The Saga of Vitamin C and Septic Shock

Vitamin C has been proposed as a drug that may help patients with sepsis due to its antioxidant effects. Earlier studies have been inconclusive. Another randomized trial was reported this week. Investigators wanted to examine if the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock.

This was a multicenter studies conducted in 10 ICU in Australia, New Zealand, and Brazil. The study was open label (treating physicians were aware of the therapy), randomized (patients were allocated to the treatment or control arm randomly) clinical trial.  Investigators recruited 216 patients fulfilling the Sepsis-3 definition of septic shock.

Patients in the vitamin C arm (n = 109) received intravenous vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours). Patients in the control arm (n = 107) received only intravenous hydrocortisone (50 mg every 6 hours) alone until shock resolution or up to 10 days.

Median time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR], 76.3-145.4 hours) in the intervention group and 124.6 hours (IQR, 82.1-147.0 hours) in the control group; the median of all paired differences was –0.6 hours (95% CI, –8.3 to 7.2 hours; P = .83). Ninety-day mortality was 30/105 (28.6%) in the intervention group and 25/102 (24.5%) in the control group (hazard ratio, 1.18; 95% CI, 0.69-2.00). No serious adverse events were reported.

The findings strengthen the clinical data, which is in contrast to the basic science data, that vitamin C may have clinical benefit in septic patients. At the minimum, the study findings suggest that treatment with intravenous vitamin C, hydrocortisone, and thiamine does not lead to a more rapid resolution of septic shock compared with intravenous hydrocortisone alone. For some, this might be end of vitamin C story, others may still want to examine vitamin C potential little more.