It’s that time of year again when the Trauma Care UK conference comes around and I get to talk about 10 interesting trauma papers from the last 12 months or so. This is a regular event and ordinarily would mean a trip to the Midlands to meet up with friends and colleagues from across the UK and Ireland to talk all things trauma.

Sadly, this year we are still on remote learning which is a bit of a shame as I am really starting to miss the camaraderie and sharing of ideas that face to face conferences bring. In recent months I feel that we have done a good job of keeping things going using online meetings, but I do think that innovation is much harder in cyberspace and I cannot wait to get back to meeting colleagues face to face at great meetings like TraumaCareUK.

That said, it is always an honour to do the top 10 papers talk. It gives me time to reflect on what’s happened over the last year, and in this case it’s a good reminder that not everything is COVID related. This blog and talk will be (mostly) COVID free, which is again something that we are all looking forward to (Ed- if that is it ever happens).

Choosing the top 10 is an imprecise and personal decision. I try to pick papers that will either change practice, that will make us challenge current practice or bring in new ideas. I also look for methodological rigour, but in truth it’s my opinion and if your favourite paper is not here I am sorry. If it’s one that you wrote then I am really, really sorry. I’ve taken papers from September 2019-2020 to reflect the timing of the conference.

One thing to note this year is that the COVID pandemic has certainly affected trial recruitment and a number of trials that we would have expected to have reported by now are still in recruitment phases, and a number of other trials that we might have expected to start are yet to get going. I expect that it will take a few years for things to settle down.

So on with the papers

1. STAAMP Trial

The STAAMP trial is a randomised controlled trial of TXA in the prehospital setting. It’s important because it’s a North American based RCT of TXA, an area of the world where TXA is treated with a degree of scepticism. Published in JAMA Surgery this trial randomised 827 patients to either 1g of TXA prehospital or to placebo. The principle outcome was mortality at 28 days. Interestingly the headlines on this study were that TXA did not make a difference, but we need to delve a little deeper. Mortality in the TXA group was 8.1% and was 9.9% in the placebo group. This did not reach statistical significance and so the authors and many other commentators concluded that it was evidence that TXA was not effective.

However, this trial is considerably smaller than other trials of TXA such as the CRASH studies and therefore does not have the power to detect what might be clinically important differences. In fact the absoluted difference in mortality in this study is 1.7% which is actually larger than that found in the CRASH-2 study. In sub-group analysis the authors also found a statistically significant difference if TXA was given within 1-hour (4.6% vs. 7.6%) or when given to patients with severe shock (18.5% vs. 35.5%).

The bottom line for me is that this is an underpowered study that suggests similar efficacy to other large trials of TXA in major trauma patients. We should continue to give it, and give it early.

2. After 800 MTP Events, Mortality due To Hemorrhagic Shock Remains High And Unchanged Despite Several In-Hospital Hemorrhage Control Advancement.

We have heard and read a lot about major haemorrhage protocols in the last decade and there is no doubt that the approach to haemorrhage control and circulatory support has changed radically, but what impact has it had? In this retrospective US study they looked back at over 800 MHP activations and examined mortality rates to see if there are any step changes that might indicate a significant impact on mortality rates. Tracking the mortality rates from 2008-2019 they found that mortality rates were relatively stable and not significantly impacted by the introduction of in-hospital interventions such as TXA and REBOA. What they did find is that the prehospital use of tourniquets in 2013 significantly reduced mortality in penetrating but not blunt trauma and again when the use of whole blood started in 2019, though an adjusted analysis suggests that only tourniquets have impacted mortality.

The authors have concluded that haemorrhage control needs to be moved further forward into the patient journey and specifically into the prehospital setting, or with the use of hybrid EDs that combine imaging, resuscitation and definitive care. For those of us in the UK we might be surprised that many of the interventions suggested are commonly used in practice in the UK (blood products as an example by HEMS services).

