| 1. |
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| 2. |
- Scaramuzzo, Gaetano, et al.
(författare)
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Influence of Positive End-Expiratory Pressure Titration on the Effects of Pronation in Acute Respiratory Distress Syndrome : A Comprehensive Experimental Study
- 2020
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Ingår i: Frontiers in Physiology. - : FRONTIERS MEDIA SA. - 1664-042X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Prone position can reduce mortality in acute respiratory distress syndrome (ARDS), but several studies found variable effects on oxygenation and lung mechanics. It is unclear whether different positive end-expiratory pressure (PEEP) titration techniques modify the effect of prone position. We tested, in an animal model of ARDS, if the PEEP titration method may influence the effect of prone position on oxygenation and lung protection. In a crossover study in 10 piglets with a two-hit injury ARDS model, we set the "best PEEP" according to the ARDS Network low-PEEP table (BPARDS) or targeting the lowest transpulmonary driving pressure (BPDPL). We measured gas exchange, lung mechanics, aeration, ventilation, and perfusion with computed tomography (CT) and electrical impedance tomography in each position with both PEEP titration techniques. The primary endpoint was the PaO2/FiO(2) ratio. Secondary outcomes were lung mechanics, regional distribution of ventilation, regional distribution of perfusion, and homogeneity of strain derived by CT scan. The PaO2/FiO(2) ratio increased in prone position when PEEP was set with BPARDS [difference 54 (19-106) mmHg, p = 0.04] but not with BPDPL [difference 17 (-24 to 68) mmHg, p = 0.99]. The transpulmonary driving pressure significantly decreased during prone position with both BPARDS [difference -0.9 (-1.5 to -0.9) cmH(2)O, p = 0.009] and BPDPL [difference -0.55 (-1.6 to -0.4) cmH(2)O, p = 0.04]. Pronation homogenized lung regional strain and ventilation and redistributed the ventilation/perfusion ratio along the sternal-to-vertebral gradient. The PEEP titration technique influences the oxygenation response to prone position. However, the lung-protective effects of prone position could be independent of the PEEP titration strategy.
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| 3. |
- Scaramuzzo, Gaetano, et al.
(författare)
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Regional Behavior of Airspaces During Positive Pressure Reduction Assessed by Synchrotron Radiation Computed Tomography
- 2019
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Scaramuzzo, Gaetano, et al.
(författare)
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The Effect of Positive End-Expiratory Pressure on Lung Micromechanics Assessed by Synchrotron Radiation Computed Tomography in an Animal Model of ARDS
- 2019
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Tricase, Angelo, et al.
(författare)
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Water-Based Conductive Ink Formulations for Enzyme-Based Wearable Biosensors
- 2024
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Ingår i: Advanced Sensor Research. - : Wiley-VCH Verlagsgesellschaft. - 2751-1219. ; 3:3
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Tidskriftsartikel (refereegranskat)abstract
- Herein, this work reports the first example of second-generation wearable biosensor arrays based on a printed electrode technology involving a water-based graphite ink, for the simultaneous detection of l-lactate and d-glucose. The water-based graphite ink is deposited onto a flexible polyethylene terephthalate sheet, namely stencil-printed graphite (SPG) electrodes, and further modified with [Os(bpy)2(Cl)(PVI)10] as an osmium redox polymer to shuttle the electrons from the redox center of lactate oxidase from Aerococcus viridans (LOx) and gluocose oxidase from Aspergillus niger (GOx). The proposed biosensor array exhibits a limit of detection as low as (9.0 ± 1.0) × 10−6 m for LOx/SPG-[Os(bpy)2(Cl)(PVI)10] and (3.0 ± 0.5) × 10−6 m for GOx/SPG-[Os(bpy)2(Cl)(PVI)10], a sensitivity as high as 1.32 μA mm−1 for LOx/SPG-[Os(bpy)2(Cl)(PVI)10] and 28.4 μA mm−1 for GOx/SPG-[Os(bpy)2(Cl)(PVI)10]. The technology is also selective when tested in buffer and artificial sweat and is endowed with an operational/storage stability of ≈80% of the initial signal retained after 20 days. Finally, the proposed array is integrated in a wristband and successfully tested for the continuous monitoring of l-lactate and d-glucose in a healthy volunteer during daily activity. This is foreseen as a real-time wearable device for sport-medicine and healthcare applications.
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| 6. |
- Ahlström, J. Zebialowicz, et al.
(författare)
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Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits
- 2019
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Ingår i: Respiratory Research. - : BMC. - 1465-9921 .- 1465-993X. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- AimIn acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS.MethodsARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (V-T 20m/kg body weight) until P/F ratio<26.7kPa. The animals were treated with two intratracheal boluses of 2.5mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf (R)), both surfactants containing 80mg phospholipids/mL, or air as control. The animals were subsequently ventilated (V-T 8-9m/kg body weight) for an additional 3h and lung function parameters were recorded. Histological appearance of the lungs, degree of lung oedema and levels of the cytokines TNF alpha IL-6 and IL-8 in lung homogenates were evaluated.ResultsBoth surfactant preparations improved lung function vs. the control group and also reduced inflammation scores, production of pro-inflammatory cytokines, and formation of lung oedema to similar degrees. Poractant alfa improved compliance at 1h, P/F ratio and PaO2 at 1.5h compared to rSP-C33Leu surfactant.ConclusionThis study indicates that treatment of experimental ARDS with synthetic lung surfactant based on rSP-C33Leu improves lung function and attenuates inflammation.
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| 7. |
- Auckburally, Adam, et al.
(författare)
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Development of a method to measure regional perfusion of the lung in anesthetized ponies using computed tomography angiography and the maximum slope model
- 2022
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Ingår i: American Journal of Veterinary Research. - : AMER VETERINARY MEDICAL ASSOC. - 0002-9645 .- 1943-5681. ; 83:2, s. 162-170
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To develop a method based on CT angiography and the maximum slope model (MSM) to measure regional lung perfusion in anesthetized ponies. ANIMALS 6 ponies. PROCEDURES Anesthetized ponies were positioned in dorsal recumbency in the CT gantry. Contrast was injected, and the lungs were imaged while ponies were breathing spontaneously and while they were mechanically ventilated. Two observers delineated regions of interest in aerated and atelectatic lung, and perfusion in those regions was calculated with the MSM. Measurements obtained with a computerized method were compared with manual measurements, and computerized measurements were compared with previously reported measurements obtained with microspheres. RESULTS Perfusion measurements obtained with the MSM were similar to previously reported values obtained with the microsphere method. While ponies were spontaneously breathing, mean +/- SD perfusion for aerated and atelectatic lung regions were 4.0 +/- 1.9 and 5.0 +/- 1.2 mL/min/g of lung tissue, respectively. During mechanical ventilation, values were 4.6 +/- 1.2 and 2.7 +/- 0.7 mL/min/g of lung tissue at end expiration and 4.1 +/- 0.5 and 2.7 +/- 0.6 mL/min/g of lung tissue at peak inspiration. Intraobserver agreement was acceptable, but interobserver agreement was lower. Computerized measurements compared well with manual measurements.
