The influence of the post-hepatic septum and abdominal volume on breathing mechanics in the lizard Salvator merianae (Squamata: Teiidae).

Teiid lizards possess an incomplete post-hepatic septum (PHS) separating the lungs and liver from the remaining viscera, and within this group, Salvator merianae has the most complete PHS. In this study, we explored the combined effects of the presence of the PHS and alterations in abdominal volume on the mechanics of the respiratory system. The PHS is believed to act as a mechanical barrier, mitigating the impact of the viscera on the lungs. Using established protocols, we determined static (Cstat) and dynamic (Cdyn) compliance, lung volume and work of breathing for the respiratory system in tegu lizards with intact (PHS+) or removed (PHS-) PHS, combined with (balloon+) or without (balloon-) increased abdominal volume. The removal of the PHS significantly reduced resting lung volume and Cdyn, as well as significantly increasing the work of breathing. An increase in abdominal volume significantly reduced Cstat, Cdyn, and resting and maximum lung volume. However, the work of breathing increased less in the PHS+/balloon+ treatment than in the PHS- treatments. These results highlight the barrier function of the PHS within the tegu lizard's body cavity. The septum effectively reduces the impact of the viscera on the respiratory system, enabling the lungs to be ventilated at a low work level, even when abdominal volume is increased. The presence of the PHS in teiid lizards underscores how extrapulmonary structures, such as septal divisions of the body cavity, can profoundly affect pulmonary breathing mechanics.

Hourly Analysis of Mechanical Ventilation Parameters in Critically Ill Adult Covid-19 Patients: Association with Mortality.

Objective: There exists controversy about the pathophysiology and lung mechanics of COVID-19 associated acute respiratory distress syndrome (ARDS), because some report severe hypoxemia with preserved respiratory system mechanics, contrasting with "classic" ARDS. We performed a detailed hourly analysis of the characteristics and time course of lung mechanics and biochemical analysis of patients requiring invasive mechanical ventilation (IMV) for COVID-19-associated ARDS, comparing survivors and non-survivors. Methods: Retrospective analysis of the data stored in the ICU information system of patients admitted in our hospital ICU that required IMV due to confirmed SARS-CoV-2 pneumonia between March 5th and April 30th, 2020. We compare respiratory system mechanics and gas exchange during the first ten days of IMV, discriminating volume and pressure controlled modes, between ICU survivors and non-survivors. Results: 140 patients were included, analyzing 11 138 respiratory mechanics recordings. Global mortality was 38.6%. Multivariate analysis showed that age (OR 1.092, 95% (CI 1.014-1.176)) and need of renal replacement therapies (OR 10.15, (95% CI 1.58-65.11)) were associated with higher mortality. Previous use of Angiotensin Converting Enzyme inhibitor (ACEI)/angiotensin-receptor blockers (ARBs) also seemed to show an increased mortality (OR 4.612, (95% CI 1.19-17.84)) although this significance was lost when stratifying by age. Respiratory variables start to diverge significantly between survivors and non-survivors after the 96 to 120 hours (hs) from mechanical ventilation initiation, particularly respiratory system compliance. In non survivors, mechanical power at 24 and 96 hs was higher regardless ventilatory mode. Conclusions: In patients admitted for SARS-CoV-2 pneumonia and requiring mechanical ventilation, non survivors have different respiratory system mechanics than survivors in the first 10 days of ICU admission. We propose a checkpoint at 96-120 hs to assess patients improvement or worsening in order to consider escalating to extracorporeal therapies.

Computed tomography assessment of PEEP-induced alveolar recruitment in patients with severe COVID-19 pneumonia.

