EXPLORING THE ROLE OF CENTRAL VENOUS OXYGEN SATURATION IN THE EVALUATION AND MANAGEMENT OF SEVERE HYPOXEMIA IN MECHANICALLY VENTILATED PATIENTS.

ABSTRACT: Background: Although central venous oxygen saturation (ScvO 2 ) has been used as an endpoint for the treatment of circulatory shock, its role in guiding the evaluation and treatment of patients with severe hypoxemia remains to be assessed. The aim of this study was to assess the incidence of low ScvO 2 in a cohort of hypoxemic patients and the association of this finding with differences in clinical management and patient outcomes. Methods: Retrospective review of data from adult intensive care unit patients with hypoxemia who required invasive mechanical ventilation for over 24 h and had at least one ScvO 2 measured within 6 h of a PaO 2 /FiO 2 ratio <200. Results: Of 442 mechanically ventilated patients with severe hypoxemia, 249 (56%) had an ScvO 2 <70%. When compared with patients with ScvO 2 ≥70%, those with low ScvO 2 had worse systemic oxygenation and hemodynamic parameters and were more likely to receive red blood cell transfusions (31.7% vs. 18.1%, P = 0.001), epinephrine (27.3% vs. 16.6%, P = 0.007), and inodilators. Outcomes such as median intensive care unit length of stay (7.5 vs. 8.3 days, P = 0.337) and hospital mortality (39.8% vs. 35.7%, P = 0.389) were not different between groups. When stratified by the central venous-to-arterial CO 2 difference (∆PCO 2 ), patients with a low ScvO 2 and normal ∆PCO 2 had lower median PaO 2 and hemoglobin levels and received more red blood cell transfusions, whereas those with an increased ∆PCO 2 had a lower pulse pressure and cardiac index and were more likely to receive epinephrine and milrinone. Conclusion: Low ScvO 2 is frequently observed in mechanically ventilated patients with severe hypoxemia, and these patients receive different interventions. Clinicians often use therapies targeting systemic oxygen delivery to correct low ScvO 2 . Prospective research is needed to identify patients with severe hypoxemia that might benefit from interventions targeting systemic oxygen delivery.

A 64-year-Old patient assigned male at birth with COPD and worsening dyspnea while on estrogen and antiandrogen agents.

Among patients with COPD, ventilatory inefficiency in response to exercise can be due to respiratory muscle dysfunction or expiratory flow limitation causing air-trapping and dynamic hyperinflation. We discuss a case of severe ventilatory limitation in response to exercise due to reduced respiratory muscle mass in the setting of gender-affirming hormone therapy (GAHT), and how the interpretation of pulmonary function testing (PFT) and respiratory symptoms among transgender and gender diverse (TGD) patients can be influenced by GAHT.

[Latin American research in heart failure: visual and bibliometric analysis of the last 20 years]. / Investigación latinoamericana en falla cardiaca: análisis visual y bibliométrico de los últimos 20 años.

Objective: To visually and bibliometrically analyze Latin American research on heart failure in the last 20 years. Materials and methods: A bibliometric study using the Scopus database. A non-systematic search was carried out to collect data, which were analyzed using Bibliometrix, a tool of the R programming language. Results: A total of 10204 documents were included in a period between 2003 to 2023. Of these, 66.9% (n=6824) corresponded to original articles, followed by review articles (15.5%; n=1583). International collaboration was present in 38.41% (n=3919) of the articles. Brazil stood out with the highest number of prolific authors and institutions (70% and 60%, respectively), consolidating its position as leader in the region, followed by Argentina and Mexico. These countries also presented the papers with the highest impact and most outstanding metrics. Conclusions: This study identified a significant increase in heart failure research in Latin America over the last two decades, with Brazil, Argentina, and Mexico being the main drivers of this trend. Extensive and strong collaboration, mainly with high-income countries, appears to be critical to the momentum and the advancement of research in this area. Data systematization and resynchronization therapy are some of the topics of greatest interest at present.

Hypertension in Prenatally Undernourished Young-Adult Rats Is Maintained by Tonic Reciprocal Paraventricular-Coerulear Excitatory Interactions.

