Thanks for joining us again at the Canadian Breakpoint,
a Canadian infectious diseases podcast by Canadian
infectious diseases physicians. I'm Summer Stewart
here with Dr. Rupina Pirawal, Pediatric Infectious
Diseases Physician in Saskatoon. For today's
episode, we invite Dr. Alison Fox Robichaud.
to discuss sepsis and some of the important sepsis
initiatives that her team is involved with here
in Canada. Dr. Pierwal. Perfect. So welcome to
another episode of our podcast, the Canadian
Breakpoint. Today, we have a very special guest
with us. It's Dr. Alison Fox Robichaux, who,
as many of you might be aware. has done a lot
of work around an important topic that we're
going to be discussing today, which is sepsis.
So to give a formal introduction, Dr. Fox Robichaux
is a professor of medicine, the Hamilton Health
Sciences Chair in Sepsis Research at McMaster
University, and a critical care medicine specialist,
head of service for the critical care response
team, and the director of medical education at
Hamilton Health Sciences. She's also the scientific
director of Sepsis Canada. She has over 160 peer
-reviewed publications reflecting broad academic
interests, including animal models of sepsis,
translational medicine, health services research,
and clinical trials. A leader in the critical
care community, she was the first female president
of the Canadian Critical Care Society from 2015
to 2018 and the first female chair of the Canadian
Critical Care Examination Board. Well done. Internationally,
she's also a member of the Global Sepsis Alliance
Board, the Advisory Board of the International
Society for Rapid Response Systems, the Council
of the World Federation of Intensive and Critical
Care. She is the organizing chair of the 17th
World Congress of Intensive and Critical Care
to be held in Vancouver this September. She's
been honored nationally for her work in electronic
early warning scores to prevent patient deterioration
and received the King Charles III Coronation
Medal for her national sepsis leadership. Internationally,
in 2018, the Global Sepsis Alliance awarded her
an individual award for her sepsis leadership.
So as you can see, we have an expert with us
today, and we're really fortunate to have you
today. Thank you very much, Dr. Perwell, for
inviting me to speak on your podcast. I'm honored
to be here. Thank you. So, you know, I've been
wanting to talk about sepsis for a while, just
because it's, as we all know, a very important
topic, something we... as healthcare professionals
of kind of nurses, specialists, you know, if
you're at the forefront, even family doctors,
pharmacists, critical care physicians, obviously,
are always involved in. I think there's a lot
of information that has changed or is ongoing.
There's a lot of research in this area. So I
think for our listeners and also for myself,
it would be nice if we could maybe start with
the basics and let's just define sepsis. So how
is it diagnosed? Are there clinical criteria?
And are these being applied in clinical practice?
I'm going to take it a step back. I think when
sepsis and the word sepsis has been around since
the Greeks, they called it poisoning. And recognize
that it was a condition with a high mortality
when, you know, people got an infection, got
really, really sick with it. But the modern definitions
have changed. And I really think that intensivists
have gotten too smart sometimes in terms of that's
been our biggest community. We are, you know,
this is our disease and I'm going to call it
a disease. We've been calling it a condition,
a syndrome, but I'm going to call it a disease,
same way as oncologists call cancer a disease,
because I think that's important for the audience
to understand. And it means that it's a disorder
that affects how your body functions. It's more
likely to have a known cause. And in this case,
the known cause of sepsis is infections. And
more likely in a distinct course. That is, there
is a pattern to this. And the pattern for sepsis
is organ dysfunction. That varies based on what
the pathogen is, whether it's bacterial or viral
or fungal. The host factors, whether your immune
system's up to par or not. And some environmental
and probably social factors that may make us,
some individuals, more at risk than others. And
it has some established treatments, maybe not
enough in our field. But that definition now
culminates in something that we call life -threatening
organ dysfunction due to a host response to that
infection. So it's really driven by how our body
responds to infections. And some people can have
an infection and not get sick at all. And other
people get organ dysfunction that ends them up
in our ICU. Yeah. So really a clinical like spectrum
that we see. So are there some key warning signs?
Because sepsis can obviously deterioration can
happen very quickly. So are there any distinct
warning signs or like you mentioned, there are
obviously a risk factors. So you can you know
that individuals are predisposed or may be predisposed
to having this. But are there anything that physicians
can look for? I think this is probably our biggest
challenge. So unlike a heart attack, where we
have biomarkers, you come into the hospital,
you do it. We don't have the same thing for sepsis.
So there's a lot of it depends on patient intuition.
Something's wrong with me. I seek help. I've
not felt like this before. And a lot of it depends
on clinician intuition. This is an infection.
