September 26, 2025 • 31 mins
This week we review a recent report of the use of phenoxybenzamine for the reduction of SVR in children undergoing congenital heart surgery in India. How does this agent work and what might be the advantage versus other agents like nitroprusside or milrinone which are more commonly used? How does the cost of this agent (or phentolamine) compare with newer agents? We speak with Dr. Rohit Loomba of Lurie Children's Hospital. For those interested, in addition to working as a critical care cardiologist, Dr. Loomba is also a noted cardiac morphologist and his wonderful videos can be seen at the following web address:
https://www.youtube.com/@Talking_Hearts
Today's paper:
DOI: 10.4103/jpbs.jpbs_868_25
https://www.youtube.com/@Talking_Hearts
Today's paper:
DOI: 10.4103/jpbs.jpbs_868_25
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:16):
Welcome to Pedheart Pediatric Cardiology Today. My name is doctor
Robert Pass and I'm the host of this podcast. I
am Professor of Pediatrics at the Icon School of Medicine
at Mount SINAI thank you for joining me for this
three hundred and fifty sixth episode of Pdheart. I hope
everybody enjoyed last week's replay episode, in which we spoke
about post operative actomic atrial tachy cardia and its mechanism.
(00:38):
For those of you interested in post operative a rhythmias,
i'd certainly recommend you take to listen to last week's episode.
As I say most weeks, if you'd like to get
in touch with me, my email is easy to remember.
It's pdheart at gmail dot com. This week we move
into the world of pediatric cardiac critical care. The title
of the work we'll be reviewing is Finaxi Benzamine Old
(01:00):
Wine in a Bright New Bottle, Taming the wild Side
of Venaxi Benzamine. The first author of this work is
our Benedict Raj and the senior author Goot Prakash Ready
and the authors come to us from the Department of
Pediatric Cardiology and Cardiac Surgery at the Children's Heart Institute
ast Ramesh Hospitals in India. When we're done reviewing this paper,
(01:22):
doctor Rowheat Lumba of Luri Children's Hospital, who's a cardiac
critical care physician, has graciously agreed to speak with us
about it. Therefore, let's move straight onto the article and
then a conversation with doctor Lumba. This week's paper that
we'll be reviewing is a very brief one, but I
thought it brought up an important topic that we've reviewed
previously in prior years, which is the maintenance of good
(01:42):
cardiac output in the post operative congenital heart disease patient
following surgery. And you may recall conversations we've had in
the past on two occasions with doctor Anthony Rossi of
Nicholas Children's Hospital about his efforts over thirty years ago
to use things like mixed venus saturation to better understand
and in real time the output of hearts of single
(02:02):
ventricle patients following first stage pallid of procedures. This work
revisits the use of finoxi benzamine for the treatment or
improvement of cardiac output following surgery to those less familiar
phenoxy benzamine is a non selective and irreversible alpha adrenergic
antagonist that blocks both alpha one and two receptors. Blocking
(02:25):
the alpha one receptors will result in systemic and pulmonary
vasodilation with possible afterload reduction effects, which could be very
important or helpful for the post operative heart patient. Alpha
two blockade will increase nore epi release, which can lead
to tachycardia and maybe even increases in cardiac oxygen demand.
This agent is perhaps best known for those undergoing surgery
(02:48):
for fiochromocytoma, but it was popularized for use in the
ICU after repairs such as things like hypoplastic left heart syndrome,
most notably by the master surgeon, doctor Jim Twiddle, when
he was working in Wisconsin in the Elite nineteen nineties.
At that time, doctor Twittle was having extraordinary outcomes with
hypoplastic left heart syndrome patients following the Norwood and though
(03:10):
I think we would all agree that this was largely
related to his outstanding surgical skills, he and the team
in Wisconsin were concerned or convinced that this agent fanoxi
benzamine was at least part of the reason that outcomes
were so good. It should also be noted that it
can be used for pulmonary hypertensive crises, as it can
affect pulmonary vascular tone as well, and it's thought that
(03:32):
it could possibly be of benefit when repairing certain lesions
that are more associated with post operative pulmonary hypertension, such
as truncus arteriosis. Though effective for these indications, phinoxy benzamine's
use has faded to a degree because the agent has
a very long duration of action and the hypotension that
can occur with this agent can be difficult to manage,
(03:53):
and the reflex tachycardia and unpredictable hemodynamics due to the
Alpha two receptor blockade are also desirable features. Alternative, shorter acting,
more precise agents like milernown or nitroproscide or prostacycline or
even sildeniphil have largely replaced this agent, but there are
many small series that have demonstrated that despite newer agents
(04:14):
that have worked well to achieve many of these goals,
phonaxi benzamine has been demonstrated to work well in the
post operative setting, despite the fact that newer agents have
supplanted it in many centers with this as a background.
The authors of this work, which comes to us from
the Giawata, India, which is in the eastern part of India,
report to us their experience with finoxi benzamine when used
(04:37):
in a strictly protocolized approach, which they hypothesize has allowed
the practitioners to get the powerful positive benefits of this
agent while mitigating its risks. And the authors explain that
it is relatively inexpensive in that country and so may
offer the ability to be both safe and effective while
also being relatively cheap, essentially a possible win win. This
(04:59):
was prospective observational case series from twenty fifteen to twenty
twenty at a large single tertiary center in India with
five hundred and twenty patients getting phinoxibenzamine during cardiopulmonary bypass,
and the authors explained that it was used for patients
who had an increase in pulmonary blood flow or those
who needed reduced systemic vascular resistance, and they suggested that
(05:21):
such situations would be a VSD thapvr dtga ivy canal defects,
microvalve repairs, and pulmonary artery banding. The authors explained that
those who had reduced pulmonary blood flow with cyanotic heart disease,
or those over ten years or weighing more than twenty
kilos were excluded due to hypotension risk. In this center
(05:42):
and study, finoxi benzamine was given in the cardiopulmonary bypass
reservoir at a dose of two milligrams per kilogram, and
there was no post operative dosing. The authors explained that
for patients who still had pulmonary hypertension, oxygen millernone or
sidenophil was also used. Two hundred and fifty nine of
the f five hundred and twenty cases were less than
a month of age, two hundred and five were one
(06:04):
to twelve months, and fifty six were one to five
years of age, so the majority less than a year
of age. The diagnoses were sixty nine percent VSD, twelve
and a half percent, AV canal defect, eleven and a
half percent total an almost pulmonary venus return, six percent DTGA,
and seven patients who had an ap window, so importantly,
(06:24):
no single ventrical patients in this work. The office provided
the cardiopulmonary parameters and they were all within normal limits
with a bypass time of seventy five minutes in this work,
So what happened postoperatively to these patients. Well, the mean
ventilation time was twenty two hours and there was only
one case of pulmonary hypertensive crisis constituting zero point two
(06:45):
percent of the entire cohort. No patients had significant hypotension
requiring the use of vasa pressen or other inotropes, and
the majority of patients were extavated on the day of surgery.
