Correlation between normally aerated lung and respiratory system compliance at clinical high positive end-expiratory pressure in patients with COVID-19.

Normally aerated lung tissue on computed tomography (CT) is correlated with static respiratory system compliance (Crs) at zero end-expiratory pressure. In clinical practice, however, patients with acute respiratory failure are often managed using elevated PEEP levels. No study has validated the relationship between lung volume and tissue and Crs at the applied positive end-expiratory pressure (PEEP). Therefore, this study aimed to demonstrate the relationship between lung volume and tissue on CT and Crs during the application of PEEP for the clinical management of patients with acute respiratory distress syndrome due to COVID-19. Additionally, as a secondary outcome, the study aimed to evaluate the relationship between CT characteristics and Crs, considering recruitability using the recruitment-to-inflation ratio (R/I ratio). We analyzed the CT and respiratory mechanics data of 30 patients with COVID-19 who were mechanically ventilated. The CT images were acquired during mechanical ventilation at PEEP level of 15 cmH2O and were quantitatively analyzed using Synapse Vincent system version 6.4 (Fujifilm Corporation, Tokyo, Japan). Recruitability was stratified into two groups, high and low recruitability, based on the median R/I ratio of our study population. Thirty patients were included in the analysis with the median R/I ratio of 0.71. A significant correlation was observed between Crs at the applied PEEP (median 15 [interquartile range (IQR) 12.2, 15.8]) and the normally aerated lung volume (r = 0.70 [95% CI 0.46-0.85], P < 0.001) and tissue (r = 0.70 [95% CI 0.46-0.85], P < 0.001). Multivariable linear regression revealed that recruitability (Coefficient = - 390.9 [95% CI - 725.0 to - 56.8], P = 0.024) and Crs (Coefficient = 48.9 [95% CI 32.6-65.2], P < 0.001) were significantly associated with normally aerated lung volume (R-squared: 0.58). In this study, Crs at the applied PEEP was significantly correlated with normally aerated lung volume and tissue on CT. Moreover, recruitability indicated by the R/I ratio and Crs were significantly associated with the normally aerated lung volume. This research underscores the significance of Crs at the applied PEEP as a bedside-measurable parameter and sheds new light on the link between recruitability and normally aerated lung.

Is there a connection between spine alignment, chest mobility, shoulder joint and respiratory parameters of patients with ankylosing spondylitis?

INTRODUCTION: Ankylosing spondylitis is chronic progressive disease, which decrease functions of musculoskeletal system including chest area. Those changes influences respiratory mechanics, worsen conditions of proper ventilation of lungs. OBJECTIVES: Rating of functional and respiratory parameters and dependence between them at patients with ankylosing spondylitis. MATERIALS & METHODS: The study included 45 patients with diagnosed ankylosing spondylitis. Chest and upper limbs mobility, resting spinal curvature alignment were assessed, and respiratory parameters were measured in a plethysmographic chamber JAGGER MasterScreen Body. RESULTS: Ankylosing spondylitis patients had lower respiratory parameters especially sReff, and FRC. Restriction of chest and upper limbs mobility was also demonstrated. Forward head extension was observed based on the occipital wall test. Correlations between functional parameters and correlations between functional and respiratory parameters were shown, in particular MIP, MEP, sReff, Rtot, TLC, ERV. CONCLUSIONS: The study confirmed a decrease in functional and respiratory parameters in the examined patients with ankylosing spondylitis compared to the applicable standards. A significant relationship was found between functional parameters in the upper body and respiratory parameters, which worsen with increasing thoracic dysfunction. The obtained results indicate the directions of therapy that should be taken into account to improve respiratory parameters and reduce respiratory dysfunction in these patients. Chest-focused physiotherapy appears to be an important element in improving function in patients with ankylosing spondylitis.

Stress-strain curve and elastic behavior of the fibrotic lung with usual interstitial pneumonia pattern during protective mechanical ventilation.

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.

Measurement of thoraco-abdominal synchrony using respiratory inductance plethysmography: technical aspects and a proposal to overcome its limitations.

