Venovenous extracorporeal membrane oxygenation (VV-ECMO) is an effective lung protection strategy that avoids ventilator-induced lung injury. However, appropriate respiratory settings for VV-ECMO are yet to be established. This study aimed to elucidate the effects of ventilation under VV-ECMO using a newly developed rat VV-ECMO model and analyzed gene expression profiles.

Rats were assigned to three groups of five rats each: spontaneous breathing, conventional-protective ventilation, and ultra-protective ventilation. The conventional protective and ultraprotective ventilation groups received volume-controlled ventilation at a frequency of 60 and 20 beats/min, with tidal volumes of 6 and 3 mL/kg, respectively. VV-ECMO was performed at a pump flow rate of 20-30 mL/kg/min. At 120 min post initiation of VV-ECMO, rats were euthanized, and their lungs were harvested. Changes in gene expression were assessed using microarray analysis.

Gene expression profile analyses revealed lowest expression of inflammation/immune promotion, cytotoxicity, and cell proliferation related genes (Defa5, Prg2, Siglec8, Atf3, Rnd1, Ctsg, and Gc), and the highest expression of inflammation/immune suppression related genes (Pp2d1) in the spontaneous breathing group as compared to that in the other two mechanical ventilation groups.

The findings of this study demonstrated that spontaneous breathing was the least invasive respiratory setting under VV-ECMO. Further, mechanical ventilation may be associated with lung injury even at low ventilation frequency and tidal volume.

Mechanical power (MP) could serve as a valuable parameter in clinical practice to estimate the likelihood of adverse outcomes. However, the safety thresholds for MP in mechanical ventilation remain underexplored and contentious.

This study aims to investigate the association between MP and hospital mortality across varying degrees of lung disease severity, classified by Pao2/Fio2 ratios.

This is a retrospective cohort study using automatically extracted data. Patients admitted to the ICU of a tertiary referral hospital in The Netherlands between 2018 and 2024 and ventilated in pressure-controlled mode were included.

Logistic regression, adjusted for age, sex, Acute Physiology and Chronic Health Evaluation-IV score, and Pao2/Fio2 ratio, was used to calculate the odds ratio (OR) for all-cause in-hospital mortality.

A total of 2184 patients were analyzed, with a mean age of 62.5 ± 13.8 years, of whom 1508 (70.2%) were male. The mean MP was highest in patients with the lowest Pao2/Fio2 ratios (21.5 ± 6.5 J/min) compared with those with the highest ratios (12.0 ± 3.8 J/min; p < 0.001). Adjusted analyses revealed that increased MP was associated with higher mortality (OR, 1.06; 95% CI, 1.03-1.09 per J/min increase). Similarly, MP normalized for body weight showed a stronger association with mortality (OR, 1.004; 95% CI, 1.002-1.006 per J/min/kg increase). An increase in mortality was seen when MP exceeded 16-18 J/min.

Our findings demonstrate a significant association between MP and hospital mortality, even after adjusting for key confounders. Mortality increases notably when MP exceeds 16-18 J/min. Normalized MP presents an even stronger association with mortality. These results underscore the need for further research into ventilation strategies that consider MP adjustments.

Acute Respiratory Distress Syndrome (ARDS) necessitates personalized treatment strategies due to its heterogeneity, aiming to mitigate Ventilator-Induced Lung Injury (VILI). Advanced monitoring techniques, including imaging, driving pressure, transpulmonary pressure, and mechanical power, present potential avenues for tailored interventions.

To review some of the most important techniques for achieving greater personalization of mechanical ventilation in ARDS patients as evaluated in randomized clinical trials, by analyzing their effect on three clinically relevant aspects: mortality, ventilator-free days, and gas exchange.

Following PRISMA guidelines, we conducted a systematic review and meta-analysis of Randomized Clinical Trials (RCTs) involving adult ARDS patients undergoing personalized ventilation adjustments. Outcomes were mortality (primary end-point), ventilator-free days, and oxygenation improvement.

Among 493 identified studies, 13 RCTs (n = 1255) met inclusion criteria. No personalized ventilation strategy demonstrated superior outcomes compared to traditional protocols. Meta-analysis revealed no significant reduction in mortality with image-guided (RR 0.88, 95 % CI 0.70-1.11), driving pressure-guided (RR 0.61, 95 % CI 0.29-1.30), or transpulmonary pressure-guided (RR 0.85, 95 % CI 0.58-1.24) strategies. Ventilator-free days and oxygenation outcomes showed no significant differences.

Our study does not support the superiority of personalized ventilation techniques over traditional protocols in ARDS patients. Further research is needed to standardize ventilation strategies and determine their impact on mechanical ventilation outcomes.

Unregulated expiratory flow may contribute to ventilator-induced lung injury. The amount of energy dissipated into the lungs with tidal mechanical ventilation may be used to quantify potentially injurious ventilation. Previously reported devices for variable expiratory flow regulation (FLEX) require, either computer-controlled feedback, or an initial expiratory flow trigger. In this bench study we present a novel passive expiratory flow regulation device.

The device was tested using a commercially available mechanical ventilator with a range of settings (tidal volume 420 ml and 630 ml, max. inspiratory flow rate 30 L/min and 50 L/min, respiratory rate 10 min-1, positive end-expiratory pressure 5 cmH2O), and a test lung with six different combinations of compliance and resistance settings. The effectiveness of the device was evaluated for reduction in peak expiratory flow, expiratory time, mean airway pressure, and the reduction of tidal dissipated energy (measured as the area within the airway pressure-volume loop).

Maximal and minimal reduction in peak expiratory flow was from 97.18 ± 0.41 L/min to 25.82 ± 0.07 L/min (p < 0.001), and from 44.11 ± 0.42 L/min to 26.30 ± 0.06 L/min, respectively. Maximal prolongation in expiratory time was recorded from 1.53 ± 0.06 s to 3.64 ± 0.21 s (p < 0.001). As a result of the extended expiration, the maximal decrease in I:E ratio was from 1:1.15 ± 0.03 to 1:2.45 ± 0.01 (p < 0.001). The greatest increase in mean airway pressure was from 10.04 ± 0.03 cmH2O to 17.33 ± 0.03 cmH2O. Dissipated energy was significantly reduced with the device under all test conditions (p < 0.001). The greatest reduction in dissipated energy was from 1.74 ± 0.00 J to 0.84 ± 0.00 J per breath. The least reduction in dissipated energy was from 0.30 ± 0.00 J to 0.16 ± 0.00 J per breath. The greatest and least percentage reduction in dissipated energy was 68% and 33%, respectively.

