January 21, 2025 • 21 mins
Join us as we explore fluid therapy in anesthetized cats with our guests, Drs. Stefania Gelendi and Ben Liao. Discover how mild hypothermia reshapes the way fluids are processed in feline bodies, challenging traditional treatment methods and offering a fresh perspective on veterinary medicine. With insights into feline shock management and the complex interplay of temperature and anesthesia, this episode promises to elevate your understanding of fluid dynamics and the unique physiological traits of our feline friends.
Explore the groundbreaking revelations of volume kinetic analysis as Stefania and Ben unravel the unexpected enlargement of the central compartment during hypothermia. This fascinating development reveals less effective fluid administration. This episode is a must-listen for anyone intrigued by the delicate art of feline fluid therapy.
AJVR article: https://doi.org/10.2460/ajvr.24.09.0279
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Sarah Wright (00:01):
You're listening to Veterinary Vertex, a podcast
of the AVMA Journals.
In this episode, we chat abouthow mild hypothermia is
associated with altered volume,kinetic parameters of an
intravenous crystalloid fluid,bolus and healthy isoflurane
anesthetized cats with ourguests Stefania Gelendi and Ben
Liao.
Lisa Fortier (00:21):
Welcome to Veterinary Vertex.
I'm Editor-in-Chief LisaFortier, and I'm joined by
Associate Editor Sarah Wright.
Today, we have Stefania and Benjoining us.
Thank you so much, each of you,for taking time out of your
busy schedules to share yourpodcast with us today.
Stefania Gelendi (00:38):
Thank you for having us.
Ben Liao (00:40):
Yeah, thank you for having us.
Sarah Wright (00:42):
All right, let's dive right in Stefania.
Your AJVR article discusses howmild hypothermia is associated
with altered volume.
Kinetic parameters of anintravenous crystalloid fluid
bolus and healthy isofluraneanesthetized cats.
Please share with our listenersthe background on this article.
Stefania Gelendi (01:00):
Thank you for the question.
So, the study stems from theclinical challenge we face when
we treat cats in shock.
Cats are especially tricky totreat because of their unique
physiology, as you know.
So, they're not only prone tobradycardia, hypotension and
hypothermia, but also aretotally predisposed to volume
overload, and this makes fluidtherapy a delicate balancing act
(01:23):
.
To better understand how fluidbehaves in cats under this
condition, we used for our studyvolume kinetics or volume
kinetic analysis.
And volume kinetics isessentially pharmacokinetics,
but for fluid, and so with thatwe can analyze how fluid
(01:44):
distribute and are eliminated inthe body.
While there are quite already afew publications on volume
kinetics in human medicine,veterinary medicine has only
recently begun to explore itspotential.
The first study was done atOntario Veterinary College by Dr
Zhu and Bettman they're both inmy paper and following this, a
couple of studies here at Auburndemonstrated its feasibility in
(02:06):
healthy cats.
So, building on that foundation, we wanted to investigate how
mild apothermia specificallyimpacts the behavior of a fluid
bolus in anesthetized cats.
So it's worth noting thatvolume kinetics in itself is not
easy, but then the hardest partis actually to identify a
relevant research question.
So this is particularly truebecause there is a general lack
(02:29):
of evidence in cats, and ourunderstanding of shocks and its
treatment in feline patients ismostly based on anecdotal
observations, and so this gap inknowledge made us particularly
excited about this study.
But then why hypothermia?
We believe that cats, when theyexperience shock, the body may
handle fluid differently.
For example, in humans,hypotension slows fluid
(02:53):
elimination.
That has been demonstrated.
But on the other hand, thereare some studies saying that
hypothermia is still to actuallyincrease urinary production,
which is a phenomenon known ascold diuresis, which could lead
to faster fluid elimination.
However, we don't know if theseprocesses occur at all in cats
and, if they do, how they mayinteract.
(03:14):
Additionally, we've been taughtthat cats in shock often do not
respond to fully bonelessresuscitations, but there is no
really clear explanation forthis.
So, based on the literature, weknow that in anesthetized cats,
hypothermia induces bradycardiaand hypotension, which
clinically mimics thepresentation of cats in shock.
So, for this reason, our aimwas to investigate volume
(03:35):
kinetics under conditions ofmild hypothermia, and our
hypothesis was that hypothermiawas low in the distribution, but
that cold diuresis wouldincrease elimination, make it
faster.
Sarah Wright (03:48):
Yeah, really important study, so thank you
for undertaking this.
So what are some importanttake-home messages from this
AJVR article?
Stefania Gelendi (03:56):
I'll say the big takeaway from our study is
that mild hypothermia actuallychanges how high V fluids are
handled in cats andspecifically we found that
hypothermia increases thecentral compartment volume,
which essentially means that thefluid bolus has less effect on
plasma volume expansionscompared to when given to a
normal thermic cat, and thiscould make fluids less effective
(04:19):
in those conditions.
