Continuous vs Intermittent ß-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis: The BLING III Randomized Clinical Trial.

Importance: Whether ß-lactam antibiotics administered by continuous compared with intermittent infusion reduces the risk of death in patients with sepsis is uncertain. Objective: To evaluate whether continuous vs intermittent infusion of a ß-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all-cause mortality at 90 days in critically ill patients with sepsis. Design, Setting, and Participants: An international, open-label, randomized clinical trial conducted in 104 intensive care units (ICUs) in Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the United Kingdom. Recruitment occurred from March 26, 2018, to January 11, 2023, with follow-up completed on April 12, 2023. Participants were critically ill adults (≥18 years) treated with piperacillin-tazobactam or meropenem for sepsis. Intervention: Eligible patients were randomized to receive an equivalent 24-hour dose of a ß-lactam antibiotic by either continuous (n = 3498) or intermittent (n = 3533) infusion for a clinician-determined duration of treatment or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was all-cause mortality within 90 days after randomization. Secondary outcomes were clinical cure up to 14 days after randomization; new acquisition, colonization, or infection with a multiresistant organism or Clostridioides difficile infection up to 14 days after randomization; ICU mortality; and in-hospital mortality. Results: Among 7202 randomized participants, 7031 (mean [SD] age, 59 [16] years; 2423 women [35%]) met consent requirements for inclusion in the primary analysis (97.6%). Within 90 days, 864 of 3474 patients (24.9%) assigned to receive continuous infusion had died compared with 939 of 3507 (26.8%) assigned intermittent infusion (absolute difference, -1.9% [95% CI, -4.9% to 1.1%]; odds ratio, 0.91 [95% CI, 0.81 to 1.01]; P = .08). Clinical cure was higher in the continuous vs intermittent infusion group (1930/3467 [55.7%] and 1744/3491 [50.0%], respectively; absolute difference, 5.7% [95% CI, 2.4% to 9.1%]). Other secondary outcomes were not statistically different. Conclusions and Relevance: The observed difference in 90-day mortality between continuous vs intermittent infusions of ß-lactam antibiotics did not meet statistical significance in the primary analysis. However, the confidence interval around the effect estimate includes the possibility of both no important effect and a clinically important benefit in the use of continuous infusions in this group of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03213990.

A Genome-Wide Association Study of Serum Metabolite Profiles in Septic Shock Patients.

OBJECTIVES: We sought to assess whether genetic associations with metabolite concentrations in septic shock patients could be used to identify pathways of potential importance for understanding sepsis pathophysiology. DESIGN: Retrospective multicenter cohort studies of septic shock patients. SETTING: All participants who were admitted to 27 participating hospital sites in three countries (Australia, New Zealand, and the United Kingdom) were eligible for inclusion. PATIENTS: Adult, critically ill, mechanically ventilated patients with septic shock (n = 230) who were a subset of the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock trial (ClinicalTrials.gov number: NCT01448109). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A genome-wide association study was conducted for a range of serum metabolite levels for participants. Genome-wide significant associations (p ≤ 5 × 10-8) were found for the two major ketone bodies (3-hydroxybutyrate [rs2456680] and acetoacetate [rs2213037] and creatinine (rs6851961). One of these single-nucleotide polymorphisms (SNPs) (rs2213037) was located in the alcohol dehydrogenase cluster of genes, which code for enzymes related to the metabolism of acetoacetate and, therefore, presents a plausible association for this metabolite. None of the three SNPs showed strong associations with risk of sepsis, 28- or 90-day mortality, or Acute Physiology and Chronic Health Evaluation score (a measure of sepsis severity). CONCLUSIONS: We suggest that the genetic associations with metabolites may reflect a starvation response rather than processes involved in sepsis pathophysiology. However, our results require further investigation and replication in both healthy and diseased cohorts including those of different ancestry.

O escore da American Society of Anesthesiologists: ainda útil após 60 anos? Resultados do estudo EuSOS / American Society of Anesthesiologists Score: still useful after 60 years? Results of the EuSOS Study

RESUMO Objetivo: O European Surgical Outcomes Study foi um estudo que descreveu a mortalidade após a cirurgia de pacientes internados. Em uma análise multivariada, foram identificados diversos fatores capazes de prever maus resultados, os quais incluem idade, urgência do procedimento, gravidade e porte, assim como o escore da American Association of Anaesthesia. Este estudo descreveu, com mais detalhes, o relacionamento entre o escore da American Association of Anaesthesia e a mortalidade pós-operatória. Métodos: Os pacientes neste estudo de coorte com duração de sete dias foram inscritos em abril de 2011. Foram incluídos e seguidos, por no máximo 60 dias, pacientes consecutivos com idade de 16 anos ou mais, internados e submetidos à cirurgia não cardíaca e com registro do escore da American Association of Anaesthesia em 498 hospitais, localizados em 28 países europeus. O parâmetro primário foi mortalidade hospitalar. Foi utilizada uma árvore decisória, com base no sistema CHAID (SPSS), para delinear os nós associados à mortalidade. Resultados: O estudo inscreveu um total de 46.539 pacientes. Em função de valores faltantes, foram excluídos 873 pacientes, resultando na análise 45.666. Aumentos no escore da American Association of Anaesthesia se associaram com o acréscimo das taxas de admissão à terapia intensiva e de mortalidade. Apesar do relacionamento progressivo com mortalidade, a discriminação foi fraca, com uma área sob a curva ROC de 0,658 (IC 95% 0,642 - 0,6775). Com o uso das árvores de regressão (CHAID), foram identificadas quatro discretas associações dos nós da American Association of Anaesthesia com mortalidade, estando o escore American Association of Anaesthesia 1 e o escore da American Association of Anaesthesia 2 comprimidos em um mesmo nó. Conclusão: O escore da American Association of Anaesthesia pode ser utilizado para determinar grupos de pacientes cirúrgicos de alto risco, porém os médicos não podem utilizá-lo para ...

