RESUMO
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.
Assuntos
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
BACKGROUND: High intraoperative PEEP with recruitment manoeuvres may improve perioperative outcomes. We re-examined this question by conducting a patient-level meta-analysis of three clinical trials in adult patients at increased risk for postoperative pulmonary complications who underwent non-cardiothoracic and non-neurological surgery. METHODS: The three trials enrolled patients at 128 hospitals in 24 countries from February 2011 to February 2018. All patients received volume-controlled ventilation with low tidal volume. Analyses were performed using one-stage, two-level, mixed modelling (site as a random effect; trial as a fixed effect). The primary outcome was a composite of postoperative pulmonary complications within the first week, analysed using mixed-effect logistic regression. Pre-specified subgroup analyses of nine patient characteristics and seven procedure and care-delivery characteristics were also performed. RESULTS: Complete datasets were available for 1913 participants ventilated with high PEEP and recruitment manoeuvres, compared with 1924 participants who received low PEEP. The primary outcome occurred in 562/1913 (29.4%) participants randomised to high PEEP, compared with 620/1924 (32.2%) participants randomised to low PEEP (unadjusted odds ratio [OR]=0.87; 95% confidence interval [95% CI], 0.75-1.01; P=0.06). Higher PEEP resulted in 87/1913 (4.5%) participants requiring interventions for desaturation, compared with 216/1924 (11.2%) participants randomised to low PEEP (OR=0.34; 95% CI, 0.26-0.45). Intraoperative hypotension was associated more frequently (784/1913 [41.0%]) with high PEEP, compared with low PEEP (579/1924 [30.1%]; OR=1.87; 95% CI, 1.60-2.17). CONCLUSIONS: High PEEP combined with recruitment manoeuvres during low tidal volume ventilation in patients undergoing major surgery did not reduce postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT03937375 (Clinicaltrials.gov).
Assuntos
Pneumopatias , Respiração com Pressão Positiva , Adulto , Humanos , Pulmão , Pneumopatias/epidemiologia , Pneumopatias/etiologia , Respiração com Pressão Positiva/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Volume de Ventilação PulmonarRESUMO
Introdução: O transplante de fígado melhorar significativamente a taxa de sobrevivência de crianças e adolescentes com doença hepática terminal. Os pacientes, uma vez que tinha um prognóstico fatal, hoje podem ser submetidos a transplante de fígado (TF), com taxas de sobrevida de aproximadamente 90% em um ano. A atresia biliar é a principal indicação para a população pediátrica e para aqueles sofreram uma portoenterostomia e não obtiveram bons resultados com a mesma, representando mais de 50% das crianças menores de 2 anos na Europa e nos EUA. O transplante representa a única opção restante de sobrevivência com um bom benefício terapêutico. Os avanços nos cuidados cirúrgicos e clínicos, levaram a melhoria das técnicas para aumentar a sobrevida dos pacientes submetidos a transplante de fígado. Porém, a hemorragia e as complicações biliares representam o tendão de Aquiles do desenvolvimento deste processo. Além disso, a escassez de órgãos para a população pediátrica motiva o desenvolvimento de novas modalidades de enxertos de fígado, como a redução do enxerto de fígado, o transplante de fígado dividido, e mais recentemente o de doadores vivos. As complicações arteriais e biliares continuam a ser uma importante causa de morbidade, mortalidade e perda do enxerto após o transplante...
Introduction: Liver transplantation greatly improved the survival rate of children and adolescents with terminal liver diseases. Patients, who once had a fatal prognosis, today can be submitted to liver transplantation (LxT), with survival rates of approximately 90% in one year. The biliary atresia is the main indication in the pediatric population and for those for whom underwent a portoenterostomy and did not obtain good results with it, representing more than 50% of children under the age of 2 years in Europe and the U.S, transplantation represents the only remaining therapeutic option with good survival benefit. Advances in clinical care and surgical techniques led to improved survival of patients undergoing liver transplantation, but still the arterial and biliary complications represent the Achilles tendon in the development of this procedure. Moreover, the shortage of organs for the pediatric population motivate the development of new modalities of liver grafts, such as reduced liver graft, the split-liver transplantation and more recently the living donors. Despite the improved results, vascular arterial and biliary remain an important cause of morbidity, mortality and graft loss after transplantation. Methods: Survey in Pubmed and Lilacs to gather data related complications of pediatric liver transplantation between 1999 to 2009...