Browsing by Author "Cruces, Pablo"
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- ItemA machine-learning regional clustering approach to understand ventilator-induced lung injury: a proof-of-concept experimental study(2024) Cruces, Pablo; Retamal, Jaime; Damián, Andrés; Lago, Graciela; Blasina, Fernanda; Oviedo, Vanessa; Medina, Tania; Pérez, Agustín; Vaamonde, Lucía; Dapueto, Rosina; González-Dambrauskas, Sebastian; Serra, Alberto; Monteverde-Fernandez, Nicolas; Namías, Mauro; Martínez, Javier; Hurtado, Daniel E.Background The spatiotemporal progression and patterns of tissue deformation in ventilator-induced lung injury (VILI) remain understudied. Our aim was to identify lung clusters based on their regional mechanical behavior over space and time in lungs subjected to VILI using machine-learning techniques. Results Ten anesthetized pigs (27±2 kg) were studied. Eight subjects were analyzed. End-inspiratory and endexpiratory lung computed tomography scans were performed at the beginning and after 12 h of one-hit VILI model. Regional image-based biomechanical analysis was used to determine end-expiratory aeration, tidal recruitment, and volumetric strain for both early and late stages. Clustering analysis was performed using principal component analysis and K-Means algorithms. We identifed three diferent clusters of lung tissue: Stable, Recruitable Unstable, and Non-Recruitable Unstable. End-expiratory aeration, tidal recruitment, and volumetric strain were signifcantly diferent between clusters at early stage. At late stage, we found a step loss of end-expiratory aeration among clusters, lowest in Stable, followed by Unstable Recruitable, and highest in the Unstable Non-Recruitable cluster. Volumetric strain remaining unchanged in the Stable cluster, with slight increases in the Recruitable cluster, and strong reduction in the Unstable Non-Recruitable cluster. Conclusions VILI is a regional and dynamic phenomenon. Using unbiased machine-learning techniques we can identify the coexistence of three functional lung tissue compartments with diferent spatiotemporal regional biomechanical behavior.
- ItemA physiological approach to understand the role of respiratory effort in the progression of lung injury in SARS-CoV-2 infection(2020) Cruces, Pablo; Retamal Montes, Jaime; Hurtado Sepúlveda, Daniel; Erranz, Benjamín; Iturrieta, Pablo; González, Carlos; Díaz, FrancoAbstract Deterioration of lung function during the first week of COVID-19 has been observed when patients remain with insufficient respiratory support. Patient self-inflicted lung injury (P-SILI) is theorized as the responsible, but there is not robust experimental and clinical data to support it. Given the limited understanding of P-SILI, we describe the physiological basis of P-SILI and we show experimental data to comprehend the role of regional strain and heterogeneity in lung injury due to increased work of breathing. In addition, we discuss the current approach to respiratory support for COVID-19 under this point of view.
- ItemAcute respiratory distress syndrome resulting from inhalation of powdered copper(TAYLOR & FRANCIS LTD, 2007) Donoso, Alejandro; Cruces, Pablo; Camacho, Jorge; Rios, Juan Carlos; Paris, Enrique; Mieres, Juan JoseBackground. Copper is an essential element. Poisoning with elemental copper is infrequent and manifestations rarely include the ones that our case presented. Case report. A previously healthy 2-year-old female patient unintentionally inhaled copper dust, developed respiratory failure a few hours later, and required mechanical ventilation. On hospital day three, the patient developed acute respiratory distress syndrome and was treated with high-frequency oscillatory ventilation for six days. She also developed hemolytic anemia, liver failure, oliguric renal failure, and evidence of acute tubular injury. During her stay in the intensive care unit she received inotropic support, packed red cells transfusion, and diuretics. A sample of bronchoalveolar lavage showed macrophages that stained positive for copper. Serum and urine copper concentrations were within the normal range after several days. Extubation was successfully achieved after two weeks and the patient was discharged on day 30 without sequelae. This is the first report of acute respiratory distress syndrome secondary to copper aspiration in a pediatric patient. Conclusion. To our knowledge, this is the first case reported of acute respiratory distress syndrome secondary to elemental copper aspiration. It is important to the clinician to be aware of acute respiratory distress syndrome as a differential diagnosis to copper aspiration by treating the patient aggressively in an adequate clinical setting.
