Minneci, 2004

5- to 7-day courses of physiological dose hydrocortisone increase survival rates and shock reversal in patients with vasorpressor dependant septic shock.

Level of Evidence: 1⁺

Lead author's name and fax: PC Menneci. Critical care Medicine Department, National Instutute of Health, 10 Center Drive, Building 10, Room 7D43, Bethesda, MD 20892; pminneci@mail.cc.nih.gov

Three-part Clinical Question: Dose the administration of corticosteroids to patients with sepsis reverse shock or improve survival

Study Selection: Randomized, controlled trial design; enrollment of adult patients who ,et criteria for sepsis or septic shock; and a primary end point, included either the discontinuation of vasopressor therapy or a change in survival comparing glucocorticoid treatment with control group with placebo. Similar management of control and intervention groups with the exception of the trial drug.

Data Extraction: Presence of sepsis, severe sepsis, or septic shock; type, dose and duration of steroid; incidence and severity of secondary infection; response to ACTH test; number of patients with shock reversal; the number of deaths.
The studies were multiple independent reviews of individual reports. They were tested for heterogeneity.

Mortality: 13 studies included in the mortality analysis. Overall there was no survival benefit with steroids (Relative Survival Benefit 1.01 (95%CI 0.94-1.09) but there was significant heterogeneity within this group. When the 4 studies published after 1997 were considered separately there was a significant outcome benefit (RSB 1.23 (1.01-1.5). All of these studies used low dose steroids for 5-7 days. There studies demonstrated significant homogeneity.

Shock Reversal: 3 of the 4 trials published after 1997 demonstrated significant shock reversal with steroids.

ACTH Testing: Three of the studies published after 1997 stratified their patients into responders and non-responders to an ACTH stimulation test. The definitions of response differed between the studies. The treatment effect of steroids on mortality or shock reversal did not differ significantly on the basis of this division when these trials were combined (p=0.2 for all).

1) Do the methods allow accurate testing of the hypothesis? Yes
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
4) Did results get omitted, and why? No (interesting to note that one study was excluded from this meta-analysis which was included in Annane’s (Chawla et al, 1999), as no outcome data was presented in the published abstract)
5) Did they suggest areas of further research? Yes – To determine whether physiological doses of hydrocortisone are beneficial if administered to septic patients who do not develop shock or patients who develop shock but have not yet advanced to a pressor-dependant state.
6) Did they make any recommendations based on the results and were they appropriate? Yes – Patients with vasopressor dependant shock of between 2 and 72 hours duration should be given a 5-7 day course of 200-300mg hydrocortisone followed by a 5-7 day taper. This is not dependant on response to ACTH. Seems a reasonable conclusion. The author of this review claimed that by using p values based on the events ratios there was not a significant difference in response to steroid between responders and non-responders. In the original papers, where there was a difference, the authors used a test that compared time to event. This paper should be read in conjunction with Annane’s meta-analysis, which came to different conclusions.
7) Is the study relevant to my clinical practice? Yes
8) What level of evidence does this study represent? 1⁺
9) What grade of recommendation can I make on this result alone? A

10) What grade of recommendation can I make when this study is considered along with other available evidence? A
11) Should I change my practice because of these results? Yes
12) Should I audit my current practice because of these results? Yes

Appraised by: Dr Chris Cairns. Department of Anaesthesia & Critical Care. Stirling Royal Infirmary, Livilands, Stirling, FK8 2AU; Wednesday, October 20, 2004

Citation: EBM Critical Appraisals. Scottish Intensive Care Society EBM Group. Cairns CJS. 2004. Minneci PC, et al. Meta-analysis: The Effect of Steroids on Survival and Shock during Sepsis Depends on the Dose. Ann Int Med. 2004;141:47-56

Sepsis: Low dose steroids improve outcome and reverse shock