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An innovative ovine model of severe cardiopulmonary failure supported by veno-arterial extracorporeal membrane oxygenation.

ABSTRACT: Refractory cardiogenic shock (CS) often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion. Current animal models result in heterogenous cardiac injury and frequent episodes of refractory ventricular fibrillation. Thus, we aimed to develop an innovative, clinically relevant, and titratable model of severe cardiopulmonary failure. Six sheep (60 ± 6 kg) were anaesthetized and mechanically ventilated. VA-ECMO was commenced and CS was induced through intramyocardial injections of ethanol. Then, hypoxemic/hypercapnic pulmonary failure was achieved, through substantial decrease in ventilatory support. Echocardiography was used to compute left ventricular fractional area change (LVFAC) and cardiac Troponin I (cTnI) was quantified. After 5 h, the animals were euthanised and the heart was retrieved for histological evaluations. Ethanol (58 ± 23 mL) successfully induced CS in all animals. cTnI levels increased near 5000-fold. CS was confirmed by a drop in systolic blood pressure to 67 ± 14 mmHg, while lactate increased to 4.7 ± 0.9 mmol/L and LVFAC decreased to 16 ± 7%. Myocardial samples corroborated extensive cellular necrosis and inflammatory infiltrates. In conclusion, we present an innovative ovine model of severe cardiopulmonary failure in animals on VA-ECMO. This model could be essential to further characterize CS and develop future treatments.

SUBMITTER: Heinsar S

PROVIDER: S-EPMC8516938 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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An innovative ovine model of severe cardiopulmonary failure supported by veno-arterial extracorporeal membrane oxygenation.

Heinsar Silver S Jung Jae-Seung JS Colombo Sebastiano Maria SM Rozencwajg Sacha S Wildi Karin K Sato Kei K Ainola Carmen C Wang Xiaomeng X Abbate Gabriella G Sato Noriko N Dyer Wayne Bruce WB Livingstone Samantha Annie SA Pimenta Leticia Pretti LP Bartnikowski Nicole N Bouquet Mahe Jeannine Patricia MJP Passmore Margaret M Vidal Bruno B Palmieri Chiara C Reid Janice D JD Haqqani Haris M HM McGuire Daniel D Wilson Emily Susan ES Rätsep Indrek I Lorusso Roberto R Suen Jacky Y JY Bassi Gianluigi Li GL Fraser John F JF

Scientific reports 20211014 1

Refractory cardiogenic shock (CS) often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion. Current animal models result in heterogenous cardiac injury and frequent episodes of refractory ventricular fibrillation. Thus, we aimed to develop an innovative, clinically relevant, and titratable model of severe cardiopulmonary failure. Six sheep (60 ± 6 kg) were anaesthetized and mechanically ventilated. VA-ECMO was commenced and CS was induced through ...[more]

PMID: 34650063

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Project description:BackgroundEEG-based prognostication studies in intensive care units often rely on a standard 21-electrode montage (stdEEG) requiring substantial human, technical, and financial resources. We here evaluate whether a simplified 4-frontal electrode montage (4-frontEEG) can detect EEG patterns associated with poor outcomes in adult patients under veno-arterial extracorporeal membrane oxygenation (VA-ECMO).MethodsWe conducted a reanalysis of EEG data from a prospective cohort on 118 adult patients under VA-ECMO, in whom EEG was performed on admission to intensive care. EEG patterns of interest included background rhythm, discontinuity, reactivity, and the Synek's score. They were all reassessed by an intensivist on a 4-frontEEG montage, whose analysis was then compared to an expert's interpretation made on stdEEG recordings. The main outcome measure was the degree of correlation between 4-frontEEG and stdEEG montages to identify EEG patterns of interest. The performance of the Synek scores calculated on 4-frontEEG and stdEEG montage to predict outcomes (i.e., 28-day mortality and 90-day Rankin score [Formula: see text]) was investigated in a secondary exploratory analysis.ResultsThe detection of EEG patterns using 4-frontEEG was statistically similar to that of stdEEG for background rhythm (Spearman rank test, ρ = 0.66, p < 0.001), discontinuity (Cohen's kappa, [Formula: see text] = 0.955), reactivity ([Formula: see text] = 0.739) and the Synek's score (ρ = 0.794, p < 0.001). Using the Synek classification, we found similar performances between 4-frontEEG and stdEEG montages in predicting 28-day mortality (AUC 4-frontEEG 0.71, AUC stdEEG 0.68) and for 90-day poor neurologic outcome (AUC 4-frontEEG 0.71, AUC stdEEG 0.66). An exploratory analysis confirmed that the Synek scores determined by 4 or 21 electrodes were independently associated with 28-day mortality and poor 90-day functional outcome.ConclusionIn adult patients under VA-ECMO, a simplified 4-frontal electrode EEG montage interpreted by an intensivist, detected common EEG patterns associated with poor outcomes, with a performance similar to that of a standard EEG montage interpreted by expert neurophysiologists. This simplified montage could be implemented as part of a multimodal evaluation for bedside prognostication.

