Sepsis: Annane

Question 1

Annane Clinical Question

Answer 1

Among patients with septic shock and relative adrenal insufficiency, do corticosteroids reduce 28-day mortality

Question 2

Annane Bottom Line

Answer 2

Among patients with septic shock and relative adrenal insufficiency, administration of corticosteroids reduces 28-day mortality, although this finding was not confirmed in the follow-up CORTICUS, HYPRESS, or ADRENAL trials, but confirmed in APROCCHSS.

Question 3

Annane Design and n

Answer 3

Randomized, prospective, double-blind, parallel-group, placebo-controlled trial,N=300

Question 4

Annane inclusion criteria

Answer 4

• Age ≥18 years
• Hospitalized in ICU
• Documented site or strong suspicion of infection
• Temperature ≥38.3°C or ≤35.6°C
• Heart rate ≥90 BPM
• SBP <90 mmHg for ≥1 hour despite IVF, dopamine >5mcg/kg/min, any epinephrine, or any norepinephrine
• Urine output ≤0.5 mL/kg for ≥1 hour or the PaO2/FiO2 -≤280 mmHg
• Lactate levels ≥2 mmol/L
• Mechanical ventilation

Question 5

Annane exclusion criteria

Answer 5

Pregnancy
MI
PE
Advanced cancer
AIDS
Contraindication for corticosteroids
Etomidate in the previous 6 hours (late amendment to protocol)

Question 6

Annane criticisms

Answer 6

• Some of the “nonresponders” had a pre-ACTH cortisol level of <34mcg/dL [<938 nmol/L] and therefore may have been classified as having absolute adrenal insufficiency.
• The study’s generalizability is limited because patients receiving etomidate were excluded, patients were generally more ill, and all patients received mechanical ventilation.

Question 7

Annane Interventions

Answer 7

• Hydrocortisone 50mg IV q6h and fludrocortisone 50mcg daily for 7 days
• Placebo