Thank you very much, Sonny, and good morning everyone.
So what I've been charged with this morning is to review the management of congenital
diaphragmatic hernia over the last three decades.
And it's a particular pleasure to do this because this is an area that has been essentially
my career in the 35 years I spent in Sick Kids.
So I'm going to review three decades of management of congenital diaphragmatic hernia, and how
things have evolved and how survival has improved, but perhaps at some cost to the patients who
actually leave the intensive care unit.
So let me start with this man here.
And to many people in this room, and Peter Lawson would recognize this gentleman instantly.
This is Robert E Gross, who was the father of pediatric surgery.
A remarkable man.
For several decades he was the surgeon-in-chief in Boston Children's Hospital.
And had many firsts to his name.
He did the first ductus ligation, and the first coaptation repair.
So he had many things to his credit.
And one of the things he did was pioneer the management of congenital diaphragmatic hernia.
And he published his paper in 1946 in the American Journal of Diseases of Children,
a case series of seven repairs of congenital diaphragmatic hernia with 100% survival.
No one has ever achieved that sort of survival in the succeeding decades.
But of course, the law of natural selection worked to his advantage because these were
not postnatal diaphragmatic hernias.
These were patients who had survived for a period of time and then came to surgical attention.
It's inching that post-op care consisted of a nasogastric tube and some high flow oxygen,
and that was about it.
So he thought he had solved the problem congenital diaphragmatic hernia.
And to surgeons of his generation, it seemed an eminently surgical problem.
You had a defect in the diaphragm, usually on the left side.
The intestines were up in the left pleural space.
All you needed to do was a simple operation.
Pull the guts out, take the liver down, repair the defect, and the lung would expand.
And the baby would oxygenate perfectly, and all would be well.
But of course, as we now know several decades later, it is far from a simple surgical problem.
But certainly when I started my fellowship in Sick Kids, it was the quintessential neonatal
surgical emergency.
So the baby was born, the defect was diagnosed shortly after birth because pre-natal diagnosis
didn't exist in those days.
And the baby would be rushed to the PICU looking very blue, followed by the surgeon who was
organizing the operating room.
So the baby would go straight to be OR, repair the defect, and things would be better.
Well, they weren't.
And it became apparent to us that certainly the very severely affected diaphragmatic hernias
were extremely hypoxic when they went into the operating room, and they were even worse
when they came out.
So serendipitously what we did was we thought, well OK, if they're looking so sick and so
hypoxic before they have their repair, let's try a new innovative therapy, which in our
hands in those days was high frequency oscillation.
So when you put a baby on oscillator with diaphragmatic hernia, first of all, the CO2
comes down remarkably quickly.
The pH rises, the ductal shunting at least temporarily seems to improve, and the baby
seems to improve somewhat.
And it gave us time to think about, well perhaps we shouldn't go directly to the operating
room.
But of course, to persuade a surgeon that he didn't need to do an operation right away
was somewhat problematic.
So with Hiro Sakai, he was one of our Japanese Fellows who was with us at the time, we started
to do some measurements.
And what we did was measured compliance.
Because it was apparent to us that after the defect had been repaired, the diaphragm was
pulled down, the closure was frequently very difficult.
And the compliance probably was worse after the repair than it was before.
So you can see in this small case series, which we published in 1987, we showed that
if you looked at the compliance, chest wall compliance, pre and post, in most cases it
became worse.
And a worse compliance translates obviously into a higher CO2, and a demand to increase
ventilation.
So we managed to persuade the surgeon that this was actually not an urgent surgical situation
because we could improve the baby, at least temporarily, and persuade them that they could
do a delayed or deferred surgical repair.
So in that period, we developed this delayed surgical repair strategy.
And it became apparent to us and this is obviously not a simple surgical problem, this was a
problem maldevelopment.
And it was not only maldevelopmental of the ipsilateral, or frequently left-sided lung,
but there was maldevelopment of the pulmonary vascular bed in terms of reduced pulmonary
vascular bed, high pulmonary vascular resistance, which was responsible for the right to left
shunting.
So it's a developmental problem with no simple or urgent surgical solution.
So in the 1980s to the 1990s, we were an era of rescue therapies.
And preoperative stabilization, in our hands, it was used the use of high frequency oscillator
reventilation.
In many other centers the rescue therapy was to go to extracorporeal membrane oxygenation.
And we felt perhaps that we could manage these babies well without having to resort to ECMO.
So in order to try and prove that or disprove that, we combined with Jay Wilson, who is
a very eminent pediatric surgeon in Boston Children's, who has a lifelong interest and
experience with congenital diaphragmatic hernia and together, with Kenny Azarow-- who was
a surgical fellow with Bob Filler-- we did this comparative study of outcome between
Boston and Toronto.
And of course they were using ECMO, we were using HFO.
And their practice was somewhat different because all our babies with diaphragmatic
hernias with de novo diaphragmatic hernias, whereas in Boston they inherited some second
hand repairs that had not turned out well and be transferred in for ECMO therapy.
But when we looked retrospectively at over 200 in our institution, and almost 200 at
Boston Children's, the overall survival was pretty poor, but essentially the same.
We're talking about 55% versus 53% survival.
So our rescue therapy was HFO, their evolution of therapies was actually one from using ECMO
with conventional ventilation and preoperative stabilization to, in the last era of their
retrospective review in '91 to '94, they had got the message that they needed to change
ventilation practice.
