Use of novel oxygenated right ventricular assist device hybrid ECLS for adolescents with refractory hypoxemic respiratory dailure due to Covid-19 pneumonia

Objectives: To describe institutional experience using Oxygenated Right Ventricular Assist Device (OxyRVAD) Hybrid ECLS for adolescents with respiratory failure due to SARS-CoV-2 pneumonia. Method(s): Between September and December 2021, 44 Covid-19+ patients were admitted to our regional Pediatric Intensive Care Unit (PICU), including 4 adolescents who required Extracorporeal life support (ECLS) due to refractory hypoxemia. Two patients were initially cannulated onto Veno-Venous (VV) ECLS and converted to Oxy-RVAD ECLS due to refractory hypoxemia;the others were cannulated directly onto Oxy-RVAD ECLS. Two patients had observed right ventricular (RV) dysfunction or failure on echocardiography. Cannulations were performed in the cardiac catheterization suite by an interventional cardiologist using percutaneous technique under fluoroscopy. Circuit construction was varied and included the use of a dedicated RVAD cannula or standard cannula used for VA/VV ECLS. All patients were connected to Cardiohelp systems with built in centrifugal pumps and oxygenators. Result(s): Two patients were initially placed on VV-ECLS and converted to Oxy-RVAD ECLS days into their course due to severe, refractory hypoxemia with one having improvement in hypoxemia after the conversion. Two patients received renal replacement therapy (RRT) without complications, the others did not have indications for renal support. Two patients underwent tracheostomy on ECMO though none were able to separate from mechanical ventilation. Three patients survived to discharge. No incidents of circuit air or clotting were noted. The patient with the longest ECLS run required one circuit change and was the only patient to develop a superinfection: a successfully-treated fungal infection. All patients were mobilized on ECLS to sitting in a chair;one was able to ambulate. Conclusion(s): Oxy-RVAD hybrid ECLS can be used to effectively support adolescents with severe respiratory disease from conditions associated with RV dysfunction. Pediatric providers can collaborate with adult critical care colleagues to use novel methods to support these patients. RRT can also be used with this circuit. While more experience and data on this modality is needed, Oxy-RVAD ECLS should be considered in patients with severe RV dysfunction and associated refractory hypoxemia. (Figure Presented).

Prolonged oxygenator usage for VV ECMO for COVID ARDS: A clinical experience

Objectives: Its known that with the prolonged use of ECMO, because of the thrombogenic activations -minor/majorclot formations may ocur at the oxygenator and eventually it fails to function properly. Physicians take some precautions to prevent or postpone this process but usually exchange the circuit. In this study we share our follow up strategy and prolonged oxygenator use for the COVID-ARDS patients. Method(s): A total of 68 patients who were followed more than 7 days were included in this study. Sorin/LivaNova oxygenators and VV-ECMO circuit were used for all of the patients. Bivaluridin infusion was used for routine anticoagulation protocol. Result(s): Mean age of the patients was 44.1 +/-12.2 years. The patients were followed for a total of 2705 days with a total of 103 oxygenators [mean 26.2 +/-18.3(104-7) days for per oxygenator] Mean duration of ECMO support was 40.3 +/-24.4 days . The oxygenator use per patient was 1.5 +/-0.89. There was no major hypoxic period experience for the patients. Survival rate was 43.2 %. Conclusion(s): With using bivaluridin for anticoagulation, daily washing of oxygenators and close follow up methods we can protect the oxygenators and use them for longer periods safely like in our experience which can save us from serious additional costs and interventions.

Use of Carboxyhemoglobin as an Early Sign of Oxygenator Dysfunction in Patients Supported by Extracorporeal Membrane Oxygenation.

