, and improvement and deterioration of ventricular function by increasing and decreasing ventricular contractility. The SL‐TWC was compared to constant speed control where RBP speed was set to restore cardiac output to 5.0 L/min at rest. Left ventricular suction occurred with constant speed control during pulmonary hypertension but was prevented with the SL‐TWC. During simulated exercise, the SL‐TWC demonstrated reduced LVSW (0.51 J) and greater RBP flow (9.2 L/min) compared to constant speed control (LVSW: 0.74 J and RBP flow: 6.4 L/min). In instances of increased ventricular contractility, the SL‐TWC reduced RBP hydraulic work while maintaining cardiac output similar to the rest condition. In comparison, constant speed overworked and increased cardiac output. The SL‐TWC balanced circulatory volumes by mimicking the Starling mechanism, while also considering changes in ventricular workload. Compared to constant speed control, the SL‐TWC may reduce complications associated with volume imbalances, adapt to changes in ventricular function and improve patient quality of life. [ABSTRACT FROM AUTHOR]

The article inform undifferentiated breathlessness is a common presenting symptom in the Emergency Department (ED). Topic include Heated Humidified High-Flow Nasal Cannula (HHFNC)is seen as a useful therapy providing degree of respiratory support, thus bridging the dyspnoea management gap between oxygen therapy and Non-Invasive Ventilation (NIV) or intubation.

Background: Cryopreservation extends platelet (PLT) shelf life from 5 to 7 days to 2 to 4 years. However, only 73 patients have been transfused cryopreserved PLTs in published randomized controlled trials (RCTs), making safety data insufficient for regulatory approval.Study Design and Methods: The Cryopreserved vs. Liquid Platelet (CLIP) study was a double-blind, pilot, multicenter RCT involving high-risk cardiothoracic surgical patients in four Australian hospitals. The objective was to test, as the primary outcome, the feasibility and safety of the protocol. Patients were allocated to study group by permuted block randomization, with patients and clinicians blinded by use of an opaque shroud placed over each study PLT unit. Up to 3 units of cryopreserved or liquid-stored PLTs were administered per patient. No other aspect of patient care was affected. Adverse events were actively sought.Results: A total of 121 patients were randomized, of whom 23 received cryopreserved PLTs and 18 received liquid-stored PLTs. There were no differences in blood loss (median, 715 mL vs. 805 mL at 24 hr; difference between groups 90 mL [95% CI, -343.8 to 163.8 mL], p = 0.41), but the Bleeding Academic Research Consortium criterion for significant postoperative hemorrhage in cardiac surgery composite bleeding endpoint occurred in nearly twice as many patients in the liquid-stored group (55.6% vs. 30.4%, p = 0.10). Red blood cell transfusion requirements were a median of 3 units in the cryopreserved group versus 4 units with liquid-stored PLTs (difference between groups, 1 unit [95% CI, -3.1 to 1.1 units]; p = 0.23). Patients in the cryopreserved group were more likely to be transfused fresh-frozen plasma (78.3% vs. 27.8%, p = 0.002) and received more study PLT units (median, 2 units vs. 1 unit; difference between groups, 1 unit [95% CI, -0.03 to 2.0 units]; p = 0.012). There were no between-group differences in potential harms including deep venous thrombosis, myocardial infarction, respiratory function, infection, and renal function. No patient had died at 28 days, and postoperative length of stay was similar in each group.Conclusion: In this pilot RCT, compared to liquid-stored PLTs, cryopreserved PLTs were associated with no evidence of harm. A definitive study testing safety and hemostatic effectiveness is warranted. [ABSTRACT FROM AUTHOR]

Objective: There is uncertainty about the optimal i.v. fluid volume and timing of vasopressor commencement in the resuscitation of patients with sepsis and hypotension. We aim to study current resuscitation practices in EDs in Australia and New Zealand (the Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In Emergency Department Sepsis [ARISE FLUIDS] observational study). Methods: ARISE FLUIDS is a prospective, multicentre observational study in 71 hospitals in Australia and New Zealand. It will include adult patients presenting to the ED during a 30 day period with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation. We will obtain data on baseline demographics, clinical and laboratory variables, all i.v. fluid given in the first 24 h, vasopressor use, time to antimicrobial administration, admission to intensive care, organ failure and in‐hospital mortality. We will specifically describe (i) the volume of fluid administered at the following time points: when meeting eligibility criteria, in the first 6 h, at 24 h and prior to vasopressor commencement and (ii) the frequency and timing of vasopressor use in the first 6 h and at 24 h. Screening logs will provide reliable estimates of the proportion of ED patients meeting eligibility criteria for a subsequent randomised controlled trial. Discussion: This multicentre, observational study will provide insight into current haemodynamic resuscitation practices in patients with sepsis and hypotension as well as estimates of practice variation and patient outcomes. The results will inform the design and feasibility of a multicentre phase III trial of early haemodynamic resuscitation in patients presenting to ED with sepsis and hypotension. [ABSTRACT FROM AUTHOR]

