Traumatic brain injury and ketamine: Another bubbe meisa?
Vanessa Mazandi, MD and Justin L. Lockman, MD, MSEd
Over the past year, we’ve challenged a variety of anesthetic beliefs, really dogmas instilled in us by our founding fathers/mothers/teachers/textbooks in the Pediatric Anesthesia Article of the Day. many of which lack significant evidence for their benefit. These myths, or bubbe meises, (“old wives’ tales”) include long fasting (NPO) times for clears and breast milk before surgery, the use of cricoid pressure during rapid sequence intubation, and today, the fear of using ketamine in patients with, or at risk of developing, increased intracranial pressure (ICP). Despite decades of research and clinical practice guidelines in increased ICP management, I think many of you will be as surprised as I was in reading today’s PAAD at the paucity of evidence demonstrating which sedatives and analgesics are the best choice in the management of traumatic brain injury. Our reviewers are Justin Lockman, the PAAD’s ICU editor, and his fellow and mentee Vanessa Mazandi. As a rule, the executive council of the PAAD has decided to avoid having resident or fellow authorship of the PAADs. Because Vanessa is in the quadruple board process (pediatrics, anesthesia, pediatric anesthesia and pediatric critical care medicine), I decided to make an exception today. I think you’ll all agree that it was a wise decision. Myron Yaster MD
Jeffcote T, Weir T, Anstey J, McNamara R, Bellomo R, Udy A. The Impact of Sedative Choice on Intracranial and Systemic Physiology in Moderate to Severe Traumatic Brain Injury: A Scoping Review. J Neurosurg Anesthesiol. Feb 10 2022. PMID 35142704
When I (VM) was a pediatrics resident, I came away from my PICU rotation with two pearls: 1) between mask ventilation and intubation, the former is the more important skill and 2): don’t use ketamine when you’re worried about intracranial pressure (ICP). Like most trainees and many faculty, I trusted that the textbooks and teachings were right. Later, in my anesthesia residency, I only rarely used ketamine for induction of anesthesia in adults (propofol and phenylephrine make for nice companions); it wasn’t until I started PICU fellowship at CHOP that my perspective changed. First, I participated in a simulation for a patient with traumatic brain injury and was shocked (yes, Myron, think: Claude Raines “I’m shocked, just shocked that gambling is going on here!”) when during the debriefing from one of our brilliant neurointensivists, the feedback was that for induction I should have used ketamine. How was it that I’d “missed the memo” on ketamine?
Soon after the start of my PICU fellowship, one of my mentors – by way of the Myron Yaster School of Pediatric Anesthesia – Justin Lockman, pointed me towards old articles from the 1970s that gave ketamine its initial bad rap. In all of them, there were issues. The sample sizes were small and many were case reports,1 some patients had fixed obstructive hydrocephalus that required frequent drainage to reduce intracranial hypertension prior to induction with ketamine.2 In one of the “larger” of these studies (n=11), even when ICP was noted to go up, it didn’t go up much, and mean arterial blood pressures went up more, indicating preservation of and even improved cerebral perfusion pressure.3
Today’s PAAD is a scoping review of sedative medication use in the setting of moderate to severe traumatic brain injury. The authors included a total of 40 articles, which were mostly randomized controlled trials as well as observational and retrospective trials. All studies looked at patients 18 years of age and older who were in an ICU setting for moderate to severe TBI. The primary outcome was effect of the sedative/analgesics on ICP. Secondary outcomes included medication effects on cerebral perfusion pressure (CPP), cerebral autoregulation, markers of cerebral metabolism, cerebral biomarkers used in TBI (such as S100B), mean arterial pressure, heart rate, delirium, mortality and neurologic outcome. The results were presented based on medication and included opioids, benzodiazepines, propofol and ketamine.
Despite the weak evidence, ketamine’s contraindication for patients with intracranial hypertension has been dogmatically taught for 50 years. However, this review examined studies that included ketamine and ketamine versus other medications and did not find any harm in TBI patients who received ketamine. Of the studies that examined ketamine’s effects alone, the studies were not as robust (median size 10); however, one that looked at bolus doses of ketamine noted a decrease in ICP without altering CPP, jugular venous oxygen saturation or middle cerebral artery flow velocity.
Studies that compared ketamine versus other drugs had a larger sample size (sample size range 24 to 115 patients) and while they revealed no significant differences between ketamine and benzodiazepines or opioids, one study found decreased cortical spreading depolarizations in patients with TBI who had ketamine infusions compared to midazolam, boosting ketamine’s reputation as an anti-epileptic agent and as protective following TBI. Due to exclusion of studies in patients < 18 years of age, one of the more compelling studies examining ketamine sedation was not included in this review. Bar-Joseph4 looked at bolus doses of ketamine in 30 critically-ill children with invasive ICP monitors in place who received ketamine either prior to a noxious intervention (e.g., suctioning the ETT) or for sustained ICP > 18 mmHg. In both groups, ketamine prevented spikes in ICP; it also led to a decrease in ICP by 33% in the latter (those with sustained ICP > 18 mmHg) group.
As Kinoshita5 explains in his review of the pathophysiology of traumatic brain injury, with blood pressure spikes, the concomitant rise in cerebral perfusion pressure causes autoregulatory cerebral vasoconstriction. This lowers cerebral blood volume, which lowers ICP, which may be why in certain patients, ketamine is associated with a decrease in ICP. In contrast, allowing systemic blood pressure to fall by using other agents such as opioids causes a drop in cerebral perfusion pressure with reactive cerebral vasodilation; the resultant increase in cerebral blood volume increases ICP – exactly what we’re looking to avoid! Additionally, in reference to the Bar-Joseph study where ketamine was found to lower ICP in 33% of those who received it, this most likely has to do with the level of sedation providers felt comfortable providing in TBI patients – you can imagine a scenario where a patient may cough or gag due to inadequate sedation resulting from rightful concern of dropping CPP with an agent such as propofol.
Mental simulations of physiology like these assume that autoregulation is still intact, which may be erroneous thinking in patients with severe TBI (at least regionally). Clearly, more investigation and larger studies, are needed – not just to undo dogmatic fears of ketamine, but to establish best practice for these patients. For several years now at CHOP, we have used ketamine as the drug of choice for children with intracranial hypertension in the ED, PICU, and OR, and we are in the process of publishing our data. In the meantime, the publicly-available CHOP Clinical Pathway for Severe TBI (available here) list ketamine as one of the two preferred induction drugs for the airway management subsection (as seen here); the other drug is etomidate. We’d love to know what your practice is, and whether this discussion has changed your mind. Please post your thoughts in the chat! - Vanessa Mazandi, MD and Justin L. Lockman, MD, MSEd
1. Wyte SR, Shapiro HM, Turner P, Harris AB. Ketamine-induced intracranial hypertension. Anesthesiology. Feb 1972;36(2):174-176.
2. List WF, Crumrine RS, Cascorbi HF, Weiss MH. Increased cerebrospinal fluid pressure after ketamine. Anesthesiology. Jan 1972;36(1):98-99.
3. Gibbs JM. The effect of intravenous ketamine on cerebrospinal fluid pressure. Br J Anaesth. Dec 1972;44(12):1298-1302.
4. Bar-Joseph G, Guilburd Y, Tamir A, Guilburd JN. Effectiveness of ketamine in decreasing intracranial pressure in children with intracranial hypertension. J Neurosurg Pediatr. Jul 2009;4(1):40-46.
5. Kinoshita K. Traumatic brain injury: pathophysiology for neurocritical care. J Intensive Care. 2016;4:29.