But it also depends on doing some measurements,
the simplest of which is, are your vital signs
normal? Things like your respiratory rate, your
blood pressure, your heart rate. Now, young people
can hide that away sometimes and elder people
may not get a fever. But those abnormal vital
signs that include confusion, our patients, when
they tell us about experiencing sepsis, can say
it feels like everything from, you know, I'm
not thinking clearly, I can't make urine, I've
got nausea, vomiting, through to, you know, I
just feel horrible and I'm not sure what's going
on with me. And then I know like in the past,
there's obviously some like vital sign parameters
that we can use. So like somebody has, you know,
a really elevated temperature, a very low temperature
that could be in correlation if they have a really
fast heart rate, as we see with that. So those,
some of those criteria are being assessed at
that time to kind of see if this patient is currently
as critically ill as we think they are. I'm part
of the upcoming Surviving Sepsis Campaign Guidelines.
And one of the things is looking for those diagnostic
tools. May not have great biomarkers yet, but
we have that constellation of our vital signs
put together into some things such as early warning
scores. And some of my work, I say, well, is
she working on early warning scores for patient
deterioration? It's because I know that that's
one of those things to pick up those early. signs
of this infection is affecting the whole body
and my body's ability to maintain homeostasis
and that may show up before you have measurable
organ dysfunction creatinine rising o2 sats falling
platelet count dropping Yeah. And I guess like
we mentioned some of the biomarkers, or you mentioned
biomarkers in general. So in my world, I think
in some of the other hospitals too, of some of
the listeners that are tuning in today, there's
a few that are commonly used, I would say. So
like procalcitonin in certain centers is being
used now, even sometimes more frequently than
CRP. And obviously CRP has like historically
been used a lot. So what are your thoughts on
this? I mean, obviously we have to interpret
medicine from like the patient and their clinical
standpoint, and we shouldn't be using a lot of
the diagnostic criteria, but they're supporting
evidence in certain situations. But what do you
feel about that? So let me start with most of
the biomarker, diagnostic biomarker work in sepsis
has unfortunately been done in the critically
ill and not where 80 % of the septic patients
present the emergency department. Probably the
last time I wrote a little study on this was
about only about 11 studies may have seen the
headlines in the Globe and Mail this week that
our colleagues and some of our colleagues in
the network in Toronto have think they've got
this panel of genomic markers that may may have
and that they're working on this lovely device
that so there are some signals from genomics,
but I think we need to. quarterback sort of pull
all of this together. So if I talk about procalcitonin,
the evidence for procalcitonin is probably strongest
in the patient population you look after, which
is the neonates. And there's at least one really
good study that shows that tells me whether I
really can continue the antibiotics or I can
stop the antibiotics. Similarly, in the adult
population, it tells me I can stop antibiotics
because it's less likely to be a bacterial infection.
Unfortunately, people haven't changed this in
their practice to actually do that when you go
back and look at you know has that been translated
it's not so great in the diagnostic end because
it has some bacterias don't cause an elevated
procalcitonin it's lousy for viruses and for
fungal infections Similarly, CRP, well, CRP is
just running the rounds of who's going to use
it, the latest biomarker. The cardiologists were
using it for a while. Now we're using it, but
it's an acute phase reactant. So it goes up,
like fibrinogen goes up and albumin goes down.
So it really just tells you you've got an acute
inflammatory reaction that's been turned on.
And so people are looking at pancreatic stone
protein and other markers in the inflammatory
cascade. And we've been doing some work because
we understand that coagulation is intimately
linked to this inflammatory response from the
very earliest stages. So we've actually been
looking at some coagulation markers that may.
be equally important. And surprisingly, it's
not their going up that's important. It's their
going down that's important. Yeah, that's fair.
And so I guess economically, so I know some centers
don't have procalcitonin because it's a little
bit more expensive, as I find in kind of talking
to microbiologists and other lab techs. And so
how does that kind of I guess, impact which biomarkers
are in which. I think many centers are now using
CRP because it had been used by the cardiologist.
So it's a good rough screen that just says, you
know what, this person's got an ongoing inflammatory
reaction and we've got organ dysfunction. And
maybe we've got to go looking for other markers
of coagulation or other things that may be disrupted
that says there's an ongoing. immunothrombotic,
there's a new word for people perhaps, where
the immune system and the clotting system have
been over activated as part of the response to
infection. Got it. Yeah. And so it's a good thing
you mentioned. It's more of a spot test, I would
say, instead of some people are using procalcitonin
and trending it. And I always find that very
difficult to explain because it really isn't
a trend. Like, I don't think that we have good
information in terms of its clearance from the
body. And there haven't been a lot of studies
that look at it mostly as a spot check. Right.
