Stress & strain in mechanically nonuniform alveoli using clinical input variables: a simple conceptual model.

Clinicians currently monitor pressure and volume at the airway opening, assuming that these observations relate closely to stresses and strains at the micro level. Indeed, this assumption forms the basis of current approaches to lung protective ventilation. Nonetheless, although the airway pressure applied under static conditions may be the same everywhere in healthy lungs, the stresses within a mechanically non-uniform ARDS lung are not. Estimating actual tissue stresses and strains that occur in a mechanically non-uniform environment must account for factors beyond the measurements from the ventilator circuit of airway pressures, tidal volume, and total mechanical power. A first conceptual step for the clinician to better define the VILI hazard requires consideration of lung unit tension, stress focusing, and intracycle power concentration. With reasonable approximations, better understanding of the value and limitations of presently used general guidelines for lung protection may eventually be developed from clinical inputs measured by the caregiver. The primary purpose of the present thought exercise is to extend our published model of a uniform, spherical lung unit to characterize the amplifications of stress (tension) and strain (area change) that occur under static conditions at interface boundaries between a sphere's surface segments having differing compliances. Together with measurable ventilating power, these are incorporated into our perspective of VILI risk. This conceptual exercise brings to light how variables that are seldom considered by the clinician but are both recognizable and measurable might help gauge the hazard for VILI of applied pressure and power.

Clinical validation of a capnodynamic method for measuring end-expiratory lung volume in critically ill patients.

RATIONALE: End-expiratory lung volume (EELV) is reduced in mechanically ventilated patients, especially in pathologic conditions. The resulting heterogeneous distribution of ventilation increases the risk for ventilation induced lung injury. Clinical measurement of EELV however, remains difficult. OBJECTIVE: Validation of a novel continuous capnodynamic method based on expired carbon dioxide (CO2) kinetics for measuring EELV in mechanically ventilated critically-ill patients. METHODS: Prospective study of mechanically ventilated patients scheduled for a diagnostic computed tomography exploration. Comparisons were made between absolute and corrected EELVCO2 values, the latter accounting for the amount of CO2 dissolved in lung tissue, with the reference EELV measured by computed tomography (EELVCT). Uncorrected and corrected EELVCO2 was compared with total CT volume (density compartments between - 1000 and 0 Hounsfield units (HU) and functional CT volume, including density compartments of - 1000 to - 200HU eliminating regions of increased shunt. We used comparative statistics including correlations and measurement of accuracy and precision by the Bland Altman method. MEASUREMENTS AND MAIN RESULTS: Of the 46 patients included in the final analysis, 25 had a diagnosis of ARDS (24 of which COVID-19). Both EELVCT and EELVCO2 were significantly reduced (39 and 40% respectively) when compared with theoretical values of functional residual capacity (p < 0.0001). Uncorrected EELVCO2 tended to overestimate EELVCT with a correlation r2 0.58; Bias - 285 and limits of agreement (LoA) (+ 513 to - 1083; 95% CI) ml. Agreement improved for the corrected EELVCO2 to a Bias of - 23 and LoA of (+ 763 to - 716; 95% CI) ml. The best agreement of the method was obtained by comparison of corrected EELVCO2 with functional EELVCT with a r2 of 0.59; Bias - 2.75 (+ 755 to - 761; 95% CI) ml. We did not observe major differences in the performance of the method between ARDS (most of them COVID related) and non-ARDS patients. CONCLUSION: In this first validation in critically ill patients, the capnodynamic method provided good estimates of both total and functional EELV. Bias improved after correcting EELVCO2 for extra-alveolar CO2 content when compared with CT estimated volume. If confirmed in further validations EELVCO2 may become an attractive monitoring option for continuously monitor EELV in critically ill mechanically ventilated patients. TRIAL REGISTRATION: clinicaltrials.gov (NCT04045262).

Potential for the lung recruitment and the risk of lung overdistension during 21 days of mechanical ventilation in patients with COVID-19 after noninvasive ventilation failure: the COVID-VENT observational trial.

