One of the challenges with critical care in kids is we’re often left trying to choose the best course using evidence not quite purpose built for EBM. There’s any number of examples of this but Andrew Weatherall, who combines a bit of prehospital medicine with paeds anaesthesia, takes the example of TXA, particularly in the setting of trauma to explore this a little more.
I don’t do DIY. This is partly because in the same way I wouldn’t expect a carpenter to have a crack at fixing their kids’ bones in preference to seeing an orthopod, I think it makes sense to use professionals.
It’s also because I’m just not that great at it. Anything I did make would end up looking like something trying to squeeze itself into the shape of the thing it is sort of supposed to be. And I’m fond enough of my family to want to protect them from the risks of my own handiwork.
Anyway, I do paediatric anaesthesia. I get to spend more than enough time trying to make things that aren’t quite right for the situation fit in with what I need. Why DIY at home when you have to DIY at work?
Making Things Fit
The problem with paeds practice is that kids are sometimes kids and sometimes little adults and often forgotten in research. Or if not forgotten put in the category of “the ethics and logistics of that will be so painful I’d rather remove my spleen via my auditory canal”. And in trauma care we’re also dealing with total numbers that are lower than is the case for adults.
So what we end up with is lots of extrapolation from adult data and lots of retrospective studies sprinkled with the occasional fairy dust of a small case series. Then we have to try and mash those leftovers together to come up with a plan for a very specific situation.
An example: how about tranexamic acid in trauma?
Making It Up
Following on from CRASH-2 and MATTERs, what to do in the younger generation is an obvious question. A big prospective study in kids after trauma would be perfect. And a pipe dream.
So if you turn to the literature what you see is a large number of people trying out archery on summer camp and hitting many, many different targets while all shooting vaguely in the same area.
To corral some of them in one spot, take the review by Faraoni and Goobie looking at antifibrinolytics in non-cardiac surgery in kids. All of the following values are listed as loading doses in the scoliosis and craniofacial groups: 10, 15, 20, 50, 100 and 1000 mg/kg with infusions anywhere from 1 mg/kg/hr up to 100 mg/kg/hr. In the scoliosis patients there are total numbers of up to 80 patients and slightly baffling figures suggesting total blood loss is decreased but transfusion requirement pretty much the same. Or that in the craniofacial surgery group it seems like probably there might be slightly less blood loss and transfusion needs.
But in paediatric cardiac surgery there might be more seizures too, even though the overall safety profile looked pretty good. Nothing definitive though. Such clarity.
So now the job is to consider how to take this magnificently imperfect evidence and apply it to a specific and different clinical scenario, trauma.
The Royal College of Paeditrics and Child Health and the National Paediatric Pharmacists Group Joint Committee had exactly this challenge back in 2012. It’s the intellectual equivalent of trying to catch pancake batter. Messy.
Ultimately they chose what they termed the pragmatist’s option – 15 mg/kg loading (up to 1 g) over 10 minutes then an infusion of 2 mg/kg/hr. Maybe enough to do something, but with a low dose (maybe even homeopathic) infusion so you were unlikely to get complications. Entirely rational in the absence of evidence too.
But what if there was another approach?
What they didn’t have access to was some recent data out of the UK military Afghanistan experience in Camp Bastion. TXA had become standard for adult trauma patients under certain conditions after the release of CRASH-2 and both editions of MATTERs. These sort of treatment centres don’t just receive adults though and they must have been wrestling with what to do in smaller patients.
What they describe is another type of pragmatic approach. Rather than any adjustment they just did what they were already doing. Tranexamic acid in a 1 g dose for all comers and more on the basis of medical assessment (though it looks like no one got another dose).
This gets past lots of problems, particularly with getting accurate weights or ages and the need to learn different treatment regimes. It also comes with a certain amount of glee, not because you’re sort of saying “kids are just little adults” and you know that would break plenty of people. You’re actually saying “kids are adults”. If you say that 3 times while drawing a pentagram in a circle of candles, somewhere a paediatrician will be woken with a pain between their shoulder blades.
They describe a breakdown of 66 patients under 18 getting TXA and 700 without TXA. Having severe abdominal or extremity injuries and showing evidence of severe metabolic acidosis were significant predictors that TXA would be used. TXA use was independently associated with reduced mortality but no great difference in packed red blood cell/fresh frozen plasma transfusion ratios. Intriguingly in those getting a large volume transfusion, receiving TXA was associated with greatly improved neurologic status at the time of discharge. Now that opens up a need for more work. They didn’t note an increased risk of thromboembolic complications (but they probably don’t have the numbers to be sure about that).
Overall, we’re talking about kids with an average age of 11 so using the equation of (3 x age) + 7, the weight might be about 40 kg (though I’m not certain if the weights might be a bit less than algorithms from developed countries). That would mean a starting dose averaging round 25 mg/kg.
The Other Extra Bit
That 2014 review also mentions an additional titbit that’s a little useful. Some pharmacokinetic work has been done in patients with craniofacial surgery patients and it appears that an upfront dose of 10 mg/kg then an infusion of 5 mg/kg/hr is optimal for establishing appropriate drug levels. This is far more useful information than cardiac surgery pharmacokinetics where additional considerations of dilution by bypass circuits, potential for pre-existing cyanosis and a variety of other factoids make it hard to draw comparisons. So 10 mg/kg might be enough initially but the subsequent infusion should probably be more than a scattering of holy water (as in more than 2 mg/kg).
The Bottom Line
We’re still stuck with not enough information about paediatric patients. Will there be a bigger study in paeds trauma soon? Probably not. But we can say with more confidence than before that doses that are pretty big seem to be OK.
So what would I do now? I’d modify the pragmatic plan and go with a 20 mg/kg loading dose (or 0.2 mL/kg of our current stock) and once in hospital I’d go with an infusion of 5-10 mg/kg/hr.
And I’d still hope someone is going to try to build a better shack.
References and notes:
This post was first put up over at www.careflightcollective.com
Are you after that review? It’s Faraoni D and Goobie SM. The Efficacy of Antifibrinolytic Drugs in Children Undergoing Noncardiac Surgery: A Systematic Review of the Literature. Anesth Analg 2014;118:628-36.
Or maybe the RCPCH statement on using TXA in trauma – try here.
And here’s the Pubmed listing for the newer trauma study – Eckert MJ, Wertin TM, Tyner SD et al. Tranexamic acid administration to pediatric trauma patients in a combat setting: The pediatric trauma and tranexamic acid study (PED-TRAX). J Trauma Acute Care Surg. 2014;77:852-8.
And in case you didn’t have it already, here’s the spot for the [(3 x age) + 7] calculation. Luscombe MD, Owens BD, Burke D. Weight estimation in paediatrics: a comparison of the APLS formula and the formula ‘Weight = 3(age)+7’ Emerg Med J 2011;28:590-3.
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