Impact on the ability of healthcare professionals to correctly identify patient-ventilator asynchronies of the simultaneous visualization of estimated muscle pressure curves on the ventilator display: a randomized study (Pmus study).

BACKGROUND: Patient-ventilator asynchronies are usually detected by visual inspection of ventilator waveforms but with low sensitivity, even when performed by experts in the field. Recently, estimation of the inspiratory muscle pressure (Pmus) waveforms through artificial intelligence algorithm has been proposed (Magnamed®, São Paulo, Brazil). We hypothesized that the display of these waveforms could help healthcare providers identify patient-ventilator asynchronies. METHODS: A prospective single-center randomized study with parallel assignment was conducted to assess whether the display of the estimated Pmus waveform would improve the correct identification of asynchronies in simulated clinical scenarios. The primary outcome was the mean asynchrony detection rate (sensitivity). Physicians and respiratory therapists who work in intensive care units were randomized to control or intervention group. In both groups, participants analyzed pressure and flow waveforms of 49 different scenarios elaborated using the ASL-5000 lung simulator. In the intervention group the estimated Pmus waveform was displayed in addition to pressure and flow waveforms. RESULTS: A total of 98 participants were included, 49 per group. The sensitivity per participant in identifying asynchronies was significantly higher in the Pmus group (65.8 ± 16.2 vs. 52.94 ± 8.42, p < 0.001). This effect remained when stratifying asynchronies by type. CONCLUSIONS: We showed that the display of the Pmus waveform improved the ability of healthcare professionals to recognize patient-ventilator asynchronies by visual inspection of ventilator tracings. These findings require clinical validation. TRIAL REGISTRATION: ClinicalTrials.gov: NTC05144607. Retrospectively registered 3 December 2021.

Does Regional Lung Strain Correlate With Regional Inflammation in Acute Respiratory Distress Syndrome During Nonprotective Ventilation? An Experimental Porcine Study.

OBJECTIVE: It is known that ventilator-induced lung injury causes increased pulmonary inflammation. It has been suggested that one of the underlying mechanisms may be strain. The aim of this study was to investigate whether lung regional strain correlates with regional inflammation in a porcine model of acute respiratory distress syndrome. DESIGN: Retrospective analysis of CT images and positron emission tomography images using [F]fluoro-2-deoxy-D-glucose. SETTING: University animal research laboratory. SUBJECTS: Seven piglets subjected to experimental acute respiratory distress syndrome and five ventilated controls. INTERVENTIONS: Acute respiratory distress syndrome was induced by repeated lung lavages, followed by 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressures (mean, 4 cm H2O) and high inspiratory pressures (mean plateau pressure, 45 cm H2O). All animals were subsequently studied with CT scans acquired at end-expiration and end-inspiration, to obtain maps of volumetric strain (inspiratory volume - expiratory volume)/expiratory volume, and dynamic positron emission tomography imaging. Strain maps and positron emission tomography images were divided into 10 isogravitational horizontal regions-of-interest, from which spatial correlation was calculated for each animal. MEASUREMENTS AND MAIN RESULTS: The acute respiratory distress syndrome model resulted in a decrease in respiratory system compliance (20.3 ± 3.4 to 14.0 ± 4.9 mL/cm H2O; p < 0.05) and oxygenation (PaO2/FIO2, 489 ± 80 to 92 ± 59; p < 0.05), whereas the control animals did not exhibit changes. In the acute respiratory distress syndrome group, strain maps showed a heterogeneous distribution with a greater concentration in the intermediate gravitational regions, which was similar to the distribution of [F]fluoro-2-deoxy-D-glucose uptake observed in the positron emission tomography images, resulting in a positive spatial correlation between both variables (median R = 0.71 [0.02-0.84]; p < 0.05 in five of seven animals), which was not observed in the control animals. CONCLUSION: In this porcine acute respiratory distress syndrome model, regional lung strain was spatially correlated with regional inflammation, supporting that strain is a relevant and prominent determinant of ventilator-induced lung injury.

Esophageal balloon catheter system identification to improve respiratory effort time features and amplitude determination.

