So it depends on when you get someone with sepsis, at what stage, what expression you
are going to get.
And this is what we usually grapple with.
So I won't go through this entire thing, but what the point I'd like to make is that when
we have a child with sepsis, we do not want to get them at this end of the spectrum with
multi-organ failure, where it's very obvious.
We would like to be upstream here, where there's a local infection or signs and symptoms that
are quite subtle, because in many cases in the world, there are no ICUs with a lot of
resources, and all that is available is simple treatments-- some oxygen, antibiotics, some
fluid, maybe some minimal respiratory support.
The other issue with children is that-- this is a study from Kenya that shows that most
of the death from those children who are bacteremic, they come very early within the first day,
almost 75%.
So therefore, if you are going to make a difference in their lives, you've got to make the diagnosis
again, as I said, very early, and go upstream.
The problem is that many other children arrive later on, when it's obvious and when treatment
does not make much of a difference.
And the setting that-- the context in which many of these children present are large crowded
waiting areas.
They compete with others for care.
There's a lot of young kids, as you can see.
And the point is that again, that in those situation, we have to be able to pick up the
children with sepsis very early.
In many cases, what we fail is we fail with having good triage mechanisms to identify
those who are ill in need.
And then there are vulnerable populations.
The children who present unimmunized with meningitis, malnutrition, postoperative patients.
The issue of zoonosis, animals being in close proximity to these children, also put them
at risk.
So in areas in which there are no diagnostic tests and no sophisticated laboratory-- as
we heard, many of the diagnostic tests do not really help us very early on-- one of
the ways of grappling with management of children sepsis is the syndromic management.
And this is again work from Kenya, where what they were trying to do is identify children
who were critically ill, in need of early antibiotic therapy.
And they were using observable criteria, things they can observe, with minimal or no laboratory
tests.
And what they did is a study of looking at about almost 12,000 children They were able
to identify about 6,000 children who, in their estimation, fit the criteria, a case finding
for syndromic sepsis.
And what they found from that group is that 12% died, with a sensitivity to predict death
was 93%.
The rest, only 1% died, so the negative predictive value was 99%.
So the usefulness of this can be used in a resource-limited environment.
But it identified not only those children who were septic, but most of the children
who were critically ill in those areas.
And indeed, in many of those areas, most of the children who are critically ill have some
form of infection.
So syndromic sepsis is one way that it has been used to diagnose.
In North America, this is a Society of Critical Care Medicine guideline that we've just updated
recently again.
We spoke about recognizing decreased mental status and perfusion as the underlying marker
of someone who is in severe sepsis.
But I think this gives us the idea of only when we go downstream, and with very severe
sepsis, again, I think we have to go upstream.
The issue we face, I think, as I said, the first line, what is sepsis?
We said it's a time-sensitive issue and depends on signs and symptoms of different areas.
What we have is myocardial depression.
We have endothelial dysfunction, and thrombosis, and bleeding.
And the relative contributions of each one of these in early sepsis varies.
The ultimate final sort of common pathway is failure of organ perfusion.
But if we look at the contributors to this pattern, we have dengue, cholera, gastroenteritis,
malaria, bacterial sepsis, mixed infections, superimposed on anemia and malnutrition, they
all play into this triumvirate.
And if we look at, say, malaria, one can see that anemia may be a major contributor.
There's some endothelial dysfunction, and capillary leak, and mitochondrial dysfunction,
and acidosis.
And hence, the recognition and treatment is slightly different from this sort of situation,
where this is dengue fever, where capillary leak, endothelial leak, and hypovolemia is
a major contributor.
Myocardial depression is less.
So, how do we diagnose sepsis?
And in this talk, I'm just going to concentrate on the SIRS criteria, physical examination,
and lactate level, because I'm saying that in most instances where we are asked these
questions, it's limited resources.
So we look at the SIRS criteria in diagnosing sepsis.
We know what the SIRS criteria is.
In children, it is slightly modified, where we have at least two of the following, and
we say one of which must be abnormal temperature or leukocyte count.
The fact is that in many parts of the world now-- and we are doing some studies in Uganda
that's showing that if you choose temperature, and heart rate, and respiratory rate only,
tachycardia and tachypnea, without a leukocyte count, this sensitivity does not really change.
What's needed is the specificity.
And in areas in which leuokocyte count is difficult to get, it is problematic.
You heard from Conrad that even leukocyte count may not help.
And we found some similar data in children, which I'll come to.
So we look at SIRS in neonates.
And there's this recent study looking at 13 neonates with early onset sepsis.
Only 53% fully fulfills this criteria.
So again, it's not very useful.
