Digital twin mathematical models suggest individualized hemorrhagic shock resuscitation strategies.

BACKGROUND: Optimizing resuscitation to reduce inflammation and organ dysfunction following human trauma-associated hemorrhagic shock is a major clinical hurdle. This is limited by the short duration of pre-clinical studies and the sparsity of early data in the clinical setting. METHODS: We sought to bridge this gap by linking preclinical data in a porcine model with clinical data from patients from the Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) study via a three-compartment ordinary differential equation model of inflammation and coagulation. RESULTS: The mathematical model accurately predicts physiologic, inflammatory, and laboratory measures in both the porcine model and patients, as well as the outcome and time of death in the PROMMTT cohort. Model simulation suggests that resuscitation with plasma and red blood cells outperformed resuscitation with crystalloid or plasma alone, and that earlier plasma resuscitation reduced injury severity and increased survival time. CONCLUSIONS: This workflow may serve as a translational bridge from pre-clinical to clinical studies in trauma-associated hemorrhagic shock and other complex disease settings.

Research to improve survival in patients with severe bleeding after major trauma presents many challenges. Here, we created a computer model to simulate the effects of severe bleeding. We refined this model using data from existing animal studies to ensure our simulations were accurate. We also used patient data to further refine the simulations to accurately predict which patients would live and which would not. We studied the effects of different treatment protocols on these simulated patients and show that treatment with plasma (the fluid portion of blood that helps form blood clots) and red blood cells jointly, gave better results than treatment with intravenous fluid or plasma alone. Early treatment with plasma reduced injury severity and increased survival time. This modelling approach may improve our ability to evaluate new treatments for trauma-associated bleeding and other acute conditions.

First 24-Hour-Long Intensive Care Unit Testing of a Clinical-Scale Microfluidic Oxygenator in Swine: A Safety and Feasibility Study.

Microfluidic membrane oxygenators are designed to mimic branching vasculature of the native lung during extracorporeal lung support. To date, scaling of such devices to achieve clinically relevant blood flow and lung support has been a limitation. We evaluated a novel multilayer microfluidic blood oxygenator (BLOx) capable of supporting 750-800 ml/min blood flow versus a standard hollow fiber membrane oxygenator (HFMO) in vivo during veno-venous extracorporeal life support for 24 hours in anesthetized, mechanically ventilated uninjured swine (n = 3/group). The objective was to assess feasibility, safety, and biocompatibility. Circuits remained patent and operated with stable pressures throughout 24 hours. No group differences in vital signs or evidence of end-organ damage occurred. No change in plasma free hemoglobin and von Willebrand factor multimer size distribution were observed. Platelet count decreased in BLOx at 6 hours (37% dec, P = 0.03), but not in HFMO; however, thrombin generation potential was elevated in HFMO (596 ± 81 nM·min) versus BLOx (323 ± 39 nM·min) at 24 hours ( P = 0.04). Other coagulation and inflammatory mediator results were unremarkable. BLOx required higher mechanical ventilator settings and showed lower gas transfer efficiency versus HFMO, but the stable device performance indicates that this technology is ready for further performance scaling and testing in lung injury models and during longer use conditions.

Intravenous Autologous Bone Marrow-derived Mesenchymal Stromal Cells Delay Acute Respiratory Distress Syndrome in Swine.

