Prediction of Thrombus Formation within an Oxygenator via Bioimpedance Analysis.

Blood clot formation inside the membrane oxygenator (MO) remains a risk in extracorporeal membrane oxygenation (ECMO). It is associated with thromboembolic complications and normally detectable only at an advanced stage. Established clinical monitoring techniques lack predictive capabilities, emphasizing the need for refinement in MO monitoring towards an early warning system. In this study, an MO was modified by integrating four sensor fibers in the middle of the hollow fiber mat bundle, allowing for bioimpedance measurement within the MO. The modified MO was perfused with human blood in an in vitro test circuit until fulminant clot formation. The optical analysis of clot residues on the extracted hollow fibers showed a clot deposition area of 51.88% ± 14.25%. This was detectable via an increased bioimpedance signal with a significant increase 5 min in advance to fulminant clot formation inside the MO, which was monitored by the clinical gold standard (pressure difference across the MO (dp-MO)). This study demonstrates the feasibility of detecting clot growth early and effectively by measuring bioimpedance within an MO using integrated sensor fibers. Thus, bioimpedance may even outperform the clinical gold standard of dp-MO as a monitoring method by providing earlier clot detection.

Comparative analysis of oxygenator dysfunction in polymethylpentene oxygenators: A pilot study.

INTRODUCTION: Polymethylpentene (PMP) oxygenators serve as the primary oxygenator type utilized for ECMO. With the number of PMP oxygenators available, it has become increasingly important to determine differences among each oxygenator type that can lead to varying metrics of oxygenator dysfunction. METHODS: This study was a retrospective, single-center analysis of adult patients supported on ECMO between December 2020 to December 2021 with varying PMP oxygenators including the Medtronic Nautilus Smart (Minneapolis, MA), the Eurosets AMG PMP (Medolla, Italy) and Getinge Quadrox-iD and the Getinge Cardiohelp HLS Module Advanced System (Gothenberg, Sweden). RESULTS: A total of 19 patients were included in our study. 10 patients (52.6%) were supported with a Medtronic Nautilus Smart oxygenator, 5 patients (26.3%) were supported with an Eurosets AMG PMP Oxygenator, and 4 patients (21.1%) were supported with either a Getinge Quadrox-iD oxygenator or Getinge Cardiohelp HLS system. Patients supported with Eurosets AMG PMP oxygenators experienced higher resistance and lower post-oxygenator PaO2 in comparison to other cohorts (p < .02 and < .002 respectively). There was no difference in measured oxygen transfer between cohorts (p = .667). Two patients, both supported by Eurosets AMG PMP, experienced oxygenator failure (p = .094). CONCLUSION: Radial flow oxygenators are prone to higher resistance and lower post-oxygenator PaO2when compared to transverse flow oxygenators. Future larger multicenter studies are required to fully discern the differences between flow-varying polymethylpentene oxygenators and their appropriate cutoffs for oxygenator dysfunction.

Predictors of membrane oxygenator failure in pediatric extracorporeal membrane oxygenation.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is increasingly utilized in pediatric patients. Failure to recognize membrane oxygenator failure can lead to critical complications due to rapid deterioration of membrane oxygenator function. Therefore, identifying the predictors for membrane oxygenator exchange is crucial. However, risk factors for membrane oxygenator exchange in pediatric V-A ECMO remain unclear; therefore, this study aimed to evaluate these risk factors. METHODS: This retrospective cohort study enrolled all pediatric patients aged <18 years who received V-A ECMO between August 2018 and July 2023 at a tertiary-care pediatric hospital in Japan. The Cox proportional hazards model was used to evaluate the predictors of membrane oxygenator failure within 72 h after initiation. RESULTS: During the study period, membrane oxygenator failure occurred in 18/55 (32.7%) children within 72 h; membrane oxygenator failure within 72 h occurred in 4/29 (13.8%) and 14/26 (53.8%) in the groups with ratio of blood flow divided by the blood flow limit of the membrane oxygenator (B/L) of <0.5 and ≥0.5, respectively (adjusted hazards ratio, 4.97 [95% confidence interval, 1.33-18.5]; p = 0.017). After adjusting for delta pressure of the oxygenator, an increase in body weight and aspartate aminotransferase levels were associated with an increase in early membrane oxygenator failure. CONCLUSIONS: This retrospective study demonstrated that a B/L ratio >0.5, an increase in body weight, and elevated aspartate aminotransferase were independent risk factors for early membrane oxygenator failure in pediatric V-A ECMO. However, a prospective multicenter study with an appropriate sample size is warranted to mitigate potential bias, and enhance generalizability for further investigation of the association between a B/L ratio and early membrane oxygenator failure.