Prenatally malnourished rats develop hypertension in adulthood, in part through increased α1-adrenoceptor-mediated outflow from the paraventricular nucleus (PVN) to the sympathetic system. We studied whether both α1-adrenoceptor-mediated noradrenergic excitatory pathways from the locus coeruleus (LC) to the PVN and their reciprocal excitatory CRFergic connections contribute to prenatal undernutrition-induced hypertension. For that purpose, we microinjected either α1-adrenoceptor or CRH receptor agonists and/or antagonists in the PVN or the LC, respectively. We also determined the α1-adrenoceptor density in whole hypothalamus and the expression levels of α1A-adrenoceptor mRNA in the PVN. The results showed that: (i) agonists microinjection increased systolic blood pressure and heart rate in normotensive eutrophic rats, but not in prenatally malnourished subjects; (ii) antagonists microinjection reduced hypertension and tachycardia in undernourished rats, but not in eutrophic controls; (iii) in undernourished animals, antagonist administration to one nuclei allowed the agonists recover full efficacy in the complementary nucleus, inducing hypertension and tachycardia; (iv) early undernutrition did not modify the number of α1-adrenoceptor binding sites in hypothalamus, but reduced the number of cells expressing α1A-adrenoceptor mRNA in the PVN. These results support the hypothesis that systolic pressure and heart rate are increased by tonic reciprocal paraventricular-coerulear excitatory interactions in prenatally undernourished young-adult rats.

Etiology, incidence, and outcomes of patient-ventilator asynchrony in critically-ill patients undergoing invasive mechanical ventilation.

Patient-ventilator asynchrony (PVA) is commonly encountered during mechanical ventilation of critically ill patients. Estimates of PVA incidence vary widely. Type, risk factors, and consequences of PVA remain unclear. We aimed to measure the incidence and identify types of PVA, characterize risk factors for development, and explore the relationship between PVA and outcome among critically ill, mechanically ventilated adult patients admitted to medical, surgical, and medical-surgical intensive care units in a large academic institution staffed with varying provider training background. A single center, retrospective cohort study of all adult critically ill patients undergoing invasive mechanical ventilation for ≥ 12 h. A total of 676 patients who underwent 696 episodes of mechanical ventilation were included. Overall PVA occurred in 170 (24%) episodes. Double triggering 92(13%) was most common, followed by flow starvation 73(10%). A history of smoking, and pneumonia, sepsis, or ARDS were risk factors for overall PVA and double triggering (all P < 0.05). Compared with volume targeted ventilation, pressure targeted ventilation decreased the occurrence of events (all P < 0.01). During volume controlled synchronized intermittent mandatory ventilation and pressure targeted ventilation, ventilator settings were associated with the incidence of overall PVA. The number of overall PVA, as well as double triggering and flow starvation specifically, were associated with worse outcomes and fewer hospital-free days (all P < 0.01). Double triggering and flow starvation are the most common PVA among critically ill, mechanically ventilated patients. Overall incidence as well as double triggering and flow starvation PVA specifically, portend worse outcome.

Updated guidance on the management of COVID-19: from an American Thoracic Society/European Respiratory Society coordinated International Task Force (29 July 2020).

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. METHODS: An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. RESULTS: The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. CONCLUSIONS: The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities.

Early postnatal environmental enrichment restores neurochemical and functional plasticities of the cerebral cortex and improves learning performance in hidden-prenatally-malnourished young-adult rats.

Moderate reduction of dietary protein (from 25% to 8% casein) in pregnant rats, calorically compensated by carbohydrates, gives rise to 'hidden prenatal malnutrition' (HPM) in the offspring since it does not alter body and brain weights of pups at birth. However, this dietary treatment leads to decreased ß-adrenoceptor signaling and brain derived neurotrophic factor (BDNF) levels in the pup' brain, altogether with defective cortical long-term potentiation (LTP) and lowered visuospatial memory performance. Since early postnatal environmental enrichment (EE) has been shown to exert plastic effects on the developing brain and neuroprotection both on cognition and on structural properties of the neocortex, in the present study we addressed the question of whether early postnatal EE during the lactation period could exert compensatory changes in the expression of ®-adrenergic receptors and BDNF in the neocortex of HPM rats, and if these effects are associated with an improvement or even a restore of both neocortical LTP in vivo and cognitive performance induced by HPM. The results obtained show that EE restored ß-adrenoceptor density, BDNF expression and the ability to support LTP at prefrontal and occipital cortices of HPM rats. Besides, EE improved learning performance in visuospatial and operant conditioning tasks. The latter support the notion that adequate maternal protein nutrition during pregnancy is required for proper brain development and function. Further, the results highlight the role of environmental enrichment during early postnatal life in increasing later brain plasticity and exerting neuroprotection against brain deficits induced by prenatal malnutrition.

Hypercapnia Alters Alveolar Epithelial Repair by a pH-Dependent and Adenylate Cyclase-Mediated Mechanism.