Rationale: Early post injury mitigation strategies in ARDS are in short supply. Treatments with allogeneic stromal cells are administered after ARDS develops, require specialized expertise and equipment, and to date have shown limited benefit. Objectives: Assess the efficacy of immediate post injury intravenous administration of autologous or allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) for the treatment of acute respiratory distress syndrome (ARDS) due to smoke inhalation and burns. Methods: Yorkshire swine (n = 32, 44.3 ± 0.5 kg) underwent intravenous anesthesia, placement of lines, severe smoke inhalation, and 40% total body surface area flame burns, followed by 72 hours of around-the-clock ICU care. Mechanical ventilation, fluids, pressors, bronchoscopic cast removal, daily lung computed tomography scans, and arterial blood assays were performed. After injury and 24 and 48 hours later, animals were randomized to receive autologous concentrated bone marrow aspirate (n = 10; 3 × 106 white blood cells and a mean of 56.6 × 106 platelets per dose), allogeneic MSCs (n = 10; 6.1 × 106 MSCs per dose) harvested from healthy donor swine, or no treatment in injured control animals (n = 12). Measurements and Main Results: The intravenous administration of MSCs after injury and at 24 and 48 hours delayed the onset of ARDS in swine treated with autologous MSCs (48 ± 10 h) versus control animals (14 ± 2 h) (P = 0.004), reduced ARDS severity at 24 (P < 0.001) and 48 (P = 0.003) hours, and demonstrated visibly diminished consolidation on computed tomography (not significant). Mortality at 72 hours was 1 in 10 (10%) in the autologous group, 5 in 10 (50%) in the allogeneic group, and 6 in 12 (50%) in injured control animals (not significant). Both autologous and allogeneic MSCs suppressed systemic concentrations of TNF-α (tumor necrosis factor-α). Conclusions: The intravenous administration of three doses of freshly processed autologous bone marrow-derived MSCs delays ARDS development and reduces its severity in swine. Bedside retrieval and administration of autologous MSCs in swine is feasible and may be a viable injury mitigation strategy for ARDS.

Quantitative Analysis of Clot Deposition on Extracorporeal Life Support Membrane Oxygenators Using Digital and Scanning Electron Microscopy Imaging Techniques.

Device-induced thrombosis remains a major complication of extracorporeal life support (ECLS). To more thoroughly understand how blood components interact with the artificial surfaces of ECLS circuit components, assessment of clot deposition on these surfaces following clinical use is urgently needed. Scanning electron microscopy (SEM), which produces high-resolution images at nanoscale level, allows visualization and characterization of thrombotic deposits on ECLS circuitry. However, methodologies to increase the quantifiability of SEM analysis of ECLS circuit components have yet to be applied clinically. To address these issues, we developed a protocol to quantify clot deposition on ECLS membrane oxygenator gas transfer fiber sheets through digital and SEM imaging techniques. In this study, ECLS membrane oxygenator fiber sheets were obtained, fixed, and imaged after use. Following a standardized process, the percentage of clot deposition on both digital images and SEM images was quantified using ImageJ through blind reviews. The interrater reliability of quantitative analysis among reviewers was evaluated. Although this protocol focused on the analysis of ECLS membrane oxygenators, it is also adaptable to other components of the ECLS circuits such as catheters and tubing. Key features • Quantitative analysis of clot deposition using digital and scanning electron microscopy (SEM) techniques • High-resolution images at nanoscale level • Extracorporeal life support (ECLS) devices • Membrane oxygenators • Blood-contacting surfaces Graphical overview.

A Clinical-Scale Microfluidic Respiratory Assist Device with 3D Branching Vascular Networks.

Recent global events such as COVID-19 pandemic amid rising rates of chronic lung diseases highlight the need for safer, simpler, and more available treatments for respiratory failure, with increasing interest in extracorporeal membrane oxygenation (ECMO). A key factor limiting use of this technology is the complexity of the blood circuit, resulting in clotting and bleeding and necessitating treatment in specialized care centers. Microfluidic oxygenators represent a promising potential solution, but have not reached the scale or performance required for comparison with conventional hollow fiber membrane oxygenators (HFMOs). Here the development and demonstration of the first microfluidic respiratory assist device at a clinical scale is reported, demonstrating efficient oxygen transfer at blood flow rates of 750 mL min⁻1 , the highest ever reported for a microfluidic device. The central innovation of this technology is a fully 3D branching network of blood channels mimicking key features of the physiological microcirculation by avoiding anomalous blood flows that lead to thrombus formation and blood damage in conventional oxygenators. Low, stable blood pressure drop, low hemolysis, and consistent oxygen transfer, in 24-hour pilot large animal experiments are demonstrated - a key step toward translation of this technology to the clinic for treatment of a range of lung diseases.

