Viral reactivations and co-infections in COVID-19 patients: a systematic review.

BACKGROUND: Viral reactivations and co-infections have been reported among COVID-19 patients. However, studies on the clinical outcomes of different viral reactivations and co-infections are currently in limit. Thus, the primary purpose of this review is to perform an overarching investigation on the cases of latent virus reactivation and co-infection in COVID-19 patients to build collective evidence contributing to improving patient health. The aim of the study was to conduct a literature review to compare the patient characteristics and outcomes of reactivations and co-infections of different viruses. METHODS: Our population of interest included confirmed COVID-19 patients who were diagnosed with a viral infection either concurrently or following their COVID-19 diagnosis. We extracted the relevant literature through a systematic search using the key terms in the online databases including the EMBASE, MEDLINE, Latin American Caribbean Health Sciences Literature (LILACS), from inception onwards up to June 2022. The authors independently extracted data from eligible studies and assessed the risk of bias using the Consensus-based Clinical Case Reporting (CARE) guidelines and the Newcastle-Ottawa Scale (NOS). Main patient characteristics, frequency of each manifestation, and diagnostic criteria used in studies were summarized in tables. RESULTS: In total, 53 articles were included in this review. We identified 40 reactivation studies, 8 coinfection studies, and 5 studies where concomitant infection in COVID-19 patients was not distinguished as either reactivation or coinfection. Data were extracted for 12 viruses including IAV, IBV, EBV, CMV, VZV, HHV-1, HHV-2, HHV-6, HHV-7, HHV-8, HBV, and Parvovirus B19. EBV, HHV-1, and CMV were most frequently observed within the reactivation cohort, whereas IAV and EBV within the coinfection cohort. In both reactivation and coinfection groups, patients reported cardiovascular disease, diabetes, and immunosuppression as comorbidities, acute kidney injury as complication, and lymphopenia and elevated D-dimer and CRP levels from blood tests. Common pharmaceutical interventions in two groups included steroids and antivirals. CONCLUSION: Overall, these findings expand our knowledge on the characteristics of COVID-19 patients with viral reactivations and co-infections. Our experience with current review indicates a need for further investigations on virus reactivation and coinfection among COVID-19 patients.

Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients with COVID-19: An Open-label, Randomized Clinical Trial.

Background: Serotonin is a mediator of pulmonary hypoxic vasoconstriction. Experimental studies have shown that serotonin-mediated pulmonary vasoconstriction can be inhibited by cyproheptadine. The aim of this study is to assess whether treatment with cyproheptadine compared to usual care increases ventilatory support-free days during the first 28 days in patients with coronavirus disease 2019 (COVID-19) requiring ventilatory support. Materials and methods: This randomized, single-center, open-label clinical trial included patients who were admitted to the intensive care unit (ICU) requiring ventilatory support due to COVID-19. Patients allocated to the intervention group received cyproheptadine for 10 days. The primary outcome was ventilator-free days during the first 28 days. Results: Nineteen patients were randomized to receive cyproheptadine and 21 to the control group. The number of ventilatory support-free days during the first 28 days was not different between the two groups (15.0; 95% CI, 0.0-24.0 days in the control group vs 7.0; 95% CI, 0.0-19.0 days in the intervention group; p = 0.284). Conclusion: In patients with COVID-19 and in need of ventilatory support, the use of cyproheptadine plus usual care, compared with usual care alone, did not increase the number of ventilatory support-free days in 28 days. How to cite this article: Boniatti MM, Nedel WL, Rihl MF, Schwarz P, Parolo E, Moretti MMS, et al. Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients with COVID-19: An Open-label, Randomized Clinical Trial. Indian J Crit Care Med 2023;27(7):517-521.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Daily Chlorhexidine Bath for Health Care Associated Infection Prevention (CLEAN-IT): protocol for a multicenter cluster randomized crossover open-label trial.

