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.

Identification of Distinct Clinical Phenotypes of Critically Ill COVID-19 Patients: Results from a Cohort Observational Study.

Purpose: COVID-19 presents complex pathophysiology, and evidence collected points towards an intricate interaction between viral-dependent and individual immunological mechanisms. Identifying phenotypes through clinical and biological markers may provide a better understanding of the subjacent mechanisms and an early patient-tailored characterization of illness severity. Methods: A multicenter prospective cohort study was performed in 5 hospitals in Portugal and Brazil for one year between 2020-2021. All adult patients with an Intensive Care Unit admission with SARS-CoV-2 pneumonia were eligible. COVID-19 was diagnosed using clinical and radiologic criteria with a SARS-CoV-2 positive RT-PCR test. A two-step hierarchical cluster analysis was made using several class-defining variables. Results: 814 patients were included. The cluster analysis revealed a three-class model, allowing for the definition of three distinct COVID-19 phenotypes: 407 patients in phenotype A, 244 patients in phenotype B, and 163 patients in phenotype C. Patients included in phenotype A were significantly older, with higher baseline inflammatory biomarkers profile, and a significantly higher requirement of organ support and mortality rate. Phenotypes B and C demonstrated some overlapping clinical characteristics but different outcomes. Phenotype C patients presented a lower mortality rate, with consistently lower C-reactive protein, but higher procalcitonin and interleukin-6 serum levels, describing an immunological profile significantly different from phenotype B. Conclusions: Severe COVID-19 patients exhibit three different clinical phenotypes with distinct profiles and outcomes. Their identification could have an impact on patients' care, justifying different therapy responses and inconsistencies identified across different randomized control trial results.

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.

Impact of Subsyndromal Delirium Occurrence and Its Trajectory during ICU Stay.

Despite recent advances in the field, the association between subsyndromal delirium (SSD) in the ICU and poor outcomes is not entirely clear. We performed a retrospective multicentric observational study analyzing mental status during the first 72 h of ICU stay. Of the 681 patients included, SSD occurred in 22.7%. Considering the worst cognitive assessment during the first 72 h, 233 (34%) patients had normal mental status, 124 (18%) patients had SSD and 324 (48%) patients had delirium or coma. SSD was not independently associated with an increased risk of death when compared with normal mental status (OR 95%IC 1.0 vs. 1.35 [0.73−1.49], p = 0.340), but was associated with a longer ICU LOS (7.0 (4−12) vs. 4 (3−8) days, p < 0.001). SSD patients who deteriorated to delirium or coma (21%) had a longer ICU LOS in comparison with those who improved or maintained mental status (8 (5−11) vs. 6 (4−8) days, p = 0.025), but did not have an increase in mortality. The main factors associated with the progression from SSD to delirium or coma were the use of mechanical ventilation, the use of intravenous benzodiazepines and a baseline APACHE II score > 23 points. Our findings support the association of SSD with increased ICU LOS, but not with ICU mortality. Monitoring the trajectory of SSD early at ICU admission can help to identify patients with increased risk of conversion from SSD to delirium or coma.

COVID-19 Infection in Rheumatic Patients on Chronic Antimalarial Drugs: A Systematic Review and Meta-Analysis.

The ongoing chronic use of hydroxychloroquine or chloroquine (HCQ/CQ) in rheumatic patients might impact their outcomes after a SARS-CoV-2 infection. Therefore, we sought to assess the mortality in rheumatic patients with chronic HCQ/CQ use who developed a COVID-19 infection through a comparison between individuals chronically using HCQ/CQ with those not taking these drugs. We performed a systematic review and meta-analysis of studies on PubMed, Embase, and Cochrane Central. We included full-length reports, prospective observational cohorts, and clinical trials of adult patients (aged ≥ 18 years) who were diagnosed with a COVID-19 infection. Case studies, case series, letters, comments, and editorials were excluded. The main outcome was all-cause mortality. This study is registered with PROSPERO (CRD42022341678). We identified 541 studies, of which 20 studies were included, comprising 236,997 patients. All-cause mortality was significantly lower in patients with prior chronic use of HCQ/CQ compared to those with no previous usage (OR 0.76; 95% CI 0.62-0.94; p = 0.01). There was a considerably lower incidence of hospitalization among patients with chronic HCQ/CQ use compared to their counterparts without HCQ/CQ usage (OR 0.80; 95% CI 0.65-0.99; p = 0.04). All-cause mortality and hospitalization were significantly lower in rheumatic patients with chronic HCQ/CQ use who developed a COVID-19 infection.

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.

Dapagliflozin and Kidney Outcomes in Hospitalized Patients with COVID-19 Infection: An Analysis of the DARE-19 Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Patients who were hospitalized with coronavirus disease 2019 (COVID-19) infection are at high risk of AKI and KRT, especially in the presence of CKD. The Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial showed that in patients hospitalized with COVID-19, treatment with dapagliflozin versus placebo resulted in numerically fewer participants who experienced organ failure or death, although these differences were not statistically significant. We performed a secondary analysis of the DARE-19 trial to determine the efficacy and safety of dapagliflozin on kidney outcomes in the overall population and in prespecified subgroups of participants defined by baseline eGFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The DARE-19 trial randomized 1250 patients who were hospitalized (231 [18%] had eGFR <60 ml/min per 1.73 m2) with COVID-19 and cardiometabolic risk factors to dapagliflozin or placebo. Dual primary outcomes (time to new or worsened organ dysfunction or death, and a hierarchical composite end point of recovery [change in clinical status by day 30]), and the key secondary kidney outcome (composite of AKI, KRT, or death), and safety were assessed in participants with baseline eGFR <60 and ≥60 ml/min per 1.73 m2. RESULTS: The effect of dapagliflozin versus placebo on the primary prevention outcome (hazard ratio, 0.80; 95% confidence interval, 0.58 to 1.10), primary recovery outcome (win ratio, 1.09; 95% confidence interval, 0.97 to 1.22), and the composite kidney outcome (hazard ratio, 0.74; 95% confidence interval, 0.50 to 1.07) were consistent across eGFR subgroups (P for interaction: 0.98, 0.67, and 0.44, respectively). The effects of dapagliflozin on AKI were also similar in participants with eGFR <60 ml/min per 1.73 m2 (hazard ratio, 0.71; 95% confidence interval, 0.29 to 1.77) and ≥60 ml/min per 1.73 m2 (hazard ratio, 0.69; 95% confidence interval, 0.37 to 1.29). Dapagliflozin was well tolerated in participants with eGFR <60 and ≥60 ml/min per 1.73 m2. CONCLUSIONS: The effects of dapagliflozin on primary and secondary outcomes in hospitalized participants with COVID-19 were consistent in those with eGFR below/above 60 ml/min per 1.73 m2. Dapagliflozin was well tolerated and did not increase the risk of AKI in participants with eGFR below or above 60 ml/min per 1.73 m2.

