Dependent Lung Regions Research Articles

Regional Differences in Lung Ventilation During the Early Transition Period in Late Preterm and Term Neonates Assessed by Electrical Impedance Tomography

Background: Changes in lung ventilation are well documented in term neonates while in late preterm neonates these patterns are poorly understood despite their increased risk of respiratory morbidity. Objectives: The study aimed to compare and clarify the differences in regional lung ventilation of late preterm and term neonates during the early adaptation period using electrical impedance tomography (EIT). Material and methods: The case-control study was conducted in the years 2020–2022. It included 51 late preterm neonates (LPN, Study group) and 45 term neonates (TN, Control) born by normal vaginal delivery (NVD). EIT examinations were performed with a Swisstom BB2 (Switzerland) equipment. The data recordings were performed no later than 30 (I Record), 60 (II), and 90 (III) minutes after the birth. Results: Statistically significant differences between LPN and TN were observed in the non-dependent lung areas at I record, with more silent spaces observed in the LPN (p < 0.001). Differences in the dependent lung regions were observed across all recordings, with LPN demonstrating more silent spaces (p < 0.001). LPN demonstrated greater stretch-related changes in the 10% and 20% stretch categories across all recordings, while TN showed greater changes in the 50%, 70%, and 90% categories. Tidal volumes in the right lung of TN are distributed more towards the ventral and central ventral regions. In contrast, tidal volumes of LPN are distributed to the central dorsal and dorsal regions of the right lung. Conclusions: LPN during the first 90 min after the birth show reduced lung ventilation assessed by EIT, suggesting a possible impairment of early postnatal adaptation.

Effects of starting one lung ventilation and applying individualized PEEP right after patients are placed in lateral decubitus position on intraoperative oxygenation for patients undergoing thoracoscopic pulmonary lobectomy: study protocol for a randomized controlled trial

BackgroundFor patients receiving one lung ventilation in thoracic surgery, numerous studies have proved the superiority of lung protective ventilation of low tidal volume combined with recruitment maneuvers (RM) and individualized PEEP. However, RM may lead to overinflation which aggravates lung injury and intrapulmonary shunt. According to CT results, atelectasis usually forms in gravity dependent lung regions, regardless of body position. So, during anesthesia induction in supine position, atelectasis usually forms in the dorsal parts of lungs, however, when patients are turned into lateral decubitus position, collapsed lung tissue in the dorsal parts would reexpand, while atelectasis would slowly reappear in the lower flank of the lung. We hypothesize that applying sufficient PEEP without RM before the formation of atelectasis in the lower flank of the lung may beas effective to prevent atelectasis and thus improve oxygenation as applying PEEP with RM.MethodsA total of 84 patients scheduled for elective pulmonary lobe resection necessitating one lung ventilation will be recruited and randomized totwo parallel groups. For all patients, one lung ventilation is initiated the right after patients are turned into lateral decubitus position. For patients in the study group, individualized PEEP titration is started the moment one lung ventilation is started, while patients in the control group will receive a recruitment maneuver followed by individualized PEEP titration after initiation of one lung ventilation. The primary endpoint will be oxygenation index measured at T4. Secondary endpoints will include intrapulmonary shunt, respiratory mechanics, PPCs, and hemodynamic indicators.DiscussionNumerous previous studies compared the effects of individualized PEEP applied alone with that applied in combination with RM on oxygenation index, PPCs, intrapulmonary shunt and respiratory mechanics after atelectasis was formed in patients receiving one lung ventilation during thoracoscopic surgery. In this study, we will apply individualized PEEP before the formation of atelectasis while not performing RM in patients allocated to the study group, and then we’re going to observe its effects on the aspects mentioned above. The results of this trial will provide a ventilation strategy that may be conductive to improving intraoperative oxygenation and avoiding the detrimental effects of RM for patients receiving one lung ventilation.Trial registrationwww.Chictr.org.cn ChiCTR2400080682. Registered on February 5, 2024.

