Predicting intradialytic hypotension in critically ill patients undergoing intermittent hemodialysis: a prospective observational study.

BACKGROUND: Hypotension during dialysis arises from vasomotor tone alterations and hypovolemia, with disrupted counterregulatory mechanisms in acute kidney injury (AKI) patients. This study investigated the predictive value of preload dependency, assessed by the passive leg raising (PLR) test, and arterial tone, measured by dynamic elastance (Eadyn), for intradialytic hypotension (IDH). METHODS: In this prospective observational study conducted in a tertiary hospital ICU, hemodynamic parameters were collected from critically ill AKI patients undergoing intermittent hemodialysis using the FloTrac/Vigileo system. Baseline measurements were recorded before KRT initiation, including the PLR test and Eadyn calculation. IDH was defined as mean arterial pressure (MAP) < 65 mmHg during dialysis. Logistic regression was used to identify predictors of IDH, and Kaplan-Meier analysis assessed 90-day survival. RESULTS: Of 187 patients, 27.3% experienced IDH. Preload dependency, identified by positive PLR test, was significantly associated with IDH (OR 8.54, 95% CI 5.25-27.74), while baseline Eadyn was not predictive of IDH in this cohort. Other significant predictors of IDH included norepinephrine use (OR 16.35, 95% CI 3.87-68.98) and lower baseline MAP (OR 0.96, 95% CI 0.94-1.00). IDH and a positive PLR test were associated with lower 90-day survival (p < 0.001). CONCLUSIONS: The PLR test is a valuable tool for predicting IDH in critically ill AKI patients undergoing KRT, while baseline Eadyn did not demonstrate predictive value in this setting. Continuous hemodynamic monitoring, including assessment of preload dependency, may optimize patient management and potentially improve outcomes. Further research is warranted to validate these findings and develop targeted interventions to prevent IDH.

Mecánica respiratoria en anestesia general: Revisión de conceptos / Respiratory mechanics in general anesthesia: Concepts review

In anesthesia practice, mechanical ventilation is a fundamental tool, and its correct configuration is essential in the patients care. Airway pressure is often assumed to reflect the forces applied to the lung and is used to monitor mechanical ventilation. This assumption is erroneous because pressure acts on the respiratory system as a whole and the impact on its components will depend on the ratio of lung and respiratory system elastances. In turn, patients' lungs with the same body size and ventilated with the same tidal volume, may be subjected to different forces depending on their functional size. This is expressed under the concepts of stress and strain. Its surrogate owners, the Paw plateau and the Vt, have shown a poor correlation compared to transpulmonary pressure and the airway driving pressure. This review aims to provide the theoretical-practical tools necessary to optimize mechanical ventilation for each patient.

En la práctica anestésica, la ventilación mecánica es una herramienta fundamental, y su correcta configuración es esencial en el cuidado de los pacientes. La presión de la vía aérea es, muchas veces, asumida como el reflejo de las fuerzas aplicadas en el pulmón y es utilizada para monitorizar la ventilación mecánica. Esta asunción es errónea porque la presión actúa sobre el sistema respiratorio en su totalidad y la repercusión sobre sus componentes va a depender de la relación de elastancias del pulmón y el sistema respiratorio. A su vez, los pulmones de pacientes con el mismo tamaño corporal y ventilados con el mismo volumen corriente, pueden estar sujetos a diferentes fuerzas dependiendo de su tamaño funcional. Esto es expresado bajo los conceptos de stress y strain. Sus respectivos subrogantes, Pawplateau y el Vt, han demostrado tener una pobre correlación en comparación con la presión transpulmonar y la airway driving pressure. Esta revisión pretende brindar las herramientas teórico-prácticas necesarias para optimizar la ventilación mecánica para cada paciente.

Intracranial Compliance Concepts and Assessment: A Scoping Review.