The device bench tested in this study demonstrated a significant reduction in peak expiratory flow rate and dissipated energy, compared to ventilation with unregulated expiratory flow. Application of the device warrants further experimental and clinical evaluation.

An 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 acute respiratory distress syndrome (ARDS), including patients with COVID-19 (COVID-19-related acute respiratory distress syndrome (C-ARDS)) undergoing IMV, has not been rigorously evaluated. The use of emulations of a target trial in intensive care unit research remains in its infancy. To inform future, large ARDS target trials, we explored using a target trial emulation approach to analyse data from a cohort of IMV adults with C-ARDS to determine whether maintaining daily ∆p<15 cm H2O (in addition to traditional low tidal volume ventilation (LTVV) (tidal volume 5-7 cc/PBW+plateau pressure (Pplat) ≤30 cm H2O), compared with LTVV alone, affects the 28-day mortality.

To emulate a target trial, adults with C-ARDS requiring >24 hours of IMV were considered to be assigned to limited ∆P or LTVV. Lung mechanics were measured twice daily after ventilator setting adjustments were made. To evaluate the effect of each lung-protective ventilation (LPV) strategy on the 28-day mortality, we fit a stabilised inverse probability weighted marginal structural model that adjusted for baseline and time-varying confounders known to affect protection strategy use/adherence or survival.

Among the 92 patients included, 27 (29.3%) followed limited ∆P ventilation, 23 (25.0%) the LTVV strategy and 42 (45.7%) received no LPV strategy. The adjusted estimated 28-day survival was 47.0% (95% CI 23%, 76%) in the limited ∆P group, 70.3% in the LTVV group (95% CI 37.6%, 100%) and 37.6% (95% CI 20.8%, 58.0%) in the no LPV strategy group.

Limiting ∆P may not provide additional survival benefits for patients with C-ARDS over LTVV. Our results help inform the development of future target trial emulations focused on evaluating LPV strategies, including reduced ∆P, in adults with ARDS.

Ventilator-induced lung injury (VILI) is one of the severe complications in the clinic concerning mechanical ventilation (MV). Capsaicin (CAP) has anti-inflammatory and inhibitory effects on oxidative stress, which is a significant element causing cellular ferroptosis. Nevertheless, the specific role and potential mechanistic pathways through which CAP modulates ferroptosis in VILI remain elusive.

VILI was established in vivo, and the pulmonary epithelial cell injury model induced by circulation stretching (CS) was established in vitro. Both mice and cells were pretreated with CAP. Transmission electron microscopy, ELISA, Western blot, immunofluorescence, RT-PCR, fluorescent probes, and other experimental methods were used to clarify the relationship between iron death and VILI in alveolar epithelial cells, and whether capsaicin alleviates VILI by inhibiting iron death and its specific mechanism.

Ferroptosis was involved in VILI by utilizing in vivo models. CAP inhibited ferroptosis and alleviated VILI's lung damage and inflammation, and this protective effect of CAP was dependent on maintaining mitochondrial redox system through SITR3 signaling. In the CS-caused lung epithelial cell injury models, CAP reduced pathological CS-caused ferroptosis and cell injury. Knockdown SIRT3 reversed the role of CAP on the maintaining mitochondria dysfunction under pathological CS and eliminated its subsequent advantageous impacts for ferroptosis against overstretching cells.

The outcomes showed that CAP alleviated ferroptosis in VILI via improving the activity of SITR3 to suppressing mitochondrial oxidative damage and maintaining mitochondrial redox homeostasis, illustrating its possibility as a novel therapeutic goal for VILI.

To evaluate how the prone position influences mechanical power (MP) during elective surgical procedures.

In this prospective study carried out at Karadeniz Ereğli Government Hospital, Zonguldak, Turkey, from January 2024 to February 2024, 76 patients under general anesthesia were evaluated at different time points during the surgical procedure. Hemodynamic, laboratory, and mechanical ventilation data were also recorded.

The MP increased in the prone position at the beginning of surgery. Transitioning to the supine position at the end of surgery led to a decrease in MP. At the end of surgery, the mean MP in supine and prone positions was found to be higher compared to those measured in the first hour of surgery. Mechanical power and body mass index (BMI) exhibited a significant positive correlation.

Position changes influence MP. Returning to the prone position increases MP. An increase in BMI is associated with an increase in MP.ANZCTR Reg. No.: ACTRN12623001281684.

Mechanical power of ventilation, a summary parameter reflecting the energy transferred from the ventilator to the respiratory system, has associations with outcomes. INTELLiVENT-Adaptive Support Ventilation is an automated ventilation mode that changes ventilator settings according to algorithms that target a low work-and force of breathing. The study aims to compare mechanical power between automated ventilation by means of INTELLiVENT-Adaptive Support Ventilation and conventional ventilation in critically ill patients.

International, multicenter, randomized crossover clinical trial in patients that were expected to need invasive ventilation > 24 hours. Patients were randomly assigned to start with a 3-hour period of automated ventilation or conventional ventilation after which the alternate ventilation mode was selected. The primary outcome was mechanical power in passive and active patients; secondary outcomes included key ventilator settings and ventilatory parameters that affect mechanical power.

A total of 96 patients were randomized. Median mechanical power was not different between automated and conventional ventilation (15.8 [11.5-21.0] versus 16.1 [10.9-22.6] J/min; mean difference -0.44 (95%-CI -1.17 to 0.29) J/min; P = 0.24). Subgroup analyses showed that mechanical power was lower with automated ventilation in passive patients, 16.9 [12.5-22.1] versus 19.0 [14.1-25.0] J/min; mean difference -1.76 (95%-CI -2.47 to -10.34J/min; P < 0.01), and not in active patients (14.6 [11.0-20.3] vs 14.1 [10.1-21.3] J/min; mean difference 0.81 (95%-CI -2.13 to 0.49) J/min; P = 0.23).

In this cohort of unselected critically ill invasively ventilated patients, automated ventilation by means of INTELLiVENT-Adaptive Support Ventilation did not reduce mechanical power. A reduction in mechanical power was only seen in passive patients.

Clinicaltrials.gov (study identifier NCT04827927), April 1, 2021.

https://clinicaltrials.gov/study/NCT04827927?term=intellipower&rank=1.