ABSTRACT Objective: The European Surgical Outcomes Study described mortality following in-patient surgery. Several factors were identified that were able to predict poor outcomes in a multivariate analysis. These included age, procedure urgency, severity and type and the American Association of Anaesthesia score. This study describes in greater detail the relationship between the American Association of Anaesthesia score and postoperative mortality. Methods: Patients in this 7-day cohort study were enrolled in April 2011. Consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery with a recorded American Association of Anaesthesia score in 498 hospitals across 28 European nations were included and followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Decision tree analysis with the CHAID (SPSS) system was used to delineate nodes associated with mortality. Results: The study enrolled 46,539 patients. Due to missing values, 873 patients were excluded, resulting in the analysis of 45,666 patients. Increasing American Association of Anaesthesia scores were associated with increased admission rates to intensive care and higher mortality rates. Despite a progressive relationship with mortality, discrimination was poor, with an area under the ROC curve of 0.658 (95% CI 0.642 - 0.6775). Using regression trees (CHAID), we identified four discrete American Association of Anaesthesia nodes associated with mortality, with American Association of Anaesthesia 1 and American Association of Anaesthesia 2 compressed into the same node. Conclusion: The American Association of Anaesthesia score can be used to determine higher risk groups of surgical patients, but clinicians cannot use the score to discriminate between grades 1 and 2. Overall, the discriminatory power of the model was less than acceptable for widespread use. .

Otimização hemodinâmica em trauma grave: uma revisão sistemática e metanálise / Hemodynamic optimization in severe trauma: a systematic review and meta-analysis

Objetivo: O trauma grave pode associar-se a ocorrência de importante choque hemorrágico e ao comprometimento da perfusão dos órgãos. Formulamos a hipótese de que o tratamento direcionado por objetivo conferiria benefícios em termos de morbidade e mortalidade, em casos graves de trauma. Métodos: Realizamos uma busca sistemática nas bases de dados MedLine, Embase e Cochrane Controlled Clinical Trials Register com relação a pacientes vítimas de trauma grave. A mortalidade foi o desfecho primário dessa revisão. Os desfechos secundários incluíram taxas de complicações, duração da permanência no hospital e na unidade de terapia intensiva, e o volume de fluidos administrados. A metanálise foi realizada utilizando o programa de computador RevMan, e os dados apresentados são as odds ratios (OR) para desfechos dicotomizados e as diferenças médias e diferenças médias padrão para desfechos contínuos. Resultados: Foram analisados quatro estudos clínicos randomizados e controlados, que incluíram 419 pacientes. O risco de mortalidade foi significantemente reduzido nos pacientes com tratamento direcionado por objetivo, em comparação ao grupo controle (OR=0,56; IC95%: 0,34-0,92). A duração da permanência na unidade de terapia intensiva (DM: 3,7 dias; IC95%: 1,06-6,5) e no hospital (DM: 3,5 dias; IC95%: 2,75-4,25) foi significantemente mais curta ...

Objective: Severe trauma can be associated with significant hemorrhagic shock and impaired organ perfusion. We hypothesized that goal-directed therapy would confer morbidity and mortality benefits in major trauma. Methods: The MedLine, Embase and Cochrane Controlled Clinical Trials Register databases were systematically searched for randomized, controlled trials of goal-directed therapy in severe trauma patients. Mortality was the primary outcome of this review. Secondary outcomes included complication rates, length of hospital and intensive care unit stay, and the volume of fluid and blood administered. Meta-analysis was performed using RevMan software, and the data presented are as odds ratios for dichotomous outcomes and as mean differences (MDs) and standard MDs for continuous outcomes. Results: Four randomized, controlled trials including 419 patients were analyzed. Mortality risk was significantly reduced in goal-directed therapy-treated patients, compared to the control group (OR=0.56, 95%CI: 0.34-0.92). Intensive care (MD: 3.7 days 95%CI: 1.06-6.5) and hospital length of stay (MD: 3.5 days, 95%CI: 2.75-4.25) were significantly shorter in the protocol group patients. There were no differences in reported total fluid volume or blood transfusions administered. Heterogeneity in reporting among the studies prevented quantitative analysis of complications. Conclusion: Following severe trauma, early goal-directed therapy was associated with lower ...