Anti-factor Xa vs aPTT for heparin monitoring in extracorporeal membrane oxygenation.

PURPOSE: The goal of this study was to evaluate the correlation of anti-factor Xa (anti-Xa) and activated partial thromboplastin time (aPTT) measures with heparin dosing in adult patients on extracorporeal membrane oxygenation (ECMO) support. METHODS: This was a retrospective cohort study evaluating adult patients managed on ECMO for at least 24 hours who received unfractionated heparin for systemic anticoagulation and were monitored per protocol using anti-Xa and/or aPTT coagulation assays. The primary outcome was the correlation between aPTT and anti-Xa measures. The secondary outcomes included, but were not limited to, the number of hemorrhagic and thrombotic events. RESULTS: Twenty-seven patients were included in this study. In the 227 events where both laboratory values were collected, a weak correlation was found between anti-Xa and aPTT (Spearman's correlation coefficient = 0.4, P = 0). In the 12 hemorrhagic events that occurred, aPTT was collected for only 10 events. Fifty percent of those events were associated with supratherapeutic aPTT, while none of the hemorrhagic events were associated with a supratherapeutic anti-Xa level. Two thrombotic events occurred, one of which had subtherapeutic anti-Xa and aPTT and the other of which had neither an anti-Xa nor aPTT measure on the day the event occurred. CONCLUSION: In a population of patients on ECMO, many of whom had coronavirus disease 2019 (COVID-19), there was a weak association between aPTT and anti-Xa measures. Hemorrhagic evens were more common than thrombotic events; however, a relationship between these events and aPTT or anti-Xa levels was not determined. The applicability of these findings to an ECMO population without COVID-19 is unknown and will require further study.

A Comparison of Long-Term Outcomes in Patients Managed With Venovenous Extracorporeal Membrane Oxygenation in the First and Second Waves of the COVID-19 Pandemic in the United Kingdom.

OBJECTIVES: Early studies of venovenous extracorporeal membrane oxygenation (ECMO) in COVID-19 have revealed similar outcomes to historical cohorts. Changes in the disease and treatments have led to differences in the patients supported on venovenous ECMO in the first and second waves. We aimed to compare these two groups in both the acute and follow-up phase. DESIGN: Retrospective single-center cohort study comparing mortality at censoring date (November 30, 2021) and decannulation, patient characteristics, complications and lung function and quality of life (QOL-by European Quality of Life 5 Dimensions 3 Level Version) at first follow-up in patients supported on venovenous ECMO between wave 1 and wave 2 of the COVID-19 pandemic. SETTING: Critical care department of a severe acute respiratory failure service. PATIENTS: Patients supported on ECMO for COVID-19 between wave 1 (March 17, 2020, to August 31, 2020) and wave 2 (January 9, 2020, to May 25, 2021). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-three patients were included in our analysis. Survival at censoring date (χ 2 , 6.35; p = 0.012) and decannulation (90.4% vs 70.0%; p < 0.001) was significantly lower in the second wave, while duration of ECMO run was longer (12.0 d [18.0-30.0 d] vs 29.5 d [15.5-58.3 d]; p = 0.005). Wave 2 patients had longer application of noninvasive ventilation (NIV) prior to ECMO and a higher frequency of barotrauma. Patient age and NIV use were independently associated with increased mortality (odds ratio 1.07 [1.01-1.14]; p = 0.025 and 3.37 [1.12-12.60]; p = 0.043, respectively). QOL and lung function apart from transfer coefficient of carbon monoxide corrected for hemoglobin was similar at follow-up across the waves. CONCLUSIONS: Most patients with COVID-19 supported on ECMO in both waves survived in the short and longer term. At follow-up patients had similar lung function and QOL across the two waves. This suggests that ECMO has an ongoing role in the management of a carefully selected group of patients with COVID-19.