Background: Intracranial compliance (ICC) has been studied to complement the interpretation of intracranial pressure (ICP) in neurocritical care and help predict brain function deterioration. It has been reported that ICC is related to maintaining ICP stability despite changes in intracranial volume. However, this has not been properly translated to clinical practice. Therefore, the main objective of this scoping review was to map the key concepts of ICC in the literature. This review also aimed to characterize the relationship between ICC and ICP and systematically describe the outcomes used to assess ICC using both invasive and non-invasive measurement methods. Methods: This review included the following: (1) population: animal and humans, (2) concept of compliance or its inverse "elastance," and (3) context: neurocritical care. Therefore, literature searches without a time frame were conducted on several databases using a combination of keywords and descriptors. Results and Discussion: 43,339 articles were identified, and 297 studies fulfilled the inclusion criteria after the selection process. One hundred and five studies defined ICC. The concept was organized into three main components: physiological definition, clinical interpretation, and localization of the phenomena. Most of the studies reported the concept of compliance related to variations in volume and pressure or its inverse (elastance), primarily in the intracranial compartment. In addition, terms like "accommodation," "compensation," "reserve capacity," and "buffering ability" were used to describe the clinical interpretation. The second part of this review describes the techniques (invasive and non-invasive) and outcomes used to measure ICC. A total of 297 studies were included. The most common method used was invasive, representing 57-88% of the studies. The most commonly assessed variables were related to ICP, especially the absolute values or pulse amplitude. ICP waveforms should be better explored, along with the potential of non-invasive methods once the different aspects of ICC can be measured. Conclusion: ICC monitoring could be considered a complementary resource for ICP monitoring and clinical examination. The combination and validation of invasive/non-invasive or non-invasive measurement methods are required.

Left ventricle end-systolic elastance, arterial-effective elastance, and ventricle-arterial coupling in Epilepsy.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is a tragic event. Cardiac models of sudden death state that, paradoxically, healthy individuals compose most of the victims of this event. Exploration of cardiac physiological variables related to outcome could help unveil risk markers for sudden death in epilepsy. We investigated left ventricle end-systolic elastance, arterial-effective elastance and ventricle-arterial coupling (VAC) in PWE compared with controls. MATERIAL & METHODS: Adult patients with temporal lobe epilepsy without known cardiovascular diseases were submitted to treadmill test and transthoracic echocardiogram. Individuals without epilepsy matched by sex, age, and body mass index composed the control group. Cardiac risk factors, exercise performance, autonomic data from treadmill test, systolic and diastolic function, morphological cardiac data, and left ventricle pressure-volume loop were recorded. RESULTS: Sixty subjects were consecutively enrolled (30 PWE and 30 controls). Epilepsy duration was 22.5 ± 10.7 years (age of onset 15.2 ± 10.1 years). Treadmill variables were significantly worse in TLE patients compared with controls. End-systolic elastance, arterial-effective elastance, and ventricle-arterial coupling were similar between groups. Female sex, percentage of maximal predicted heart rate achieved in exercise, exercise time, and epilepsy duration explained 28,4% of VAC in PWE in multiple stepwise linear regression (P = .018). CONCLUSIONS: Some aspects of the cardiac pressure-volume curves, mainly linked to left ventricle systolic performance, contractile function and their interaction with afterload appears normal in young PWE and cannot explain their increase risk to adverse outcomes or lower physical fitness.

Regional distribution of transpulmonary pressure.

The pressure across the lung, so-called transpulmonary pressure (PL), represents the main force acting toward to provide lung movement. During mechanical ventilation, PL is provided by respiratory system pressurization, using specific ventilator setting settled by the operator, such as: tidal volume (VT), positive end-expiratory pressure (PEEP), respiratory rate (RR), and inspiratory airway flow. Once PL is developed throughout the lungs, its distribution is heterogeneous, being explained by the elastic properties of the lungs and pleural pressure gradient. There are different methods of PL calculation, each one with importance and some limitations. Among the most known, it can be quoted: (I) direct measurement of PL; (II) elastance derived method at end-inspiration of PL; (III) transpulmonary driving pressure. Recent studies using pleural sensors in large animal models as also in human cadaver have added new and important information about PL heterogeneous distribution across the lungs. Due to this heterogeneous distribution, lung damage could happen in specific areas of the lung. In addition, it is widely accepted that high PL can cause lung damage, however the way it is delivered, whether it's compressible or tensile, may also further damage despite the values of PL achieved. According to heterogeneous distribution of PL across the lungs, the interstitium and lymphatic vessels may also interplay to disseminate lung inflammation toward peripheral organs through thoracic lymph tracts. Thus, it is conceivable that juxta-diaphragmatic area associated strong efforts leading to high values of PL may be a source of dissemination of inflammatory cells, large molecules, and plasma contents able to perpetuate inflammation in distal organs.

