Clinical review: The implications of experimental and clinical studies of recruitment maneuvers in acute lung injury

Mechanical ventilation can cause and perpetuate lung injury if alveolar overdistension, cyclic collapse, and reopening of alveolar units occur. The use of low tidal volume and limited airway pressure has improved survival in patients with acute lung injury or acute respiratory distress syndrome. The use of recruitment maneuvers has been proposed as an adjunct to mechanical ventilation to re-expand collapsed lung tissue. Many investigators have studied the benefits of recruitment maneuvers in healthy anesthetized patients and in patients ventilated with low positive end-expiratory pressure. However, it is unclear whether recruitment maneuvers are useful when patients with acute lung injury or acute respiratory distress syndrome are ventilated with high positive end-expiratory pressure, and in the presence of lung fibrosis or a stiff chest wall. Moreover, it is unclear whether the use of high airway pressures during recruitment maneuvers can cause bacterial translocation. This article reviews the intrinsic mechanisms of mechanical stress, the controversy regarding clinical use of recruitment maneuvers, and the interactions between lung infection and application of high intrathoracic pressures

Bench-to-bedside review: Brain-lung interaction in the critically ill – a pending issue revisited

Brain and/or lung injury is the most frequent cause of admission to critical care units and patients in this setting frequently develop multiple organ dysfunction with high rates of morbidity and mortality. Mechanical ventilation is commonly used in the management of these critically ill patients and the consequent inflammatory response, together with other physiological factors, is also thought to be involved in distal organ dysfunction. This peripheral imbalance is based on a multiple-pathway cross-talk between the lungs and other organs, including the brain. Interestingly, acute respiratory distress syndrome survivors frequently present some cognitive deterioration at discharge. Such neurological dysfunction might be a secondary marker of injury and the neuroanatomical substrate for downstream impairment of other organs. Brain-lung interactions have received little attention in the literature, but recent evidence suggests that both the lungs and brain are promoters of inflammation through common mediators. This review addresses the current status of evidence regarding brain-lung interactions, their pathways and current interventions in critically ill patients receiving mechanical ventilation

Injurious mechanical ventilation affects neuronal activation in ventilated rats

Survivors of critical illness often have significant long-term brain dysfunction, and routine clinical procedures like mechanical ventilation (MV) may affect long-term brain outcome. We aimed to investigate the effect of the increase of tidal volume (Vt) on brain activation in a rat model. Male Sprague Dawley rats were randomized to three groups: 1) Basal: anesthetized unventilated animals, 2) low Vt (LVt): MV for three hours with Vt 8 ml/kg and zero positive end-expiratory pressure (ZEEP), and 3) high Vt (HVt) MV for three hours with Vt 30 ml/kg and ZEEP. We measured lung mechanics, mean arterial pressure (MAP), arterial blood gases, and plasma and lung levels of cytokines. We used immunohistochemistry to examine c-fos as a marker of neuronal activation. An additional group of spontaneously breathing rats was added to discriminate the effect of surgical procedure and anesthesia in the brain. After three hours on LVt, PaOdecreased and PaCOincreased significantly. MAP and compliance remained stable in MV groups. Systemic and pulmonary inflammation was higher in MV rats than in unventilated rats. Plasma TNFα was significantly higher in HVt than in LVt. Immunopositive cells to c-fos in the retrosplenial cortex and thalamus increased significantly in HVt rats but not in LVt or unventilated rats. MV promoted brain activation. The intensity of the response was higher in HVt animals, suggesting an iatrogenic effect of MV on the brain. These findings suggest that this novel cross-talking mechanism between the lung and the brain should be explored in patients undergoing MV

