Objective: Mechanical ventilation (MV) itself can directly contribute to lung injury. Therefore, the aim of the present study was to investigate early biomarkers concerning oxidant/antioxidant balance, oxidative stress, and inflammation caused by short-term MV in healthy mouse lungs. Methods: Twenty male C57BL/6 mice were randomly divided into two groups: MV, submitted to low tidal volume (VT, 6 mL/kg) MV for 30 min; and spontaneous respiration (SR), used as controls. Lung homogenate samples were tested regarding the activity of various antioxidant enzymes, lipid peroxidation, and TNF-α expression. Results: In comparison with the SR group, the MV group showed a significant decrease in the activity of superoxide dismutase (≈35%; p < 0.05), together with an increase in the activity of catalase (40%; p < 0.01), glutathione peroxidase (500%; p < 0.001), and myeloperoxidase (260%; p < 0.001), as well as a reduction in the glutathione/oxidized glutathione ratio (≈50%; p < 0.05) and an increase in TNF-α expression in the MV group. Oxidative damage, assessed by lipid peroxidation, was also greater in the MV group (45%; p < 0.05). Conclusions: Our results show that short-term low VT MV can directly contribute to lung injury, generating oxidative stress and inflammation in healthy mouse lungs.

Keywords: Lesão pulmonar induzida por ventilação mecânica; Respiração artificial; Estresse oxidativo; Inflamação; Camundongos.

Objective: To evaluate the effects that early and late systemic administration of methylprednisolone have on lungs in a rat model of brain death. Methods: Twenty-four male Wistar rats were anesthetized and randomly divided into four groups (n = 6 per group): sham-operated (sham); brain death only (BD); brain death plus methylprednisolone (30 mg/kg i.v.) after 5 min (MP5); and brain death plus methylprednisolone (30 mg/kg i.v.) after 60 min (MP60). In the BD, MP5, and MP60 group rats, we induced brain death by inflating a balloon catheter in the extradural space. All of the animals were observed and ventilated for 120 min. We determined hemodynamic and arterial blood gas variables; wet/dry weight ratio; histological score; levels of thiobarbituric acid reactive substances (TBARS); superoxide dismutase (SOD) activity; and catalase activity. In BAL fluid, we determined differential white cell counts, total protein, and lactate dehydrogenase levels. Myeloperoxidase activity, lipid peroxidation, and TNF-α levels were assessed in lung tissue. Results: No significant differences were found among the groups in terms of hemodynamics, arterial blood gases, wet/dry weight ratio, BAL fluid analysis, or histological score-nor in terms of SOD, myeloperoxidase, and catalase activity. The levels of TBARS were significantly higher in the MP5 and MP60 groups than in the sham and BD groups (p < 0.001). The levels of TNF-α were significantly lower in the MP5 and MP60 groups than in the BD group (p < 0.001). Conclusions:áIn this model of brain death, the early and late administration of methylprednisolone had similar effects on inflammatory activity and lipid peroxidation in lung tissue.

Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO) and total reactive antioxidant potential (TRAP), in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.); acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days); and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels.

Keywords: Lung; Methylprednisolone; Glucocorticoids; Lipid peroxidation; Antioxidant response elements.

Diabetes mellitus is an endocrine/metabolic disorder characterized by hyperglycemia. Its impact on the respiratory system is characterized by functional changes and alterations in gas exchange. The objective of this study was to evaluate the increase in oxidative stress and the potential damages to the lung structure in an experimental model of streptozotocin-induced diabetes. We conducted histological, biochemical and blood gas analyses in the lungs of diabetic rats. We concluded that the effects of experimental diabetes mellitus include oxidative stress, structural changes in the lung tissue and altered gas exchange.

Keywords: Lung; Diabetes mellitus; Oxidative stress; Diabetes mellitus, experimental; Free radicals.

