Faculty Bibliography

Introduction: The multicenter CTC Registry study collected patientlevel data in COVID-19 patients receiving CytoSorb therapy under FDA Emergency Use Authorization. An earlier report on the first 52 CTC patients on ECMO treated with CytoSorb showed 69% overall survival [1]. The current analysis focuses on changes in pulmonary function relative to the time of CytoSorb therapy.
Method(s): A total of 56 patients from 5 U.S. centers were included. Data on demographics, mechanical ventilation (MV), ECMO, and arterial blood gases during CytoSorb therapy were analyzed. Linear regression was used to evaluate the relationship between the timing of initiation of CytoSorb therapy to lung oxygenation according to changes in PaO2/FiO2 ratio.
Result(s): In the current analysis, 71% (40/56) overall survival was observed. For these survivors, time to CytoSorb start after ICU admission, MV start, and ECMO start was 138 +/- 171.3 h, 83 +/- 111.0 h, and 55 +/- 156.5 h, respectively, with mean duration of CytoSorb therapy of 83 +/- 29.1 h. At the first 24 h following CytoSorb therapy, oxygenation was improved evidenced by decreased MV FiO2 and ECMO FdO2 requirements and an increased PaO2/FiO2 ratio (90.2 +/- 58.13 mmHg to 166.3 +/- 98.67 mmHg, p < 0.001, N = 21). Linear regression analysis suggested that earlier initiation of CytoSorb therapy following ICU admission may be correlated to greater improvements in PaO2/FiO2 ratio (r = -0.37, p = 0.103), however, this trend did not achieve statistical significance.
Conclusion(s): High survival rates have been observed with adjunct CytoSorb therapy in critically ill COVID-19 patients on ECMO. The current analysis suggests that early initiation of hemoadsorption following ICU admission may contribute to earlier improvements in native lung oxygenation

BACKGROUND AND AIM/OBJECTIVE: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/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.

Transplanting hepatitis C viremic donor organs into hepatitis C virus (HCV)-negative recipients is becoming increasingly common; however, practices for posttransplant direct-acting antiviral (DAA) treatment vary widely. Protracted insurance authorization processes for DAA therapy often lead to treatment delays.

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.

Thoracic organs from Hepatitis C virus (HCV) positive donors are not commonly used for transplantation. The development of direct-acting antivirals (DAA) for HCV treatment has led to renewed interest in using HCV-positive organs. We evaluated HCV transmission rates, viremia clearance, and short-term outcomes in HCV-negative patients who received HCV-positive thoracic organs at our institution. From January 1, 2018 to May 31, 2019, 38 patients underwent HCV-positive thoracic organ transplantation (16 lungs and 22 hearts). Heart recipients were started on glecaprevir/pibrentasvir, a pangenotypic DAA, when they developed HCV viremia. Lung recipients were empirically started on glecaprevir/pibrentasvir within the first three post-transplant days. The primary outcome was cure of HCV defined as sustained virologic response at 12 weeks (SVR12). All heart recipients developed HCV viremia with median initial viral load of 64,565 IU/mL (interquartile range: 1660 to 473,151). The median time from DAA initiation to viremia clearance was 19 days (confidence interval: 15-27 days). 11 out of 16 (68.8%) lung recipients developed HCV viremia with median initial viral load of 26 IU/mL (interquartile range: 15 to 143). The median time from DAA initiation to viremia clearance was 10 days (confidence interval: 6-17 days). 5 out of 16 (31.3%) lung recipients never became viremic. All patients demonstrated SVR12. Thoracic organ transplantation from HCV viremic donors is safe with excellent short-term survival. Early initiation of HCV treatment results in rapid viremia clearance and SVR12. Long-term outcomes and optimal timing of DAA initiation remains to be determined.