Ventilator Settings Research Articles

A randomized control trial evaluating the advice of a physiological-model/digital twin-based decision support system on mechanical ventilation in patients with acute respiratory distress syndrome

BackgroundAcute respiratory distress syndrome (ARDS) is highly heterogeneous, both in its clinical presentation and in the patient’s physiological responses to changes in mechanical ventilator settings, such as PEEP. This study investigates the clinical efficacy of a physiological model-based ventilatory decision support system (DSS) to personalize ventilator therapy in ARDS patients.MethodsThis international, multicenter, randomized, open-label study enrolled patients with ARDS during the COVID-19 pandemic. Patients were randomized to either receive active advice from the DSS (intervention) or standard care without DSS advice (control). The primary outcome was to detect a reduction in average driving pressure between groups. Secondary outcomes included several clinically relevant measures of respiratory physiology, ventilator-free days, time from control mode to support mode, number of changes in ventilator settings per day, percentage of time in control and support mode ventilation, ventilation- and device-related adverse events, and the number of times the advice was followed.ResultsA total of 95 patients were randomized in this study. The DSS showed no significant effect on average driving pressure between groups. However, patients in the intervention arm had a statistically improved oxygenation index when in support mode ventilation (−1.41, 95% CI: −2.76, −0.08; p = 0.0370). Additionally, the ventilatory ratio significantly improved in the intervention arm for patients in control mode ventilation (−0.63, 95% CI: −1.08, −0.17, p = 0.0068). The application of the DSS led to a significantly increased number of ventilator changes for pressure settings and respiratory frequency.ConclusionThe use of a physiological model-based decision support system for providing advice on mechanical ventilation in patients with COVID-19 and non-COVID-19 ARDS showed no significant difference in driving pressure as a primary outcome measure. However, the application of approximately 60% of the DSS advice led to improvements in the patient’s physiological state.Clinical trial registrationclinicaltrials.gov, NCT04115709.

Adherence to Lung Protective Ventilation in ARDS: A Mixed Methods Study Using Real-Time Continuously Monitored Ventilation Data.

Lung-protective ventilation is a standard intervention for mitigating ventilator-induced lung injury in patients with ARDS. Despite its efficacy, adherence to contemporary evidence-based guidelines remains suboptimal. We aimed to identify factors that affect the adherence of staff to applying lung-protective ventilation guidelines by analyzing real-time, continuously monitored ventilation data over a 5-year longitudinal period. We conducted retrospective cohort and qualitative studies. Subjects with billing code J80 who survived at least 48 h of continuous mandatory ventilation with volume control in critical care settings between January 1, 2018, and December 31, 2022, were eligible. Tidal volume was measured dynamically (1-min resolution) and averaged hourly. The lung-protective ventilation setting studied was ≤ 6 mL/kg predicted body weight. A subgroup analysis was conducted by considering COVID-19 status. Focus groups of critical-care providers were convened to investigate the possible reasons for the non-utilization of lung-protective ventilation. Among 1,055 subjects, 42.4% were on lung-protective ventilation settings at 48 h. Male sex was correlated with lung-protective ventilation (odds ratio [OR] 1.63, 95% CI 1.08-2.47), whereas age ≥ 60 y was associated with no lung-protective ventilation use (OR 0.61, 95% CI 0.39-0.94] in the subjects with non-COVID-19 etiologies. Improved staff adherence was observed in the subjects with COVID-19 early in the pandemic when COVID-19 (OR 1.48, 95% CI 1.07-2.04), male sex (OR 2.42, 95% CI 1.79-3.29), and neuromuscular blocking agent use within 48 h (OR 1.69, 95% CI 1.25-2.29) were correlated with staff placing subjects on lung-protective ventilation. However, lung-protective ventilation use occurred less frequently by staff managing subjects with cancer (OR 0.59, 95% CI 0.35-0.99) and hypertension (OR 0.62, 95% CI 0.45-0.85). Focus groups supported these findings and highlighted the need for an accurate height measurement on unit admission to determine the appropriate target tidal volume. Staff are not yet universally adherent to lung-protective ventilation best practices. Strategies, for example, continuous monitoring, with frequent feedback to clinical teams may help.