Pneumothorax risk reduction during CT-guided lung biopsy – Effect of fluid application to the pleura before lung puncture and the gravitational effect of pleural pressure

PurposeThis study investigated strategies to reduce pneumothorax risk in CT-guided lung biopsy. The approach involved administering 10 ml of 1 % lidocaine fluid in the subpleural or pleural space before lung puncture and utilizing the gravitational effect of pleural pressure with specific patient positioning. MethodWe retrospectively analyzed 72 percutaneous CT-guided lung biopsies performed at a single center between January 2020 and April 2023. These were grouped based on fluid administration during the biopsy and whether the biopsies were conducted in dependent or non-dependent lung regions. Confounding factors like patient demographics, lesion characteristics, and procedural details were assessed. Patient characteristics and the occurrence of pneumothoraces were compared using a Kurskal-Wallis test for continuous variables and a Fisher’s exact test for categorical variables. Multivariable logistic regression was used to identify potential confounders. ResultsSubpleural or pleural fluid administration and performing biopsies in dependent lung areas were significantly linked to lower peri-interventional pneumothorax incidence (n = 15; 65 % without fluid in non-dependent areas, n = 5; 42 % without fluid in dependent areas, n = 5; 36 % with fluid in non-dependent areas,n = 0; 0 % with fluid in dependent areas; p = .001). Even after adjusting for various factors, biopsy in dependent areas and fluid administration remained independently associated with reduced pneumothorax risk (OR 0.071, p<=.01 for lesions with fluid administration; OR 0.077, p = .016 for lesions in dependent areas). ConclusionsPre-puncture fluid administration to the pleura and consideration of gravitational effects during patient positioning can effectively decrease pneumothorax occurrences in CT-guided lung biopsy.

Flow-controlled ventilation decreases mechanical power in postoperative ICU patients

BackgroundMechanical power (MP) is the energy delivered by the ventilator to the respiratory system and combines factors related to the development of ventilator-induced lung injury (VILI). Flow-controlled ventilation (FCV) is a new ventilation mode using a constant low flow during both inspiration and expiration, which is hypothesized to lower the MP and to improve ventilation homogeneity. Data demonstrating these effects are scarce, since previous studies comparing FCV with conventional controlled ventilation modes in ICU patients suffer from important methodological concerns.ObjectivesThis study aims to assess the difference in MP between FCV and pressure-controlled ventilation (PCV). Secondary aims were to explore the effect of FCV in terms of minute volume, ventilation distribution and homogeneity, and gas exchange.MethodsThis is a physiological study in post-cardiothoracic surgery patients requiring mechanical ventilation in the ICU. During PCV at baseline and 90 min of FCV, intratracheal pressure, airway flow and electrical impedance tomography (EIT) were measured continuously, and hemodynamics and venous and arterial blood gases were obtained repeatedly. Pressure–volume loops were constructed for the calculation of the MP.ResultsIn 10 patients, optimized FCV versus PCV resulted in a lower MP (7.7 vs. 11.0 J/min; p = 0.004). Although FCV did not increase overall ventilation homogeneity, it did lead to an improved ventilation of the dependent lung regions. A stable gas exchange at lower minute volumes was obtained.ConclusionsFCV resulted in a lower MP and improved ventilation of the dependent lung regions in post-cardiothoracic surgery patients on the ICU.Trial registration Clinicaltrials.gov identifier: NCT05644418. Registered 1 December 2022, retrospectively registered.

Pendelluft in patients with acute respiratory distress syndrome during trigger and reverse triggering breaths

Pendelluft, the shift of air from non-dependent to dependent lung regions, is known to occur during active breathing in ventilated patients. However, information about pendelluft in ARDS patients under assisted mechanical ventilation is limited. In this prospectively collected and retrospectively analyzed study, we combined electrical impedance tomography and respiratory mechanics monitoring to quantitatively examine pendelluft in trigger and reverse triggering breaths in 20 mechanically ventilated patients with ARDS during the transition from controlled to active breaths under volume-cycled ventilation. Besides the 10 resting breaths in each patient, 20% of the counted active breaths were selected based on three levels of esophageal pressure swing (∆Pes): low (< 5 cm H2O, breaths = 471), moderate (≥ 5, < 10 cm H2O, breaths = 906), and high effort (≥ 10 cm H2O, breaths = 565). The pendelluft response to breathing efforts was significantly greater in trigger breaths than in reverse triggering breaths (p < 0.0001). Based on the pendelluft-∆Pes slope (ml/cmH2O), there were two distinct patterns of effort-related pendelluft (high vs. low pendelluft group). For trigger breaths, the high pendelluft group (n = 9, slope 0.7–2.4 ml/cmH2O) was significantly associated with lower peak airway/plateau pressure and lower respiratory system/lung elastance than the low pendelluft group (n = 11, slope − 0.1 to 0.3 ml/cmH2O). However, there was no difference in respiratory mechanics between high and low pendelluft groups for reverse triggering breathes. The use of ∆Pes to predict pendelluft was found to have a low positive predictive value.