The use of veno-veno-arterial ECMO as a successful strategy in acute mitral regurgitation secondary to papillary muscle rupture causing cardiogenic shock and profound hypoxemia: a case report.

Acute mitral regurgitation (MR) secondary to papillary muscle rupture is a rare mechanical complication of acute myocardial infarction occurring in 0.05-0.26% of all cases of myocardial infarction. The only treatment is emergency mitral valve surgery with high operative mortality reaching up to 39%. The use of extracorporeal membrane oxygenator (ECMO) as a stabilization strategy and a bridge to recovery may potentially improve the outcome of such cases. Here, we report a case of acute MR presenting with cardiogenic shock and severe hypoxia that required insertion of veno-veno-arterial ECMO initially and followed by emergency mitral valve replacement. This strategy proved useful with full recovery of the patient.

Impact of Extracorporeal Membrane Oxygenation Circuitry on Remdesivir.

OBJECTIVES: This study aimed to determine the oxygenator impact on alterations of remdesivir (RDV) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extracorporeal membrane -oxygenation (ECMO) circuit including the Quadrox-i oxygenator. METHODS: One-quarter-inch and a 3/8-inch, simulated closed-loop ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A 1-time dose of RDV was administered into the circuits and serial preoxygenator and postoxygenator concentrations were obtained at 0 to 5 minutes, and 1-, 2-, 3-, 4-, 5-, 6-, 8-, 12-, and 24-hour time points. The RDV was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation. RESULTS: For the 1/4-inch circuits with an oxygenator, there was a 35% to 60% RDV loss during the study period. For the 1/4-inch circuits without an oxygenator, there was a 5% to 20% RDV loss during the study period. For the 3/8-inch circuit with and without an oxygenator, there was a 60% to 70% RDV loss during the study period. CONCLUSIONS: There was RDV loss within the circuit during the study period and the RDV loss was more pronounced with the larger 3/8-inch circuit when compared with the 1/4-inch circuit. The impact of the -oxygenator on RDV loss appears to be variable and possibly dependent on the size of the circuit and -oxygenator. These preliminary data suggest RDV dosing may need to be adjusted for concern of drug loss via the ECMO circuit. Additional single- and multiple-dose studies are needed to validate these findings.

The effect of excessive gas to blood ratios in an ECMO oxygenator.

INTRODUCTION: Oxygenators for paediatric Extracorporeal Membrane Oxygenation (ECMO) are required to operate over a wide range of flow rates, in a patient group ranging from neonates through to fully grown adolescents. ECMO oxygenators typically have a manufacturer's stated maximum gas: blood flow rate (GBFR) ratio of 2:1, however, many patients require greater ratios than this for adequate CO2 removal. Mismatches in GBFR in theory could result in high gas phase pressures. These increased pressures in theory could cause the formation of gross gaseous microemboli (GME) placing the child at higher risk of neurological injury. METHODS: We evaluated 6 paediatric and 6 adult A.L.ONE™ ECMO oxygenators and assessed their gas phase pressures and GME release, in an ex vivo setting, in GBFR ratios up to greater than 2, across a range of gas flow (1L - 10 L/min) rates with a fraction of inspired oxygen (FiO2) content of 50% and 100%. RESULTS: There were no increases above 10 mmHg observed in gas phase pressures in GBFR >= 2:1 in either adult or paediatric oxygenators. Laboratory examination of GME activity demonstrated a small increase in post-membrane GME release over the study period. GME release was unaffected by FiO2 setting or gas flow rate, with a maximum volume of < 6 µL in both paediatric and adult oxygenators. CONCLUSIONS: In an ex vivo setting, increasing GBFR above 2:1 in a paediatric oxygenator, and to a GBFR of 2:1 in an adult oxygenator did not significantly increase gas phase pressures, and no oxygenator membrane rupture was observed. There were no associations between gas flow rates and GME production.

