There have long been concerns for increases in ICP with the administration of ketamine. These increases were described in the Neurosurgery and Neuroanesthesia literature primarily in patients usually with CSF outflow obstruction undergoing elective neurosurgical procedures. In the time since these articles were published, the use of ketamine in a wide variety of patients with neurologic conditions has been reported. Indeed, there have been a couple of recent systematic reviews that aimed to synthesize the available literature. These systematic reviews have essentially analyzed all the same existing literature (which is generally poor in quality).

Here are a couple worth looking at along with some quotes from their conclusions:

Zeiler, F., Teitelbaum, J., West, M., & Gilman, L. M. (2014) The Ketamine Effect on ICP in Traumatic Brain Injury. Neurocritical Care. 21 (1). 163-173

"when utilized in bolus dosing, ketamine seems to provide a dramatic decrease in ICP, whether at baseline or during an episode of ICP elevation. This further highlights the lack of an uncontrolled ICP increase with ketamine, on contrary to previous thoughts. However, again these patients were on background sedatives, and the effect of ketamine bolus in isolation is unknown. It could be postulated that if pCO2 was controlled by mechanical ventilation, that bolus ketamine in isolation would be well tolerated without ICP fluctuations. Finally, the use of ketamine in severe TBI patients that are sedated and ventilated has little serious adverse effects, as demonstrated by the lack of complications identified in our review"

Chang, L. C., Raty, S. R., Ortiz, J., Bailard, N. S., & Mathew, S. J. (2013). The Emerging Use of Ketamine for Anesthesia and Sedation in Traumatic Brain Injuries. CNS Neuroscience & Therapeutics, 19(6), 390–395. doi:10.1111/cns.12077

"In conclusion, while there are promising signs that the use of ketamine during TBI procedures may increase in the future, the data are too sparse to provide firm guidance at this time. As discussed, studies examining the use of ketamine for induction, maintenance, and sedation in patients with TBI have had promising results. The use of ketamine in a controlled ventilation setting and in combination with other sedative agents has demonstrated no increase in ICP, which is the major concern of anesthesiologists regarding ketamine for patients with TBI."

Cohen, L., Athaide, V., Wickham, M., Doyle-Waters, M., Rose, N., & Hohl, C. (2015) The Effect of Ketamine on Intracranial and Cerebral Perfusion Pressure and Health Outcomes: A Systematic Review. Annals of Emergency Medicine. 65 (1). 43-51. doi:10.1016/j.annemergmed.2014.06.018

"The use of ketamine as an induction agent for rapid sequence intubation in undifferentiated critically ill patients in whom neurologic injury has not been ruled out remains an important point of debate for emergency physicians: Researchers have established a strong association between the degree and duration of hypotension and neurologic outcomes in patients with traumatic brain injury. Therefore, clinicians generally avoid using induction agents that cause or may exacerbate preexisting hemodynamic instability such as the opioids, propofol, or benzodiazepines in this population."

and from their limitations section:

"The quality of reporting for most studies was modest. We were able to classify only 1 of the 9 reviewed studies as low risk for bias in all quality domains. None of the other studies reported optimal methods to randomize patients, conceal treatment allocation, or ensure blinding of study participants, treating personnel, and outcomes assessors. Only 1 randomized trial reported a sample size calculation, and none for the study outcomes we were interested in. Therefore, our finding of no difference between ketamine and the comparator induction agents may be the result of lack of power of the individual studies to detect a difference. Accordingly, the results presented in our review should be interpreted with caution."

There is a lack of literature addressing a patient population that is keenly interesting to prehospital providers, EM, and ICU practitioners alike: the moderate to severe TBI patient in need of RSI. To help sort through the choice of induction agent in these patients (and post-intubation sedation), we invited Dr. Ketaminh himself, Minh Le Cong to engage in a spirited discussion of the literature with our own Dr. Chris Zammit (himself an EM-Neurointensivist and author of this blog post that started the debate). To preface their verbal sparing, Critical Care PharmD Chris Droege joined us to give some excellent background on ketamine and its pharmacology.

Listen to the podcast and let us know what you think in the comments!