Maternal transfer of IgA and IgG SARS-CoV-2 specific antibodies transplacentally and via breast milk feeding.

BACKGROUND: Although there have been many studies on antibody responses to SARS-CoV-2 in breast milk, very few have looked at the fate of these in the infant, and whether they are delivered to immunologically relevant sites in infants. METHODS: Mother/infant pairs (mothers who breast milk fed and who were SARS-CoV-2 vaccinated before or after delivery) were recruited for this cross-sectional study. Mother blood, mother breast milk, infant blood, infant nasal specimen, and infant stool was tested for IgA and IgG antibodies against SARS-CoV-2 spike trimer. RESULTS: Thirty-one mother/infant pairs were recruited. Breast milk fed infants acquired systemic anti-spike IgG antibodies only if their mothers were vaccinated antepartum (100% Antepartum; 0% Postpartum; P<0.0001). Breast milk fed infants acquired mucosal anti-spike IgG antibodies (in the nose) only if their mothers were vaccinated antepartum (89% Antepartum; 0% Postpartum; P<0.0001). None of the infants in either group had anti-spike IgA in the blood. Surprisingly, 33% of the infants whose mothers were vaccinated antepartum had high titer anti-spike IgA in the nose (33% Antepartum; 0% Postpartum; P = 0.03). Half-life of maternally transferred plasma IgG antibodies in the Antepartum infant cohort was ~70 days. CONCLUSION: Vaccination antepartum followed by breast milk feeding appears to be the best way to provide systemic and local anti-SARS-CoV-2 antibodies for infants. The presence of high titer SARS-CoV-2-specific IgA in the nose of infants points to the potential importance of breast milk feeding early in life for maternal transfer of mucosal IgA antibodies. Expectant mothers should consider becoming vaccinated antepartum and consider breast milk feeding for optimal transfer of systemic and mucosal antibodies to their infants.

Spinal Cord Infarction With Prolonged Femoral Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: There have been sporadic reports of ischemic spinal cord injury (SCI) during venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. The authors observed a troubling pattern of this catastrophic complication and evaluated the potential mechanisms of SCI related to ECMO. DESIGN: This study was a case series. SETTING: This study was performed at a single institution in a University setting. PARTICIPANTS: Patients requiring prolonged VA-ECMO were included. INTERVENTIONS: No interventions were done. This was an observational study. MEASUREMENTS AND MAIN RESULTS: Four hypotheses of etiology were considered: (1) hypercoagulable state/thromboembolism, (2) regional hypoxia/hypocarbia, (3) hyperperfusion and spinal cord edema, and (4) mechanical coverage of spinal arteries. The SCI involved the lower thoracic (T7-T12 level) spinal cord to the cauda equina in all patients. Seven out of 132 (5.3%) patients with prolonged VA-ECMO support developed SCI. The median time from ECMO cannulation to SCI was 7 (range: 6-17) days.There was no evidence of embolic SCI or extended regional hypoxia or hypocarbia. A unilateral, internal iliac artery was covered by the arterial cannula in 6/7 86%) patients, but flow into the internal iliac was demonstrated on imaging in all available patients. The median total flow (ECMO + intrinsic cardiac output) was 8.5 L/min (LPM), and indexed flow was 4.1 LPM/m2. The median central venous oxygen saturation was 88%, and intracranial pressure was measured at 30 mmHg in one patient, suggestive of hyperperfusion and spinal cord edema. CONCLUSIONS: An SCI is a serious complication of extended peripheral VA-ECMO support. Its etiology remains uncertain, but the authors' preliminary data suggested that spinal cord edema from hyperperfusion or venous congestion could contribute.

Contralateral Lower Extremity Ischemia on Femoral Veno-Arterial Extracorporeal Membrane Oxygenation.