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| 8. |
- Barrueta Tenhunen, Annelie
(författare)
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Adjuvant therapies to fluid resuscitation in experimental sepsis : Intervention studies in models of ARDS and peritonitis
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Fluid resuscitation is essential to antagonize the deleterious effects of tissue hypo-perfusion in sepsis. If not thoroughly monitored and individually tailored, fluid therapy increases the risk of volume overload. Volume overload is associated with higher mortality in sepsis. Although considerable progress has been made to understand the complex nature of the cardiovascular derangements in sepsis and septic shock, the optimal fluid resuscitation strategy is yet to be defined. Current guidelines recommend balanced crystalloids and albumin for resuscitation; synthetic colloids are harmful and no longer in use. In search of adjuvant therapies to fluid resuscitation in sepsis and sepsis related complications with a volume sparing potential, this doctoral thesis aimed at exploring the effects of two endogenous molecules involved in fluid homeostasis.In Study I, the peptide containing the active site of the endogenous protein antisecreterory factor (AF-16) reduced lung edema formation, as reflected in a reduction in extra vascular lung water (EVLW), in a model of ventilator induced lung injury (VILI). The aim of Study I was to test the intervention AF-16 in a well-established porcine model of lung edema and capillary leak.In Study II, the intervention AF-16 was tested in a model of fecal peritonitis sepsis. The first aim of Study II was to elaborate a clinically relevant porcine model of fecal peritonitis-sepsis, including a standardized resuscitation protocol. Second aim was to test the effect of the intervention on volume status and inflammation. Wet-to-dry ratio was lower in liver samples of the intervention group, indicating less edema formation. No other differences were detected between intervention and control groups.In Study III, the intervention high molecular weight hyaluronan (HMW-HA) was tested in our model of fecal peritonitis as adjuvant to standardized fluid resuscitation. Fluid balance and the inflammatory response were comparable throughout the experiment in the intervention and control groups. The intervention counteracted the increase in proportion of fragmented hyaluronan associated with peritonitis-sepsis and was associated with lower modified shock index (MSI) than placebo.In Study IV, we administered an increased dose of HMW-HA directly after induction of peritonitis. The aim of Study IV was to study the effects of the intervention in a fluid restrictive model, to reduce a potentially negative effect of crystalloid infusion per se on the endothelial glycocalyx layer. In Study IV, hemodynamics and surrogate markers of endothelial damage were comparable in the intervention and control groups. The intervention was associated with an increase in cardiac output and diastolic blood pressure during the infusion, these effects disappeared as the experiment proceeded. Lactate was higher in the intervention group as a function of time.
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| 9. |
- Barrueta Tenhunen, Annelie, et al.
(författare)
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Does the antisecretory peptide AF-16 reduce lung oedema in experimental ARDS?
- 2019
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 124:4, s. 246-253
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Tidskriftsartikel (refereegranskat)abstract
- Background: Acute respiratory distress syndrome (ARDS) is an acute inflammatory condition with pulmonary capillary leakage and lung oedema formation. There is currently no pharmacologic treatment for the condition. The antisecretory peptide AF-16 reduces oedema in experimental traumatic brain injury. In this study, we tested AF-16 in an experimental porcine model of ARDS. Methods: Under surgical anaesthesia 12 piglets were subjected to lung lavage followed by 2 hours of injurious ventilation. Every hour for 4 hours, measurements of extravascular lung water (EVLW), mechanics of the respiratory system, and hemodynamics were obtained. Results: There was a statistically significant (p = 0.006, two-way ANOVA) reduction of EVLW in the AF-16 group compared with controls. However, this was not mirrored in any improvement in the wet-to-dry ratio of lung tissue samples, histology, inflammatory markers, lung mechanics, or gas exchange. Conclusions: This pilot study suggests that AF-16 might improve oedema resolution as indicated by a reduction in EVLW in experimental ARDS.
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| 10. |
- Barrueta Tenhunen, Annelie, et al.
(författare)
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Fluid restrictive resuscitation with high molecular weight hyaluronan infusion in early peritonitis sepsis
- 2023
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Ingår i: Intensive Care Medicine Experimental. - : Springer Nature. - 2197-425X. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis is a condition with high morbidity and mortality. Prompt recognition and initiation of treatment is essential. Despite forming an integral part of sepsis management, fluid resuscitation may also lead to volume overload, which in turn is associated with increased mortality. The optimal fluid strategy in sepsis resuscitation is yet to be defined. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water is an important constituent of the endothelial glycocalyx. We hypothesized that exogenously administered hyaluronan would counteract intravascular volume depletion and contribute to endothelial glycocalyx integrity in a fluid restrictive model of peritonitis. In a prospective, blinded model of porcine peritonitis sepsis, we randomized animals to intervention with hyaluronan (n = 8) or 0.9% saline (n = 8). The animals received an infusion of 0.1% hyaluronan 6 ml/kg/h, or the same volume of saline, during the first 2 h of peritonitis. Stroke volume variation and hemoconcentration were comparable in the two groups throughout the experiment. Cardiac output was higher in the intervention group during the infusion of hyaluronan (3.2 ± 0.5 l/min in intervention group vs 2.7 ± 0.2 l/min in the control group) (p = 0.039). The increase in lactate was more pronounced in the intervention group (3.2 ± 1.0 mmol/l in the intervention group and 1.7 ± 0.7 mmol/l in the control group) at the end of the experiment (p < 0.001). Concentrations of surrogate markers of glycocalyx damage; syndecan 1 (0.6 ± 0.2 ng/ml vs 0.5 ± 0.2 ng/ml, p = 0.292), heparan sulphate (1.23 ± 0.2 vs 1.4 ± 0.3 ng/ml, p = 0.211) and vascular adhesion protein 1 (7.0 ± 4.1 vs 8.2 ± 2.3 ng/ml, p = 0.492) were comparable in the two groups at the end of the experiment. In conclusion, hyaluronan did not counteract intravascular volume depletion in early peritonitis sepsis. However, this finding is hampered by the short observation period and a beneficial effect of HMW-HA in peritonitis sepsis cannot be discarded based on the results of the present study.
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| 11. |
- Bayat, Sam, et al.
(författare)
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Imaging Regional Lung Structure and Function in Small Animals Using Synchrotron Radiation Phase-Contrast and K-Edge Subtraction Computed Tomography
- 2022
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Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 13
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Forskningsöversikt (refereegranskat)abstract
- Synchrotron radiation offers unique properties of coherence, utilized in phase-contrast imaging, and high flux as well as a wide energy spectrum which allow the selection of very narrow energy bands of radiation, used in K-edge subtraction imaging (KES) imaging. These properties extend X-ray computed tomography (CT) capabilities to quantitatively assess lung morphology, and to map regional lung ventilation, perfusion, inflammation, aerosol particle distribution and biomechanical properties, with microscopic spatial resolution. Four-dimensional imaging, allows the investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. These techniques have proven to be very useful for revealing the regional differences in both lung structure and function which is crucial for better understanding of disease mechanisms as well as for evaluating treatment in small animal models of lung diseases. Here, synchrotron radiation imaging methods are described and examples of their application to the study of disease mechanisms in preclinical animal models are presented.