Sudden pump stop may cause air release in oxygenators, 'The Hammer Effect ': An in vitro evaluation.

BACKGROUND: Oxygenators, as used in cardiopulmonary bypass (CPB) circuits, are components with good air removal properties. However, under some conditions the semipermeable characteristics of hollow fibers allow air to accidentally enter the blood side of the CPB circuit. This may occur when a fluid in motion is stopped suddenly by which the rapid change in momentum may cause a relative negative pressure drop, the so-called hammer effect. The hammer effect is not yet described in literature related to CPB. The aim of this in vitro study was to reproduce the hammer effect. METHODS: The in vitro setup consisted of a CPB circuit with a fully occluded roller pump and one of four test oxygenators. The hammer test was performed by a sudden pump stop. The pressure wave was measured and after the test the residual air present in the oxygenator was forced into the arterial line and measured with a bubble detector. RESULTS: We showed that a sudden pump stop could lead to the hammer effect, represented as a relative negative pressure drop in the arterial line. This hammer effect resulted in air release through the semipermeable fibers as we showed in two of the four tested brands of oxygenators. CONCLUSIONS: We conclude that the hammer effect may occur before connection of the CPB system to the patient, and this may result in air release into the arterial blood side of the oxygenator. The hammer effect can be caused by clamping of the tubing in combination with a centrifugal pump, or by suddenly stopping the roller pump. With this study we would like to raise awareness of the hammer effect.

3D porous structure imaging of membranes for medical devices using scanning probe microscopy and electron microscopy: from membrane science points of view.

The evolution of hemodialysis membranes (dialyzer, artificial kidney) was remarkable, since Dow Chemical began manufacturing hollow fiber hemodialyzers in 1968, especially because it involved industrial chemistry, including polymer synthesis and membrane manufacturing process. The development of hemodialysis membranes has brought about the field of medical devices as a major industry. In addition to conventional electron microscopy, scanning probe microscopy (SPM), represented by atomic force microscopy (AFM), has been used in membrane science research on porous membranes for hemodialysis, and membrane science contributes greatly to the hemodialyzer industry. Practical studies of membrane porous structure-function relationship have evolved, and methods for analyzing membrane cross-sectional morphology were developed, such as the ion milling method, which was capable of cutting membrane cross sections on the order of molecular size to obtain smooth surface structures. Recently, following the global pandemic of SARS-CoV-2 infection, many studies on new membranes for extracorporeal membrane oxygenator have been promptly reported, which also utilize membrane science researches. Membrane science is playing a prominent role in membrane-based technologies such as separation and fabrication, for hemodialysis, membrane oxygenator, lithium ion battery separators, lithium recycling, and seawater desalination. These practical studies contribute to the global medical devices industry.

Hypobaric type oxygenators - physics and physiology.

Brain injury is still a serious complication after cardiac surgery. Gaseous microemboli (GME) are known to contribute to both short and longer-term brain injury after cardiac surgery. Hypobaric and novel dual-chamber oxygenators use the physical behaviors and properties of gases to reduce GME. The aim of this review was to present the basic physics of the gases, the mechanism in which the hypobaric and dual-chamber oxygenators reduce GME, their technical performance, the preclinical studies, and future directions. The gas laws are reviewed as an aid to understanding the mechanisms of action of oxygenators. Hypobaric-type oxygenators employ a high oxygen, no nitrogen environment creating a steep concentration gradient of nitrogen out of the blood and into the oxygenator, reducing the risk of GMEs forming. Adequately powered clinical studies have never been carried out with a hypobaric or dual-chamber oxygenator. These are required before such technology can be recommended for widespread clinical use.

Platelet volume indices and von Willebrand factor levels in blood exposed to polymer- or heparin-coated membrane oxygenators.