Adverse Outcomes Associated With Atrial Arrhythmias After Veno-Venous Extracorporeal Membrane Oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) is used as a treatment modality in those who fail to respond to conventional care. Hypoxia and medications used in the intensive care unit may increase risk for atrial arrhythmias (AA). This study aims to evaluate the impact of AA on post-VV ECMO outcome. A retrospective review of patients who were placed on VV ECMO between October 2016 and October 2021. One hundred forty-five patients were divided into two groups, AA and no AA. Baseline characteristic and potential risk factors were assessed. Uni- and multivariate analysis using logistic regression models were constructed to evaluate the predictors of mortality between groups. Survival between groups was estimated by the Kaplan-Meier method using the log-rank test. Advanced age with history of coronary artery disease and hypertension were associated with increased risk to develop AA post-VV ECMO placement ( p value < 0.05). Length on ECMO, time intubated, hospital length of stay, and sepsis were significantly increased in patients in the AA group ( p value < 0.05). There was no difference in the overall mortality between the two groups. AAs were associated with worse hospital course and complications but no difference in overall mortality rate. Age and cardiovascular disease seem to be predisposing risk factors for this. Further studies are needed to investigate potential strategies to prevent AAs development in this population.

A case series evaluating the effect of esmolol therapy to treat hypoxemia in COVID-19 patients on VV-ECMO.

When COVID-19 ARDS abolishes pulmonary function, VV-ECMO can provide gas exchange. If oxygenation remains insufficient despite maximal VV-ECMO support, the addition of esmolol has been proposed. Conflict exists, however, as to the oxygenation level which should trigger beta-blocker initiation. We evaluated the effect of esmolol therapy on oxygenation and oxygen delivery in patients with negligible native lung function and various degrees of hypoxemia despite maximal VV-ECMO support. We found that, in COVID-19 patients with negligible pulmonary gas exchange, the generalized use of esmolol administration to raise arterial oxygenation by slowing heart rate and thereby match native cardiac output to maximal attainable VV ECMO flows actually reduces systemic oxygen delivery in many cases.

Outcomes Following Extracorporeal Membrane Oxygenation for Severe COVID-19 in Pregnancy or Post Partum.

Importance: Existing reports of pregnant patients with COVID-19 disease who require extracorporeal membrane oxygenation (ECMO) are limited, with variable outcomes noted for the maternal-fetal dyad. Objective: To examine maternal and perinatal outcomes associated with ECMO used for COVID-19 with respiratory failure during pregnancy. Design, Setting, and Participants: This retrospective multicenter cohort study examined pregnant and postpartum patients who required ECMO for COVID-19 respiratory failure at 25 hospitals across the US. Eligible patients included individuals who received care at one of the study sites, were diagnosed with SARS-CoV-2 infection during pregnancy or up to 6 weeks post partum by positive nucleic acid or antigen test, and for whom ECMO was initiated for respiratory failure from March 1, 2020, to October 1, 2022. Exposures: ECMO in the setting of COVID-19 respiratory failure. Main outcome and measures: The primary outcome was maternal mortality. Secondary outcomes included serious maternal morbidity, obstetrical outcomes, and neonatal outcomes. Outcomes were compared by timing of infection during pregnancy or post partum, timing of ECMO initiation during pregnancy or post partum, and periods of circulation of SARS-CoV-2 variants. Results: From March 1, 2020, to October 1, 2022, 100 pregnant or postpartum individuals were started on ECMO (29 [29.0%] Hispanic, 25 [25.0%] non-Hispanic Black, 34 [34.0%] non-Hispanic White; mean [SD] age: 31.1 [5.5] years), including 47 (47.0%) during pregnancy, 21 (21.0%) within 24 hours post partum, and 32 (32.0%) between 24 hours and 6 weeks post partum; 79 (79.0%) had obesity, 61 (61.0%) had public or no insurance, and 67 (67.0%) did not have an immunocompromising condition. The median (IQR) ECMO run was 20 (9-49) days. There were 16 maternal deaths (16.0%; 95% CI, 8.2%-23.8%) in the study cohort, and 76 patients (76.0%; 95% CI, 58.9%-93.1%) had 1 or more serious maternal morbidity events. The largest serious maternal morbidity was venous thromboembolism and occurred in 39 patients (39.0%), which was similar across ECMO timing (40.4% pregnant [19 of 47] vs 38.1% [8 of 21] immediately postpartum vs 37.5% postpartum [12 of 32]; P > .99). Conclusions and Relevance: In this multicenter US cohort study of pregnant and postpartum patients who required ECMO for COVID-19-associated respiratory failure, most survived but experienced a high frequency of serious maternal morbidity.