Lung cell injury and repair is a hallmark of the acute respiratory distress syndrome (ARDS). Lung protective mechanical ventilation strategies in these patients may lead to hypercapnia (HC). Although HC has been explored in the clinical context of ARDS, its effect upon alveolar epithelial cell (AEC) wounding and repair remains poorly understood. We have previously reported that HC alters the likelihood of AEC repair by a pH-sensitive but otherwise unknown mechanism. Adenylate cyclase (AC) is an attractive candidate as a putative AEC CO2 sensor and effector as it is bicarbonate sensitive and controls key mediators of AEC repair. The effect of HC on AC activity and plasma membrane (PM) wound repair was measured in AEC type 1 exposed to normocapnia (NC, 40 Torr) or HC (80 Torr), ± tromethamine (THAM) or sodium bicarbonate (HCO3) ± AC probes in a micropuncture model of AEC injury relevant to ARDS. Intracellular pH and AC activity were measured and correlated with repair. HC decreased intracellular pH 0.56, cAMP by 37%, and absolute PM repair rate by 26%. Buffering or pharmacologic manipulation of AC reduced or reversed the effects of HC on AC activity (THAM 103%, HCO3 113% of NC cAMP, ns; Forskolin 168%, p < 0.05) and PM repair (THAM 87%, HCO3 108% of NC likelihood to repair, ns; Forskolin 160%, p < 0.01). These findings suggest AC to be a putative AEC CO2 sensor and modulator of AEC repair, and may have implications for future pharmacologic targeting of downstream messengers of the AC-cAMP axis in experimental models of ARDS.

Physiology-guided management of hemodynamics in acute respiratory distress syndrome.

Skillfully implemented mechanical ventilation (MV) may prove of immense benefit in restoring physiologic homeostasis. However, since hemodynamic instability is a primary factor influencing mortality in acute respiratory distress syndrome (ARDS), clinicians should be vigilant regarding the potentially deleterious effects of MV on right ventricular (RV) function and pulmonary vascular mechanics (PVM). During both spontaneous and positive pressure MV (PPMV), tidal changes in pleural pressure (PPL), transpulmonary pressure (PTP, the difference between alveolar pressure and PPL), and lung volume influence key components of hemodynamics: preload, afterload, heart rate, and myocardial contractility. Acute cor pulmonale (ACP), which occurs in 20-25% of ARDS cases, emerges from negative effects of lung pathology and inappropriate changes in PPL and PTP on the pulmonary microcirculation during PPMV. Functional, minimally invasive hemodynamic monitoring for tracking cardiac performance and output adequacy is integral to effective care. In this review we describe a physiology-based approach to the management of hemodynamics in the setting of ARDS: avoiding excessive cardiac demand, regulating fluid balance, optimizing heart rate, and keeping focus on the pulmonary circuit as cornerstones of effective hemodynamic management for patients in all forms of respiratory failure.

Positional effects on the distributions of ventilation and end-expiratory gas volume in the asymmetric chest-a quantitative lung computed tomographic analysis.

BACKGROUND: Body positioning affects the configuration and dynamic properties of the chest wall and therefore may influence decisions made to increase or decrease ventilating pressures and tidal volume. We hypothesized that unlike global functional residual capacity (FRC), component sector gas volumes and their corresponding regional tidal expansions would vary markedly in the setting of unilateral pleural effusion (PLEF), owing to shifting distributions of aeration and collapse as posture changed. METHODS: Six deeply anesthetized swine underwent tracheostomy, thoracostomy, and experimental PLEF with 10 mL/kg of radiopaque isotonic fluid randomly instilled into either pleural space. Animals were ventilated at VT = 10 mL/kg, frequency = 15 bpm, I/E = 1:2, PEEP = 1 cmH2O, and FiO2 = 0.5. Quantitative lung computed tomographic (CT) analysis of regional aeration and global FRC measurements by nitrogen wash-in/wash-out technique was performed in each of these randomly applied positions: semi-Fowler's (inclined 30° from horizontal in the sagittal plane); prone, supine, and lateral positions with dependent PLEF and non-dependent PLEF. RESULTS: No significant differences in total FRC were observed among the horizontal positions, either at baseline (p = 0.9037) or with PLEF (p = 0.58). However, component sector total gas volumes in each phase of the tidal cycle were different within all studied positions with and without PLEF (p = < .01). Compared to other positions, prone and lateral positions with non-dependent PLEF had more homogenous VT distributions among quadrants (p = .051). Supine position was associated with most dependent collapse and greatest tendency for tidal recruitment (48 vs ~ 22%, p = 0.0073). CONCLUSIONS: Changes in body position in the setting of effusion-caused chest asymmetry markedly affected the internal distributions of gas volume, collapse, ventilation, and tidal recruitment, even though global FRC measurements provided little indication of these potentially important positional changes.

