Corticosteroid Therapy For Sepsis: A Clinical Practice Guideline & Updated Evidence
Do corticosteroids reduce death or improve recovery in people with sepsis or septic shock?
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.
Two new trials of corticosteroid treatment for sepsis came to differing conclusions. One trial showed lower sepsis-related mortality (APROCCHSS), and one did not (ADRENAL). With that background, participants in the BMJ Rapid Recommendations project- who respond to new evidence by providing timely practice guidelines in many fields - used an updated meta-analysis (with 42 randomized trials and >10,000 patients) to construct a clinical practice guideline on use of systemic corticosteroids for patients with septic shock.
“Our panel makes 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”, the authors write in the research paper published in the BMJ.
Sepsis-related organ failure assessment (SOFA) score to help diagnose sepsis
Current recommendations for corticosteroid therapy in patients with sepsis
Understanding the recommendation
• There was better survival in the group taking corticosteroids, but this was not certain. This drives a weak rather than strong recommendation.
• Corticosteroids may reduce mortality in the first month after admission to an ICCU by approximately 2%.
• Corticosteroids may reduce the length of ICU and hospital stay by less than a day each (moderate quality evidence).
• The impact of corticosteroids on other patient-important outcomes such as stroke and myocardial infarction was extremely uncertain.
• They may increase the risk of neuromuscular weakness by a small amount (low quality evidence from seven RCTs). Possible explanations include the toxic effects on nerve and muscle cells, and hyperglycaemia from corticosteroid use.
• This recommendation applies to all patients with sepsis. There was no meaningful difference in the efficacy of corticosteroids in different groups of patients including those with septic shock, pneumonia, acute respiratory distress syndrome, or other sources of sepsis, or those who were sicker.
• However, the absolute reduction in mortality from corticosteroids will be greater in patients with a higher risk of death. The absolute harm (such as neuromuscular weakness) will also be greater in sicker patients.
• The typical hydrocortisone dose for an adult in the RCTs was 200-300mg/day, given either as an infusion or as boluses every six hours. If an infusion is chosen, a bolus of 50-100mg can be given before the infusion.
• In the RCTs the duration of treatment was typically 7-14 days, or less for those who were rapidly improving. Inflammation may recur after discontinuing corticosteroid therapy, especially when it is stopped abruptly.
• Clinicians should carefully monitor all patients after discontinuing corticosteroids. In patients who deteriorate after stopping corticosteroids (such as development of shock or need for mechanical ventilation), reinitiating corticosteroid therapy could be helpful, although this is highly speculative.
• Whether corticosteroids should be tapered rather than stopped abruptly is unclear. Corticosteroid induced adrenal suppression is probably duration dependent, and so patients who receive longer courses of corticosteroids (such as >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.