Heart transplantation from donation after circulatory death: Impact on waitlist time and transplant rate.

The effect of using donation after circulatory death (DCD) hearts on waitlist outcomes has not been substantiated. We retrospectively analyzed 184 heart transplant (HT) candidates at our institution from 2019 to 2021. Patients were stratified into 2 observation periods centered on September 12, 2020, when the adult DCD HT program officially began. The primary outcome was a comparison of transplant rate between period 1 (pre-DCD) and period 2 (post-DCD). Secondary outcomes included waitlist time-to-transplant, waitlist mortality rate, independent predictors of incidence of HT, and posttransplant outcomes. A total of 165 HTs (n = 92 in period 1 and n = 73 in period 2) were performed. The median waitlist time-to-transplant decreased from 47.5 to 19 days in periods 1 and 2, respectively (P = .004). The transplant rate increased from 181 per 100 patient-years in period 1 to 579 per 100 patient-years in period 2 (incidence rate ratio, 1.87; 95% CI, 1.04-3.38; P = .038). There were no statistical differences in waitlist mortality rate (P = .566) and 1-year survival (P = .699) between the 2 periods. DCD HTs (n = 36) contributed to 49.3% of overall HT activity in period 2. We concluded that utilization of DCD hearts significantly reduced waitlist time and increased transplant rate. Short-term posttransplant outcomes were comparable between the pre-DCD and post-DCD periods.

Surface Modification of Oxygenator Fibers with a Catalytically Active Metal-Organic Framework to Generate Nitric Oxide: An Ex Vivo Pilot Study.

Coating all portions of an extracorporeal membrane oxygenation (ECMO) circuit with materials exhibiting inherent, permanent antithrombotic properties is an essential step to prevent thrombus-induced complications. However, developing antithrombotic coatings for oxygenator fibers within membrane oxygenators of ECMO systems has proven challenging. We have used polydopamine (PDA) to coat oxygenator fibers and immobilize a Cu-based metal-organic framework (MOF) on the surface to act as a nitric oxide (NO) catalyst. Importantly, the PDA/MOF coating will produce NO indefinitely from endogenous S-nitrosothiols and it has not previously been applied to ECMO oxygenator fibers.

A dual-action nitric oxide-releasing slippery surface for extracorporeal organ support: Dynamic in vitro hemocompatibility evaluation.

Numerous biomaterials have been developed for application in blood-contacting medical devices to prevent thrombosis; however, few materials have been applied to full-scale devices and evaluated for hemocompatibility under clinical blood flow conditions. We applied a dual-action slippery liquid-infused (LI) nitric oxide (NO)-releasing material modification (LINO) to full-scale blood circulation tubing for extracorporeal lung support and evaluated the tubing ex vivo using swine whole blood circulated for 6 h at a clinically relevant flow. LINO tubing was compared to unmodified tubing (CTRL) and isolated LI and NO-releasing modifications (n = 9/group). The primary objective was to evaluate safety and blood compatibility of this approach, prior to progression to in vivo testing of efficacy in animal models. The secondary objective was to evaluate coagulation outcomes relevant to hemocompatibility. No untoward effects of the coating, such as elevated methemoglobin fraction, were observed. Additionally, LINO delayed platelet loss until 6 h versus the reduction in platelet count in CTRL at 3 h. At 6 h, LINO significantly reduced the concentration of platelets in an activated P-selectin expressing state versus CTRL (32 ± 1% decrease, p = .02). Blood clot deposition was significantly reduced on LINO blood pumps (p = .007) and numerically reduced on tubing versus CTRL. Following blood exposure, LINO tubing continued to produce a measurable NO-flux (0.20 ± 0.06 × 10-10  mol cm-2  min-1 ). LINO is a potential solution to reduce circuit-related bleeding and clotting during extracorporeal organ support, pending future extended testing in vivo using full-scale extracorporeal lung support devices.

K+ontrol rapidly and efficiently reduces potassium in donor blood during ex vivo circulation.