Although rotary blood pumps (RBPs) sustain life, blood exposure to continuous supra‐physiological shear stress induces adverse effects (e.g., thromboembolism); thus, pulsatile flow in RBPs represents a potential solution. The present study introduced pulsatile flow to the HeartWare HVAD using a custom‐built controller and compared hemocompatibility biomarkers (i.e., platelet aggregation, concentrations for ADAMTS13, von Willebrand factor (vWf), and free‐hemoglobin in plasma (pfHb), red blood cell (RBC) deformability, and RBC‐nitric oxide synthase (NOS) activity) between continuous and pulsatile flow in a blood circulation loop over 5 h. The HeartWare HVAD was operated using a custom‐built controller, at continuous speed (3282 rev/min) or in a pulsatile mode (mean speed = 3273 rev/min, amplitude = 430 rev/min, frequency = 1 Hz) to generate a blood flow rate of 5.0 L/min, HVAD differential pressure of 90 mm Hg for continuous flow and 92 mm Hg for pulsatile flow, and systolic and diastolic pressures of 121/80 mm Hg. For both flow regimes, the current study found; (i) ADP‐ and collagen‐induced platelet aggregation, and ADAMTS13 concentration significantly decreased after 5 h (P < 0.01; P < 0.05), (ii) ristocetin‐induced platelet aggregation significantly increased after 45 min (P < 0.05), (iii) vWf concentration did not significantly differ at any time point, (iv) pfHb significantly increased after 5 h (P < 0.01), (v) RBC deformability improved during the continuous flow regime (P < 0.05) but not during pulsatile flow, and (vi) RBC‐NOS activity significantly increased during continuous flow (15 min), and pulsatile flow (5 h; P < 0.05). The current study demonstrated: (i) speed modulation does not improve hemocompatibility of the HeartWare HVAD based on no observable differences being detected for routine biomarkers, and (ii) the time‐course for increased RBC‐NOS activity observed during continuous flow may have improved RBC deformability. [ABSTRACT FROM AUTHOR]

Objectives: Delirium is common in the intensive care unit (ICU), often affecting older patients. A bedside electronic tool has the potential to revolutionise delirium screening. Our group describe a novel approach to the design and development of delirium screening questions for the express purpose of use within an electronic device. Preliminary results are presented. Methods: Our group designed a series of tests which targeted the clinical criteria for delirium according to Diagnostic and Statistical Manual of Mental Disorders -- Fifth Edition (DSM-5) criteria against predefined requirements, including applicability to older patients. Results: Candidate questions, including tests of attention and awareness, were devised and then refined by an expert multidisciplinary group, including geriatricians. A scoring scheme was constructed, with testing to failure an indicator of delirium. The device was tested in healthy controls, aged 20-80 years, who were recorded as being without delirium. Conclusion: e-Screening for delirium requires a novel approach to instrument design but may revolutionise recognition of delirium in ICU. [ABSTRACT FROM AUTHOR]

Abstract: Although comprehensive guidelines for treatment of sepsis exist, current research continues to refine and revise several aspects of management. Imperatives for rapid administration of broad‐spectrum antibiotics for all patients with sepsis may not be supported by contemporary data. Many patients may be better served by a more judicious approach allowing consideration of investigation results and evidence‐based guidelines. Conventional fluid therapy has been challenged with early evidence supporting balanced, restricted fluid and early vasopressor use. Albumin, vasopressin and hydrocortisone have each been shown to support blood pressure and reduce catecholamine requirements but without effect on mortality, and as such should be considered for ED patients with septic shock on a case‐by‐case basis. Measurement of quality care in sepsis should incorporate quality of blood cultures and guideline‐appropriateness of antibiotics, as well as timeliness of therapy. Local audit is an essential and effective means to improve practice. Multicentre consolidation of data through agreed minimum sepsis data sets would provide baseline quality data, required for the design and evaluation of interventions. [ABSTRACT FROM AUTHOR]