We also found that temperature,body weight and anesthesia all
interact to influence fluidtherapy in our anesthetized cats
and this finding could help usrefine how we approach fluid
administration in both emergencybut also surgical settings.
But we need more research toconfirm these results and
explore how they apply to awakeand critically ill cats.
(04:41):
Also, contrary to our initialthought, mild hypothermia didn't
cause a significant increase inurine output in our study
population, so we didn't see anycold diuresis in our cold
anesthetized cats.
We think that this was due tothe effect of anesthesia that
might have counteracted thateffect, but that's an
interesting area for futureresearch.
Lisa Fortier (05:02):
Yeah, you're so right, Stefania.
The cats are sounder-researched, so we really
appreciate you sharing this withus and our listeners.
Stefania Gelendi (05:10):
Thank you.
Lisa Fortier (05:10):
Ben.
What's Sorry, go ahead.
Stefania Gelendi (05:13):
Thank you,
Lisa Fortier (05:15):
Hey, Ben.
What sparked your researchinterest in fluid therapy?
Ben Liao (05:19):
Yeah.
So, I think I started to haveinterest in fluid therapy,
mostly from.
I'm actually more interested inhemodynamic management in a QK
setting.
and fluid therapy is kind of atopic that kind of connects the
(05:45):
dots in hemodynamic managementit is a treatment and response
different indications and kindof recent interest in the
revised Starling principle andglycocalyx kind of reaffirmed my
interest in this area.
So that's kind of a longtimeinterest but kind of a recent
spark.
Lisa Fortier (06:01):
Starling's law.
I haven't heard that one for along time.
I'm an equine orthopedist.
We don't think about Starling'slaw very often.
Ben Liao (06:08):
Right.
Lisa Fortier (06:08):
Stefania, how about you?
What sparked your researchinterest in fluid therapy?
Stefania Gelendi (06:13):
So actually I started being interested in
fluids during the first absolutebad job I got as a new graduate
in Italy.
At university we didn't reallycover much about fluid therapy.
So when I attended my firstemergency and critical care
course, it was in Rome, and Iremember the first lecture was
about fluid therapy and I wasvery captivated of it.
(06:36):
And then one of the bigtakeaways was, of course, the
fluids are not just basictreatments but they are drugs,
so they can save lives when usedcorrectly, but also can cause
harm if mismanaged, and so thisconcept really sparkled my
curiosity to learn more.
And then, when I started myresidency at Auburn, Ben
(06:57):
introduced me to the concept ofvolume kinetics, and I remember
on the whiteboard he explainedit in such a clear and
straightforward way thatimmediately clicked for me.
It made so much sense and Ithought it was a brilliant idea.
So just use pharmacokineticsprinciple to see how fluid
behaves in the body.
At first it seemed so simpleand straightforward, but then I
(07:20):
started reading more aboutvolume kinetics and I quickly
realized how actuallycomplicated it is, and I spent
about six or even more monthsjust reading papers and studying
about volume kinetics justbefore even starting this
project.
So yeah, I've been passionateabout it ever since, because
there's so much to learn and tounderstand to start with.
Lisa Fortier (07:41):
Well done, Ben, to fan that flame that was already
burning in Stefania Earlier.
Stefania then talked about someof the really important
findings from this article, butalways when we do things,
there's things that surprise us.
When you were looking at theresults and thinking about it,
what things did you findsurprising when putting this
article together?
Ben Liao (08:03):
Yeah, I think what surprised us was our hypothesis
was all on the kind of oppositedirection.
So in our study basically wefound that two compartment
models fit our data the best.
So essentially and kind ofbriefly explaining, this is the
(08:26):
fluid we gave behaves like thereare two compartments in the
body, one central, oneperipheral, and their micro
constant kind of control therate of fluid going either
direction or going out of thebody.
So that would be theelimination constant.
So what we found we thought themicro constant would be changed
by the hypothermia but it turnsout it was the central
(08:47):
compartment that got bigger.
So kind of briefly mentioned byStefania, that that's kind of
our key finding and what thismeans.
What interesting is the microconstant didn't change but the
central compartment got biggerwith hypothermia.
So what that means is the fluidis less effective.
So when we give the same amountof fluid when the cats are cold
(09:13):
, the percentage increase inplasma volume is smaller.
So on the other way you canalso say this you know that if
you give the same amount offluid, say 10 ml per kilo of
bolus, you will induce lesspercentage increase in the
plasma volume expansion in acold cat, a little bit like when
(09:34):
you are pouring a glass ofwater in an empty pool versus
another empty glass.
So the percentage increase ismuch higher when they are normal
thermic.
So that's very interesting.
That's kind of surprising to us.
But we did have some plausiblehypothesis of why this happened.
