1. |
- Crockett, Douglas C., et al.
(author)
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Validating the inspired sinewave technique to measure the volume of the 'baby lung' in a porcine lung-injury model
- 2020
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In: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 124:3, s. 345-353
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Journal article (peer-reviewed)abstract
- Background: Bedside lung volume measurement could personalise ventilation and reduce driving pressure in patients with acute respiratory distress syndrome (ARDS). We investigated a modified gas-dilution method, the inspired sinewave technique (IST), to measure the effective lung volume (ELV) in pigs with uninjured lungs and in an ARDS model. Methods: Anaesthetised mechanically ventilated pigs were studied before and after surfactant depletion by saline lavage. Changes in PEEP were used to change ELV. Paired measurements of absolute ELV were taken with IST (ELVIST) and compared with gold-standard measures (sulphur hexafluoride wash in/washout [ELVSF6] and computed tomography (CT) [ELVCT]). Measured volumes were used to calculate changes in ELV (Delta ELV) between PEEP levels for each method (Delta ELVIST, Delta ELVSF6, and Delta ELVCT). Results: The coefficient of variation was <5% for repeated ELVIST measurements (n=13 pigs). There was a strong linear relationship between ELVIST and ELVSF6 in uninjured lungs (r(2)=0.97), and with both ELVSF6 and ELVCT in the ARDS model (r(2)=0.87 and 0.92, respectively). ELVIST had a mean bias of -12 to 13% (95% limits=+/- 17 - 25%) compared with ELVSF6 and ELVCT. Delta ELVIST was concordant with Delta ELVSF6 and Delta ELVCT in 98-100% of measurements, and had a mean bias of -73 to -77 ml (95% limits=+/- 128 - 186 ml) compared with Delta ELVSF6 and -1 ml (95% limits +/- 333 ml) compared with Delta ELVCT. Conclusions: IST provides a repeatable measure of absolute ELV and shows minimal bias when tracking PEEP-induced changes in lung volume compared with CT in a saline-lavage model of ARDS.
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2. |
- Cronin, John N, et al.
(author)
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Dynamic single-slice CT estimates whole-lung dual-energy CT variables in pigs with and without experimental lung injury
- 2019
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In: Intensive Care Medicine Experimental. - : Springer. - 2197-425X. ; 7:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Dynamic single-slice CT (dCT) is increasingly used to examine the intra-tidal, physiological variation in aeration and lung density in experimental lung injury. The ability of dCT to predict whole-lung values is unclear, especially for dual-energy CT (DECT) variables. Additionally, the effect of inspiration-related lung movement on CT variables has not yet been quantified.METHODS: Eight domestic pigs were studied under general anaesthesia, including four following saline-lavage surfactant depletion (lung injury model). DECT, dCT and whole-lung images were collected at 12 ventilatory settings. Whole-lung single energy scans images were collected during expiratory and inspiratory apnoeas at positive end-expiratory pressures from 0 to 20 cmH2O. Means and distributions of CT variables were calculated for both dCT and whole-lung images. The cranio-caudal displacement of the anatomical slice was measured from whole-lung images.RESULTS: Mean CT density and volume fractions of soft tissue, gas, iodinated blood, atelectasis, poor aeration, normal aeration and overdistension correlated between dCT and the whole lung (r2 0.75-0.94) with agreement between CT density distributions (r 0.89-0.97). Inspiration increased the matching between dCT and whole-lung values and was associated with a movement of 32% (SD 15%) of the imaged slice out of the scanner field-of-view. This effect introduced an artefactual increase in dCT mean CT density during inspiration, opposite to that caused by the underlying physiology.CONCLUSIONS: Overall, dCT closely approximates whole-lung aeration and density. This approximation is improved by inspiration where a decrease in CT density and atelectasis can be interpreted as physiological rather than artefactual.
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3. |
- Cronin, John N., et al.
(author)
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Intra-tidal PaO2 oscillations associated with mechanical ventilation : a pilot study to identify discrete morphologies in a porcine model
- 2023
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In: Intensive Care Medicine Experimental. - : Springer Nature. - 2197-425X. ; 11:1
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Journal article (peer-reviewed)abstract
- Background: Within-breath oscillations in arterial oxygen tension (PaO2) can be detected using fast responding intra-arterial oxygen sensors in animal models. These PaO2 signals, which rise in inspiration and fall in expiration, may represent cyclical recruitment/derecruitment and, therefore, a potential clinical monitor to allow titration of ventilator settings in lung injury. However, in hypovolaemia models, these oscillations have the potential to become inverted, such that they decline, rather than rise, in inspiration. This inversion suggests multiple aetiologies may underlie these oscillations. A correct interpretation of the various PaO2 oscillation morphologies is essential to translate this signal into a monitoring tool for clinical practice. We present a pilot study to demonstrate the feasibility of a new analysis method to identify these morphologies.Methods Seven domestic pigs (average weight 31.1 kg) were studied under general anaesthesia with muscle relaxation and mechanical ventilation. Three underwent saline-lavage lung injury and four were uninjured. Variations in PEEP, tidal volume and presence/absence of lung injury were used to induce different morphologies of PaO2 oscillation. Functional principal component analysis and k-means clustering were employed to separate PaO2 oscillations into distinct morphologies, and the cardiorespiratory physiology associated with these PaO2 morphologies was compared.Results PaO2 oscillations from 73 ventilatory conditions were included. Five functional principal components were sufficient to explain = 95% of the variance of the recorded PaO2 signals. From these, five unique morphologies of PaO2 oscillation were identified, ranging from those which increased in inspiration and decreased in expiration, through to those which decreased in inspiration and increased in expiration. This progression was associated with the estimates of the first functional principal component (P < 0.001, R-2 = 0.88). Intermediate morphologies demonstrated waveforms with two peaks and troughs per breath. The progression towards inverted oscillations was associated with increased pulse pressure variation (P = 0.03).Conclusions Functional principal component analysis and k-means clustering are appropriate to identify unique morphologies of PaO2 waveform associated with distinct cardiorespiratory physiology. We demonstrated novel intermediate morphologies of PaO2 waveform, which may represent a development of zone 2 physiologies within the lung. Future studies of PaO2 oscillations and modelling should aim to understand the aetiologies of these morphologies.