BACKGROUND: Patients with kidney failure are at risk for lethal complications from hyperkalemia. Resuscitation, medications, and hemodialysis are used to mitigate increased potassium (K+) levels in circulating blood; however, these approaches may not always be readily available or effective, especially in a resource limited environment. We tested a sorbent cartridge (KC, K+ontrol CytoSorbents Medical Inc., Monmouth Junction, New Jersey) which contains a resin adsorber for K+. The objective of this study was to test the utility of KC in an ex vivo circulation system. We hypothesized that KC reduces K+ levels in extracorporeal circulation of donor swine whole blood infused with KCl. METHODS: A six-hour circulation study was carried out using KC, a NxStage (NxStage Medical, Inc., Lawrence, MA) membrane, blood bag containing heparinized whole blood with KCl infusion, 3/16-inch ID tubing, a peristaltic pump, and flow sensors. The NxStage permeate line was connected back to the main circuit in the Control group (n = 6), creating a recirculation loop. For KC group (n = 6), KC was added to the recirculation loop, and a continuous infusion of KCl at 10 mEq/hour was administered for two hours. Blood samples were acquired at baseline and every hour for 6 h. RESULTS: In the control group, K+ levels remained at ∼9 mmol/L; 9.1 ± 0.4 mmol/L at 6 h. In the KC group, significant decreases in K+ at hour 1 (4.3 ± 0.3 mmol/L) and were sustained for the experiment duration equilibrating at 4.6 ± 0.4 mmol/L after 6 h (p = 0.042). Main loop blood flow was maintained under 400 mL/min; recirculation loop flow varied between 60 and 70 mL/min in the control group and 45-55 mL/min in the KC group. Decreases in recirculation loop flow in KC group required 7% increase of pump RPM. CONCLUSIONS: During ex-vivo extracorporeal circulation using donor swine blood, KC removed approximately 50% of K+, normalizing circulating levels.

Multilayer Scaling of a Biomimetic Microfluidic Oxygenator.

Extracorporeal membrane oxygenation (ECMO) has been advancing rapidly due to a combination of rising rates of acute and chronic lung diseases as well as significant improvements in the safety and efficacy of this therapeutic modality. However, the complexity of the ECMO blood circuit, and challenges with regard to clotting and bleeding, remain as barriers to further expansion of the technology. Recent advances in microfluidic fabrication techniques, devices, and systems present an opportunity to develop new solutions stemming from the ability to precisely maintain critical dimensions such as gas transfer membrane thickness and blood channel geometries, and to control levels of fluid shear within narrow ranges throughout the cartridge. Here, we present a physiologically inspired multilayer microfluidic oxygenator device that mimics physiologic blood flow patterns not only within individual layers but throughout a stacked device. Multiple layers of this microchannel device are integrated with a three-dimensional physiologically inspired distribution manifold that ensures smooth flow throughout the entire stacked device, including the critical entry and exit regions. We then demonstrate blood flows up to 200 ml/min in a multilayer device, with oxygen transfer rates capable of saturating venous blood, the highest of any microfluidic oxygenator, and a maximum blood flow rate of 480 ml/min in an eight-layer device, higher than any yet reported in a microfluidic device. Hemocompatibility and large animal studies utilizing these prototype devices are planned. Supplemental Visual Abstract, http://links.lww.com/ASAIO/A769.

Development and Blood Compatibility of a Stable and Bioactive Metal-Organic Framework Composite Coating for Blood-Circulation Tubing.

