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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.

SUBMITTER: Luo J

PROVIDER: S-EPMC8546177 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceAlthough most critically ill patients receive invasive mechanical ventilation (IMV), few studies have characterized how IMV is discontinued in practice.ObjectiveTo describe practice variation in IMV discontinuation internationally, associations between initial discontinuation events and outcomes, and factors associated with the use of select discontinuation strategies and failed initial spontaneous breathing trials (SBTs).Design, setting, and participantsProspective, multinational, observational study of critically ill adults who received IMV for at least 24 hours from 142 intensive care units (ICUs) in 19 countries within 6 regions (27 in Canada, 23 in India, 22 in the UK, 26 in Europe, 21 in Australia/New Zealand, and 23 in the US).ExposuresReceiving IMV.Main outcomes and measuresPrimary analyses characterized types of initial IMV discontinuation events (extubation, SBT, or tracheostomy) and associations with clinical outcomes (including duration of ventilation, ICU and hospital mortality, and ICU and hospital length of stay). Secondary analyses examined the associations between SBT outcome and SBT timing and clinical outcomes.ResultsAmong 1868 patients (median [interquartile range] age, 61.8 [48.9-73.1] years; 1173 [62.8%] men) 424 (22.7%) underwent direct extubation, 930 (49.8%) had an initial SBT (761 [81.8%] successful), 150 (8.0%) underwent direct tracheostomy, and 364 (19.5%) died before a weaning attempt. Across regions, there was variation in the use of written directives to guide care, daily screening, SBT techniques, ventilator modes, and the roles played by clinicians involved in weaning. Compared with initial direct extubation, patients who had an initial SBT had higher ICU mortality (20 [4.7%] vs 96 [10.3%]; absolute difference, 5.6% [95% CI, 2.6%-8.6%]), longer duration of ventilation (median of 2.9 vs 4.1 days; absolute difference, 1.2 days [95% CI, 0.7-1.6]), and longer ICU stay (median of 6.7 vs 8.1 days; absolute difference, 1.4 days [95% CI, 0.8-2.4]). Patients whose initial SBT failed (vs passed) had higher ICU mortality (29 [17.2%] vs 67 [8.8%]; absolute difference, 8.4% [95% CI, 2.0%-14.7%]), longer duration of ventilation (median of 6.1 vs 3.5 days; absolute difference, 2.6 days [95% CI, 1.6-3.6]), and longer ICU stay (median of 10.6 vs 7.7 days; absolute difference, 2.8 days [95% CI, 1.1-5.2]). Compared with patients who underwent early initial SBTs, patients who underwent late initial SBTs (>2.3 days after intubation) had longer duration of ventilation (median of 2.1 vs 6.1 days; absolute difference, 4.0 days [95% CI, 3.7-4.5]), longer ICU stay (median of 5.9 vs 10.8 days; absolute difference, 4.9 days [95% CI, 4.0-6.3]), and longer hospital stay (median of 14.3 vs 22.8 days; absolute difference, 8.5 days [95% CI, 6.0-11.0]).Conclusions and relevanceIn this observational study of invasive mechanical ventilation discontinuation in 142 ICUs in Canada, India, the UK, Europe, Australia/New Zealand, and the US from 2013 to 2016, weaning practices varied internationally.Trial registrationClinicalTrials.gov Identifier: NCT03955874.

Project description:Mechanical ventilation (MV) is currently considered a life-saving intervention. However, growing evidence highlighted that prolonged MV significantly affects functional outcomes and length of stay. In this scenario, controversies are still open about the optimal rehabilitation strategies for improving MV duration in ICU patients. In addition, the efficacy of physiotherapy interventions in critical ill patients without positive history of chronic respiratory conditions is still debated. Therefore, this systematic review of randomized controlled trials (RCTs) with meta-analysis aimed at characterizing the efficacy of a comprehensive physiotherapy intervention in critically ill patients. PubMed, Scopus, and Web of Science databases were systematically searched up to October 22, 2021 to identify RCTs assessing acute patients mechanical ventilated in ICU setting undergoing a rehabilitative intervention. The primary outcomes were MV duration, extubation, and weaning time. The secondary outcomes were weaning successful rate, respiratory function, ICU discharge rate and length of stay. Out of 2503 records, 12 studies were included in the present work. The meta-analysis performed in 6 RCTs showed a significant improvement in terms of MV duration (overall effect size: -3.23 days; 95% CI = -5.79, -0.67, p = 0.01; Z = 2.47) in patients treated with a comprehensive physiotherapy intervention including early mobilization, positioning, airway clearance techniques, lung expansion and respiratory muscle training. The quality assessment underlined 9 studies (75%) of good quality and 3 studies of fair quality according to the PEDro scale. In conclusion, our results provided previously unavailable data about the role of comprehensive physiotherapy intervention in improving MV duration in critical ill patients without chronic respiratory conditions. Further studies are needed to better characterize the optimal combination of rehabilitation strategies enhancing the improvements in critical ill patients without chronic respiratory disorders.

Project description:Systemic inflammation is a key characteristic of sepsis but also also in non-infectious conditions such as post-cardiac arrest syndrome. Cytokine adsorption and extracorporeal membrane oxygenation are emerging therapies applied in these critically ill patients, but the experience with their concurrent use is limited. We evaluated cytokine adsorption in critically ill patients requiring support with either veno-venous (vv) or veno-arterial (va) extracorporeal membrane oxygenation (ECMO) support and hypothesized that adsorber incorporation into the ECMO circuit was technically feasible and not associated with imminent risk. We analyzed data from the first six cases of a prospective single-center registry of patients undergoing veno-venous (vv) or veno-arterial (va) ECMO therapy. While in most published cases cytokine adsorbers were inserted into a hemofiltration circuit, we directly incorporated the adsorber into the ECMO circuit without interruption of continuous ECMO support. We observed no relevant side effects attributable to cytokine adsorption. Thirty-day mortality was 83% (predicted mortality 87%), indicating that the decision for adding cytokine adsorption may have been considered as an ultima ratio decision in severe cases with poor prognosis. Vasopressor or inotrope use, lactate level, and fluid balance did not change significantly when comparing pre- vs. post-cytokine adsorption values. Interestingly, the real-time course of the mentioned three surrogate parameters remained unaltered in all but two cases, regardless of cytokine removal. Beneficial effects of cytokine adsorption are plausible in two va-ECMO-treated patient, where increasing lactate began to drop after initiation of cytokine adsorption. Taken together, these data suggest that incorporation of cytokine adsorption into the management of critically ill patients requiring continued ECMO support is feasible and easy to handle. Whether cytokine removal improves clinical outcome in ECMO-treated patients should now be investigated in randomized controlled trials.

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

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