Stress Dose Steroids for Sepsis

ClinicalScenario

34 year-old immuno-suppressed male with severe erythrodermic psoriasis develops hypotension and suspected septic shock. In addition to antibiotics, fluids, and vasopressors, stress dose steroids are administered in the hopes of improving hemodynamics.

Clinical Question

In critically ill patients with sepsis, does the use of stress-dose hydrocortisone reduce the severity/duration of shock?

Article

“Stress doses of hydrocortisione reverse hyperdynamic septic shock: A prospective randomized, double blind, single center study,” Briegel J, et al. Critical Care Medicine. April 1999, 27,4.

Critical Review

I. Are the results valid?

1. Was the assignment of patients to treatments randomized? Yes, 40 patients were randomized into 2 arms of the study. 20 patients received IV hydrocortisone and 20 patients to receive IV saline.

2. Were all the patients who entered the trial properly accounted for and attributed at its conclusion? Yes, all patients were followed until vasopressors were discontinued or death and then up to a year. All deaths of patients still on vasopressors were counted as treatment failures.

3. Were all patients, health workers, and study personnel masked to treatment? Yes, this was a double blind study. The drug preparations was mixed by research assistance who were not involved in patient care or the study.

4. Were the groups similar at the start of the trial? Yes, the baseline characteristics are similar. There are no statistically significant differences in the 2 groups. (Table 1)

5. Aside from experimental intervention, were the groups treated equally? Yes, the concomitant therapies had no statistically significant differences. (Table 2)

II. What are the results?

1. How large was a treatment effect? Patients in the treatment group recovered hemodynamic stability (as defined as cessation of vasopressors) quicker than the placebo group. The median days to cessation of vasopressors in the treatment group was 2 days (1^st and 3^rd quartiles, 1 and 6 days), as compared to 7 days (1^st and 3^rd quartiles, 3 and 19 days) in the placebo group. There are no clear chronologic endpoints. (oops)

The data was extrapolated: (2 random days picked days 3 and 7 from Figure 3)

Day 3 – CER 0.9, EER 0.5, RRR 0.44, ARR 0.4 (95% CI : 0.14-0.66), NNT 2.5

Day 7 – CER 0.4, EER 0.15, RRR 0.0.625, ARR 0.25 (95% CI : 0.02-0.52), NNT 4

(CER – Control Event Rate, EER – Experimental Event Rate)

Shock reversal was achieved in 18/20 in the hydrocortisone group and 16/20 in the control group. Overall shock reversal and mortality were not different. 30 patients survived discharge (4 deaths in treatment group and 6 in control group) 14/20 in treatment group and 14 in placebo group alive at 1 year.

2. How precise was the estimate of the treatment effect? The confidence intervals were large, so it is difficult to assess the treatment effect. Still, the confidence intervals did not cross zero. This indicates that the steroids probably have a positive effect.

III. Will the results help me in caring for my patients?

1. Can the results be applied to my patient care? Yes, we frequently treat patients in the MICU in their 40-50’s with sepsis excluding those with hemorrhage, MI, etc.

2. Were all clinically important outcomes considered? Most, the primary endpoint is time to resolution of sepsis but secondary endpoints were hemodynamic monitoring and organ failure. Patients were followed up to 1 year and total mortality was calculated. This finding was not significantly different. This study was not intended to study mortality and probably was not powered to do so.

3. Are the likely treatment benefits worth the potential harm and costs? Unclear. Patients did appear to hemodynamically improve quicker on the hydrocortisone. Overall, cost was not addressed but the cost of hydrocortisone is vastly lower than vasopressors and the hemodynamic monitoring involved in their use. The only questionable harm was a GI bleed in the treatment group. Whether or not that was directly caused by the drug is unknown. Still, I do not think that I would give stress dose steroids because of the unclear effects and no mortality benefit shown in this and many other studies.