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.

Hematic Antegrade Repriming Reduces Emboli on Cardiopulmonary Bypass: A Randomized Controlled Trial.

Particulate and gaseous microemboli (GME) are side effects of cardiac surgery that interfere with postoperative recovery by causing endothelial dysfunction and vascular blockages. GME sources during surgery are multiple, and cardiopulmonary bypass (CPB) is contributory to this embolic load. Hematic antegrade repriming (HAR) is a novel procedure that combines the benefits of repriming techniques with additional measures, by following a standardized procedure to provide a reproducible hemodilution of 300 ml. To clarify the safety of HAR in terms of embolic load delivery, a prospective and controlled study was conducted, by applying Doppler probes to the extracorporeal circuit, to determine the number and volume of GME released during CPB. A sample of 115 patients (n = 115) was considered for assessment. Both groups were managed under strict normothermia, and similar clinical conditions and protocols, receiving the same open and minimized circuit. Significant differences in GME volume delivery (control group [CG] = 0.28 ml vs. HAR = 0.08 ml; p = 0.004) and high embolic volume exposure (>1 ml) were found between the groups (CG = 30.36% vs. HAR = 4.26%; p = 0.001). The application of HAR did not represent an additional embolic risk and provided a four-fold reduction in the embolic volume delivered to the patient (coefficient, 0.24; 95% CI, 0.08-0.72; p = 0.01), which appears to enhance GME clearance of the oxygenator before CPB initiation.

Thrombosis in Extracorporeal Membrane Oxygenation (ECMO) Circuits.

Thrombosis in extracorporeal membrane oxygenation (ECMO) circuits remains a frequent complication. We characterize the location, extent, structure, and clinical implications of thrombi in 53 ECMO circuits from 46 pediatric patients. The tubing, pump, and oxygenator were examined for visible thrombi. Representative samples of thrombi were collected for histologic, immunofluorescence, and immunohistochemical analysis. Thrombi were found in 81% of ECMO circuits. The most clinically significant were inflow oxygenator membrane surface thrombi (11% of circuits), arterial tubing thrombi (30%), and venous tubing (26%) or connector thrombi (26%). Oxygenator membrane surface thrombi resulted in rapidly increasing delta pressure across the oxygenator over 1-2 days, oxygenator failure, and circuit replacement. Oxygenator membrane surface thrombi were associated with intravascular venous thrombosis and bacterial infection before starting ECMO. Arterial cannula/tubing thrombi led in one case to aortic and mesenteric artery thrombosis followed by bowel infarction. In 11% of cases, venous tubing thrombi grew large enough to break off and embolize to the pump, resulting in increased hemolysis. Antifibrinolytic therapy during ECMO was associated with an increased risk of pump thromboembolism. Other less clinically significant thrombi included pump axle thrombi with thrombus fragments trapped in the oxygenator (45%), and deep oxygenator membrane thrombi (15%). Examination of ECMO circuits after removal is a useful quality improvement tool that can elucidate the cause of circuit problems, indicate patients at increased risk of thrombosis, and suggest areas for possible improvements.

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.

Particulate generation with different oxygen delivery devices.

BACKGROUND: The Coronavirus pandemic has a high mortality rate in patients that are mechanically ventilated, which has led to an ever increasing interest in noninvasive forms of oxygenation. The use of these devices has the theoretical risk of increased exposure risk because of possible particulate generation. This study aimed to quantify the particulate generation associated with different oxygen devices. METHODS: This was a prospective single center study conducted during September 2020 using ten healthy adult volunteers. Testing was conducted in a negative pressure hospital room using a light scattering particle counter. The oxygen devices used were a nasal cannula, an OxyMask™, a non-rebreathing mask, and a high flow system. Particle measurements were obtained at baseline in the room and then with each oxygen delivery device and pre-specified oxygen flow rates. These measurements were obtained different distances from the volunteer with their mouth open. A Wilcoxon/Kruskal-Wallis test was performed on each separate oxygen modality with all flow rates as one model. RESULTS: The particle concentrations were slightly non-significantly increased with the OxyMask™ and non-rebreathing mask at the closest distance measured. As the distance increased, these counts decreased closer to ambient levels. The nasal cannula and high flow nasal cannula particle counts were not significantly different from ambient measurements at either distance. CONCLUSION: Nasal cannula, OxyMask™, non-rebreathing mask, and high flow oxygen did not generate any additional aerosols or droplets above a baseline room measurement, but further studies are necessary to determine infectious risk.

