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Ketamine in Modern Neuroanesthesia Practice

  • Neuroanesthesia (D Sharma, Section Editor)
  • Published:
Current Anesthesiology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Ketamine has a number of clinical uses and properties that suggest a role for the drug in neuroanestheisa practice. “Dogma” and “myths” persist with regard to its effects on cerebral hemodynamics and intracranial pressure which have limited its use in Neuroanesthesia and care of the critically ill brain-injured patient. This review aims to educate the clinician on the possible role of ketamine in modern neuroanesthesia practice.

Recent Findings

A number of systemic reviews support the use of ketamine in patients with acute brain injury and raised intracranial pressure (ICP). Pre-clinical work suggests that ketamine may have mechanisms of action compatible with neuroprotection including modifying glutamate excitatory-driven mechanisms of brain injury. There is emerging clinical evidence to suggest that ketamine may inhibit spreading depolarizations (SDs), a cortical electrical phenomenon associated with brain injury.

Summary

Ketamine is no longer contraindicated in the care of the brain-injured patient, and its properties of potent analgesia, dissociative anesthesia, and minimal effects on both the hemodynamic and respiratory system are being utilized in the pre-hospital and emergency room setting. Good grade data on meaningful clinical outcomes is presently lacking to support the use of ketamine as a drug with neuroprotection properties but is an area of ongoing interest.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Domino EF. Taming the ketamine tiger. 1965. Anesthesiology. 2010;113(3):678–84. https://doi.org/10.1097/ALN.0b013e3181ed09a2.

    Article  PubMed  Google Scholar 

  2. White PF, Way WL, Trevor AJ. Ketamine--its pharmacology and therapeutic uses. Anesthesiology. 1982;56(2):119–36. https://doi.org/10.1097/00000542-198202000-00007.

    Article  CAS  PubMed  Google Scholar 

  3. • Green SM, Johnson NE. Ketamine sedation for pediatric procedures: Part 2, Review and implications. Ann Emerg Med. 1990;19(9):1033–46. https://doi.org/10.1016/s0196-0644(05)82569-7Editorial by an Emergency Medicine Physician critical of Anesthesiologists for adopting the dogma that ketamine is contraindicated in patients with raised ICP.

    Article  CAS  PubMed  Google Scholar 

  4. Zietlow J, Berns K, Jenkins D, Zietlow S. Prehospital use of ketamine: effectiveness in critically ill and injured patients. Mil Med. 2019;184(Suppl 1):542–4. https://doi.org/10.1093/milmed/usy422.

    Article  PubMed  Google Scholar 

  5. Anis NA, Berry SC, Burton NR, Lodge D. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol. 1983;79(2):565–75. https://doi.org/10.1111/j.1476-5381.1983.tb11031.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Himmelseher S, Durieux ME. Revising a dogma: ketamine for patients with neurological injury? Anesth Analg. 2005;101(2):524–34, table of contents. https://doi.org/10.1213/01.ANE.0000160585.43587.5B.

    Article  CAS  PubMed  Google Scholar 

  7. Chang LC, Raty SR, Ortiz J, Bailard NS, Mathew SJ. The emerging use of ketamine for anesthesia and sedation in traumatic brain injuries. CNS Neurosci Ther. 2013;19(6):390–5. https://doi.org/10.1111/cns.12077.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. • Bell JD. In Vogue: Ketamine for neuroprotection in acute neurologic injury. Anesth Analg. 2017;124(4):1237–43. https://doi.org/10.1213/ANE.0000000000001856An up to date summary of the possible mechanisms of neuroprotection by Ketamine.

    Article  CAS  PubMed  Google Scholar 

  9. •• Gregers MCT, Mikkelsen S, Lindvig KP, Brøchner AC. Ketamine as an anesthetic for patients with acute brain injury: a systematic review. Neurocrit Care. 2020;33(1):273–82. https://doi.org/10.1007/s12028-020-00975-7Most up to date systemic review of studies supporting the safe use of Ketamine in patients with brain injury.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. • Godoy DA, Badenes R, Pelosi P, Robba C. Ketamine in acute phase of severe traumatic brain injury “an old drug for new uses?”. Crit Care. 2021;25(1):19. https://doi.org/10.1186/s13054-020-03452-xDiscusses the potential benefits and pitfalls of Ketamine use in TBI patients.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Takeshita H, Okuda Y, Sari A. The effects of ketamine on cerebral circulation and metabolism in man. Anesthesiology. 1972 Jan;36(1):69–75. https://doi.org/10.1097/00000542-197201000-00013.

