Advancing insights in critical COVID-19: unraveling lymphopenia through propensity score matching - Findings from the Multicenter LYMPH-COVID Study.

OBJECTIVE: To elucidate the impact of lymphopenia on critical COVID-19 patient outcomes. METHODS: We conducted a multicenter prospective cohort study across five hospitals in Portugal and Brazil from 2020 to 2021. The study included adult patients admitted to the intensive care unit with SARS-CoV-2 pneumonia. Patients were categorized into two groups based on their lymphocyte counts within 48 hours of intensive care unit admission: the Lymphopenia Group (lymphocyte serum count < 1 × 109/L) and the Nonlymphopenia Group. Multivariate logistic regression, propensity score matching, Kaplan‒Meier survival curve analysis and Cox proportional hazards regression analysis were used. RESULTS: A total of 912 patients were enrolled, with 191 (20.9%) in the Nonlymphopenia Group and 721 (79.1%) in the Lymphopenia Group. Lymphopenia patients displayed significantly elevated disease severity indices, including Sequential Organ Failure Assessment and Simplified Acute Physiology Score 3 scores, at intensive care unit admission (p = 0.001 and p < 0.001, respectively). Additionally, they presented heightened requirements for vasopressor support (p = 0.045) and prolonged intensive care unit and in-hospital stays (both p < 0.001). Multivariate logistic regression analysis after propensity score matching revealed a significant contribution of lymphopenia to mortality, with an odds ratio of 1,621 (95%CI: 1,275 - 2,048; p < 0.001). Interaction models revealed an increase of 8% in mortality for each decade of longevity in patients with concomitant lymphopenia. In the subanalysis utilizing three-group stratification, the Severe Lymphopenia Group had the highest mortality rate, not only in direct comparisons but also in Kaplan‒Meier survival analysis (log-rank test p = 0.0048). CONCLUSION: Lymphopenia in COVID-19 patients is associated with increased disease severity and an increased risk of mortality, underscoring the need for prompt support for critically ill high-risk patients. These findings offer important insights into improving patient care strategies for COVID-19 patients.

Antisense therapy to block the Kallikrein-kinin pathway in COVID-19: The ASKCOV randomized controlled trial.

PURPOSE: To assess the effect of antisense therapy to block kallikrein-kinin pathway in COVID-19 patients. MATERIAL AND METHODS: Randomized, placebo-controlled, double blind, controlled trial enrolling hospitalized COVID-19 patients that required supplementary oxygen to sustain peripheral oxygen saturation. Key exclusion criteria included use of mechanical ventilation or vasopressors, and patients with more than 10 days since symptom onset or more than 48 h of oxygen use. Patients were randomized to either one subcutaneous dose of ISIS721744, an antisense that blocks prekallikrein, or placebo. The primary outcome was the number of days alive and free of oxygen support up to 15 days (DAFOR15). Secondary endpoints included organ failure score, need and duration of mechanical ventilation up to 15 days, and all-cause mortality at 30 days. Exploratory endpoints included physiological parameters, biomarkers, and quality of life. RESULTS: From October 10, 2020, to December 09, 2020, 111 patients were randomized at thirteen sites in Brazil (56 to treatment and 55 to control group). Average age was 57.5 years, and most patients were male (68.5%). There were no significant differences in DAFOR15 between groups (5.9 ± 5.2 days for the intervention arm and 7.7 ± 5.1 for the control group; mean difference - 0.65, 95% confidence intervals from -2.95 to 1.36, p = 0.520). CONCLUSION: Antisense therapy designed to block the kallikrein-kinin pathway did not demonstrate clinical benefits in increasing days-alive without respiratory support at 15 days in patients with COVID-19 during the first wave in 2020. GOV IDENTIFIER: NCT04549922.

Predictors of bleeding and thrombotic events among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the action randomized clinical trial

Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377.

Predictors of bleeding and thrombotic events among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomized clinical trial.

Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377.