Objective. Understanding a patient's respiratory effort and mechanics is essential for the provision of individualized care during mechanical ventilation. However, measurement of transpulmonary pressure (the difference between airway and pleural pressures) is not easily performed in practice. While airway pressures are available on most mechanical ventilators, pleural pressures are measured indirectly by an esophageal balloon catheter. In many cases, esophageal pressure readings take other phenomena into account and are not a reliable measure of pleural pressure.Approach.A system identification approach was applied to provide accurate pleural measures from esophageal pressure readings. First, we used a closed pressurized chamber to stimulate an esophageal balloon and model its dynamics. Second, we created a simplified version of an artificial lung and tried the model with different ventilation configurations. For validation, data from 11 patients (five male and six female) were used to estimate respiratory effort profile and patient mechanics.Main results.After correcting the dynamic response of the balloon catheter, the estimates of resistance and compliance and the corresponding respiratory effort waveform were improved when compared with the adjusted quantities in the test bench. The performance of the estimated model was evaluated using the respiratory pause/occlusion maneuver, demonstrating improved agreement between the airway and esophageal pressure waveforms when using the normalized mean squared error metric. Using the corrected muscle pressure waveform, we detected start and peak times 130 ± 50 ms earlier and a peak amplitude 2.04 ± 1.46 cmH2O higher than the corresponding estimates from esophageal catheter readings.Significance.Compensating the acquired measurements with system identification techniques makes the readings more accurate, possibly better portraying the patient's situation for individualization of ventilation therapy.

Temporal trends of severity and outcomes of critically ill patients with COVID-19 after the emergence of variants of concern: A comparison of two waves.

BACKGROUND: The emergence of SARS-CoV-2 variants led to subsequent waves of COVID-19 worldwide. In many countries, the second wave of COVID-19 was marked by record deaths, raising the concern that variants associated with that wave might be more deadly. Our aim was to compare outcomes of critically-ill patients of the first two waves of COVID-19. METHODS: This retrospective cohort included critically-ill patients admitted between March-June 2020 and April-July 2021 in the largest academic hospital in Brazil, which has free-access universal health care system. We compared admission characteristics and hospital outcomes. The main outcome was 60-day survival and we built multivariable Cox model based on a conceptual causal diagram in the format of directed acyclic graph (DAG). RESULTS: We included 1583 patients (1315 in the first and 268 in the second wave). Patients in the second wave were younger, had lower severity scores, used prone and non-invasive ventilatory support more often, and fewer patients required mechanical ventilation (70% vs 80%, p<0.001), vasopressors (60 vs 74%, p<0.001), and dialysis (22% vs 37%, p<0.001). Survival was higher in the second wave (HR 0.61, 95%CI 0.50-0.76). In the multivariable model, admission during the second wave, adjusted for age, SAPS3 and vaccination, was not associated with survival (aHR 0.85, 95%CI 0.65-1.12). CONCLUSIONS: In this cohort study, patients with COVID-19 admitted to the ICU in the second wave were younger and had better prognostic scores. Adjusted survival was similar in the two waves, contrasting with record number of hospitalizations, daily deaths and health system collapse seen across the country in the second wave. Our findings suggest that the combination of the burden of severe cases and factors such as resource allocation and health disparities may have had an impact in the excess mortality found in many countries in the second wave.

Quantitative analysis of pulmonary perfusion with dual-energy CT angiography: comparison of two quantification methods in patients with pulmonary embolism.

The study aimed to evaluate a quantification method of pulmonary perfusion with Dual-Energy CT Angiography (DE-CTA) normalized by lung density in the prediction of outcome in acute pulmonary embolism (PE). In this prospective study with CTA scans acquired with different breathing protocols, two perfusion parameters were calculated: %PBV (relative value of PBV, expressed per unit volume) and PBVm (PBV normalized by lung density, expressed per unit mass). DE-CTA parameters were correlated with simplified pulmonary embolism severity index (sPESI) and with outcome groups, alone and in combinationwith tomographic right-to-left ventricular ratios (RV/LV). PBVm showed significant correlation with sPESI. PBVm presented higher accuracy than %PBV In the prediction of ICU admission or death in patients with PE, with the best performance when combined with RV/LV volumetric ratio.

Functional recovery of chronically critically ill patients in the first days after discharge from the intensive care unit: Feasibility of the 6-minute step test.