Ipsilateral lower extremity ischemia is a common and morbid complication during veno-arterial extracorporeal membrane oxygenation (VA-ECMO). The cannula can impede ipsilateral distal arterial flow leading to critical limb ischemia. Cannula size, placement, and utilization of distal perfusion catheters are strategies that have been used to prevent this complication. We report the novel case of a 19-year-old female on VA-ECMO complicated by contralateral lower extremity ischemia. Diagnosis was made by computed tomography, and with repositioning of the femoral arterial cannula, she had a complete resolution of symptoms.

A descriptive evaluation of causes of death in venovenous extracorporeal membrane oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become an important support modality for patients with acute respiratory failure refractory to optimal medical therapy, such as low tidal volume mechanical ventilator support, early paralytic infusion, and early prone positioning. The objective of this cohort study was to investigate the causes and timing of in-hospital mortality in patients on VV ECMO. All patients, excluding trauma and bridge to lung transplant, admitted 8/2014-6/2019 to a specialty ICU for VV ECMO were reviewed. Two hundred twenty-five patients were included. In-hospital mortality was 24.4% (n = 55). Most non-survivors (46/55, 84%) died prior to lung recovery and decannulation from VV ECMO. Most common cause of death (COD) for patients who died on VV ECMO was removal of life sustaining therapy (LST) in setting of multisystem organ failure (MSOF) (n = 24). Nine patients died a median of 9 days [6, 11] after decannulation. Most common COD in these patients was palliative withdrawal of LST due to poor prognosis (n = 3). Non-survivors were older and had worse predictive mortality scores than survivors. We found that death in patients supported with VV ECMO in our study most often occurs prior to decannulation and lung recovery. This study demonstrated that the most common cause of death in patients supported with VV ECMO was removal of LST due MSOF. Acute hemorrhage (systemic or intracranial) was not found to be a common cause of death in our patient population.

Body mass index does not impact survival in COVID-19 patients requiring veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: With the increased demand for veno-venous extracorporeal membrane oxygenation (VV ECMO) during the COVID-19 pandemic, guidelines for patient candidacy have often limited this modality for patients with a body mass index (BMI) less than 40 kg/m2. We hypothesize that COVID-19 VV ECMO patients with at least class III obesity (BMI ≥ 40) have decreased in-hospital mortality when compared to non-COVID-19 and non-class III obese COVID-19 VV ECMO populations. METHODS: This is a single-center retrospective study of COVID-19 VV ECMO patients from January 1, 2014, to November 30, 2021. Our institution used BMI ≥ 40 as part of a multi-disciplinary VV ECMO candidate screening process in COVID-19 patients. BMI criteria were not considered for exclusion criteria in non-COVID-19 patients. Univariate and multivariable analyses were performed to assess in-hospital mortality differences. RESULTS: A total of 380 patients were included in our analysis: The COVID-19 group had a lower survival rate that was not statistically significant (65.7% vs.74.9%, p = .07). The median BMI between BMI ≥ 40 COVID-19 and non-COVID-19 patients was not different (44.5 vs 45.5, p = .2). There was no difference in survival between the groups (73.3% vs. 78.5%, p = .58), nor was there a difference in survival between the COVID-19 BMI ≥ 40 and BMI < 40 patients (73.3, 62.7, p= .29). Multivariable logistic regression with the outcome of in-hospital mortality was performed and BMI was not found to be significant (OR 0.99, 95% CI 0.89, 1.01; p = .92). CONCLUSION: BMI ≥ 40 was not an independent risk factor for decreased in-hospital survival in this cohort of VV ECMO patients at a high-volume center. BMI should not be the sole factor when deciding VV ECMO candidacy in patients with COVID-19.

