The vitamin C cocktail for severe sepsis and septic shock

I know I’m a little late with this. Here’s the paper published in Chest. Form the paper:

Methods

In this retrospective before-after clinical study, we compared the outcome and clinical course of consecutive septic patients treated with intravenous vitamin C, hydrocortisone and thiamine during a 7-month period (treatment group) compared to a control group treated in our ICU during the preceding 7 months. The primary outcome was hospital survival. A propensity score was generated to adjust the primary outcome.

Findings

There were 47 patients in both treatment and control groups with no significant differences in baseline characteristics between the two groups. The hospital mortality was 8.5% (4 of 47) in the treatment group compared to 40.4% (19 of 47) in the control group (p less than 0.001). The propensity adjusted odds of mortality in the patients treated with the vitamin C protocol was 0.13 (95% CI 0.04-0.48, p=002). The SOFA score decreased in all patients in the treatment group with none developing progressive organ failure. Vasopressors were weaned off all patients in the treatment group, a mean of 18.3 ± 9.8 hours after starting treatment with vitamin C protocol. The mean duration of vasopressor use was 54.9 ± 28.4 hours in the control group (p less than 0.001).

Conclusion

Our results suggest that the early use of intravenous vitamin C, together with corticosteroids and thiamine may prove to be effective in preventing progressive organ dysfunction including acute kidney injury and reducing the mortality of patients with severe sepsis and septic shock. Additional studies are required to confirm these preliminary findings.

A post at the Skeptics’ Guide to EM has a nice discussion and critical appraisal, and several notables from the FOAM community weighed in. The participants were unanimous in saying that this study is only hypothesis generating and should not change practice at the moment.

The problems with this study are obvious. Issues that concerned me in particular were:

1) There were three interventions. If the effect is true, which one(s) worked?

2) It seems too good to be true.

3) What are we to make of the 40.4% mortality in the control group?

Some would ask why not just give it to septic patients, since it is harmless, right? Others would counter that you could say the same thing about homeopathy. But wait, homeopathy has no plausible mechanism of action. Vitamin C does. Several, in fact.

It’s interesting that the folks at East Virginia don’t feel there is equipoise for a randomized controlled trial. As experience accumulates I expect to see more and more low level evidence published, from that institution and elsewhere. If that experience repeatedly and consistently points toward a therapeutic effect, especially a very large one as suggested in this study, then we may never feel there’s equipoise and it will gradually become accepted into sepsis care. More likely we’ll see results that are not so good, leading eventually to a randomized trial. My bottom line today is that, while it would be difficult to fault someone for incorporating this into sepsis care, the Marik study should be considered hypothesis generating only, in need of further study, and not a mandate for practice change.