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.

Subsyndromal Delirium in Critically Ill Patients-Cognitive and Functional Long-Term Outcomes.

Subsyndromal delirium (SSD) in the Intensive Care Unit (ICU) is associated with an increased morbidity with unknown post-discharge functional and cognitive outcomes. We performed a prospective multicenter study to analyze the mental status of patients during their first 72 h after ICU admission and its trajectory, with follow-ups at 3 and 6 months after hospital discharge. Amongst the 106 included patients, SSD occurred in 24.5% (n = 26) and was associated with the duration of mechanical ventilation (p = 0.003) and the length of the ICU stay (p = 0.002). After the initial 72 h, most of the SSD patients (30.8%) improved and no longer had SSD; 19.2% continued to experience SSD and one patient (3.8%) progressed to delirium. The post-hospital discharge survival rate for the SSD patients was 100% at 3 months and 87.5% at 6 months. At admission, 96.2% of the SSD patients were fully independent in daily living activities, 66.7% at 3-month follow-up, and 100% at 6-month follow-up. Most SSD patients demonstrated a cognitive decline from admission to 3-month follow-up and improved at 6 months (IQCODE-SF: admission 3.13, p < 0.001; 3 months 3.41, p = 0.019; 6 months 3.19, p = 0.194). We concluded that early SSD is associated with worse outcomes, mainly a transitory cognitive decline after hospital discharge at 3 months, with an improvement at 6 months. This highlights the need to prevent and identify this condition during ICU stays.

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.

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.

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.

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.

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.

The impact of SARS-CoV-2 in dementia across Latin America: A call for an urgent regional plan and coordinated response.

The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region. Implementation of best practices for mitigation and containment faces particularly steep challenges in LACs. Based upon our consideration of these issues, we urgently call for a coordinated action plan, including the development of inexpensive mass testing and multilevel regional coordination for dementia care and related actions. Brain health diplomacy should lead to a shared and escalated response across the region, coordinating leadership, and triangulation between governments and international multilateral networks.

Fatal Human Case of Zika and Chikungunya Virus Co-Infection with Prolonged Viremia and Viruria.

Zika virus (ZIKV) infection usually presents as a mild and self-limited illness, but it may be associated with severe outcomes. We describe a case of a 30-year-old man with systemic erythematous lupus and common variable immunodeficiency who became infected with both Zika (ZIKV) and Chikungunya (CHIKV) virus during the 2016 outbreak in Rio de Janeiro, Brazil. The patient presented with intense wrist and right ankle arthritis, and ZIKV RNA and virus particles were detected in synovial tissue, blood and urine, and CHIKV RNA in serum sample, at the time of the diagnosis. During the follow up, ZIKV RNA persisted for 275 days post symptoms onset. The patient evolved with severe arthralgia/arthritis and progressive deterioration of renal function. Fatal outcome occurred after 310 days post ZIKV and CHIKV co-infection onset. The results show the development of severe disease and fatal outcome of ZIKV infection in an immunosuppressed adult. The data suggests a correlation between immunodeficiency and prolonged ZIKV RNA shedding in both blood and urine with progressive disease. The results also indicate a possible role for arbovirus co-infections as risk factors for severe and fatal outcomes from ZIKV infection.

A Comparison of the Quick-SOFA and Systemic Inflammatory Response Syndrome Criteria for the Diagnosis of Sepsis and Prediction of Mortality: A Systematic Review and Meta-Analysis.

BACKGROUND: Several studies were published to validate the quick Sepsis-related Organ Failure Assessment (qSOFA), namely in comparison with the systemic inflammatory response syndrome (SIRS) criteria. We performed a systematic review and meta-analysis with the aim of comparing the qSOFA and SIRS in patients outside the ICU. METHODS: We searched MEDLINE, CINAHL, and the Web of Science database from February 23, 2016 until June 30, 2017 to identify full-text English-language studies published after the Sepsis-3 publication comparing the qSOFA and SIRS and their sensitivity or specificity in diagnosing sepsis, as well as hospital and ICU length of stay and hospital mortality. Data extraction from the selected studies followed the recommendations of the Meta-analyses of Observational Studies in Epidemiology group and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: From 4,022 citations, 10 studies met the inclusion criteria. Pooling all the studies, a total of 229,480 patients were evaluated. The meta-analysis of sensitivity for the diagnosis of sepsis comparing the qSOFA and SIRS was in favor of SIRS (risk ratio [RR], 1.32; 95% CI, 0.40-2.24; P < .0001; I2 = 100%). One study described the specificity for the diagnosis of infection comparing SIRS (84.4%; 95% CI, 76.2-90.6) with the qSOFA (97.3%; 95% CI < 92.1-99.4); the qSOFA demonstrated better specificity. The meta-analysis of the area under the receiver operating characteristic curve of six studies comparing the qSOFA and SIRS favored the qSOFA (RR, 0.03; 95% CI, 0.01-0.05; P = .002; I2 = 48%) as a predictor of inhospital mortality. CONCLUSIONS: The SIRS was significantly superior to the qSOFA for sepsis diagnosis, and the qSOFA was slightly better than the SIRS in predicting hospital mortality. The association of both criteria could provide a better model to initiate or escalate therapy in patients with sepsis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017067645.

Outcomes of subsyndromal delirium in ICU: a systematic review and meta-analysis.

BACKGROUND: Subsyndromal delirium (SSD) is a frequent condition and has been commonly described as an intermediate stage between delirium and normal cognition. However, the true frequency of SSD and its impact on clinically relevant outcomes in the intensive care unit (ICU) remains unclear. METHODS: We performed a systematic search in PubMed, Embase, CINAHL, Cochrane Library, and PsychINFO, with no language restrictions, up to 1 October 2016 to identify publications that evaluated SSD in ICU patients. RESULTS: The six eligible studies were evaluated. SSD was present in 950 (36%) patients. Four studies evaluated only surgical patients. Four studies used the Intensive Care Delirium Screening Checklist (ICDSC) and two used the Confusion Assessment Method (CAM) score to diagnose SSD. The meta-analysis showed an increased hospital length of stay (LOS) in SSD patients (0.31, 0.12-0.51, p = 0.002; I 2 = 34%). Hospital mortality was described in two studies but it was not significant (hazard ratio 0.97, 0.61-1.55, p = 0.90 and 5% vs 9%, p = 0.05). The use of antipsychotics in SSD patients to prevent delirium was evaluated in two studies but it did not modify ICU LOS (6.5 (4-8) vs 7 (4-9) days, p = 0.66 and 2 (2-3) vs 3 (2-3) days, p = 0.517) or mortality (9 (26.5%) vs 7 (20.6%), p = 0.55). CONCLUSIONS: SSD occurs in one-third of the ICU patients and has limited impact on the outcomes. The current literature concerning SSD is composed of small-sample studies with methodological differences, impairing a clear conclusion about the association between SSD and progression to delirium or worse ICU clinical outcomes.