Introduction: Plasma free hemoglobin is the gold standard for monitoring hemolysis in extracorporeal membrane oxygenation (ECMO) but its routine use has some limitations. Carboxyhemoglobin (HbCO) is also a marker of intravascular hemolysis. We aimed to investigate HbCO as a marker of both hemolysis and oxygenator dysfunction in patients supported by ECMO. Methods: Retrospective analysis of patients on ECMO in an adult ICU in a tertiary hospital. HbCO was recorded every 6 h in the 48 h before and after oxygenator change in adult patients on ECMO support with an oxygenator dysfunction and replacement. Results: The investigation of 27 oxygenators replacements in 19 patients demonstrated that HbCO values progressively increased over time and then significantly decreased after oxygenator change. Median oxygenator lifespan was 14 days [interquartile range (IQR) 8-21] and there was no correlation between HbCO and oxygenator lifespan [Spearman coefficient 0.23 (p = 0.23)]. HbCO values at oxygenator change [HbCO median 2.7 (IQR 2.5-3.5)] were significantly higher than the HbCO values 1 week before [HbCO median 2.07 (IQR 1.86-2.8)] (p value < 0.001). Conclusion: Our data highlight the potential role of HbCO as a novel marker for ECMO oxygenator dysfunction.

Use of Novel Oxygenated Right Ventricular Assist Device Hybrid ECLS for Adolescents with Refractory Hypoxemic Respiratory Failure due to Covid-19 Pneumonia

Objective: To describe institutional experience using Oxygenated Right Ventricular Assist Device Oxy-RVAD) Hybrid ECLS for adolescents with respiratory failure due to SARS-CoV-2 pneumonia. Method(s): Between September and December 2021, 44 Covid-19+ patients were admitted to our regional Pediatric Intensive Care Unit (PICU) including 4 adolescents who required Extracorporeal life support (ECLS) due to refractory hypoxemia. Two patients were initially cannulated onto Veno-Venous (VV) ECLS and converted to Oxy-RVAD ECLS due to refractory hypoxemia;the others were cannulated directly onto Oxy-RVAD ECLS. Two patients had observed right ventricular dysfunction (RV) or failure on echocardiography. Cannulations were performed in the cardiac catheterization suite by an interventional cardiologist using percutaneous technique under fluoroscopy. Circuit construction was varied and included the use of a dedicated RVAD cannula or standard cannula used for VA/VV ECLS. All patients were connected to CardiohelpTM systems with built-in centrifugal pumps and oxygenators. Result(s): Two patients were initially placed on VV-ECLS and converted to Oxy-RVAD ECLS days into their course due to severe, refractory hypoxemia with one having improvement in hypoxemia after the conversion. Two patients were cannulated directly to Oxy-RVAD ECLS support. Two patients received renal replacement therapy (RRT) without complications, the others did not have indications for renal support. Two patients underwent tracheostomy on ECMO though none were able to separate from mechanical ventilation. Three patients survived to discharge. No incidents of circuit air or clotting were noted. The patient with the longest ECLS run required one circuit change and was the only patient to develop a superinfection: a successfully-treated fungal infection. All patients were mobilized on ECLS to sitting in a chair;one was able to ambulate. Conclusion(s): Oxy-RVAD hybrid ECLS can be used to effectively support adolescents with severe respiratory disease from conditions associated with RV dysfunction. Pediatric providers can collaborate with adult-focused colleagues to use novel methods to support these patients. RRT can also be used with this circuit. While more experience and data on this modality is needed, Oxy-RVAD ECLS should be considered in patients with severe RV dysfunction and associated refractory hypoxemia.

