Shaun D. Gregory

Optimal Management of the Critically Ill: Anaesthesia, Monitoring, Data Capture, and Point-of-Care Technological Practices in Ovine Models of Critical Care

Animal models of critical illness are vital in biomedical research. They provide possibilities for the investigation of pathophysiological processes that may not otherwise be possible in humans. In order to be clinically applicable, the model should simulate the critical care situation realistically, including anaesthesia, monitoring, sampling, utilising appropriate personnel skill mix, and therapeutic interventions. There are limited data documenting the constitution of ideal technologically advanced large animal critical care practices and all the processes of the animal model. In this paper, we describe the procedure of animal preparation, anaesthesia induction and maintenance, physiologic monitoring, data capture, point-of-care technology, and animal aftercare that has been successfully used to study several novel ovine models of critical illness. The relevant investigations are on respiratory failure due to smoke inhalation, transfusion related acute lung injury, endotoxin-induced proteogenomic alterations, haemorrhagic shock, septic shock, brain death, cerebral microcirculation, and artificial heart studies. We have demonstrated the functionality of monitoring practices during anaesthesia required to provide a platform for undertaking systematic investigations in complex ovine models of critical illness.

Theoretical foundations of a Starling-like controller for rotary blood pumps

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 (r(2) (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.

Biventricular Assist Devices: A Technical Review

The optimal treatment option for end stage heart failure is transplantation; however, the shortage of donor organs necessitates alternative treatment strategies such as mechanical circulatory assistance. Ventricular assist devices (VADs) are employed to support these cases while awaiting cardiac recovery or transplantation, or in some cases as destination therapy. While left ventricular assist device (LVAD) therapy alone is effective in many instances, up to 50% of LVAD recipients demonstrate clinically significant postoperative right ventricular failure and potentially need a biventricular assist device (BiVAD). In these cases, the BiVAD can effectively support both sides of the failing heart. This article presents a technical review of BiVADs, both clinically applied and under development. The BiVADs which have been used clinically are predominantly first generation, pulsatile, and paracorporeal systems that are bulky and prone to device failure, thrombus formation, and infection. While they have saved many lives, they generally necessitate a large external pneumatic driver which inhibits normal movement and quality of life for many patients. In an attempt to alleviate these issues, several smaller, implantable second and third generation devices that use either immersed mechanical blood bearings or hydrodynamic/magnetic levitation systems to support a rotating impeller are under development or in the early stages of clinical use. Although these rotary devices may offer a longer term, completely implantable option for patients with biventricular failure, their control strategies need to be refined to compete with the inherent volume balancing ability of the first generation devices. The BiVAD systems potentially offer an improved quality of life to patients with total heart failure, and thus a viable alternative to heart transplantation is anticipated with continued development.

Flow Analysis of Ventricular Assist Device Inflow and Outflow Cannula Positioning Using a Naturally Shaped Ventricle and Aortic Branch

Tip geometry and placement of rotary blood pump inflow and outflow cannulae influence the dynamics of flow within the ventricle and aortic branch. Cannulation, therefore, directly influences the potential for thrombus formation and end-organ perfusion during ventricular assist device (VAD) support or cardiopulmonary bypass (CPB). The purpose of this study was to investigate the effect of various inflow/outflow cannula tip geometries and positions on ventricular and greater vessel flow patterns to evaluate ventricular washout and impact on cerebral perfusion. Transparent models of a dilated cardiomyopathic ventricle and an aortic branch were reconstructed from magnetic resonance imaging data to allow flow measurements using particle image velocimetry (PIV). The contractile function of the failing ventricle was reproduced pneumatically, and supported with a rotary pump. Flow patterns were visualized around VAD inflow cannulae, with various tip geometries placed in three positions in the ventricle. The outflow cannula was placed in the subclavian artery and at several positions in the aorta. Flow patterns were measured using PIV and used to validate an aortic flow computational fluid dynamic study. The PIV technique indicated that locating the inflow tip in the left ventricular outflow tract improved complete ventricular washout while the tip geometry had a smaller influence. However, side holes in the inflow cannula improved washout in all cases. The PIV results confirmed that the positioning and orientation of the outflow cannula in the aortic branch had a high impact on the flow pattern in the vessels, with a negative blood flow in the right carotid artery observed in some cases. Cannula placement within the ventricle had a high influence on chamber washout. The positioning of the outflow cannula directly influences the flow through the greater vessels, and may be responsible for the occasional reduction in cerebral perfusion seen in clinical CPB.

Simulation and Enhancement of a Cardiovascular Device Test Rig

Cardiovascular assist devices are tested in mock circulation loops (MCLs) prior to animal and clinical testing. These MCLs rely on characteristics such as pneumatic parameters to create pressure and flow, and pipe dimensions to replicate the resistance, compliance and fluid inertia of the natural cardiovascular system. A mathematical simulation was developed in SIMULINK to simulate an existing MCL. Model validation was achieved by applying the physical MCL characteristics to the simulation and comparing the resulting pressure traces. These characteristics were subsequently altered to improve and thus predict the performance of a more accurate physical system. The simulation was successful in simulating the physical MCL, and proved to be a useful tool in the development of improved cardiovascular device test rigs.

Atrial Versus Ventricular Cannulation for a Rotary Ventricular Assist Device

The ventricular assist device inflow cannulation site is the primary interface between the device and the patient. Connecting these cannulae to either atria or ventricles induces major changes in flow dynamics; however, there are little data available on precise quantification of these changes. The objective of this investigation was to quantify the difference in ventricular/vascular hemodynamics during a range of left heart failure conditions with either atrial (AC) or ventricular (VC) inflow cannulation in a mock circulation loop with a rotary left VAD. Ventricular ejection fraction (EF), stroke work, and pump flow rates were found to be consistently lower with AC compared with VC over all simulated heart failure conditions. Adequate ventricular ejection remained with AC under low levels of mechanical support; however, the reduced EF in cases of severe heart failure may increase the risk of thromboembolic events. AC is therefore more suitable for class III, bridge to recovery patients, while VC is appropriate for class IV, bridge to transplant/destination patients.

Replication of the Frank-Starling response in a mock circulation loop

Mock circulation loops (MCLs) are used to evaluate cardiovascular devices prior to in-vivo trials; however they lack the vital autoregulatory responses that occur in humans. This study aimed to develop and implement a left and right ventricular Frank-Starling response in a MCL. A proportional controller based on ventricular end diastolic volume was used to control the driving pressure of the MCLs pneumatically operated ventricles. Ventricular pressure-volume loops and end systolic pressure-volume relationships were produced for a variety of healthy and pathological conditions and compared with human data to validate the simulated Frank-Starling response. The non-linear Frank-Starling response produced in this study successfully altered left and right ventricular contractility with changing preload and was validated with previously reported data. This improvement to an already detailed MCL has resulted in a test rig capable of further refining cardiovascular devices and reducing the number of in-vivo trials.

Mechanical Circulatory Support in the New Era: An Overview

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2016. Other selected articles can be found online at http://www.biomedcentral.com/collections/annualupdate2016. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.

In Vitro and In Vivo Characterization of Three Different Modes of Pump Operation When Using a Left Ventricular Assist Device as a Right Ventricular Assist Device

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 VentrAssist 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/cm(5)), 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.

In Vitro Evaluation of a Compliant Inflow Cannula Reservoir to Reduce Suction Events With Extracorporeal Rotary Ventricular Assist Device Support

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.