Delirium severity and outcomes of critically ill COVID-19 patients / Gravidade do delirium e desfechos de pacientes críticos com COVID-19

ABSTRACT Objective: To investigate the impact of delirium severity in critically ill COVID-19 patients and its association with outcomes. Methods: This prospective cohort study was performed in two tertiary intensive care units in Rio de Janeiro, Brazil. COVID-19 patients were evaluated daily during the first 7 days of intensive care unit stay using the Richmond Agitation Sedation Scale, Confusion Assessment Method for Intensive Care Unit (CAM-ICU) and Confusion Method Assessment for Intensive Care Unit-7 (CAM-ICU-7). Delirium severity was correlated with outcomes and one-year mortality. Results: Among the 277 COVID-19 patients included, delirium occurred in 101 (36.5%) during the first 7 days of intensive care unit stay, and it was associated with a higher length of intensive care unit stay in days (IQR 13 [7 - 25] versus 6 [4 - 12]; p < 0.001), higher hospital mortality (25.74% versus 5.11%; p < 0.001) and additional higher one-year mortality (5.3% versus 0.6%, p < 0.001). Delirium was classified by CAM-ICU-7 in terms of severity, and higher scores were associated with higher in-hospital mortality (17.86% versus 34.38% versus 38.46%, 95%CI, p value < 0.001). Severe delirium was associated with a higher risk of progression to coma (OR 7.1; 95%CI 1.9 - 31.0; p = 0.005) and to mechanical ventilation (OR 11.09; 95%CI 2.8 - 58.5; p = 0.002) in the multivariate analysis, adjusted by severity and frailty. Conclusion: In patients admitted with COVID-19 in the intensive care unit, delirium was an independent risk factor for the worst prognosis, including mortality. The delirium severity assessed by the CAM-ICU-7 during the first week in the intensive care unit was associated with poor outcomes, including progression to coma and to mechanical ventilation.

RESUMO Objetivo: Investigar como a gravidade do delirium afeta pacientes graves com COVID-19 e sua associação com os desfechos. Métodos: Estudo de coorte prospectivo realizado em duas unidades de terapia intensiva terciárias no Rio de Janeiro (RJ). Os pacientes com COVID-19 foram avaliados diariamente durante os primeiros 7 dias de internação na unidade de terapia intensiva usando a escala de agitação e sedação de Richmond, a Confusion Assessment Method for Intensive Care Unit (CAM-ICU) e a Confusion Assessment Method for Intensive Care Unit-7 (CAM-ICU-7). A gravidade do delirium foi correlacionada com os desfechos e a mortalidade em 1 ano. Resultados: Entre os 277 pacientes com COVID-19 incluídos, o delirium ocorreu em 101 (36,5%) durante os primeiros 7 dias de internação na unidade de terapia intensiva e foi associado a maior tempo de internação na unidade de terapia intensiva em dias (IQ: 13 [7 - 25] versus 6 [4 - 12]; p < 0,001), maior mortalidade hospitalar (25,74% versus 5,11%; p < 0,001) e maior mortalidade em 1 ano (5,3% versus 0,6%, p < 0,001). O delirium foi classificado pela CAM-ICU-7 em termos de gravidade, e escores maiores foram associados à maior mortalidade hospitalar (17,86% versus 34,38% versus 38,46%, IC95%, valor de p < 0,001). O delirium grave foi associado a um risco maior de progressão ao coma (RC de 7,1; IC95% 1,9 - 31,0; p = 0,005) e à ventilação mecânica (RC de 11,09; IC95% 2,8 - 58,5; p = 0,002) na análise multivariada, ajustada por gravidade e fragilidade Conclusão: Em pacientes internados com COVID-19 na unidade de terapia intensiva, o delirium foi fator de risco independente para o pior prognóstico, incluindo mortalidade. A gravidade do delirium avaliada pela CAM-ICU-7 durante a primeira semana na unidade de terapia intensiva foi associada a desfechos desfavoráveis, incluindo a progressão ao coma e à ventilação mecânica.

Delirium severity and outcomes of critically ill COVID-19 patients.