BACKGROUND: Survivors of chronic critical illness often experience weakness and functional dependence to various degrees after their intensive care unit (ICU) stay. Evaluating their functional status with the traditional six-minute walk test is challenging due to space constraints or patient intolerance. OBJECTIVE: Our aim was to evaluate the feasibility of using the six-minute step test (6MST) as a measure of functional capacity in chronically critically ill patients early after ICU discharge. METHODS: This prospective study was undertaken in a private Brazilian hospital. From July 2019 to July 2020, all chronically critically ill patients were asked to participate 48 hours after ICU discharge. On the day of study inclusion and a week later, those who consented underwent functional assessment comprised of the 6MST, peripheral muscle strength using handgrip strength (HGS), and mobility using the ICU mobility scale (IMS). RESULTS: A total of 40 patients were included. The 6MST was feasible in 40% on the first evaluation and 57% on the second. The median 6MST was 0 [0-5] on the first evaluation and 3.5 [0-7.75] on the second (P = 0.005). The median HGS increased from 11.50 [9.25-18] on the first evaluation to 14.5 [10-20] on the second (P = 0.006). The median IMS was 4.5 [3.25-7] on the first evaluation and 6 [3.25-7] on the second (P<0.001). Despite the significant improvement, all parameters measured remained well below normal. CONCLUSION: The 6MST was a feasible measure of functional capacity in chronically critically ill patients early after ICU discharge. Patients had functional capacity well below predicted values.

Fibrinolytic therapy in patients with COVID-19 and ARDS: protocol for a systematic review and meta-analysis.

INTRODUCTION: In COVID-19-related acute respiratory distress syndrome (ARDS), the clot play a role in gas exchange abnormalities. Fibrinolytic therapy can improve alveolar ventilation by restoring blood flow. In this systematic review and meta-analysis protocol, we aim to assess the safety and efficacy of fibrinolytic therapy in such a population. METHODS: We will perform a systematic search in MEDLINE, EMBASE, Cochrane CENTRAL and LILACS databases without language restrictions for relevant randomised controlled trials (RCTs) and quasi-RCTs. Two review authors will independently perform data extraction and quality assessments of data from included studies. In case of divergence, a third author will be contacted. The Cochrane handbook will be used for guidance. If the results are not appropriate for a meta-analysis, a descriptive analysis will be performed. DISCUSSION: This systematic review and meta-analysis protocol will provide current evidence about the safety and efficacy of fibrinolytic therapy in patients with COVID-19 and ARDS. These findings will provide if fibrinolytic therapy might be an option for a desperate clinical setting, where all medical efforts have been used. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020187482. ETHICS AND DISSEMINATION: Ethics committee approval is not necessary. We intend to update the public registry, report any protocol amendments and publish the results in a widely accessible journal.

Ninety-day outcomes in patients diagnosed with COVID-19 in São Paulo, Brazil: a cohort study.

OBJECTIVE: COVID-19 has been associated with a significant burden to those who survive the acute phase. We aimed to describe the quality of life and symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) at 90 days after hospital discharge of COVID-19 patients. METHODS: Patients with COVID-19 admitted to a private hospital in the city of São Paulo, Brazil, between April of 2020 and April of 2021 were interviewed by telephone at 30 and 90 days after discharge to assess the quality of life and symptoms of depression, anxiety, and PTSD. RESULTS: A total of 2,138 patients were included. The mean age was 58.6 ± 15.8 years, and the median length of hospital stay was 9.0 (5.0-15.8) days. Between the two time points, depression increased from 3.1% to 7.2% (p < 0.001), anxiety increased from 3.2% to 6.2% (p < 0.001), and PTSD increased from 2.3% to 5.0% (p < 0.001). At least one physical symptom related to COVID-19 diagnosis persisted in 32% of patients at day 90. CONCLUSIONS: Persistence of physical symptoms was high even at 90 days after discharge. Although the prevalence of symptoms of anxiety, depression, and PTSD was low, these symptoms persisted for three months, with a significant increase between the time points. This finding indicates the need to identify at-risk patients so that they can be given an appropriate referral at discharge.