The mortality rate in this study was two point seven
percent or fourteen death with one percent of the VSDs
or five total patients dying, followed by three avcanal patient
(07:05):
deaths and two deaths each amongst the TAPVR and DTGA patients.
Of note, this is a very short report and there
is no control group or even hemodenamic information other than
that the majority of patients were fine and no one
needed intravenous inotropes or vasopressin AFT surgery. The author's discussion
begins with the statement and I quote this study reaffirms
(07:28):
the utility of phinoxybenzamine as a safe and effective vasodilator
in pediatric cardiac surgeries involving cardiopulmonary bypass administered via a
structured protocol. Phinoxybenzomine successfully maintained stable perfusion pressures and consistent
cardiopulmonary bypass flows without the need for intraoperative vasopressin or
additional vasopressors. Most patients achieved early extabation, and postoperati hypotension
(07:53):
was readily managed with fluids and low dose adrenaline, minimizing
ICU interventions. Importantly, the use the incidence of pulmonary arterial
hypertension crisis was nearly negligible, with the only one reported
case among five hundred and twenty patients. The authors suggest
that they believe that this work demonstrating generally good outcomes
support the use of this agent. They mention that they
(08:15):
believe the absence of hypotension in this work is related
to the patient selection and also dosing. They explain that
miler known is part of the pulmonary hypertensive protocol for
post opera patients, but strangely don't share who or how
many receive this agent. They similarly do not mention what
percentage or patients received low dose adrenaline to use. Their
terminology The authors conclude by suggesting that when this agent
(08:38):
is administered during bypass, it results in a predictable rapid
cardiac recovery in low SVR, and that hypotension was not
observed when it was given in this study. They suggest
that the use of this agent improved post operative survival
and suggest that it is a good agent for a
resource strapped setting like India. Well, this is an interesting
(08:58):
work more because of what they are describing than for
the scientific rigor of this work. There is, of course,
no way to know if the use of finoxi benzamine
in this group was the reason that the patients generally
did well, as most of these cases are cases that
would be expected to do well with or without this agent.
Though the agent is not really studied in a rigorous manner,
(09:19):
I do wonder if there is perhaps a signal here
that could be of value and maybe has been overlooked
by our surgical and cardiac critical care colleagues in the
recent past. I do think it's also noteworthy that some
percentage to patients did need intravenous einotropes, despite the statement
by the authors that few patients, if any, needed them
In the interests of time, Let's move forward to a
(09:39):
conversation with critical care cardiologists from Louri Children's Hospital, doctor
Roehitt Lumba. Tuining us now to discuss this week's work
is doctor Roeheat Lumba, who is a pediatric cardiac critical
care physician at Louri Children's Hospital. Doctor Lumba is a
graduate of Rosalind Franklin University's Chicago Medical School and completed
his residency and fellowship training in pediatric cardiology at Children's
(10:02):
Hospital of Wisconsin. Following this, he completed a fellowship in
pediatric cardiac intensive care at Cincinnati Children's Hospital. Review of
his resume and the times that he worked there seemed
to suggest that he may have well worked with doctor Twittle,
who favored finoxi benzamine and the management of his post
operative single metrical patients. And so I am hopeful that
we have really identified a true expert on this topic
(10:24):
to discuss it this week. I should also mention that
doctor Lumba is a cardiac morphologist and currently curates the
Faruk Idris Archive in Chicago, and he has posted many
YouTube videos of his wonderful lectures online and I'm going
to put a link to some of his work there
with today's show notes, it's it's like to have him
join us. Welcome doctor Lumba to PDHART. I'm here now
(10:45):
with doctor Rowet Lumba of Lori Children's Hospital. Doctor Lumba,
thank you very much for joining us this week on PDHART.
Speaker 2 (10:51):
Oh, thank you for having me. It's an honor. The
podcast has turned out wonderfully well. Congrats on the success.
Speaker 1 (10:57):
Thank you very very much. You know, doctor Limba, the
topic of this week's paper is the use of finoxy
benzamine for the post operative care of children following congenle
heart disease surgery. Can you explain to the audience who
may be less familiar, what the experience in general has
been with this agent, which I know you have used
(11:18):
previously with the wonderful doctor Jim Twittle, and why it's
less commonly used in deference to agents like miler known
nitropruss side, or even on the pulmonary side, nitric oxide.
Speaker 2 (11:30):
Yeah, for sure. I think I'll start my answer at
a more fundamental level and say that in the care
of any patient, specifically I critically ailed post operative patients,
the body and its constituent organs need oxygen and the
purpose of the cardiovascular system is simply to use blood
as a transport medium to get auction to all the organs,
and systemic auction delivery, as we all know, is the
(11:52):
product of auction content and partiac output. Partiac output further
breaks down into heart rate time, stroke volume, and then
volume further breaks down and is modulated by threeload, afterload,
and contractility. And so within this oxymetric framework, we know
that a low afterload, high contractility state or low SDR
(12:12):
hy partic output state leads to the best clinical outcomes
and this is maintained across ages and circulatory phenotypes. And
so this is where alpha blockade comes in because alpha
blockade with either phinoxidbenzamine or phantolamine has been used to
reduce afterload by discreasing systemic bascular resistance. And then not
(12:34):
only does alpha blockade help decrease systemic vascular resistance, it
also helps minimizing the variability in SDR as well. And
then once you have SDR low, you can augment contractility
by using inotropes in the background, something like epinephrine in
addition to your alpha blockade, really trying to utilize them
(12:55):
in inodilat or strategy in these patients. And the main
difference between PHENOXIDNSS and pantolamine is that phenoxy benzamine is
an irreversible alpha blocker which can lead to our reduction
in SVR for up to twenty four to forty eight
hours after a single dose. Phantolamine, on the other hand,
is a reversible alpha blocker, has a shorter lasting effect
(13:16):
on SVR and the effect can wear off after ten
to thirty minutes after getting a single ib BOIS dose
or within two hours of stopping and infusion. Now, the
big concern with phenoxidenzamine is does this hypotension which may
truly not even be a problem to the body as
long as systemic auction delivery is adequate, but in the
event that the circulation is having difficulty being maintained due
(13:38):
to low SDR, vasopressin has been shown to be helpful
to help augment SVR while the phenoxy benzamine wears all.