BACKGROUND: Critically ill patients are at increased risk of health care-associated infections due to various devices (central line-associated bloodstream infection, catheter-associated urinary tract infection, and ventilator-associated pneumonia), which pose a significant threat to this population. Among several strategies, daily bathing with chlorhexidine digluconate, a water-soluble antiseptic, has been studied as an intervention to decrease the incidence of health care-associated infections in the intensive care unit; however, its ability to reduce all health care-associated infections due to various devices is unclear. We designed the Daily Chlorhexidine Bath for Health Care Associated Infection Prevention (CLEAN-IT) trial to assess whether daily chlorhexidine digluconate bathing reduces the incidence of health care-associated infections in critically ill patients compared with soap and water bathing. METHODS: The CLEAN-IT trial is a multicenter, open-label, cluster randomized crossover clinical trial. All adult patients admitted to the participating intensive care units will be included in the trial. Each cluster (intensive care unit) will be randomized to perform either initial chlorhexidine digluconate bathing or soap and water bathing with crossover for a period of 3 to 6 months, depending on the time of each center's entrance to the study, with a 1-month washout period between chlorhexidine digluconate bathing and soap and water bathing transitions. The primary outcome is the incidence of health care-associated infections due to devices. The secondary outcomes are the incidence of each specific health care-associated infection, rates of microbiological cultures positive for multidrug-resistant pathogens, antibiotic use, intensive care unit and hospital length of stay, and intensive care unit and hospital mortality. CONCLUSION: The CLEAN-IT trial will be used to study feasible and affordable interventions that might reduce the health care-associated infection burden in critically ill patients.

Association between time of day for rapid response team activation and mortality.

PURPOSE: To evaluate the frequency of rapid response team (RRT) calls by time of day and their association with in-hospital mortality. MATERIALS AND METHODS: This was a retrospective cohort study of all RRT calls at a tertiary teaching hospital in Porto Alegre, Brazil. Patients were categorized according to the time of initial RRT activation. Activations were classified as daytime (7:00-18:59) or nighttime (19:00-6:59). The primary outcome was in-hospital mortality rate. The secondary outcome was ICU admission within 48 h of RRT assessment. RESULTS: During the study period, 4522 patients were included in the final analysis. Cardiovascular and respiratory changes were more common causes of nighttime activation, whereas neurological and laboratory changes were more common during the daytime. The in-hospital mortality rate was 23.9% (1081/4522). Nighttime RRT calls were not associated with worse outcomes than daytime calls. However, a decrease in the number of calls was observed during nursing handover periods (7:00, 13:00 and 19:00). Two time periods were associated with increased adjusted odds for mortality: 12:00-13:00 (adjusted OR 2.277; 95% CI 1.392-3.725) and 19:00-20:00 (adjusted OR 1.873; CI 1.873; 95% 1.099-3.190). CONCLUSION: We found that nighttime RRT calls were not associated with worse outcomes than daytime RRT calls. However, a decrease in the number of calls and higher mortality was observed during nursing handover periods.

Association between acute disease severity and one-year quality of life among post-hospitalisation COVID-19 patients: Coalition VII prospective cohort study.

PURPOSE: To assess the association between acute disease severity and 1-year quality of life in patients discharged after hospitalisation due to coronavirus disease 2019 (COVID-19). METHODS: We conducted a prospective cohort study nested in 5 randomised clinical trials between March 2020 and March 2022 at 84 sites in Brazil. Adult post-hospitalisation COVID-19 patients were followed for 1 year. The primary outcome was the utility score of EuroQol five-dimension three-level (EQ-5D-3L). Secondary outcomes included all-cause mortality, major cardiovascular events, and new disabilities in instrumental activities of daily living. Adjusted generalised estimating equations were used to assess the association between outcomes and acute disease severity according to the highest level on a modified ordinal scale during hospital stay (2: no oxygen therapy; 3: oxygen by mask or nasal prongs; 4: high-flow nasal cannula oxygen therapy or non-invasive ventilation; 5: mechanical ventilation). RESULTS: 1508 COVID-19 survivors were enrolled. Primary outcome data were available for 1156 participants. At 1 year, compared with severity score 2, severity score 5 was associated with lower EQ-5D-3L utility scores (0.7 vs 0.84; adjusted difference, - 0.1 [95% CI - 0.15 to - 0.06]); and worse results for all-cause mortality (7.9% vs 1.2%; adjusted difference, 7.1% [95% CI 2.5%-11.8%]), major cardiovascular events (5.6% vs 2.3%; adjusted difference, 2.6% [95% CI 0.6%-4.6%]), and new disabilities (40.4% vs 23.5%; adjusted difference, 15.5% [95% CI 8.5%-22.5]). Severity scores 3 and 4 did not differ consistently from score 2. CONCLUSIONS: COVID-19 patients who needed mechanical ventilation during hospitalisation have lower 1-year quality of life than COVID-19 patients who did not need mechanical ventilation during hospitalisation.

