This week I am presenting (virtually) at the Liverpool Trauma Seminar. This is a new initiative that aims to provide a multispeciality, multidisciplinary trauma conference in the North West of England. It’s run out of Aintree hospital, a level 1 trauma centre, with support from a wider variety of organisations.
The plan was to have a two day conference this week, but COVID-19 scuppered that and so it is now being delivered in 1-hour sessions every Tuesday and Thursday. You can find the links to the free seminars and details on how to book in below.
My task was to present a short review of important clinical trauma research from the last year. I’ve done a few of these sorts of ‘top-10’ presentations over the years and they roughly follow these principles to get included. Papers have to score at least 2 out of 3 for the following.
- Methodologically sound
- Interesting (to me)
- Practice changing
This is, of course, entirely subjective, so if you disagree I am sorry (not sorry), but if I’ve missed something important please add your suggestions to the comments. In the presentation I will focus on 10 papers, but here in the blog I will add a few more at the end that did not make the cut, but which you will benefit from reading.
1. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial1
Unless you have been living under a rock then this is a trial that you must have heard about. It’s the largest trial of tranexamic acid (TXA) in brain injured patients. We covered the trial on the blog in detail here, concluding that on the balance of probabilities TXA should be given to patients with head injuries who were GCS 4-13 and reactive pupils.
- If your patient as a GCS of 9-15 with any blood on CT then you need to treat 59 patients with TXA to save one head injury related death at 28 days.
- If your patient has bilaterally reactive pupils you need to treat 58 patients with TXA to save head injury related death at 28 days
- If your patient does not have unreactive pupils and is not GCS 3 then you need to treat 67 patients to save one head injured related death at 28 days.
There are those who are not convinced by the data, largely due to concerns about over-interpreting sub group analyses, and around the outcomes used here which are deaths due to head injury rather than all cause mortality. These are valid concerns, but on the balance of probabilities I think we should give TXA to the subgroups above,
2. A Multicenter Trial of Vena Cava Filters in Severely Injured PatientsHo KM et al. NEJM 2019; DOI: 10.1056/NEJMoa18065152
Thromboembolism is a significant cause of mortality and morbidity in major trauma patients. All of our patients are at risk and therefore deserve to receive thromboprophylaxis. However, that’s not always as straightforward as we might think. Many of our sickest major trauma patients are also (and perhaps paradoxically) at risk of thromboembolism, but also at risk of bleeding. As an example think of a patient with a fractured pelvis, a complex lower leg injury and a traumatic sub-arachnoid bleed. A combination of injuries that both require treatment and also which are contra-indicated.
One solution in these complex patients has been to place a filter in the IVC to stop any clots reaching the central circulation. At face value a great idea, but does it work?
In this RCT of 240 patients with severe trauma they found that there was no difference in the composite outcome of death or symptomatic PE at 90 days post enrolment, although there were fewer PEs in the intervention group.
The answer, if you are in the UK at least, is yes. This is something that we don’t do in the early phases of haemorrhagic shock. However, when we did a simulation competition at the EuSEM conference in Glasgow we were surprised to find that many of our European colleagues do use vasoconstrictive inotropes far earlier than we do. This year there is an interesting paper in JAMA, an RCT in fact, looking at the early use of Vasopressin in trauma patients.
Interestingly the trial found improved outcomes in those treated with Vasopressin. However, the outcomes were around the use of blood products rather than more patient orientated outcomes like death (which was 12% in both groups).
4 Association of Prehospital Plasma Transfusion With Survival in Trauma Patients With Hemorrhagic Shock When Transport Times Are Longer Than 20 Minutes. A Post Hoc Analysis of the PAMPer and COMBAT Clinical Trials4
The COMBAT5 AND PAMPer6 trials both investigated the early use of plasma in trauma patients. The COMBAT trial did not show a big difference in mortality, whereas the PAMPer trial showed a 30% reduction in mortality. This may be due to several reasons but location and transportation may be one of them (PAMPer was HEMS based, COMBAT was ground EMS). Both trials administered 2U of FFP before blood.
In this post hoc analysis of the combined trials the authors examined the effects across both trials. They found that overall there was still a positive impact for plasma with an NNT of about 12. This was not surprising owing to the dramatic effect seen in the PAMPer trial.
More interestingly they found a strong association between time to hospital with regard to plasma administration with the largest effect being seen in those patients with prehospital transport times greater than 20 minutes.