Mechanical ventilation (MV) is an important strategy for improving the survival of patients with respiratory failure. However, MV is associated with aggravation of lung injury, with ventilator-induced lung injury (VILI) becoming a major concern. Thus, ventilation protection strategies have been developed to minimize complications from MV, with the goal of relieving excessive breathing workload, improving gas exchange, and minimizing VILI. By opting for lower tidal volumes, clinicians seek to strike a balance between providing adequate ventilation to support gas exchange and preventing overdistension of the alveoli, which can contribute to lung injury. Additionally, other factors play a role in optimizing lung protection during MV, including adequate positive end-expiratory pressure levels, to maintain alveolar recruitment and prevent atelectasis as well as careful consideration of plateau pressures to avoid excessive stress on the lung parenchyma.

Patients with acute exacerbation of lung fibrosis with usual interstitial pneumonia (EUIP) pattern are at increased risk for ventilator-induced lung injury (VILI) and mortality when exposed to mechanical ventilation (MV). Yet, lack of a mechanical model describing UIP-lung deformation during MV represents a research gap. Aim of this study was to develop a constitutive mathematical model for UIP-lung deformation during lung protective MV based on the stress-strain behavior and the specific elastance of patients with EUIP as compared to that of acute respiratory distress syndrome (ARDS) and healthy lung. Partitioned lung and chest wall mechanics were assessed for patients with EUIP and primary ARDS (1:1 matched based on body mass index and PaO2/FiO2 ratio) during a PEEP trial performed within 24 h from intubation. Patient's stress-strain curve and the lung specific elastance were computed and compared with those of healthy lungs, derived from literature. Respiratory mechanics were used to fit a novel mathematical model of the lung describing mechanical-inflation-induced lung parenchyma deformation, differentiating the contributions of elastin and collagen, the main components of lung extracellular matrix. Five patients with EUIP and 5 matched with primary ARDS were included and analyzed. Global strain was not different at low PEEP between the groups. Overall specific elastance was significantly higher in EUIP as compared to ARDS (28.9 [22.8-33.2] cmH2O versus 11.4 [10.3-14.6] cmH2O, respectively). Compared to ARDS and healthy lung, the stress/strain curve of EUIP showed a steeper increase, crossing the VILI threshold stress risk for strain values greater than 0.55. The contribution of elastin was prevalent at lower strains, while the contribution of collagen was prevalent at large strains. The stress/strain curve for collagen showed an upward shift passing from ARDS and healthy lungs to EUIP lungs. During MV, patients with EUIP showed different respiratory mechanics, stress-strain curve and specific elastance as compared to ARDS patients and healthy subjects and may experience VILI even when protective MV is applied. According to our mathematical model of lung deformation during mechanical inflation, the elastic response of UIP-lung is peculiar and different from ARDS. Our data suggest that patients with EUIP experience VILI with ventilatory setting that are lung-protective for patients with ARDS.

The incidence of acute respiratory insufficiency has continued to increase among patients admitted to modern-day cardiovascular intensive care units. Positive pressure ventilation (PPV) remains the mainstay of treatment for these patients. Alterations in intrathoracic pressure during PPV has distinct effects on both the right and left ventricles, affecting cardiovascular performance. Lung-protective ventilation (LPV) minimizes the risk of further lung injury through ventilator-induced lung injury and, hence, an understanding of LPV and its cardiopulmonary interactions is beneficial for cardiologists.

We investigated driving pressure (ΔP) and mechanical power (MP) and associations with clinical outcomes in critically ill patients ventilated for reasons other than ARDS.

Individual patient data analysis of a pooled database that included patients from four observational studies of ventilation. ΔP and MP were compared among invasively ventilated non-ARDS patients with sepsis, with pneumonia, and not having sepsis or pneumonia. The primary endpoint was ΔP; secondary endpoints included MP, ICU mortality and length of stay, and duration of ventilation.

This analysis included 372 (11%) sepsis patients, 944 (28%) pneumonia patients, and 2040 (61%) patients ventilated for any other reason. On day 1, median ΔP was higher in sepsis (14 [11-18] cmH2O) and pneumonia patients (14 [11-18]cmH2O), as compared to patients not having sepsis or pneumonia (13 [10-16] cmH2O) (P < 0.001). Median MP was also higher in sepsis and pneumonia patients. ΔP, as opposed to MP, was associated with ICU mortality in sepsis and pneumonia patients.

The intensity of ventilation differed between patients with sepsis or pneumonia and patients receiving ventilation for any other reason; ΔP was associated with higher mortality in sepsis and pneumonia patients.

This post hoc analysis was not registered; the individual studies that were merged into the used database were registered at clinicaltrials.gov: NCT01268410 (ERICC), NCT02010073 (LUNG SAFE), NCT01868321 (PRoVENT), and NCT03188770 (PRoVENT-iMiC).

Ventilator dyssynchrony may be associated with increased delivered tidal volumes (V t s) and dynamic transpulmonary pressure (ΔP L,dyn ), surrogate markers of lung stress and strain, despite low V t ventilation. However, it is unknown which types of ventilator dyssynchrony are most likely to increase these metrics or if specific ventilation or sedation strategies can mitigate this potential.

A prospective cohort analysis to delineate the association between ten types of breaths and delivered V t , ΔP L,dyn , and transpulmonary mechanical energy.

Patients admitted to the medical ICU.

Over 580,000 breaths from 35 patients with acute respiratory distress syndrome (ARDS) or ARDS risk factors.

None.

Patients received continuous esophageal manometry. Ventilator dyssynchrony was identified using a machine learning algorithm. Mixed-effect models predicted V t , ΔP L,dyn , and transpulmonary mechanical energy for each type of ventilator dyssynchrony while controlling for repeated measures. Finally, we described how V t , positive end-expiratory pressure (PEEP), and sedation (Richmond Agitation-Sedation Scale) strategies modify ventilator dyssynchrony's association with these surrogate markers of lung stress and strain. Double-triggered breaths were associated with the most significant increase in V t , ΔP L,dyn , and transpulmonary mechanical energy. However, flow-limited, early reverse-triggered, and early ventilator-terminated breaths were also associated with significant increases in V t , ΔP L,dyn , and energy. The potential of a ventilator dyssynchrony type to increase V t , ΔP L,dyn , or energy clustered similarly. Increasing set V t may be associated with a disproportionate increase in high-volume and high-energy ventilation from double-triggered breaths, but PEEP and sedation do not clinically modify the interaction between ventilator dyssynchrony and surrogate markers of lung stress and strain.

Double-triggered, flow-limited, early reverse-triggered, and early ventilator-terminated breaths are associated with increases in V t , ΔP L,dyn , and energy. As flow-limited breaths are more than twice as common as double-triggered breaths, further work is needed to determine the interaction of ventilator dyssynchrony frequency to cause clinically meaningful changes in patient outcomes.