That perhaps reducing the peak inspiratory pressure and not aiming to reverse the ductal
shunting by hyperventilation was the way to go.
And unfortunately we were-- well, I was a bit slow to pick up on this.
And because we had been using HFOV very frequently in the severely affected diaphragms, but we
were using it with a high mean airway pressure.
And the penny really dropped when we did a post mortem review of the non surviving diaphragmatic
hernias.
So in that series of 223 babies, there were 68 autopsies done with autopsy information.
And you can see this is the typical picture we saw in a nonsurviving diaphragmatic hernia.
This is the ipsilateral lung, and with it very abnormal architecture, which is what
you would expect in a severely affected baby.
But look at the destructive things that we produce with mechanical ventilation on the
contralateral lung.
So all this pink stuff here is hyaline membrane formation.
All this stuff here is neutrophil infiltration.
So this is classic ventilator-induced lung injury.
So clearly we were doing something not very smart.
And if you put it all together in the 68 infants, the incidents, and the types of pulmonary
barotrauma were very, very evident.
So we clearly had to change our practice.
And so we got the message.
At the time we were using pressure limited ventilation.
Bring the airway pressures down, stop focusing and worrying about the ductal saturation,
especially the postductal saturation, because it's rather meaningless.
Reducing the peak inspiratory pressure to less than 25 on conventional, but using HFO
in a different way than we were using it in other forms of neonatal lung disease.
In other words not going for an aggressive recruitment strategy using low mean air pressure,
HFOV.
And by low I mean something in the range of 12-14 centimeters of water.
The use of ECMO in our institution was very infrequent, but other institutions, they adopt
the philosophy no baby can die with diaphragmatic hernia without at least one ECMO run.
And we felt that when the very severely affected infants, perhaps this was not in their best
interest.
But at the time and then also there was appearing on horizon an attempt at prenatal intervention.
So the big push from 2000 onwards was try to identify the severe forms of congenital
diaphragmatic hernia because we all know there are some babies who are mildly affected, and
then there are some babies who are severely hypoxic right from the time of birth.
And there seems to be nothing you can do about it except perhaps put them on ECMO, and perhaps
that is not the right thing to do.
So we had a rich source of data on diaphragmatic hernia from the CDH Registry, which is run
by Kevin Lally in Houston.
To date now there are over 6,000 patients in this data registry.
And in terms of postnatal identifiers of severe forms of congenital diaphragmatic hernia,
it seems that the 5-minute Apgar and the birth weight consistently appear to be reliable
predictors of the severe forms.
And perhaps we should use this data more carefully in selecting babies where ECMO support may
be indicated.
In an era when we have changed our ventilation practices to what's now called gentle ventilation,
does ECMO actually improve the outcome?
An outcome, I remind you, is survival plus the attended morbidities.
So if you look at the ELSO registry data for congenital diaphragmatic hernia, overall survival
51%.
Pretty poor when you compare that with meconium aspiration, which is over 95% survival.
And the long term morbidity absolutely is there.
And it depends how carefully you want to look for it, but certainly neurological deficits,
chronic lung disease, gastro-esophageal reflux, and musculo-skeletal abnormalities.
These severely affected forms of CDH babies with ECMO therapy, there is a significant
and perhaps not widely recognized morbidity.
This is data from the UK.
Laura Shekerdemian put this together.
And this is a all ECMO babies in the UK, where ECMO therapy was used.
It was total of 73.
And this is only a relatively limited follow up.
So we're only following these babies up to about a year of age.
But you can seen in the 73 babies that went on ECMO, first of all, the survival was pretty
poor.
And the number of alive is about down to about 50%.
But then when you follow these out, neurodevelopmental abnormalities, and musculo-skeletal, and other
abnormalities.
So how do we make progress and improve morbidity?
Well, when I wrote this paper several years ago, I advanced the thesis that CDH was a
cardio respiratory disease.
And we do need to look at things like pulmonary vasodilator therapy.
But we also need to use echo to assess the effect of pulmonary vasodilator therapy on
right ventricular function, and find out the stages of the ductus, and perhaps use prostaglandins
to maintain ductal patency.
And finally that the current intervention that's being studied is a prenatal intervention
where you can try to predict the severely affected babies before birth, and use the
ratio of lung to head ratio to predict severely affected infants.
And Jan Deprest-- who's a fetal medicine specialist from Belgium-- has pioneered this.
It's a very clever technique to actually occlude the trachea and allow the lung to expand,
and uses the LHR to identify severely affected babies, and claims an overall survival of
50%.
And this is how they do it with pre-natal ultrasound.
So finally, where are we now?
I think we're in an era of pre-natal diagnosis.
Most of these are diagnosed pre-natally now.
We use Apgar scores to identify high risk patients, keep the airway pressures down,
where conventional ventilation the use of HFOV with low amino air pressures target the
preductal saturation and don't use hyperventilation.
Delayed surgery, use of cardiac echo to assess the PA pressure and status of the ductus.
ECMO for selected patients.
Unexpected increase in morbidity and length of stay.
And finally the future.
Will we be able to improve that survival to over 80%?
I'm not sure, but I think the postnatal interventions are not going to get us there.
And I think perhaps the most likely intervention will be a pre-natal therapy intervention.
So thank you very much for your attention.