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| 12. |
- Bergmann, Astrid, et al.
(författare)
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Effect of remote ischemic preconditioning on exhaled nitric oxide concentration in piglets during and after one-lung ventilation
- 2020
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Ingår i: Respiratory Physiology & Neurobiology. - : Elsevier BV. - 1569-9048 .- 1878-1519. ; 276
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Remote ischemic preconditioning (RIP) may protect target organs from ischemia - reperfusion injury, however, little is known on pulmonary effects of RIP prior to, immediately after and several hours after one-lung ventilation (OLV). The present randomized, controlled, animal experiment was undertaken to analyze these issues.METHODS: After animal ethics committee approval, twelve piglets (26 ± 2 kg) were anesthetized and randomly assigned to a control (n = 6) or to a RIP group (n = 6). For RIP, arterial perfusion of a hind limb was suspended by an inflated blood pressure cuff (200 mmHg for 5 min) and deflated for another 5 min, this was repeated four times. After intubation, mechanical ventilation (MV) was kept constant with tidal volume 10 ml/kg, inspired oxygen fraction (FIO2) 0.40, and positive end-expiratory pressure (PEEP) 5cmH2O. FIO2 was increased to 1 after RIP in the RIP group and after the sham procedure in the control group, respectively, for the time of OLV. OLV was established by left-sided bronchial blockade. After OLV, TLV was re-established until the end of the protocol. Exhaled nitric oxide (NO) was measured by ozon chemiluminiscense and ventilatory and hemodynamic variables were assessed according to the protocol.RESULTS: Hemodynamic and respiratory data were similar in both groups. Arterial pO2 was higher in the RIP group after two hours of OLV. In the control group, exhaled NO decreased during OLV and remained at low levels for the rest of the protocol. In the RIP group, exhaled NO decreased as well during OLV but returned to baseline levels when TLV was re-established.CONCLUSIONS: RIP has no effects on hemodynamic and respiratory variables in juvenile, healthy piglets. RIP improves the oxygenation after OLV and prevents the decline of exhaled NO after OLV.
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| 13. |
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| 14. |
- Borges, João Batista, et al.
(författare)
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Zero expiratory pressure and low oxygen concentration promote heterogeneity of regional ventilation and lung densities
- 2016
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 60:7, s. 958-968
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIt is not well known what is the main mechanism causing lung heterogeneity in healthy lungs under mechanical ventilation. We aimed to investigate the mechanisms causing heterogeneity of regional ventilation and parenchymal densities in healthy lungs under anesthesia and mechanical ventilation. MethodsIn a small animal model, synchrotron imaging was used to measure lung aeration and regional-specific ventilation (sV.). Heterogeneity of ventilation was calculated as the coefficient of variation in sV. (CVsV.). The coefficient of variation in lung densities (CVD) was calculated for all lung tissue, and within hyperinflated, normally and poorly aerated areas. Three conditions were studied: zero end-expiratory pressure (ZEEP) and FIO2 0.21; ZEEP and FIO2 1.0; PEEP 12 cmH(2)O and F(I)O(2)1.0 (Open Lung-PEEP = OLP). ResultsThe mean tissue density at OLP was lower than ZEEP-1.0 and ZEEP-0.21. There were larger subregions with low sV. and poor aeration at ZEEP-0.21 than at OLP: 12.9 9.0 vs. 0.6 +/- 0.4% in the non-dependent level, and 17.5 +/- 8.2 vs. 0.4 +/- 0.1% in the dependent one (P = 0.041). The CVsV. of the total imaged lung at PEEP 12 cmH(2)O was significantly lower than on ZEEP, regardless of FIO2, indicating more heterogeneity of ventilation during ZEEP (0.23 +/- 0.03 vs. 0.54 +/- 0.37, P = 0.049). CVD changed over the different mechanical ventilation settings (P = 0.011); predominantly, CVD increased during ZEEP. The spatial distribution of the CVD calculated for the poorly aerated density category changed with the mechanical ventilation settings, increasing in the dependent level during ZEEP. ConclusionZEEP together with low FIO2 promoted heterogeneity of ventilation and lung tissue densities, fostering a greater amount of airway closure and ventilation inhomogeneities in poorly aerated regions.
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| 15. |
- Broche, Ludovic, et al.
(författare)
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Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung
- 2017
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 45:4, s. 687-694
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 16. |
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| 17. |
- Broche, Ludovic, et al.
(författare)
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Individual Airway Closure Characterized In Vivo by Phase-Contrast CT Imaging in Injured Rabbit Lung
- 2019
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Ingår i: Critical Care Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0090-3493 .- 1530-0293. ; 47:9, s. E774-E781
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 18. |
- Cercos-Pita, Jose-Luis, et al.
(författare)
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Lung tissue biomechanics imaged with synchrotron phase contrast microtomography in live rats
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The magnitude and distribution of strain imposed on the peripheral airspaces by mechanical ventilation at the microscopic level and the consequent deformations are unknown despite their importance for understanding the mechanisms occurring at the onset of ventilator-induced lung injury. Here a 4-Dimensional (3D + time) image acquisition and processing technique is developed to assess pulmonary acinar biomechanics at microscopic resolution. Synchrotron radiation phase contrast CT with an isotropic voxel size of 6 mu m(3) is applied in live anesthetized rats under controlled mechanical ventilation. Video animations of regional acinar and vascular strain are acquired in vivo. Maps of strain distribution due to positive-pressure breaths and cardiovascular activity in lung acini and blood vessels are derived based on CT images. Regional strain within the lung peripheral airspaces takes average values of 0.09 +/- 0.02. Fitting the expression S = kV(n), to the changes in peripheral airspace area (S) and volume (V) during a positive pressure breath yields an exponent n = 0.82 +/- 0.03, suggesting predominant alveolar expansion rather than ductal expansion or alveolar recruitment. We conclude that this methodology can be used to assess acinar conformational changes during positive pressure breaths in intact peripheral lung airspaces.
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| 19. |
- Cereda, Maurizio, et al.
