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INTRODUCTION: hemorrhagic shock is a significant cause of trauma-related deaths in Brazil and worldwide. This study aims to compare BE and lactate values at ICU admission and twenty-four hours after in identifying tissue hypoperfusion and mortality. METHODS: examines a historical cohort of trauma patients over eitheen years old submittet to damage control resuscitation approch upon hospital admission and were then admitted to the ICU. We collected and analyzed ISS, mechanism and type of trauma, need for renal replacement therapy, massive transfusion. BE, lactate, pH, bicarbonate at ICU admission and twenty-four hours later, and mortality data. The patients were grouped based on their BE values (≥-6 and <-6mmol/L), which were previously identified in the literature as predictors of severity. They were subsequently redivided using the most accurate values found in this sample. In addition to performing multivariate binary logistic regression. The data were compared using several statistical tests due to diversity and according to the indication for each variable. RESULTS: there were significant changes in perfusion upon admission to the Intensive Care Unit. BE is a statistically significant value for predicting mortality, as determined by using values from previous literature and from this study. CONCLUSION: the results demonstrate the importance of monitoring BE levels in the prediction of ICU mortality. BE proves to be a valuable bedside marker with quick results and wide availability.
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Biomarcadores , Ácido Láctico , Choque Hemorrágico , Humanos , Choque Hemorrágico/mortalidade , Choque Hemorrágico/sangue , Masculino , Feminino , Ácido Láctico/sangue , Adulto , Biomarcadores/sangue , Pessoa de Meia-Idade , Estudos de Coortes , Unidades de Terapia IntensivaRESUMO
Importance: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown. Objective: To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023. Intervention: Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models. Results: Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group. Conclusion and Relevance: The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin. Trial Registration: ClinicalTrials.gov Identifier: NCT05558098.
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Compostos Benzidrílicos , Estado Terminal , Glucosídeos , Insuficiência de Múltiplos Órgãos , Inibidores do Transportador 2 de Sódio-Glicose , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Benzidrílicos/uso terapêutico , Estado Terminal/terapia , Glucosídeos/uso terapêutico , Glucosídeos/efeitos adversos , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Tempo de Internação , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/mortalidade , Terapia de Substituição Renal , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , BrasilRESUMO
ABSTRACT Introduction: hemorrhagic shock is a significant cause of trauma-related deaths in Brazil and worldwide. This study aims to compare BE and lactate values at ICU admission and twenty-four hours after in identifying tissue hypoperfusion and mortality. Methods: examines a historical cohort of trauma patients over eitheen years old submittet to damage control resuscitation approch upon hospital admission and were then admitted to the ICU. We collected and analyzed ISS, mechanism and type of trauma, need for renal replacement therapy, massive transfusion. BE, lactate, pH, bicarbonate at ICU admission and twenty-four hours later, and mortality data. The patients were grouped based on their BE values (≥-6 and <-6mmol/L), which were previously identified in the literature as predictors of severity. They were subsequently redivided using the most accurate values found in this sample. In addition to performing multivariate binary logistic regression. The data were compared using several statistical tests due to diversity and according to the indication for each variable. Results: there were significant changes in perfusion upon admission to the Intensive Care Unit. BE is a statistically significant value for predicting mortality, as determined by using values from previous literature and from this study. Conclusion: the results demonstrate the importance of monitoring BE levels in the prediction of ICU mortality. BE proves to be a valuable bedside marker with quick results and wide availability.