We thought this could be a kindof vasodilation and spleen
(09:57):
omegaly from sympatheticactivity being decreased and
responsiveness decreased.
But we couldn't verify thisfinding based on our study, so
that would be something for thefuture to find out.
Maybe we'll combine anultrasound or CT study to look
at the spleen volume orsomething like that.
And another interestinghypothesis we had was if the
(10:20):
central compartment would reducein size when the cats are
re-warmed.
Like that's our clinical goal,we're clinically trying to not
give too much fluid and warm itup and see what happens if you
go in and need it.
So if the central compartmentdoes decrease in size when they
are re-warmed, it perhaps canexplain why they would show
(10:42):
fluid overload once they areresuscitated, because it's like
the central compartment beingtightened down and the fluid we
gave being pressurized and thenit started to cause problems
like pleural effusion, pulmonaryedema, congestion, those kind
of things.
So we got some interestinghypotheses generated from this
study.
But this is not a.
(11:05):
It's a pharmacokinetic study.
It's more hypotheses generatingthis.
What we can do with this studyis I cannot really verify all
these hypotheses, but it'sinteresting.
All the models are wrong, butit teaches something.
Sarah Wright (11:21):
That's fascinating .
So what are the next steps forresearch in this topic?
Ben Liao (11:25):
Yeah, so kind of piggyback on what I mentioned.
There are so many interestingresearch topics.
Some of the next steps could bewe study the effects of
rewarming.
So, we just get cat cold, givefluids and then we warm and give
another one Kind of compare thefluid volume kinetic between
the two states.
(11:45):
We can look at the hypothermiaeffect through the volume
kinetic but also at the sametime look at the hemodynamic
data to kind of have a PKB-TDDRcombination.
Otherwise, I think eventuallyall this done in research
(12:06):
animals, it would be really moreuseful to look at clinical
patients and that would be kindof a couple interesting next
steps.
Sarah Wright (12:16):
So AI is a very hot topic right now.
Do you see a role for AI inthis area of research?
Ben Liao (12:22):
Yeah, I think there are definitely, you know,
exploration of using AI in thepharmacokinetic field.
There are a lot of interestingdirection it is going.
I think ultimately,pharmacokware Kinetic is
modeling and maybe AI will beable to handle a complicated or
(12:42):
complex process.
But I think one thing that'skind of critical in my simple
mind I'm not an AI expert isthat AI is very data-hungry and
veterinary medicine isdata-lacking.
So, it's really hard I think togenerate enough data unless
(13:03):
there's enough drive to developreally good electronic health
system for us to justautomatically plug in all this
electronic health system thatmaybe in the long term we'll be
able to get all this data, putit into the AI to help us
process it.
But I think right now I'm justcautiously optimistic.
Sarah Wright (13:25):
Yeah, yeah, very sure what you said about there
being not enough data inveterinary medicine, something
that we're definitely workingtowards and, for those of you
just joining us, we'rediscussing how mild hypothermia
is associated with alteredvolume Kinetic parameters of an
intravenous crystalloid fluidbolus in healthy isoflurane
anesthetized cats, with ourguests Stefania and Ben.
Lisa Fortier (13:50):
Stefania, you talked about working in private
practice in Italy and then aresidency in Auburn.
How did that training andexperience prepare you to write
this article?
Stefania Gelendi (14:00):
Well, this was actually my first time being
fully responsible for aprospective study like this one,
so it was all pretty new to me.
When I started, I had tonavigate a lot of different
aspects, as you can imagine,from preparing the grant
proposal to coordinating withmultiple people, organize
everything, prepare the studytimeline, order, supplies and
(14:20):
learn everything about justliterature.
I also had to learn a lot abouthow to manage a project on this
scale and honestly, it was areal learning experience.
There were definitely a lot oftimes where I would miss details
or feel unsure about the nextsteps, but luckily Ben, as my
supervisor, was a huge support.
He let me take charge andhandle everything on my own, but
(14:42):
then he would kind of make sureI didn't go off track.
And the other investigatorsalso support me a lot.
Dr Ewan Battelman and Dr Raviswere always available to clarify
volume kinetics concept andalso questions I had, as they
were the one performing the dataanalysis and the most familiar
(15:02):
with volume kinetics.
Dr Johnson oversees theuniversity cat colony that we
rented the cats from and helpedme organize that.
And then Dr Koh and Dr Gerkenare actually also my residency
mentors and for sure they werethere during the most
challenging times, ready toprovide me mainly moral support
but also guidance for theproject.
(15:24):
And again, it was a reallearning experience for me.
It taught me a lot aboutmanaging a study from start to
finish, and I mean it wasstressful at times but also
incredibly rewarding, and ithelped me grow both
professionally and personally.
Lisa Fortier (15:41):
That's a fantastic answer and it's really nice to
know from Ben and your othercolleagues that mentorship is
alive and well.
Stefania Gelendi (15:47):
Yeah.