So there are strategies for this, and I should add
that phenoxy benzamine isn't commercially available in the US anymore
and really needs to be specially compounded, and phantolamine is
still available in the US, but not as readily available
(13:59):
at all institutions. So then you have agents like millernone, nipartopene,
and nitropus side that are more commonly and frequently used,
and these also allow for after load reduction with better
ability to try trade them on a more minute to
minute basis, And an agent like millernone also has other
benefits like increasing contractility as well.
Speaker 1 (14:21):
You know, I'm wondering you've been an intensivist for a while,
You've obviously had great success with these alpha blocking agents.
Do you use phantolamine any longer? And could you comment
on your personal observations of what it does or did
that was good or bad, superior inferior to the more
(14:43):
commonly used technique of more reliance on PD three inhibitors
like millernone. And when you've used it, have you administered
it post up or were you giving it just during
surgery as was described in this work from India.
Speaker 2 (14:56):
Yeah, so in my younger days, I did care for patients,
specifically Norwood, who had been administered a dose of phinoxi
benzamine in the operating room. Now, the group in Milwaukee
published data regarding their experience with finoxi benzamine specifically in
the Norwood population. And this early experience was published back
in nineteen ninety nine and compared patients who received phinoxy
(15:17):
benzamine to those who didn't after the Norwood and they
found that the group that received pinoxy benzamine had a
higher systemic venus auction saturation, had a more narrow arteriovenous
auction saturation difference at a lower ratio of plumated systemic
blood flow, and lower systemic mascular resistance. Now, obviously these
are all important clinical effects, but what the study also found,
(15:42):
which I think is very interesting, is related to clinical
monitor and it found that arterial blood pressure, which is
often used to titrate clinical care across all the patients,
was associated with systemic vascular resistance in the patients who
had not received anoxy benzamine, but was actually associated with
systemic auction delivery in those who cab receive phinoxydenzamine, really
(16:04):
coupling those two together. Now, this is an important finding
because blood pressure is often used to titrate care, but
arterial blood pressure is a product of systemic flow and
systemic mascular resistance. The blood pressure can be increased simply
by increasing SDR, even with a simultaneous decrease in cardiac output,
which the body won't like, since cardiac output is what
(16:26):
contains oxygen. The venus auction saturation, directly measured by venus
blood gases or estimated bineers can help sort this out,
but there are centers that don't routinely use these data,
and thus they may be assuming that an increase in
blood pressure may be an indicator of increased systemic auction delivery,
when in reality it isn't. The alpha blockade actually helps
(16:46):
to make a clinic clinically a clinical monitoring metric more
helpful as well. Now in my personal experience, I've also
used to phenotamine to accomplish a similar effects. Once phnoxydezamine
was no longer available. I haven't used either for some
time just because of availability, but I do miss having
it as a tool. In my experience with phenoxidenzamine, patients
(17:09):
received a dose while going on pump and then some
of them had an infusion started postoperatively as well. And
then when I was using pentolamine, I would just started
in the postoperative period. Now I should add that a
few colleagues and myself published a paper using a national
database to try to study the effect of alpha blockade
(17:29):
in pediatric cardiac cervical patients. In the ear that we studied,
five point three percent of admissions for pediatric cardiac surgery
utilized alpha blockade. Ninety nine percent of this alpha blockade
came in the form of pentolamine, mostly because of the
years that we studied in the availability of fanaxidnzamine. Those
(17:50):
undergoing and norwin were most likely to be alpha blockaded.
And there was a significant independent association that we found
with ALCA blockade and a reduction in inpatient mortality and
we're talking about twenty percent reduction in inpatient mortality and
then at total hospital length of stay that was decreased
by about three point five days. Now, obviously these are
(18:12):
associations and not causality, but some signals here as well,
and then nested within the study, we were able to
find some signals comparing milanown and alpha blockade as well,
and there does seem to be an indication that alpha
blockade mediates a statistically significant reduction in inpatient mortality and
(18:32):
total length of stay compared to mine. While they both
seem to have a protective effect. It seems that alpha
blockade had a greater magnitude of it. Overall, I don't
think there's great comparative data head to head between the
agents themselves, but certainly some soft signals in that study
we had published.
Speaker 1 (18:52):
Seems to me like the availability of agents and the
ability to titrate. It has been probably the most most
important reason that there's been a move away from these
alpha blocking agents, you know, doctor lumber. My perception of
this work that we're reviewing this week is that the
authors really did not make a great argument for its use,
(19:14):
as the cases generally did well but would sort of
be expected to do well, and there's really very little
detail regarding how many received miler known or even how
many received dino troupes. In one part they say nobody
received dinatroups. In the other part they said it's a
number of patients got some amount of adrenaline. Do you
think the authors make much of an argument and what
(19:36):
do you take away from this work for general use
in congeneral heart patients. Are there people who should still
be having this approach in your view?
