Extracorporeal Membrane Oxygenation Impacts Host Transcriptomic Response in Severe Coronavirus

BACKGROUND Evidence suggests that critically ill COVID-19 patients have a dysregulated host immune response that contributes to end-organ damage. Extracorporeal membrane oxygenation (ECMO) has been utilized in this population with varying degrees of success. This study was performed to evaluate the impact of ECMO on the host immunotranscriptomic response in these patients. METHODS Eleven critically ill COVID-19 patients requiring ECMO underwent an analysis of cytokines and immunotranscriptomic pathways pre-ECMO (T1), after ECMO for 24 hours (T2), and 2 hours after ECMO decannulation (T3). A Multiplex Human Cytokine panel was used to identify cytokine changes and immunotranscriptomic changes in peripheral leukocytes were evaluated by PAXgene and NanoString nCounter. RESULTS Differential gene expression (DGE) of 11 host immune genes was noted at T2 compared to T1. The most significant genes were MD2 and MRC1, which are binding ligands for the activation of toll-like receptors (TLR) 2 and 4. Reactome analyses of DGE demonstrated an impact on many of the body's most important immune inflammatory pathways. CONCLUSIONS These findings suggest a temporal impact of ECMO on the host immunotranscriptomic response in critically ill patients with COVID-19.

Experience of Nurses Caring for COVID-19 Patients Supported by Venovenous Extracorporeal Membrane Oxygenation (ECMO) After ECMO Educational Crash Course.

During a 6 week period beginning early March 2020, 30 patients with severe coronavirus disease 2019 (COVID-19) were supported with venovenous extracorporeal membrane oxygenation (ECMO). This volume increase mandated rapidly training 116 nurses with no prior ECMO experience via a 2 hour crash course. A qualitative study using semistructured, in-depth interviews was conducted to evaluate the experiences of this unique nursing cohort. Fourteen registered nurses meeting inclusion criteria of no prior ECMO experience, attendance of ECMO educational crash course, direct assignment of COVID-19 patients requiring ECMO, and willingness to consent to recorded interviews participated in the study. Two semistructured interviews were conducted, audio recorded, and transcribed verbatim. Thematic analysis of the interviews was completed using Colaizzi's phenomenological method. Six themes identified were anxiety and fear of patient harm, isolation and depersonalization, value of didactic education with reinforced clinical experience, professional growth, importance of team collaboration, and pride and gratitude. Subthemes were additionally extracted. Nurses faced multiple obstacles during the pandemic. ECMO added a layer of complexity, as these patients required labor-intensive, high acuity nursing care. The impact of the pandemic and its unique challenges on nursing and medical staff warrants further investigation.

Impact of CytoSorb Hemoadsorption on Sedation Requirements in Patients With Severe COVID-19 on Venovenous Extracorporeal Membrane Oxygenation.

Hemoadsorption with CytoSorb has been used as an adjunct in the treatment of severe coronavirus disease 2019 (COVID-19)-related respiratory failure. It remains unknown if CytoSorb hemoadsorption will alter sedative and analgesic dosing in critically ill patients on venovenous extracorporeal membrane oxygenation (VV-ECMO). We conducted a retrospective review of patients with severe COVID-19 requiring VV-ECMO for respiratory support. Patients who were enrolled in a clinical study of CytoSorb were compared with patients on VV-ECMO alone. Data were collected for the 72-hour CytoSorb therapy and an additional 72 hours post-CytoSorb, or a corresponding control time period. Sedative and analgesic doses were totaled for each day and converted to midazolam or fentanyl equivalents, respectively. The primary endpoint, change in sedative and analgesic requirements over time, were compared using a two-way mixed analysis of variance. Of the 30 patients cannulated for VV-ECMO for COVID-19, 4 were excluded, leaving 8 patients in the CytoSorb arm and 18 in the Control. There was no effect of CytoSorb therapy on midazolam equivalents over the 72-hour therapy (p = 0.71) or the 72 hours post-CytoSorb (p = 0.11). In contrast, there was a significant effect of CytoSorb therapy on fentanyl equivalents over the first 72 hours (p = 0.01), but this was not consistent over the 72-hours post-CytoSorb (p = 0.23). CytoSorb therapy led to significant increases in analgesic requirements without impacting sedative requirements. Further research is needed to define the relevance of CytoSorb hemoadsorption on critical care pharmacotherapy.

