Tag Archives: blood

Practical Things, Prehospital Trauma

Making Things Clot

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It’s been a solid break but here is Andrew Weatherall returning with a bit about just one approach to getting access to plasma in the field. 

In prehospital medicine there aren’t really many limits to what we can carry. Ultrasounds are routine. Intubation gear is boring. We even carry patients some of the time.

Plus since 1987 we’ve carried red cells for transfusion. Which is excellent. And we’ve used plenty. Sometimes though you want to change things up and changing things takes time. Like say, changing what you carry for transfusion. Which only took us 30 years or so.

 

How you get it done…

Us carrying red cells has been reality through a range of different attitudes to transfusion. Where we find ourselves now of course is thinking that if you need fluids in the setting of trauma then the fluid should not be see through. For a while though we’ve been trying to figure out how to extend beyond red cells.

The thing is that now that we know that acute traumatic coagulopathy (ATC) is a thing, and we’ve known that for a pretty decent amount of time now, you need to be wrestling with how to try and deal with the coagulopathy bit, not just dish out the vampire-sating stuff.

 

So what to use…

If you go to look at the literature, for a while there’s been plenty out there saying that fibrinogen might be a useful thing to go with. So we’ve been waiting a while for freeze-dried cryoprecipitate but last time we looked it came out as a little bit pricey for our taste but there was something more significant.

Time.

djim-loic-69263-unsplash
Blurry, blurry time.

The more significant thing for our work profile was just the fact that preparing FCCs takes a bit of time and would probably take a team member out of action for too long. That might be a different story if we were doing retrieval or more remote pick-ups, but for metropolitan responses it just didn’t quite seem to fit.

So we kept giving the red cells. Then when TXA gained some evidence, we added that. That one’s quick.

Trauma centres kept publishing on the role of viscoelastic testing but that didn’t fit our work profile either. So we were stuck there.

And whole blood was not on the table in our neck of the woods.

It kept nagging at us though. What’s the other thing we should be giving?

Which is why we went to chat to a clever person at the place we pick up our blood.

 

The Ideas Bank

At this point something we’d discounted as an option suddenly became an option. Plasma.

It just hadn’t seemed like an option for us because of the issues around thawing time and the need to use it within 4 hours. That’s not true anymore though. Extended life plasma (ELP) is now available and is OK to use for 4 days after thawing. Add that to some evidence that group A ELP is suitable for use as a donor unit in the adult patient population (rather than having to always use group AB) and our blood bank contact had come up with a plan to do something different.

So this was the plan:

  • Switch what was in our blood esky from 3 units of O- red cells to 2 units of O- red cells and 2 units of group A ELP.
  • At the end of the shift (this operation is running one shift per day), return the products as usual to the blood bank.
  • The ELP can then go back into the pool used by the hospital blood bank.

And we figured we’d start the plasma early, maybe after the first lot of red cells.

There were to be some limits of course, particularly when it comes to kids. Try as we might, we just couldn’t find guidance for kids under 11 to see if group A ELP alone would be appropriate. Same story for the paeds haematologists. So kids were out.

 

The Introduction

The whole thing got moving within a few short months and the plasma hit the esky in April. It was introduced with lots of discussion and education and an undertaking to keep track of the results.

 It really was seamless. We just sort of needed the evidence to back up the expert advice of the haematologists.

 

Catching Up

And this is where another bit of fortuitous timing worked in our favour. A trial came out.

PAMPer reared up in the NEJM showing a very solid difference in mortality in those given plasma in the prehospital phase. This was patients between the age of 18 and 90 and with evidence of haemodynamic things that matter – systolic blood pressure under 90 mmHg (or a single reading hitting 70 or below) and heart rate above 108/minute. 5 minutes of being arrested was also enough to get a number of people kicked to the side.

It’s also worth mentioning that they just gave their 2 units of plasma in their entirety. Some of the centres were carrying red cells so if they were being treated as recruitment centres administering “standard” resuscitation for a particular day, there was a total of 13 of the 27 centres who might go ahead and give some red cells.

A total of 501 participants were eventually randomised. 30 days after the patients were randomised the number of deaths in the standard care group was 89. This is significant compared to the 53 deaths in the plasma group. After regression analysis, those in the plasma group had a risk of death 39% lower than standard care. There were also mortality differences at 24 hours and in the “in-hospital” cohort.