Ben Liao (15:47):
Yeah.
Lisa Fortier (15:49):
It also gives you a whole other level of respect,
when you're reading otherresearch articles, to know how
long it took for that team toget that.
Maybe one nugget of information.
Stefania Gelendi (16:00):
Absolutely
Lisa Fortier (16:02):
Speaking of nuggets of information, if you
were going to distill this down,what would be the one piece of
information the veterinarianshould know about this topic
area?
Stefania Gelendi (16:12):
I feel like veterinarians should know that
our experiment model is verydifferent from what happened in
clinical shock cases andfindings should be verified in a
clinical population.
So, while our study providesvaluable insights and it's
crucial to recognize thathealthy anesthetized cats may
not represent what actuallyhappens in cats in shocks.
(16:39):
However, studying volumekinetics in sick cats is also
very challenging, so, mainly interms of designing ethical and
practical studies.
So, for instances, these studiesusually require frequent blood
sampling as we need repeatedmeasurements of PAC Cell volume
to feed data for the dataanalysis as input, basically for
the volume kinetic model.
(17:00):
And this necessitates like thismake designing studies that are
ethical very hard, because insick animals you don't want to
get all the blood out for allthe sampling and so many times.
If you want to perform one ofthose studies in sick animals,
you need to go for a terminalstudy to collect accurate data
(17:20):
and personally I find ituncomfortable to conduct
terminal studies due to, ofcourse, the significant ethical
concerns and challenges theypresent.
But despite these barriers,there's population
pharmacokinetics that allow usto model fluid dynamics using
like sparse data from manypatients, and this approach can
help us gather insight withoutextensive sampling.
(17:41):
But yeah, we just need toacknowledge this limitation and
highlight the potential forfuture studies, so that
veterinarians can bettercontextualize our findings and
appreciate the ongoing nature ofresearch in this area.
Sarah Wright (17:58):
So, on the other side of the relationship, what's
one thing clients should knowabout this topic area?
Stefania Gelendi (18:03):
So I feel like .
For clients, it's crucial tounderstand that cats in shock
are a significant challenge forveterinarians and their body
temperature can affect howintravenous fluids are handled
during treatment.
And this means thatveterinarian needs to carefully
adjust fluid therapy to ensureproper hydration without risking
all the complications thatderive from it.
Additionally, our study foundthat cats' body weight
(18:27):
significantly influences fluidelimination, meaning bigger cats
showed a decreased eliminationrate of fluid, which was quite
surprising for us.
We don't know if this is arepeatable result, but if it is
true, this highlights howimportant it is of maintaining a
healthy weight for your cat, asobesity can complicate fluid
therapy during medicalprocedures, and keeping your cat
(18:49):
at an ideal body weight notonly benefits their overall
health, but also preventscomplications when intravenous
fluids are necessary.
And these findings underscorewhy veterinarians take extra
precautions to monitor andmaintain your cat's body
temperature and why they may askor comment about the cat's
weight during treatment planning.
And by understanding thesefactors, clients also can better
(19:13):
appreciate the complexity ofveterinary care and the
importance of preventativehealth measures for their pets.
Lisa Fortier (19:20):
Really, really well said.
Thank you as we wind down again.
Thank you both for submittingthis to AJVR and for joining us
here today on the podcast.
We'd like to ask a little bitmore of a fun question, so we'll
start while we have you.
Stefania, if you could have asuperpower, what would it be and
why?
Stefania Gelendi (19:39):
I feel like it might sound like an expected
answer, but ever since I was achild, I've always wished I
could actually instantlycommunicate with animals.
Now, as a vet, that desire iseven stronger.
Especially when they're indistress and working in
emergency and critical care, Ioften find myself wishing I
could truly understand whatthey're experiencing or what
they need in those criticalmoments.
(20:00):
Being able to do that will makea world of a difference, I feel
, in providing them with thebest care possible.
But that being said, afterworking in the field for a while
, I feel sometimes I canactually have full conversations
with them, and I think we willend up talking to our
hospitalized patients anyway,don't we?
Lisa Fortier (20:20):
Yes, we do.
Not just our patients, our petsas well.
Stefania Gelendi (20:25):
Yeah.
Lisa Fortier (20:27):
Ben for you.
What is your favorite animalfact?
Ben Liao (20:32):
I was thinking about this for a while but I would go
with.
Octopus has three hearts.
That was pretty cool.
They have two that pumps bloodinto the gills and one that kind
of just works our regular heartthat pumps blood into the whole
body.
So pretty interesting anatomyand physiology for me.
Sarah Wright (20:51):
We actually just learned another fun octopus
animal fact.
Last week on the podcast too,we had an ophthalmologist and
she was sharing how theyactually might have like a hole
in their cornea that providescommunication to the anterior
chamber of the eye, so reallyfascinating.