Lung perfusion during veno-venous extracorporeal membrane oxygenation in a model of hypoxemic respiratory failure.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (ECMO) provides blood oxygenation and carbon dioxide removal in acute respiratory distress syndrome. However, during ECMO support, the native lungs still play an important role in gas exchange, functioning as a second oxygenator in series with ECMO. The hypoxic vasoconstriction mechanism diverts regional blood flow within the lungs away from regions with low oxygen levels, optimizing ventilation/perfusion matching. ECMO support has the potential to reduce this adaptive pulmonary response and worsen the ventilation/perfusion mismatch by raising venous oxygen partial pressure. Thus, the objective of this study was to evaluate the effect of ECMO on regional pulmonary perfusion and pulmonary hemodynamics during unilateral ventilation and posterior lung collapse. METHODS: Five Agroceres pigs were instrumented, monitored and submitted to ECMO. We used the Electrical Impedance Tomography (EIT) to evaluate lung ventilation and perfusion in all protocol steps. Effects of ECMO support on pulmonary hemodynamics and perfusion involving two different scenarios of ventilation/perfusion mismatch: (1) right-lung selective intubation inducing collapse of the normal left lung and (2) dorsal lung collapse after repeated lung lavage. Data including hemodynamics, respiratory, lung perfusion/ventilation, and laboratory data over time were analyzed with a mixed generalized model using the subjects as a random factor. RESULTS: The initiation of ECMO support provided a significant reduction in Mean Pulmonary Artery Pressure (PAPm) in both situations of ventilation/perfusion mismatch. However, distribution of lung perfusion did not change with the use of ECMO support. CONCLUSIONS: We found that the use of ECMO support with consequent increase in venous oxygen pressure induced a significant drop in PAPm with no detectable effect on regional lung perfusion in different scenarios of ventilation/perfusion mismatch.

Burnout syndrome in intensive care physicians in time of the COVID-19: a cross-sectional study.

OBJECTIVES: To assess the prevalence of burnout syndrome among intensive care physicians working in a tertiary private hospital as well as their perceived impact of the COVID-19 pandemic on their life. DESIGN: A cross-sectional study. SETTING: Intensive care units dedicated to the care of COVID-19 in Hospital Sirio-Libanes, Sao Paulo, Southeastern part of Brazil. PARTICIPANTS: Intensive care physicians. INTERVENTIONS: Each participant received an envelope with a questionnaire composed of demographic and occupational variables, information related to their personal and professional experiences facing the COVID-19 pandemic and the Maslach Burnout Inventory questionnaire. PRIMARY AND SECONDARY OUTCOMES MEASURES: The primary outcome was to assess the prevalence of burnout syndrome among physicians working in an intensive care unit dedicated to the care of COVID-19. RESULTS: A total of 51 from the universe of 63 (82%) intensive care physicians participated in the study. Nineteen (37.2%) met the criteria for burnout syndrome. In the three domains that characterise burnout syndrome, we found a low level of personal achievement in 96.1% of physicians interviewed, a high level of depersonalisation in 51.0% and 51.0% with a high level of emotional exhaustion. Decision-making conflicts between the intensive care unit team and other attending physicians were frequent (50% of all conflicts). A third of the participants had been diagnosed with COVID-19, 22 (43.1%) reported having a family member infected and 8 (15.7%) lost someone close to the COVID-19 pandemic. Participants felt that fear of infecting their loved ones was the aspect of their lives that changed most as compared with the prepandemic period. CONCLUSIONS: Burnout syndrome was frequent among intensive care unit physicians treating patients with COVID-19 in a large tertiary private hospital. Future studies should expand our results to other private and public hospitals and test strategies to promote intensive care unit physicians' mental health.

Hereditary Breast Cancer in the Brazilian State of Ceará (The CHANCE Cohort): Higher-Than-Expected Prevalence of Recurrent Germline Pathogenic Variants.

Purpose: There is a significant lack of epidemiological data on hereditary cancer in Northeast Brazil. This is the largest study on the prevalence and mutational spectrum of cancer predisposition genes conducted in this region and the first in the State of Ceará. Methods: Patients ≥18 years of age that were referred to CHANCE (Grupo de Câncer Hereditário do Ceará) from March 2014 to December 2020 with testing criteria for breast cancer susceptibility genes according to NCCN v.1.2021 were eligible to participate. The inclusion of patients was limited to one individual per family and to those born in the State of Ceará. All patients underwent a hereditary cancer panel testing with at least 30 genes. Results: A total of 355 patients were included, and 97 (27.3%) carried a P/LP germline variant in 18 different genes. Among the 97 P/LP carriers, BRCA1 (31, 31.9%) and BRCA2 (25, 25.7%) were the most frequently mutated genes, followed by PALB2 (10, 10.3%), CHEK2 (7, 7.2%) and ATM (4, 4.1%). A small number of recurrent variants (detected in three or more individuals) in BRCA1, BRCA2, CHEK2 and ATM represented the majority of the P/LP variants described in this cohort. Conclusion: In this cohort, the prevalence of L/PL was high, particularly involving the BRCA1, BRCA2, PALB2, CHEK2 and ATM genes and, to a lesser extent than expected, the TP53 gene. A high frequency of recurrent variants was also observed, for which further and larger analyses should clarify the presence of any possible founder effect. Characterizing the mutational profile of cancer predisposition genes in diverse populations may contribute to cancer prevention and therapeutic management.