S3 Guideline: Treating Chronic Respiratory Failure with Non-invasive Ventilation

The S3 guideline on non-invasive ventilation as a treatment for chronic respiratory failure was published on the website of the Association of the Scientific Medical Societies in Germany (AWMF) in July 2024. It offers comprehensive recommendations for the treatment of chronic respiratory failure in various underlying conditions, such as COPD, thoraco-restrictive diseases, obesity-hypoventilation syndrome, and neuromuscular diseases. An important innovation is the separation of the previous S2k guideline dating back to 2017, which included both invasive and non-invasive ventilation therapy. Due to increased scientific evidence and a significant rise in the number of affected patients, these distinct forms of therapy are now addressed separately in two different guidelines.The aim of the guideline is to improve the treatment of patients with chronic respiratory insufficiency using non-invasive ventilation and to make the indications and therapy recommendations accessible to all involved in the treatment process. It is based on the latest scientific evidence and replaces the previous guideline. This revised guideline provides detailed recommendations on the application of non-invasive ventilation, ventilation settings, and the subsequent follow-up of treatment.In addition to the updated evidence, important new features of this S3 guideline include new recommendations on patient care and numerous detailed treatment pathways that make the guideline more user-friendly. Furthermore, a completely revised section is dedicated to ethical issues and offers recommendations for end-of-life care. This guideline is an important tool for physicians and other healthcare professionals to optimize the care of patients with chronic respiratory failure. This version of the guideline is valid for three years, until July 2027.

Hemodynamic monitoring during weaning from mechanical ventilation in critically ill pediatric patients: a prospective observational study

BackgroundCardiovascular dysfunction is a significant factor contributing to weaning failure in mechanically ventilated children. Understanding the cardiopulmonary pathophysiological changes that occur during weaning is a prerequisite for the early recognition of weaning failure of cardiovascular origin. This study aimed to assess the effect of weaning trials on central hemodynamics and to identify the indices predictive of cardiac-related weaning failure.MethodsThis prospective observational study was conducted in the Pediatric Intensive Care Unit (PICU) and included mechanically ventilated patients aged between 2 and 30 months who were on minimal ventilatory settings and ready for weaning. Patients who were hemodynamically unstable, diagnosed with neuromuscular diseases, or diagnosed with cardiac diseases were excluded. Hemodynamic parameters were evaluated during weaning from ventilation via echocardiography and noninvasive cardiometry during pressure support (PS) ventilation and at the end of the spontaneous breathing trial (SBT).ResultsThe study included 50 patients, comprising 30 males (60%) and 20 females (40%) with ages ranging from 2 to 30 months. Echocardiography revealed a significant increase in the cardiac index (CI), tricuspid annular plane systolic excursion (TAPSE), and the E/A ratio at the end of SBT. Moreover, right ventricular systolic pressure (RVSP) significantly decreased. Noninvasive cardiometry revealed a significant increase in the index of contractility (ICON) and CI at the end of SBT (p-value = 0.023 and < 0.001, respectively). Of the 12 (25%) patients who failed their first extubation trial, they exhibited a significantly lower CI and TAPSE (p values = 0.001 and 0.001, respectively).ConclusionThis study identified that weaning from mechanical ventilation in children is associated with hemodynamic changes, which can impact weaning success and reveal potential ventricular dysfunction. Bedside echocardiography was found to detect cardiac dysfunctions during weaning, and noninvasive cardiometry was considered a reliable tool that supports echocardiography for detecting changing trends in CI in PICUs. However, accurate values should be confirmed by echocardiography.

The Impact of Pneumoperitoneum on Mean Expiratory Flow Rate: Observational Insights from Patients with Healthy Lungs

Background/Objectives: Surgical pneumoperitoneum (PP) significantly impacts volume-controlled ventilation, characterized by reduced respiratory compliance, elevated peak inspiratory pressure, and an accelerated expiratory phase due to an earlier onset of the airway pressure gradient. We hypothesized that this would shorten expiratory time, potentially increasing expiratory flow rate compared to pneumoperitoneum conditions. Calculations were performed to establish correlations between respiratory parameters and the mean increase in expiratory flow rate relative to baseline. Methods: Mechanical ventilation parameters were recorded for 67 patients both pre- and post-PP. Ventilator settings were standardized with a tidal volume of 6 mL/kg, a respiratory rate of 12 breaths per minute, a PEEP of 3 cmH2O, an inspiratory time of 2 s, and an inspiratory-to-expiratory ratio of 1:1.5 (I:E). Results: The application of PP increased both peak inspiratory pressure and mean expiratory flow rate by 28% compared to baseline levels. The elevated intra-abdominal pressure of 20 cmH2O resulted in a 34% reduction in dynamic chest compliance, a 50% increase in elastance, and a 20% increase in airway resistance. The mean expiratory flow rate increments relative to baseline showed a significant negative correlation with elastance (p = 0.0119) and a positive correlation with dynamic compliance (p = 0.0028) and resistance (p = 0.0240). Conclusions: A PP of 20 cmH2O resulted in an increase in the mean expiratory flow rate in the conventional I:E ratio in the volume-ventilated mode. PP reduces lung and chest wall compliance by elevating the diaphragm, compressing the thoracic cavity, and increasing airway pressures. Consequently, the lungs and chest wall stiffen, requiring greater ventilatory effort and accelerating expiratory flow due to increased airway resistance and altered pulmonary mechanics. Prolonging the inspiratory phase through I:E ratio adjustment helps maintain peak inspiratory pressures closer to baseline levels, and this method enhances the safety and efficacy of mechanical ventilation in maintaining optimal respiratory function during laparoscopic surgery.