As a bonus, patients in the plasma group received fewer units of blood components overall. Plus they had no documented cases of transfusion-related lung injury during the trial.

So that was enough to make us tweak things a little more and consider the plasma as our first line resuscitation in most instances, followed by the red cells.

 

What makes it work?

So for now this solution works in our context. That’s not to say it would work for everyone or would be the best choice for different work profiles. We note that London’s excellent HEMS service has just recently introduced bags with both red cells and FFP in them and that’s a different approach again which will be worth watching. And even more recently the crew from Kent Surrey Sussex Air Ambulance Trust have published a retrospective study sharing their success with freeze-dried plasma.

It’s also not to say we won’t seek to tweak things in the future. There are a few key things that made the use of ELP work for us:

  1. Local experts

There’s no doubt that the ‘who you know’ factor helped in setting this up. Being able to approach the local expert, in our case Dr Leo Pasalic (full credentials below), who could think laterally when we approached with a query opened up an avenue we had dismissed. Leo was also able to place it in the context of a broader understanding of the literature. There’s no literature search that’s a replacement for long experience and cultivated expertise.

  1. A very excellent blood bank

A nearby blood bank that supports that expert person with great service is a pretty crucial part of the mix. As clever as Leo is (and he is pretty clever), the whole plan hinges on other clever people who pull off the ‘let’s make this happen’ bit and have that extra understanding of the science and logistics. For us those other key people were Dr Kifah Shahin and Hayley Keenan (you should check their full credentials below too). From the time of deciding to do this to actually carrying the ELP was weeks at most and the logistics have never been an issue. They added the packs and made it work.

  1. Reduce, reuse, recycle

When giving blood products we are, naturally, also trying to nourish our inner greenie. I mean, as it is we’re aiming to reduce the overall usage of blood products throughout the admission. We also want to make sure we’re not thawing the ELP and not being able to use it. Blood products are a precious resource and the cost of production is also high. To date, not a single unit of ELP has gone unused. It’s thawed for the prehospital service, returned at the end of shift and invariably used well within the permitted timeframe by the very big hospital for other patients.

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This is a terrible place for blood products to end up.
  1. The follow-up plan

The plan for tracking the experience of use is already in place so we can confirm our local experience with this new option. Trial evidence is great but ongoing real world monitoring has to come with the territory.

We’ve come a fair distance from our early forays into prehospital blood administration which involved the side of a road, a hospital somewhere nearby and police doing high speed runs to deliver those units.

It’d be good if the next step took less than 30 years though.

 

Notes:

Before we get into the references, we would really like to acknowledge the support of the NSW Health Pathology through their Blood Bank at Westmead Hospital and the brilliant staff working there.

Dr Leo Pasalic is a staff specialist in laboratory and clinical haematology and transfusion medicine and gets to cover the medical supervising responsibilities at the Blood Bank at Westmead Hospital.

Dr Kifah Shahin is the Transfusion Lead Scientist for the West, Rural and Regional laboratories in NSW Health Pathology.

Hayley Keenan is a Transfusion Senior Scientist at NSW Health Pathology Westmead.

That Blood Bank they work at is part of the Department of Haematology at the Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead Hospital. The hospital has been on that location for 40 years. The ICPMR got there first, having been on the site for 41 years.

Now, the reading list.

Here’s the link to the PAMPer thing again:

Sperry JL, Fuyette FX, Brown JB, et al. Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock. New Engl J Med. 2018;279:315-26.

This isn’t the only story out there of course. The paper from Moore et al is worth a look.

Moore HB, Moore EE, Chapman MP, et al. Plasma-first resuscitation to treat hemorrhagic shock during emergency ground transportation in an urban area: a randomised trial. Lancet 2018;392:283-91. 

And that Kent paper again:

Oakeshott JE, Griggs JE, Wareham GM, Lyon RM. Feasibility of prehospital freeze-dried plasma administration in a UK Helicopter Emergency Medical Service. Eur J Emerg Med. doi:10.1097/MEJ.0000000000000585

Now, some others:

Winearls J. Fibrinogen in Traumatic Haemorrhage: A Narrative Review. Injury. 2017; 48:230-42.

Lance MD, Ninivaggi M, Schols SEM, et al. Perioperative dilution coagulopathy treated with fresh frozen plasma and fibrinogen concentrate: a prospective randomised intervention trial. Vox Sanguinis. 2012;103:25-34. 

