CPC 2016: Denervation and Neurolysis in Resistant Hypertension

CPC 2016: Denervation and Neurolysis in Resistant Hypertension

August 30, 2019 0 By Bertrand Dibbert


– Ladies and gentlemen, I
think we’re ready to start. This is a very special session, and I hope more members of
the audience will arrive. It’s sort of strange start because it overlaps with
sessions. Sorry for this. This is a session funded by
American Heart Association on behalf of our journal Hypertension. And the idea is that two teams, and this time these are
home teams from here, from South Korea will present
very interesting cases and we’re going to have very good and very informed discussion both during presentation
and after presentation. This is an interactive session. Now the good things about this for both the presenters
and the audience are that you are being filmed
so you’re now film stars. But also that the authors
and the discussants will have a paper in Hypertension
if everything goes well. The vigorous discussion is essential and on my right there,
there is Denise Kuo. Denise, stand up and wave, yeah. And the Denise will take
your names afterwards as you contributed vigorously
to discussion of both cases. You’re both film stars and
the authors in Hypertension just after being here
for an hour and a half, I think that’s a good deal. So, without any further ado, I’ll pass the sharing of the first case to Professor Rhian Touyz,
the president of ISH. Rhian. – So Anna. Yeah. Anna, it’s really such a pleasure to have the American Heart Association
participate in this session at the International
Society of Hypertension. Certainly the first of such an association and hopefully not the last. With that, I would like to welcome our presenters for the first case and that is entitled A Case
of Refractory Hypertension Controlled by Repeated Renal Denervation and Celiac Plexus Block: A Case of Refractory Sympathetic Overload. And this presentation is going to be given by doctors Lee, Woo,
Kim, Yoon, Lee and Park from here in Korea. So, thank you so much
for your contributions. – Thank you, chairman. It’s my great honor to
make a presentation in ISH. In November 2011, 31-year old female patient was referred to cardiology division for uncontrolled hypertension. She was hospitalized due
to urinary tract infection. Her systolic blood
pressure was greater than 200 millimeter mercury. She was very obese, her BMI was 32.9 kilogram
per square meter. It was very rare among Koreans. She has past history of ulcerative colitis with remission status and she had preeclampsia five
years ago and three years ago. She had two children. Also she had type 2 diabetes and on regular oral medication. She had type 2 diabetes
on regular oral medication and she also had recurrent
urinary tract infection. She complained headache, nausea, vomiting and blurred vision. It’s some results of her
blood and urine tests. Except fasting glucose and hemoglobin A1C, most tests was within reference range. Her thyroid function was normal and albumin creatinine
ratio in urinary analysis was slightly over reference range. It was 41.34. Her electrocardiography,
electrocardiogram showed no evidence of left
ventricular hypertrophy and any other abnormal findings. Her LV systolic function was normal and LV mass index was 61.8
gram per square meter. It was within normal range. She complained blurred vision so we consultated ophthalmology division and ophthalmology answered that she had no abnormality on both retina. We performed the approach
to resistant hypertension as follow algorithm. First, exclude pseudoresistance,
white coat hypertension. Second, identify and
reverse contributing factor. Third, we try to discontinue and minimize interfering substance and screening for secondary
causes of hypertension. First, it is her ambulatory blood pressure monitoring result. It showed very high
ambulatory blood pressure so we excluded white coat hypertension. It’s her central pressure wave form and it showed very high
central pressure as well, And for ruling out coarctation of aorta we measured four limbs blood pressure and there were no differences. We evaluated the pheochromocytoma. Her plasma metanephrine
and normetanephrine were within reference range and we performed a
20-hour urinary collection for correctional metanephrine repetitively but they were within reference range. Next, we performed PET-CT for evaluating the abnormal mass because she had unknown,
fever of unknown origin. Fever of unknown origin so
she was performed PET-CT five months ago and it showed no other abnormal FDG
uptake suggesting malignant. Also, we did MR imaging and it showed there was no abnormal
anatomy of adrenal gland. It was I-MIBG scan, it showed
no abnormal MIBG uptake. For evaluating renovascular hypertension, MR imaging of renal vasculature showed intact renal arteries. And for evaluating hyperaldosteronism
or Cushing syndrome the renin/aldosterone level were measured and aldosterone renin
ratio was not elevated. And overnight Dexamethasone
suppression test revealed normal response, and 24 urinary cortisol level