Enhancing the estimation of PaCO2 from etCO2 during ventilation through non-invasive parameters in the ovine model

BackgroundIn mechanically ventilated neonates, the arterial partial pressure of CO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {CO}_{2}$$\\end{document} (PaCO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {PaCO}_{2}$$\\end{document}) is an important indicator for the adequacy of ventilation settings. Determining the PaCO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {PaCO}_{2}$$\\end{document} is commonly done using invasive blood gas analyses, which constitute risks for neonates and are typically only available infrequently. An accurate, reliable, and continuous estimation of PaCO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {PaCO}_{2}$$\\end{document} is of high interest for medical staff, giving the possibility of a closer monitoring and faster reactions to changes. We aim to present a non-invasive estimation method for PaCO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {PaCO}_{2}$$\\end{document} in neonates on the basis of end-tidal CO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {CO}_{2}$$\\end{document} (etCO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {etCO}_{2}$$\\end{document}) with inclusion of different physiological and ventilation parameters. The estimation method should be more accurate than an estimation by unaltered etCO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {etCO}_{2}$$\\end{document} measurements with regard to the mean absolute error and the standard deviation.MethodsSecondary data from 51 preterm lambs are used, due to its high comparability to preterm human data. We utilize robust linear regression on 863 PaCO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {PaCO}_{2}$$\\end{document} measurements below or equal to 75 mmHg from the first day of life. etCO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {etCO}_{2}$$\\end{document} along with a set of ventilation settings and measurements as well as vital parameters are included in the regression. Included independent variables are chosen iteratively by highest Pearson correlation to the remaining estimation deviation.ResultsThe evaluation is carried out on 12 additional neonatal lambs with 246 PaCO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {PaCO}_{2}$$\\end{document} measurements below or equal to 75 mmHg from the first two days of life. The estimation method shows a mean absolute error of 3.80 mmHg with a 4.92 mmHg standard deviation of differences and a standard error of 0.31 mmHg in comparison to measured PaCO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {PaCO}_{2}$$\\end{document} by blood gas analysis.ConclusionsThe estimation of PaCO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {PaCO}_{2}$$\\end{document} by the proposed equation is less biased than unaltered etCO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {etCO}_{2}$$\\end{document}. The usage of this method in clinical practice or in applications like the automation of ventilation needs further investigation.

Anesthetic Gas Scavenging System for Gas Evacuation in the ICU.

Inhaled sedation is increasing in ICUs, with active carbon filters (ACFs) commonly used for evacuating halogenated gases. However, the potential benefits of a waste anesthetic gas system (WAGS) similar to the ones used in operating rooms should be explored. To limit the suction over the flow sensor where the WAGS is connected on ICU ventilators, an anesthetic gas receiving system (AGRS) is required, constituting with the WAGS an active gas receiving and scavenging system (AGRSS). Ensuring that this whole device does not compromise the flow sensor reliability is crucial. The aim of this study was to compare various gas evacuation devices and assess the reliability of AGRSS on ICU ventilators. In this experimental study, pressures and flows were recorded during the ventilation of a test lung using various ventilator settings and gas evacuation methods: no device (reference condition), ACF, the WAGS alone, AGRSS (WAGS and AGRS together), and the expiratory valve connected to the medical vacuum system with the AGRS in between. Visual comparisons of the pressure and flow curves followed by a statistical analysis comparing median pressures and flows of each device to the reference were performed. The test lung model demonstrated consistent comparability in pressures and flows among all devices, except for the WAGS alone, which exhibited discordance through significant overestimation or underestimation. These findings indicate that using a WAGS with the AGRS system appeared to be reliable for managing gas evacuation in ICUs without compromising pressure or flow delivery. The data from this experimental trial should be confirmed with clinical studies involving human subjects. Given the increasing use of inhaled sedation in ICUs, these results support the daily application of the WAGS with the AGRS for gas evacuation, similar to its established use in anesthesiology.