Advanced respiratory monitoring encompasses a diverse range of mini- or noninvasive tools used to evaluate various aspects of respiratory function in patients experiencing acute respiratory failure, including those requiring extracorporeal membrane oxygenation (ECMO) support. Among these techniques, key modalities include esophageal pressure measurement (including derived pressures), lung and respiratory muscle ultrasounds, electrical impedance tomography, the monitoring of diaphragm electrical activity, and assessment of flow index. These tools play a critical role in assessing essential parameters such as lung recruitment and overdistention, lung aeration and morphology, ventilation/perfusion distribution, inspiratory effort, respiratory drive, respiratory muscle contraction, and patient-ventilator synchrony. In contrast to conventional methods, advanced respiratory monitoring offers a deeper understanding of pathological changes in lung aeration caused by underlying diseases. Moreover, it allows for meticulous tracking of responses to therapeutic interventions, aiding in the development of personalized respiratory support strategies aimed at preserving lung function and respiratory muscle integrity. The integration of advanced respiratory monitoring represents a significant advancement in the clinical management of acute respiratory failure. It serves as a cornerstone in scenarios where treatment strategies rely on tailored approaches, empowering clinicians to make informed decisions about intervention selection and adjustment. By enabling real-time assessment and modification of respiratory support, advanced monitoring not only optimizes care for patients with acute respiratory distress syndrome but also contributes to improved outcomes and enhanced patient safety.

To establish a new machine learning-based method to adjust positive end-expiratory pressure (PEEP) using only already routinely measured data.

Retrospective observational study.

Intensive care unit (ICU).

51811 mechanically ventilated patients in multiple ICUs in the USA (data from MIMIC-III and eICU databases).

No interventions.

Success parameters of ventilation (arterial partial pressures of oxygen and carbon dioxide and respiratory system compliance) RESULTS: The multi-tasking neural network model performed significantly best for all target tasks in the primary test set. The model predicts arterial partial pressures of oxygen and carbon dioxide and respiratory system compliance about 45 min into the future with mean absolute percentage errors of about 21.7%, 10.0% and 15.8%, respectively. The proposed use of the model was demonstrated in case scenarios, where we simulated possible effects of PEEP adjustments for individual cases.

Our study implies that machine learning approach to PEEP titration is a promising new method which comes with no extra cost once the infrastructure is in place. Availability of databases with most recent ICU patient data is crucial for the refinement of prediction performance.

Mechanical ventilation (MV) has played a crucial role in the medical field, particularly in anesthesia and in critical care medicine (CCM) settings. MV has evolved significantly since its inception over 70 years ago and the future promises even more advanced technology. In the past, ventilation was provided manually, intermittently, and it was primarily used for resuscitation or as a last resort for patients with severe respiratory or cardiovascular failure. The earliest MV machines for prolonged ventilatory support and oxygenation were large and cumbersome. They required a significant amount of skills and expertise to operate. These early devices had limited capabilities, battery, power, safety features, alarms, and therefore these often caused harm to patients. Moreover, the physiology of MV was modified when mechanical ventilators moved from negative pressure to positive pressure mechanisms. Monitoring systems were also very limited and therefore the risks related to MV support were difficult to quantify, predict and timely detect for individual patients who were necessarily young with few comorbidities. Technology and devices designed to use tracheostomies versus endotracheal intubation evolved in the last century too and these are currently much more reliable. In the present, positive pressure MV is more sophisticated and widely used for extensive period of time. Modern ventilators use mostly positive pressure systems and are much smaller, more portable than their predecessors, and they are much easier to operate. They can also be programmed to provide different levels of support based on evolving physiological concepts allowing lung-protective ventilation. Monitoring systems are more sophisticated and knowledge related to the physiology of MV is improved. Patients are also more complex and elderly compared to the past. MV experts are informed about risks related to prolonged or aggressive ventilation modalities and settings. One of the most significant advances in MV has been protective lung ventilation, diaphragm protective ventilation including noninvasive ventilation (NIV). Health care professionals are familiar with the use of MV and in many countries, respiratory therapists have been trained for the exclusive purpose of providing safe and professional respiratory support to critically ill patients. Analgo-sedation drugs and techniques are improved, and more sedative drugs are available and this has an impact on recovery, weaning, and overall patients' outcome. Looking toward the future, MV is likely to continue to evolve and improve alongside monitoring techniques and sedatives. There is increasing precision in monitoring global "patient-ventilator" interactions: structure and analysis (asynchrony, desynchrony, etc). One area of development is the use of artificial intelligence (AI) in ventilator technology. AI can be used to monitor patients in real-time, and it can predict when a patient is likely to experience respiratory distress. This allows medical professionals to intervene before a crisis occurs, improving patient outcomes and reducing the need for emergency intervention. This specific area of development is intended as "personalized ventilation." It involves tailoring the ventilator settings to the individual patient, based on their physiology and the specific condition they are being treated for. This approach has the potential to improve patient outcomes by optimizing ventilation and reducing the risk of harm. In conclusion, MV has come a long way since its inception, and it continues to play a critical role in anesthesia and in CCM settings. Advances in technology have made MV safer, more effective, affordable, and more widely available. As technology continues to improve, more advanced and personalized MV will become available, leading to better patients' outcomes and quality of life for those in need.

Describe the rationale for concern and accumulating pathophysiologic evidence regarding the adverse effects of high-level positive end expiratory pressure (PEEP) on excessive mechanical stress and ventilator-induced lung injury (VILI).

Although the inclusion of PEEP in numerical estimates of mechanical power may be theoretically debated, its potential to increase stress, strain, and mean airway pressure are not. Recent laboratory data in a variety of animal models demonstrate that higher levels of PEEP coupled with additional fluids needed to offset its impediment of hemodynamic function are associated with increased VILI. Moreover, counteracting end-tidal hyperinflation by external chest wall pressure may paradoxically improve respiratory mechanics, indicating that lower PEEP helps protect the small 'baby lung' of advanced acute respiratory distress syndrome (ARDS).

The potentially adverse effects of PEEP on VILI can be considered in three broad categories. First, the contribution of PEEP to total mechanical energy expressed through mechanical power, raised mean airway pressure, and end-tidal hyperinflation; second, the hemodynamic consequences of altered cardiac loading, heightened pulmonary vascular stress and total lung water; and third, the ventilatory consequences of compromised carbon dioxide eliminating efficiency. Minimizing ventilation demands, optimized body positioning and care to avoid unnecessary PEEP are central to lung protection in all stages of ARDS.

