Multifaceted bench comparative evaluation of latest intensive care unit ventilators.

BACKGROUND: Independent bench studies using specific ventilation scenarios allow testing of the performance of ventilators in conditions similar to clinical settings. The aims of this study were to determine the accuracy of the latest generation ventilators to deliver chosen parameters in various typical conditions and to provide clinicians with a comprehensive report on their performance. METHODS: Thirteen modern intensive care unit ventilators were evaluated on the ASL5000 test lung with and without leakage for: (i) accuracy to deliver exact tidal volume (VT) and PEEP in assist-control ventilation (ACV); (ii) performance of trigger and pressurization in pressure support ventilation (PSV); and (iii) quality of non-invasive ventilation algorithms. RESULTS: In ACV, only six ventilators delivered an accurate VT and nine an accurate PEEP. Eleven devices failed to compensate VT and four the PEEP in leakage conditions. Inspiratory delays differed significantly among ventilators in invasive PSV (range 75-149 ms, P=0.03) and non-invasive PSV (range 78-165 ms, P<0.001). The percentage of the ideal curve (concomitantly evaluating the pressurization speed and the levels of pressure reached) also differed significantly (range 57-86% for invasive PSV, P=0.04; and 60-90% for non-invasive PSV, P<0.001). Non-invasive ventilation algorithms efficiently prevented the decrease in pressurization capacities and PEEP levels induced by leaks in, respectively, 10 and 12 out of the 13 ventilators. CONCLUSIONS: We observed real heterogeneity of performance amongst the latest generation of intensive care unit ventilators. Although non-invasive ventilation algorithms appear to maintain adequate pressurization efficiently in the case of leakage, basic functions, such as delivered VT in ACV and pressurization in PSV, are often less reliable than the values displayed by the device suggest.

Defective exercise-related expiratory muscle recruitment in patients with PHOX2B mutations: A clue to neural determinants of the congenital central hypoventilation syndrome.

INTRODUCTION AND OBJECTIVES: The human congenital central hypoventilation syndrome (CCHS) is caused by mutations in the PHOX2B (paired-like homeobox 2B) gene. Genetically engineered PHOX2B rodents exhibit defective development of the brainstem retrotrapezoid nucleus (RTN), a carbon dioxide sensitive structure that critically controls expiratory muscle recruitment. This has been linked to a blunted exercise ventilatory response. Whether this can be extrapolated to human CCHS is unknown and represents the objective of this study. MATERIALS AND METHODS: Thirteen adult CCHS patients and 13 healthy participants performed an incremental symptom-limited cycle cardiopulmonary exercise test. Responses were analyzed using guideline approaches (ventilation V'E, tidal volume VT, breathing frequency, oxygen consumption, carbon dioxide production) complemented by a breathing pattern analysis (i.e. expiratory and inspiratory reserve volume, ERV and IRV). RESULTS: A ventilatory response occurred in both study groups, as follows: V'E and VT increased in CCHS patients until 40 W and then decreased, which was not observed in the healthy participants (p<0.001). In the latter, exercise-related ERV and IRV decreases attested to concomitant expiratory and inspiratory recruitment. In the CCHS patients, inspiratory recruitment occurred but there was no evidence of expiratory recruitment (absence of any ERV decrease, p<0.001). CONCLUSIONS: Assuming a similar organization of respiratory rhythmogenesis in humans and rodents, the lack of exercise-related expiratory recruitment observed in our CCHS patients is compatible with a PHOX2B-related defect of a neural structure that would be analogous to the rodents' RTN. Provided corroboration, ERV recruitment could serve as a physiological outcome in studies aiming at correcting breathing control in CCHS.

Residual sleepiness in obstructive sleep apnoea: phenotype and related symptoms.