Monitoring and modulating respiratory drive in mechanically ventilated patients.

Respiratory drive is frequently deranged in the ICU, being associated with adverse clinical outcomes. Monitoring and modulating respiratory drive to prevent potentially injurious consequences merits attention. This review gives a general overview of the available monitoring tools and interventions to modulate drive. Airway occlusion pressure (P0.1) is an excellent measure of drive and is displayed on ventilators. Respiratory drive can also be estimated based on the electrical activity of respiratory muscles and measures of respiratory effort; however, high respiratory drive might be present in the context of low effort with neuromuscular weakness. Modulating a deranged drive requires a multifaceted intervention, prioritizing treatment of the underlying cause and adjusting ventilator settings for comfort. Additional tools include changes in PEEP, peak inspiratory flow, fraction of inspired oxygen, and sweep gas flow (in patients receiving extracorporeal life-support). Sedatives and opioids have differential effects on drive according to drug category. Monitoring response to any intervention is warranted and modulating drive should not preclude readiness to wean assessment or delay ventilation liberation. Monitoring and modulating respiratory drive are feasible based on physiological principles presented in this review. However, evidence arising from clinical trials will help determine precise thresholds and optimal interventions.

Respiratory Effects of Maximal Lung Recruitment Maneuvers Using Single-Breath Estimation in ARDS.

Determining which patients with ARDS are most likely to benefit from lung recruitment maneuvers is challenging for physicians. The aim of this study was to assess whether the single-breath simplified decremental PEEP maneuver, which evaluates potential lung recruitment, may predict a subject's response to lung recruitment maneuvers, followed by PEEP titration. We conducted a pilot prospective single-center cohort study with a 3-step protocol that defined sequential measurements. First, potential lung recruitment was assessed by the single-breath maneuver in the volume controlled mode. Second, the lung recruitment maneuver was performed in the pressure controlled mode, with a fixed driving pressure of 15 cm H2O and a maximum PEEP of 30 cm H2O. Third, the lung recruitment maneuver was followed by decremental PEEP titration to determine the optimal PEEP, defined as the lowest driving pressure. Responders to the lung recruitment maneuver were defined by an improvement in PaO2 /FIO2 > 20% between the baseline state and the end of the PEEP titration phase. Forty-two subjects with moderate-to-severe ARDS were included. The mean ± SD lung recruitment was 149 ± 104 mL. A threshold lung recruitment of 195 mL (area under the receiver operator characteristic curve 0.62, 95% CI 0.43-0.80) predicted a positive response to the maximal lung recruitment maneuver. The lung recruitment maneuver, followed by PEEP titration, resulted in a modification of PEEP in 74% of the subjects. PEEP was increased in more than two thirds of the responders and decreased in almost half of the non-responders to the lung recruitment maneuver. In addition, a decrease in driving pressure and an increase in respiratory system compliance were reported in 62% and 67% of the subjects, respectively. The single-breath maneuver for evaluating lung recruitability predicted, with poor accuracy, the subjects who responded to the lung recruitment maneuver based on PaO2 /FIO2 improvement. Nevertheless, the lung recruitment maneuver, followed by PEEP titration, improved ventilator settings and respiratory mechanics in a majority of subjects.

Reinforcement Learning to Optimize Ventilator Settings for Patients on Invasive Mechanical Ventilation: Retrospective Study.