Recruitment maneuvers with subsequent positive-end-expiratory-pressure (PEEP) have proven effective in recruiting lung volume and preventing alveoli collapse. However, determining a safe, effective, and patient-specific PEEP is not standardized, and this more optimal PEEP level evolves with patient condition, requiring personalised monitoring and care approaches to maintain optimal ventilation settings.

This research examines 3 physiologically relevant basis function sets (exponential, parabolic, cumulative) to enable better prediction of elastance evolution for a virtual patient or digital twin model of MV lung mechanics, including novel elements to model and predict distension elastance. Prediction accuracy and robustness are validated against recruitment maneuver data from 18 volume-controlled ventilation (VCV) patients at 7 different baseline PEEP levels (0 to 12 cmH2O) and 14 pressure-controlled ventilation (PCV) patients at 4 different baseline PEEP levels (6 to 12 cmH2O), yielding 623 and 294 prediction cases, respectively. Predictions were made up to 12 cmH2O of added PEEP ahead, covering 6 × 2 cmH2O PEEP steps.

The 3 basis function sets yield median absolute peak inspiratory pressure (PIP) prediction error of 1.63 cmH2O for VCV patients, and median peak inspiratory volume (PIV) prediction error of 0.028 L for PCV patients. The exponential basis function set yields a better trade-off of overall performance across VCV and PCV prediction than parabolic and cumulative basis function sets from other studies. Comparing predicted and clinically measured distension prediction in VCV demonstrated consistent, robust high accuracy with R2 = 0.90-0.95.

The results demonstrate recruitment mechanics are best captured by an exponential basis function across different mechanical ventilation modes, matching physiological expectations, and accurately capture, for the first time, distension mechanics to within 5-10 % accuracy. Enabling the risk of lung injury to be predicted before changing ventilator settings. The overall outcomes significantly extend and more fully validate this digital twin or virtual mechanical ventilation patient model.

Mechanical ventilation, a critical support strategy for individuals enduring severe respiratory failure and general anesthesia, paradoxically engenders ventilator-induced lung injury (VILI). Ferrostatin-1 mitigates lung injury via ferroptosis inhibition, yet the specific ferroptosis genes contributing significantly to VILI remain obscure.

Leveraging the Gene Expression Omnibus database, we acquired VILI-associated datasets and identified differentially expressed genes (DEGs). To identify the hub genes, we constructed a protein-protein interaction network and used three parameters from CytoHubba. Consequently, we identified hub genes and ferroptosis genes as ferroptosis hub genes for VILI (VFHGs). We conducted enrichment analysis and established receiver operating characteristic (ROC) curves for VFHGs. Subsequently, to confirm the correctness of the VFHGs, control group mice and VILI mouse models, as well as external dataset validation, were established. For further research, a gene-miRNA network was established. Finally, the CIBERSORT algorithm was used to fill the gap in the immune infiltration changes in the lung during VILI.

We identified 64 DEGs and 4 VFHGs (Il6,Ptgs2,Hmox1 and Atf3) closely related to ferroptosis. ROC curves demonstrated the excellent diagnostic performance of VFHGs in VILI. PCR and external dataset validation of the VILI model demonstrated the accuracy of VFHGs. Subsequently, the gene-miRNA network was successfully established. Ultimately, an Immune cell infiltration analysis associated with VILI was generated.

The results emphasize the importance of 4 VFHGs and their involvement in ferroptosis in VILI, confirming their potential as diagnostic biomarkers for VILI.

Acute respiratory distress syndrome (ARDS) alters the dynamics of lung inflation during mechanical ventilation. Repetitive alveolar collapse and expansion (RACE) predisposes the lung to ventilator-induced lung injury (VILI). Two broad approaches are currently used to minimize VILI: (1) low tidal volume (LVT) with low-moderate positive end-expiratory pressure (PEEP); and (2) open lung approach (OLA). The LVT approach attempts to protect already open lung tissue from overdistension, while simultaneously resting collapsed tissue by excluding it from the cycle of mechanical ventilation. By contrast, the OLA attempts to reinflate potentially recruitable lung, usually over a period of seconds to minutes using higher PEEP used to prevent progressive loss of end-expiratory lung volume (EELV) and RACE. However, even with these protective strategies, clinical studies have shown that ARDS-related mortality remains unacceptably high with a scarcity of effective interventions over the last two decades. One of the main limitations these varied interventions demonstrate to benefit is the observed clinical and pathologic heterogeneity in ARDS. We have developed an alternative ventilation strategy known as the Time Controlled Adaptive Ventilation (TCAV) method of applying the Airway Pressure Release Ventilation (APRV) mode, which takes advantage of the heterogeneous time- and pressure-dependent collapse and reopening of lung units. The TCAV method is a closed-loop system where the expiratory duration personalizes VT and EELV. Personalization of TCAV is informed and tuned with changes in respiratory system compliance (CRS) measured by the slope of the expiratory flow curve during passive exhalation. Two potentially beneficial features of TCAV are: (i) the expiratory duration is personalized to a given patient's lung physiology, which promotes alveolar stabilization by halting the progressive collapse of alveoli, thereby minimizing the time for the reopened lung to collapse again in the next expiration, and (ii) an extended inspiratory phase at a fixed inflation pressure after alveolar stabilization gradually reopens a small amount of tissue with each breath. Subsequently, densely collapsed regions are slowly ratcheted open over a period of hours, or even days. Thus, TCAV has the potential to minimize VILI, reducing ARDS-related morbidity and mortality.

Mechanical power (MP) is the total energy released into the entire respiratory system per minute which mainly comprises three components: elastic static power, Elastic dynamic power and resistive power. However, the energy to overcome resistance to the gas flow is not the key factor in causing lung injury, but the elastic power (EP) which generates the baseline stretch of the lung fibers and overcomes respiratory system elastance may be closely related to the ARDS severity. Thus, this study aimed to investigate whether EP is superior to other ventilator variables for predicting the severity of lung injury in ARDS patients.

We retrieved patient data from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The retrieved data involved adults (≥ 18 years) diagnosed with ARDS and subjected to invasive mechanical ventilation for ≥ 48 h. We employed univariate and multivariate logistic regression analyses to investigate the correlation between EP and development of moderate-severe ARDS. Furthermore, we utilized restricted cubic spline models to assess whether there is a linear association between EP and incidence of moderate-severe ARDS. In addition, we employed a stratified linear regression model and likelihood ratio test in subgroups to identify potential modifications and interactions.