The characteristics of residual excessive sleepiness (RES), defined by an Epworth score >10 in adequately treated apnoeic patients, are unknown. 40 apnoeic patients, with (n = 20) and without (n = 20) RES, and 20 healthy controls underwent clinical interviews, cognitive and biological tests, polysomnography, a multiple sleep latency test, and 24-h sleep monitoring. The marked subjective sleepiness in the RES group (mean ± sd score 16.4 ± 3) contrasted with moderately abnormal objective measures of sleepiness (90% of patients with RES had daytime sleep latencies >8 min). Compared with patients without RES, the patients with RES had more fatigue, lower stage N3 percentages, more periodic leg movements (without arousals), lower mean sleep latencies and longer daytime sleep periods. Most neuropsychological dimensions (morning headaches, memory complaints, spatial memory, inattention, apathy, depression, anxiety and lack of self-confidence) were not different between patients with and without RES, but gradually altered from controls to apnoeic patients without and then with RES. RES in apnoeic patients differs markedly from sleepiness in central hypersomnia. The association between RES, periodic leg movements, apathy and depressive mood parallels the post-hypoxic lesions in noradrenaline, dopamine and serotonin systems in animals exposed to intermittent hypoxia.

Diaphragm pacing restores olfaction in tetraplegia.

High cervical spinal cord injuries induce extreme handicap and tactile isolation. Tracheotomised tetraplegic patients are also bound to be olfaction deprived. By restoring negative pressure inspiration, diaphragm pacing (DP) should improve olfaction. We tested olfaction in 10 consecutive tetraplegics during positive pressure mechanical ventilation and DP, using the University of Pennsylvania Smell Identification Test (UPSIT). Quality of life was assessed using the Satisfaction with Life Scale (SWLS). Self-perceived benefits of DP were studied using an in-house questionnaire. Olfaction was very poor during positive pressure mechanical ventilation (UPSIT, mean+/-SD 17.1+/-6.4, anosmia or severe microsmia). It improved during DP (35.2+/-1.9, normosmia or mild microsmia; p<0.0001) and SWLS was 18.5+/-4.2. Nine patients stated that DP had improved their quality of life. This was driven by better mobility (ranked first), improved self-image and relationships with others (ranked second), improved olfaction and better feeling of security (both ranked third). Improved olfaction is among the benefits of DP and should be mentioned to patients considered for this therapy. Furthermore, attention to olfaction is warranted in tracheotomised ventilator-dependent patients, as a putative path towards improvement of quality of life.

Contribution of endobronchial ultrasound elastography to the characterization of mediastinal lymphadenopathy: A single-center, prospective, observational study.

BACKGROUND: Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a reliable technique providing high diagnostic yield in mediastinal lymphadenopathy. However, mediastinoscopy is sometimes necessary to eliminate false-negative results. Elastography is a recent technique that can be combined with EBUS to evaluate the elasticity and consequently the nature of a tissue. The primary objective was to evaluate the diagnostic performance of EBUS-TBNA combined with elastography for the assessment of mediastinal lymph nodes. METHODS: Single-center, prospective study in patients with mediastinal lymphadenopathy. EBUS-TBNA combined with elastography was performed in each patient. Several elastographic parameters were studied: colorimetric score, average elasticity, elasticity ratio, percentage of hard areas. The final diagnosis was that obtained by TBNA cytology, histology of a surgical biopsy, when performed, or follow-up CT and PET-CT at 6 months. RESULTS: Overall, 110 lymph nodes were examined in 87 patients: 44 were malignant according to TBNA. These nodes had significantly higher elasticity ratio, percentage of hard areas and colorimetric score and significantly lower average elasticity compared to benign nodes (P<0.001). With a negative predictive value of 100%, the cut-offs defined by receiver operating characteristic curves were 1.4 for elasticity ratio, 84.8 for average elasticity, 32.6 for percentage of hard areas and 3 for colorimetric score. No adverse events were observed. CONCLUSION: Endobronchial ultrasound elastography is a non-invasive technique that can contribute to prediction of the nature of lymph nodes by distinguishing malignant from benign nodes. Although EBUS cannot replace histological examination, elastography can provide reliable complementary information when combined with EBUS.

Neuroergonomic and psychometric evaluation of full-face crew oxygen masks respiratory tolerance: a proof-of-concept study.

