Silicon Membranes for Extracorporeal Membrane Oxygenation (ECMO)

In cases of severe lung or heart failure, extracorporeal membrane oxygenation (ECMO) is a life-saving therapy in which a patient’s blood is passed into a circuit outside of their body to provide respiratory support. The circuit’s main component is the membrane oxygenator that drives oxygen into the blood from a sweep gas source and removes excess carbon dioxide from the blood. At present, clinical use of ECMO is limited by its high risk profile, owing to two intertwined risks: thrombosis from the large circuit, and bleeding from the anticoagulation needed to prevent thrombosis. Improvements to the gas exchange efficiency and hemocompatibility of the oxygenator could enable the development of a longer-term supportive ECMO therapy, intended as a bridge-to-transplant or destination therapy for chronic lung failure. Here we describe a novel blood oxygenator concept based on parallel plate silicon membranes developed for high precision geometry, mechanical rigidity, and high efficiency membrane transport. Using these membranes, we create blood oxygenator prototypes consisting of arrays of silicon membranes, and endeavor to improve the efficiency and hemocompatibility of this concept.First, multiple types of silicon membranes were evaluated systematically for mechanical rigidity and oxygen exchange efficiency, indicators of suitability for a future oxygenator. The combination of a silicon micropore membrane (SµM) and a 5 µm-thick polydimethylsiloxane (PDMS) layer maximized both qualities, withstanding over 260 cmHg of applied pressure and producing 0.03 mL/min of O2 flux. These membranes were then assembled into prototype flow cells, and tested for in vitro and in vivo oxygenation, successfully yielding an oxygen permeability of 1.92 ± 1.04 ml O2 STP/min/m2/cmHg. From this benchmark, we then attempted to optimize the surface hemocompatibility of the Si-PDMS composite through application of multiple polyethylene glycol (PEG)-based coatings. Although successful application of PEG to the surfaces was demonstrated, none of the coatings appeared to reduce protein adhesion to the SµM -PDMS membranes. Finally, we inserted turbulence-inducing spacer meshes into the channels of the SµM-PDMS prototypes to disrupt the transport boundary layer adjacent to the membranes, with the goal of substantially improving oxygenation. Though a threefold increase in oxygen flux was observed in vitro with the spacer meshes, the disruptive turbulence resulted in thrombosis and channel occlusion within the channels despite heavy anticoagulation of the blood. In summary, the work in this dissertation demonstrates the successful construction and testing of SµM-PDMS oxygenator prototypes, laying the foundation for future work to optimize this concept and create a large-scale blood oxygenator that can expand the clinical use of this life-saving therapy

VAD in failing Fontan: simulation of ventricular, cavo-pulmonary and biventricular assistance in systolic/diastolic ventricular dysfunction and in pulmonary vascular resistance increase.

Aim: Due to the lack of donors, VADs could be an alternative to heart transplantation for Failing Fontan patients (PTs). Considering the complex physiopathology and the type of VAD connection, a numerical model (NM) could be useful to support clinical decisions. The aim of this work is to test a NM simulating the VADs effects on failing Fontan for systolic dysfunction (SD), diastolic dysfunction (DD) and pulmonary vascular resistance increase (PRI). Methods: Data of 10 Fontan PTs were used to simulate the PTs baseline using a dedicated NM. Then, for each PTs a SD, a DD and a PRI were simulated. Finally, for each PT and for each pathology, the VADs implantation was simulated. Results: NM can well reproduce PTs baseline. In the case of SD, LVAD increases the cardiac output (CO) (35%) and the arterial systemic pressure (ASP) (25%). With cavo-pulmonary assistance (RVAD) a decrease of inferior vena cava pressure (IVCP) (39%) was observed with 34% increase of CO. With the BIVAD an increase of ASP (29%) and CO (37%) was observed. In the case of DD, the LVAD increases CO (42%), the RVAD decreases the IVCP. In the case of PRI, the highest CO (50%) and ASP (28%) increase is obtained with an RVAD together with the highest decrease of IVCP (53%). Conclusions: The use of NM could be helpful in this innovative field to evaluate the VADs implantation effects on specific PT to support PT and VAD selection

An investigation into the effects of commencing haemodialysis in the critically ill

