Saturday, 28 July 2012

Stop the bleeding: questioning emergency trauma care

When trauma patients arrive at hospital with multiple injuries and haemodynamic instability (significant blood loss, low blood pressure, increased risk of dying), apart from resuscitating them (usually by giving blood and other things like clotting factors) the treatment is summed up by the phrase: “Stop the bleeding”.

“Stopping bleeding” is a biologically plausible mechanism for saving life that I will accept on face value. My question is: do our noble attempts to stop the bleeding actually influence the chance of dying? Looking at previous treatments that have fallen out of favour, I would say not. And the treatments currently in vogue are supported by as little evidence as those they replaced.

Now I know there are other outcomes apart from death, like organ failure, infection, quality of life, time in intensive care etc., but with patients like this, your main aim is really to keep them alive and to sort out the rest later. So what can we do? Read on, or skip to the bottom line.

Splenectomy
A ruptured spleen was thought to be associated with 90 – 100% mortality without surgical splenectomy. Now up to 90% of them are treated non-operatively – the results are better, as they don’t die, and we now avoid all the complications of splenectomy (yes, the spleen has a purpose – overwhelming infections may occur without it). The history of splenectomy is provided here. Angiographic embolization (AE) may have helped drive non-operative treatment, but I can find little evidence that it helps (see section below on AE).

Clotting agents
Recently, there has been interest in newer clotting agents. Factor VII is a naturally occurring clotting factor that can now be produced in the lab (for a price - about $10,000 per patient). It makes blood clot by bypassing the other clotting factors that often get depleted in a sick, bleeding patient. It makes sense. The large placebo controlled trial for Factor VII showed a (small) reduction in the need for blood transfusion, but interestingly it had no significant effect on the overall rate of death (the placebo group did slightly better). This is interesting because the decrease in blood loss (or at least in blood transfusions required) was not matched by a decrease in mortality.
The other clotting agent recently tested is tranexamic acid (TXA). This has been shown to reduce overall mortality in trauma patients (in a large study of over 20,000 patients) by about 1.5%. Further analyses of this study showed that TXA was particularly effective if it was given within 1 hour of injury (not always possible) and that it was harmful (actually increased mortality) if given after the 3 hour mark (here). So while I agree that TXA may have some benefit in this situation, you will have to admit that the benefit is not large, and that you may need to be careful about when you give the drug.

Tourniquets
Nothing stops bleeding like a tourniquet, right? These days, there is much talk of applying tourniquets in the field. Commonly in trauma care things go in and out of fashion, and tourniquets were definitely out of fashion when I did my training and they are definitely in fashion now, largely a result of military studies from the middle east. There are plenty of studies looking at how often tourniquets are used, what types, how long, and survival rates (here, here, here and here) but there are no good comparative studies at all, not even a good before-and-after study, and they are the best ones for showing that something works because they nearly always show an improvement in the "after" group, no matter how ineffective the intervention.

Am I being crazy? Of course they save lives, you say. Maybe, and the lack of good evidence doesn’t mean that they don’t work. But remember, the conviction with which tourniquets are currently being promoted is no greater than the conviction behind all the other emergency interventions listed above and below, and the previous call for not using a tourniquet. A good overview of the history of tourniquet use, up to the present day, is provided here.

If tourniquet use is going to save lives, I guess military casualties where rapid evacuation to a controlled environment is where they will work. Do tourniquets cause harm? Of course: from the moment you apply a tourniquet the timer is running, and there are plenty of examples of harm from tourniquets being too tight or left on for too long. And this assumes that you apply it correctly, because inadequate application is associated with increased blood loss – a common problem, historically. Without any comparative trials however, we are going to have to rely on the opinions of the people with experience. Just don’t be surprised if that opinion changes over time.

Replacing precious bodily fluids
In my day, we gave copious amounts of colloid solutions (more expensive, supposedly stayed in the bloodstream, made sense) instead of saline-type solutions intravenously to resuscitate bleeding patients. Ends up they made no difference the whole time (Cochrane review) and are being withdrawn in Europe (here). We were also taught to infuse as much fluid as possible to resuscitate these patients. Now it appears that this was harmful, and we should be performing ‘low-volume resuscitation’, also termed 'permissive hypotension' (here and here). This provides a good example of changing the biological mechanism to fit the current thinking. Originally it was “restore the intravascular volume by giving fluids, to keep the blood pressure and tissue perfusion up”. Now it is “raising the blood pressure will increase bleeding by disturbing clots ('popping the clot')”.  For a more detailed review, read this. For a more confusing account of the pathophysiology, read this.

Pre-hospital fluid resuscitation was also considered important (again, made sense), but later prospective studies (like this one) showed that pre-hospital fluids led to worse outcomes. Similarly for Intensive Care resuscitation, colloids don't help (here).

