The use of corticosteroids in the treatment of septic shock has long been a subject of debate and investigation. Despite numerous trials and study-level meta-analyses, a clear consensus regarding the role of corticosteroids in septic shock management has remained elusive. Now, a patient-level meta-analysis offers a comprehensive perspective, shedding light on the efficacy of hydrocortisone in this critical condition as published in the New England Journal Of Medicine Evidence by Romain Pirracchio and colleagues.


Septic shock, a life-threatening complication of severe infections, demands effective treatment strategies to improve patient outcomes. In this context, corticosteroids have been considered as potential adjunctive therapies, aiming to modulate the immune response and reduce inflammation. However, the diverse results of previous studies have fueled uncertainty about the benefits of corticosteroids in septic shock.
A recent patient-level meta-analysis sought to provide more precise estimates of treatment effects and subgroup effects of hydrocortisone in septic shock management. Pooled individual patient data from 17 trials involving 7,882 participants were analyzed, with the primary outcome being 90-day all-cause mortality.
● The findings of this comprehensive analysis revealed intriguing insights. The relative risk (RR) for 90-day mortality with hydrocortisone versus placebo was 0.93, suggesting no significant reduction in mortality (P=0.22; moderate certainty).

● When hydrocortisone was combined with fludrocortisone, the RR decreased to 0.86, indicating a potential positive effect.
● However, when hydrocortisone was used without fludrocortisone, the RR increased to 0.96, reflecting a lack of significant impact.
Crucially, the analysis did not identify a significant differential treatment effect across predefined subgroups, suggesting that the impact of hydrocortisone remains consistent regardless of specific patient characteristics.
While the primary outcome did not demonstrate a substantial reduction in mortality, the study also assessed secondary outcomes. Notably, hydrocortisone exhibited little to no difference in most secondary outcomes, except for vasopressor-free days, which showed a notable mean difference. Additionally, hydrocortisone did not appear to significantly increase the risk of superinfection, hyperglycemia, or gastroduodenal bleeding.
However, the analysis did indicate that hydrocortisone might be associated with an increased risk of hypernatremia and muscle weakness, albeit with low certainty.
These findings challenge previous assumptions about the efficacy of hydrocortisone in septic shock management. As patient-level meta-analyses provide a more granular perspective, they serve as valuable tools for clinicians and researchers to make informed decisions based on robust evidence.
In conclusion, this patient-level meta-analysis underscores the complex nature of septic shock management and the potential limitations of hydrocortisone as an adjunctive therapy. While not definitively dismissing its utility, the study emphasizes the need for ongoing research and critical evaluation of treatment approaches in septic shock, a condition where timely and effective interventions can make a life-saving difference.
Reference:
Pirracchio, R., Annane, D., Waschka, A. K., Lamontagne, F., Arabi, Y. M., Bollaert, P.-E., Billot, L., Du, B., Briegel, J., Cohen, J., Finfer, S., Gordon, A., Hammond, N., Hyvernat, H., Keh, D., Li, Y., Liu, L., Meduri, G. U., Mirea, L., … Delaney, A. (2023). Patient-level meta-analysis of low-dose hydrocortisone in adults with septic shock. NEJM Evidence, 2(6). https://doi.org/10.1056/evidoa2300034.