<b>Introduction:</b> We have aimed to describe haemodynamic changes when haemodialysis is instituted in the critically ill. 3 hypotheses are tested: 1)The initial session is associated with cardiovascular instability, 2)The initial session is associated with more cardiovascular instability compared to subsequent sessions, and 3)Looking at unstable sessions alone, there will be a greater proportion of potentially harmful changes in the initial sessions compared to subsequent ones. <b>Methods:</b> Data was collected for 209 patients, identifying 1605 dialysis sessions. Analysis was performed on hourly records, classifying sessions as stable/unstable by a cutoff of >+/-20% change in baseline physiology (HR/MAP). Data from 3 hours prior, and 4 hours after dialysis was included, and average and minimum values derived. 3 time comparisons were made (pre-HD:during, during HD:post, pre-HD:post). Initial sessions were analysed separately from subsequent sessions to derive 2 groups. If a session was identified as being unstable, then the nature of instability was examined by recording whether changes crossed defined physiological ranges. The changes seen in unstable sessions could be described as to their effects: being harmful/potentially harmful, or beneficial/potentially beneficial. <b>Results:</b> Discarding incomplete data, 181 initial and 1382 subsequent sessions were analysed. A session was deemed to be stable if there was no significant change (>+/-20%) in the time-averaged or minimum MAP/HR across time comparisons. By this definition 85/181 initial sessions were unstable (47%, 95% CI SEM 39.8-54.2). Therefore Hypothesis 1 is accepted. This compares to 44% of subsequent sessions (95% CI 41.1-46.3). Comparing these proportions and their respective CI gives a 95% CI for the standard error of the difference of -4% to 10%. Therefore Hypothesis 2 is rejected. In initial sessions there were 92/1020 harmful changes. This gives a proportion of 9.0% (95% CI SEM 7.4-10.9). In the subsequent sessions there were 712/7248 harmful changes. This gives a proportion of 9.8% (95% CI SEM 9.1-10.5). Comparing the two unpaired proportions gives a difference of -0.08% with a 95% CI of the SE of the difference of -2.5 to +1.2. Hypothesis 3 is rejected. Fisher’s exact test gives a result of p=0.68, reinforcing the lack of significant variance. <b>Conclusions:</b> Our results reject the claims that using haemodialysis is an inherently unstable choice of therapy. Although proportionally more of the initial sessions are classed as unstable, the majority of MAP and HR changes are beneficial in nature

From Benchtop to Beside: Patient-specific Outcomes Explained by Invitro Experiment

Study: Recent analyses show that females have higher early postoperative (PO) mortality and right ventricular failure (RVF) than males after left ventricular assist device (LVAD) implantation; and that this association is partially mediated by smaller LV size in females. Benchtop experiments allow us to investigate patient-specific (PS) characteristics in a reproducible way given the fact that the PS anatomy and physiology is mimicked accurately. With multiple heart models of varying LV size, we can directly study the individual effects of titrating the LVAD speed and the resulting bi-ventricular volumes, shedding light on the interplay between LV and RV as well as resulting inter-ventricular septum (IVS) positions, which may cause the different outcomes pertaining to sex. Methods: In vitro, we studied the impact of the heart size to IVS position using two smaller and two larger sized PS silicone heart phantoms derived from clinical CT images (Fig. 1A). With ultrasound crystals that were integrated on a placeholder inflow cannula, the IVS position was measured during LV and RV volume changes (dV) mimicking varying ventricular loading states (Fig. 1B). Figure 1 A Two small (blue) and two large PS heart phantoms (orange) on B benchtop. C Median septum curvature results. LVEDD/LVV/RVV: LV enddiastolic diameter/LV and RV volume. Results: Going from small to large dV, at zero curvature, the septum starts to shift towards the left; for smaller hearts at dV = -40 mL and for larger hearts at dV = -50 mL (Fig. 1C). This result indicates that smaller hearts are more prone to an IVS shift to the left than larger hearts. We conclude that smaller LV size may therefore mediate increased early PO LVAD mortality and RVF observed in females compared to males. Novel 3D silicone printing technology enables us to study accurate, PS heart models across a heterogeneous patient population. PS relationships can be studied simultaneously to clinical assessments and support the decision-making prior to LVAD implantation