Question special

The mortality rates among the treatment and control groups in both the ADRENAL and APROCCHSS differ significantly – enough perhaps to suggest these may be two different patient populations being studied. The mortality rates of septic shock and standard of care have certainly improved over the past 2 decades since the Rivers trial; however, despite the recency of these trials there is still a significant difference in all-cause mortality from septic shock. Also, the patients in the APROCCHSS trial appear to be sicker at baseline. Do you think this is perhaps why we see a benefit of hydrocortisone/fludrocortisone in these patients?

Given the difference between scoring symptoms (APACHE II for ADRENAL and SAPS for APROCCHS) are we still able to compare these study populations and draw any meaningful conclusions?

Additionally, it looks like surgical ICU patients (about 1/3rd of the study population) were included in the ADRENAL trial. Do you think this also changes the patient population and may contribute to a lack of steroid benefit?