INTRODUCTION: To understand the behavior of platelet volume indices and the von Willebrand factor (VWF), in vitro experiments using whole human blood were performed with extracorporeal circulation (ECC) circuits, including membrane oxygenators coated with acrylate copolymer (ACP) or immobilized heparin (IHP). METHODS: Heparinized blood was circulated through two distinct experimental circuits: an ACP-coated reservoir and tubes, as well as membranes coated with either ACP or IHP (comprising five pieces of each type). The platelet distribution width, mean platelet volume (MPV), platelet large cell ratio (P-LCR), VWF quantity (VWFQ), and VWF activity (VWFA) were measured at 0, 8, 16, 24, and 32 h in each experiment. A two-way analysis of variance (ANOVA) was performed to determine whether the coating type or circulation duration affected the transition of each measurement. RESULTS: Two-way ANOVA indicated that the transitions of MPV, P-LCR, and VWFA were significantly affected by the circulation duration (p = 0.030, 0.001, and <0.001, respectively) and that the transitions of VWFQ and VWFA were significantly affected by the coating type (p = 0.022 and 0.006, respectively). Factor interactions between the coating type and circulation duration were not observed for each transition (p > 0.05). CONCLUSIONS: Our findings suggest that P-LCR is a good index for platelet activation in blood-circulating ECC and that VWFA and VWFQ are significantly attenuated in blood-circulating ECC with ACP-coated membranes, indicating the advantage of IHP coating regarding platelet activation.

Optimization of the IntraVascular Oxygenator Catheter Using Angular Oscillation.

We demonstrate a methodology which both improves oxygen transport and reduces or eliminates bubble formation in a novel hyperbaric membrane oxygenator catheter model system. Angular oscillations were introduced to a bundle of hollow fiber membranes (HFMs) supplied with hyperbaric 100% oxygen at average gauge pressures up to 0.35 barg. Oscillating bundles enabled delivery of an oxygen flux of up to 400 mL min-1 m-2 in an aqueous solution, a doubling over a previous non-oscillating setup. Similarly, the addition of angular oscillations facilitated a five-fold reduction in pressure to achieve similar oxygen flux. The increased angular speed of oscillation improved flux, while the addition of angular micro-oscillation variations resulted in flux reductions of 7-20% compared to continuous macro-oscillation only, depending on mixing conditions. However, semi-quantitative visual observation demonstrated that angular oscillations reduced or eliminated the instance of oxygen bubble formation on the HFMs. The modeled mass transfer coefficients indicated a quasi linear relationship between rotational velocity and flux, suggesting that faster oscillation speeds could further improve oxygen mass transport allowing for HFM bundles to maintain high oxygen fluxes while eliminating bubble formation. This encourages further development of our compact oxygenating catheter that could be used intravascularly.

Asymmetric Triple-Functional Janus Membrane for Blood Oxygenation.

The oxygenation membrane, a core material of extracorporeal membrane oxygenation (ECMO), is facing challenges in balancing anti-plasma leakage, gas exchange efficiency, and hemocompatibility. Here, inspired by the asymmetric structural features of alveolus pulmonalis, a novel triple-functional membrane for blood oxygenation with a Janus architecture is proposed, which is composed of a hydrophobic polydimethylsiloxane (PDMS) layer to prevent plasma leakage, an ultrathin polyamide layer to enhance gas exchange efficiency with a CO2 :O2 permeance ratio of ≈10.7, and a hydrophilic polyzwitterionic layer to improve the hemocompatibility. During the simulated ECMO process, the Janus oxygenation membrane exhibits excellent performance in terms of thrombus formation and plasma leakage prevention, as well as adequate O2 transfer rate (17.8 mL min-1 m-2 ) and CO2 transfer rate (70.1 mL min-1 m-2 ), in comparison to the reported oxygenation membranes. This work presents novel concepts for the advancement of oxygenation membranes and demonstrates the application potential of the asymmetric triple-functional Janus oxygenation membrane in ECMO.

Early Blood Clot Detection Using Forward Scattering Light Measurements Is Not Superior to Delta Pressure Measurements.