Efficacy of proning in acute respiratory distress syndrome on extracorporeal membrane oxygenation.

Objectives: Proning patients with acute respiratory distress syndrome (ARDS) has been associated with increased survival, although few data exist evaluating the safety and feasibility of proning patients with ARDS on extracorporeal membrane oxygenation (ECMO). Methods: A single-institution retrospective review of all patients with ARDS placed on ECMO between March 1 and May 31, 2020, was performed. All proning events were evaluated for complications, as well as change in compliance, sweep, oxygenation, and flow. The primary outcome of this study was the rate major morbidity associated with proning while on ECMO. Results: In total, 30 patients were placed on ECMO for ARDS, with 12 patients (40%) proned while on ECMO. A total of 83 proning episodes occurred, with a median of 7 per patient (interquartile range, 3-9). No ECMO cannula-associated bleeding, cannula displacement, or endotracheal tune dislodgements occurred (0%). Oropharyngeal bleeding occurred twice (50%). Four patients were proned with chest tubes in place, and none had complications (0%). Lung compliance improved after proning in 70 events (84%), from a mean of 15.4 mL/mm Hg preproning to 20.6 mL/mm Hg postproning (P < .0001). Sweep requirement decreased in 36 events (43%). Oxygenation improved in 63 events (76%), from a mean partial pressure of oxygen of 86 preproning to 103 postproning (P < .0001). Mean ECMO flow was unchanged. Conclusions: Proning in patients with ARDS on ECMO is safe with an associated improvement in lung mechanics. With careful planning and coordination, these data support the practice of appropriately proning patients with severe ARDS, even if they are on ECMO.

COVID-19-Associated Large- and Medium-Sized-Vessel Pathology: A Case Series.

BACKGROUND: Coronavirus disease-19 (COVID-19) remains a public health crisis. The epidemiology of COVID-19-associated large- and medium-sized-vessel pathology is not well characterized. The aim of this study is to identify patients with possible COVID-19-associated large- and medium-sized-vessel pathology based on computed tomography (CT) imaging to provide insight into this rare, but potentially devastating, cardiovascular manifestation. METHODS: This is a single-center retrospective review of patients with CT chest, abdomen, and/or pelvis concerning for large- and medium-vessel pathology and confirmed COVID-19 infection from March 1, 2020 to October 31, 2020. RESULTS: During the study period, 6,553 CT reports were reviewed and pertinent imaging was identified in 139 patients. Of these, 8 patients (median age: 59 years, range 51-82) were COVID-19 positive. All patients had preexisting cardiovascular risk factors and three (37.5%) had an autoimmune disease. Four patients were never hospitalized for COVID-19. Among these, two presented to the hospital at a median of 39 days (range: 27-50) after their initial COVID-19 test with chest and back pain where imaging revealed extensive aortic pathology. One patient required surgical management for aortic pathology. All other patients were treated with expectant management and outpatient follow-up. CONCLUSION: The clinical and radiological presentations of COVID-19-associated large- and medium-vessel pathology are heterogeneous and can be a late finding after COVID-19 recovery. Close clinical follow-up and surveillance imaging for large- and medium-sized-vessel pathology may be warranted in COVID-19 patients.