Moderate-severe ARDS occurred in 73.4% (296/403) of the patients analyzed. EP and MP were significantly associated with moderate-severe ARDS (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.15-1.28, p < 0.001; and OR 1.15, 95%CI 1.11-1.20, p < 0.001; respectively), but EP showed a higher area-under-curve (95%CI 0.72-0.82, p < 0.001) than plateau pressure, driving pressure, and static lung compliance in predicting ARDS severity. The optimal cutoff value for EP was 14.6 J/min with a sensitivity of 75% and specificity of 66%. Quartile analysis revealed that the relationship between EP and ARDS severity remained robust and reliable in subgroup analysis.

EP is a good ventilator variable associated with ARDS severity and can be used for grading ARDS severity. Close monitoring of EP is advised in patients undergoing mechanical ventilation. Additional experimental trials are needed to investigate whether adjusting ventilator variables according to EP can yield significant improvements in clinical outcomes.

The decision to intubate and ventilate a patient is mainly clinical. Both delaying intubation (when needed) and unnecessarily invasively ventilating (when it can be avoided) are harmful. We recently developed an algorithm predicting respiratory failure and invasive mechanical ventilation in COVID-19 patients. This is an internal validation study of this model, which also suggests a categorized "time-weighted" model.

We used a dataset of COVID-19 patients who were admitted to Rabin Medical Center after the algorithm was developed. We evaluated model performance in predicting ventilation, regarding the actual endpoint of each patient. We further categorized each patient into one of four categories, based on the strength of the prediction of ventilation over time. We evaluated this categorized model performance regarding the actual endpoint of each patient.

881 patients were included in the study; 96 of them were ventilated. AUC of the original algorithm is 0.87-0.94. The AUC of the categorized model is 0.95.

A minor degradation in the algorithm accuracy was noted in the internal validation, however, its accuracy remained high. The categorized model allows accurate prediction over time, with very high negative predictive value.

The exposure of blood to the artificial circuit during extracorporeal membrane oxygenation (ECMO) can induce an inflammatory response. C-reactive protein (CRP) is a commonly used biomarker of systemic inflammation.

In this retrospective observational study, we analyzed results of daily plasma CRP measurements in 110 critically ill patients, treated with ECMO. We compared CRP levels during the first 5 days of ECMO operation, between different groups of patients according to ECMO configurations, Coronavirus disease 2019 (COVID-19) status, and mechanical ventilation parameters.

There was a statistically significant decrease in CRP levels during the first 5 days of veno-venous (VV) ECMO (173 ± 111 mg/L, 154 ± 107 mg/L, 127 ± 97 mg/L, 114 ± 100 mg/L and 118 ± 90 mg/L for days 1-5 respectively, p < 0.001). Simultaneously, there was a significant reduction in ventilatory parameters, as represented by the mechanical power (MP) calculation, from 24.02 ± 14.53 J/min to 6.18 ± 4.22 J/min within 3 h of VV ECMO initiation (p < 0.001). There was non-significant trend of increase in CRP level during the first 5 days of veno arterial (VA) ECMO (123 ± 80 mg/L, 179 ± 91 mg/L, 203 ± 90 mg/L, 179 ± 95 mg/L and 198 ± 93 for days 1-5 respectively, p = 0.126) and no significant change in calculated MP (from 14.28 ± 8.56 J/min to 10.81 ± 8.09 J/min within 3 h if ECMO initiation, p = 0.071).

We observed a significant decrease in CRP levels during the first 5 days of VV ECMO support, and suggest that the concomitant reduction in ventilatory MP may have mitigated the degree of alveolar stress and strain that could have contributed to a decrease in the systemic inflammatory process.

The oxygen saturation index (OSI), defined by FIO2/SpO2 multiplied by the mean airway pressure, has been reported to exceed the Berlin definition in predicting the mortality of acute respiratory distress syndrome (ARDS). The OSI has served as an alternative to the Berlin definition in categorizing pediatric ARDS. However, the use of the OSI for the stratification of adult ARDS has not been reported. A total of 379 invasively ventilated adult ARDS patients were retrospectively studied. The ARDS patients were classified into three groups by their incidence rate of mortality: mild (OSI < 14.69), moderate (14.69 < OSI < 23.08) and severe (OSI > 23.08). OSI-based categorization was highly correlated with the Berlin definition by a Kendall's tau of 0.578 (p < 0.001). The Kaplan-Meier curves of the three OSI-based groups were significantly different (p < 0.001). By the Berlin definition, the hazard ratio for 28-day mortality was 0.58 (0.33-1.05) and 0.95 (0.55-1.67) for the moderate and severe groups, respectively (compared to the mild group). In contrast, the corresponding hazard ratio was 1.01 (0.69-1.47) and 2.39 (1.71-3.35) for the moderate and severe groups defined by the OSI. By multivariate analysis, OSI-based severe ARDS was independently associated with 28-D or 90-D mortality. In conclusion, we report the first OSI-based stratification for adult ARDS and find that it serves well as an alternative to the Berlin definition.

To explore the predictive value of the new comprehensive respiratory mechanics parameters elastic power (EP) and elastic power normalized to the compliance (Cst-EP) in the evaluation of the severity and 28-day prognosis of ARDS patients.

The MIMIC-III database was used to identify ARDS patients under invasive mechanical ventilation for at least 48 h. Their baseline data and ventilatory variables were collected. EP, elastic energy, driving pressure and mechanical power were calculated according to the corresponding formulas. Their value in assessing the severity of ARDS was evaluated. The correlation between Cst-EP and 28-day prognosis of ARDS patients was analyzed.

EP was independently associated with the severity of the ARDS and the odds ratio (OR) was 1.301 [95% CI (1.190-1.423), p < 0.001]. It has higher accuracy for the severity of ARDS, with an optimal cut-off value of 14.6 J/min. The Cst-EP was significantly associated with increased risk of death and the hazard ratio (HR) per 100 J/min × cmH2O/ml × 10-3 was 1.169 [95% CI (1.093-1.250), p < 0.001]. In addition, the 28-day cumulative survival rate of the high Cst-EP group was significantly lower than that of the low Cst-EP group.

EP can be used to predict the severity of ARDS, and Cst-EP is associated with mortality during controlled mechanical ventilation in ARDS.