Physiological effects of awake prone position in acute hypoxemic respiratory failure

BackgroundThe effects of awake prone position on the breathing pattern of hypoxemic patients need to be better understood. We conducted a crossover trial to assess the physiological effects of awake prone position in patients with acute hypoxemic respiratory failure.MethodsFifteen patients with acute hypoxemic respiratory failure and PaO2/FiO2 < 200 mmHg underwent high-flow nasal oxygen for 1 h in supine position and 2 h in prone position, followed by a final 1-h supine phase. At the end of each study phase, the following parameters were measured: arterial blood gases, inspiratory effort (ΔPES), transpulmonary driving pressure (ΔPL), respiratory rate and esophageal pressure simplified pressure–time product per minute (sPTPES) by esophageal manometry, tidal volume (VT), end-expiratory lung impedance (EELI), lung compliance, airway resistance, time constant, dynamic strain (VT/EELI) and pendelluft extent through electrical impedance tomography.ResultsCompared to supine position, prone position increased PaO2/FiO2 (median [Interquartile range] 104 mmHg [76–129] vs. 74 [69–93], p < 0.001), reduced respiratory rate (24 breaths/min [22–26] vs. 27 [26–30], p = 0.05) and increased ΔPES (12 cmH2O [11–13] vs. 9 [8–12], p = 0.04) with similar sPTPES (131 [75–154] cmH2O s min−1 vs. 105 [81–129], p > 0.99) and ΔPL (9 [7–11] cmH2O vs. 8 [5–9], p = 0.17). Airway resistance and time constant were higher in prone vs. supine position (9 cmH2O s arbitrary units−3 [4–11] vs. 6 [4–9], p = 0.05; 0.53 s [0.32–61] vs. 0.40 [0.37–0.44], p = 0.03). Prone position increased EELI (3887 arbitrary units [3414–8547] vs. 1456 [959–2420], p = 0.002) and promoted VT distribution towards dorsal lung regions without affecting VT size and lung compliance: this generated lower dynamic strain (0.21 [0.16–0.24] vs. 0.38 [0.30–0.49], p = 0.004). The magnitude of pendelluft phenomenon was not different between study phases (55% [7–57] of VT in prone vs. 31% [14–55] in supine position, p > 0.99).ConclusionsProne position improves oxygenation, increases EELI and promotes VT distribution towards dependent lung regions without affecting VT size, ΔPL, lung compliance and pendelluft magnitude. Prone position reduces respiratory rate and increases ΔPES because of positional increases in airway resistance and prolonged expiratory time. Because high ΔPES is the main mechanistic determinant of self-inflicted lung injury, caution may be needed in using awake prone position in patients exhibiting intense ΔPES.Clinical trail registeration: The study was registered on clinicaltrials.gov (NCT03095300) on March 29, 2017.

Real-time effects of lateral positioning on regional ventilation and perfusion in an experimental model of acute respiratory distress syndrome.

Low-volume lung injury encompasses local concentration of stresses in the vicinity of collapsed regions in heterogeneously ventilated lungs. We aimed to study the effects on ventilation and perfusion distributions of a sequential lateral positioning (30°) strategy using electrical impedance tomography imaging in a porcine experimental model of early acute respiratory distress syndrome (ARDS). We hypothesized that such strategy, including a real-time individualization of positive end-expiratory pressure (PEEP) whenever in lateral positioning, would provide attenuation of collapse in the dependent lung regions. A two-hit injury acute respiratory distress syndrome experimental model was established by lung lavages followed by injurious mechanical ventilation. Then, all animals were studied in five body positions in a sequential order, 15min each: Supine 1; Lateral Left; Supine 2; Lateral Right; Supine 3. The following functional images were analyzed by electrical impedance tomography: ventilation distributions and regional lung volumes, and perfusion distributions. The induction of the acute respiratory distress syndrome model resulted in a marked fall in oxygenation along with low regional ventilation and compliance of the dorsal half of the lung (gravitational-dependent in supine position). Both the regional ventilation and compliance of the dorsal half of the lung greatly increased along of the sequential lateral positioning strategy, and maximally at its end. In addition, a corresponding improvement of oxygenation occurred. In conclusion, our sequential lateral positioning strategy, with sufficient positive end-expiratory pressure to prevent collapse of the dependent lung units during lateral positioning, provided a relevant diminution of collapse in the dorsal lung in a porcine experimental model of early acute respiratory distress syndrome.

