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  • Van Daele, R, et al. (author)
  • A Large Retrospective Assessment of Voriconazole Exposure in Patients Treated with Extracorporeal Membrane Oxygenation
  • 2021
  • In: Microorganisms. - : MDPI AG. - 2076-2607. ; 9:7
  • Journal article (peer-reviewed)abstract
    • Background: Voriconazole is one of the first-line therapies for invasive pulmonary aspergillosis. Drug concentrations might be significantly influenced by the use of extracorporeal membrane oxygenation (ECMO). We aimed to assess the effect of ECMO on voriconazole exposure in a large patient population. Methods: Critically ill patients from eight centers in four countries treated with voriconazole during ECMO support were included in this retrospective study. Voriconazole concentrations were collected in a period on ECMO and before/after ECMO treatment. Multivariate analyses were performed to evaluate the effect of ECMO on voriconazole exposure and to assess the impact of possible saturation of the circuit’s binding sites over time. Results: Sixty-nine patients and 337 samples (190 during and 147 before/after ECMO) were analyzed. Subtherapeutic concentrations (<2 mg/L) were observed in 56% of the samples during ECMO and 39% without ECMO (p = 0.80). The median trough concentration, for a similar daily dose, was 2.4 (1.2–4.7) mg/L under ECMO and 2.5 (1.4–3.9) mg/L without ECMO (p = 0.58). Extensive inter-and intrasubject variability were observed. Neither ECMO nor squared day of ECMO (saturation) were retained as significant covariates on voriconazole exposure. Conclusions: No significant ECMO-effect was observed on voriconazole exposure. A large proportion of patients had voriconazole subtherapeutic concentrations.
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  • Belliato, M, et al. (author)
  • Mechanical Power during Veno-Venous Extracorporeal Membrane Oxygenation Initiation: A Pilot-Study
  • 2021
  • In: Membranes. - : MDPI AG. - 2077-0375. ; 11:1
  • Journal article (peer-reviewed)abstract
    • Mechanical power (MP) represents a useful parameter to describe and quantify the forces applied to the lungs during mechanical ventilation (MV). In this multi-center, prospective, observational study, we analyzed MP variations following MV adjustments after veno-venous extra-corporeal membrane oxygenation (VV ECMO) initiation. We also investigated whether the MV parameters (including MP) in the early phases of VV ECMO run may be related to the intensive care unit (ICU) mortality. Thirty-five patients with severe acute respiratory distress syndrome were prospectively enrolled and analyzed. After VV ECMO initiation, we observed a significant decrease in median MP (32.4 vs. 8.2 J/min, p < 0.001), plateau pressure (27 vs. 21 cmH2O, p = 0.012), driving pressure (11 vs. 8 cmH2O, p = 0.014), respiratory rate (RR, 22 vs. 14 breaths/min, p < 0.001), and tidal volume adjusted to patient ideal body weight (VT/IBW, 5.5 vs. 4.0 mL/kg, p = 0.001) values. During the early phase of ECMO run, RR (17 vs. 13 breaths/min, p = 0.003) was significantly higher, while positive end-expiratory pressure (10 vs. 14 cmH2O, p = 0.048) and VT/IBW (3.0 vs. 4.0 mL/kg, p = 0.028) were lower in ICU non-survivors, when compared to the survivors. The observed decrease in MP after ECMO initiation did not influence ICU outcome. Waiting for large studies assessing the role of these parameters in VV ECMO patients, RR and MP monitoring should not be underrated during ECMO.
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  • Broman, LM (author)
  • When antithrombin substitution strikes back
  • 2020
  • In: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 35:1_suppl, s. 34-37
  • Journal article (peer-reviewed)abstract
    • Commercially available products used for antithrombin supplementation, for example, in extracorporeal life support, may contain latent antithrombin, a hyper-stable strongly procoagulative and anti-angiogenic residue. Latent antithrombin is associated with severe thrombosis in the critically ill. In the manufacturing process of fractionated antithrombin from plasma, heat treatment, citrate, and freeze drying speed up the transformation of native antithrombin to latent antithrombin. Manufacturers are not required to assess and report the latent antithrombin content of their products. When reported, the latent antithrombin fractions in their product range from <1% to 40% of total antithrombin compared with <3% in the healthy adult and less in children. The aims of this work were (1) to convey increased awareness to clinicians who may experience defaulted, expected effect after antithrombin supplementation in, for example, heparin anticoagulation during extracorporeal life support and (2) to urge manufacturers to assess and disclose latent antithrombin content in their products.