Speaker 2 (19:45):
Yeah, so, you know, I think the study lists their
objectives as to value the safety and efficacy of a
Finazi Benjamin based basil plegic strategy during cardiopulmary bypass. Now,
the study had five hundred and twenty patients, all of
whom received benzamin across a variety of different circulatory physiologies,
although left to right shunts specifically VSDs were the most common. Now,
(20:08):
they administered the pnoxy benzamine into the bypass reservoir and
then characterize ventilation time homely hypertensive crises, the intraoperative hypotension,
and then excavation within twenty four hours postoperatively is kind
of their outcomes. Now, they demonstrated that no patients required
vasopressence for hypotension and that one patient at a pulmonary
(20:29):
hypertensive crisis. So I think they did a nice job
of characterizing safety and the effects of pinoxy benzamine. But
I don't think they can truly comment on efficacy with
not having a comparison group. So I think if they
had some patients who received pinoxybenzamine and some who didn't,
they could have better kind of commented on fixie, but
they didn't here, So I do think the paper is
(20:51):
helpful to demonstrate safety and to revisit a strategy. Perhaps
many don't think about anymore forgotten about, but they don't
go into much grat detail about the vasoactive support as
you mentioned, which would have been I think insightful.
Speaker 1 (21:05):
Well for those of you in the audience who are
listening now, Doctor Lumbo was nice enough to speak with
me right in the middle of his afternoon. He's a
busy morphologist and intensivists. So I'm gonna finish up with
my last question, and I was just wondering do you
have any sense regarding the cost of I guess we've
learned from you today that phenoxy benzamine in the US
(21:26):
is not available, but pantolamine, do you have any sense
of the cost of that in comparison to some of
the more commonly used agents like we've been discussing, like
nitroprusside or mil renone. And I know that nitric oxide
is really used for sort of something different, more pulmonary
vaso dilation. But how would this agent or these agents
(21:47):
compare with things like milernonne or nypride for they indication
of lowering SVR.
Speaker 2 (21:53):
Yeah, so I'll revisit the database study that I had
mentioned earlier that some of my colleagues and I had
conducted which showed that neither finoxidenzimine or phantolamine added a
significant amount overall ill charges when comparing patients who did
and did not receive alpha blockade. Now, in general, there
are a lot of issues with analyzing comparative cost in
(22:15):
some of these agents, just because different countries have different pricing,
different institutions within the same country can negotiate different pricing
as well, and the data is not entirely transparent. Now,
hospitals also charage additional pharmacy fees, preparation fees, et cetera.
So it can become a little difficult. But let's just
(22:36):
assume the acquisition cost of the drugs themselves, and if
we assume US dollars in twenty twenty five an account
for wasted drug as well, then we can come up
with some figures. So for let's say twenty four hours
of milanown at about zero point five Mike's percuila per minute,
you're looking at about five dollars in terms of acquisition cost.
(22:58):
This is not build charges. Now, nitropress side at a
dose of one mic perkilo per minute, you're looking at
an acquisition cost of about forty dollars, and then nicardipine
at the dose of one mic pekilo perm minute would
be approximately forty dollars as well, and then pantolamine is
approximately seven hundred dollars, and a single dose of phenoxy
(23:19):
benzamine is described in the study is about twenty dollars.
So phenoxi benzamine is on the cheaper side along with
milerno and in terms of acquisition cost, but that's not
really to come in on build charges or related charges local,
you know, to local preparation and local setup. Now, nitric
oxide is even more expensive, and there's a few thousand
(23:42):
dollars setup fee for the nitric oxide, and then nitric
oxide usually costs about one hundred dollars to two hundred
dollars an hour after the initial setup while you're running it.
But a lot of hospitals do have a kind of
use all you can type arrangement with some of the
nitric oxide vendors where they might spend a million dollars
(24:03):
a year and then that's their flat charge. But once again,
that's not the build charge to the patient. That's just
the hospital's apposition charge.
Speaker 1 (24:12):
I see so very challenging to figure out exactly whether
this would be financially advantageous. There's just so many factors involved.
Certainly from what you've described, it doesn't sound like it
would be massively different. Although phantolemine, I guess, at least
on first blush seems to be more expensive, but that
perhaps that's important because it's not used as often, and
(24:35):
maybe it's just more expensive to get an agent that's
not being used like water like miller Own presently is
in most ICUs in the US and probably throughout the world. Well,
doctor Lumba, I can't thank you enough for joining us
this week to discuss this paper. For those in the audience,
I've already mentioned that doctor Lumba has a whole other
life where he provides us with expert descriptions and demonstrations
(24:59):
of cardiac pathol, and there will be a link to
that website on YouTube for those of you interested to
look at the wonderful lectures he offers. Doctor Lumba, thank
you very much for joining us this week. Great pleasure
to meet you.
Speaker 2 (25:11):
Yes, likewise, thank you, Doctor Pass.
Speaker 1 (25:13):
Thank you well. Not too much to add, as doctor
Lumba is obviously a very clear speaker, and he echoed
in his comments many of the physiological principles that we
have previously reviewed a few years back now with doctor
Anthony Rossi. I think it was interesting to learn that
finaxi benzamine is no longer commercially available in the United States,
but it does seem that fantolamine is. It's not at
(25:35):
all clear off alpha blockade with agents like pantolamine is
superior to more commonly used afterload reducing SVR reducing agents
like nitro presside or milernown. But I think discussing this
question is of value, and certainly, reviewing the physiological principles
of oxygen delivered at the tissues of post operative patients
and how to maximize cardiac output is an evergreen topic
(25:58):
that will interest all critical care cardiologists now and likely forever.
I'd once again like to thank doctor Lumba for taking
time to speak with us this.
Speaker 3 (26:06):
Week on Pedi Heart.
Speaker 1 (26:08):
To conclude this week's episode of Pedi Heart, we hear
the wonderful Roman tenor Cesare Velletti. Valetti was what is
often an opera referred to as a tenore di grazia,
denoting his lightweight graceful singing which was so well suited
to belcanto composers like Billini, Donizetti or Rossini. Today we
hear him in the magnificent love duet Prendi lanelle tidono
(26:32):
from La Sonambula by Billini, and what is considered one
of the greatest pirate recordings of all time, in which
he is paired with the incomparable Maria Cullis in a
live performance from Lascala with the wonderful Leonard Bernstein conductor. Wow.
What an extraordinary group of artists. Thank you so much
for listening this week to the podcast, and thanks once
(26:52):
again to our guests.
Speaker 3 (26:54):
I hope all have a good week ahead.
