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To characterize clusters of double triggering and ineffective inspiratory efforts throughout mechanical ventilation and investigate their associations with mortality and duration of ICU stay and mechanical ventilation.Registry-based, real-world study.Asynchronies during invasive mechanical ventilation can occur as isolated events or in clusters and might be related to clinical outcomes.Adults requiring mechanical ventilation greater than 24 hours for whom greater than or equal to 70% of ventilator waveforms were available.We identified clusters of double triggering and ineffective inspiratory efforts and determined their power and duration. We used Fine-Gray's competing risk model to analyze their effects on mortality and generalized linear models to analyze their effects on duration of mechanical ventilation and ICU stay.We analyzed 58,625,796 breaths from 180 patients. All patients had clusters (mean/d, 8.2 [5.4-10.6]; mean power, 54.5 [29.6-111.4]; mean duration, 20.3 min [12.2-34.9 min]). Clusters were less frequent during the first 48 hours (5.5 [2.5-10] vs 7.6 [4.4-9.9] in the remaining period [p = 0.027]). Total number of clusters/d was positively associated with the probability of being discharged alive considering the total period of mechanical ventilation (p = 0.001). Power and duration were similar in the two periods. Power was associated with the probability of being discharged dead (p = 0.03), longer mechanical ventilation (p0.001), and longer ICU stay (p = 0.035); cluster duration was associated with longer ICU stay (p = 0.027).Clusters of double triggering and ineffective inspiratory efforts are common. Although higher numbers of clusters might indicate better chances of survival, clusters with greater power and duration indicate a risk of worse clinical outcomes.

[EN] Surface electromyography (sEMG) can be used for the evaluation of respiratory muscle activity. Recording sEMG involves the use of surface electrodes in a bipolar configuration. However, electrocardiographic (ECG) interference and electrode orientation represent considerable drawbacks to bipolar acquisition. As an alternative, concentric ring electrodes (CREs) can be used for sEMG acquisition and offer great potential for the evaluation of respiratory muscle activity due to their enhanced spatial resolution and simple placement protocol, which does not depend on muscle fiber orientation. The aim of this work was to analyze the performance of CREs during respiratory sEMG acquisitions. Respiratory muscle sEMG was applied to the diaphragm and sternocleidomastoid muscles using a bipolar and a CRE configuration. Thirty-two subjects underwent four inspiratory load spontaneous breathing tests which was repeated after interchanging the electrode positions. We calculated parameters such as (1) spectral power and (2) median frequency during inspiration, and power ratios of inspiratory sEMG without ECG in relation to (3) basal sEMG without ECG (R-ins/noise), (4) basal sEMG with ECG (R-ins/cardio) and (5) expiratory sEMG without ECG (R-ins/exp). Spectral power, R-ins/noise and R-ins/cardio increased with the inspiratory load. Significantly higher values (p < 0.05) of R-ins/cardio and significantly higher median frequencies were obtained for CREs. R-ins/noise and R-ins/exp were higher for the bipolar configuration only in diaphragm sEMG recordings, whereas no significant differences were found in the sternocleidomastoid recordings. Our results suggest that the evaluation of respiratory muscle activity by means of sEMG can benefit from the remarkably reduced influence of cardiac activity, the enhanced detection of the shift in frequency content and the axial isotropy of CREs which facilitates its placement., This work was supported in part by the CERCA Program/Generalitat de Catalunya, in part by the Secretaria d'Universitats i Recerca de la Generalitat de Catalunya under Grant GRC 2017 SGR 01770, in part by the Spanish Grants RTI2018-098472-B-I00, RTI2018-094449-A-I00-AR (MCIU/AEI/FEDER, UE) and DPI2015-68397-R (MINECO/FEDER), and in part by the Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN, Instituto de Salud Carlos III/FEDER). The first author was supported by the IFARHU-SENACYT Scholarship Program from the Panama Government under Grant 270-2012-273.