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  • Cvetkovic, M, et al. (author)
  • International survey of neuromonitoring and neurodevelopmental outcome in children and adults supported on extracorporeal membrane oxygenation in Europe
  • 2023
  • In: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 38:2, s. 245-260
  • Journal article (peer-reviewed)abstract
    • Adverse neurological events during extracorporeal membrane oxygenation (ECMO) are common and may be associated with devastating consequences. Close monitoring, early identification and prompt intervention can mitigate early and late neurological morbidity. Neuromonitoring and neurocognitive/neurodevelopmental follow-up are critically important to optimize outcomes in both adults and children. Objective: To assess current practice of neuromonitoring during ECMO and neurocognitive/neurodevelopmental follow-up after ECMO across Europe and to inform the development of neuromonitoring and follow-up guidelines. Methods: The EuroELSO Neurological Monitoring and Outcome Working Group conducted an electronic, web-based, multi-institutional, multinational survey in Europe. Results: Of the 211 European ECMO centres (including non-ELSO centres) identified and approached in 23 countries, 133 (63%) responded. Of these, 43% reported routine neuromonitoring during ECMO for all patients, 35% indicated selective use, and 22% practiced bedside clinical examination alone. The reported neuromonitoring modalities were NIRS ( n = 88, 66.2%), electroencephalography ( n = 52, 39.1%), transcranial Doppler ( n = 38, 28.5%) and brain injury biomarkers ( n = 33, 24.8%). Paediatric centres (67%) reported using cranial ultrasound, though the frequency of monitoring varied widely. Before hospital discharge following ECMO, 50 (37.6%) reported routine neurological assessment and 22 (16.5%) routinely performed neuroimaging with more paediatric centres offering neurological assessment (65%) as compared to adult centres (20%). Only 15 (11.2%) had a structured longitudinal follow-up pathway (defined followup at regular intervals), while 99 (74.4%) had no follow-up programme. The majority ( n = 96, 72.2%) agreed that there should be a longitudinal structured follow-up for ECMO survivors. Conclusions: This survey demonstrated significant variability in the use of different neuromonitoring modalities during and after ECMO. The perceived importance of neuromonitoring and follow-up was noted to be very high with agreement for a longitudinal structured follow-up programme, particularly in paediatric patients. Scientific society endorsed guidelines and minimum standards should be developed to inform local protocols.
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  • Di Nardo, M, et al. (author)
  • A narrative review of the technical standards for extracorporeal life support devices (pumps and oxygenators) in Europe
  • 2018
  • In: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 33:7, s. 553-561
  • Journal article (peer-reviewed)abstract
    • This review summarizes the European rules to control the market when introducing new products. In particular, it shows all the steps to achieve the European Conformity (CE Mark), a certification that all new medical products must achieve before being used in Europe. Extracorporeal membrane oxygenation (ECMO) devices are exposed to the same procedures. Hereby, we present some regulatory issues regarding pumps and oxygenators, providing technical details as released by the manufacturers on their websites and information charts.
