Levosimendan for VA-ECMO weaning: the silver lining.
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ABSTRACT:
SUBMITTER: Kaddoura R
PROVIDER: S-EPMC8788139 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AimsVenoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used in circulatory failure. The main indications are cardiogenic shock, post-cardiotomy cardiac failure, and refractory cardiac arrest. However, VA-ECMO weaning is particularly challenging, and weaning failure is reported to be as high as 50%, with increased related mortality. Levosimendan is a novel long acting effect inodilator used in cardiogenic shock and terminal heart failure decompensation. Levosimendan use in VA-ECMO patients seems to reduce weaning failure regardless of the initial aetiology and to reduce mortality when administrated early after VA-ECMO initiation. However, studies are limited to retrospective analyses and reported case series. The aim of the WEANILEVO trial is to evaluate whether administration of levosimendan before VA-ECMO weaning is associated with a reduced rates of weaning failure and recourse to other temporary circulatory support.Methods and resultsWEANILEVO is a randomized, prospective, multicentre, double-blind, parallel-group, controlled trial. One hundred eighty patients will be enrolled if they had acute circulatory heart failure treated with VA-ECMO and for whom weaning is expected within 48 h. The study drugs are either levosimendan (0.2 μg/kg/min for 24 h) or a placebo. The primary endpoint of the trial is the absence of VA-ECMO weaning, recourse to another VA-ECMO, or other temporary circulatory assistance or death within 7 days of VA-ECMO weaning.ConclusionsLevosimendan use in VA-ECMO appears to be beneficial for reducing weaning failure and mortality. The results of WEANILEVO should significantly influence decisions regarding the use of levosimendan for VA-ECMO weaning.
| S-EPMC8318420 | biostudies-literature
Project description:BACKGROUNDVeno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly adopted for the treatment of cardiogenic shock (CS). However, a marker of successful weaning remains largely unknown. Our hypothesis was that successful weaning is associated with sustained microcirculatory function during ECMO flow reduction. Therefore, we sought to test the usefulness of microcirculatory imaging in the same sublingual spot, using incident dark field (IDF) imaging in assessing successful weaning from VA-ECMO and compare IDF imaging with echocardiographic parameters.METHODSWeaning was performed by decreasing the VA-ECMO flow to 50% (F50) from the baseline. The endpoint of the study was successful VA-ECMO explantation within 48 hours after weaning. The response of sublingual microcirculation to a weaning attempt (WA) was evaluated. Microcirculation was measured in one sublingual area (single spot (ss)) using CytoCam IDF imaging during WA. Total vessel density (TVDss) and perfused vessel density (PVDss) of the sublingual area were evaluated before and during 50% flow reduction (TVDssF50, PVDssF50) after a WA and compared to conventional echocardiographic parameters as indicators of the success or failure of the WA.RESULTSPatients (n = 13) aged 49 ± 18 years, who received VA-ECMO for the treatment of refractory CS due to pulmonary embolism (n = 5), post cardiotomy (n = 3), acute coronary syndrome (n = 2), myocarditis (n = 2) and drug intoxication (n = 1), were included. TVDssF50 (21.9 vs 12.9 mm/mm2, p = 0.001), PVDssF50 (19.7 vs 12.4 mm/mm2, p = 0.01) and aortic velocity-time integral (VTI) at 50% flow reduction (VTIF50) were higher in patients successfully weaned vs not successfully weaned. The area under the curve (AUC) was 0.99 vs 0.93 vs 0.85 for TVDssF50 (small vessels) >12.2 mm/mm2, left ventricular ejection fraction (LVEF) >15% and aortic VTI >11 cm. Likewise, the AUC was 0.91 vs 0.93 vs 0.85 for the PVDssF50 (all vessels) >14.8 mm/mm2, LVEF >15% and aortic VTI >11 cm.CONCLUSIONThis study identified sublingual microcirculation as a novel potential marker for identifying successful weaning from VA-ECMO. Sustained values of TVDssF50 and PVDssF50 were found to be specific and sensitive indicators of successful weaning from VA-ECMO as compared to echocardiographic parameters.