Speaker 4 (27:29):
Coming school slot she mocking the cops the stock school.
Speaker 2 (28:49):
Who's you.
Speaker 4 (29:04):
Suppose your voice? Oh notcut?
Speaker 1 (29:34):
Be a man?
Speaker 4 (29:47):
Ye? Maybe your class in your par not in all
(30:56):
its full long call back
Speaker 1 (31:10):
He h
Welcome to Pedheart Pediatric Cardiology Today. My name is doctor
Robert Pass and I'm the host of this podcast. I
am Professor of Pediatrics at the Icon School of Medicine
at Mount SINAI thank you for joining me for this
three hundred and fifty sixth episode of Pdheart. I hope
everybody enjoyed last week's replay episode, in which we spoke
about post operative actomic atrial tachy cardia and its mechanism.
(00:38):
For those of you interested in post operative a rhythmias,
i'd certainly recommend you take to listen to last week's episode.
As I say most weeks, if you'd like to get
in touch with me, my email is easy to remember.
It's pdheart at gmail dot com. This week we move
into the world of pediatric cardiac critical care. The title
of the work we'll be reviewing is Finaxi Benzamine Old
(01:00):
Wine in a Bright New Bottle, Taming the wild Side
of Venaxi Benzamine. The first author of this work is
our Benedict Raj and the senior author Goot Prakash Ready
and the authors come to us from the Department of
Pediatric Cardiology and Cardiac Surgery at the Children's Heart Institute
ast Ramesh Hospitals in India. When we're done reviewing this paper,
(01:22):
doctor Rowheat Lumba of Luri Children's Hospital, who's a cardiac
critical care physician, has graciously agreed to speak with us
about it. Therefore, let's move straight onto the article and
then a conversation with doctor Lumba. This week's paper that
we'll be reviewing is a very brief one, but I
thought it brought up an important topic that we've reviewed
previously in prior years, which is the maintenance of good
(01:42):
cardiac output in the post operative congenital heart disease patient
following surgery. And you may recall conversations we've had in
the past on two occasions with doctor Anthony Rossi of
Nicholas Children's Hospital about his efforts over thirty years ago
to use things like mixed venus saturation to better understand
and in real time the output of hearts of single
(02:02):
ventricle patients following first stage pallid of procedures. This work
revisits the use of finoxi benzamine for the treatment or
improvement of cardiac output following surgery to those less familiar
phenoxy benzamine is a non selective and irreversible alpha adrenergic
antagonist that blocks both alpha one and two receptors. Blocking
(02:25):
the alpha one receptors will result in systemic and pulmonary
vasodilation with possible afterload reduction effects, which could be very
important or helpful for the post operative heart patient. Alpha
two blockade will increase nore epi release, which can lead
to tachycardia and maybe even increases in cardiac oxygen demand.
This agent is perhaps best known for those undergoing surgery
(02:48):
for fiochromocytoma, but it was popularized for use in the
ICU after repairs such as things like hypoplastic left heart syndrome,
most notably by the master surgeon, doctor Jim Twiddle, when
he was working in Wisconsin in the Elite nineteen nineties.
At that time, doctor Twittle was having extraordinary outcomes with
hypoplastic left heart syndrome patients following the Norwood and though
(03:10):
I think we would all agree that this was largely
related to his outstanding surgical skills, he and the team
in Wisconsin were concerned or convinced that this agent fanoxi
benzamine was at least part of the reason that outcomes
were so good. It should also be noted that it
can be used for pulmonary hypertensive crises, as it can
affect pulmonary vascular tone as well, and it's thought that
(03:32):
it could possibly be of benefit when repairing certain lesions
that are more associated with post operative pulmonary hypertension, such
as truncus arteriosis. Though effective for these indications, phinoxy benzamine's
use has faded to a degree because the agent has
a very long duration of action and the hypotension that
can occur with this agent can be difficult to manage,
(03:53):
and the reflex tachycardia and unpredictable hemodynamics due to the
Alpha two receptor blockade are also desirable features. Alternative, shorter acting,
more precise agents like milernown or nitroproscide or prostacycline or
even sildeniphil have largely replaced this agent, but there are
many small series that have demonstrated that despite newer agents
(04:14):
that have worked well to achieve many of these goals,
phonaxi benzamine has been demonstrated to work well in the
post operative setting, despite the fact that newer agents have
supplanted it in many centers with this as a background.
The authors of this work, which comes to us from
the Giawata, India, which is in the eastern part of India,
report to us their experience with finoxi benzamine when used
(04:37):
in a strictly protocolized approach, which they hypothesize has allowed
the practitioners to get the powerful positive benefits of this
agent while mitigating its risks. And the authors explain that
it is relatively inexpensive in that country and so may
offer the ability to be both safe and effective while
also being relatively cheap, essentially a possible win win. This
(04:59):
was prospective observational case series from twenty fifteen to twenty
twenty at a large single tertiary center in India with
five hundred and twenty patients getting phinoxibenzamine during cardiopulmonary bypass,
and the authors explained that it was used for patients
who had an increase in pulmonary blood flow or those
who needed reduced systemic vascular resistance, and they suggested that
(05:21):
such situations would be a VSD thapvr dtga ivy canal defects,
microvalve repairs, and pulmonary artery banding. The authors explained that
those who had reduced pulmonary blood flow with cyanotic heart disease,
or those over ten years or weighing more than twenty
kilos were excluded due to hypotension risk. In this center
(05:42):
and study, finoxi benzamine was given in the cardiopulmonary bypass
reservoir at a dose of two milligrams per kilogram, and
there was no post operative dosing. The authors explained that
for patients who still had pulmonary hypertension, oxygen millernone or
sidenophil was also used. Two hundred and fifty nine of
the f five hundred and twenty cases were less than
a month of age, two hundred and five were one
(06:04):
to twelve months, and fifty six were one to five
years of age, so the majority less than a year
of age. The diagnoses were sixty nine percent VSD, twelve
and a half percent, AV canal defect, eleven and a
half percent total an almost pulmonary venus return, six percent DTGA,
and seven patients who had an ap window, so importantly,
(06:24):
no single ventrical patients in this work. The office provided
the cardiopulmonary parameters and they were all within normal limits
with a bypass time of seventy five minutes in this work,
So what happened postoperatively to these patients. Well, the mean
ventilation time was twenty two hours and there was only
one case of pulmonary hypertensive crisis constituting zero point two
(06:45):
percent of the entire cohort. No patients had significant hypotension
requiring the use of vasa pressen or other inotropes, and
the majority of patients were extavated on the day of surgery.