Clinical outcomes and lung mechanics characteristics between COVID-19 and non-COVID-19-associated acute respiratory distress syndrome: a propensity score analysis of two major randomized trials. / Desfechos clínicos e características da mecânica pulmonar entre a síndrome do desconforto respiratório agudo associada à COVID-19 e a não associada à COVID-19: uma análise de escore de propensão de dois importantes ensaios randomizados.

OBJECTIVE: To compare the lung mechanics and outcomes between COVID-19-associated acute respiratory distress syndrome and non-COVID-19-associated acute respiratory distress syndrome. METHODS: We combined data from two randomized trials in acute respiratory distress syndrome, one including only COVID-19 patients and the other including only patients without COVID-19, to determine whether COVID-19-associated acute respiratory distress syndrome is associated with higher 28-day mortality than non-COVID-19 acute respiratory distress syndrome and to examine the differences in lung mechanics between these two types of acute respiratory distress syndrome. RESULTS: A total of 299 patients with COVID-19-associated acute respiratory distress syndrome and 1,010 patients with non-COVID-19-associated acute respiratory distress syndrome were included in the main analysis. The results showed that non-COVID-19 patients used higher positive end-expiratory pressure (12.5cmH2O; SD 3.2 versus 11.7cmH2O SD 2.8; p < 0.001), were ventilated with lower tidal volumes (5.8mL/kg; SD 1.0 versus 6.5mL/kg; SD 1.2; p < 0.001) and had lower static respiratory compliance adjusted for ideal body weight (0.5mL/cmH2O/kg; SD 0.3 versus 0.6mL/cmH2O/kg; SD 0.3; p = 0.01). There was no difference between groups in 28-day mortality (52.3% versus 58.9%; p = 0.52) or mechanical ventilation duration in the first 28 days among survivors (13 [IQR 5 - 22] versus 12 [IQR 6 - 26], p = 0.46). CONCLUSION: This analysis showed that patients with non-COVID-19-associated acute respiratory distress syndrome have different lung mechanics but similar outcomes to COVID-19-associated acute respiratory distress syndrome patients. After propensity score matching, there was no difference in lung mechanics or outcomes between groups.

OBJETIVO: Comparar a mecânica pulmonar e os desfechos entre a síndrome do desconforto respiratório agudo associada à COVID-19 e a síndrome do desconforto respiratório agudo não associada à COVID-19. MÉTODOS: Combinamos dados de dois ensaios randomizados sobre a síndrome do desconforto respiratório agudo, um incluindo apenas pacientes com COVID-19 e o outro incluindo apenas pacientes sem COVID-19, para determinar se a síndrome do desconforto respiratório agudo associada à COVID-19 está associada à maior mortalidade aos 28 dias do que a síndrome do desconforto respiratório agudo não associada à COVID-19 e também examinar as diferenças na mecânica pulmonar entre esses dois tipos de síndrome do desconforto respiratório agudo. RESULTADOS: Foram incluídos na análise principal 299 pacientes com síndrome do desconforto respiratório agudo associada à COVID-19 e 1.010 pacientes com síndrome do desconforto respiratório agudo não associada à COVID-19. Os resultados mostraram que os pacientes sem COVID-19 utilizaram pressão positiva expiratória final mais alta (12,5cmH2O; DP 3,2 versus 11,7cmH2O; DP 2,8; p < 0,001), foram ventilados com volumes correntes mais baixos (5,8mL/kg; DP 1,0 versus 6,5mL/kg; DP 1,2; p < 0,001) e apresentaram menor complacência respiratória estática ajustada para o peso ideal (0,5mL/cmH2O/kg; DP 0,3 versus 0,6mL/cmH2O/kg; DP 0,3; p = 0,01). Não houve diferença entre os grupos quanto à mortalidade aos 28 dias (52,3% versus 58,9%; p = 0,52) ou à duração da ventilação mecânica nos primeiros 28 dias entre os sobreviventes (13 [IQ 5 - 22] dias versus 12 [IQ 6 - 26] dias; p = 0,46). CONCLUSÃO: Esta análise mostrou que os pacientes com síndrome do desconforto respiratório agudo não associada à COVID-19 têm mecânica pulmonar diferente, mas desfechos semelhantes aos dos pacientes com síndrome do desconforto respiratório agudo associada à COVID-19. Após pareamento por escore de propensão, não houve diferença na mecânica pulmonar e nem nos desfechos entre os grupos.