Medical devices that require substantial contact between blood and a foreign surface would be dramatically safer if constructed from materials that prevent clot formation and coagulation disturbance at the blood-biomaterial interface. Nitric oxide (NO), an endogenous inhibitor of platelet activation in the vascular endothelium, could provide anticoagulation at the blood-surface interface when applied to biomaterials. We investigated an application of a copper-based metal-organic framework, H3[(Cu4Cl)3(BTTri)8-(H2O)12]·72H2O where H3BTTri = 1,3,5-tris(1H-1,2,3-triazole-5-yl)benzene] (CuBTTri), which has been shown to be an effective catalyst to generate NO from S-nitrosothiols that are endogenously present in blood. A method was developed to apply a CuBTTri composite coating to Tygon medical tubing used for extracorporeal lung support devices. The stability and activity of the coating were evaluated during 72 h dynamic saline flow testing (1.5-2.5 L/min, n = 3) with scanning electron microscopy imaging and inductively coupled mass-spectroscopy analysis. Compatibility of the coating with whole blood was assessed with a panel of hemocompatibility tests during 6 h circulation of swine donor blood in an ex vivo circulation loop constructed with CuBTTri tubing or unmodified Tygon (1.5 L/min blood flow rate, n = 8/group). Thrombus deposition and catalytic activity of the CuBTTri tubing were assessed following blood exposure. The coating remained stable during 72 h saline flow experiments at clinically relevant flow rates. No adverse effects were observed relative to controls during blood compatibility testing, to include no significant changes in platelet count (p = 0.42), platelet activation indicated by P-selectin expression (p = 0.57), coagulation panel values, or methemoglobin fraction (p = 0.18) over the 6 h circulation period. CuBTTri within the coating generated NO following blood exposure in the presence of biologically relevant concentrations of an NO donor. CuBTTri composite coating was stable and blood compatible in this pilot study and requires further investigation of efficacy using in vivo models conducted with clinically relevant blood flow rates and study duration.

In vitro hemocompatibility screening of a slippery liquid impregnated surface coating for extracorporeal organ support applications.

INTRODUCTION: Clot formation, infection, and biofouling are unfortunate but frequent complications associated with the use of blood-contacting medical devices. The challenge of blood-foreign surface interactions is exacerbated during medical device applications involving substantial blood contact area and extended duration of use, such as extracorporeal life support (ECLS). We investigated a novel surface modification, a liquid-impregnated surface (LIS), designed to minimize protein adsorption and thrombus development on medical plastics. METHODS: The hemocompatibility and efficacy of LIS was investigated first in a low-shear model with LIS applied to the lumen of blood incubation vials and exposed to human whole blood. Additionally, LIS was evaluated in a 6 h ex vivo circulation model with swine blood using full-scale ECLS circuit tubing and centrifugal pumps with clinically relevant flow rate (1.5 L/min) and shear conditions for extracorporeal carbon dioxide removal. RESULTS: Under low-shear, LIS preserved fibrinogen concentration in blood relative to control polymers (+40 ± 6 mg/dL vs polyvinyl chloride, p < .0001), suggesting protein adsorption was minimized. A fibrinogen adhesion assay demonstrated a dramatic reduction in protein adsorption under low shear (87% decrease vs polyvinyl chloride, p = .01). Thrombus deposition and platelet adhesion visualized by scanning electron microscopy were drastically reduced. During the 6 h ex vivo circulation, platelets in blood exposed to LIS tubing did not become significantly activated or procoagulant, as occurred with control tubing; and again, thrombus deposition was visually reduced. CONCLUSIONS: A LIS coating demonstrated potential to reduce thrombus formation on medical devices. Further testing is needed specialized to clinical setting and duration of use for specific medical target applications.

Development and In Vitro Whole Blood Hemocompatibility Screening of Endothelium-Mimetic Multifunctional Coatings.

Multifunctional antithrombotic surface modifications for blood-contacting medical devices have emerged as a solution for foreign surface-mediated coagulation disturbance. Herein, we have developed and evaluated an endothelium-inspired strategy to reduce the thrombogenicity of medical plastics by imparting nitric oxide (NO) elution and heparin immobilization on the material surface. This dual-action approach (NO+Hep) was applied to polyethylene terephthalate (PET) blood incubation vials and compared to isolated modifications. Vials were characterized to evaluate NO surface flux as well as heparin density and activity. Hemocompatibility was assessed in vitro using whole blood from human donors. Compared to unmodified surfaces, blood incubated in the NO+Hep vials exhibited reduced platelet aggregation (15% decrease AUC, p = 0.040) and prolonged plasma clotting times (aPTT = 147% increase, p < 0.0001, prothrombin time = 5% increase, p = 0.0002). Prolongation of thromboelastography reaction time and elevated antifactor Xa levels in blood from NO+Hep versus PET vials suggests some heparin leaching from the vial surface, confirmed by post-blood incubation heparin density assessment. Results suggest NO+Hep surface modification is a promising approach for blood-contacting plastics; however, careful tuning of NO flux and heparin stabilization are essential and require assessment using human blood as performed here.

