So what happens in the last decades about transfusion medicine and critical care units.
First of all, I have nothing to disclose with respect to conflict of interest. So we'll
talk about red cell transfusion. I will not talk about the plasma and platelets. We don't
have the time. And most of my talk will be about safety issues, limiting red cell transfusions,
and a few words about length of storage of red cells units.
What's the problem? Well, the problem is that anemia is common in critically ill children.
It is up to 74% of all patients. And there is a clear association between anemia and
mortality. But I will say that again and again. It is not because there is an association
that there is a cause/effect relationship. But there is an association. And there can
be a cause/effect relationship. Well, we find the same kind of relationship between red
cell transfusion and mortality.
So red cell transfusion is the only rapid way to restore hematocrit. But is it safe?
And is it better than just looking at the patient and not giving any transfusion? Remember
that in the 70s-- I started as a resident in pediatric in the 70s-- and when there was
anemia, you have to do something. And I was told red cell units are safe. You can give
it if you believe it can help patients. The only concerns were incompatibility, hemolysis,
and things like that. And they were quite well controlled.
In the 80s, we start to be concerned with transfusion transmitted infectious disease.
Remember that in the late 70s and in the 80s we start to have strong data showing that
transfusion can cause hepatitis and then HIV and then many other viral diseases. So we
start to be aware of all those things. And it's still a problem presently. Well these
are data from Canada two years ago. And as you can see the risk to contract HIV, hepatitis,
and even a bacterial infection is very low.
Presently, the red cells unit are safer than ever. And they are safer in Canada and countries
like that. Remember that, for example in African countries, they just don't test for virus.
They can't. So it's safe in some countries. It's not the case elsewhere. And there will
always be some concerns for those who provide blood products because of emerging disease.
Like babesiosis or Chagas disease, Dengue, et cetera. There will be a new virus that
will come out like maybe Ebola presently.
Nevertheless, in the last two decades, we shift our attention in transfusion mid-scene
to what we name NISHOT. NISHOT means noninfectious serious hazards of transfusion. If you want
to get a definition of all the NISHOT there, go to the site of the Hemovigilance system
in UK. It's a great site. NISHOT is for serious as art of transfusion, it's easy to remember.
And you will see on that site that there are many concerns, but the MODS is one transfusion
related acute lung injury transfusion associated, circulatory overload, all those things are
more and more frequently reported and recognized as a complication of red cell transfusion.
Is it a problem in critically ill children? Probably more than any other kids because
almost all our patients present a system inflammatory response syndrome, if not MODS. And if you
shoot something like red cells units that contains all the time some inflammatory mediators
and many other stuff that we don't like so much, you just increase the risk that this
becomes a second hit and that you cause a MODS or that you worsen MODS.
So to give you an example, in my own unit we put attention in the last two years on
what we name the transfusion associated respiratory complications. Why? Because we believe that
these are under-diagnosed and under-reported. And this is the case because presently the
definition of transfusion associated respiratory complication, those definitions are appropriate
for patients who are asymptomatic. But in those definitions, it's written that the patient
should be asymptomatic before they start a transfusion. So it eliminates all our patients
because most of our patients that receive a transfusion already have respiratory symptoms.
So we just look at what we name progressive respiratory dysfunction.
The question was, can we see some worsening of respiratory function after a transfusion?
And well, we observed such deterioration of the respiratory function in 52% of transfused
patients in that small preliminary studies. Most of them present what we name respiratory
dysfunction-- progressive respiratory dysfunction-- because we observe a 20% deterioration in
blood gas and things like that. We observed also a few what has been named delayed TRALI,
transfusion early to the acute lung injury that happened more than six hours after a
transfusion. Is this a problem? I show that slide just because I believe it questions
people. It must question you. And there is room for research there. But I believe that
we are missing something with respect to the impact of the red cell transfusion on the
respiratory function of our patient.
In the 90s, then, we shift our attention from, as I told you, infectious disease to another
question. Is it safe to give less red cell transfusion? Because if there is an association,
the first reaction will be, can we give less red cell transfusion. Some of you are aware
of the TRIPICU study. That study, I just want to raise the point, and remember people that
the first question was not about threshold hemoglobin. The first question was, is this
patient stable? And the definition of stable was exactly what is written there. The mean
arterial pressure is not less than 2 standard deviations below normal mean for age. And
there was no increase in the cardiovascular support in that patient in the last two hours.
If the patient was stable as defined, then they were eligible for TRIPICU. And then we
look at the hemoglobin level.
And in that study there were two thresholds as you know that. And patients were allocated
to restricted groups. These are the results, show no difference at all. What is funny also
is when we look at the outcome in all cell groups. And it's on purpose, you can see there
was many planned subgroup analyses and unplanned. In all subgroups we get the same results.
There was great consistency of results. And this is not so common in RCTs. So the lesson
there is that the results of TRIPICU are applicable to all those patients.
Now presently, what's the main concern? Well their main concern is about age of lung. I
have just a few slides left. I want to remember that the determination of the upper limit
of red cell shelf life, which is 42 days in Canada, was not determined by scientific means
or something like that. It was determined on criteria that can be questioned quite a lot.
Two studies have been done on that. The ARIPI study has been done in neonatology, we'll
not go through those slides. But Dean Fergusson completed a nice study showing that giving
fresher blood to prematures rather than older blood does not really make a difference. And
I want to raise the point that presently there are six ongoing RCTs on length of storage,
five in adults. The ABLE study, their first results will be presented this afternoon.
And the ABC-PICU study that is run by Marisa Tucci, Phil Spinella and myself.
And adults there is one study that has been, not published, but presented at the AABB.
And they found no difference in patients who received fresher blood. These were adult cardiac
patients. And they find absolutely no difference in what was the primary outcomes to measure
of that study which was MODS score. So no difference.
In conclusion, there are severe anemias is common in our patients. The red blood cell
transfusions are also associated with mortality. There is evidence that too many red cell transfusions
are still given to critically ill children. What determinant should drive us to prescribe
red cell transfusion to particular children is still unclear presently. But remember,
hemoglobin concentration is always in the picture. More attention must be put on NISHOT.
And we don't know presently if fresh blood is better than old blood. So what's the future?
The future is about probably not only age of blood, but also cost benefit studies, knowledge
application, and things like that.
Thank you for your attention. You have a list of other research projects that can be done
in the field. Thank you.