LITFL has an excellent synopsis of the current BTF guidelines, which is a well-referenced revision resource. The BTF guidelines also form the basis of the summary detailed below. An extensive rambling discussion of these recommendations is also available at the end of this chapter, but it has diminished relevance in the context of pre-exam panic. Links to discussions with greater detail are made available for those who are interested. Specific SAQs interrogating this topic consist of Question 15 from the first paper of 2013 and Question 27 from the first paper of 2016; however there are numerous questions which indirectly address this issue by asking about the management of raised intracranial pressure.
Maintaining cerebral oxygen supply:
Decreasing cerebral oxygen demand:
Other chapters of interest would have to include
This is based on the Brain Trauma Foundation guidelines which deal with this topic exhaustively.
For the time-poor exam candidate, the brief summary made available above will suffice, and they should stop reading at this point.
Question 27 of the first paper of 2014 asks for a defiition of secondary brain injury. What the hell is it? Well. A definition for this concept is actually rather difficult to find.
Many have struggled. For instance, the Encyclopedia of Clinical Neuropsychology gives this unsatisfying definition:
Secondary brain injury occurs after the primary mechanisms of injury have run their course.
The term seems to have appeared in the 1990s. In 1993, Doberstein Hovda and Becker speak of "secondary insults" which included hypoxia, hypotension, etc etc. Since then, the term has come to be accepted as the explanation for any brain injury which is not the direct effect of brain trauma.
From the available sources, one could synthesise a definition of one's own:
Secondary brain injury is the preventable negative effect of several associated physiological variables on the neurological outcome from a primary brain injury.
..There, that's all better. Those "physiological variables" are not all associated with the primary brain injury, as one can see:
Some are due to the injury itself, whereas others (eg. hyper and hypoglycaemia) are factors which have been found to be associated with a poorer outcome, and are though to play a contributing role.
Thus, the actions of preventing secondary brain injury are largely actions of maintaining normality.
As one might imagine, having a poorly perfused brain is bad enough, but having it poorly perfused with poorly oxygenated blood is even worse. One need not elaborate any further. However, for the sake of numbers and number-driven guidelines, let us set a lower limit of 60mmHg, to have something.
There was an era in TBI management when CO2 was kept artificially low by hyperventilation, because of the effect this has on intracerebral blood volume. We now know this is a bad idea, and the most recent (4th ed) BTF guidelines recommend against this practice (Level IIB). The old 3rd edition still suggested that you try this hyperventilation for acute spikes in uncontrollable ICP, but in 2016 they decided that this recommendation does not meet their new standards for evidence, and withdrew it. No specific range for CO2 is recommended, but hypercapnia is certainly bad for ICP, and so some normal or low-normal range is probably safe.
How much blood pressure could be viewed as normotesion? Surely whatever is normo for me is hypo for some crusty geriatric relic with calcified cerebral vasculature.
Unfortunately, there is no agreement.
A systolic of 90mmHg had always been the conventional lowermost value. However, the BTF people do mention that this is essentially an arbitrary endpoint. They shrug their shoulders, lamenting the disconnection between systolic and mean arterial pressures. The consensus of experts is, however, that a systolic of 90 or below should be avoided.
Measure the MAP
Keep the SBP >90
As is explored elsewhere, there are few firm recommendations here.
However, it is generally accepted that the ICP should be kept under 20mmHg.
To monitor it with an EVD is the gold standard, although there have been no good studies to explore the most recent developments in fibreoptic intracranial monitor technology, and these may potentially be as good, or better, than the EVD.
How much blood pressure one ought to have is inextricably linked to the ICP.
Thus, one might be tempted to target the CPP without much concern for the other variables (its all about getting oxygen to the brain right?)... But, in actual fact, its probably better to look at everything all at once.
Cerebral perfusion pressure is not cerebral perfusion - it is a poor surrogate, merely the pressure gradient along which blood flow is occurring, as is explored elsewhere.
Still. Having it too low is obviously bad. Under 50 seems to be the generally agreed-upon threshold.
Having it too high (by artificially increasing MAP with vasopressors and fluids) also tends to lead to complications which outweigh the benefits.
In short, the BTF recommends a CPP be kept between 60 and 70mmHg.
We are talking about jugular venous saturation (SjVO2) and brain tissue oxygen tension (PbrO2).
These things are far from new - people have been monitoring jugular bulb saturation since the early 1990s, and brain parenchyma saturation since the late 1990s. However, there remains little interest in them as surrogate markers for the efficiency of cerebral metabolism. Why? Who can say. Perhaps it is the expense.
In any case, these techniques only merit a lukewarm Level III recommendation from the BTF.
They recommend the SjVO2 remains above 50%, and the PbrO2 remains above 55 mmHg.
