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Ketamine in TBIs

Is ketamine safe to use in TBI patients (or anyone with increased ICP)?

The usual answer is “heck no!”, but where does this come from, and is it true?

This week, Karl and I talk about the origin of this believe and the evidence behind the safety of ketamine in TBIs (and how it might actually improve outcome…)

Literature Referenced:

Original Lancet letter that started everything. Four cases of increased ICP after ketamine administration.

Evans, J., Rosen, M., Weeks, R., Wise, C. (1971). Ketamine in neurosurgical procedures. Lancet (London, England) 1(7688), 40-1. https://www.ncbi.nlm.nih.gov/pubmed/4099342

Additional case reports at the time.

Gardner, A., Olson, B., Lichticer, M. (1971). Cerebrospinal-fluid Pressure during Dissociative Anesthesia with Ketamine. Anesthesiology 35(2), 226-8. https://dx.doi.org/10.1097/00000542-197108000-00029

List, W., Crumrine, R., Cascorbi, H., Weiss, M. (1972). Increased Cerebrospinal Fluid Pressure after Ketamine Anesthesiology 36(1), 98-99. https://dx.doi.org/10.1097/00000542-197201000-00023

GANER, A., DANNEMILLER, F., DEAN, D. (1972). Intracranial Cerebrospinal Fluid Pressure in Man During Ketamine Anesthesia. Anesthesia & Analgesia 51(5), 741. https://dx.doi.org/10.1213/00000539-197209000-00019

SHAPIRO, H., WYTE, S., HARRIS, A. (1972). KETAMINE ANAESTHESIA IN PATIENTS WITH INTRACRANIAL PATHOLOGY BJA: British Journal of Anaesthesia 44(11), 1200-4. https://dx.doi.org/10.1093/bja/44.11.1200

Wyte, S., Shapiro, H., Turner, P., Harris, A. (1972). Ketamine-induced intracranial hypertension. Anesthesiology 36(2), 174-6. https://www.ncbi.nlm.nih.gov/pubmed/5059108

Gibbs, J. (1972). The effect of intravenous ketamine on cerebrospinal fluid pressure. British journal of anaesthesia 44(12), 1298-302. https://www.ncbi.nlm.nih.gov/pubmed/4650346

Animal study in pigs showing that ketamine reduces CBF.

Björkman, S., Akeson, J., Nilsson, F., Messeter, K., Roth, B. (1992). Ketamine and midazolam decrease cerebral blood flow and consequently their own rate of transport to the brain: an application of mass balance pharmacokinetics with a changing regional blood flow. Journal of pharmacokinetics and biopharmaceutics 20(6), 637-52. https://www.ncbi.nlm.nih.gov/pubmed/1302766

First well designed human trial of ketamine administration in humans with intracranial pathology (tumors and SAH). Showed a decrease in ICP and CBF.

Mayberg, T., Lam, A., Matta, B., Domino, K., Winn, H. (1995). Ketamine does not increase cerebral blood flow velocity or intracranial pressure during isoflurane/nitrous oxide anesthesia in patients undergoing craniotomy. Anesthesia and analgesia 81(1), 84-9. https://www.ncbi.nlm.nih.gov/pubmed/7598288

First human trial of ketamine in TBI patients.

Albanèse, J., Arnaud, S., Rey, M., Thomachot, L., Alliez, B., Martin, C. (1997). Ketamine decreases intracranial pressure and electroencephalographic activity in traumatic brain injury patients during propofol sedation. Anesthesiology 87(6), 1328-34. https://www.ncbi.nlm.nih.gov/pubmed/9416717

Meta-analyses/reviews demonstrating the safety of ketamine in neuro patients.

Zeiler, F., Teitelbaum, J., West, M., Gillman, L. (2014). The Ketamine Effect on ICP in Traumatic Brain Injury Neurocritical Care 21(1), 163-173. https://dx.doi.org/10.1007/s12028-013-9950-y

Wang, X., Ding, X., Tong, Y., Zong, J., Zhao, X., Ren, H., Li, Q. (2014). Ketamine does not increase intracranial pressure compared with opioids: meta-analysis of randomized controlled trials Journal of Anesthesia 28(6), 821-827. https://dx.doi.org/10.1007/s00540-014-1845-3

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.e2. https://dx.doi.org/10.1016/j.annemergmed.2014.06.018

Small study demonstrating ketamine reduces spreading depolarizations in neuro patients.

Sakowitz, O., Kiening, K., Krajewski, K., Sarrafzadeh, A., Fabricius, M., Strong, A., Unterberg, A., Dreier, J. (2009). Preliminary evidence that ketamine inhibits spreading depolarizations in acute human brain injury. Stroke 40(8), e519-22. https://dx.doi.org/10.1161/STROKEAHA.109.549303

Study of infants on cardiac bypass using MRI and serum markers to show reduced brain glutamate levels and neuroinflammatory products using ketamine .

Bhutta, A., Schmitz, M., Swearingen, C., James, L., Wardbegnoche, W., Lindquist, D., Glasier, C., Tuzcu, V., Prodhan, P., Dyamenahalli, U., Imamura, M., Jaquiss, R., Anand, K. (2012). Ketamine as a neuroprotective and anti-inflammatory agent in children undergoing surgery on cardiopulmonary bypass Pediatric Critical Care Medicine 13(3), 328-337. https://dx.doi.org/10.1097/PCC.0b013e31822f18f9

Study showing improved memory outcomes after CABG when using ketamine intraoperatively.

HUDETZ, J., IQL, Z., GANDHI, S., PATTERSON, K., BYE, A., HUDETZ, A., PAGEL, P., WARLTIER, D. (2009). Ketamine attenuates post‐operative cognitive dysfunction after cardiac surgery Acta Anaesthesiologica Scandinavica 53(7), 864-872. https://dx.doi.org/10.1111/j.1399-6576.2009.01978.x

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