Objective: To assess possible alterations in the tidal volume and peak inspiratory pressure delivered by seven models of manually operated self-inflating resuscitation bags as a function of the oxygen supply rate used. Methods: The resuscitation bags tested were the following: Oxigel, models A and B; CE Reanimadores; ProtecSolutions; Missouri; Axmed; and Narcosul. For the measurements, a wall oxygen flow meter, a flow meter/respirometer, a resuscitation bag, a sensor (Tracer 5 unit), and a test lung were connected. In addition, the Tracer 5 unit was connected to a notebook computer. Oxygen supply rates of 1, 5, 10, and 15 L/min were used. Results: The tidal volume delivered by the Oxigel model A resuscitation bag when receiving oxygen at a rate of 15 L/min was approximately 99% greater than that delivered when receiving oxygen at a rate of 1 L/min. Similarly, peak inspiratory pressure was approximately 155% greater. Under the same conditions, the tidal volume delivered by the Narcosul resuscitation bag was 48% greater, and peak inspiratory pressure was 105% greater. The remaining resuscitation bags tested showed no significant alterations in the tidal volume or peak inspiratory pressure delivered. Conclusions: Under the resistance and compliance conditions used, the resuscitation bags in which the oxygen inflow is directed to the interior of the bag had the patient valve stuck at the inspiratory position when receiving oxygen at a rate ≥ 5 L/min, significantly increasing the tidal volume and peak inspiratory pressure delivered. This did not occur with the resuscitation bags in which the oxygen inflow is directed to the exterior of the bag.

Keywords: Oxygen/administration & dosage; Resuscitation; Equipment and supplies; Pulmonary ventilation; Intensive care.

Patients with obstructive lung disease often require ventilatory support via invasive or noninvasive mechanical ventilation, depending on the severity of the exacerbation. The use of inhaled bronchodilators can significantly reduce airway resistance, contributing to the improvement of respiratory mechanics and patient-ventilator synchrony. Although various studies have been published on this topic, little is known about the effectiveness of the bronchodilators routinely prescribed for patients on mechanical ventilation or about the deposition of those drugs throughout the lungs. The inhaled bronchodilators most commonly used in ICUs are beta adrenergic agonists and anticholinergics. Various factors might influence the effect of bronchodilators, including ventilation mode, position of the spacer in the circuit, tube size, formulation, drug dose, severity of the disease, and patient-ventilator synchrony. Knowledge of the pharmacological properties of bronchodilators and the appropriate techniques for their administration is fundamental to optimizing the treatment of these patients.

Keywords: Bronchial hyperreactivity; Drug delivery systems; Respiration, artificial.

Worldwide, COPD is a major cause of morbidity and mortality. The clinical and functional manifestations of COPD result from lung injury occurring through various mechanisms, including oxidative stress, inflammation, protease-antiprotease imbalance and apoptosis. Oxidative stress is central to the pathogenesis of COPD, since it can directly damage lung structures and exacerbate the other mechanisms involved. The cellular and molecular events involved in such lung injury are believed to occur long before the clinical and functional expression of COPD. Although the use of bronchodilators is currently the principal treatment for COPD, bronchodilators have little or no effect on disease progression. A better understanding of the pathogenesis of COPD, together with renewed efforts in basic and clinical research, will allow the diagnosis of COPD at a pre-clinical stage and provide more appropriate monitoring of disease activity, as well as leading to the development of novel therapeutic agents that will effectively prevent the progression of the disease.

Keywords: Pulmonary disease, chronic obstructive; Oxidative stress; Oxidants; Antioxidants; Inflammation.

We evaluated the effect of aminoguanidine on pulmonary oxidative stress and lung structure in an experimental model of diabetes mellitus. Thiobarbituric acid reactive substances (TBARS), histology and arterial blood gases were evaluated in animals with diabetes mellitus (DM group), animals with diabetes mellitus treated with aminoguanidine (DM+AG group), and controls. The TBARS levels were significantly higher in the DM group than in the control and DM+AG groups (2.90 ± 1.12 vs. 1.62 ± 0.28 and 1.68 ± 0.04 nmol/mg protein, respectively), as was PaCO2 when compared with that of the control group (49.2 ± 1.65 vs. 38.12 ± 4.85 mmHg), and PaO2 was significantly higher in the control group (104.5 ± 6.3 vs. 16.30 ± 69.48 and 97.05±14.02 mmHg, respectively). In this experimental model of diabetes mellitus, aminoguanidine reduced oxidative stress, structural tissue alterations, and gas exchange.

Keywords: Oxidative stress; Diabetes mellitus, experimental; Lung.