The mortality rate in this study was two point seven
percent or fourteen death with one percent of the VSDs
or five total patients dying, followed by three avcanal patient
(07:05):
deaths and two deaths each amongst the TAPVR and DTGA patients.
Of note, this is a very short report and there
is no control group or even hemodenamic information other than
that the majority of patients were fine and no one
needed intravenous inotropes or vasopressin AFT surgery. The author's discussion
begins with the statement and I quote this study reaffirms
(07:28):
the utility of phinoxybenzamine as a safe and effective vasodilator
in pediatric cardiac surgeries involving cardiopulmonary bypass administered via a
structured protocol. Phinoxybenzomine successfully maintained stable perfusion pressures and consistent
cardiopulmonary bypass flows without the need for intraoperative vasopressin or
additional vasopressors. Most patients achieved early extabation, and postoperati hypotension
(07:53):
was readily managed with fluids and low dose adrenaline, minimizing
ICU interventions. Importantly, the use the incidence of pulmonary arterial
hypertension crisis was nearly negligible, with the only one reported
case among five hundred and twenty patients. The authors suggest
that they believe that this work demonstrating generally good outcomes
support the use of this agent. They mention that they
(08:15):
believe the absence of hypotension in this work is related
to the patient selection and also dosing. They explain that
miler known is part of the pulmonary hypertensive protocol for
post opera patients, but strangely don't share who or how
many receive this agent. They similarly do not mention what
percentage or patients received low dose adrenaline to use. Their
terminology The authors conclude by suggesting that when this agent
(08:38):
is administered during bypass, it results in a predictable rapid
cardiac recovery in low SVR, and that hypotension was not
observed when it was given in this study. They suggest
that the use of this agent improved post operative survival
and suggest that it is a good agent for a
resource strapped setting like India. Well, this is an interesting
(08:58):
work more because of what they are describing than for
the scientific rigor of this work. There is, of course,
no way to know if the use of finoxi benzamine
in this group was the reason that the patients generally
did well, as most of these cases are cases that
would be expected to do well with or without this agent.
Though the agent is not really studied in a rigorous manner,
(09:19):
I do wonder if there is perhaps a signal here
that could be of value and maybe has been overlooked
by our surgical and cardiac critical care colleagues in the
recent past. I do think it's also noteworthy that some
percentage to patients did need intravenous einotropes, despite the statement
by the authors that few patients, if any, needed them
In the interests of time, Let's move forward to a
(09:39):
conversation with critical care cardiologists from Louri Children's Hospital, doctor
Roehitt Lumba. Tuining us now to discuss this week's work
is doctor Roeheat Lumba, who is a pediatric cardiac critical
care physician at Louri Children's Hospital. Doctor Lumba is a
graduate of Rosalind Franklin University's Chicago Medical School and completed
his residency and fellowship training in pediatric cardiology at Children's
(10:02):
Hospital of Wisconsin. Following this, he completed a fellowship in
pediatric cardiac intensive care at Cincinnati Children's Hospital. Review of
his resume and the times that he worked there seemed
to suggest that he may have well worked with doctor Twittle,
who favored finoxi benzamine and the management of his post
operative single metrical patients. And so I am hopeful that
we have really identified a true expert on this topic
(10:24):
to discuss it this week. I should also mention that
doctor Lumba is a cardiac morphologist and currently curates the
Faruk Idris Archive in Chicago, and he has posted many
YouTube videos of his wonderful lectures online and I'm going
to put a link to some of his work there
with today's show notes, it's it's like to have him
join us. Welcome doctor Lumba to PDHART. I'm here now
(10:45):
with doctor Rowet Lumba of Lori Children's Hospital. Doctor Lumba,
thank you very much for joining us this week on PDHART.
Speaker 2 (10:51):
Oh, thank you for having me. It's an honor. The
podcast has turned out wonderfully well. Congrats on the success.
Speaker 1 (10:57):
Thank you very very much. You know, doctor Limba, the
topic of this week's paper is the use of finoxy
benzamine for the post operative care of children following congenle
heart disease surgery. Can you explain to the audience who
may be less familiar, what the experience in general has
been with this agent, which I know you have used
(11:18):
previously with the wonderful doctor Jim Twittle, and why it's
less commonly used in deference to agents like miler known
nitropruss side, or even on the pulmonary side, nitric oxide.
Speaker 2 (11:30):
Yeah, for sure. I think I'll start my answer at
a more fundamental level and say that in the care
of any patient, specifically I critically ailed post operative patients,
the body and its constituent organs need oxygen and the
purpose of the cardiovascular system is simply to use blood
as a transport medium to get auction to all the organs,
and systemic auction delivery, as we all know, is the
(11:52):
product of auction content and partiac output. Partiac output further
breaks down into heart rate time, stroke volume, and then
volume further breaks down and is modulated by threeload, afterload,
and contractility. And so within this oxymetric framework, we know
that a low afterload, high contractility state or low SDR
(12:12):
hy partic output state leads to the best clinical outcomes
and this is maintained across ages and circulatory phenotypes. And
so this is where alpha blockade comes in because alpha
blockade with either phinoxidbenzamine or phantolamine has been used to
reduce afterload by discreasing systemic bascular resistance. And then not
(12:34):
only does alpha blockade help decrease systemic vascular resistance, it
also helps minimizing the variability in SDR as well. And
then once you have SDR low, you can augment contractility
by using inotropes in the background, something like epinephrine in
addition to your alpha blockade, really trying to utilize them
(12:55):
in inodilat or strategy in these patients. And the main
difference between PHENOXIDNSS and pantolamine is that phenoxy benzamine is
an irreversible alpha blocker which can lead to our reduction
in SVR for up to twenty four to forty eight
hours after a single dose. Phantolamine, on the other hand,
is a reversible alpha blocker, has a shorter lasting effect
(13:16):
on SVR and the effect can wear off after ten
to thirty minutes after getting a single ib BOIS dose
or within two hours of stopping and infusion. Now, the
big concern with phenoxidenzamine is does this hypotension which may
truly not even be a problem to the body as
long as systemic auction delivery is adequate, but in the
event that the circulation is having difficulty being maintained due
(13:38):
to low SDR, vasopressin has been shown to be helpful
to help augment SVR while the phenoxy benzamine wears all.
