Evaluating the physiologic effects of varying depths of propofol sedation on patient-ventilator interaction and synchrony during pressure support ventilation and neurally adjusted ventilatory assist. Prospective crossover randomized controlled trial. University hospital ICU. Fourteen intubated patients mechanically ventilated for acute respiratory failure. Six 25-minute trials randomly performed applying both pressure support ventilation and neurally adjusted ventilatory assist during wakefulness and with two doses of propofol, administered by Target Control Infusion, determining light (1.26 ± 0.35 μg/mL) and deep (2.52 ± 0.71 μg/mL) sedation, as defined by the bispectral index and Ramsay Sedation Scale. We measured electrical activity of the diaphragm to assess neural drive and calculated its integral over time during 1 minute (∫electrical activity of the diaphragm/min) to estimate diaphragm energy expenditure (effort), arterial blood gases, airway pressure, tidal volume and its coefficient of variation, respiratory rate, neural timing components, and calculated the ineffective triggering index. Increasing the depth of sedation did not cause significant modifications of respiratory timing, while determined a progressive significant decrease in neural drive (with both modes) and effort (in pressure support ventilation only). In pressure support ventilation, the difference in ineffective triggering index between wakefulness and light sedation was negligible (from 5.9% to 7.6%, p = 0.97); with deep sedation, however, ineffective triggering index increased up to 21.8% (p < 0.0001, compared to both wakefulness and light sedation). With neurally adjusted ventilatory assist, ineffective triggering index fell to 0%, regardless of the depth of sedation. With both modes, deep sedation caused a significant increase in PaCO2, which resulted, however, from different breathing patterns and patient-ventilator interactions. In pressure support ventilation, deep propofol sedation increased asynchronies, while light sedation did not. Propofol reduced the respiratory drive, while breathing timing was not significantly affected. Gas exchange and breathing pattern were also influenced by propofol infusion to an extent that varied with the depth of sedation and the mode of ventilation.

Introduction: The aim of this study was to validate an automated, objective and standardized algorithm for quantifying and displaying patient-ventilator interaction. Methods: Using a new method to detect patient-ventilator synchrony, the present study re-analyzed previously acquired and published data from 24 mechanically ventilated adult patients (Colombo et al., Crit Care Med. 2011 Nov;39(11):2452–7). Patient-ventilator interactions were evaluated by comparing ventilator pressure and diaphragm electrical activity (EAdi) waveforms, recorded during pressure support ventilation. The EAdi and ventilator pressure waveforms were analyzed for their timings (manually and automatically determined), and the error between the two waveforms was quantified. A new index of patient-ventilator interaction (NeuroSync index), which is standardized and automated, was validated and compared to manual analysis and previously published indices of asynchrony. Results: The comparison of manual and automated detection methods produced high test-retest and inter-rater reliability (Intraclass correlation coefficient = 0.95). The NeuroSync index increased the sensitivity of detecting dyssynchronies, compared to previously published indices, which were found to only detect asynchronies. Conclusion: The present study introduces an automated method and the NeuroSync index to determine patient-ventilator interaction with a more sensitive analysis method than those previously described. A dashboard-style of graphical display allows a rapid overview of patient-ventilator interaction and breathing pattern at the bedside.

Non-invasive ventilation (NIV) has been shown to be effective in avoiding intubation and improving survival in patients with acute hypoxemic respiratory failure (ARF) when compared to conventional oxygen therapy. However, NIV is associated with high failure rates due, in most cases, to patient discomfort. Therefore, increasing attention has been paid to all those interventions aimed at enhancing patient's tolerance to NIV. Several practical aspects have been considered to improve patient adaptation. In particular, the choice of the interface and the ventilatory setting adopted for NIV play a key role in the success of respiratory assistance. Among the different NIV interfaces, tolerance is poorest for the nasal and oronasal masks, while helmet appears to be better tolerated, resulting in longer use and lower NIV failure rates. The choice of fixing system also significantly affects patient comfort due to pain and possible pressure ulcers related to the device. The ventilatory setting adopted for NIV is associated with varying degrees of patient comfort: patients are more comfortable with pressure-support ventilation (PSV) than controlled ventilation. Furthermore, the use of electrical activity of the diaphragm (EADi)-driven ventilation has been demonstrated to improve patient comfort when compared to PSV, while reducing neural drive and effort. If non-pharmacological remedies fail, sedation can be employed to improve patient's tolerance to NIV. Sedation facilitates ventilation, reduces anxiety, promotes sleep, and modulates physiological responses to stress. Judicious use of sedation may be an option to increase the chances of success in some patients at risk for intubation because of NIV intolerance consequent to pain, discomfort, claustrophobia, or agitation. During the Coronavirus Disease-19 (COVID-19) pandemic, NIV has been extensively employed to face off the massive request for ventilatory assistance. Prone positioning in non-intubated awake COVID-19 patients may improve oxygenation, reduce work of breathing, and, possibly, prevent intubation. Despite these advantages, maintaining prone position can be particularly challenging because poor comfort has been described as the main cause of prone position discontinuation. In conclusion, comfort is one of the major determinants of NIV success. All the strategies aimed to increase comfort during NIV should be pursued.

