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.
Hemoadsorption for management of patients on veno-venous ECMO support for severe COVID-19 acute respiratory distress syndrome
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.
Commentary: Can we pump our way out of heart failure with preserved ejection fraction? Not so soon [Editorial]
Impact of Early Initiation of Direct-Acting Antiviral Therapy in Thoracic Organ Transplantation from Hepatitis C Virus Positive Donors
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.
Comparison of Outcomes of Enoxaparin Bridge Therapy in HeartMate II versus HeartWare HVAD Recipients
BACKGROUND/UNASSIGNED:There is a lack of robust data evaluating outcomes of enoxaparin "bridge" therapy in left ventricular assist device (LVAD) patients. METHODS/UNASSIGNED:We performed a retrospective study of HeartMate II (HM II) and HeartWare HVAD recipients that received therapeutic enoxaparin as "bridge" therapy to describe bleeding and thrombotic events and compare outcomes between devices. The primary endpoint was the incidence of bleeding within 30 days of "bridge" episode. Major bleeding was defined by INTERMACS criteria. RESULTS/UNASSIGNED:= .02). We observed 3 (1%) thromboembolic events in 2 (4%) patients with an HVAD device. On multivariate analysis, the presence of a HM II device was associated with a 4-fold increased risk of bleeding. CONCLUSION/UNASSIGNED:We found the use of enoxaparin "bridge" therapy to be associated with a higher incidence of bleeding in patients with a HM II device compared with an HVAD device. Assessment of device- and patient-specific factors should be evaluated to minimize bleeding events.
Commentary: The future is now-heart donation after circulatory death [Editorial]
A novel protocol to reduce bleeding associated with alteplase treatment of HVAD pump thrombosis
Pump thrombosis remains a feared complication for patients implanted with durable left ventricular assist devices. Optimal treatment is unknown, but consists of either pharmacologic fibrinolysis or surgical pump exchange. Fibrinolysis is less invasive, but carries a significant risk of intracerebral hemorrhage. We present four cases of LVAD pump thrombosis successfully treated with a novel protocol that consists of low-dose four-factor prothrombin complex concentrate to reverse baseline INR elevation prior to alteplase administration to minimize the risk for intracerebral hemorrhage.
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 exists regarding the utility of extracorporeal membrane oxygenation (ECMO) in these critically ill patients shows poor overall outcomes. This paper describes our institutional practice regarding the application and management of ECMO support for patients with Covid-19 and reports promising early outcomes. METHODS:>60 mmHg 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:Of 321 patients intubated for Covid-19, 77 (24%) patients were evaluated for ECMO support with 27 (8.4%) patients placed on ECMO. All patients were placed on veno-venous ECMO. Current survival is 96.3%, with only one mortality to date in over 350 days of total ECMO support. Thirteen patients (48.1%) remain on ECMO support, while 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 four are on room-air. No healthcare workers that 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.
Letter on The Society of Thoracic Surgeons Intermacs 2019 Annual Report [Letter]
A Simple Prioritization Change to Lung Transplant Allocation May Result in Improved Outcomes
BACKGROUND:The Lung Allocation Score (LAS) significantly improved outcomes and waitlist mortality in lung transplantation. However, mortality remains high for the sickest waitlist candidates despite additional changes to allocation distance. Regulatory considerations of overhauling the current lung allocation system has met significant resistance, and would require years to implement. This study evaluates if a modest change to the current system by prioritization of only high-LAS lung transplant candidates would result in lowered waitlist mortality. METHODS:The Thoracic Simulated Allocation Model was used to evaluate all lung transplant candidates and donor lungs recovered between July 1, 2009 and June 30, 2011. Current lung allocation rules (initial offer within 250 nautical-mile radius for ABO-identical then compatible offers) were run. Allocation was then changed for only patients with an LASâ‰¥50 (high-LAS) to be prioritized within a 500 nautical-mile radius with no stratification between ABO-identical and compatible offers. Ten iterations of each model were run. Primary endpoints were waitlist mortality and post-transplant 1-year survival. RESULTS:6,538 waitlist candidates and transplant recipients were evaluated per iteration, for a total of 130,760 simulated patients. Compared with current allocation, the adjusted model had a 23.3% decrease in waitlist mortality. Post-transplant 1-year survival was minimally affected. CONCLUSIONS:Without overhauling the entire system, simple prioritization changes to the allocation system for high-LAS candidates may lead to decreased waitlist mortality and increased organ utilization. Importantly, these changes do not appear to lead to clinically significant changes in post-transplant 1-year survival.