- ItemDistribution and Magnitude of Regional Volumetric Lung Strain and Its Modification by PEEP in Healthy Anesthetized and Mechanically Ventilated Dogs(2022) Araos, Joaquin; Cruces, Pablo; Martin-Flores, Manuel; Donati, Pablo; Gleed, Robin D.; Boullhesen-Williams, Tomas; Perez, Agustin; Staffieri, Francesco; Retamal, Jaime; Melo, Marcos Vidal F.; Hurtado, Daniel E.The present study describes the magnitude and spatial distribution of lung strain in healthy anesthetized, mechanically ventilated dogs with and without positive end-expiratory pressure (PEEP). Total lung strain (LSTOTAL) has a dynamic (LSDYNAMIC) and a static (LSSTATIC) component. Due to lung heterogeneity, global lung strain may not accurately represent regional total tissue lung strain (TSTOTAL), which may also be described by a regional dynamic (TSDYNAMIC) and static (TSSTATIC) component. Six healthy anesthetized beagles (12.4 +/- 1.4 kg body weight) were placed in dorsal recumbency and ventilated with a tidal volume of 15 ml/kg, respiratory rate of 15 bpm, and zero end-expiratory pressure (ZEEP). Respiratory system mechanics and full thoracic end-expiratory and end-inspiratory CT scan images were obtained at ZEEP. Thereafter, a PEEP of 5 cmH(2)O was set and respiratory system mechanics measurements and end-expiratory and end-inspiratory images were repeated. Computed lung volumes from CT scans were used to evaluate the global LSTOTAL, LSDYNAMIC, and LSSTATIC during PEEP. During ZEEP, LSSTATIC was assumed zero; therefore, LSTOTAL was the same as LSDYNAMIC. Image segmentation was applied to CT images to obtain maps of regional TSTOTAL, TSDYNAMIC, and TSSTATIC during PEEP, and TSDYNAMIC during ZEEP. Compliance increased (p = 0.013) and driving pressure decreased (p = 0.043) during PEEP. PEEP increased the end-expiratory lung volume (p < 0.001) and significantly reduced global LSDYNAMIC (33.4 +/- 6.4% during ZEEP, 24.0 +/- 4.6% during PEEP, p = 0.032). LSSTATIC by PEEP was larger than the reduction in LSDYNAMIC; therefore, LSTOTAL at PEEP was larger than LSDYNAMIC at ZEEP (p = 0.005). There was marked topographic heterogeneity of regional strains. PEEP induced a significant reduction in TSDYNAMIC in all lung regions (p < 0.05). Similar to global findings, PEEP-induced TSSTATIC was larger than the reduction in TSDYNAMIC; therefore, PEEP-induced TSTOTAL was larger than TSDYNAMIC at ZEEP. In conclusion, PEEP reduced both global and regional estimates of dynamic strain, but induced a large static strain. Given that lung injury has been mostly associated with tidal deformation, limiting dynamic strain may be an important clinical target in healthy and diseased lungs, but this requires further study.
- ItemEffect of a lung rest strategy during ECMO in a porcine acute lung injury model(2015) Araos, J.; Tapia, Pablo; Alegría, Leyla; García Cañete, Patricia; Rodríguez, F.; Amthauer, M.; Castro, G.; Soto, Dagoberto; Damiani Rebolledo, L. Felipe; Bugedo Tarraza, Guillermo; Bruhn, Alejandro; Cruces, Pablo; Salomon, Tatiana; Erranz, B.; Carreño, P.; Medina, T.
