Non-invasive assessment of left ventricular contractility by myocardial work index in veno-arterial membrane oxygenation patients: rationale and design of the MIX-ECMO multicentre observational study.

Introduction and aims: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an increasingly utilized therapeutic choice in patients with cardiogenic shock, however, high complication rate often counteracts with its beneficial cardiopulmonary effects. The assessment of left ventricular (LV) function in key in the management of this population, however, the most commonly used measures of LV performance are substantially load-dependent. Non-invasive myocardial work is a novel LV functional measure which may overcome this limitation and estimate LV function independent of the significantly altered loading conditions of VA-ECMO therapy. The Usefulness of Myocardial Work IndeX in ExtraCorporeal Membrane Oxygenation Patients (MIX-ECMO) study aims to examine the prognostic role of non-invasive myocardial work in VA-ECMO-supported patients. Methods: The MIX-ECMO is a multicentric, prospective, observational study. We aim to enroll 110 patients 48-72 h after the initiation of VA-ECMO support. The patients will undergo a detailed echocardiographic examination and a central echocardiography core laboratory will quantify conventional LV functional measures and non-invasive myocardial work parameters. The primary endpoint will be failure to wean at 30 days as a composite of cardiovascular mortality, need for long-term mechanical circulatory support or heart transplantation at 30 days, and besides that other secondary objectives will also be investigated. Detailed clinical data will also be collected to compare LV functional measures to parameters with established prognostic role and also to the Survival After Veno-arterial-ECMO (SAVE) score. Conclusions: The MIX-ECMO study will be the first to determine if non-invasive myocardial work has added prognostic value in patients receiving VA-ECMO support.

Cost-effectiveness analysis of an ambulance service-operated specialised cardiac vehicle with mobile extracorporeal cardiopulmonary resuscitation capacity for out-of-hospital cardiac arrests in Queensland, Australia.

OBJECTIVE: Extracorporeal CPR (E-CPR) has been primarily limited to the in-hospital setting. A few systems around the world have implemented pre-hospital mobile E-CPR in the form of a dedicated cardiac vehicle fitted with specialised equipment and clinicians required for the performance of E-CPR on-scene. However, evidence of the outcomes and cost-effectiveness of mobile E-CPR remain to be established. We evaluated the cost-effectiveness of a hypothetical mobile E-CPR vehicle operated by Queensland Ambulance Service in the state of Queensland, Australia. METHODS: We adapted our published mathematical model to estimate the cost-effectiveness of pre-hospital mobile E-CPR relative to current practice. In the model, a specialised cardiac vehicle with mobile E-CPR capability is deployed to selected OHCA patients, with eligible candidates receiving pre-hospital E-CPR in-field and rapid transport to the closest appropriate centre for in-hospital E-CPR. For comparison, non-candidates receive standard ACLS from a conventional ambulance response. Cost-effectiveness was expressed as Australian dollars ($, 2021 value) per quality-adjusted life year (QALY) gained. RESULTS: Pre-hospital mobile E-CPR improves outcomes compared to current practice at a cost of $27 323 per QALY gained. The cost-effectiveness of pre-hospital mobile E-CPR is sensitive to the assumption around the number of patients who are the targets of the vehicle, with higher patient volume resulting in improved cost-effectiveness. CONCLUSIONS: Pre-hospital E-CPR may be cost-effective. Successful implementation of a pre-hospital E-CPR programme requires substantial planning, training, logistics and operational adjustments.

Novel weaning assessment for veno-arteriovenous to veno-venous extracorporeal membrane oxygenation using pump-controlled retrograde trial off.

INTRODUCTION: Pump-controlled retrograde trial off (PCRTO) is described as an effective weaning strategy for veno-arterial extracorporeal membrane oxygenation (ECMO) in the guidelines. Contrastingly, there is no established weaning strategy for veno-arteriovenous (V-AV) ECMO. We report a novel application of PCRTO in a patient undergoing V-AV ECMO. CASE REPORT: A 49-year-old man had pneumonia and a history of kidney transplantation. Two days after intubation, respiratory failure progressed and veno-venous (V-V) ECMO was introduced. On day 7 after ECMO, the configuration was changed to V-AV ECMO owing to septic cardiomyopathy due to suspected cholangitis. On day 15, with partial haemodynamic improvement and persistent respiratory failure, PCRTO was performed; the patient was safely returned to V-V ECMO. DISCUSSION: In patients undergoing V-AV ECMO, PCRTO could have the potential to accurately simulate decannulation of the arterial cannula. CONCLUSION: This novel weaning strategy could be considered in patients undergoing V-AV ECMO.