Objective: To use an experimental model to evaluate the effect of heart failure on oxidative stress in the rat diaphragm. Methods: The model of myocardial infarction was developed through left coronary artery ligation. On day 42 after coronary artery ligation, the animals were killed, after which the diaphragms were collected and homogenized. Oxidative stress was evaluated in diaphragm homogenates through measurement of lipid peroxidation and assays of the activity of antioxidant enzymes, including catalase and glutathione peroxidase (enzymes that reduce hydrogen peroxide to water), as well as superoxide dismutase (an antioxidant enzyme that reduces superoxide anions to hydrogen peroxide). Results: The coronary artery ligation model was found to be effective in causing heart failure. In the animals submitted to coronary artery ligation, the mean infarcted area of the left ventricle was 39%. Lipid peroxidation was 217% greater in the diaphragms of ligated animals than in those of controls. The activity of catalase and glutathione peroxidase was 77% and 20% lower, respectively, in study rats than in control rats. Infarction did not modify superoxide dismutase activity. Conclusion: The results suggest that left coronary artery ligation results in oxidative stress in the diaphragm.

Keywords: Myocardial infarction; Oxidative stress; Congestive heart failure; Antioxidants; Diaphragm; Rats

Objective: The aim of this study was to describe practices for weaning from mechanical ventilation (MV), in terms of the use of protocols, methods, and criteria, in pediatric ICUs (PICUs), neonatal ICUs (NICUs), and mixed neonatal/pediatric ICUs (NPICUs) in Brazil. Methods: This was a cross-sectional survey carried out by sending an electronic questionnaire to a total of 298 NICUs, PICUs, and NPICUs throughout Brazil. Results: Completed questionnaires were assessed for 146 hospitals, NICUs accounting for 49.3% of the questionnaires received, whereas PICUs and NPICUs accounted for 35.6% and 15.1%, respectively. Weaning protocols were applied in 57.5% of the units. In the NICUs and NPICUs that used weaning protocols, the method of MV weaning most commonly employed (in 60.5% and 50.0%, respectively) was standardized gradual withdrawal from ventilatory support, whereas that employed in most (53.0%) of the PICUs was spontaneous breathing trial (SBT). During the SBTs, the most common ventilation mode, in all ICUs, was pressure-support ventilation (10.03 ± 3.15 cmH2O) with positive end-expiratory pressure. The mean SBT duration was 35.76 ± 29.03 min in the NICUs, compared with 76.42 ± 41.09 min in the PICUs. The SBT parameters, weaning ventilation modes, and time frame considered for extubation failure were not found to be dependent on the age profile of the ICU population. The findings of the clinical evaluation and arterial blood gas analysis are frequently used as criteria to assess readiness for extubation, regardless of the age group served by the ICU. Conclusions: In Brazil, the clinical practices for weaning from MV and extubation appear to vary depending on the age group served by the ICU. It seems that weaning protocols and SBTs are used mainly in PICUs, whereas gradual withdrawal from ventilatory support is more widely used in NICUs and NPICUs.

Keywords: Ventilator weaning/methods; Respiration, artificial; Airway extubation/methods; Intensive care units, pediatric/standards; Intensive care units, neonatal/standards.

Background: Open lung biopsy is regarded as the gold standard for the diagnosis of diffuse pulmonary infiltrates. Objective: To determine the diagnostic yield, therapeutic changes, complications and mortality attributed to open lung biopsy in patients with diffuse pulmonary infiltrates and on mechanical ventilation. Method: We reviewed, retrospectively, the charts of 24 patients, ranging from 26 to 89 years of age, admitted to the intensive care units of two private hospitals and submitted to open lung biopsy. Results: Diagnostic positivity was found in 100% of patients, resulting in an alteration in the treatment regimen in 75%. Postoperative complications occurred in five patients (20.8%). There were no biopsy-related deaths, although global mortality was 45.8%. Conclusion: Open lung biopsy is a safe and high yield procedure for diagnosing diffuse pulmonary infiltrate in patients on mechanical ventilation. Despite the fact that no mortality impact factor has been assigned to such patients, data in the literature regarding prognosis must be taken into consideration.

Keywords: Biopsy. Respiratory insufficiency. Respiration artificial.