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

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.

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.

Brazilian guidelines for the management of brain-dead potential organ donors. The task force of the Associação de Medicina Intensiva Brasileira, Associação Brasileira de Transplantes de Órgãos, Brazilian Research in Critical Care Network, and the General Coordination of the National Transplant System. / Diretrizes brasileiras para o manejo de potenciais doadores de órgãos em morte encefálica. Uma força-tarefa composta por Associação de Medicina Intensiva Brasileira, Associação Brasileira de Transplantes de Órgãos, Brazilian Research in Critical Care Network e Coordenação Geral do Sistema Nacional de Transplantes.

OBJECTIVE: To contribute to updating the recommendations for brain-dead potential organ donor management. METHODS: A group of 27 experts, including intensivists, transplant coordinators, transplant surgeons, and epidemiologists, answered questions related to the following topics were divided into mechanical ventilation, hemodynamics, endocrine-metabolic management, infection, body temperature, blood transfusion, and checklists use. The outcomes considered were cardiac arrests, number of organs removed or transplanted as well as function / survival of transplanted organs. The quality of evidence of the recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system to classify the recommendations. RESULTS: A total of 19 recommendations were drawn from the expert panel. Of these, 7 were classified as strong, 11 as weak and 1 was considered a good clinical practice. CONCLUSION: Despite the agreement among panel members on most recommendations, the grade of recommendation was mostly weak.

OBJETIVO: Fornecer recomendações para nortear o manejo clínico do potencial doador em morte encefálica. MÉTODOS: O presente documento foi formulado em dois painéis compostos por uma força tarefa integrada por 27 especialistas de diferentes áreas que responderam a questões dirigidas aos seguintes temas: ventilação mecânica, hemodinâmica, suporte endócrino-metabólico, infecção, temperatura corporal, transfusão sanguínea, e uso de checklists. Os desfechos considerados foram: parada cardíaca, número de órgãos retirados ou transplantados e função/sobrevida dos órgãos transplantados. A qualidade das evidências das recomendações foi avaliada pelo sistema Grading of Recommendations Assessment, Development, and Evaluation. RESULTADOS: Foram geradas 19 recomendações a partir do painel de especialistas. Dessas, 7 foram classificadas como fortes, 11 fracas e uma foi considerada boa prática clínica. CONCLUSÃO: Apesar da concordância entre os membros do painel em relação à maior parte das recomendações, o grau de recomendação é fraco em sua maioria.

Quality of life and long-term outcomes after hospitalization for COVID-19: Protocol for a prospective cohort study (Coalition VII). / Qualidade de vida e desfechos em longo prazo após hospitalização por COVID-19: Protocolo para um estudo de coorte prospectivo (Coalizão VII).