Homogenizing effect of PEEP on tidal volume distribution during neurally adjusted ventilatory assist: study of an animal model of acute respiratory distress syndrome

BackgroundThe physiological response and the potentially beneficial effects of positive end-expiratory pressure (PEEP) for lung protection and optimization of ventilation during spontaneous breathing in patients with acute respiratory distress syndrome (ARDS) are not fully understood. The aim of the study was to compare the effect of different PEEP levels on tidal volume distribution and on the ventilation of dependent lung region during neurally adjusted ventilatory assist (NAVA).MethodsARDS-like lung injury was induced by using saline lavage in 10 anesthetized and spontaneously breathing farm-bred pigs. The animals were ventilated in NAVA modality and tidal volume distribution as well as dependent lung ventilation were assessed using electric impedance tomography during the application of PEEP levels from 0 to 15 cmH20, in steps of 3 cmH20. Tidal volume distribution and dependent fraction of ventilation were analysed using Wilcoxon signed rank test. Furthermore, airway, esophageal and transpulmonary pressure, as well as airway flow and delivered volume, were continuously measured during the assisted spontaneous breathing.ResultsIncreasing PEEP improved oxygenation and re-distributed tidal volume. Specifically, ventilation distribution changed from a predominant non-dependent to a more even distribution between non-dependent and dependent areas of the lung. Dependent fraction of ventilation reached 47 ± 9% at PEEP 9 cmH20. Further increasing PEEP led to a predominant dependent ventilation.ConclusionDuring assisted spontaneous breathing in this model of induced ARDS, PEEP modifies the distribution of ventilation and can achieve a homogenizing effect on its spatial arrangement. The study indicates that PEEP is an important factor during assisted spontaneous breathing and that EIT can be of valuable interest when titrating PEEP level during spontaneous breathing, by indicating the most homogeneous distribution of gas volumes throughout the PEEP spectrum.

Inflammatory biomarkers and pendelluft magnitude in ards patients transitioning from controlled to partial support ventilation

The transition from controlled to partial support ventilation is a challenge in acute respiratory distress syndrome (ARDS) patients due to the risks of patient-self-inflicted lung injury. The magnitude of tidal volume (VT) and intrapulmonary dyssynchrony (pendelluft) are suggested mechanisms of lung injury. We conducted a prospective, observational, physiological study in a tertiary academic intensive care unit. ARDS patients transitioning from controlled to partial support ventilation were included. On these, we evaluated the association between changes in inflammatory biomarkers and esophageal pressure swing (ΔPes), transpulmonary driving pressure (ΔPL), VT, and pendelluft. Pendelluft was defined as the percentage of the tidal volume that moves from the non-dependent to the dependent lung region during inspiration, and its frequency at different thresholds (− 15, − 20 and − 25%) was also registered. Blood concentrations of inflammatory biomarkers (IL-6, IL-8, TNF-α, ANGPT2, RAGE, IL-18, Caspase-1) were measured before (T0) and after 4-h (T4) of partial support ventilation. Pendelluft, ΔPes, ΔPL and VT were recorded. Nine out of twenty-four patients (37.5%) showed a pendelluft mean ≥ 10%. The mean values of ΔPes, ΔPL, and VT were − 8.4 [− 6.7; − 10.2] cmH2O, 15.2 [12.3–16.5] cmH2O and 8.1 [7.3–8.9] m/kg PBW, respectively. Significant associations were observed between the frequency of high-magnitude pendelluft and IL-8, IL-18, and Caspase-1 changes (T0/T4 ratio). These results suggest that the frequency of high magnitude pendelluft may be a potential determinant of inflammatory response related to inspiratory efforts in ARDS patients transitioning to partial support ventilation. Future studies are needed to confirm these results.