| S-EPMC5658964 | biostudies-literature
Project description:BACKGROUND:Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been increasingly used over the last decade in patients with refractory cardiogenic shock. ECMO weaning can, however, be challenging and lead to circulatory failure and death. Recent data suggest a potential benefit of levosimendan for ECMO weaning. We sought to further investigate whether the use of levosimendan could decrease the rate of ECMO weaning failure in adult patients with refractory cardiogenic shock. METHODS:We performed an observational single-center cohort study. All patients undergoing VA-ECMO from January 2012 to December 2018 were eligible and divided into two groups: group levosimendan and group control (without levosimendan). The primary endpoint was VA-ECMO weaning failure defined as death during VA-ECMO treatment or within 24?h after VA-ECMO removal. Secondary outcomes were mortality at day 28 and at 6 months. The two groups were compared after propensity score matching. P?<?0.05 was considered statistically significant. RESULTS:Two hundred patients were analyzed (levosimendan group: n?=?53 and control group: n?=?147). No significant difference was found between groups on baseline characteristics except for ECMO duration, which was longer in the levosimendan group (10.6?±?4.8 vs. 6.5?±?4.7?days, p?<?0.001). Levosimendan administration started 6.6?±?5.4?days on average following ECMO implantation. After matching of 48 levosimendan patients to 78 control patients, the duration of ECMO was similar in both groups. The rate of weaning failure was 29.1% and 35.4% in levosimendan and control groups, respectively (OR: 0.69, 95%CI: 0.25-1.88). No significant difference was found between groups for all secondary outcomes. CONCLUSION:Levosimendan did not improve the rate of successful VA-ECMO weaning in patients with refractory cardiogenic shock. TRIAL REGISTRATION:ClinicalTrials.gov, NCT04323709 .
| S-EPMC7367381 | biostudies-literature
Project description:Venovenous (VV) and venoarterial (VA) extracorporeal membrane oxygenation (ECMO) are effective support modalities to treat critically ill patients. ECMO-associated hemolysis remains a serious complication. The aim was to disclose similarities and differences in VA- and VV ECMO-associated hemolysis. This is a retrospective single-center analysis (January 2012 to September 2018) including 1,063 adult consecutive patients (VA, n = 606; VV, n = 457). Severe hemolysis (free plasma hemoglobin, fHb > 500 mg/l) during therapy occurred in 4% (VA) and 2% (VV) (p≤0.001). VV ECMO showed significantly more hemolysis by pump head thrombosis (PHT) compared to VA ECMO (9% vs. 2%; p≤0.001). Pretreatments (ECPR, cardiac surgery) of patients who required VA ECMO caused high fHb pre levels which aggravates the proof of ECMO-induced hemolysis (median (interquartile range), VA: fHb pre: 225.0 (89.3-458.0); VV: fHb pre: 72.0 (42.0-138.0); p≤0.001). The survival rate to discharge from hospital differed depending on ECMO type (40% (VA) vs. 63% (VV); p≤0.001). Hemolysis was dominant in VA ECMO patients, mainly caused by different indications and not by the ECMO support itself. PHT was the most severe form of ECMO-induced hemolysis that occurs in both therapies with low frequency, but more commonly in VV ECMO due to prolonged support time.
| S-EPMC6984694 | biostudies-literature
Project description:BackgroundVenoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in patients with critical cardiopulmonary failure. To investigate the association between hospital VA-ECMO procedure volume and outcomes in a large, nationwide registry.MethodsBy using administrative data from the German Federal Health Monitoring System, we analyzed all VA-ECMO procedures performed in Germany from 2013 to 2016 regarding the association of procedural volumes with outcomes and complications.ResultsDuring the study period, 10,207 VA-ECMO procedures were performed; mean age was 61?years, 43.4% had prior CPR, and 71.2% were male patients. Acute coronary syndrome was the primary diagnosis for VA-ECMO implantation (n?=?6202, 60.8%). The majority of implantations (n?=?5421) were performed at hospitals in the lowest volume category (??50 implantations per year). There was a significant association between annualized volume of VA-ECMO procedures and 30-day in-hospital mortality for centers with lower vs. higher volume per year. Multivariable logistic regression showed an increased 30-day in-hospital mortality at hospitals with the lowest volume category (adjusted odds ratio 1.13, 95% confidence interval [CI] 1.01-1.27, p?=?0.034). Similarly, higher likelihood for complications was observed at hospitals with lower vs. higher annual VA-ECMO volume (adjusted odds ratio 1.46, 95% CI 1.29-1.66, p?=?0.001).ConclusionsIn this analysis of more than 10,000 VA-ECMO procedures for cardiogenic shock, the majority of implantations were performed at hospitals with the lowest annual volume. Thirty-day in-hospital mortality and likelihood for complications were higher at hospitals with the lowest annual VA-ECMO volume.