Effect of intra-arrest transport, extracorporeal cardiopulmonary resuscitation and immediate invasive assessment in refractory out-of-hospital cardiac arrest: a long-term follow-up of the Prague OHCA trial.

BACKGROUND: Randomized data evaluating the impact of the extracorporeal cardiopulmonary resuscitation (ECPR) approach on long-term clinical outcomes in patients with refractory out-of-hospital cardiac arrest (OHCA) are lacking. The objective of this follow-up study was to assess the long-term clinical outcomes of the ECPR-based versus CCPR approach. METHODS: The Prague OHCA trial was a single-center, randomized, open-label trial. Patients with witnessed refractory OHCA of presumed cardiac origin, without return of spontaneous circulation, were randomized during ongoing resuscitation on scene to conventional CPR (CCPR) or an ECPR-based approach (intra-arrest transport, ECPR if ROSC is not achieved prehospital and immediate invasive assessment). RESULTS: From March 2013 to October 2020, 264 patients were randomized during ongoing resuscitation on scene, and 256 patients were enrolled. Long-term follow-up was performed 5.3 (interquartile range 3.8-7.2) years after initial randomization and was completed in 255 of 256 patients (99.6%). In total, 34/123 (27.6%) patients in the ECPR-based group and 26/132 (19.7%) in the CCPR group were alive (log-rank P = 0.01). There were no significant differences between the treatment groups in the neurological outcome, survival after hospital discharge, risk of hospitalization, major cardiovascular events and quality of life. Of long-term survivors, 1/34 (2.9%) in the ECPR-based arm and 1/26 (3.8%) in the CCPR arm had poor neurological outcome (both patients had a cerebral performance category score of 3). CONCLUSIONS: Among patients with refractory OHCA, the ECPR-based approach significantly improved long-term survival. There were no differences in the neurological outcome, major cardiovascular events and quality of life between the groups, but the trial was possibly underpowered to detect a clinically relevant difference in these outcomes. Trial registration ClinicalTrials.gov Identifier: NCT01511666, Registered 19 January 2012.

Platelet Function Testing to Guide Cangrelor Dosing in Patients with Temporary Mechanical Circulatory Support or as a Bridge to Procedure.

Cangrelor is a rapid-acting, intravenous P2Y12 inhibitor that can be used in patients after percutaneous coronary intervention who require mechanical circulatory support or as a bridge to procedure. We retrospectively reviewed adult patients who received platelet function testing (PFT) with the VerifyNow P2Y12 assay while on cangrelor from March 2021 through November 2022. All patients were initiated on 0.75 mcg/kg/min of cangrelor with P2Y12 reaction unit (PRU) values collected 12-24 h after initiation. Cangrelor doses were adjusted per protocol to maintain PRU values of 85-208. A total of 42 patients were included. Thirty-eight patients (90.5%) required temporary mechanical circulatory support while on cangrelor, and 4 patients (9.5%) received cangrelor as a bridge to procedure. The median cangrelor maintenance dose was 0.5 (interquartile range [IQR]: 0.375-0.75) mcg/kg/min, and the median time in therapeutic range with a PRU value between 85 and 208 was 66.6% (IQR: 39.6%-100%). No patients experienced stent thrombosis. A composite major adverse cardiovascular event occurred in 4 patients (9.5%), and major bleeding occurred in 16 patients (38.1%). Compared to empiric cangrelor dosing of 0.75 mcg/kg/min, PFT-guided cangrelor dose adjustment was associated with a median drug cost savings of $1605.60 (IQR: $0-4281.56). Utilizing PFT with cangrelor may allow for lower, individualized dosing while preventing stent thrombosis.

