Detecting Oxygenator Thrombosis in ECMO: A Review of Current Techniques and an Exploration of Future Directions.

Extracorporeal membrane oxygenation (ECMO) is a life-support technique used to treat cardiac and pulmonary failure, including severe cases of COVID-19 (coronavirus disease 2019) involving acute respiratory distress syndrome. Blood clot formation in the circuit is one of the most common complications in ECMO, having potentially harmful and even fatal consequences. It is therefore essential to regularly monitor for clots within the circuit and take appropriate measures to prevent or treat them. A review of the various methods used by hospital units for detecting blood clots is presented. The benefits and limitations of each method are discussed, specifically concerning detecting blood clots in the oxygenator, as it is concluded that this is the most critical and challenging ECMO component to assess. We investigate the feasibility of solutions proposed in the surrounding literature and explore two areas that hold promise for future research: the analysis of small-scale pressure fluctuations in the circuit, and real-time imaging of the oxygenator. It is concluded that the current methods of detecting blood clots cannot reliably predict clot volume, and their inability to predict clot location puts patients at risk of thromboembolism. It is posited that a more in-depth analysis of pressure readings using machine learning could better provide this information, and that purpose-built imaging could allow for accurate, real-time clotting analysis in ECMO components.

Computational fluid dynamics-based design and in vitro characterization of a novel pediatric pump-lung.

BACKGROUND: Although extracorporeal membrane oxygenation (ECMO) has been used to provide temporary support for pediatric patients suffering severe respiratory or cardiac failure since 1970, ECMO systems specifically designed for pediatric patients, particularly for long-term use, remain an unmet clinical need. We sought to develop a new pediatric ECMO system, that is, pediatric pump-lung (PPL), consisting of a unique cylinder oxygenator with an outside-in radial flow path and a centrifugal pump. METHODS: Computational fluid dynamics was used to analyze the blood fluid field for optimized biocompatible and gas exchange performances in terms of flow characteristics, hemolysis, and gas transfer efficiency. Ovine blood was used for in vitro hemolysis and gas transfer testing. RESULTS: Both the computational and experimental data showed that the pressure drop through the PPL's oxygenator is significantly low, even at a flow rate of more than 3.5 L/min. The PPL showed better hemolysis performance than a commercial ECMO circuit consisting of the Quadrox-iD pediatric oxygenator and the Rotaflow pump at a 3.5 L/min flow rate and 250 mm Hg afterload pressure. The oxygen transfer rate of the PPL can reach over 200 mL/min at a flow rate of 3.5 L/min. CONCLUSIONS: The PPL has the potential to provide adequate blood pumping and excellent respiratory support with minimal risk of hemolysis for a wide range of pediatric patients.

α-Fe2O3@Au-PEG-Ce6-Gd Nanoparticles as Acidic H2O2-Driven Oxygenators for Multimodal Imaging and Synergistic Tumor Therapy.

Nanoparticles with visual imaging capabilities and synergistic therapeutics have a bright future in antitumor applications. However, most of the current nanomaterials lack multiple imaging-guided therapeutic capabilities. In this study, a novel enhanced photothermal photodynamic antitumor nanoplatform with photothermal imaging, fluorescence (FL) imaging, and MRI-guided therapeutic capabilities was constructed by grafting gold, dihydroporphyrin Ce6, and Gd onto α-iron trioxide. This antitumor nanoplatform can convert NIR light into local hyperthermia at a temperature of up to 53 °C under NIR light irradiation, while Ce6 can generate singlet oxygen, which further synergizes the tumor-killing effect. At the same time, α-Fe2O3@Au-PEG-Ce6-Gd can also have significant photothermal imaging effect under light irradiation, which can guide to see the temperature change near the tumor tissue. It is worth noting that α-Fe2O3@Au-PEG-Ce6-Gd can have obvious MRI and FL imaging effects after tail vein injection in mice with blood circulation, realizing imaging-guided synergistic antitumor therapy. α-Fe2O3@Au-PEG-Ce6-Gd NPs provide a new solution for tumor imaging and treatment.

Innovative experimental animal models for real-time comparison of antithrombogenicity between two oxygenators using dual extracorporeal circulation circuits and indocyanine green fluorescence imaging.