Although I agree with the authors ideas about moving control forward we must be mindful that this is a single centre study that is observational in design. It can then only really be considered hypothesis generating. Having said that the principle that everything that happens to a trauma patient in the time period between injury and definitive care must be carefully evaluated and of value.

3. Emergency Scalpel Cricothyroidotomy use in a prehospital trauma service: a 20-year review.

I’m sure that many of us worry about the time that we might need to do a surgical cricothyroidotomy. Although the actual procedure itself is not especially complicated it’s usually done at a time when stress levels are high and where it must be achieved with a great deal of urgency. In my career I’ve seen only a small number despite working in quite busy emergency departments, and in truth I’ve not seen one at all for a few years now. My experience is perhaps understandable when we look at this paper reviewing surgical airways in the London via the London HEMS team over 20 years.

The service has a pretty robust data collection system that allows the authors to track trends and to see not just the number but also trends in practice and the impact of specific innovations in airway care.

The headline figure is that even in the London HEMS population the requirement for surgical cricothyroidotomy is rare with 72 performed amongst 37725 patients (roughly 2 per thousand patients attended). The majority were as rescue procedures (76.4%) with the rest being primary airways typically because of access/entrapment issues. Survival was low, which is unsurprising as these patients are typically severely injured and 57% of them were in cardiac arrest at the time of the procedure. Sadly only 5 of the 72 patients survived to leave hospital with their neuro outcomes being undescribed in this paper.

Amongst those patients who had a prehospital anaesthetic 30 (or roughly 0.5%) had a surgical airway performed.

What’s even more interesting is the trend over time. Better training and devices, notably the use of supraglottic airways has significantly reduced the requirement for surgical airways in the service. Prior to SGAs the cric rate in PHEA was 0.9%, whereas following the introduction of the i-Gel device the rate has fallen to 0.2%. Of course this association does not prove causation and there will be other factors involved but the implication is that this procedure is becoming an ever more rare requirement in practice.

4. Fibrinogen Early In Severe Trauma studY (FEISTY): results from an Australian multicentre randomised controlled pilot trial

The FEISTY trial is a multicentre feasibility study from Australia. In this RCT they compared fibrinogen concentrate to cryoprecipitate, primarily to look at ease and speed of administration. As you know there is a lot of interest in the use of clotting products early in the trauma journey. Studies such as the PAMPER trial have suggested that this may have a big impact on mortality and the current CRYOSTAT-2 trial is looking at the use of early cryoprecipitate in bleeding trauma. We are a recruiting centre for CRYOSTAT-2 and it’s interesting to see that it often takes quite a long time from randomisation to actually getting the product into the patient via the blood bank systems. Fibrinogen concentrate has the advantage of being a dried powder that can be drawn up at the bedside and this perhaps may lead to faster administration and ultimately patient benefit. We should also remember that Cryoprecipitate also contains factors VIII, XIII and vWF.

The authors randomised 100 patients with severe trauma (ISS averaged 26) to either Fibrinogen concentrate or Cryoprecipitate. They found that FC was much faster to administer (29 vs. 60 mins). They also showed that both products were effective at replacing fibrinogen levels in a population with a 62% hypofibrinogen states.

Obviously there is more work to do here, but the prospect of treating trauma related coagulopathies with easy to prepare drugs is potentially very useful indeed.

5. Association of Prehospital Plasma With Survival in Patients With Traumatic Brain Injury. A Secondary Analysis of the PAMPer Cluster Randomized Clinical Trial

You probably remember the PAMPer trial as published in the NEJM. It is a randomised controlled trial of early plasma in severely injured patients. It showed a significant improvement in mortality if plasma was given, and it’s certainly changed practice in many services (though sadly not yet in Virchester unless HEMS bring the patient in). In the original paper it was noted that not all patient types showed similar benefits. This study is interesting as it’s similar to a number of other papers published this year that suggest the importance of coagulation control in head injured patients.