In terms of its diagnosis. Okay, fantastic. Yeah.
And so going back to obviously our sepsis and
the disease that we're talking about today. So
I mean, the important things, and I think you
have seen this in your clinical world a lot,
is the acute complications that you can get from
this type of disease and why we're talking about
it and why it's so important to identify. So
do you have any shared experiences that you want
to share today with our audience in terms of
some of the both either acute or long -term consequences
just to kind of weigh some light or shine some
light on this disease? Well, let's talk the acute.
The most common cause of sepsis in North America,
at least, is pneumonia. It's still the most common
cause. In many parts of the world, sub -Saharan
Africa, for example, it's diarrheal disease.
But in North America, it's pneumonia. We still
see urinary tract infections leading to sepsis
in the elderly. bad intra -abdominal infections,
whether it's your gallbladder or your appendix
can lead to that, and skin infections, right?
So skin infections, diabetics from some work
that we've done are not necessarily at increased
risk, short -term risk for getting sepsis, but
there's long -term complications of diabetics
having sepsis. Yeah, and so definitely I think
the acute deterioration and the multi -organ
dysfunction are some of the challenges that you
guys probably see. Oh, like supporting organs.
So, you know, certainly the organ support that
we do. ventilators so people on ventilators long
times on like months on ventilators you know
i've got young patients young people who've ended
up with legionella and then that's a bad one
because the liver fails the kidney fails and
we've seen a rise in legionella in the last little
while you know i'm not sure people are cleaning
out their ventilation systems And then the other
one that we're seeing is a lot of rise in Staph
aureus. And this is the worst year I've ever
seen for group A strep. So skin -based inspections,
like it's just a bad season. And I get all the
notifications for the contact tracing in the
hospital and yet another group A strep contact
tracing. Yeah. We've seen an uptick of that too.
I don't even, I can't recall in my sort of 25
years as an attending in the ICU that I've had
four. And this year I had four patients with
group A strep, two of them very sick and two
of them just with wounds that, you know, whether
we caught it early or otherwise. And I guess
one of the things with, you know, like obviously
many diseases you want to pick up early with
sepsis, I think the, we always talk about, you
know, starting treatment very early in this condition,
right? Or in this disease. And so, and so it
has that. Any of the, you know, obviously there's
the early warning signs, some of the vital signs
of the critically ill, and you're thinking about
sepsis. You know, we all talk about that golden
hour, the original, where we want to start soon.
So in your world, is that something over the
years, has that, have you seen less complications
since those guidelines have come out? Or is that
something you guys are working with to see if,
you know, is that one hour mark ideal? So certainly
surviving sepsis campaign says if you're in shock
and you have an obvious source of infection,
that golden hour, less than an hour is really
important. If you have a suspicion of sepsis,
that golden hour is important. And you know where
the source of infection. If you're not so sure,
then you've got a little time to wait, do some
cultures, wait for some things to come back from
the lab. You know, we've shifted from. relying
on lab work immediately waiting for that cbc
to come back for example as like this is obviously
they've got a source of infection and they're
obviously got organ dysfunction or they're not
perfusing jump on it have i seen less i Don't
think we have enough data in Canada, particularly
unlike Australia and other places, to say we've
moved the bar from if you end up in an ICU with
sepsis, your mortality rate is still around 20
to 25 percent. If you're older, it's going to
be higher. If you're immunosuppressed, it's going
to be higher. And the complications therein afterwards
as well. Yeah. And I would assume that the earlier
you start, the earlier you pick up the disease.
It's always like the earlier you pick it up,
the more likely we are to reverse the organ dysfunction
and be able to get people shorter stays through
the hospital. And so then that leads me to the
next point, because we actually, I first heard
about, you know, more the work that you guys
have been doing with Sepsis Canada at an AMR,
antimicrobial resistance symposium that was back
in November in Toronto. And, you know, it was
really interesting to see because there's this,
you know, choosing wisely, making sure that we
are using, you know, antibiotics appropriately,
because we do have that. concern with the growing
concerns of antimicrobial resistance as well.
So for our audience who, you know, is kind of
thinking, you know, we're saying basically you
need to treat if there is sepsis and there's
an infection. How do you balance that with the
growing concerns of AMR? So let's start with
what we know between the AMR and sepsis burden.
Some great data that's come out of John Hopkins
and the antimicrobial resistance collaborators.
So if we estimate that there are currently about
13 million deaths due to sepsis globally, and
about almost 9 million of those are due to bacterial
infections, then 5 million of those are due to
resistant organisms. OK, and associated or attributable,
you know, is one point. So it's a huge problem.