Clinical Implications of Determining Individualized Positive End-Expiratory Pressure Using Electrical Impedance Tomography in Post-Cardiac Surgery Patients: A Prospective, Non-Randomized Interventional Study.

Optimal positive end-expiratory pressure (PEEP) can induce sustained lung function improvement. This prospective, non-randomized interventional study aimed to investigate the effect of individualized PEEP determined using electrical impedance tomography (EIT) in post-cardiac surgery patients (n = 35). Decremental PEEP trials were performed from 20 to 4 cmH2O in steps of 2 cmH2O, guided by EIT. PEEP levels preventing ventilation loss in dependent lung regions (PEEPONLINE) were set. Ventilation distributions and oxygenation before the PEEP trial, and 5 min and 1 h after the PEEPONLINE setting were examined. Furthermore, we analyzed the saved impedance data offline to determine the PEEP levels that provided the best compromise between overdistended and collapsed lung (PEEPODCL). Ventilation distributions of dependent regions increased at 5 min after the PEEPONLINE setting compared with those before the PEEP trial (mean ± standard deviation, 41.3 ± 8.5% vs. 49.1 ± 9.3%; p < 0.001), and were maintained at 1 h thereafter (48.7 ± 9.4%, p < 0.001). Oxygenation also showed sustained improvement. Rescue oxygen therapy (high-flow nasal cannula, noninvasive ventilation) after extubation was less frequent in patients with PEEPONLINE ≥ PEEPODCL than in those with PEEPONLINE < PEEPODCL (1/19 vs. 6/16; p = 0.018). EIT-guided individualized PEEP stabilized the improvement in ventilation distribution and oxygenation. Individual PEEP varies with EIT measures, and may differentially affect oxygenation after cardiac surgery.

High-flow nasal cannula and noninvasive ventilation: effects on alveolar recruitment and overdistension.

Both high-flow nasal cannula and noninvasive ventilation are subject to pulmonary complications https://bit.ly/3jFCSG9

Global and Regional Tidal Volume Distribution in Spontaneously Breathing Mechanically Ventilated Children.

Allowing the ventilated adult patient to breathe spontaneously may improve tidal volume (VT) distribution toward the dependent lung regions, reduce shunt fraction, and decrease dead space. It has not been studied if these effects under various levels of ventilatory support also occur in children. We sought to explore the effect of level of ventilatory support on VT distribution and end-expiratory lung volume (EELV) in spontaneously breathing ventilated children in the recovery phase of their acute respiratory failure. This is a secondary analysis of data from a prospective clinical trial comparing 2 different ventilator modes during weaning in mechanically ventilated children < 5 y: CPAP + pressure support ventilation (PSV) and pressure control (PC)/intermittent mandatory ventilation (IMV) + PSV with the mandatory breath rate set at 25% of baseline. Using electrical impedance tomography (EIT), we assessed VT distribution by calculating the center of ventilation. Polynomial functions of the second degree were plotted to evaluate regional lung filling characteristics. Changes in end-expiratory impedance were calculated to assess changes in EELV. Baseline measurements were compared with measurements during CPAP/PSV, PC/IMV + PSV, and during a downward titration of the level of pressure support. Thirty-five subjects with a median age 4.5 (2.1-12.9) months and a median ventilation time of 4.9 (3.3-6.9) d were studied. The overall median coefficient of variation was 50.1% and not different between CPAP/PSV or PC/synchronized IMV + PSV. Regional filling characteristics of the lung identified a homogeneous VT distribution under all study conditions. Downtapering of the level of PSV resulted in a significant shift of the coefficient of variation toward the dependent lung regions. Our data showed that allowing ventilated children in the recovery phase of respiratory failure to breathe spontaneously in a continuous spontaneous ventilation mode did not negatively affect VT distribution or EELV.

Transoesophageal Ultrasound Assessment of Lung Aeration in Patients With Acute Respiratory Distress Syndrome.