Decreased PRESET-Score corresponds with improved survival in COVID-19 veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: The PREdiction of Survival on ECMO Therapy Score (PRESET-Score) predicts mortality while on veno-venous extracorporeal membrane oxygenation (VV ECMO) for acute respiratory distress syndrome. The aim of our study was to assess the association between PRESET-Score and survival in a large COVID-19 VV ECMO cohort. METHODS: This was a single-center retrospective study of COVID-19 VV ECMO patients from 15 March 2020, to 30 November 2021. Univariable and Multivariable analyses were performed to assess patient survival and score differences. RESULTS: A total of 105 patients were included in our analysis with a mean PRESET-Score of 6.74. Overall survival was 65.71%. The mean PRESET-Score was significantly lower in the survivor group (6.03 vs 8.11, p < 0.001). Patients with a PRESET-Score less than or equal to six had improved survival compared to those with a PRESET-Score greater than or equal to 8 (97.7% vs. 32.5%, p < 0.001). In a multivariable logistic regression, a lower PRESET-Score was also predictive of survival (OR 2.84, 95% CI 1.75, 4.63, p < 0.001). CONCLUSION: We demonstrate that lower PRESET scores are associated with improved survival. The utilization of this validated, quantifiable, and objective scoring system to help identify COVID-19 patients with the greatest potential to benefit from VV-ECMO appears feasible. The incorporation of the PRESET-Score into institutional ECMO candidacy guidelines can help insure and improve access of this limited healthcare resource to all critically ill patients.

Nicorandil attenuates ventricular dysfunction and organ injury after cardiopulmonary bypass.

BACKGROUND: Nicorandil, an adenosine triphosphate-sensitive potassium channel agonist and nitric oxide donor, is a coronary vasodilator used to treat ischemia-induced chest pain, but it's potential cardioprotective benefits during open heart surgery have not been thoroughly investigated. The study objective was to assess the impact of nicorandil on postoperative ventricular dysfunction and end-organ injury in an established experimental model of open-heart surgery with cardiopulmonary bypass (CPB) and cardioplegic arrest. We hypothesized that nicorandil would attenuate myocardial ischemia-reperfusion (IR) injury, preserve ventricular function, and reduce end-organ injury. METHODS: Rabbits were cannulated for CPB, followed by 60 min of aortic cross-clamp (ACC) with cold cardioplegic arrest, and 120 min of recovery after ACC removal. Nicorandil (or normal saline vehicle) was given intravenously 5 min before ACC and continued throughout the recovery period. Left ventricular developed pressure (LVDP), systolic contractility (LV + dP/dt), and diastolic relaxation (LV -dP/dt) were continuously recorded, and blood and tissue samples were collected for measurement of oxidant stress (OS), inflammation, apoptosis, and organ injury. RESULTS: Nicorandil significantly attenuated IR-induced LV dysfunction compared to saline control (R-120: LV + dP/dt: 1596 ± 397 vs. 514 ± 269 mmHg/s, p = 0.010; LV -dP/dt: -1524 ± 432 vs. -432 ± 243 mmHg/s, p < 0.001; LVDP: 55 ± 11 vs. 22 ± 5 mmHg, p = 0.046). Furthermore, nicorandil inhibited IR-induced increases in OS, inflammation, apoptosis, and organ injury. CONCLUSIONS: Nicorandil exhibits myocardial protection by attenuation of IR-induced LV dysfunction associated with OS, inflammation, apoptosis, and organ injury. Nicorandil should be explored further as a potential therapeutic strategy for limiting global IR injury during open-heart surgery in humans.

