Sometimes there's this moment you read about medical research in the news... sometimes you read lots of rubbish on medical issues in the news... but sometimes you stop and read, and you don't know what to think. This happened to quite some of us a couple of days ago when reading the headlines in the British Independent:
Well, it's not very often you read the term sepsis in the news but the word 'cure' causes estonishment or rather misbelief. Further reading certainly catches your attention: 'A doctor in the US state of Virginia claims to have found his own cure for sepsis' and 'Since then, he has used it to treat 150 sepsis patients. Just one has died of the condition, claims Dr Marik'. And it's not an article from some remote pseude magazine... no, it has been published in 'Chest'! And all this is not due to some novel molecule... it's all about Vitamin C!
Thanks to #FOAMed quite some smart brains have looked into this topic already...
So here's the most important facts you need to know - in short:
What's the Story?
Paul Marik et al. have published a
single-centre retrospective cohort study
in which they have treated
47 consecutive septic patients over a periode of 7 months with intravenous vitamin C (1.5g 6-hourly), hydrocortisone (50mg 6-hourly) and thiamine (200mg 12-hourly)
and then compared these patients to
47 septic patients treated in their unit during the preceding 7 months
Propensity score matching
An overall hospital mortality of 40.4% in the control group compared to 8.5% in the intervention group
An absolute risk reduction of 31.9% and also according to the authors none of the patients in the intervention arm died of sepsis!
What Does This Mean?
These results are quite amazing on the first look, but there's more behind these numbers. Paul Marik has first of all published an observational study: unblinded, uncontrolled, retrospective and low in patient numbers.
There are several limitations that go hand in hand with studies as such and unblinded before-and-after studies have a lot. A major challenge in conducting observational studies is to draw inferences that are acceptably free from influences by overt biases, as well as to assess the influence of potential hidden biases. One of the biggest drawbacks in this current study is the timely/ seasonal difference when patients have been selected.
If you are interested to have a closer look on this you should read Dan's blog entry on stemlynsblog.org HERE.
Studies like this one are an important part of science, but observational studies are observational... not proof!
Why Vitamin C in Sepsis?
There is a scientific rationale behind all of this. As mentioned by Paul in his paper vitamin C levels do fall low in sepsis and the most efficient way to administer it is intravenously. The same is true for thiamin which also goes low in up to one third of all septic patients.
There are two rather small randomised control trials suggesting that vitamin C is safe in septic patients and might actually be of some degree of benefit for the patient.
- Neutralizes free radicals and has therefore antioxydative properties
- Is an important conenzyme for the procollagen-proline dioxygenase, which itself is necessary for the biosynthesis of stable collagen in our body. Vitamin C deficiency leeds to unstable collagen and therefore scurvy
- Is an important cofactor in the synthesis of steroids like cortisol and catecholamines like dopamine and noradrenalin as well
- and it has many more functions that go beyond the scope of this blog entry!
However, the importance of vitamin C in the treatment and prevention of diseases like e.g. the common cold or influenza remains highly contrversial. The observation of some moderate positive influence on the course of disease in some studies could not be reproduced in other trials.
Under normal circumstances vitamin C deficiency is practically non-existent in Europe, but becomes a fact during sepsis. If this is clinically relevant in septic patients seems plausible but remains to be elucidated.
Shailja Chambial, Shailendra Dwivedi, Kamla Kant Shukla, Placheril J. John, and Praveen Sharma. Vitamin C in Disease Prevention and Cure: An Overview. Indian Journal of Clinical Biochemistry. Oktober 2013; 28(4): S. 314–328
H. Hemilä, E. Chalker: Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews. 2013
R. M. Douglas, E. B. Chalker, B. Treacy: Vitamin C for preventing and treating the common cold. In: Cochrane Database of Systematic Reviews. 2000; 2:CD000980.
Another great read into the details: Josh Farkas from pulmcrit
More Ifs and Buts
Sepsis is not a disease, its a clinical syndrome that has physiologic, biologic and biochemical abnormalities caused by a dysregulated inflammatory response to infection. The fact that different definitions have evolved since the early 1990s shows that we still struggle to definde sepsis as a single entity. This is one reason why a single therapy might not always be the best for each diesease causing sepsis.
Paul Marik’s publication is interesting and deserves respect. It’s an observational study but provides no evidence by far. Vitamin C might be an interesting novel approach to sepsis but the term ‘cure’ used in the media is inappropriate and misleading.
The term ‘cure for sepsis’ also implicates that vitamin C is a cure for all infections causing sepsis and is therefore problematic.
The Current Bottom Line
- The study published by Marik et al. is purely observational and provides no proof at all.
- Just because vitamine C might be safe in Sepsis does not mean this has to be given. At this stage no recommendation can be made for the use of vitamin C in sepsis.
- Studies like these are an part of research itself - However, the use of the term 'cure' seem problematic and inappropriate in this context.
Marik et. al, J Chest 2017