BACKGROUND: Data on the lung respiratory mechanics and gas exchange in the time course of COVID-19-associated respiratory failure is limited. This study aimed to explore respiratory mechanics and gas exchange, the lung recruitability and risk of overdistension during the time course of mechanical ventilation. METHODS: This was a prospective observational study in critically ill mechanically ventilated patients (n = 116) with COVID-19 admitted into Intensive Care Units of Sechenov University. The primary endpoints were: «optimum¼ positive end-expiratory pressure (PEEP) level balanced between the lowest driving pressure and the highest SpO2 and number of patients with recruitable lung on Days 1 and 7 of mechanical ventilation. We measured driving pressure at different levels of PEEP (14, 12, 10 and 8 cmH2O) with preset tidal volume, and with the increase of tidal volume by 100 ml and 200 ml at preset PEEP level, and calculated static respiratory system compliance (CRS), PaO2/FiO2, alveolar dead space and ventilatory ratio on Days 1, 3, 5, 7, 10, 14 and 21. RESULTS: The «optimum¼ PEEP levels on Day 1 were 11.0 (10.0-12.8) cmH2O and 10.0 (9.0-12.0) cmH2O on Day 7. Positive response to recruitment was observed on Day 1 in 27.6% and on Day 7 in 9.2% of patients. PEEP increase from 10 to 14 cmH2O and VT increase by 100 and 200 ml led to a significant decrease in CRS from Day 1 to Day 14 (p < 0.05). Ventilatory ratio was 2.2 (1.7-2,7) in non-survivors and in 1.9 (1.6-2.6) survivors on Day 1 and decreased on Day 7 in survivors only (p < 0.01). PaO2/FiO2 was 105.5 (76.2-141.7) mmHg in non-survivors on Day 1 and 136.6 (106.7-160.8) in survivors (p = 0.002). In survivors, PaO2/FiO2 rose on Day 3 (p = 0.008) and then between Days 7 and 10 (p = 0.046). CONCLUSION: Lung recruitability was low in COVID-19 and decreased during the course of the disease, but lung overdistension occurred at «intermediate¼ PEEP and VT levels. In survivors gas exchange improvements after Day 7 mismatched CRS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04445961 . Registered 24 June 2020-Retrospectively registered.

Estimation of changes in cyclic lung strain by electrical impedance tomography: Proof-of-concept study.

RATIONALE: Cyclic strain may be a determinant of ventilator-induced lung injury. The standard for strain assessment is the computed tomography (CT), which does not allow continuous monitoring and exposes to radiation. Electrical impedance tomography (EIT) is able to monitor changes in regional lung ventilation. In addition, there is a correlation between mechanical deformation of materials and detectable changes in its electrical impedance, making EIT a potential surrogate for cyclic lung strain measured by CT (StrainCT ). OBJECTIVES: To compare the global StrainCT with the change in electrical impedance (ΔZ). METHODS: Acute respiratory distress syndrome patients under mechanical ventilation (VT 6 mL/kg ideal body weight with positive end-expiratory pressure 5 [PEEP 5] and best PEEP according to EIT) underwent whole-lung CT at end-inspiration and end-expiration. Biomechanical analysis was used to construct 3D maps and determine StrainCT at different levels of PEEP. CT and EIT acquisitions were performed simultaneously. Multilevel analysis was employed to determine the causal association between StrainCT and ΔZ. Linear regression models were used to predict the change in lung StrainCT between different PEEP levels based on the change in ΔZ. MAIN RESULTS: StrainCT was positively and independently associated with ΔZ at global level (P < .01). Furthermore, the change in StrainCT (between PEEP 5 and Best PEEP) was accurately predicted by the change in ΔZ (R2 0.855, P < .001 at global level) with a high agreement between predicted and measured StrainCT . CONCLUSIONS: The change in electrical impedance may provide a noninvasive assessment of global cyclic strain, without radiation at bedside.

A physiological approach to understand the role of respiratory effort in the progression of lung injury in SARS-CoV-2 infection.

Deterioration of lung function during the first week of COVID-19 has been observed when patients remain with insufficient respiratory support. Patient self-inflicted lung injury (P-SILI) is theorized as the responsible, but there is not robust experimental and clinical data to support it. Given the limited understanding of P-SILI, we describe the physiological basis of P-SILI and we show experimental data to comprehend the role of regional strain and heterogeneity in lung injury due to increased work of breathing.In addition, we discuss the current approach to respiratory support for COVID-19 under this point of view.

The effects of low tidal ventilation on lung strain correlate with respiratory system compliance.