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  • Di Nardo, M, et al. (author)
  • Evaluation of a New Extracorporeal CO2 Removal Device in an Experimental Setting
  • 2021
  • In: Membranes. - : MDPI AG. - 2077-0375. ; 11:1
  • Journal article (peer-reviewed)abstract
    • Background: Ultra-protective lung ventilation in acute respiratory distress syndrome or early weaning and/or avoidance of mechanical ventilation in decompensated chronic obstructive pulmonary disease may be facilitated by the use of extracorporeal CO2 removal (ECCO2R). We tested the CO2 removal performance of a new ECCO2R (CO2RESET) device in an experimental animal model. Methods: Three healthy pigs were mechanically ventilated and connected to the CO2RESET device (surface area = 1.8 m2, EUROSETS S.r.l., Medolla, Italy). Respiratory settings were adjusted to induce respiratory acidosis with the adjunct of an external source of pure CO2 (target pre membrane lung venous PCO2 (PpreCO2): 80–120 mmHg). The amount of CO2 removed (VCO2, mL/min) by the membrane lung was assessed directly by the ECCO2R device. Results: Before the initiation of ECCO2R, the median PpreCO2 was 102.50 (95.30–118.20) mmHg. Using fixed incremental steps of the sweep gas flow and maintaining a fixed blood flow of 600 mL/min, VCO2 progressively increased from 0 mL/min (gas flow of 0 mL/min) to 170.00 (160.00–200.00) mL/min at a gas flow of 10 L/min. In particular, a high increase of VCO2 was observed increasing the gas flow from 0 to 2 L/min, then, VCO2 tended to progressively achieve a steady-state for higher gas flows. No animal or pump complications were observed. Conclusions: Medium-flow ECCO2R devices with a blood flow of 600 mL/min and a high surface membrane lung (1.8 m2) provided a high VCO2 using moderate sweep gas flows (i.e., >2 L/min) in an experimental swine models with healthy lungs.
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  • Falk, L, et al. (author)
  • Conversion from Venovenous to Venoarterial Extracorporeal Membrane Oxygenation in Adults
  • 2021
  • In: Membranes. - : MDPI AG. - 2077-0375. ; 11:3
  • Journal article (peer-reviewed)abstract
    • No major study has been performed on the conversion from venovenous (VV) to venoarterial (VA) extracorporeal membrane oxygenation (ECMO) in adults. This single-center retrospective cohort study aimed to investigate the incidence, indication, and outcome in patients who converted from VV to VA ECMO. All adult patients (≥18 years) who commenced VV ECMO at our center between 2005 and 2018 were screened. Of 219 VV ECMO patients, 21% (n = 46) were converted to VA ECMO. The indications for conversion were right ventricular failure (RVF) (65%), cardiogenic shock (26%), and other (9%). In the converted patients, there was a significant increase in Sequential Organ Failure Assessment (SOFA) scores between admission 12 (9–13) and conversion 15 (13–17, p < 0.001). Compared to non-converted patients, converted patients also had a higher mortality rate (62% vs. 16%, p < 0.001) and a lower admission Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score (p < 0.001). Outcomes were especially unfavorable in those converted due to RVF. These results indicate that VA ECMO, as opposed to VV ECMO, should be considered as the first mode of choice in patients with respiratory failure and signs of circulatory impairment, especially in those with impaired RV function. For the remaining patients, Pre-admission RESP score, daily echocardiography, and SOFA score trajectories may help in the early identification of those where conversion from VV to VA ECMO is warranted. Multi-centric studies are warranted to validate these findings.
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  • Falk, L, et al. (author)
  • Differential hypoxemia and the clinical significance of venous drainage position during extracorporeal membrane oxygenation
  • 2023
  • In: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 38:4, s. 818-825
  • Journal article (peer-reviewed)abstract
    • Differential hypoxemia (DH) has been recognized as a clinical problem during veno-arterial extracorporeal membrane oxygenation (VA ECMO) although its features and consequences have not been fully elucidated. This single center retrospective study aimed to investigate the clinical characteristics of patients manifesting DH as well as the impact of repositioning the drainage point from the inferior vena cava (IVC) to the superior vena cava to alleviate DH. All patients (>15 years) commenced on VA ECMO at our center between 2009 and 2020 were screened. Of 472 eligible patients seven were identified with severe DH. All patients had the drainage cannula tip in the IVC or at the junction between the IVC and right atrium. The mean peripheral capillary saturation increased from 54 (±6.6) to 86 (±6.6) %, ( p = <0.001) after repositioning of the cannula. Pre-oxygenator saturation increased from 62 (±8.9) % prior to adjustment to 74 (±3.7) %, ( p = 0.016) after repositioning. Plasma lactate tended to decrease within 24 h after adjustment. Five patients (71%) survived ECMO treatment, to discharge from hospital, and were alive at 1-year follow-up. Although DH has been described in several studies, the condition has not been investigated in a clinical setting comparing the effect on upper body saturation before and after repositioning of the drainage cannula. This study shows that moving the drainage zone into the upper part of the body has a marked positive effect on upper body saturation in patients with DH.
