Vitamins for Septic Shock: Let’s Face It, They Don’t Work
Despite the hope, preliminary data suggest they don’t make a difference. In fact, they may even be harmful.
Septic shock is a devastating illness. It kills thousands of people around the world each year. It killed my own daughter, in fact. And so, anything that can possibly help treat this horrible illness is most welcome.
Hence the great enthusiasm that greeted the initial study that suggested high dose vitamins improved mortality in septic shock. Vitamins are low risk medications, relatively inexpensive, and easy to administer. And if they can reduce the mortality of septic shock, fabulous!
Based on this initial — and, admittedly, low quality — study, vitamins were widely adopted by critical care clinicians around the world, including me. The “purists,” many of my colleagues among them, told me that I should not use them because, there is no evidence they work. What they mean by this that there is no randomized, double-blinded, controlled clinical trial that has demonstrated that vitamins improve outcome — especially mortality — in septic shock.
“Who cares?” said the enthusiasts like me. “They are pretty safe medications, and if they may work, then what’s the harm?” Well, the purists, it seems, were right.
In a multinational study, 216 patients with septic shock were randomized to receive IV vitamins with steroids versus steroids alone. There was no difference between the groups:
treatment with intravenous vitamin C, hydrocortisone, and thiamine, compared with intravenous hydrocortisone alone, did not significantly improve the duration of time alive and free of vasopressor administration over 7 days (122.1 hours vs 124.6 hours, respectively).
In fact, the mortality rate in the group that received the vitamins was actually higher than the control group (28.6% vs 24.5%), but this difference was not statistically significant. Let’s face it, folks, it seems vitamins just don’t work in improving the outcome of septic shock.
Now, there are several more studies that are currently ongoing, and hopefully they can shed more light on this question. And, the true believers in vitamins for septic shock have not accepted the results of this study as definitive. In fact, speaking to NPR after the study was published, Dr. Paul Marik (the first to publish success with vitamins) immediately rejected its findings:
Marik, who remains a strong proponent of this approach, rejects the findings of the study. He tells NPR that by his reckoning, patients in the study received treatment far too late in the course of their disease. “It’s like giving it to a patient who’s dead,” he says. “It’s of no benefit. The horse was out of the barn miles beforehand.”
Marik, at Eastern Virginia Medical School, gives his patients the vitamin C infusion as quickly as he recognizes signs of sepsis. That’s impossible to do in a study in which participants must be enrolled in a study and then randomized into one of the two comparison groups before treatment can begin.
“The question is, why does this study not replicate real-life experience and the experience of hundreds of clinicians around the world?” he asks.
In fact, he was at the conference where the findings of the study were first presented.
And this is exactly what the enthusiasts are saying, echoing Marik: the vitamins were given too late. The thing is, as noted above, it’s impossible to give vitamins immediately when one suspects sepsis in a clinical trial. How can that objectively measured and operationalized in a study? Further, patients in the study were given vitamins after about 12 hours…which is pretty fast in the real world. And still, there was no difference in outcome.
What’s even more interesting is that I haven’t seen anyone mention the fact that the 90-day mortality trended in the wrong direction: more people in the group that received the vitamins died 3 months after the study. Again, it’s not statistically significant, but it is worrying nonetheless.
We’ve tried so many things to try and alter the outcome of this devastating disease. Most have failed. That’s why none of us want to give up on vitamins for sepsis. It’s seems like a miracle cure.
At the same time, we need to be honest with ourselves as clinicians. As much as we may not want to admit it, it seems vitamins may need to be added to the long list of treatments that once had promise but were later found to be ineffective. Of course, I’m waiting for more data to come out. In the meantime, though, we need to face the facts: vitamins, it seems, don’t work for septic shock. In fact, they may even be harmful.