Cognitive reserve in healthy older adults

Introduction: Cognitive reserve is a protective factor against neurodegenerative diseases with the capacity to modify the relationship between a pathology and its symptomatic manifestation. For this reason, its study in the elderly population is of great importance, as well as having an adequate scale to do so. Volume 6 Issue 2 - 2021 Grasso Lina,1 Aceiro María Agustina,1 Aschiero María Belén,1 González Aguilar,1 María Josefina,1 Iglesia Fabiola,2 López Magdalena2 Objective: To describe and relate sociodemographic characteristics of cognitive reserve in older adults in the city of Buenos Aires throughout the Cognitive Reserve Questionnaire. Methodology: Quantitative, observational, analytical, and cross-sectional design. Sample: 174 older adults between 60 and 92 years old (X= 72.7; SD= 7.4), 74% women. Results: Adequate values were found for the CRC reliability index (Cronbach’s alpha: 0.72). The mean for cognitive reserve was 12.93 (SD: 4.6) indicating a medium-high cognitive reserve level. A positive and significant correlation of CRQ with semantic fluency, phonological fluency, CDT and MMSE was found. Differences in favor of men were found in the Studies, Languages, Occupation and Total Score dimensions. A linear regression indicates that CRQ score is significantly influenced by years of education. Conclusion: The CRQ is a quick and reliable tool to assess levels of cognitive reserve and its use in neuropsychological assessment provides relevant information. In addition, education could stimulate the pursuit of intellectual enrichment and favor the cognitive and functional performance of older adults.Fil: Grasso, Lina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Psicología y Psicopedagogía. Centro de Investigaciones en Psicología y Psicopedagogía; ArgentinaFil: Aceiro, María Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Psicología y Psicopedagogía. Centro de Investigaciones en Psicología y Psicopedagogía; ArgentinaFil: Aschiero, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Psicología y Psicopedagogía. Centro de Investigaciones en Psicología y Psicopedagogía; ArgentinaFil: Gonzalez Aguilar, Maria Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Psicología y Psicopedagogía. Centro de Investigaciones en Psicología y Psicopedagogía; ArgentinaFil: Iglesia, Maria Fabiola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Catolica Argentina "santa Maria de Los Bs. As.". Facultad Teresa de Avila. Centro de Investigacion Interdisciplinar En Valores, Integracion y Desarrollo Social.; ArgentinaFil: López, Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Catolica Argentina "santa Maria de Los Bs. As.". Facultad Teresa de Avila. Centro de Investigacion Interdisciplinar En Valores, Integracion y Desarrollo Social.; Argentin

Proanthocyanidin characterization and bioactivity of extracts from different parts of Uncaria tomentosa L. (cat’s claw)

This article belongs to the Special Issue Dietary Antioxidants and Health Promotion.-- et al.Apart from alkaloids, bioactive properties of Uncaria tomentosa L. have been attributed to its phenolic constituents. Although there are some reports concerning low-molecular-weight polyphenols in U. tomentosa, its polymeric phenolic composition has been scarcely studied. In this study, phenolic-rich extracts from leaves, stems, bark and wood (n = 14) of Uncaria tomentosa plants from several regions of Costa Rica were obtained and analysed in respect to their proanthocyanidin profile determined by a quadrupole-time-of-flight analyser (ESI-QTOF MS). Main structural characteristics found for U. tomentosa proanthocyanidins were: (a) monomer composition, including pure procyanidins (only composed of (epi)catechin units) and propelargonidins (only composed of (epi)afzelechin units) as well as mixed proanthocyanidins; and (b) degree of polymerization, from 3 up to 11 units. In addition, U. tomentosa phenolic extracts were found to exhibit reasonable antioxidant capacity (ORAC (Oxygen Radical Absorbance Capacity) values between 1.5 and 18.8 mmol TE/g) and antimicrobial activity against potential respiratory pathogens (minimum IC of 133 µg/mL). There were also found to be particularly cytotoxic to gastric adenocarcinoma AGS and colon adenocarcinoma SW620 cell lines. The results state the particularities of U. tomentosa proanthocyanidins and suggest the potential value of these extracts with prospective use as functional ingredients.This project was partially funded by grant from the Spanish International Development Cooperation Agency (AECID) (Ref. A/023397/09 and A/030037/10) and a joint grant from the Costa Rica-USA Foundation (CRUSA) and the Spanish Scientific Research Council (CSIC) (Ref. CR0024). Authors also thank financial support from the Comunidad de Madrid (Spain) and European funding from FEDER program (projects AVANSECAL-CM S2013/ABI-3028 and ALIBIRD-CM S2013/ABI-2728) and from the University of Costa Rica. Special thanks are due to Eng. Juan Jose Cordero from Costa Rican National Production Council (CNP).Peer Reviewe