Objective: To develop and apply a competency-based test to assess learning among internal medicine residents during a respiratory ICU rotation at a university hospital. Methods: We developed a test comprising 19 multiple-choice questions regarding knowledge of mechanical ventilation (MV) and 4 self-assessment questions regarding the degree of confidence in the management of MV. The test was applied on the first and last day of a 30-day respiratory ICU rotation (pre-rotation and post-rotation, respectively). During the rotation, the residents had lectures, underwent simulator training, and shadowed physicians on daily bedside rounds focused on teaching MV management. Results: Fifty residents completed the test at both time points. The mean score increased from 6.9 ± 1.2 (pre-rotation) to 8.6 ± 0.8 (post-rotation; p < 0.001). On questions regarding the approach to hypoxemia, the recognition of patient-ventilator asynchrony, and the recognition of risk factors for extubation failure, the post-rotation scores were significantly higher than the pre-rotation scores. Confidence in airway management increased from 6% before the rotation to 22% after the rotation (p = 0.02), whereas confidence in making the initial MV settings increased from 31% to 96% (p < 0.001) and confidence in adjusting the ventilator modes increased from 23% to 77% (p < 0.001). Conclusions: We developed a competency-based test to assess knowledge of MV among residents before and after an rotation in a respiratory ICU. Resident performance increased significantly after the rotation, as did their confidence in caring for patients on MV.

Keywords: Education, medical; Respiration, artificial; Surveys and questionnaires; internship and residency; Competency-based education; Educational measurement.

Background: It is questionable whether pressure-controlled ventilation (PCV) has advantages over volume-cycled ventilation (VCV). Objectives: To compare PCV to VCV with decelerating flow profile during assisted and controlled modes in an acute lung injury experimental model. Methods: Severe acute lung injury (PaO2/FIO2 < 100 mmHg) was induced by oleic acid IV infusion (0.05 mg/kg) in seven dogs. The animals were submitted to PCV and VCV in a randomized sequence. After 40 minutes in the assisted mode, ventilation was changed to the controlled mode after neuromuscular blockade. The tidal volume and the inspiratory time were kept constant throughout the experiment. Results: There were no differences in gas exchange (PaO2 and PaCO2), cardiac output or oxygen delivery (DO2) between VCV and PCV. The same was observed regarding maximum airway and plateau pressures, and also to the static compliance. Oxygen consumption (VO2) after neuromuscular blockade was 124 ± 48 in VCV versus 143 ± 50 ml/min in PCV, p = 0.42. In the assisted mode, there was a statistical trend of a higher VO2 in PCV (219 ± 72 versus 154 ± 67 ml/min in VCV, p = 0.06), that was associated with a statistical trend of a higher oxygen cost of breathing (OCB) during assisted PCV, although without statistical significance (31 ± 77 in VCV versus 75 ± 96 ml/min in PCV, p = 0.23), and also in a lower PvO2 (34 ± 7 in PCV versus 42 ± 6 ml/min in VCV, p = 0.02). These occurred despite a higher maximum inspiratory flow in the assisted mode in PCV (58 ± 9 versus 48 ± 4 L/min in VCV, p = 0.01). In both VCV and PCV the institution of controlled ventilation reduced cardiac debit and DO2 in as much as 20% relative to the assisted mode. Conclusions: The implementation of controlled ventilation improved the oxygen delivery/consumption relationship in this severe and with high OCB acute lung injury model. The PCV offered no additional benefits to VCV and it was associated with a higher OCB during the assisted mode.

Keywords: Artificial respiration. Pulmonary gas exchange. Tidal volume.

Objective: To compare pre-extubation physiological characteristics and ultrasound variables between patients intubated for COVID-19 compared to a clinical population and those intubated for other reasons. Methods: This was a secondary analysis of a prospective cohort study of patients undergoing invasive mechanical ventilation (IMV) for more than 48 h. Patients were divided into two groups: those intubated for COVID-19-induced ARDS and those intubated for other clinical reasons. Ultrasound assessment of lung and diaphragm function was performed before extubation. The results were compared between the two groups of patients. Results: In comparison with the patients without COVID-19, those with the disease were younger (a median age of 58 [46-76] years vs. a median age of 75 [69-85] years; p = 0.01), had fewer comorbidities (a median Charlson Comorbidity Index of 2 [1-4] vs. a median Charlson Comorbidity Index of 5 [4-6]; p < 0.01), and were less severely ill at admission (a median APACHE II score of 9 [8-14] vs. a median APACHE II score of 18 [13-22]; p < 0.01). In addition, the median duration of IMV was longer in the COVID-19 patients (11 [9-23] days vs. 6 [3-8] days; p < 0.01). Although extubation success rates were similar between the COVID-19 and non-COVID-19 groups (22 [71%] vs. 35 [77.8%]), median lung ultrasound score differed between the two groups (23 [18-25] vs. 15 [11-18]; p < 0.01), as did median diaphragmatic excursion (2.1 [1.7-2.4] vs. 1.7 [1.2-2.0]; p < 0.01). Conclusions: Although patients with COVID-19 requiring ventilatory support are younger and have fewer comorbidities than those intubated for other clinical reasons, they experience longer hospital stays. Although lung ultrasound score can differ between patients with and without COVID-19, these differences do not significantly translate into extubation success rates. Therefore, the utility of ultrasound scores in weaning COVID-19 patients from IMV needs further study.