BACKGROUND: Antithrombogenicity of extracorporeal membrane oxygenation (ECMO) devices, particularly oxygenators, is a current problem, with numerous studies and developments underway. However, there has been limited progress in developing methods to accurately compare the antithrombogenicity of oxygenators. Animal experiments are commonly conducted to evaluate the antithrombogenicity of devices; however, it is challenging to maintain a steady experimental environment. We propose an innovative experimental animal model to evaluate different devices in a constant experimental environment in real-time. METHODS: This model uses two venous-arterial ECMO circuits attached to one animal (one by jugular vein and carotid artery, one by femoral vein and artery) and real-time assessment of thrombus formation in the oxygenator by indocyanine green (ICG) fluorescence imaging. Comparison studies were conducted using three pigs: one to compare different oxygenators (MERA vs. CAPIOX) (Case 1), and two to compare antithrombotic properties of the oxygenator (QUADROX) when used under different hydrodynamic conditions (continuous flow vs. pulsatile flow) (Cases 2 and 3). RESULTS: Thrombi, visualized using ICG imaging, appeared as black dots on a white background in each oxygenator. In Case 1, differences in the site of thrombus formation and rate of thrombus growth were observed in real-time in two oxygenators. In Case 2 and 3, the thrombus region was smaller in pulsatile than in continuous conditions. CONCLUSIONS: We devised an innovative experimental animal model for comparison of antithrombogenicity in ECMO circuits. This model enabled simultaneous evaluation of two different ECMO circuits under the same biological conditions and reduced the number of sacrificed experimental animals.

Development and evaluation of a variable, miniaturized oxygenator for various test methods.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) became an accepted therapy for the treatment of severe acute respiratory distress syndrome and chronic obstructive pulmonary disease. However, ECMO systems are still prone to thrombus formation and decrease of gas exchange over time. Therefore, it is necessary to conduct qualified studies to identify parameters for optimization of ECMO systems, and especially the oxygenator. However, commercially marketed oxygenators are not always appropriate and available for certain research use cases. Therefore, we aimed to design an oxygenator, which is suitable for various test conditions such as blood tests, numerical simulation, and membrane studies, and can be modified in membrane area size and manufactured in laboratory. METHODS: Main design criteria are a homogeneous blood flow without stagnation zones, low pressure drop, manufacturability in the lab, size variability with one set of housing parts and cost-efficiency. Our newly designed oxygenator was tested comparatively regarding blood cell damage, gas transfer performance and pressure drop to prove the validity of the design in accordance with a commercial device. RESULTS: No statistically significant difference between the tested oxygenators was detected and our new oxygenator demonstrated sufficient hemocompatibility. Furthermore, our variable oxygenator has proven that it can be easily manufactured in the laboratory, allows to use various membrane fiber configurations and can be reopened easily and non-destructively for analysis after use, and the original geometry is available for numerical simulations. CONCLUSION: Therefore, we consider this newly developed device as a valuable tool for basic experimental and numerical research on the optimization of oxygenators.

Clinical evaluation of two adult oxygenator systems in terms of mortality and major adverse events.

PURPOSE: The primary aim of this study was to examine the effects of two oxygenator systems on major adverse events and mortality. METHODS: A total of 181 consecutive patients undergoing coronary artery bypass grafting in our clinic were retrospectively analyzed. The patients were divided into two groups according to the oxygenator used: Group M, in which a Medtronic Affinity (Medtronic Operational Headquarters, Minneapolis, MN, USA) oxygenator was used, and Group S, in which a Sorin Inspire (Sorin Group Italia, Mirandola, Italy) oxygenator was used. RESULTS: Group S consisted of 89 patients, whereas Group M included 92 patients. No statistically significant differences were found between the two groups in terms of age (p = .112), weight (p = .465), body surface area (p = .956), or gender (p = .484). There was no statistically significant difference in hemorrhage on the first or second postoperative day (p = .318 and p = .455, respectively). No statistically significant differences were observed in terms of red blood cell (p = .468), fresh frozen plasma (p = .116), or platelet concentrate transfusion (p = .212). Infections, wound complications, and delayed sternal closure were significantly more common in Group M (p = .006, p = .023, and p = .019, respectively). Extracorporeal membrane oxygenators and intra-aortic balloon pumps were required significantly more frequently in Group S (p = .025 and p = .013, respectively). Major adverse events occurred in 16 (18%) patients in Group S and 14 (15.2%) patients in Group M (p = .382). Mortality was observed in six (6.7%) patients in Group S and three (3.3%) patients in Group M (p = .232). No statistically significant difference was found between the two groups in terms of length of hospital stay (p = .451). CONCLUSION: The clinical outcomes of the two oxygenator systems, including mortality, major adverse events, hemorrhage, erythrocyte and platelet transfusions, and length of hospital stay, were similar.