Nitric oxide added to the sweep gas of the oxygenator during cardiopulmonary bypass in infants: A pilot randomized controlled trial.

Our objective was to assess the effect of nitric oxide added to the sweep gas of the oxygenator during cardiopulmonary bypass (CPB) in infants on platelet count, platelet function, clinical outcomes, and safety. A randomized, double-blinded, placebo-controlled clinical trial in infants less than a year of age undergoing cardiac surgery requiring CPB was undertaken. Nitric oxide at a dose of 20 ppm was added to the sweep gas in the treatment group. Blood was collected at baseline and prior to separation from CPB to measure platelet count and function as determined by responsiveness to specific agonists. Clinical outcomes were observed through hospital discharge. Methemoglobin levels were measured preoperatively, at the conclusion of CPB, and upon admission to the ICU. Forty patients consented and were randomized in the trial. Eighteen patients were randomized to the treatment group and 22 were included in the placebo group. The groups were similar in terms of age, weight, gender, and surgical complexity. No significant differences were found in measures of platelet count, platelet response to agonist, or clinical outcomes. Patients in the treatment group had higher methemoglobin levels after receiving nitric oxide, but no levels approached toxicity (maximum 2.4%). Nitric oxide added to the sweep gas of the oxygenator during CPB in infants did not have an appreciable effect on the preservation of platelet count, platelet responsiveness to agonist, or clinical outcomes. Methemoglobin levels were increased after receiving nitric oxide but were far below a toxic level of 15%.

Acute oxygenator occlusion in two cases of polycythemia vera: Bailout strategies.

Polycytemia vera (PV) is a rare myeloproliferative neoplasm associated with microcirculatory disturbances, thrombosis and bleeding. Patients suffering from PV have a high risk of perioperative adverse events, but the literature regarding on-pump procedures in PV patients is scarce. We report two cases of acute and severe oxygenator failure during cardiopulmonary bypass and present valid exit scenarios.

Administration of mesenchymal stem cells during ECMO results in a rapid decline in oxygenator performance.

Mesenchymal stem cells (MSCs) have attracted attention as a potential therapy for Acute Respiratory Distress Syndrome (ARDS). At the same time, the use of extracorporeal membrane oxygenation (ECMO) has increased among patients with severe ARDS. To date, early clinical trials of MSCs in ARDS have excluded patients supported by ECMO. Here we provide evidence from an ex-vivo model of ECMO to suggest that the intravascular administration of MSCs during ECMO may adversely impact the function of a membrane oxygenator. The addition of clinical grade MSCs resulted in a reduction of flow through the circuit in comparison to controls (0.6 ±0.35 L min-1vs 4.12 ± 0.03 L min-1, at 240 minutes) and an increase in the transoygenator pressure gradient (101±9 mmHg vs 21±4 mmHg, at 240 minutes). Subsequent immunohistochemistry analysis demonstrated quantities of MSCs highly adherent to membrane oxygenator fibres. This study highlights the potential harm associated with MSC therapy during ECMO and suggests further areas of research required to advance the translation of cell therapy in this population.

Effects of Pulsatile Control Algorithms for Diagonal Pump on Hemodynamic Performance and Hemolysis.