Peripheral cannulation for extracorporeal membrane oxygenation yields superior neurologic outcomes in adult patients who experienced cardiac arrest following cardiac surgery.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest has improved mortality in post-cardiac surgery patients; however, loss of neurologic function remains one of the main and devastating complications. We reviewed our experience with ECPR and investigated the effect of cannulation strategy on neurologic outcome in adult patients who experienced cardiac arrest following cardiac surgery that was managed with ECPR. METHODS: Patients were categorized by central versus percutaneous peripheral VA-extracorporeal membrane oxygenation (ECMO) cannulation strategy. We reviewed patient records and evaluated in-hospital mortality, cause of death, and neurologic status 72 hours after cannulation. RESULTS: From January 2010 to September 2019, 44 patients underwent post-cardiac surgery ECPR for cardiac arrest. Twenty-six patients received central cannulation; 18 patients received peripheral cannulation. Mean post-operative day of the cardiac arrest was 3 and 9 days (p = 0.006), and mean time between initiation of CPR and ECMO was 40 ± 24 and 28 ± 22 minutes for central and peripheral cannulation, respectively. After 72 hours of VA-ECMO support, 30% of centrally cannulated patients versus 72% of peripherally cannulated patients attained cerebral performance status 1-2 (p = 0.01). Anoxic brain injury was the cause of death in 26.9% of centrally cannulated and 11.1% of peripherally cannulated patients. Survival to discharge was 31% and 39% for central and peripheral cannulation, respectively. CONCLUSIONS: Peripheral VA-ECMO allows for continuous CPR and systemic perfusion while obtaining vascular access. Compared to central cannulation, a peripheral cannulation strategy is associated with improved neurologic outcomes and decreased likelihood of anoxic brain death.

Precannulation International Normalized Ratio is Independently Associated With Mortality in Veno-Arterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: To explore whether precannulation international normalized ratio (INR) is associated with in-hospital mortality in venoarterial extracorporeal membrane oxygenation (VA-ECMO) patients. DESIGN: A retrospective, observational cohort study. SETTING: A quaternary care academic medical center. PARTICIPANTS: Patients with cardiogenic shock on VA-ECMO for >24 hours. INTERVENTIONS: None, observational study. MEASUREMENTS AND MAIN RESULTS: A total of 188 patients who were on VA-ECMO were included over three years. Patients were stratified into three groups based on their pre-ECMO INR: INR <1.5, INR 1.5 to 1.8, and INR >1.8. For all patients, demographics, comorbidities, and ECMO details were recorded. The study's primary outcome was in-hospital mortality and secondary outcomes included major bleeding, minor bleeding, allogeneic transfusion, ischemic stroke, intracranial hemorrhage, acute renal failure, acute liver failure, gastrointestinal bleeding, intensive care unit and hospital lengths of stay. A multivariate logistic regression was used to determine whether precannulation INR was associated independently with in-hospital mortality. In-hospital mortality differed significantly by INR group (51.6% INR >1.8 v 42.3% INR 1.5-1.8 v 24.3% INR <1.5; p = 0.004). In a multivariate logistic regression model, precannulation INR >1.8 was associated independently with an increased odds of mortality (odds ratio, 2.48; 95% confidence interval, 1.05-6.04) after controlling for sex, Survival after VA- ECMO score, and ECMO indication. An INR within 1.5 to 1.8 did not confer an increased mortality risk. CONCLUSIONS: An INR >1.8 before VA-ECMO cannulation is associated independently with in-hospital mortality. Precannulation INR should be considered by clinicians so that ECMO resources can be better allocated and risks of organ failure and intracranial hemorrhage can be better understood.

A Comparison of Anticoagulation Strategies in Veno-venous Extracorporeal Membrane Oxygenation.

Bleeding remains a major source of morbidity associated with veno-venous extracorporeal membrane oxygenation (VV-ECMO). Moreover, there remains significant controversy, and a paucity of data regarding the ideal anticoagulation strategy for VV-ECMO patients. All patients undergoing isolated, peripheral VV-ECMO between January 2009 and December 2014 at our institution were retrospectively reviewed. Patients (n = 123) were stratified into one of three sequential eras of anticoagulation strategies: activated clotting time (ACT: 160-180 seconds, n = 53), high-partial thromboplastin time (H-PTT: 60-80 seconds, n = 25), and low-PTT (L-PTT: 45-55 seconds, n = 25) with high-flow (>4 L/min). Pre-ECMO APACHE II scores, SOFA scores, and Murray scores were not significantly different between the groups. Patients in the L-PTT group required less red blood cell units on ECMO than the ACT or H-PTT group (2.1 vs. 1.3 vs. 0.9; p < 0.001) and patients in the H-PTT and L-PTT group required less fresh frozen plasma than the ACT group (0.33 vs. 0 vs. 0; p = 0.006). Overall, major bleeding events were significantly lower in the L-PTT group than in the ACT and H-PTT groups. There was no difference in thrombotic events. In this single-institution experience, a L-PTT, high-flow strategy on VV-ECMO was associated with fewer bleeding and no difference in thrombotic events than an ACT or H-PTT strategy.

