There was no statistical difference in developing septic shock within 14 days in the placebo arm versus the hydrocortisone arm (difference, −1.8%; 95% CI; −10.7% to 7.2%; P = .70). There was no statistical differences in mortality at 28, 90, or 180 days. More delirium was noted in the placebo arm versus the hydrocortisone arm. There was no statistical difference in adverse events except more episodes of hyperglycemia in the hydrocortisone arm versus the placebo arm (see Table 1).
1) Power: One issue with the study is its power to detect a difference. It was designed to detect an absolute difference of 15 percent between the hydrocortisone group and placebo group with a significance level of 0.05 (P value) and power of 0.8. It only found a 1.8 percent difference favoring hydrocortisone that was not statistically significant. Perhaps, a larger sample size would have confirmed this difference. It also assumed 40 percent of the patients in the placebo group would have septic shock, but the observed rate was only 23 percent. As prevalence goes down, the required sample size goes up. In the end, this resulted in an underpowered study.
2) Measurement Bias: Another issue is measurement bias. Progression from severe sepsis to septic shock is not a very precise measure and exists on a continuum. It is somewhat subjective despite being based on quantitative measures.
3) Clinical Versus Statistical Significance: One of the most important problems with this study is the issue of clinical versus statistical significance. Even if the study was properly sized to detect a smaller difference that was statistically significant, it may not be clinically significant. Progression from severe sepsis to septic shock is a disease-oriented outcome, not a patient-oriented outcome like mortality.
This underpowered study failed to detect a statistical difference in a surrogate marker between IV hydrocortisone and placebo in adult patients with severe sepsis.
The use of IV hydrocortisone cannot be recommended at this time to treat adult patients with severe sepsis in order to prevent septic shock.
You choose not to start IV hydrocortisone but continue with IV fluids, IV antibiotics, and supplemental oxygen.
Thank you to Dr. Salim Rezaie from REBEL EM for his help with this review. Dr. Rezaie is an emergency physician from San Antonio, Texas.