INTRODUCTION: The long-term effects caused by COVID-19 are unknown. The present study aims to assess factors associated with health-related quality of life and long-term outcomes among survivors of hospitalization for COVID-19 in Brazil. METHODS: This is a multicenter prospective cohort study nested in five randomized clinical trials designed to assess the effects of specific COVID-19 treatments in over 50 centers in Brazil. Adult survivors of hospitalization due to proven or suspected SARS-CoV-2 infection will be followed-up for a period of 1 year by means of structured telephone interviews. The primary outcome is the 1-year utility score of health-related quality of life assessed by the EuroQol-5D3L. Secondary outcomes include all-cause mortality, major cardiovascular events, rehospitalizations, return to work or study, physical functional status assessed by the Lawton-Brody Instrumental Activities of Daily Living, dyspnea assessed by the modified Medical Research Council dyspnea scale, need for long-term ventilatory support, symptoms of anxiety and depression assessed by the Hospital Anxiety and Depression Scale, symptoms of posttraumatic stress disorder assessed by the Impact of Event Scale-Revised, and self-rated health assessed by the EuroQol-5D3L Visual Analog Scale. Generalized estimated equations will be performed to test the association between five sets of variables (1- demographic characteristics, 2- premorbid state of health, 3- characteristics of acute illness, 4- specific COVID-19 treatments received, and 5- time-updated postdischarge variables) and outcomes. ETHICS AND DISSEMINATION: The study protocol was approved by the Research Ethics Committee of all participant institutions. The results will be disseminated through conferences and peer-reviewed journals.

INTRODUÇÃO: Os efeitos provocados pela COVID-19 em longo prazo são desconhecidos. O presente estudo tem como objetivo avaliar os fatores associados com a qualidade de vida relacionada à saúde e os desfechos em longo prazo em sobreviventes à hospitalização por COVID-19 no Brasil. MÉTODOS: Este será um estudo multicêntrico de coorte prospectivo, aninhado em cinco ensaios clínicos randomizados desenhados para avaliar os efeitos dos tratamentos específicos para COVID-19 em mais de 50 centros no Brasil. Pacientes adultos sobreviventes à hospitalização por infecção por SARS-CoV-2 comprovada ou suspeita serão seguidos por um período de 1 ano, por meio de entrevistas telefônicas estruturadas. O desfecho primário é o escore de utilidade para qualidade de vida relacionada à saúde após 1 ano, avaliado segundo o questionário EuroQol-5D3L. Os desfechos secundários incluirão mortalidade por todas as causas, eventos cardiovasculares graves, reospitalizações, retorno ao trabalho ou estudo, condição funcional física avaliada pelo instrumento Lawton-Brody Instrumental Activities of Daily Living, dispneia avaliada segundo a escala de dispneia modificada do Medical Research Council, necessidade de suporte ventilatório em longo prazo, sintomas de ansiedade e depressão avaliados segundo a Hospital Anxiety and Depression Scale, sintomas de transtorno de estresse pós-traumático avaliados pela ferramenta Impact of Event Scale-Revised e autoavaliação da condição de saúde, conforme a Escala Visual Analógica do EuroQol-5D3L. Serão utilizadas equações de estimativas generalizada para testar a associação entre cinco conjuntos de variáveis (1 - características demográficas, 2 - condição de saúde pré-morbidade, 3 - características da doença aguda, 4 - terapias específicas para COVID-19 recebidas e 5 - variáveis pós-alta atualizadas) e desfechos. ÉTICA E DISSEMINAÇÃO: O protocolo do estudo foi aprovado pelos Comitês de Ética em Pesquisa de todas as instituições participantes. Os resultados serão disseminados por meio de conferências e periódicos revisados por pares.

Hemodynamically stable oliguric patients usually do not respond to fluid challenge. / Pacientes oligúricos hemodinamicamente estáveis geralmente não respondem ao desafio hídrico.

OBJECTIVE: To evaluate renal responsiveness in oliguric critically ill patients after a fluid challenge. METHODS: We conducted a prospective observational study in one university intensive care unit. Patients with urine output < 0.5mL/kg/h for 3 hours with a mean arterial pressure > 60mmHg received a fluid challenge. We examined renal fluid responsiveness (defined as urine output > 0.5mL/kg/h for 3 hours) after fluid challenge. RESULTS: Forty-two patients (age 67 ± 13 years; APACHE II score 16 ± 6) were evaluated. Patient characteristics were similar between renal responders and renal nonresponders. Thirteen patients (31%) were renal responders. Hemodynamic or perfusion parameters were not different between those who did and those who did not increase urine output before the fluid challenge. The areas under the receiver operating characteristic curves were calculated for mean arterial pressure, heart rate, creatinine, urea, creatinine clearance, urea/creatinine ratio and lactate before the fluid challenge. None of these parameters were sensitive or specific enough to predict reversal of oliguria. CONCLUSION: After achieving hemodynamic stability, oliguric patients did not increase urine output after a fluid challenge. Systemic hemodynamic, perfusion or renal parameters were weak predictors of urine responsiveness. Our results suggest that volume replacement to correct oliguria in patients without obvious hypovolemia should be done with caution.