Regional Lung Recruitability During Pneumoperitoneum Depends on Chest Wall Elastance - A Mechanical and Computed Tomography Analysis in Rats.

Background: Laparoscopic surgery with pneumoperitoneum increases respiratory system elastance due to the augmented intra-abdominal pressure. We aim to evaluate to which extent positive end-expiratory pressure (PEEP) is able to counteract abdominal hypertension preventing progressive lung collapse and how rib cage elastance influences PEEP effect. Methods: Forty-four Wistar rats were mechanically ventilated and randomly assigned into three groups: control (CTRL), pneumoperitoneum (PPT) and pneumoperitoneum with restricted rib cage (PPT-RC). A pressure-volume (PV) curve followed by a recruitment maneuver and a decremental PEEP trial were performed in all groups. Thereafter, animals were ventilated using PEEP of 3 and 8 cmH2O divided into two subgroups used to evaluate respiratory mechanics or computed tomography (CT) images. In 26 rats, we compared respiratory system elastance (Ers) at the two PEEP levels. In 18 animals, CT images were acquired to calculate total lung volume (TLV), total volume and air volume in six anatomically delimited regions of interest (three along the cephalo-caudal and three along the ventro-dorsal axes). Results: PEEP of minimal Ers was similar in CTRL and PPT groups (3.8 ± 0.45 and 3.5 ± 3.89 cmH2O, respectively) and differed from PPT-RC group (9.8 ± 0.63 cmH2O). Chest restriction determined a right- and downward shift of the PV curve, increased Ers and diminished TLV and lung aeration. Increasing PEEP augmented TLV in CTRL group (11.8 ± 1.3 to 13.6 ± 2 ml, p < 0.05), and relative air content in the apex of PPT group (3.5 ± 1.4 to 4.6 ± 1.4% TLV, p < 0.03) and in the middle zones in PPT-RC group (21.4 ± 1.9 to 25.3 ± 2.1% TLV cephalo-caudally and 18.1 ± 4.3 to 22.0 ± 3.3% TLV ventro-dorsally, p < 0.005). Conclusion: Regional lung recruitment potential during pneumoperitoneum depends on rib cage elastance, reinforcing the concept of PEEP individualization according to the patient's condition.

Effects of formaldehyde exposure on the development of pulmonary fibrosis induced by bleomycin in mice.

Environmental and Occupational pollution has been extensively studied because of its serious implications on the human health. Formaldehyde (FA) is a pollutant widely employed in several industries and also in anatomy, pathology and histology laboratories. Studies have shown the correlation between FA exposure and development or worsening of asthma. However, the effect of FA exposure on the pulmonary fibrosis (PF) is unknown. PF is a progressive and chronic lung disease with high incidence and considerable morbidity and mortality. Few studies have shown a worsening of PF after pollutants exposure such as ozone and nitrogen dioxide. Therefore, our objective was to assess the effects of FA on the PF. Male mice C57BL6 were treated or not with bleomycin (1,5 U/kg) and exposed or not to FA inhalation (0.92 mg/m3, 1 h/day, 5 days/week during 2 weeks). Non-manipulated mice were used as control. Our data showed that FA exposure in fibrotic mice increased the number of granulocytes in the bronchoalveolar lavage followed by elevated levels of interleukin 1 beta and interleukin 17. In addition, FA exposure in fibrotic mice enhanced the gene expression of C-X-C motif chemokine ligand 1 (CXCL1) and tumor necrosis factor alpha (TNF-α) in the lung. We also showed an increase in the collagen production, while lung elastance was reduced. No differences were found in the mucus production, oedema and interstitial thickening in the lung tissue of fibrotic mice after FA exposure. In conclusion our study showed that FA exposure aggravates the lung neutrophils influx and collagen production, but did not alter the lung elastance, mucus production, oedema and interstitial tickening. This work contributes to understand the effects of pollution in the development of PF.