Outcomes and prognostic factors of decompensated pulmonary hypertension in the intensive care unit.

BACKGROUND: Patients with acute decompensation of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) admitted to intensive care unit (ICU) have high in-hospital mortality. We hypothesized that pulmonary hypertension (PH) severity, measured by a simplified version of European Society of Cardiology/European Respiratory Society (ESC/ERS) risk assessment, and the severity of organ dysfunction upon ICU admission, measured by sequential organ failure assessment score (SOFA) were associated with in-hospital mortality in decompensated patients with PAH and CTEPH. We also described clinical and laboratory variables during ICU stay. METHODS: Observational study including adults with decompensated PAH or CTEPH with unplanned ICU admission between 2014 and 2019. Multivariate logistic regression models were used to evaluate the association of ESC/ERS risk assessment and SOFA score with in-hospital mortality. ESC/ERS risk assessment and SOFA score were included in a decision tree to predict in-hospital mortality. RESULTS: 73 patients were included. In-hospital mortality was 41.1%. ESC/ERS high-risk group (adjusted odds ratio = 95.52) and SOFA score (adjusted odds ratio = 1.80) were associated with in-hospital mortality. The decision tree identified four groups with in-hospital mortality between 8.1% and 100%. Nonsurvivors had a lower central venous oxygen saturation, higher arterial lactate and higher brain natriuretic peptide in the end of first week in the ICU. CONCLUSIONS: High-risk on a simplified version of ERS/ESC risk assessment and SOFA score upon ICU admission are associate with in-hospital mortality. A decision tree based on ESC/ERS risk assessment and SOFA score identifies four groups with in-hospital mortality between 8.1% and 100%.

Protective ventilation and outcomes of critically ill patients with COVID-19: a cohort study.

BACKGROUND: Approximately 5% of COVID-19 patients develop respiratory failure and need ventilatory support, yet little is known about the impact of mechanical ventilation strategy in COVID-19. Our objective was to describe baseline characteristics, ventilatory parameters, and outcomes of critically ill patients in the largest referral center for COVID-19 in Sao Paulo, Brazil, during the first surge of the pandemic. METHODS: This cohort included COVID-19 patients admitted to the intensive care units (ICUs) of an academic hospital with 94 ICU beds, a number expanded to 300 during the pandemic as part of a state preparedness plan. Data included demographics, advanced life support therapies, and ventilator parameters. The main outcome was 28-day survival. We used a multivariate Cox model to test the association between protective ventilation and survival, adjusting for PF ratio, pH, compliance, and PEEP. RESULTS: We included 1503 patients from March 30 to June 30, 2020. The mean age was 60 ± 15 years, and 59% were male. During 28-day follow-up, 1180 (79%) patients needed invasive ventilation and 666 (44%) died. For the 984 patients who were receiving mechanical ventilation in the first 24 h of ICU stay, mean tidal volume was 6.5 ± 1.3 mL/kg of ideal body weight, plateau pressure was 24 ± 5 cmH2O, respiratory system compliance was 31.9 (24.4-40.9) mL/cmH2O, and 82% of patients were ventilated with protective ventilation. Noninvasive ventilation was used in 21% of patients, and prone, in 36%. Compliance was associated with survival and did not show a bimodal pattern that would support the presence of two phenotypes. In the multivariable model, protective ventilation (aHR 0.73 [95%CI 0.57-0.94]), adjusted for PF ratio, compliance, PEEP, and arterial pH, was independently associated with survival. CONCLUSIONS: During the peak of the epidemic in Sao Paulo, critically ill patients with COVID-19 often required mechanical ventilation and mortality was high. Our findings revealed an association between mechanical ventilation strategy and mortality, highlighting the importance of protective ventilation for patients with COVID-19.

Cancer-Related Characteristics Associated With Invasive Mechanical Ventilation or In-Hospital Mortality in Patients With COVID-19 Admitted to ICU: A Cohort Multicenter Study.