BACKGROUND: There is a paucity of data concerning the optimal ventilator management in patients with COVID-19 pneumonia; particularly, the optimal levels of positive-end expiratory pressure (PEEP) are unknown. We aimed to investigate the effects of two levels of PEEP on alveolar recruitment in critically ill patients with severe COVID-19 pneumonia. METHODS: A single-center cohort study was conducted in a 39-bed intensive care unit at a university-affiliated hospital in Genoa, Italy. Chest computed tomography (CT) was performed to quantify aeration at 8 and 16 cmH2O PEEP. The primary endpoint was the amount of alveolar recruitment, defined as the change in the non-aerated compartment at the two PEEP levels on CT scan. RESULTS: Forty-two patients were included in this analysis. Alveolar recruitment was median [interquartile range] 2.7 [0.7-4.5] % of lung weight and was not associated with excess lung weight, PaO2/FiO2 ratio, respiratory system compliance, inflammatory and thrombophilia markers. Patients in the upper quartile of recruitment (recruiters), compared to non-recruiters, had comparable clinical characteristics, lung weight and gas volume. Alveolar recruitment was not different in patients with lower versus higher respiratory system compliance. In a subgroup of 20 patients with available gas exchange data, increasing PEEP decreased respiratory system compliance (median difference, MD - 9 ml/cmH2O, 95% CI from - 12 to - 6 ml/cmH2O, p < 0.001) and the ventilatory ratio (MD - 0.1, 95% CI from - 0.3 to - 0.1, p = 0.003), increased PaO2 with FiO2 = 0.5 (MD 24 mmHg, 95% CI from 12 to 51 mmHg, p < 0.001), but did not change PaO2 with FiO2 = 1.0 (MD 7 mmHg, 95% CI from - 12 to 49 mmHg, p = 0.313). Moreover, alveolar recruitment was not correlated with improvement of oxygenation or venous admixture. CONCLUSIONS: In patients with severe COVID-19 pneumonia, higher PEEP resulted in limited alveolar recruitment. These findings suggest limiting PEEP strictly to the values necessary to maintain oxygenation, thus avoiding the use of higher PEEP levels.

Impact of high tidal volume ventilation on surfactant metabolism and lung injury in infant rats.

The poorly understood tolerance toward high tidal volume (VT) ventilation observed in critically ill children and age-equivalent animal models may be explained by surfactant homeostasis. The aim of our prospective animal study was to test whether high VT with adequate positive end-expiratory pressure (PEEP) is associated with surfactant de novo synthesis and secretion, leading to improved lung function, and whether extreme mechanical ventilation affects intracellular lamellar body formation and exocytosis. Rats (14 days old) were allocated to five groups: nonventilated controls, PEEP 5 cmH2O with VT of 8, 16, and 24 mL/kg, and PEEP 1 cmH2O with VT 24 mL/kg. Following 6 h of ventilation, lung function, surfactant proteins and phospholipids, and lamellar bodies were assessed by forced oscillation technique, quantitative real-time polymerase chain reaction, mass spectrometry, immunohistochemistry, and transmission electron microscopy. High VT (24 mL/kg) with PEEP of 5 cmH2O improved respiratory system mechanics and was not associated with lung injury, elevated surfactant protein expression, or surfactant phospholipid content. Extreme ventilation with VT 24 mL/kg and PEEP 1 cmH2O produced a mild inflammatory response and correlated with higher surfactant phospholipid concentrations in bronchoalveolar lavage fluid without affecting lamellar body count and morphology. Elevated phospholipid concentrations in the potentially most injurious strategy (VT 24 mL/kg, PEEP 1 cmH2O) need further evaluation and might reflect accumulation of biophysically inactive small aggregates. In conclusion, our data confirm the resilience of infant rats toward high VT-induced lung injury and challenge the relevance of surfactant synthesis, storage, and secretion as protective factors.

Effect of individualized PEEP titration guided by intratidal compliance profile analysis on regional ventilation assessed by electrical impedance tomography - a randomized controlled trial.