INTRODUCTION: Preventing in-flight hypoxia in pilots is typically achieved by wearing oxygen masks. These masks must be as comfortable as possible to allow prolonged and repeated use. The consequences of mask-induced facial contact pressure have been extensively studied, but little is known about mask-induced breathing discomfort. Because breathlessness is a strong distractor and engages cerebral resources, it could negatively impact flying performances. METHODS: Seventeen volunteers (age 20-32) rated respiratory discomfort while breathing with no mask and with two models of quick-donning full-face crew oxygen masks with regulators (mask A, mask B). Electroencephalographic recordings were performed to detect a putative respiratory-related cortical activation in response to inspiratory constraint (experiment 1, n=10). Oxygen consumption was measured using indirect calorimetry (experiment 2, n=10). RESULTS: With mask B, mild respiratory discomfort was reported significantly more frequently than with no mask or mask A (experiment 1: median respiratory discomfort on visual analogue scale 0.9 cm (0.5-1.4), experiment 1; experiment 2: 2 cm (1.7-2.9)). Respiratory-related cortical activation was present in 1/10 subjects with no mask, 1/10 with mask A and 6/10 with mask B (significantly more frequently with mask B). Breathing pattern, sigh frequency and oxygen consumption were not different. CONCLUSIONS: In a laboratory setting, breathing through high-end aeronautical full-face crew oxygen masks can induce mild breathing discomfort and activate respiratory-related cortical networks. Whether or not this can occur in real-life conditions and have operational consequences remains to be investigated. Meanwhile, respiratory psychometric and neuroergonomic approaches could be worth integrating to masks development and evaluation processes.

CARE-rCortex: A Matlab toolbox for the analysis of CArdio-REspiratory-related activity in the Cortex.

BACKGROUND: Although cardio-respiratory (CR) system is generally controlled by the autonomic nervous system, interactions between the cortex and these primary functions are receiving an increasing interest in neurosciences. NEW METHOD: In general, the timing of such internally paced events (e.g. heartbeats or respiratory cycles) may display a large variability. For the analysis of such CR event-related EEG potentials, a baseline must be correctly associated to each cycle of detected events. The open-source toolbox CARE-rCortex provides an easy-to-use interface to detect CR events, define baselines, and analyse in time-frequency (TF) domain the CR-based EEG potentials. RESULTS: CARE-rCortex provides some practical tools to detect and validate these CR events. Users can define baselines time-locked to a phase of respiratory or heart cycle. A statistical test has also been integrated to highlight significant points of the TF maps with respect to the baseline. We illustrate the use of CARE-rCortex with the analysis of two real cardio-respiratory datasets. COMPARISON WITH EXISTING METHODS: Compared to other open-source toolboxes, CARE-rCortex allows users to automatically detect CR events, to define and check baselines for each detected event. Different baseline normalizations can be used in the TF analysis of EEG epochs. CONCLUSIONS: The analysis of CR-related EEG activities could provide valuable information about cognitive or pathological brain states. CARE-rCortex runs in Matlab as a plug-in of the EEGLAB software, and it is publicly available at https://github.com/FannyGrosselin/CARE-rCortex.

[Fibreoptic bronchoscopy and anti-platelet agents: a risk-benefit analysis]. / Bronchoscopie souple et antiagrégants plaquettaires: analyse du rapport bénéfices-risques.

INTRODUCTION: Respiratory physicians are confronted increasingly often by patients, in whom a fibreoptic bronchoscopy (FB) is planned, who are taking anti-platelet agents (APAs) prescribed by their cardiologist. It is necessary therefore to weigh the indications for bronchoscopy and the subsequent benefits against the risks, not only of haemorrhage, but of thrombosis if the APAs are withdrawn. METHODS/RESULTS: In the absence of agreed guidelines on the subject this article reviews the literature and reports the results of a survey conducted among 138 members of the French Respiratory Endoscopy Group. Five questions were considered: 1) what is the risk of haemorrhage during the procedure? 2) what are the pharmacological characteristics of current APAs? 3) what is the risk of thrombosis on withdrawal of APAs? 4) what are the circumstances in which the FB may be delayed? 5) what should be the therapeutic strategy if the APAs are withdrawn? CONCLUSIONS: While awaiting clinical studies that will allow a better understanding of these questions, and the subsequent publication of practice guidelines, it is crucial that respiratory physicians are aware of the need, prior to FB, to inquire routinely about treatment with APAs, to identify the indication, and never to interrupt such treatment without consulting the prescriber.

Riemannian Geometry Applied to Detection of Respiratory States From EEG Signals: The Basis for a Brain-Ventilator Interface.