(författare)
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Imaging the Injured Lung : Mechanisms of Action and Clinical Use
- 2019
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Ingår i: Anesthesiology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-3022 .- 1528-1175. ; 131:3, s. 716-749
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Forskningsöversikt (refereegranskat)abstract
- Acute respiratory distress syndrome (ARDS) consists of acute hypoxemic respiratory failure characterized by massive and heterogeneously distributed loss of lung aeration caused by diffuse inflammation and edema present in interstitial and alveolar spaces. It is defined by consensus criteria, which include diffuse infiltrates on chest imaging-either plain radiography or computed tomography. This review will summarize how imaging sciences can inform modern respiratory management of ARDS and continue to increase the understanding of the acutely injured lung. This review also describes newer imaging methodologies that are likely to inform future clinical decision-making and potentially improve outcome. For each imaging modality, this review systematically describes the underlying principles, technology involved, measurements obtained, insights gained by the technique, emerging approaches, limitations, and future developments. Finally, integrated approaches are considered whereby multimodal imaging may impact management of ARDS.
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| 20. |
- Cronin, John N., et al.
(författare)
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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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Ingår i: Intensive Care Medicine Experimental. - : Springer Nature. - 2197-425X. ; 11:1
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Tidskriftsartikel (refereegranskat)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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| 21. |
- Derosa, Savino, et al.
(författare)
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Reabsorption atelectasis in a porcine model of ARDS : regional and temporal effects of airway closure, oxygen, and distending pressure
- 2013
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 115:10, s. 1464-1473
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the small airways dysfunction in acute respiratory distress syndrome (ARDS). By computed tomography (CT) imaging in a porcine experimental model of early ARDS, we aimed at studying the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction (FIO2). Six piglets were mechanically ventilated under anesthesia and muscle relaxation. Four animals underwent saline-washout lung injury, and two served as healthy controls. Beyond the site of assumed airway closure, gas was expected to be trapped in the injured lungs, promoting alveolar collapse. This was tested by ventilation with an FIO2 of 0.25 and 1 in sequence during low and high distending pressures. In the most dependent regions, the gas/tissue ratio of end-expiratory CT, after previous ventilation with FIO2 0.25 low-driving pressure, was significantly higher than after ventilation with FIO2 1; with high-driving pressure, this difference disappeared. Also, significant reduction in poorly aerated tissue and a correlated increase in nonaerated tissue in end-expiratory CT with FIO2 1 low-driving pressure were seen. When high-driving pressure was applied or after previous ventilation with FIO2 0.25 and low-driving pressure, this pattern disappeared. The findings suggest that low distending pressures produce widespread dependent airway closure and with high FIO2, subsequent absorption atelectasis. Low FIO2 prevented alveolar collapse during the study period because of slow absorption of gas behind closed airways.
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| 22. |
- Galmén, Karolina, et al.
(författare)
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Quantitative assessment of atelectasis formation under high frequency jet ventilation during liver tumour ablation : A computer tomography study
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHigh frequency jet ventilation (HFJV) can be used to minimise sub-diaphragmal organ displacements. Treated patients are in a supine position, under general anaesthesia and fully muscle relaxed. These are factors that are known to contribute to the formation of atelectasis. The HFJV-catheter is inserted freely inside the endotracheal tube and the system is therefore open to atmospheric pressure.AimThe aim of this study was to assess the formation of atelectasis over time during HFJV in patients undergoing liver tumour ablation under general anaesthesia.MethodIn this observational study twenty-five patients were studied. Repeated computed tomography (CT) scans were taken at the start of HFJV and every 15 minutes thereafter up until 45 minutes. From the CT images, four lung compartments were defined: hyperinflated, normoinflated, poorly inflated and atelectatic areas. The extension of each lung compartment was expressed as a percentage of the total lung area.ResultAtelectasis at 30 minutes, 7.9% (SD 3.5, p = 0.002) and at 45 minutes 8,1% (SD 5.2, p = 0.024), was significantly higher compared to baseline 5.6% (SD 2.5). The amount of normoinflated lung volumes were unchanged over the period studied. Only a few minor perioperative respiratory adverse events were noted.ConclusionAtelectasis during HFJV in stereotactic liver tumour ablation increased over the first 45 minutes but tended to stabilise with no impact on normoinflated lung volume. Using HFJV during stereotactic liver ablation is safe regarding formation of atelectasis.
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| 23. |
- Gudmundsson, Magni, et al.
(författare)
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Transpulmonary driving pressure during mechanical ventilation-validation of a non-invasive measurement method
- 2020
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 64:2, s. 211-215
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Tidskriftsartikel (refereegranskat)abstract
- Background Transpulmonary driving pressure plays an important role in today's understanding of ventilator induced lung injury. We have previously validated a novel non‐invasive method based on stepwise increments of PEEP to assess transpulmonary driving pressure in anaesthetised patients with healthy lungs. The aim of this study was to validate the method in patients who were mechanically ventilated for different diagnoses requiring intensive care. Methods We measured transpulmonary pressure (Ptp) and calculated transpulmonary driving pressure (ΔPtp) in 31 patients undergoing mechanical ventilation in an intensive care unit. Parallel triplicate measurements were performed with the PEEP step method (PtpPSM) and the conventional oesophageal balloon method (Ptpconv). Their agreement was compared using the intraclass correlation coefficient (ICC) and the Bland Altman plot. Result The coefficient of variation for the repeated measurements was 4,3 for ΔPtpPSM and 9,2 for ΔPtpconv. The ICC of 0,864 and the Bland Altman plot indicate good agreement between the two methods. Conclusion The non‐invasive method can be applied in mechanically ventilated patients to measure transpulmonary driving pressure with good repeatability and accuracy comparable to the traditional oesophageal balloon method.
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| 24. |
- Hedenstierna, Göran, et al.
(författare)
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Andningsfysiologi
- 2020
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Ingår i: <em>Intensivvård</em>. - : Liber. ; , s. 278-293
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Bokkapitel (refereegranskat)
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| 25. |
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| 26. |
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| 27. |
- Hultström, Michael, 1978-, et al.
(författare)
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Limitations of the ARDS criteria during high-flow oxygen or non-invasive ventilation : evidence from critically ill COVID-19 patients
- 2022
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Ingår i: Critical Care. - : Springer Nature. - 1364-8535 .- 1466-609X. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ratio of partial pressure of arterial oxygen to inspired oxygen fraction (PaO2/FIO2) during invasive mechanical ventilation (MV) is used as criteria to grade the severity of respiratory failure in acute respiratory distress syndrome (ARDS). During the SARS-CoV2 pandemic, the use of PaO2/FIO2 ratio has been increasingly used in non-invasive respiratory support such as high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV). The grading of hypoxemia in non-invasively ventilated patients is uncertain. The main hypothesis, investigated in this study, was that the PaO2/FIO2 ratio does not change when switching between MV, NIV and HFNC.Methods: We investigated respiratory function in critically ill patients with COVID-19 included in a single-center prospective observational study of patients admitted to the intensive care unit (ICU) at Uppsala University Hospital in Sweden. In a steady state condition, the PaO2/FIO2 ratio was recorded before and after any change between two of the studied respiratory support techniques (i.e., HFNC, NIV and MV).Results: A total of 148 patients were included in the present analysis. We find that any change in respiratory support from or to HFNC caused a significant change in PaO2/FIO2 ratio. Changes in respiratory support between NIV and MV did not show consistent change in PaO2/FIO2 ratio. In patients classified as mild to moderate ARDS during MV, the change from HFNC to MV showed a variable increase in PaO2/FIO2 ratio ranging between 52 and 140 mmHg (median of 127 mmHg). This made prediction of ARDS severity during MV from the apparent ARDS grade during HFNC impossible.Conclusions: HFNC is associated with lower PaO2/FIO2 ratio than either NIV or MV in the same patient, while NIV and MV provided similar PaO2/FIO2 and thus ARDS grade by Berlin definition. The large variation of PaO2/FIO2 ratio indicates that great caution should be used when estimating ARDS grade as a measure of pulmonary damage during HFNC.