Keywords: COVID-19; Ventilator weaning; Diaphragm; Ultrasound/diagnosis; Lung.

Objective: To determine the efficacy of chest compression accompanied by a 10-cmH2O increase in baseline inspiratory pressure on pressure support ventilation, in comparison with that of aspiration alone, in removing secretions, normalizing hemodynamics, and improving respiratory mechanics in patients on mechanical ventilation. Methods: This was a randomized crossover clinical trial involving patients on mechanical ventilation for more than 48 h in the ICU of the Porto Alegre Hospital de Clínicas, in the city of Porto Alegre, Brazil. Patients were randomized to receive aspiration alone (control group) or compression accompanied by a 10-cmH2O increase in baseline inspiratory pressure on pressure support ventilation (intervention group). We measured hemodynamic parameters, respiratory mechanics parameters, and the amount of secretions collected. Results: We included 34 patients. The mean age was 64.2  14.6 years. In comparison with the control group, the intervention group showed a higher median amount of secretions collected (1.9 g vs. 2.3 g; p = 0.004), a greater increase in mean expiratory tidal volume (16  69 mL vs. 56  69 mL; p = 0.018), and a greater increase in mean dynamic compliance (0.1  4.9 cmH2O vs. 2.8  4.5 cmH2O; p = 0.005). Conclusions: In this sample, chest compression accompanied by an increase in pressure support significantly increased the amount of secretions removed, the expiratory tidal volume, and dynamic compliance. (ClinicalTrials.gov Identifier:NCT01155648 [http://www.clinicaltrials.gov/])

Keywords: Physical therapy modalities; Respiration, Artificial; Intensive care units; Respiratory therapy.

Objective: Ventilator-associated pneumonia (VAP) is a serious complication of mechanical ventilation (MV). However, data on VAP in patients on prolonged MV (PMV) are scarce. We aimed to describe the characteristics of VAP patients on PMV and to identify factors associated with mortality. Methods: This was a retrospective cohort study including VAP patients on PMV. We recorded baseline characteristics, as well as 30-day and 90-day mortality rates. Variables associated with mortality were determined by Kaplan-Meier survival analysis and Cox regression model. Results: We identified 80 episodes of VAP in 62 subjects on PMV. The medians for age, Charlson Comorbidity Index, SOFA score, and days on MV were, respectively, 69.5 years, 5, 4, and 56 days. Episodes of VAP occurred between days 21 and 50 of MV in 28 patients (45.2%) and, by day 90 of MV, in 48 patients (77.4%). The 30-day and 90-day mortality rates were 30.0% and 63.7%, respectively. There were associations of 30-day mortality with the SOFA score (hazard ratio [HR] = 1.30; 95% CI: 1.12-1.52; p < 0.001) and use of vasoactive agents (HR = 4.0; 95% CI: 1.2-12.9; p = 0.02), whereas 90-day mortality was associated with age (HR = 1.03; 95% CI: 1.00-1.05; p = 0.003), SOFA score (HR = 1.20; 95% CI: 1.07-1.34; p = 0.001), use of vasoactive agents (HR = 4.07; 95% CI: 1.93-8.55; p < 0.001), and COPD (HR = 3.35; 95% CI: 1.71-6.60; p < 0.001). Conclusions: Mortality rates in VAP patients on PMV are considerably high. The onset of VAP can occur various days after MV initiation. The SOFA score is useful for predicting fatal outcomes. The factors associated with mortality could help guide therapeutic decisions and determine prognosis.

Keywords: Pneumonia, ventilator-associated; Critical care; Ventilators, mechanical.