was within reference range. As you showed previous slide there was no abnormal
uptake or mass on PET-CT and MR imaging of
adrenal gland and kidney. She complained of blurred
vision and headache so we performed the MR imaging of brain. No focal lesion pituitary
fossa or brain parenchyma so we exclude it, we could
exclude it the pituitary adenoma. Next we evaluated, we examined
the growth hormone level. The plasma hormone levels were
also within reference range and insulin-induced hypoglycemia
test showed normal result. We identified she had poor urinary output in spite of taking diuretics. She drank more than two or three liter water daily but urinary output was
just below one liter. Her plasma BUN and creatinine
level did not change. We suspected malignant nephropathy so we did DTA renogram and it showed normal range of GFR. Therefore, we suspected
urinary tract problem so we performed urodynamic
study and it showed acontractile detrusor. Therefore, we educated her how to use intermittent catheterization but blood pressure was not improved. Next, we evaluated presence
of obstructive sleep apnea because she was very obese. Her polysomnography results showed hypopnea index was just 0.5, it was normal. This is a summary of her
antihypertensive medication. She took a lot of oral
anti-hypertension medication including angiotensin receptor blocker, beta blocker, calcium channel
blocker and diuretics. But her blood pressure
remained uncontrolled so we used IV nicardipine,
calcium channel blocker and sometimes her blood
pressure was controlled. We want to medication
change for reduced IV use of calcium channel blocker. We tried to modify
medication to oral medication but it was failed. – [Rhian] Thank you so much for
the introduction to the case and it’s very nice that at this point, you have proposed a number of
questions about this patient, and I guess you’re going to
help us in terms of discussing whether you maintained the patient on oral medication as it is, whether you will change the
medication, her oral medication, and I guess you want to
suggest possible alternatives, and the role for
non-pharmacological treatment. We look forward to, for the discussion. – Yes. I’m the attending physician
for this particular patient and if I summarize, it was a
very obese female in her 30’s. She had diabetes and she initially had a
very high blood pressure that was absolutely unresponsive
to all oral medications. Initially because the echo, the EKG and the fundus was actually very benign. We initially suspected
white coat hypertension but when we did an ambulatory
blood pressure monitoring as you could see it was
very extremely high level. I don’t think it was a case
of a white coat effect, rather maybe the blood pressure elevation happened very recently. This is just a cross sectional slide to show the types of medications that we were using at this period, but we tried also third combination, different combinations. We used different types of beta blockers, different types of ARBs, ACE inhibitors, anything we could do, any
medications that were available and just, she wasn’t responsive, yes. I was wondering if any of you
experts have any suggestion, what you would do with
this particular patient at this moment.
– All right. Perhaps while the audience is
thinking of some questions, I’d just like to ask you in
terms of the patient profile. I think there were two
significant factors. The one being that she
had had preeclampsia. – Yes. – [Rhian] Did this come into your, it must have come into your consideration, perhaps you could tell us how
you took this into account in terms of this very complex
severely hypertensive patient. – Preeclampsia itself is a risk factor for future hypertension
but her history was she had preeclampsia three
years before she was admitted. And after her second delivery, she didn’t have hypertension actually. – [Rhian] And did she remain obese or was the obesity–
– She was obese. I think she, from my memory, she gained close to 20 kilograms
during her pregnancy. – And she remained
– Yeah. – Obese thereafter.
– Yes, yes. – [Rhian] And one more
question I’d like to ask you just in terms of what
you’ve shared with us, I don’t recall seeing
heart rate variability and characterization of her heart rate. Could you comment on the heart rate? – The heart rate was relatively high, it was around 80, between 80 and a hundred despite us using full dose beta blockers. – Okay.
– Yes. – [Rhian] With that,
we have the floor open for some questions. Anna, do you want to? – [Anna] If I can start. First of all, I would
like to go a step back. In order to exclude
secondary hypertension, you did enormous and very, very detailed set of investigations and I understand this is an extreme case, very high blood pressure,
very, very difficult but I’m not sure I would have gone to for example MIBG scan
with completely normal catecholamines and metabolites. There were the number of tests and the detail of the testing is more than I think we would have
done in a European patient. Can you explain this
difference of approach and may I ask a second, sorry.
