What you need to know Sepsis is a syndrome of life threatening infection with organ dysfunction, and most guidelines do not advise use of corticosteroids to treat it in the absence of refractory shock Two new trials of corticosteroid treatment for sepsis came to differing conclusions Corticosteroids may reduce the risk of death by a small amount and increase neuromuscular weakness by a small amount, but the evidence is not definitive This guideline makes a weak recommendation for corticosteroids in patients with sepsis; both steroids and no steroids are reasonable management options Fully informed patients who value avoiding death over quality of life and function would likely choose corticosteroids Do corticosteroids reduce death or improve recovery in people with sepsis or septic shock? Our panel make a weak recommendation to give corticosteroids to people with all types and severity of sepsis, based on new evidence. Because we are not certain that they are beneficial, it is also reasonable not to prescribe them. Patients’ values and preferences may guide this decision-making process. This rapid recommendation was triggered by two trials, with differing conclusions whose results might change practice: ADRENAL (3658 patients who had septic shock) found no statistically significant difference in 90 day mortality between the hydrocortisone and placebo groups.1 APROCCHSS (1241 patients who had septic shock) found that hydrocortisone plus fludrocortisone reduced 90 day mortality.2 The trials are incorporated into a linked systematic review comparing corticosteroids with placebo.3 This BMJ Rapid Recommendation promptly and transparently translates this evidence using GRADE methodology for trustworthy guidelines. Sepsis is a life threatening organ dysfunction from infection. Currently most guidelines advise against giving corticosteroids in sepsis in the absence of refractory shock, but these guidelines have not taken into account the new evidence. We do not anticipate that new clinical trials will substantively alter the evidence suggesting a small but uncertain mortality reduction. Box 1 shows publications linked in this Rapid Recommendation package. The main infographic provides an overview of the absolute benefits and harms. The table at the end of the article shows any evidence that has emerged since the publication of this guideline. Box 1 Linked articles in the BMJ Rapid Recommendation cluster Lamontagne F, Rochwerg B, Lytvyn L, et al. Corticosteroid therapy for sepsis: a clinical practice guideline. BMJ 2018;362:k3284 Summary of the results from the Rapid Recommendation process Rochwerg B, Oczkowski SJ, Siemieniuk RAC, et al. Corticosteroids in sepsis: an updated systematic review and meta-analysis. Crit Care Med 2018. doi:10.1097/CCM.0000000000003262 3 Review and meta-analysis of all available randomised trials that assessed corticosteroid therapy for sepsis MAGICapp (https://app.magicapp.org/public/guideline/EZ1w8n) Expanded version of the results with multilayered recommendations, evidence summaries, and decision aids for use on all devices Current understanding Sepsis is life threatening organ dysfunction caused by a dysregulated host response to infection.4 In practice, a sepsis-related organ failure assessment (SOFA) score of ≥2 in patients with infections is sepsis (table 1).4 5 Worldwide, about 30 million people are hospitalised with sepsis every year and up to six million of them die.6 Table 1 Sepsis-related organ failure assessment (SOFA) score to help diagnose sepsis (adapted from Vincent et al5)* System or organ and measure SOFA score 0 1 2 3 4 Respiratory: PaO2/FiO2, mm Hg ≥400 300-399 200-299 100-199 with respiratory support 204 (12.0) Circulatory: Mean arterial pressure, mm Hg ≥70 440 (5.0) Urine output, mL/day – – – 14 days) might be particularly likely to benefit from a taper before discontinuing and an evaluation of hypothalamo-pituitary-adrenal axis function if in doubt.12 Costs Corticosteroids are typically inexpensive and widely available. The impact of corticosteroids on the overall costs to patients and to health systems is uncertain and would be driven mostly by ICU and hospital lengths of stay or prolonged periods of rehabilitation. Future research With the exception of the awaited analysis of quality of life in the ADRENAL trial, there are currently no planned or ongoing RCTs in patients who have sepsis that are likely to substantively change the overall effect estimates for the key outcomes. Given remaining uncertainty regarding the effect of corticosteroids in different subgroups, additional analyses of existing data to explore heterogeneity of treatment effects are logical next steps before more patients are enrolled in similar trials. Such work mandates individual patient-data meta-analyses that rely on investigators sharing the data from their RCTs and cooperation among research networks. It is possible that additional adaptive RCTs could help to resolve remaining uncertainty. Key research questions to inform decision makers and future guidelines are: What is the impact of corticosteroid therapy on quality of life in the short and long term? What is the impact of corticosteroid therapy on functional recovery? What is the impact of corticosteroid therapy on healthcare costs? Are there subgroups of patients with sepsis who benefit more or less from corticosteroid therapy? Are there differences between bolus and infusion dosing? Does the addition of fludrocortisone improve outcomes? Updates to this article The final table shows evidence that has emerged since the publication of this article. As new evidence is published, a group will assess the new evidence and make a judgment on to what extent it is expected to alter the recommendation. New evidence which has emerged after initial publication Date New evidence Citation Findings Implications for recommendation(s) There are currently no updates to the article.
