Pulmonary Co-Infections Detected Premortem Underestimate Postmortem Findings in a COVID-19 Autopsy Case Series.

Bacterial and fungal co-infections are reported complications of coronavirus disease 2019 (COVID-19) in critically ill patients but may go unrecognized premortem due to diagnostic limitations. We compared the premortem with the postmortem detection of pulmonary co-infections in 55 fatal COVID-19 cases from March 2020 to March 2021. The concordance in the premortem versus the postmortem diagnoses and the pathogen identification were evaluated. Premortem pulmonary co-infections were extracted from medical charts while applying standard diagnostic definitions. Postmortem co-infection was defined by compatible lung histopathology with or without the detection of an organism in tissue by bacterial or fungal staining, or polymerase chain reaction (PCR) with broad-range bacterial and fungal primers. Pulmonary co-infection was detected premortem in significantly fewer cases (15/55, 27%) than were detected postmortem (36/55, 65%; p < 0.0001). Among cases in which co-infection was detected postmortem by histopathology, an organism was identified in 27/36 (75%) of cases. Pseudomonas, Enterobacterales, and Staphylococcus aureus were the most frequently identified bacteria both premortem and postmortem. Invasive pulmonary fungal infection was detected in five cases postmortem, but in no cases premortem. According to the univariate analyses, the patients with undiagnosed pulmonary co-infection had significantly shorter hospital (p = 0.0012) and intensive care unit (p = 0.0006) stays and significantly fewer extra-pulmonary infections (p = 0.0021). Bacterial and fungal pulmonary co-infection are under-recognized complications in critically ill patients with COVID-19.

Treatment of hyperammonemia using in-line renal replacement and hyperosmolar therapies within an extracorporeal membrane oxygenation circuit.

After orthotopic lung transplantation, hyperammonemia can be a rare complication secondary to infection by organisms that produce urease or inhibit the urea cycle. This can cause neurotoxicity, cerebral edema, and seizures. Ammonia is unique in that it has a large volume of distribution. However, it is also readily dialyzable given its small molecular weight. As such, removal of ammonia requires renal replacement modalities that can both rapidly remove ammonia from the plasma space and allow for continuous removal to prevent rebound accumulation from intracellular stores. Prevention of iatrogenic osmotic lowering in this setting is required to prevent worsening of cerebral edema. Herein, we describe use of sequential in-line renal replacement therapy using both intermittent hemodialysis and continuous venovenous hemofiltration within an extracorporeal membrane oxygenation circuit in conjunction with higher sodium dialysate and 7.5% hypertonic saline to achieve these treatment goals.

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.

SARS-CoV-2 infection and persistence in the human body and brain at autopsy.

Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction1-3 during acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients experiencing prolonged symptoms, termed post-acute sequelae of SARS-CoV-2 (refs. 4,5). However, the burden of infection outside the respiratory tract and time to viral clearance are not well characterized, particularly in the brain3,6-14. Here we carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients, to map and quantify the distribution, replication and cell-type specificity of SARS-CoV-2 across the human body, including the brain, from acute infection to more than seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite extensive distribution of SARS-CoV-2 RNA throughout the body, we observed little evidence of inflammation or direct viral cytopathology outside the respiratory tract. Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.

Veno-Arterial Extracorporeal Membrane Oxygenation for Pulmonary Embolism after Systemic Thrombolysis.

Massive pulmonary embolism (PE) is a life-threatening condition with a high mortality. Both systemic thrombolytics and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) have been used in the management of massive PE. However, the safety of VA- ECMO in the setting of recent thrombolytic administration is not clear. The purpose of this study is to analyze the outcomes of patients who received VA-ECMO in the setting of systemic thrombolytics (ST). A single institution retrospective study of PE patients treated with VA-ECMO between December 2015 and December 2020 was performed. Patients who received ST were compared with those who did not receive ST. Outcomes, including mortality, major bleeding, duration of mechanical ventilation, need for renal replacement therapy, and length of hospital stay, were compared. A total of 83 patients with PE required VA-ECMO support and 18 of these received systemic thrombolytics. There was no statistically significant difference in survival to discharge between the patients who received ST compared with those who did not (88.9% vs 84.6%; p = 0.94). Major bleeding events occurred more often in patients who received ST (61.1% vs 26.2%; p = 0.01). There was no significant difference in time on mechanical ventilation, need for renal replacement therapy, or length of stay between the groups. Reasonable survival can be achieved despite an increased frequency of major bleeding events in patients that receive ST prior to VA-ECMO for PE. ST administration should not be considered an absolute contraindication to VA-ECMO. Further multi-center studies are needed to corroborate these findings.

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.

Inferior Vena Cava Filter Placement Through a Venovenous Extracorporeal Membrane Oxygenation Circuit.

We present a technique for performing endovascular procedures by obtaining vascular access directly through a venovenous extracorporeal membrane oxygenation (VV ECMO) circuit. This technique is demonstrated in a lung transplant recipient, supported on VV ECMO, whose course was complicated by an extensive right femoral vein and inferior vena cava deep venous thrombosis. The patient was successfully managed by the placement of an inferior vena cava filter using the VV ECMO circuit as a point of access to the circulatory system before cessation of VV ECMO support and decannulation.

