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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: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.

Project description:INTRODUCTION: Optimal management of mechanical ventilation and weaning requires dynamic and collaborative decision making to minimize complications and avoid delays in the transition to extubation. In the absence of collaboration, ventilation decision making may be fragmented, inconsistent, and delayed. Our objective was to describe the professional group with responsibility for key ventilation and weaning decisions and to examine organizational characteristics associated with nurse involvement. METHODS: A multi-center, cross-sectional, self-administered survey was sent to nurse managers of adult intensive care units (ICUs) in Denmark, Germany, Greece, Italy, Norway, Switzerland, Netherlands and United Kingdom (UK). We summarized data as proportions (95% confidence intervals (CIs)) and calculated odds ratios (OR) to examine ICU organizational variables associated with collaborative decision making. RESULTS: Response rates ranged from 39% (UK) to 92% (Switzerland), providing surveys from 586 ICUs. Interprofessional collaboration (nurses and physicians) was the most common approach to initial selection of ventilator settings (63% (95% CI 59 to 66)), determination of extubation readiness (71% (67 to 75)), weaning method (73% (69 to 76)), recognition of weaning failure (84% (81 to 87)) and weaning readiness (85% (82 to 87)), and titration of ventilator settings (88% (86 to 91)). A nurse-to-patient ratio other than 1:1 was associated with decreased interprofessional collaboration during titration of ventilator settings (OR 0.2, 95% CI 0.1 to 0.6), weaning method (0.4 (0.2 to 0.9)), determination of extubation readiness (0.5 (0.2 to 0.9)) and weaning failure (0.4 (0.1 to 1.0)). Use of a weaning protocol was associated with increased collaborative decision making for determining weaning (1.8 (1.0 to 3.3)) and extubation readiness (1.9 (1.2 to 3.0)), and weaning method (1.8 (1.1 to 3.0). Country of ICU location influenced the profile of responsibility for all decisions. Automated weaning modes were used in 55% of ICUs. CONCLUSIONS: Collaborative decision making for ventilation and weaning was employed in most ICUs in all countries although this was influenced by nurse-to-patient ratio, presence of a protocol, and varied across countries. Potential clinical implications of a lack of collaboration include delayed adaptation of ventilation to changing physiological parameters, and delayed recognition of weaning and extubation readiness resulting in unnecessary prolongation of ventilation.

Project description:The ideal moment to withdraw respiratory supply of patients under Mechanical Ventilation at Intensive Care Units (ICU), is not easy to be determined for clinicians. Although the Spontaneous Breathing Trial (SBT) provides a measure of the patients' readiness, there is still around 15-20% of predictive failure rate. This work is a proof of concept focused on adding new value to the prediction of the weaning outcome. Heart Rate Variability (HRV) and Cardiopulmonary Coupling (CPC) methods are evaluated as new complementary estimates to assess weaning readiness. The CPC is related to how the mechanisms regulating respiration and cardiac pumping are working simultaneously, and it is defined from HRV in combination with respiratory information. Three different techniques are used to estimate the CPC, including Time-Frequency Coherence, Dynamic Mutual Information and Orthogonal Subspace Projections. The cohort study includes 22 patients in pressure support ventilation, ready to undergo the SBT, analysed in the 24 h previous to the SBT. Of these, 13 had a successful weaning and 9 failed the SBT or needed reintubation -being both considered as failed weaning. Results illustrate that traditional variables such as heart rate, respiratory frequency, and the parameters derived from HRV do not differ in patients with successful or failed weaning. Results revealed that HRV parameters can vary considerably depending on the time at which they are measured. This fact could be attributed to circadian rhythms, having a strong influence on HRV values. On the contrary, significant statistical differences are found in the proposed CPC parameters when comparing the values of the two groups, and throughout the whole recordings. In addition, differences are greater at night, probably because patients with failed weaning might be experiencing more respiratory episodes, e.g. apneas during the night, which is directly related to a reduced respiratory sinus arrhythmia. Therefore, results suggest that the traditional measures could be used in combination with the proposed CPC biomarkers to improve weaning readiness.

Dataset Information

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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