OBJETIVO: Avaliar a responsividade renal após desafio hídrico em pacientes oligúricos na unidade de terapia intensiva. MÉTODO: Conduzimos um estudo observacional prospectivo em uma unidade de terapia intensiva universitária. Pacientes com débito urinário inferior a 0,5mL/kg/hora por 3 horas, com pressão arterial média acima de 60mmHg receberam um desafio hídrico. Examinamos a responsividade renal aos fluidos (definida como débito urinário acima de 0,5mL/kg/hora por 3 horas) após o desafio hídrico. RESULTADOS: Avaliaram-se 42 pacientes (idade 67 ± 13 anos; APACHE II 16 ± 6). As características dos pacientes foram similares entre os respondedores e os não respondedores renais. Treze pacientes (31%) foram respondedores renais. Antes do desafio hídrico, os parâmetros hemodinâmicos e de perfusão não foram diferentes entre os pacientes que apresentaram aumento do débito urinário e os que não apresentaram. Calcularam-se as áreas sob a curva receiver operating characteristic para os níveis pré-desafio hídrico de pressão arterial média, frequência cardíaca, creatinina, ureia, depuração de creatinina, proporção ureia/creatinina e lactato. Nenhum desses parâmetros foi sensível ou suficientemente específico para predizer a reversão da oligúria. CONCLUSÃO: Após obtenção de estabilidade hemodinâmica, os pacientes oligúricos não alcançaram aumento do débito urinário em resposta ao desafio hídrico. Os parâmetros de hemodinâmica sistêmica, perfusão ou renais foram preditores fracos de responsividade urinária. Nossos resultados sugerem que a reposição de volume com objetivo de corrigir oligúria em pacientes sem hipovolemia óbvia deve ser realizada com cautela.

Statistical analysis plan for the Balanced Solution versus Saline in Intensive Care Study (BaSICS). / Plano de análise estatística para o estudo Balanced Solution versus Saline in Intensive Care Study (BaSICS).

OBJECTIVE: To report the statistical analysis plan (first version) for the Balanced Solutions versus Saline in Intensive Care Study (BaSICS). METHODS: BaSICS is a multicenter factorial randomized controlled trial that will assess the effects of Plasma-Lyte 148 versus 0.9% saline as the fluid of choice in critically ill patients, as well as the effects of a slow (333mL/h) versus rapid (999mL/h) infusion speed during fluid challenges, on important patient outcomes. The fluid type will be blinded for investigators, patients and the analyses. No blinding will be possible for the infusion speed for the investigators, but all analyses will be kept blinded during the analysis procedure. RESULTS: BaSICS will have 90-day mortality as its primary endpoint, which will be tested using mixed-effects Cox proportional hazard models, considering sites as a random variable (frailty models) adjusted for age, organ dysfunction and admission type. Important secondary endpoints include renal replacement therapy up to 90 days, acute renal failure, organ dysfunction at days 3 and 7, and mechanical ventilation-free days within 28 days. CONCLUSION: This manuscript provides details on the first version of the statistical analysis plan for the BaSICS trial and will guide the study's analysis when follow-up is finished.