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.

Evidence of SARS-CoV-2-Specific T-Cell-Mediated Myocarditis in a MIS-A Case.

A 26-year-old otherwise healthy man died of fulminant myocarditis. Nasopharyngeal specimens collected premortem tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Histopathological evaluation of the heart showed myocardial necrosis surrounded by cytotoxic T-cells and tissue-repair macrophages. Myocardial T-cell receptor (TCR) sequencing revealed hyper-dominant clones with highly similar sequences to TCRs that are specific for SARS-CoV-2 epitopes. SARS-CoV-2 RNA was detected in the gut, supporting a diagnosis of multisystem inflammatory syndrome in adults (MIS-A). Molecular targets of MIS-associated inflammation are not known. Our data indicate that SARS-CoV-2 antigens selected high-frequency T-cell clones that mediated fatal myocarditis.

Venoarterial Extracorporeal Membrane Oxygenation via Direct Axillary Artery Cannulation.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an effective means of support for patients awaiting cardiac or cardiopulmonary transplantation. Typically, peripheral cannulation via the femoral vessels is preferred. However, an alternative is use of the axillary or subclavian artery, which is typically performed via a graft. Here we present the case of a patient who required VA-ECMO for cardiogenic shock with severe pulmonary hypertension as a bridge to heart-lung transplantation. Initially cannulated via the femoral artery, he was converted to a direct axillary cannulation strategy with a distal perfusion catheter and successfully bridged to transplantation. This technique avoids the use of an interposition graft and mitigates problems associated with it.

Catheter-based interventions versus medical and surgical approaches in acute pulmonary embolism.

OBJECTIVE: Catheter-based intervention (CBI) has become an increasingly popular option for treating pulmonary embolism (PE); however, the real benefits are unknown. The purpose of the present study was to compare the outcomes of patients treated with CBI with the outcomes of those treated with medical or surgical approaches. METHODS: We performed a retrospective analysis of patients admitted from October 2015 to December 2017 with a diagnosis of acute PE. We compared patients aged ≥18 years with a diagnosis of acute PE treated with CBI against a control group identified by propensity score matching. The control group was divided into those who had undergone surgical pulmonary embolectomy (SPE) as the surgical group and those who had not undergone SPE as the medical group. The primary outcome was mortality (in-hospital and overall mortality). The secondary outcomes were major bleeding, length of hospital stay, thrombus resolution, right ventricle improvement in systolic function and dilatation, and recurrent PE. RESULTS: Of the 108 patients, 30 were in the CBI group and 78 were in the control group (62 in the medical group and 16 in the surgical group). The patient characteristics on admission were similar, except for the body mass index, which was greater in the CBI group (P = .03). No difference was found in clinical severity, clot burden, right ventricle function, or biomarkers. Recurrent PE was less frequent in the CBI group than in the medical group (0% vs 6.4%). Otherwise, no significant differences were found in the outcomes between the CBI and medical groups. When CBI was compared with the surgical group, SPE was associated with improved mortality (0% vs 16.6%) but a longer median length of hospital stay (median, 7 days; interquartile range, 3-12 days; vs median, 8 days; interquartile range, 6.5-17 days). CONCLUSIONS: The use of CBI reduced the number of recurrent PE events compared with the medically treated patients; however, the mortality was higher than that in the surgical group.

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.

Clinical Outcomes of Perioperative Desensitization in Heart Transplant Recipients.

BACKGROUND: Sensitization remains a barrier to heart transplantation (HT). Perioperative desensitization strategies have been described; however, a paucity of evidence exists to demonstrate efficacy and safety in HT. METHODS: This single-center, retrospective study consisted of adults who received an HT. Perioperative desensitization was initiated if virtual crossmatch or flow-cytometry crossmatch was positive. Therapy consisted of plasmapheresis, intravenous immunoglobulin, and rabbit antithymocyte globulin. Historical controls received standard immunosuppression or induction. The primary endpoint was survival at 12 mo. Secondary endpoints included freedom from acute rejection, cardiac allograft vasculopathy (CAV), and infectious complications. RESULTS: Of the 104 patients included, 48 received no induction, 46 received induction, and 10 underwent perioperative desensitization. No differences were observed in the primary endpoint at 12 mo (90.0% versus 97.9%, P = 0.25 for desensitization versus no-induction; 90.0% versus 100%, P = 0.72 for desensitization versus induction). Rates of acute rejection were lower with induction and desensitization compared with no-induction. There were no significant differences in CAV between the groups. Infectious complications were also similar among the groups (10.0% versus 16.7%, P = 0.62 for desensitization versus no-induction; 10.0% versus 30.4%, P = 0.34 for desensitization versus induction). CONCLUSIONS: This study suggests that a perioperative desensitization strategy triggered by positive virtual crossmatch or flow-cytometry crossmatch allows for successful transplantation of sensitized HT recipients and results in acceptable rates of survival, rejection, CAV, and infection at 12 mo.