The MAST suit
Military Anti Shock Trousers (MAST suits) were once considered life saving. Every ambulance in my day had one, and they were used for most major trauma patients. The suit was wrapped around the patient’s pelvis and legs and inflated, theoretically pushing the fluid back into the upper (more important) half of the body to counter the shock. It was later considered dangerous because it also pushed the abdominal contents up through a ruptured diaphragm, blocked circulation to the legs, and in this randomised trial, led to more deaths in the MAST suit group. The history of the MAST suit is detailed here and there is also a Cochrane review. The MAST suit is no longer used.

Fixing the pelvis
External fixation (placing pins into each side of the pelvis, and connecting them with a rod to stabilise the bones) was all the rage when I was doing my training. It made sense (somehow, I’m sure) and people swore that patients got better as soon as you fixed the pelvis. There are many reports of patients getting better after pelvic fixation, and many reports now talk about new ways of placing the external fixator (even internally), and others talk about timing of fixation. Some papers even publish great results when they deliberately don’t use pelvic external fixation (here), but without any comparative studies it is hard to say if it does anything. And biologically speaking, I really cannot see any advantage over a pelvic binder (a sheet wrapped around the pelvis) in the acute period.

The pelvic C clamp was similarly touted as a life saving device. This is basically a big clamp with large pins that go through the skin, into the pelvic bones, and the device squeezes the two halves of the broken pelvis together. The principle is similar to a pelvic external fixator or a blinder, but it had theoretical advantages. Like pelvic packing (below) there were reports of it being effective, but no good comparative studies were performed. The only studies are small case series with mortality rates of about 25-35%, which doesn’t fill me with confidence that this device is a life saver. Also, the C clamp has been associated with some pretty nasty complications, like driving the pins through the pelvis into the internal organs and dislocating the pelvis.

Packing the pelvis
In a before-and-after study of pelvic packing versus initial angiography (here), there was no significant difference in mortality. In a similar study (here), they concluded that packing was better than angiography, but when you are comparing 40% mortality to 60% mortality with 10 patients in each group, it is hard to make any firm conclusions.

Pelvic packing is still associated with a high mortality, and there have been no good comparative studies, so it gets relegated to the “at least we are trying something” group – a group with a bad track record. This 2009 review doesn’t offer any comparative studies.

And when authors use the term “paradigm shift” in the title (here) to talk about the treatment, and then go on to describe a 25% mortality rate and conclude that the treatment is effective, without any control group, it is time to look skeptically at that particular treatment.

Angiographic embolization (AE)
I know what you are thinking: “All those things don’t matter any more, because we now embolize all the bleeding arteries via percutaneous angiographic techniques”. That is why I saved this one until last. Nothing, except maybe a tourniquet (applied correctly, to an appropriate injury, of course) stops bleeding like embolization. I mean, you see this artery bleeding on the screen and then Bam! You just blocked it off. How can I argue my way out of this one? Firstly, consider that embolization only blocks arteries, not veins (which also bleed, a lot); that it simply diverts blood to other areas that may also be bleeding; and that the arteries don’t always stay blocked for very long.

Studies like this one simply show how effective AE is in stopping bleeding, but nothing about its effect on mortality. Are there any controlled studies? Not really. There is a before-and-after study that shows that it might be worse than pelvic packing, but not much else.

This review of pelvic trauma in Germany over two decades did not show much change in mortality, despite all the changes in practice referred to above.

The bottom line
If I am treating a patient bleeding in front of me, will I stop the bleeding? Yes, if I can do it without adding to the bleeding or increasing the risk. And apart from stopping the bleeding, I will replace the blood and plasma that he has lost. However, it is likely that the treatments we used to provide (high volume infusions, colloid infusions, pre-hospital care, splenectomy, pelvic external fixation, MAST suits, etc.) probably never worked in the first place, despite our beliefs and the ‘evidence’ at the time. And much of the stuff we do now (pelvic packing, angiography, tourniquets, etc.) is based on a similar level of evidence.

If we can question our interventions to stop bleeding in trauma patients, which is probably the best biological mechanism I have ever heard, then what other accepted, seemingly obvious medical treatments should we also be questioning?

2 comments:

  1. Thanks for a great article Dr Skeptic, but it actually leaves me with more questions than answers, the most important of which is: faced with the clinical scenario of a haemodynamically unstable patient with a pelvic fracture (and no other sources of bleeding) - what should I do, based on the current evidence?

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    1. Thanks Abhinav,
      Firstly, don't ever assume that you have to do something, that is what gets us into so much trouble: not accepting that doing nothing is sometimes better than doing something.

      Secondly, do no harm. Temporary binding with a sheet might not have any good evidence, but it probably does little harm. At the other end of the spectrum, open surgery to pack the pelvis or ligate bleeders has significant risks without good supporting evidence.

      Thirdly, use the evidence. The lack of RCTs doesn't mean there is no evidence, it means we have to use other evidence, even to the point where we have to rely on expert opinion. I feel that expert opinion in this field is biased towards intervention (for all the reasons mentioned throughout this blog), but even the experts will accept that to some degree.

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