Introduction (Article introduction authored by ICU Editorial Team) The use of corticosteroids in managing sepsis and septic shock remains contentious despite extensive evaluation in randomized controlled trials (RCTs), systematic reviews, and meta-analyses. While some previous analyses suggest a potential decrease in mortality, the evidence supporting this is often of low certainty. Conversely, more robust evidence indicates that corticosteroids can effectively reverse shock and improve organ dysfunction compared to standard care or placebo. Nevertheless, significant uncertainties persist, particularly regarding which specific patient groups might benefit most from corticosteroid therapy and whether variations in dosage, duration, or type of corticosteroid affect treatment outcomes. To address these uncertainties, recent years have seen a proliferation of new RCTs investigating the efficacy and safety of corticosteroids in sepsis and septic shock patients. By integrating findings from these latest studies, the aim is to refine evidence summaries and offer clinicians clearer guidance on the appropriate use of corticosteroids in managing sepsis, ultimately aiming to enhance patient outcomes in this critical condition. Methods The study protocol was registered on Open Science Framework and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligibility criteria encompassed randomized controlled trials (RCTs) focusing on corticosteroid use in critically ill adults and pediatric patients with sepsis or septic shock, excluding case reports and observational studies. Data collection included trial specifics, patient demographics, intervention details, and outcomes such as mortality, shock reversal, and adverse events. Risk of bias was assessed using the modified Cochrane tool, with statistical methods including pairwise and dose-response meta-analyses. A thorough search strategy was employed to identify relevant studies, updated from a previous review, covering trials released between January 1, 2018, and January 1, 2023. Two independent reviewers screened titles and abstracts, proceeding to full-text screening for potentially relevant studies. Data extraction involved capturing trial characteristics and outcome measures. Subgroup analyses were conducted based on corticosteroid type, patient demographics, and treatment duration, alongside sensitivity analyses including meta-regression and dose-response meta-analysis. The certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, providing a comprehensive assessment of corticosteroid efficacy and safety in managing sepsis and septic shock. Results The search yielded 1702 unique citations, identifying 11 new eligible RCTs since the previous review. Among these, seven RCTs assessed combination therapy involving corticosteroids, ascorbic acid, and thiamine, which were excluded from the primary analysis. In total, 45 RCTs were included in the updated analysis, comprising 42 trials from the previous review and three newly identified RCTs. Among these, seven trials were part of a secondary sensitivity analysis. Of the 45 RCTs, 20 were conducted across multiple centers, while 25 were single-center studies. Twenty-seven trials specifically targeted patients with septic shock, while others enrolled patients with conditions such as community-acquired pneumonia (CAP), acute respiratory distress syndrome (ARDS), or both. Hydrocortisone was the most frequently used corticosteroid, administered at varying doses across studies. All included trials enrolled patients based on previous Sepsis 1 or Sepsis 2 diagnostic criteria.