BACKGROUND: The effect of alterations in tidal volume on mortality of acute respiratory distress syndrome (ARDS) is determined by respiratory system compliance. We aimed to investigate the effects of different tidal volumes on lung strain in ARDS patients who had various levels of respiratory system compliance. METHODS: Nineteen patients were divided into high (Chigh group) and low (Clow group) respiratory system compliance groups based on their respiratory system compliance values. We defined compliance ≥0.6 ml/(cmH2O/kg) as Chigh and compliance <0.6 ml/(cmH2O/kg) as Clow. End-expiratory lung volumes (EELV) at various tidal volumes were measured by nitrogen wash-in/washout. Lung strain was calculated as the ratio between tidal volume and EELV. The primary outcome was that lung strain is a function of tidal volume in patients with various levels of respiratory system compliance. RESULTS: The mean baseline EELV, strain and respiratory system compliance values were 1873 ml, 0.31 and 0.65 ml/(cmH2O/kg), respectively; differences in all of these parameters were statistically significant between the two groups. For all participants, a positive correlation was found between the respiratory system compliance and EELV (R = 0.488, p = 0.034). Driving pressure and strain increased together as the tidal volume increased from 6 ml/kg predicted body weight (PBW) to 12 ml/kg PBW. Compared to the Chigh ARDS patients, the driving pressure was significantly higher in the Clow patients at each tidal volume. Similar effects of lung strain were found for tidal volumes of 6 and 8 ml/kg PBW. The "lung injury" limits for driving pressure and lung strain were much easier to exceed with increases in the tidal volume in Clow patients. CONCLUSIONS: Respiratory system compliance affected the relationships between tidal volume and driving pressure and lung strain in ARDS patients. These results showed that increasing tidal volume induced lung injury more easily in patients with low respiratory system compliance. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01864668 , Registered 21 May 2013.

End-Expiratory Lung Volume in Patients with Acute Respiratory Distress Syndrome: A Time Course Analysis.

PURPOSE: Lung injury can be caused by ventilation and non-physiological lung stress (transpulmonary pressure) and strain [inflated volume over functional residual capacity ratio (FRC)]. FRC is severely decreased in patients with acute respiratory distress syndrome (ARDS). End-expiratory lung volume (EELV) is FRC plus lung volume increased by the applied positive end-expiratory pressure (PEEP). Measurement using the modified nitrogen multiple breath washout technique may help titrating PEEP during ARDS and allow determining dynamic lung strain (tidal volume over EELV) in patients ventilated with PEEP. In this observational study, we measured EELV for up to seven consecutive days in patients with ARDS at different PEEP levels. RESULTS: Thirty sedated patients with ARDS (10 mild, 14 moderate, 6 severe) underwent decremental PEEP testing (20, 15, 10, 5 cm H2O) for up to 7 days after inclusion. At all PEEP levels examined, over a period of 7 days the measured absolute EELVs showed no significant change over time [PEEP 20 cm H2O 2464 ml at day 1 vs. 2144 ml at day 7 (p = 0.78), PEEP 15 cm H2O 2226 ml vs. 1990 ml (p = 0.36), PEEP 10 1835 ml vs. 1858 ml (p = 0.76) and PEEP 5 cm H2O 1487 ml vs. 1612 ml (p = 0.37)]. In relation to the predicted body weight (pbw), no significant change in EELV/kg pbw over time could be detected either at any PEEP level or over time [PEEP 20 36 ml/kg pbw at day 1 vs. 33 ml/kg pbw at day 7 (p = 0.66); PEEP 15 33 vs. 29 ml/kg pbw (p = 0.32); PEEP 10 27 vs. 27 ml/kg pbw (p = 0.70) and PEEP 5 22 vs. 24 ml/kg pbw (p = 0.70)]. Oxygenation significantly improved over time from PaO2/FiO2 of 169 mmHg at day 1 to 199 mmHg at day 7 (p < 0.01). CONCLUSIONS: EELV did not change significantly for up to 7 days in patients with ARDS. By contrast, PaO2/FiO2 improved significantly. Bedside measurement of EELV may be a novel approach to individualise lung-protective ventilation on the basis of calculation of dynamic strain as the ratio of VT to EELV.

A machine-learning regional clustering approach to understand ventilator-induced lung injury: a proof-of-concept experimental study.