Blood filtering system for COVID-19 management: novel modality of the cytokine storm therapeutics.

The newly emerged coronavirus (SARS-CoV-2) is virulent, contagious, and has rapidly gained many mutations, which makes it highly infectious and swiftly transmissible around the world. SARS-CoV-2 infects people of all ages and targets all body organs and their cellular compartments, starting from the respiratory system, where it shows many deleterious effects, to other tissues and organs. Systemic infection can lead to severe cases that require intensive intervention. Multiple approaches were elaborated, approved, and successfully used in the intervention of the SARS-CoV-2 infection. These approaches range from the utilization of single and/or mixed medications to specialized supportive devices. For critically ill COVID-19 patients with acute respiratory distress syndrome, both extracorporeal membrane oxygenation (ECMO) and hemadsorption are utilized in combination or individually to support and release the etiological factors responsible for the "cytokine storm" underlying this condition. The current report discusses hemadsorption devices that can be used as part of supportive treatment for the COVID-19-associated cytokine storm.

Year in Review 2022: Noteworthy Literature in Cardiothoracic Critical Care.

The past year in critical care medicine was notable for ongoing sequelae of the COVID-19 pandemic, including nationwide shortages and critical care demand in many regions in excess of usual operating capacity. Despite these challenges, evidence-based medicine and investigations into the optimal management of the critically ill continued to be at the forefront. This article is a collection of studies published in 2022 which are specifically relevant to cardiothoracic critical care. These noteworthy publications add to the existing literature across a broad spectrum of topics, from optimal timing of mechanical circulatory support (MCS), delirium prevention, updates in nutrition guidelines, alternative defibrillation techniques, novel ventilator management, and observing the downstream psychological impact of extracorporeal membrane oxygenation (ECMO) therapy.

Extracorporeal Membrane Oxygenation in Children With COVID-19: A Systematic Review and Meta-Analysis.

OBJECTIVES: The indication, complications, and outcomes of extracorporeal membrane oxygenation (ECMO) in children with COVID-19-related illnesses remain unelucidated. Our study aimed to investigate the characteristics and outcomes of ECMO in children with COVID-19-related illnesses. DATA SOURCES: We searched PubMed and EMBASE databases in March 2022. STUDY SELECTION: We retrieved all studies involving children (age ≤ 18 yr) with COVID-19-related illnesses who received ECMO. DATA EXTRACTION: Two authors independently extracted data and assessed the risk of bias. Mortality, successful weaning rate, and complications while on ECMO were synthesized by a one-group meta-analysis using a random-effect model. Meta-regression was performed to explore the risk factors for mortality. DATA SYNTHESIS: We included 18 observational studies, four case series, and 22 case reports involving 110 children with COVID-19-related illnesses receiving ECMO. The median age was 8 years (range, 10 d to 18 yr), and the median body mass index was 21.4 kg/m 2 (range, 12.3-56.0 kg/m 2 ). The most common comorbidities were obesity (11% [7/63]) and congenital heart disease (11% [7/63]), whereas 48% (30/63) were previously healthy. The most common indications for ECMO were multisystem inflammatory syndrome in children (52% [47/90]) and severe acute respiratory distress syndrome (40% [36/90]). Seventy-one percent (56/79) received venoarterial-ECMO. The median ECMO runtime was 6 days (range, 3-51 d) for venoarterial ECMO and 11 days (range, 3-71 d) for venovenous ECMO. The mortality was 26.6% (95% CI, 15.9-40.9), and the successful weaning rate was 77.0% (95% CI, 55.4-90.1). Complications were seen in 37.0% (95% CI, 23.1-53.5) while on ECMO, including stroke, acute kidney injury, pulmonary edema, and thromboembolism. Corticosteroids and IV immunoglobulin therapies were associated with lower mortality. CONCLUSIONS: The mortality of children on ECMO for COVID-19 was relatively low. This invasive treatment can be considered as a treatment option for critically ill children with COVID-19.