Introduction: The effect of positive end-expiratory pressure (PEEP) depends closely on the potential for lung recruitment. Bedside assessment of lung recruitability is crucial for personalized lung-protective mechanical ventilation in acute respiratory distress syndrome (ARDS) patients.Methods: We developed a transoesophageal lung ultrasound (TE-LUS) method in which a quantitative (computer-assisted) grayscale determination served as a guide to PEEP-induced lung recruitment. The method is based on the following hypothesis: when the PEEP increases, inflation of the recruited alveoli leads to significant changes in the air/water ratio. Normally ventilated areas are hypoechoic because the ultrasound waves are weakly reflected while poorly aerated areas or non-aerated areas are hyperechoic. We calculated the TE-LUS re-aeration score (RAS) as the ratio of the mean gray scale level at low PEEP to that value at high PEEP for the lower and upper lobes. A RAS > 1 indicated an increase in ventilated area. We used this new method to detect changes in ventilation in patients with a low (<0.5) vs. high (≥0.5) recruitment-to-inflation (R/I) ratio (i.e., the ratio between the recruited lung compliance and the respiratory system compliance at low PEEP).Results: We included 30 patients with moderate-to-severe ARDS. In patients with a high R/I ratio, the TE-LUS RAS was significantly higher in the lower lobes than in the upper lobes (1.20 [1.12–1.63] vs. 1.05 [0.89–1.38]; p = 0.05). Likewise, the TE-LUS RAS in the lower lobes was significantly higher in the high R/I group than in the low R/I group (1.20 [1.12–1.63] vs. 1.07 [1.00–1.20]; p = 0.04).Conclusion: The increase in PEEP induces a substantial gain in the ventilation detected by TE-LUS of poorly or non-aerated lower lobes (dependent lung regions), especially in patients with a high R/I ratio.

Effect of positive end-expiratory pressure on lung injury and haemodynamics during experimental acute respiratory distress syndrome treated with extracorporeal membrane oxygenation and near-apnoeic ventilation

BackgroundLung rest has been recommended during extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). Whether positive end-expiratory pressure (PEEP) confers lung protection during ECMO for severe ARDS is unclear. We compared the effects of three different PEEP levels whilst applying near-apnoeic ventilation in a model of severe ARDS treated with ECMO. MethodsAcute respiratory distress syndrome was induced in anaesthetised adult male pigs by repeated saline lavage and injurious ventilation for 1.5 h. After ECMO was commenced, the pigs received standardised near-apnoeic ventilation for 24 h to maintain similar driving pressures and were randomly assigned to PEEP of 0, 10, or 20 cm H2O (n=7 per group). Respiratory and haemodynamic data were collected throughout the study. Histological injury was assessed by a pathologist masked to PEEP allocation. Lung oedema was estimated by wet-to-dry-weight ratio. ResultsAll pigs developed severe ARDS. Oxygenation on ECMO improved with PEEP of 10 or 20 cm H2O, but did not in pigs allocated to PEEP of 0 cm H2O. Haemodynamic collapse refractory to norepinephrine (n=4) and early death (n=3) occurred after PEEP 20 cm H2O. The severity of lung injury was lowest after PEEP of 10 cm H2O in both dependent and non-dependent lung regions, compared with PEEP of 0 or 20 cm H2O. A higher wet-to-dry-weight ratio, indicating worse lung injury, was observed with PEEP of 0 cm H2O. Histological assessment suggested that lung injury was minimised with PEEP of 10 cm H2O. ConclusionsDuring near-apnoeic ventilation and ECMO in experimental severe ARDS, 10 cm H2O PEEP minimised lung injury and improved gas exchange without compromising haemodynamic stability.

Therapeutic benefits of proning to improve pulmonary gas exchange in severe respiratory failure: focus on fundamentals of physiology.

