Ketamine for Patients with Acute Brain Injury
Summary by Keith Andrews DO, 12.14.21
Background:
Ketamine has historically been avoided in patients with traumatic brain injury and/or concern for elevated ICP based on evidence from the 1970's from healthy patients that linked ketamine at induction doses with increased cerebral blood flow and increased ICP post induction, but without any detrimental effect long term. Since patients with trauma frequently would benefit from the hemodynamic stability typically offered by ketamine, there has been ongoing research to determine it's safety in TBI. Furthermore, it has been proposed that ketamine may actually be beneficial by reducing something called "spreading depolarizations" (SD), which are an EEG finding in TBI patients associated with poor outcomes.
Methods:
This paper is a retrospective review of current evidence regarding ketamine use and ICP, cerebral perfusion pressure, spreading depolarizations, and outcomes on patients with TBI who receive ketamine. Randomized trials, prospective trials, and retrospective trials were analyzed, and patients receiving ketamine for operative procedures without an element of TBI e.g. abdominal and heart surgery were excluded. After all this, they came up with 11 studies to include in the analysis. Unfortunately, most of these 11 were prospective trials and the authors caution that while they were of sound design, they were not blinded and thus prone to bias in analysis of data. Also there was very little standardization across these studies in terms of dosing, duration and measured data
Results:
In general, the results suggested that there probably is a slight increase in ICP following ketamine administration. However it is probably very transient, generally between 4 and 8 mm Hg, and is not associated with any difference in mortality or long term negative outcomes compared to patients who do not receive ketamine. Only one study demonstrated elevated cerebral perfusion pressure with ketamine administration, with an increase of 3.9 mmHg. It was unclear whether there is definitive benefit in reducing SD's, as one study suggested ketamine does reduce SD and theoretically can reduce brain damage, while another one showed it was equivocal. In that same vein, more data is needed to even elucidate the validity of SD as a marker of complications following TBI.
Discussion:
First off, there is a HUGE variance in ketamine dosing from these studies --anywhere between 0.3 mg / kg/h to 200 mg/h, some with boluses, some without-- so it is hard to make generalizations since we know that a sub anesthetic infusion is very different than a wallop induction dose of ketamine as a bolus. Plus, in all of these studies there were additional medications used such as fentanyl and propofol infusions, which have more clearly documented effects of CPP and ICP. The authors even admit that it is hard to draw many conclusions from their analyses given the small sample size (334 patients total) and relatively poor data collection. And yet they do conclude that "ketamine does not cause worse outcomes" but with the caveat that all this really shows is that we can't say for sure yet but more evidence is needed.
TLDR: the idea that ketamine is an absolute contraindication in TBI or circumstances where elevating ICP may be catastrophic is not based on robust or recent evidence. It seems likely that in the near future, the dogma that ketamine should never be used in a patient with concern for elevated ICP will be challenged further. However, at this time, there is not robust or recent evidence to prove that it is safe. Ongoing efforts are being made to demonstrate if it is, and if so, what kind of dosing may be safe. In the future, we may learn more about ketamine in TBI that will prove some benefit, but again, it's too early to draw that conclusion just yet.