BACKGROUND: The spatiotemporal progression and patterns of tissue deformation in ventilator-induced lung injury (VILI) remain understudied. Our aim was to identify lung clusters based on their regional mechanical behavior over space and time in lungs subjected to VILI using machine-learning techniques. RESULTS: Ten anesthetized pigs (27 ± 2 kg) were studied. Eight subjects were analyzed. End-inspiratory and end-expiratory lung computed tomography scans were performed at the beginning and after 12 h of one-hit VILI model. Regional image-based biomechanical analysis was used to determine end-expiratory aeration, tidal recruitment, and volumetric strain for both early and late stages. Clustering analysis was performed using principal component analysis and K-Means algorithms. We identified three different clusters of lung tissue: Stable, Recruitable Unstable, and Non-Recruitable Unstable. End-expiratory aeration, tidal recruitment, and volumetric strain were significantly different between clusters at early stage. At late stage, we found a step loss of end-expiratory aeration among clusters, lowest in Stable, followed by Unstable Recruitable, and highest in the Unstable Non-Recruitable cluster. Volumetric strain remaining unchanged in the Stable cluster, with slight increases in the Recruitable cluster, and strong reduction in the Unstable Non-Recruitable cluster. CONCLUSIONS: VILI is a regional and dynamic phenomenon. Using unbiased machine-learning techniques we can identify the coexistence of three functional lung tissue compartments with different spatiotemporal regional biomechanical behavior.

Feasibility of Setting the Tidal Volume Based on End-Expiratory Lung Volume: A Pilot Clinical Study.

OBJECTIVES: To assess the feasibility of setting the tidal volume (TV) as 25% of the actual aerated lung volume (rather than on ideal body weight) in patients with Acute Respiratory Distress Syndrome (ARDS). DESIGN: Physiologic prospective single-center pilot study. SETTING: Medical ICU specialized in the care of patients with ARDS. PATIENTS: Patients with moderate-severe ARDS deeply sedated or paralyzed, undergoing controlled mechanical ventilation with a ventilator able to measure the end-expiratory lung volume (EELV) with a washin, washout technique. INTERVENTIONS: Three-phase study (baseline, strain-selected TV setting, ventilation with strain-selected TV for 24 hr). The TV was calculated as 25% of the measured EELV minus the static strain due to the applied positive end-expiratory pressure. MEASUREMENTS AND MAIN RESULTS: Gas exchanges and respiratory mechanics were measured and compared in each phase. In addition, during the TV setting phase, driving pressure (DP) and lung strain (TV/EELV) were measured at different TVs to assess the correlation between the two measurements. The maintenance of the set strain-selected TV for 24 hours was safe and feasible in 76% of the patients enrolled. Three patients dropped out from the study because of the need to set a respiratory rate higher than 35 breaths per minute to avoid respiratory acidosis. The DP of the respiratory system was a satisfactory surrogate for strain in this population. CONCLUSIONS: In our population of 17 patients with moderate to severe ARDS, setting TV based on the actual lung size was feasible. DP was a reliable surrogate of strain in these patients, and DP less than or equal to 8 cm H2O corresponded to a strain less than 0.25.

Recruitment-to-inflation ratio reflects the impact of peep on dynamic lung strain in a highly recruitable model of ARDS.

BACKGROUND: The recruitment-to-inflation ratio (R/I) has been recently proposed to bedside assess response to PEEP. The impact of PEEP on ventilator-induced lung injury depends on the extent of dynamic strain reduction. We hypothesized that R/I may reflect the potential for lung recruitment (i.e. recruitability) and, consequently, estimate the impact of PEEP on dynamic lung strain, both assessed through computed tomography scan. METHODS: Fourteen lung-damaged pigs (lipopolysaccharide infusion) underwent ventilation at low (5 cmH2O) and high PEEP (i.e., PEEP generating a plateau pressure of 28-30 cmH2O). R/I was measured through a one-breath derecruitment maneuver from high to low PEEP. PEEP-induced changes in dynamic lung strain, difference in nonaerated lung tissue weight (tissue recruitment) and amount of gas entering previously nonaerated lung units (gas recruitment) were assessed through computed tomography scan. Tissue and gas recruitment were normalized to the weight and gas volume of previously ventilated lung areas at low PEEP (normalized-tissue recruitment and normalized-gas recruitment, respectively). RESULTS: Between high (median [interquartile range] 20 cmH2O [18-21]) and low PEEP, median R/I was 1.08 [0.88-1.82], indicating high lung recruitability. Compared to low PEEP, tissue and gas recruitment at high PEEP were 246 g [182-288] and 385 ml [318-668], respectively. R/I was linearly related to normalized-gas recruitment (r = 0.90; [95% CI 0.71 to 0.97) and normalized-tissue recruitment (r = 0.69; [95% CI 0.25 to 0.89]). Dynamic lung strain was 0.37 [0.29-0.44] at high PEEP and 0.59 [0.46-0.80] at low PEEP (p < 0.001). R/I was significantly related to PEEP-induced reduction in dynamic (r = - 0.93; [95% CI - 0.78 to - 0.98]) and global lung strain (r = - 0.57; [95% CI - 0.05 to - 0.84]). No correlation was found between R/I and and PEEP-induced changes in static lung strain (r = 0.34; [95% CI - 0.23 to 0.74]). CONCLUSIONS: In a highly recruitable ARDS model, R/I reflects the potential for lung recruitment and well estimates the extent of PEEP-induced reduction in dynamic lung strain.

