Conservative or liberal oxygen targets in patients on venoarterial extracorporeal membrane oxygenation.

PURPOSE: Patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) frequently develop arterial hyperoxaemia, which may be harmful. However, lower oxygen saturation targets may also lead to harmful episodes of hypoxaemia. METHODS: In this registry-embedded, multicentre trial, we randomly assigned adult patients receiving VA-ECMO in an intensive care unit (ICU) to either a conservative (target SaO2 92-96%) or to a liberal oxygen strategy (target SaO2 97-100%) through controlled oxygen administration via the ventilator and ECMO gas blender. The primary outcome was the number of ICU-free days to day 28. Secondary outcomes included ICU-free days to day 60, mortality, ECMO and ventilation duration, ICU and hospital lengths of stay, and functional outcomes at 6 months. RESULTS: From September 2019 through June 2023, 934 patients who received VA-ECMO were reported to the EXCEL registry, of whom 300 (192 cardiogenic shock, 108 refractory cardiac arrest) were recruited. We randomised 149 to a conservative and 151 to a liberal oxygen strategy. The median number of ICU-free days to day 28 was similar in both groups (conservative: 0 days [interquartile range (IQR) 0-13.7] versus liberal: 0 days [IQR 0-13.7], median treatment effect: 0 days [95% confidence interval (CI) - 3.1 to 3.1]). Mortality at day 28 (59/159 [39.6%] vs 59/151 [39.1%]) and at day 60 (64/149 [43%] vs 62/151 [41.1%] were similar in conservative and liberal groups, as were all other secondary outcomes and adverse events. The conservative group experienced 44 (29.5%) major protocol deviations compared to 2 (1.3%) in the liberal oxygen group (P < 0.001). CONCLUSIONS: In adults receiving VA-ECMO in ICU, a conservative compared to a liberal oxygen strategy, did not affect the number of ICU-free days to day 28.

Implementing enhanced extracorporeal membrane oxygenation for CPR (ECPR) in the emergency department.

Refractory out-of-hospital cardiac arrest (OHCA) has a very poor prognosis, with survival rates at around 10%. Extracorporeal membrane oxygenation (ECMO) for patients in refractory arrest, known as ECPR, aims to provide perfusion to the patient whilst the underlying cause of arrest can be addressed. ECPR use has increased substantially, with varying survival rates to hospital discharge. The best outcomes for ECPR occur when the time from cardiac arrest to implementation of ECPR is minimised. To reduce this time, systems must be in place to identify the correct patient, expedite transfer to hospital, facilitate rapid cannulation and ECMO circuit flows. We describe the process of activation of ECPR, patient selection, and the steps that emergency department clinicians can utilise to facilitate timely cannulation to ensure the best outcomes for patients in refractory cardiac arrest. With these processes in place our survival to hospital discharge for OHCA patients is 35%, with most patients having a good neurological function.

An intensivist-led ECMO accreditation pathway and safety data over the first 4 years.

Objective: To describe the training and accreditation process behind an intensivist-led extracorporeal membrane oxygenation (ECMO) cannulation program, and identify the rate of complications associated with the ECMO cannulation procedure. Design: A narrative review of the accreditation process, and a retrospective review of complications related to cannulation during the first four years of the intensivist program. Setting: Royal Prince Alfred Hospital, a quaternary referral hospital in Sydney. Participants: All patients initiated onto ECMO during the first four years of the intensivist cannulation program (August 2018 to August 2022).Main outcome measures: All cases were reviewed for identification of 14 pre-defined adverse events which were classified as low, medium or high clinical significance complications. Results: A total of 402 cannulations were attempted by the intensivist group in 194 separate cannulation episodes involving 179 patients. This included 93 V-V initiations, 69 V-A initiations (36 of these ECMO-CPR), 3 V-AV (veno-arteriovenous) initiations, 25 ECMO reconfigurations and four patients cannulated for peripheral cardiopulmonary bypass in cardiothoracic theatre. One of the 402 cannulations was halted as resuscitation was ceased, and one was halted and the patient transferred to theatre for central arterial cannulation. 394 out of the remaining 400 cannulations were successful (98.5%). Of 402 total cannulations, 32 complication events occurred (7.96% event rate), of which 15 (3.7% event rate) were low significance complications, 10 medium significance (2.5% event rate), and seven high clinical significance (1.7% event rate). Conclusions: Our experience of the first four years of an intensivist-led ECMO service demonstrates that our training process and cannulation technique result in the provision of a complex therapy with low levels of complications, on par with those in the published literature.

Platelet Adhesion and Activation in an ECMO Thrombosis-on-a-Chip Model.

Use of extracorporeal membrane oxygenation (ECMO) for cardiorespiratory failure remains complicated by blood clot formation (thrombosis), triggered by biomaterial surfaces and flow conditions. Thrombosis may result in ECMO circuit changes, cause red blood cell hemolysis, and thromboembolic events. Medical device thrombosis is potentiated by the interplay between biomaterial properties, hemodynamic flow conditions and patient pathology, however, the contribution and importance of these factors are poorly understood because many in vitro models lack the capability to customize material and flow conditions to investigate thrombosis under clinically relevant medical device conditions. Therefore, an ECMO thrombosis-on-a-chip model is developed that enables highly customizable biomaterial and flow combinations to evaluate ECMO thrombosis in real-time with low blood volume. It is observed that low flow rates, decelerating conditions, and flow stasis significantly increased platelet adhesion, correlating with clinical thrombus formation. For the first time, it is found that tubing material, polyvinyl chloride, caused increased platelet P-selectin activation compared to connector material, polycarbonate. This ECMO thrombosis-on-a-chip model can be used to guide ECMO operation, inform medical device design, investigate embolism, occlusion and platelet activation mechanisms, and develop anti-thrombotic biomaterials to ultimately reduce medical device thrombosis, anti-thrombotic drug use and therefore bleeding complications, leading to safer blood-contacting medical devices.