BACKGROUND: The application of positive end-expiratory pressure (PEEP) may reduce dynamic strain during mechanical ventilation. Although numerous approaches for PEEP titration have been proposed, there is no accepted strategy for titrating optimal PEEP. By analyzing intratidal compliance profiles, PEEP may be individually titrated for patients. METHODS: After obtaining informed consent, 60 consecutive patients undergoing general anesthesia were randomly allocated to mechanical ventilation with PEEP 5 cmH2O (control group) or PEEP individually titrated, guided by an analysis of the intratidal compliance profile (intervention group). The primary endpoint was the frequency of each nonlinear intratidal compliance (CRS) profile of the respiratory system (horizontal, increasing, decreasing, and mixed). The secondary endpoints measured were respiratory mechanics, hemodynamic variables, and regional ventilation, which was assessed via electrical impedance tomography. RESULTS: The frequencies of the CRS profiles were comparable between the groups. Besides PEEP [control: 5.0 (0.0), intervention: 5.8 (1.1) cmH2O, p < 0.001], the respiratory and hemodynamic variables were comparable between the two groups. The compliance profile analysis showed no significant differences between the two groups. The loss of ventral and dorsal regional ventilation was higher in the control [ventral: 41.0 (16.3)%; dorsal: 25.9 (13.8)%] than in the intervention group [ventral: 29.3 (17.6)%; dorsal: 16.4 (12.7)%; p (ventral) = 0.039, p (dorsal) = 0.028]. CONCLUSIONS: Unfavorable compliance profiles indicating tidal derecruitment were found less often than in earlier studies. Individualized PEEP titration resulted in slightly higher PEEP. A slight global increase in aeration associated with this was indicated by regional gain and loss analysis. Differences in dorsal to ventral ventilation distribution were not found. TRIAL REGISTRATION: This clinical trial was registered at the German Register for Clinical Trials (DRKS00008924) on August 10, 2015.

Dependency of respiratory system mechanics on positive end-expiratory pressure and recruitment maneuvers in lung healthy pediatric patients-A randomized crossover study.

BACKGROUND: The lungs of pediatric patients are subjected to tidal derecruitment during mechanical ventilation and in contrast to adult patients this unfavorable condition cannot be resolved with small c increases. This raises the question if higher end-expiratory pressure increases or recruitment maneuvers may resolve tidal derecruitment in pediatric patients. AIMS: We hypothesized that higher PEEP resolves tidal derecruitment in pediatric patients and that recruitment maneuvers between the pressure changes support the improvement of respiratory system mechanics. METHODS: The effects of end-expiratory pressure changes from 3 to 7 cmH2 O and vice versa without and with intermediate recruitment maneuvers on respiratory system mechanics and regional ventilation were investigated in 57 mechanically ventilated pediatric patients. The intratidal respiratory system compliance was determined from volume and pressure data before and after PEEP changes and categorized to indicate tidal derecruitment. RESULTS: Tidal derecruitment occurred comparably frequently at PEEP 3 cmH2 O without (13 out of 14 cases) and with recruitment maneuver (14 out of 14 cases) and at PEEP 7 cmH2 O without (13 out of 14 cases) and with recruitment maneuver (13 out of 15 cases). CONCLUSIONS: We conclude that contrary to our hypothesis, PEEP up to 7 cmH2 O is not sufficient to resolve tidal derecruitment and that recruitment maneuvers may be dispensable in mechanically ventilated pediatric patients.

Hyperoxia-induced lung structure-function relation, vessel rarefaction, and cardiac hypertrophy in an infant rat model.