The objective of this study is to compare hemodynamic performances under different pulsatile control algorithms between Medos DeltaStream DP3 and i-cor diagonal pumps in simulated pediatric and adult ECLS systems. An additional pilot study was designed to test hemolysis using two pumps during 12h-ECLS. The experimental circuit consisted of parallel combined pediatric and adult ECLS circuits using an i-cor pump head and either an i-cor console or Medos DeltaStream MDC console, a Medos Hilite 2400 LT oxygenator for the pediatric ECLS circuit, and a Medos Hilite 7000 LT oxygenator for the adult ECLS circuit. The circuit was primed with lactated Ringer's solution and human packed red blood cells (hematocrit 40%). Trials were conducted at various flow rates (pediatric circuit: 0.5 and 1L/min; adult circuit: 2 and 4L/min) under nonpulsatile and pulsatile modes (pulsatile amplitude: 1000-5000rpm [1000 rpm increments] for i-cor pump, 500-2500rpm [500 rpm increments] for Medos pump) at 36°C. In an additional protocol, fresh whole blood was used to test hemolysis under nonpulsatile and pulsatile modes using the two pump systems in adult ECLS circuits. Under pulsatile mode, energy equivalent pressures (EEP) were always greater than mean pressures for the two systems. Total hemodynamic energy (THE) and surplus hemodynamic energy (SHE) levels delivered to the patient increased with increasing pulsatile amplitude and decreased with increasing flow rate. The i-cor pump outperformed at low flow rates, but the Medos pump performed superiorly at high flow rates. There was no significant difference between two pumps in percentage of THE loss. The plasma free hemoglobin level was always higher in the Medos DP3 pulsatile group at 4 L/min compared to others. Pulsatile control algorithms of Medos and i-cor consoles had great effects on pulsatility. Although high pulsatile amplitudes delivered higher levels of hemodynamic energy to the patient, the high rotational speeds increased the risk of hemolysis. Use of proper pulsatile amplitude settings and intermittent pulsatile mode are suggested to achieve better pulsatility and decrease the risk of hemolysis. Further optimized pulsatile control algorithms are needed.

Epoprostenol for the treatment of increasing oxygenator pressure drop during cardiopulmonary bypass. A case report.

A change of oxygenator during cardiopulmonary bypass is a technically high-risk procedure with potential for a serious adverse event for the patient. This case report describes a case of increased pressure drop and pre-oxygenator blood pressure during cardiopulmonary bypass successfully treated with pre-oxygenator-administered epoprostenol.

Use of Volatile Anesthetic Agent in Extracorporeal Circuit as a Cause of Break in Polycarbonate Connector-Lessons Learnt.

Mishaps, near misses, and lethal incidents are known to occur during cardiopulmonary bypass. We share one such rare case of break in polycarbonate connector because of the use of isoflurane in extracorporeal circuit and its successful management.

An In-Vitro Study Comparing the GME Handling of Two Contemporary Oxygenators.

Gaseous microemboli (GME) are a potential complication of cardiopulmonary bypass (CPB). Though it is difficult to prove that GME is the only major cause of neurological deficits, it may increase the chance of post-operative cognitive dysfunction if not removed. The objectives of this research were to compare LivaNova-Sorin Inspire (Inspire) oxygenator with a Medtronic arterial filter to the Medtronic Fusion (Fusion) oxygenator with and without a Medtronic arterial filter based on each system's ability to handle GME. The Inspire and Fusion systems were evaluated in vitro. GME handling was observed by introducing air in the sampling manifold connected to the venous return at a 60 mL bolus or 1 liter per minute (LPM). The emboli detection and classification (EDAC) system measured GME preand post-oxygenator/arterial filter. The Inspire with a filter was able to remove a statistically significant greater amount of total emboli per second during the 60 mL bolus and 1 LPM tests than the Fusion with and without an arterial filter. The Inspire with an arterial filter was more efficient in removing GME during a 60 mL bolus and 1 LPM than the Fusion and Fusion with an arterial filter. However, the Fusion with an arterial filtered performed better than the Fusion system without the arterial filter.

Clinical evaluation of the air-handling properties of contemporary oxygenators with integrated arterial filter.

