In her pioneering work, Calfee et al. [1] addressed the clinical and biological heterogeneity of acute respiratory distress syndrome (ARDS), a factor likely contributing to the poor track record of randomized trials (RCTs) in this patient population. Using latent class (or profile) analysis (LCA), a method for identifying unobserved subgroups from observed data, they identified two distinct ARDS sub-phenotypes (hypo- and hyperinflammatory), which showed association with clinical outcomes and, crucially, heterogeneity of treatment effect (HTE) [2], demonstrating different responses to higher vs. lower PEEP regimes. [...]

Background
Switching from controlled to assisted ventilation is crucial in the trajectory of intensive care unit (ICU) stay, but no guidelines exist. We described current practices, analyzed patient characteristics associated with switch success or failure, and explored the feasibility to predict switch failure.

Methods
In this retrospective study, we obtained highly granular longitudinal ICU data sets from three medical centers, covering demographics, severity scores, vital signs, ventilation, and laboratory parameters. The primary endpoint was switch success, considering a switch attempt to be successful if a patient did not return to controlled ventilation for the next 72 h while alive, and to be failed otherwise. We compared the characteristics of patients with successful vs. failed first switch attempts at ICU admission, immediately before, and 3 h after the attempt. We trained LASSO logistic regression models to predict switch failure.

Results
In 4524/6715 (67%) patients attempting a switch, the first attempt failed. The first switch attempt, regardless of success or failure, was generally made at normalized PaCO2 and pH levels, with PEEP < 10 cmH2O and PaO2/FiO2 indicating mild injury. Despite very similar baseline disease severity, switch failure was associated with significantly worse outcomes, including a 28-day mortality of 27% vs. 16% and median ventilator-free days of 16 vs. 22 (p < 0.001). Failed attempts were initiated significantly earlier than successful ones (median 1.8 vs. 1.3 days, p < 0.001). Before the switch, PaO2/FiO2, if measured at PEEP > 10 cmH2O, and respiratory system compliance was lower in patients with switch failure (median 185 vs. 205 mmHg, p < 0.001; 39 vs. 41 mL/cmH2O, P = 0.001), and post-switch, patients with switch failure experienced greater deterioration in gas exchange and minimal improvement in ventilatory parameters post-switch. Contrary to our hypotheses, patient characteristics for failed vs. successful switches were surprisingly similar, resulting in prediction models with limited discriminative performance.

Conclusions
Approximately two-thirds of attempts to switch patients to assisted ventilation fail, which are associated with significantly worse clinical outcomes, despite similar baseline disease severity. Contrary to our hypotheses, patients with successful and failed attempts showed similar characteristics, making switch failure difficult to predict. These findings underscore the importance of preventing switch failures and, given the retrospective nature of this study, highlight the need for prospective studies to better understand the reasons for switch failure and when spontaneous breathing can be safely initiated.

Introduction: Although many preterm born infants require invasive mechanical ventilation, it is also associated with detrimental effects. Early extubation should be pursued, but extubation failure is yet common. The critical transition to noninvasive ventilation is characterized by respiratory physiological changes, warranting noninvasive monitoring. We aimed to determine whether electrical impedance tomography (EIT) could provide insights into the respiratory mechanics of neonates around extubation, and if findings were different between successful and failed extubation. Methods: Single-center observational study where EIT and transcutaneous CO2 measurements were performed in preterm born infants <32 weeks gestational age. Measurements were performed from 24 h before up to 48 h after extubation. EIT parameters extracted from the hour before and after extubation were analyzed to evaluate the shortterm physiological changes. Results: Twenty-one patients were included and 6 (29%) were reintubated. End-expiratory lung impedance and tidal impedance variation were stable around extubation (p = 0.86 and p = 0.47, respectively). Compared to successfully extubated patients, reintubated patients showed more lung inhomogeneity (GI index) after extubation (0.75 vs. 0.84, p = 0.03). The percentage of nondependent silent spaces decreased after extubation in successfully extubated patients (p < 0.001). Body position and ventilator mode influenced these findings. Conclusion: EIT measurements in preterm neonates provide valuable insight into the respiratory physiology during the transition from invasive to noninvasive ventilation, with significant differences in ventilation distribution and lung homogeneity between successfully extubated and reintubated patients. EIT has the potential to guide personalized respiratory support by assessing ventilation distribution and quantifying inhomogeneity, aiding in the optimization of ventilation settings.