– Yes, yes. – [Anna] And my second question is whether you are 101% sure that she takes all these complex cocktails of drugs. Have you checked both
by direct observation and the levels whether the
drugs are truly consumed everyday all the time? – That is an excellent point. This PET scan, PET-CT scan
was actually performed before she was referred to me because she had an FU. We’re just showing that
in previous PET scan that was performed several months ago there weren’t any bad uptakes. And this MIBG scan was,
actually the history is because nothing was
responsive for this patient, we actually sent her
to get a second opinion to Seoul National University,
our second presenter actually. He took care of her for several months and this MIBG scan was actually performed at Seoul National University. In essence in our hospital, the urine catecholamine was performed and renal angio MRI was
essentially performed through a secondary hypertension case. – [Rhian] So just getting
back to the medication and you said and we saw she was on this very complex cocktail of all the different antihypertensives, and I’m sorry, I keep going
back to it, the heart rate and the fact that she remained to have a relative
tachycardia despite the fact that she was on all these beta
blockers and other blockers. – Of course. – Did you at some point then say, first, is she compliant because that’s always a good indication and secondly of course, may it in fact be related to sympathetic hyperactivity? – She was admitted to the
ward for a long duration during the follow up period and because we suspected
a poor compliance, we made sure that our
attending physicians, our house staffs and our nurses made sure that she took the medications. That’s how we ruled out non-compliance. – [Rhian] Okay, so this is time now really for us to have open discussion and please, I welcome you to come to the microphone and I see that there’s Garry Jennings who’s always very actively involved in these clinical case presentations
has a question for you. – Firstly a comment, I
think we have to accept that sometimes we do find these patients with very high blood pressure and no evidence of target organ damage that we can’t explain. This lady is being worked up as well as anybody you could ever see. And I think most of my
questions have just been asked. I’ve got one more, it’s the curious issue of her fluid balance because I think you gave us
some records over nine days when she was theoretically
accumulating a liter a day. You’re suggesting that
was all in her bladder and did it come off when
she was catheterized or was she somehow doing something with her urine collection? – To tell you the truth, this patient is probably one of the most
famous cases in our hospital because she sort of had
a primary polydipsia and she would take three or
four liters of water per day even when she was admitted, while we told her not to do that she would just drink water. And the fluid balances
would be incredible, it would be like four liters of intake and only 500 cc of output. It was very, very bizarre. In two or three weeks she would gain like five kilograms of weight just
by drinking a lot of fluid. Then we couldn’t explain why she didn’t have a good,
adequate urine output so we evaluated for maybe
it was a neurogenic bladder with fluid reflux and
obstructive uropathy. But as we demonstrated
when we did a evaluation, she had neurogenic bladder but, I’m sorry. When we did a renogram, her
kidney function was okay and she didn’t have any VU refluxes. Why she has such a low urine
output I cannot explain but later on when I show you the progress when a cystostomy was
performed at Seoul National, the urine output was normalized. It may have had to do
with neurogenic bladder. – [Rhian] Okay. Are there any other
question, yes please come and please if you introduce yourself and from where you come. – I’m from Catholic
University Seoul, Korea and my question is also I want to need, want to know her heart rate and I’m sure I believe that you used enough thickness of cuffs when you measure all (mumbles)
blood pressure, right? – Yes, yes.
– Yes. And did you ever try to measure her blood pressure invasively? – Invasively?
– Yes because her left ventricular mass is quite normal under 70 I remember, 70
gram her body surface area so it’s too normal for her blood pressure. Have you ever tried to measure arterial blood pressure invasively? Another thing is have you
ever take her history of current ginseng medication
or heart medication? – Again, she was a long duration
among the follow up period, she was actually admitted
during the hospital so we made sure she
didn’t take any ginseng or anything like that. And no, your answer to
the question whether we evaluated for invasive blood
pressure, we didn’t do that because yeah, it would be too invasive for this kind of patient, but to answer your question. When we were doing another procedure, we’re gonna talk about this instance, this is a case of renal denervation. We were doing renal
denervation and she received IV anesthesia, the blood
pressure decreased to 130, yeah. – 130.
– 130. I think may have to do extreme anxiety, increased sympathetic nervous system activity.