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.

Clinical course and outcomes of critically ill patients with COVID-19 infection: a systematic review.

OBJECTIVES: Coronavirus disease 19 (COVID-19) is a major cause of hospital admission and represents a challenge for patient management during intensive care unit (ICU) stay. We aimed to describe the clinical course and outcomes of COVID-19 pneumonia in critically ill patients. METHODS: We performed a systematic search of peer-reviewed publications in MEDLINE, EMBASE and the Cochrane Library up to 15th August 2020. Preprints and reports were also included if they met the inclusion criteria. Study eligibility criteria were full-text prospective, retrospective or registry-based publications describing outcomes in patients admitted to the ICU for COVID-19, using a validated test. Participants were critically ill patients admitted in the ICU with COVID-19 infection. RESULTS: From 32 articles included, a total of 69 093 patients were admitted to the ICU and were evaluated. Most patients included in the studies were male (76 165/128 168, 59%, 26 studies) and the mean patient age was 56 (95%CI 48.5-59.8) years. Studies described high ICU mortality (21 145/65 383, 32.3%, 15 studies). The median length of ICU stay was 9.0 (95%CI 6.5-11.2) days, described in five studies. More than half the patients admitted to the ICU required mechanical ventilation (31 213/53 465, 58%, 23 studies) and among them mortality was very high (27 972/47 632, 59%, six studies). The duration of mechanical ventilation was 8.4 (95%CI 1.6-13.7) days. The main interventions described were the use of non-invasive ventilation, extracorporeal membrane oxygenation, renal replacement therapy and vasopressors. CONCLUSIONS: This systematic review, including approximately 69 000 ICU patients, demonstrates that COVID-19 infection in critically ill patients is associated with great need for life-sustaining interventions, high mortality, and prolonged length of ICU stay.

Identification of distinct clinical phenotypes in mechanically ventilated patients with acute brain dysfunction using cluster analysis.

Acute brain dysfunction (ABD) is a frequent and severe syndrome occurring in critically ill patients and early identification of high-risk patients is paramount. In the present analysis, we propose a clinically applicable model for early phenotype identification of ABD at the bedside in mechanically ventilated patients, improving the recognition of patients with prolonged ABD.Prospective cohort with 629 mechanically ventilated patients in two medical-surgical intensive care units at academic centers. We applied cluster analysis to identify phenotypes using clinical and biological data. We then tested the association of phenotypes and its respective clinical outcomes. We performed a validation on a new cohort of patients select on subsequent patients admitted to the participants intensive care units.A model with 3 phenotypes best described the study population. A 4-variable model including medical admission, sepsis diagnosis, simplified acute physiologic score II and basal serum C-reactive protein (CRP) accurately classified each phenotype (area under curve 0.82; 95% CI, 0.79-0.86). Phenotype A had the shorter duration of ABD (median, 1 day), while phenotypes B and C had progressively longer duration of ABD (median, 3 and 6 days, respectively; P < .0001). There was an association between the duration of ABD and the baseline CRP levels and simplified acute physiology score II score (sensitivity and specificity of 80%). To increase the sensitivity of the model, we added CRP kinetics. By day 1, a CRP < 1.0 times the initial level was associated with a shorter duration of ABD (specificity 0.98).A model based on widely available clinical variables could provide phenotypes associated with the duration of ABD. Phenotypes with longer duration of ABD (phenotypes B and C) are characterized by more severe inflammation and by significantly worse clinical outcomes.

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.

The current status of biomarkers for the diagnosis of nosocomial pneumonias.

PURPOSE OF REVIEW: Nosocomial pneumonia is a frequent and severe nosocomial infection divided in two distinct groups: hospital-acquired pneumonia and ventilator-associated pneumonia (VAP). In this context, the VAP is notoriously difficult to diagnose clinically, resulting from the lack of a 'gold standard' method of diagnosis. RECENT FINDINGS: The use of biomarkers may potentially improve the early diagnosis of infections allowing earlier and better identification and treatment. An exhausting list of biomarkers has been studied and although far from perfect, procalcitonin (PCT) and C-reactive protein (CRP) are the most studied biomarkers used in clinical practice. Data coming from literature suggests the use of PCT for VAP prognosis and as a based algorithm tool for the reduction of duration of pneumonia therapy, as well as, the use of the CRP dynamics to the early prediction of VAP and the response to the antibiotics. SUMMARY: The evidence for the use of biomarkers to diagnose nosocomial pneumonia as a stand-alone tool is low to moderate. Improved performance for both PCT and CRP can be obtained by using them in association with clinical features or scoring systems but prospective studies are still needed to validate this hypothesis.