Resource Utilization in a Post-pandemic World

Extracorporeal Membrane Oxygenation is a resource intensive therapy;heavily reliant upon specialized equipment, unique disposables, and skilled staff. The Covid-19 pandemic and following events exposed flaws in multiple phases of the care delivery system. The combination of high patient census, acuity, manufacturing delays, and supply chain disruptions led to our center's reassessment of the way in which limited resources are utilized. As a combined pediatric and adult center, we possess the ability to share resources amongst all patient populations. Currently, the majority of our equipment and disposables support a heavier use of Centrimag. We adjusted our general weight guidelines in order to best serve the most patients. (<8kg Sorin Rollerhead, 8-20kg Sorin Revolution, >20kg Centrimag.) Presently, a major challenge is the cessation of production of the -inch Better Bladder. The ECMO Coordinator team collaborated with key physician stakeholders. It was decided that the fluid reservoir and air trap benefits of a bladder outweighed the risks of running without one on our Sorin Rollerhead circuit. We designed a circuit with a 3/8 Bigger Better Bladder. Recognizing the increased risk of clotting with the 3/8 segment, we added a post-oxygenator shunt. This allows for adequate blood flow to maintain circuit integrity, while limiting the amount of flow to the patient. The nationwide nursing shortage is well-known. Though our multidisciplinary ECMO Specialist Team supports nursing and respiratory therapy, the nursing shortage still impacts our staffing models, resulting in the inability to safely staff bedside nurses and ECMO specialists. At times of high census, ECMO patients are cohorted into one geographical location. This allows for a temporary 2:1 staffing model for Centrimag patients. Our goal remains to staff pediatric cases as a 1:1 ECMO Specialist assignment. The ability to obtain this is assessed shift to shift;factoring patient stability, experience of the ECMO specialist, and unit staffing. The collaboration with ICU Nurse Managers, Hospital Supervisors and Central Staffing Office is imperative to the success of staffing model alterations. Our ECMO department has increased its FTEs, implementing a core team to be preassigned to two ECMO beds. The objective is to alleviate the burden on ICU staffing, limiting the number of nurses pulled from staffing grids. In uncertain times, flexibility is vital. It is important to remain vigilant and proactive. Our ECMO program feels that continuous assessment of supplies, equipment, and open communication has been the key to successfully serving our patients.

ECMO Program Quality Improvement Through Educational Resources Amidst Pandemic Staffing Crisis

The COVID-19 pandemic tasked affected healthcare programs to find creative solutions for preserving staff competency amidst high staffing turnover, limited resources, and increased patient acuity. In 2022, our ECMO leadership team aimed to provide additional educational resources to our ECMO specialist team, without adding to the workload of staff burnout. Prior to 2020, our educational structure involved an extensive onboarding process for new ECMO specialists, quarterly hands-on drill simulations, and a yearly recertification exam. From 2020 to 2021, we saw a significant amount of turnover within our ECMO department amidst the pandemic. We ended 2020 with 36 specialists and 2021 with 18 specialists, hiring 12 new specialists. Our ECMO census continued to increase with 72 total runs and average daily census of 2.2 in 2021, up to 99 total runs and average daily census of 2.4 in 2022. 2021 ELSO data showed that 60% of our patient runs contained mechanical errors including air entrainment, cannula problems, circuit exchanges, oxygenator failure, and thrombosis. In order to support our staff with so many new specialists who are expected to care for a higher quantity of patients with more complex morbidities, at the same exceptional quality as our most senior staff, we provided a variety of additional educational resources in 2022. Visual aids were created for our 3 ECMO pumps including pump physiology, basic handling skills, emergencies, and advanced scenarios. We also created a pocket guide combining the educational information taught in the onboarding class with other various resources provided to our staff. ECMO staff members can keep the pocket guide to reference, and to add their own notes as needed. Lastly, a monthly newsletter sent to our staff, containing programmatic updates, educational tips and quizzes, reminders, and helpful links. After surveying our specialists at the end of 2022, we found that >80% of the specialists watch the videos before or during shifts, 100% watch the videos to prepare for water drills, and >80% own a pocket guide. 75% found the additional resources helpful to succeed in water drills and staying prepared to sit pump. Our 2022 ELSO data also showed a decrease to 43% of patient runs containing mechanical errors. MUSC is ELSO-designated platinum-level for both the pediatric and adult ECMO program, signifying the highest level of performance, innovation, satisfaction, and quality. Our goal is to use current practices combined with mentioned innovative strategies to retain this status in the upcoming year.

Novel Size-Variable Dedicated Rodent Oxygenator for ECLS Animal Models-Introduction of the "RatOx" Oxygenator and Preliminary In Vitro Results.

The overall survival rate of extracorporeal life support (ECLS) remains at 60%. Research and development has been slow, in part due to the lack of sophisticated experimental models. This publication introduces a dedicated rodent oxygenator ("RatOx") and presents preliminary in vitro classification tests. The RatOx has an adaptable fiber module size for various rodent models. Gas transfer performances over the fiber module for different blood flows and fiber module sizes were tested according to DIN EN ISO 7199. At the maximum possible amount of effective fiber surface area and a blood flow of 100 mL/min, the oxygenator performance was tested to a maximum of 6.27 mL O2/min and 8.2 mL CO2/min, respectively. The priming volume for the largest fiber module is 5.4 mL, while the smallest possible configuration with a single fiber mat layer has a priming volume of 1.1 mL. The novel RatOx ECLS system has been evaluated in vitro and has demonstrated a high degree of compliance with all pre-defined functional criteria for rodent-sized animal models. We intend for the RatOx to become a standard testing platform for scientific studies on ECLS therapy and technology.