BACKGROUND: Hyperoxia-induced bronchopulmonary dysplasia (BPD) models are essential for better understanding and impacting on long-term pulmonary, cardiovascular, and neurological sequelae of this chronic disease. Only few experimental studies have systematically compared structural alterations with lung function measurements. METHODS: In three separate and consecutive series, Sprague-Dawley infant rats were exposed from day of life (DOL) 1 to 19 to either room air (0.21; controls) or to fractions of inspired oxygen (FiO2) of 0.6, 0.8, and 1.0. Our primary outcome parameters were histopathologic analyses of heart, lungs, and respiratory system mechanics, assessed via image analysis tools and the forced oscillation technique, respectively. RESULTS: Exposure to FiO2 of 0.8 and 1.0 resulted in significantly lower body weights and elevated coefficients of lung tissue damping (G) and elastance (H) when compared with controls. Hysteresivity (η) was lower due to a more pronounced increase of H when compared with G. A positive structure-function relation was demonstrated between H and the lung parenchymal content of α-smooth muscle actin (α-SMA) under hyperoxic conditions. Moreover, histology and morphometric analyses revealed alveolar simplification, fewer pulmonary arterioles, increased α-SMA content in pulmonary vessels, and right heart hypertrophy following hyperoxia. Also, in comparison to controls, hyperoxia resulted in significantly lower plasma levels of vascular endothelial growth factor (VEGF). Lastly, rats in hyperoxia showed hyperactive and a more explorative behaviour. CONCLUSIONS: Our in vivo infant rat model mimics clinical key features of BPD. To the best of our knowledge, this is the first BPD rat model demonstrating an association between lung structure and function. Moreover, we provide additional evidence that infant rats subjected to hyperoxia develop rarefaction of pulmonary vessels, augmented vascular α-SMA, and adaptive cardiac hypertrophy. Thus, our model provides a clinically relevant tool to further investigate diseases related to O2 toxicity and to evaluate novel pharmacological treatment strategies.

Determination of respiratory system compliance during pressure support ventilation by small variations of pressure support.

In mechanically ventilated patients, measurement of respiratory system compliance (Crs) is of high clinical interest. Spontaneous breathing activity during pressure support ventilation (PSV) can impede the correct assessment of Crs and also alter the true Crs by inducing lung recruitment. We describe a method for determination of Crs during PSV and assess its accuracy in a study on 20 mechanically ventilated patients. To assess Crs during pressure support ventilation (Crs,PSV), we performed repeated changes in pressure support level by ± 2 cmH2O. Crs,PSV was calculated from the volume change induced by these changes in pressure support level, taking into account the inspiration time and the expiratory time constant. As reference methods, we used Crs, measured during volume controlled ventilation (Crs,VCV). In a post-hoc analysis, we assessed Crs during the last 20% of the volume-controlled inflation (Crs,VCV20). Values were compared by linear regression and Bland-Altman methods comparison. Comparing Crs,PSV to the reference value Crs,VCV, we found a coefficient of determination (r2) of 0.90, but a relatively high bias of - 7 ml/cm H2O (95% limits of agreement - 16.7 to + 2.7 ml/cmH2O). Comparison with Crs,VCV20 resulted in a negligible bias (- 1.3 ml/cmH2O, 95% limits of agreement - 13.9 to + 11.3) and r2 of 0.81. We conclude that the novel method provides an estimate of end-inspiratory Crs during PSV. Despite its limited accuracy, it might be useful for non-invasive monitoring of Crs in patients undergoing pressure support ventilation.

Pneumoperitoneum deteriorates intratidal respiratory system mechanics: an observational study in lung-healthy patients.

BACKGROUND: Pneumoperitoneum during laparoscopic surgery leads to atelectasis and impairment of oxygenation. Positive end-expiratory pressure (PEEP) is supposed to counteract atelectasis. We hypothesized that the derecruiting effects of pneumoperitoneum would deteriorate the intratidal compliance profile in patients undergoing laparoscopic surgery. METHODS: In 30 adult patients scheduled for surgery with pneumoperitoneum, respiratory variables were measured during mechanical ventilation. We calculated the dynamic compliance of the respiratory system (C RS) and the intratidal volume-dependent C RS curve using the gliding-SLICE method. The C RS curve was then classified in terms of indicating intratidal recruitment/derecruitment (increasing profile) and overdistension (decreasing profile). During the surgical interventions, the PEEP level was maintained nearly constant at 7 cm H2O. Data are expressed as mean [confidence interval]. RESULTS: Baseline C RS was 60 [54-67] mL cm H2O-1. Application of pneumoperitoneum decreased C RS to 40 [37-43] mL cm H2O-1 which partially recovered to 54 [50-59] mL cm H2O-1 (P < 0.001) after removal but remained below the value measured before pneumoperitoneum (P < 0.001). Baseline compliance profiles indicated intratidal recruitment/derecruitment in 48 % patients. After induction of pneumoperitoneum, intratidal recruitment/derecruitment was indicated in 93 % patients (P < 0.01), and after removal intratidal recruitment/derecruitment was indicated in 59 % patients. Compliance profiles showing overdistension were not observed. CONCLUSIONS: Analyses of the intratidal compliance profiles reveal that pneumoperitoneum during laparoscopic surgery causes intratidal recruitment/derecruitment which partly persists after its removal. The analysis of the intratidal volume-dependent C RS profiles could be used to guide intraoperative PEEP adjustments during elevated intraabdominal pressure.