Background: Noninvasive respiratory support (NIRS) has been diffusely employed outside the intensive care unit (ICU) to face the high request of ventilatory support due to the massive influx of patients with acute respiratory failure (ARF) caused by coronavirus-19 disease (COVID-19). We sought to summarize the evidence on clinically relevant outcomes in COVID-19 patients supported by NIV outside the ICU.Methods: We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials register, along with medRxiv and bioRxiv repositories for pre-prints, for observational studies and randomized controlled trials, from inception to the end of February 2021. Two authors independently selected the investigations according to the following criteria: (1) observational study or randomized clinical trials enrolling ≥ 50 hospitalized patients undergoing NIRS outside the ICU, (2) laboratory-confirmed COVID-19, and (3) at least the intra-hospital mortality reported. Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed. Data extraction was independently performed by two authors to assess: investigation features, demographics and clinical characteristics, treatments employed, NIRS regulations, and clinical outcomes. Methodological index for nonrandomized studies tool was applied to determine the quality of the enrolled studies. The primary outcome was to assess the overall intra-hospital mortality of patients under NIRS outside the ICU. The secondary outcomes included the proportions intra-hospital mortalities of patients who underwent invasive mechanical ventilation following NIRS failure and of those with ‘do-not-intubate’ (DNI) orders.Results: Seventeen investigations (14 peer-reviewed and 3 pre-prints) were included with a low risk of bias and a high heterogeneity, for a total of 3377 patients. The overall intra-hospital mortality of patients receiving NIRS outside the ICU was 36% [30–41%]. 26% [21–30%] of the patients failed NIRS and required intubation, with an intra-hospital mortality rising to 45% [36–54%]. 23% [15–32%] of the patients received DNI orders with an intra-hospital mortality of 72% [65–78%]. Oxygenation on admission was the main source of between-study heterogeneity.Conclusions: During COVID-19 outbreak, delivering NIRS outside the ICU revealed as a feasible strategy to cope with the massive demand of ventilatory assistance.Registration: PROSPERO,https://www.crd.york.ac.uk/prospero/, CRD42020224788, December 11, 2020.

BACKGROUND: Early identification of noninvasive ventilation (NIV) outcome predictors in patients with COPD who are experiencing acute hypercapnic respiratory failure consequent to exacerbation or pneumonia is a critical issue. The primary aim of this study was to investigate the feasibility of performing diaphragmatic ultrasound for excursion, thickness, and thickening fraction in highly dyspneic subjects with COPD admitted to the emergency department for exacerbation or pneumonia, before starting NIV (T0) and after the first (T1) and second hour (T2) of treatment. Secondarily, we determined whether these variables predicted early NIV failure. METHODS: Adult subjects with COPD admitted to the emergency department for exacerbation or pneumonia requiring NIV were eligible. Right-sided diaphragmatic excursion, bilateral thickness, thickening fraction, and arterial blood gas analyses were performed at T0, T1, and T2. Feasibility was estimated by considering the number of subjects whose diaphragmatic function could be evaluated at each time point. At T2, subjects were classified in 2 subgroups according to early NIV failure, which was defined as the inability to achieve a pH ≥ 7.35; the ability to achieve pH ≥ 7.35 indicated NIV success. RESULTS: Of the 22 subjects enrolled, 21 underwent complete diaphragm ultrasound evaluation (ie, right excursion and bilateral thickness at T0, T1, and T2) for a total of 63 excursion and 126 thickness assessments. At T2, 12 NIV successes and 9 NIV failures were recorded. Diaphragmatic excursion was greater in NIV successes than in NIV failures at T0 (1.92 [1.22–2.54] cm versus 1.00 [0.60–1.41] cm, P = .02), at T1 (2.14 [1.76–2.77] cm versus 0.93 [0.82–1.27] cm, P = .007), and at T2 (1.99 [1.63–2.54] cm versus 1.20 [0.79–1.41] cm, P = .008), respectively. Diaphragmatic thickness and thickening fraction were similar in both groups. CONCLUSIONS: In our emergency department setting, diaphragm ultrasound was a feasible and reliable tool to monitor highly dyspneic acute hypercapnic respiratory failure subjects with COPD undergoing NIV. (ClinicalTrials.gov registration NCT03314883.)