So there are strategies for this, and I should add
that phenoxy benzamine isn't commercially available in the US anymore
and really needs to be specially compounded, and phantolamine is
still available in the US, but not as readily available
(13:59):
at all institutions. So then you have agents like millernone, nipartopene,
and nitropus side that are more commonly and frequently used,
and these also allow for after load reduction with better
ability to try trade them on a more minute to
minute basis, And an agent like millernone also has other
benefits like increasing contractility as well.
Speaker 1 (14:21):
You know, I'm wondering you've been an intensivist for a while,
You've obviously had great success with these alpha blocking agents.
Do you use phantolamine any longer? And could you comment
on your personal observations of what it does or did
that was good or bad, superior inferior to the more
(14:43):
commonly used technique of more reliance on PD three inhibitors
like millernone. And when you've used it, have you administered
it post up or were you giving it just during
surgery as was described in this work from India.
Speaker 2 (14:56):
Yeah, so in my younger days, I did care for patients,
specifically Norwood, who had been administered a dose of phinoxi
benzamine in the operating room. Now, the group in Milwaukee
published data regarding their experience with finoxi benzamine specifically in
the Norwood population. And this early experience was published back
in nineteen ninety nine and compared patients who received phinoxy
(15:17):
benzamine to those who didn't after the Norwood and they
found that the group that received pinoxy benzamine had a
higher systemic venus auction saturation, had a more narrow arteriovenous
auction saturation difference at a lower ratio of plumated systemic
blood flow, and lower systemic mascular resistance. Now, obviously these
are all important clinical effects, but what the study also found,
(15:42):
which I think is very interesting, is related to clinical
monitor and it found that arterial blood pressure, which is
often used to titrate clinical care across all the patients,
was associated with systemic vascular resistance in the patients who
had not received anoxy benzamine, but was actually associated with
systemic auction delivery in those who cab receive phinoxydenzamine, really
(16:04):
coupling those two together. Now, this is an important finding
because blood pressure is often used to titrate care, but
arterial blood pressure is a product of systemic flow and
systemic mascular resistance. The blood pressure can be increased simply
by increasing SDR, even with a simultaneous decrease in cardiac output,
which the body won't like, since cardiac output is what
(16:26):
contains oxygen. The venus auction saturation, directly measured by venus
blood gases or estimated bineers can help sort this out,
but there are centers that don't routinely use these data,
and thus they may be assuming that an increase in
blood pressure may be an indicator of increased systemic auction delivery,
when in reality it isn't. The alpha blockade actually helps
(16:46):
to make a clinic clinically a clinical monitoring metric more
helpful as well. Now in my personal experience, I've also
used to phenotamine to accomplish a similar effects. Once phnoxydezamine
was no longer available. I haven't used either for some
time just because of availability, but I do miss having
it as a tool. In my experience with phenoxidenzamine, patients
(17:09):
received a dose while going on pump and then some
of them had an infusion started postoperatively as well. And
then when I was using pentolamine, I would just started
in the postoperative period. Now I should add that a
few colleagues and myself published a paper using a national
database to try to study the effect of alpha blockade
(17:29):
in pediatric cardiac cervical patients. In the ear that we studied,
five point three percent of admissions for pediatric cardiac surgery
utilized alpha blockade. Ninety nine percent of this alpha blockade
came in the form of pentolamine, mostly because of the
years that we studied in the availability of fanaxidnzamine. Those
(17:50):
undergoing and norwin were most likely to be alpha blockaded.
And there was a significant independent association that we found
with ALCA blockade and a reduction in inpatient mortality and
we're talking about twenty percent reduction in inpatient mortality and
then at total hospital length of stay that was decreased
by about three point five days. Now, obviously these are
(18:12):
associations and not causality, but some signals here as well,
and then nested within the study, we were able to
find some signals comparing milanown and alpha blockade as well,
and there does seem to be an indication that alpha
blockade mediates a statistically significant reduction in inpatient mortality and
(18:32):
total length of stay compared to mine. While they both
seem to have a protective effect. It seems that alpha
blockade had a greater magnitude of it. Overall, I don't
think there's great comparative data head to head between the
agents themselves, but certainly some soft signals in that study
we had published.
Speaker 1 (18:52):
Seems to me like the availability of agents and the
ability to titrate. It has been probably the most most
important reason that there's been a move away from these
alpha blocking agents, you know, doctor lumber. My perception of
this work that we're reviewing this week is that the
authors really did not make a great argument for its use,
(19:14):
as the cases generally did well but would sort of
be expected to do well, and there's really very little
detail regarding how many received miler known or even how
many received dino troupes. In one part they say nobody
received dinatroups. In the other part they said it's a
number of patients got some amount of adrenaline. Do you
think the authors make much of an argument and what
(19:36):
do you take away from this work for general use
in congeneral heart patients. Are there people who should still
be having this approach in your view?
Speaker 2 (19:45):
Yeah, so, you know, I think the study lists their
objectives as to value the safety and efficacy of a
Finazi Benjamin based basil plegic strategy during cardiopulmary bypass. Now,
the study had five hundred and twenty patients, all of
whom received benzamin across a variety of different circulatory physiologies,
although left to right shunts specifically VSDs were the most common. Now,
(20:08):
they administered the pnoxy benzamine into the bypass reservoir and
then characterize ventilation time homely hypertensive crises, the intraoperative hypotension,
and then excavation within twenty four hours postoperatively is kind
of their outcomes. Now, they demonstrated that no patients required
vasopressence for hypotension and that one patient at a pulmonary
(20:29):
hypertensive crisis. So I think they did a nice job
of characterizing safety and the effects of pinoxy benzamine. But
I don't think they can truly comment on efficacy with
not having a comparison group. So I think if they
had some patients who received pinoxybenzamine and some who didn't,
they could have better kind of commented on fixie, but
they didn't here, So I do think the paper is
(20:51):
helpful to demonstrate safety and to revisit a strategy. Perhaps
many don't think about anymore forgotten about, but they don't
go into much grat detail about the vasoactive support as
you mentioned, which would have been I think insightful.