One of the significant changes in intensive care medicine over the past 2 decades is the acknowledgment that improper mechanical ventilation settings substantially contribute to pulmonary injury in critically ill patients. Artificial intelligence (AI) solutions can optimize mechanical ventilation settings in intensive care units (ICUs) and improve patient outcomes. Specifically, machine learning algorithms can be trained on large datasets of patient information and mechanical ventilation settings. These algorithms can then predict patient responses to different ventilation strategies and suggest personalized ventilation settings for individual patients. In this study, we aimed to design and evaluate an AI solution that could tailor an optimal ventilator strategy for each critically ill patient who requires mechanical ventilation. We proposed a reinforcement learning-based AI solution using observational data from multiple ICUs in the United States. The primary outcome was hospital mortality. Secondary outcomes were the proportion of optimal oxygen saturation and the proportion of optimal mean arterial blood pressure. We trained our AI agent to recommend low, medium, and high levels of 3 ventilator settings-positive end-expiratory pressure, fraction of inspired oxygen, and ideal body weight-adjusted tidal volume-according to patients' health conditions. We defined a policy as rules guiding ventilator setting changes given specific clinical scenarios. Off-policy evaluation metrics were applied to evaluate the AI policy. We studied 21,595 and 5105 patients' ICU stays from the e-Intensive Care Unit Collaborative Research (eICU) and Medical Information Mart for Intensive Care IV (MIMIC-IV) databases, respectively. Using the learned AI policy, we estimated the hospital mortality rate (eICU 12.1%, SD 3.1%; MIMIC-IV 29.1%, SD 0.9%), the proportion of optimal oxygen saturation (eICU 58.7%, SD 4.7%; MIMIC-IV 49%, SD 1%), and the proportion of optimal mean arterial blood pressure (eICU 31.1%, SD 4.5%; MIMIC-IV 41.2%, SD 1%). Based on multiple quantitative and qualitative evaluation metrics, our proposed AI solution outperformed observed clinical practice. Our study found that customizing ventilation settings for individual patients led to lower estimated hospital mortality rates compared to actual rates. This highlights the potential effectiveness of using reinforcement learning methodology to develop AI models that analyze complex clinical data for optimizing treatment parameters. Additionally, our findings suggest the integration of this model into a clinical decision support system for refining ventilation settings, supporting the need for prospective validation trials.

Dynamic shunt flow alterations through patent foramen ovale during off-pump coronary artery bypass grafting induced by airway pressure changes: a case report.

Interatrial right-to-left shunt flow through a patent foramen ovale (PFO) can be caused by changes in heart position for anastomosis during off-pump coronary artery bypass (OPCAB). We herein present a case in which the direction of PFO shunt flow changed with heart position during OPCAB and the ventilation settings after sternal closure. A 66-year-old man with interstitial pneumonia underwent OPCAB. Preoperative transesophageal echocardiography revealed right-to-left shunt flow through a PFO induced by the Valsalva maneuver. During OPCAB, heart displacement resulted in right-to-left shunting and acute hypoxemia, which quickly improved with increase of inspired oxygen fraction. After chest closure, bidirectional shunt flow developed under increased airway pressure. Vigilant intraoperative monitoring with TEE and postoperative airway pressure management are important to address shunt flow and hypoxemia due to PFO.

Induction of subject-ventilator asynchrony by variation of respiratory parameters in a lung injury model in pigs

BackgroundSubject-ventilator asynchrony (SVA) was shown to be associated with negative clinical outcomes. To elucidate pathophysiology pathways and effects of SVA on lung tissue histology a reproducible animal model of artificially induced asynchrony was developed and evaluated.MethodsAlterations in ventilator parameters were used to induce the three main types of asynchrony: ineffective efforts (IE), auto-triggering (AT), and double-triggering (DT). Airway flow and pressure, as well as oesophageal pressure waveforms, were recorded, asynchrony cycles were manually classified and the asynchrony index (AIX) was calculated. Bench tests were conducted on an active lung simulator with ventilator settings altered cycle by cycle. The developed algorithm was evaluated in three pilot experiments and a study in pigs ventilated for twelve hours with AIX = 25%.ResultsIE and AT were induced reliably and fail-safe by end-expiratory hold and adjustment of respiratory rate, respectively. DT was provoked using airway pressure ramp prolongation, however not controlled specifically in the pilots. In the subsequent study, an AIX = 28.8% [24.0%-34.4%] was induced and maintained over twelve hours.ConclusionsThe method allows to reproducibly induce and maintain three clinically relevant types of SVA observed in ventilated patients and may thus serve as a useful tool for future investigations on cellular and inflammatory effects of asynchrony.