RESUMO Introdução: o choque hemorrágico é a principal causa reversível de morte no trauma no Brasil e no mundo. Objetivo: comparar o valor de BE ao do lactato na admissão da UTI e vinte e quatro horas após o internamento na identificação de hipoperfusão tecidual e predição de mortalidade Método: coorte histórica de pacientes traumatizados, maiores de dezoito anos, submetidos à estratégia de controle de danos na admissão hospitalar, seguido de internamento em UTI. Foram coletados e analisados ISS, mecanismo e tipo de trauma, necessidade de terapia de substituição renal e transfusão maciça; BE, lactato, pH e bicarbonato coletados na admissão da UTI e vinte e quatro horas após, e a mortalidade. Os pacientes foram divididos em grupos conforme valores de BE (≥-6 e <-6mmol/L) já descritos na literatura como preditores de gravidade, e após redivididos de acordo com os valores de melhor acurácia encontrados nesta amostra, além de realização de regressão logística binária multivariada. Os dados foram comparados através de diversos testes estatísticos devido a diversidade e conforme a indicação para cada variável. Resultados: houve alterações perfusionais impactantes já na admissão da UTI. BE manteve-se com valor estatisticamente significativo para predição de mortalidade tanto quando utilizado os valores já conhecidos da literatura como quando aplicados os valores neste estudo identificados. Conclusão: valores de BE e de lactato foram capazes de predizer hipoperfusão tecidual e mortalidade nos dois momentos estudados, quando comparados, o BE tem boa performance como preditor de mortalidade, com rápido resultado e ampla disponibilidade.
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OBJECTIVE: To evaluate the accuracy of the persistent AKI risk index (PARI) in predicting acute kidney injury within 72 hours after admission to the intensive care unit, persistent acute kidney injury, renal replacement therapy, and death within 7 days in patients hospitalized due to acute respiratory failure. METHODS: This study was done in a cohort of diagnoses of consecutive adult patients admitted to the intensive care unit of eight hospitals in Curitiba, Brazil, between March and September 2020 due to acute respiratory failure secondary to suspected COVID-19. The COVID-19 diagnosis was confirmed or refuted by RT-PCR for the detection of SARS-CoV-2. The ability of PARI to predict acute kidney injury at 72 hours, persistent acute kidney injury, renal replacement therapy, and death within 7 days was analyzed by ROC curves in comparison to delta creatinine, SOFA, and APACHE II. RESULTS: Of the 1,001 patients in the cohort, 538 were included in the analysis. The mean age was 62 ± 17 years, 54.8% were men, and the median APACHE II score was 12. At admission, the median SOFA score was 3, and 83.3% had no renal dysfunction. After admission to the intensive care unit, 17.1% had acute kidney injury within 72 hours, and through 7 days, 19.5% had persistent acute kidney injury, 5% underwent renal replacement therapy, and 17.1% died. The PARI had an area under the ROC curve of 0.75 (0.696 - 0.807) for the prediction of acute kidney injury at 72 hours, 0.71 (0.613 - 0.807) for renal replacement therapy, and 0.64 (0.565 - 0.710) for death. CONCLUSION: The PARI has acceptable accuracy in predicting acute kidney injury within 72 hours and renal replacement therapy within 7 days of admission to the intensive care unit, but it is not significantly better than the other scores.
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Injúria Renal Aguda , COVID-19 , Insuficiência Respiratória , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Teste para COVID-19 , Unidades de Terapia Intensiva , Injúria Renal Aguda/diagnóstico , COVID-19/diagnóstico , Insuficiência Respiratória/diagnósticoRESUMO
BACKGROUND: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated. METHODS: DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study. CONCLUSION: DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients. CLINICALTRIALS.GOV REGISTRY: NCT05558098.