New Findings What is the topic of this review? The use of proning for improving pulmonary gas exchange in critically ill patients. What advances does it highlight? Proning places the lung in its ‘natural’ posture, and thus optimises the ventilation‐perfusion distribution, which enables lung protective ventilation and the alleviation of potentially life‐threatening hypoxaemia in COVID‐19 and other types of critical illness with respiratory failure. The survival benefit of proning patients with acute respiratory distress syndrome (ARDS) is well established and has recently been found to improve pulmonary gas exchange in patients with COVID‐19‐associated ARDS (CARDS). This review outlines the physiological implications of transitioning from supine to prone on alveolar ventilation‐perfusion (V˙A--Q˙) relationships during spontaneous breathing and during general anaesthesia in the healthy state, as well as during invasive mechanical ventilation in patients with ARDS and CARDS. Spontaneously breathing, awake healthy individuals maintain a small vertical (ventral‐to‐dorsal) V˙A/Q˙ ratio gradient in the supine position, which is largely neutralised in the prone position, mainly through redistribution of perfusion. In anaesthetised and mechanically ventilated healthy individuals, a vertical V˙A/Q˙ ratio gradient is present in both postures, but with better V˙A--Q˙ matching in the prone position. In ARDS and CARDS, the vertical V˙A/Q˙ ratio gradient in the supine position becomes larger, with intrapulmonary shunting in gravitationally dependent lung regions due to compression atelectasis of the dorsal lung. This is counteracted by proning, mainly through a more homogeneous distribution of ventilation combined with a largely unaffected high perfusion dorsally, and a consequent substantial improvement in arterial oxygenation. The data regarding proning as a therapy in patients with CARDS is still limited and whether the associated improvement in arterial oxygenation translates to a survival benefit remains unknown. Proning is nonetheless an attractive and lung protective manoeuvre with the potential benefit of improving life‐threatening hypoxaemia in patients with ARDS and CARDS.

Effects of Lung Injury on Regional Aeration and Expiratory Time Constants: Insights From Four-Dimensional Computed Tomography Image Registration.

Rationale: Intratidal changes in regional lung aeration, as assessed with dynamic four-dimensional computed tomography (CT; 4DCT), may indicate the processes of recruitment and derecruitment, thus portending atelectrauma during mechanical ventilation. In this study, we characterized the time constants associated with deaeration during the expiratory phase of pressure-controlled ventilation in pigs before and after acute lung injury using respiratory-gated 4DCT and image registration.Methods: Eleven pigs were mechanically ventilated in pressure-controlled mode under baseline conditions and following an oleic acid model of acute lung injury. Dynamic 4DCT scans were acquired without interrupting ventilation. Automated segmentation of lung parenchyma was obtained by a convolutional neural network. Respiratory structures were aligned using 4D image registration. Exponential regression was performed on the time-varying CT density in each aligned voxel during exhalation, resulting in regional estimates of intratidal aeration change and deaeration time constants. Regressions were also performed for regional and total exhaled gas volume changes.Results: Normally and poorly aerated lung regions demonstrated the largest median intratidal aeration changes during exhalation, compared to minimal changes within hyper- and non-aerated regions. Following lung injury, median time constants throughout normally aerated regions within each subject were greater than respective values for poorly aerated regions. However, parametric response mapping revealed an association between larger intratidal aeration changes and slower time constants. Lower aeration and faster time constants were observed for the dependent lung regions in the supine position. Regional gas volume changes exhibited faster time constants compared to regional density time constants, as well as better correspondence to total exhaled volume time constants.Conclusion: Mechanical time constants based on exhaled gas volume underestimate regional aeration time constants. After lung injury, poorly aerated regions experience larger intratidal changes in aeration over shorter time scales compared to normally aerated regions. However, the largest intratidal aeration changes occur over the longest time scales within poorly aerated regions. These dynamic 4DCT imaging data provide supporting evidence for the susceptibility of poorly aerated regions to ventilator-induced lung injury, and for the functional benefits of short exhalation times during mechanical ventilation of injured lungs.

Atelectasis, Shunt, and Worsening Oxygenation Following Reduction of Respiratory Rate in Healthy Pigs Undergoing ECMO: An Experimental Lung Imaging Study

Rationale: Reducing the respiratory rate during extracorporeal membrane oxygenation (ECMO) decreases the mechanical power, but it might induce alveolar de-recruitment. Dissecting de-recruitment due to lung edema vs. the fraction due to hypoventilation may be challenging in injured lungs.Objectives: We characterized changes in lung physiology (primary endpoint: development of atelectasis) associated with progressive reduction of the respiratory rate in healthy animals on ECMO.Methods: Six female pigs underwent general anesthesia and volume control ventilation (Baseline: PEEP 5 cmH2O, Vt 10 ml/kg, I:E = 1:2, FiO2 0.5, rate 24 bpm). Veno-venous ECMO was started and respiratory rate was progressively reduced to 18, 12, and 6 breaths per minute (6-h steps), while all other settings remained unchanged. ECMO blood flow was kept constant while gas flow was increased to maintain stable PaCO2.Measurements and Main Results: At Baseline (without ECMO) and toward the end of each step, data from quantitative CT scan, electrical impedance tomography, and gas exchange were collected. Increasing ECMO gas flow while lowering the respiratory rate was associated with an increase in the fraction of non-aerated tissue (i.e., atelectasis) and with a decrease of tidal ventilation reaching the gravitationally dependent lung regions (p = 0.009 and p = 0.018). Intrapulmonary shunt increased (p < 0.001) and arterial PaO2 decreased (p < 0.001) at lower rates. The fraction of non-aerated lung was correlated with longer expiratory time spent at zero flow (r = 0.555, p = 0.011).Conclusions: Progressive decrease of respiratory rate coupled with increasing CO2 removal in mechanically ventilated healthy pigs is associated with development of lung atelectasis, higher shunt, and poorer oxygenation.