PEEP titration: the effect of prone position and abdominal pressure in an ARDS model.

BACKGROUND: Prone position and PEEP can both improve oxygenation and other parameters, but their interaction has not been fully described. Limited data directly compare selection of mechanically "optimal" or "best" PEEP in both supine and prone positions, either with or without changes in chest wall compliance. To compare best PEEP in these varied conditions, we used an experimental ARDS model to compare the mechanical, gas exchange, and hemodynamic response to PEEP titration in supine and prone position with varied abdominal pressure. METHODS: Twelve adult swine underwent pulmonary saline lavage and injurious ventilation to simulate ARDS. We used a reversible model of intra-abdominal hypertension to alter chest wall compliance. Response to PEEP levels of 20,17,14,11, 8, and 5 cmH2O was evaluated under four conditions: supine, high abdominal pressure; prone, high abdominal pressure; supine, low abdominal pressure; and prone, low abdominal pressure. Using lung compliance determined with esophageal pressure, we recorded the "best PEEP" and its corresponding target value. Data were evaluated for relationships among abdominal pressure, PEEP, and position using three-way analysis of variance and a linear mixed model with Tukey adjustment. RESULTS: Prone position and PEEP independently improved lung compliance (P < .0001). There was no interaction. As expected, intra-abdominal hypertension increased the PEEP needed for the best lung compliance (P < .0001 supine, P = .007 prone). However, best PEEP was not significantly different between prone (12.8 ± 2.4 cmH2O) and supine (11.0 ± 4.2 cmH2O) positions when targeting lung compliance CONCLUSIONS: Despite complementary mechanisms, prone position and appropriate PEEP exert their positive effects on lung mechanics independently of each other.

Acute Exacerbation of Interstitial Lung Disease After Cryobiopsy.

Cryotherapy has been used in treatment of lung cancer for decades. The utility of cryotechnology in diagnosis of lung diseases is emerging and gaining popularity. Cryobiopsy (CB) of the lung, when compared with conventional transbronchial forceps lung biopsy, has proposed to have a higher diagnostic yield in interstitial lung disease by providing larger biopsy specimen and less crush artifact. Acute exacerbation of interstitial lung disease (AEILD) has been well described with surgical lung biopsies and, rarely, with conventional transbronchial forceps biopsy. The incidence of AEILD after CB is not known. Here we are presenting a case of AEILD after CB.

The Effect of Compartmental Asymmetry on the Monitoring of Pulmonary Mechanics and Lung Volumes.

BACKGROUND: Esophageal pressure measurement for computation of transpulmonary pressure (Ptp) has begun to be incorporated into clinical use for evaluating forces across the lungs. Gaps exist in our understanding of how esophageal pressure (and therefore Ptp), a value measured at a single site, responds when respiratory system compartments are asymmetrically affected by whole-lung atelectasis or unilateral injury as well as changes in chest wall compliance. We reasoned that Ptp would track with aerated volume changes as estimated by functional residual capacity (FRC) and tidal volume. We examined this hypothesis in the setting of asymmetric lungs and changes in intra-abdominal pressure. METHODS: This study was conducted in the animal laboratory of a university-affiliated hospital. Models of unilateral atelectasis and unilateral and bilateral lung injury exposed to intra-abdominal hypertension (IAH) in 10 deeply sedated mechanically ventilated swine. Atelectasis was created by balloon occlusion of the left main bronchus. Unilateral lung injury was induced by saline lavage of isolated right lung. Diffuse lung injury was induced by saline lavage of both lungs. The peritoneum was insufflated with air to create a model of pressure-regulated IAH. We measured esophageal pressures, airway pressures, FRC by gas dilution, and oxygenation. RESULTS: FRC was reduced by IAH in normal lungs (P < .001) and both asymmetric lung pathologies (P < .001). Ptp at end-expiration was decreased by IAH in bilateral (P = .001) and unilateral lung injury (P = .003) as well as unilateral atelectasis (P = .019). In the setting of both lung injury models, end-expiratory Ptp showed a moderate correlation in tracking with FRC. CONCLUSIONS: Ptp tracks with aerated lung volume in the setting of thoracic asymmetry and changes in intra-abdominal pressure. However, used alone, it cannot distinguish the relative contributions of air-space distention and recruitment of lung units.