Virtual Reality-Based Early Neurocognitive Stimulation in Critically Ill Patients : A Pilot Randomized Clinical Trial

This study focuses on the application of a non-immersive virtual reality (VR)-based neurocognitive intervention in critically ill patients. Our aim was to assess the feasibility of direct outcome measures to detect the impact of this digital therapy on patients' cognitive and emotional outcomes. Seventy-two mechanically ventilated adult patients were randomly assigned to the "treatment as usual" (TAU, n = 38) or the "early neurocognitive stimulation" (ENRIC, n = 34) groups. All patients received standard intensive care unit (ICU) care. Patients in the ENRIC group also received adjuvant neurocognitive stimulation during the ICU stay. Outcome measures were a full neuropsychological battery and two mental health questionnaires. A total of 42 patients (21 ENRIC) completed assessment one month after ICU discharge, and 24 (10 ENRIC) one year later. At one-month follow-up, ENRIC patients had better working memory scores (p = 0.009, d = 0.363) and showed up to 50% less non-specific anxiety (11.8% vs. 21.1%) and depression (5.9% vs. 10.5%) than TAU patients. A general linear model of repeated measures reported a main effect of group, but not of time or group-time interaction, on working memory, with ENRIC patients outperforming TAU patients (p = 0.008, η 2 = 0.282). Our results suggest that non-immersive VR-based neurocognitive stimulation may help improve short-term working memory outcomes in survivors of critical illness. Moreover, this advantage could be maintained in the long term. An efficacy trial in a larger sample of participants is feasible and must be conducted

Novel experimental model of maintained acute lung injury

Trabajo presentado en el 23rd Annual Congress European Respiratory Society (ERS) celebrado del 7 al 11 de septiembre de 2013 en Barcelona (España)Abstract publicado en "European Respiratory Journal" 42 (Suppl 57): 50s-51s (2013)Rationale: Several animal models have been developed to study acute lung injury (ALI); however the majority of these studies are focused on different mechanisms within the acute phase. These models do not allow studying the mechanisms in the later phases or testing any possible long-term treatment. The aim of this study was to develop an experimental ALI model simulating bronchial aspiration of gastric contents with bacterial superinfection with alveolar epithelial damage persisting over time. Methods: Sprague-Dawley rats (200-250g) were anesthetized with isofl uorane. ALI was induced by intratracheal instillation of HCl (1 μl/g, 0.1 mol/L pH=1.4) followed by instillation of LPS from Escherichia coli O55:B5 (0, 10, 20, 30 or 40μg/g b.w.) two hours later. Control rats were treated with intratracheal instillations of saline. After 72h, the animals were sacrifi ced and bronchoalveolar lavage fl uid (BALF) was sampled for further analysis of total protein concentration by bicinchoninic acid method. Results: At 72 h, rats suffered a signifi cant loss of weight proportional to the administered dose of LPS (5.6% with 10μg/g b.w, 12.6% with 20μg/g b.w, 14.2% with 30μg/g b.w and 17.7% with 40μg/g b.w). Control rats gained in weight at 72h. LPS at 10, 20, 30 and 40μg/g b.w induced a 1.7, 2.5, 2.9 and 3.4 fold increase in total protein concentration in BAL fl uid, respectively, refl ecting a substantial increase proportional to the LPS dose. Conclusion: The degree of weight loss and the increase of total protein concentration in BAL fl uid in the current model may refl ect disease severity and progression. This model would be useful in future for new therapeutical optionsGrant acknowledgements: FIS-PI12/02548 and Fundació Parc TaulíPeer Reviewe

