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+1. Great article, as usual.I like Josh Farkas's takes on the new guidelines: https://emcrit.org/pulmcrit/sepsis-myths/
Somewhat relevant...
Doctor Turns Up Possible Treatment For Deadly Sepsis
Let the eye-rolling begin... (though I think some sort of combined immunotherapy is probably the right direction. Also, some of the best discoveries happened by random chance, but all that being said... I'll put on my skeptic hat)
. Granted I get this is a clinical talk, but one of the anti-oxidant properties of Vitamin C is reportedly on increased tetrahydrobiopterin synthesis increasing eNOS coupled and reduced superoxide production. Except that eNOS coupling has nothing to do with NF-kB and has no effect on micovascular permeability, so immediately this hypothesis is false. I honestly don't care about the hypothesis or mechanism at this point, but about the outcomes. I am not practicing CCM this year, but I really don't see much downside in trying it out in a septic patient with high pressor needs. I also trust the source, despite Dr. Marik's historical tendencies for being passionate. I think that, overall, he is a great intensivist and educator.
Oh I know people give steroids. People measure cortisol levels of 30 and still give steroids. That drug will continue to be given in the foreseeable future, despite that fact that 30 years of research and its never been shown to improve outcomes (outside of weaning off pressors faster). I heard a talk about steroids and epigentics in sepsis and the comment was made "It is embarrassing that we don't know the role of steroids in sepsis after all this time"... all I can say is "yep"Many of us would at least try a dose of steroids, once the pressor needs go up. So I don't see much downside to 50 of hydrocortisone. Also, he says that the effects tend to be visible within a few hours, before the next dose.
"Usual care" is pretty different in 2017 than in 1997 though. At least somewhat thanks to EGDT.EGDT is dead....Long live usual care.
Hmmm... the slide that said "Mechanistic Pathways in Sepsis"... Vitamin C reduces NF-kB by being an antioxidant... made me. Granted I get this is a clinical talk, but one of the anti-oxidant properties of Vitamin C is reportedly on increased tetrahydrobiopterin synthesis increasing eNOS coupled and reduced superoxide production. Except that eNOS coupling has nothing to do with NF-kB and has no effect on micovascular permeability, so immediately this hypothesis is false.
Again, maybe he is on to something, but in a study of a treatment on 47 patients with a hypothesis that is wishy-washy... I'm not getting my hopes up.
There are also papers that show that NF-kB can be reduced by Vitamin C in a redox-independent manner. Maybe I was wrong to state the hypothesis is "false" but it isn't necessarily a true statement as to the cause and effect of anti-oxidants in sepsis. Is knocking down NF-kB even a good thing, since counter-regulatory mechanism are also NF-kB dependent?Actually the fact that it is an important antioxidant is why cells will readily take it in. It is then oxidized and this oxidized form directly causes downregulation of NFKB. So for the message he is trying to convey, he isn't wrong.
There's just so little that we know...
Honestly, I hope he is right... I'm just not convinced there is a cure all. I do think treatments aimed at genetic signatures in septic patients is where the field is heading, the technology is just not there yet to make it useful in real-time.True that. Our understanding of these cellular are definitely too simplistic. We are knocking out/upregulating whole pathways or giving medications that do 100 different things that we don't understand fully understand.
He definitely makes some leaps in his assumptions but I like the picture he is painting overall. Definitely makes me think about this stuff.