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.
Objective Conservative oxygen strategy is recommended in acute illness while its benefit in ICU patients remains controversial. Therefore, we sought to conduct a systematic review and meta-analysis to examine such oxygen strategies’ effect and safety in ICU patients. Methods We searched PubMed, Embase, and the Cochrane database from inception to Feb 15, 2021. Randomized controlled trials (RCTs) that compared a conservative oxygen strategy to a conventional strategy in critically ill patients were included. Results were expressed as mean difference (MD) and risk ratio (RR) with a 95% confidence interval (CI). The primary outcome was the longest follow-up mortality. Heterogeneity, sensitivity analysis, and publication bias were also investigated to test the robustness of the primary outcome. Results We included seven trials with a total of 5265 patients. In general, the conventional group had significantly higher SpO2 or PaO2 than that in the conservative group. No statistically significant differences were found in the longest follow-up mortality (RR, 1.03; 95% CI, 0.97–1.10; I2=18%; P=0.34) between the two oxygen strategies when pooling studies enrolling subjects with various degrees of hypoxemia. Further sensitivity analysis showed that ICU patients with mild-to-moderate hypoxemia (PaO2/FiO2 >100 mmHg) had significantly lower mortality (RR, 1.24; 95% CI, 1.05–1.46; I2=0%; P=0.01) when receiving conservative oxygen therapy. These findings were also confirmed in other study periods. Additional, secondary outcomes of the duration of mechanical ventilation, the length of stay in the ICU and hospital, change in sequential organ failure assessment score, and adverse events were comparable between the two strategies. Conclusions Our findings indicate that conservative oxygen therapy strategy did not improve the prognosis of the overall ICU patients. The subgroup of ICU patients with mild to moderate hypoxemia might obtain prognosis benefit from such a strategy without affecting other critical clinical results.
Objectives Heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) are associated with significant morbidity and mortality, as well as growing health and economic burden. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are very promising for the outcome improvement of patients with HFpEF or HFmrEF. The meta-analysis was performed to investigate the effects of SGLT2 inhibitors in HFpEF or HFmrEF, by pooling data from all clinically randomized controlled trials (RCTs) available to increase power to testify. Methods Studies were searched in electronic databases from inception to November, 2022. We performed a meta-analysis to estimate the effect of SGLT2 inhibitors on clinical endpoints in patients with HFpEF or HFmrEF, using trial-level data with consistent endpoint definitions. The primary outcome was the composite of heart failure (HF) hospitalization or cardiovascular death. Hazard ratio (HR) was pooled with 95% confidence interval (CI) for dichotomous data. This study was registered with INPLASY 2022110095. Results Six studies involving 15,989 participants were included into the final analysis. Pooled analyses revealed that SGLT2 inhibitors significantly reduced the composite of HF hospitalization or cardiovascular death [HR: 0.79 (0.72–0.85); I2 = 0%; P < 0.00001] and HF hospitalizations [HR: 0.74 (0.67–0.82); I2 = 0%; P < 0.00001]. This finding was seen in both HFmrEF trials [HR: 0.76 (0.67–0.87); I2 = 49%; P < 0.0001] and HFpEF subgroup studies [HR: 0.70 (0.53–0.93); I2 = 0%; P = 0.01]. The incidence of any serious adverse events [OR: 0.89 (0.83–0.96); I2 = 0%; P = 0.002] was significantly lower in the SGLT2 inhibitor arm. No significant differences were observed between the two groups with regard to cardiovascular death and all-cause death. Conclusions This meta-analysis of patients with heart failure of left ventricular ejection fraction (LVEF) > 40% showed that SGLT2 inhibitors significantly reduce the risk of the composite of cardiovascular death and hospitalization for heart failure, but not cardiovascular death and all-cause death. Nevertheless, given that SGLT2 inhibitors may reduce the risk of hospitalization for heart failure, they should be considered the fundamental treatment for all patients with HFpEF or HFmrEF.
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