Association of Volume Status During Veno-Venous Extracorporeal Membrane Oxygenation with Outcome.

Fluid overload in acute respiratory distress syndrome is associated with increased mortality. The purpose of this study was to investigate the association of cumulative fluid balance (CFB) during the first 7 days of veno-venous extracorporeal membrane oxygenation (VV ECMO) and mortality. Adult patients on VV ECMO for greater than 168 hours, between November 2015 and October 2019, were included. CFB during the first 7 ECMO days was compared between survivors and nonsurvivors, and survival was analyzed using Kaplan-Meier analysis and cox proportional hazards modeling. One hundred forty-six patients were included. Median age was 45 years [32, 55], respiratory ECMO survival prediction score was 3 [0, 5], and P/F ratio was 70 [55, 85]. CFB for ECMO days 1-3 was +2,350 cc [-540, 5,941], days 4-7 -3,070 cc [-6,545, 437], and days 1-7 -341 cc [-4,579, 5,290]. One hundred seventeen patients (80%) survived to hospital discharge. Survivors were younger (41 years [31, 53] vs. 53 years [45, 60], p < 0.001) and had a higher respiratory ECMO survival prediction score, (3 [1, 5] vs. 1.5 [-1, 3], p = 0.002). VV ECMO survivors had a significantly more negative CFB during the first 7 days of VV ECMO (-1,311 cc [-4,755, 4,217] vs. 3,617 cc [-2,764, 9,413], p = 0.02), and CFB was an independent predictor of 90 day mortality (HR = 1.07 [1.01, 1.14], p = 0.02). Further studies are needed to determine the causal relationship between fluid balance and survival during VV ECMO.

Ultrasound-assisted catheter directed thrombolysis for pulmonary embolus during extracorporeal membrane oxygenation.

BACKGROUND: Acute pulmonary embolism (PE) is the third most common cause of cardiovascular death. For patients who are hemodynamically unstable, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support has been shown to provide hemodynamic stability, and allow time for definitive treatment and recovery. Ultrasound-assisted catheter directed thrombolysis (USAT) has the potential to be a safe adjunct and expedite right ventricular (RV) recovery for patients requiring VA-ECMO for PE. METHODS: A review of all VA-ECMO patients from January 2017 to September 2019 was performed. A total of 49 of these patients were cannulated due to a PE. USAT therapy was used as an adjunct in 6 (12%) of these patients. These 6 patients were given standardized USAT therapy with EKOs catheters at 1 mg/h of tissue plasminogen activator with an unfractionated heparin infusion for additional systemic anticoagulation. Outcomes, including in-hospital death, 90-day survival, RV recovery, and complications, were examined in the cohort of patients that received USAT as an adjunct to ECMO. RESULTS: Median age was 54 years old. Five of the six patients presented with a massive PE and had a PE severity score of Class V. One patient presented with a submassive PE with a Bova score of 2, but was cannulated to VA-ECMO in the setting of worsening RV function. All patients demonstrated recovery of RV function, were free from in-hospital death, and were alive at 90-day follow-up. CONCLUSION: Ekosonic endovascular system therapy may be a safe and feasible adjunct for patients on VA-ECMO for PE, and allow for survival with RV recovery with minimal complications.

A Dedicated Veno-Venous Extracorporeal Membrane Oxygenation Unit during a Respiratory Pandemic: Lessons Learned from COVID-19 Part I: System Planning and Care Teams.