But thank you so much, Stefaniaand Ben, for being here today
and for also contributing yourmanuscript to AJVR.
Ben Liao (21:12):
Thank you very much.
Sarah Wright (21:14):
And to our listeners.
You can read Stefania and Ben'sarticle on AJVR.
I'm Sarah Wright with LisaFortier.
Be on the lookout for nextweek's episode and don't forget
to leave us a rating and reviewon Apple Podcasts or whatever
platform you listen to.
You're listening to Veterinary Vertex, a podcast
of the AVMA Journals.
In this episode, we chat abouthow mild hypothermia is
associated with altered volume,kinetic parameters of an
intravenous crystalloid fluid,bolus and healthy isoflurane
anesthetized cats with ourguests Stefania Gelendi and Ben
Liao.
Lisa Fortier (00:21):
Welcome to Veterinary Vertex.
I'm Editor-in-Chief LisaFortier, and I'm joined by
Associate Editor Sarah Wright.
Today, we have Stefania and Benjoining us.
Thank you so much, each of you,for taking time out of your
busy schedules to share yourpodcast with us today.
Stefania Gelendi (00:38):
Thank you for having us.
Ben Liao (00:40):
Yeah, thank you for having us.
Sarah Wright (00:42):
All right, let's dive right in Stefania.
Your AJVR article discusses howmild hypothermia is associated
with altered volume.
Kinetic parameters of anintravenous crystalloid fluid
bolus and healthy isofluraneanesthetized cats.
Please share with our listenersthe background on this article.
Stefania Gelendi (01:00):
Thank you for the question.
So, the study stems from theclinical challenge we face when
we treat cats in shock.
Cats are especially tricky totreat because of their unique
physiology, as you know.
So, they're not only prone tobradycardia, hypotension and
hypothermia, but also aretotally predisposed to volume
overload, and this makes fluidtherapy a delicate balancing act
(01:23):
.
To better understand how fluidbehaves in cats under this
condition, we used for our studyvolume kinetics or volume
kinetic analysis.
And volume kinetics isessentially pharmacokinetics,
but for fluid, and so with thatwe can analyze how fluid
(01:44):
distribute and are eliminated inthe body.
While there are quite already afew publications on volume
kinetics in human medicine,veterinary medicine has only
recently begun to explore itspotential.
The first study was done atOntario Veterinary College by Dr
Zhu and Bettman they're both inmy paper and following this, a
couple of studies here at Auburndemonstrated its feasibility in
(02:06):
healthy cats.
So, building on that foundation, we wanted to investigate how
mild apothermia specificallyimpacts the behavior of a fluid
bolus in anesthetized cats.
So it's worth noting thatvolume kinetics in itself is not
easy, but then the hardest partis actually to identify a
relevant research question.
So this is particularly truebecause there is a general lack
(02:29):
of evidence in cats, and ourunderstanding of shocks and its
treatment in feline patients ismostly based on anecdotal
observations, and so this gap inknowledge made us particularly
excited about this study.
But then why hypothermia?
We believe that cats, when theyexperience shock, the body may
handle fluid differently.
For example, in humans,hypotension slows fluid
(02:53):
elimination.
That has been demonstrated.
But on the other hand, thereare some studies saying that
hypothermia is still to actuallyincrease urinary production,
which is a phenomenon known ascold diuresis, which could lead
to faster fluid elimination.
However, we don't know if theseprocesses occur at all in cats
and, if they do, how they mayinteract.
(03:14):
Additionally, we've been taughtthat cats in shock often do not
respond to fully bonelessresuscitations, but there is no
really clear explanation forthis.
So, based on the literature, weknow that in anesthetized cats,
hypothermia induces bradycardiaand hypotension, which
clinically mimics thepresentation of cats in shock.
So, for this reason, our aimwas to investigate volume
(03:35):
kinetics under conditions ofmild hypothermia, and our
hypothesis was that hypothermiawas low in the distribution, but
that cold diuresis wouldincrease elimination, make it
faster.
Sarah Wright (03:48):
Yeah, really important study, so thank you
for undertaking this.
So what are some importanttake-home messages from this
AJVR article?
Stefania Gelendi (03:56):
I'll say the big takeaway from our study is
that mild hypothermia actuallychanges how high V fluids are
handled in cats andspecifically we found that
hypothermia increases thecentral compartment volume,
which essentially means that thefluid bolus has less effect on
plasma volume expansionscompared to when given to a
normal thermic cat, and thiscould make fluids less effective
(04:19):
in those conditions.
We also found that temperature,body weight and anesthesia all
interact to influence fluidtherapy in our anesthetized cats
and this finding could help usrefine how we approach fluid
administration in both emergencybut also surgical settings.
But we need more research toconfirm these results and
explore how they apply to awakeand critically ill cats.