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  • Falk, L, et al. (author)
  • Differential hypoxemia during venoarterial extracorporeal membrane oxygenation
  • 2019
  • In: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 34:1_suppl, s. 22-29
  • Journal article (peer-reviewed)abstract
    • Venoarterial extracorporeal membrane oxygenation, indicated for severe cardio-respiratory failure, may result in anatomic regional differences in oxygen saturation. This depends on cannulation, hemodynamic state, and severity of respiratory failure. Differential hypoxemia, often discrete, may cause clinical problems in peripheral femoro-femoral venoarterial extracorporeal membrane oxygenation, when the upper body is perfused with low saturated blood from the heart and the lower body with well-oxygenated extracorporeal membrane oxygenation blood. The key is to diagnose and manage fulminant differential hypoxemia, that is, a state that may develop where the upper body is deprived of oxygen. We summarize physiology, assessment of diagnosis, and management of fulminant differential hypoxemia during venoarterial extracorporeal membrane oxygenation. A possible solution is implantation of an additional jugular venous return cannula. In this article, we propose an even better solution, to drain the venous blood from the superior vena cava. Drainage from the superior vena cava provides superiority to venovenoarterial configuration in terms of physiological rationale, efficiency, safety, and simplicity in clinical circuit design.
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  • Falk, L, et al. (author)
  • The authors reply
  • 2019
  • In: Critical care medicine. - 1530-0293. ; 47:12, s. E1040-E1040
  • Journal article (other academic/artistic)
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  • Fisser, C, et al. (author)
  • Recirculation in single lumen cannula venovenous extracorporeal membrane oxygenation: A non-randomized bi-centric trial
  • 2022
  • In: Frontiers in medicine. - : Frontiers Media SA. - 2296-858X. ; 9, s. 973240-
  • Journal article (peer-reviewed)abstract
    • Recirculation is a common problem in venovenous (VV) extracorporeal membrane oxygenation (ECMO). The aims of this study were to compare recirculation fraction (Rf) between femoro-jugular and jugulo-femoral VV ECMO configurations, to identify risk factors for recirculation and to assess the impact on hemolysis.MethodsPatients in the medical intensive care unit (ICU) at the University Medical Center Regensburg, Germany receiving VV ECMO with femoro-jugular, and jugulo-femoral configuration at the ECMO Center Karolinska, Sweden, were included in this non-randomized prospective study. Total ECMO flow (QEC), recirculated flow (QREC), and recirculation fraction Rf = QREC/QEC were determined using ultrasound dilution technology. Effective ECMO flow (QEFF) was defined as QEFF = QEC * (1–Rf). Demographics, cannula specifics, and markers of hemolysis were assessed. Survival was evaluated at discharge from ICU.ResultsThirty-seven patients with femoro-jugular configuration underwent 595 single-point measurements and 18 patients with jugulo-femoral configuration 231 measurements. Rf was lower with femoro-jugular compared to jugulo-femoral configuration [5 (0, 11) vs. 19 (13, 28) %, respectively (p &lt; 0.001)], resulting in similar QEFF [2.80 (2.21, 3.39) vs. 2.79 (2.39, 3.08) L/min (p = 0.225)] despite lower QEC with femoro-jugular configuration compared to jugulo-femoral [3.01 (2.40, 3.70) vs. 3.57 (3.05, 4.06) L/min, respectively (p &lt; 0.001)]. In multivariate regression analysis, the type of configuration, distance between the two cannula tips, ECMO flow, and heart rate were significantly associated with Rf [B (95% CI): 25.8 (17.6, 33.8), p &lt; 0.001; 960.4 (960.7, 960.1), p = 0.009; 4.2 (2.5, 5.9), p &lt; 0.001; 960.1 (960.2, 0.0), p = 0.027]. Hemolysis was similar in subjects with Rf &gt; 8 vs. ≤ 8%. Explorative data on survival showed comparable results in the femoro-jugular and the jugulo-femoral group (81 vs. 72%, p = 0.455).ConclusionVV ECMO with femoro-jugular configuration caused less recirculation. Further risk factors for higher Rf were shorter distance between the two cannula tips, higher ECMO flow, and lower heart rate. Rf did not affect hemolysis.