And in resource-limited settings, as I said, no laboratory tests, complex organ dysfunction,
and core temperature measurement precludes the use of SIRS to help us identify or point
towards sepsis.
And this is a point prevalence study of SIRS in hospitalized children.
In this study, the issue with this, with SIRS criteria-- this is from Latvia-- there are
two time periods that looked at children with-- 943 children came into the hospital.
Children with fever were 92, with SIRS, 66, and very few came out with having sepsis.
What it showed me, and the issue that we're grappling with my own institution and several
institution across North America, is the fact that the SIRS criteria screens a large body
of children.
In the emergency department, we may screen thousands of children with very little yield.
And to some extent, the staff gets very sort of complacent after a period of time, so SIRS
may not help us.
This is a study we just completed in China.
11 regional hospitals serving over 800,000 children.
And we looked at 1,606 who had SIRS criteria, sepsis or severe sepsis.
The worrisome thing is that there is a group of patients-- we had 79 with no SIRS, but
they end up with having severe sepsis and died.
So without international guidelines or the international SIRS criteria, it's troublesome.
And I'm glad-- well, I'm glad I was-- it was good to hear today that it's troublesome even
in adults.
You heard about Rory Staunton.
I won't tell you much more.
Conrad mentioned it already.
But this is part of the issue, the troublesome issue, because they did a sepsis screening
on Rory.
But the adult criteria we use-- and even with this adult criteria, where the respiratory
rate greater than 20 and heart rate greater than 90, those are most kids.
So in this hospital, if they were using this to screen kits, it would be quite useless.
But at the end of the day, they missed-- his white count was high.
His segs was high.
And they missed the diagnosis.
And I think part of the problem is that we know what screening should be.
But again, people get complacent with it.
But physical exam.
We talk about capillary refill and several issues with capillary refill.
How to do it properly is an issue that even in pediatrics, many people don't.
So it's not surprising when you look at-- even shock, when a child comes in a shock
that is very obvious.
This is 100 consecutive children in a ward in Kenya-- trained in clinical recognition
of signs.
But you can see the [INAUDIBLE] variability, moderate variability, temperature gradient.
They found it reasonable.
But capillary refill, weak pulse, et cetera, you can see it's not very-- gives you great
comfort that the trainees and everyone will recognize those signs.
Lactate levels, I won't say much.
This is a recent study, again, emergency department, looking at lactate levels and inclusion criteria
in those with SIRS.
And a lactate level of greater than 4 was able to predict those who are going to get
organ dysfunction and those sort of things, those who are going to have a positive blood
culture, those who are going to get ICU admission.
But again, the overwhelming evidence is that it is not very helpful in early sepsis, and
neither is it available in many parts of the world that these children are.
So let us look at a few of the different ways that's used to recognize sepsis.
And this is the UK that said, pediatric sepsis six, what needs to be done.
It says look at a core temperature, high or low temperature, tachycardia, altered mental
status, or reduced peripheral perfusion.
That is their signs and systems for recognition.
This is one from Texas.
And again, you can see there are some high-risk patients with oncological emergencies, asplenia,
et cetera.
But beyond that, it's very similar criteria.
Looking at abnormal pulse, respiratory rate, and heart rate, and following these patients.
This, again, is one from Utah.
Again, heart rate, respiratory rate, pulses, central capillary refill.
And another one from Boston Children's, "Recognize altered mental status and poor perfusion."
Doesn't really help us much.
And as Conrad said, there is nothing specific that you can lay your eyes on, as he pointed
out on cardiovascular disease, such as myocardial infarction.
We have problems with signs.
Medecins Sans Frontieres, they looked at capillary refill again, fast pulse, cold peripheries.
And this is a project that we are doing in Bangladesh.
Again, you can see not feeling well, feel feverish, poor feeding, feeble cry, drowsy,
et cetera for children and newborns with sepsis.
So we have suspicion in the community.
And we have a case finding form, which, again, incorporates hypothermia, hypothermia convulsions,
et cetera.
With the neonates, we put hyperthermia as one of the signs in the older children, because
so many children are there with fever, we thought that would overwhelm the medical system.
So it's not really a very-- what would I say?
It's not a very ideal sort of situation.
But the fact is that under the circumstances in which these children present is the best
that we can do.
Now, ultimately, I think that you've been hearing some of the other exciting new developments.
I think ultimately, integration of clinical and laboratory data, metabolomic, genomic,
and proteomic has some sort of, I would say, potential, and I think would be of great benefit
in the future.
But at the end of the day, as we heard, it's the clinical signs and symptoms that I've
just mentioned.
So that's it.
I'd like to thank you very much for your time.