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4. |
- Cronin, John N., et al.
(author)
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Mechanical Ventilation Redistributes Blood to Poorly Ventilated Areas in Experimental Lung Injury*
- 2020
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In: Critical Care Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0090-3493 .- 1530-0293. ; 48:3, s. E200-E208
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Journal article (peer-reviewed)abstract
- Objectives: Determine the intra-tidal regional gas and blood volume distributions at different levels of atelectasis in experimental lung injury. Test the hypotheses that pulmonary aeration and blood volume matching is reduced during inspiration in the setting of minimal tidal recruitment/derecruitment and that this mismatching is an important determinant of hypoxemia.Design: Preclinical study.Setting: Research laboratory.Subjects: Seven anesthetized pigs 28.7 kg (sd, 2.1 kg).Interventions: All animals received a saline-lavage surfactant depletion lung injury model. Positive end-expiratory pressure was varied between 0 and 20 cm H2O to induce different levels of atelectasis.Measurements and Main Results: Dynamic dual-energy CT images of a juxtadiaphragmatic slice were obtained, gas and blood volume fractions within three gravitational regions calculated and normalized to lung tissue mass (normalized gas volume and normalized blood volume, respectively). Ventilatory conditions were grouped based upon the fractional atelectatic mass in expiration (< 20%, 20-40%, and >= 40%). Tidal recruitment/derecruitment with fractional atelectatic mass in expiration greater than or equal to 40% was less than 7% of lung mass. In this group, inspiration-related increase in normalized gas volume was greater in the nondependent (818 mu L/g [95% CI, 729-908 mu L/g]) than the dependent region (149 mu L/g [120-178 mu L/g]). Normalized blood volume decreased in inspiration in the nondependent region (29 mu L/g [12-46 mu L/g]) and increased in the dependent region (39 mu L/g [30-48 mu L/g]). Inspiration-related changes in normalized gas volume and normalized blood volume were negatively correlated in fractional atelectatic mass in expiration greater than or equal to 40% and 20-40% groups (r(2) = 0.56 and 0.40), but not in fractional atelectatic mass in expiration less than 20% group (r(2) = 0.01). Both the increase in normalized blood volume in the dependent region and fractional atelectatic mass in expiration negatively correlated with Pao(2)/Fio(2) ratio (rho = -0.77 and -0.93, respectively).Conclusions: In experimental atelectasis with minimal tidal recruitment/derecruitment, mechanical inspiratory breaths redistributed blood volume away from well-ventilated areas, worsening Pao(2)/Fio(2).
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5. |
- Formenti, Federico, et al.
(author)
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Respiratory oscillations in alveolar oxygen tension measured in arterial blood.
- 2017
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Journal article (peer-reviewed)abstract
- Arterial oxygen partial pressure can increase during inspiration and decrease during expiration in the presence of a variable shunt fraction, such as with cyclical atelectasis, but it is generally presumed to remain constant within a respiratory cycle in the healthy lung. We measured arterial oxygen partial pressure continuously with a fast intra-vascular sensor in the carotid artery of anaesthetized, mechanically ventilated pigs, without lung injury. Here we demonstrate that arterial oxygen partial pressure shows respiratory oscillations in the uninjured pig lung, in the absence of cyclical atelectasis (as determined with dynamic computed tomography), with oscillation amplitudes that exceeded 50 mmHg, depending on the conditions of mechanical ventilation. These arterial oxygen partial pressure respiratory oscillations can be modelled from a single alveolar compartment and a constant oxygen uptake, without the requirement for an increased shunt fraction during expiration. Our results are likely to contribute to the interpretation of arterial oxygen respiratory oscillations observed during mechanical ventilation in the acute respiratory distress syndrome.
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6. |
- Tran, Minh C, et al.