BACKGROUND: Thoraco-abdominal asynchrony (TAA) is usually assessed by respiratory inductance plethysmography. The main parameter used for its assessment is the calculation of the phase angle based on Lissajous plots. However, there are some mathematical limitations to its use. RESEARCH DESIGN AND METHODS: Sequences of five breaths were selected from a) normal subjects, b) COPD patients, both at rest and during exercise, and c) patients with obstructive apnea syndrome. Automated analysis was performed calculating phase angle, loop rotation (clockwise or counterclockwise), global phase delay and loop area. TAA severity was estimated quantitatively and in subgroups. RESULTS: 2290 cycles were analyzed (55% clockwise rotation). Phase angle ranged from -86.90 to + 88.4 degrees, while global phase delay ranged from -179.75 to + 178.54. Despite a good correlation with global phase delay (p < 0.01, ANOVA test), phase angle and loop area were not able to correctly classify breaths with severe deviation and paradoxical movements (p=ns, Bonferroni post hoc test). CONCLUSIONS: Global phase delay covers the whole spectrum of TAA situations in a single value. It may be a relevant parameter for diagnosis and follow-up of clinical conditions leading to TAA. CLINICAL TRIAL REGISTRATION: The trial from which the traces were obtained was registered at ClinicalTrials.gov ;(identifier: NCT04597606).

Differential Effects of Intra-Abdominal Hypertension and ARDS on Respiratory Mechanics in a Porcine Model.

Background and Objectives: Intra-abdominal hypertension (IAH) and acute respiratory distress syndrome (ARDS) are common concerns in intensive care unit patients with acute respiratory failure (ARF). Although both conditions lead to impairment of global respiratory parameters, their underlying mechanisms differ substantially. Therefore, a separate assessment of the different respiratory compartments should reveal differences in respiratory mechanics. Materials and Methods: We prospectively investigated alterations in lung and chest wall mechanics in 18 mechanically ventilated pigs exposed to varying levels of intra-abdominal pressures (IAP) and ARDS. The animals were divided into three groups: group A (IAP 10 mmHg, no ARDS), B (IAP 20 mmHg, no ARDS), and C (IAP 10 mmHg, with ARDS). Following induction of IAP (by inflating an intra-abdominal balloon) and ARDS (by saline lung lavage and injurious ventilation), respiratory mechanics were monitored for six hours. Statistical analysis was performed using one-way ANOVA to compare the alterations within each group. Results: After six hours of ventilation, end-expiratory lung volume (EELV) decreased across all groups, while airway and thoracic pressures increased. Significant differences were noted between group (B) and (C) regarding alterations in transpulmonary pressure (TPP) (2.7 ± 0.6 vs. 11.3 ± 2.1 cmH2O, p < 0.001), elastance of the lung (EL) (8.9 ± 1.9 vs. 29.9 ± 5.9 cmH2O/mL, p = 0.003), and elastance of the chest wall (ECW) (32.8 ± 3.2 vs. 4.4 ± 1.8 cmH2O/mL, p < 0.001). However, global respiratory parameters such as EELV/kg bodyweight (-6.1 ± 1.3 vs. -11.0 ± 2.5 mL/kg), driving pressure (12.5 ± 0.9 vs. 13.2 ± 2.3 cmH2O), and compliance of the respiratory system (-21.7 ± 2.8 vs. -19.5 ± 3.4 mL/cmH2O) did not show significant differences among the groups. Conclusions: Separate measurements of lung and chest wall mechanics in pigs with IAH or ARDS reveals significant differences in TPP, EL, and ECW, whereas global respiratory parameters do not differ significantly. Therefore, assessing the compartments of the respiratory system separately could aid in identifying the underlying cause of ARF.

Transpulmonary pressure monitoring in critically ill patients: pros and cons.