5 Relationship between the Injury Severity Score and the need for life-saving interventions in trauma patients in the UK7
This may seem like a fairly obvious fact, but it’s important, and good to see it proven as it has implications for how we organise and deliver trauma care.
The authors interrogated the TARN database to see if there was an association between life saving interventions and injury severity score (ISS). Although there is a loose association the correlation is far from perfect, especially so at low levels of ISS. What this means is that many patients who require timely intervention never appear in major trauma research or funding streams. It may also infer that early LSIs may result in a successful outcome despite relatively low levels of injury. A good example might be impact brain apnoea where simple airway care may save a person who has relatively modest injury.
The implication is that we cannot define major trauma solely on the basis. of anatomical injury, but also need to include the needs for interventions that make a difference. This is in keeping with previous work I did around major incident triage where again it is not the injury that is m ost important, but rather what needs to be done about it.
6 Forgot calcium? Admission ionized-calcium in two civilian randomized controlled trials of prehospital plasma for traumatic hemorrhagic shock8
This is another paper from a re-analysis of the PAMPer and COMBAT trials. In this study they examined the ionised calcium levels on arrival. It’s not news that patients with major trauma and transfusion suffer from hypocalcaemia but we have not seen this effect from plasma in the pre-hospital setting.
This analysis demonstrated that over half the plasma receiving patients and about a third of the control groups had ionised calciums less than 1. Hypocalcaemia was also independently associated with mortality in both groups. FFP contains citrate which chelates calcium ions in the blood.
This study tells us that we need to be mindful of hypocalcaemia in these patients, and to look for and treat it, it does not tell us that doing so will affect mortality (as this is not an intervention trial). Despite this, please check the calcium on your patients and correct it.
This pre-hospital study used postmortem data and a panel of experts to identify patients who might have survived with early and appropriate intervention in the pre-hospital and early ED phases of their care. It’s similar to a highly influential study published in the BMJ back in 1988 which identified the gap in trauma care in the UK10.
The authors examined 316 deaths and estimated that 12% were avoidable, but that in order to solve this interventions would need to be delivered earlier and more rapidly than they currently are. The authors highlight a number of interventions related to the control of haemmorhage, notably non compressible bleeding.
There were similar findings and conclusions in another study from Houston this year11.
Improvements will need a change to the way pre-hospital care is delivered in many parts of the US (and in other countries). It’s worth reading the thread from Zaf below.
8 Whole blood transfusion versus component therapy in trauma resuscitation: a systematic review and meta‐analysis12
Whole blood is better than transfusing as components…..right? Well, if you’ve been following twitter for your CPD you might think that this not really a question as OF COURSE it’s better, but is it? I like studies that question our beliefs and values in resuscitation and this is one of them.
A systematic review and meta-analysis that looked through 1759 studies but only found 3 that might answer the question. Of those, none were of high quality and there was just one RCT. Even then they found no convincing signal to a benefit of whole blood with 30-day mortality.
At the moment there is true clinical equipoise as to what is best to use as we await further data. Fortunately, there are at least 2 RCTs pending on this question, one in the US and one with London HEMS13.
9 A Decade of Damage Control Resuscitation: New Transfusion Practice, new Survivors, New Directions.14
This paper outlines changes in practice and outcome for bleeding patients presenting to the Royal London Hospital and the London HEMS service from 2008-2017. During that time 1169 patients activated the major haemorrhage protocol and received at least one unit red cells.
Over that time mortality has fallen from 45% to 27% with. arange of interventions potentially responsible for this dramatic improvement. Early deaths have shown a particular decline leading to a proportionate increase in the number of patients dying later on the ICU as a result of multi-organ failure and brain injury. The latest intervention made has been in the use of targeted interventions on coagulopathy. A trial examining this (iTactic) is due to be published very soon and will be worth close review.
10 Prehospital critical care is associated with increased survival in adult trauma patients in Scotland15
There has been a huge investment in the provision of advanced pre-hospital care in the UK/ Here in the NW the Air Ambulance now provides cover using three rotor based teams and cars in bad weather. Other areas of the country have progressed to 24-hour responses at even greater expense, but does it really make a difference to patients? This should be a simple thing to test, just randomise a PHEM response as we would in any RCT, but that’s not really realistic. The ethics of randomising a team to not go for the purposes of a trial will probably never happen. We must therefore look to databases and retrospective data as a lesser, but important indicator.