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| 28. |
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| 29. |
- Höstman, Staffan, et al.
(författare)
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THAM administration reduces pulmonary carbon dioxide elimination in hypercapnia : an experimental porcine study
- 2018
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 62:6, s. 820-828
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Tidskriftsartikel (refereegranskat)abstract
- Background: In a previous study, we found a rebound of arterial carbon dioxide tension (PaCO2) after stopping THAM buffer administration. We hypothesized that this was due to reduced pulmonary CO2 elimination during THAM administration. The aim of this study was to investigate this hypothesis in an experimental porcine hypercapnic model.Methods: In seven, initially normoventilated, anesthetized pigs (22-27 kg) minute ventilation was reduced by 66% for 7 h. Two hours after commencing hypoventilation, THAM was infused IV for 3 h in a dose targeting a pH of 7.35 followed by a 2 h observation period. Acid-base status, blood-gas content and exhaled CO2 were measured.Results: THAM raised pH (7.07 0.04 to 7.41 +/- 0.04, P < 0.05) and lowered PaCO2 (15.2 +/- 1.4 to 12.2 +/- 1.1 kPa, P < 0.05). After the infusion, pH decreased and PaCO2 increased again. At the end of the observation period, pH and PaCO2 were 7.24 +/- 0.03 and 16.6 +/- 1.2 kPa, respectively (P < 0.05). Pulmonary CO2 excretion decreased from 109 +/- 12 to 74 +/- 12 ml/min (P < 0.05) during the THAM infusion but returned at the end of the observation period to 111 +/- 15 ml/min (P < 0.05). The estimated reduction of pulmonary CO2 elimination during the infusion was 5800 ml.Conclusions: In this respiratory acidosis model, THAM reduced PaCO2, but seemed not to increase the total CO2 elimination due to decreased pulmonary CO2 excretion(,) suggesting only cautious use of THAM in hypercapnic acidosis.
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| 30. |
- Karbing, D. S., et al.
(författare)
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Journal of Clinical Monitoring and Computing 2017 end of year summary : respiration
- 2018
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Ingår i: Journal of clinical monitoring and computing. - : Springer Science and Business Media LLC. - 1387-1307 .- 1573-2614. ; 32:2, s. 197-205
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Forskningsöversikt (refereegranskat)abstract
- This paper reviews 32 papers or commentaries published in Journal of Clinical Monitoring and Computing in 2016, within the field of respiration. Papers were published covering airway management, ventilation and respiratory rate monitoring, lung mechanics and gas exchange monitoring, in vitro monitoring of lung mechanics, CO2 monitoring, and respiratory and metabolic monitoring techniques.
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| 31. |
- Karbing, D. S., et al.
(författare)
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Journal of Clinical Monitoring and Computing 2018-2019 end of year summary : respiration
- 2020
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Ingår i: Journal of clinical monitoring and computing. - : Springer Science and Business Media LLC. - 1387-1307 .- 1573-2614. ; 34:2, s. 197-205
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Forskningsöversikt (refereegranskat)abstract
- This paper reviews 28 papers or commentaries published in Journal of Clinical Monitoring and Computing in 2018 and 2019, within the field of respiration. Papers were published covering endotracheal tube cuff pressure monitoring, ventilation and respiratory rate monitoring, lung mechanics monitoring, gas exchange monitoring, CO2 monitoring, lung imaging, and technologies and strategies for ventilation management.
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| 32. |
- Karbing, Dan S., et al.
(författare)
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What is new in respiratory monitoring?
- 2022
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Ingår i: Journal of clinical monitoring and computing. - : Springer Berlin/Heidelberg. - 1387-1307 .- 1573-2614. ; 36:3, s. 599-607
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Forskningsöversikt (refereegranskat)abstract
- This paper provides a review of a selection of papers published in the Journal of Clinical Monitoring and Computing in 2020 and 2021 highlighting what is new within the field of respiratory monitoring. Selected papers cover work in pulse oximetry monitoring, acoustic monitoring, respiratory system mechanics, monitoring during surgery, electrical impedance tomography, respiratory rate monitoring, lung ultrasound and detection of patient-ventilator asynchrony.
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| 33. |
- Lo Mauro, Antonella, et al.
(författare)
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Physiological changes and compensatory mechanisms by the action of respiratory muscles in a porcine model of phrenic nerve injury
- 2021
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 130:3, s. 813-826
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Tidskriftsartikel (refereegranskat)abstract
- Phrenic nerve damage may occur as a complication of specific surgical procedures, prolonged mechanical ventilation, or physical trauma. The consequent diaphragmatic paralysis or dysfunction can lead to major complications. The purpose of this study was to elucidate the role of the nondiaphragmatic respiratory muscles during partial or complete diaphragm paralysis induced by unilateral and bilateral phrenic nerve damage at different levels of ventilatory pressure support in an animal model. Ten pigs were instrumented, the phrenic nerve was exposed from the neck, and spontaneous respiration was preserved at three levels of pressure support, namely, high, low, and null, at baseline condition, after left phrenic nerve damage, and after bilateral phrenic nerve damage. Breathing pattern, thoracoabdominal volumes and asynchrony, and pressures were measured at each condition. Physiological breathing was predominantly diaphragmatic and homogeneously distributed between right and left sides. After unilateral damage, the paralyzed hemidiaphragm was passively dragged by the ipsilateral rib cage muscles and the contralateral hemidiaphragm. After bilateral damage, the drive to and the work of breathing of rib cage and abdominal muscles increased, to compensate for diaphragmatic paralysis, ensuing paradoxical thoracoabdominal breathing. Increasing level of pressure support ventilation replaces this muscle group compensation. When the diaphragm is paralyzed (unilaterally and/or bilaterally), there is a coordinated reorganization of nondiaphragmatic respiratory muscles as compensation that might be obscured by high level of pressure support ventilation. Noninvasive thoracoabdominal volume and asynchrony assessment could be useful in phrenic nerve-injured patients to estimate the extent and type of inspiratory muscle dysfunction.
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| 34. |
- Meyhoff, Christian S., et al.
(författare)
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In Reply
- 2018
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Ingår i: Anesthesiology. - : Lippincott Williams & Wilkins. - 0003-3022 .- 1528-1175. ; 128:1, s. 222-224
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Tidskriftsartikel (refereegranskat)
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| 35. |
- Pellegrini, Mariangela, et al.