– Yes. And this is also I want to know how is the amount of urinary
excretion of sodium level? Because she is too much
she drink water I think. – We didn’t evaluate
for 24-hour urine sodium but I think that’s a great point, yes. – [Rhian] Okay. Perhaps we’d like to learn a little bit more about the patient and then we can see
how we can approach the medication question that
you’ve posed over here. – Okay. Should I go on now?
– Yes, yes. – [Dr. Sungha] Okay, so
due to her being refractory to all these medications, at this point in Korea we started the renal denervation
SYMPLICITY Korean registry and we enrolled this patient
into the registry trial. And initially this, in April of 2012, we performed renal denervation. We had eight ablations
to the right renal artery and six to the left. Initially, we thought
there was some response but you know, as you can see after follow up, continued follow up there was absolutely no response to the renal denervation during the three more months of follow up. After this, I actually didn’t
have any more options left, I didn’t know what to do with this patient so I suggested that maybe
she could get evaluated at another top class hospital in Korea so Seoul National University. I sent the patient to Dr.
Lee, the next presenter. After renal denervation, what other treatment options are there? Are there other treatment options that you are aware of that we could select at this time? I think some input from the
audience would be very helpful. – [Rhian] Okay, so we’ve got
this very complex patient who’s been on everything. Could you tell us at this point when you felt that you
had no other options what she was taking at that point after the renal denervation. – She was still taking all the other. – [Rhian] She was taking all of those? – Yes, yes. Full dose of the medications, yes. – [Rhian] Okay. Here we have this 31-year old lady, past history with preeclampsia, some inflammatory ulcerative
colitis in the past, on eight or 10 or 12 different drugs, apparently compliant. Some ambulatory blood
pressure monitoring proved that she was truly hypertensive. You’ve done this renal
denervation that was not helpful at all, and the question is where
do you go from here? Just getting back to the ambulatory blood pressure monitoring
and the heart rate, did you see any nocturnal or 24-hour or circadian rhythm
changes in this patient? – Yes. – [Rhian] On repeated testing. – You mean repeated ABPM?
– Yes. – [Dr. Sungha] This is actually the ambulatory blood pressure data, yeah. You can see the nocturnal
blood pressure was actually. – [Rhian] She’s actually, has evidence of probably reverse dipping
which of course as we all know is a really bad marker
of cardiovascular risk and worse cardiovascular outcomes. Interestingly, despite the fact that she hasn’t got evidence
as determined clinically and by very specially investigations, she doesn’t have evidence at this point at the age of 31 of target organ damage. She’s showing us
something very significant in terms of her ambulatory
blood pressure monitoring of this reverse I guess
dipping phenomenon. – [Anna] Could I add? This is one of the sort of
one case in the lifetime, yes, that is almost unresolvable. And it is puzzling
because it is very similar to a case that was presented
approximately two weeks ago in Orlando at the meeting of
American Heart Association Council for Hypertension. And this was a case presented by a team of a physician and neurosurgeon because the patient after having been and been through all these procedures including renal denervation, et cetera, has asked to have a
neurosurgical procedure, a deep brain stimulation that has helped. But this was N equals one, only one such case was done in this center in Bristol in United Kingdom and this would be case
that has also been filmed and will be in due course, written up. I think there is uncanny similarity between these two cases and I think there must be
some neurogenic mechanism that is driving this hypertension. Have you looked more at
sympathetic nerve activity? Have you thought that maybe
you can look at kidneys again, maybe there is still a hope
to do another procedure? Because I think the
tablets are not working. I think we know that the
tablets are not working. We have some experts in the audience in sympathetic nerve activity
and renal denervation, maybe we can hear some
comments from the experts? I’m looking at one at the moment. – In Korea, muscle sympathetic
nervous activity measurement isn’t available, so yeah. – Thank you Professor Anna Dominiczak. My name is Dagmara Hering, I
am originally from the Gdansk currently working in Australia. And this, it’s very difficult case to find the best approach and I’m still wondering whether
this kind of anxiety level in this patient and stress-related which some patient may not tolerate ABPM and they are a little bit stressed, and we don’t have tool to