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.

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.

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.

Mortality rate in patients with SAR-COV-2 infection treated with extracorporeal membrane oxygenator: A systematic review and meta-analysis.

BACKGROUND: Extracorporeal membrane oxygenator (ECMO) is one of the life-saving modalities for the treatment of multiple organs dysfunction, particularly the heart and the lungs. OBJECTIVE: To evaluate the benefit of ECMO for the treatment of SAR-COV-2 infection and its outcomes, complications, and mortality rate. METHODS: A comprehensive search for articles was performed using MEDLINE and SCOPUS from December 2019 to December 2020. Two independent reviewers selected eligible studies, extracted the data, assessed the quality of the studies, reviewed the full study protocols, and reported the findings according to the PRISMA protocol. The meta-analyses were performed using the Comprehensive Meta-Analysis software version 2.0. RESULTS: Pooled data from 57 studies was analyzed. There were 7,035 patients with SAR-COV-2 infection with event rate of ECMO treatment was 58.10% (95%CI: 43.70-71.20). The mortality rate was 16.66% (95%CI: 11.49-23.53). The mean mortality rate of ECMO supported patients was 35.60% (95%CI: 30.60 to 41.00). Thirty-one percent (95%CI: 24.50-38.40) of the patients had venous thromboembolic events, 30.90% (95%CI: 17.90-47.80) of the patients had ECMO circuit thrombosis, and 24.50% (95%CI: 12.50-42.40) of the patients had bleeding. In the subgroup analysis, the mortality rate was higher among patients who were treated with ECMO, the pooled odds ratio was 4.47 (95%CI: 2.39-8.35, p < 0.001), and was significantly higher in Asia with an odds ratio of 7.88 (95%CI: 2.40-25.85, p = 0.001). CONCLUSION: Mortality rate among patients who received ECMO therapy was high. A system of care, including patient selection, resource management and referral system, can impact the outcomes of ECMO therapy.

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.

Combining cell therapy and extracorporeal membrane oxygenation for Acute Respiratory Distress Syndrome: Back to no future?

Introduction: After more than 50 years of research we are yet to develop an effective treatment for the Acute Respiratory Distress Syndrome (ARDS). This stands in contrast to the advances made in supportive care, a prime example of which is the maturation of Extracorporeal Membrane Oxygenation (ECMO). While technologies such as ECMO 'buy time' for recovery, the identification of a therapy remains crucial to improving outcomes. Recently, mesenchymal stem cells (MSCs) have shown promise as a novel treatment.1 Importantly, cell therapy may represent a means to overcome the hurdles associated with successful pharmacological intervention in ARDS. Little is known about the interaction between cell therapy and ECMO. This is a deficiency, given that those receiving ECMO for ARDS are among the most severely ill and therefore most likely to benefit. This programme of work was designed to close that gap. Objectives: Using a translational pipeline, our objective was to assess the safety and efficacy of MSCs during ECMO for ARDS. Methods: We employed several diverse methods to address our objectives, including an ex-vivo ECMO simulation, complex sheep models of ARDS and ARDS and venovenous ECMO, systematic review methodology, and unsupervised machine learning techniques. Results: In our ex-vivo model, we were the first to demonstrate potential harms associated with MSC therapy during ECMO.2 When 40 × 10∧6 clinical-grade human MSCs (Cynata Therapeutics Ltd., Australia) were added to fresh whole human blood and subjected to extracorporeal circulation using commercial components, oxygenator and pump performance was severely impaired within 4 hours. These experiments also demonstrated benefits associated with MSCs, including trends toward lower inflammatory cytokine concentrations and less neutrophil activation.3 To validate our findings, we sought to test hMSCs in a clinicallyrelevant sheep model. At the outset we undertook a systematic review of existing pre-clinical models of ARDS and ECMO.4 This has since produced an international collaborative effort to characterise pre-clinical models of ECMO across a range of indications. We subsequently described a 'double-hit' model of ARDS which combines oleic acid and intra-tracheal E. coli lipopolysaccharide. Using cluster analysis, we showed that this model shares qualitative similarities with the 'hypo-inflammatory' phenotype identified in clinical cohorts [Millar JE et al. Physiological Reports 2021. In Press]. Finally, in a 24-hour model, combining our novel injury method, VV-ECMO, and best practice ventilatory and supportive care, we performed a controlled trial of intra-tracheal hMSC therapy5 [Editorial: Del Sorbo L, Fan E. AJRCCM 2020]. This study showed that hMSCs reduce histological evidence of lung injury and ameliorate shock. However, hMSC-mediated impairment of oxygenator function was evident again. Conclusion: This work addresses a gap in our understanding of cell therapy in critical illness. The findings are of direct clinical relevance, highlighting the potential harms of cell therapy during extracorporeal circulation. With a recent explosion in the number of registered clinical trials of MSCs for severe COVID-19 in mind, the use of MSCs during ECMO cannot be recommended.