Expeditionary Mechanical Ventilation in Conjunction With Extracorporeal Life Support During Ground Transport.

BACKGROUND: We assessed the use of an FDA-cleared transport ventilator with limited functions and settings during ground transport in a swine model of ground evacuation. We hypothesized that when used as an adjunct to extracorporeal life support (ECLS), the device would enable safe mobile ventilatory support during ground evacuation. METHODS: Female Yorkshire swine (n = 11; mean, 52.4 ± 1.3 kg) were sedated and anesthetized and received mechanical ventilation (MV) with a standard intensive care unit (ICU) ventilator and were transitioned to the Simplified Automated Ventilator II (SAVe II; AutoMedx) during ground transport. MV served as an adjunct to ECLS in all animals. Ventilator performance was assessed in the uninjured state on day 1 and after bilateral pulmonary contusion on day 2. Data were collected pre- and post-transport on both days. RESULTS: During 33 transports, the SAVe II provided similar ventilation support as the ICU ventilator. Mean total transport time was 38.8 ± 2.1 minutes. The peak inspiratory pressure (PIP) limit was the only variable to show consistent differences pre- and post-transport and between ventilators. No adverse events occurred. CONCLUSION: As an adjunctive supportive device during ground transport, the SAVe II performed adequately without failure or degradation in subject status. Further testing is warranted to elucidate the clinical limits of this device during standalone use.

Regional blood acidification inhibits coagulation during extracorporeal carbon dioxide removal (ECCO2 R).

BACKGROUND: Consumption of platelets and coagulation factors during extracorporeal carbon dioxide removal (ECCO2 R) increases bleeding complications and associated mortality. Regional infusion of lactic acid enhances ECCO2 R by shifting the chemical equilibrium from bicarbonate to carbon dioxide. Our goal was to test if regional blood acidification during ECCO2 R inhibits platelet function and coagulation. METHODS: An ECCO2 R system containing a hemofilter circulated blood at 0.25 L/min in eight healthy ewes (Ovis aries) for 36 h. Three of the sheep received ECCO2 R with no recirculation compared to five sheep that received ECCO2 R plus 12 h of regional blood acidification via the hemofilter, placed upstream from the oxygenator, into which 4.4 M lactic acid was infused. Blood gases, platelet count and function, thromboelastography, coagulation-factor activity, and von Willebrand factor activity (vWF:Ag) were measured at baseline, at start of lactic acid infusion, and after 36 h of extracorporeal circulation. RESULTS: Twelve hours of regional acid infusion significantly inhibited platelet aggregation response to adenosine diphosphate; vWF; and platelet expression of P-selectin compared to control. It also significantly reduced consumption of fibrinogen and of coagulation factors V, VII, IX, compared to control. CONCLUSIONS: Regional acidification reduces platelet activation and vitamin-K-dependent coagulation-factor consumption during ECCO2 R. This is the first report of a simple method that may enhance effective anticoagulation for ECCO2 R.

HMGB1 Inhibition to Ameliorate Organ Failure and Increase Survival in Trauma.