The use of transpulmonary pressure monitoring based on measurement of esophageal pressure has contributed importantly to the personalization of mechanical ventilation based on respiratory pathophysiology in critically ill patients. However, esophageal pressure monitoring is still underused in the clinical practice. This technique allows partitioning of the respiratory mechanics between the lungs and the chest wall, provides information on lung recruitment and risk of barotrauma, and helps titrating mechanical ventilation settings in patients with respiratory failure. In assisted ventilation modes and during non-invasive respiratory support, esophageal pressure monitoring provides important information on the inspiratory effort and work of breathing. Nonetheless, several controversies persist on technical aspects, interpretation and clinical decision-making based on values derived from this monitoring technique. The aim of this review is to summarize the physiological bases of esophageal pressure monitoring, discussing the pros and cons of its clinical applications and different interpretations in critically ill patients undergoing invasive and non-invasive respiratory support.

Effect of different lung recruitment strategies and airway device on oscillatory mechanics in children under general anaesthesia.

BACKGROUND: Atelectasis has been reported in 68 to 100% of children undergoing general anaesthesia, a phenomenon that persists into the recovery period. Children receiving recruitment manoeuvres have less atelectasis and fewer episodes of oxygen desaturation during emergence. The optimal type of recruitment manoeuvre is unclear and may be influenced by the airway device chosen. OBJECTIVE: We aimed to investigate the different effects on lung mechanics as assessed by the forced oscillation technique (FOT) utilising different recruitment strategies: repeated inflations vs. one sustained inflation and different airway devices, a supraglottic airway device vs. a cuffed tracheal tube. DESIGN: Pragmatic enrolment with randomisation to the recruitment strategy. SETTING: We conducted this single-centre trial between February 2020 and March 2022. PARTICIPANTS: Seventy healthy patients (53 boys) aged between 2 and 16 years undergoing general anaesthesia were included. INTERVENTIONS: Forced oscillations (5 Hz) were superimposed on the ventilator waveform using a customised system connected to the anaesthesia machine. Pressure and flow were measured at the inlet of the airway device and used to compute respiratory system resistance and reactance. Measurements were taken before and after recruitment, and again at the end of surgery. MAIN OUTCOME MEASURES: The primary endpoint measured is the change in respiratory reactance. RESULTS: Statistical analysis (linear model with recruitment strategy and airway device as factors) did not show any significant difference in resistance and reactance between before and after recruitment. Baseline reactance was the strongest predictor for a change in reactance after recruitment: prerecruitment Xrs decreased by mean (standard error) of 0.25 (0.068) cmH 2 O s l -1 per  1 cmH 2 O -1  s l -1 increase in baseline Xrs ( P  < 0.001). After correcting for baseline reactance, the change in reactance after recruitment was significantly lower for sustained inflation compared with repeated inflation by mean (standard error) 0.25 (0.101) cmH 2 O ( P  = 0.0166). CONCLUSION: Although there was no significant difference between airway devices, this study demonstrated more effective recruitment via repeated inflations than sustained inflation in anaesthetised children. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12619001434189.

Monitoring lung recruitment.

PURPOSE OF REVIEW: This review explores lung recruitment monitoring, covering techniques, challenges, and future perspectives. RECENT FINDINGS: Various methodologies, including respiratory system mechanics evaluation, arterial bold gases (ABGs) analysis, lung imaging, and esophageal pressure (Pes) measurement are employed to assess lung recruitment. In support to ABGs analysis, the assessment of respiratory mechanics with hysteresis and recruitment-to-inflation ratio has the potential to evaluate lung recruitment and enhance mechanical ventilation setting. Lung imaging tools, such as computed tomography scanning, lung ultrasound, and electrical impedance tomography (EIT) confirm their utility in following lung recruitment with the advantage of radiation-free and repeatable application at the bedside for sonography and EIT. Pes enables the assessment of dorsal lung tendency to collapse through end-expiratory transpulmonary pressure. Despite their value, these methodologies may require an elevated expertise in their application and data interpretation. However, the information obtained by these methods may be conveyed to build machine learning and artificial intelligence algorithms aimed at improving the clinical decision-making process. SUMMARY: Monitoring lung recruitment is a crucial component of managing patients with severe lung conditions, within the framework of a personalized ventilatory strategy. Although challenges persist, emerging technologies offer promise for a personalized approach to care in the future.