Assessment of the prognosis, frequency, and isolated bacteria in ventilator-associated pneumonia among patients with severe coronavirus disease 2019 pneumonia: A single-center retrospective observational study.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) due to severe coronavirus disease 2019 (COVID-19) pneumonia is associated with a high incidence of ventilator-associated pneumonia (VAP). We aimed to evaluate the epidemiology of VAP associated with severe COVID-19 pneumonia. METHODS: This retrospective observational study recruited patients with COVID-19-associated ARDS admitted to our center from April 1, 2020, to September 30, 2021. The primary outcome was the survival-to-discharge rate. The secondary outcomes were the VAP rate, time to VAP, length of ICU stay, length of ventilator support, and isolated bacteria. RESULTS: Sixty-eight patients were included in this study; 23 developed VAP. The survival-to-discharge rate was 60.9 % in the VAP group and 84.4 % in the non-VAP group. The median time to VAP onset was 16 days. The median duration of ventilator support and of ICU stay were higher in the VAP group than in the non-VAP group. The VAP rate was 33.8 %. The most common isolated species was Stenotrophomonas maltophilia. On admission, carbapenems were used in a maximum number of cases (75 %). Furthermore, the median body mass index (BMI) was lower and the median sequential organ failure assessment (SOFA) score on admission was higher in the VAP group than in the non-VAP group. CONCLUSIONS: The survival-to-discharge rate in VAP patients was low. Moreover, VAP patients tended to have long ICU stays, low BMI, and high SOFA scores on admission. Unusually, S. maltophilia was the most common isolated bacteria, which may be related to the frequent use of carbapenems.

Costo-efectividad de la oxigenación con membrana extracorpórea en pacientes con síndrome de dificultad respiratoria aguda en Colombia / Cost-effectiveness of extracorporeal membrane oxygenation in patients with acute respiratory distress syndrome in Colombia

Introducción. La terapia con oxigenación con membrana extracorpórea es costosa y, aunque existe existen indicios en la literatura de que puede ser una intervención costo-efectiva en los países desarrollados, hay dudas sobre su costo-efectividad en un país con un producto interno bruto per cápita bajo, como Colombia. Objetivo. Determinar el incremento de la relación costo-efectividad de la terapia con oxigenación con membrana extracorpórea en pacientes con síndrome de dificultad respiratoria aguda en Colombia. Materiales y métodos. Se eligieron pacientes adultos con diagnóstico de síndrome de dificultad respiratoria aguda para el análisis de costo-efectividad desde la perspectiva del sistema de salud. Se compararon aquellos pacientes con asistencia respiratoria mecánica con volúmenes bajos con aquellos tratados con oxigenación con membrana extracorpórea. Se determinaron los costos médicos directos de la atención y el incremento de la relación costo-efectividad a los 6 meses. Resultados. El costo esperado por paciente en asistencia respiratoria mecánica protectora fue de COP$ 17'609.909. El costo del soporte mediante terapia de oxigenación con membrana extracorpórea fue de COP$ 98'784.116. La relación de costo-efectividad promedio fue de COP$ 141'662.435 por cada vida salvada (USD$ 41.276). Conclusiones. El soporte con terapia de oxigenación con membrana extracorpórea tuvo un costo promedio de COP$ 141'662.435 por cada vida salvada, equivalente a USD$ 41.276 dólares y el incremento de la relación costo-efectividad fue de COP$ 608'783.750 (USD$ 177.384), casi diez veces superior a la regla de decisión de 3 PBI per cápita (COP$ 59'710.479).

Introduction: Extracorporeal membrane oxygenation therapy is expensive. There is evidence in the literature that it can be a cost-effective intervention in developed countries; however, in countries with low gross domestic product per capita, such as Colombia, there are still some doubts. Objective: To determine the incremental cost-effectiveness ratio of extracorporeal membrane oxygenation in patients with acute respiratory distress syndrome in Colombia. Materials and methods: Cost-effectiveness analysis in healthcare in relation to adult patients diagnosed with acute respiratory distress syndrome with mechanical ventilation with low volumes compared to extracorporeal membrane oxygenation. The direct medical costs and the incremental cost-effectiveness ratio were determined at 6 months. Results: The expected cost per patient on protective mechanical ventilation was COP$ 17,609,909. The cost of extracorporeal membrane oxygenation therapy support in surviving patients was COP$ 98,784,116. The average cost-effectiveness ratio of extracorporeal membrane oxygenation was COP$ 141,662,435 for each life saved (USD$ 41,276). Conclusions: Support with extracorporeal membrane oxygenation therapy had an average cost of COP$ 141,662,435 for each life saved equivalent to USD$ 41,276. The incremental cost-effectiveness ratio COP$ was 608,783,750 (USD$ 177,384); almost ten times higher than the decision rule of three gross domestic product per capita (COP$ 59,710,479).