Schöchl H, Nienaber U, Maegele M, et al. Transfusion in trauma: thromboelasfometry-guided coagulation factor concentrate-based therapy versus standard fresh frozen plasma-based therapy. Critical Care. 2011;15:R83. 

Shackleford SA, del Junco DJ, Powell-Dunford N, et al. Association of Prehospital Blood Product Transfusion During Medical Evacuation of Combat Casualties in Afghanistan With Acute and 30-Day Survival. JAMA. 2017;318:1581-11. 

 

Prehospital Trauma, Research

Does the Thing in the Box Do What it Says?

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Sometimes really simple questions don’t get asked. Here’s a joint post from Alan Garner and Andrew Weatherall on places you end up when you ask simple questions about ways of warming blood. 

Carriage of packed red blood cells (PRBC) by HEMS crews has become increasingly common in the last several years in both Europe and North America.  CareFlight was an early adopter in this regard and has been carrying PRBCs to prehospital incident scenes since the 1980s.  We reported a case of a massive prehospital transfusion in the 1990s (worth a read to see how much Haemaccel was given before we arrived on the scene and how much things have changed in fluid management).  In that case we tried to give plasma and platelets as well but the logistics were very difficult.  This remains the case in Australia with plasma and platelets still not viable in a preparation that is practical for prehospital use.

Returning to the PRBCs however the issue of warming them was something that always vexed us.  We experimented with a chemical heat packs in the late 1990s and early 2000s but could not find a method that we felt was reliable enough.  We also looked at the Thermal Angel device from the US when it appeared on the market nearly 15 years ago, but as the battery weighed the best part of 3kg we decided that it still had not reached a point where the technology was viable for us to be carrying on our backs (battery technology has moved on a long way in the last 10 years and Thermal Angel now have a battery weighing 550gms).

Fast Forward

Hence we were pretty excited when we found that there was a new device available in the Australian market, the Belmont Buddy Lite, where the whole set up to warm blood or fluid weighs less than a kg.  We have been using the device for 3 years now, and our clinical impression was somewhere between impressed and “finally”.

Still, one of our docs, James Milligan, thought it worth validating this new technology. Part of that was about checking that the machine does what it says on the box. Is it just marketing or is it really that good?

The other thing we wanted to assess was how a commercial device compared to all those old techniques we were once stuck with. Traditional methods used by EMS in our part of the world include:

  • Stuffing the unit under your armpit inside your jacket for as long as possible prior to transfusion.
  • Putting it on a warm surface (black spine board in the sun or bonnet of a vehicle). Yep, baking.
  • That chemical heat pack method we had tried 10 years ago.

 

Fire
Some things aren’t a prehospital option. Well this isn’t anywhere maybe.

The Nuts and Bolts

Now, how would you go about testing this? The first thought bubble included a pump set, a theatres wash bowl and a standard old temperature probe that you might use at operation. Oh, and some blood. Like most bubbles that don’t involve property, it didn’t last long.

So we were left with a question: how do you try and set things up to test a system for the real world so it is actually like you’d use it in that real world, while still allowing measurements with a bit of rigour? How consistent are you when you deploy a blood-giving pump set?

Enter Martin Gill, perfusionist extraordinaire from The Children’s Hospital at Westmead. Because when we thought “how do we test prehospital blood warmers” obviously we thought about heart sugery in newborns. We turned to Martin with the following brief:

  • We want to test prehospital blood warming options.
  • We want to measure temperature really well.
  • We’re keen on being pretty rigorous about as many things as we can actually. Can we guarantee flow rate reliably?
  • We figure we could use units of blood about to be discarded and we want to be able to do the most with what we’ve got. So we want to be able to use a unit for a bunch of testing runs.

And Martin delivered. He designed a circuit (check the diagram) that would guarantee flow, measure in 3 spots, cool the blood once it had run through, and run it all through again. There are some things you could never come up with yourself. That’s just one.

Diagram copy
It looks a little different in three dimensions but you get the idea.

 

You might wonder how hard is it to get blood? Well actually it was pretty easy (thank you Sydney Children’s Hospital Network Human Research Ethics Committee and Haematology at The Children’s Hospital at Westmead).

The results have just been published online in Injury.  So this humble little idea has led us some places and told us some things. What were those things then?