Ex Vivo Porcine Experimental Model for Studying and Teaching Lung Mechanics.

Mechanical ventilation is widely used and requires specific knowledge for understanding and management. Health professionals in this field may feel insecure and lack knowledge because of inadequate training and teaching methods. Therefore, the objective of this article is to outline the steps involved in generating an ex vivo porcine lung model to be used in the future, to study and teach lung mechanics. To generate the model, five porcine lungs were carefully removed from the thorax following the guidelines of the Animal Research Ethics Committee with adequate care and were connected to the mechanical ventilator through a tracheal cannula. These lungs were then subjected to the alveolar recruitment maneuver. Respiratory mechanics parameters were recorded, and video cameras were used to obtain videos of the lungs during this process. This process was repeated for five consecutive days. When not used, the lungs were kept refrigerated. The model showed different lung mechanics after the alveolar recruitment maneuver every day; not being influenced by the days, only by the maneuver. Therefore, we conclude that the ex vivo lung model can provide a better understanding of lung mechanics and its effects, and even of the alveolar recruitment maneuver through visual feedback during all stages of the process.

Bronchodilator response assessment through impulse oscillometry system and spirometry in children and adolescents with cystic fibrosis.

OBJECTIVE: To investigate the effect of bronchodilator on the respiratory mechanics and pulmonary function of children and adolescents with cystic fibrosis. METHODS: Cross-sectional study on clinically stable children and adolescents with cystic fibrosis aged from six to 15 years. Participants underwent impulse oscillometry and spirometry evaluations before and 15 minutes after bronchodilator inhalation. The Kolmogorov-Smirnov test was applied to verify the sample distribution, and the Student's t-test and Wilcoxon test were used to compare the data before and after bronchodilator inhalation. RESULTS: The study included 54 individuals with a mean age of 9.7±2.8 years. The analysis showed a statistically significant improvement in impulse oscillometry and spirometry parameters after bronchodilator inhalation. However, according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) recommendations (2020 and 2021), this improvement was not sufficient to classify it as a bronchodilator response. CONCLUSIONS: The use of bronchodilator medication improved respiratory mechanics and pulmonary function parameters of children and adolescents with cystic fibrosis; however, most patients did not show bronchodilator response according to ATS/ERS recommendations.

Continuous estimation of respiratory system compliance and airway resistance during pressure-controlled ventilation without end-inspiration occlusion.

BACKGROUND: Assessing mechanical properties of the respiratory system (Cst) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an end-inspiratory occlusion maneuver. This lung model study aimed to observe the effect of airflow obstruction on the accuracy of respiratory mechanical properties during pressure-controlled ventilation (PCV) by analyzing dynamic signals. METHODS: A Hamilton C3 ventilator was attached to a lung simulator that mimics lung mechanics in healthy, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) models. PCV and volume-controlled ventilation (VCV) were applied with tidal volume (VT) values of 5.0, 7.0, and 10.0 ml/kg. Performance characteristics and respiratory mechanics were assessed and were calibrated by virtual extrapolation using expiratory time constant (RCexp). RESULTS: During PCV ventilation, drive pressure (DP) was significantly increased in the ARDS model. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) gradually declined with increasing severity of airflow obstruction, while DP, end-inspiration flow (EIF), and inspiratory cycling ratio (EIF/PIF%) increased. Similar estimated values of Crs and airway resistance (Raw) during PCV and VCV ventilation were obtained in healthy adult and mild obstructive models, and the calculated errors did not exceed 5%. An underestimation of Crs and an overestimation of Raw were observed in the severe obstruction model. CONCLUSION: Using the modified dynamic signal analysis approach, respiratory system properties (Crs and Raw) could be accurately estimated in patients with non-severe airflow obstruction in the PCV mode.