- ItemEffect of positive end expiratory pressure on lung injury and haemodynamics during experimental acute respiratory distress syndrome treated with extracorporeal membrane oxygenation and near-apnoeic ventilation(2021) Araos, Joaquin; Alegría Vargas, Leyla; Garcia, Aline; Cruces, Pablo; Soto Muñoz, Dagoberto Igor; Erranz, Benjamín; Salomon, Tatiana; Medina, Tania; García Valdes, Patricio Hernán; Dubo, Sebastian; Bachmann Barron, María Consuelo; Basoalto Escobar, Roque Ignacio; Valenzuela, Emilio Daniel; Rovegno Echavarría, Maximiliano David; Vera Alarcón, María Magdalena; Retamal Montes, Jaime; Cornejo Rosas, Rodrigo Alfredo; Bugedo Tarraza, Guillermo; Bruhn, AlejandroBackground: Lung rest has been recommended during extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). Whether positive end-expiratory pressure (PEEP) confers lung protection during ECMO for severe ARDS is unclear. We compared the effects of three different PEEP levels whilst applying near-apnoeic ventilation in a model of severe ARDS treated with ECMO. Methods: Acute respiratory distress syndrome was induced in anaesthetised adult male pigs by repeated saline lavage and injurious ventilation for 1.5 h. After ECMO was commenced, the pigs received standardised near-apnoeic ventilation for 24 h to maintain similar driving pressures and were randomly assigned to PEEP of 0, 10, or 20 cm H2O (n¼7 per group). Respiratory and haemodynamic data were collected throughout the study. Histological injury was assessed by a pathologist masked to PEEP allocation. Lung oedema was estimated by wet-to-dry-weight ratio. Results: All pigs developed severe ARDS. Oxygenation on ECMO improved with PEEP of 10 or 20 cm H2O, but did not in pigs allocated to PEEP of 0 cm H2O. Haemodynamic collapse refractory to norepinephrine (n¼4) and early death (n¼3) occurred after PEEP 20 cm H2O. The severity of lung injury was lowest after PEEP of 10 cm H2O in both dependent and non-dependent lung regions, compared with PEEP of 0 or 20 cm H2O. A higher wet-to-dry-weight ratio, indicating worse lung injury, was observed with PEEP of 0 cmH2O. Histological assessment suggested that lung injury was minimised with PEEP of 10 cm H2O. Conclusions: During near-apnoeic ventilation and ECMO in experimental severe ARDS, 10 cm H2O PEEP minimised lung injury and improved gas exchange without compromising haemodynamic stability.
- ItemMechanical and morphological characterization of the emphysematous lung tissue(2024) Villa, Benjamin; Erranz, Benjamin; Cruces, Pablo; Retamal, Jaime; Hurtado, Daniel E.Irreversible alveolar airspace enlargement is the main characteristic of pulmonary emphysema, which has been extensively studied using animal models. While the alterations in lung mechanics associated with these morphological changes have been documented in the literature, the study of the mechanical behavior of parenchymal tissue from emphysematous lungs has been poorly investigated. In this work, we characterize the mechanical and morphological properties of lung tissue in elastase-induced emphysema rat models under varying severity conditions. We analyze the non-linear tissue behavior using suitable hyperelastic constitutive models that enable to compare different non-linear responses in terms of hyperelastic material parameters. We further analyze the effect of the elastase dose on alveolar morphology and tissue material parameters and study their connection with respiratory -system mechanical parameters. Our results show that while the lung mechanical function is not significantly influenced by the elastase treatment, the tissue mechanical behavior and alveolar morphology are markedly affected by it. We further show a strong association between alveolar enlargement and tissue softening, not evidenced by respiratory -system compliance. Our findings highlight the importance of understanding tissue mechanics in emphysematous lungs, as changes in tissue properties could detect the early stages of emphysema remodeling. Statement of significance Gas exchange is vital for life and strongly relies on the mechanical function of the lungs. Pulmonary emphysema is a prevalent respiratory disease where alveolar walls are damaged, causing alveolar enlargement that induces harmful changes in the mechanical response of the lungs. In this work, we study how the mechanical properties of lung tissue change during emphysema. Our results from animal models show that tissue properties are more sensitive to alveolar enlargement due to emphysema than other mechanical properties that describe the function of the whole respiratory system. (c) 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
- ItemNoninvasive Continuous Positive Airway Pressure Is a Lung- and Diaphragm-protective Approach in Self-inflicted Lung Injury(2024) Cruces, Pablo; Erranz, Benjamín; Pérez, Agustín; Reveco, Sonia; González, Carlos; Retamal, Jaime; Poblete Navarro, Daniela Andrea; Hurtado, Daniel E.; Diaz, Franco