The effects of nifedipine on respiratory mechanics investigated by theend-inflation occlusion method in the rat.

CONTEXT: Calcium channel blockers may theoretically exhibit relaxing effects not only on vascular smooth muscle but also on airway smooth muscle. OBJECTIVE: To investigate possible effects of nifedipine on respiratory mechanics in the rat. METHODS: Respiratory system mechanical parameters were measured by the end-inflation occlusion method in the rat in vivo before and after the intraperitoneal administration of nifedipine. RESULTS: We found that nifedipine affects respiratory mechanics, inducing a reduction of airway resistance and of respiratory system elastance, probably because of a relaxing action on airway and parenchimal smooth muscle cells. CONCLUSION: Should these results be further confirmed by human investigations, a possible role of nifedipine in pharmacological respiratory system's diseases treatment may be suggested.

A review of the effects of some endocrinological factors on respiratory mechanics.

CONTEXT: Endocrinological factors have been recently described to affect respiratory mechanics. OBJECTIVE: To review recent literature data, most of all obtained by the end-inflation occlusion method, describing the effects of molecules of endocrinological interest such as endothelin, erythropoietin and renin-angiotensin, on respiratory mechanics parameters. METHODS: The papers considered in this review were found by inserting in Pubmed/Medline the following indexing terms: hormones, endothelin, erythropoietin, angiotensin and respiratory mechanics. RESULTS: It was found that the above cited molecules, beside their well known physiological main effects, exhibit influences on respiratory mechanics, most of all on the airflow resistance, which was described to be increased by endothelin and angiotensin, and decreased by erythropoietin. CONCLUSIONS: A number of molecules of biological interest exhibit unexpected influences on respiratory mechanics. The clinical effects depend on the consequences of modified inspiratory pressure values the respiratory muscles have to perform for a given breathing pattern.

Intraoperative positive end-expiratory pressure evaluation using the intratidal compliance-volume profile.

BACKGROUND: Lung-protective mechanical ventilation during general surgery including the application of PEEP can reduce postoperative pulmonary complications. In a prospective clinical observation study, we evaluated volume-dependent respiratory system compliance in adult patients undergoing ear-nose-throat surgery with ventilation settings chosen empirically by the attending anaesthetist. METHODS: In 40 patients, we measured the respiratory variables during intraoperative mechanical ventilation. All measurements were subdivided into 5 min intervals. Dynamic compliance (CRS) and the intratidal volume-dependent CRS curve was calculated for each interval and classified into one of the six specific compliance profiles indicating intratidal recruitment/derecruitment, overdistension or all. We retrospectively compared the occurrences of the respective compliance profiles at PEEP levels of 5 cm H2O and at higher levels. RESULTS: The attending anaesthetists set the PEEP level initially to 5 cm H2O in 29 patients (83%), to 7 cm H2O in 5 patients (14%), and to 8 cm H2O in 2 patients (6%). Across all measurements the mean CRS was 61 (11) ml cm H2O(-1) (40-86 ml cm H2O(-1)) and decreased continuously during the procedure. At PEEP of 5 cm H2O the compliance profile indicating strong intratidal recruitment/derecruitment occurred more often (18.6%) compared with higher PEEP levels (5.5%, P<0.01). Overdistension was practically never observed. CONCLUSIONS: In most patients, a PEEP of 5 cm H2O during intraoperative mechanical ventilation is too low to prevent intratidal recruitment/derecruitment. The analysis of the intratidal compliance profile provides the rationale to individually titrate a PEEP level that stabilizes the alveolar recruitment status of the lung during intraoperative mechanical ventilation. TRIAL REGISTRATION NUMBER: DRKS00004286.