Nebulized aminoglycosides for ventilator-associated pneumonia: Methodological considerations and lessons from experimental studies

Aminoglycosides are concentration-dependent antibiotics exerting a bactericidal effect when concentrations at the site of infection are equal to or greater than 5 times the minimum inhibitory concentrations (MIC). When administered intravenously, they exhibit poor lung penetration and high systemic renal and ototoxicity, imposing to restrict their administration to 5 days. Experimental studies conducted in anesthetized and mechanically ventilated sheep and pigs provide evidence that high doses of nebulized aminoglycosides induce a rapid and potent bacterial killing in the infected lung parenchyma. They also confirm that the alveolar-capillary membrane, either normal or injured by the infectious process, restricts the penetration of intravenous aminoglycosides in the infected lung parenchyma, precluding a bactericidal effect at the site of infection. However, injury of the alveolar-capillary membrane promotes the systemic diffusion of nebulized aminoglycosides. Based on experimental data obtained in animals with inoculation pneumonia, it challenges the classical belief that nebulization protects against systemic toxicity. Loss of lung aeration decreases the lung penetration of nebulized aminoglycosides. Nevertheless, lung tissue concentrations measured in non-aerated lung regions with severe and extended pneumonia are most often greater than 5 times the MICs, resulting in a bactericidal effect followed by a progressive pulmonary reaeration. It is likely that the penetration into the consolidated lung, results from the bronchial diffusion of nebulized aminoglycosides toward adjacent non-aerated infected alveolar spaces and their penetration into mechanical ventilation-induced intraparenchymal pseudocysts and distended bronchioles. In animals receiving nebulized aminoglycosides, epithelial lining fluid concentrations grossly overestimate lung interstitial fluid concentrations because of the bronchial contamination of the distal tip of the bronchoscope during the bronchoalveolar procedures. Lung microdialysis is the only technique able to accurately assess lung pharmacokinetics in animals with inoculation pneumonia treated by nebulized aminoglycosides. In 2024, the European Investigators Network for Nebulized Antibiotics in Ventilator-associated Pneumonia (ENAVAP) called for the creation of an international research network for Lung Microdialysis applied to Nebulized Antibiotics (LUMINA) to promote multicentered, experimental, randomized, and controlled studies addressing lung pharmacokinetics of intravenous vs. nebulized antibiotics, using different dosing and ventilator settings.

Comparing the impact of targeting limited driving pressure to low tidal volume ventilation on mortality in mechanically ventilated adults with COVID-19 ARDS: an exploratory target trial emulation

BackgroundAn association between driving pressure (∆P) and the outcomes of invasive mechanical ventilation (IMV) may exist. However, the effect of a sustained limitation of ∆P on mortality in patients with...

Elevating Prehospital Traumatic Brain Injury Care: A Comparative Analysis of Civilian and Military Air Transport Guidelines

ObjectiveTraumatic brain injuries (TBIs) are a leading cause of death and disability worldwide. Establishing TBI guidelines is crucial for prehospital management. Civilian medical practices are often influenced by military trauma guidelines. This study provides a comparative analysis of prehospital TBI management by a civilian air medical evacuation service using civilian guidelines and military clinical practice guidelines from the Joint Trauma System of the Department of Defense. MethodsA retrospective review of 100 deidentified patient transport logs from a prominent civilian air medical service was conducted. The logs were compared with the service's patient care guidelines and the 2023 Joint Trauma System Clinical Practice Guidelines. Data were analyzed for adherence to 14 metrics. ResultsPatients showed improvement in preflight and postflight Glasgow Coma Scale scores and were managed according to recommendations on head elevation, oxygenation, blood pressure, and temperature by both organizations. Discrepancies between guidelines included differences in the management of ventilator settings, blood pressure, oxygenation, temperature, serum glucose, intracranial hypertension, suspected brain herniation, serum sodium levels, and seizure prophylaxis. ConclusionComparing civilian and military guidelines highlights areas for potential improvements in TBI management, such as integrating advanced monitoring and the implementation of (i-STAT, Abbott Laboratories, Chicago, IL) testing in air transport to enhance patient care and outcomes.

Saving lives, one breath at a time: The key role of noninvasive ventilation interfaces.

Home noninvasive ventilation (NIV) for children must consider the key role of the interface, in addition to selecting the ventilatory mode and settings. Acceptance and adherence to NIV often depend on the time spent selecting the right mask, as well as on regular and careful attention to preventing and addressing various issues that arise during NIV.

Detectable Concentrations With Inhaled Tobramycin in Critically Ill Infants and Children Following Implementation of Standardized Protocol.