- ItemProgression of regional lung strain and heterogeneity in lung injury: assessing the evolution under spontaneous breathing and mechanical ventilation(2020) Hurtado Sepúlveda, Daniel; Sarabia Vallejos, Mauricio; Iturrieta, Pablo; Erranz, Benjamín; Lillo, Felipe; Morales, Felipe; Blaha, Katherine; Medina, Tania; Diaz, Franco; Cruces, PabloAbstract Background Protective mechanical ventilation (MV) aims at limiting global lung deformation and has been associated with better clinical outcomes in acute respiratory distress syndrome (ARDS) patients. In ARDS lungs without MV support, the mechanisms and evolution of lung tissue deformation remain understudied. In this work, we quantify the progression and heterogeneity of regional strain in injured lungs under spontaneous breathing and under MV. Methods Lung injury was induced by lung lavage in murine subjects, followed by 3 h of spontaneous breathing (SB-group) or 3 h of low Vt mechanical ventilation (MV-group). Micro-CT images were acquired in all subjects at the beginning and at the end of the ventilation stage following induction of lung injury. Regional strain, strain progression and strain heterogeneity were computed from image-based biomechanical analysis. Three-dimensional regional strain maps were constructed, from which a region-of-interest (ROI) analysis was performed for the regional strain, the strain progression, and the strain heterogeneity. Results After 3 h of ventilation, regional strain levels were significantly higher in 43.7% of the ROIs in the SB-group. Significant increase in regional strain was found in 1.2% of the ROIs in the MV-group. Progression of regional strain was found in 100% of the ROIs in the SB-group, whereas the MV-group displayed strain progression in 1.2% of the ROIs. Progression in regional strain heterogeneity was found in 23.4% of the ROIs in the SB-group, while the MV-group resulted in 4.7% of the ROIs showing significant changes. Deformation progression is concurrent with an increase of non-aerated compartment in SB-group (from 13.3% ± 1.6% to 37.5% ± 3.1%), being higher in ventral regions of the lung. Conclusions Spontaneous breathing in lung injury promotes regional strain and strain heterogeneity progression. In contrast, low Vt MV prevents regional strain and heterogeneity progression in injured lungs.
- ItemRenal decapsulation prevents intrinsic renal compartment syndrome in ischemia-reperfusion - Induced acute kidney injury : a physiologic approach(2018) Cruces, Pablo; Lillo, Pablo; Salas, Camila; Salomon, Tatiana; Lillo, Felipe; González, Carlos; Pacheco, Alejandro; Hurtado Sepúlveda, Daniel
- ItemSpontaneous breathing promotes lung injury in an experimental model of alveolar collapse(2022) Bachmann, María Consuelo; Cruces, Pablo; Díaz, Franco; Oviedo, Vanessa; Goich, Mariela; Fuenzalida, José; Damiani Rebolledo, L. Felipe; Basoalto, Roque; Jalil, Yorschua F.; Carpio Cordero, David; Hamidi Vadeghani, Niki; Cornejo, Rodrigo; Rovegno Echavarria, Maximiliano; Bugedo Tarraza, Guillermo; Bruhn, Alejandro; Retamal Montes, JaimeVigorous spontaneous breathing has emerged as a promotor of lung damage in acute lung injury, an entity known as “patient self-inflicted lung injury”. Mechanical ventilation may prevent this second injury by decreasing intrathoracic pressure swings and improving regional air distribution. Therefore, we aimed to determine the effects of spontaneous breathing during the early stage of acute respiratory failure on lung injury and determine whether early and late controlled mechanical ventilation may avoid or revert these harmful effects. A model of partial surfactant depletion and lung collapse was induced in eighteen intubated pigs of 32 ±4 kg. Then, animals were randomized to (1) SB‐group: spontaneous breathing with very low levels of pressure support for the whole experiment (eight hours), (2) Early MV-group: controlled mechanical ventilation for eight hours, or (3) Late MV-group: first half of the experiment on spontaneous breathing (four hours) and the second half on controlled mechanical ventilation (four hours). Respiratory, hemodynamic, and electric impedance tomography data were collected. After the protocol, animals were euthanized, and lungs were extracted for histologic tissue analysis and cytokines quantification. SB-group presented larger esophageal pressure swings, progressive hypoxemia, lung injury, and more dorsal and inhomogeneous ventilation compared to the early MV-group. In the late MV-group switch to controlled mechanical ventilation improved the lung inhomogeneity and esophageal pressure swings but failed to prevent hypoxemia and lung injury. In a lung collapse model, spontaneous breathing is associated to large esophageal pressure swings and lung inhomogeneity, resulting in progressive hypoxemia and lung injury. Mechanical ventilation prevents these mechanisms of patient self-inflicted lung injury if applied early, before spontaneous breathing occurs, but not when applied late.