Abstract: Sepsis is characterised by organ dysfunction resulting from infection, with no reliable single objective test and current diagnosis based on clinical features and results of investigations. In the ED, investigations may be conducted to diagnose infection as the cause of the presenting illness, identify the source, distinguish sepsis from uncomplicated infection (i.e. without organ dysfunction) and/ or risk stratification. Appropriate sample collection for microbiological testing remains key for subsequent confirmation of diagnosis and rationalisation of antimicrobials. Routine laboratory investigations such as creatinine, bilirubin, platelet count and lactate are now critical elements in the diagnosis of sepsis and septic shock. With no biomarker sufficiently validated to rule out bacterial infection in the ED, there remains substantial interest in biomarkers representing various pathogenic pathways. New technologies for screening multiple genes and proteins are identifying unique network ‘signatures’ of clinical interest. Other future directions include rapid detection of bacterial DNA in blood, genes for antibiotic resistance and EMR‐based computational biomarkers that collate multiple information sources. Reliable, cost‐effective tests, validated in the ED to promptly and accurately identify sepsis, and to guide initial antibiotic choices, are important goals of current research efforts. [ABSTRACT FROM AUTHOR]

Right ventricular failure is a common complication associated with rotary left ventricular assist device (LVAD) support. Currently, there is no clinically approved long-term rotary right ventricular assist device (RVAD). Instead, clinicians have implanted a second rotary LVAD as RVAD in biventricular support. To prevent pulmonary hypertension, the RVAD must be operated by either reducing pump speed or banding the outflow graft. These modes differ in hydraulic performance, which may affect the pulmonary valve opening (PVO) and subsequently cause fusion, valvular insufficiency, and thrombus formation. This study aimed to compare PVO with the RVAD operated at reduced speed or with a banded outflow graft. Baseline conditions of systemic normal, hypo, and hypertension with severe biventricular failure were simulated in a mock circulation loop. Biventricular support was provided with two rotary VentrAssist LVADs with cardiac output restored to 5 L/min in banded outflow and reduced speed conditions, and systemic and pulmonary vascular resistances (PVR) were manipulated to determine the range of conditions that allowed PVO without causing left ventricular suction. Finally, RVAD sine wave speed modulation (±550 rpm) strategies (co- and counter-pulsation) were implemented to observe the effect on PVO. For each condition, outflow banding had higher PVR (97 ± 20 dyne/s/cm5 higher) for when the pulmonary valve closed compared to reduced speed. In addition, counter-pulsation demonstrated greater PVO than co-pulsation and constant speed. For the purpose of reducing the risks of pulmonary valve insufficiency, fusion, and thrombotic event, this study recommends a RVAD with a steeper H-Q gradient by banding and further exploration of RVAD speed modulation. [ABSTRACT FROM AUTHOR]

Rotary blood pumps (RBPs) are used for mechanical circulatory support in heart failure patients but exhibit a reduced response to preload changes, which can lead to ventricular suction events. A passive control system, in the form of a compliant inflow cannula (IC), has been developed to mitigate suction, although this device may cause significant hemolysis. This study compared the incidence of mechanically induced hemolysis of two compliant IC designs (strutted and nonstrutted) with a rigid IC (control) in a blood circulation loop over 90 min. The nonstrutted compliant IC introduced high frequency and high amplitude oscillations in RBP inlet pressure and RBP IC resistance. These oscillations were correlated with a significant increase in plasma-free hemoglobin (pfHb) and hemolysis: pfHb increased to 2.005 ± 0.665 g/L, while normalized index of hemolysis (NIH) and modified index of hemolysis (MIH) increased to 0.04945 ± 0.01276 g/100 L and 4.0505 ± 0.6589 after 90 min ( P < 0.05). In contrast, the strutted compliant IC performed similar to the clinically utilized rigid IC and did not increase pfHb (0.300 ± 0.090 and 0.320 ± 0.171 g/L, respectively) and rate of hemolysis (NIH 0.00435 ± 0.00155 and 0.00543 ± 0.00371 g/100 L; MIH 0.3896 ± 0.1749 and 0.4261 ± 0.2792, respectively) within the RBP circuit. These data indicated that strutted, compliant ICs meet the hemocompatibility of clinically used rigid ICs while also offering a potential solution to prevent ventricular suction events. [ABSTRACT FROM AUTHOR]

Preventing ventricular suction and venous congestion through balancing flow rates and circulatory volumes with dual rotary ventricular assist devices ( VADs) configured for biventricular support is clinically challenging due to their low preload and high afterload sensitivities relative to the natural heart. This study presents the in vivo evaluation of several physiological control systems, which aim to prevent ventricular suction and venous congestion. The control systems included a sensor-based, master/slave ( MS) controller that altered left and right VAD speed based on pressure and flow; a sensor-less compliant inflow cannula ( IC), which altered inlet resistance and, therefore, pump flow based on preload; a sensor-less compliant outflow cannula ( OC) on the right VAD, which altered outlet resistance and thus pump flow based on afterload; and a combined controller, which incorporated the MS controller, compliant IC, and compliant OC. Each control system was evaluated in vivo under step increases in systemic ( SVR ∼1400-2400 dyne/s/cm5) and pulmonary ( PVR ∼200-1000 dyne/s/cm5) vascular resistances in four sheep supported by dual rotary VADs in a biventricular assist configuration. Constant speed support was also evaluated for comparison and resulted in suction events during all resistance increases and pulmonary congestion during SVR increases. The MS controller reduced suction events and prevented congestion through an initial sharp reduction in pump flow followed by a gradual return to baseline (5.0 L/min). The compliant IC prevented suction events; however, reduced pump flows and pulmonary congestion were noted during the SVR increase. The compliant OC maintained pump flow close to baseline (5.0 L/min) and prevented suction and congestion during PVR increases. The combined controller responded similarly to the MS controller to prevent suction and congestion events in all cases while providing a backup system in the event of single controller failure. [ABSTRACT FROM AUTHOR]