The effort to minimize VILI risk must be multi-pronged. The need to adequately ventilate, a key determinant of hazardous power, is reduced by judicious permissive hypercapnia, reduction of innate oxygen demand, and by prone body positioning that promotes both efficient pulmonary gas exchange and homogenous distributions of local stress. Modifiable ventilator-related determinants of lung protection include reductions of tidal volume, plateau pressure, driving pressure, PEEP, inspiratory flow amplitude and profile (using longer inspiration to expiration ratios), and ventilation frequency. Underappreciated conditional cofactors of importance to modulate the impact of local specific power may include lower vascular pressures and blood flows. Employed together, these measures modulate ventilation power with the intent to avoid VILI while achieving clinically acceptable targets for pulmonary gas exchange.

Mechanical ventilation (MV) provides basic organ support for patients who have acute hypoxemic respiratory failure, with acute respiratory distress syndrome as the most severe form. The use of excessive ventilation forces can exacerbate the lung condition and lead to ventilator-induced lung injury (VILI); mechanical energy (ME) or power can characterize such forces applied during MV. The ME metric combines all MV parameters affecting the respiratory system (ie, lungs, chest, and airways) into a single value. Besides evaluating the overall ME, this parameter can be also related to patient-specific characteristics, such as lung compliance or patient weight, which can further improve the value of ME for characterizing the aggressiveness of lung ventilation. High ME is associated with poor outcomes and could be used as a prognostic parameter and indicator of the risk of VILI. ME is rarely determined in everyday practice because the calculations are complicated and based on multiple equations. Although low ME does not conclusively prevent the possibility of VILI (eg, due to the lung inhomogeneity and preexisting damage), individualization of MV settings considering ME appears to improve outcomes. This article aims to review the roles of bedside assessment of mechanical power, its relevance in mechanical ventilation, and its associations with treatment outcomes. In addition, we discuss methods for ME determination, aiming to propose the most suitable method for bedside application of the ME concept in everyday practice.

The driving pressure (ΔP) has an independent association with outcome in patients with acute respiratory distress syndrome (ARDS). INTELLiVENT-Adaptive Support Ventilation (ASV) is a closed-loop mode of ventilation that targets the lowest work and force of breathing.

To compare transpulmonary and respiratory system ΔP between closed-loop ventilation and conventional pressure controlled ventilation in patients with moderate-to-severe ARDS.

Single-center randomized cross-over clinical trial in patients in the early phase of ARDS. Patients were randomly assigned to start with a 4-h period of closed-loop ventilation or conventional ventilation, after which the alternate ventilation mode was selected. The primary outcome was the transpulmonary ΔP; secondary outcomes included respiratory system ΔP, and other key parameters of ventilation.

Thirteen patients were included, and all had fully analyzable data sets. Compared to conventional ventilation, with closed-loop ventilation the median transpulmonary ΔP with was lower (7.0 [5.0-10.0] vs. 10.0 [8.0-11.0] cmH₂O, mean difference - 2.5 [95% CI - 2.6 to - 2.1] cmH₂O; P = 0.0001). Inspiratory transpulmonary pressure and the respiratory rate were also lower. Tidal volume, however, was higher with closed-loop ventilation, but stayed below generally accepted safety cutoffs in the majority of patients.

In this small physiological study, when compared to conventional pressure controlled ventilation INTELLiVENT-ASV reduced the transpulmonary ΔP in patients in the early phase of moderate-to-severe ARDS. This closed-loop ventilation mode also led to a lower inspiratory transpulmonary pressure and a lower respiratory rate, thereby reducing the intensity of ventilation. Trial registration Clinicaltrials.gov, NCT03211494, July 7, 2017. https://clinicaltrials.gov/ct2/show/NCT03211494?term=airdrop&draw=2&rank=1 .

The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.

Changing trunk inclination affects lung function in patients with ARDS. However, its impacts on PEEP titration remain unknown. The primary aim of this study was to assess, in mechanically ventilated patients with COVID-19 ARDS, the effects of trunk inclination on PEEP titration. The secondary aim was to compare respiratory mechanics and gas exchange in the semi-recumbent (40° head-of-the-bed) and supine-flat (0°) positions following PEEP titration.

Twelve patients were positioned both at 40° and 0° trunk inclination (randomized order). The PEEP associated with the best compromise between overdistension and collapse guided by Electrical Impedance Tomography (PEEPEIT) was set. After 30 min of controlled mechanical ventilation, data regarding respiratory mechanics, gas exchange, and EIT parameters were collected. The same procedure was repeated for the other trunk inclination.

PEEPEIT was lower in the semi-recumbent than in the supine-flat position (8 ± 2 vs. 13 ± 2 cmH2O, p < 0.001). A semi-recumbent position with optimized PEEP resulted in higher PaO2:FiO2 (141 ± 46 vs. 196 ± 99, p = 0.02) and a lower global inhomogeneity index (46 ± 10 vs. 53 ± 11, p = 0.008). After 30 min of observation, a loss of aeration (measured by EIT) was observed only in the supine-flat position (-153 ± 162 vs. 27 ± 203 mL, p = 0.007).

A semi-recumbent position is associated with lower PEEPEIT and results in better oxygenation, less derecruitment, and more homogenous ventilation compared to the supine-flat position.

Respiratory failure occurs with some frequency in seriously burned patients, driven by a combination of inflammatory and infection factors. Inhalation injury contributes to respiratory failure in some burn patients via direct mucosal injury and indirect inflammation. In burn patients, respiratory failure leading to acute respiratory distress syndrome, with or without inhalation injury, is effectively managed using principles evolved for non-burn critically ill patients.

Adults and children who require extracorporeal membrane oxygenation for respiratory failure remain at risk for ongoing lung injury if ventilator management is not optimized. This review serves as a guide to assist the bedside clinician in ventilator titration for patients on extracorporeal membrane oxygenation, with a focus on lung-protective strategies. Existing data and guidelines for extracorporeal membrane oxygenation ventilator management are reviewed, including non-conventional ventilation modes and adjunct therapies.

Supraglottic airway (SGA) may have advantages over endotracheal tube (ETT) regarding laryngospasm, coughing, sore throat, and hemodynamic changes; however, studies on the use of SGA in laparoscopic donor nephrectomy (LDN) are lacking. Here, we aimed to confirm the safety and feasibility of second-generation SGA in LDN and compare them with those of ETT. Enrolled adult donors (aged > 18 years) who underwent LDN between August 2018 and November 2021 were divided into two groups-ETT vs. SGA. Airway pressure, lung compliance, desaturation, and hypercapnia were recorded during surgery. After propensity score matching for baseline characteristics and surgical duration, 82 and 152 donors were included in the ETT and SGA groups, respectively, and their outcomes were compared. The peak airway pressure was lower in the SGA group than in the ETT group 5 min after pneumoperitoneum. Dynamic lung compliance was higher in the SGA group than in the ETT group during surgery. There were no cases of intraoperative desaturation, hypercapnia, or postoperative aspiration pneumonitis. The use of second-generation SGA, a safe alternative to ETT for LDN, resulted in reduced airway resistance and increased lung compliance, which suggests its benefits for airway management in kidney donors.