Gaseous microemboli (GME) may originate from the extracorporeal circuit and enter the arterial circulation of the patient. GME are thought to contribute to cerebral deficit and to adverse outcome after cardiac surgery. The arterial filter is a specially designed component for removing both gaseous and solid microemboli. Integration of an arterial filter with an oxygenator is a contemporary concept, reducing both prime volume and foreign surface area. This study aims to determine the air-handling properties of four contemporary oxygenator devices with an integrated arterial filter. Two oxygenator devices, the Capiox FX25 and the Fusion, showed significant increased volume of GME reduction rates (95.03 ± 3.13% and 95.74 ± 2.69%, respectively) compared with both the Quadrox-IF (85.23 ± 5.84%) and the Inspire 6F M (84.41 ± 12.93%). Notably, both the Quadrox-IF and the Inspire 6F M as well as the Capiox FX 25 and the Fusion showed very similar characteristics in volume and number reduction rates and in detailed distribution properties. The Capiox FX25 and the Fusion devices showed significantly increased number and volume reduction rates compared with the Quadrox-IF and the Inspire 6F M devices. Despite the large differences in design of all four devices, our study results suggest that the oxygenator devices can be subdivided into two groups based on their fibre design, which results in screen filter (Quadrox-IF and Inspire 6F M) and depth filter (Capiox FX25 and Fusion) properties. Depth filter properties, as present in the Capiox FX25 and Fusion devices, reduced fractionation of air and may ameliorate GME removal.

Acute oxygenator failure: a new presentation of heparin-induced thrombocytopenia in a patient undergoing venovenous extracorporeal membrane oxygenation support.

A 58-year-old man with medical history of thrombocytopenia was admitted to an outside hospital for a 6-day history of worsening dyspnoea requiring mechanical ventilator support. He was transferred to our institution for extracorporeal membrane oxygenation (ECMO) given his refractory hypoxaemia. On arrival, H1N1 influenza virus was confirmed and all measures to improve oxygenation were ineffective. Thus, the decision was made to start venovenous (VV)-ECMO. Although a low baseline platelet count was recognised (60-70×109/L), a sudden further decrease occurred (30×109/L) and platelet transfusion was initiated. A substantial increase in the pressure across the ECMO oxygenator was identified, and the diagnosis of type II heparin-induced thrombocytopenia was suspected and confirmed. Heparin was discontinued, the oxygenator was exchanged and argatroban was used for anticoagulation. After 28 days on VV-ECMO support, the decision was made to withdraw organ support in conjunction with the patient and family wishes.

Removal of Gross Air Embolization from Cardiopulmonary Bypass Circuits with Integrated Arterial Line Filters: A Comparison of Circuit Designs.

Advances in technology, the desire to minimize blood product transfusions, and concerns relating to inflammatory mediators have lead many practitioners and manufacturers to minimize cardiopulmonary bypass (CBP) circuit designs. The oxygenator and arterial line filter (ALF) have been integrated into one device as a method of attaining a reduction in prime volume and surface area. The instructions for use of a currently available oxygenator with integrated ALF recommends incorporating a recirculation line distal to the oxygenator. However, according to an unscientific survey, 70% of respondents utilize CPB circuits incorporating integrated ALFs without a path of recirculation distal to the oxygenator outlet. Considering this circuit design, the ability to quickly remove a gross air bolus in the blood path distal to the oxygenator may be compromised. This in vitro study was designed to determine if the time required to remove a gross air bolus from a CPB circuit without a path of recirculation distal to the oxygenator will be significantly longer than that of a circuit with a path of recirculation distal to the oxygenator. A significant difference was found in the mean time required to remove a gross air bolus between the circuit designs (p = .0003). Additionally, There was found to be a statistically significant difference in the mean time required to remove a gross air bolus between Trial 1 and Trials 4 (p = .015) and 5 (p =.014) irrespective of the circuit design. Under the parameters of this study, a recirculation line distal to an oxygenator with an integrated ALF significantly decreases the time it takes to remove an air bolus from the CPB circuit and may be safer for clinical use than the same circuit without a recirculation line.

Oxygenator safety evaluation: a focus on connection grip strength and arterial temperature measurement accuracy.

