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Pellegrini, MariangelaORCID iD iconorcid.org/0000-0001-5668-7399
Publications (10 of 15) Show all publications
Broche, L., Pisa, P., Porra, L., Degrugilliers, L., Bravin, A., Pellegrini, M., . . . Bayat, S. (2019). Individual Airway Closure Characterized In Vivo by Phase-Contrast CT Imaging in Injured Rabbit Lung. Critical Care Medicine, 47(9), E774-E781
Open this publication in new window or tab >>Individual Airway Closure Characterized In Vivo by Phase-Contrast CT Imaging in Injured Rabbit Lung
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2019 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 47, no 9, p. E774-E781Article in journal (Refereed) Published
Abstract [en]

Objectives: Airway closure is involved in adverse effects of mechanical ventilation under both general anesthesia and in acute respiratory distress syndrome patients. However, direct evidence and characterization of individual airway closure is lacking. Here, we studied the same individual peripheral airways in intact lungs of anesthetized and mechanically ventilated rabbits, at baseline and following lung injury, using high-resolution synchrotron phase-contrast CT.

Design: Laboratory animal investigation.

Setting: European synchrotron radiation facility.

Subjects: Six New-Zealand White rabbits.

Interventions: The animals were anesthetized, paralyzed, and mechanically ventilated in pressure-controlled mode (tidal volume, 6 mL/kg; respiratory rate, 40; Fio(2), 0.6; inspiratory:expiratory, 1:2; and positive end-expiratory pressure, 3 cm H2O) at baseline. Imaging was performed with a 47.5 x 47.5 x 47.5 mu m voxel size, at positive end-expiratory pressure 12, 9, 6, 3, and 0 cm H2O. The imaging sequence was repeated after lung injury induced by whole-lung lavage and injurious ventilation in four rabbits. Cross-sections of the same individual airways were measured.

Measurements and Main Results: The airways were measured at baseline (n = 48; radius, 1.7 to 0.21 mm) and after injury (n = 32). Closure was observed at 0 cm H2O in three of 48 airways (6.3%; radius, 0.350.08 mm at positive end-expiratory pressure 12) at baseline and five of 32 (15.6%; radius, 0.28 +/- 0.09 mm) airways after injury. Cross-section was significantly reduced at 3 and 0 cm H2O, after injury, with a significant relation between the relative change in cross-section and airway radius at 12 cm H2O in injured, but not in normal lung (R = 0.60; p < 0.001).

Conclusions: Airway collapsibility increases in the injured lung with a significant dependence on airway caliber. We identify "compliant collapse" as the main mechanism of airway closure in initially patent airways, which can occur at more than one site in individual airways.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2019
Keywords
airway closure, mechanical ventilation, phase-contrast imaging, respiratory distress syndrome, adult, tomography, x-ray computed, ventilator-induced lung injury
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-394204 (URN)10.1097/CCM.0000000000003838 (DOI)000484224200007 ()31162202 (PubMedID)
Available from: 2019-10-04 Created: 2019-10-04 Last updated: 2019-10-04Bibliographically approved
Scaramuzzo, G., Broche, L., Pellegrini, M., Porra, L., Derosa, S., Tannoia, A. P., . . . Perchiazzi, G. (2019). Regional Behavior of Airspaces During Positive Pressure Reduction Assessed by Synchrotron Radiation Computed Tomography. Frontiers in Physiology, 10, Article ID 719.
Open this publication in new window or tab >>Regional Behavior of Airspaces During Positive Pressure Reduction Assessed by Synchrotron Radiation Computed Tomography
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2019 (English)In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 719Article in journal (Refereed) Published
Abstract [en]

Introduction: The mechanisms of lung inflation and deflation are only partially known. Ventilatory strategies to support lung function rely upon the idea that lung alveoli are isotropic balloons that progressively inflate or deflate and that lung pressure/volume curves derive only by the interplay of critical opening pressures, critical closing pressures, lung history, and position of alveoli inside the lung. This notion has been recently challenged by subpleural microscopy, magnetic resonance, and computed tomography (CT). Phase-contrast synchrotron radiation CT (PC-SRCT) can yield in vivo images at resolutions higher than conventional CT.