A protocol was established for ventilator-associated tracheitis or pneumonia using inhaled tobramycin 300 mg every 12 hours in mechanically ventilated children via a vibrating mesh nebulizer, 30 cm from the endotracheal tube in the inspiratory loop of the mechanical ventilator. The primary objective was to determine the incidence of detectable tobramycin trough concentrations >0.5 µg/mL. Secondary objectives included a comparison of clinical characteristics between those with and without detectable concentrations and identification of patients with acute kidney injury (AKI) as defined by the Kidney Diseases Improving Global Outcomes (KDIGO) criteria. This was a single-center retrospective study of critically ill children <18 years without cystic fibrosis receiving inhaled tobramycin between July 1, 2016, and August 31, 2021. Data collection included demographics, tobramycin regimen, and renal function. Analysis was performed using SAS 9.4, with a P-value <0.05, and a multivariable regression model was performed to identify factors for detectable concentrations and AKI. Forty-four patients (66 courses) were included, with an overall age of 0.83 years. Thirty (68%) patients had detectable concentrations and 9 (20.5%) developed AKI. No significant differences in demographics, diagnosis, mechanical ventilation settings, and number of nephrotoxins were noted between those with and without detectable concentrations or AKI. Multivariable regressions did not identify factors associated with detectable concentrations or AKI. Detectable concentrations occurred with the majority of courses, with AKI associated with approximately one-fourth of courses. Clinicians should consider utilizing trough monitoring for all mechanically ventilated critically ill children receiving inhaled tobramycin.

Imaging of ventilation and lung injury with low-frequency tomographic ultrasound.

Mechanical ventilation in the intensive care unit (ICU) is a life-saving technique for patients with acute respiratory failure, but is also associated with a high incidence of complications in the injured lung. Currently, there is no widely used monitoring technique to guide the ventilator setting to facilitate a precision medicine approach or to provide a real-time alert for developing adverse pulmonary conditions. Conventional ultrasound has been used as a thoracic bedside technology, but the lack of signal penetration into lung tissue results in images that often contain more information in their artifacts than in the images themselves. Perhaps the greatest obstacle to using traditional ultrasound in the ICU is the need for highly skilled technicians to perform the data collection. In contrast, low-frequency ultrasound (50-500 kHz) has been shown to penetrate the lung, and can detect air trapping in patients with chronic obstructive pulmonary disease (COPD). Here, we present a method of collecting low-frequency ultrasound computed tomographic (USCT) data in vivo on a mechanically ventilated porcine model and computing tomographic reconstructions of airflow during tidal breathing and induced lung injuries. We evaluate the ability of the novel low-frequency USCT system to image regional changes in sound speed in the thorax due to changes in airflow during tidal breathing and induced lung injuries. This represents the first study of low-frequency tomographic ultrasound imaging in vivo and the first to produce tomographic images of ventilatory changes invivo. USCT and computed tomography (CT) scan data were collected alternately on a mechanically ventilated Landrace pig weighing approximately 75 kg during tidal breathing, induced pneumothorax, atelectasis, and pleural effusion. The pneumothorax was induced by injecting air through a 5 mm thick intrathoracic tube inserted in the 8th posterior intercostal space. After removing the air, atelectasis was induced by ventilating the animal with a high concentration of oxygen and low tidal volumes. The pleural effusion was induced by injecting a saline solution through the tube. The USCT data were collected at 125 kHz using the USCT low-frequency ultrasound tomography (LUFT) system on a transducer belt placed around the animal's thorax. Tomographic reconstructions were computed from the USCT data using a regularized refraction-corrected Gauss-Newton-based time-of-flight reconstructionalgorithm. Cyclic changes in computed lung area during tidal breathing were demonstrated to agree with the respiratory rate on the mechanical ventilator. Reconstructed images computed at time steps during the procedure demonstrate regional changes consistent with what would be expected during the induced lung injury. No ground truth was available for images during the procedures since CT scans could only be taken before and after each established lunginjury. In this work, we have demonstrated in the first in vivo study using a mechanically ventilated porcine animal model that low-frequency ultrasound tomography has the ability to image regional changes in sound speed in the thorax corresponding to changes in airflow during tidal breathing and induced lung injury. The results show promise for using low-frequency USCT as a bedside imaging technique in the future for patients with acute respiratory distresssyndrome.

