TBI: The Final Frontier…

Summer hols and quiet times for many of us at present, so apologies for lack of posts. 

There is always stuff going on in the background however, and several of us in Virchester were pleased to see the recent publication of this BMJ uncertainties piece on severe Traumatic Brain Injury (TBI).1 

https://www.bmj.com/content/378/bmj-2020-061960.long

We thought it might be helpful to highlight this and talk through some of it. As an aside, it is really worth a look at the BMJ uncertainties catalogue – these are short articles which summarise the current state of the evidence on a given topic, the controversies, the current research landscape and what to do in the face of uncertainty. All in around 1500 words and 20 or so references, often authored by senior investigators. There is a lot of bang for your reading buck here. 

TBI management will be bread and butter stuff for many of you, but it often gets adrenaline surging in departments that see it infrequently. And for those who see it all the time, it is often worth a recap on the state of play – prevention of secondary brain injury remains a research priority for emergency medicine and we all know the tremendous degree of morbidity and mortality which accompanies the condition.2-4 So – what do you need to know, what is the current direction of research travel and what should we do while waiting for more evidence?

What you need to know about management

The first thing to get straight about severe TBI is that it is very often an issue of marginal gains. Rarely does an immediate craniotomy trump all other interventions. The vast majority of severe injuries where active treatment is appropriate are managed conservatively on a neurosciences unit, with tailored monitoring and carefully considered surgical intervention over the following days to weeks. As such, the initial priorities for an emergency physician are usually about performing simple but effective sequential interventions, all designed to rapidly obtain necessary imaging, optimise cerebral perfusion pressure and reduce the potential for secondary brain injury.5 Many of these interventions can be done outside a neurosciences centre, without intracranial pressure (ICP) monitoring. 

From open access: Hawryluk GWJ, Aguilera S, Buki A, et al. A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC). Intensive Care Med. 2019;45(12):1783-1794.

If you are to take away one thing from this article, it should be the crystallisation of this process as a tiered management strategy. The recent Seattle consensus guideline on the management of severe TBI provides an excellent example of tiered strategies for use in patients with and without ICP monitoring.6

Tiers are an excellent way of mitigating some of the human factor challenges in these situations; they ensure that you do the basics right and then provide a blueprint for consideration of second line therapies, and a schema for  rescue therapies you may need to consider. Working through tiers ensure the effective interventions are done well prior to use of less evidence-based techniques; people so often reach for the mannitol without sitting a patient up, loosening neck ties or adjusting the head position. Tiers can also help you determine when to deescalate, after you gain control. A simple figure is available in the BMJ article that describes common interventions in tiers 0/1/2/3 but I would also recommend a read of the Seattle consensus document if you have time. 

You will already know most of the stuff in these tiers, but a few reminders – early sedation, muscle relaxation and mechanical ventilation are the optimum methods to reduce cerebral metabolism, avoid ICP spikes (pain/coughing/vomiting) and control PaCO2. Speaking of which, we are aiming for normocapnia (4.5-5kPa) in tier 1, unless there are signs of impending brain stem herniation. Hyperventilation can be dangerous so don’t fall in to the trap of believing that a PaCo2 of 3kPa might be doing good and probably won’t do any harm. Also – if someone is sedated and relaxed, then get the collar off and sit them up as soon as you can. Positioning goes a long way in ICP reduction, as we see on the unit when our patients have ICP monitoring in situ. If there is a concomitant spinal fracture – check with your service about positioning, rather than assume the default of FULL SPINAL PRECAUTIONS AND FLAT BED REST and make the case for neuroprotection. You’ll be surprised how malleable the spinal opinion can sometimes be, once you point out the harms associated with recommendations and ask for accountability. 

When you are past the basics and wondering how to optimise your patient for transfer – did you know that when we measure the mean arterial pressure (MAP) in a patient with ICP monitoring on the neuroscience ICU, we transduce at the level of the tragus, rather than the heart? Be clEAR where you transduce in TBI, as we say locally….