Objectives: We aimed to assess the numerosity (ASden) and the extension of the surface of airspaces (ASext) in healthy conditions at different volumes, during stepwise lung deflation, in concentric regions of the lung. Methods: The study was conducted in seven anesthetized New Zealand rabbits. They underwent PC-SRCT scans (resolution of 47.7 mu m) of the lung at five decreasing positive end expiratory pressure (PEEP) levels of 12, 9, 6, 3, and 0 cmH(2)O during end-expiratory holds. Three concentric regions of interest (ROIs) of the lung were studied: subpleural, mantellar, and core. The images were enhanced by phase contrast algorithms. ASden and ASext were computed by using the Image Processing Toolbox for MatLab. Statistical tests were used to assess any significant difference determined by PEEP or ROI on ASden and ASext.

Results: When reducing PEEP, in each ROI the ASden significantly decreased. Conversely, ASext variation was not significant except for the core ROI. In the latter, the angular coefficient of the regression line was significantly low.

Conclusion: The main mechanism behind the decrease in lung volume at PEEP reduction is derecruitment. In our study involving lung regions laying on isogravitational planes and thus equally influenced by gravitational forces, airspace numerosity and extension of surface depend on the local mechanical properties of the lung.

Keywords
recruitment, VILI, alveoli, kinetics, SRCT
National Category
Respiratory Medicine and Allergy Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-389594 (URN)10.3389/fphys.2019.00719 (DOI)000471313900001 ()31231245 (PubMedID)
Funder
Swedish Research Council, K2015-99X-22731-01-4Swedish Heart Lung Foundation
Available from: 2019-07-25 Created: 2019-07-25 Last updated: 2019-07-25Bibliographically approved
Pellegrini, M. (2019). Regional Lung Mechanics and Influence of an Active Diaphragm in Experimental Lung Injury. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Regional Lung Mechanics and Influence of an Active Diaphragm in Experimental Lung Injury
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Despite being an essential life-support strategy in severe respiratory failure, mechanical ventilation can, if not optimally set and monitored, lead to injury of the lung parenchyma and diaphragm. These conditions are called ventilator-induced lung injury and ventilator-induced diaphragmatic dysfunction (VIDD), respectively. Although substantial progress has been made in the ventilator management of severely lung-injured patients, we are still far from a fully protective mechanical ventilation. In consideration of this gap of knowledge, this doctoral thesis aimed at investigating regional lung mechanics during both inspiration and expiration, in both controlled and assisted ventilation. Particular emphasis was placed on the expiratory phase, which is involved in expiratory flow limitation, airway closure and atelectasis formation, although commonly considered non-harmful.

A novel methodological approach has been the fundamental basis for this research project. The combination of respiratory mechanics, diaphragmatic electromyographic activity and lung imaging enabled a breath-by-breath analysis at high temporal and spatial resolution.

In Study I, the gravitational field affected the distribution of gas and transpulmonary pressures, as previously shown. This effect differed between healthy and injured lungs. Moreover, lung injury induced a heterogeneous distribution of gas within the lungs, as well as an increased gravitational gradient in transpulmonary pressure. Study I was mainly aimed at testing the new methodological approach centred on the investigation of regional lung mechanics.

In Study II, the focus was on assisted ventilation and the phenomenon of gas redistribution within the lungs. Large pendelluft events had been demonstrated in disproportionate inspiratory efforts. In Study II, we showed that large pendelluft resulting from pathological respiratory drive could be attenuated by high positive end expiratory pressure (PEEP). Moreover, we showed that transient and widespread small gas redistribution events occur at all times during inspiration. Assisted ventilation and high PEEP reduced the size of gas redistribution as compared with controlled ventilation and low PEEP.

In Study III, we demonstrated a diaphragmatic expiratory contraction in lungs prone to collapse, serving to brake the expiratory flow. It preserved end expiratory lung volume (EELV) and counteracted tidal atelectasis. However, the expiratory brake induced by diaphragmatic contraction is a known cause of VIDD.