Background Transthoracic echocardiography ( TTE) during extra corporeal membrane oxygenation ( ECMO) is important but can be technically challenging. Contrast-specific TTE can improve imaging in suboptimal studies. These contrast microspheres are hydrodynamically labile structures. This study assessed the feasibility of contrast echocardiography ( CE) during venovenous ( VV) ECMO in a validated ovine model. Method Twenty-four sheep were commenced on VV ECMO. Parasternal long-axis (Plax) and short-axis (Psax) views were obtained pre- and postcontrast while on VV ECMO. Endocardial definition scores ( EDS) per segment were graded: 1 = good, 2 = suboptimal 3 = not seen. Endocardial border definition score index ( EBDSI) was calculated for each view. Endocardial length ( EL) in the Plax view for the left ventricle ( LV) and right ventricle ( RV) was measured. Results Summation EDS data for the LV and RV for unenhanced TTE ( UE) versus CE TTE imaging: EDS 1 = 289 versus 346, EDS 2 = 38 versus 10, EDS 3 = 33 versus 4, respectively. Wilcoxon matched-pairs rank-sign tests showed a significant ranking difference (improvement) pre- and postcontrast for the LV (P < 0.0001), RV (P < 0.0001) and combined ventricular data (P < 0.0001). EBDSI for CE TTE was significantly lower than UE TTE for the LV (1.05 ± 0.17 vs. 1.22 ± 0.38, P = 0.0004) and RV (1.06 ± 0.22 vs. 1.42 ± 0.47, P = 0.0.0006) respectively. Visualized EL was significantly longer in CE versus UE for both the LV (58.6 ± 11.0 mm vs. 47.4 ± 11.7 mm, P < 0.0001) and the RV (52.3 ± 8.6 mm vs. 36.0 ± 13.1 mm, P < 0.0001), respectively. Conclusions Despite exposure to destructive hydrodynamic forces, CE is a feasible technique in an ovine ECMO model. CE results in significantly improved EDS and increased EL. [ABSTRACT FROM AUTHOR]

Biventricular support with dual rotary ventricular assist devices (VADs) has been implemented clinically with restriction of the right VAD (RVAD) outflow cannula to artificially increase afterload and, therefore, operate within recommended design speed ranges. However, the low preload and high afterload sensitivity of these devices increase the susceptibility of suction events. Active control systems are prone to sensor drift or inaccurate inferred (sensor-less) data, therefore an alternative solution may be of benefit. This study presents the in vitro evaluation of a compliant outflow cannula designed to passively decrease the afterload sensitivity of rotary RVADs and minimize left-sided suction events. A one-way fluid-structure interaction model was initially used to produce a design with suitable flow dynamics and radial deformation. The resultant geometry was cast with different initial cross-sectional restrictions and concentrations of a softening diluent before evaluation in a mock circulation loop. Pulmonary vascular resistance (PVR) was increased from 50 dyne s/cm5 until left-sided suction events occurred with each compliant cannula and a rigid, 4.5 mm diameter outflow cannula for comparison. Early suction events (PVR ∼ 300 dyne s/cm5) were observed with the rigid outflow cannula. Addition of the compliant section with an initial 3 mm diameter restriction and 10% diluent expanded the outflow restriction as PVR increased, thus increasing RVAD flow rate and preventing left-sided suction events at PVR levels beyond 1000 dyne s/cm5. Therefore, the compliant, restricted outflow cannula provided a passive control system to assist in the prevention of suction events with rotary biventricular support while maintaining pump speeds within normal ranges of operation. [ABSTRACT FROM AUTHOR]

