After trauma, the injured brain is made up of three areas. One is the area of tissue that's already dead - this is damaged beyond repair, irreversible and irretrievable - there's no saving this. Another is the area of tissue that's entirely unharmed - this doesn't need saving. In between the two is an area of vulnerable tissue, the penumbra. With appropriate and timely management, we can protect it and prevent the development of a "secondary brain injury". This is the same model we apply after stroke - all our treatment is designed with one thing in mind: protecting this penumbra.
Neuroprotective care is underpinned by several key concepts - all of which are designed to defend cerebral oxygen delivery to that region of vulnerable but salvageable brain.
We want to minimise oxygen consumption by injured tissue (CMRO2) - by keeping patients well sedated and preventing seizures - but we also want to maximise oxygen delivery (DO2).
The latter is largely a function of the amount of oxygen in blood and the amount of blood that reaches the injured tissue. This means maintaining sufficient oxygenation (SpO2 92-94% / PaO2 80-120mmHg) and maintaining a sufficient blood pressure (usually aiming for a MAP ~85mmHg). This is crucial, because hypotension (SBP <90mmHg) doubles your risk of death [1,2], and hypoxia increases your odds of dying by about three times [2]. The two combined have an additive effect, increasing your odds of death by a phenomenal six times [2]. Given that these factors are some of the only variables within our control (and are relatively easy to manipulate, even in a pre-hospital environment) these should be our main focus in the treatment of head injuries.*
If you read nothing further - that is the take home point: in treating head injury, maintaining normoxia and normotension are the two most important factors influencing survival.
There's a bit more nuance to this however, because the blood pressure your heart generates is not the perfusion pressure that your brain tissue gets, because it must pump against the pressure inside your skull. If that pressure is high (due to a large haematoma, a depressed skull fracture, or diffuse tissue oedema), the perfusion pressure supplying the brain tissue will go down. In other words, the cerebral perfusion pressure (CPP) is the mean arterial pressure (MAP) minus the intracranial pressure (ICP).
CPP = MAP - ICP
Normally the brain has incredibly sophisticated methods of auto-regulating its blood supply, but those mechanisms are often defective following injury - and so we have to be the ones to control the variables ourselves.
Optimising MAP
If we assume a raised ICP (>22mmHg) and aim to defend a target CPP of 60-70mmHg [3], we must have a slightly higher MAP target than we would normally aim for (~80-90mmHg). If the patient is not achieving this for themselves, we can assist them with crystalloids until fluid replete and/or the use of vasopressors.
But I don't routinely carry vasopressors?
Yes you do - adrenaline should be one of your ACLS medications. Mixing a 1mg ampoule into 100mL saline will yield a concentration of 10mcg/mL (the same concentration you would make up for a push-dose pressor syringe). Your starting rate will be ~0.03mcg/kg/min (at this concentration, roughly 10-20mL/h). Depending on requirements to achieve your desired MAP target, this little adrenaline infusion should last a few hours until help arrives.
But I don't carry an infusion pump? You don't need to. Back in ye olden days, fluid rates were calculated based on drops per minute. Using an adult giving set (with a macro drop factor of 20 drops per mL):
(Drops per minute / 20) x 60 minutes = infusion rate (mL/h)
or put more simply
Drops per minute x 3 = infusion rate (mL/h)
So, to start at ~10-20mL/h, simply start at 3-6 drops per minute (one every 10-20s). From there, titrate up or down to achieve the required effect, and if you want to work out what dose is being given, simply use the formula above. If (for weight related reasons) you have minimal 0.9% saline and want to make supplies last longer, you can make up double-strength by adding two 1mg adrenaline ampoules to your 100mL bag for a concentration of 20mcg/mL. The infusion rates will be half that of a 10mcg/mL bag, and your infusion will therefore last twice as long.
But I won't have central venous access?
It's long since been demonstrated that peripheral vasopressors are safe [4,5]. Large meta-analyses have told us that extravasation events are rare, usually minor, and typically occur with prolonged use (>24h) [6]. Besides which, the adrenaline infusion above is a mere 10% of the strength our centre uses, so the risk should be acceptably low, especially when good IV access has been obtained and especially in an emergent situation where benefits outweigh these risks.
How do we titrate these to effect in the field? Well, the parameters that automated non-invasive blood pressure cuffs are most accurate in providing are MAP values (the SBP/DBP are usually a calculated value, whereas the MAP is the only measured value) - so in the absence of invasive arterial access, it is not unreasonable to titrate our vasopressor dose against an NIBP MAP value. If you only have a manual sphygmomanometer, you can titrate to achieve an SBP that is at the very least >90mmHg (but probably higher), since most of our evidence looking at hypotension in TBI uses that as a cut off for "hypotension")
But raising MAP is only half the battle - to defend our target CPP we can increase MAP, but we should also reduce ICP. Lots of measures can be employed to do this, many of which are simple and common sense.
Minimising obstructions to venous drainage
Use gravity to your advantage by elevating the head of bed (30-45° has been shown to create the largest effect on ICP reduction [7]). The difference between 30° and 0° can be as much as 7.4mmHg [8].
Keep the patient's head facing the midline without undue cervical flexion - as turning to the left or right has been shown to increase ICP from from 10mmHg to 16.7-22.2mmHg, depending on which side dominant venous flow occurs in [9].