Photobiomodulation therapy improves both inflammatory and fibrotic parameters in experimental model of lung fibrosis in mice.

Lung fibrosis (LF) is a chronic and progressive lung disease characterized by pulmonary parenchyma progressive lesion, inflammatory infiltration, and interstitial fibrosis. It is developed by excessive collagen deposition and other cellular matrix components, resulting in severe changes in the alveolar architecture. Considering the absence of effective treatment, the aim of this study was to investigate the effect of photobiomodulation therapy (PBMT) on the development of PF. For this purpose, we used C57BL6 mice subjected to induction of LF by bleomycin administration (1.5 U/kg) by orotracheal route and, after 14 days of the induction, mice were treated with PBMT applied to the thorax 1×/day for 8 days (wavelength 660 ± 20 nm, power 100 mW, radiant exposure 5 J/cm2, irradiance 33.3 mW/cm2, spot size 2.8cm2, total energy 15 J, time of irradiation: 150 s) and inflammatory and fibrotic parameters were evaluated with or without PBMT. Our results showed that PBMT significantly reduced the number of inflammatory cells in the alveolar space, collagen production, interstitial thickening, and static and dynamic pulmonary elastance. In addition, we observed reduced levels of IL-6 e CXCL1/KC released by pneumocytes in culture as well as reduced level of CXCL1/KC released by fibroblasts in culture. We can conclude that the PBMT improves both inflammatory and fibrotic parameters showing a promising therapy which is economical and has no side effects.

Variability in Tidal Volume Affects Lung and Cardiovascular Function Differentially in a Rat Model of Experimental Emphysema.

In experimental elastase-induced emphysema, mechanical ventilation with variable tidal volumes (VT) set to 30% coefficient of variation (CV) may result in more homogenous ventilation distribution, but might also impair right heart function. We hypothesized that a different CV setting could improve both lung and cardiovascular function. Therefore, we investigated the effects of different levels of VT variability on cardiorespiratory function, lung histology, and gene expression of biomarkers associated with inflammation, fibrogenesis, epithelial cell damage, and mechanical cell stress in this emphysema model. Wistar rats (n = 35) received repeated intratracheal instillation of porcine pancreatic elastase to induce emphysema. Seven animals were not ventilated and served as controls (NV). Twenty-eight animals were anesthetized and assigned to mechanical ventilation with a VT CV of 0% (BASELINE). After data collection, animals (n = 7/group) were randomly allocated to VT CVs of 0% (VV0); 15% (VV15); 22.5% (VV22.5); or 30% (VV30). In all groups, mean VT was 6 mL/kg and positive end-expiratory pressure was 3 cmH2O. Respiratory system mechanics and cardiac function (by echocardiography) were assessed continuously for 2 h (END). Lung histology and molecular biology were measured post-mortem. VV22.5 and VV30 decreased respiratory system elastance, while VV15 had no effect. VV0, VV15, and VV22.5, but not VV30, increased pulmonary acceleration time to pulmonary ejection time ratio. VV22.5 decreased the central moment of the mean linear intercept (D2 of Lm) while increasing the homogeneity index (1/ß) compared to NV (77 ± 8 µm vs. 152 ± 45 µm; 0.85 ± 0.06 vs. 0.66 ± 0.13, p < 0.05 for both). Compared to NV, VV30 was associated with higher interleukin-6 expression. Cytokine-induced neutrophil chemoattractant-1 expression was higher in all groups, except VV22.5, compared to NV. IL-1ß expression was lower in VV22.5 and VV30 compared to VV0. IL-10 expression was higher in VV22.5 than NV. Club cell protein 16 expression was higher in VV22.5 than VV0. SP-D expression was higher in VV30 than NV, while SP-C was higher in VV30 and VV22.5 than VV0. In conclusion, VV22.5 improved respiratory system elastance and homogeneity of airspace enlargement, mitigated inflammation and epithelial cell damage, while avoiding impairment of right cardiac function in experimental elastase-induced emphysema.

