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Effects of levosimendan on respiratory muscle function in patients weaning from mechanical ventilation.

ABSTRACT: 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.

SUBMITTER: Roesthuis L

PROVIDER: S-EPMC6773912 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Effects of levosimendan on respiratory muscle function in patients weaning from mechanical ventilation.

Roesthuis Lisanne L van der Hoeven Hans H Sinderby Christer C Frenzel Tim T Ottenheijm Coen C Brochard Laurent L Doorduin Jonne J Heunks Leo L

Intensive care medicine 20191001 10

<h4>Purpose</h4>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 ...[more]

PMID: 31576436

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Project description:BackgroundPatients who need prolonged mechanical ventilation (MV) have high resource utilization and relatively poor outcomes. The pathophysiologic mechanisms leading to weaning failure in this group may be complex and multifactorial. The aim of this study was to investigate the factors associated with prolonged weaning based on the Weaning Outcome according to a New Definition (WIND) classification.MethodsThis is a prospective observational study with consecutive adult patients receiving MV for at least two calendar days in medical intensive care units from 1 November 2017 to 30 September 2020. Eligible patients were divided in a non-prolonged weaning group, including short and difficult weaning, and in a prolonged weaning group according to the WIND classification. The risk factors at the time of first separation attempt associated with prolonged weaning were analyzed using a multivariable logistic regression model.ResultsOf the total 915 eligible patients, 172 (18.8%) patients were classified as prolonged weaning. A higher proportion of the prolonged weaning group had previous histories of endotracheal intubation, chronic lung disease, and hematologic malignancies. When compared with the non-prolonged weaning group, the median duration of MV before the first spontaneous breathing trial (SBT) was longer and the proportion of tracheostomized patients was higher in prolonged weaning group. In addition, the prolonged weaning group used higher peak inspiratory pressures and yielded lower PaO2/FiO2 ratios at the day of the first SBT compared with the non-prolonged weaning group. In multivariate analyses, the duration of MV before first SBT (adjusted odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.06-1.22, p < 0.001), tracheostomy state (adjusted OR = 1.95, 95% CI = 1.04-3.63, p = 0.036), PaO2/FiO2 ratio (adjusted OR = 1.00, 95% CI = 0.99-1.00, p = 0.023), and need for renal replacement therapy (adjusted OR = 2.68, 95% CI = 1.16-6.19, p = 0.021) were independently associated with prolonged weaning. After the exclusion of patients who underwent tracheostomy before the SBTs, similar results were obtained.ConclusionLonger duration of MV before the first SBT, tracheostomy status, poor oxygenation, and need for renal replacement therapy at the time of first SBT can predict prolonged weaning.Trial registrationClinicalTrials.gov Identifier NCT05134467.

Project description:ImportanceIn adults in whom weaning from invasive mechanical ventilation is difficult, noninvasive ventilation may facilitate early liberation, but there is uncertainty about its effectiveness in a general intensive care patient population.ObjectiveTo investigate among patients with difficulty weaning the effects of protocolized weaning with early extubation to noninvasive ventilation on time to liberation from ventilation compared with protocolized invasive weaning.Design, setting, and participantsRandomized, allocation-concealed, open-label, multicenter clinical trial enrolling patients between March 2013 and October 2016 from 41 intensive care units in the UK National Health Service. Follow-up continued until April 2017. Adults who received invasive mechanical ventilation for more than 48 hours and in whom a spontaneous breathing trial failed were enrolled.InterventionsPatients were randomized to receive either protocolized weaning via early extubation to noninvasive ventilation (n = 182) or protocolized standard weaning (continued invasive ventilation until successful spontaneous breathing trial, followed by extubation) (n = 182).Main outcomes and measuresPrimary outcome was time from randomization to successful liberation from all forms of mechanical ventilation among survivors, measured in days, with the minimal clinically important difference defined as 1 day. Secondary outcomes were duration of invasive and total ventilation (days), reintubation or tracheostomy rates, and survival.ResultsAmong 364 randomized patients (mean age, 63.1 [SD, 14.8] years; 50.5% male), 319 were evaluable for the primary effectiveness outcome (41 died before liberation, 2 withdrew, and 2 were discharged with ongoing ventilation). The median time to liberation was 4.3 days in the noninvasive group vs 4.5 days in the invasive group (adjusted hazard ratio, 1.1; 95% CI, 0.89-1.40). Competing risk analysis accounting for deaths had a similar result (adjusted hazard ratio, 1.1; 95% CI, 0.86-1.34). The noninvasive group received less invasive ventilation (median, 1 day vs 4 days; incidence rate ratio, 0.6; 95% CI, 0.47-0.87) and fewer total ventilator days (median, 3 days vs 4 days; incidence rate ratio, 0.8; 95% CI, 0.62-1.0). There was no significant difference in reintubation, tracheostomy rates, or survival. Adverse events occurred in 45 patients (24.7%) in the noninvasive group compared with 47 (25.8%) in the invasive group.Conclusions and relevanceAmong patients requiring mechanical ventilation in whom a spontaneous breathing trial had failed, early extubation to noninvasive ventilation did not shorten time to liberation from any ventilation.Trial registrationISRCTN Identifier: ISRCTN15635197.

Project description:BackgroundDiaphragmatic pacing can improve diaphragm function, which is beneficial for the prognosis of patients treated with prolonged mechanical ventilation (MV). While most previous studies have focused on the role of implanted diaphragm pacing (IDP), our study is the first to examine the effects of external diaphragmatic pacing (EDP) in mechanically ventilated patients. Specifically, the effect of EDP on diaphragm function, the success rate of weaning, the duration of MV (DMV), and the intensive care unit (ICU) length of stay (ILOS) were assessed.MethodsFrom September 2019 to December 2020, a total of 51 mechanically ventilated patients in the ICU of the Sun Yat-sen Memorial Hospital, Sun Yat-sen University were enrolled and randomly divided into an EDP group of 27 patients and a control group of 24 patients. The control group received routine treatment, and the EDP group received EDP treatment in addition to routine treatment. The diaphragm excursion (DE), diaphragm thickening fraction (DTF), DMV, ILOS, and average survival time were recorded to evaluate efficacy.ResultsPatients treated with EDP had increased DE [exp(B) =1.86, 95% CI: 1.39 to 2.50, P<0.001] and DTF [exp(B) =1.35, 95% CI: 1.05 to 1.76, P=0.022], shortened weaning time (P=0.026) and prolonged average survival time (P<0.001) compared to patients who did not receive EDP therapy. Especially in cases with difficult weaning, the improvement of DE and DTF in the EDP treatment group was more obvious than that in the control group (P=0.013 and P=0.032). Moreover, the DTF upon attempted spontaneous breathing trial (SBT) was negatively correlated with the fraction of inspired oxygen (FiO2) [r=-0.54; 95% confidence interval (CI): -0.77 to -0.19; P=0.004], the arterial partial pressure of oxygen (PaO2) (r=-0.58; 95% CI: -0.79 to -0.25; P=0.001), the PaO2/FiO2 ratio (r=-0.52; 95% CI: -0.75 to -0.16; P=0.006), and the serum lactate concentration (Lac) (r=-0.39; 95% CI: -0.68 to 0.003; P=0.046).ConclusionsEDP treatment can effectively reduce the DMV and prolong the average survival time of mechanically ventilated patients.Trial registrationChinese Clinical Trial Registry ChiCTR1900024096.

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Effects of levosimendan on respiratory muscle function in patients weaning from mechanical ventilation.

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Effects of levosimendan on respiratory muscle function in patients weaning from mechanical ventilation.

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