Several preclinical and clinical reports have demonstrated that levels of circulating high mobility group box 1 protein (HMGB1) are increased early after trauma and are associated with systemic inflammation and clinical outcomes. However, the mechanisms of the interaction between HMGB1 and inflammatory mediators that lead to the development of remote organ damage after trauma remain obscure. HMGB1 and inflammatory mediators were analyzed in plasma from 54 combat casualties, collected on admission to a military hospital in Iraq, and at 8 and 24 h after admission. In total, 45 (83%) of these patients had traumatic brain injury (TBI). Nine healthy volunteers were enrolled as controls. HMGB1 plasma levels were significantly increased in the first 8 h after admission, and were found to be associated with systemic inflammatory responses, injury severity score, and presence of TBI. These data provided the rationale for designing experiments in rats subjected to blast injury and hemorrhage, to explore the effect of HMGB1 inhibition by CX-01 (2-O, 3-O desulfated heparin). Animals were cannulated, then recovered for 5-7 days before blast injury in a shock tube and volume-controlled hemorrhage. Blast injury and hemorrhage induced an early increase in HMGB1 plasma levels along with severe tissue damage and high mortality. CX-01 inhibited systemic HMGB1 activity, decreased local and systemic inflammatory responses, significantly reduced tissue and organ damage, and tended to increase survival. These data suggest that CX-01 has potential as an adjuvant treatment for traumatic hemorrhage.

Dynamics of appearance and decay of gaseous microemboli during in vitro extracorporeal circulation.

INTRODUCTION: Extracorporeal life support (ECLS) patients are at risk for complications caused by gaseous microemboli (GME). GMEs can cause hypoxia, inflammation, coagulation, and end-organ damage. The objective of this in vitro study was to assess dynamics of GME formation during circulation of whole blood or a glycerol blood surrogate. We hypothesized that there is no difference in GME counts and sizes between whole blood and the glycerol blood surrogate and that the membrane lung reduces GME counts over time. METHODS: A circulation platform was developed using the Cardiohelp ECLS system to run either donor blood or glycerol solution. We conducted 10 repetitions consisting of three phases of ultrasound GME detection using the EDAC™ Quantifier (Luna Innovations, Charlottesville, VA, USA) for each group. Phases were 3-minute recordings at the initiation of 2 L/min flow (Phase 1), post-injection of a GME suspension (Phase 2), and 10 minutes after injection (Phase 3). The number and size of GME pre- and post-ML were recorded separately and binned based on diameter ranges. RESULTS: In Phase 1, GME count in blood was higher than in glycerol. In Phase 2, there was a large increase in GME counts; however, most GME were reduced post-membrane in both groups. In Phase 3, there was a significant decrease in GME counts compared to Phase 2. GME > 100 µm in glycerol decreased post membrane. CONCLUSIONS: We demonstrated GME formation and decay dynamics during in vitro circulation in an ECLS system with blood and glycerol. GME counts were higher in blood, likely due to varying rheological properties. There were decreases in GME levels post membrane in both groups after GME injection, with the membrane lung effectively trapping the GME, and additional reduction 10 minutes after GME injection.

Adjunct Use of Continuous Renal Replacement Therapy with Extracorporeal Membrane Oxygenation Achieves Negative Fluid Balance and Enhances Oxygenation Which Improves Survival in Critically Ill Patients without Kidney Failure.

INTRODUCTION: Fluid overload in extracorporeal membrane oxygenation (ECMO) patients has been associated with increased mortality. Patients receiving ECMO and continuous renal replacement therapy (CRRT) who achieve a negative fluid balance have improved survival. Limited data exist on the use of CRRT solely for fluid management in ECMO patients. METHODS: We performed a single-center retrospective review of 19 adult ECMO patients without significant renal dysfunction who received CRRT for fluid management. These patients were compared to a cohort of propensity-matched controls. RESULTS: After 72 h, the treatment group had a fluid balance of -3840 mL versus + 425 mL (p ≤ 0.05). This lower fluid balance correlated with survival to discharge (odds ratio 2.54, 95% confidence interval 1.10-5.87). Improvement in the ratio of arterial oxygen content to fraction of inspired oxygen was also significantly higher in the CRRT group (102.4 vs. 0.7, p ≤ 0.05). We did not observe any significant difference in renal outcomes. CONCLUSIONS: The use of CRRT for fluid management is effective and, when resulting in negative fluid balance, improves survival in adult ECMO patients without significant renal dysfunction.