What if my job is to give kids poison?

When I’m trying to explain to kids and families my job, I have a standard set of lines. Like,

“I’m the sleepy doctor and I look after the being comfy and being safe part of the operation” or,

“The surgeon is going to look after that little bit of you, I’ll be looking after the rest of you”.

And yet, for most of my (relatively short) kids’ anaesthetics career, there’s been a lingering question – what if when I’m doing the  helping, I’m actually providing kids with a very particular kind of poison?

Not that sort - then I'd have to be reported. [via hairbangersradio.ning.com]

Not that sort – then I’d have to be reported. [via hairbangersradio.ning.com]

Anaesthesia and Delicate Kids

It is quite hard to fathom now, but it’s relatively recently that general anaesthesia has been offered routinely to really small kids having surgery. In fact, you don’t even have to look that far back to find review articles trying to persuade the medical community that newborns actually do feel pain.

But these days we provide general anaesthesia for the sort of procedures previously thought off limits by anaesthetists. A win all round, right? Well, of course. However, over the last decade there has been an increasing interest in exploring the potential extra effects of those anaesthetics. The ones beyond the implantation of gnarly dream states with flying pink marmosets into tiny minds.

What has emerged is the possibility that the same anaesthetic agents that give the kind of controlled sleep parents could only dream of at home may cause damage to neurones in the rapidly developing nervous system. The sort of rapidly developing nervous system that you might find, say, in a newborn suddenly assailed with all the stimuli of a big new world, with the additional need to start getting on with surviving. You can see why that would not be thrilling news for a paediatric anaesthetist.

The Animals Speak … Confusingly

Unsurprisingly, this information comes from animal research. Studies have shown that exposure of rodents to common anaesthetic agents during the period where their little synapses are being created at neck-snapping speed seems to result in the process of programmed cell death, called apoptosis, being kicked into action. In rodent, and now primate models, this apoptosis is widespread and is also associated with less growth of nerve cells.

This isn’t enough to leap in and change everything we do. There are still uncertainties with all of this. The first big area of the debate is whether the animal models even match the newborn human brain and spinal cord. Rodent studies are classically done at about day 7 of furry critter life. While there’s some who would say that’s perfect as kids’ brains are rapidly developing to the age of 2, there are others loudly proclaiming that this correlates with the young human at about 24 weeks along during the pregnancy. That would be an extremely premature delivery.

Then there’s the anaesthetic. The animals are often given an anaesthetic for up to a day. A day of life in a rodent whose period of synaptogenesis over a week or so correlates with 3 months of a pregnancy equates to a very, very long anaesthetic. Sometimes in the animal research, the anaesthetic dose given would be enough for you and your next 10 neighbours. What we need is someone to look at what happens in actual people.

Trying to Bring it Back to Real People

Enter the Danes. Research recently released by a group in Denmark (I’ve provided the paper at the end) provides a little reassurance for any parents trying to stake a claim at a selective pre-school. They’ve followed up kids who had a general anaesthetic for a relatively small operation that gets done in kids under the age of 3 months. It’s an operation called a pyloromyotomy, and it’s what you do when a young whippersnapper turns up vomiting because the exit of their stomach has an overgrown bit that needs some surgical relief. It’s less than an hour through theatres, and involves minimal discomfort afterwards.

Pyloric stenosis in picture form. Someone should do an operation or something. [via www.pedsurg.ucsf.edu]

Pyloric stenosis in picture form. Someone should do an operation or something. [via http://www.pedsurg.ucsf.edu]

It turns out that the Danes have an impressive background in maintaining databases about their people, pre-dating anything the NSA got going with the aid of your local digital behemoth. The researchers tracked down every single kid born in Denmark between the years of 1986-1990 who had this operation, a total of 779 kids (whittled down to 748 with a few exclusions). They then used the database to provide a sampling of 5% of the general population, giving 13,723 kids for comparison. Then they compared standardised education scores that are obtained by pretty much all Danish kids at the age of 15-16 years.

What they found was that the average test scores were similar between the two groups. In fact, when adjusting for the potential confounders of gender, birth weight, parental age and parental education, the estimated mean in the group who had anaesthesia was 0.01 below the control group who hadn’t had the operation and anaesthetic before 3 months of age.

Phew! Well, actually there’s still more to the story. The exposed group did have a higher rate of “non-attainment” of testing scores. Non-attainment may be the result of kids having some form of special need that stops them doing the standard ninth grade curriculum. It can also just be because kids drop out and some go to schools that don’t do the testing. It is possible thought that there is a group experiencing some form of neurocognitive effects that are being missed from this follow-up.