We do this to ensure the most accurate possible calculation of cerebral perfusion pressure (MAP-ICP), by ensuring that when we refer to MAP we are really talking about cerebral mean arterial pressure. But of course what this really means, is that when we in a neuroscience unit are aiming for a MAP target of 90, we need to use more vasopressor to get there, because we position the transducer higher after zeroing. And there is gold in this detail – early vasopressor use and augmentation of MAP is rapidly becoming the cornerstone of conservative TBI management. We push hard, and early, given the potential failure of cerebral autoregulation in the context of significant injury. We do so to optimise perfusion of the ischaemic penumbra as a baseline, but we are increasingly finding that patients with severe injury appear to lack autoregulation and respond well to hypertensive challenge. 

From open access: Hawryluk GWJ, Aguilera S, Buki A, et al. A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC). Intensive Care Med. 2019;45(12):1783-1794.

What are the key uncertainties and what is being done about them?

There are lots of uncertainties in severe TBI, but we only really had word count to touch on a couple in this article. The limited evidence for osmotherapy is highlighted and in particular we cover the ongoing debate on mannitol vs hypertonic saline. This is the subject of a current NIHR funded trial in the UK, which has recruited >100 patients to date and we hope will offer more information on this area over the next few years.7 In the meantime, osmotherapy of any sort remains a tier 1 option. Just make sure you know your doses. Trying to remember how many mg of mannitol there are in 100mls of 10% and how much you need to give someone who weights 68kg can be stressful. Take a look at the SOS trial protocol if you want to see a lovely equimolar dosing table, which covers the correct dosing strategy for all concentrations of both mannitol and hypertonic saline and is freely available online:

From https://fundingawards.nihr.ac.uk/award/17/120/01

Individualised MAP targets are getting a lot of press as well. TBI guidelines have often discussed the miracle MAP target of 90mmHg, but the Seattle consensus document now talks about this as accepted baseline, with further use of a ‘hypertensive challenge’ in the context of continually raised ICP. Publication of this intervention within tier two strategies at last gives final recognition to the long-standing nursing wisdom seen for centuries on neuroscience ICUs, verbalised astutely as  “This patient just seems to like a higher MAP……”.

Experienced nurses often say this and they would be absolutely right; a higher MAP target would reduce the measured ICP and improve the cerebral perfusion pressure remarkably. We now think this is probably a result of impaired autoregulation in the more severe injuries, further limiting perfusion and responding to augmented MAP targets. But is it worth the cost? We already know about the harms of injudicious fluid therapy and we know that vasopressors can lead to a plethora of iatrogenic side effects.8-10

Some authors have taken this further and developed software to evaluate cerebral autoregulation and ascribe individual patient MAP targets. Results from a four centre feasibility study have been promising, but require external validation in a broader patient population prior to implementation.11-13 What can we do in the meantime? Well, for those patients without additional bleeding injuries, it seems we need to potentially embrace robust delivery of elevated MAP targets and early consideration of hypertensive trials, with appropriate monitoring. For the Emergency physician, this probably translates to earlier consideration of central access and use of a titratable, multifaceted vasopressor with alpha and beta agonism (such as noradrenaline) rather than push dose pure alpha agonists. 

The final key uncertainty mentioned is that of brain tissue oxygen monitoring. A reasonable hypothesis – surely it’s a good idea to measure brain oxygen content, so that we can identify when things are bad and optimise as required.14,15 Lots of questions here though – are we measuring diffuse or local PBto2? What do we do about it when it’s low? Does this translate to improved patient outcomes? Several studies in the pipeline, all highlighted in the review.16,17  

Any final take home messages?

A lot of the BMJ article is aimed at neurointensivists. However, I think we all engage in the management of severe TBI, so it’s important to recap best practice and unknowns. In addition, there is accountability here. 

You may think that the best treatment for severe TBI is early removal from your department and immediate transfer to a neurosciences ICU. Fair enough. But remember when you are making this point in your transfer and trauma governance meetings, that there is evidence to suggest an ICP >22 for more than 37 minutes translates to worse functional outcomes.18

Even if you have the best oiled sedation/ventilation/transfer system in the country, identifying a severe TBI patient and transferring them to another hospital is likely to take you more than half an hour. As such, it is imperative that we all start the process of tiered ICP management as early as possible, so that we can optimise cerebral perfusion and give our patients the best possible chance of a good functional outcome. 

As one of my colleagues locally put it recently (thanks Oli), we are in this to get people back to work and life; not just to keep them alive. 