(författare)
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A quantitative analysis of extension and distribution of lung injury in COVID-19 : a prospective study based on chest computed tomography
- 2021
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Ingår i: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTypical features differentiate COVID-19-associated lung injury from acute respiratory distress syndrome. The clinical role of chest computed tomography (CT) in describing the progression of COVID-19-associated lung injury remains to be clarified. We investigated in COVID-19 patients the regional distribution of lung injury and the influence of clinical and laboratory features on its progression.MethodsThis was a prospective study. For each CT, twenty images, evenly spaced along the cranio-caudal axis, were selected. For regional analysis, each CT image was divided into three concentric subpleural regions of interest and four quadrants. Hyper-, normally, hypo- and non-inflated lung compartments were defined. Nonparametric tests were used for hypothesis testing (alpha =0.05). Spearman correlation test was used to detect correlations between lung compartments and clinical features.ResultsTwenty-three out of 111 recruited patients were eligible for further analysis. Five hundred-sixty CT images were analyzed. Lung injury, composed by hypo- and non-inflated areas, was significantly more represented in subpleural than in core lung regions. A secondary, centripetal spread of lung injury was associated with exposure to mechanical ventilation (p<0.04), longer spontaneous breathing (more than 14 days, p<0.05) and non-protective tidal volume (p<0.04). Positive fluid balance (p<0.01), high plasma D-dimers (p<0.01) and ferritin (p<0.04) were associated with increased lung injury.ConclusionsIn a cohort of COVID-19 patients with severe respiratory failure, a predominant subpleural distribution of lung injury is observed. Prolonged spontaneous breathing and high tidal volumes, both causes of patient self-induced lung injury, are associated to an extensive involvement of more central regions. Positive fluid balance, inflammation and thrombosis are associated with lung injury.Trial registration Study registered a priori the 20th of March, 2020. Clinical Trials ID NCT04316884.
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| 36. |
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| 37. |
- Pellegrini, Mariangela, et al.
(författare)
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Effects of superimposed tissue weight on regional compliance of injured lungs
- 2016
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Ingår i: Respiratory Physiology & Neurobiology. - : Elsevier BV. - 1569-9048 .- 1878-1519. ; 228, s. 16-24
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Tidskriftsartikel (refereegranskat)abstract
- Computed tomography (CT), together with image analysis technologies, enable the construction of regional volume (V-REG) and local transpulmonary pressure (P-TP,P-REG) maps of the lung. Purpose of this study is to assess the distribution of V-REG vs P-TP,P-REG along the gravitational axis in healthy (HL) and experimental acute lung injury conditions (eALI) at various positive end-expiratory pressures (PEEPS) and inflation volumes. Mechanically ventilated pigs underwent inspiratory hold maneuvers at increasing volumes simultaneously with lung CT scans. eALI was induced via the iv administration of oleic acid. We computed voxel-level V-REG vs P-TP,P-REG curves into eleven isogravitational planes by applying polynomial regressions. Via F-test, we determined that V-REG vs P-TP,P-REG curves derived from different anatomical planes (p-values < 1.4E-3), exposed to different PEEPs (p-values < 1.5E-5) or subtending different lung status (p-values < 3E-3) were statistically different (except for two cases of adjacent planes). Lung parenchyma exhibits different elastic behaviors based on its position and the density of superimposed tissue which can increase during lung injury.
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| 38. |
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| 39. |
- Pellegrini, Mariangela, et al.
(författare)
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Expiratory Diaphragm Activity Reduces Atelectasis Formation
- 2016
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Konferensbidrag (refereegranskat)abstract
- Rationale. If the diaphragm, known as the major inspiratory muscle, is active also during expiration, it will limit closure of the smallairways as well as cyclic opening and closing of airways and alveoli. We investigated the expiratory role of the diaphragm in conditionsthat promote lung collapse. Methods. Acute lung injury was induced in 8 anesthetized, tracheostomized pigs by repeated lung lavages, targeting a PaO2/FiO2 of 250mmHg. After stabilization, the animals were switched to spontaneous breathing (SB) and underwent a decremental continuous positiveend-expiratory pressure (PEEP) trial of 15, 12, 9, 6, 3 and 0 cmH2O. During steady state conditions, para-diaphragmatic dynamic-CT scans(dCTs) were obtained together with measurements of respiratory variables. In 4 pigs, the same protocol was repeated during mechanicalpressure control ventilation (PCV) in fully muscle-paralyzed animals. The electrical diaphragmatic activity was continuously recordedduring the expiration (EAdiexp) and during apnea (EAdimin). The EAdiexp recording from end-inspiration to end-expiration was dividedinto 4 quartiles (Q1, Q2, Q3, Q4) and the mean value for each of them was expressed as percentage of the EAdi peak. During SB and PCV,the dCT scans collected at end-expiration and half-expiration were identified and the amount of collapse (atelectasis) in that cut wascalculated. The atelectatic tissue was defined as the sum of voxels with a density between -100 and +100 Hounsfield Units. Results. When, during spontaneous breathing, PEEP was lowered from 15 to 6 cmH2O, the EAdiexp increased significantly in all 4quartiles of the expiratory curve (see Figure, left panel). The EAdimin increased when PEEP was reduced from 12 to 0 cmH2O. However,atelectasis did not increase in size until PEEP was below 9 cmH2O. Larger atelectasis was seen during PCV (with no measurable EAdi) thanduring SB at PEEP levels from 9 to 0 cmH2O. This was seen not only at end-expiration, but already half way down the expiration (seeFigure, right panels). Conclusions. The increasing diaphragm activity with decreasing airway pressure during the expiration will protect against atelectasisformation. The effects of the diaphragmatic activity are visible already half way down the expiration. These findings have potentialimplications how to design ventilatory support strategies in a wide range of pathological lung conditions, from chronic obstructivepulmonary disease to acute lung injury.
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| 40. |
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| 41. |
- Pellegrini, Mariangela, et al.