This report describes the assessment of three specific safety-related specifications in the consideration of an alternate oxygenator; first the grip strength relationship between various oxygenator connectors and SMARxT tubing, second, the grip strength of various biopassive tubings and an isolated SMARxT connector, and finally, the accuracy of the arterial outlet temperature measurement. Grip strength experiments for the connections between the SMARxT tubing and the venous reservoir outlet and the oxygenator venous inlet and oxygenator arterial outlet of the Medtronic Affinity, Sorin Synthesis, Sorin Primox, and Terumo Capiox RX25 oxygenators were performed. In addition we compared the grip strength of polyvinyl chloride, Physio, Trillium, Carmeda, X-Coating, and SMARxT tubing. The accuracy of the integrated arterial outlet temperature probes was determined by comparing the temperatures measured by the integrated probe with a precision reference thermometer. Connector grip strength comparisons for the evaluation oxygenators with SMARxT tubing showed significant variation between oxygenators and connections (p = .02). Evaluation of the arterial outlet showed significant variation between evaluation oxygenators, while at the venous reservoir outlet and oxygenator inlet, there were no significant differences. Grip strength comparison data for the various tubing types demonstrated a main effect for tubing type F(5, 18) = 8.01, p = .002, eta(p)(2) = .77. Temperature accuracy measurements demonstrated that all oxygenators overread the arterial outlet temperature at 15 degrees C, whilst at temperatures > or = 25 degrees C, all oxygenators underread the arterial outlet temperature. The integrity of SMARxT tubing connection is influenced by the connector type, and may decline over time, highlighting the importance to not consider interchanging components of the bypass circuit as inconsequential.

Clinical evaluation of new generation oxygenators with integrated arterial line filters for cardiopulmonary bypass.

New generation oxygenators with integrated arterial line filters have been marketed to improve the efficacy of cardiopulmonary bypass (CPB). Differences in designs, materials, coating surfaces, pore size of arterial filter, and static prime exist between the oxygenators. Despite abundant preclinical data, literature lacks clinical studies. From September 2010 to March 2011, 80 consecutive patients were randomized to CPB using Terumo Capiox FX25 (40 patients, Group-T) or Sorin Synthesis (40 patients, Group-S) oxygenators. Pressure drop and gas exchange efficacy were registered during CPB. High-sensitivity C-reactive protein (hs-CRP), white blood cells (WBCs), fluid balance, activated clotting time, international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, platelets (PLTs), serum albumin, and total proteins were measured perioperatively at different timepoints. Clinical outcome was recorded. Repeated measure analysis of variance and nonparametric statistics assessed between-groups and during time differences. The two groups showed similar baseline and intraoperative variables. No differences were recorded in pressure drop and gas exchange (group-P and group*time-P = N.S. for all) during CPB. Despite similar fluid balance (P = N.S. for static/dynamic priming and ΔVolume administered intraoperatively), Group-T showed higher hs-CRP (group-P = 0.034), aPTT (group-P = 0.0001), and INR (group-P= 0.05), with lower serum albumin (group-P = 0.014), total proteins (group-P = 0.0001), fibrinogen (group-P = 0.041), and PLTs (group-P = 0.021). Group-T also showed higher postoperative bleeding (group-P = 0.009) and need for transfusions (P = 0.008 for packed red cells and P = 0.0001 for fresh frozen plasma and total transfused volumes). However, clinical outcome was comparable (P = N.S. for all clinical endpoints). Both oxygenators proved effective and resulted in comparable clinical outcomes. However, Sorin Synthesis seems to reduce inflammation and better preserve the coagulative cascade and serum proteins, resulting in lower transfusions and post-CPB inflammatory response.

Improving oxygenator performance using computational simulation and flow field-based parameters.

Current goals in the development of oxygenators are to reduce extrinsic surface contact area, thrombus formation, hemolysis, and priming volume. To achieve these goals and provide a favorable concentration gradient for the gas exchange throughout the fiber bundle, this study attempts to find an optimized inlet and outlet port geometry to guide the flow of a hexagonal-shaped oxygenator currently under development. Parameters derived from numerical flow simulations allowed an automated quantitative evaluation of geometry changes of flow distribution plates. This led to a practical assessment of the quality of the flow. The results were validated qualitatively by comparison to flow visualization results. Two parameters were investigated, the first based on the velocity distribution and the second calculated from the residence time of massless particles representing erythrocytes. Both approaches showed significant potential to improve the flow pattern in the fiber bundle, based on one of the parameters of up to 66%. Computational fluid dynamics combined with a parameterization proved to be a powerful tool to quickly improve oxygenator designs.