This study focuses on the application of a non-immersive virtual reality (VR)-based neurocognitive intervention in critically ill patients. Our aim was to assess the feasibility of direct outcome measures to detect the impact of this digital therapy on patients’ cognitive and emotional outcomes. Seventy-two mechanically ventilated adult patients were randomly assigned to the “treatment as usual” (TAU, n = 38) or the “early neurocognitive stimulation” (ENRIC, n = 34) groups. All patients received standard intensive care unit (ICU) care. Patients in the ENRIC group also received adjuvant neurocognitive stimulation during the ICU stay. Outcome measures were a full neuropsychological battery and two mental health questionnaires. A total of 42 patients (21 ENRIC) completed assessment one month after ICU discharge, and 24 (10 ENRIC) one year later. At onemonth follow-up, ENRIC patients had better working memory scores (p = 0.009, d = 0.363) and showed up to 50% less non-specific anxiety (11.8% vs. 21.1%) and depression (5.9% vs. 10.5%) than TAU patients. A general linear model of repeated measures reported a main effect of group, but not of time or group–time interaction, on working memory, with ENRIC patients outperforming TAU patients (p = 0.008, ¿p2 = 0.282). Our results suggest that non-immersive VR-based neurocognitive stimulation may help improve short-term working memory outcomes in survivors of critical illness. Moreover, this advantage could be maintained in the long term. An efficacy trial in a larger sample of participants is feasible and must be conducted. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

BACKGROUND: This was a pilot study to analyze the effects of tracheostomy on patient-ventilator asynchronies and respiratory system mechanics. Data were extracted from an ongoing prospective, real-world database that stores continuous output from ventilators and bedside monitors. Twenty adult subjects were on mechanical ventilation and were tracheostomized during an ICU stay: 55% were admitted to the ICU for respiratory failure and 35% for neurologic conditions; the median duration of mechanical ventilation before tracheostomy was 12 d; and the median duration of mechanical ventilation was 16 d. METHODS: We compared patient-ventilator asynchronies (the overall asynchrony index and the rates of specific asynchronies) and respiratory system mechanics (respiratory-system compliance and airway resistance) during the 24 h before tracheostomy versus the 24 h after tracheostomy. We analyzed possible differences in these variables among the subjects who underwent surgical versus percutaneous tracheostomy. To compare longitudinal changes in the variables, we used linear mixed-effects models for repeated measures along time in different observation periods. A total of 920 h of mechanical ventilation were analyzed. RESULTS: Respiratory mechanics and asynchronies did not differ significantly between the 24-h periods before and after tracheostomy: compliance of the respiratory system median (IQR) (47.9 [41.3 – 54.6] mL/cm H(2)O vs 47.6 [40.9 – 54.3] mL/cm H(2)O; P = .94), airway resistance (9.3 [7.5 – 11.1] cm H(2)O/L/s vs 7.0 [5.2 – 8.8] cm H(2)O/L/s; P = .07), asynchrony index (2.0% [1.1 – 3.6%] vs 4.1% [2.3 – 7.6%]; P = .09), ineffective expiratory efforts (0.9% [0.4 – 1.8%] vs 2.2% [1.0 – 4.4%]; P = .08), double cycling (0.5% [0.3 – 1.0%] vs 0.9% [0.5 – 1.9%]; P = .24), and percentage of air trapping (7.6% [4.2 – 13.8%] vs 10.6% [5.9 – 19.2%]; P = .43). No differences in respiratory mechanics or patient-ventilator asynchronies were observed between percutaneous and surgical procedures. CONCLUSIONS: Tracheostomy did not affect patient-ventilator asynchronies or respiratory mechanics within 24 h before and after the procedure

Mechanical ventilation in critically ill patients has to effectively unload inspiratory muscles and provide a safe ventilation (enhancing gas exchange and protecting the lungs and the diaphragm). To do that, the ventilator should be in synchrony with patient’s respiratory rhythm. Dyssynchrony between the patient and the ventilator may induce several deleterious effects, and a proper physiological understanding is required in order to recognize and manage. Different tools have been developed and proposed besides the careful analysis of the ventilator waveforms that aim to help physicians in the decision-making strategy. Additionally, appropriate handling of asynchronies requires clinical skills, physiological knowledge, and suitable drug management. Moreover, new technologies and devices are currently changing our daily practice, going from automated real-time recognition of asynchronies and their distribution during mechanical ventilation to smart-alarm-personalized medicine. Our goal as clinicians relies in careful care of patients based on the more accurate and current knowledge, and incorporate new technological methods that aims to facilitate and improve the care of the critically ill.

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. ispartof: SCIENTIFIC REPORTS vol:11 issue:1 ispartof: location:England status: published

Actualmente, la Prueba de Respiración Espontánea (SBT), indica si un paciente está listo para el destete de la ventilación mecánica. Sin embargo, en torno al 20% de los pacientes “preparados” para ser desintubados, realmente no lo estaban. En este trabajo, se ha estudiado la Capacidad del Barorreflejo durante la hora anterior a la SBT, y se ha visto que existen diferencias significativas entre los pacientes listos para el destete y los que realmente no lo estaban, sugiriendo que la predicción del éxito del destete puede ser mejorada con este nuevo índice.