OBJECTIVE: To investigate the impact of delirium severity in critically ill COVID-19 patients and its association with outcomes. METHODS: This prospective cohort study was performed in two tertiary intensive care units in Rio de Janeiro, Brazil. COVID-19 patients were evaluated daily during the first 7 days of intensive care unit stay using the Richmond Agitation Sedation Scale, Confusion Assessment Method for Intensive Care Unit (CAM-ICU) and Confusion Method Assessment for Intensive Care Unit-7 (CAM-ICU-7). Delirium severity was correlated with outcomes and one-year mortality. RESULTS: Among the 277 COVID-19 patients included, delirium occurred in 101 (36.5%) during the first 7 days of intensive care unit stay, and it was associated with a higher length of intensive care unit stay in days (IQR 13 [7 - 25] versus 6 [4 - 12]; p < 0.001), higher hospital mortality (25.74% versus 5.11%; p < 0.001) and additional higher one-year mortality (5.3% versus 0.6%, p < 0.001). Delirium was classified by CAM-ICU-7 in terms of severity, and higher scores were associated with higher in-hospital mortality (17.86% versus 34.38% versus 38.46%, 95%CI, p value < 0.001). Severe delirium was associated with a higher risk of progression to coma (OR 7.1; 95%CI 1.9 - 31.0; p = 0.005) and to mechanical ventilation (OR 11.09; 95%CI 2.8 - 58.5; p = 0.002) in the multivariate analysis, adjusted by severity and frailty. CONCLUSION: In patients admitted with COVID-19 in the intensive care unit, delirium was an independent risk factor for the worst prognosis, including mortality. The delirium severity assessed by the CAM-ICU-7 during the first week in the intensive care unit was associated with poor outcomes, including progression to coma and to mechanical ventilation.

IMPACTO-MR: um estudo brasileiro de plataforma nacional para avaliar infecções e multirresistência em unidades de terapia intensiva / IMPACTO-MR: a Brazilian nationwide platform study to assess infections and multidrug resistance in intensive care units

RESUMO Objetivo: Descrever o IMPACTO-MR, um estudo brasileiro de plataforma nacional em unidades de terapia intensiva focado no impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. Métodos: Descrevemos a plataforma IMPACTO-MR, seu desenvolvimento, critérios para seleção das unidades de terapia intensiva, caracterização da coleta de dados, objetivos e projetos de pesquisa futuros a serem realizados na plataforma. Resultados: Os dados principais foram coletados por meio do Epimed Monitor System® e consistiram em dados demográficos, dados de comorbidades, estado funcional, escores clínicos, diagnóstico de internação e diagnósticos secundários, dados laboratoriais, clínicos e microbiológicos e suporte de órgãos durante a internação na unidade de terapia intensiva, entre outros. De outubro de 2019 a dezembro de 2020, 33.983 pacientes de 51 unidades de terapia intensiva foram incluídos no banco de dados principal. Conclusão: A plataforma IMPACTO-MR é um banco de dados clínico brasileiro de unidades de terapia intensiva focado na pesquisa do impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. Essa plataforma fornece dados para o desenvolvimento e pesquisa de unidades de terapia intensiva individuais e ensaios clínicos observacionais e prospectivos multicêntricos.

ABSTRACT Objective: To describe the IMPACTO-MR, a Brazilian nationwide intensive care unit platform study focused on the impact of health care-associated infections due to multidrug-resistant bacteria. Methods: We described the IMPACTO-MR platform, its development, criteria for intensive care unit selection, characterization of core data collection, objectives, and future research projects to be held within the platform. Results: The core data were collected using the Epimed Monitor System® and consisted of demographic data, comorbidity data, functional status, clinical scores, admission diagnosis and secondary diagnoses, laboratory, clinical, and microbiological data, and organ support during intensive care unit stay, among others. From October 2019 to December 2020, 33,983 patients from 51 intensive care units were included in the core database. Conclusion: The IMPACTO-MR platform is a nationwide Brazilian intensive care unit clinical database focused on researching the impact of health care-associated infections due to multidrug-resistant bacteria. This platform provides data for individual intensive care unit development and research and multicenter observational and prospective trials.

Percepções e práticas sobre sedação superficial em pacientes sob ventilação mecânica: um inquérito sobre as atitudes de médicos intensivistas brasileiros / Perceptions and practices regarding light sedation in mechanically ventilated patients: a survey on the attitudes of Brazilian critical care physicians