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Estado Terminal , Inibidores do Transportador 2 de Sódio-Glicose , Adulto , Humanos , Estado Terminal/terapia , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Estudos Multicêntricos como AssuntoRESUMO
ABSTRACT Objective: To compare, within a cohort of patients with acute respiratory failure, the phenotypes of patients with and without COVID-19 in the context of the pandemic and evaluate whether COVID-19 is an independent predictor of intensive care unit mortality. Methods: This historical cohort study evaluated 1001 acute respiratory failure patients with suspected COVID-19 admitted to the intensive care unit of 8 hospitals. Patients were classified as COVID-19 cases and non-COVID-19 cases according to real-time polymerase chain reaction results. Data on clinical and demographic characteristics were collected on intensive care unit admission, as well as daily clinical and laboratory data and intensive care unit outcomes. Results: Although the groups did not differ in terms of APACHE II or SOFA scores at admission, the COVID-19 group had more initial symptoms of fever, myalgia and diarrhea, had a longer duration of symptoms, and had a higher prevalence of obesity. They also had a lower PaO2/FiO2 ratio, lower platelet levels than non-COVID-19 patients, and more metabolic changes, such as higher levels of blood glucose, C-reactive protein, and lactic dehydrogenase. Patients with non-COVID-19 acute respiratory failure had a higher prevalence of chronic obstructive pulmonary disease/asthma and cardiopathy. Patients with COVID-19 stayed in the hospital longer and had more complications, such as acute kidney failure, severe acute respiratory distress syndrome and severe infection. The all-cause mortality rate was also higher in this group (43.7% in the COVID-19 group versus 27.4% in the non-COVID-19 group). The diagnosis of COVID-19 was a predictor of intensive care unit mortality (odds ratio, 2.77; 95%CI, 1.89 - 4.07; p < 0.001), regardless of age or Charlson Comorbidity Index score. Conclusion: In a prospective cohort of patients admitted with acute respiratory failure, patients with COVID-19 had a clearly different phenotype and a higher mortality than non-COVID-19 patients. This may help to outline more accurate screening and appropriate and timely treatment for these patients.
RESUMO Objetivo: Comparar, em uma coorte de pacientes com insuficiência respiratória aguda, os fenótipos de pacientes com e sem COVID-19, no contexto da pandemia, e avaliar se a COVID-19 é um preditor independente de mortalidade na unidade de terapia intensiva. Métodos: Este estudo de coorte histórico avaliou 1.001 pacientes com insuficiência respiratória aguda e suspeita de COVID-19 internados na unidade de terapia intensiva de oito hospitais. Os pacientes foram classificados como casos com e sem COVID-19 segundo os resultados da RT-PCR. Foram coletados dados sobre características clínicas e demográficas na admissão à unidade de terapia intensiva, bem como dados clínicos e laboratoriais diários e desfechos da unidade de terapia intensiva. Resultados: Embora os grupos não tenham diferido nos escores APACHE II ou SOFA na admissão, o grupo COVID-19 apresentou mais sintomas iniciais de febre, mialgia e diarreia e teve maior duração dos sintomas e maior prevalência de obesidade. Eles também apresentaram menor relação PaO2/FiO2 e níveis mais baixos de plaquetas do que os pacientes sem COVID-19 e mais alterações metabólicas, como níveis mais altos de glicemia, proteína C-reativa e desidrogenase lática. Os pacientes com insuficiência respiratória aguda sem COVID-19 apresentaram maior prevalência de doença pulmonar obstrutiva crônica/asma e cardiopatia. Os pacientes com COVID-19 permaneceram mais tempo no hospital e tiveram mais complicações, como insuficiência renal aguda, síndrome do desconforto respiratório agudo grave e infecção grave. A taxa de mortalidade por todas as causas também foi maior nesse grupo (43,7% no grupo com COVID-19 versus 27,4% no grupo sem COVID-19). O diagnóstico de COVID-19 foi um preditor de mortalidade na unidade de terapia intensiva (razão de chances de 2,77; IC95% 1,89 - 4,07; p < 0,001), independentemente da idade ou da pontuação do Índice de Comorbidade de Charlson. Conclusão: Em uma coorte prospectiva de pacientes admitidos com insuficiência respiratória aguda, os pacientes com COVID-19 apresentaram fenótipo claramente diferente e uma mortalidade mais alta do que os pacientes sem COVID-19. Isso pode ajudar a traçar uma triagem mais precisa e um tratamento adequado e oportuno para esses pacientes.