Remove circumferential structures around the neck (e.g. remove cervical collars in favour of sandbags, loosen ties on endotracheal tubes etc.). Cervical collars have been shown to increase ICP by 4.6mmHg, with greater effects seen when ICP was already elevated [10].
Minimise increases in intrathoracic pressure that will impede venous return (e.g. provide anti-emetics to reduce vomiting, ensure sedation is optimised to prevent coughing or bucking if intubated, and ensure analgesia is optimised (these also assist in reducing CMRO2 - serving a dual purpose). Note that while PEEP will increase intrathoracic pressure, the relative benefits as they apply to oxygenation should be weighed against the increase in ICP. A PEEP of 5cmH2O has no demonstrable effect on ICP [11], and the best quality evidence I could find suggested that for every 1cmH2O of PEEP, ICP increased by 0.31mmHg and CPP decreased by 0.85mmHg [12]. Minimise PEEP if possible, and attempt to titrate FiO2 to reach the target SpO2.
Utilising osmotherapeutic agents
There are a number of options, but via a peripheral line you are largely limited to either 20% mannitol (0.25-1g/kg IV) or 3% hypertonic saline (2-3mL/kg). The relative benefits and evidence for each remain a topic of heated debate, and what you use will largely depend on what you have available - you can review the literature at your leisure to decide if you wish to pack one or the other for your field hospital / base camp etc. In the absence of either, an alternative may be 8.4% NaHCO3 - regular ampoules of sodium bicarbonate. For an excellent break down of their potential utility as an osmotherapy, see Josh Farkas' PulmCrit article [13]. A small study has shown 85mL of 8.4% NaHCO3 given over 30 minutes could reduce ICP from 28.5mmHg to 10.33mmHg with only minimal changes to pH and Na+, and no changes to MAP or PCO2 [14]. A subsequent small RCT found this dose equally effective in reducing ICP as a 100mL dose of 5% NaCl [15]. If you're equipped with an iStat and are beginning to dip your toes into very-prolonged field care, you'll want to aim for a serum Na+ of 145-150mmol/L.
We haven't delved further into the subject of reducing cerebral metabolic rate of O2 (CMRO2) consumption here, but appropriate sedation and seizure prophylaxis may also be required depending on clinical context and severity of injury.
Notes:
*There are some caveats to this - hyperoxia has also been shown to increase mortality - this is likely due to a contribution to oxidative damage done by additional reactive oxygen species produced within the injured tissue. More oxygen is not necessarily better, so try to keep your PaO2 / SpO2 within the ranges shown. Also note that more research is constantly being produced on the subject of liberal vs conservative oxygen strategies and these targets may change with further research.
References:
[1] Chesnut RM, Marshall SB, Piek J, et al. Early and late systemic hypotension as a frequent and fundamental source of cerebral ischemia following severe brain injury in the Traumatic Coma Data Banl. Acta Neurochir Suppl (Wien). 1993;59:121-5.
[2] Spaite DW, Hu C, Bobrow BJ, et al. The effect of combined out-of-hospital hypotension and hypoxia on mortality in major brain injury. Ann Emerg Med. 2017;69(1):62-72.
[3] Brain Trauma Foundation. Guidelines for the management of severe TBI 4th Ed. Available from: https://braintrauma.org/coma/guidelines/guidelines-for-the-management-of-severe-tbi-4th-ed.
[4] Tian DH, Smyth C, Keijzers G, et al. Safety of peripheral administration of vasopressor medications: a systematic review. Emerg Med Australas. 2020;32(2):220-7.
[5] Permpikul C, Tongyoo S, Viarasilpa T, et al. Early use of norepinephrine in septic shock resuscitation (CENSER). A randomized trial. Am J Respir Crit Care Med. 2019;199(9):1097-105.
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[9] Khawari S, Al-Mohammad A, Pandit A, et al. ICP during head movement: significance of the venous system. Acta Neurochir (Wien). 2023;165(11):3243-7.
[10] Hunt K, Hallsworth S, Smith M. The effects of rigid collar placement on intracranial and cerebral perfusion pressures. Anaesthesia. 2001;56(6):511-3.
[11] McGuire G, Crossley D, Richards J, Wong D. Effects of varying levels of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure. Crit Care Med. 1997;25(6):1059-62.
[12] Boone MD, Jinadasa SP, Mueller A, et al. The effect of positive end-expiratory pressure on intracranial pressure and cerebral hemodynamics. Neurocrit care. 2017;26(2):174-81.
[13] PulmCrit. Emergent treatment of hyponatraemia or elevated ICP with bicarb ampules. 2015. Available from: https://emcrit.org/pulmcrit/emergent-treatment-of-hyponatremia-or-elevated-icp-with-bicarb-ampules/.
[14] Bourdeaux CP, Brown JM. Sodium bicarbonate lowers intracranial pressure after traumatic brain injury. Neurocrit care. 2010;13(1):24-8.
[15] Bourdeaux CP, Brown JM. Randomized controlled trial comparing the effect of 8.4% sodium bicarbonate and 5% sodium chloride on raised intracranial pressure after traumatic brain injury. Neurocrit care. 2011;15(1):42-5.