Characterization of a Mouse Model of Emphysema Induced by Multiple Instillations of Low-Dose Elastase.

Many experimental models have been proposed to study the pathophysiological features of emphysema, as well as to search for new therapeutic approaches for acute or chronically injured lung parenchyma. We aimed to characterize an emphysema model induced by multiple instillations of elastase by tracking changes in inflammation, remodeling, and cardiac function after each instillation. Forty-eight C57BL/6 mice were randomly assigned across two groups. Emphysema (ELA) animals received 1, 2, 3, or 4 intratracheal instillations of pancreatic porcine elastase (PPE, 0.2 IU) with a 1-week interval between them. Controls (C) received saline following the same protocol. Before and after implementation of the protocol, animals underwent echocardiographic analysis. After the first instillation of PPE, the percentage of mononuclear cells in the lung parenchyma increased compared to C (p = 0.0001). The second instillation resulted in hyperinflated alveoli, increased mean linear intercept, and reduced elastic fiber content in lung parenchyma compared to C (p = 0.0197). Following the third instillation, neutrophils and collagen fiber content in alveolar septa and airways increased, whereas static lung elastance was reduced compared to C (p = 0.0094). After the fourth instillation, the percentage of M1 macrophages in lungs; levels of interleukin-1ß (IL-1ß), keratinocyte-derived chemokine, hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF); and collagen fiber content in the pulmonary vessel wall were increased compared to C (p = 0.0096). At this time point, pulmonary arterial hypertension was apparent, with increased diastolic right ventricular wall thickness. In conclusion, the initial phase of emphysema was characterized by lung inflammation with predominance of mononuclear cells, whereas at the late stage, impairment of pulmonary and cardiovascular functions was observed. This model enables analysis of therapies at different time points during controlled progression of emphysema. Accordingly, early interventions could focus on the inflammatory process, while late interventions should focus on restoring cardiorespiratory function.

Comparison between Variable and Conventional Volume-Controlled Ventilation on Cardiorespiratory Parameters in Experimental Emphysema.

Emphysema is characterized by loss of lung tissue elasticity and destruction of structures supporting alveoli and capillaries. The impact of mechanical ventilation strategies on ventilator-induced lung injury (VILI) in emphysema is poorly defined. New ventilator strategies should be developed to minimize VILI in emphysema. The present study was divided into two protocols: (1) characterization of an elastase-induced emphysema model in rats and identification of the time point of greatest cardiorespiratory impairment, defined as a high specific lung elastance associated with large right ventricular end-diastolic area; and (2) comparison between variable (VV) and conventional volume-controlled ventilation (VCV) on lung mechanics and morphometry, biological markers, and cardiac function at that time point. In the first protocol, Wistar rats (n = 62) received saline (SAL) or porcine pancreatic elastase (ELA) intratracheally once weekly for 4 weeks, respectively. Evaluations were performed 1, 3, 5, or 8 weeks after the last intratracheal instillation of saline or elastase. After identifying the time point of greatest cardiorespiratory impairment, an additional 32 Wistar rats were randomized into the SAL and ELA groups and then ventilated with VV or VCV (n = 8/group) [tidal volume (VT) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 3 cmH2O, fraction of inspired oxygen (FiO2) = 0.4] for 2 h. VV was applied on a breath-to-breath basis as a sequence of randomly generated VT values (mean VT = 6 mL/kg), with a 30% coefficient of variation. Non-ventilated (NV) SAL and ELA animals were used for molecular biology analysis. The time point of greatest cardiorespiratory impairment, was observed 5 weeks after the last elastase instillation. At this time point, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (CINC)-1, amphiregulin, angiopoietin (Ang)-2, and vascular endothelial growth factor (VEGF) mRNA levels were higher in ELA compared to SAL. In ELA animals, VV reduced respiratory system elastance, alveolar collapse, and hyperinflation compared to VCV, without significant differences in gas exchange, but increased right ventricular diastolic area. Interleukin-6 mRNA expression was higher in VCV and VV than NV, while surfactant protein-D was increased in VV compared to NV. In conclusion, VV improved lung function and morphology and reduced VILI, but impaired right cardiac function in this model of elastase induced-emphysema.