Effect of Individualized PEEP Guided by Driving Pressure on Diaphragm Function in Patients Undergoing Laparoscopic Radical Resection of Colorectal Cancer: A Randomized Controlled Trial.

BACKGROUND The concept of driving pressure (ΔP) has been established to optimize mechanical ventilation-induced lung injury. However, little is known about the specific effects of setting individualized positive end-expiratory pressure (PEEP) with driving pressure guidance on patient diaphragm function. MATERIAL AND METHODS Ninety patients were randomized into 3 groups, with PEEP set to 0 in group C; 5 cmH2O in group F; and individualized PEEP in group I, based on esophageal manometry. Diaphragm ultrasound was performed in the supine position at 6 consecutive time points from T0-T5: diaphragm excursion, end-expiratory diaphragm thickness (Tdi-ee), and diaphragm thickening fraction (DTF) were measured. Primary indicators included diaphragm excursion, Tdi-ee, and DTF at T0-T5, and the correlation between postoperative DTF and ΔP. Secondary indicators included respiratory mechanics, hemodynamic changes at intraoperative d0-d4 time points, and postoperative clinical pulmonary infection scores. RESULTS (1) Diaphragm function parameters reached the lowest point at T1 in all groups (P<0.001). (2) Compared with group C, diaphragm excursion decreased, Tdi-ee increased, and DTF was lower in groups I and F at T1-T5, with significant differences (P<0.05), but the differences between groups I and F were not significant (P>0.05). (3) DTF was significantly and positively correlated with mean intraoperative ΔP in each group at T3, and the correlation was stronger at higher levels of ΔP. CONCLUSIONS Individualized PEEP, achieved by esophageal manometry, minimizes diaphragmatic injury caused by mechanical ventilation based on lung protection, but its protection of the diaphragm during laparoscopic surgery is not superior to that of conventional ventilation strategies.

Dynamic hyperinflation on exercise and its relationship with lung mechanics at rest in adults with central obesity.

This study aimed to evaluate the presence of dynamic hyperinflation (DH) during the Glittre-ADL test (TGlittre) coupled to the dynamic ventilation measurements in people with central obesity (pwCO) and to correlate it with lung mechanics at rest. Sixty-four pwCO underwent TGlittre and the following resting lung function tests: spirometry and impulse oscillometry system (IOS). On TGlittre, 22 participants presented DH at the end of the test (DH group), while 42 did not present DH (NDH group). Body mass index (BMI), waist circumference (WC), and hip circumference (HC) were higher in the DH group than in the NDH group. IOS abnormalities were more common in the DH group compared to the NDH group. TGlittre time significantly correlated with BMI, WC, waist-to-hip ratio (WHR), and neck circumference (NC). Delta inspiratory capacity correlated significantly with WC, HC, NC, and resonance frequency measured by IOS. Thus, pwCO perform worse on TGlittre, and DH is frequent in those with higher anthropometric indices and worse lung mechanics.

A novel method to quantify breathing effort from respiratory mechanics and esophageal pressure.

Breathing effort is important to quantify to understand mechanisms underlying central and obstructive sleep apnea, respiratory-related arousals, and the timing and effectiveness of invasive or noninvasive mechanically assisted ventilation. Current quantitative methods to evaluate breathing effort rely on inspiratory esophageal or epiglottic pressure swings or changes in diaphragm electromyographic (EMG) activity, where units are problematic to interpret and compare between individuals and to measured ventilation. This paper derives a novel method to quantify breathing effort in units directly comparable with measured ventilation by applying respiratory mechanics first principles to convert continuous transpulmonary pressure measurements into "attempted" airflow expected to have arisen without upper airway obstruction. The method was evaluated using data from 11 subjects undergoing overnight polysomnography, including six patients with obesity with severe obstructive sleep apnea (OSA), including one who also had frequent central events, and five healthy-weight controls. Classic respiratory mechanics showed excellent fits of airflow and volume to transpulmonary pressures during wake periods of stable unobstructed breathing (means ± SD, r2 = 0.94 ± 0.03), with significantly higher respiratory system resistance in patients compared with healthy controls (11.2 ± 3.3 vs. 7.1 ± 1.9 cmH2O·L-1·s, P = 0.032). Subsequent estimates of attempted airflow from transpulmonary pressure changes clearly highlighted periods of acute and prolonged upper airway obstruction, including within the first few breaths following sleep onset in patients with OSA. This novel technique provides unique quantitative insights into the complex and dynamically changing interrelationships between breathing effort and achieved airflow during periods of obstructed breathing in sleep.NEW & NOTEWORTHY Ineffective breathing efforts with snoring and obstructive sleep apnea (OSA) are challenging to quantify. Measurements of esophageal or epiglottic pressure swings and diaphragm electromyography are useful, but units are problematic to interpret and compare between individuals and to measured ventilation. This paper derives a novel method that uses esophageal pressure and respiratory mechanics first principles to quantify breathing effort as "attempted" flow and volume in units directly comparable with measured airflow, volume, and ventilation.

