welcome to another MedCram lecture we're going to talk about vasopressin
and some exciting new information about vasopressin so what our vasopressors
vasopressors are substances that we put into people's bodies because their blood
pressure is too low the use of vasopressin be complex and if you want
more information and a more pathophysiological basis for this
information I encourage you to visit med cram comm for the entire series I'm
going to talk about this specifically in the sense of sepsis
so sepsis is when you have an infection that causes your body to go into a low
blood pressure state because there's vasodilation there's usually increased
cardiac output at the very beginning and your immune system basically goes wild
and you have this hypotension and you give fluids in these situations but
still sometimes the blood pressure doesn't get up to where it needs to
which is a map of 65 and you've got to give vasopressors so the reason why
you've got to actually give patients vasopressors is because they don't have
enough endogenous vasopressors of their own and the two big vasopressors that
you should know about norepinephrine and epinephrine and of course these are
secreted from the adrenal gland as it turns out in the biosynthesis pathway
norepinephrine goes to epinephrine but if we go backwards actually
norepinephrine is simply synthesized from a compound called dopamine
and dopamine in turn is synthesized from a compound called dopa specifically it's
l-dopa and of course l-dopa you may know this is synthesized from something
called tyrosine this is the synthetic pathway that the body goes through to
make the final product which is epinephrine the problem is this there's
just not enough of it and that's why we have to give more in patients with
sepsis well if we look at the enzymes along
here there is something called tyrosine hydroxylase and there's a very specific
vitamin that's implicated in the activity of tyrosine hydroxylase and
that is vitamin C now vitamin C is named a vitamin because it comes from the term
vital amine because it's one of those amines that was vital for the human body
to have and humans with just a few other mammals are the only mammals that cannot
synthesize their own vitamin C and that's why it's called the vitamin of
course as we just mentioned so many years ago and actually this has been
looked at for several years the question is whether or not the addition of
vitamin C would help push this pathway down to the final product which are the
vasopressors norepinephrine and epinephrine and would help with micro
vascular problems in terms of perfusion in septic shock and so that's what we're
gonna look at today because there's been some interesting studies that have come
out that have looked at just that patients in septic shock who have been
given high doses of vitamin C so what Marik and his colleagues did and
published in chest a 2060 and got the reference there at the bottom is they
basically looked at 47 patients that had the standard treatment and then they
looked at the 47 patients after a specific time point that did not have
the standard treatment but in fact had something called the Merrick protocol so
we have standard here and then we had something called the Merrick protocol so
what is the Merrick protocol well the Merrick protocol is actually
pretty straightforward it is vitamin C and it is 1500 milligrams IV Q six hours
and this is for four days or until the patient
the intensive care unit the next thing that that is given is thymine and it's
200 milligrams IV Q 12 hours this is also given for those four days and the
reason why this is given is it's to help prevent a formation of kidney stones and
crystallization in the kidneys and this is a low risk of doing it but they
wanted to make sure that it did not happen and they've done safety trials
and they looked at this in it and it just didn't happen the other one that
they gave was hydrocortisone 50 milligrams IV Q six hours and this was
given up to seven days if they need it and then remember hydrocortisone is a
steroid that closely resembles both the glucocorticoid and mineral corticoid
activity of the adrenal cortex and so it was thought actually in early
goal-directed therapy that giving hydrocortisone in patients who needed
vasopressors was good but there's been some studies that have shown that
hydrocortisone by itself is maybe not completely everything that you need and
so these three together or what was done as opposed to just standard therapy and
these 47 patients here were consecutive and these 47 patients here were
consecutive after this break and so that's how the study was done it was not
a randomized placebo-controlled trial so let's take a look and see what the
results were from standard therapy which is listed here on the left versus the
marek protocol which we've just described in those 47 patients so the
first thing we're gonna look at is hospital mortality so how many people
died in the conventional group it was 19 patients that died out of the 47
patients so that works out to be about 40% whereas in the merit protocol there
was 4 out of 47 patients that died and that's only about 9% so there was a huge
difference there and the p-value on that will just squeeze it in over here was
significant at 0.001 now what the ICU length of stay the ICU length of
stay was actually four but it was anywhere between four and ten days in
the intensive care unit was in the treatment group it was a verge of four
but the range was three to five days and that was not statistically significantly
different here's the real key though vasopressors how much exogenously
suppressors were needed in the standard group in terms of hours there was about
fifty four point nine hours of vasopressors that was the average use
per patient now if vitamin C is gonna work it's the thing that's going to
actually cause your body to make norepinephrine and epinephrine we think
based on the biological pathway and this is where we saw the biggest difference
because the average hours of use for vasopressors in the treatment group was