The occurrence of thrombus formation within an extracorporeal membrane oxygenator is a common complication during extracorporeal membrane oxygenation therapy and can rapidly result in a life-threatening situation due to arterial thromboembolism, causing stroke, pulmonary embolism, and limb ischemia in the patient. The standard clinical practice is to monitor the pressure at the inlet and outlet of oxygenators, indicating fulminant, obstructive clot formation indicated by an increasing pressure difference (ΔP). However, smaller blood clots at early stages are not detectable. Therefore, there is an unmet need for sensors that can detect blood clots at an early stage to minimize the associated thromboembolic risks for patients. This study aimed to evaluate if forward scattered light (FSL) measurements can be used for early blood clot detection and if it is superior to the current clinical gold standard (pressure measurements). A miniaturized in vitro test circuit, including a custom-made test chamber, was used. Heparinized human whole blood was circulated through the test circuit until clot formation occurred. Four LEDs and four photodiodes were placed along the sidewall of the test chamber in different positions for FSL measurements. The pressure monitor was connected to the inlet and the outlet to detect changes in ΔP across the test chamber. Despite several modifications in the LED positions on the test chamber, the FSL measurements could not reliably detect a blood clot within the in vitro test circuit, although the pressure measurements used as the current clinical gold standard detected fulminant clot formation in 11 independent experiments.

Acute coronary syndrome associated cardiogenic shock in the catheterization laboratory: peripheral veno-arterial extracorporeal membrane oxygenator management and recommendations.

Cardiogenic shock (CS) in acute coronary syndrome (ACS) is a critical disease with high mortality rates requiring complex treatment to maximize patient survival chances. Emergent coronary revascularization along with circulatory support are keys to saving lives. Mechanical circulatory support may be instigated in severe, yet still reversible instances. Of these, the peripheral veno-arterial extracorporeal membrane oxygenator (pVA-ECMO) is the most widely used system for both circulatory and respiratory support. The aim of our work is to provide a review of our current understanding of the pVA-ECMO when used in the catheterization laboratory in a CS ACS setting. We detail the workings of a Shock Team: pVA-ECMO specifics, circumstances, and timing of implantations and discuss possible complications. We place emphasis on how to select the appropriate patients for potential pVA-ECMO support and what characteristics and parameters need to be assessed. A detailed, stepwise implantation algorithm indicating crucial steps is also featured for practitioners in the catheter laboratory. To provide an overall aspect of pVA-ECMO use in CS ACS we further gave pointers including relevant human resource, infrastructure, and consumables management to build an effective Shock Team to treat CS ACS via the pVA-ECMO method.

Post-Mortem Extracorporeal Membrane Oxygenation Perfusion Rat Model: A Feasibility Study.

The development of biomedical soft- or hardware frequently includes testing in animals. However, large efforts have been made to reduce the number of animal experiments, according to the 3Rs principle. Simultaneously, a significant number of surplus animals are euthanized without scientific necessity. The primary aim of this study was to establish a post-mortem rat perfusion model using extracorporeal membrane oxygenation (ECMO) in surplus rat cadavers and generate first post vivo results concerning the oxygenation performance of a recently developed ECMO membrane oxygenator. Four rats were euthanized and connected post-mortem to a venous-arterial ECMO circulation for up to eight hours. Angiographic perfusion proofs, blood gas analyses and blood oxygenation calculations were performed. The mean preparation time for the ECMO system was 791 ± 29 s and sufficient organ perfusion could be maintained for 463 ± 26 min, proofed via angiographic imaging and a mean femoral arterial pressure of 43 ± 17 mmHg. A stable partial oxygen pressure, a 73% rise in arterial oxygen concentration and an exponentially increasing oxygen extraction ratio up to 4.75 times were shown. Considering the 3Rs, the established post-mortal ECMO perfusion rat model using surplus animals represents a promising alternative to models using live animals. Given the preserved organ perfusion, its use could be conceivable for various biomedical device testing.

A new approach towards extracorporeal gas exchange and first in vitro results.