Comparison of bubble removal performances of five membrane oxygenators with and without a pre-filter.

When employing minimal invasive extracorporeal circulation (MiECC), the removal of bubbles in the circuit is important to prevent air embolism. We investigated the bubble removal performance of the FHP oxygenator with a pre-filter and compared it with that of four oxygenators, including the Fusion oxygenator, Quadrox oxygenator, Inspire oxygenator, and FX oxygenator. A closed test circuit filled with an aqueous glycerin solution was used. Air injection (10 mL) was performed prior to the oxygenator, and the number and volume of the bubbles were measured at the inlet and outlet of each oxygenator. At the inlet of the five oxygenators, there were no significant differences in the total number of bubbles detected. At the outlet, bubbles were classified into two groups according to the bubble size: ≥100 µm and <100 µm. Tests were performed at pump flow rates of 4 and 5 L/min. For bubbles ≥100 µm, which are considered clinically detrimental, the FHP was the lowest number and volume of bubbles at both pump flow rates compared to the other oxygenators. Regarding the bubbles <100 µm, the number of bubbles was higher in the FHP than those in others; however, the volume of bubbles was significantly lower at 4 L/min and tended to be lower at 5 L/min. The use of the FHP with the pre-filter removed more bubbles ≥100 µm in the circuit than that by the other oxygenators.

The novel ProtekDuo ventricular assist device: Configurations, technical aspects, and present evidence.

The ProtekDuo, single site dual lumen cannula can be used in a multitude of configurations. In the medical literature, the ProtekDuo is described as right ventricular assist device (RVAD), as left ventricular assist device (LVAD), as biventricular assist device (BiVAD) when combined with an Impella device or other LVAD's, as double lumen drainage cannula on cardiopulmonary bypass (CPB), as RVAD with oxygenator, in veno-pulmonary (V-P) ECMO configuration, venovenous-pulmonary (VV-P) ECMO configuration with additional drainage cannula, and in veno-venopulmonary (V-VP) ECMO configuration as double lumen return cannula. Improvements in flow and oxygenation have been recognized in various settings and need further scientific evaluation. We summarized the above-mentioned configurations, technical aspects, and the present literature available for the ProtekDuo.

Evaluation of the effects of three designs of oxygenators with integrated filters on clinical and haematological outcomes at an Australasian cardiothoracic unit.

INTRODUCTION: Cardiopulmonary bypass (CPB) machines have oxygenators with integrated filters and unique biocompatible coatings to combat systemic inflammatory response syndrome (SIRS) and mitigate coagulopathy. Contemporary oxygenators have undergone comparative studies; however, our study aimed to identify the most appropriate oxygenator for our regional Cardiothoracic unit in Australasia. METHODS: A prospective audit consecutively recruited one-hundred and fifty patients undergoing cardiac surgery at Waikato Hospital, New Zealand between the periods of 29th January 2018 and 31st July 2018. Fifty patients were recruited for each oxygenator arm: Sorin INSPIRE' (Group-S); Terumo CAPIOX'FX (Group-T); and Medtronic Affinity Fusion' (Group-M). The clinical outcomes were transfusions, chest drain output, reoperation and length of hospital stay (LOHS). Routine blood testing protocol included: haemoglobin, protein, albumin, white cell count (WCC), C-reactive protein (CRP), platelet count and coagulations tests including international normalized ratio (INR). RESULTS: Comparing Groups S, T and M there was no statistical difference in chest drain output (650 vs. 500 vs. 595 ml respectively, p = 0.45), transfusions (61 vs. 117 vs. 70 units, p = 0.67), reoperation (6 vs. 8 vs. 12%, p = 0.99) and LOHS (median 7.4 vs. 7.6 vs. 9.5 days, p = 0.42). Group-T had fewer SIRS cases but similar increase in CRP (p = 0.12) and WCC (p = 0.35). Group-M had a significant rise in post-op INR (p = 0.005) but no associated increase in chest drain output (p = 0.62). Group-S and -M required more 4%-albumin and Group-T had more transfusions. Only fresh frozen plasma (FFP) and red blood cell (RBC) transfusion had a significant relationship with LOHS (p < 0.05). CONCLUSION: Biochemically, there was slight difference among the oxygenators which did not translate into clinical difference in outcomes. The oxygenator design and perfusionist choice aided in our decision-making process.