In this study the Scottish prehospital care team’s work was compared against comparable cases attended by the regular Scottish Ambulance Service teams. They specifically looked at trauma patients using a dataset of 17157 patients of whom 776 were attended by PHEM teams.
The headline figure is that those patients attended to by the PHEM teams did better in a multivariate analysis with an OR for 30-day mortality of 0.56 (95% CI 0.36-0.86) which is impressive, but there are caveats.
The patients were different in the groups. Those attended to by PHEM were more likely to be male, transported to an MTC, have suffered severe trauma or to have had a head injury. This is tricky as if the groups were pre-selected to be different at baseline can we really compare them as equal? Despite this, it is likely that the results are true. although the magnitude of the effect may well be influenced by other factors (such as treatment at an MTC), and may not be reproducible in other settings such as urban areas.
11. The Zero Point Survey16
Cheekily I added the zero point survey paper that I co-authored a little before this last year. Why you may ask? It’s because of all the things I’ve done this year it’s the easiest, quickest, cheapest and most effective to deliver in practice16.
We don’t have the evidence yet, but it makes sense and I’d strongly recommend you consider putting it into your practice. Read more about the ZPS here.
- 1Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial. The Lancet 2019; : 1713–23.
- 2Ho KM, Rao S, Honeybul S, et al. A Multicenter Trial of Vena Cava Filters in Severely Injured Patients. N Engl J Med 2019; : 328–37.
- 3Sims CA, Holena D, Kim P, et al. Effect of Low-Dose Supplementation of Arginine Vasopressin on Need for Blood Product Transfusions in Patients With Trauma and Hemorrhagic Shock. JAMA Surg 2019; : 994.
- 4Pusateri AE, Moore EE, Moore HB, et al. Association of Prehospital Plasma Transfusion With Survival in Trauma Patients With Hemorrhagic Shock When Transport Times Are Longer Than 20 Minutes. JAMA Surg 2020; : e195085.
- 5Moore HB, Moore EE, Chapman MP, et al. Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial. The Lancet 2018; : 283–91.
- 6Sperry JL, Guyette FX, Brown JB, et al. Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock. N Engl J Med 2018; : 315–26.
- 7Vassallo J, Fuller G, Smith JE. Relationship between the Injury Severity Score and the need for life-saving interventions in trauma patients in the UK. Emerg Med J 2020; : emermed-2019-209092.
- 8Carroll S, Dye D, Smedley W, et al. Early and prehospital trauma deaths: Who might benefit from advanced resuscitative care? J Trauma Acute Care Surg 2020; 88: 776–82.
- 9Carroll SL, Dye DW, Smedley WA, et al. Early and prehospital trauma deaths. Journal of Trauma and Acute Care Surgery 2020; : 776–82.
- 10Anderson ID, Woodford M, de Dombal FT, Irving M. Retrospective study of 1000 deaths from injury in England and Wales. BMJ 1988; : 1305–8.
- 11Kalkwarf KJ, Drake SA, Yang Y, et al. Bleeding to Death in a Big City. Journal of Trauma and Acute Care Surgery 2020; published online June 24. DOI:10.1097/ta.0000000000002833.
- 12Crowe E, DeSantis SM, Bonnette A, et al. Whole blood transfusion versus component therapy in trauma resuscitation: a systematic review and meta‐analysis. Journal of the American College of Emergency Physicians Open 2020; published online May 29. DOI:10.1002/emp2.12089.
- 13Qasim Z. Everything old is new again- whole blood in the trauma bay. St Emlyn’s. 2018; published online Sept. https://www.stemlynsblog.org/whole-blood-in-trauma-st-emlyns/ (accessed July 2020).
- 14Cole E, Weaver A, Gall L, et al. A Decade of Damage Control Resuscitation. Annals of Surgery 2019; published online Oct 22. DOI:10.1097/sla.0000000000003657.
- 15Maddock A, Corfield AR, Donald MJ, et al. Prehospital critical care is associated with increased survival in adult trauma patients in Scotland. Emerg Med J 2020; : 141–5.
- 16Reid C, Brindley P, Hicks C, et al. Zero point survey: a multidisciplinary idea to STEP UP resuscitation effectiveness. Clin Exp Emerg Med 2018; : 139–43.