OBJECTIVES: Extracorporeal life support (ECLS) pertains to therapeutic and prophylactic techniques utilized in a wide range of medical applications, with severe pulmonary diseases being the most prominent cases. Over the past decades, little progress has been made in advancing the basic principles and properties of gas exchangers. Here, in an unconventional approach, dialysis hollow fibers are handled with silicone to create a purely diffusive coating that prevents plasma leakage and promotes gas exchange. METHODS: Commercial dialyzers of varying surface area and fiber diameter have been coated with silicone, to determine the impact of each parameter on performance. The impermeability of the silicone layer has been validated by pressurization and imaging methods. SEM images have revealed a homogeneous silicone film coating the lumen of the capillaries, while fluid dynamic investigations have confirmed its purely diffusive nature. RESULTS: The hemodynamic behavior and the gas exchange efficiency of the silicone-coated prototypes have been investigated in vitro with porcine blood under various operating conditions. Their performance has been found to be similar to that of a commercial PMP oxygenator. CONCLUSIONS: This novel class of gas exchangers is characterized by high versatility and expeditious manufacturing. Intraoperability between conventional ECLS systems and dialysis machines broadens the range of application infinitely. Ultimately, long-term clinical applicability ought to be determined over in vivo animal investigations.

Device updates in pediatric and neonatal ECMO.

Since the early use of extracorporeal life support (ECLS), new innovations and technological advancements have augmented the ability to use this technology in children and neonates. Cannulae have been re-designed to maintain structure and allow for single cannula venovenous (VV) ECLS in smaller patients. Circuit technology, including pumps and tubing, has evolved to permit smaller priming volumes and lower flow rates with fewer thrombotic or hemolytic complications. New oxygenator developments also improve efficiency of gas exchange. This paper serves as an overview of recent device developments in ECLS delivery to pediatric and neonatal patients.

Broad and narrow complex tachycardia resulting in cardiorespiratory arrest in a child: what is the optimal treatment strategy?

Background: We describe a child with a broad and narrow complex tachycardia causing haemodynamic collapse. Case summary: A 9-year-old girl (weight 26 kg, height 114 cm) with a 5-year history of refractory 'epilepsy' presented with cardiorespiratory arrest and tonic-clonic seizure, witnessed by her mother. Electrocardiogram documented recurrent episodes of simultaneous broad and narrow tachycardias associated with haemodynamic compromise. Diagnostic electrophysiologic study (EPS) confirmed a dual tachycardia mechanism. The challenge in selecting the optimal treatment strategy is discussed. A diagnosis of dual tachycardia was made with catecholaminergic polymorphic ventricular tachycardia (CPVT) and simultaneous focal atrial tachycardia. Discussion: Bidirectional ventricular tachycardia (VT) induced by isoproterenol in this clinical scenario is strongly suggestive of CPVT. Diagnostic EPS can be useful in challenging clinical situations to understand the mechanism of arrhythmias and to tailor the most appropriate treatment strategy. Combination therapy with nadolol and flecainide is highly effective in ventricular arrhythmia control. Implantable cardioverter defibrillator implantation is not without risk in CPVT as there is a potential of electrical storm driven by shock therapy that increases adrenergic drive. Cervical sympathectomy may be considered if further VTs occur in future despite optimum medical therapy.

Comparison of Serial and Parallel Connections of Membrane Lungs against Refractory Hypoxemia in a Mock Circuit.

Extracorporeal membrane oxygenation (ECMO) is an important rescue therapy method for the treatment of severe hypoxic lung injury. In some cases, oxygen saturation and oxygen partial pressure in the arterial blood are low despite ECMO therapy. There are case reports in which patients with such instances of refractory hypoxemia received a second membrane lung, either in series or in parallel, to overcome the hypoxemia. It remains unclear whether the parallel or serial connection is more effective. Therefore, we used an improved version of our full-flow ECMO mock circuit to test this. The measurements were performed under conditions in which the membrane lungs were unable to completely oxygenate the blood. As a result, only the photometric pre- and post-oxygenator saturations, blood flow and hemoglobin concentration were required for the calculation of oxygen transfer rates. The results showed that for a pre-oxygenator saturation of 45% and a total blood flow of 10 L/min, the serial connection of two identical 5 L rated oxygenators is 17% more effective in terms of oxygen transfer than the parallel connection. Although the idea of using a second membrane lung if refractory hypoxia occurs is intriguing from a physiological point of view, due to the invasiveness of the solution, further investigations are needed before this should be used in a wider clinical setting.