RESUMO Objetivo: Caracterizar o conhecimento e as atitudes percebidas em relação às intervenções farmacológicas para sedação superficial em pacientes sob ventilação mecânica e entender as lacunas atuais, comparando a prática atual com as recomendações das Diretrizes de Prática Clínica para a Prevenção e Tratamento da Dor, Agitação/Sedação, Delirium, Imobilidade e Interrupção do Sono em Pacientes Adultos na Unidade de Terapia Intensiva. Métodos: Trata-se de estudo de coorte transversal baseado na aplicação de um questionário eletrônico centrado nas práticas de sedação. Resultados: Responderam ao inquérito 303 médicos intensivistas. A maioria dos entrevistados relatou uso de rotina de uma escala de sedação estruturada (281; 92,6%). Quase metade dos entrevistados relatou realizar interrupções diárias da sedação (147; 48,4%), e a mesma percentagem de participantes (48,0%) concordou com a afirmação de que os pacientes costumam ser sedados em excesso. Durante a pandemia da COVID-19, os participantes relataram que os pacientes tinham maior chance de receber midazolam do que antes da pandemia (178; 58,8% versus 106; 34,0%; p = 0,05); além disso, a sedação profunda foi mais comum durante a pandemia da COVID-19 (241; 79,4% versus 148; 49,0%; p = 0,01). Conclusão: Este inquérito fornece dados valiosos sobre as atitudes percebidas dos médicos intensivistas brasileiros em relação à sedação. Embora a interrupção diária da sedação fosse um conceito bem conhecido e as escalas de sedação fossem frequentemente utilizadas pelos entrevistados, foi colocado esforço insuficiente no monitoramento frequente, no uso de protocolos e na implementação sistemática de estratégias de sedação. Apesar da percepção dos benefícios associados à sedação superficial, há necessidade de identificar metas de melhoria para se proporem estratégias educacionais que melhorem as práticas atuais.

ABSTRACT Objective: To characterize the knowledge and perceived attitudes toward pharmacologic interventions for light sedation in mechanically ventilated patients and to understand the current gaps comparing current practice with the recommendations of the Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the Intensive Care Unit. Methods: This was a cross-sectional cohort study based on the application of an electronic questionnaire focused on sedation practices. Results: A total of 303 critical care physicians provided responses to the survey. Most respondents reported routine use of a structured sedation scale (281; 92.6%). Almost half of the respondents reported performing daily interruptions of sedation (147; 48.4%), and the same percentage of participants (48.0%) agreed that patients are often over sedated. During the COVID-19 pandemic, participants reported that patients had a higher chance of receiving midazolam compared to before the pandemic (178; 58.8% versus 106; 34.0%; p = 0.05), and heavy sedation was more common during the COVID-19 pandemic (241; 79.4% versus 148; 49.0%; p = 0.01). Conclusion: This survey provides valuable data on the perceived attitudes of Brazilian intensive care physicians regarding sedation. Although daily interruption of sedation was a well-known concept and sedation scales were often used by the respondents, insufficient effort was put into frequent monitoring, use of protocols and systematic implementation of sedation strategies. Despite the perception of the benefits linked with light sedation, there is a need to identify improvement targets to propose educational strategies to improve current practices.

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.

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 / 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

RESUMO 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.

ABSTRACT 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.

Perceptions and practices regarding light sedation in mechanically ventilated patients: a survey on the attitudes of Brazilian critical care physicians. / Percepções e práticas sobre sedação superficial em pacientes sob ventilação mecânica: um inquérito sobre as atitudes de médicos intensivistas brasileiros.

OBJECTIVE: To characterize the knowledge and perceived attitudes toward pharmacologic interventions for light sedation in mechanically ventilated patients and to understand the current gaps comparing current practice with the recommendations of the Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the Intensive Care Unit. METHODS: This was a cross-sectional cohort study based on the application of an electronic questionnaire focused on sedation practices. RESULTS: A total of 303 critical care physicians provided responses to the survey. Most respondents reported routine use of a structured sedation scale (281; 92.6%). Almost half of the respondents reported performing daily interruptions of sedation (147; 48.4%), and the same percentage of participants (48.0%) agreed that patients are often over sedated. During the COVID-19 pandemic, participants reported that patients had a higher chance of receiving midazolam compared to before the pandemic (178; 58.8% versus 106; 34.0%; p = 0.05), and heavy sedation was more common during the COVID-19 pandemic (241; 79.4% versus 148; 49.0%; p = 0.01). CONCLUSION: This survey provides valuable data on the perceived attitudes of Brazilian intensive care physicians regarding sedation. Although daily interruption of sedation was a well-known concept and sedation scales were often used by the respondents, insufficient effort was put into frequent monitoring, use of protocols and systematic implementation of sedation strategies. Despite the perception of the benefits linked with light sedation, there is a need to identify improvement targets to propose educational strategies to improve current practices.