GOAL: During mechanical ventilation, patient-ventilator disharmony is frequently observed and may result in increased breathing effort, compromising the patient's comfort and recovery. This circumstance requires clinical intervention and becomes challenging when verbal communication is difficult. In this study, we propose a brain-computer interface (BCI) to automatically and noninvasively detect patient-ventilator disharmony from electroencephalographic (EEG) signals: a brain-ventilator interface (BVI). METHODS: Our framework exploits the cortical activation provoked by the inspiratory compensation when the subject and the ventilator are desynchronized. Use of a one-class approach and Riemannian geometry of EEG covariance matrices allows effective classification of respiratory states. The BVI is validated on nine healthy subjects that performed different respiratory tasks that mimic a patient-ventilator disharmony. RESULTS: Classification performances, in terms of areas under receiver operating characteristic curves, are significantly improved using EEG signals compared to detection based on air flow. Reduction in the number of electrodes that can achieve discrimination can be often desirable (e.g., for portable BCI systems). By using an iterative channel selection technique, the common highest order ranking, we find that a reduced set of electrodes (n = 6) can slightly improve for an intrasubject configuration, and it still provides fairly good performances for a general intersubject setting. CONCLUSION: Results support the discriminant capacity of our approach to identify anomalous respiratory states, by learning from a training set containing only normal respiratory epochs. SIGNIFICANCE: The proposed framework opens the door to BVIs for monitoring patient's breathing comfort and adapting ventilator parameters to patient respiratory needs.

Vivid dreams, hallucinations, psychosis and REM sleep in Guillain-Barré syndrome.

We conducted a prospective controlled study of the clinical and biological determinants of the mental status abnormalities in 139 patients with Guillain-Barré syndrome (GBS) and 55 patients without GBS placed in the intensive care unit (ICU controls). There were mental status changes in 31% of GBS patients and in 16% of controls (odds ratio = 2.3; P = 0.04). In GBS patients, they included vivid dreams (19%), illusions (30%, including an illusory body tilt), hallucinations (60%, mainly visual) and delusions (70%, mostly paranoid). They appeared a median 9 days after disease onset (range 1-40 days, during the progression or the plateau of the disease), and lasted a median 8 days. Seven (16%) patients experienced the symptoms before their admission to the ICU. Hallucinations were frequently hypnagogic, occurring as soon as the patients closed their eyes. Autonomic dysfunction, assisted ventilation and high CSF protein levels were significant risk factors for abnormal mental status in GBS patients. CSF hypocretin-1 (a hypothalamic neuropeptide deficient in narcolepsy) levels, measured in 20 patients, were lower in GBS patients with hallucinations (555 +/- 132 pg/ml) than in those without (664 +/- 71 pg/ml, P = 0.03). Since the mental status abnormalities had dream-like aspects, we examined their association with rapid eye movement sleep (REM sleep) using continuous sleep monitoring in 13 GBS patients with (n = 7) and without (n = 6) hallucinations and 6 tetraplegic ICU controls without hallucinations. Although sleep was short and fragmented in all groups, REM sleep latency was shorter in GBS patients with hallucinations (56 +/- 115 min) than in GBS patients without hallucinations (153 +/- 130 min) and in controls (207 +/- 179 min, P < 0.05). In addition, sleep structure was highly abnormal in hallucinators, with sleep onset in REM sleep periods (83%), abnormal eye movements during non-REM sleep (57%), high percentages of REM sleep without atonia (92 +/- 22%), REM sleep behaviour disorders and autonomic dysfunction (100%), reminiscent of a status dissociatus. The sleep abnormalities, that were almost absent in non-hallucinated GBS patients, were not exclusively related to ICU conditions, since they also appeared out of ICU, and were reversible, disappearing when the mental status abnormalities vanished while the patients were still in ICU. In conclusion, the mental status abnormalities experienced by GBS patients are different from the ICU delirium, are strongly associated with autonomic dysfunction, severe forms of the disease and possibly with a transitory hypocretin-1 transmission decrease. Sleep studies suggest that mental status abnormalities are wakeful dreams caused by a sleep and dream-associated disorder (status dissociatus).

[Pleural procedures in patients treated by platelet aggregation inhibitors: An opinion survey]. / Gestes pleuraux sous antiagrégants plaquettaires : une enquête d'opinion.