| S-EPMC7275456 | biostudies-literature
Project description:PURPOSE:Respiratory muscle weakness frequently develops in critically ill patients and is associated with adverse outcome, including difficult weaning from mechanical ventilation. Today, no drug is approved to improve respiratory muscle function in these patients. Previously, we have shown that the calcium sensitizer levosimendan improves calcium sensitivity of human diaphragm muscle fibers in vitro and contractile efficiency of the diaphragm in healthy subjects. The main purpose of this study is to investigate the effects of levosimendan on diaphragm contractile efficiency in mechanically ventilated patients. METHODS:In a double-blind randomized placebo-controlled trial, mechanically ventilated patients performed two 30-min continuous positive airway pressure (CPAP) trials with 5-h interval. After the first CPAP trial, study medication (levosimendan 0.2 µg/kg/min continuous infusion or placebo) was administered. During the CPAP trials, electrical activity of the diaphragm (EAdi), transdiaphragmatic pressure (Pdi), and flow were measured. Neuromechanical efficiency (primary outcome parameter) was calculated. RESULTS:Thirty-nine patients were included in the study. Neuromechanical efficiency was not different during the CPAP trial after levosimendan administration compared to the CPAP trial before study medication. Tidal volume and minute ventilation were higher after levosimendan administration (11 and 21%, respectively), whereas EAdi and Pdi were higher in both groups in the CPAP trial after study medication compared to the CPAP trial before study medication. CONCLUSIONS:Levosimendan does not improve diaphragm contractile efficiency.
| S-EPMC6773912 | biostudies-literature
Project description:Background: Cardiopulmonary support, as extracorporeal membrane oxygenation (ECMO) or mechanical ventilation (MV), is crucial for ICU patients. However, some of these patients are difficult to wean. Therefore, we aimed to assess the efficacy and safety of levosimendan in facilitating weaning from cardiorespiratory support in this patient population. Methods: We searched for potentially relevant articles in PubMed, Embase, China National Knowledge Infrastructure, Wanfang, and the Cochrane database from inception up to Feb 30, 2021. Studies focusing on weaning data in MV/ECMO adult patients who received levosimendan compared to controls were included. We used the Cochrane risk of bias tool or the Newcastle-Ottawa Quality Assessment Scale to evaluate the study quality. The primary outcome was the weaning rate from MV/ECMO. Secondary outcomes were mortality, duration of MV, and ICU stay. Subgroup analysis, sensitivity analysis, and publication bias were also conducted. Results: Eighteen studies with 2,274 patients were included. The quality of the included studies was low to moderate. Overall, levosimendan effectively improved weaning rates from MV/ECMO [odds ratio (OR) = 2.32; 95%CI, 1.60-3.36; P < 0.00001, I 2 = 68%]. Subgroup analyses confirmed the higher successful weaning rates in ventilated patients with low left ventricular ejection fractions (OR = 4.06; 95%CI, 2.16-7.62), patients with ECMO after cardiac surgery (OR = 2.04; 95%CI, 1.25-3.34), and patients with ECMO and cardiogenic shock (OR = 1.98; 95%CI, 1.34-2.91). However, levosimendan showed no beneficial effect on patients with MV weaning difficulty (OR = 2.28; 95%CI, 0.72-7.25). Additionally, no differences were found concerning the secondary outcomes between the groups. Conclusions: Levosimendan therapy significantly increased successful weaning rates in patients with cardiopulmonary support, especially patients with combined cardiac insufficiency. Large-scale, well-designed RCTs will be needed to define the subgroup of patients most likely to benefit from this strategy.
| S-EPMC8546177 | biostudies-literature
Project description:COVID-19 has led to an unprecedented reduction in demand for energy for transportation and electricity, a crash in prices and employment in the fossil fuel industries and record-breaking reductions in global carbon emissions. This paper discusses whether this "demand destruction" could spell the beginning of the end for fossil fuels or a temporary recession and the imperative to recover from the current crisis by "building back better" and not the same as before. There are encouraging signs for the renewable energy industry that could make COVID-19 a cloud with a silver lining; whether this is the case will depend not only on the technological realities and social response to the crisis but also on political will and foresight.
| S-EPMC7675242 | biostudies-literature
Project description:Recent studies conclude that the global coronavirus (COVID-19) pandemic decreased power sector CO2 emissions globally and in the United States. In this paper, we analyze the statistical significance of CO2 emissions reductions in the U.S. power sector from March through December 2020. We use Gaussian process (GP) regression to assess whether CO2 emissions reductions would have occurred with reasonable probability in the absence of COVID-19 considering uncertainty due to factors unrelated to the pandemic and adjusting for weather, seasonality, and recent emissions trends. We find that monthly CO2 emissions reductions are only statistically significant in April and May 2020 considering hypothesis tests at 5% significance levels. Separately, we consider the potential impact of COVID-19 on coal-fired power plant retirements through 2022. We find that only a small percentage of U.S. coal power plants are at risk of retirement due to a possible COVID-19-related sustained reduction in electricity demand and prices. We observe and anticipate a return to pre-COVID-19 CO2 emissions in the U.S. power sector.
| S-EPMC8333368 | biostudies-literature