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APROCCHSS

"Corticosteroids in Septic Shock: The APROCCHSS Trial".The New England Journal of Medicine. 2018. 378:236-249. PubMed•Full

Links to original sources: Wiki Journal Post Full Journal Article

Contents 1 Clinical Question 2 Bottom Line 3 Major Points 4 Guidelines 5 Design 6 Population 6.1 Inclusion Criteria 6.2 Exclusion Criteria 6.3 Baseline Characteristics 7 Interventions 8 Outcomes 8.1 Primary Outcome 8.2 Secondary Outcomes 9 Criticisms 10 Funding 11 Further Reading

Clinical Question


In adult patients with septic shock, does the addition of hydrocortisone plus fludrocortisone therapy result in reduced all-cause mortality at 90 days?

Bottom Line


In adult patients with septic shock, the addition of hydrocortisone plus fludrocortisone significantly reduced 90-day all-cause mortality compared to placebo.

Major Points


Septic shock is associated with high mortality rates and long-term cognitive decline in survivors. Hydrocortisone plus fludrocortisone therapy may modulate the host response and potentially improve outcomes in septic shock. The APROCCHSS trial evaluated the combination therapy's impact on 90-day all-cause mortality in septic shock patients.

Guidelines


As of 2018, there are varying guidelines regarding the use of corticosteroids in septic shock. This trial may inform future updates to these guidelines.

Design


- Multicenter, double-blind, randomized trial - N=1,241 adult patients with septic shock - Hydrocortisone (50mg IV q6h) plus fludrocortisone (50 μg tablet once daily) vs. placebo - Primary outcome: 90-day all-cause mortality - Secondary outcomes: Mortality at ICU discharge, hospital discharge, day 28, and day 180; number of days alive and free of vasopressors, mechanical ventilation, or organ failure - Intervention period: 7 days without tapering

Population


- Inclusion Criteria: Adult ICU patients with septic shock for less than 24 hours - Exclusion Criteria: Septic shock for at least 24 hours, high bleeding risk, pregnancy or lactation, life-threatening comorbidities, hypersensitivity to the study drugs, or previous corticosteroid therapy - Baseline Characteristics: Similar across groups, with most patients having severe septic shock, high severity-of-illness scores, and community-acquired infections

Interventions


- Patients received hydrocortisone plus fludrocortisone therapy or placebo for 7 days

Outcomes


- Primary Outcome: 90-day mortality was 43.0% in the treatment group vs. 49.1% in the placebo group (P=0.03) - Secondary Outcomes: - Lower mortality at ICU and hospital discharge in the treatment group - Shorter time to weaning from vasopressors and mechanical ventilation in the treatment group - More vasopressor-free and organ-failure-free days in the treatment group - No significant difference in secondary infections or gastrointestinal bleeding, but higher risk of hyperglycemia in the treatment group

Criticisms


- The trial was underpowered to assess the effect of drotrecogin alfa (activated) after its withdrawal from the market - The imbalance in the distribution of pathogens, with slightly more viral infections in the treatment group

Funding


- Programme Hospitalier de Recherche Clinique 2007 of the French Ministry of Social Affairs and Health (contract P070128)

Further Reading


- Full text is available on The New England Journal of Medicine website