Background ICU patients undergoing invasive mechanical ventilation experience cognitive decline associated with their critical illness and its management. The early detection of different cognitive phenotypes might reveal the involvement of diverse pathophysiological mechanisms and help to clarify the role of the precipitating and predisposing factors. Our main objective is to identify cognitive phenotypes in critically ill survivors 1 month after ICU discharge using an unsupervised machine learning method, and to contrast them with the classical approach of cognitive impairment assessment. For descriptive purposes, precipitating and predisposing factors for cognitive impairment were explored. Methods A total of 156 mechanically ventilated critically ill patients from two medical/surgical ICUs were prospectively studied. Patients with previous cognitive impairment, neurological or psychiatric diagnosis were excluded. Clinical variables were registered during ICU stay, and 100 patients were cognitively assessed 1 month after ICU discharge. The unsupervised machine learning K-means clustering algorithm was applied to detect cognitive phenotypes. Exploratory analyses were used to study precipitating and predisposing factors for cognitive impairment. Results K-means testing identified three clusters (K) of patients with different cognitive phenotypes: K1 (n = 13), severe cognitive impairment in speed of processing (92%) and executive function (85%); K2 (n = 33), moderate-to-severe deficits in learning-memory (55%), memory retrieval (67%), speed of processing (36.4%) and executive function (33.3%); and K3 (n = 46), normal cognitive profile in 89% of patients. Using the classical approach, moderate-to-severe cognitive decline was recorded in 47% of patients, while the K-means method accurately classified 85.9%. The descriptive analysis showed significant differences in days (p = 0.016) and doses (p = 0.039) with opioid treatment in K1 vs. K2 and K3. In K2, there were more women, patients were older and had more comorbidities (p = 0.001) than in K1 or K3. Cognitive reserve was significantly (p = 0.001) higher in K3 than in K1 or K2. Conclusion One month after ICU discharge, three groups of patients with different cognitive phenotypes were identified through an unsupervised machine learning method. This novel approach improved the classical classification of cognitive impairment in ICU survivors. In the exploratory analysis, gender, age and the level of cognitive reserve emerged as relevant predisposing factors for cognitive impairment in ICU patients. Trial registration ClinicalTrials.gov Identifier:NCT02390024; March 17,2015.

Introduction: The muscle mechanomyogram (sMMG) quantifies the lateral oscillations of contracting muscle fibres. There is a close relationship between lower intercostal space sMMG (sMMGlic) and inspiratory muscle force during inspiratory threshold loading (ITL) in healthy subjects. We hypothesized that the slope of relationship between sMMGlic and inspiratory muscle force during ITL would be similar in chronic obstructive pulmonary disease (COPD) and in COPD-heart failure overlap (COPD-HF). Methods: Bilateral sMMGlic was recorded simultaneous with mouth pressure (Pmo) in 11 COPD (9 male, 66 (64-77) years, FEV1 44.7 (37.6-61.0) %pred, maximal inspiratory mouth pressure (PImax) 56.4 (49.7-74.8) cmH2O), and in 4 COPD-HF patients (3 male, 82 (72-82) years, FEV1 51.0 (41.2-70.8) %pred, PImax 35.9 (23.9-57.4) cmH2O) during ITL to 36% of PImax. sMMGlic signals were analysed using fixed sample entropy (fSampEn). Relationships between area under the curve of fSampEn sMMGlic and Pmo were assessed by correlation analysis. Results: Similar positive relationships between sMMGlic and Pmo in both COPD and COPD-HF groups (Fig. 1) were observed. Conclusions: These data suggest the potential value of sMMGlic as a novel index of inspiratory muscle activation in both COPD and COPD-HF. Further quantitative analysis of sMMGlic in COPD and COPD-HF in larger cohorts of these patients is required.