The application of impulse oscillometry system based on machine learning algorithm in the diagnosis of chronic obstructive pulmonary disease.

Objective. Diagnosing chronic obstructive pulmonary disease (COPD) using impulse oscillometry (IOS) is challenging due to the high level of clinical expertise it demands from doctors, which limits the clinical application of IOS in screening. The primary aim of this study is to develop a COPD diagnostic model based on machine learning algorithms using IOS test results.Approach. Feature selection was conducted to identify the optimal subset of features from the original feature set, which significantly enhanced the classifier's performance. Additionally, secondary features area of reactance (AX) were derived from the original features based on clinical theory, further enhancing the performance of the classifier. The performance of the model was analyzed and validated using various classifiers and hyperparameter settings to identify the optimal classifier. We collected 528 clinical data examples from the China-Japan Friendship Hospital for training and validating the model.Main results. The proposed model achieved reasonably accurate diagnostic results in the clinical data (accuracy = 0.920, specificity = 0.941, precision = 0.875, recall = 0.875).Significance. The results of this study demonstrate that the proposed classifier model, feature selection method, and derived secondary feature AX provide significant auxiliary support in reducing the requirement for clinical experience in COPD diagnosis using IOS.

Flow-controlled expiration (FLEX) homogenizes pressure distribution in a four compartment physical model of the respiratory system with chest wall compliance.

Objective.Flow-controlled expiration (FLEX) has been shown to attenuate ventilator-induced lung injury in animal models. It has also shown to homogenize compartmental pressure distribution in a physical model of the inhomogeneous respiratory system having independent compartments. We hypothesized that the homogenizing effects of FLEX are also effective in this regard when the independence of compartments is suspended by simulated chest wall compliance.Approach.A four compartment physical model of the respiratory system having chest wall compliance (137 ml/cmH2O) was developed. Two of the four compartments had high compliance (18 ml/cmH2O) and two had low compliance (10 ml/cmH2O). These compartments were each combined with either high (6.8 cmH2O·s/l) or low resistance (3.5 cmH2O·s/l). The model was ventilated in the volume-controlled ventilation mode with either passive expiration or with FLEX. The maximal pressure differences (ΔPmax) and the maximal differences of mean pressure (ΔPmean) between the compartments during expiration were determined.Main results.With passive expiration ΔPmaxreached up to 3.4 ± 0.03 cmH2O but only 0.9 ± 0.01 cmH2O with FLEX (p < 0.001). Maximal differences of ΔPmeanwere significantly lower with FLEX as compared to passive expiration (extending up to 0.4 ± 0.04 cmH2O versus 2.0 ± 0.15 cmH2O,p < 0.001).Significance.The homogenizing effects of FLEX on compartmental pressure distribution could be reproduced in a more complex physical model of the inhomogeneous respiratory system having chest wall compliance and might be a mechanism underlying the lung protective effects of ventilation with FLEX.

Physiological and quantitative CT-scan characterization of COVID-19 and typical ARDS: a matched cohort study.