There were 166 patients in the PAMPer trial with traumatic brain injury (TBI), 74 of whom received plasma prehospitally. Patients were much less likely to die if given plasma (but only if transferred direct from the scene and not as secondary transfers). The headline figure is that 51% of patients in the standard care group died as compared to 26% in the plasma group. The adjusted analysis for confounders showed a hazard ratio of 0.55 (95% CI 0.33-0.94).

Although this is a relatively small subgroup analysis and thus we should be cautious of over interpreting the results, there are other studies that show similar signals. CRASH-3 with TXA and iTactic as discussed below both hinting towards the potential benefits of understanding and managing coagulopathy in head injured patients.

6. Understanding the neuroprotective effect of tranexamic acid: an exploratory analysis of the CRASH-3 randomised trial

This is another paper looking at the impact of the management of clotting in head injured trauma patients. This papers uses data from CRASH-2 and CRASH-3 to look at the impact of TXA on head injured patients. CRASH-3 showed no benefit to those patients with a GCS of 3 or bilaterally unreactive pupils. It is therefore a subset of the original patients and thus this study analysed 7637 patients. Early deaths were reduced in the TXA group (2.9% vs. 3.9% RR 0.74, CI 0.58-0.94), but deaths beyond 24 hours were not statistically significantly different in this cohort, though there were better outcomes in the TXA group.

The authors then pooled data from CRASH-2 and CRASH-3 which then did show a statistically significant difference in all cause mortality at 28 days. This is important as CRASH-3 was criticised for reporting head injury deaths rather than all cause mortality.

This is interesting work, but should be treated with some caution owing to the exploratory nature of the analysis and pooling from 2 different trials conducted across a range of years. However, it further supports the use of TXA as a tool in the treatment of major trauma patients.

7. ITACTIC trial

The iTactic trial is one that I’ve been looking forward to for some time. It’s a randomised trial of the use of viscoelastography in the management of bleeding trauma patients. It was conducted across a range of European trauma units and involved patients being treated empirically with blood products or with targeted blood products based on viscoelastography (using either ROTEM or TEG machines). I’ll admit that I was someone who thought that this might be a game changer in trauma as we know that trauma associated coagulopathy is a very bad thing to have and that perhaps by targetting our treatment of this we would see more survivors.

In fact the trial did not demonstrate a clear difference between the two approaches. Amongst the 396 patients randomised, the 24 hour mortality (or free from massive transfusion) was 67% in the VEG group was and 64% in the standard of care group. So it all sounds very negative, but there was some interesting data amongst the patients with traumatic brain injury. In this pre-specified sub group there was a survival advantage (64% vs. 46%), but it was a small group and can only be hypothesis generating at this stage. I know quite a few places that are planning on using VEG in resus (including in Virchester) and so it will be interesting to see how influential these findings are in practice. It’s also worth noting that this trial was probably underpowered owing to the unexpectedly smaller number of patients arriving at the ED with an established coagulopathy.

8. Effect of Continuous Infusion of Hypertonic Saline vs Standard Care on 6-Month Neurological Outcomes in Patients With Traumatic Brain Injury: The COBI Randomized Clinical Trial

There are very few trials that show a benefit to drugs in moderate and severe head injury, but the use of hypertonic saline has gained a lot of traction in the last decade or so. In this randomised controlled trial of ICU patients with moderate and severe head injury patients were given either a continuous 20% saline infusion or the usual standard of care practices. The outcome measure was the GOS-E at 6 months which is good to see as longer term neurological outcomes are what we need to see in these trials (as opposed to monitor based or short term outcomes). Some would even argue that 6 months is too soon.

In any case the trial did not find any benefit to the routine use of 20% saline and so we can no longer recommend it as a routine treatment.

9. Effect of Prophylactic Embolization on Patients With Blunt Trauma at High Risk of Splenectomy: A Randomized Clinical Trial.

One of the major changes to practice I’ve seen in the last decade is in the management of splenic trauma. Open splenectomies are now relatively rare procedures, with interventional radiology, or conservative management commonly used. However, there are still some controversies around the managment of more significant splenic injuries and whether an injured spleen should be prophylactically embolised or whether a watch and wait policy is reasonable.