Corrigendum to "Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) trial: Study protocol and statistical analysis plan" [Crit Care Resuscit 25 (2023) 118-125].

[This corrects the article DOI: 10.1016/j.ccrj.2023.06.001.].

Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) Trial: Study Protocol and Statistical Analysis Plan.

Introduction: Critically ill patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO) are at risk of developing severe arterial hyperoxia, which has been associated with increased mortality. Lower saturation targets in this population may lead to deleterious episodes of severe hypoxia. This manuscript describes the protocol and statistical analysis plan for the Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) Trial. Design: The BLENDER trial is a pragmatic, multicentre, registry-embedded, randomised clinical trial., registered at ClinicalTrials.gov (NCT03841084) and approved by The Alfred Hospital Ethics Committee project ID HREC/50486/Alfred-2019. Participants and setting: Patients supported by VA ECMO for cardiogenic shock or cardiac arrest who are enrolled in the Australian national ECMO registry. Intervention: The study compares a conservative oxygenation strategy (target arterial saturations 92-96%) with a liberal oxygenation strategy (target 97-100%). Main Outcome Measures: The primary outcome is the number of intensive care unit (ICU)-free days for patients alive at day 60. Secondary outcomes include duration of mechanical ventilation, ICU and hospital mortality, the number of hypoxic episodes, neurocognitive outcomes, and health economic analyses. The 300-patient sample size enables us to detect a 3-day difference in ICU-free days at day 60, assuming a mean ICU-free days of 11 days, with a risk of type 1 error of 5% and power of 80%. Data will be analysed according to a predefined analysis plan. Findings will be disseminated in peer-reviewed publications. Conclusions: This paper details the protocol and statistical analysis plan for the BLENDER trial, a registry-embedded, multicentre interventional trial comparing liberal and conservative oxygenation strategies in VA ECMO.

Expert consensus on training and accreditation for extracorporeal cardiopulmonary resuscitation an international, multidisciplinary modified Delphi Study.

BACKGROUND: A multidisciplinary group of stakeholders were used to identify: (1) the core competencies of a training program required to perform in-hospital ECPR initiation (2) additional competencies required to perform pre-hospital ECPR initiation and; (3) the optimal training method and maintenance protocol for delivering an ECPR program. METHODS: A modified Delphi process was undertaken utilising two web based survey rounds and one virtual meeting. Experts rated the importance of different aspects of ECPR training, competency and governance on a 9-point Likert scale. A diverse, representative group was targeted. Consensus was achieved when greater than 70% respondents rated a domain as critical (> or = 7 on the 9 point Likert scale). RESULTS: 35 international ECPR experts from 9 countries formed the expert panel, with a median number of 14 years of ECMO practice (interquartile range 11-38). Participant response rates were 97% (survey round one), 63% (virtual meeting) and 100% (survey round two). After the second round of the survey, 47 consensus statements were formed outlining a core set of competencies required for ECPR provision. We identified key elements required to safely train and perform ECPR including skill pre-requisites, surrogate skill identification, the importance of competency-based assessment over volume of practice and competency requirements for successful ECPR practice and skill maintenance. CONCLUSIONS: We present a series of core competencies, training requirements and ongoing governance protocols to guide safe ECPR implementation. These findings can be used to develop training syllabus and guide minimum standards for competency as the growth of ECPR practitioners continues.

Fulminant Delta COVID-19 myocarditis: a case report of fatal primary cardiac dysfunction.

Background: Whilst myocarditis or myocardial injury due to severe acute respiratory syndrome coronavirus 2 infection is commonly reported, profound primary cardiac dysfunction requiring mechanical circulatory support, with the development of fulminant myocarditis prior to respiratory failure, is rarely described. The endomyocardial biopsy (EMB) findings in these patients is seldom reported, the findings are varied, and effective treatment unknown. Case summary: A 39-year-old female with no significant past medical history and confirmed Delta variant coronavirus disease 2019 (COVID-19) infection (Day 3), presented with a 1 day history of diarrhoea, vomiting, and abdominal pain. The patient denied respiratory symptoms and chest X-ray was clear. Lactate level was 6.3, initial troponin T 118 ng/L. Despite resuscitation, the patient significantly deteriorated in the emergency department, resulting in pulseless electrical activity arrest requiring veno-arterial extra-corporeal membrane oxygenation cardiopulmonary resuscitation. Over the following 36 h, cardiac function deteriorated to near-complete left ventricular (LV) standstill. Coronary angiography revealed normal coronary arteries with slow flow. Endomyocardial biopsy showed diffuse interstitial macrophage infiltrate and small vessel thromboses. Left ventricular function did not improve over the following 7 days, and despite treatment with tocilizumab, high-dose steroids, and intravenous immunoglobulin, she eventually died due to disease-related complications. Discussion: Primary cardiac dysfunction secondary to COVID-19 infection is rarely reported. Little is known about the incidence, natural history, and pathophysiology of fulminant COVID-19 myocarditis. We present the most severe case of cardiac dysfunction due to COVID-19 reported in a young patient without respiratory compromise who never recovered from any cardiac function.