Sleep Easy Then

Well yes, and no. There’s still enough here to say that we’re raising more questions than we’re answering. This is one of the biggest papers looking at long-term outcomes in kids. And it tries to deal with some of the confounders that plague the area. Often babies having surgery are getting that surgery precisely because they are very ill to start with, and they therefore have lots of other reasons to potentially have neurological changes later. The confounders make it really hard to be definitive about much though.

There is also a small problem with the long time frame for sampling. The kids in this study got a great anaesthetic no doubt. Up to 27 years ago. 27 years ago Michael Jordan, the guy on so many shoes, hadn’t won a basketball championship. Not only have the drugs got better, but the monitors have got better and the surgery has evolved. The constant looking back to outdated practices will continue to be a research challenge in this area. It also potentially highlights that we need to look just as carefully at how we give the anaesthetic, not just at what we give in the anaesthetic.

What we can definitely say is that more work needs to be done. This is news only to the garden gnome hiding in the old wing of the hospital and the FDA has partnered up with the International Anesthesia Research Society to support this sort of work (and provide good resources for families). The animal research definitely shows anaesthetic agents can induce changes to nerve cells. What we still need to figure out is whether this correlates with meaningful impacts on kids. What we definitely know is that anaesthesia has provided safe surgery for little kids for many years with little in the way of evidence to suggest big effects. It remains a question to be explored through. Unlike the sound of one hand clapping – that’s sorted.

So the recommendation for surgery for now is not to do surgery in kids under 2 unless they really need it. Of course, we do that anyway. The other thing we really need is more research on better ways to do the general conduct of anaesthesia.

This whole topic is a good reminder that the introduction of any excellent advance requires constant surveillance to look for potential issues. And I’d absolutely back anaesthesia as way less scarring than the soft rock from the band in the first picture.

(Here’s The Danish Paper)

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6 thoughts on “What if my job is to give kids poison?

  1. Really interesting post, Andrew.

    Mr 10 had a whopper of an anaesthetic at 8 days old for his Arterial Switch Operation. (I assume he’d have had a sedation of some sort for the balloon septostomy they did in the first 24 hours ….)

    He was part of a study done at CHW looking at developmental outcomes of neonates who underwent major heart/gut surgery. Sharon Laing was the one who asked us to be part of it so I assume you could ask her for the research?

    We filled in questionnaires about his development for the first couple of years then at about 2.5 years of age we were visited at home by a couple of child psychs who conducted an assessment of him.

    He did really well, perhaps better than expected (I’ve got his report somewhere if you want to read it), but I recall that later on Sharon mentioned that out of the survey cohort a significant number of children had not done as well and some had some major problems. Chicken or egg?

    We are lucky.

    I’d understood there was a risk of brain damage from being on heart/lung bypass?

    Anyway, you know where Pete and I are if you want to dig a little more.

    Cheers!

    • Interesting. Sounds like the DAISy Study – I have a feeling the guys found that there was indeed a proportion who had developmental delay after major surgery, but I don’t know that they were able to separate out the effects of the illness/big surgery vs anaesthesia per se. You’ve reminded me chase it up.

      Yes, for a septostomy you’re sedated at the time. Yes bypass does have a risk of brain damage associated with it (multiple causes including microbubbles being created). There’s complexity there too though – some kids with really major cardiac disease (don’t think the TGA kids) have abnormalities on brain imaging before you do anything to them.

      Interesting thing here is that the operation they chose is (relatively) minor which should minimise the confounder of the illness. I haven’t seen a clinical follow-up study which suggests big changes. Also, nothing I’m aware of yet on whether in kids who do have issues what you can do about it.

      This story will probably evolve through my whole career in a big way.

      Glad to have illustrious people enjoy it. Even more glad Mr 10 is good.

      Cheers.

  2. Yes, you can always rely on The Simpsons for the answers to life’s big questions! And is that Bon Jovi? They did a ‘Poison’ song, from memory…?
    Like the old debate over animals feeling pain, I have trouble understanding how people could deny newborns feeling pain. Would they have put that down to being weak and womanish in some way?

    • That is in fact the band known as Poison. I thought Bon Jovi might still have the reek of success on them. Alice Cooper also did a song called ‘Poison’ I think but he has way too much cred.

      As to the newborns and pain thing, it was definitely the prevailing view and not that long ago. I suspect the thinking was that newborns can’t really conceptualise it so it’s not pain. Not sure if there were any theories that fundamental pain pathways hadn’t developed.

      Gives scope to reflect on how recently our thinking on pain has evolved. On an even bigger scale, maybe it reflects how recently the concept of children as individuals has emerged?

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