Challenges and Strategies for Veno Venous (VV) Extracorporeal Membrane Oxygenation (ECMO) in COVID-19 Acute Respiratory Distress Syndrome (ARDS) During Second Wave of Pandemic: A Case Series

Case series: Extracorporeal membrane oxygenation (ECMO) use for severe acute respiratory distress syndrome due to coronavirus disease 2019 (COVID-19) patients has increased during the second wave of the pandemic. However, there are many complications associated with the management of ECMO in critically ill COVID- 19 patients. We report a case series of challenges and strategies for managing critically ill COVID-19 patients on ECMO support for severe ARDS. Seven COVID-19 patients required VV ECMO of which three were women and four were men of median age of 43 years. Among seven, three cases (42%) recovered. We experienced multiple challenges and complications in the management of the patients, being a non-ECMO centre with limited resources, in heavy workload during the second wave of the pandemic. All the patients required multiple invasive procedures like placement of invasive lines, frequent bronchoscopies for bronchial toileting. Displacement of both ECMO cannulas required repositioning under ultrasound guidance, four patients underwent percutaneous tracheostomy on ECMO. Three patients had ECMO-oxygenator failure that required the exchange of a new ECMO circuit. ACT was monitored for the management of anticoagulation. A challenging task is to achieve a balance between bleeding and thrombotic events, for which anticoagulation had to be stopped for the acceptable ACT, required transfusion of multiple blood products for correcting coagulopathy. One patient developed HIT antibodies and managed with bivalirudin for the management of anticoagulation which was challenging in titrating the drug dose and ACT. Two patients had an intracranial haemorrhage on ECMO support, managed conservatively despite anticoagulation. Pseudoaneurysm of femoral vein diagnosed and managed with ultrasound-guided thrombin injection. Four patients got decannulated from ECMO. One patient had unexplained severe haemolysis immediately after initiation of ECMO, unfortunately, he could not recover. Management of VV ECMO in resource-limited, non-ECMO centre in a pandemic is challenging. Mortality depends on various factors, despite expertise, advanced critical care management in COVID- 19 ARDS and ECMO. Increased use of VV ECMO during the second wave of pandemic reported significant changes in strategies for management of challenges, though further studies are still required for the best outcome.

Perinatally Acquired COVID-19 Requiring ECMO with Severe Hematologic Complications

Case Report: Perinatal acquisition of COVID-19 in neonates is uncommon and development of severe pulmonary disease remains extremely rare. Thus far, there have been no reports of otherwise healthy neonates requiring extracorporeal life support (ECLS) for ARDS secondary to COVID-19. Further, little is known about the hematologic implications of COVID-19 in the neonatal population. We report the first perinatally acquired case of COVID-19 requiring ECLS and describe associated hematologic complications. The patient was a 35-week gestational age twin infant, born to an asymptomatic COVID-19 positive mother. The infant was COVID-19 PCR positive just after birth, though asymptomatic. She presented on day of life 9 with respiratory distress and hypoxia. She had progressive respiratory failure and at 2 weeks of life was placed on veno-venous (VV) extracorporeal life support (ECLS). On post-operative day 1 there was development of a bi-atrial clot requiring open thrombectomy and conversion to veno-arterial (VA) ECLS with an open chest. Three days post-thrombectomy, despite therapeutic anticoagulation with heparin, the circuit oxygenator developed significant clot burden leading to oxygenator failure and requiring circuit change. Five days post-thrombectomy, patient developed severe, persistent hemorrhage after chest closure despite discontinuation of heparin anti-coagulation therapy and was transitioned to comfort care per parental request. Whole exome sequencing was negative with no evidence of innate hematologic disease. Conclusion: This case highlights the rare, though significant, risk COVID-19 infection can potentially impose on pulmonary and hematologic systems of an infected neonate.