Risk factors and treatment of oxygenator high-pressure excursions during cardiopulmonary bypass.

INTRODUCTION: A high-pressure excursion (HPE) is a sudden increase in oxygenator inlet pressure during cardiopulmonary bypass (CPB). The aims of this study were to identify factors associated with HPE, to describe a treatment protocol utilizing epoprostenol in severe cases, and to assess early outcome in HPE patients. METHODS: Patients who underwent cardiac surgery with cardiopulmonary bypass at Sahlgrenska University Hospital 2016-2018 were included in a retrospective observational study. Pre- and post-operative data collected from electronic health records, local databases, and registries were compared between HPE and non-HPE patients. Factors associated with HPE were identified with logistic regression models. RESULTS: In total, 2024 patients were analyzed, and 37 (1.8%) developed HPE. Large body surface area (adjusted Odds Ratio (aOR): 1.43 per 0.1 m2; 95% confidence interval (CI): 1.16-1.76, p < 0.001), higher hematocrit during CPB (aOR: 1.20 per 1%; (1.09-1.33), p < 0.001), acute surgery (aOR: 2.98; (1.26-6.62), p = 0.018), and previous stroke (aOR: 2.93; (1.03-7.20), p = 0.027) were independently associated with HPE. HPE was treated with hemodilution (n = 29, 78.4%), and/or extra heparin (n = 23, 62.2%), and/or epoprostenol (n = 12, 32.4%). No oxygenator change-out was necessary. While there was no significant difference in 30-day mortality (2.7% vs 3.2%, p = 1.0), HPE was associated with a higher perioperative stroke rate (8.1% vs 1.8%, aOR 5.09 (1.17-15.57), p = 0.011). CONCLUSIONS: Large body surface area, high hematocrit during CPB, previous stroke and acute surgery were independently associated with HPE. A treatment protocol including epoprostenol appears to be a safe option. Perioperative stroke rate was increased in HPE patients.

Hemodynamic oxygenator exchange-related effects during veno-venous extracorporeal membrane oxygenation for the treatment of acute SARS-CoV-2 respiratory distress syndrome.

Few patients with coronavirus disease 2019-associated severe acute respiratory distress syndrome (ARDS) require veno-venous extracorporeal membrane oxygenation (VV-ECMO). Prolonged VV-ECMO support necessitates repeated oxygenator replacement, increasing the risk for complications. Transient hypoxemia, induced by VV-ECMO stop needed for this procedure, may induce transient myocardial ischemia and acutely declining cardiac output in critically ill patients without residual pulmonary function. This is amplified by additional activation of the sympathetic nervous system (tachycardia, pulmonary vasoconstriction, and increased systemic vascular resistance). Immediate reinjection of the priming solution of the new circuit and induced acute iatrogenic anemia are other potentially reinforcing factors. The case of a critically ill patient presented here provides an instructive illustration of the hemodynamic relationships occurring during VV-ECMO support membrane oxygenator exchange.

IoT-based mock oxygenator for extracorporeal membrane oxygenation simulator.

BACKGROUND: Training is an essential aspect of providing high-quality treatment and ensuring patient safety in any medical practice. Because extracorporeal membrane oxygenation (ECMO) is a complicated operation with various elements, variables, and irregular situations, doctors must be experienced and knowledgeable about all conventional protocols and emergency procedures. The conventional simulation approach has a number of limitations. The approach is intrinsically costly since it relies on disposable medical equipment (i.e., oxygenators, heat exchangers, and pumps) that must be replaced regularly due to the damage caused by the liquid used to simulate blood. The oxygenator, which oxygenates the blood through a tailored membrane in ECMO, acts as a replacement for the patient's natural lung. For the context of simulation-based training (SBT) oxygenators are often expensive and cannot be recycled owing to contamination issues. METHODS: Consequently, it is advised that the training process include a simulated version of oxygenators to optimize reusability and decrease training expenses. Toward this goal, this article demonstrates a mock oxygenator for ECMO SBT, designed to precisely replicate the real machine structure and operation. RESULTS: The initial model was reproduced using 3D modeling and printing. Additionally, the mock oxygenator could mimic frequent events such as pump noise and clotting. Furthermore, the oxygenator is integrated with the modular ECMO simulator using cloud-based communication technology that goes in hand with the internet of things technology to provide remote control via an instructor tablet application. CONCLUSIONS: The final 3D modeled oxygenator body was tested and integrated with the other simulation modules at Hamad Medical Corporation with several participants to evaluate the effectiveness of the training session.