One-Year Outcomes With Venovenous Extracorporeal Membrane Oxygenation Support for Severe COVID-19.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) can cause acute respiratory failure requiring mechanical ventilation. Venovenous (VV) extracorporeal membrane oxygenation (ECMO) has been used in patients in whom conventional mechanical ventilatory support has failed. To date, published data have focused on survival from ECMO and survival to discharge. In addition to survival to discharge, this study reports 1-year follow-up data for patients who were successfully discharged from the hospital. METHODS: A single-institution, retrospective review of all patients with severe COVID-19 who were cannulated for VV-ECMO between March 10, 2020 and May 1, 2020 was performed. A multidisciplinary ECMO team evaluated, selected, and managed patients with ECMO support. The primary outcome of this study was survival to discharge. Available 1-year follow-up data are also reported. RESULTS: A total of 30 patients were supported with VV-ECMO, and 27 patients (90%) survived to discharge. All patients were discharged home or to acute rehabilitation on room air, except for 1 patient (3.7%), who required supplemental oxygen therapy. At a median follow-up of 10.8 months (interquartile range [IQR], 8.9-14.4 months) since ECMO cannulation, survival was 86.7%, including 1 patient who underwent lung transplantation. Of the patients discharged from the hospital, 44.4% (12/27) had pulmonary function testing, with a median percent predicted forced expiratory volume of 100% (IQR, 91%-110%). For survivors, a 6-minute walk test was performed in 59.3% (16/27), with a median value of 350 m (IQR, 286-379 m). CONCLUSIONS: A well-defined patient selection and management strategy of VV-ECMO support in patients with severe COVID-19 resulted in exceptional survival to discharge that was sustained at 1-year after ECMO cannulation.

Hemoadsorption for management of patients on veno-venous ECMO support for severe COVID-19 acute respiratory distress syndrome.

BACKGROUND AND AIM: Patients with severe coronavirus disease 2019 (COVID-19) develop a profound cytokine-mediated pro-inflammatory response. This study reports outcomes in 10 patients with COVID-19 supported on veno-venous extracorporeal membrane oxygenation (VV-ECMO) who were selected for the emergency use of a hemoadsorption column integrated in the ECMO circuit. MATERIALS AND METHODS: Pre and posttreatment, clinical data, and inflammatory markers were assessed to determine the safety and feasibility of using this system and to evaluate the clinical effect. RESULTS: During hemoadsorption, median levels of interleukin (IL)-2R, IL-6, and IL-10 decreased by 54%, 86%, and 64%, respectively. Reductions in other markers were observed for lactate dehydrogenase (-49%), ferritin (-46%), d-dimer (-7%), C-reactive protein (-55%), procalcitonin (-76%), and lactate (-44%). Vasoactive-inotrope scores decreased significantly over the treatment interval (-80%). The median hospital length of stay was 53 days (36-85) and at 90-days post cannulation, survival was 90% which was similar to a group of patients without the use of hemoadsorption. CONCLUSIONS: Addition of hemoadsorption to VV-ECMO in patients with severe COVID-19 is feasible and reduces measured cytokine levels. However, in this small series, the precise impact on the overall clinical course and survival benefit still remains unknown.

Lobectomy for Hemorrhagic Lobar Infarction in a Patient With COVID-19.

Patients with severe coronavirus disease 2019 from infection with severe acute respiratory syndrome coronavirus 2 mount a profound inflammatory response and are predisposed to thrombotic complications. Pulmonary vein thrombosis is a rare disease process resulting in pulmonary congestion, infarction, and potential mortality. This report describes a patient with coronavirus disease 2019 requiring venovenous extracorporeal membrane oxygenation for hypoxic respiratory failure who developed hemorrhagic infarction of the right lower lobe. During emergency exploration the patient was found to have a right inferior vein thrombosis and marked lobar hemorrhage mandating lobectomy.

Pulmonary Embolism Response Team activation during the COVID-19 pandemic in a New York City Academic Hospital: a retrospective cohort analysis.

Coronavirus disease 2019 (COVID-19) is associated with increased rates of deep vein thrombosis (DVT) and pulmonary embolism (PE). Pulmonary Embolism Response Teams (PERT) have previously been associated with improved outcomes. We aimed to investigate whether PERT utilization, recommendations, and outcomes for patients diagnosed with acute PE changed during the COVID-19 pandemic. This is a retrospective cohort study of all adult patients with acute PE who received care at an academic hospital system in New York City between March 1st and April 30th, 2020. These patients were compared against historic controls between March 1st and April 30th, 2019. PE severity, PERT utilization, initial management, PERT recommendations, and outcomes were compared. There were more cases of PE during the pandemic (82 vs. 59), but less PERT activations (26.8% vs. 64.4%, p < 0.001) despite similar markers of PE severity. PERT recommendations were similar before and during the pandemic; anticoagulation was most recommended (89.5% vs. 86.4%, p = 0.70). During the pandemic, those with PERT activations were more likely to be female (63.6% vs. 31.7%, p = 0.01), have a history of DVT/PE (22.7% vs. 1.7%, p = 0.01), and to be SARS-CoV-2 PCR negative (68.2% vs. 38.3% p = 0.02). PERT activation during the pandemic is associated with decreased length of stay (7.7 ± 7.7 vs. 13.2 ± 12.7 days, p = 0.02). PERT utilization decreased during the COVID-19 pandemic and its activation was associated with different biases. PERT recommendations and outcomes were similar before and during the pandemic, and led to decreased length of stay during the pandemic.