In this French study, haemodynamically stable patients with Grade 3,4, and 5 injuries were randomised to either early interventional radiology or a watch and wait approach. The principle outcome was whether they had a functioning spleen at one month post injury Of the 140 patients randomised most were grade 3 injuries the rest mostly grade 4 and only a few grade 5 injuries.

At one month there was no statistically significant difference (98% for prophylactic group and 93% for observation), but it should be noted that length of stay was longer in the observation group and that 35% of those in the observation group subsequently needed intervention.

It’s great to see a trauma surgery RCT in print, but in terms of conclusions I’m not sure that these are truly equivalent or whether the study is underpowered and/or to focused in the primary outcome. Although both approaches seem reasonable, the high failure rate from observation probably means that these patients need to be managed in a centre capable of delivering timely intervention when required.

10. Emergency Resuscitative Thoracotomy: A Nationwide Analysis of Outcomes and Predictors of Futility

This is an interesting registry study of 1.4 Million US patients, 2012 of whom underwent an emergency room thoracotomy. The key finding is that the survival rate from thoracotomy is much higher than in previous studies at roughly 20%. The reasons for this are not entirely clear but I would infer that it’s because a number of these are done in patients who are not already dead. Predictors of survival were those that you might expect such as age, heart rate >60, signs of life in the ER, stab wounds rather than gunshots etc. In fact the highest rate of survival is in those patients aged less than 60, with signs of life in the ED and with a stab wound where the survival approaches 50%. That’s much higher than we see in Virchester and so I suspect that they are performing thoracotomies on a different cohort of patients.

They did find that there were no survivors for blunt trauma with no sign of life which is perhaps not that surprising.

The paper is worth a read and a consideration of whether ED thoractomy is a last hope procedure or whether it might appear earlier in ther resuscitation process.

Final thoughts

Another top 10 is complete. Not necessarilly the best papers, but hopefully those that will make you think about your practice and on how we can improve patients outcomes through research. Let’s hope that COVID calms down enough to get more high quality clinical trials in trauma completed and ready to share for next year.

References

After 800 MTP Events, Mortality due To Hemorrhagic Shock Remains High And Unchanged Despite Several In-Hospital Hemorrhage Control Advancements. https://journals.lww.com/shockjournal/abstract/9000/after_800_mtp_events,_mortality_due_to_hemorrhagic.97235.aspx

Emergency Scalpel Cricothyroidotomy use in a prehospital trauma service: a 20-year review. https://emj.bmj.com/content/38/5/349

Fibrinogen Early In Severe Trauma studY (FEISTY): results from an Australian multicentre randomised controlled pilot trial. https://ccr.cicm.org.au/journal-editions/2021/march/toc-march-2021/original-articles/article-6

Association of Prehospital Plasma With Survival in Patients With Traumatic Brain Injury: A Secondary Analysis of the PAMPer Cluster Randomized Clinical Trial. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2771732

Understanding the neuroprotective effect of tranexamic acid: an exploratory analysis of the CRASH-3 randomised trial https://ccforum.biomedcentral.com/track/pdf/10.1186/s13054-020-03243-4.pdf

Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial. https://pubmed.ncbi.nlm.nih.gov/33048195/

Effect of Continuous Infusion of Hypertonic Saline vs Standard Care on 6-Month Neurological Outcomes in Patients With Traumatic Brain Injury: The COBI Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/34032829/

Effect of Prophylactic Embolization on Patients With Blunt Trauma at High Risk of Splenectomy: A Randomized Clinical Trial. https://jamanetwork.com/journals/jamasurgery/fullarticle/2770272

Emergency Resuscitative Thoracotomy: A Nationwide Analysis of Outcomes and Predictors of Futility https://www.sciencedirect.com/science/article/abs/pii/S0022480420303218

Top 10 Trauma Papers for Trauma UK conference. 2020-2021. St Emyln’s