The aim of this study was to assess the safety and efficacy of 2 protocols for automatic lung recruitment maneuvers (LRMs) using stepwise increases in PEEP in a neonatal ARDS model. These protocols were designed with lower maximum opening pressures than traditional methods and differ each one in the duration of the opening phases (short vs prolonged). We described hemodynamic changes through invasive monitoring, and we analyzed if the behavior of the variables depends on the duration of the opening phase of the LRM.

We designed a prospective, experimental study with 10 Landrace x Large White pigs < 48 h old. Under general anesthesia, tracheal intubation, invasive hemodynamic monitoring with a pediatric arterial thermodilution catheter was performed. An ARDS model was developed with bronchoalveolar lavages. Two types of LRMs were performed in each piglet, with a maximum peak inspiratory pressure (PIP) of 30 cm H2O and a PEEP 15 cm H2O applied during 8.5 s in the short LRM and 17 s in the prolonged LRM. A comparative analysis by virtue of the Wilcoxon signed-rank test and a regression analysis using generalized estimation equation were performed.

We found that both LRMs were effective regarding oxygenation and respiratory mechanics. Shortening the duration of the opening phase and lowering the maximum opening pressures to PIP 30 and PEEP 15 cm H2O were above the critical opening pressure to reverse alveolar collapse in our neonatal ARDS model. Although we observed hemodynamic variations during both types of LRMs, these were well tolerated.

Our LRM protocols exceeded critical opening pressures to reverse alveolar collapse in our neonatal ARDS model. This range of pressures might involve less hemodynamic disturbance. Duration of the maximum opening pressure step is a determining factor for hemodynamic alterations.

Prolonged high flow nasal oxygen (HFNO) application might delay intubation and increase mortality in acute hypoxemic respiratory failure (AHRF) patients. Intubation in coronavirus disease 2019 (COVID-19) AHRF (CAHRF) patients 24 to 48 hours after HFNO initiation has been associated with increased mortality in previous studies. This cut-off period is variable in previous studies. A time series analysis could reflect more robust data on outcome in relation to HFNO duration before intubation in CAHRF.

A retrospective study was conducted at 30-bedded ICU of a tertiary care teaching hospital from July 2020 to August 2021. The study cohort comprised 116 patients who required HFNO and were subsequently intubated following HFNO failure. A time series analysis of patient outcomes on each day of HFNO application prior to invasive mechanical ventilation (IMV) was done.

ICU and hospital mortality was 67.2%. Beyond day 4 of HFNO application, there was a trend towards increased risk-adjusted ICU and hospital mortality for each day delay in intubation of CAHRF patients on HFNO [OR 2.718; 95% CI 0.957-7.721; P 0.061]. This trend was maintained till day 8 of HFNO application, after which there was 100% mortality. Taking day four as a cut-off in the timeline of HFNO application, we have observed an absolute mortality benefit of 15% with early intubation despite a higher APACHE-IV score than the late intubation group.

IMV beyond the 4^th day of HFNO initiation in CAHRF patients increases mortality.

In on-pump cardiac surgery, lungs are at high risk of periprocedural organ impairment because of atelectasis formation, ventilator-induced lung injury, and hyperinflammation due to the cardiopulmonary bypass which results in postoperative pulmonary complications in half of this patient population. The new ventilation mode flow-controlled ventilation (FCV) uniquely allows full control of ins- and expiratory airway flows. This approach reduces the mechanical power of invasive ventilation as a possible cause of ventilator-induced lung injury. The scope of FLOWVENTIN HEARTSURG is to compare perioperative individualized FCV with best clinical practice pressure-controlled ventilation (PVC) modes in patients with elective on-pump cardiac surgery procedures. We hypothesize that the postoperative inflammatory response can be reduced by the perioperative application of FCV compared to PCV.

FLOWVENTIN HEARTSURG is a single-center, randomized, parallel-group trial with two intervention arms: perioperative PCV modes (n = 70, PCV group) with an individualized positive end-expiratory pressure (PEEP) and a tidal volume of 6-8 ml/kg predicted bodyweight compared to perioperative FCV (n = 70, FCV group) with an individualized PEEP and driving pressure, resulting in a liberal tidal volume. As the primary study endpoint interleukin 8 plasma level is assessed 6 h after cardiopulmonary bypass as a surrogate biomarker of systemic and pulmonary inflammation. As secondary aims clinically relevant patient outcomes are analyzed, e.g., perioperative lung function regarding oxygenation indices, postoperative pulmonary and extra-pulmonary complications, SIRS-free days as well as ICU and total inpatient stays. As additional sub-studies with an exploratory approach perioperative right ventricular function parameters are assessed by echocardiography and perioperative lung aeration by electrical impedance tomography.

Current paradigms regarding protective low tidal volume ventilation are consciously left in the FCV intervention group in order to reduce mechanical power as a determinant of ventilator-induced lung injury in this high-risk patient population and procedures. This approach will be compared in a randomized controlled trial with current best clinical practice PCV in FLOWVENTIN HEARTSURG.

German Clinical Trials Register DRKS00018956 . Registered on 12 June 2020 (Version 1), last update on 22 August 2022 (Version 4).

We compared the effects of pressure-controlled volume-guaranteed ventilation (PCV) and volume-controlled ventilation (VCV) on respiratory mechanics and mechanical power (MP) in elderly patients undergoing laparoscopy. Fifty patients aged 65-80 years scheduled for laparoscopic cholecystectomy were randomly assigned to either the VCV group (n = 25) or the PCV group (n = 25). The ventilator had the same settings in both modes. The change in MP over time was insignificant between the groups (p = 0.911). MP significantly increased during pneumoperitoneum in both groups compared with anesthesia induction (IND). The increase in MP from IND to 30 min after pneumoperitoneum (PP30) was not different between the VCV and PCV groups. The change in driving pressure (DP) over time were significantly different between the groups during surgery, and the increase in DP from IND to PP30 was significantly higher in the VCV group than in the PCV group (both p = 0.001). Changes in MP during PCV and VCV were similar in elderly patients, and MP increased significantly during pneumoperitoneum in both groups. However, MP did not reach clinical significance (≥12 J/min). In contrast, the PCV group had a significantly lower increase in DP after pneumoperitoneum than the VCV group.