(04:41):
Also, contrary to our initialthought, mild hypothermia didn't
cause a significant increase inurine output in our study
population, so we didn't see anycold diuresis in our cold
anesthetized cats.
We think that this was due tothe effect of anesthesia that
might have counteracted thateffect, but that's an
interesting area for futureresearch.
Lisa Fortier (05:02):
Yeah, you're so right, Stefania.
The cats are sounder-researched, so we really
appreciate you sharing this withus and our listeners.
Stefania Gelendi (05:10):
Thank you.
Lisa Fortier (05:10):
Ben.
What's Sorry, go ahead.
Stefania Gelendi (05:13):
Thank you,
Lisa Fortier (05:15):
Hey, Ben.
What sparked your researchinterest in fluid therapy?
Ben Liao (05:19):
Yeah.
So, I think I started to haveinterest in fluid therapy,
mostly from.
I'm actually more interested inhemodynamic management in a QK
setting.
and fluid therapy is kind of atopic that kind of connects the
(05:45):
dots in hemodynamic managementit is a treatment and response
different indications and kindof recent interest in the
revised Starling principle andglycocalyx kind of reaffirmed my
interest in this area.
So that's kind of a longtimeinterest but kind of a recent
spark.
Lisa Fortier (06:01):
Starling's law.
I haven't heard that one for along time.
I'm an equine orthopedist.
We don't think about Starling'slaw very often.
Ben Liao (06:08):
Right.
Lisa Fortier (06:08):
Stefania, how about you?
What sparked your researchinterest in fluid therapy?
Stefania Gelendi (06:13):
So actually I started being interested in
fluids during the first absolutebad job I got as a new graduate
in Italy.
At university we didn't reallycover much about fluid therapy.
So when I attended my firstemergency and critical care
course, it was in Rome, and Iremember the first lecture was
about fluid therapy and I wasvery captivated of it.
(06:36):
And then one of the bigtakeaways was, of course, the
fluids are not just basictreatments but they are drugs,
so they can save lives when usedcorrectly, but also can cause
harm if mismanaged, and so thisconcept really sparkled my
curiosity to learn more.
And then, when I started myresidency at Auburn, Ben
(06:57):
introduced me to the concept ofvolume kinetics, and I remember
on the whiteboard he explainedit in such a clear and
straightforward way thatimmediately clicked for me.
It made so much sense and Ithought it was a brilliant idea.
So just use pharmacokineticsprinciple to see how fluid
behaves in the body.
At first it seemed so simpleand straightforward, but then I
(07:20):
started reading more aboutvolume kinetics and I quickly
realized how actuallycomplicated it is, and I spent
about six or even more monthsjust reading papers and studying
about volume kinetics justbefore even starting this
project.
So yeah, I've been passionateabout it ever since, because
there's so much to learn and tounderstand to start with.
Lisa Fortier (07:41):
Well done, Ben, to fan that flame that was already
burning in Stefania Earlier.
Stefania then talked about someof the really important
findings from this article, butalways when we do things,
there's things that surprise us.
When you were looking at theresults and thinking about it,
what things did you findsurprising when putting this
article together?
Ben Liao (08:03):
Yeah, I think what surprised us was our hypothesis
was all on the kind of oppositedirection.
So in our study basically wefound that two compartment
models fit our data the best.
So essentially and kind ofbriefly explaining, this is the
(08:26):
fluid we gave behaves like thereare two compartments in the
body, one central, oneperipheral, and their micro
constant kind of control therate of fluid going either
direction or going out of thebody.
So that would be theelimination constant.
So what we found we thought themicro constant would be changed
by the hypothermia but it turnsout it was the central
(08:47):
compartment that got bigger.
So kind of briefly mentioned byStefania, that that's kind of
our key finding and what thismeans.
What interesting is the microconstant didn't change but the
central compartment got biggerwith hypothermia.
So what that means is the fluidis less effective.
So when we give the same amountof fluid when the cats are cold
(09:13):
, the percentage increase inplasma volume is smaller.
So on the other way you canalso say this you know that if
you give the same amount offluid, say 10 ml per kilo of
bolus, you will induce lesspercentage increase in the
plasma volume expansion in acold cat, a little bit like when
(09:34):
you are pouring a glass ofwater in an empty pool versus
another empty glass.
So the percentage increase ismuch higher when they are normal
thermic.
So that's very interesting.
That's kind of surprising to us.
But we did have some plausiblehypothesis of why this happened.
We thought this could be a kindof vasodilation and spleen
(09:57):
omegaly from sympatheticactivity being decreased and
responsiveness decreased.
But we couldn't verify thisfinding based on our study, so
that would be something for thefuture to find out.
Maybe we'll combine anultrasound or CT study to look
at the spleen volume orsomething like that.
And another interestinghypothesis we had was if the
(10:20):
central compartment would reducein size when the cats are
re-warmed.
Like that's our clinical goal,we're clinically trying to not
give too much fluid and warm itup and see what happens if you
go in and need it.