Cardiopulmonary Bypass Emergencies and Intraoperative Issues.

Cardiopulmonary bypass (CPB) is a complex biomechanical engineering undertaking and an essential component of cardiac surgery. However, similar to all complex bioengineering systems, CPB activities are prone to a variety of safety and biomechanical issues. In this narrative review article, the authors discuss the preventative and intraoperative management strategies for a number of intraoperative CPB emergencies, including cannulation complications (dissection, malposition, gas embolism), CPB equipment issues (heater-cooler failure, oxygenator issues, electrical failure, and tubing rupture), CPB circuit thrombosis, medication issues, awareness during CPB, and CPB issues during transcatheter aortic valve replacement.

Novel hybrid total artificial heart with integrated oxygenator.

There continues to be an unmet therapeutic need for an alternative treatment strategy for respiratory distress and lung disease. We are developing a portable cardiopulmonary support system that integrates an implantable oxygenator with a hybrid, dual-support, continuous-flow total artificial heart (TAH). The TAH has a centrifugal flow pump that is rotating about an axial flow pump. By attaching the hollow fiber bundle of the oxygenator to the base of the TAH, we establish a new cardiopulmonary support technology that permits a patient to be ambulatory during usage. In this study, we investigated the design and improvement of the blood flow pathway from the inflow-to-outflow of four oxygenators using a mathematical model and computational fluid dynamics (CFD). Pressure loss and gas transport through diffusion were examined to assess oxygenator design. The oxygenator designs led to a resistance-driven pressure loss range of less than 35 mmHg for flow rates of 1-7 L/min. All of the designs met requirements. The configuration having an outside-to-inside blood flow direction was found to have higher oxygen transport. Based on this advantageous flow direction, two designs (Model 1 and 3) were then integrated with the axial-flow impeller of the TAH for simulation. Flow rates of 1-7 L/min and speeds of 10,000-16,000 RPM were analyzed. Blood damage studies were performed, and Model 1 demonstrated the lowest potential for hemolysis. Future work will focus on developing and testing a physical prototype for integration into the new cardiopulmonary assist system.

Nitric Oxide on Extracorporeal Life Support-Circuit Modifications for a Safe Therapy.

Nitric oxide (NO) incorporation into the sweep gas of the extracorporeal life support (ECLS) circuit has been proposed as a strategy to ameliorate the insults caused by the systemic inflammatory response. This technical study describes circuit modifications allowing nitric oxide to be incorporated into the circuit and describing and validating the oxygenator sweep flow rates necessary to achieve consistent safe delivery of the therapy. For patients requiring sweep rates less than 2 L/min, a simplified setup, incorporating a pressure relief valve/low flow meter in the gas delivery line, was placed in line between the blender/NO injector module and the NO sampling port/oxygenator. This setup allows titration of sweep to low flows without the need to blend in CO2 while maintaining the manufacturer recommendation of a minimum 2 L/min of sweep gas to safely deliver NO without nitric dioxide (NO2) buildup. This setup was tested three times at three different FiO2 rates and eleven different desired low sweep flows to test for reproducibility and safety to build an easy-to-follow chart for making gas flow changes. For patients requiring oxygenator sweep rates greater than 2 L/min, the pressure relief valve/low flow meter apparatus is not needed. Maintaining consistent sweep rate and nitric oxide delivery is required in order to utilize this therapy in ECLS. We demonstrated gas delivery across all flow rates. There were no issues delivering 20 parts per million of NO and negligible NO2 detection. The results from testing this setup were used to provide the specialist a chart at which to set the low flow meter to produce the desired flow rate at which the patient needs. This has been used clinically on 15 ECLS patients with success.

Alagille Syndrome and Repeat Oxygenator Failure during Cardiopulmonary Bypass: A Word of Caution.