BACKGROUND: The most critically ill patients with coronavirus disease 2019 (COVID-19) may require advanced support modalities, such as veno-venous extracorporeal membrane oxygenation (VV-ECMO). A systematic, methodical approach to a respiratory pandemic on a state and institutional level is critical. METHODS: We conducted retrospective review of our institutional response to the COVID-19 pandemic, focusing on the creation of a dedicated airlock biocontainment unit (BCU) to treat patients with refractory COVID-19 acute respiratory distress syndrome (CARDS). Data were collected through conversations with staff on varying levels in the BCU, those leading the effort to make the BCU and hospital incident command system, email communications regarding logistic changes being implemented, and a review of COVID-19 patient census at our institution from March through June 2020. RESULTS: Over 2100 patients were successfully admitted to system hospitals; 29% of these patients required critical care. The response to this respiratory pandemic augmented intensive care physician staffing, created a 70-member nursing team, and increased the extracorporeal membrane oxygenation (ECMO) capability by nearly 200%. During this time period, 40 COVID-19 patients on VV-ECMO were managed in the BCU. Challenges in an airlock unit included communication, scarcity of resources, double-bunking, and maintaining routine care. CONCLUSIONS: Preparing for a surge of critically ill patients during a pandemic can be a daunting task. The implementation of a coordinated, system-level approach can help with the allocation of resources as needed. Focusing on established strengths of hospitals within the system can guide triage based on individual patient needs. The management of ECMO patients is still a specialty care, and a systematic and hospital based approach requiring an ECMO team composed of multiple experienced individuals is paramount during a respiratory viral pandemic.

A Dedicated Veno-Venous Extracorporeal Membrane Oxygenation Unit during a Respiratory Pandemic: Lessons Learned from COVID-19 Part II: Clinical Management.

(1) Background: COVID-19 acute respiratory distress syndrome (CARDS) has several distinctions from traditional acute respiratory distress syndrome (ARDS); however, patients with refractory respiratory failure may still benefit from veno-venous extracorporeal membrane oxygenation (VV-ECMO) support. We report our challenges caring for CARDS patients on VV-ECMO and alterations to traditional management strategies. (2) Methods: We conducted a retrospective review of our institutional strategies for managing patients with COVID-19 who required VV-ECMO in a dedicated airlock biocontainment unit (BCU), from March to June 2020. The data collected included the time course of admission, VV-ECMO run, ventilator length, hospital length of stay, and major events related to bleeding, such as pneumothorax and tracheostomy. The dispensation of sedation agents and trial therapies were obtained from institutional pharmacy tracking. A descriptive statistical analysis was performed. (3) Results: Forty COVID-19 patients on VV-ECMO were managed in the BCU during this period, from which 21 survived to discharge and 19 died. The criteria for ECMO initiation was altered for age, body mass index, and neurologic status/cardiac arrest. All cannulations were performed with a bedside ultrasound-guided percutaneous technique. Ventilator and ECMO management were routed in an ultra-lung protective approach, though varied based on clinical setting and provider experience. There was a high incidence of pneumothorax (n = 19). Thirty patients had bedside percutaneous tracheostomy, with more procedural-related bleeding complications than expected. A higher use of sedation was noted. The timing of decannulation was also altered, given the system constraints. A variety of trial therapies were utilized, and their effectiveness is yet to be determined. (4) Conclusions: Even in a high-volume ECMO center, there are challenges in caring for an expanded capacity of patients during a viral respiratory pandemic. Though institutional resources and expertise may vary, it is paramount to proceed with insightful planning, the recognition of challenges, and the dynamic application of lessons learned when facing a surge of critically ill patients.

Extracorporeal Life Support Organization (ELSO): Guidelines for Pediatric Cardiac Failure.