Electrical impedance tomography (EIT) is a non-invasive and continuous advanced respiratory monitoring tool for assessing regional lung ventilation distribution and aeration [1]. It generates images based on impedance differences in the intrathoracic area. Recently, its application has extended to monitoring of preterm neonates admitted to the intensive care unit (ICU), facilitated by the availability of EIT belts in small sizes, accommodating thorax circumferences ranging from 19 to 40 cm.

Objective. Geometrical region of interest (ROI) selection in electrical impedance tomography (EIT) monitoring may lack sensitivity to subtle changes in ventilation distribution. Therefore, we demonstrate a new physiological method for ROI definition. This is relevant when using ROIs to compute subsequent EIT-parameters, such as the ventral-to-dorsal ratio during a positive end-expiratory pressure (PEEP) trial.Approach.Our physiological approach divides an EIT image to ensure exactly 50% tidal impedance variation in the ventral and dorsal region. To demonstrate the effects of our new method, EIT measurements during a decremental PEEP trial in 49 mechanically ventilated ICU-patients were used. We compared the center of ventilation (CoV), a robust parameter for changes in ventro-dorsal ventilation distribution, to our physiological ROI selection method and different commonly used ROI selection methods. Moreover, we determined the impact of different ROI selection methods on the PEEP level corresponding to a ventral-to-dorsal ratio closest to 1.Main results.The division line separating the ventral and dorsal ROI was closer to the CoV for our new physiological method for ROI selection compared to geometrical ROI definition. Moreover, the PEEP level corresponding to a ventral-to-dorsal ratio of 1 is strongly influenced by the chosen ROI selection method, which could have a profound clinical impact; the within-subject range of PEEP level was 6.2 cmH2O depending on the chosen ROI selection method.Significance.Our novel physiological method for ROI definition is sensitive to subtle ventilation-induced changes in regional impedance (i.e. due to (de)recruitment) during mechanical ventilation, similar to the CoV.

Objective. Electrical impedance tomography (EIT) produces clinical useful visualization of the distribution of ventilation inside the lungs. The accuracy of EIT-derived parameters can be compromised by the cardiovascular signal. Removal of these artefacts is challenging due to spectral overlapping of the ventilatory and cardiovascular signal components and their time-varying frequencies. We designed and evaluated advanced filtering techniques and hypothesized that these would outperform traditional low-pass filters. Approach. Three filter techniques were developed and compared against traditional low-pass filtering: multiple digital notch filtering (MDN), empirical mode decomposition (EMD) and the maximal overlap discrete wavelet transform (MODWT). The performance of the filtering techniques was evaluated (1) in the time domain (2) in the frequency domain (3) by visual inspection. We evaluated the performance using simulated contaminated EIT data and data from 15 adult and neonatal intensive care unit patients. Main result. Each filter technique exhibited varying degrees of effectiveness and limitations. Quality measures in the time domain showed the best performance for MDN filtering. The signal to noise ratio was best for DLP, but at the cost of a high relative and removal error. MDN outbalanced the performance resulting in a good SNR with a low relative and removal error. MDN, EMD and MODWT performed similar in the frequency domain and were successful in removing the high frequency components of the data. Significance. Advanced filtering techniques have benefits compared to traditional filters but are not always better. MDN filtering outperformed EMD and MODWT regarding quality measures in the time domain. This study emphasizes the need for careful consideration when choosing a filtering approach, depending on the dataset and the clinical/research question.