Preoperative arterial and venous cannulation in redo cardiac surgery: from the safety and cost-effectiveness points of view

Abstract Objective: To investigate the safety and cost-effectiveness of preoperative cannulation and conventional approach techniques. Methods: Sixty-one patients who underwent redo open cardiac procedures between September 2015 and November 2018 were divided into two groups - Group A (n: 30), patients who underwent conventional cannulation after sternotomy, and Group B (n: 31), those who underwent cannulation before sternotomy. Patients were evaluated retrospectively for general complication rates and total hospital costs. Results: Mortality occurred in four patients from Group A and in one patient from Group B. Four patients required extracorporeal membrane oxygenation (ECMO) in Group A, whereas two required ECMO in Group B. Duration of total operation, cardiopulmonary bypass, and cross-clamp times were longer in the conventional surgery group than in the pre-sternotomy cannulation group (420.29±188.84 vs. 314.77±187.38, P=0.036; 171.87±85.59 vs. 141.7±82.47, P=0.089; and 102.94±70.67 vs. 60.97±52.81, P=0.009; respectively). Total blood and blood product usage were higher in Group A than in Group B. Postoperative intensive care unit stay was 62.77±145.3 hours vs. 25.13±73.11 hours, ventilation time was 5.16±5.09 hours vs. 3.03±2.78 hours, duration of ward stay was 5.23±2.52 days vs. 5.57±2.16 days, and duration of hospital stay was 9.58±5.85 days vs. 9.8±5.31 days in conventional sternotomy and pre-sternotomy cannulation groups, respectively. Total hospital costs were calculated 35863.52±20803.99 Turkish Liras (TL) in Group A and 25744.74±16472.03 TL in Group B (P=0,042). Conclusion: Venous and arterial cannulations before sternotomy decreased myocardial injury and complication rates, blood and blood product usage, hospital stay, and, consequently, hospital costs in our modest cohort.

Fatores associados à regulação da pressão parcial de oxigênio e da pressão parcial de gás carbônico durante suporte respiratório com oxigenação por membrana extracorpórea: dados de um modelo em suínos / Factors associated with blood oxygen partial pressure and carbon dioxide partial pressure regulation during respiratory extracorporeal membrane oxygenation support: data from a swine model

RESUMO Objetivo: Explorar os fatores associados aos níveis sanguíneos da pressão parcial de oxigênio e da pressão parcial de gás carbônico. Métodos: Os fatores associados com a regulação do oxigênio e de gás carbônico foram investigados em um modelo com porcos em apneia com suporte de oxigenação por membrana extracorpórea venovenosa. Foi testada uma sequência predefinida de fluxos de sangue e gás. Resultados: A oxigenação associou-se principalmente com o fluxo da oxigenação por membrana extracorpórea (coeficiente beta = 0,036mmHg/mL/minuto), débito cardíaco (coeficiente beta = -11,970mmHg/L/minuto) e shunt pulmonar (coeficiente beta = -0,232mmHg/%). As mensurações iniciais da pressão parcial de oxigênio e da pressão parcial de gás carbônico também se associaram com oxigenação, com coeficientes beta de 0,160 e 0,442mmHg/mmHg, respectivamente. A pressão parcial de gás carbônico se associou com débito cardíaco (coeficiente beta = 3,578mmHg/L/minuto), fluxo de gás (coeficiente beta = -2,635mmHg/L/minuto), temperatura (coeficiente beta = 4,514mmHg/°C), pH inicial (coeficiente beta = -66,065mmHg/0,01 unidade) e hemoglobina (coeficiente beta = 6,635mmHg/g/dL). Conclusão: Elevações nos fluxos de sangue de gás em um modelo de oxigenação por membrana extracorpórea venovenosa durante apneia resultaram em aumento da pressão parcial de oxigênio e redução da pressão parcial de gás carbônico, respectivamente. Ainda, sem a possibilidade de uma inferência causal, a pressão parcial de oxigênio associou-se negativamente com o shunt pulmonar e o débito cardíaco, e a pressão parcial de gás carbônico teve associação positiva com o débito cardíaco, temperatura central e hemoglobina inicial.