These guidelines are applicable to neonates and children with cardiac failure as indication for extracorporeal life support. These guidelines address patient selection, management during extracorporeal membrane oxygenation, and pathways for weaning support or bridging to other therapies. Equally important issues, such as personnel, training, credentialing, resources, follow-up, reporting, and quality assurance, are addressed in other Extracorporeal Life Support Organization documents or are center-specific.

Extracorporeal Life Support (ECLS): A Review and Focus on Considerations for COVID-19.

ABSTRACT: Extracorporeal life support (ECLS) is a support modality for patients with severe acute respiratory distress syndrome (ARDS) who have failed conventional treatments including low tidal volume ventilation, prone positioning, and neuromuscular blockade. In addition, ECLS can be used for hemodynamic support for patients with cardiogenic shock or following cardiac arrest. Injured patients may also require ECLS support for ARDS and other indications. We review the use of ECLS for ARDS patients, trauma patients, cardiogenic shock patients, and post-cardiac arrest patients. We then describe how these principles are applied in the management of the novel coronavirus disease 2019 pandemic. Indications, predictors, procedural considerations, and post-cannulation management strategies are discussed.

Mortality Risk Assessment in COVID-19 Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: A life-threatening complication of coronavirus disease 2019 (COVID-19) is acute respiratory distress syndrome (ARDS) refractory to conventional management. Venovenous (VV) extracorporeal membrane oxygenation (ECMO) (VV-ECMO) is used to support patients with ARDS in whom conventional management fails. Scoring systems to predict mortality in VV-ECMO remain unvalidated in COVID-19 ARDS. This report describes a large single-center experience with VV-ECMO in COVID-19 and assesses the utility of standard risk calculators. METHODS: A retrospective review of a prospective database of all patients with COVID-19 who underwent VV-ECMO cannulation between March 15 and June 27, 2020 at a single academic center was performed. Demographic, clinical, and ECMO characteristics were collected. The primary outcome was in-hospital mortality; survivor and nonsurvivor cohorts were compared by using univariate and bivariate analyses. RESULTS: Forty patients who had COVID-19 and underwent ECMO were identified. Of the 33 patients (82.5%) in whom ECMO had been discontinued at the time of analysis, 18 patients (54.5%) survived to hospital discharge, and 15 (45.5%) died during ECMO. Nonsurvivors presented with a statistically significant higher Prediction of Survival on ECMO Therapy (PRESET)-Score (mean ± SD, 8.33 ± 0.8 vs 6.17 ± 1.8; P = .001). The PRESET score demonstrated accurate mortality prediction. All patients with a PRESET-Score of 6 or lowers survived, and a score of 7 or higher was associated with a dramatic increase in mortality. CONCLUSIONS: These results suggest that favorable outcomes are possible in patients with COVID-19 who undergo ECMO at high-volume centers. This study demonstrated an association between the PRESET-Score and survival in patients with COVID-19 who underwent VV-ECMO. Standard risk calculators may aid in appropriate selection of patients with COVID-19 ARDS for ECMO.

Breathing Life Back Into the Kidney-Continuous Renal Replacement Therapy and Veno-Venous Extracorporeal Membrane Oxygenation.