Background: Prolonged weaning from mechanical ventilation is associated with poor clinical outcome. Therefore, choosing the right moment for weaning and extubation is essential. Electrical Impedance Tomography (EIT) is a promising innovative lung monitoring technique, but its role in supporting weaning decisions is yet uncertain. We aimed to evaluate physiological trends during a T-piece spontaneous breathing trail (SBT) as measured with EIT and the relation between EIT parameters and SBT success or failure. Methods: This is an observational study in which twenty-four adult patients receiving mechanical ventilation performed an SBT. EIT monitoring was performed around the SBT. Multiple EIT parameters including the end-expiratory lung impedance (EELI), delta Tidal Impedance (ΔZ), Global Inhomogeneity index (GI), Rapid Shallow Breathing Index (RSBI_EIT), Respiratory Rate (RR_EIT) and Minute Ventilation (MV_EIT) were computed on a breath-by-breath basis from stable tidal breathing periods. Results: EELI values dropped after the start of the SBT (p < 0.001) and did not recover to baseline after restarting mechanical ventilation. The ΔZ dropped (p < 0.001) but restored to baseline within seconds after restarting mechanical ventilation. Five patients failed the SBT, the GI (p = 0.01) and transcutaneous CO₂ (p < 0.001) values significantly increased during the SBT in patients who failed the SBT compared to patients with a successful SBT. Conclusion: EIT has the potential to assess changes in ventilation distribution and quantify the inhomogeneity of the lungs during the SBT. High lung inhomogeneity was found during SBT failure. Insight into physiological trends for the individual patient can be obtained with EIT during weaning from mechanical ventilation, but its role in predicting weaning failure requires further study.

Objective. The respiratory rate (RR) is considered one of the most informative vital signals. A well-validated standard for RR measurement in mechanically ventilated patient is capnography; a noninvasive technique for expiratory CO2measurements. Reliable RR measurements in spontaneously breathing patients remains a challenge as continuous mainstream capnography measurements are not available. This study aimed to assess the accuracy of RR measurement using electrical impedance tomography (EIT) in healthy volunteers and intensive care unit (ICU) patients on mechanical ventilation and spontaneously breathing post-extubation. Comparator methods included RR derived from both capnography and bioimpedance electrocardiogram (ECG) measurements.Approach. Twenty healthy volunteers wore an EIT belt and ECG electrodes while breathing through a capnometer within a 10-40 breaths per minute (BPM) range. Nineteen ICU patients underwent similar measurements during pressure support ventilation and spontaneously breathing after extubation from mechanical ventilation. Stable periods with regular breathing and no artefacts were selected, and agreement between measurement methods was assessed using Bland-Altman analysis for repeated measurements.Main result. Bland-Altman analysis revealed a bias less than 0.2 BPM, with tight limits of agreement (LOA) ±1.5 BPM in healthy volunteers and ventilated ICU patients when comparing EIT to capnography. Spontaneously breathing ICU patients had wider LOA (±2.5 BPM) when comparing EIT to ECG bioimpedance, but gold standard comparison was unavailable. RR measurements were stable for 91% of the time for capnography, 68% for EIT, and 64% of the ECG bioimpedance signals. After extubation, the percentage of stable periods decreased to 48% for EIT signals and to 55% for ECG bioimpedance.Significance. In periods of stable breathing, EIT demonstrated excellent RR measurement accuracy in healthy volunteers and ICU patients. However, stability of both EIT and ECG bioimpedance RR measurements declined in spontaneously breathing patients to approximately 50% of the time.

The accuracy of diaphragm electromyogram (EMGdi) derived parameters, as used in critically ill intensive care unit (ICU) patients, can be compromised due to electrocardiographic (ECG) interference in the EMGdi signal. Removal of ECG contamination from the esophageal recordings of the EMGdi is challenging due to spectral overlapping of EMG and ECG signals and because of variability in ECG shape and amplitude. Therefore, we designed an Estimated ECG Subtraction (EES) method, based on three steps: (1) identification of the timing of the ECG artifact without an ECG reference channel, (2) estimation of the normalized ECG, considering the EMGdi as noise, and (3) subtraction of the denormalized ECG estimate from the EMGdi recordings. We evaluated the EES method against the use of a single wavelet-based adaptive filter. Using EMGdi signals of ten ICU patients and simulated contaminated EMG, we demonstrated that the EES method yields uncontaminated EMGdi, and showed that it is more effective than a wavelet-based adaptive filter only. Implementation of this technique may offer means to improve diaphragm activity monitoring and control in clinical practice.