  1. As you will note, the commercial warmer was the only method that reliably warmed the blood to something like a physiological level.
  2. The change in temperature as the products pass through the line itself was more than we’d expected. Even the measurement of temperature just a little bit distal to the bag of blood showed a sharp step up temperature (that mean was 9.40C).
  3. Any of the options that weren’t the commercially available device here guaranteed very cold blood reaching the end of the line. After all, 180C is the temperature we aim for when setting up deep hypothermic circulatory arrest in the operating suite. It is very cold. Should you even consider packed red blood cells if you aren’t going to warm them effectively?

In some ways, these aren’t super surprising items but small things like this can still be valuable. This was a humble little bench study of a simple question. Still, finding out that a device does what it says on the box by direct observation is reassuring. But …

 

We Have Questions

Research is very often an iterative process. Ask a question, provide answers to one small element of the initial puzzle, find another puzzle along the way and define a new question to explore. Each new question contributes more to the picture. On top of that, finding our way to the lab set-up and squeezing in the measurements around other work has taken a bit of time and things have moved along. This itself suggests new questions to ask.

Will everyone’s questions be the same? Well here are ours, so you tell us.

  1. Now that we’ve come up with a lab set-up to test the manufacturer’s recommended use, what about testing a situation that more closely matches how the warming device is used at the roadside? As noted in the discussion, we don’t use machines pumping blood at a steady rate of 50 mL/min. How will a warmer perform at the much higher flow rates we demand in prehospital use? Will it still be a warmer or more of a tepid infusion system?
  2. Are all devices the same? We didn’t choose the Buddy Lite because we were after a sweet, sweet money deal. It was the only prehospital fluid warmer with Therapeutic Goods Administration registration in Australia. There are now at least 2 other devices weighing less than 1 kg on the international market. They also advertise an ability to work at higher flow rates of up to 200 mL/min.
  3. Are there are other potential problems when you warm the blood with these low dead space solutions? Let’s just imagine for a second you’re a red blood cell rushing through a warmer. In a pretty small area you’ll be put through a temperature change of over 200C within a system aiming to maximise that heat transfer in a very small bit of space. That implies the pressure change across the warming device could be pretty sizeable. When you get to the end of that little warming chamber having effectively passed through a very high pressure furnace, is there a chance you might feel like you’re going to disintegrate at the end of it all? What we’re alluding to is maybe, just maybe, does making red blood cells change temperature quickly while rushing through the system at up to 200 mL/min leave those red cells happy or is haemolysis a risk? If it was a risk, would the patient benefit from receiving smashed up bits of red cell?

 

Now that we’ve established a good model that will let us do rigorous testing,we can ask those new questions. Without the simpler first question, we wouldn’t be so ready to get going. Those new questions would seem to be how do modern devices perform at flow rates useful for the clinician rather than the marketing pamphlet? And what happens to the red cells in the process?

That’s the space to watch. Because that’s where we’re going next.

 

 

Notes and References:

Here’s the link to the prehospital massive transfusion case report mentioned near the start.

Garner AA, Bartolacci RA Massive prehospital transfusion in multiple blunt trauma. Med J Aust. 1999;170:23-5.

And here’s link to the early online version of the blood warmer paper:

Milligan J, Lee A, Gill M, Weatherall A, Tetlow C, Garner AA. Performance comparison of improved prehospital blood warming techniques and a commercial blood warmer. Injury. [in press]

That image of the fire is from flickr’s Creative Commons area and is unaltered from the post via the account “Thomas’s Pics”.

And did you get this far? Good for you. Much respect to all those who read to the end of a thing. For this you get a reminder that you can follow along by signing up to receive updates when we post.

You also get the word of the week: colophon [kol-uh-fon] which is a publlisher’s or printer’s distinctive emblem used as an identifying device on books or other works. Alternatively it can be the inscription at the end of a book or manuscript.

 

 

Paediatrics, Prehospital Trauma

DIY to Stop the Blood

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This thing comes from Dr Andrew Weatherall, paediatric anaesthetist and prehospital doc. He also blogs over at www.theflyingphd.wordpress.com

 

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.

Here's one I prepared earlier (via CC and flickr user mhlradio)
Here’s one I prepared earlier (via CC and flickr user mhlradio)

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.

Go.

 

The Pragmatist

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 homeopathic infusion so you were unlikely to get complications. Entirely rational in the absence of evidence too.

But what if there was another approach?

 

Another Way

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:

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.