Ketamine for Acute Agitation

  • Richard ChildersEmail author
  • Gary Vilke
Behavioral Health (L Zun, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Behavioral Health


Purpose of Review

This review describes the use of ketamine for acutely agitated patients in the emergency care setting. Evidence for its efficacy will be reviewed and practical suggestions for using ketamine in this scenario will be presented.

Recent Findings

The available observational literature on the topic of ketamine for agitation was recently summarized in a systematic review. This review found that ketamine effectively and quickly sedates acutely agitated patients. However, it did raise some concerns about an increased intubation rate in patients administered ketamine.


In severely agitated patients, particularly those presumed to be caused by stimulant drug use, who need immediate sedation to ensure the safety of the patient and staff, ketamine is a reasonable and safe choice. Emergency practitioners can consider giving ketamine 4-6 mg/kg IM (500 mg for most adults). Once given, it is important to closely monitor the patient for adverse effects and that the examination continue to determine the etiology of the patient’s agitation.


Ketamine Agitation Emergency services Pre-hospital 


Compliance With Ethical Standards

Conflict of Interest

Rich Childers, MD, has no conflict of interest. Gary Vilke, MD, occasionally serves as a paid legal consultant.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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

  1. 1.
    Lindenmayer JP. The pathophysiology of agitation. J Clin Psychiatry. 2000;61(Suppl 14):5–10.Google Scholar
  2. 2.
    Miner JR, Klein LR, Cole JB, Driver BE, Moore JC, Ho JD. The characteristics and prevalence of agitation in an urban county emergency department. Ann Emerg Med. 2018;72(4):361–70. Scholar
  3. 3.
    Maguire BJ, Smith S. Injuries and fatalities among emergency medical technicians and paramedics in the United States. Prehosp Disaster Med. 2013;28(4):376–82. Scholar
  4. 4.
    Wilson MP, Pepper D, Currier GW, Holloman GH Jr, Feifel D. The psychopharmacology of agitation: consensus statement of the american association for emergency psychiatry project Beta psychopharmacology workgroup. West J Emerg Med. 2012;13(1):26–34. Scholar
  5. 5.
    • Zaman H, Sampson SJ, Beck AL, Sharma T, Clay FJ, Spyridi S, et al. Benzodiazepines for psychosis-induced aggression or agitation. Cochrane Database Syst Rev. 2017;12:Cd003079. High-quality review of a class of medications commonly used for the treatment of acute agitation. Google Scholar
  6. 6.
    • Ostinelli EG, Brooke-Powney MJ, Li X, Adams CE. Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation). Cochrane Database Syst Rev. 2017;7:CD009377 High-quality review of a class of medications commonly used for the treatment of acute agitation. Google Scholar
  7. 7.
    Hatta K, Takahashi T, Nakamura H, Yamashiro H, Asukai N, Matsuzaki I, et al. The association between intravenous haloperidol and prolonged QT interval. J Clin Psychopharmacol. 2001;21(3):257–61.Google Scholar
  8. 8.
    Zun LS. Evidence-based review of pharmacotherapy for acute agitation. Part 1: onset of efficacy. J Emerg Med. 2018;54(3):364–74. Scholar
  9. 9.
    Vilke GM, DeBard ML, Chan TC, Ho JD, Dawes DM, Hall C, et al. Excited delirium syndrome (ExDS): defining based on a review of the literature. J Emerg Med. 2012;43(5):897–905. Scholar
  10. 10.
    Ho JD, Dawes DM, Nelson RS, Lundin EJ, Ryan FJ, Overton KG, et al. Acidosis and catecholamine evaluation following simulated law enforcement “use of force” encounters. Acad Emerg Med. 2010;17(7):e60–8. Scholar
  11. 11.
    Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Ann Emerg Med. 2011;57(5):449–61. Scholar
  12. 12.
    Mion G, Villevieille T. Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings). CNS Neurosci Ther. 2013;19(6):370–80. Scholar
  13. 13.
    Hax SD, Davis K, Stone B, Bledsoe B, Hodnick R. From the operating room to the streets: a comprehensive review of the most versatile item in your drug box. JEMS. 2017;42(2):44–9 63.Google Scholar
  14. 14.
    Ostinelli EG, Jajawi S, Spyridi S, Sayal K, Jayaram MB. Aripiprazole (intramuscular) for psychosis-induced aggression or agitation (rapid tranquillisation). Cochrane Database Syst Rev. 2018;8:Cd008074. Scholar