Post-insufflation diaphragm contractions in patients receiving various modes of mechanical ventilation

BackgroundDuring mechanical ventilation, post-insufflation diaphragm contractions (PIDCs) are non-physiologic and could be injurious. PIDCs could be frequent during reverse-triggering, where diaphragm contractions follow the ventilator rhythm. Whether PIDCs happens with different modes of assisted ventilation is unknown. In mechanically ventilated patients with hypoxemic respiratory failure, we aimed to examine whether PIDCs are associated with ventilator settings, patients’ characteristics or both.MethodsOne-hour recordings of diaphragm electromyography (EAdi), airway pressure and flow were collected once per day for up to five days from intubation until full recovery of diaphragm activity or death. Each breath was classified as mandatory (without-reverse-triggering), reverse-triggering, or patient triggered. Reverse triggering was further subclassified according to EAdi timing relative to ventilator cycle or reverse triggering leading to breath-stacking. EAdi timing (onset, offset), peak and neural inspiratory time (Tineuro) were measured breath-by-breath and compared to the ventilator expiratory time. A multivariable logistic regression model was used to investigate factors independently associated with PIDCs, including EAdi timing, amplitude, Tineuro, ventilator settings and APACHE II.ResultsForty-seven patients (median[25%-75%IQR] age: 63[52–77] years, BMI: 24.9[22.9–33.7] kg/m2, 49% male, APACHE II: 21[19–28]) contributed 2 ± 1 recordings each, totaling 183,962 breaths. PIDCs occurred in 74% of reverse-triggering, 27% of pressure support breaths, 21% of assist-control breaths, 5% of Neurally Adjusted Ventilatory Assist (NAVA) breaths. PIDCs were associated with higher EAdi peak (odds ratio [OR][95%CI] 1.01[1.01;1.01], longer Tineuro (OR 37.59[34.50;40.98]), shorter ventilator inspiratory time (OR 0.27[0.24;0.30]), high peak inspiratory flow (OR 0.22[0.20;0.26]), and small tidal volumes (OR 0.31[0.25;0.37]) (all P ≤ 0.008). NAVA was associated with absence of PIDCs (OR 0.03[0.02;0.03]; P < 0.001). Reverse triggering was characterized by lower EAdi peak than breaths triggered under pressure support and associated with small tidal volume and shorter set inspiratory time than breaths triggered under assist-control (all P < 0.05). Reverse triggering leading to breath stacking was characterized by higher peak EAdi and longer Tineuro and associated with small tidal volumes compared to all other reverse-triggering phenotypes (all P < 0.05).ConclusionsIn critically ill mechanically ventilated patients, PIDCs and reverse triggering phenotypes were associated with potentially modifiable factors, including ventilator settings. Proportional modes like NAVA represent a solution abolishing PIDCs.

Respiratory effects of prone position in COVID-19 acute respiratory distress syndrome differ according to the recruitment-to-inflation ratio: a prospective observational study

BackgroundImprovements in oxygenation and lung mechanics with prone position (PP) in patients with acute respiratory distress syndrome (ARDS) are inconstant. The objectives of the study were (i) to identify baseline variables, including the recruitment-to-inflation ratio (R/I), associated with a positive response to PP in terms of oxygenation (improvement of the ratio of arterial oxygen partial pressure over the inspired oxygen fraction (PaO2/FiO2) ≥ 20 mmHg) and lung mechanics; (ii) to evaluate whether the response to the previous PP session is associated with the response to the next session.MethodsIn this prospective, observational, single-center study in patients who underwent PP for ARDS due to COVID-19, respiratory variables were assessed just before PP and at the end of the session. Respiratory variables included mechanical ventilation settings and respiratory mechanics variables, including R/I, an estimate of the potential for lung recruitment compared to lung overinflation.ResultsIn 50 patients, 201 PP sessions lasting 19 ± 3 h were evaluated. Neuromuscular blockades were used in 116 (58%) sessions. The PaO2/FiO2 ratio increased from 109 ± 31 mmHg to 165 ± 65 mmHg, with an increase ≥ 20 mmHg in 142 (71%) sessions. In a mixed effect logistic regression, only pre-PP PaO2/FiO2 (OR 1.12 (95% CI [1.01–1.24])/every decrease of 10 mmHg, p = 0.034) in a first model and improvement in oxygenation at the previous PP session (OR 3.69 (95% CI [1.27–10.72]), p = 0.017) in a second model were associated with an improvement in oxygenation with PP. The R/I ratio (n = 156 sessions) was 0.53 (0.30–0.76), separating lower- and higher-recruiters. Whereas PaO2/FiO2 improved to the same level in both subgroups, driving pressure and respiratory system compliance improved only in higher-recruiters (from 14 ± 4 to 12 ± 4 cmH2O, p = 0.027, and from 34 ± 11 to 38 ± 13 mL/cmH2O, respectively, p = 0.014).ConclusionsA lower PaO2/FiO2 at baseline and a positive O2-response at the previous PP session are associated with a PP-induced improvement in oxygenation. In higher-recruiters, lung mechanics improved along with oxygenation. Benefits of PP could thus be greater in these patients.