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Acute neurological emergencies are highly prevalent in intensive care units (ICUs) and impose a substantial burden on patients. This study aims to describe the epidemiology of patients requiring neurocritical care in Brazil, and their differences based on primary acute neurological diagnoses and to identify predictors of mortality and unfavourable outcomes, along with the disease burden of each condition at intensive care unit admission. This prospective cohort study included patients requiring neurocritical care admitted to 36 ICUs in four Brazilian regions who were followed for 30 days or until ICU discharge (Aug-Sep in 2018, 1 month). Of 4245 patients admitted to the participating ICUs, 1194 (28.1%) were patients with acute neurological disorders requiring neurocritical care and were included. Patients requiring neurocritical care had a mean mortality rate 1.7 times higher than ICU patients not requiring neurocritical care (17.21% versus 10.1%, respectively). Older age, emergency admission, higher number of potential secondary injuries, and worse APACHE II, SAPS III, SOFA, and Glasgow coma scale scores on ICU admission are independent predictors of mortality and poor outcome among patients with acute neurological diagnoses. The estimated total DALYs were 4482.94 in the overall cohort, and the diagnosis with the highest DALYs was traumatic brain injury (1634.42). Clinical, epidemiological, treatment, and ICU outcome characteristics vary according to the primary neurologic diagnosis. Advanced age, a lower GCS score and a higher number of potential secondary injuries are independent predictors of mortality and unfavourable outcomes in patients requiring neurocritical care. The findings of this study are essential to guide education policies, prevention, and treatment of severe acute neurocritical diseases.
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Efeitos Psicossociais da Doença , Unidades de Terapia Intensiva , Humanos , Brasil/epidemiologia , Estudos Prospectivos , Escala de Coma de Glasgow , Estudos RetrospectivosRESUMO
ABSTRACT Background: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated. Methods: DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study. Conclusion: DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients. ClinicalTrials.gov registry: NCT05558098
RESUMO Antecedentes: A doença crítica é um importante ônus permanente da assistência médica em todo o mundo e está associada a altas taxas de mortalidade. Os inibidores do cotransportador de sódio-glicose do tipo 2 têm demonstrado consistentemente benefícios nos desfechos cardiovasculares e renais. Os efeitos dos inibidores do cotransportador de sódio-glicose do tipo 2 em doenças agudas ainda não foram devidamente investigados. Métodos: O DEFENDER é um estudo de iniciativa do investigador, multicêntrico, randomizado, aberto, desenhado para avaliar a eficácia e a segurança da dapagliflozina em 500 participantes adultos com disfunção orgânica aguda hospitalizados na unidade de terapia intensiva. Os participantes aptos serão randomizados 1:1 para receber 10mg de dapagliflozina e o tratamento padrão por até 14 dias ou apenas o tratamento padrão. O desfecho primário é um composto hierárquico de mortalidade hospitalar, início de terapia renal substitutiva e tempo de internação na unidade de terapia intensiva, até 28 dias. O monitoramento da segurança será rigoroso durante todo o estudo. Conclusão: O DEFENDER é o primeiro estudo desenvolvido para investigar o uso de um inibidor do cotransportador de sódio-glicose do tipo 2 em pacientes de unidade de terapia intensiva geral com disfunção orgânica aguda. O estudo fornecerá informações relevantes sobre o uso de medicamentos dessa classe promissora em pacientes críticos. Registro ClincalTrials.gov: NCT05558098
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ABSTRACT Objective: To evaluate the accuracy of the persistent AKI risk index (PARI) in predicting acute kidney injury within 72 hours after admission to the intensive care unit, persistent acute kidney injury, renal replacement therapy, and death within 7 days in patients hospitalized due to acute respiratory failure. Methods: This study was done in a cohort of diagnoses of consecutive adult patients admitted to the intensive care unit of eight hospitals in Curitiba, Brazil, between March and September 2020 due to acute respiratory failure secondary to suspected COVID-19. The COVID-19 diagnosis was confirmed or refuted by RT-PCR for the detection of SARS-CoV-2. The ability of PARI to predict acute kidney injury at 72 hours, persistent acute kidney injury, renal replacement therapy, and death within 7 days was analyzed by ROC curves in comparison to delta creatinine, SOFA, and APACHE II. Results: Of the 1,001 patients in the cohort, 538 were included in the analysis. The mean age was 62 ± 17 years, 54.8% were men, and the median APACHE II score was 12. At admission, the median SOFA score was 3, and 83.3% had no renal dysfunction. After admission to the intensive care unit, 17.1% had acute kidney injury within 72 hours, and through 7 days, 19.5% had persistent acute kidney injury, 5% underwent renal replacement therapy, and 17.1% died. The PARI had an area under the ROC curve of 0.75 (0.696 - 0.807) for the prediction of acute kidney injury at 72 hours, 0.71 (0.613 - 0.807) for renal replacement therapy, and 0.64 (0.565 - 0.710) for death. Conclusion: The PARI has acceptable accuracy in predicting acute kidney injury within 72 hours and renal replacement therapy within 7 days of admission to the intensive care unit, but it is not significantly better than the other scores.