Dual rotary left ventricular assist devices ( LVADs) have been used clinically to support patients with biventricular failure. However, due to the lower vascular resistance in the pulmonary circulation compared with its systemic counterpart, excessively high pulmonary flow rates are expected if the right ventricular assist device ( RVAD) is operated at its design LVAD speed. Three possible approaches are available to match the LVAD to the pulmonary circulation: operating the RVAD at a lower speed than the LVAD (mode 1), operating both pumps at their design speeds (mode 2) while relying on the cardiovascular system to adapt, and operating both pumps at their design speeds while restricting the diameter of the RVAD outflow graft (mode 3). In this study, each mode was characterized using in vitro and in vivo models of biventricular heart failure supported with two Ventr Assist LVADs. The effect of each mode on arterial and atrial pressures and flow rates for low, medium, and high vascular resistances and three different contractility levels were evaluated. The amount of speed/diameter adjustment required to accommodate elevated pulmonary vascular resistance ( PVR) during support with mode 3 was then investigated. Mode 1 required relatively low systemic vascular resistance to achieve arterial pressures less than 100 mm Hg in vitro, resulting in flow rates greater than 6 L/min. Mode 2 resulted in left atrial pressures above 25 mm Hg, unless left heart contractility was near-normal. In vitro, mode 3 resulted in expected arterial pressures and flow rates with an RVAD outflow diameter of 6.5 mm. In contrast, all modes were achievable in vivo, primarily due to higher RVAD outflow graft resistance (more than 500 dyn·s/cm5), caused by longer cannula. Flow rates could be maintained during instances of elevated PVR by increasing the RVAD speed or expanding the outflow graft diameter using an externally applied variable graft occlusion device. In conclusion, suitable hemodynamics could be produced by either restricting or not restricting the right outflow graft diameter; however, the latter required an operation of the RVAD at lower than design speed. Adjustments in outflow restriction and/or RVAD speed are recommended to accommodate varying PVR. [ABSTRACT FROM AUTHOR]

Background Acid suppression medications are routinely used in general intensive care unit patients for prevention of stress-related gastric mucosal bleeding. Their use has been extrapolated to include elective postoperative cardiac surgical patients. The evidence for their use in this group of patients remains inconclusive (Shin and Abah, Interact Cardiovasc Thorac Surg, 2012; 14: 622-8). Aim To audit the use of acid suppression therapy in postoperative cardiac surgical patients as inpatients and after discharge, and ascertain whether these patients experienced postoperative gastrointestinal bleeding. Method A retrospective chart review was undertaken, focusing on cases of cardiac surgical intensive care patients to investigate the use of stress ulcer prophylaxis and the occurrence of post-surgical gastrointestinal bleeding. The continuation of therapy after discharge was also audited. Results The cases of 78 patients were included in the audit: all received stress ulcer prophylaxis, and no patients experienced gastrointestinal bleeding postoperatively. In all, 27% of these patients were dispensed acid suppression therapy without a valid indication at the time of discharge. Conclusions It cannot be conclusively determined if the absence of postoperative gastrointestinal bleeding was due to the administration of prophylaxis. An alternative explanation is that stress ulcers were not likely to occur in this cohort of patients. Despite not having any indication for continuation of acid suppression, 20 patients were discharged with these medications. [ABSTRACT FROM AUTHOR]

Aims Perfluorocarbon administration increases cerebral blood flow. This can be mitigated by preventing a rise in carbon dioxide by adjusting pressure-controlled ventilation. Volume-controlled ventilation should prevent increases in arterial carbon dioxide and cerebral blood flow. This study aims to determine if cerebral blood flow is increased during administration of 10 mL/kg of perfluorocarbon while using volume-controlled ventilation. Methods Two New Zealand white rabbits, ventilated with volume-control, were each allocated to six dosing events where each dosing event was randomly allocated to one of two dosing strategies: a control group - given a sham dose of air (10 mL/kg) over 20 min; or a partial liquid ventilation group - given 10 mL/kg FC-77 slowly over 20 min. Data were recorded for 1 min before and 30 min after the start of each dosing event. No adjustment of ventilation (except fraction of inspired oxygen) was allowed during each dosing event. Results There were no significant changes over time and no differences between groups for carotid blood flow ( P = 0.48 at the end of the dose). There were slight increases in cortical cerebral blood flow in both groups; there was no statistically significant difference between groups ( P = 0.56 at end dose and P = 0.49 at time of maximum difference). There was no difference between groups for the variability in carotid blood flow or cortical cerebral blood flow. Conclusions Cerebral blood flow was not significantly increased during administration of a dose of 10 mL/kg of perfluorocarbon during commencement of partial liquid ventilation when using volume-controlled ventilation. [ABSTRACT FROM AUTHOR]