Safe and effective administration of multiple recombinant factors on VA-ECMO via post-oxygenator pigtail during acute massive pulmonary hemorrhage

Introduction: Massive bleeding on extracorporeal membrane oxygenation (ECMO) is associated with multiple coagulation defects, including depletion of coagulation factors and development of acquired von Willebrand syndrome (AVWS). The use of recombinant factors, in particular recombinant activated factor VII (rFVIIa, Novoseven), to treat severe refractory hemorrhage in ECMO has been described. However, the use of multiple recombinant factors has been avoided in large part due to concern for circuit complications and thrombosis. Here, we describe the safe and effective administration of rFVIIa and recombinant von Willebrand factor complex (vWF/ FVIII, Humate-P) via post-oxygenator pigtail catheter on VA-ECMO for the treatment of massive pulmonary hemorrhage. Case Description: A 21-month-old (13.4 kg) girl with a recent history of COVID-19 infection presented to an outside hospital with parainfluenza bronchiolitis resulting in acute refractory hypoxemic respiratory failure (oxygenation index 58), refractory septic shock, and myocardial dysfunction. She was cannulated to VA-ECMO and subsequently diagnosed with necrotizing pneumonia from Pseudomonas and herpes simplex infections. Her course was complicated by a large left-sided pneumatocele and bronchopleural fistula requiring multiple chest tubes. She also had right mainstem bronchus obstruction from necrotic airway debris and complete right lung atelectasis. She was noted to have prolonged episodes of mucosal and cutaneous bleeding (oropharynx, chest tube insertion sites, peripheral IV insertion sites) associated with absent high molecular weight von Willebrand multimers consistent with AVWS. Tranexamic acid infusion was initiated and bivalirudin anticoagulation was discontinued. VA-ECMO flows were escalated to 140-160 ml/kg/min to maintain circuit integrity and meet high patient metabolic demand in the absence of anticoagulation. On ECMO day 26, she underwent bronchoscopy to clear necrotic debris from her airway to assist with lung recruitment. The procedure was notable for mucosal bleeding requiring topical epinephrine and rFVIIa. Post-procedure, she developed acute hemorrhage from her right mainstem bronchus, resulting in significant hemothorax (estimated 950 ml) with mediastinal shift, increased venous pressures, desaturation and decreased ECMO blood flow rate, necessitating massive transfusion of 2,050 ml (150 ml/kg) of packed red blood cells, platelets, plasma and cryoprecipitate. An airway blocker was placed in the mid-trachea to control bleeding. In addition to transfusion of appropriate blood products and continuation of tranexamic acid infusion, she was given both rFVIIa (100mcg/kg) and vWF-FVIII (70 units vWF/kg loading dose on the day of hemorrhage, followed by 40 units vWF/kg every 12 hours for 3 additional doses). Both products were administered over 10 minutes through a post-oxygenator pigtail to allow the product to circulate throughout the patient prior to entering the ECMO circuit. The circuit was closely monitored during administration and no changes to circuit integrity were noted in the subsequent hours while hemostasis was achieved. The ECMO circuit remained without thrombosis for 9 days after the bleeding event. Discussion: Balancing anticoagulation and hemostasis is a central challenge in maintaining ECMO support, especially given the prevalence of acquired coagulopathies such as AVWS. For our patient, AVWS contributed to mucosal bleeding necessitating cessation of anticoagulation and utilization of a high ECMO blood flow strategy to minimize circuit clot burden. This was further complicated by absent native lung function and minimal myocardial function, resulting in complete dependence on ECMO. An acute massive pulmonary hemorrhage was treated with multiple recombinant factors (rFVIIa and vWF/FVIII), that are often avoided on ECMO. To minimize clotting risk to the circuit and to maximize transit of these factors to our patient, we added a post-oxygenator pigtail for administration. While this approach was the result of extreme circumstances, th use of a post-oxygenator pigtail for administration of recombinant factors may represent a viable strategy for refractory hemorrhage while on ECMO.

