We appreciate the opportunity to further clarify our findings in response to the insightful comments from Shota Yamamoto and colleagues and Luis Felipe Reyes and Ignacio Martin-Loeches regarding our recent community-acquired pneumonia (CAP) study. [...]@en

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.

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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.

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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.

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In the intensive care unit (ICU), infection-related mortality is high. Although adequate antibiotic treatment is essential in infections, beta-lactam target non-attainment occurs in up to 45% of ICU patients, which is associated with a lower likelihood of clinical success. To optimize antibiotic treatment, we aimed to develop beta-lactam target non-attainment prediction models in ICU patients. Patients from two multicenter studies were included, with intravenous intermittent beta-lactam antibiotics administered and blood samples drawn within 12–36 h after antibiotic initiation. Beta-lactam target non-attainment models were developed and validated using random forest (RF), logistic regression (LR), and naïve Bayes (NB) models from 376 patients. External validation was performed on 150 ICU patients. We assessed performance by measuring discrimination, calibration, and net benefit at the default threshold probability of 0.20. Age, sex, serum creatinine, and type of beta-lactam antibiotic were found to be predictive of beta-lactam target non-attainment. In the external validation, the RF, LR, and NB models confirmed good discrimination with an area under the curve of 0.79 [95% CI 0.72–0.86], 0.80 [95% CI 0.73–0.87], and 0.75 [95% CI 0.67–0.82], respectively, and net benefit in the RF and LR models. We developed prediction models for beta-lactam target non-attainment within 12–36 h after antibiotic initiation in ICU patients. These online-accessible models use readily available patient variables and help optimize antibiotic treatment. The RF and LR models showed the best performance among the three models tested.@en

Background: Timely identification of deteriorating COVID-19 patients is needed to guide changes in clinical management and admission to intensive care units (ICUs). There is significant concern that widely used Early warning scores (EWSs) underestimate illness severity in COVID-19 patients and therefore, we developed an early warning model specifically for COVID-19 patients. Methods: We retrospectively collected electronic medical record data to extract predictors and used these to fit a random forest model. To simulate the situation in which the model would have been developed after the first and implemented during the second COVID-19 ‘wave’ in the Netherlands, we performed a temporal validation by splitting all included patients into groups admitted before and after August 1, 2020. Furthermore, we propose a method for dynamic model updating to retain model performance over time. We evaluated model discrimination and calibration, performed a decision curve analysis, and quantified the importance of predictors using SHapley Additive exPlanations values. Results: We included 3514 COVID-19 patient admissions from six Dutch hospitals between February 2020 and May 2021, and included a total of 18 predictors for model fitting. The model showed a higher discriminative performance in terms of partial area under the receiver operating characteristic curve (0.82 [0.80–0.84]) compared to the National early warning score (0.72 [0.69–0.74]) and the Modified early warning score (0.67 [0.65–0.69]), a greater net benefit over a range of clinically relevant model thresholds, and relatively good calibration (intercept = 0.03 [− 0.09 to 0.14], slope = 0.79 [0.73–0.86]). Conclusions: This study shows the potential benefit of moving from early warning models for the general inpatient population to models for specific patient groups. Further (independent) validation of the model is needed.

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