Inadequate Energy Delivery Is Frequent among COVID-19 Patients Requiring ECMO Support and Associated with Increased ICU Mortality.

BACKGROUND: Patients receiving extracorporeal membrane oxygenation (ECMO) support are at high risk for malnutrition. There are currently no general nutrition guidelines for coronavirus disease 2019 (COVID-19) patients during ECMO therapy. METHODS: We conducted a retrospective analysis of COVID-19 patients requiring venovenous ECMO support at a large tertiary hospital center. Nutrition goals were calculated using 25 kcal/kg body weight (BW)/day. Associations between nutrition support and outcome were evaluated using Kaplan-Meier and multivariable Cox regression analyses. RESULTS: Overall, 102 patients accounted for a total of 2344 nutrition support days during ECMO therapy. On 40.6% of these days, nutrition goals were met. Undernutrition was found in 40.8%. Mean daily calorie delivery was 73.7% of calculated requirements, mean daily protein delivery was 0.7 g/kg BW/d. Mean energy intake of ≥70% of calculated targets was associated with significantly lower ICU mortality independently of age, disease severity at ECMO start and body mass index (adjusted hazard ratio: 0.372, p = 0.007). CONCLUSIONS: Patients with a mean energy delivery of ≥70% of calculated targets during ECMO therapy had a better ICU survival compared to patients with unmet energy goals. These results indicate that adequate nutritional support needs to be a major priority in the treatment of COVID-19 patients requiring ECMO support.

Pharmacokinetics of cefiderocol during extracorporeal membrane oxygenation: A case report.

Patients with extracorporeal membrane oxygenation (ECMO) support do frequently receive broad-spectrum antibiotics, due to the high frequency of infection by multidrug resistant microorganisms. The extracorporeal circuit can alter the pharmacokinetics (PK) of administered drugs, and in the case of antibiotics this may lead to treatment failure. Cefiderocol is a new cephalosporin that exhibits excellent in vitro activity against many multidrug-resistant (MDR) microorganisms, but there is no published data about the modifications of its PK in patients with ECMO support. Herein we report the results of a pharmacokinetic investigation of cefiderocol in a critically ill patient receiving extracorporeal respiratory support.

An Intensivist-Led Extracorporeal Membrane Oxygenation Program: Design, Implementation, and Outcomes of the First Five Years.

We describe the development, implementation, and outcomes of an intensivist-led adult extracorporeal life support (ECLS) program using intensivists both to perform venovenous (V-V), venoarterial (V-A), and extracorporeal cardiopulmonary resuscitation (ECPR) cannulations, and to manage patients on ECLS throughout their ICU course. All adults supported with ECLS at the University of New Mexico Hospital (UNMH) from February 1, 2017 to December 31, 2021 were retrospectively analyzed. A total of 203 ECLS cannulations were performed in 198 patients, including 116 V-A cannulations (including 65 during ECPR) and 87 V-V cannulations (including 38 in patients with COVID-19). UNMH intensivists performed 195 cannulations, with 9 cannulation complications. Cardiothoracic surgeons performed 8 cannulations. Overall survival to hospital discharge or transfer was 46.5%. Survival was 32.3% in the ECPR group and 56% in the non-ECPR V-A group. In the V-V cohort, survival was 66.7% in the COVID-19-negative patients and 34.2% in the COVID-19-positive patients. This large series of intensivist-performed ECLS cannulations-including V-A, V-V, and ECPR modalities-demonstrates the successful implementation of a comprehensive intensivist-led ECLS program. With outcomes comparable to those in the literature, our program serves as a model for the initiation and development of ECLS programs in settings with limited access to local subspecialty cardiothoracic surgical services.

Remdesivir for the Treatment of Covid-19 - Final Report.

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).