Case Report of a COVID-19 patient treated with Seraph® 100 on Extracorporeal Life Support

Background: The Seraph® 100 Microbind ® Affinity Blood Filter (Seraph ®100) is an extracorporeal broad-spectrum sorbent hemoperfusion filter that removes pathogens and cytokines from the blood and has Emergency Use Authorization (EUA) for the treatment of severe COVID-19. Seraph® 100 can be adapted and primed to a NxStage continuous renal replacement therapy (CRRT) machine and connected to the patient's ECMO circuit. This form of hemofiltration provided a safe and effective approach to decreasing pathogen response within the blood and was tested in our center. Case Review: A 42-year-old male with a past medical history of obesity, hypertension and hypothyroidism was admitted for acute hypoxemic respiratory failure secondary to COVID-19. His 65 day ECMO course was complicated by encephalopathy, right heart dysfunction, severe epistaxis, esophageal ulcers and enterococcus faecalis bacteremia. On ECMO day 16, the patient became febrile, C-reactive protein increased to 215 mg/L and he became hypotensive. In addition to appropriate antibiotics, the multidisciplinary team decided to initiate Seraph® 100 for the E.faecalis bacteremia. The filter was adapted and primed into the NxStage machine by the nurse caring for the patient. The NxStage lines were then connected to the ECMO circuit via pigtail connections. The blood was cycled from the post-oxygenator pigtail to the NxStage and returned to the pre-oxygenator pigtail on the ECMO circuit. The target time for continuous Seraph® 100 therapy is between 24-48 hours. Cultures were collected from the NxStage line pre-filter and again, six hours later, from a port post-filter. The pre-filter cultures came back positive for E.faecalis and the post-filter cultures were negative. Additional blood cultures collected the following day remained negative. The patient's condition improved rapidly and allowed him to begin physical therapy and reduce ventilator support over the next 48 days on ECMO. He was discharged from the hospital to rehab for two weeks before going home. Discussion: Introduction of hemofiltration by Exthera provided an additional therapy that has proven to be effective in the reduction of sepsis causing pathogens when used in conjunction with conventional care for patients with COVID-19 suffering from bacteremia. In this case, incorporating hemofiltration via the ECMO circuit showed no increase in undue risk to the patient with an efficacy in decreasing bacteremia, contributing to the survival of the patient.

A Case Report of ECMO Patient with Cerebrovascular Complication Caused by a Broken Dual Lumen Cannula

Introduction: Dual-lumen cannula is used for extracorporeal membrane perfusion (ECMO) to support patients with ARDS due to COVID-19 as a bridge to lung recovery. It tends to be a longer support and there are several factors that can degrade the physical structure of the ECMO cannula and put the cannula at risk for breakage. Case Report: A 63-year-old woman was admitted to the hospital with COVID-19 pneumonia. Two days later, she was intubated and VV-ECMO was initiated due to treatment-resistant acute respiratory failure;a 28Fr CrescentTM dual-lumen cannula (Medtronic, MN) was inserted through the left subclavian vein and connected to a centrifugal oxygen pump with a centrifugal oxygenator. Within six weeks after onset, the patient was unable to be weaned from the ventilator and was transferred to our center with ECMO connected for consideration of lung transplantation. Two days after transfer, the patient developed acute aphasia, altered mental status, disturbed consciousness, and left arm seizures. A suction sound was heard from the left subclavian cannula insertion site and the ECMO bubble detector alarmed, but local inspection, chest X-rays, and CT scans of the brain and chest showed no obvious abnormalities. The patient was reintubated for encephalopathy and subsequently underwent a tracheostomy. The patient regained normal neurological function over the next 7 days. However, the air bubble sensor alarmed and suction sound was heard at the cannulation site again, and air bubbles were seen in the oxygenator. Due to concerns about air entrapment and cannula failure, we changed to a dual-canal VV-ECMO configuration using a right internal cervical and a left femoral cannula. The removed cannula had a 2 cm fracture distal to the skin insertion site. After resumption of ECMO, no new neurological episodes occurred. While awaiting lung transplantation, the patient died due to sepsis and multiple organ failure. An autopsy revealed a possible cause of cerebrovascular disease patent foramen ovale and air embolism to the brain. If a patient has been on ECMO for a long time and the bubble sensor warns of air detection, cannula breakage and impending air embolism should be suspected clinically, even if the defect is not found on examination and is not evident on imaging. If the COVID-19 epidemic continues, increased transport events may increase ECMO cannula breakage.