OBJETIVO: Caracterizar o conhecimento e as atitudes percebidas em relação às intervenções farmacológicas para sedação superficial em pacientes sob ventilação mecânica e entender as lacunas atuais, comparando a prática atual com as recomendações das Diretrizes de Prática Clínica para a Prevenção e Tratamento da Dor, Agitação/Sedação, Delirium, Imobilidade e Interrupção do Sono em Pacientes Adultos na Unidade de Terapia Intensiva. MÉTODOS: Trata-se de estudo de coorte transversal baseado na aplicação de um questionário eletrônico centrado nas práticas de sedação. RESULTADOS: Responderam ao inquérito 303 médicos intensivistas. A maioria dos entrevistados relatou uso de rotina de uma escala de sedação estruturada (281; 92,6%). Quase metade dos entrevistados relatou realizar interrupções diárias da sedação (147; 48,4%), e a mesma percentagem de participantes (48,0%) concordou com a afirmação de que os pacientes costumam ser sedados em excesso. Durante a pandemia da COVID-19, os participantes relataram que os pacientes tinham maior chance de receber midazolam do que antes da pandemia (178; 58,8% versus 106; 34,0%; p = 0,05); além disso, a sedação profunda foi mais comum durante a pandemia da COVID-19 (241; 79,4% versus 148; 49,0%; p = 0,01). CONCLUSÃO: Este inquérito fornece dados valiosos sobre as atitudes percebidas dos médicos intensivistas brasileiros em relação à sedação. Embora a interrupção diária da sedação fosse um conceito bem conhecido e as escalas de sedação fossem frequentemente utilizadas pelos entrevistados, foi colocado esforço insuficiente no monitoramento frequente, no uso de protocolos e na implementação sistemática de estratégias de sedação. Apesar da percepção dos benefícios associados à sedação superficial, há necessidade de identificar metas de melhoria para se proporem estratégias educacionais que melhorem as práticas atuais.

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3-0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59-1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61-8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation. FUNDING: Coalition COVID-19 Brazil, Bayer SA.

Traqueobronquite associada à ventilação mecânica: uma atualização / Ventilator-associated tracheobronchitis: an update

RESUMO As infecções do trato respiratório inferior associadas à ventilação mecânica são uma das complicações mais frequentes em pacientes em ventilação mecânica. Há muitos anos, a traqueobronquite associada à ventilação mecânica tem sido considerada uma doença que não demanda antibioticoterapia. Na última década, diversos estudos demonstraram que a traqueobronquite associada à ventilação mecânica deve ser considerada um processo intermediário que leva à pneumonia associada à ventilação mecânica, uma vez que apesar de ter impacto limitado sobre a mortalidade dos pacientes gravemente enfermos internados nas unidades de terapia intensiva, em contrapartida, demonstra associação significativa com o aumento dos custos hospitalares desses pacientes, assim como do tempo de internação na unidade de terapia intensiva e hospitalar, do uso de antibióticos, e da duração da ventilação mecânica. Embora ainda necessitemos de evidências científicas mais robustas, especialmente no que tange às modalidades terapêuticas, os dados atuais a respeito da traqueobronquite associada à ventilação mecânica salientam que há desfechos suficientemente importantes que exigem vigilância epidemiológica e controle clínico adequados.

ABSTRACT Ventilator-associated lower respiratory tract infection is one of the most frequent complications in mechanically ventilated patients. Ventilator-associated tracheobronchitis has been considered a disease that does not warrant antibiotic treatment by the medical community for many years. In the last decade, several studies have shown that tracheobronchitis could be considered an intermediate process that leads to ventilator-associated pneumonia. Furthermore, ventilator-associated tracheobronchitis has a limited impact on overall mortality but shows a significant association with increased patient costs, length of stay, antibiotic use, and duration of mechanical ventilation. Although we still need clear evidence, especially concerning treatment modalities, the present study on ventilator-associated tracheobronchitis highlights that there are important impacts of including this condition in clinical management and epidemiological and infection surveillance.

Ventilator-associated tracheobronchitis: an update. / Traqueobronquite associada à ventilação mecânica: uma atualização.