OBJETIVO: Relatar o plano de análise estatística (primeira versão) para o estudo Balanced Solutions versus Saline in Intensive Care Study (BaSICS). MÉTODOS: O estudo BaSICS é um ensaio multicêntrico fatorial e randomizado que avaliará os efeitos da administração dos fluidos Plasma-Lyte 148 em comparação com solução salina 0,9% como fluido de escolha em pacientes críticos, assim como os efeitos de uma velocidade de infusão lenta (333mL/hora) em comparação com uma velocidade de infusão rápida (999mL/hora) durante desafios com volume, em importantes desfechos do paciente. O tipo de fluido será mantido cego para os investigadores, pacientes e nas análises. Não será possível, entretanto, ocultar dos investigadores a velocidade de infusão, mas os procedimentos de análise serão mantidos cegos quanto a esse aspecto. RESULTADOS: O estudo BaSICS terá como parâmetro primário a mortalidade em 90 dias, que será testada com utilização de modelos de risco proporcional de Cox de efeitos mistos, considerando os centros de estudo como variável randômica (modelos de fragilidade) ajustada por idade, disfunção de órgãos e tipo de admissão. Os parâmetros secundários importantes incluem terapia de substituição renal até 90 dias, insuficiência renal aguda, disfunção de órgãos nos dias 3 e 7 e dias sem ventilação mecânica em 28 dias. CONCLUSÃO: Este artigo fornece detalhes referentes à primeira versão do plano de análise estatística para o estudo BaSICS e orientará a análise do estudo após a conclusão do seguimento.

Is red blood cell distribution width a marker of severity in patients discharged from the ICU?

We have read the study about the association between high red blood cell distribution width and higher ward mortality after intensive care unit discharge. The study increases the evidence that RDW may be a marker of severity for patients discharged from the ICU. However, in this letter, we comment on issues that need further discussion.

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.

Early mobilization practices of mechanically ventilated patients: a 1-day point-prevalence study in southern Brazil.

OBJECTIVES: To assess early mobilization practices of mechanically ventilated patients in southern Brazilian intensive care units (ICUs) and to identify barriers associated with early mobilization and possible complications. METHODS: A prospective, observational, multicenter, 1-day point-prevalence study was conducted across 11 ICUs and included all mechanically ventilated adult patients. Hospital and ICU characteristics and patients' demographic data, the highest level of mobilization achieved in the 24 hours prior to the survey and related barriers, and complications that occurred during mobilization were collected in the hospital and the ICU. RESULTS: A total of 140 patients were included with a mean age of 57±17 years. The median and interquartile range was 7 (3-17) days for the length of ICU stay to the day of the survey and 7 (3-16) days for the duration of mechanical ventilation (MV). The 8-level mobilization scale was classified into two categories: 126 patients (90%) remained in bed (level 1-3) and 14 (10%) were mobilized out of bed (level 4-8). Among patients with an endotracheal tube, tracheostomy, and noninvasive ventilation, 2%, 23%, and 50% were mobilized out of bed, respectively (p<0.001 for differences among the three groups). Weakness (20%), cardiovascular instability (19%), and sedation (18%) were the most commonly observed barriers to achieving a higher level of mobilization. No complications were reported. CONCLUSIONS: In southern Brazilian ICUs, the prevalence of patient mobilization was low, with only 10% of all mechanically ventilated patients and only 2% of patients with an endotracheal tube mobilized out of bed as part of routine care.

Elevated red blood cell distribution width at ICU discharge is associated with readmission to the intensive care unit.

BACKGROUND: Red blood cell distribution width (RDW) is a predictor of mortality in critically ill patients. Our objective was to investigate the association between the RDW at ICU discharge and the risk of ICU readmission or unexpected death in the ward. METHODS: A secondary analysis of prospectively collected data study was conducted including patients discharged alive from the ICU to the ward. The target variable was the RDW collected at ICU discharge. Elevated RDW was defined as an RDW > 16%. Outcomes of interest included readmission to the ICU, unexpected death in the ward and in-hospital death. Variables with a p-value <0.1 in the univariate analysis or with biological plausibility for the occurrence of the outcome were included in the Cox proportional hazards model for adjustment. RESULTS: We included 813 patients. A total of 138 readmissions to the ICU and 44 unexpected deaths in the ward occurred. Elevated RDW at ICU discharge was independently associated with readmission to the ICU or unexpected death in the ward after multivariable adjustment (HR: 1.901; 95% CI 1.357-2.662). Other variables associated with this outcome included age, tracheostomy and mean corpuscular volume (MCV) at ICU discharge. Similar results were obtained after the exclusion of unexpected deaths in the ward (HR 1.940; CI 1.312-2.871) and for in-hospital deaths (HR 1.716; 95% CI 1.141-2.580). CONCLUSIONS: Elevated RDW at ICU discharge is independently associated with ICU readmission and in-hospital death.