Patient-ventilator asynchronies during mechanical ventilation : current knowledge and research priorities

Mechanical ventilation is common in critically ill patients. This life-saving treatment can cause complications and is also associated with long-term sequelae. Patient-ventilator asynchronies are frequent but underdiagnosed, and they have been associated with worse outcomes. Asynchronies occur when ventilator assistance does not match the patient's demand. Ventilatory overassistance or underassistance translates to different types of asynchronies with different effects on patients. Underassistance can result in an excessive load on respiratory muscles, air hunger, or lung injury due to excessive tidal volumes. Overassistance can result in lower patient inspiratory drive and can lead to reverse triggering, which can also worsen lung injury. Identifying the type of asynchrony and its causes is crucial for effective treatment. Mechanical ventilation and asynchronies can affect hemodynamics. An increase in intrathoracic pressure during ventilation modifies ventricular preload and afterload of ventricles, thereby affecting cardiac output and hemodynamic status. Ineffective efforts can decrease intrathoracic pressure, but double cycling can increase it. Thus, asynchronies can lower the predictive accuracy of some hemodynamic parameters of fluid responsiveness. New research is also exploring the psychological effects of asynchronies. Anxiety and depression are common in survivors of critical illness long after discharge. Patients on mechanical ventilation feel anxiety, fear, agony, and insecurity, which can worsen in the presence of asynchronies. Asynchronies have been associated with worse overall prognosis, but the direct causal relation between poor patient-ventilator interaction and worse outcomes has yet to be clearly demonstrated. Critical care patients generate huge volumes of data that are vastly underexploited. New monitoring systems can analyze waveforms together with other inputs, helping us to detect, analyze, and even predict asynchronies. Big data approaches promise to help us understand asynchronies better and improve their diagnosis and management. Although our understanding of asynchronies has increased in recent years, many questions remain to be answered. Evolving concepts in asynchronies, lung crosstalk with other organs, and the difficulties of data management make more efforts necessary in this field

Development and validation of a sample entropy-based method to identify complex patient-ventilator interactions during mechanical ventilation

Patient-ventilator asynchronies can be detected by close monitoring of ventilator screens by clinicians or through automated algorithms. However, detecting complex patient-ventilator interactions (CP-VI), consisting of changes in the respiratory rate and/or clusters of asynchronies, is a challenge. Sample Entropy (SE) of airway flow (SE-Flow) and airway pressure (SE-Paw) waveforms obtained from 27 critically ill patients was used to develop and validate an automated algorithm for detecting CP-VI. The algorithm’s performance was compared versus the gold standard (the ventilator’s waveform recordings for CP-VI were scored visually by three experts; Fleiss’ kappa = 0.90 (0.87–0.93)). A repeated holdout cross-validation procedure using the Matthews correlation coefficient (MCC) as a measure of effectiveness was used for optimization of different combinations of SE settings (embedding dimension, m, and tolerance value, r), derived SE features (mean and maximum values), and the thresholds of change (Th) from patient’s own baseline SE value. The most accurate results were obtained using the maximum values of SE-Flow (m = 2, r = 0.2, Th = 25%) and SE-Paw (m = 4, r = 0.2, Th = 30%) which report MCCs of 0.85 (0.78–0.86) and 0.78 (0.78–0.85), and accuracies of 0.93 (0.89–0.93) and 0.89 (0.89–0.93), respectively. This approach promises an improvement in the accurate detection of CP-VI, and future study of their clinical implications.This work was funded by projects PI16/01606, integrated in the Plan Nacional de R+D+I and co-funded by the ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). RTC-2017-6193-1 (AEI/FEDER UE). CIBER Enfermedades Respiratorias, and Fundació Parc Taulí