What is going on with VITAMIN C in Critical Care? From basics to current day conundrums. #FOAMed #FOAMcc #VitaminC You can use the @threadreaderapp to read this Tweetorial! 
First - let's look at what Vitamin C is. Unlike most mammals, we can't actually synthesise it! It's a water-soluble vitamin: lpi.oregonstate.edu/mic/vitamins/v…
Which is why it needs ingested, or... supplemented.
Which is why it needs ingested, or... supplemented.
It's most important function (from a critical care perspective) likely comes from its function as an anti-oxidant. #FOAMed #FOAMcc intechopen.com/books/vitamin-…
Used in normal growth and development + is an essential enzyme cofactor for several enzymes in the post-translational hydroxylation of collagen, biosynthesis of carnitine, conversion of the neurotransmitter dopamine to norepinephrine, peptide amidation, and in tyrosine metabolism
Stop taking vitamin C when healthy = can take around 30 days (prob longer...) to develop issues such as Scurvy --> dermnetnz.org/topics/scurvy/ But, due to consumptive metabolism etc - critically ill patients become deplete much faster.... #FOAMed #FOAMcc
Indeed, in cancer patients - low vit C levels are associated with poorer outcomes: journals.sagepub.com/doi/abs/10.119… #FOAMcc #FOAMed
It's certainly not the only Vitamin of interest in Critical Care patients as my colleague and friend @79ka2011 wrote about in 2018: link.springer.com/article/10.100…
What's the rationale behind Vit C in Critical Care? Well... Vit C scavenges reactive oxygen species such as superoxide and peroxynitrite in plasma and cells (preventing damage to proteins, lipids and DNA), prevents occludin dephosphorylation and loosening of the tight junctions.
Ascorbate improves microcirculatory flow impairment by inhibiting TNF-induced intracellular adhesion molecule expression, which triggers leukocyte stickiness and slugging. Clinical trials in sepsis, trauma and major burns testing high-dose vitamin C showed clinical benefit.
We've looked at its role in immune function, lung injury and bioenergetics within the critically ill. On paper, this anti-oxidant has huge potential. But a lot of questions remained.. researchgate.net/publication/27…
Low levels were discovered in the critically ill, despite routine replacement (by TPN for example) - sciencedirect.com/science/articl… - this study 'only' went up to a max of 3g/day IV to try and achieve normal values. We then needed to look at 'supraphysiological' dosing #FOAMed #FOAMcc
Given the host of proposed benefits that Vit C can give a critically ill - we needed to look at dosing regimes and actually start doing RCT's to look at Vitamin C's role in ICM... ncbi.nlm.nih.gov/pmc/articles/P…
Multiple studies have looked at doses between 6-16g per day... ncbi.nlm.nih.gov/pubmed/29864039 So where do we begin on such a spectrum? #FOAMed #FOAMcc
Many of the studies also look at Vitamin C in relation to other treatments (or in combination) which may act as confounders to looking at the effect of Vit C on its own. ncbi.nlm.nih.gov/pmc/articles/P… #FOAMed #FOAMcc
To frame some of the most recent research in context - you should read about the role of hydrocortisone in sepsis: bmj.com/content/362/bm… - some have tried to 'bolster' hydrocortisone with thiamine and Vit C in a sort of 'cocktail'. #FOAMed #FOAMcc
In 2017 - Prof Marik published journal.chestnet.org/article/S0012-… a paper that would set the tone of research in this area for the next number of years. This retrospective study claimed benefit towards: AKI, reducing organ dysfunction and improving mortality. #FOAMed #FOAMcc
Indeed, we'll see an update on this retrospective study to be an RCT in the VICTAS trial that was announced in December 2019. clinicaltrials.gov/ct2/show/NCT03…
We have already seen results from VITAMINS by @tomoko_ICU and @DogICUma in January 2020 which seem to say: "vitamin C, hydrocortisone, and thiamine does not lead to a more rapid resolution of septic shock compared with intravenous hydrocortisone alone." jamanetwork.com/journals/jama/…
and @stevemathieu75 has summarised the issue well in the VITAMINS edition of TBL: thebottomline.org.uk/summaries/icm/…
@stevemathieu75 Let's go back to more basic Q's about Vit C....
How much MIGHT someone need to maintain a normal level... 0.1g per day of vit C can maintain a normal plasma level in healthy persons --> ?up to 4g per day, are needed for crit ill patients to increase their plasma vit C levels to the range of 'normal' helsinki.fi/en/news/health…
This 2018 study from NL looked at 2g vs 10g dosing per day: ncbi.nlm.nih.gov/pubmed/29522710
And in December 2019 - @tomoko_ICU et al published findings that 1.5g 6 hourly was sufficient to achieve normal or elevated Vit C levels in the critically ill. #FOAMed #FOAMcc ncbi.nlm.nih.gov/pubmed/31778629
Don't forget Thiamine is poorly absorbed orally - which is why IV is preferred for a period of time.... Some say that oral is usually satisfactory: ncbi.nlm.nih.gov/pmc/articles/P… - it was in healthy people - those with GI insufficiency/alcoholism it is decreased: glowm.com/resources/glow…
Males, smokers, persons using drugs of abuse, individuals infected with H. pylori or parasitic infx and those with low-HDL chol have lower plasma levels of vitC vs females, non-smokers and normal healthy subjects free from drugs of abuse and infections + normal HDL #FOAMed
A 2006 publication from Pakistan heralded that the prevalence of vitamin C deficiency (plasma levels <2 µg/ml) is highest among Indians and people of South Asian origin compared to other races except the Mexican population. #FOAMed #FOAMcc pjms.com.pk/issues/julsep0…
The safety profile of Vit C in the critically ill is rather good. Many studies were not designed to look at adverse events - BUT in those that did there was little-to-no issues reported. One study (previously mentioned) saw some metabolic alkalosis in the 10g/day cohort. #FOAMed