Speaker 1 (21:05):
Well for those of you in the audience who are
listening now, Doctor Lumbo was nice enough to speak with
me right in the middle of his afternoon. He's a
busy morphologist and intensivists. So I'm gonna finish up with
my last question, and I was just wondering do you
have any sense regarding the cost of I guess we've
learned from you today that phenoxy benzamine in the US
(21:26):
is not available, but pantolamine, do you have any sense
of the cost of that in comparison to some of
the more commonly used agents like we've been discussing, like
nitroprusside or mil renone. And I know that nitric oxide
is really used for sort of something different, more pulmonary
vaso dilation. But how would this agent or these agents
(21:47):
compare with things like milernonne or nypride for they indication
of lowering SVR.
Speaker 2 (21:53):
Yeah, so I'll revisit the database study that I had
mentioned earlier that some of my colleagues and I had
conducted which showed that neither finoxidenzimine or phantolamine added a
significant amount overall ill charges when comparing patients who did
and did not receive alpha blockade. Now, in general, there
are a lot of issues with analyzing comparative cost in
(22:15):
some of these agents, just because different countries have different pricing,
different institutions within the same country can negotiate different pricing
as well, and the data is not entirely transparent. Now,
hospitals also charage additional pharmacy fees, preparation fees, et cetera.
So it can become a little difficult. But let's just
(22:36):
assume the acquisition cost of the drugs themselves, and if
we assume US dollars in twenty twenty five an account
for wasted drug as well, then we can come up
with some figures. So for let's say twenty four hours
of milanown at about zero point five Mike's percuila per minute,
you're looking at about five dollars in terms of acquisition cost.
(22:58):
This is not build charges. Now, nitropress side at a
dose of one mic perkilo per minute, you're looking at
an acquisition cost of about forty dollars, and then nicardipine
at the dose of one mic pekilo perm minute would
be approximately forty dollars as well, and then pantolamine is
approximately seven hundred dollars, and a single dose of phenoxy
(23:19):
benzamine is described in the study is about twenty dollars.
So phenoxi benzamine is on the cheaper side along with
milerno and in terms of acquisition cost, but that's not
really to come in on build charges or related charges local,
you know, to local preparation and local setup. Now, nitric
oxide is even more expensive, and there's a few thousand
(23:42):
dollars setup fee for the nitric oxide, and then nitric
oxide usually costs about one hundred dollars to two hundred
dollars an hour after the initial setup while you're running it.
But a lot of hospitals do have a kind of
use all you can type arrangement with some of the
nitric oxide vendors where they might spend a million dollars
(24:03):
a year and then that's their flat charge. But once again,
that's not the build charge to the patient. That's just
the hospital's apposition charge.
Speaker 1 (24:12):
I see so very challenging to figure out exactly whether
this would be financially advantageous. There's just so many factors involved.
Certainly from what you've described, it doesn't sound like it
would be massively different. Although phantolemine, I guess, at least
on first blush seems to be more expensive, but that
perhaps that's important because it's not used as often, and
(24:35):
maybe it's just more expensive to get an agent that's
not being used like water like miller Own presently is
in most ICUs in the US and probably throughout the world. Well,
doctor Lumba, I can't thank you enough for joining us
this week to discuss this paper. For those in the audience,
I've already mentioned that doctor Lumba has a whole other
life where he provides us with expert descriptions and demonstrations
(24:59):
of cardiac pathol, and there will be a link to
that website on YouTube for those of you interested to
look at the wonderful lectures he offers. Doctor Lumba, thank
you very much for joining us this week. Great pleasure
to meet you.
Speaker 2 (25:11):
Yes, likewise, thank you, Doctor Pass.
Speaker 1 (25:13):
Thank you well. Not too much to add, as doctor
Lumba is obviously a very clear speaker, and he echoed
in his comments many of the physiological principles that we
have previously reviewed a few years back now with doctor
Anthony Rossi. I think it was interesting to learn that
finaxi benzamine is no longer commercially available in the United States,
but it does seem that fantolamine is. It's not at
(25:35):
all clear off alpha blockade with agents like pantolamine is
superior to more commonly used afterload reducing SVR reducing agents
like nitro presside or milernown. But I think discussing this
question is of value, and certainly, reviewing the physiological principles
of oxygen delivered at the tissues of post operative patients
and how to maximize cardiac output is an evergreen topic
(25:58):
that will interest all critical care cardiologists now and likely forever.
I'd once again like to thank doctor Lumba for taking
time to speak with us this.
Speaker 3 (26:06):
Week on Pedi Heart.
Speaker 1 (26:08):
To conclude this week's episode of Pedi Heart, we hear
the wonderful Roman tenor Cesare Velletti. Valetti was what is
often an opera referred to as a tenore di grazia,
denoting his lightweight graceful singing which was so well suited
to belcanto composers like Billini, Donizetti or Rossini. Today we
hear him in the magnificent love duet Prendi lanelle tidono
(26:32):
from La Sonambula by Billini, and what is considered one
of the greatest pirate recordings of all time, in which
he is paired with the incomparable Maria Cullis in a
live performance from Lascala with the wonderful Leonard Bernstein conductor. Wow.
What an extraordinary group of artists. Thank you so much
for listening this week to the podcast, and thanks once
(26:52):
again to our guests.
Speaker 3 (26:54):
I hope all have a good week ahead.
Speaker 4 (27:29):
Coming school slot she mocking the cops the stock school.
Speaker 2 (28:49):
Who's you.
Speaker 4 (29:04):
Suppose your voice? Oh notcut?
Speaker 1 (29:34):
Be a man?
Speaker 4 (29:47):
Ye? Maybe your class in your par not in all
(30:56):
its full long call back
Speaker 1 (31:10):
He h
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