(författare)
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Expiratory Resistances Prevent Expiratory Diaphragm Contraction, Flow Limitation, and Lung Collapse
- 2020
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - : AMER THORACIC SOC. - 1073-449X .- 1535-4970. ; 3:7
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Tidal expiratory flow limitation (tidal-EFL) is not completely avoidable by applying positive end-expiratory pressure and may cause respiratory and hemodynamic complications in ventilated patients with lungs prone to collapse. During spontaneous breathing, expiratory diaphragmatic contraction counteracts tidal-EFL. We hypothesized that during both spontaneous breathing and controlled mechanical ventilation, external expiratory resistances reduce tidal-EFL.Objectives: To assess whether external expiratory resistances 1) affect expiratory diaphragmatic contraction during spontaneous breathing, 2) reduce expiratory flow and make lung compartments more homogeneous with more similar expiratory time constants, and 3) reduce tidal atelectasis, preventing hyperinflation.Methods: Three positive end-expiratory pressure levels and four external expiratory resistances were tested in 10 pigs after lung lavage. We analyzed expiratory diaphragmatic electric activity and respiratory mechanics. On the basis of computed tomography scans, four lung compartments-not inflated (atelectasis), poorly inflated, normally inflated, and hyperinflated-were defined.Measurements and Main Results: Consequently to additional external expiratory resistances, and mainly in lungs prone to collapse (at low positive end-expiratory pressure), 1) the expiratory transdiaphragmatic pressure decreased during spontaneous breathing by >10%, 2) expiratory flow was reduced and the expiratory time constants became more homogeneous, and 3) the amount of atelectasis at end-expiration decreased from 24% to 16% during spontaneous breathing and from 32% to 18% during controlled mechanical ventilation, without increasing hyperinflation.Conclusions: The expiratory modulation induced by external expiratory resistances preserves the positive effects of the expiratory brake while minimizing expiratory diaphragmatic contraction. External expiratory resistances optimize lung mechanics and limit tidal-EFL and tidal atelectasis, without increasing hyperinflation.
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| 42. |
- Pellegrini, Mariangela, et al.
(författare)
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Expiratory Resistances Prevent Expiratory Diaphragm Contraction, Flow Limitation, and Lung Collapse.
- 2020
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Ingår i: American journal of respiratory and critical care medicine. - 1535-4970. ; 201:10, s. 1218-1229
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Tidal expiratory flow limitation (tidal-EFL) is not completely avoidable by applying positive end-expiratory pressure and may cause respiratory and hemodynamic complications in ventilated patients with lungs prone to collapse. During spontaneous breathing, expiratory diaphragmatic contraction counteracts tidal-EFL. We hypothesized that during both spontaneous breathing and controlled mechanical ventilation, external expiratory resistances reduce tidal-EFL.Objectives: To assess whether external expiratory resistances 1) affect expiratory diaphragmatic contraction during spontaneous breathing, 2) reduce expiratory flow and make lung compartments more homogeneous with more similar expiratory time constants, and 3) reduce tidal atelectasis, preventing hyperinflation.Methods: Three positive end-expiratory pressure levels and four external expiratory resistances were tested in 10 pigs after lung lavage. We analyzed expiratory diaphragmatic electric activity and respiratory mechanics. On the basis of computed tomography scans, four lung compartments-not inflated (atelectasis), poorly inflated, normally inflated, and hyperinflated-were defined.Measurements and Main Results: Consequently to additional external expiratory resistances, and mainly in lungs prone to collapse (at low positive end-expiratory pressure), 1) the expiratory transdiaphragmatic pressure decreased during spontaneous breathing by >10%, 2) expiratory flow was reduced and the expiratory time constants became more homogeneous, and 3) the amount of atelectasis at end-expiration decreased from 24% to 16% during spontaneous breathing and from 32% to 18% during controlled mechanical ventilation, without increasing hyperinflation.Conclusions: The expiratory modulation induced by external expiratory resistances preserves the positive effects of the expiratory brake while minimizing expiratory diaphragmatic contraction. External expiratory resistances optimize lung mechanics and limit tidal-EFL and tidal atelectasis, without increasing hyperinflation.
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| 43. |
- Pellegrini, Mariangela, et al.
(författare)
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Inspiratory Efforts, Positive End-Expiratory Pressure, and External Resistances Influence Intraparenchymal Gas Redistribution in Mechanically Ventilated Injured Lungs
- 2021
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Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Potentially harmful lung overstretch can follow intraparenchymal gas redistribution during mechanical ventilation. We hypothesized that inspiratory efforts characterizing spontaneous breathing, positive end-expiratory pressure (PEEP), and high inspiratory resistances influence inspiratory intraparenchymal gas redistribution.Methods: This was an experimental study conducted on a swine model of mild acute respiratory distress syndrome. Dynamic computed tomography and respiratory mechanics were simultaneously acquired at different PEEP levels and external resistances, during both spontaneous breathing and controlled mechanical ventilation. Images were collected at two cranial-caudal levels. Delta-volume images (ΔVOLs) were obtained subtracting pairs of consecutive inspiratory images. The first three ΔVOLs, acquired for each analyzed breath, were used for the analysis of inspiratory pendelluft defined as intraparenchymal gas redistribution before the start of inspiratory flow at the airway opening. The following ΔVOLs were used for the analysis of gas redistribution during ongoing inspiratory flow at the airway opening.Results: During the first flow-independent phase of inspiration, the pendelluft of gas was observed only during spontaneous breathing and along the cranial-to-caudal and nondependent-to-dependent directions. The pendelluft was reduced by high PEEP (p < 0.04 comparing PEEP 15 and PEEP 0 cm H2O) and low external resistances (p < 0.04 comparing high and low external resistance). During the flow-dependent phase of inspiration, two patterns were identified: (1) gas displacing characterized by large gas redistribution areas; (2) gas scattering characterized by small, numerous areas of gas redistribution. Gas displacing was observed at low PEEP, high external resistances, and it characterized controlled mechanical ventilation (p < 0.01, comparing high and low PEEP during controlled mechanical ventilation).Conclusions: Low PEEP and high external resistances favored inspiratory pendelluft. During the flow-dependent phase of the inspiration, controlled mechanical ventilation and low PEEP and high external resistances favored larger phenomena of intraparenchymal gas redistribution (gas displacing) endangering lung stability.
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| 44. |
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| 45. |
- Pellegrini, Mariangela, et al.
(författare)
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The Diaphragm Acts as a Brake During Expiration to Prevent Lung Collapse
- 2017
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 195:12, s. 1608-1616
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The diaphragm is the major inspiratory muscle and is assumed to relax during expiration. However, electrical postinspiratory activity has been observed. Whether there is an expiratory diaphragmatic contraction that preserves lung patency has yet to be explored.Objectives: We hypothesized the occurrence of an expiratory diaphragmatic contraction directed at stabilizing peripheral airways and preventing or reducing cyclic expiratory lung collapse.Methods: Mild acute respiratory distress syndrome was induced in 10 anesthetized, spontaneously breathing pigs. Lung volume was decreased by lowering end-expiratory airway pressure in a stepwise manner. We recorded the diaphragmatic electric activity during expiration, dynamic computed tomographic scans, and respiratory mechanics. In five pigs, the same protocol was repeated during mechanical ventilation after muscle paralysis.Measurements and Main Results: Diaphragmatic electric activity during expiration increased by decreasing end-expiratory lung volume during spontaneous breathing. This enhanced the diaphragm muscle force, to a greater extent with lower lung volume, indicating a diaphragmatic electromechanical coupling during spontaneous expiration. In turn, the resulting diaphragmatic contraction delayed and reduced the expiratory collapse and increased lung aeration compared with mechanical ventilation with muscle paralysis and absence of diaphragmatic activity.Conclusions: The diaphragm is an important regulator of expiration. Its expiratory activity seems to preserve lung volume and to protect against lung collapse. The loss of diaphragmatic expiratory contraction during mechanical ventilation and muscle paralysis may be a contributing factor to unsuccessful respiratory support.