Minimally Invasive Left Ventricular Assist Device Insertion Facilitates Subsequent Heart Transplant.

OBJECTIVE: We have observed that minimally invasive left ventricular assist device (LVAD) insertion leads to more facile re-entry and easier cardiac transplantation. We hypothesize minimally invasive LVAD implantation results in improved outcomes at the time of subsequent heart transplant. METHODS: All adults undergoing cardiac transplantation between October 2015 and March 2019 at our institution were retrospectively reviewed. Those bridged to transplantation with a HeartWare HVAD were identified and divided into 2 cohorts based upon the surgical approach: those who underwent HVAD placement by conventional sternotomy versus minimally invasive insertion via lateral thoracotomy and hemisternotomy (LTHS). Patient demographics, as well as perioperative transplant outcomes, including survival, length of stay (LOS), blood utilization, ischemic time, bypass time, and postoperative extracorporeal membrane oxygenation (ECMO) were compared between cohorts. RESULTS: Forty-two patients were bridged to heart transplant with a HVAD implanted via either sternotomy (n = 22) or LTHS technique (n = 20). Demographics were similar between groups. There was 1 predischarge death in the sternotomy group and none in the LTHS group. Body surface area, cardiopulmonary bypass time, ischemic time, ECMO utilization, and reoperation for bleeding were similar. Red blood cell units transfused were significantly lower in the LTHS cohort (3.0 [1.0-5.0] vs 6.0 [2.5-10.0] P = 0.046). The LTHS cohort had a significantly shorter hospital LOS (12.0 [11.0-28.0] vs 22.5 [15.7-41.7] P = 0.022) with a trend toward shorter intensive care unit LOS (6.0 [5.0-10.5] vs 11.0 [6.0-21.5] days P = 0.057). CONCLUSIONS: Minimally invasive HVAD implantation improves outcomes at subsequent heart transplantation, resulting in shorter LOS and less red cell transfusion. Larger multi-institutional studies are necessary to validate these findings.

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.

Intoxication and overdose should not preclude veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: Acute intoxication (AI) related morbidity and mortality are increasing in the United States. For patients with severe respiratory failure in the setting of an acute ingestion, veno-venous extracorporeal membrane oxygenation (VV ECMO) can provide salvage therapy. The purpose of this study was to evaluate outcomes in patients with overdose-related need for VV ECMO. METHODS: We performed a retrospective review of all patients admitted to a specialty VV ECMO unit between August 2014 and August 2018. Patients were stratified by those whose indication for VV ECMO was directly related to an acute ingestion (alcohol, illicit drug, or prescription drug overdose) and those with unrelated diagnoses. Demographics, pre-cannulation clinical characteristics, ECMO parameters, and outcomes data was collected and analyzed with parametric and non-parametric statistics as indicated. RESULTS: 189 patients were enrolled with 27 (14%) diagnosed with AI. Patients requiring VV ECMO for an AI were younger, had lower median BMI and PaO2/FiO2, and higher RESP scores than non-AI patients (p = 0.002, 0.01, 0.03 and 0.01). There was no difference in pre-cannulation pH, lactate, or SOFA scores between the two groups (p = 0.24, 0.5, 0.6). There was no difference in survival to discharge (p = 0.95). Among survivors, there was no difference in ECMO time or hospital stay (p = 0.24, 0.07). CONCLUSION: We demonstrate no survival difference for patients with and without an AI-related need for VV ECMO. AI patients should be supported with VV ECMO when traditional therapies fail despite potential stigma against acceptance on referral.

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.

High Right Ventricular Afterload Is Associated with Impaired Exercise Tolerance in Patients with Left Ventricular Assist Devices.

Patients with left ventricular assist device (LVAD) have poor exercise tolerance. We aimed to characterize relationship between right ventricular (RV) afterload and exercise capacity, RV reserve, and adaptation to load. Twelve well-compensated LVAD subjects underwent right heart catheterization at rest and during symptom-limited exercise. Cardiopulmonary exercise tests were also performed. Hemodynamics were compared with age- and sex-matched subjects with pulmonary arterial hypertension (PAH) and normal non-athletes. Hemodynamic changes were expressed as Δ(exercise - rest). At rest, LVAD subjects had normal biventricular pressures and cardiac output (CO). On exercise, despite similar increases in pulmonary artery wedge pressure (PAWP) between three groups, RV afterload increased only in LVAD cohort (pulmonary elastance [ΔEa] LVAD: 0.4, PAH: 0.1, normal: 0.1 mmHg/ml, p = 0.0024). This afterload increase coincided with the largest rise in right atrial pressure (RAP), lowest change in RV stroke work index, and smallest CO augmentation (ΔCO LVAD: 1.5, PAH: 4.3, normal: 5.7 L/min, p = 0.0014). Peak VO2 negatively correlated with RV afterload (Ea) (r = -0.8, p = 0.0101), while VE/VCO2 slope had the inverse correlation. During exercise, pulmonary artery pulsatility index worsened while RAP:PAWP ratio was unchanged in LVAD subjects. Well-compensated LVAD patients had poor RV reserve and adaptation to load on exercise compared with PAH and normal subjects.