(author)
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Bedside monitoring of lung volume available for gas exchange
- 2021
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In: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 9
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Journal article (peer-reviewed)abstract
- BACKGROUND: Bedside measurement of lung volume may provide guidance in the personalised setting of respiratory support, especially in patients with the acute respiratory distress syndrome at risk of ventilator-induced lung injury. We propose here a novel operator-independent technique, enabled by a fibre optic oxygen sensor, to quantify the lung volume available for gas exchange. We hypothesised that the continuous measurement of arterial partial pressure of oxygen (PaO2) decline during a breath-holding manoeuvre could be used to estimate lung volume in a single-compartment physiological model of the respiratory system.METHODS: Thirteen pigs with a saline lavage lung injury model and six control pigs were studied under general anaesthesia during mechanical ventilation. Lung volumes were measured by simultaneous PaO2 rate of decline (VPaO2) and whole-lung computed tomography scan (VCT) during apnoea at different positive end-expiratory and end-inspiratory pressures.RESULTS: A total of 146 volume measurements was completed (range 134 to 1869 mL). A linear correlation between VCT and VPaO2 was found both in control (slope = 0.9, R2 = 0.88) and in saline-lavaged pigs (slope = 0.64, R2 = 0.70). The bias from Bland-Altman analysis for the agreement between the VCT and VPaO2 was - 84 mL (limits of agreement ± 301 mL) in control and + 2 mL (LoA ± 406 mL) in saline-lavaged pigs. The concordance for changes in lung volume, quantified with polar plot analysis, was - 4º (LoA ± 19°) in control and - 9° (LoA ± 33°) in saline-lavaged pigs.CONCLUSION: Bedside measurement of PaO2 rate of decline during apnoea is a potential approach for estimation of lung volume changes associated with different levels of airway pressure.
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7. |
- Tran, Minh Cong, et al.
(author)
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Lung heterogeneity and deadspace volume in acute respiratory distress syndrome animals using the inspired sinewave test
- 2020
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In: Physiological Measurement. - : IOP Publishing. - 0967-3334 .- 1361-6579. ; 41:11
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Journal article (peer-reviewed)abstract
- The acute respiratory distress syndrome is associated with a high rate of morbidity and mortality, as patients undergoing mechanical ventilation are at risk of ventilator-induced lung injuries.OBJECTIVE: To measure the lung heterogeneity and deadspace volume to find safer ventilator strategies. Then, the ventilator settings could offer homogeneous ventilation and theoretically equalise and reduce tidal strain/stress in the lung parenchyma.APPROACH: The Inspired Sinewave Test (IST) is a non-invasive lung measurement tool, which does not require patients' cooperation. The IST can measure the effective lung volume, pulmonary blood flow and deadspace volume. We developed a computational simulation of the cardiopulmonary system to allow lung heterogeneity to be quantified using data solely derived from the IST. Then, the method to quantify lung heterogeneity using two IST tracer gas frequencies (180s and 60s) was introduced and experimented in the simulation lungs and in animal models. Thirteen anaesthetised pigs were studied with the IST, both before and after experimental lung injury (saline-lavage ARDS model). The deadspace volume is compared between IST and the SF_{6} Washout method.RESULTS: The IST could measure the lung heterogeneity using two frequencies tracer gases. Furthermore, the value of IST ventilation heterogeneity in ARDS lungs were higher than in control lungs at PEEP 10cmH_{2}O (AuC=0.85, p<0.001). Deadspace volume values measured by the IST has a strong relationship with the measured values of the SF_{6} (9mL bias and limits of agreement from -79mL to 57mL in control animals).SIGNIFICANCE: the potential impact of the IST technique in the identification of ventilation and perfusion heterogeneity during ventilator support.
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8. |
- Tran, Minh C., et al.
(author)
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Quantifying heterogeneity in an animal model of acute respiratory distress syndrome, a comparison of inspired sinewave technique to computed tomography
- 2024
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14
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Journal article (peer-reviewed)abstract
- The inspired sinewave technique (IST) is a non-invasive method to measure lung heterogeneity indices (including both uneven ventilation and perfusion or heterogeneity), which reveal multiple conditions of the lung and lung injury. To evaluate the reproducibility and predicted clinical outcomes of IST heterogeneity values, a comparison with a quantitative lung computed tomography (CT) scan is performed. Six anaesthetised pigs were studied after surfactant depletion by saline-lavage. Paired measurements of lung heterogeneity were then taken with both the IST and CT. Lung heterogeneity measured by the IST was calculated by (a) the ratio of tracer gas outputs measured at oscillation periods of 180 s and 60 s, and (b) by the standard deviation of the modelled log-normal distribution of ventilations and perfusions in the simulation lung. In the CT images, lungs were manually segmented and divided into different regions according to voxel density. A quantitative CT method to calculate the heterogeneity (the Cressoni method) was applied. The IST and CT show good Pearson correlation coefficients in lung heterogeneity measurements (ventilation: 0.71, and perfusion, 0.60, p < 0.001). Within individual animals, the coefficients of determination average ventilation (R2 = 0.53) and perfusion (R2 = 0.68) heterogeneity. Strong concordance rates of 98% in ventilation and 89% when the heterogeneity changes were reported in pairs measured by CT scanning and IST methods. This quantitative method to identify heterogeneity has the potential to replicate CT lung heterogeneity, and to aid individualised care in ARDS.
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