The purpose of this study was to evaluate the incidence of continuous renal replacement therapy (CRRT) in patients supported with veno-venous extracorporeal membrane oxygenation (VV ECMO). Secondary outcomes included mortality and the need for hemodialysis on hospital discharge. We performed a retrospective cohort study of all patients admitted to a specialty unit on VV ECMO between August 2014 and August 2018. Trauma and bridge to lung transplant patients were excluded. Demographics, comorbidities, pre-ECMO, ECMO, and renal replacement therapy outcome data were collected and analyzed with parametric and nonparametric statistics as appropriate. One hundred eighty-seven patients were enrolled. Median age was 45 (32, 55) years; precannulation pH, 7.21 (7.12, 7.30); PaO2/FiO2 ratio, 69 (56, 86); respiratory ECMO survival prediction score, 3 (0, 5); sequential organ failure assessment score, 12 (10, 14); and creatinine, 1.45 (0.93, 2.35) mg/dL. Overall survival to hospital discharge was 74.6%. Ninety-four (50.3%) patients had CRRT while on VV ECMO. Median time on CRRT was 14 (7, 21) days with 59 (61.4%) of these patients surviving to hospital discharge. Four (6.8%) patients, none with documented preexisting renal disease, required hemodialysis on discharge. CRRT patients had a statistically higher precannulation sequential organ failure assessment score, creatinine, total bilirubin and lower precannulation pH, respiratory ECMO survival prediction score, and platelet count compared with non-CRRT patients. Survival was 61.4% vs. 88.1% (p < 0.001). More than half of our patients received CRRT while on VV ECMO. CRRT was used in a more critically ill patient population and was associated with higher in-hospital mortality. However, for patients who survived to hospital discharge, the majority have full renal recovery.

Exosomes isolated from human cardiosphere-derived cells attenuate pressure overload-induced right ventricular dysfunction.

OBJECTIVES: Cardiosphere-derived cell (CDC) transplantation has been shown to attenuate right ventricular (RV) dysfunction in patients with hypoplastic left heart syndrome. However, live cell transplantation requires complex handling protocols that may limit its use. Exosomes are protein and nucleic acid-containing nanovesicles secreted by many cell types, including stem cells, which have been shown to exert a cardioprotective effect comparable with whole cells following myocardial injury. We therefore sought to evaluate 3 human CDC-derived exosome preparations in a juvenile porcine model of acute pressure-induced RV dysfunction. METHODS: Twenty immunocompetent juvenile Yorkshire pigs (7-10 kg) underwent pulmonary arterial banding followed by intramyocardial test agent administration: control (n = 6), XO-1 (n = 4), XO-2 (n = 5), and XO-3 (n = 5). Animals were monitored for 28 days postoperatively with periodic phlebotomy and echocardiography, followed by extensive postmortem gross and histopathologic analysis. RESULTS: All animals survived the banding operation. One died suddenly on postoperative day 1; another was excluded due to nonstandard response to banding. Of the remaining animals, there were no clinical concerns. RV fractional area change was improved in the XO-1 and XO-2 groups relative to controls at postoperative day 28. On histologic analysis, exosome-treated groups exhibited decreased cardiomyocyte hypertrophy with respect to controls. CONCLUSIONS: Human CDC-derived exosome administration was associated with significant preservation of RV systolic function in the setting of acute pressure overload. Such acellular preparations may prove superior to whole cells and may represent a novel therapeutic approach to clinical myocardial injury.

Outcomes of Venovenous Extracorporeal Membrane Oxygenation When Stratified by Age: How Old Is Too Old?

The purpose of this study was to evaluate survival to hospital discharge for patients on venovenous extracorporeal membrane oxygenation (VV ECMO) when stratified by age. We performed a retrospective study at single, academic, tertiary care center intensive care unit for VV ECMO. All patients, older than 17 years of age, on VV ECMO admitted to a specialized intensive care unit for the management of VV ECMO between August 2014 and May 2018 were included in the study. Trauma and bridge-to-lung transplant patients were excluded for this analysis. Demographics, pre-ECMO and ECMO data were collected. Primary outcome was survival to hospital discharge when stratified by age. Secondary outcomes included time on VV ECMO and hospital length of stay (HLOS). One hundred eighty-two patients were included. Median P/F ratio at time of cannulation was 69 [56-85], and respiratory ECMO survival prediction (RESP) score was 3 [1-5]. Median time on ECMO was 319 [180-567] hours. Overall survival to hospital discharge was 75.8%. Lowess and cubic spline curves demonstrated an inflection point associated with increased mortality at age >45 years. Kaplan-Meier analysis demonstrated significantly greater survival in patients <45 years of age (p = 0.0001). Survival to hospital discharge for those