BACKGROUND: Coexistence of cancer and COVID-19 is associated with worse outcomes. However, the studies on cancer-related characteristics associated with worse COVID-19 outcomes have shown controversial results. The objective of the study was to evaluate cancer-related characteristics associated with invasive mechanical ventilation use or in-hospital mortality in patients with COVID-19 admitted to intensive care unit (ICU). METHODS: We designed a cohort multicenter study including adults with active cancer admitted to ICU due to COVID-19. Seven cancer-related characteristics (cancer status, type of cancer, metastasis occurrence, recent chemotherapy, recent immunotherapy, lung tumor, and performance status) were introduced in a multilevel logistic regression model as first-level variables and hospital was introduced as second-level variable (random effect). Confounders were identified using directed acyclic graphs. RESULTS: We included 274 patients. Required to undergo invasive mechanical ventilation were 176 patients (64.2%) and none of the cancer-related characteristics were associated with mechanical ventilation use. Approximately 155 patients died in hospital (56.6%) and poor performance status, measured with the Eastern Cooperative Oncology Group (ECOG) score was associated with increased in-hospital mortality, with odds ratio = 3.54 (1.60-7.88, 95% CI) for ECOG =2 and odds ratio = 3.40 (1.60-7.22, 95% CI) for ECOG = 3 to 4. Cancer status, cancer type, metastatic tumor, lung cancer, and recent chemotherapy or immunotherapy were not associated with in-hospital mortality. CONCLUSIONS: In patients with active cancer and COVID-19 admitted to ICU, poor performance status was associated with in-hospital mortality but not with mechanical ventilation use. Cancer status, cancer type, metastatic tumor, lung cancer, and recent chemotherapy or immunotherapy were not associated with invasive mechanical ventilation use or in-hospital mortality.

Improving Airways Patency and Ventilation Through Optimal Positive Pressure Identified by Noninvasive Mechanical Ventilation Titration in Mounier-Kuhn Syndrome: Protocol for an Interventional, Open-Label, Single-Arm Clinical Trial.

BACKGROUND: Mounier-Kuhn syndrome or congenital tracheobronchomegaly is a rare disease characterized by dilation of the trachea and the main bronchi within the thoracic cavity. The predominant signs and symptoms of the disease include coughing, purulent and abundant expectoration, dyspnea, snoring, wheezing, and recurrent respiratory infection. Symptoms of the disease in some patients are believed to be pathological manifestations arising due to resident tracheobronchomalacia. Although treatment options used for the management of this disease include inhaled bronchodilators, corticosteroids, and hypertonic solution, there is no consensus on the treatment. The use of continuous positive airway pressure (CPAP) has been reported as a potential therapeutic option for tracheobronchomalacia, but no prospective studies have demonstrated its efficacy in this condition. OBJECTIVE: The purpose of this is to identify the presence of tracheobronchomalacia and an optimal CPAP pressure that reduces the tracheobronchial collapse in patients with Mounier-Kuhn syndrome and to analyze the repercussion in pulmonary ventilation. In parallel, we aim to evaluate the prevalence of obstructive sleep apnea/hypopnea syndrome. METHODS: This interventional, open-label, single-arm clinical trial will enroll patients who are diagnosed Mounier-Kuhn syndrome. Patient evaluation will be conducted in an outpatient clinic and involve 3 visits. Visit 1 will involve the collection and registration of social demographic, clinical, and functional data. Visit 2 will entail polysomnography, bronchoscopy for the evaluation of tracheobronchomalacia, titration of the optimal pressure that reduces the degree of collapse of the airway, and electrical impedance tomography. In visit 3, patients exhibiting a reduction in collapse areas will be requested to undergo chest computed tomography during inspiration and forced expiration with and without positive pressure (titrated to determine optimal CPAP pressure). RESULTS: This protocol is a doctorate project. The project was submitted to the institutional review board on January 24, 2017, and approval was granted on February 2, 2017 (Brazilian Research database number CAAE 64001317.4.000.0068). Patient evaluations started in April 2018. Planned recruitment is based on volunteers' availability and clinical stability, and interventions will be conducted at least once a month to finish the project at the end of 2020. A preliminary analysis of each case will be performed after each intervention, but detailed results are expected to be reported in the first quarter of 2021. CONCLUSIONS: There is no consensus on the best treatment options for managing Mounier-Kuhn syndrome. The use of positive pressure could maintain patency of the collapsed airways, functioning as a "pneumatic stent" to reduce the degree of airflow obstruction. This, in turn, could promote mobilization of thoracic secretion and improve pulmonary ventilation. TRIAL REGISTRATION: ClinicalTrails.gov NCT03101059; https://clinicaltrials.gov/ct2/show/NCT03101059. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14786.