In Study IV, we tested the effects of external expiratory resistances (ExpR). We showed that, by applying ExpR, an expiratory brake was induced. The beneficial effects on EELV were retained, while the diaphragm could quickly relax during the expiration, thus reducing the risk of VIDD.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 80
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1606
Keywords
acute respiratory distress syndrome, artificial respiration, diaphragm, pulmonary atelectasis, lung imaging, respiratory system, animal model
National Category
Anesthesiology and Intensive Care Physiology Respiratory Medicine and Allergy
Research subject
Physiology; Anaesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-394305 (URN)978-91-513-0790-9 (ISBN)
Public defence
2019-12-16, Akademiska sjukhuset, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2019-11-22 Created: 2019-10-07 Last updated: 2019-11-27
Scaramuzzo, G., Broche, L., Pellegrini, M., Porra, L., Derosa, S., Tannoia, A. P., . . . Perchiazzi, G. (2019). The Effect of Positive End-Expiratory Pressure on Lung Micromechanics Assessed by Synchrotron Radiation Computed Tomography in an Animal Model of ARDS. JOURNAL OF CLINICAL MEDICINE, 8(8), Article ID 1117.
Open this publication in new window or tab >>The Effect of Positive End-Expiratory Pressure on Lung Micromechanics Assessed by Synchrotron Radiation Computed Tomography in an Animal Model of ARDS
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2019 (English)In: JOURNAL OF CLINICAL MEDICINE, ISSN 2077-0383, Vol. 8, no 8, article id 1117Article in journal (Refereed) Published
Abstract [en]

Modern ventilatory strategies are based on the assumption that lung terminal airspaces act as isotropic balloons that progressively accommodate gas. Phase contrast synchrotron radiation computed tomography (PCSRCT) has recently challenged this concept, showing that in healthy lungs, deflation mechanisms are based on the sequential de-recruitment of airspaces. Using PCSRCT scans in an animal model of acute respiratory distress syndrome (ARDS), this study examined whether the numerosity (ASnum) and dimension (ASdim) of lung airspaces change during a deflation maneuver at decreasing levels of positive end-expiratory pressure (PEEP) at 12, 9, 6, 3, and 0 cmH(2)O. Deflation was associated with significant reduction of ASdim both in the whole lung section (passing from from 13.1 +/- 2.0 at PEEP 12 to 7.6 +/- 4.2 voxels at PEEP 0) and in single concentric regions of interest (ROIs). However, the regression between applied PEEP and ASnum was significant in the whole slice (ranging from 188 +/- 52 at PEEP 12 to 146.4 +/- 96.7 at PEEP 0) but not in the single ROIs. This mechanism of deflation in which reduction of ASdim is predominant, differs from the one observed in healthy conditions, suggesting that the peculiar alveolar micromechanics of ARDS might play a role in the deflation process.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
ARDS, recruitment, VILI, alveoli, kinetics, synchrotron radiation computed tomography
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-394162 (URN)10.3390/jcm8081117 (DOI)000483737700125 ()31357677 (PubMedID)
Funder
Swedish Research Council, K2015-99X-22731-01-4
Available from: 2019-10-09 Created: 2019-10-09 Last updated: 2019-10-09Bibliographically approved
Gudmundsson, M., Perchiazzi, G., Pellegrini, M., Vena, A., Hedenstierna, G. & Rylander, C. (2018). Atelectasis is inversely proportional to transpulmonary pressure during weaning from ventilator support in a large animal model. Acta Anaesthesiologica Scandinavica, 62(1), 94-104
Open this publication in new window or tab >>Atelectasis is inversely proportional to transpulmonary pressure during weaning from ventilator support in a large animal model
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2018 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 62, no 1, p. 94-104Article in journal (Refereed) Published
Abstract [en]

Background

In mechanically ventilated, lung injured, patients without spontaneous breathing effort, atelectasis with shunt and desaturation may appear suddenly when ventilator pressures are decreased. It is not known how such a formation of atelectasis is related to transpulmonary pressure (PL) during weaning from mechanical ventilation when the spontaneous breathing effort is increased. If the relation between PL and atelectasis were known, monitoring of PL might help to avoid formation of atelectasis and cyclic collapse during weaning. The main purpose of this study was to determine the relation between PL and atelectasis in an experimental model representing weaning from mechanical ventilation.

Methods

Dynamic transverse computed tomography scans were acquired in ten anaesthetized, surfactant-depleted pigs with preserved spontaneous breathing, as ventilator support was lowered by sequentially reducing inspiratory pressure and positive end expiratory pressure in steps. The volumes of gas and atelectasis in the lungs were correlated with PL obtained using oesophageal pressure recordings. Work of breathing (WOB) was assessed from Campbell diagrams.

Results

Gradual decrease in PL in both end-expiration and end-inspiration caused a proportional increase in atelectasis and decrease in the gas content (linear mixed model with an autoregressive correlation matrix; P < 0.001) as the WOB increased. However, cyclic alveolar collapse during tidal ventilation did not increase significantly.

Conclusion

We found a proportional correlation between atelectasis and PL during the ‘weaning process’ in experimental mild lung injury. If confirmed in the clinical setting, a gradual tapering of ventilator support can be recommended for weaning without risk of sudden formation of atelectasis.