BACKGROUND: When pleural procedures (thoracocentesis, blind pleural biopsies and chest tube insertion) are required in patients taking long-term platelet aggregation inhibitors, the risk of bleeding must be balanced against the risk of arterial thrombosis. Currently, the bleeding risk of pleural procedures is poorly understood. OBJECTIVE: The objective of the survey was to gather the opinion of respiratory physicians regarding the bleeding risk of pleural procedures in patients taking platelet aggregation inhibitors. METHODS: We emailed a standardized questionnaire designed by the French National Authority for Health to 2697 French respiratory physicians. RESULTS: One hundred and eighty-eight of the 2697 questionnaires were returned (response rate: 7 %). The respiratory physicians declared that they performed an average of 8 pleural procedures per month. One hundred and seventy-five responders (95 %) practised pleural procedures in patients receiving platelet aggregation inhibitors; 68 of them (39 %) reported experiencing haemorrhagic complications. The bleeding risk associated with thoracentesis and chest tube insertion was considered minor by 97.8 and 65 % of responders respectively, whereas it was considered major for blind pleural biopsies by 73.4 %. Respiratory physicians were more reticent about performing pleural procedures in patients treated with clopidogrel than in those taking aspirin. CONCLUSION: This study provides an overview of how respiratory physicians perceive the bleeding risk associated with pleural procedures in patients taking platelet aggregation inhibitors.

Neurally adjusted ventilatory assist as an alternative to pressure support ventilation in adults: a French multicentre randomized trial.

PURPOSE: Neurally adjusted ventilatory assist (NAVA) is a ventilatory mode that tailors the level of assistance delivered by the ventilator to the electromyographic activity of the diaphragm. The objective of this study was to compare NAVA and pressure support ventilation (PSV) in the early phase of weaning from mechanical ventilation. METHODS: A multicentre randomized controlled trial of 128 intubated adults recovering from acute respiratory failure was conducted in 11 intensive care units. Patients were randomly assigned to NAVA or PSV. The primary outcome was the probability of remaining in a partial ventilatory mode (either NAVA or PSV) throughout the first 48 h without any return to assist-control ventilation. Secondary outcomes included asynchrony index, ventilator-free days and mortality. RESULTS: In the NAVA and PSV groups respectively, the proportion of patients remaining in partial ventilatory mode throughout the first 48 h was 67.2 vs. 63.3 % (P = 0.66), the asynchrony index was 14.7 vs. 26.7 % (P < 0.001), the ventilator-free days at day 7 were 1.0 day [1.0-4.0] vs. 0.0 days [0.0-1.0] (P < 0.01), the ventilator-free days at day 28 were 21 days [4-25] vs. 17 days [0-23] (P = 0.12), the day-28 mortality rate was 15.0 vs. 22.7 % (P = 0.21) and the rate of use of post-extubation noninvasive mechanical ventilation was 43.5 vs. 66.6 % (P < 0.01). CONCLUSIONS: NAVA is safe and feasible over a prolonged period of time but does not increase the probability of remaining in a partial ventilatory mode. However, NAVA decreases patient-ventilator asynchrony and is associated with less frequent application of post-extubation noninvasive mechanical ventilation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02018666.

Expiratory flow limitation as a determinant of orthopnea in acute left heart failure.

OBJECTIVES: To assess the contribution of expiratory flow limitation (FL) in orthopnea during acute left heart failure (LHF). BACKGROUND: Orthopnea is typical of acute LHF, but its mechanisms are not completely understood. In other settings, such as chronic obstructive pulmonary disease, dyspnea correlates best with expiratory FL and can, therefore, be interpreted as, in part, the result of a hyperinflation-related increased load to the inspiratory muscles. As airway obstruction is common in acute LHF, postural FL could contribute to orthopnea. METHODS: Flow limitation was assessed during quiet breathing by applying a negative pressure at the mouth throughout tidal expiration (negative expiratory pressure [NEP]). Flow limitation was assumed when expiratory flow did not increase during NEP. Twelve patients with acute LHF aged 40-98 years were studied seated and supine and compared with 10 age-matched healthy subjects. RESULTS: Compared with controls, patients had rapid shallow breathing with slightly increased minute ventilation and mean inspiratory flow. Breathing pattern was not influenced by posture. Flow limitation was observed in four patients when seated and in nine patients when supine. In seven cases, FL was induced or aggravated by the supine position. This coincided with orthopnea in six cases. Only one out of the five patients without orthopnea had posture dependent FL. Control subjects did not exhibit FL in either position. CONCLUSIONS: Expiratory FL appears to be common in patients with acute LHF, particularly so when orthopnea is present. Its postural aggravation could contribute to LHF-related orthopnea.