Air distribution within the lungs after total liquid ventilation in a neonatal ovine model

ObjectiveTo gain insight into the total and regional lung aeration dynamics at the transition from total liquid ventilation (TLV) to conventional mechanical ventilation (GV). MethodsNeonatal lambs received either TLV for 4 h followed by GV (n = 15) or GV only (n = 11, controls). Monitoring was performed in the prone position with both videofluoroscopy and electrical impedance tomography (EIT) for the first 10 min of the transition. ResultsTotal and regional end-expiratory lung volumes were stable throughout the transition (p < 0.05). The percentage of tidal volume, liquid and/or gaseous, distributed to the different regions was stable (p < 0.05). Radiopacity of the nondependent regions markedly decreased at end-expiration (p < 0.01), reflecting the progressive transition to a gaseous end-expiratory lung volume. ConclusionWeaning to GV did not increase total or regional lung volumes, suggesting that the risk of overdistention was not increased. Residual perfluorocarbon in the dependent lung regions might account for the high O2 needs we observed in the first minutes of GV after TLV.

Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome.

Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients’ outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem. After induction of ARDS, 26 pigs were randomized into three groups: (1) control (Sham), (2) perfluorohexyloctane (F6H8), and (3) F6H8-ibuprofen. Using a nebulization catheter, (2) received 1 mL/kg F6H8 while (3) received 1 mL/kg F6H8 with 6 mg/mL ibuprofen. Ibuprofen plasma and lung tissue concentration, bronchoalveolar lavage (BAL) fluid concentration of TNF-α, IL-8, and IL-6, and lung mechanics were measured. The ibuprofen concentration was equally distributed to the dependent parts of the right lungs. Pharmacokinetic data demonstrated systemic absorption of ibuprofen proofing a transport across the alveolo-capillary membrane. A significantly lower TNF-α concentration was observed in (2) and (3) when compared to the control group (1). There were no significant differences in IL-8 and IL-6 concentrations and lung mechanics. F6H8 aerosol seemed to be a suitable carrier for pulmonary drug delivery to dependent ARDS lung regions without having negative effects on lung mechanics.

Personalisation of Therapies in COVID-19 Associated Acute Respiratory Distress Syndrome, Using Electrical Impedance Tomography.

IntroductionEach patient suffering from severe coronavirus COVID-19-associated acute respiratory distress syndrome (ARDS), requiring mechanical ventilation, shows different lung mechanics and disease evolution. Therefore, lung protective strategies should be personalised for the individual patient.Case presentationA 64-year-old male patient was intubated ten days after the symptoms of COVID-19 infection presented. He was placed in the prone position for sixteen hours, resulting in a marked improvement in oxygenation. However, after being returned to the supine position, his SpO2 rapidly dropped from 98% to 91%, and electrical impedance tomography showed less ventilation at the dorsal region and a ventral shift of ventilation distribution. An incremental and decremental PEEP trial under electrical impedance tomography monitoring was carried out, confirming that the dependent lung regions were recruited with increased pressures and homogenous ventilation distribution could be provided with 14 cmH2O of PEEP. The optimal settings were reassessed next day after returning from the second session of the prone position. After four prone position-sessions in five days, oxygenation was stabilised and eventually the patient was discharged.ConclusionsPatients with COVID-19 associated ARDS require individualised ventilation support depending on the stage of their disease. Daily PEEP trial monitored by electrical impedance tomography can provide important information to tailor the respiratory therapies.