Project description:BackgroundExtracorporeal membrane oxygenation (ECMO) is an effective extracorporeal life support technology that has been applied to treat cardiorespiratory failure patients. Some medical centers have started using ECMO on awake, non-intubated, spontaneously breathing patients, as this strategy offers several benefits over mechanical ventilation. However, most awake-ECMO methods focus on venovenous ECMO, and few cases of awake veno-arterial ECMO (V-A ECMO) have been reported, especially in perioperative acute heart failure. Therefore, our study aimed to examine awake-V-A ECMO cases that were not given continuous sedation or invasive mechanical ventilation (IMV) during perioperative heart failure.MethodIn total, 40 ECMO patients from December 2013 to November 2019 were divided into 2 groups (the awake-ECMO group and the asleep-ECMO group) according to the ventilation use. The demographics, patient outcomes, and ECMO parameters were collected and retrospectively analyzed.ResultsWe identified 12 cases of awake ECMO without continuous ventilation, and 28 cases of simultaneous IMV and ECMO (asleep ECMO). Awake-ECMO patients showed fewer complications and better outcomes compared to ventilation patients. All patients in the awake group were successfully weaned off ECMO, while only 5 (18%) patients were weaned off ECMO in the asleep group. Furthermore, 9 (75%) patients survived until discharge in the awake group vs. 3 (11%) in the asleep group; 3 patients died of septic shock after weaning in the awake group, while 25 patients died of septic shock, hemodynamic disorder, bleeding, cerebral hemorrhage, etc., in the asleep group. These complications, including bleeding, pneumonia, hemolysis, and abdominal distension, etc., occurred less frequently in the asleep group compared to the awake group (P<0.05).ConclusionsAwake V-A ECMO is an effective, feasible, and safe strategy in patients with perioperatively acute heart failure and can be applied as a bridge to cardiac function recovery or transplantation.

Project description:Background Hemostatic complications and the need for large amounts of blood products are major obstacles during veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Additionally, the occurrence of coagulopathy after cardiopulmonary bypass (CPB) affects systemic heparinization in pediatric post-cardiotomy patients. This study compares hemostatic complications in pediatric post-cardiotomy VA-ECMO patients for failure to wean from CPB with those who received post-cardiotomy VA-ECMO for other indications, while also exploring the relationship between different stages-hemostatic complications and the timing of systemic heparinization. Methods We retrospectively analyzed 146 pediatric patients who received post-cardiotomy VA-ECMO support (CPB-ECMO, n=96 vs. non-CPB-ECMO, n=50) from January 2005 to June 2020. Patients were divided into survivors (n=46) and non-survivors (n=50) according to in-hospital mortality in the CPB-ECMO group. We compared clinical outcomes between the groups, then examined the associations between the timing of systemic heparinization after ECMO implantation and different stages-hemostatic complications, in the CPB-ECMO group. Results We found that the risk of early bleeding was significantly increased in patients who failed to wean from CPB. The presence of early bleeding was accompanied by the higher demand for blood products transfusion in the CPB-ECMO group, and for treatment the patients received a longer delayed continuous heparin infusion. As a result of using delayed systemic heparinization to avoid early bleeding, early hemolysis increased in the CPB-ECMO group. A delayed systemic heparinization of 9.5 hours showed the best Youden index results and the overall greatest accuracy in predicting early hemolysis. Conclusions A direct transition from CPB to ECMO in pediatric post-cardiotomy patients significantly increases early bleeding. Delayed systemic heparinization to reduce early bleeding has good discrimination for predicting early hemolysis in the CPB-ECMO group. Coagulopathy is complex in pediatric post-cardiotomy VA-ECMO patients who failed to wean from CPB, and, as such, it is extremely important to monitor coagulation-related indicators in multiple dimensions to determine the timing of systemic heparinization.

Project description:ObjectiveVeno-venous (V-V) extracorporeal membrane oxygenation (ECMO) is increasingly used to support patients with severe acute respiratory distress syndrome (ARDS). In case of additional cardio-circulatory failure, some experienced centers upgrade the V-V ECMO with an additional arterial return cannula (termed V-VA ECMO). Here we analyzed short- and long-term outcome together with potential predictors of mortality.DesignMulticenter, retrospective analysis between January 2008 and September 2021.SettingThree tertiary care ECMO centers in Germany (Hannover, Bonn) and Switzerland (Zurich).PatientsSeventy-three V-V ECMO patients with ARDS and additional acute cardio-circulatory deterioration required an upgrade to V-VA ECMO were included in this study.Measurements and main resultsFifty-three patients required an upgrade from V-V to V-VA and 20 patients were directly triple cannulated. Median (Interquartile Range) age was 49 (28-57) years and SOFA score was 14 (12-17) at V-VA ECMO upgrade. Vasoactive-inotropic score decreased from 53 (12-123) at V-VA ECMO upgrade to 9 (3-37) after 24 h of V-VA ECMO support. Weaning from V-VA and V-V ECMO was successful in 47 (64%) and 40 (55%) patients, respectively. Duration of ECMO support was 12 (6-22) days and ICU length of stay was 32 (16-46) days. Overall ICU mortality was 48% and hospital mortality 51%. Two additional patients died after hospital discharge while the remaining patients survived up to two years (with six patients being lost to follow-up). The vast majority of patients was free from higher degree persistent organ dysfunction at follow-up. A SOFA score > 14 and higher lactate concentrations at the day of V-VA upgrade were independent predictors of mortality in the multivariate regression analysis.ConclusionIn this analysis, the use of V-VA ECMO in patients with ARDS and concomitant cardiocirculatory failure was associated with a hospital survival of about 50%, and most of these patients survived up to 2 years. A SOFA score > 14 and elevated lactate levels at the day of V-VA upgrade predict unfavorable outcome.

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An innovative ovine model of severe cardiopulmonary failure supported by veno-arterial extracorporeal membrane oxygenation.

Publications

An innovative ovine model of severe cardiopulmonary failure supported by veno-arterial extracorporeal membrane oxygenation.

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