PURPOSE: To investigate whether COVID-19-ARDS differs from all-cause ARDS. METHODS: Thirty-two consecutive, mechanically ventilated COVID-19-ARDS patients were compared to two historical ARDS sub-populations 1:1 matched for PaO2/FiO2 or for compliance of the respiratory system. Gas exchange, hemodynamics and respiratory mechanics were recorded at 5 and 15 cmH2O PEEP. CT scan variables were measured at 5 cmH2O PEEP. RESULTS: Anthropometric characteristics were similar in COVID-19-ARDS, PaO2/FiO2-matched-ARDS and Compliance-matched-ARDS. The PaO2/FiO2-matched-ARDS and COVID-19-ARDS populations (both with PaO2/FiO2 106 ± 59 mmHg) had different respiratory system compliances (Crs) (39 ± 11 vs 49.9 ± 15.4 ml/cmH2O, p = 0.03). The Compliance-matched-ARDS and COVID-19-ARDS had similar Crs (50.1 ± 15.7 and 49.9 ± 15.4 ml/cmH2O, respectively) but significantly lower PaO2/FiO2 for the same Crs (160 ± 62 vs 106.5 ± 59.6 mmHg, p < 0.001). The three populations had similar lung weights but COVID-19-ARDS had significantly higher lung gas volume (PaO2/FiO2-matched-ARDS 930 ± 644 ml, COVID-19-ARDS 1670 ± 791 ml and Compliance-matched-ARDS 1301 ± 627 ml, p < 0.05). The venous admixture was significantly related to the non-aerated tissue in PaO2/FiO2-matched-ARDS and Compliance-matched-ARDS (p < 0.001) but unrelated in COVID-19-ARDS (p = 0.75), suggesting that hypoxemia was not only due to the extent of non-aerated tissue. Increasing PEEP from 5 to 15 cmH2O improved oxygenation in all groups. However, while lung mechanics and dead space improved in PaO2/FiO2-matched-ARDS, suggesting recruitment as primary mechanism, they remained unmodified or worsened in COVID-19-ARDS and Compliance-matched-ARDS, suggesting lower recruitment potential and/or blood flow redistribution. CONCLUSIONS: COVID-19-ARDS is a subset of ARDS characterized overall by higher compliance and lung gas volume for a given PaO2/FiO2, at least when considered within the timeframe of our study.

Variable Ventilation Improved Respiratory System Mechanics and Ameliorated Pulmonary Damage in a Rat Model of Lung Ischemia-Reperfusion.

Lung ischemia-reperfusion injury remains a major complication after lung transplantation. Variable ventilation (VV) has been shown to improve respiratory function and reduce pulmonary histological damage compared to protective volume-controlled ventilation (VCV) in different models of lung injury induced by endotoxin, surfactant depletion by saline lavage, and hydrochloric acid. However, no study has compared the biological impact of VV vs. VCV in lung ischemia-reperfusion injury, which has a complex pathophysiology different from that of other experimental models. Thirty-six animals were randomly assigned to one of two groups: (1) ischemia-reperfusion (IR), in which the left pulmonary hilum was completely occluded and released after 30 min; and (2) Sham, in which animals underwent the same surgical manipulation but without hilar clamping. Immediately after surgery, the left (IR-injured) and right (contralateral) lungs from 6 animals per group were removed, and served as non-ventilated group (NV) for molecular biology analysis. IR and Sham groups were further randomized to one of two ventilation strategies: VCV (n = 6/group) [tidal volume (VT) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 2 cmH2O, fraction of inspired oxygen (FiO2) = 0.4]; or VV, which was applied on a breath-to-breath basis as a sequence of randomly generated VT values (n = 1200; mean VT = 6 mL/kg), with a 30% coefficient of variation. After 5 min of ventilation and at the end of a 2-h period (Final), respiratory system mechanics and arterial blood gases were measured. At Final, lungs were removed for histological and molecular biology analyses. Respiratory system elastance and alveolar collapse were lower in VCV than VV (mean ± SD, VCV 3.6 ± 1.3 cmH20/ml and 2.0 ± 0.8 cmH20/ml, p = 0.005; median [interquartile range], VCV 20.4% [7.9-33.1] and VV 5.4% [3.1-8.8], p = 0.04, respectively). In left lungs of IR animals, VCV increased the expression of interleukin-6 and intercellular adhesion molecule-1 compared to NV, with no significant differences between VV and NV. Compared to VCV, VV increased the expression of surfactant protein-D, suggesting protection from type II epithelial cell damage. In conclusion, in this experimental lung ischemia-reperfusion model, VV improved respiratory system elastance and reduced lung damage compared to VCV.

Compensating Artificial Airway Resistance via Active Expiration Assistance.