And if we know that within the next five years
or more, the amount of AMR is going to continue
to rise, particularly in countries in the world
who have not had the tight regulation that we
have had over many of our antibiotics. I talked
to colleagues in India. colleagues in Saudi Arabia,
where it's a huge problem, where their first
line antibiotics are meropenem, and they still
have resistance to it. I know. It's terrifying.
So I think, you know, are we in good shape? Because
we've controlled to a certain extent, some of
the misuse of antibiotics, right? Do we have
good antimicrobial stewardship programs in our
hospitals, at least our academic centers? We
do. It helps to say, OK, are we getting evidence
like the balance trial that says if you've got
a gram negative bacteremia, you don't need 14
days, seven days is adequate. So we're not persisting.
And some really interesting work coming about
being careful about what antibiotics you're using.
for the most sick because you may be adding to
the problem. Some fantastic work coming out of
Michigan where a natural experiment where they
lost Peptazole. They didn't have it for a period
of time. And they were only using gram -negative
coverage. And in fact, they had better outcomes,
statistically significant better outcomes during
that period. And so they're now going and looking
at this. But, you know, sometimes you don't kill
the anaerobes. And I would say pneumonia is probably
our biggest gap. Like don't kill the anaerobes
there. And certain skin infections don't kill
the anaerobes, right? They may in fact be beneficial.
Yeah. Yeah. And so definitely, I think. Like
you mentioned, an important thing is knowing
kind of your local system and having, you know,
the pharmacists involved. I think like what we've
done locally, even if you don't have an established
stewardship program, is working with the local
pharmacist to create stop dates and that type
of thing, which even if you are, you know, worried
about sepsis and you're going to start antibiotics
and kind of reminding ourselves that we can follow
cultures, you can follow the patient. clinically
and getting them off as soon as possible and
remember sepsis is the body's response to that
infection it doesn't mean the infection's continuing
the organ dysfunction may be continuing you've
killed the antibiotics with the appropriate things
you just don't want to add to the antimicrobial
resistance problem yeah so it's a really like
a fine balance um and and why like there's multidisciplinary
teams that are involved yeah in these cases yeah
Perfect. So moving forward. So you mentioned
some of the research that you guys are doing.
So what is the future in sepsis research? What
does it look like? Are we going to get more information
on some of these biomarkers or novel biomarkers
or just overall defining sepsis in general? So
we've done some really great work in the network
over the past six years. I think we're still
working on getting that. prevalence across the
country. That's hard data. We're relying on two
things. First of all, we're relying on discharge
abstract data, which means people have to write
that on the chart. If somebody's septic, write
it on the chart, please. And so we're starting
to pull that. We've got this conflict between
the modern research definitions, SEP3, organ
dysfunction, and what we currently use for discharge
abstracting, which is ICD -10 codes. We're not
at ICD -10. ICD -11, which gives a little better
definition. And everybody's had a version of
how many codes do you put in? We've published
some work looking at probably what is a broader
definition for sepsis, and we're applying that
to some CHI -HI data along with some traditional
ones. So look for that coming. The other thing
we've done is look at both the costs and the
outcomes of sepsis. The cost is staggering. Even
before the pandemic in a province of Ontario,
sepsis cost the province approximately a billion
dollars a year in Ontario. And that was only
the adults. It wasn't the kitties. It wasn't
the long -term outcomes. And that mortality after
sepsis was 50 % in the next five years. So you
had 20 % not survive if you're in ICU, another
50%. And the why of that we're starting to understand.
Part of that why is cardiovascular disease. ongoing
thrombosis, strokes, heart attacks. I said that,
you know, diabetics are at particular risk. So
if you're not a diabetic, that risk in the next
five years is about 10 % for cardiovascular disease
after an episode of sepsis. If you're diabetic,
that goes up to 40%. So the combination of the
endothelial damage that occurs with diabetes
gets exacerbated with sepsis and makes your risk
for cardiovascular disease even higher. The other
thing we've learned is that those survivors of
sepsis become the highest cost users, at least
in the province of Ontario, based on ICS data
for the next 90 days, like the top 1%, even after
hospital discharge, they cost the healthcare
system a lot of money. So I think the next big
field is. understanding why that mortality beyond
cardiovascular disease, what treatments can we
apply? And what impact can we have? So in fact,
we're working right now as text going on, I can
hear them background on my phone, because we're
working on a meeting grant to start talking about
a registry for sepsis survivors, we don't have
any way of tracking those survivors afterwards.
