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Three Part Question

In adults with [severe sepsis or septic shock] do [low dose steroids] improve [outcome]?

Clinical Scenario

You were called to see a 56 year old woman who was admitted to a medical ward two days before with a right basal pneumonia. She was in respiratory failure, hypotensive and oliguric. After intubation, ventilation, resuscitation with fluids she remains hypotensive and a vasopressor has been started. You wonder whether she would benefit from low-dose steroids?

Search Strategy

Medline: 2002 to August 2004 using the Ovid interface
[(exp SEPSIS/ or exp SEPSIS SYNDROME/ or sepsis.mp.) OR (exp Shock, Septic/ or septic shock.mp.)] AND [(exp STEROIDS/ or steroids.mp.) OR (exp Adrenal Cortex Hormones/ or corticosteroids.mp.) OR (exp GLUCOCORTICOIDS/ or glucocorticoids.mp.)] limit to human

Search Outcome

353 citations identified. By limiting this startegy to clinical trials and meta-analyses the citations were reduced to 33. Only 6 appeared relevant to the question. One was a meta-analysis (Minneci 2004). There were three relevant trials, one trial in ARDS, and one best evidence summary. A further meta-analysis (Annane 2004) not yet on Medline had previously been identified. As there were no trials not covered by the meta-analyses only these were reviewed.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Annane 2004 France		Meta-analysis	All cause mortality	Relative risk 0.80 (95% CI, 0.67 to 0.95, P=0.01)
			ICU mortality	Relative risk 0.83 (95% CI, 0.70 to 0.97, P=0.02)
			Hospital mortality	Relative risk 0.83 (95% CI, 0.71 to 0.97, P=0.02)
			Shock reveral at day 7	Relative risk 1.60 (95% CI, 1.27 to 2.03, P<0.0001)
			Shock reversal at day 28	Relative risk 1.26 (95% CI, 1.04 to 1.52, P=0.02)
Minneci 2004 USA		Meta-analysis	Survival	Relative risk 1.23 (95% CI, 1.01 to 1.50, P=0.036)	Only 4 of the 5 studies presented data for shock reversal
			Shock reversal	Relative risk 1.71 (95% CI, 1.29 to 2.26, P<0.001)

Comment(s)

Both meta-analyses identified the same 5 randomised controlled trials of low dose steroids in severe sepsis and septic shock. These included 463 patients, however nearly 70% were from one study by Annane et al (2002). Only 3 studies included data on responses to corticotropin stimulation testing.

Clinical Bottom Line

Patients with severe sepsis or septic shock should be given low dose steroids (200-300 mg hydrocortisone) for 5-7 days.

References

1. Annane D, Bellisant E, Bollaert PE, Briegel J, Keh D, Kupfer Y Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis BMJ 2004; 326: 480-488
2. Minneci PC, Deans KJ, Banks SM, Eichacker PQ, Natanson C Meta-analysis: the effects of steroids on survival and shock during sepsis depends on dose Annals of Internal Medicine 2004; 141: 47-56