measure the blood pressure. One approach is the automated unobserved blood pressure measurements
when we leave the room and then we leave patient alone, and then we may get
similar readings to ABPM. And with patient who are obese they not often tolerate the arm cuffs which also may trigger the blood pressure. And having the polydipsia, we can exclude that she may also get up
at night time and drink which may also impact or her higher level on night time blood pressure. In this it’s very complicated case and in this scenario we
look for the procedure and maybe it’s also three
months is short term after for the effect of renal denervation. And indeed the sympathetic
nervous system activity may help us to identify whether really the neurogenic components trigger this scenario
which is not available. And that there is the
deep brain stimulation is one of the case reports and it’s one of the tools. But I also know from experience from one of the conferences
which was presented that there is also rebound
effect after 18 months which even after deep brain stimulation we’re going to the level
that there is again increased blood pressure after the base approaches for the treatment
like interventional. We still don’t know whether it’s related to central anastomosis,
deep brain stimulation, renal denervation or
even carotid body removal because there’s no such data. But in this, I think some
patient really the anxiety level giving some maybe stress
management may help and trigger and help to
reduce the blood pressure. – Yes. I think that’s a great point, I have a lot of so-called
refractory hypertension patients who actually responds to Xanax, but in this case, I tried all kinds of anti-anxiety medications, I had psychiatric consultation and the psychiatric consultation note is she is psychiatrically normal. (snickers) It was the answer from the
psychiatric department. And she had actually no
response to Alprazolam. Very, very difficult case. Only thing that responded, only the treatment that
responded was IV drugs such as IV labetalol, IV nicardipine reduced her blood pressure
but not oral medication. – [Rhian] That brings me
onto a very important point and I think something as
clinicians we all struggle with when we see patients such as this who come with eight or nine or 12 drugs and the blood pressure remains 180 or 200. Did you at any point consider stopping all of her medication? – You mean, stopping it at– – [Rhian] Titrating the medication down. I mean, not stopping everything at once but slowly removing the medication to see if that actually impacted at all. Because sometimes this
is an approach to help even from a diagnostic point of view as to what may be working
and what maybe not from a mechanistic point of view. I’m just asking at any
point did you down titrate because what if you were adding was having absolutely no benefit? – I didn’t do any down titration, I just, after several weeks or several months I would switch medications from the same class, different drugs for example, using bisoprolol
if there wasn’t any response I would switch to nebivolol or carvedilol. But I didn’t down titrate the medications. – [Rhian] And I think you bring up something extremely interesting and that is the fact that she responded to intravenous beta blockers
but not to oral beta blockers. Which also actually
despite all the monitoring would make you think
is she actually taking her oral medication. I think we should still
be a little bit cautious in terms of how sincere she
is despite the monitoring because as we know
patients can be very clever in their maneuvers. But any other, Garry? – I’m just following up
on Dr. Hering’s comments on the sympathetic activity. We’ve learned quite a lot
about renal denervation since HTN three and
particularly about the technique and making sure that the lesions are distill in the renal circulation that multiple lesions are made. Now, I just wondered when
you went back over that whether you were satisfied, you’ve done a satisfactory technique and it just emphasizes how badly we need a simple tests of the effectiveness
of these interventions. – I think that’s a wonderful comment. At the start, she was the
second patient from the registry so our interventional
cardiologist actually, was relatively passive in his ablation. He says so himself. He did know whether too much ablation could be harmful to the patient. Relatively the number of ablation was not satisfactory to him. With increased cases, he would do more denervations for each arteries. I’m gonna show you the next procedure when he performed more ablations
of both renal arteries. – [Rhian] Let’s learn more about the progress of the patient. – Before I sent the
patient to Seoul National to get a second opinion,
I did a lot of searching. What about nitrates plus phosphodiesterase Type 5 inhibitors, will that work, you know? There was this paper from
