Levosimendan to Facilitate Weaning From Cardiorespiratory Support in Critically Ill Patients: A Meta-Analysis

Abstract

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, I2 = 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.

Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety

“…Further insights into this matter are provided by the meta-analysis of Luo et al [ 48 ] which draws on data from 2274 patients in 18 studies (RCTs or observational studies published in either Chinese or English). Pooled analysis from all 18 studies indicated that levosimendan improved MV/ECMO weaning ( n = 2274; OR 2.32; 95% CnI 1.60–3.36; p < 0.00001 vs control), albeit with high heterogeneity ( I 2 = 68%) and a general rating of evidence quality as low to moderate.…”

Early Levosimendan Administration Improved Weaning Success Rate in Extracorporeal Membrane Oxygenation in Patients With Cardiogenic Shock

“…According to previous studies, levosimendan administration significantly increased successful weaning rates in patients with cardiopulmonary support, especially in those with combined poor LV performance (23)(24)(25)(26). Regarding the issue of VA-ECMO for patients with CS, the enrolled studies were nonrandomized studies with a limited number of patients (25).…”

“…The use of levosimendan may provide a potential benefit in terms of VA-ECMO weaning success, reduce the duration of mechanical support, and minimize severe complications ( 23 , 24 ). Two studies concluded that levosimendan use in CS might reduce all-cause mortality and facilitate successful weaning from VA-ECMO ( 25 , 26 ). However, two recent studies showed that levosimendan did not improve the rate of successful VA-ECMO weaning in patients with refractory CS ( 27 , 28 ).…”

Weaning from venous-arterial extracorporeal membrane oxygenation: The hemodynamic and clinical aspects of flow challenge test

“…Venous-arterial extracorporeal membrane oxygenation (V-A ECMO) is an important circulatory support to rescue patients with refractory cardiogenic shock ( 1 , 2 ). However, the use of V-A ECMO can also lead to various complications ( 3 , 4 ), such as infection, hemorrhage, lung injury and skeletal muscle atrophy ( 5 ). Besides, prolonged V-A ECMO support was also associated with higher mortality ( 6 ), therefore, early weaning should be considered to maximize its benefits.…”

“…On the other hand, nearly one third of 10.3389/fmed.2022.989197 deceased patients had once been weaned from ECMO (7). Of note, one of the major contributors for the death after weaning was heart failure (5).…”