- ItemSpontaneous breathing promotes lung injury in an experimental model of alveolar collapse(2022) Bachmann Barrón, María Consuelo; Cruces, Pablo; Díaz, Franco; Orellana Oviedo, Vanessa Ivonne; Goich, Mariela; Fuenzalida, José; Damiani Rebolledo, L. Felipe; Basoalto Escobar, Roque Ignacio; Jalil Contreras, Yorschua Frederick; Carpio Cordero, David Bernardo; Hamidi Vadeghani, Majd Niki; Cornejo, Rodrigo; Rovegno Echavarria, David Maximiliano; Bugedo Tarraza, Guillermo; Bruhn Cruz, Alejandro; Retamal Montes, JaimeVigorous spontaneous breathing has emerged as a promotor of lung damage in acute lung injury, an entity known as “patient self-inflicted lung injury”. Mechanical ventilation may prevent this second injury by decreasing intrathoracic pressure swings and improving regional air distribution. Therefore, we aimed to determine the effects of spontaneous breathing during the early stage of acute respiratory failure on lung injury and determine whether early and late controlled mechanical ventilation may avoid or revert these harmful effects. A model of partial surfactant depletion and lung collapse was induced in eighteen intubated pigs of 32 ±4 kg. Then, animals were randomized to (1) SB‐group: spontaneous breathing with very low levels of pressure support for the whole experiment (eight hours), (2) Early MV-group: controlled mechanical ventilation for eight hours, or (3) Late MV-group: first half of the experiment on spontaneous breathing (four hours) and the second half on controlled mechanical ventilation (four hours). Respiratory, hemodynamic, and electric impedance tomography data were collected. After the protocol, animals were euthanized, and lungs were extracted for histologic tissue analysis and cytokines quantification. SB-group presented larger esophageal pressure swings, progressive hypoxemia, lung injury, and more dorsal and inhomogeneous ventilation compared to the early MV-group. In the late MV-group switch to controlled mechanical ventilation improved the lung inhomogeneity and esophageal pressure swings but failed to prevent hypoxemia and lung injury. In a lung collapse model, spontaneous breathing is associated to large esophageal pressure swings and lung inhomogeneity, resulting in progressive hypoxemia and lung injury. Mechanical ventilation prevents these mechanisms of patient self-inflicted lung injury if applied early, before spontaneous breathing occurs, but not when applied late.
- ItemVentilation-induced acute kidney injury in acute respiratory failure: Do PEEP levels matter?(Springer Nature, 2025) Benites, Martín H.; Suarez-Sipmann, Fernando; Kattan Tala, Eduardo José; Cruces, Pablo; Retamal Montes, JaimeAcute Respiratory Distress Syndrome (ARDS) is a leading cause of morbidity and mortality among critically ill patients, and mechanical ventilation (MV) plays a critical role in its management. One of the key parameters of MV is the level of positive end-expiratory pressure (PEEP), which helps to maintain an adequate lung functional volume. However, the optimal level of PEEP remains controversial. The classical approach in clinical trials for identifying the optimal PEEP has been to compare “high” and “low” levels in a dichotomous manner. High PEEP can improve lung compliance and significantly enhance oxygenation but has been inconclusive in hard clinical outcomes such as mortality and duration of MV. This discrepancy could be related to the fact that inappropriately high or low PEEP levels may adversely affect other organs, such as the heart, brain, and kidneys, which could counteract its potential beneficial effects on the lung. Patients with ARDS often develop acute kidney injury, which is an independent marker of mortality. Three primary mechanisms have been proposed to explain lung-kidney crosstalk during MV: gas exchange abnormalities, such as hypoxemia and hypercapnia; remote biotrauma; and hemodynamic changes, including reduced venous return and cardiac output. As PEEP levels increase, lung volume expands to a variable extent depending on mechanical response. This dynamic underlies two potential mechanisms that could impair venous return, potentially leading to splanchnic and renal congestion. First, increasing PEEP may enhance lung aeration, particularly in highly recruitable lungs, where previously collapsed alveoli reopen, increasing lung volume and pleural pressure, leading to vena cava compression, which can contribute to systemic venous congestion and abdominal organ impairment function. Second, in lungs with low recruitability, PEEP elevation may induce minimal changes in lung volume while increasing airway pressure, resulting in alveolar overdistension, vascular compression, and increased pulmonary vascular resistance. Therefore, we propose that high PEEP settings can contribute to renal congestion, potentially impairing renal function. This review underscores the need for further rigorous research to validate these perspectives and explore strategies for optimizing PEEP settings while minimizing adverse renal effects.