Ventilator-associated lower respiratory tract infection is one of the most frequent complications in mechanically ventilated patients. Ventilator-associated tracheobronchitis has been considered a disease that does not warrant antibiotic treatment by the medical community for many years. In the last decade, several studies have shown that tracheobronchitis could be considered an intermediate process that leads to ventilator-associated pneumonia. Furthermore, ventilator-associated tracheobronchitis has a limited impact on overall mortality but shows a significant association with increased patient costs, length of stay, antibiotic use, and duration of mechanical ventilation. Although we still need clear evidence, especially concerning treatment modalities, the present study on ventilator-associated tracheobronchitis highlights that there are important impacts of including this condition in clinical management and epidemiological and infection surveillance.

As infecções do trato respiratório inferior associadas à ventilação mecânica são uma das complicações mais frequentes em pacientes em ventilação mecânica. Há muitos anos, a traqueobronquite associada à ventilação mecânica tem sido considerada uma doença que não demanda antibioticoterapia. Na última década, diversos estudos demonstraram que a traqueobronquite associada à ventilação mecânica deve ser considerada um processo intermediário que leva à pneumonia associada à ventilação mecânica, uma vez que apesar de ter impacto limitado sobre a mortalidade dos pacientes gravemente enfermos internados nas unidades de terapia intensiva, em contrapartida, demonstra associação significativa com o aumento dos custos hospitalares desses pacientes, assim como do tempo de internação na unidade de terapia intensiva e hospitalar, do uso de antibióticos, e da duração da ventilação mecânica. Embora ainda necessitemos de evidências científicas mais robustas, especialmente no que tange às modalidades terapêuticas, os dados atuais a respeito da traqueobronquite associada à ventilação mecânica salientam que há desfechos suficientemente importantes que exigem vigilância epidemiológica e controle clínico adequados.

Preventive strategies and potential therapeutic interventions for delirium in sepsis.

Delirium is the most frequent and severe clinical presentation of brain dysfunction in critically ill septic patients with an incidence ranging from 9% to 71%. Delirium represents a significant burden for patients and relatives, as well as to the health care system, resulting in higher costs, long-term cognitive impairment and significant risk of death after 6 months. Current interventions for the prevention of delirium typically involve early recognition and amelioration of modifiable risk factors and treatment of underlying conditions that predisposes the individual to delirium. Several pharmacological interventions to prevent and treat delirium have been tested, although their effectiveness remains uncertain, especially in larger and more homogeneous subgroups of ICU patients, like in patients with sepsis. To date, there is inconsistent and conflicting data regarding the efficacy of any particular pharmacological agent, thus substantial attention has been paid to non-pharmacological interventions and preventive strategies should be applied to every patient admitted in the ICU. Future trials should be designed to evaluate the impact of these pharmacologic interventions on the prevention and treatment of delirium on clinically relevant outcomes such as length of stay, hospital mortality and long-term cognitive function. The role of specific medications like statins in delirium prevention is also yet to be evaluated.

The impact of acute brain dysfunction in the outcomes of mechanically ventilated cancer patients.

INTRODUCTION: Delirium and coma are a frequent source of morbidity for ICU patients. Several factors are associated with the prognosis of mechanically ventilated (MV) cancer patients, but no studies evaluated delirium and coma (acute brain dysfunction). The present study evaluated the frequency and impact of acute brain dysfunction on mortality. METHODS: The study was performed at National Cancer Institute, Rio de Janeiro, Brazil. We prospectively enrolled patients ventilated >48 h with a diagnosis of cancer. Acute brain dysfunction was assessed during the first 14 days of ICU using RASS/CAM-ICU. Patients were followed until hospital discharge. Univariate and multivariable analysis were performed to evaluate factors associated with hospital mortality. RESULTS: 170 patients were included. 73% had solid tumors, age 65 [53-72 (median, IQR 25%-75%)] years. SAPS II score was 54[46-63] points and SOFA score was (7 [6-9]) points. Median duration of MV was 13 (6-21) days and ICU stay was 14 (7.5-22) days. ICU mortality was 54% and hospital mortality was 66%. Acute brain dysfunction was diagnosed in 161 patients (95%). Survivors had more delirium/coma-free days [4(1,5-6) vs 1(0-2), p<0.001]. In multivariable analysis the number of days of delirium/coma-free days were associated with better outcomes as they were independent predictors of lower hospital mortality [0.771 (0.681 to 0.873), p<0.001]. CONCLUSIONS: Acute brain dysfunction in MV cancer patients is frequent and independently associated with increased hospital mortality. Future studies should investigate means of preventing or mitigating acute brain dysfunction as they may have a significant impact on clinical outcomes.