Hypertension which shows that combining nitrates with
Viagra maybe could have a significant reduction
in her blood pressure. This was a very small study that showed that in
resistant hypertension, it does reduce blood pressure. We tried that and initially it worked. There was a huge drop
in blood pressure but became refractory after several days. We waited for it to have a response but there wasn’t any response so we discarded this not effective. And then we asked her, I
contacted the Seoul National and I sent her to get a second opinion. And the evaluation there
was also all negative as expected but due to
her neurogenic bladder, they performed a cystostomy. And an interesting
thing is they were doing a therapeutic drug management study for filmasartan and
amlodipine at this time, so, Dr. Lee enrolled her into that study. And when she took 10
milligrams of amlodipine, very interesting finding was that compared to what would be
expected from normal patients, she only had about 1/3 drug
concentration for amlodipine. And for filmasartan also, the concentration was only
about 1/3 of concentration. We suspected maybe
because the blood pressure is very responsive to IV drugs
but not to oral medication, she has some sort of a absorption problem of the oral medications. There are some references to show that patients with previous history
of inflammatory bowel disease which she had but was in remission, there are cases of high
multi drug resistance with patients who fail medical therapy. And there are some cases where some polymorphisms are associated with decreased response to amlodipine
according to genotypes. Maybe this such a case but we can’t confirm anything about this, yes. After that, Seoul National
said, ah, we give up. Yeah, so they sent her back to me but before that, Dr. Lee
and I had a deep discussion about this patient and maybe he said, “Why don’t you consider a
sympathectomy for this patient?” Because although sympathectomy wasn’t, has not been performed
since the last 60 years, it has shown to be effective
for reducing blood pressure. I think she recommended to the patient but she wanted to get a second opinion and she came back to
me to get a treatment. What we decided to do after
a lot of conferences is maybe we should do a redo
denervation of this patient. And we contacted Medtronic
to get their permission to see if we could get permission to do another procedure from this patient. And studies have shown that with increasing number of ablation, there is a significantly better
reduction in blood pressure. We did a redo denervation. By this time the
interventional cardiologist had more experience doing this procedure so he had a very significant increase number of ablation of both arteries. After the second denervation, there was a slight decrease
in the blood pressure. It got our hopes up but it
started to go back up again. After three weeks, the
blood pressure was now again, about 140, 180
over 130, 180 over 140 and she was still taking all those high number of medications. What other options are left
for this patient at this time? We did a renal redo denervation. Should we at this point,
wait for several more months to see a delayed response or other non-pharmacologic treatment? But all these options were
not available at this time and is still not available in Korea such as baroreceptor modulation, AV fistula or deep brain stimulation. So, any other suggestions at this time? – [Rhian] Yes, please. – I may have add one comment that some of the patient is very rare case but actually it’s
neurovascular compression on the left side when we
performed the MRI scan. We sometimes identify the nerve particular from eight to ninth and seven, there could be compression usually on the left side
where the case report which are available they’re showing that while until eight months there is reduction in blood pressure and muscle sympathetic nerve activity in patient with resistant hypertension who have the neurovascular compression, and there is release of the procedure. There could be later on
again the rebound effect but this is different procedure to the deep brain stimulation. But some in varied case including children even with you give the high dose of angiotensin receptor blocker like Atacand, candesartan or Telmisartan, that some patient may have
the neurovascular compression. And the simple MRI and
looking at the nerve particular on the left side may identify that this is the cause of the consistently elevated blood pressure. – Do you have any data or
experience doing redo denervation and do you have experience where they didn’t have any response initially but after denervation,
after several more months there was a delayed drop
in the blood pressure? – No, I don’t have similar… I’m talking now in the
neurovascular compression within the brain separately of renal denervation.