Does SOFA predict outcomes better than SIRS in Brazilian ICU patients with suspected infection? A retrospective cohort study.

We compared the discriminatory capacity of the sequential organ failure assessment (SOFA) versus the systemic inflammatory response syndrome (SIRS) score for predicting ICU mortality, need for and length of mechanical ventilation, ICU stay, and hospitalization in patients with suspected infection admitted to a mixed Brazilian ICU. We performed a retrospective analysis of a longitudinal ICU database from a tertiary hospital in Southern Brazil. Patients were categorized according to whether they met the criteria for sepsis according to SOFA (variation ≥2 points over the baseline clinical condition) and SIRS (SIRS score ≥2 points). From January 2008 to December 2014, 1487 patients were admitted to the ICU due to suspected infection. SOFA ≥2 identified more septic patients than SIRS ≥2 (79.0% [n=1175] vs. 68.5% [n=1020], p<0.001). There was no difference between the two scores in predicting ICU mortality (area under the receiver operating characteristic curve (AUROC)=0.64 vs. 0.64, p=0.99). SOFA ≥2 was marginally better than SIRS ≥2 in predicting need for mechanical ventilation (AUROC=0.64 vs. 0.62, p=0.001), ICU stay>7 days (AUROC=0.65 vs. 0.63, p=0.004), and length of hospitalization >10 days (AUROC=0.61 vs. 0.59, p<0.001). There was no difference between the two scores in predicting mechanical ventilation >7 days.

External validation of SAPS 3 and MPM0-III scores in 48,816 patients from 72 Brazilian ICUs.

BACKGROUND: The performance of severity-of-illness scores varies in different scenarios and must be validated prior of being used in a specific settings and geographic regions. Moreover, models' calibration may deteriorate overtime and performance of such instruments should be reassessed regularly. Therefore, we aimed at to validate the SAPS 3 in a large contemporary cohort of patients admitted to Brazilian ICUs. In addition, we also compared the performance of the SAPS 3 with the MPM0-III. METHODS: This is a retrospective cohort study in which 48,816 (medical admissions = 67.9%) adult patients are admitted to 72 Brazilian ICUs during 2013. We evaluated models' discrimination using the area under the receiver operating characteristic curve (AUROC). We applied the calibration belt to evaluate the agreement between observed and expected mortality rates (calibration). RESULTS: Mean SAPS 3 score was 44.3 ± 15.4 points. ICU and hospital mortality rates were 11.0 and 16.5%. We estimated predicted mortality using both standard (SE) and Central and South American (CSA) customized equations. Predicted mortality rates were 16.4 ± 19.3% (SAPS 3-SE), 21.7 ± 23.2% (SAPS 3-CSA) and 14.3 ± 14.0% (MPM0-III). Standardized mortality ratios (SMR) obtained for each model were: 1.00 (95% CI, 0.98-0.102) for the SAPS 3-SE, 0.75 (0.74-0.77) for the SAPS 3-CSA and 1.15 (1.13-1.18) for the MPM0-III. Discrimination was better for SAPS 3 models (AUROC = 0.85) than for MPM0-III (AUROC = 0.80) (p < 0.001). We applied the calibration belt to evaluate the agreement between observed and expected mortality rates (calibration): the SAPS 3-CSA overestimated mortality throughout all risk classes while the MPM0-III underestimated it uniformly. The SAPS 3-SE did not show relevant deviations from ideal calibration. CONCLUSIONS: In a large contemporary database, the SAPS 3-SE was accurate in predicting outcomes, supporting its use for performance evaluation and benchmarking in Brazilian ICUs.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

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.