Respiratory and chest wall mechanics in very preterm infants.

Data on static compliance of the chest wall (Ccw) in preterm infants are scarce. We characterized the static compliance of the lung (CL) and Ccw to determine their relative contribution to static compliance of the respiratory system (Crs) in very preterm infants at 36 wk postmenstrual age (PMA). We also aimed to investigate how these compliances were influenced by the presence of bronchopulmonary dysplasia (BPD) and impacted breathing variables. Airway opening pressure, esophageal pressure, and tidal volume (VT) were measured simultaneously during a short apnea evoked by the Hering-Breuer reflex. We computed tidal breathing variables, airway resistance (R), and dynamic lung compliance (CL,dyn), inspiratory capacity (IC), and Crs, CL, and Ccw. Functional residual capacity was assessed by the multiple breath washout technique (FRCmbw). Breathing variables, compliances, and lung volumes were adjusted for body weight. Twenty-three preterm infants born at 27.2 ± 2.0 wk gestational age (GA) were studied at 36.6 ± 0.6 wk PMA. Median and interquartile range (IQR) Crs/kg is 0.69 (0.6), CL/kg 0.95 (1.0), and Ccw/kg 3.0 (2.4). Infants with BPD (n = 11) had lower Crs/kg (P = 0.013), CL/kg (P = 0.019), and Ccw/kg (P = 0.027) compared with infants without BPD. Ccw/CL ratio was equal between groups. FRCmbw/kg (P = 0.044) and IC/kg (P = 0.005) were decreased in infants with BPD. Infants with BPD have reduced static compliance of the respiratory system, the lungs, and chest wall. Decreased Crs, CL, and Ccw in infants with BPD explain the lower FRC and IC seen in these infants.NEW & NOTEWORTHY Data on chest wall compliance in very preterm infants in the postsurfactant era are scarce. To our knowledge, we are the first group to report data on static respiratory system compliance (Crs), lung compliance (CL), and chest wall compliance (Ccw) in preterm infants with and without bronchopulmonary dysplasia (BPD) in the postsurfactant era.

Respiratory drive heterogeneity associated with systemic inflammation and vascular permeability in acute respiratory distress syndrome.