So if the central compartmentdoes decrease in size when they
are re-warmed, it perhaps canexplain why they would show
(10:42):
fluid overload once they areresuscitated, because it's like
the central compartment beingtightened down and the fluid we
gave being pressurized and thenit started to cause problems
like pleural effusion, pulmonaryedema, congestion, those kind
of things.
So we got some interestinghypotheses generated from this
study.
But this is not a.
(11:05):
It's a pharmacokinetic study.
It's more hypotheses generatingthis.
What we can do with this studyis I cannot really verify all
these hypotheses, but it'sinteresting.
All the models are wrong, butit teaches something.
Sarah Wright (11:21):
That's fascinating .
So what are the next steps forresearch in this topic?
Ben Liao (11:25):
Yeah, so kind of piggyback on what I mentioned.
There are so many interestingresearch topics.
Some of the next steps could bewe study the effects of
rewarming.
So, we just get cat cold, givefluids and then we warm and give
another one Kind of compare thefluid volume kinetic between
the two states.
(11:45):
We can look at the hypothermiaeffect through the volume
kinetic but also at the sametime look at the hemodynamic
data to kind of have a PKB-TDDRcombination.
Otherwise, I think eventuallyall this done in research
(12:06):
animals, it would be really moreuseful to look at clinical
patients and that would be kindof a couple interesting next
steps.
Sarah Wright (12:16):
So AI is a very hot topic right now.
Do you see a role for AI inthis area of research?
Ben Liao (12:22):
Yeah, I think there are definitely, you know,
exploration of using AI in thepharmacokinetic field.
There are a lot of interestingdirection it is going.
I think ultimately,pharmacokware Kinetic is
modeling and maybe AI will beable to handle a complicated or
(12:42):
complex process.
But I think one thing that'skind of critical in my simple
mind I'm not an AI expert isthat AI is very data-hungry and
veterinary medicine isdata-lacking.
So, it's really hard I think togenerate enough data unless
(13:03):
there's enough drive to developreally good electronic health
system for us to justautomatically plug in all this
electronic health system thatmaybe in the long term we'll be
able to get all this data, putit into the AI to help us
process it.
But I think right now I'm justcautiously optimistic.
Sarah Wright (13:25):
Yeah, yeah, very sure what you said about there
being not enough data inveterinary medicine, something
that we're definitely workingtowards and, for those of you
just joining us, we'rediscussing how mild hypothermia
is associated with alteredvolume Kinetic parameters of an
intravenous crystalloid fluidbolus in healthy isoflurane
anesthetized cats, with ourguests Stefania and Ben.
Lisa Fortier (13:50):
Stefania, you talked about working in private
practice in Italy and then aresidency in Auburn.
How did that training andexperience prepare you to write
this article?
Stefania Gelendi (14:00):
Well, this was actually my first time being
fully responsible for aprospective study like this one,
so it was all pretty new to me.
When I started, I had tonavigate a lot of different
aspects, as you can imagine,from preparing the grant
proposal to coordinating withmultiple people, organize
everything, prepare the studytimeline, order, supplies and
(14:20):
learn everything about justliterature.
I also had to learn a lot abouthow to manage a project on this
scale and honestly, it was areal learning experience.
There were definitely a lot oftimes where I would miss details
or feel unsure about the nextsteps, but luckily Ben, as my
supervisor, was a huge support.
He let me take charge andhandle everything on my own, but
(14:42):
then he would kind of make sureI didn't go off track.
And the other investigatorsalso support me a lot.
Dr Ewan Battelman and Dr Raviswere always available to clarify
volume kinetics concept andalso questions I had, as they
were the one performing the dataanalysis and the most familiar
(15:02):
with volume kinetics.
Dr Johnson oversees theuniversity cat colony that we
rented the cats from and helpedme organize that.
And then Dr Koh and Dr Gerkenare actually also my residency
mentors and for sure they werethere during the most
challenging times, ready toprovide me mainly moral support
but also guidance for theproject.
(15:24):
And again, it was a reallearning experience for me.
It taught me a lot aboutmanaging a study from start to
finish, and I mean it wasstressful at times but also
incredibly rewarding, and ithelped me grow both
professionally and personally.
Lisa Fortier (15:41):
That's a fantastic answer and it's really nice to
know from Ben and your othercolleagues that mentorship is
alive and well.
Stefania Gelendi (15:47):
Yeah.
Ben Liao (15:47):
Yeah.
Lisa Fortier (15:49):
It also gives you a whole other level of respect,
when you're reading otherresearch articles, to know how
long it took for that team toget that.
Maybe one nugget of information.
Stefania Gelendi (16:00):
Absolutely
Lisa Fortier (16:02):
Speaking of nuggets of information, if you
were going to distill this down,what would be the one piece of
information the veterinarianshould know about this topic
area?