Mechanisms of ventilator-induced lung injury in healthy lungs.

Mechanical ventilation is an essential method of patient support, but it may induce lung damage, leading to ventilator-induced lung injury (VILI). VILI is the result of a complex interplay among various mechanical forces that act on lung structures, such as type I and II epithelial cells, endothelial cells, macrophages, peripheral airways, and the extracellular matrix (ECM), during mechanical ventilation. This article discusses ongoing research focusing on mechanisms of VILI in previously healthy lungs, such as in the perioperative period, and the development of new ventilator strategies for surgical patients. Several experimental and clinical studies have been conducted to evaluate the mechanisms of mechanotransduction in each cell type and in the ECM, as well as the role of different ventilator parameters in inducing or preventing VILI. VILI may be attenuated by reducing the tidal volume; however, the use of higher or lower levels of positive end-expiratory pressure (PEEP) and recruitment maneuvers during the perioperative period is a matter of debate. Many questions concerning the mechanisms of VILI in surgical patients remain unanswered. The optimal threshold value of each ventilator parameter to reduce VILI is also unclear. Further experimental and clinical studies are necessary to better evaluate ventilator settings during the perioperative period in different types of surgery.

Papain-induced experimental pulmonary emphysema in male and female mice.

In papain-induced models of emphysema, despite the existing extensive description of the cellular and molecular aspects therein involved, sexual hormones may play a complex and still not fully understood role. Hence, we aimed at exploring the putative gender-related differences in lung mechanics, histology and oxidative stress in papain-exposed mice. Thirty adult BALB/c mice received intratracheally either saline (50 µL) or papain (10 U/50 µL saline) once a week for 2 weeks. In males papain increased lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance, while females showed higher static elastance and resistive pressure only. Both genders presented similar higher parenchymal cellularity and mean alveolar diameter, and less collagen-elastic fiber content and body weight gain than their respective controls. Increased functional residual capacity was more prominent in males. Female papain-treated mice were more susceptible to oxidative stress. Thus, male and female papain-exposed mice respond differently, which should be carefully considered to avoid confounding results.

Effects of freezing/thawing on the mechanical properties of decellularized lungs.

Lung bioengineering based on decellularized organ scaffolds is a potential alternative for transplantation. Freezing/thawing, a usual procedure in organ decellularization and storage could modify the mechanical properties of the lung scaffold and reduce the performance of the bioengineered lung when subjected to the physiological inflation-deflation breathing cycles. The aim of this study was to determine the effects of repeated freezing/thawing on the mechanical properties of decellularized lungs in the physiological pressure-volume regime associated with normal ventilation. Fifteen mice lungs (C57BL/6) were decellularized using a conventional protocol not involving organ freezing and based on sodium dodecyl sulfate detergent. Subsequently, the mechanical properties of the acellular lungs were measured before and after subjecting them to three consecutive cycles of freezing/thawing. The resistance (RL ) and elastance (EL ) of the decellularized lungs were computed by linear regression fitting of the recorded signals (tracheal pressure, flow, and volume) during mechanical ventilation. RL was not significantly modified by freezing-thawing: from 0.88 ± 0.37 to 0.90 ± 0.38 cmH2 O·s·mL(-1) (mean ± SE). EL slightly increased from 64.4 ± 11.1 to 73.0 ± 16.3 cmH2 O·mL(-1) after the three freeze-thaw cycles (p = 0.0013). In conclusion, the freezing/thawing process that is commonly used for both organ decellularization and storage induces only minor changes in the ventilation mechanical properties of the organ scaffold.