Dynamic Relative Regional Lung Strain Estimated by Electrical Impedance Tomography in an Experimental Model of ARDS.

BACKGROUND: To analyze the role of PEEP on dynamic relative regional strain (DRRS) in a model of ARDS, respective maps were generated by electrical impedance tomography (EIT). METHODS: Eight ARDS pigs submitted to PEEP steps of 0, 5, 10, and 15 cm H2O at fixed ventilation were evaluated by EIT images. DRRS was calculated as (VT-EIT/EELI)/(VT-EIT[15PEEP]/EELI[15PEEP]), where the tidal volume (VT)-EIT and end-expiratory lung impedance (EELI) are the tidal and end-expiratory change in lung impedance, respectively. The measurement at 15 PEEP was taken as reference (end-expiratory transpulmonary pressure > 0 cm H2O). The relationship between EIT variables (center of ventilation, EELI, and DRRS) and airway pressures was assessed with mixed-effects models using EIT measurements as dependent variables and PEEP as fixed-effect variable. RESULTS: At constant ventilation, respiratory compliance increased progressively with PEEP (lowest value at zero PEEP 10 ± 3 mL/cm H2O and highest value at 15 PEEP 16 ± 6 mL/cm H2O; P < .001), whereas driving pressure decreased with PEEP (highest value at zero PEEP 34 ± 6 cm H2O and lowest value at 15 PEEP 21 ± 4 cm H2O; P < .001). The mixed-effect regression models showed that the center of ventilation moved to dorsal lung areas with a slope of 1.81 (1.44-2.18) % points by each cm H2O of PEEP; P < .001. EELI increased with a slope of 0.05 (0.02-0.07) (arbitrary units) for each cm H2O of PEEP; P < .001. DRRS maps showed that local strain in ventral lung areas decreased with a slope of -0.02 (-0.24 to 0.15) with each cm H2O increase of PEEP; P < .001. CONCLUSIONS: EIT-derived DRRS maps showed high strain in ventral lung zones at low levels of PEEP. The findings suggest overdistention of the baby lung.

Distribution and Magnitude of Regional Volumetric Lung Strain and Its Modification by PEEP in Healthy Anesthetized and Mechanically Ventilated Dogs.

The present study describes the magnitude and spatial distribution of lung strain in healthy anesthetized, mechanically ventilated dogs with and without positive end-expiratory pressure (PEEP). Total lung strain (LSTOTAL) has a dynamic (LSDYNAMIC) and a static (LSSTATIC) component. Due to lung heterogeneity, global lung strain may not accurately represent regional total tissue lung strain (TSTOTAL), which may also be described by a regional dynamic (TSDYNAMIC) and static (TSSTATIC) component. Six healthy anesthetized beagles (12.4 ± 1.4 kg body weight) were placed in dorsal recumbency and ventilated with a tidal volume of 15 ml/kg, respiratory rate of 15 bpm, and zero end-expiratory pressure (ZEEP). Respiratory system mechanics and full thoracic end-expiratory and end-inspiratory CT scan images were obtained at ZEEP. Thereafter, a PEEP of 5 cmH2O was set and respiratory system mechanics measurements and end-expiratory and end-inspiratory images were repeated. Computed lung volumes from CT scans were used to evaluate the global LSTOTAL, LSDYNAMIC, and LSSTATIC during PEEP. During ZEEP, LSSTATIC was assumed zero; therefore, LSTOTAL was the same as LSDYNAMIC. Image segmentation was applied to CT images to obtain maps of regional TSTOTAL, TSDYNAMIC, and TSSTATIC during PEEP, and TSDYNAMIC during ZEEP. Compliance increased (p = 0.013) and driving pressure decreased (p = 0.043) during PEEP. PEEP increased the end-expiratory lung volume (p < 0.001) and significantly reduced global LSDYNAMIC (33.4 ± 6.4% during ZEEP, 24.0 ± 4.6% during PEEP, p = 0.032). LSSTATIC by PEEP was larger than the reduction in LSDYNAMIC; therefore, LSTOTAL at PEEP was larger than LSDYNAMIC at ZEEP (p = 0.005). There was marked topographic heterogeneity of regional strains. PEEP induced a significant reduction in TSDYNAMIC in all lung regions (p < 0.05). Similar to global findings, PEEP-induced TSSTATIC was larger than the reduction in TSDYNAMIC; therefore, PEEP-induced TSTOTAL was larger than TSDYNAMIC at ZEEP. In conclusion, PEEP reduced both global and regional estimates of dynamic strain, but induced a large static strain. Given that lung injury has been mostly associated with tidal deformation, limiting dynamic strain may be an important clinical target in healthy and diseased lungs, but this requires further study.

