Sample Handout for steroids and septic shockBob Badgett

8/14/2008

Clinical question in PICO format

In patients with septic shock, can corticosteroids, as compared to placebo, reduce mortality?

Evidence TableStudy, year,

designPatients Intervention

Outcome measured

Results Comments

Spring, 2008 (CORTICUS)PMID: 18184957

RCT

499 patients with septic shock.47% with adrenal insuff (<9mcg cortisol increase after corticotropin test).

50 mg of intravenous hydrocortisone q 6 hrs for 5 days

mortality

Overall:  steroid group 55%  placebo 61% (P =.09) Adrenal normal:  steroid group 29%  placebo 29% (P =1.0)Adrenal insufficient:  steroid group 39%  placebo 36% (P =.69)

These patients were less sick than those in the Annane study (note difference in control group mortality).

Annane, 2002PMID: 17720019

RCT

300 pts, all ventilated.

76% with adrenal insuff (<9mcg cortisol increase after corticotropin test).

hydrocortisone (50 mg q 6 hrs) &fludrocortisone (50 mcg qd)

mortality

Overall:  steroid group 55%  placebo 61% (P =.09) Adrenal normal:  steroid group 61%  placebo 53% (P =.02)Adrenal insufficient:  steroid group 53%  placebo 63% (P =.02)

First study with sufficient power.

Cotreated with fludrocortisone.

Briegel, 1999PMID: 10321661

RCT

40 pts.

hydrocortisone 100 mg bolus, 0.18 mg/kg/hr(100 kg patient would receive 432 mg/d)

mortality

shock reversal

Mortality:  steroids: 20%  placebo 30%(insig)Shock reversal:  steroids:90%  placebo: 80%(insig)

Small size limits power

Bollaert, 1998PMID: 9559600

RCT

41 patients requiring pressors >48 hrs.

hydrocortisone 100 mg tid x5d

mortality Overall:  steroids: 32%  placebo: 63% (insig)Adrenal normal (n=29):  steroids 33%

Introduced role of corticotropin testing - which did not predict response to steroids.

  placebo 64%Adrenal insufficient (n=12):  steroids 25%  placebo 63%

29% were adrenal insufficient (<6mcg cortisol increase after corticotropin test)

Cronin, 1995PMID: 7634816

Systematic review of RCTs

730 patients with septic shock in 6 studies

varying regimens

mortalityRR=1.07 (95% CI 0.91, 1.26)

Much heterogeneity

Lefering, 1995PMID: 7600840

Systematic review of RCTs

1329 patients in 10 studies.

varying regimens

mortalityARR=-0.2% (CI: -9.2, 8.8)

Much heterogeneity

No differences between low- vs. high-dose or type of corticosteroid.

The Gram-negative group demonstrated better outcome (-5.6% vs. 1.8% for gram positive).

Conclusions and recommendations1. The combination of a corticosteroids and a mineralocorticoid appear to enhance survival in patients with severe septic shock who are relatively adrenal insufficient.2. Ten such patients must be treated for one to benefit.3. In patients with septic shock and a normal adrenal gland, steroids may increase mortality.

References:1. Annane D et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288:862-71. 2. Cronin L et al. Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Critical Care Medicine 1995;23:1430-1439.3. Lefering R et al. Steroid controversy in sepsis and septic shock: a meta-analysis. Critical Care Medicine 1995;23:1294-1303.4. Briegel J et al. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study.Crit Care Med. 1999;27:723-32.5. Bollaert PE et al. Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med. 1998;26:645-50.