Insights into Gradient and Anisotropic Pore Structures of Capiox® Gas Exchange Membranes for ECMO: Theoretically Verifying SARS-CoV-2 Permeability.

When using the extracorporeal capillary membrane oxygenator (sample A) for ECMO treatments of COVID-19 severely ill patients, which is dominantly used in Japan and worldwide, there is a concern about the risk of SARS-CoV-2 scattering from the gas outlet port of the membrane oxygenator. Terumo has launched two types of membranes (sample A and sample B), both of which are produced by the microphase separation processes using polymethylpentene (PMP) and polypropylene (PP), respectively. However, the pore structures of these membranes and the SARS-CoV-2 permeability through the membrane wall have not been clarified. In this study, we analyzed the pore structures of these gas exchange membranes using our previous approach and verified the SARS-CoV-2 permeation through the membrane wall. Both have the unique gradient and anisotropic pore structure which gradually become denser from the inside to the outside of the membrane wall, and the inner and outer surfaces of the membrane have completely different pore structures. The pore structure of sample A is also completely different from the other membrane made by the melt-extruded stretch process. From this, the pore structure of the ECMO membrane is controlled by designing various membrane-forming processes using the appropriate materials. In sample A, water vapor permeates through the coating layer on the outer surface, but no pores that allow SARS-CoV-2 to penetrate are observed. Therefore, it is unlikely that SARS-CoV-2 permeates through the membrane wall and scatter from sample A, raising the possibility of secondary ECMO infection. These results provide new insights into the evolution of a next-generation ECMO membrane.

Retrograde cerebral air embolism in a patient on venovenous ECMO

INTRODUCTION: Retrograde cerebral air embolism (CAE) is rarely described in literature that may be associated with manipulation of central or peripheral venous catheters. During a literature review, there were no described occurrences of CAE in patients on veno-venous (V-V) ECMO. DESCRIPTION: A 42-year-old male with ARDS secondary to COVID-19 pneumonitis was cannulated for V-V ECMO outside our facility and transferred to our cardiovascular intensive care unit. Upon arrival, he was noted to have a right femoral drainage cannula and right internal jugular (RIJ) venous antegrade cannula. On day 10 of his hospital stay he was converted to a RIJ Protek duo cannula and the right femoral drainage cannula was removed. This cannula was repositioned multiple times after placement due to flow issues. Due to poor oxygenator membrane function, it became necessary to exchange the oxygenator on day 25. During the exchange, the patient experienced sudden-onset bradycardia that progressed to several seconds of asystole. He regained spontaneous cardiac activity after a bolus dose of IV glycopyrrolate. Following this, he had several episodes of bradycardia and eventually asystole that resolved after one round of ACLS and IV atropine. The bradycardic episodes continued after this event and were associated with hypertension. On day 25, the patient suffered a decline in neurologic status from a GCS of 11T to 3T. The patient was sent emergently for non-contrast CT head. This scan revealed pneumocephalus with diffuse foci of air emboli in the subarachnoid and intraventricular spaces, the choroid plexus, and dural venous sinuses. After a family discussion, care was withdrawn from the patient on day 27. DISCUSSION: This patient suffered a massive retrograde CAE peri-ECMO circuit oxygenator exchange. It is our understanding that this a novel clinical situation for this phenomenon and not previously described in literature. This emphasizes that manipulation of any vascular cannula may result in the entrainment of air in a retrograde venous fashion into the cerebral vasculature.