Alagille syndrome is an autosomal dominant disorder that is caused by heterozygous mutation of JAG1 or NOTCH2 gene that impacts several multisystem organs including but may not be limited to the liver, heart, musculoskeletal, skin, and the eyes. The most common congenital heart defect associated with Alagille syndrome is multilevel right ventricular outflow tract obstruction with multiple central and peripheral branch pulmonary arterial stenoses occurring in up to two-thirds of these patients. We report two cases of Alagille syndrome who underwent extensive pulmonary arterial branch rehabilitation and experienced unusual oxygenator failure during cardiopulmonary bypass (CPB). We present lessons learned from these two cases and the changes that we implemented in our practice that facilitated smooth conduct of CPB in other cases that we performed subsequently.

Alterations in Pre/Post Oxygenator Flows Due to Fibrin Deposition in the CardioHelp System-A Case Report.

We present a 62-year-old patient with COVID-19 pneumonia on Veno-venous (VV) Extracorporeal Membrane Oxygenation (ECMO) with unique perturbations to pre and post oxygenator pressures due to fibrin deposition in despite being on a Heparin/Bivalirudin infusion and activated Partial Thromboplastin Time (aPTT) within therapeutic range of 60-80 seconds. On Day 8 of ECMO support, it was noticed that flows steadily decreased despite unchanged RPMs. Unlike typical blood flow to circuit pressure relationships, the circuit pressures did not correlate with the observed decreased flow. The Delta Pressure (ΔP) was not elevated. The patient's vitals were stable. On inspection post change-out, clots were noted in the oxygenator outlets. Oxygenator clots are usually associated with increased ΔP. In this scenario, clots in the oxygenator blocked 1 of the 4 outlets in the oxygenator causing the flow, pressures, and ΔP to drop consecutively. Due to reduced flow, the ΔP was not elevated despite extensive clots. The fibrin clot location in the CardioHelp ECMO circuit may lead to unexpected pressure and flow alterations. Sole reliance on ΔP as a marker for oxygenator clots may be misleading. Careful monitoring and timely diagnosis of coagulation status may lead to changes in anticoagulation goals and meaningfully impact patient outcomes.

Fraction of expired oxygen: an additional safety approach to monitor oxygen delivery to the heart lung machine oxygenator.

BACKGROUND: Monitoring oxygen delivery to the oxygenator of a heart lung machine (HLM) is typically accomplished with an O2 analyzer connected to the gas inflow line. It is assumed when the FiO2 is greater than 21% that oxygen is being delivered to the oxygenator. However, this assumption is imperfect because the connection of the inflow line to the oxygenator is downstream from the O2 analyzer. FiO2 monitoring will not alert the perfusionist if the inflow line is not actually connected to the oxygenator. Measuring the fraction of expired oxygen (FEO2) is a more reliable way of monitoring O2 delivery. METHODS: An O2 analyzer was placed on the scavenging line that is attached to the exhaust port of oxygenator (FEO2). RESULTS: Whenever the FiO2 is greater than 21%, and the inflow line is properly connected, the FEO2 exiting the oxygenator is greater than 21%. The FEO2 falls to 21% when the inflow line is not functioning. CONCLUSION: Monitoring the FEO2 is a more reliable way to verify O2 delivery to an oxygenator. An alarm can be set on the FEO2 monitor to alert the perfusionist if the FEO2 falls below a predetermined threshold so any issue with O2 delivery will always be recognized.

Effect of Nitric Oxide via Cardiopulmonary Bypass on Ventilator-Free Days in Young Children Undergoing Congenital Heart Disease Surgery: The NITRIC Randomized Clinical Trial.

