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| ==Conclusion== | | ==Conclusion== |
| Hydrocortisone increase the speed to shock reversal but does not have a mortality benefit in patients with septic shock. | | Hydrocortisone increase the speed to shock reversal. |
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| ==Major Points== | | ==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.
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| 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).
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| 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.
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| == 2012 Guidelines== | | == 2012 Guidelines== |
| '''Surviving Sepsis Campaign guidelines for severe sepsis and septic shock''' (2012)<ref>[http://www.sccm.org/Documents/SSC-Guidelines.pdf#page=19 Surviving Sepsis Campaign 2012 guidelines]</ref>
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| * Recommend against using hydrocortisone IV to treat adult septic shock if fluid resuscitation and vasopressor therapy reverse shock.
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| *Hydrocortisone 200 mg IV daily may be used at that point (grade 2C)
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| * *Recommend against ACTH stimulation test in adults with septic shock (grade 2B)
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| * *Recommend against using hydrocortisone when vasopressors aren't required (grade 2D)
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| ** Recommend against using corticosteroids in sepsis without shock (grade 1D)
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| ==Design== | | ==Design== |
| * Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial
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| * N=499
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| ** Hydrocortisone (n=251)
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| ** Placebo (n=248)
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| * Mean follow-up: 28 days
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| ==Inclusion Criteria== | | ==Inclusion Criteria== |
| * Patients 18 years and older
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| * All patients hospitalized in ICU
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| * Septic shock (SBP<90 with 20cc/kg fluid replacement or vasopressors need for >1hr) or organ dysfunction attributable to sepsis
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| ===Exclusion Criteria=== | | ===Exclusion Criteria=== |
| * Life expectancy <24h
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| * Immunosuppression
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| * Underlying disease with poor prognosis
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| * Treatment with long-term corticosteroids within past 6 months or short-term corticosteroids within past 4 weeks
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| ==Interventions== | | ==Interventions== |
| * Sixty minutes prior to administration of study drug, a high-dose (250mcg) ACTH-stimulation test was performed in all patients
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| * Patients were classified as responsive (cortisol >9 mcg/dL) or non-responsive to ACTH (cortisol ≤9 mcg/dL)
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| * Lastly patients were randomized to hydrocortisone 50mg or placebo IV q 6 hrs, tapered over a 6-day period
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| ==Outcome== | | ==Outcome== |
| ''Hydrocortisone vs. placebo.''
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| ===Primary Outcomes=== | | ===Primary Outcomes=== |
| ; 28-day mortality
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| : 34% vs. 32% (P=0.51)
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| ===Secondary Outcomes=== | | ===Secondary Outcomes=== |
| ; Reversal of shock
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| : 76% vs. 70.4% (P=0.41)
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| ; Time to reversal of shock
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| : 3.3 vs. 5.8 days (P<0.001)
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| Other outcomes were not statistically different: length of stay, reversal of organ failure, rates of new infection, hypernatremia, hyperglycemia.
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| ===Subgroup analysis=== | | ===Subgroup analysis=== |
| ''Responsive to corticotropin''
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| ; 28-day mortality
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| :39% vs. 36% (P=0.69)
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| ; Reversal of shock
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| :94.7% vs. 76.5% (P=0.13)
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| ; Time to reversal of shock
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| : 2.8 vs. 5.8 days (P<0.001)
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| ''Non-responsive to corticotropin''
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| ; 28-day mortality
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| :29% vs. 29% (P=1.00)
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| ; Reversal of shock
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| :79.7% vs. 74.2% (P=0.18)
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| ; Time to reversal of shock
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| :3.9 vs. 6.0 days (P=0.06)
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| ==Criticisms== | | ==Criticisms== |
| * The authors note that they did not each their goal enrollment of 800 patients.
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| *The CORTICUS trial questioned the outcome of the Annane Trial. Differences in the conclusions between the two trials may be due to
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| # The Annane Trial's population was more critically ill
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| # The Annane Trial’s enrollment occurring within 8 hours (vs. 72 hours in CORTICUS).
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| # The Annane Trial used hydrocortisone plus the pure mineralocorticoid fludrocortisone and CORTICUS only used hydrocortisone
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| # 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.
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| ==Funding== | | ==Funding== |
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| ==Sources== | | ==Sources== |
| <references/> | | <references/> |
| *[Sprung CL, et al. "Hydrocortisone therapy for patients with septic shock". New England Journal of Medicine. 2008. 358(2):111-24. CORTICUS Trial]
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| <references/>
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| * [http://www.nejm.org/doi/full/10.1056/NEJMc080246 NEJM Letters to the Editor]
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| * [http://www.nejm.org/doi/full/10.1056/NEJMe0708098 Concurrent editorial]
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| [[Category: Critical Care]] | | [[Category: Critical Care]] |
Complete Journal Club Article
Sprung CL, et al. "Hydrocortisone therapy for patients with septic shock".
New England Journal of Medicine. 2008. 358(2):111-24.
PubMed Full text PDF
Clinical Question
Does low-dose hydrocortisone therapy improve survival in patients with septic shock?
Conclusion
Hydrocortisone increase the speed to shock reversal.
Major Points
2012 Guidelines
Design
Inclusion Criteria
Exclusion Criteria
Interventions
Outcome
Primary Outcomes
Secondary Outcomes
Subgroup analysis
Criticisms
Funding
Supported by the European 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.
CME
Sources