Stefania Gelendi (16:12):
I feel like veterinarians should know that
our experiment model is verydifferent from what happened in
clinical shock cases andfindings should be verified in a
clinical population.
So, while our study providesvaluable insights and it's
crucial to recognize thathealthy anesthetized cats may
not represent what actuallyhappens in cats in shocks.
(16:39):
However, studying volumekinetics in sick cats is also
very challenging, so, mainly interms of designing ethical and
practical studies.
So, for instances, these studiesusually require frequent blood
sampling as we need repeatedmeasurements of PAC Cell volume
to feed data for the dataanalysis as input, basically for
the volume kinetic model.
(17:00):
And this necessitates like thismake designing studies that are
ethical very hard, because insick animals you don't want to
get all the blood out for allthe sampling and so many times.
If you want to perform one ofthose studies in sick animals,
you need to go for a terminalstudy to collect accurate data
(17:20):
and personally I find ituncomfortable to conduct
terminal studies due to, ofcourse, the significant ethical
concerns and challenges theypresent.
But despite these barriers,there's population
pharmacokinetics that allow usto model fluid dynamics using
like sparse data from manypatients, and this approach can
help us gather insight withoutextensive sampling.
(17:41):
But yeah, we just need toacknowledge this limitation and
highlight the potential forfuture studies, so that
veterinarians can bettercontextualize our findings and
appreciate the ongoing nature ofresearch in this area.
Sarah Wright (17:58):
So, on the other side of the relationship, what's
one thing clients should knowabout this topic area?
Stefania Gelendi (18:03):
So I feel like .
For clients, it's crucial tounderstand that cats in shock
are a significant challenge forveterinarians and their body
temperature can affect howintravenous fluids are handled
during treatment.
And this means thatveterinarian needs to carefully
adjust fluid therapy to ensureproper hydration without risking
all the complications thatderive from it.
Additionally, our study foundthat cats' body weight
(18:27):
significantly influences fluidelimination, meaning bigger cats
showed a decreased eliminationrate of fluid, which was quite
surprising for us.
We don't know if this is arepeatable result, but if it is
true, this highlights howimportant it is of maintaining a
healthy weight for your cat, asobesity can complicate fluid
therapy during medicalprocedures, and keeping your cat
(18:49):
at an ideal body weight notonly benefits their overall
health, but also preventscomplications when intravenous
fluids are necessary.
And these findings underscorewhy veterinarians take extra
precautions to monitor andmaintain your cat's body
temperature and why they may askor comment about the cat's
weight during treatment planning.
And by understanding thesefactors, clients also can better
(19:13):
appreciate the complexity ofveterinary care and the
importance of preventativehealth measures for their pets.
Lisa Fortier (19:20):
Really, really well said.
Thank you as we wind down again.
Thank you both for submittingthis to AJVR and for joining us
here today on the podcast.
We'd like to ask a little bitmore of a fun question, so we'll
start while we have you.
Stefania, if you could have asuperpower, what would it be and
why?
Stefania Gelendi (19:39):
I feel like it might sound like an expected
answer, but ever since I was achild, I've always wished I
could actually instantlycommunicate with animals.
Now, as a vet, that desire iseven stronger.
Especially when they're indistress and working in
emergency and critical care, Ioften find myself wishing I
could truly understand whatthey're experiencing or what
they need in those criticalmoments.
(20:00):
Being able to do that will makea world of a difference, I feel
, in providing them with thebest care possible.
But that being said, afterworking in the field for a while
, I feel sometimes I canactually have full conversations
with them, and I think we willend up talking to our
hospitalized patients anyway,don't we?
Lisa Fortier (20:20):
Yes, we do.
Not just our patients, our petsas well.
Stefania Gelendi (20:25):
Yeah.
Lisa Fortier (20:27):
Ben for you.
What is your favorite animalfact?
Ben Liao (20:32):
I was thinking about this for a while but I would go
with.
Octopus has three hearts.
That was pretty cool.
They have two that pumps bloodinto the gills and one that kind
of just works our regular heartthat pumps blood into the whole
body.
So pretty interesting anatomyand physiology for me.
Sarah Wright (20:51):
We actually just learned another fun octopus
animal fact.
Last week on the podcast too,we had an ophthalmologist and
she was sharing how theyactually might have like a hole
in their cornea that providescommunication to the anterior
chamber of the eye, so reallyfascinating.
But thank you so much, Stefaniaand Ben, for being here today
and for also contributing yourmanuscript to AJVR.
Ben Liao (21:12):
Thank you very much.
Sarah Wright (21:14):
And to our listeners.
You can read Stefania and Ben'sarticle on AJVR.
I'm Sarah Wright with LisaFortier.
Be on the lookout for nextweek's episode and don't forget
to leave us a rating and reviewon Apple Podcasts or whatever
platform you listen to.
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