Importance: In children undergoing heart surgery, nitric oxide administered into the gas flow of the cardiopulmonary bypass oxygenator may reduce postoperative low cardiac output syndrome, leading to improved recovery and shorter duration of respiratory support. It remains uncertain whether nitric oxide administered into the cardiopulmonary bypass oxygenator improves ventilator-free days (days alive and free from mechanical ventilation). Objective: To determine the effect of nitric oxide applied into the cardiopulmonary bypass oxygenator vs standard care on ventilator-free days in children undergoing surgery for congenital heart disease. Design, Setting, and Participants: Double-blind, multicenter, randomized clinical trial in 6 pediatric cardiac surgical centers in Australia, New Zealand, and the Netherlands. A total of 1371 children younger than 2 years undergoing congenital heart surgery were randomized between July 2017 and April 2021, with 28-day follow-up of the last participant completed on May 24, 2021. Interventions: Patients were assigned to receive nitric oxide at 20 ppm delivered into the cardiopulmonary bypass oxygenator (n = 679) or standard care cardiopulmonary bypass without nitric oxide (n = 685). Main Outcomes and Measures: The primary end point was the number of ventilator-free days from commencement of bypass until day 28. There were 4 secondary end points including a composite of low cardiac output syndrome, extracorporeal life support, or death; length of stay in the intensive care unit; length of stay in the hospital; and postoperative troponin levels. Results: Among 1371 patients who were randomized (mean [SD] age, 21.2 [23.5] weeks; 587 girls [42.8%]), 1364 (99.5%) completed the trial. The number of ventilator-free days did not differ significantly between the nitric oxide and standard care groups, with a median of 26.6 days (IQR, 24.4 to 27.4) vs 26.4 days (IQR, 24.0 to 27.2), respectively, for an absolute difference of -0.01 days (95% CI, -0.25 to 0.22; P = .92). A total of 22.5% of the nitric oxide group and 20.9% of the standard care group developed low cardiac output syndrome within 48 hours, needed extracorporeal support within 48 hours, or died by day 28, for an adjusted odds ratio of 1.12 (95% CI, 0.85 to 1.47). Other secondary outcomes were not significantly different between the groups. Conclusions and Relevance: In children younger than 2 years undergoing cardiopulmonary bypass surgery for congenital heart disease, the use of nitric oxide via cardiopulmonary bypass did not significantly affect the number of ventilator-free days. These findings do not support the use of nitric oxide delivered into the cardiopulmonary bypass oxygenator during heart surgery. Trial Registration: anzctr.org.au Identifier: ACTRN12617000821392.

Haemodynamics and cerebral oxygenation of neonatal piglets in the immediate ex utero period supported by mechanical ventilation or ex utero oxygenator.

KEY POINTS: The margin of human viability has extended to the extremes of gestational age (<24 weeks) when the lungs are immature and ventilator-induced lung injury is common. Artificial placenta technology aims to extend gestation ex utero in order to allow the lungs additional time to develop prior to entering an air-breathing environment. We compared the haemodynamics and cerebral oxygenation of piglets in the immediate period post-oxygenator (OXY) transition against both paired in utero measures and uniquely against piglets transitioned onto mechanical ventilation (VENT). Post-transition, OXY piglets became hypotensive with reduced carotid blood flow in comparison with both paired in utero measures and VENT piglets. The addition of a pump to the oxygenator circuit may be required to ensure haemodynamic stability in the immediate post-transition period. ABSTRACT: Gestational age at birth is a major predictor of wellbeing; the lower the gestational age, the greater the risk of mortality and morbidity. At the margins of human viability (<24 weeks gestation) immature lungs combined with the need for early ventilatory support means lung injury and respiratory morbidity is common. The abrupt haemodynamic changes consequent on birth may also contribute to preterm-associated brain injury, including intraventricular haemorrhage. Artificial placenta technology aims to support oxygenation, haemodynamic stability and ongoing fetal development ex utero until mature enough to safely transition to a true ex utero environment. We aimed to characterize the impact of birth transition onto either an oxygenator circuit or positive pressure ventilation on haemodynamic and cerebral oxygenation of the neonatal piglet. At 112 days gestation (term = 115 days), fetal pigs underwent instrumentation surgery and transitioned onto either an oxygenator (OXY, n = 5) or ventilatory support (VENT, n = 8). Blood pressure (BP), carotid blood flow and cerebral oxygenation in VENT piglets rose from in utero levels to be significantly higher than OXY piglets post-transition. OXY piglet BP, carotid blood flow and carotid oxygen delivery (DO2 ) decreased from in utero levels post-transition; however, cerebral regional oxygen saturation (rSO2 ) was maintained at fetal-like levels. OXY piglets became hypoxaemic and retained CO2 . Whether OXY piglets are able to maintain cerebral rSO2 under these conditions for a prolonged period is yet to be determined. Improvements to OXY piglet oxygenation may lie in maintaining piglet BP at in utero levels and enhancing oxygenator circuit flow.