RESUMO Objetivo: Avaliar a acurácia do persistent AKI risk index (PARI) na predição de injúria renal aguda em 72 horas após a admissão em unidade de terapia intensiva, injúria renal aguda persistente, terapia de substituição renal e óbito, em até 7 dias em pacientes internados por insuficiência respiratória aguda. Métodos: Estudo de método-diagnóstico com base em coorte de inclusão consecutiva de pacientes adultos internados em unidade de terapia intensiva de oito hospitais de Curitiba (PR) entre março e setembro de 2020, por insuficiência respiratória aguda secundária à suspeita de COVID-19, com confirmação ou refutação diagnóstica dada pelo resultado de RT-PCR para detecção do SARS-CoV-2. O potencial preditor do PARI foi analisado por curva ROC em relação a delta creatinina, SOFA e APACHE II, para os desfechos injúria renal aguda em 72 horas; injúria renal aguda persistente; terapia de substituição renal e mortalidade em até 7 dias. Resultados: Dos 1.001 pacientes da coorte, 538 foram incluídos na análise. A média de idade foi de 62 ± 17 anos, 54,8% eram homens e o APACHE II mediano foi de 12. Na admissão, o SOFA mediano era 3, e 83,3% não apresentavam disfunção renal. Após admissão na unidade de terapia intensiva, 17,1% apresentaram injúria renal aguda em 72 horas e, até o sétimo dia, 19,5% apresentaram injúria renal aguda persistente, 5% realizaram terapia de substituição renal, e 17,1% foram a óbito. O PARI apresentou área sob a curva ROC de 0,75 (0,696 - 0,807) para predição de injúria renal aguda em 72 horas, 0,71 (0,613 - 0,807) para terapia de substituição renal e 0,64 (0,565 - 0,710) para mortalidade. Conclusão: O PARI tem acurácia aceitável na predição de injúria renal aguda em 72 horas e terapia de substituição renal em até 7 dias da admissão na unidade de terapia intensiva, porém sem diferença significativa dos demais escores.
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Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones. Postmortem liver biopsies were collected to assess the presence of SARS-CoV-2 and its transporters in hepatocytes. In human hepatocytes, we studied the mechanistic bases of SARS-CoV-2 entrance and its gluconeogenic effect. SARS-CoV-2 infection was independently associated with hyperglycemia, regardless of diabetic history and beta cell function. We detected replicating viruses in human hepatocytes from postmortem liver biopsies and in primary hepatocytes. We found that SARS-CoV-2 variants infected human hepatocytes in vitro with different susceptibility. SARS-CoV-2 infection in hepatocytes yields the release of new infectious viral particles, though not causing cell damage. We showed that infected hepatocytes increase glucose production and this is associated with induction of PEPCK activity. Furthermore, our results demonstrate that SARS-CoV-2 entry in hepatocytes occurs partially through ACE2- and GRP78-dependent mechanisms. SARS-CoV-2 infects and replicates in hepatocytes and exerts a PEPCK-dependent gluconeogenic effect in these cells that potentially is a key cause of hyperglycemia in infected patients.