Epidemiology, outcomes, and the use of intensive care unit resources of critically ill patients diagnosed with COVID-19 in Sao Paulo, Brazil: A cohort study.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has brought significant challenges worldwide, with high mortality, increased use of hospital resources, and the collapse of healthcare systems. We aimed to describe the clinical outcomes of critically ill COVID-19 patients and assess the impact on the use of hospital resources and compare with critically ill medical patients without COVID-19. METHODS AND FINDINGS: In this retrospective cohort study, we included patients diagnosed with COVID-19 admitted to a private ICU in Sao Paulo, Brazil from March to June 2020. We compared these patients with those admitted to the unit in the same period of the previous year. A total of 212 consecutive patients with a confirmed diagnosis of COVID-19 were compared with 185 medical patients from the previous year. Patients with COVID-19 were more frequently males (76% vs. 56%, p<0.001) and morbidly obese (7.5% vs. 2.2%, p = 0.027), and had lower SAPS 3 (49.65 (12.19) vs. 55.63 (11.94), p<0.001) and SOFA scores (3.78 (3.53) vs. 4.48 (3.11), p = 0.039). COVID-19 patients had a longer ICU stay (median of 7 vs. 3 days, p<0.001), longer duration of mechanical ventilation (median of 9 vs. 4 days, p = 0.003), and more frequent tracheostomies (10.8 vs. 1.1%, p<0.001). Survival rates until 28 days were not statistically different (91% vs. 85.4%, p = 0.111). After multivariable adjustment for age, gender, SAPS 3, and Charlson Comorbidity Index, COVID-19 remained not associated with survival at 28 days (HR 0.59, 95% CI 0.33-1.06, p = 0.076). Among patients who underwent invasive mechanical ventilation, the observed mortality at 28-days was 16.2% in COVID-19 patients compared to 34.6% in the previous year. CONCLUSIONS: COVID-19 required more hospital resources, including invasive and non-invasive ventilation, had a longer duration of mechanical ventilation, and a more prolonged ICU and hospital length of stay. There was no difference in all-cause mortality at 28 and 60 days, suggesting that health systems preparedness be an important determinant of clinical outcomes.

Impact of a respiratory ICU rotation on resident knowledge and confidence in managing mechanical ventilation.

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.

Inflammatory Activity in Atelectatic and Normally Aerated Regions During Early Acute Lung Injury.

RATIONALE AND OBJECTIVES: Pulmonary atelectasis presumably promotes and facilitates lung injury. However, data are limited on its direct and remote relation to inflammation. We aimed to assess regional 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) kinetics representative of inflammation in atelectatic and normally aerated regions in models of early lung injury. MATERIALS AND METHODS: We studied supine sheep in four groups: Permissive Atelectasis (n = 6)-16 hours protective tidal volume (VT) and zero positive end-expiratory pressure; Mild (n = 5) and Moderate Endotoxemia (n = 6)- 20-24 hours protective ventilation and intravenous lipopolysaccharide (Mild = 2.5 and Moderate = 10.0 ng/kg/min), and Surfactant Depletion (n = 6)-saline lung lavage and 4 hours high VT. Measurements performed immediately after anesthesia induction served as controls (n = 8). Atelectasis was defined as regions of gas fraction <0.1 in transmission or computed tomography scans. 18F-FDG kinetics measured with positron emission tomography were analyzed with a three-compartment model. RESULTS: 18F-FDG net uptake rate in atelectatic tissue was larger during Moderate Endotoxemia (0.0092 ± 0.0019/min) than controls (0.0051 ± 0.0014/min, p = 0.01). 18F-FDG phosphorylation rate in atelectatic tissue was larger in both endotoxemia groups (0.0287 ± 0.0075/min) than controls (0.0198 ± 0.0039/min, p = 0.05) while the 18F-FDG volume of distribution was not significantly different among groups. Additionally, normally aerated regions showed larger 18F-FDG uptake during Permissive Atelectasis (0.0031 ± 0.0005/min, p < 0.01), Mild (0.0028 ± 0.0006/min, p = 0.04), and Moderate Endotoxemia (0.0039 ± 0.0005/min, p < 0.01) than controls (0.0020 ± 0.0003/min). CONCLUSION: Atelectatic regions present increased metabolic activation during moderate endotoxemia mostly due to increased 18F-FDG phosphorylation, indicative of increased cellular metabolic activation. Increased 18F-FDG uptake in normally aerated regions during permissive atelectasis suggests an injurious remote effect of atelectasis even with protective tidal volumes.