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Summary In vitro surrogate models of human cardiac tissue hold great promise in disease modeling, cardiotoxicity testing, and future applications in regenerative medicine. However, the generation of engineered human cardiac constructs with tissue-like functionality is currently thwarted by difficulties in achieving efficient maturation at the cellular and/or tissular level. Here, we report on the design and implementation of a platform for the production of engineered cardiac macrotissues from human pluripotent stem cells (PSCs), which we term “CardioSlice.” PSC-derived cardiomyocytes, together with human fibroblasts, are seeded into large 3D porous scaffolds and cultured using a parallelized perfusion bioreactor with custom-made culture chambers. Continuous electrical stimulation for 2 weeks promotes cardiomyocyte alignment and synchronization, and the emergence of cardiac tissue-like properties. These include electrocardiogram-like signals that can be readily measured on the surface of CardioSlice constructs, and a response to proarrhythmic drugs that is predictive of their effect in human patients., Highlights • Human iPSC-derived cardiomyocytes are cultured in ∼1-mm-thick constructs • Continuous electrical stimulation greatly enhances maturation at the tissue level • Electrostimulated constructs (CardioSlice) generate ECG-like bioelectrical signals • CardioSlice response to proarrhythmic drugs is predictive of effect in patients, In this article, Raya and colleagues design and implement a cardiac tissue-engineering platform for the production of macrotissues from human pluripotent stem cells. These human cardiac macrotissues can be electrically stimulated, and their electric activity recorded from the surface of the constructs. After 2 weeks of electrical stimulation, distinct cardiac tissue-like properties appear such as electrocardiogram-like signals and patient-like response to cardiotoxic drugs.

The electrical activity of the diaphragm measured by surface electromyography (sEMGdi) provides indirect information on neural respiratory drive. Moreover, it allows evaluating the ventilatory pattern from the onset and offset (ntoff) estimation of the neural inspiratory time. sEMGdi amplitude variation was quantified using the fixed sample entropy (fSampEn), a less sensitive method to the interference from cardiac activity. The detection of the ntoff is controversial, since it is located in an intermediate point between the maximum value and the cessation of sEMGdi inspiratory activity, evaluated by the fSampEn. In this work ntoff detection has been analyzed using thresholds between 40% and 100 % of the fSampEn peak. Furthermore, fSampEn was evaluated analyzing the r parameter from 0.05 to 0.6, using a m equal to 1 and a sliding window size equal to 250 ms. The ntoff has been compared to the offset time (toff) obtained from the airflow during a controlled respiratory protocol varying the fractional inspiratory time from 0.54 to 0.18 whilst the respiratory rate was constant at 16 bpm. Results show that the optimal threshold values were between 66.0 % to 77.0 % of the fSampEn peak value. r values between 0.25 to 0.50 were found suitable to be used with the fSampEn.

Introduction Breathlessness is a dominant, distressing, symptom of chronic obstructive pulmonary disease (COPD) which has a significant impact on quality of life. Neural respiratory drive (NRD), quantified as diaphragm electromyogram (EMGdi) activity, is closely related to breathlessness intensity in COPD. The surface mechanomyogram (sMMG), which can be recorded using skin-surface triaxial accelerometers, measures the lateral vibration of muscle fibres and is considered to be the mechanical counterpart of the surface EMG (sEMG). The principal aim of this study was to investigate the relationship between the sMMG of the diaphragm (sMMGdi) and breathlessness in COPD. We hypothesised that there would be strong positive relationships between sMMGdi and modified Borg (mBorg) breathlessness intensity during an inspiratory threshold loading protocol. Methods Nine COPD patients (7 male, median (IQR) age 70 (64–78) years, BMI 25.6 (24.8–30.1) kg/m2, FEV144.7 (37.1–63.9)%predicted), underwent an incremental inspiratory loading protocol at 12%, 24%, 36%, 48% and 60% of maximum mouth inspiratory pressure (PImax). Left and right sEMGdi and sMMGdi activity were recorded using 2 pairs of sEMG electrodes, and one pair of triaxial accelerometers, positioned over the 7th/8th intercostal spaces in the anterior axillary lines bilaterally. sEMG and sMMG signals were analysed using fixed sample entropy (fSampEn) and the relationships with mBorg breathlessness intensity during each inspiratory load were determined using correlation analysis. Results Moderate to strong correlations were observed between mBorg breathlessness intensity and the sEMG and sMMG signals, expressed as fSampEn, recorded at all sites (table 1). Conclusion The relationships observed between mBorg breathlessness intensity and sMMGdi, and sEMGdi, expressed as fSampEn, demonstrates the potential value of sMMGdi as a complementary tool to sEMGdi for the investigation of breathlessness in COPD. sMMGdi could provide a novel non-invasive physiological correlate of breathlessness intensity in COPD and other chronic respiratory diseases.