Aortic insufficiency ( AI) is usually repaired prior to rotary blood pump ( RBP) implantation but can develop during support due, in part, to the sustained RBP-induced high pressure gradient across the aortic valve. Repair of the aortic valve before or during RBP support predisposes these critically ill patients to even higher risks. This study used an in vitro mock circulation loop to identify the severity of AI and/or left heart failure ( LHF) that might benefit from valve repair while investigating RBP operating strategies to reduce the hemodynamic influence of AI. Reproduction of AI with RBP-supported LHF reduced device efficiency, particularly in the more severe cases of AI and LHF. The requirement for repair or closure of the aortic valve was demonstrated in all conditions other than those with only mild AI. When a sinusoidal RBP speed pulse was induced, small changes in systemic flow rate and regurgitant volume were observed with all degrees of AI. Variation of the pulse phase delay only resulted in minor changes to systemic flow rate, with a maximum difference of 0.17 L/min. Although the clinical implications of these small changes may be insignificant, changes in systemic flow rate and transvalvular pressure were shown when the sinusoidal RBP speed pulse was applied with no AI. In these cases, transvalvular pressure was reduced by up to 8% through sinusoidal copulsation of the RBP, which may prevent or delay the onset of AI. This in vitro study suggests that surgical intervention is required with moderate or worse AI and that RBP operating strategies should be further explored to delay the onset and reduce the harmful effects of AI. [ABSTRACT FROM AUTHOR]

This multicenter study examines in detail the spontaneous increase in pump flow at fixed speed that occurs in exercise. Eight patients implanted with the VentrAssist rotary blood pump were subjected to maximal and submaximal cycle ergometry studies, the latter being completed with patients supine and monitored with right heart catheter and echocardiography. Maximal exercise studies conducted in each patient at three different pump speeds on separate days established initially the magnitude and consistency of increases in pump flow that correlated well with changes in heart rate. However, there was considerable variation, coefficients of variation for mean heart rate and pump flow being 47.9 and 49.3%, respectively. Secondly, these studies indicated that increasing pump flows caused significant improvements in maximal exercise capacity. An increase of 2.1 L/min (35%) in maximum blood flow caused 12 W (16%) further increase in achievable work, 1.26 (9.3%) mL/kg/min in maximal oxygen uptake, and 2.3 (23%) mL/kg/min in anaerobic threshold. Mean increases in lactate were 0.85 m m (24%), but mean B-type natiuretic peptide fell by 126 m m, (−78%). From submaximal supine exercise studies, multiple linear regression of pump flow on factors thought to underlie the spontaneous increase in pump flow indicated that it was associated with increases in heart rate ( P = 0.039), pressure gradient across the left ventricle ( P = 0.032), and right atrial pressure ( P = 0.003). These changes have implications for the recently reported Starling-like controller for pump flow based on pump pulsatility values, which emulates the Starling curve relating pump output to left ventricular preload. Unmodified, the controller would not permit the full benefits of this effect to be afforded to patients implanted with rotary blood pumps. A modification to the pump control algorithm is proposed to eliminate this problem [ABSTRACT FROM AUTHOR]

BACKGROUND: Recombinant activated factor VIIa (rFVIIa) has been increasingly used to stop massive bleeding after cardiothoracic surgical procedures. However, the risk : benefit profile of such a potent hemostatic agent remains unclear in the postsurgical patient, and the cost benefit is even less clear. In patients after lung transplantation, volume of blood transfused is of major concern, and all attempts are made to minimize large blood transfusions in this cohort. We report our experience with rFVIIa in patients with refractory bleeding after lung transplant surgery. STUDY DESIGN AND METHODS: All lung transplant patients who underwent single- or double-lung transplantation who received rFVIIa in the 5-year period, from January 2005 to June 2011, were included. A total of 15 patients were identified from a total of 95 lung transplant cases operated during this study period. Patient demographics, intra- and postoperative records were reviewed to assess the efficacy and safety of rFVIIa treatment. RESULTS: Patients with major bleeding treated with rFVIIa showed improved hemostasis with rapid normalization of coagulation variables. rFVIIa treatment was not associated with an increase in mechanical ventilation time, length of intensive care unit stay, or hospital stay compared to other lung transplant patients. In addition, the use of rFVIIa was associated with reduction in transfusion requirements of red blood cells, fresh-frozen plasma, and platelets (all p < 0.001). No definite thromboembolic-related event was recorded in our cohort. CONCLUSIONS: These data demonstrate that rFVIIa was associated with reduced blood loss, improvement of coagulation variables, and decreased need for transfusions. This reduction in losses led to a reduced requirement for blood transfusion, which may translate to a decrease in transfusion-related complications. Further investigation is needed to determine rFVIIa's safety and its efficacy in improving postoperative morbidity and mortality specifically in the field of post-lung transplantation surgery. [ABSTRACT FROM AUTHOR]