BACKGROUND: Artificial airway resistance as provided by small-lumen tracheal tubes or catheters increases the risk of intrinsic PEEP (PEEPi). We hypothesized that by active expiration assistance, larger minute volumes could be generated without causing PEEPi compared with conventional mechanical ventilation when using small-lumen tracheal tubes or a cricothyrotomy catheter. METHODS: We investigated the active expiration assistance in a physical model of the respiratory system and estimated its hypothetical performance in terms of maximal flow generated with endotracheal tubes ranging from 3.0 to 8.0 mm inner diameter (ID); with microlaryngeal tubes of 4.0, 5.0, and 6.0 mm ID; and with a cricothyrotomy catheter. Furthermore, we determined the minute volumes that could be achieved without generating PEEPi by ventilating a physical lung model using conventional mechanical ventilation or using active expiration assistance. RESULTS: The inspiratory and expiratory flow during active expiration assistance increased with increasing supply flow and decreased with decreasing ID of the connected endotracheal tubes (both P < .001). With small-lumen tracheal tubes, the active expiration assistance generated similar or higher minute volumes than conventional ventilation. Conventional mechanical ventilation with PEEPi <1 cm H2O was not achievable via a microlaryngeal tube of 4.0 mm ID and smaller lumen tubes. CONCLUSIONS: For mechanical ventilation via small-lumen tubes or thin catheters, active compensation of airway resistance might be a necessary means to generate adequate minute ventilation without causing PEEPi. Active expiration assistance can generate reasonable respiratory minute volumes via small-lumen tubes or thin catheters.

Intratidal recruitment/derecruitment persists at low and moderate positive end-expiratory pressure in paediatric patients.

In paediatric patients positive end-expiratory pressure (PEEP) is traditionally set lower than in adults. We investigated whether moderately higher PEEP improves respiratory mechanics and regional ventilation. Therefore, 40 children were mechanically ventilated with PEEP 2 and 5cmH2O. Volume-dependent compliance profiles were analysed as a measure of intratidal recruitment/derecruitment. Regional ventilation was assessed using electrical impedance tomography. Mean compliance was 17.9±9.9mLcmH2O-1 (PEEP 2cmH2O), and 19.0±10.9mLcmH2O-1 (PEEP 5 cmH2O, p<0.001). Strong intratidal recruitment/derecruitment occurred in 40% of children at PEEP 2 cmH2O, and 36% at PEEP 5 cmH2O. Children showing strong recruitment/derecruitment were 33 (PEEP 2 cmH20) and 20 (PEEP 5 cmH20) months younger than children showing moderate recruitment/derecruitment. A higher PEEP improved peripheral ventilation. In conclusion, mechanically ventilated paediatric patients undergo intratidal recruitment/derecruitment which occurs more prominently in younger than in older children. A PEEP of 5cmH2O does not fully prevent intratidal recruitment/derecruitment but homogenizes regional ventilation in comparison to 2cmH2O.

High tidal volume ventilation does not exacerbate acid-induced lung injury in infant rats.

The impact of mechanical ventilation with high V(T)-low PEEP in infant rats with preinjured lungs is unknown. After tracheal instillation of saline or acid, two week old rats were ventilated with V(T) 7 mL/kg and PEEP 5 cm H2O or V(T) 21 mL/kg and PEEP 1cm H2O for 4 h. Airway resistance and the coefficient of tissue elastance, measured via low-frequency forced-oscillation technique, and quasi-static pressure-volume curves deteriorated less with high V(T)-low PEEP when compared with low V(T)-high PEEP. IL-6 concentration in bronchoalveolar lavage fluid (BALF) did not differ between all ventilated groups. Moreover, differences in BALF protein concentration and histological lung injury scores were independent of applied ventilation strategies. In contrast to experimental studies with adult rats, short-term mechanical ventilation with high V(T)-low PEEP is not deleterious when compared to low V(T)-high PEEP in both healthy and pre-injured infant rat lungs. Our results call for caution when extrapolating data from adult studies and highlight the need for age-specific animal models.