The interplay between the pressures exerted by the various components of the intracranial compartment is a vast topic, deserving of its own chapter.
Suffice to say that there are both pharmacological and non-pharmacological strategies:
Decreasing the cerebral metabolic demand with some sort of artificially induced coma is a crude but appealing way of cheating a poor cerebral perfusion. This technique has a certain reliance on the coupling of regional cerebral metabolism and regional cerebral perfusion.
Cerebral perfusion, is is thought, is driven by demand.
Thus, the decrease in cerebral metabolism should result in a decrease in intracranial pressure.
There is always propofol. Delicious propofol and its many wonderous properties are discussed in greater depth elsewhere. Its widely available and is present in every ICU no matter how little the unit. Its comfortable familiarity drives its appeal. Furthermore, it is a predictable and reliable general anaesthetic agent, which prompts the question, why not just use propofol in traumatic brain injury? Surely, every general anaesthetic agent turns the brain off to the same degree? Off is off, right?
Early efforts in this area had examined the relationship between cerebral perfusion effects and the cerebral metabolic effects of propofol. To be sure, there was a sudden (within 1 minute) drop in intracranial pressure from 25mmHg to 11mmHg. And as expected there was also a corresponding drop in cerebral perfusion pressure.
However, there is a certain dose-effect relationship to bear in mind. In order to generate a sufficient depth of coma, one must use a sufficient amount of propofol. Turns out, to achieve "burst suppression" one requires a dose of propofol so large, that it would be impractical to use it for prolonged periods for fear of propofol infusion syndrome.
In addition to this, the hemodynamic effects of propofol make it an unreliable tool for decreasing intracranial pressure, because it will also decrease cardiac output, and potentially have a negative effect on cerebral perfusion.
Overall, the Brain Trauma Foundation mentions propofol as an option at long-term sedation, rather than a neuroprotective panacea. Propofol is the workhorse of the ICU, and it would be silly to limit its responsible use in traumatic brain injury patients. However, we must reflect that it is there not as a coma-inducing cerebral metabolism modifier, but as a means to limit the patient's exposure to noxious stimuli. Stimuli which would otherwise hurt or distress the patient, and cause increased ICP.
The Brain Trauma Foundation statement hastens to remind us that most barbiturate therapy trials were run during a dark age of neurocritical care, when prolonged sustained hyperventilation, steroids and fluid restriction were the standard of care. For some reason, these studies were very pro-barbiturate, and the practice became entrenched.
In 1947, some psychiatrists used sodium pentothal to induce come in a series of healthy volunteers, and then measured the oxygen extraction ratio of their subjects by extracting blood from their jugular veins. As far as cerebral oxygen consumption, they arrived at a figure of 3.3ml/100g/min, which decreased to 2.1ml/100g/min in the state of coma - down by 36%
Clearly, oxygen demand had decreased, and the implications of this in head injury soon became a delicious topic for speculation.
However, the fact remains. Having a nice coma is not really a solution for one's crippling intracranial pressure problem. Indeed, the best evidence for any sort of genuine "neuroprotection" comes from case series of primates with clamps on their cerebral arteries. Turns out, the best way to survive a traumatic brain injury is to already be in a barbiturate coma when you sustain this injury. Clearly, this practice of prophylactic coma is not practical, and might never become popular.
The BTF people suggest titrating one's barbiturate therapy to burst suppression on EEG.
They recommend its use in the sad case when all surgical and medical interventions have failed, and the intracranial pressure remains high. Since 2007, Cochrane reviews have agreed that no mortality benefit is to be expected, and that 1 in every 4 patients receiving an infusion of thiopentone will develop hypotension, frustrating the CPP-enhancing effect.
Studies which look purely at the cerebral hemodynamics may have you believing that it does not matter which analgesic agent you use - they are all equally bad.
Indeed, it would seem that boluses of opioids increase intracranial pressure.
For instance, one study of brain-injured humans administered boluses of 2μcg/kg of fentanyl and 0.2mg/kg of morphine, thus ending up with doses of 15-20mg morphine and 150-200μcg fentanyl per person. The response to these boluses was a transient increase in intracranial pressure, lasting only 10-15 minutes, and measuring no more than 5-10mmHg.
Thus far no study has been able to discriminate among the opioids available to us, at least not on the grounds of hard outcomes or even ICP numbers.
However, experience does play a role in this. The metabolic breakdown products of morphine must surely accumulate in the fatty tissues of these long-term patients as they lay there waiting. I fail to see how marinading patients in nauseating opioids is beneficial. Perhaps fentanyl might be better here.
There is a group of patients who have been empirically identified as at risk of seizures after a traumatic brain injury. These are their characteristics:
Basically, you have to have either seriously structurally wrong with your brain, or you have to have an actual seizure to demonstrate your propensity for seizures.