Further detailed reading of our local pathways and protocols (including at neuroicu.guru, for those interested).

Hope you’ve all enjoyed the summer.

Dan @ExRCEMProf

References:

1.         Perkins GD, Horner D, Naisbitt MJ. Which treatments are safe and effective to reduce intracranial pressure following severe traumatic brain injury? BMJ. 2022;378:e061960.

2.         Smith J, Keating L, Flowerdew L, et al. An Emergency Medicine Research Priority Setting Partnership to establish the top 10 research priorities in emergency medicine. Emerg Med J. 2017;34(7):454-456.

3.         Steyerberg EW, Wiegers E, Sewalt C, et al. Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study. Lancet Neurol. 2019;18(10):923-934.

4.         Teasdale GM, Pettigrew LE, Wilson JT, Murray G, Jennett B. Analyzing outcome of treatment of severe head injury: a review and update on advancing the use of the Glasgow Outcome Scale. J Neurotrauma.1998;15(8):587-597.

5.         Chesnut RM, Marshall LF, Klauber MR, et al. The role of secondary brain injury in determining outcome from severe head injury. J Trauma. 1993;34(2):216-222.

6.         Hawryluk GWJ, Aguilera S, Buki A, et al. A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC). Intensive Care Med. 2019;45(12):1783-1794.

7.         Rowland MJ, Veenith T, Scomparin C, et al. Sugar or salt (“SOS”): A protocol for a UK multicentre randomised trial of mannitol and hypertonic saline in severe traumatic brain injury and intracranial hypertension. J Intensive Care Soc. 2022;23(2):222-232.

8.         Lloyd-Donald P, Spencer W, Cheng J, et al. In adult patients with severe traumatic brain injury, does the use of norepinephrine for augmenting cerebral perfusion pressure improve neurological outcome? A systematic review. Injury. 2020;51(10):2129-2134.

9.         Russell JA, Gordon AC, Williams MD, Boyd JH, Walley KR, Kissoon N. Vasopressor Therapy in the Intensive Care Unit. Semin Respir Crit Care Med. 2021;42(1):59-77.

10.       Wiegers EJA, Lingsma HF, Huijben JA, et al. Fluid balance and outcome in critically ill patients with traumatic brain injury (CENTER-TBI and OzENTER-TBI): a prospective, multicentre, comparative effectiveness study. Lancet Neurol. 2021;20(8):627-638.

11.       Aries MJ, Czosnyka M, Budohoski KP, et al. Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury. Crit Care Med. 2012;40(8):2456-2463.

12.       Liberti A, Beqiri E, Ercole A, et al. Patient’s Clinical Presentation and CPPopt Availability: Any Association? Acta Neurochir Suppl. 2021;131:167-172.

13.       Tas J, Beqiri E, van Kaam RC, et al. Targeting Autoregulation-Guided Cerebral Perfusion Pressure after Traumatic Brain Injury (COGiTATE): A Feasibility Randomized Controlled Clinical Trial. J Neurotrauma. 2021.

14.       Meixensberger J, Jaeger M, Vath A, Dings J, Kunze E, Roosen K. Brain tissue oxygen guided treatment supplementing ICP/CPP therapy after traumatic brain injury. J Neurol Neurosurg Psychiatry. 2003;74(6):760-764.

15.       Okonkwo DO, Shutter LA, Moore C, et al. Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II Randomized Trial. Crit Care Med. 2017;45(11):1907-1914.

16.       Barsan W, Meurer W, Shutter L, Diaz-Arrastia R, Yeatts SD. Brain Oxygen Optimization in Severe TBI, Phase 3 (BOOST3). https://clinicaltrials.gov/ct2/show/NCT03754114?term=boost3&draw=2&rank=1. Published 2022. Accessed 13/4/2022, 2022.

17.       Udy A, Vallance S. The BONANZA trial- a randomised controlled trial that is testing whether a management strategy guided by early brain tissue oxygen monitoring in patients in with severe traumatic brain injury improves long term neurological and functional outcomes. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378178&isReview=true. Published 2022. Accessed 13/4/2022, 2022.

18.       Sorrentino E, Diedler J, Kasprowicz M, et al. Critical thresholds for cerebrovascular reactivity after traumatic brain injury. Neurocrit Care. 2012;16(2):258-266.

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