ABSTRACT Objective: The aim of this study was to explore the factors associated with blood oxygen partial pressure and carbon dioxide partial pressure. Methods: The factors associated with oxygen - and carbon dioxide regulation were investigated in an apneic pig model under veno-venous extracorporeal membrane oxygenation support. A predefined sequence of blood and sweep flows was tested. Results: Oxygenation was mainly associated with extracorporeal membrane oxygenation blood flow (beta coefficient = 0.036mmHg/mL/min), cardiac output (beta coefficient = -11.970mmHg/L/min) and pulmonary shunting (beta coefficient = -0.232mmHg/%). Furthermore, the initial oxygen partial pressure and carbon dioxide partial pressure measurements were also associated with oxygenation, with beta coefficients of 0.160 and 0.442mmHg/mmHg, respectively. Carbon dioxide partial pressure was associated with cardiac output (beta coefficient = 3.578mmHg/L/min), sweep gas flow (beta coefficient = -2.635mmHg/L/min), temperature (beta coefficient = 4.514mmHg/ºC), initial pH (beta coefficient = -66.065mmHg/0.01 unit) and hemoglobin (beta coefficient = 6.635mmHg/g/dL). Conclusion: In conclusion, elevations in blood and sweep gas flows in an apneic veno-venous extracorporeal membrane oxygenation model resulted in an increase in oxygen partial pressure and a reduction in carbon dioxide partial pressure 2, respectively. Furthermore, without the possibility of causal inference, oxygen partial pressure was negatively associated with pulmonary shunting and cardiac output, and carbon dioxide partial pressure was positively associated with cardiac output, core temperature and initial hemoglobin.

Efeito econômico do uso da oxigenação extracorpórea para suporte de pacientes adultos com insuficiência respiratória grave no Brasil: uma análise hipotética / The economic effect of extracorporeal membrane oxygenation to support adults with severe respiratory failure in Brazil: a hypothetical analysis

Objetivo: Analisar o custo-utilidade do uso da oxigenação extracorpórea para pacientes com síndrome da angústia respiratória aguda grave no Brasil. Métodos: Com bancos de dados de estudos previamente publicados, foi construída uma árvore encadeada de decisões. Os custos foram extraídos da média de 3 meses do preço pago pelo Sistema Único de Saúde em 2011. Com 10 milhões de pacientes simulados com desfechos e custos predeterminados, uma análise da relação de incremento de custo e de anos de vida ganhos ajustados pela qualidade (custo-utilidade) foi realizada com sobrevida de 40 e 60% dos pacientes que usaram oxigenação extracorpórea. Resultados: A árvore de decisões resultou em 16 desfechos com técnicas diferentes de suporte à vida. Com a sobrevida de 40/60%, respectivamente, o incremento de custos foi de R$ -301,00/-14,00, com o preço pago de R$ -30.913,00/-1.752,00 por ano de vida ganho ajustado pela qualidade para 6 meses e de R$ -2.386,00/-90,00 por ano de vida ganho ajustado pela qualidade até o fim de vida, quando se analisaram todos os pacientes com síndrome da angústia respiratória aguda grave. Analisando somente os pacientes com hipoxemia grave (relação da pressão parcial de oxigênio no sangue sobre a fração inspirada de oxigênio <100mmHg), o incremento de custos foi de R$ -5.714,00/272,00, com preço por ano de vida ganho ajustado pela qualidade em 6 meses de R$ -9.521,00/293,00, e com o custo de R$ -280,00/7,00 por ano de vida ganho ajustado pela qualidade. Conclusão: A relação de custo-utilidade do uso da oxigenação extracorpórea no Brasil foi potencialmente aceitável neste estudo hipotético. .