  15. 15.
    Du M, Wang X, Yin S, Shu W, Hao R, Zhao S, et al. De-escalation techniques for psychosis-induced aggression or agitation. Cochrane Database Syst Rev. 2017;4:Cd009922. Scholar
  16. 16.
    Khokhar MA, Rathbone J. Droperidol for psychosis-induced aggression or agitation. Cochrane Database Syst Rev. 2016;12:Cd002830. Scholar
  17. 17.
    Huf G, Alexander J, Gandhi P, Allen MH. Haloperidol plus promethazine for psychosis-induced aggression. Cochrane Database Syst Rev. 2016;11:Cd005146. Scholar
  18. 18.
    Ostinelli EG, Hussein M, Ahmed U, Rehman FU, Miramontes K, Adams CE. Risperidone for psychosis-induced aggression or agitation (rapid tranquillisation). Cochrane Database Syst Rev. 2018;10:Cd009412. Scholar
  19. 19.
    Miller D. Droperidol gets dropped - emergency physicians monthly. 2018.
  20. 20.
    Kishi T, Matsunaga S, Iwata N. Intramuscular olanzapine for agitated patients: a systematic review and meta-analysis of randomized controlled trials. J Psychiatr Res. 2015;68:198–209. Scholar
  21. 21.
    Thomas H Jr, Schwartz E, Petrilli R. Droperidol versus haloperidol for chemical restraint of agitated and combative patients. Ann Emerg Med. 1992;21(4):407–13.Google Scholar
  22. 22.
    •• Mankowitz SL, Regenberg P, Kaldan J, Cole JB. Ketamine for rapid sedation of agitated patients in the prehospital and emergency department settings: a systematic review and proportional meta-analysis. J Emerg Med. 2018. Systematic review regarding the use of ketamine for acute agitation.
  23. 23.
    Daniel J. Palin. IM ketamine is not a good first-line agent for severely agitated patients. New England Journal Of Medicine Journal Watch.
  24. 24.
    Martel M, Miner J, Fringer R, Sufka K, Miamen A, Ho J, et al. Discontinuation of droperidol for the control of acutely agitated out-of-hospital patients. Prehosp Emerg Care. 2005;9(1):44–8. Scholar
  25. 25.
    Riddell J, Tran A, Bengiamin R, Hendey GW, Armenian P. Ketamine as a first-line treatment for severely agitated emergency department patients. Am J Emerg Med. 2017;35(7):1000–4. Scholar
  26. 26.
    Cole JB, Moore JC, Nystrom PC, Orozco BS, Stellpflug SJ, Kornas RL, et al. A prospective study of ketamine versus haloperidol for severe prehospital agitation. Clin Toxicol (Phila). 2016;54(7):556–62. Scholar
  27. 27.
    Cole JB, Klein LR, Nystrom PC, Moore JC, Driver BE, Fryza BJ, et al. A prospective study of ketamine as primary therapy for prehospital profound agitation. Am J Emerg Med. 2018;36(5):789–96. Scholar
  28. 28.
    Strayer R. Jon Cole on ketamine for agitation. 2017.
  29. 29.
    Duncan R, Thakore S. Decreased Glasgow Coma Scale score does not mandate endotracheal intubation in the emergency department. J Emerg Med. 2009;37(4):451–5. Scholar
  30. 30.
    Frohlich J, Van Horn JD. Reviewing the ketamine model for schizophrenia. J Psychopharmacol. 2014;28(4):287–302. Scholar
  31. 31.
    Lahti AC, Koffel B, LaPorte D, Tamminga CA. Subanesthetic doses of ketamine stimulate psychosis in schizophrenia. Neuropsychopharmacology. 1995;13(1):9–19. Scholar
  32. 32.
    Lahti AC, Weiler MA, Tamara Michaelidis BA, Parwani A, Tamminga CA. Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology. 2001;25(4):455–67. Scholar
  33. 33.
    Breier A, Malhotra AK, Pinals DA, Weisenfeld NI, Pickar D. Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers. Am J Psychiatry. 1997;154(6):805–11. Scholar
  34. 34.
    Malhotra AK, Pinals DA, Adler CM, Elman I, Clifton A, Pickar D, et al. Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in neuroleptic-free schizophrenics. Neuropsychopharmacology. 1997;17(3):141–50. Scholar
  35. 35.
    Lahti AC, Warfel D, Michaelidis T, Weiler MA, Frey K, Tamminga CA. Long-term outcome of patients who receive ketamine during research. Biol Psychiatry. 2001;49(10):869–75.Google Scholar
  36. 36.
    Le Cong M, Gynther B, Hunter E, Schuller P. Ketamine sedation for patients with acute agitation and psychiatric illness requiring aeromedical retrieval. Emerg Med J. 2012;29(4):335–7. Scholar
  37. 37.
    McCloud TL, Caddy C, Jochim J, Rendell JM, Diamond PR, Shuttleworth C et al. Ketamine and other glutamate receptor modulators for depression in bipolar disorder in adults. Cochrane Database Syst Rev. 2015(9):Cd011611. doi:
  38. 38.
    Caddy C, Amit BH, McCloud TL, Rendell JM, Furukawa TA, McShane R et al. Ketamine and other glutamate receptor modulators for depression in adults. Cochrane Database Syst Rev. 2015(9):Cd011612. doi:
  39. 39.
    Loo CK, Katalinic N, Garfield JB, Sainsbury K, Hadzi-Pavlovic D, Mac-Pherson R. Neuropsychological and mood effects of ketamine in electroconvulsive therapy: a randomised controlled trial. J Affect Disord. 2012;142(1–3):233–40. Scholar
  40. 40.
    Sos P, Klirova M, Novak T, Kohutova B, Horacek J, Palenicek T. Relationship of ketamine’s antidepressant and psychotomimetic effects in unipolar depression. Neuro Endocrinol Lett. 2013;34(4):287–93.Google Scholar
  41. 41.
    Bellolio MF, Gilani WI, Barrionuevo P, Murad MH, Erwin PJ, Anderson JR, et al. Incidence of adverse events in adults undergoing procedural sedation in the emergency department: a systematic review and meta-analysis. Acad Emerg Med. 2016;23(2):119–34. Scholar
  42. 42.
    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. Scholar
  43. 43.
    Filanovsky Y, Miller P, Kao J. Myth: ketamine should not be used as an induction agent for intubation in patients with head injury. CJEM. 2010;12(2):154–7.Google Scholar
  44. 44.
    Himmelseher S, Durieux ME. Revising a dogma: ketamine for patients with neurological injury? Anesth Analg. 2005;101(2):524–34, table of contents. Scholar
  45. 45.
    Sehdev RS, Symmons DA, Kindl K. Ketamine for rapid sequence induction in patients with head injury in the emergency department. Emerg Med Australas. 2006;18(1):37–44. Scholar
  46. 46.
    Halstead SM, Deakyne SJ, Bajaj L, Enzenauer R, Roosevelt GE. The effect of ketamine on intraocular pressure in pediatric patients during procedural sedation. Acad Emerg Med. 2012;19(10):1145–50. Scholar
  47. 47.
    Drayna PC, Estrada C, Wang W, Saville BR, Arnold DH. Ketamine sedation is not associated with clinically meaningful elevation of intraocular pressure. Am J Emerg Med. 2012;30(7):1215–8. Scholar
  48. 48.
    Blumberg D, Congdon N, Jampel H, Gilbert D, Elliott R, Rivers R, et al. The effects of sevoflurane and ketamine on intraocular pressure in children during examination under anesthesia. Am J Ophthalmol. 2007;143(3):494–9. Scholar
  49. 49.
    Green SM, Andolfatto G. Let’s “take ‘em down” with a ketamine blow dart. Ann Emerg Med. 2016;67(5):588–90. Scholar
  50. 50.
    Green SM, Johnson NE. Ketamine sedation for pediatric procedures: part 2, review and implications. Ann Emerg Med. 1990;19(9):1033–46.Google Scholar
  51. 51.
    Burnett AM, Peterson BK, Stellpflug SJ, Engebretsen KM, Glasrud KJ, Marks J, et al. The association between ketamine given for prehospital chemical restraint with intubation and hospital admission. Am J Emerg Med. 2015;33(1):76–9. Scholar
  52. 52.
    Olives TD, Nystrom PC, Cole JB, Dodd KW, Ho JD. Intubation of profoundly agitated patients treated with prehospital ketamine. Prehosp Disaster Med. 2016;31(6):593–602. Scholar
  53. 53.
    Isbister GK, Calver LA, Downes MA, Page CB. Ketamine as rescue treatment for difficult-to-sedate severe acute behavioral disturbance in the emergency department. Ann Emerg Med. 2016;67(5):581–7.e1. Scholar
  54. 54.
    Hampson-Evans D, Morgan P, Farrar M. Pediatric laryngospasm. Paediatr Anaesth. 2008;18(4):303–7. Scholar
  55. 55.
    Green SM, Roback MG, Krauss B, Brown L, McGlone RG, Agrawal D, et al. Predictors of airway and respiratory adverse events with ketamine sedation in the emergency department: an individual-patient data meta-analysis of 8,282 children. Ann Emerg Med. 2009;54(2):158–68.e1–4. Scholar
  56. 56.
    Cohen VG, Krauss B. Recurrent episodes of intractable laryngospasm during dissociative sedation with intramuscular ketamine. Pediatr Emerg Care. 2006;22(4):247–9. Scholar
  57. 57.
    Larson CP Jr. Laryngospasm–the best treatment. Anesthesiology. 1998;89(5):1293–4.Google Scholar
  58. 58.
    Nazarian DJ, Broder JS, Thiessen MEW, Wilson MP, Zun LS, Brown MD. Clinical policy: critical issues in the diagnosis and management of the adult psychiatric patient in the emergency department. Ann Emerg Med. 2017;69(4):480–98. Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Emergency MedicineUniversity of California at San Diego Medical CenterSan DiegoUSA

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