Progression of regional lung strain and heterogeneity in lung injury: assessing the evolution under spontaneous breathing and mechanical ventilation.

BACKGROUND: Protective mechanical ventilation (MV) aims at limiting global lung deformation and has been associated with better clinical outcomes in acute respiratory distress syndrome (ARDS) patients. In ARDS lungs without MV support, the mechanisms and evolution of lung tissue deformation remain understudied. In this work, we quantify the progression and heterogeneity of regional strain in injured lungs under spontaneous breathing and under MV. METHODS: Lung injury was induced by lung lavage in murine subjects, followed by 3 h of spontaneous breathing (SB-group) or 3 h of low Vt mechanical ventilation (MV-group). Micro-CT images were acquired in all subjects at the beginning and at the end of the ventilation stage following induction of lung injury. Regional strain, strain progression and strain heterogeneity were computed from image-based biomechanical analysis. Three-dimensional regional strain maps were constructed, from which a region-of-interest (ROI) analysis was performed for the regional strain, the strain progression, and the strain heterogeneity. RESULTS: After 3 h of ventilation, regional strain levels were significantly higher in 43.7% of the ROIs in the SB-group. Significant increase in regional strain was found in 1.2% of the ROIs in the MV-group. Progression of regional strain was found in 100% of the ROIs in the SB-group, whereas the MV-group displayed strain progression in 1.2% of the ROIs. Progression in regional strain heterogeneity was found in 23.4% of the ROIs in the SB-group, while the MV-group resulted in 4.7% of the ROIs showing significant changes. Deformation progression is concurrent with an increase of non-aerated compartment in SB-group (from 13.3% ± 1.6% to 37.5% ± 3.1%), being higher in ventral regions of the lung. CONCLUSIONS: Spontaneous breathing in lung injury promotes regional strain and strain heterogeneity progression. In contrast, low Vt MV prevents regional strain and heterogeneity progression in injured lungs.

Mapping regional strain in anesthetised healthy subjects during spontaneous ventilation.

Introduction: Breathing produces a phenomenon of cyclic deformation throughout life. Biomechanically, deformation of the lung is measured as strain. Regional strain recently started to be recognised as a tool in the study of lung pathophysiology, but regional lung strain has not been studied in healthy subjects breathing spontaneously without voluntary or pharmacological control of ventilation. Our aim is to generate three-dimensional (3D) regional strain and heterogeneity maps of healthy rat lungs and describe their changes over time. Methods: Micro-CT and image-based biomechanical analysis by finite element approach were carried out in six anaesthetised rats under spontaneous breathing in two different states, at the beginning of the experiment and after 3 hours of observation. 3D regional strain maps were constructed and divided into 10 isovolumetric region-of-interest (ROI) in three directions (apex to base, dorsal to ventral and costal to mediastinal), allowing to regionally analyse the volumetric strain, the strain progression and the strain heterogeneity. To describe in depth these parameters, and systematise their report, we defined regional strain heterogeneity index [1+strain SD ROI(x)]/[1+strain mean ROI(x)] and regional strain progression index [ROI(x)-mean of final strain/ROI(x)-mean of initial strain]. Results: We were able to generate 3D regional strain maps of the lung in subjects without respiratory support, showing significant differences among the three analysed axes. We observed a significantly lower regional volumetric strain in the apex sector compared with the base, with no significant anatomical systematic differences in the other directions. This heterogeneity could not be identified with physiological or standard CT methods. There was no progression of the analysed regional volumetric strain when the two time-points were compared. Discussion: It is possible to map the regional volumetric strain in the lung for healthy subjects during spontaneous breathing. Regional strain heterogeneity and changes over time can be measured using a CT image-based numerical analysis applying a finite element approach. These results support that healthy lung might have significant regional strain and its spatial distribution is highly heterogeneous. This protocol for CT image acquisition and analysis could be a useful tool for helping to understand the mechanobiology of the lung in many diseases.