Furthermore, one must consider the powerful antiepileptic effect exerted by the routine sedation infusions used in the ICU. It seems mildly ridiculous to add a petty 300mg of phenytoin to a patient who has been marinading in thiopentone for a week.
So. The DECRA trial has put a lot of interesting material on the table.
Firstly, yes - the intracranial pressure decreases.
And the duration of ventilation, and the length of ICU stay.
BUT: the outcome for the survivors is poorer.
No matter how natural it might sound, there must simply be something terribly unhealthy about living with a large portion of your brain hanging out through a hole in your skull. For one, it is possible that the effects of pushing against the edges of a craniotomy can cause local pressure effects on the brain parenchyma, decreasing perfusion of those areas and causing new neurological damage. Either way, the general opinion is that a lot of the time, a decompressing craniotomy tends to improve the survival of people who will go on to have terrible neurological outcome, ensuring that the proportion of survivors with severe disability is higher.
Therapeutic hypothermia, in theory, has sounded like a good idea to some ICU specialists. Considering that it has been so popular for the management of brain injury which is global and ischaemic, why not apply it to the management of local traumatic brain injury?
Indeed there was enough interest in this to generate a whole flurry of trials, of which 23 or so were good enough to make it into a 2009 Cochrane review of hypothermia in traumatic brain injury. Even though the Brain Trauma Foundation recommend hypothermia as something one would at least consider, the Cochrane examiners were more conservative. They erred on the side of caution, and recommended nothing. One can suppose that this review was made with the benefit of two more years, and therefore a had better overview of this issue.
The Cochrane group alluded to the concept of bias by pointing out that hypothermia looked like a better treatment only in those trials which were poorly designed. However, there is still a consensus that fever is bad, and if you are not actively cooling these patients, at the very least you might want to maintain normothermia.
Though this is a controversial issue, it has recently been the subject of RCTs and therefore has and therefore has a good chance to appear in the exam (apart from the very generic Question 9 from the first paper of 2015). It has therefore earned a chapter all to itself ("Therapeutic and prophylactic hypothermia for traumatic brain injury").
A space occupying lesion is bad for intracranial pressure, and the more space it occupies, the badder it is. From this illiterate statement, it follows that measures taken early to reduce the ultimate size of an expanding haematoma should give rise to better ICP control and better neurological outcome. This was the rationale for the use of tranexamic acid in this population. Certainly, "hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage" according to the title of an article by Davis et al (2006), such that for every 1ml increase in haematoma size, the chance of sliding down another point of the modified Rankin scale increases by 6%. Unfortunately, the recent TICH-2 trial (Sprigg et al, 2018) did not demonstrate any mortality benefit or positive effect on neurological outcome. The investigators sabotaged their own results somewhat by enrolling patients who were going to die anyway (i.e. people with haematomas of more than 60ml). However, the haematoma rate of growth was ultiimately better in the treatment group, which was a pleasing cosmetic effect.
The only thing the Brain Trauma Foundation has Level 1 evidence for is a negative finding. We now know, thanks to the CRASH trial investigators, that steroids in traumatic brain injury decrease both short-term and long-term survival in brain injury patients. As to why, it is not entirely clear. Certainly not due to the risk of GI bleeding or infections, according to the authors.
In short, steroids = bad.
The perfusion of vulnerable salvageable brain tissue is the goal of secondary injury prevention, and so from this it logically follows that anything you can do to increase the oxygen carriage by the blood would be expected to have a salutary effect on TBI. This path of reasoning could lead the reader to accept a higher transfusion threshold for TBI patients, if they were the sort that might be easily seduced by the simplicity of numeric threshold values. Though broadly in trauma there appears to be a culture of resistance to mindless automatic blood administration, in the management of TBI this aversion seems to be suspended in a large group of practitioners. When East et al (2018) looked at this topic, they reported the results of a survey where clinicians were equally divided into those who would transfuse only above a haemoglobin of 70g/L (22%), above 80g/L (28%), above 90g/L (23%) and over 10g/L (27%). The BTF are silent on this matter, and royal societies are suitably vague (usually giving a range of 70-90g as a safe range of haemoglobin, and giving no specific recommendations). Certainly, it would not do to increase the haematocrit too much, as the increased viscosity of the blood might actually harm the perfusion. Moreover, one is reminded that the cells which are infused are stored cells, gross bloated zombie erythrocytes which barely carry any oxygen and which come suspended in a soup of their own metabolic wastes. It is therefore not surprising that the randomised controlled trials whcih have looked at this issue have determined that both anaemia and trasnfusion were associated with worse outcomes. Pending more data, this matter remains unresolved.