    Article  CAS  PubMed  Google Scholar 

  12. Långsjö JW, Maksimow A, Salmi E, Kaisti K, Aalto S, Oikonen V, et al. S-ketamine anesthesia increases cerebral blood flow in excess of the metabolic needs in humans. Anesthesiology. 2005 Aug;103(2):258–68. https://doi.org/10.1097/00000542-200508000-00008.

    Article  PubMed  Google Scholar 

  13. Zeiler FA, Sader N, Gillman LM, Teitelbaum J, West M, Kazina CJ. The Cerebrovascular response to ketamine: a systematic review of the animal and human literature. J Neurosurg Anesthesiol. 2016 Apr;28(2):123–40. https://doi.org/10.1097/ANA.0000000000000234.

    Article  PubMed  Google Scholar 

  14. Shaprio HM, Wyte SR, Harris AB. Ketamine anaesthesia in patients with intracranial pathology. Br J Anaesth. 1972 Nov;44(11):1200–4. https://doi.org/10.1093/bja/44.11.1200.

    Article  CAS  PubMed  Google Scholar 

  15. Sari A, Okuda Y, Takeshita H. The effect of ketamine on cerebrospinal fluid pressure. Anesth Analg. 1972 Jul-Aug;51(4):560–5.

    Article  CAS  Google Scholar 

  16. Cohen L, Athaide V, Wickham ME, Doyle-Waters MM, Rose NG, Hohl CM. The effect of ketamine on intracranial and cerebral perfusion pressure and health outcomes: a systematic review. Ann Emerg Med. 2015;65(1):43–51.e2. https://doi.org/10.1016/j.annemergmed.2014.06.018.

    Article  PubMed  Google Scholar 

  17. Loflin R, Koyfman A. When used for sedation, does ketamine increase intracranial pressure more than fentanyl or sufentanil? Ann Emerg Med. 2015 Jan;65(1):55–6. https://doi.org/10.1016/j.annemergmed.2014.08.017.

    Article  PubMed  Google Scholar 

  18. Bar-Joseph G, Guilburd Y, Tamir A, Guilburd JN. Effectiveness of ketamine in decreasing intracranial pressure in children with intracranial hypertension. J Neurosurg Pediatr. 2009 Jul;4(1):40–6. https://doi.org/10.3171/2009.1.PEDS08319.

    Article  PubMed  Google Scholar 

  19. Zeiler FA, Teitelbaum J, West M, Gillman LM. The ketamine effect on ICP in traumatic brain injury. Neurocrit Care. 2014 Aug;21(1):163–73. https://doi.org/10.1007/s12028-013-9950-y.

    Article  CAS  PubMed  Google Scholar 

  20. Carlson AP, Abbas M, Alunday RL, Qeadan F, Shuttleworth CW. Spreading depolarization in acute brain injury inhibited by ketamine: a prospective, randomized, multiple crossover trial. J Neurosurg. 2018. https://doi.org/10.3171/2017.12.JNS171665.

  21. Telles JPM, Welling LC, Coelho ACSDS, Rabelo NN, Teixeira MJ, Figueiredo EG. Cortical spreading depolarization and ketamine: a short systematic review. Neurophysiol Clin. 2021;51(2):145–51. https://doi.org/10.1016/j.neucli.2021.01.004.

    Article  PubMed  Google Scholar 

  22. Zeiler FA, Teitelbaum J, Gillman LM, West M. NMDA antagonists for refractory seizures. Neurocrit Care. 2014 Jun;20(3):502–13. https://doi.org/10.1007/s12028-013-9939-6.

    Article  CAS  PubMed  Google Scholar 

  23. Alkhachroum A, Der-Nigoghossian CA, Mathews E, Massad N, Letchinger R, Doyle K, et al. Ketamine to treat super-refractory status epilepticus. Neurology. 2020;95(16):e2286–94. https://doi.org/10.1212/WNL.0000000000010611.

    Article  CAS  PubMed  Google Scholar 

  24. Hudetz JA, Patterson KM, Iqbal Z, Gandhi SD, Byrne AJ, Hudetz AG, et al. Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2009 Oct;23(5):651–7. https://doi.org/10.1053/j.jvca.2008.12.021.

    Article  CAS  PubMed  Google Scholar 

  25. Rascón-Martínez DM, Fresán-Orellana A, Ocharán-Hernández ME, Genis-Zarate JH, Castellanos-Olivares A. The effects of ketamine on cognitive function in elderly patients undergoing ophthalmic surgery: a pilot study. Anesth Analg. 2016;122(4):969–75. https://doi.org/10.1213/ANE.0000000000001153.