– Oh okay. – [Dr. Dagmara] But
there is some nice data and the number of patient
well from the German group who published years ago that patient with elevated blood pressure they have neurovascular decompression, the conflict within the brain and when you release the
pressure of the nerve particular eight and
nine on the left side, this related to reduction
in blood pressure and muscle sympathetic nerve activity. It’s not direct treatment for hypertension but it’s a cause which
leads to consistently elevated blood pressure. – [Rhian] Thank you, thank you. Perhaps we’ll carry on to see how you unraveled this
very, very complex patient. – I’m gonna briefly show you
the history of sympathectomy because this was something that, it was our last option to consider. It was a treatment for severe hypertension during the 1930s and ’50s but after the development of very powerful antihypertensive drugs it was discarded into the history books. It was very effective but as you can see it’s a very significant
morbidity and mortality rate. I’m gonna introduce you
to the celiac plexus. A celiac plexus is a very important plexus of sympathetic nerves. It consists of the
greater splanchnic nerve the lesser splanchnic nerve and the least splanchnic nerve, and it supplies most of the
organs of the upper abdomen. And this is a very important paper published in the JCI 1996 when they did sampling from seven subjects undergoing abdominal surgery. They sampled blood from the portal vein, the systemic arteries
and the hepatic veins. What they found was that out of the total norepinephrine spillover, 42% of the norepinephrine spillovers are contributed by the mesenteric
and the hepatic spillover. This shows that the celiac
plexus is associated with a significant portion of the total neurohormonal stimulation
in normal subjects. This is another study that
was published in Hypertension where they induced angiotensin II and salt-induced increase in
sympathetic nervous system activity in hypertension. And this study showed that in rats, celiac ganglionectomy
but not renal denervation was associated with significant
control of blood pressure. And when they analyzed for
the norepinephrine level in each major organs, the renal denervation had no changes in the norepinephrine content, but celiac ganglionectomy
had a significant reduction in the norepinephrine
content of the major organs. You can see that blocking
the celiac nervous system is more powerful than renal denervation in reducing sympathetic outflow. Currently the celiac plexus
block’s indication is intractable abdominal pain. This is a major indication
but historically, this was performed for Raynaud phenomena, ischemic ulceration,
Buerger’s, hyperhidrosis and in some people, they say hypertension. The complication rate is if
you do it with an expert hand, the serious complication
rate is less than 1%. The major complication from
this procedure is hypotension which has been reported to be up to 50% and transient diarrhea. And it has been performed since 1914 as a procedure by the anesthesiologist. We contacted the anesthesiology department and they initially performed a test block of the right celiac plexus, and she showed a significant
drop in her blood pressure. And since the test celiac
plexus block seemed to work we did a second plexus block
at the right celiac plexus with dehydrated alcohol and was associated with
also a significant drop, about close to 50
millimeters of mercury drop in her blood pressure. After that we did a third block of the left celiac plexus
with Lidocaine and ropivacaine with a similar level of blood pressure for this procedure. And after I reported this
case in a Korean meeting, there was another case reported by the Catholic University, it was a similar case, an
18-year old male patient was absolutely refractory to
all kinds of oral medications. The renal denervation failed and what they did was they performed a celiac plexus block
with botulinum toxin. And the blood pressure had been controlled and they reported this case into a journal called Toxins. For this case, a repeated
celiac plexus block has been performed two more times because after the plexus block after about three or four months, the blood pressure began
to get elevated again and the authors reported that they did it, have performed the procedure
several more times. In our case, after the
second renal denervation and the plexus block, the blood pressure started
to decrease actually. Started to decrease and at about April, she actually had symptoms of hypotension. We had to remove all the medications and currently her progress is very good. Her nocturnal blood pressure was elevated but her awake mean blood pressure with ABPM dropped to actually 134 over 83, and this was actually
without any medications. Her progress until now is
recurrent hospitalization because of some complications
from the cystostomy but she is currently normotensive without any antihypertensive
medications at this time. I still don’t understand
what the mechanism for hypertension is but after redo denervation
and celiac plexus block her blood pressure is
right now no problem. – Thank you for that really
interesting presentation. I just want to go back one more time, I know we’re running out of time but when you did the ambulatory
blood pressure monitoring, did she still exhibit the
reverse dipping phenomenon? – She still did, yeah. – She still despite the
fact that her blood pressure had come down by 50 millimeters, she still had a higher night time blood pressure.
– Yes, yes she did. – [Rhian] Which is in itself,
as I said very interesting. Anna?
– Yes. – [Anna] We need to move on but I think you succeeded which is great. We don’t understand completely why, it must be neurogenic
mechanism, but can I ask, when things were really wrong and she was on all these drugs and you were doing first
and second renal denervation and things didn’t work, how did she feel? Was she a very sick lady or somebody who just had very, very
high blood pressure but otherwise was fine when you went to see her in the morning? – It was a second case. She was, only thing she had
was elevated blood pressure and the blood pressure was
elevated above 180, 200, she has some headaches, nothing more. – Great success for you. – Thank you.
– Yes. – [Rhian] Indeed the patient is lucky. Still don’t understand the mechanism so maybe essential hypertension
after all by definition, and with that I really do
want to thank you so much for your contributions and
a fantastic discussion. Many, many thanks. – Thank you for your attention, thank you. (audience clapping)