Long-term rotary left ventricular assist devices (LVADs) are increasingly employed to bridge patients with end-stage heart failure to transplant or as a destination therapy. Significant recent device development has increased patient support times, shifting further development focus toward physiologically sensitive control of the pump operation. Sensorless control of these devices would benefit from increased observability of the ventricular volume/preload to the pump, in order to regulate flow based on preload, imitating the native Frank-Starling flow control. Monitoring the transmitted flow pulse through the pump has been used as a surrogate for preload, although means of maximizing its transmission are not clear. However, it is known that a flat hydraulic performance curve of the rotary pump induces high changes in flow for a given change in pressure head. The aim of this study was to determine geometric pump parameters responsible for increasing this flow pulse transmission and to demonstrate this increase in vitro. The sensitivity of the performance gradient to blade angles, blade heights, blade clearance, and channel areas were studied. Resulting pressure head, flow, and hydraulic efficiency were analyzed with respect to textbook designed procedures. Then pumps with comparably 'flat' and 'steep' performance curves were used to simulate LVAD support in vitro over a range of pump flow rates to observe the transmitted flow pulsatility. It was found that an outlet blade angle of 90°, inlet blade angle between 25 and 45°, and large throat area generated a 'flatter' performance curve. The transmitted flow pulsatility through a pump with a flat performance curve was 68% higher than that of a steep performance curve at a flow rate of 5 L/min. Substantial gains in the observability of LVAD preload/resident blood volume in the ventricle exist through the careful selection of specific pump geometries. [ABSTRACT FROM AUTHOR]

A clinically intuitive physiologic controller is desired to improve the interaction between implantable rotary blood pumps and the cardiovascular system. This controller should restore the Starling mechanism of the heart, thus preventing overpumping and underpumping scenarios plaguing their implementation. A linear Starling-like controller for pump flow which emulated the response of the natural left ventricle (LV) to changes in preload was then derived using pump flow pulsatility as the feedback variable. The controller could also adapt the control line gradient to accommodate longer-term changes in cardiovascular parameters, most importantly LV contractility which caused flow pulsatility to move outside predefined limits. To justify the choice of flow pulsatility, four different pulsatility measures (pump flow, speed, current, and pump head pressure) were investigated as possible surrogates for LV stroke work. Simulations using a validated numerical model were used to examine the relationships between LV stroke work and these measures. All were approximately linear ( r2 (mean ± SD) = 0.989 ± 0.013, n = 30) between the limits of ventricular suction and opening of the aortic valve. After aortic valve opening, the four measures differed greatly in sensitivity to further increases in LV stroke work. Pump flow pulsatility showed more correspondence with changes in LV stroke work before and after opening of the aortic valve and was least affected by changes in the LV and right ventricular (RV) contractility, blood volume, peripheral vascular resistance, and heart rate. The system (flow pulsatility) response to primary changes in pump flow was then demonstrated to be appropriate for stable control of the circulation. As medical practitioners have an instinctive understanding of the Starling curve, which is central to the synchronization of LV and RV outputs, the intuitiveness of the proposed Starling-like controller will promote acceptance and enable rational integration into patterns of hemodynamic management. [ABSTRACT FROM AUTHOR]

The use of rotary left ventricular assist devices (LVADs) has extended to destination and recovery therapy for end-stage heart failure. Incidence of right ventricular failure while on LVAD support requires a second device be implanted to support the failing right ventricle. Without a commercially available implantable rotary right ventricular assist device, rotary LVADs are cannulated into the right heart and operation modified to provide suitable support for the pulmonary system. While this approach can alleviate the demand for transplant through long-term biventricular support, it uncovers a new challenge with respect to controller strategies for these dual device support systems. This study compares the preload sensitivity of rotary, dual device biventricular assistance controllers in light of their ability to adjust the flow rate according to physiological demand. A Frank-Starling-like flow controller which requires both inlet pressure and flow sensors is compared to pressure controllers which maintain atrial or inlet cannula pressures through the use of a single pressure sensor. It was found that cannula selection and the location of a pressure controller's single pressure sensor can be tailored to adjust the preload sensitivity. When located within the atria, this sensitivity is effectively infinite. Moving the sensor to the base of a 450-mm cannula, however, decreased the sensitivity to 0.22 (L/min)/mm Hg. This indicates the potential for simple and reliable VAD controllers with increased preload sensitivity without the need for complex controllers requiring an array of hemodynamic sensors. [ABSTRACT FROM AUTHOR]

