A new and more effective sepsis treatment?
One can hope.
Regular readers of this blog may recall that I’ve written several times about sepsis. It’s a topic I really knew nothing about until I lost a loved one to it, and then I lost another. They both had other illnesses—cancer, to be exact—but it was sepsis that finished them both off long before the cancer seemed to be doing it. And sepsis can also hit—and kill—completely (seemingly) healthy people.
So it’s with no small excitement that I read about this:
Paul Marik, MD, chief of pulomonary and criitical care medicine at Eastern Virginia Medical School, reported in 2017 that he gave a mix of vitamin C, vitamin B1, and a steroid to nearly four dozen patients who had sepsis in his Norfolk intensive care unit. In the 7 months before he started using the treatment, 19 of 47 sepsis patients died. Of the 47 who got the treatment, all but four survived.
The results got a lot of attention. But it was a small study, comparing before-and-after patient outcomes. Now, researchers are gearing up to test the therapy with large-scale trials using patients selected at random, with some given the cocktail and others given a placebo.
“Dr. Marik feels very strongly that it’s worked in his patients, and he’s changed his practice because of his own experience,” says Jonathan Sevransky, MD, a critical care doctor at Emory University in Atlanta who is leading one of the studies. “If you think something works, it makes sense for a doctor to try something and to change their own practice. But if you want to change other people’s practices, the way to do that is do a randomized, controlled trial — and ideally, you’d have more than one randomized, controlled trial.”
It may fizzle out like so many initially promising treatments do. But it would be wonderful if it really improved the survival rates of patients with sepsis. I urge you to read this post of mine about sepsis and be aware of the signs, so that you can get help before things get to the point of no return.
Curious about Marik’s research—the article I just linked doesn’t say much—I found this. It’s a video that I can’t embed. He really gets into the meat of it at 8:20. If you listen, you can see that many of these patients were quite far gone into the sepsis process, with a prediction of 40% mortality. Their actual mortality was greatly reduced. However, the proof (or lack thereof) will be in the controlled trials:
One must ask, what was the rationale for giving “a mix of vitamin C, vitamin B1, and a steroid” to nearly four dozen patients who had sepsis in his Norfolk intensive care unit .
Were they thiamine (B-1) deficient?
Is this Linus Pauling, the Vitamin C guru, reborn?
Steroids are not uncommonly employed in sepsis, but usually in relatively low doses, since they are anti-inflammatory, and sepsis is a raging inflammatory state in which all one’s neutrophils must be mobilized, their production in the bone marrow shifted to maximum. Depends also on what the pre-sepsis illness was or is, whether it required steroids that must be continued despite sepsis ( which the steroid might have set the patient up for).
Marik must state his rationale for coming up with this cocktail. I could not force myself to listen to the full tape, in which Marik (with an English accent, BTW) says “It is what it is. It’s a story”. Not enlightening.
Frog:
If you watch the entire video he explains in some depth. I don’t know whether it will answer all your questions, but it might. He gets into the nitty-gritty after 9 minutes or so.
Frog:
And this is anecdotal, but certainly interesting:
Also this from Marik on how the whole thing started.
What company makes the steroid?
For those curious about this line of research, I’ve copied a paragraph, from Marik’s most recent paper, describing the status of a number of clinical trials. Most are in the early stages, but their progress and results can be followed at https://clinicaltrials.gov/ and http://www.anzctr.org.au/BasicSearch.aspx.
Vitamin C for the treatment of sepsis: The scientific rationale. Marik PE. Pharmacol Ther. 2018 Apr 21. pii: S0163-7258(18)30070-6
In a retrospective, propensity adjusted, before-after study, we have demonstrated that the combination of intravenous vitamin C, hydrocortisone and thiamine limited the development of organ failure and improved the outcome of patients with severe sepsis and septic shock (Marik et al., 2017). We believe that this inexpensive, readily available and extremely safe intervention has the potential to reduce the global mortality from sepsis.
However, due to the limitations of our study, additional studies are required to confirm our preliminary findings. Several randomized controlled trials are currently underway across the globe to determine the clinical benefit of vitamin C alone (clintrials.gov NCT03338569,NCT02106975, NCT02734147, ACTRN12617000793314,ACTRN12617001184369,ACTRN12617001392358p) and in combination with hydrocortisone and thiamine (clinicaltrials.gov NCT03333278, NCT03335124, NCT03258684, NCT 03380507,NCT03422159, NCT03389555).
In addition, the VICTAS study (Vitamin C, Thiamine and Steroids in Sepsis: A Randomized, Double-Blind, Parallel Group Study in Critically Ill Patients with Sepsis) is a large, multi-center study which will be performed in the USA.
Can’t argue with doing more trials. Some people just set up shop and start selling miracle cures.
I have read the full paper. I am not and never have been an ICU doc.
The rationale for the use of the three drug combo in sepsis is well-presented in the Discussion part of the paper, including that Vit C and hydrocortisone “are
required for the synthesis of catecholamines; and
increase vasopressor sensitivity.” And so boost blood pressure, which is beneficial for sure in septic shock.
I now view the prospect of a larger clinical trial with some optimism. A historical trial, as this paper reports, does in fact have some validity. The gold standard, a prospective randomized double-blinded clinical trial, takes time and may in fact show no difference between the two groups. But in the meantime, if I go into septic shock, I will want the B-1, C, plus HC combo.
In other words, the human body will repair itself if it has the requisite materials on hand. This would explain the prevalence of diseases as a result of mineral and nutrition depletion from modern agriculture practices.
We will see. Something can work without knowing why exactly – they can figure the science out later.
Color me skeptical.
My mother and father were very susceptible to claims about Vitamin C (Linus Pauling, Norman Cousins). Never knew why.
The human body repairs itself until it can’t. The process is aging and it’s called death, by cancer or disease, or just plain old wearing out.
My mother and father were very susceptible to claims about Vitamin C (Linus Pauling, Norman Cousins).
Art Deco: Linus Pauling had a phenomenal scientific career. He won a Nobel Prize in Chemistry and he makes lists of the twenty most important scientists of all time. It wasn’t unreasonable to trust his judgment.
Unfortunately he was persuaded by his own recovery from Bright’s disease using an unorthodox approach which included vitamin supplements.
Such confirmation bias was behind much of the megavitamin bandwagon which got rolling in the sixties and seventies but faded for lack of results.
For a long time I took large doses of C when I had a cold but found it didn’t help.
Sepsis comes in many forms and can have many causes. This specific cocktail may well work for some of them and the “researchers” got lucky (or stacked the deck) to get the results they were looking for.
My mother died from sepsis caused by a combination of cancer, kidney failure, and hypercalcemia.
In the end the cancer caused the hypercalcemia which couldn’t be relieved because her kidneys were incapable of handling the amount of liquids it would take to flush the toxins out of her system.
I seriously doubt giving her some vitamins and anti-inflamatories would have done her any good.
Art Deco: Linus Pauling had a phenomenal scientific career. He won a Nobel Prize in Chemistry and he makes lists of the twenty most important scientists of all time. It wasn’t unreasonable to trust his judgment.
Physiology wasn’t really his field. One of his avocations was non-electoral politics of a quasi-pacifist red haze variety, not something about which we should be inclined to trust his judgment.