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Hydrocortisone therapy for patients with septic shock

Citation/s: CORTICUS; Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. NEJM 2008; 358: 111-124.

Lead author's name and fax: Charles L Sprung

Three-part Clinical Question:

Patients: Patients with septic shock.

Intervention: Corticosteroids.

Outcome: (Primary) 28 day mortality, (Secondary) one year mortality, super infection rates, time to reversal of shock.

Search Terms: Septic shock; corticosteroids

The Study: Double-blinded randomised controlled trial with intention-to-treat.

The Study Patients: Adults (18 years and over) with onset of septic shock within the previous 72 hours and hypoperfusion or organ dysfunction due to sepsis.. (Septic shock defined as: infection with SIRS and systolic BP <90mmHg despite adequate fluid replacement or a need for vasopressors for at least one hour). It is important to note that these inclusion criteria differ from those used by Annane (JAMA, 2002).

Control group (N = 248; 248 analysed): Placebo was an identical white powder made up in identical ampoules of injectable water and was indistinguishable from active drug.

Experimental group (N = 251; 251 analysed): Hydrocortisone 50mg.

Active drug and placebo were given as a bolus every 6 hours for 5 days, then every 12 hours for days 6 to 8, then every 24 hours on days 9 to 11 and then stopped.

The Evidence:

Results in non responders to corticotropin  250 micrograms (defined as an increase of less than 248nmol/l)

Results in responders to corticotropin 250 micrograms (defined as an increase of more than 248nmol/l)

EBM Comments

1)      Do the methods allow accurate testing of the hypothesis?  Yes. This is a well designed, well conducted clinical trial, however slow recruitment led to it being relatively underpowered with only 500 patients recruited when the target had been 800. 

2)      Do the statistical tests correctly test the results to allow differentiation of statistically significant results?  Yes.

3)      Are conclusions valid in light of the results? Yes. The authors conclude that hydrocortisone cannot be recommended as general adjuvant therapy for septic shock, nor can corticotropin testing be recommended to determine which patients should receive hydrocortisone therapy.

4)      Did results get omitted, and why? Yes. One patient withdrew consent and was not analysed.

5)      Did they suggest areas of further research? No.

6)      Did they make any recommendations based on the results and were they appropriate? No.

7)      Is the study relevant to my clinical practice? Yes. The patients recruited appear to be representative of a typical cohort of patients with septic shock that may be found in Scottish ICUs.

8)      What level of evidence does this study represent? 1+

9)      What grade of recommendation can I make on this result alone? B

10)  What grade of recommendation can I make when this study is considered along with other available evidence? B

11)  Should I change my practice because of these results? Yes. In view of the lack of efficacy and possible increase in adverse effects, if you currently use corticosteroids routinely in patients with septic shock or following a synacthen test you should review your practice.  It may be appropriate to continue using steroid therapy “in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy” as stated in the surviving sepsis criteria. This would match the patient sub group identified as benefiting from steroids by Annane (JAMA, 2002).

12)  Should I audit my current practice because of these results? Yes. If you use corticosteroids in septic shock you should audit your rate of complications associated with this.

Appraised by: Kevin Sim, Intensive Care Unit, Aberdeen Royal Infirmary; 12 January 2008
Email: kevin.sim@nhs.net

Reviewed by  Chris Cairns

©SICS EBMG 2009

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