Impact of Chest Wall Modifications and Lung Injury on the Correspondence Between Airway and Transpulmonary Driving Pressures.

OBJECTIVE: Recent interest has arisen in airway driving pressure (DP(AW)), the quotient of tidal volume (V(T)), and respiratory system compliance (C(RS)), which could serve as a direct and easily measured marker for ventilator-induced lung injury risk. We aimed to test the correspondence between DP(AW) and transpulmonary driving pressure (DP(TP))-the quotient of V(T) and lung compliance (C(L)), in response to intra-abdominal hypertension and changes in positive end-expiratory pressure during different models of lung pathology. DESIGN: Well-controlled experimental setting that allowed reversible modification of chest wall compliance (C(CW)) in a variety of models of lung pathology. SETTING: Large animal laboratory of a university-affiliated hospital. SUBJECTS: Ten deeply anesthetized swine. INTERVENTIONS: Application of intra-abdominal pressures of 0 and 20 cm H2O at positive end-expiratory pressure of 1 and 10 cm H2O, under volume-controlled mechanical ventilation in the settings of normal lungs (baseline), unilateral whole-lung atelectasis, and unilateral and bilateral lung injuries caused by saline lavage. MEASUREMENTS AND MAIN RESULTS: Pulmonary mechanics including esophageal pressure and calculations of DP(AW), DP(TP), C(RS), C(L), and C(CW). When compared with normal intra-abdominal pressures, intra-abdominal hypertension increased DP(AW), during both "normal lung conditions" (p < 0.0001) and "unilateral atelectasis" (p = 0.0026). In contrast, DP(TP) remained virtually unaffected by changes in positive end-expiratory pressure or intra-abdominal pressures in both conditions. During unilateral lung injury, both DPA(W) and DP(TP) were increased by the presence of intra-abdominal hypertension (p < 0.0001 and p = 0.0222, respectively). During bilateral lung injury, intra-abdominal hypertension increased both DP(AW) (at positive end-expiratory pressure of 1 cm H2O, p < 0.0001; and at positive end-expiratory pressure of 10 cm H2O, p = 0.0091) and DP(TP) (at positive end-expiratory pressure of 1 cm H2O, p = 0.0510; and at positive end-expiratory pressure of 10 cm H2O, p = 0.0335). CONCLUSIONS: Our data indicate that DP(AW) is influenced by reductions in chest wall compliance and by underlying lung properties. As with other measures of pulmonary mechanics that are based on unmodified P(AW), caution is advised in attempting to attribute hazard or safety to any specific absolute value of DP(AW).

Unilateral mechanical asymmetry: positional effects on lung volumes and transpulmonary pressure.

BACKGROUND: Ventilated patients with asymmetry of lung or chest wall mechanics may be vulnerable to differing lung stresses or strains dependent on body position. Our purpose was to examine transpulmonary pressure (P TP) and end-expiratory lung volume (functional residual capacity (FRC)) during body positioning changes in an animal model under the influence of positive end-expiratory pressure (PEEP) or experimental pleural effusion (PLEF). METHODS: Fourteen deeply anesthetized swine were studied including tracheostomy, thoracostomy, and esophageal catheter placement. Animals were ventilated at V T = 10 ml/kg, frequency of 15, I/E = 1:2, and FIO2 = 0.5. The animals were randomized to supine, prone, right lateral, left lateral, and semi-Fowler positions with a PEEP of 1 cm H2O (PEEP1) or a PEEP of 10 cm H2O (PEEP10) applied. Experimental PLEF was generated by 10 ml/kg saline instilled into either pleural space. P TP and FRC were determined in each condition. RESULTS: No significant differences in FRC were found among the four horizontal positions. Compared to horizontal positioning, semi-Fowler's increased FRC (p < 0.001) by 56% at PEEP1 and 54% at PEEP10 without PLEF and by 131% at PEEP1 and 98% at PEEP10 with PLEF. Inspiratory or expiratory P TP showed insignificant differences across positions at both levels of PEEP. Consistently negative end-expiratory P TP at PEEP1 increased to positive values with PEEP10. CONCLUSIONS: FRC did not differ among horizontal positions; however, semi-Fowler's positioning significantly raised FRC. P TP proved insensitive to mechanical asymmetry. While end-expiratory P TP was negative at PEEP1, applying PEEP10 caused a transition to positive P TP, suggestive of reopening of initially compressed lung units.