Objective: To analyze the cost-utility of using extracorporeal oxygenation for patients with severe acute respiratory distress syndrome in Brazil. Methods: A decision tree was constructed using databases from previously published studies. Costs were taken from the average price paid by the Brazilian Unified Health System (Sistema Único de Saúde; SUS) over three months in 2011. Using the data of 10,000,000 simulated patients with predetermined outcomes and costs, an analysis was performed of the ratio between cost increase and years of life gained, adjusted for quality (cost-utility), with survival rates of 40 and 60% for patients using extracorporeal membrane oxygenation. Results: The decision tree resulted in 16 outcomes with different life support techniques. With survival rates of 40 and 60%, respectively, the increased costs were R$=-301.00/-14.00, with a cost of R$=-30,913.00/-1,752.00 paid per six-month quality-adjusted life-year gained and R$=-2,386.00/-90.00 per quality-adjusted life-year gained until the end of life, when all patients with severe ARDS were analyzed. Analyzing only patients with severe hypoxemia (i.e., a ratio of partial oxygen pressure in the blood to the fraction of inspired oxygen <100mmHg), the increased cost was R$=-5,714.00/272.00, with a cost per six-month quality-adjusted life-year gained of R$=-9,521.00/293.00 and a cost of R$=-280.00/7.00 per quality-adjusted life-year gained. Conclusion: The cost-utility ratio associated with the use of extracorporeal membrane oxygenation in Brazil is potentially acceptable according to this hypothetical study. .

Avaliação da aprotinina na redução da resposta inflamatória sistêmica em crianças operadas com circulação extracorpórea / Assessment of aprotinin in the reduction of inflammatory systemic response in children undergoing surgery with cardiopulmonary bypass

OBJETIVO: Avaliar se a aprotinina em altas doses hemostáticas pode reduzir o processo inflamatório após circulação extracorpórea (CEC) em crianças. MÉTODOS: Estudo prospectivo randomizado em crianças de 30 dias a 4 anos de idade, submetidas à correção de cardiopatia congênita acianogênica, com CEC e divididas em dois grupos, um denominado Controle (n=9) e o outro, Aprotinina (n=10). Neste, o fármaco foi administrado antes e durante a CEC. A resposta inflamatória sistêmica e disfunções hemostática e multiorgânicas foram analisadas por marcadores clínicos e bioquímicos. Foram consideradas significantes as diferenças com P<0,05. RESULTADOS: Os grupos foram semelhantes quanto às variáveis demográficas e intra-operatórias, exceto por maior hemodiluição no Grupo Aprotinina. Não houve benefício quanto aos tempos de ventilação pulmonar mecânica, permanência no CTIP e hospitalar, nem quanto ao uso de inotrópicos e função renal. A relação PaO2/FiO2 (pressão parcial de oxigênio arterial/fração inspirada de oxigênio) apresentou queda significativa com 24 h pós-operatório, no Grupo Controle. As perdas sanguíneas foram semelhantes nos dois grupos. No grupo Aprotinina surgiu leucopenia significativa, em CEC, seguida de leucocitose. Fator de necrose tumoral alfa (TNF-α), Interleucinas (IL)-6, IL-8, IL-10, proporção IL-6/IL-10 não apresentaram diferenças marcantes intergrupos. A proporção IL-6/IL-10 PO aumentou no grupo Controle. Não houve complicações com o uso da aprotinina. CONCLUSÃO: Nesta casuística, a Aprotinina em altas doses hemostáticas não minimizou as manifestações clínicas e os marcadores séricos de resposta inflamatória sistêmica.

OBJECTIVE: To evaluate if the hemostatic high-dose aprotinin seems to reduce the inflammatory process after extracorporeal circulation (ECC) in children. METHODS: A prospective randomized study was conducted on children aged 30 days to 4 years submitted to correction of acyanogenic congenital heart disease with ECC and divided into two groups: Control (n=9) and Aprotinin (n=10). In the Aprotinin Group the drug was administered before and during ECC and the systemic inflammatory response and hemostatic and multiorgan dysfunctions were analyzed on the basis of clinical and biochemical markers. Differences were considered to be significant when P<0.05. RESULTS: The groups were similar regarding demographic and intraoperative variables, except for a greater hemodilution in the Aprotinin Group. The drug had no benefit regarding time of mechanical pulmonary ventilation, permanence in the postoperative ICU and length of CONCLUSION: In this series, hemostatic high-dose aprotinin did not minimize the clinical manifestations or serum markers of the inflammatory systemic response.