Lung volumes and lung volume recruitment in ARDS: a comparison between supine and prone position.

BACKGROUND: The use of positive end-expiratory pressure (PEEP) and prone position (PP) is common in the management of severe acute respiratory distress syndrome patients (ARDS). We conducted this study to analyze the variation in lung volumes and PEEP-induced lung volume recruitment with the change from supine position (SP) to PP in ARDS patients. METHODS: The investigation was conducted in a multidisciplinary intensive care unit. Patients who met the clinical criteria of the Berlin definition for ARDS were included. The responsible physician set basal PEEP. To avoid hypoxemia, FiO2 was increased to 0.8 1 h before starting the protocol. End-expiratory lung volume (EELV) and functional residual capacity (FRC) were measured using the nitrogen washout/washin technique. After the procedures in SP, the patients were turned to PP and 1 h later the same procedures were made in PP. RESULTS: Twenty-three patients were included in the study, and twenty were analyzed. The change from SP to PP significantly increased FRC (from 965 ± 397 to 1140 ± 490 ml, p = 0.008) and EELV (from 1566 ± 476 to 1832 ± 719 ml, p = 0.008), but PEEP-induced lung volume recruitment did not significantly change (269 ± 186 ml in SP to 324 ± 188 ml in PP, p = 0.263). Dynamic strain at PEEP decreased with the change from SP to PP (0.38 ± 0.14 to 0.33 ± 0.13, p = 0.040). CONCLUSIONS: As compared to supine, prone position increases resting lung volumes and decreases dynamic lung strain.

Respiratory mechanics and lung stress/strain in children with acute respiratory distress syndrome.

BACKGROUND: In sedated and paralyzed children with acute respiratory failure, the compliance of respiratory system and functional residual capacity were significantly reduced compared with healthy subjects. However, no major studies in children with ARDS have investigated the role of different levels of PEEP and tidal volume on the partitioned respiratory mechanic (lung and chest wall), stress (transpulmonary pressure) and strain (inflated volume above the functional residual capacity). METHODS: The end-expiratory lung volume was measured using a simplified closed circuit helium dilution method. During an inspiratory and expiratory pause, the airway and esophageal pressure were measured. Transpulmonary pressure was computed as the difference between airway and esophageal pressure. RESULTS: Ten intubated sedated paralyzed healthy children and ten children with ARDS underwent a PEEP trial (4 and 12 cmH2O) with a tidal volume of 8, 10 and 12 ml/kgIBW. The two groups were comparable for age and BMI (2.5 [1.0-5.5] vs 3.0 [1.7-7.2] years and 15.1 ± 2.4 vs 15.3 ± 3.0 kg/m(2)). The functional residual capacity in ARDS patients was significantly lower as compared to the control group (10.4 [9.1-14.3] vs 16.6 [11.7-24.6] ml/kg, p = 0.04). The ARDS patients had a significantly lower respiratory system and lung compliance as compared to control subjects (9.9 ± 5.0 vs 17.8 ± 6.5, 9.3 ± 4.9 vs 16.9 ± 4.1 at 4 cmH2O of PEEP and 11.7 ± 5.8 vs 23.7 ± 6.8, 10.0 ± 4.9 vs 23.4 ± 7.5 at 12 cmH2O of PEEP). The compliance of the chest wall was similar in both groups (76.7 ± 30.2 vs 94.4 ± 76.4 and 92.6 ± 65.3 vs 90.0 ± 61.7 at 4 and 12 cmH2O of PEEP). The lung stress and strain were significantly higher in ARDS patients as compared to control subjects and were poorly related to airway pressure and tidal volume normalized for body weight. CONCLUSIONS: Airway pressures and tidal volume normalized to body weight are poor surrogates for lung stress and strain in mild pediatric ARDS. TRIAL REGISTRATION: Clinialtrials.gov NCT02036801. Registered 13 January 2014.