BACKGROUND: In acute respiratory distress syndrome (ARDS), respiratory drive often differs among patients with similar clinical characteristics. Readily observable factors like acid-base state, oxygenation, mechanics, and sedation depth do not fully explain drive heterogeneity. This study evaluated the relationship of systemic inflammation and vascular permeability markers with respiratory drive and clinical outcomes in ARDS. METHODS: ARDS patients enrolled in the multicenter EPVent-2 trial with requisite data and plasma biomarkers were included. Neuromuscular blockade recipients were excluded. Respiratory drive was measured as PES0.1, the change in esophageal pressure during the first 0.1 s of inspiratory effort. Plasma angiopoietin-2, interleukin-6, and interleukin-8 were measured concomitantly, and 60-day clinical outcomes evaluated. RESULTS: 54.8% of 124 included patients had detectable respiratory drive (PES0.1 range of 0-5.1 cm H2O). Angiopoietin-2 and interleukin-8, but not interleukin-6, were associated with respiratory drive independently of acid-base, oxygenation, respiratory mechanics, and sedation depth. Sedation depth was not significantly associated with PES0.1 in an unadjusted model, or after adjusting for mechanics and chemoreceptor input. However, upon adding angiopoietin-2, interleukin-6, or interleukin-8 to models, lighter sedation was significantly associated with higher PES0.1. Risk of death was less with moderate drive (PES0.1 of 0.5-2.9 cm H2O) compared to either lower drive (hazard ratio 1.58, 95% CI 0.82-3.05) or higher drive (2.63, 95% CI 1.21-5.70) (p = 0.049). CONCLUSIONS: Among patients with ARDS, systemic inflammatory and vascular permeability markers were independently associated with higher respiratory drive. The heterogeneous response of respiratory drive to varying sedation depth may be explained in part by differences in inflammation and vascular permeability.

Electrical impedance tomography-guided positive end-expiratory pressure titration in ARDS: a systematic review and meta-analysis.

PURPOSE: Assessing efficacy of electrical impedance tomography (EIT) in optimizing positive end-expiratory pressure (PEEP) for acute respiratory distress syndrome (ARDS) patients to enhance respiratory system mechanics and prevent ventilator-induced lung injury (VILI), compared to traditional methods. METHODS: We carried out a systematic review and meta-analysis, spanning literature from January 2012 to May 2023, sourced from Scopus, PubMed, MEDLINE (Ovid), Cochrane, and LILACS, evaluated EIT-guided PEEP strategies in ARDS versus conventional methods. Thirteen studies (3 randomized, 10 non-randomized) involving 623 ARDS patients were analyzed using random-effects models for primary outcomes (respiratory mechanics and mechanical power) and secondary outcomes (PaO2/FiO2 ratio, mortality, stays in intensive care unit (ICU), ventilator-free days). RESULTS: EIT-guided PEEP significantly improved lung compliance (n = 941 cases, mean difference (MD) = 4.33, 95% confidence interval (CI) [2.94, 5.71]), reduced mechanical power (n = 148, MD = - 1.99, 95% CI [- 3.51, - 0.47]), and lowered driving pressure (n = 903, MD = - 1.20, 95% CI [- 2.33, - 0.07]) compared to traditional methods. Sensitivity analysis showed consistent positive effect of EIT-guided PEEP on lung compliance in randomized clinical trials vs. non-randomized studies pooled (MD) = 2.43 (95% CI - 0.39 to 5.26), indicating a trend towards improvement. A reduction in mortality rate (259 patients, relative risk (RR) = 0.64, 95% CI [0.45, 0.91]) was associated with modest improvements in compliance and driving pressure in three studies. CONCLUSIONS: EIT facilitates real-time, individualized PEEP adjustments, improving respiratory system mechanics. Integration of EIT as a guiding tool in mechanical ventilation holds potential benefits in preventing ventilator-induced lung injury. Larger-scale studies are essential to validate and optimize EIT's clinical utility in ARDS management.

Comparison of volume-controlled ventilation, pressure-controlled ventilation and pressure-controlled ventilation-volume guaranteed in infants and young children in the prone position: A prospective randomized study.

