VITAMINS

What is the effect of the combination of vitamin C, hydrocortisone, and thiamine among patients with septic shock?

Study design

Population

216 patients (78 female, 133 male)
Inclusion criteria: patients in ICUs fulfilling the Sepsis-3 definition of septic shock
Key exclusion criteria: age younger than 18 years, a do-not-resuscitate order, imminent death, diagnosis of septic shock > 24 hours ago, known or suspected disease with a strong indication or contraindication for any of the study drugs, and another indication for hydrocortisone than septic shock

Interventions

N=109 vitamin C, hydrocortisone and thiamine (vitamin C 1.5 g IV 96h, hydrocortisone 50 mg IV 96h, and thiamine 200 mg IV g12h until shock resolution or up to 10 days)
N=107 hydrocortisone (hydrocortisone 50 mg IV 96h, until shock resolution or up to 10 days)

Primary outcome

No significant difference in hours alive and vasopressor-free up to day 7 (122.1 hours vs. 124.6 hours; AD -0.6 hours, 95% CI -8.3 to 7.2)

Secondary outcomes

No significant difference in death at day 90 (28.6% vs. 24.5%; AD 4.1%, 95% CI-8 to 16.1)
No significant difference in cumulative vasopressor-free days at day 28 (25.6 days vs. 25.8 days; AD -0.2 days, 95% Cl-1.7 to 1.2)
No significant difference in cumulative mechanical ventilation-free days at day 28 (25.3 days vs. 24.8 days; AD 0.4 days, 95% CI -2.6 to 3.4)

Safety outcomes

No significant differences in adverse events such as fluid overload, gastrointestinal bleeding, or hyperglycemia.
Significant difference in the absolute change in SOFA score at day 3 (-2 vs. -1).

Conclusion

In patients in ICUs fulfilling the Sepsis-3 definition of septic shock, vitamin C, hydrocortisone and thiamine were not superior to hydrocortisone with respect to hours alive and vasopressor-free up to day 7.