Ver el código de «EBQ:CORTICUS Trial»

{{JC info
| title= Hydrocortisone therapy for patients with septic shock
| abbreviation=CORTICUS
| expansion=Corticosteroid Therapy of Septic Shock
| published=2008-01 
| author=Sprung CL, et al
| journal=New England Journal of Medicine
| year=2008
| volume=358
| issue=2
| pages=111-24
| pmid=18184957
| fulltexturl=http://www.nejm.org/doi/full/10.1056/NEJMoa071366
| pdfurl=http://www.nejm.org/doi/pdf/10.1056/NEJMoa071366
| status= Complete
}}


==Clinical Question==
Does low-dose hydrocortisone therapy improve survival in patients with septic shock?

==Conclusion==
Hydrocortisone increase the speed to shock reversal.

==Major Points== 
This trial was performed to address the suggestion that there was a survival benefit with hydrocortisone and fludrocortisone administration to patients in septic shock with insufficiency <ref>Annane D, et al. "Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock". Journal of the American Medical Association. 2002. 288(7):862-871</ref>.  The Annane Trial caused epiric corticosteroid administration to be the standard of care in patients with sepsis and resumed adrenal insufficiency.

The Corticosteroid Therapy of Septic Shock (CORTICUS) trial randomized 499 patients with septic shock to hydrocortisone or placebo administration. Prior to treatment, all patients received an ACTH stimulation test and were classified as responders (cortisol rise >9 mcg/dL) or non-responders (cortisol rise ≤9 mcg/dL). 

In contrast to the Annane Trial, CORTICUS demonstrated that hydrocortisone does not improve survival in patients with septic shock, regardless of response to ACTH. While there was no survival benefit, hydrocortisone conferred a more rapid reversal of shock in all subgroups studied.


==Current Guidelines==
{{Sepsis Guidelines Steroids}}

==Design== 
* Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial
* N=499
** Hydrocortisone (n=251)
** Placebo (n=248)
* Mean follow-up: 28 days

==Inclusion Criteria== 
* Patients 18 years and older
* All patients hospitalized in ICU
* Septic shock (SBP<90 with 20cc/kg fluid replacement or vasopressors need for >1hr) or organ dysfunction attributable to sepsis

===Exclusion Criteria=== 
* Life expectancy <24h
* Immunosuppression
* Underlying disease with poor prognosis
* Treatment with long-term corticosteroids within past 6 months or short-term corticosteroids within past 4 weeks

==Interventions== 
* Sixty minutes prior to administration of study drug, a high-dose (250mcg) ACTH-stimulation test was performed in all patients
* Patients were classified as responsive (cortisol >9 mcg/dL) or non-responsive to ACTH (cortisol ≤9 mcg/dL)
* Lastly patients were randomized to hydrocortisone 50mg or placebo IV q 6 hrs, tapered over a 6-day period


==Outcome==

===Primary Outcomes===
; 28-day mortality
: Hydrocortisone 34% vs. placebo 32% (P=0.51)

===Secondary Outcomes=== 
; Reversal of shock
: Hydrocortisone 76% vs. placebo 70.4% (P=0.41)

; Time to reversal of shock
: Hydrocortisone 3.3 vs. placebo 5.8 days (P<0.001)

===Subgroup analysis===
''Responsive to corticotropin''
; 28-day mortality
:Hydrocortisone 39% vs. placebo 36% (P=0.69)
; Reversal of shock
:Hydrocortisone 94.7% vs. placebo 76.5% (P=0.13)
; Time to reversal of shock
: Hydrocortisone 2.8 vs. placebo 5.8 days (P<0.001)

''Non-responsive to corticotropin''
; 28-day mortality
:Hydrocortisone 29% vs. placebo 29% (P=1.00)
; Reversal of shock
:Hydrocortisone 79.7% vs. placebo 74.2% (P=0.18)
; Time to reversal of shock
:Hydrocortisone 3.9 vs. placebo 6.0 days (P=0.06)

==Further Discussion==
* The authors note that they did not each their goal enrollment of 800 patients.

*The CORTICUS trial questioned the outcome of the Annane Trial.  Differences in the conclusions between the two trials may be due to
# The Annane Trial's population was more critically ill 
# The Annane Trial’s enrollment occurring within 8 hours (vs. 72 hours in CORTICUS). 
# The Annane Trial used hydrocortisone plus the pure mineralocorticoid fludrocortisone and CORTICUS only used hydrocortisone
# In 2013 Boonen et al<ref>[http://www.nejm.org/doi/full/10.1056/NEJMoa1214969 Boonen E et al. "Reduced cortisol metabolism during critical illness." ''The New England Journal of Medicine.'' 2013;368:1477-1488.]</ref> in the NEJM questioned conventional plasma measurements of the cortisone during critical illness since there was a reduction in mediators of cortisol degradation in ICU patients.  The ACTH stimulation test may be an inaccurate measurement of adrenal insufficiency during critical illness.

==Funding==
Eu- ropean Commission, the European Society of Intensive Care Medicine, the European Critical Care Research Network, the International Sepsis Forum, and the Gorham Foundation. Roche Diagnostics provided the Elecsys cortisol immunoassay

==Sources==
<references/>


[[Category: Critical Care]]
[[Category:EBQ]]