Impediment in upper airway stabilizing forces assessed by phrenic nerve stimulation in sleep apnea patients.

BACKGROUND: The forces developed during inspiration play a key role in determining upper airway stability and the occurrence of nocturnal breathing disorders. Phrenic nerve stimulation applied during wakefulness is a unique tool to assess Upper airway dynamic properties and to measure the overall mechanical effects of the inspiratory process on UA stability. OBJECTIVES: To compare the flow/pressure responses to inspiratory and expiratory twitches between sleep apnea subjects and normal subjects. METHODS: Inspiratory and expiratory twitches using magnetic nerve stimulation completed in eleven untreated sleep apnea subjects and ten normal subjects. RESULTS: In both groups, higher flow and pressure were reached during inspiratory twitches. The two groups showed no differences in expiratory twitch parameters. During inspiration, the pressure at which flow-limitation occurred was more negative in normals than in apneic subjects, but not reaching significance (p = 0.07). The relationship between pharyngeal pressure and flow adequately fitted with a polynomial regression model providing a measurement of upper airway critical pressure during twitch. This pressure significantly decreased in normals from expiratory to inspiratory twitches (-11.1 +/- 1.6 and -15.7 +/- 1.0 cm H2O respectively, 95% CI 1.6-7.6, p < 0.01), with no significant difference between the two measurements in apneic subjects. The inspiratory/expiratory difference in critical pressure was significantly correlated with the frequency of nocturnal breathing disorders. CONCLUSION: Inspiratory-related upper airway dilating forces are impeded in sleep apnea patients.

Putative protective effect of inspiratory threshold loading against exercise-induced supraspinal diaphragm fatigue.

The present investigation was intended to assess the consequences of an inspiratory load on the diaphragm central component of fatigue during exercise. We recorded the motor potential evoked (MEP) by transcranial magnetic stimulation of the motor cortex in 10 subjects. The diaphragm and rectus femoris were studied before and 10, 20, and 40 min after two 16-min cycling exercise (E) trials requiring 55% of maximal oxygen uptake: 1) one with an inspiratory threshold load (E + ITL), corresponding to 10% of maximal inspiratory pressure; and 2) the other without the load (E). Dyspnea, heart rate, electromyographic activity of the sternocleidomastoid, and diaphragm work were significantly higher in E + ITL than in E. Neither trial affected the response to phrenic magnetic stimulation, which was performed 15 and 25 min postexercise, or the maximal inspiratory pressure (116 and 120 cm H(2)O before E and E + ITL, respectively, and 110 and 114 cm H(2)O at 30 min postexercise). Whereas the amplitude of the diaphragm MEP was unaffected by E + ITL (+2.1 +/- 29.4%), a significant decrease was observed 10 min after E compared with baseline (-37.1 +/- 22.3%) and compared with E + ITL. The MEP amplitude of rectus femoris remained unchanged with E and E + ITL. The recruitment of synergistic agonists during E + ITL may have normalized the major ventilatory stress and reset up the excitability of the diaphragm pathway.

Diffusional screening in real 3D human acini--a theoretical study.

Gas exchange at the acinar level involves several physico-chemical phenomena within a complex geometry. A gas transport model, which takes into account both the diffusion into the acinus and the diffusion across the alveolar membrane, is used to understand gas mixing in realistic systems. It is first shown that the behaviour of the system, computed on model geometries in 3D, only depends on the topological structure of the acinus. Taking advantage of this property, a new efficient method based on random walks on a lattice is used to compute gas diffusion in structures taken from real morphological data. This approach shows that, at rest, the human acinus efficiency is only 30-40%. These results provide a new evidence of the existence of diffusional screening at the acinar level. This implies permanent spatial inhomogeneity of oxygen and carbon dioxide partial pressure. The notion of an "alveolar gas" is reinterpreted as a spatial average of the gas distribution. This model casts new light on the respiratory properties of other gas mixtures, such as helium-oxygen.