only eighteen point three hours and that was very statistically significant less
than 0.001 now if we can get blood pressure up more quickly then we can
also save the patient from acute renal failure and we saw that again in the
standard group we saw 11 out of 30 patients or about 33% of them going into
renal replacement therapy which means dialysis or acute kidney injury however
in the marek protocol group only 3 out of 31 patients or only about 10% needing
renal replacement therapy and that was statistically significant at 0.02 now
what about the sofa scores what's a sofa score it's basically a measurement of
illness and if you see a big change in sofa scores that means you're seeing a
big change in how fast that patient is getting better so what was the change in
sofa score at 72 hours only 0.9 whereas in the merit protocol group it was 4.8
and that was statistically significant finally how fast did we see
procalcitonin levels come down and so this is not as intuitive right because
we're looking at blood pressure improvement not necessarily clearance of
procalcitonin but you can imagine that if you have better
perfusion to the areas that are infected you're gonna get procalcitonin clearance
improved and that's exactly what we saw so in the control group we saw about a
thirty three point nine percent clearance of procalcitonin whereas in
the Merrick protocol we saw at eighty six point four percent clearance and
that again was statistically significant so here we have it again the America
call vitamin C 1500 milligrams IV Q six times four days or until ICU discharge
number two is thiamine two hundred milligrams IV q twelve hours times four
days or ICU discharge and then three hydrocortisone fifty milligrams IV Q six
times seven days or I see you discharged so what were the advantages or the
disadvantages or let's say the good things are the bad things about this
study so some of the good things is that the two groups were very similar so it's
probably that these changes these differences that we see in these two
groups are probably real and these were consecutive patients the other thing
about this is let's face it vitamin C thiamine hydrocortisone these
are not exactly dangerous medications right they've been in use there's been
some studies that have shown this dose of vitamin C with thymine it's pretty
safe and I think this is the key here now what are some of the bad things when
I say bad what are some of the limitations of this study it's the same
limitations that will see with anything that's not a randomized
placebo-controlled trial and that is it's not a randomized controlled trial
that's the highest level of evidence and we still need to have that it's a small
study okay we need to have a bigger study but interestingly it's a small
study yet it still show pretty significant difference which is pretty
impressive this is a single Center study so maybe there was something about the
patients at this hospital that would have benefited from vitamin C that maybe
your Hospital might not benefit from vitamin C but it's hard to say that and
again as we said it's not controlled it's not randomized so there's all sorts
of biases that can come in right if you know your
to do a trial and now you're about to start in on the 47 people that you're
about to try your new treatment on you might treat them better right and so you
might be seeing improve results from that so we really need to have a
randomized controlled trial and it's got to be a large study and it's got to be
multi center that's really what we need here that being said however the
question is would you use this protocol at your hospital and that's another
interesting discussion now for that analysis this is what I look at look
there's only two possibilities on either side either I use it in my ICU or I
don't use it in my ICU and either it turns out that after we study this thing
it either works or it doesn't work so I don't know if it works right now or not
but I do have a choice of whether or not I can use it or not and so what are the
four possibilities if I look at this if I use it or if I don't use it so if I
use it and it works then I've saved people and I didn't expose anybody to
adverse events if it doesn't work and I used it the question is is did I cause
any harm question of harm and there is good evidence that this is safe and so
therefore there is no harm okay other than the fact that you're spending money
on a medication that's not going to work now if it works and I don't use it then
there's people that I lost because I wasn't using it during the time that I
didn't know it worked right and if it doesn't work and I'm not using it
obviously there's no harm because I didn't use it right didn't save any
people so the question is is where do you want to operate on this two by two
punnett square we don't know if it works or doesn't work it seems like it works
and so I've used it in my ICU and the reason why I've done it is because I
would rather be in this category than in this category it's kind of a personal
decision you have to look at the risks and the benefits I don't see
big downside and giving people high dose of vitamin C because the studies have
shown that it's pretty safe so there's not much to lose so the worst you can be
if you decide to use it is the worst thing that you can be is in this
category and in this situation you're not causing much harm but as it turns
out it may not work if you decide not to use it the worst thing that can happen
is that you might lose people that you could have treated that you didn't treat
so this discussion kicks off a talk about vasopressors how they're used
what's the safe way to use them whether or not you need a central line and for
that I invite you to join me at Meg cram comm for discussion on faze oppressors
in terms of vitamin C and vasopressors I would be remiss if I did not thank my
friend and outstanding nurse tim taylor who works with me in the intensive care
unit for his enthusiasm and his championing the whole cause of vitamin C
in our ICU thanks for joining us