Extracorporeal Membrane Oxygenation Support in Severe COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) remains a worldwide pandemic with a high mortality rate among patients requiring mechanical ventilation. The limited data that exist regarding the utility of extracorporeal membrane oxygenation (ECMO) in these critically ill patients show poor overall outcomes. This report describes our institutional practice regarding the application and management of ECMO support for patients with COVID-19 and reports promising early outcomes. METHODS: All critically ill patients with confirmed COVID-19 evaluated for ECMO support from March 10, 2020, to April 24, 2020, were retrospectively reviewed. Patients were evaluated for ECMO support based on a partial pressure of arterial oxygen/fraction of inspired oxygen ratio of less than 150 mm Hg or pH of less than 7.25 with a partial pressure of arterial carbon dioxide exceeding 60 mm Hg with no life-limiting comorbidities. Patients were cannulated at bedside and were managed with protective lung ventilation, early tracheostomy, bronchoscopies, and proning, as clinically indicated. RESULTS: Among 321 patients intubated for COVID-19, 77 patients (24%) were evaluated for ECMO support, and 27 patients (8.4%) were placed on ECMO. All patients were supported with venovenous ECMO. Current survival is 96.3%, with only 1 death to date in more than 350 days of total ECMO support. Thirteen patients (48.1%) remain on ECMO support, and 13 patients (48.1%) have been successfully decannulated. Seven patients (25.9%) have been discharged from the hospital. Six patients (22.2%) remain in the hospital, of which 4 are on room air. No health care workers who participated in ECMO cannulation developed symptoms of or tested positive for COVID-19. CONCLUSIONS: The early outcomes presented here suggest that the judicious use of ECMO support in severe COVID-19 may be clinically beneficial.

Novel Percutaneous Tracheostomy for Critically Ill Patients With COVID-19.

BACKGROUND: Coronavirus 2019 (COVID-19) is a worldwide pandemic, with many patients requiring prolonged mechanical ventilation. Tracheostomy is not recommended by current guidelines as it is considered a superspreading event owing to aerosolization that unduly risks health care workers. METHODS: Patients with severe COVID-19 who were on mechanical ventilation for 5 days or longer were evaluated for percutaneous dilational tracheostomy. We developed a novel percutaneous tracheostomy technique that placed the bronchoscope alongside the endotracheal tube, not inside it. That improved visualization during the procedure and continued standard mechanical ventilation after positioning the inflated endotracheal tube cuff in the distal trachea. This technique offers a significant mitigation for the risk of virus aerosolization during the procedure. RESULTS: From March 10 to April 15, 2020, 270 patients with COVID-19 required invasive mechanical ventilation at New York University Langone Health Manhattan's campus; of those, 98 patients underwent percutaneous dilational tracheostomy. The mean time from intubation to the procedure was 10.6 ± 5 days. Currently, 32 patients (33%) do not require mechanical ventilatory support, 19 (19%) have their tracheostomy tube downsized, and 8 (8%) were decannulated. Forty patients (41%) remain on full ventilator support, and 19 (19%) are weaning from mechanical ventilation. Seven patients (7%) died as a result of respiratory and multiorgan failure. Tracheostomy-related bleeding was the most common complication (5 patients). None of health care providers has had symptoms or tested positive for COVID-19. CONCLUSIONS: Our percutaneous tracheostomy technique appears to be safe and effective for COVID-19 patients and safe for health care workers.