STUDY OBJECTIVE: To explore if the pressure-controlled ventilation (PCV) and pressure-controlled ventilation-volume guaranteed (PCV-VG) modes are superior to volume-controlled ventilation (VCV) in optimizing intraoperative respiratory mechanics in infants and young children in the prone position. DESIGN: A single-center prospective randomized study. SETTING: Children's Hospital, Zhejiang University School of Medicine. PATIENTS: Pediatric patients aged 1 month to 3 years undergoing elective spinal cord detethering surgery. INTERVENTIONS: Patients were randomly allocated to the VCV group, PCV group and PCV-VG group. The target tidal volume (VT) was 8 mL/kg and the respiratory rate (RR) was adjusted to maintain a constant end tidal CO2. MEASUREMENTS: The primary outcome was intraoperative peak airway pressure (Ppeak). Secondary outcomes included other respiratory and ventilation variables, gas exchange values, serum lung injury biomarkers concentration, hemodynamic parameters and postoperative respiratory complications. MAIN RESULTS: A total of 120 patients were included in the final analysis (40 in each group). The VCV group showed higher Ppeak at T2 (10 min after prone positioning) and T3 (30 min after prone positioning) than the PCV and PCV-VG groups (T2: P = 0.015 and P = 0.002, respectively; T3: P = 0.007 and P = 0.009, respectively). The prone-related decrease in dynamic compliance was prevented by PCV and PCV-VG ventilation modalities at T2 and T3 than by VCV (T2: P = 0.008 and P = 0.015, respectively; T3: P = 0.015 and P = 0.014, respectively). Additionally, there were no significant differences in other secondary outcomes among the three groups. CONCLUSION: In infants and young children undergoing spinal cord detethering surgery in the prone position, PCV-VG may be a better ventilation mode due to its ability to mitigate the increase in Ppeak and decrease in Cdyn while maintaining consistent VT.

Intraoperative effects of an alveolar recruitment manoeuvre in patients undergoing laparoscopic colon surgery.

INTRODUCTION: Pulmonary atelectasis is common in patients undergoing laparoscopic abdominal surgery under general anaesthesia, which increases the risk of perioperative respiratory complications. Alveolar recruitment manoeuvres (ARM) are used to open up the lung parenchyma with atelectasis, although the duration of their benefit has not been clearly established. The aim of this study was to determine the effectiveness of an ARM in laparoscopic colon surgery, the duration of response over time, and its haemodynamic impact. METHODS: Twenty-five patients undergoing laparoscopic colon surgery were included. After anaesthetic induction and initiation of surgery with pneumoperitoneum, an ARM was performed, and then optimal PEEP determined. Respiratory mechanics and gas exchange variables, and haemodynamic parameters, were analysed before the manoeuvre and periodically over the following 90 min. RESULTS: Three patients were excluded for surgical reasons. The alveolar arterial oxygen gradient went from 94.3 (62.3-117.8) mmHg before to 60.7 (29.6-91.0) mmHg after the manoeuvre (P < .05). This difference was maintained during the 90 min of the study. Dynamic compliance of the respiratory system went from 31.3 ml/cmH2O (26.1-39.2) before the manoeuvre to 46.1 ml/cmH2O (37.5-53.5) after the manoeuvre (P < .05). This difference was maintained for 60 min. No significant changes were identified in any of the haemodynamic variables studied. CONCLUSION: In patients undergoing laparoscopic colon surgery, performing an intraoperative ARM improves the mechanics of the respiratory system and oxygenation, without associated haemodynamic compromise. The benefit of these manoeuvres lasts for at least one hour.

A vagal reflex evoked by airway closure.

Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and, on a moment-by-moment basis, enact vital reflexes to maintain respiratory function1,2. Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax or airway compression. Here we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch. Vagal neurons expressing PVALB mediate airway closure responses and innervate clusters of lung epithelial cells called neuroepithelial bodies (NEBs). Stimulating NEBs or vagal PVALB neurons evoked gasping in the absence of airway threats, whereas ablating NEBs or vagal PVALB neurons eliminated gasping in response to airway closure. Single-cell RNA sequencing revealed that NEBs uniformly express the mechanoreceptor PIEZO2, and targeted knockout of Piezo2 in NEBs eliminated responses to airway closure. NEBs were dispensable for the Hering-Breuer inspiratory reflex, which indicated that discrete terminal structures detect airway closure and inflation. Similar to the involvement of Merkel cells in touch sensation3,4, NEBs are PIEZO2-expressing epithelial cells and, moreover, are crucial for an aspect of lung mechanosensation. These findings expand our understanding of neuronal diversity in the airways and reveal a dedicated vagal pathway that detects airway closure to help preserve respiratory function.