    Article  CAS  PubMed  Google Scholar 

  26. •• Avidan MS, Maybrier HR, Abdallah AB, Jacobsohn E, Vlisides PE, Pryor KO, et al. PODCAST Research Group. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet. 2017;390(10091):267–75. https://doi.org/10.1016/S0140-6736(17)31467-8Large prospective multi centered pragmatic trial that was not able to demonstrate any benefit of ketamine in preventing delirium in surgical patients.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Eikermann M, Grosse-Sundrup M, Zaremba S, Henry ME, Bittner EA, Hoffmann U, et al. Ketamine activates breathing and abolishes the coupling between loss of consciousness and upper airway dilator muscle dysfunction. Anesthesiology. 2012;116(1):35–46. https://doi.org/10.1097/ALN.0b013e31823d010a.

    Article  CAS  PubMed  Google Scholar 

  28. Torres AC, Bebarta VS, April MD, Maddry JK, Herson PS, Bebarta EK, et al. Ketamine administration in prehospital combat injured patients with traumatic brain injury: a 10-year report of survival. Cureus. 2020;12(7):e9248. https://doi.org/10.7759/cureus.9248.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Morgan MM, Perina DG, Acquisto NM, Fallat ME, Gallagher JM, Brown KM, et al. Ketamine use in prehospital and hospital treatment of the acute trauma patient: a joint position statement. Prehosp Emerg Care. 2020 Aug;27:1–5. https://doi.org/10.1080/10903127.2020.1801920.

    Article  Google Scholar 

  30. Bhardwaj A, Panda N, Chauhan R, Bloria SD, Bharti N, Bhagat H, et al. Comparison of ketofol (combination of ketamine and propofol) and propofol anesthesia in aneurysmal clipping surgery: a prospective randomized control trial. Asian J Neurosurg. 2020;15(3):608–13. https://doi.org/10.4103/ajns.AJNS_346_19.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Mayberg TS, Lam AM, Matta BF, Domino KB, Winn HR. Ketamine does not increase cerebral blood flow velocity or intracranial pressure during isoflurane/nitrous oxide anesthesia in patients undergoing craniotomy. Anesth Analg. 1995 Jul;81(1):84–9. https://doi.org/10.1097/00000539-199507000-00017.

    Article  CAS  PubMed  Google Scholar 

  32. • Loftus RW, Yeager MP, Clark JA, Brown JR, Abdu WA, Sengupta DK, et al. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology. 113(3):639–46. https://doi.org/10.1097/ALN.0b013e3181e90914Ketamine reduces opiate consumption in opiate-dependent patients with chronic pain after spine surgery.

  33. Dagal A, Bellabarba C, Bransford R, Zhang F, Chesnut RM, O'Keefe GE, et al. Enhanced perioperative care for major spine surgery. Spine (Phila Pa 1976). 2019;44(13):959–66. https://doi.org/10.1097/BRS.0000000000002968.

    Article  Google Scholar 

  34. Maheshwari K, Avitsian R, Sessler DI, Makarova N, Tanios M, Raza S, et al. Multimodal analgesic regimen for spine surgery: a randomized placebo-controlled trial. Anesthesiology. 2020;132(5):992–1002. https://doi.org/10.1097/ALN.0000000000003143.

    Article  PubMed  Google Scholar 

  35. Gamble JJ, Bi H, Bowen R, Weisgerber G, Sanjanwala R, Prasad R, et al. Ketamine-based anesthesia improves electroconvulsive therapy outcomes: a randomized-controlled study. Can J Anaesth. 2018;65(6):636–46. English. https://doi.org/10.1007/s12630-018-1088-0.

    Article  PubMed  Google Scholar 

  36. Zhang M, Rosenheck R, Lin X, Li Q, Zhou Y, Xiao Y, et al. A randomized clinical trial of adjunctive ketamine anesthesia in electro-convulsive therapy for depression. J Affect Disord. 2018 Feb;227:372–8. https://doi.org/10.1016/j.jad.2017.11.034.

    Article  CAS  PubMed  Google Scholar 

  37. Carspecken CW, Borisovskaya A, Lan ST, Heller K, Buchholz J, Ruskin D, et al. Ketamine anesthesia does not improve depression scores in electroconvulsive therapy: a randomized clinical trial. J Neurosurg Anesthesiol. 2018 Oct;30(4):305–13. https://doi.org/10.1097/ANA.0000000000000511.

    Article  PubMed  Google Scholar 

  38. Mashour GA, Ben Abdallah A, Pryor KO, El-Gabalawy R, Vlisides PE, Jacobsohn E, et al. Avidan MS; PODCAST Research Group. Intraoperative ketamine for prevention of depressive symptoms after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Br J Anaesth. 2018;121(5):1075–83. https://doi.org/10.1016/j.bja.2018.03.030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to David R Wright.

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Wright, D.R. Ketamine in Modern Neuroanesthesia Practice. Curr Anesthesiol Rep 11, 189–194 (2021). https://doi.org/10.1007/s40140-021-00465-2

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