We propose a deadbeat controller for the control of pulsatile pump flow ( Qp) in an implantable rotary blood pump (IRBP). Noninvasive measurements of pump speed and current are used as inputs to a dynamical model of Qp estimation, previously developed and verified in our laboratory. The controller was tested using a lumped parameter model of the cardiovascular system (CVS), in combination with the stable dynamical models of Qp and differential pressure (head) estimation for the IRBP. The control algorithm was tested with both constant and sinusoidal reference Qp as input to the CVS model. Results showed that the controller was able to track the reference input with minimal error in the presence of model uncertainty. Furthermore, Qp was shown to settle to the desired reference value within a finite number of sampling periods. Our results also indicated that counterpulsation yields the minimum left ventricular stroke work, left ventricular end diastolic volume, and aortic pulse pressure, without significantly affecting mean cardiac output and aortic pressure. [ABSTRACT FROM AUTHOR]

Limited preload sensitivity of rotary left ventricular assist devices (LVADs) renders patients susceptible to harmful atrial or ventricular suction events. Active control systems may be used to rectify this problem; however, they usually depend on unreliable sensors or potentially inaccurate inferred data from, for example, motor current. This study aimed to characterize the performance of a collapsible inflow cannula reservoir as a passive control system to eliminate suction events in extracorporeal, rotary LVAD support. The reservoir was evaluated in a mock circulation loop against a rigid cannula under conditions of reduced preload and increased LVAD speed in both atrial and ventricular cannulation scenarios. Both cases demonstrated the ease with which chamber suction events can occur with a rigid cannula and confirm that the addition of the reservoir maintained positive chamber volumes with reduced preload and high LVAD speeds. Reservoir performance was dependent on height with respect to the cannulated chamber, with lower placement required in atrial cannulation due to reduced filling pressures. This study concluded that a collapsible inflow cannula is capable of minimizing suction events in extracorporeal, rotary LVAD support. [ABSTRACT FROM AUTHOR]

In vitro cardiovascular device performance evaluation in a mock circulation loop (MCL) is a necessary step prior to in vivo testing. A MCL that accurately represents the physiology of the cardiovascular system accelerates the assessment of the device's ability to treat pathological conditions. To serve this purpose, a compact MCL measuring 600 × 600 × 600 mm (L × W × H) was constructed in conjunction with a computer mathematical simulation. This approach allowed the effective selection of physical loop characteristics, such as pneumatic drive parameters, to create pressure and flow, and pipe dimensions to replicate the resistance, compliance, and fluid inertia of the native cardiovascular system. The resulting five-element MCL reproduced the physiological hemodynamics of a healthy and failing heart by altering ventricle contractility, vascular resistance/compliance, heart rate, and vascular volume. The effects of interpatient anatomical variability, such as septal defects and valvular disease, were also assessed. Cardiovascular hemodynamic pressures (arterial, venous, atrial, ventricular), flows (systemic, bronchial, pulmonary), and volumes (ventricular, stroke) were analyzed in real time. The objective of this study is to describe the developmental stages of the compact MCL and demonstrate its value as a research tool for the accelerated development of cardiovascular devices. [ABSTRACT FROM AUTHOR]

The article presents a study which assessed evidence in support of therapies to prevent and treat cardiogenic shock (CS) after acute myocardial infarction that can be initiated in hospitals without invasive cardiac facilities. It states that prevention of CS is achieved in regional centres with early fibrinolysis before hospital arrival. Thrombolysis, early transfer for coronary revascularisation, and intra-aortic balloon pump insertion should reportedly be considered for patients of all ages unless contraindicated.

Ventricular assist devices (VADs) are an important part of the management of patients with end stage heart disease either as a bridge to cardiac transplantation or as definitive therapy in patients who for one reason or another are not eligible for transplantation. When a patient with a VAD undergoes heart transplantation, the driveline is removed from the patient and thrown in the contaminated waste. One patient in one institution was transplanted and a common sense transplant co-ordinator saved the explanted driveline. [Extracted from the article]

Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response to burn injury has not been ascertained. We present a fetal model of thermal injury and subsequent analysis of fetal and lamb response to burn injury. A reproducible deep dermal burn injury was created in the fetus by application of water at 66°C for 7 seconds, and at 82°C for 10 seconds to the lamb. Macroscopically, the area of fetal scald was undetectable from day 7 post injury, while all lamb scalds were readily identified and eventually healed with scarring. Using a five-point histopathology scoring system for alteration in tissue morphology, differences were detected between control and scalded skin at all stages in lamb postburn, but no difference was detected in the fetal model after day 7. There were also large differences in content ofα-smooth muscle actin and transforming growth factor-β1 between control and scalded lamb and these differences were statistically significant at day 14 (P < 0.01). This novel model of fetal and lamb response to deep dermal injury indicates that the fetus heals a deep burn injury in a scarless fashion. Further elucidation of this specific fetal process of burn injury repair may lead to improved outcome for patients with burn injury. [ABSTRACT FROM AUTHOR]