National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology and Intensive Care; Clinical Physiology
Identifiers
urn:nbn:se:uu:diva-342403 (URN)10.1111/aas.13015 (DOI)000417184800010 ()29058315 (PubMedID)
Funder
Swedish Research Council, 2008-5315; 2011-5315
Available from: 2018-02-20 Created: 2018-02-20 Last updated: 2018-03-05Bibliographically approved
Perchiazzi, G., Pellegrini, M., Hedenstierna, G., Roneus, A. & Larsson, A. S. (2018). Multiple Transients of Local Gas Redistribution During Spontaneous Breathing Are Influenced by Ventilatory Settings. Paper presented at International Conference of the American-Thoracic-Society, MAY 18-23, 2018, San Diego, CA.. American Journal of Respiratory and Critical Care Medicine, 197
Open this publication in new window or tab >>Multiple Transients of Local Gas Redistribution During Spontaneous Breathing Are Influenced by Ventilatory Settings
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2018 (English)In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 197Article in journal, Meeting abstract (Other academic) Published
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-373348 (URN)000449980304539 ()
Conference
International Conference of the American-Thoracic-Society, MAY 18-23, 2018, San Diego, CA.
Funder
Swedish Research CouncilSwedish Heart Lung Foundation
Note

Meeting Abstract: A7213

Available from: 2019-01-15 Created: 2019-01-15 Last updated: 2019-01-21Bibliographically approved
Pellegrini, M., Hedenstierna, G., Roneus, A., Larsson, A. S. & Perchiazzi, G. (2018). Onset and Magnitude of Pendelluft During Spontaneous Breathing Depend on Lung Volume. Paper presented at International Conference of the American-Thoracic-Society, MAY 18-23, 2018, San Diego, CA.. American Journal of Respiratory and Critical Care Medicine, 197
Open this publication in new window or tab >>Onset and Magnitude of Pendelluft During Spontaneous Breathing Depend on Lung Volume
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2018 (English)In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 197Article in journal, Meeting abstract (Other academic) Published
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-373347 (URN)000449980301157 ()
Conference
International Conference of the American-Thoracic-Society, MAY 18-23, 2018, San Diego, CA.
Funder
Swedish Research CouncilSwedish Heart Lung Foundation
Note

Meeting Abstract: A5126

Available from: 2019-01-15 Created: 2019-01-15 Last updated: 2019-01-21Bibliographically approved
Broche, L., Perchiazzi, G., Porra, L., Tannoia, A., Pellegrini, M., Derosa, S., . . . Bayat, S. (2017). Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung. Critical Care Medicine, 45(4), 687-694
Open this publication in new window or tab >>Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung
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2017 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 4, p. 687-694Article in journal (Refereed) Published
Abstract [en]

Objectives: Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathologic process remains elusive. The goal of this study was to describe recruitment/derecruitment at acinar length scales over short-time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of recruitment/derecruitment, using a computational model. Design: Experimental animal study. Setting: International synchrotron radiation laboratory. Subjects: Four anesthetized rabbits, ventilated in pressure controlled mode. Interventions: The lung was consecutively imaged at - 1.5-minute intervals using phase-contrast synchrotron imaging, at positive end expiratory pressures of 12, 9, 6, 3, and 0 cm H2O before and after lavage and mechanical ventilation induced injury. The extent and spatial distribution of recruitment/derecruitment was analyzed by subtracting subsequent images. In a realistic lung structure, we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and recruited lung fractions (F-derecruaed, F-recruited) were computed based on the comparison of the aerated volumes at successive time points. Measurements and Main Results: Alternative recruitment/derecruitment occurred in neighboring alveoli over short-time scales in all tested positive end-expiratory pressure levels and despite stable pressure controlled mode. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of F-derecruited and F-recruited when mechanical interdependence was included, while its exclusion gave F-recruited values of zero at positive end -expiratory pressure greater than or equal to 3 cm H2O. Conclusions: These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent recruitment/derecruitment and subsequent lung damage.

