Extracorporeal membrane oxygenation and Extracorporeal Membrane Oxygenation Cardiopulmonary Resusciation (ECPR) research priorities in Australia: A clinician survey.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) for cardiorespiratory failure and during cardiopulmonary resuscitation has increased significantly and is resource intensive. High-quality evidence to guide management of patients on ECMO is limited. OBJECTIVES: The objective of this study was to determine the research priorities of clinicians for ECMO and Extracorporeal Membrane Oxygenation Cardiopulmonary Resusciation (ECPR) in Australia and New Zealand. METHODS: A prospective, binational survey of clinicians was conducted in May 2022. RESULTS: There were 133 respondents; 110 (84%) worked at an Australian ECMO centre; 28 (21%) were emergency, 45 (34%) were intensive care, and 41 (31%) were nursing clinicians. All aspects of ECMO care were identified by respondents as being important for further research; however, appropriate patient selection and determining long-term outcomes were ranked the highest. While most believed ECMO was efficacious, they felt that there was insufficient evidence to determine cost-effectiveness. There was uncertainty of the best model of ECPR provision. Equipoise exists for randomised studies into anticoagulation, blood product usage, and ECPR. CONCLUSIONS: This survey found strong support amongst clinicians for further research into the optimal use of ECMO and ECPR and provides a frame work for prioritising future clinical trials and research agendas.

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.

The effect of restrictive versus liberal selection criteria on survival in ECPR: a retrospective analysis of a multi-regional dataset.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is an established rescue therapy for both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). However, there remains significant heterogeneity in populations and outcomes across different studies. The primary aim of this study was to compare commonly used selection criteria and their effect on survival and utilisation in an Australian ECPR cohort. METHODS: We performed a retrospective, observational study of three established ECPR centres in Australia, including cases from 1 January 2013 to 31 December 2020 to establish the baseline cohort. We applied five commonly used ECPR selection criteria, ranging from restrictive to liberal. RESULTS: The baseline cohort included 199 ECPR cases: 95 OHCA and 104 IHCA patients. Survival to hospital discharge was 20% for OHCA and 41.4% for IHCA. For OHCA patients, strictly applying the most restrictive criteria would have resulted in the highest survival rate 7/16 (43.8%) compared to the most liberal criteria 16/73 (21.9%). However, only 16/95 (16.8%) in our cohort strictly met the most restrictive criteria versus 73/95 (76.8%) with the most liberal criteria. Similarly, in IHCA, the most restrictive criteria would have resulted in a higher survival rate in eligible patients 10/15 (66.7%) compared to 27/59 (45.8%) with the most liberal criteria. With all criteria a large portion of survivors in IHCA would not have been eligible for ECMO if strictly applying criteria, 33/43 (77%) with restrictive and 16/43 (37%) with the most liberal criteria. CONCLUSIONS: Adherence to different selection criteria impacts both the ECPR survival rate and the total number of survivors. Commonly used selection criteria may be unsuitable to select IHCA ECPR patients.

Long-term outcomes of adults with acute respiratory failure treated with veno-venous extracorporeal membrane oxygenation.

Veno-venous extracorporeal membrane oxygenation is increasingly used for severe but potentially reversible acute respiratory failure in adults; however, there are limited data regarding long-term morbidity. At our institution, most patients requiring veno-venous extracorporeal membrane oxygenation have been followed up by a single physician. Our primary aim was to describe the serial long-term morbidity for respiratory, musculoskeletal and psychological functioning.A retrospective audit of inpatient and outpatient medical records was conducted. A total of 125 patients treated with veno-venous extracorporeal membrane oxygenation for primary respiratory failure were included. The patients were young (mean (standard deviation) age 43.7 (4.1) years), obese (mean (standard deviation) body mass index 30.8 (10.4) kg/m2), and mostly were male (59%). Most patients (60%) had no comorbidities.The survival rate to discharge was 70%, with body mass index and the number of comorbidities being independent predictors of survival on multiple logistic regression analysis. Over half (57%) of the Australian survivors had regular outpatient follow-up. They had a median of three reviews (range 1-9) over a median of 11.8 months (range 1.5-79) months. Breathlessness and weakness resolved in most within six months, with lung function abnormalities taking longer to resolve. Over half (60%) returned to employment within six months of discharge. Over a quarter (29%) displayed symptoms of anxiety, depression or post-traumatic stress disorder.

Hemostasis, coagulation and thrombin in venoarterial and venovenous extracorporeal membrane oxygenation: the HECTIC study.

Extracorporeal membrane oxygenation (ECMO) support has a high incidence of both bleeding and thrombotic complications. Despite clear differences in patient characteristics and pathologies between veno-venous (VV) and veno-arterial (VA) ECMO support, anticoagulation practices are often the same across modalities. Moreover, there is very little data on their respective coagulation profiles and comparisons of thrombin generation in these patients. This study compares the coagulation profile and thrombin generation between patients supported with either VV and VA ECMO. A prospective cohort study of patients undergoing VA and VV ECMO at an Intensive care department of a university hospital and ECMO referral centre. In addition to routine coagulation testing and heparin monitoring per unit protocol, thromboelastography (TEG), multiplate aggregometry (MEA), calibrated automated thrombinography (CAT) and von-Willebrand's activity (antigen and activity ratio) were sampled second-daily for 1 week, then weekly thereafter. VA patients had significantly lower platelets counts, fibrinogen, anti-thrombin and clot strength with higher d-dimer levels than VV patients, consistent with a more pronounced consumptive coagulopathy. Thrombin generation was higher in VA than VV patients, and the heparin dose required to suppress thrombin generation was lower in VA patients. There were no significant differences in total bleeding or thrombotic event rates between VV and VA patients when adjusted for days on extracorporeal support. VA patients received a lower median daily heparin dose 8500 IU [IQR 2500-24000] versus VV 28,800 IU [IQR 17,300-40,800.00]; < 0.001. Twenty-eight patients (72%) survived to hospital discharge; comprising 53% of VA patients and 77% of VV patients. Significant differences between the coagulation profiles of VA and VV patients exist, and anticoagulation strategies for patients of these modalities should be different. Further research into the development of tailored anticoagulation strategies that include the mode of ECMO support need to be completed.

Inhibitors of lysine biosynthesis as antibacterial agents.

Bacterial biosynthesis of lysine has come under increased scrutiny as a target for novel antibacterial agents as it provides both lysine for protein synthesis and meso-diaminopimelate for construction of the bacterial peptidoglycan cell wall. Recent studies of the enzymes of the lysine biosynthetic pathway, development of inhibitors and investigations of their antibacterial properties are discussed.