Tuesday, May 29, 2018

APROCCHSS trial - Hydrocort plus Fludricort in septic shock

Hydrocortisone plus Fludrocortisone for Adults with Septic Shock


  • Djillali Annane, et al. 
  • for the CRICS-TRIGGERSEP Network*
    N Engl J Med 2018; 378:809-818

BACKGROUND
Septic shock is characterized by dysregulation of the host response to infection, with circulatory, cellular, and metabolic abnormalities. We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa (activated), which can modulate the host response, would improve the clinical outcomes of patients with septic shock.
HYPOTHESIS -  
therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa (activated), which can modulate the host response, would improve the clinical outcomes of patients with septic shock.

METHODS
  •  multicenter, double-blind, randomized trial with a 2-by-2 factorial design, 
  • evaluated the effect of hydrocortisone-plus-fludrocortisone therapy, drotrecogin alfa (activated), the combination of the three drugs, or their respective placebos. 
  • primary outcome - 90-day all-cause mortality. 
  • Secondary outcomes - mortality at intensive care unit (ICU) discharge and hospital discharge and at day 28 and day 180 and the number of days alive and free of vasopressors, mechanical ventilation, or organ failure. 
  • After drotrecogin alfa (activated) was withdrawn from the market, the trial continued with a two-group parallel design. The analysis compared patients who received hydrocortisone plus fludrocortisone with those who did not (placebo group).
RESULTS
  • 1241 patients included in the trial, the 90-day mortality was 43.0% (264 of 614 patients) in the hydrocortisone-plus-fludrocortisone group and 49.1% (308 of 627 patients) in the placebo group (P=0.03). 
  • The relative risk of death in the hydrocortisone-plus-fludrocortisone group was 0.88 (95% confidence interval, 0.78 to 0.99). 
  • Mortality was significantly lower in the hydrocortisone-plus-fludrocortisone group than in the placebo group at ICU discharge (35.4% vs. 41.0%, P=0.04), hospital discharge (39.0% vs. 45.3%, P=0.02), and day 180 (46.6% vs. 52.5%, P=0.04) but not at day 28 (33.7% and 38.9%, respectively; P=0.06). 
  • The number of vasopressor-free days to day 28 was significantly higher in the hydrocortisone-plus-fludrocortisone group than in the placebo group (17 vs. 15 days, P<0.001), as was the number of organ-failure–free days (14 vs. 12 days, P=0.003). 
  • The number of ventilator-free days was similar in the two groups (11 days in the hydrocortisone-plus-fludrocortisone group and 10 in the placebo group, P=0.07). 
  • The rate of serious adverse events did not differ significantly between the two groups, but hyperglycemia was more common in hydrocortisone-plus-fludrocortisone group.
CONCLUSIONS

In this trial involving patients with septic shock, 90-day all-cause mortality was lower among those who received hydrocortisone plus fludrocortisone than among those who received placebo.

To read the article , click here

No comments:

Post a Comment

Disclaimer

Information provided here is for medical education only. It is not intended as and does not substitute for medical advice. If you are a patient, please see your doctor for evaluation of your individual case. The web site should not be used as a substitute for competent medical advice from a licensed physician. By accessing the web site, the visitors acknowledge that there is no physician-patient relationship between them and the author. Under no circumstances will the author be liable to you for any direct or indirect damages arising in connection with use of this website.

The appearance of external hyperlinks to other websites does not constitute endorsement. The author does not verify, endorse, or take responsibility for the accuracy, currency, completeness or quality of the content contained in these sites.

All information provided here is from textbooks/journals. I have provided references and given credit where applicable. I would be glad to take off any images/posts that you think violates your copyright policy. Please shoot an email to fnbcriticare@gmail.com