Keywords
acute respiratory distress syndrome, assisted ventilation, imaging/computed tomography, pulmonary oedema, synchrotron
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-321336 (URN)10.1097/CCM.0000000000002234 (DOI)000396798700016 ()28107207 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Research CouncilNIH (National Institute of Health)
Available from: 2017-05-31 Created: 2017-05-31 Last updated: 2017-05-31Bibliographically approved
Perchiazzi, G., Rylander, C., Pellegrini, M., Larsson, A. & Hedenstierna, G. (2017). Monitoring of total positive end-expiratory pressure during mechanical ventilation by artificial neural networks. Journal of clinical monitoring and computing, 31(3), 551-559
Open this publication in new window or tab >>Monitoring of total positive end-expiratory pressure during mechanical ventilation by artificial neural networks
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2017 (English)In: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 31, no 3, p. 551-559Article in journal (Refereed) Published
Abstract [en]

Ventilation treatment of acute lung injury (ALI) requires the application of positive airway pressure at the end of expiration (PEEPapp) to avoid lung collapse. However, the total pressure exerted on the alveolar walls (PEEPtot) is the sum of PEEPapp and intrinsic PEEP (PEEPi), a hidden component. To measure PEEPtot, ventilation must be discontinued with an end-expiratory hold maneuver (EEHM). We hypothesized that artificial neural networks (ANN) could estimate the PEEPtot from flow and pressure tracings during ongoing mechanical ventilation. Ten pigs were mechanically ventilated, and the time constant of their respiratory system (τRS) was measured. We shortened their expiratory time (TE) according to multiples of τRS, obtaining different respiratory patterns (Rpat). Pressure (PAW) and flow (V'AW) at the airway opening during ongoing mechanical ventilation were simultaneously recorded, with and without the addition of external resistance. The last breath of each Rpat included an EEHM, which was used to compute the reference PEEPtot. The entire protocol was repeated after the induction of ALI with i.v. injection of oleic acid, and 382 tracings were obtained. The ANN had to extract the PEEPtot, from the tracings without an EEHM. ANN agreement with reference PEEPtot was assessed with the Bland-Altman method. Bland Altman analysis of estimation error by ANN showed -0.40 ± 2.84 (expressed as bias ± precision) and ±5.58 as limits of agreement (data expressed as cmH2O). The ANNs estimated the PEEPtot well at different levels of PEEPapp under dynamic conditions, opening up new possibilities in monitoring PEEPi in critically ill patients who require ventilator treatment.

Keywords
Artificial neural networks, Acute lung injury, Intrinsic positive end expiratory pressure, Animal model
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-307912 (URN)10.1007/s10877-016-9874-0 (DOI)000400077100009 ()27067075 (PubMedID)
Funder
Swedish Heart Lung Foundation
Available from: 2016-11-22 Created: 2016-11-22 Last updated: 2017-05-30Bibliographically approved
Perchiazzi, G., Rylander, C., Pellegrini, M., Larsson, A. & Hedenstierna, G. (2017). Robustness of two different methods of monitoring respiratory system compliance during mechanical ventilation.. Medical and Biological Engineering and Computing, 55(10), 1819-1828
Open this publication in new window or tab >>Robustness of two different methods of monitoring respiratory system compliance during mechanical ventilation.
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2017 (English)In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 55, no 10, p. 1819-1828Article in journal (Refereed) Published
Abstract [en]

Robustness measures the performance of estimation methods when they work under non-ideal conditions. We compared the robustness of artificial neural networks (ANNs) and multilinear fitting (MLF) methods in estimating respiratory system compliance (C RS) during mechanical ventilation (MV). Twenty-four anaesthetized pigs underwent MV. Airway pressure, flow and volume were recorded at fixed intervals after the induction of acute lung injury. After consecutive mechanical breaths, an inspiratory pause (BIP) was applied in order to calculate CRS using the interrupter technique. From the breath preceding the BIP, ANN and MLF had to compute CRS in the presence of two types of perturbations: transient sensor disconnection (TD) and random noise (RN). Performance of the two methods was assessed according to Bland and Altman. The ANN presented a higher bias and scatter than MLF during the application of RN, except when RN was lower than 2% of peak airway pressure. During TD, MLF algorithm showed a higher bias and scatter than ANN. After the application of RN, ANN and MLF maintain a stable performance, although MLF shows better results. ANNs have a more stable performance and yield a more robust estimation of C RS than MLF in conditions of transient sensor disconnection.

Keywords
Acute lung injury, Lung compliance, Mechanical ventilation, Neural networks, Robustness
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-334171 (URN)10.1007/s11517-017-1631-0 (DOI)000411111100009 ()28243966 (PubMedID)
Funder
Swedish Heart Lung Foundation
Available from: 2017-11-21 Created: 2017-11-21 Last updated: 2017-12-13Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-5668-7399

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