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  • Fisser, C, et al. (author)
  • Validation of Prognostic Scores in Extracorporeal Life Support: A Multi-Centric Retrospective Study
  • 2021
  • In: Membranes. - : MDPI AG. - 2077-0375. ; 11:2
  • Journal article (peer-reviewed)abstract
    • Multiple prognostic scores have been developed for both veno-arterial (VA) and veno-venous (VV) extracorporeal membrane oxygenation (ECMO), mostly in single-center cohorts. The aim of this study was to compare and validate different prediction scores in a large multicenter ECMO-population. Methods: Data from five ECMO centers included 300 patients on VA and 329 on VV ECMO support (March 2008 to November 2016). Different prognostic scores were compared between survivors and non-survivors: APACHE II, SOFA, SAPS II in all patients; SAVE, modified SAVE and MELD-XI in VA ECMO; RESP, PRESET, ROCH and PRESERVE in VV ECMO. Model performance was compared using receiver-operating-curve analysis and assessment of model calibration. Survival was assessed at intensive care unit discharge. Results: The main indication for VA ECMO was cardiogenic shock; overall survival was 51%. ICU survivors had higher Glasgow Coma Scale scores and pH, required cardiopulmonary resuscitation (CPR) less frequently, had lower lactate levels and shorter ventilation time pre-ECMO at baseline. The best discrimination between survivors and non-survivors was observed with the SAPS II score (area under the curve [AUC] of 0.73 (95% CI 0.67–0.78)). The main indication for VV ECMO was pneumonia; overall survival was 60%. Lower PaCO2, higher pH, lower lactate and lesser need for CPR were observed among survivors. The best discrimination between survivors and non-survivors was observed with the PRESET score (AUC 0.66 (95% CI 0.60–0.72)). Conclusion: The prognostic performance of most scores was moderate in ECMO patients. The use of such scores to decide about ECMO implementation in potential candidates should be discouraged.
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  • Iacobelli, R, et al. (author)
  • Predictors of brain infarction in adult patients on extracorporeal membrane oxygenation: an observational cohort study
  • 2021
  • In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 3809-
  • Journal article (peer-reviewed)abstract
    • Non-hemorrhagic brain infarction (BI) is a recognized complication in adults treated with extracorporeal membrane oxygenation (ECMO) and associated with increased mortality. However, predictors of BI in these patients are poorly understood. The aim of this study was to identify predictors of BI in ECMO-treated adult patients. We conducted an observational cohort study of all adult patients treated with venovenous or venoarterial (VA) ECMO at our center between 2010 and 2018. The primary endpoint was a computed tomography (CT) verified BI. Logistic regression models were employed to identify BI predictors. In total, 275 patients were included, of whom 41 (15%) developed a BI. Pre-ECMO Simplified Acute Physiology Score III, pre-ECMO cardiac arrest, VA ECMO and conversion between ECMO modes were identified as predictors of BI. In the multivariable analysis, VA ECMO demonstrated independent risk association. VA ECMO also remained the independent BI predictor in a sub-group analysis excluding patients who did not undergo a head CT scan during ECMO treatment. The incidence of BI in adult ECMO patients may be higher than previously believed and is independently associated with VA ECMO mode. Larger prospective trials are warranted to validate these findings and ascertain their clinical significance.
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