And many of them have significant cognitive impairment,
organs that are barely functioning. I shared
a story recently in the media about a young girl
who is a quad amputee. And we have a number of
amputees who work in the network who have had
such bad septic shock that, and with the supports
that we have to provide, that they've lost limbs.
And that's a big complication. Yeah. We're learning
a lot about who's being taught about sepsis as
healthcare professionals. Right. And how we might
teach even school children. One of my honors
thesis students just completed a little pilot
study with a bunch of high school students and
their teachers about sepsis and what they could
learn. So educating the public is really important.
Figuring out what the barriers are in the emergency
department. We have all of these lovely, we have
stroke protocols and we have trauma teams. And
the evidence for team sepsis or code sepsis teams
not as strong. Literature suggesting maybe if
we just improve the performance in the hospitals,
we don't need to go to specialized units like
we do for strokes and trauma, but that's an involving
literature. And then finally, what tools do we
have to treat this? Vic2 is not doing well. We
have a serious problem that 30 plus years of
really not having any novel therapeutics aside
from antibiotics, fluid and supportive care.
So looking for novel therapeutics, we've got
trials running based out of Winnipeg where plasma
exchange might be. And I know there's people
thinking, oh, this is the latest greatest, but
we need to study it and find out if it actually
is going to work. I've got colleagues in Ottawa
who are starting a stem cell therapy for septic
shock patients. Colleague today just registered
another support. What other? ways can we support
for blood pressure? You know, there's a double
edged sword for supporting with the medications
we use to support blood pressure. Can we use
other adjuncts to support blood pressure in the
ICU? So those are some of the clinical trials
going on. And then we're really doing some innovative
work to try and understand the pathophysiology
better as well with preclinical work. So a lot
of work that's, you know, even in years and years,
like this is not a disease. But it's just, I
guess, like not very well understood and parts
we know of it. But again, like you mentioned,
it's a clinical spectrum, right? So not everybody
presents the same way. And I think that's probably
the challenging part here. And look at, you know,
if you compare us to the oncology field and how
long it took to get. precision treatments and
more understanding of each individual kind of
cancer and what treatments you could or could
not use. I think we're behind with sepsis as
a disease. Will we get there eventually? I hope
so, in a coordinated effort, but it's a similar
problem, but just a shorter time frame, right?
We've got minutes to hours as opposed to something
that's a little more slowly. to evolve. Yeah,
that's fantastic. You're doing some really good
work out there and a lot of your colleagues.
And so it's obviously something that we deal
with all the time in infectious diseases. We're
working very closely with those that are in sepsis
and septic shock. So yeah, it would be really
interesting to see some of the findings of those
research projects. So I guess just to end off
today, because that was a wealth of information
for myself as well, but also for I'm sure our
listeners that are really fortunate to have tuned
into today's episode. So what's one key message,
I guess, that, I mean, there's multiple messages
you probably want to send out, but one key message,
if you want our listeners today to take away
from this episode. I think similar to the thing
we're asking our patients to do, we're asking
health professionals just to think about this.
Educate. We know there's gaps in health professional
education related to sepsis. It's not being taught
in programs. It's not being taught in a lot of
subspecialty programs. Could it be sepsis? Just
ask yourself that question. Could it be sepsis,
this unwell patient? And that includes, oh, it's
just flu, but could it be flu -associated sepsis
where secondary infections can occur and where
the mortality rate is so high? It's higher than
myocardial infarctions in this country, right?
Higher than the top three cancers combined, right?
So definitely something that we should be aware
of. And for those, you know, the family docs
who see on one end, but particularly after end,
like think about the complications that if somebody
says, oh, I came to the hospital, I was in the
ICU with my infection, that means they had sepsis.
And that means they may need psychological support,
extra rehab, other things that we have not. considered.
You know, we're building this syndrome called
post -sepsis syndrome, and it's clear that there
are things that these patients have. So on the
front end, could it be sepsis? On the back end,
what are the complications if you've survived
a hospital stay -in or an ICU, say, with a bad
infection? Yeah, well, that's really important
and really key information. Thank you so much.
And we really appreciate you coming again on
the podcast, supporting the podcast and talking
about a very, very important topic today. And
yeah, thank you for taking the time to do that.
You're very welcome. It's a pleasure. Thank you,
Dr. Fox Robichaud for joining us. For links to
more information, educational material and to
Sepsis Canada, please see the episode description.
Have a topic suggestion? Or would you like to
talk about your infectious diseases research?
Email us at thecanadianbreakpoint at gmail .com
or X us, is that a thing, at cabreakpoint. See
you again soon at the Canadian Breakpoint.