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| 46. |
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| 47. |
- Perchiazzi, Gaetano, et al.
(författare)
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Acute Respiratory Distress Syndrome (ARDS) : Pathophysiological Insights and Lung Imaging
- 2019
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 8:12
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Acute respiratory distress syndrome (ARDS) is in the center of the scientific debate both for its complex pathophysiology and for the discussion about the remedies that could contribute to its healing. The intricate interplay of different body systems that characterizes ARDS is mirrored by two main research threads, one centered on the pathophysiological mechanisms of the disease and the other on the new approaches to lung imaging. In this Special Issue of the Journal of Clinical Medicine are presented studies using imaging technologies based on electrical impedance tomography, synchrotron radiation computed tomography and intravital probe-based confocal laser endomicroscopy. The studies on the pathophysiological mechanisms pertain to the evaluation of the biomarkers of the disease and the platelet disfunction during extracorporeal membrane oxygenation. These contributions witness the intensity of ARDS research as many of the key problems of the disease are only in part resolved.
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| 48. |
- Perchiazzi, Gaetano, 1967-
(författare)
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Artificial Neural Networks (ANN) in the Assessment of Respiratory Mechanics
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to test the capability of Artificial Neural Networks (ANN) to estimate respiratory mechanics during mechanical ventilation (MV). ANNs are universal function approximators and can extract information from complex signals. We evaluated, in an animal model of acute lung injury, whether ANN can assess respiratory system resistance (RRS) and compliance (CRS) using the tracings of pressure at airways opening (PAW), inspiratory flow (V’) and tidal volume, during an end-inspiratory hold maneuver (EIHM). We concluded that ANN can estimate CRS and RRS during an EIHM. We also concluded that the use of tracings obtained by non-biological models in the learning process has the potential of substituting biological recordings.We investigated whether ANN can extract CRS using tracings of PAW and V’, without any intervention of an inspiratory hold maneuver during continuous MV. We concluded that CRS can be estimated by ANN during volume control MV, without the need to stop inspiratory flow.We tested whether ANN, fed by inspiratory PAW and V’, are able to measure static total positive end-expiratory pressure (PEEPtot,stat) during ongoing MV. In an animal model we generated dynamic pulmonary hyperinflation by shortening expiratory time. Different levels of external PEEP (PEEPAPP) were applied. Results showed that ANN can estimate PEEPtot,stat reliably, without any influence from the level of PEEPAPP.We finally compared the robustness of ANN and multi-linear fitting (MLF) methods in extracting CRS when facing signals corrupted by perturbations. We observed that during the application of random noise, ANN and MLF maintain a stable performance, although in these conditions MLF may show better results. ANN have more stable performance and yield a more robust estimation of CRS than MLF in conditions of transient sensor disconnection.We consider ANN to be an interesting technique for the assessment of respiratory mechanics.
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| 49. |
- Perchiazzi, Gaetano, et al.
(författare)
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Chest dual-energy CT to assess the effects of steroids on lung function in severe COVID-19 patients
- 2022
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Ingår i: Critical Care. - : Springer Nature. - 1364-8535 .- 1466-609X. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- Background: Steroids have been shown to reduce inflammation, hypoxic pulmonary vasoconstriction (HPV) and lung edema. Based on evidence from clinical trials, steroids are widely used in severe COVID-19. However, the effects of steroids on pulmonary gas volume and blood volume in this group of patients are unexplored.Objective: Profiting by dual-energy computed tomography (DECT), we investigated the relationship between the use of steroids in COVID-19 and distribution of blood volume as an index of impaired HPV. We also investigated whether the use of steroids influences lung weight, as index of lung edema, and how it affects gas distribution.Methods: Severe COVID-19 patients included in a single-center prospective observational study at the intensive care unit at Uppsala University Hospital who had undergone DECT were enrolled in the current study. Patients' cohort was divided into two groups depending on the administration of steroids. From each patient's DECT, 20 gas volume maps and the corresponding 20 blood volume maps, evenly distributed along the cranial-caudal axis, were analyzed. As a proxy for HPV, pulmonary blood volume distribution was analyzed in both the whole lung and the hypoinflated areas. Total lung weight, index of lung edema, was estimated.Results: Sixty patients were analyzed, whereof 43 received steroids. Patients not exposed to steroids showed a more extensive non-perfused area (19% vs 13%, p < 0.01) and less homogeneous pulmonary blood volume of hypoinflated areas (kurtosis: 1.91 vs 2.69, p < 0.01), suggesting a preserved HPV compared to patients treated with steroids. Moreover, patients exposed to steroids showed a significantly lower lung weight (953 gr vs 1140 gr, p = 0.01). A reduction in alveolar-arterial difference of oxygen followed the treatment with steroids (322 +/- 106 mmHg at admission vs 267 +/- 99 mmHg at DECT, p = 0.04).Conclusions The use of steroids might cause impaired HPV and might reduce lung edema in severe COVID-19. This is consistent with previous findings in other diseases. Moreover, a reduced lung weight, as index of decreased lung edema, and a more homogeneous distribution of gas within the lung were shown in patients treated with steroids. Trial registration: Clinical Trials ID: NCT04316884, Registered March 13, 2020.
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| 50. |
- Perchiazzi, Gaetano, et al.
(författare)
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Estimating respiratory system compliance during mechanical ventilation using artificial neural networks
- 2003
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Ingår i: Veterinary Anaesthesia and Analgesia. - 1467-2987 .- 1467-2995. ; 97:4, s. 1143-1148
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Tidskriftsartikel (refereegranskat)abstract
- In this study we evaluated whether a technology based on artificial neural networks (ANN) could estimate the static compliance (C(RS)) of the respiratory system, even in the absence of an end-inspiratory pause, during continuous mechanical ventilation. A porcine model of acute lung injury was used to provide recordings of different respiratory mechanics conditions. Each recording consisted of 10 or more consecutive breaths in volume-controlled mechanical ventilation, followed by a breath having an end-inspiratory pause used to calculate C(RS) according to the interrupter technique (IT). The volume-pressure loop of the breath immediately preceding the one with pause was given to the ANN for the training, together with the C(RS) separately calculated by the IT. The prospective phase consisted of giving only the loops to the trained ANN and comparing the results yielded by it to the compliance separately calculated by the investigators. Determination of measurement agreement between ANN and IT methods showed an error of -0.67 +/- 1.52 mL/cm H(2)O (bias +/- SD). We could conclude that ANN, during volume-controlled mechanical ventilation, can extract C(RS) without needing to stop inspiratory flow.IMPLICATIONS:We studied the application of artificial neural networks (ANN) to the estimation of respiratory compliance during mechanical ventilation. The study was performed on an animal model of acute lung injury, testing the performance of ANN in both healthy and diseased conditions of the lung.
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