The relationship between surface diaphragm mechanomyography (sMMGdi), as a noninvasive measure of inspiratory muscle mechanical activation, and crural diaphragm electromyography (oesEMGdi), as the invasive gold standard measure of diaphragm electrical activation, had not previously been examined. To investigate this relationship, oesEMGdi and sMMGdi were measured simultaneously in 6 healthy subjects during an incremental inspiratory threshold loading protocol, and analyzed using fixed sample entropy (fSampEn). A positive curvilinear relationship was observed between mean fSampEn sMMGdi and oesEMGdi (r = 0.67). Accordingly, an increasing electromechanical ratio was also observed with increasing inspiratory load. These findings suggest that sMMGdi could provide useful noninvasive measures of inspiratory muscle mechanical activation.

Introduction The current gold standard assessment of diaphragm contractility involves invasive measures of transdiaphragmatic pressure (Pdi) (ATS/ERS 2002). Surface mechanomyography (sMMG) is a non-invasive measure of muscle fibre vibration during contraction. Sarlabous et al (ERJ 2015) reported a high correlation between diaphragm sMMG (sMMGdi) amplitude and inspiratory mouth pressure, a measure of global respiratory muscle function. To further validate the technique, the relationship between sMMGdi and Pdi was examined in this study, hypothesising that there would be a close relationship between sMMGdi and Pdi in healthy subjects. Methods Pdi and sMMGdi (right lateral chest) were measured in 12 healthy subjects (6 male, age 33 (30–38) years, BMI 22.2 (20.6–24.2) kg/m2) during an increasing inspiratory threshold loading protocol. sMMGdi signals were analysed using fixed sample entropy (fSampEn). Mean and peak values, and the area under the curve of inspiratory Pdi and fSampEn sMMGdi, were calculated and compared. Results Strong correlations between the non-invasive sMMGdi and the invasive Pdi measures were observed for all three parameters (figure 1). Conclusion The strong correlation between measures of sMMGdi and Pdi in healthy subjects suggests that sMMGdi could provide a clinically applicable noninvasive index of respiratory muscle contractility in patients with respiratory muscle weakness for diagnosis and monitoring.

Fixed sample entropy (fSampEn) is a robust technique that allows the evaluation of inspiratory effort in diaphragm electromyography (EMGdi) signals, and has potential utility in sleep studies. To appropriately estimate respiratory effort, fSampEn requires the adjustment of several parameters. The aims of the present study were to evaluate the influence of the embedding dimension m, the tolerance value r, the size of the moving window, and the sampling frequency, and to establish recommendations for estimating the respiratory activity when using the fSampEn on surface EMGdi recorded for different inspiratory efforts. Values of m equal to 1 and r ranging from 0.1 to 0.64, and m equal to 2 and r ranging from 0.13 to 0.45, were found to be suitable for evaluating respiratory activity. fSampEn was less affected by window size than classical amplitude parameters. Finally, variations in sampling frequency could influence fSampEn results. In conclusion, the findings suggest the potential utility of fSampEn for estimating muscle respiratory effort in further sleep studies.

The use of non-invasive methods for the study of respiratory muscle signals can provide clinical information for the evaluation of the respiratory muscle function. The aim of this study was to evaluate time-frequency characteristics of the electrical activity of the sternocleidomastoid muscle recorded superficially by means of concentric ring electrodes (CREs) in a bipolar configuration. The CREs enhance the spatial resolution, attenuate interferences, as the cardiac activity, and also simplify the orientation problem associated to the electrode location. Five healthy subjects underwent a respiratory load test in which an inspiratory load was imposed during the inspiratory phase. During the test, the electromyographic signal of the sternocleidomastoid muscle (EMGsc) and the inspiratory mouth pressure (Pmouth) were acquired. Time-frequency characteristics of the EMGsc signal were analyzed by means of eight timefrequency representations (TFRs): the spectrogram (SPEC), the Morlet scalogram (SCAL), the Wigner-Ville distribution (WVD), the Choi-Williams distribution (CHWD), two generalized exponential distributions (GED1 and GED2), the Born- Jordan distribution (BJD) and the Cone-Kernel distribution (CKD). The instantaneous central frequency of the EMGsc showed an increasing behavior during the inspiratory cycle and with the increase of the inspiratory load. The bilinear TFRs (WVD, CHWD, GEDs and BJD) were less sensitive to cardiac activity interference than classical TFRs (SPEC and SCAL). The GED2 was the TFR that shown the best results for the characterization of the instantaneous central frequency of the EMGsc.