The effective dose of ketamine in the management of acute agitation in emergency departments

Ketamine therapy is considered a novel treatment for agitation. Ketamine has a rapid onset and short half-life, can be administered in various formulations, and delivers sedation reliably with a single dose. However, providing a well-defined dose of ketamine for acute agitation, particularly as an intravenous (IV) bolus, is questionable. This study aims to define an effective dose of ketamine for treating acute agitation in the emergency department (ED). A multi-center retrospective observational study was conducted from June 2015 to March 2022 to examine agitated patients presented to four EDs in Saudi Arabia and were administered ketamine as the initial calming medication. The study included a total of 20 patients, most of whom were males (70%) in their adult ages (65%) who were mainly presented to the ED with behavioral, cognitive or psychiatric disorders (55%). Only six patients (28.6%) needed an additional calming agent. The 50 mg IV bolus was the most common initial (n = 6) and cumulative (n = 5) fixed dose and achieved a success rate of 66.7% in both doses. The most common initial weight-based dose was 0.5 mg/kg in 7 cases (71.4% success rate), followed by 0.7–0.8 mg/kg in 6 cases (66.7% success rate). Meanwhile, the doses 0.5 mg/kg in 6 cases (83.3% success rate) and 0.7–0.8 mg/kg in 6 cases (66.7% success rate) were major cumulative weight-based doses. The results were interpreted using descriptive statistics. Overall, ketamine showed neutral effects on the respiratory and cardiac markers. It is seldom used as an initial medication for acute agitation in the ED. A starting dose of 0.5–1 mg/kg or 50 mg of ketamine as an IV bolus injection showed reasonable effectiveness and appropriate safe properties in calming agitated patients in the ED.

Ketamine; Agitation; Emergency; Dose; Medication

[1] Gonin P, Beysard N, Yersin B, Carron P. Excited delirium: a systematic review. Academic Emergency Medicine. 2017; 25: 552–565.

[2] Knott JC, Bennett D, Rawet J, Taylor DM. Epidemiology of unarmed threats in the emergency department. Emergency Medicine Australasia. 2005; 17: 351–358.

[3] Tadros A, Kiefer C. Violence in the emergency department. Psychiatric Clinics of North America. 2017; 40: 575–584.

[4] American College of Emergency Physicians Excited Delirium Task Force. White paper report on excited delirium syndrome. 2009. Available at: https://www.prisonlegalnews.org/media/publications/acep_report_on_excited_delirium_syndrome_sept_2009.pdf (Accessed: 02 July 2023).

[5] Vilke GM, Payne-James J, Karch SB. Excited delirium syndrome (ExDS): redefining an old diagnosis. Journal of Forensic and Legal Medicine. 2012; 19: 7–11.

[6] Lipsedge M. Excited delirium: a psychiatric review. Medicine, Science and the Law. 2016; 56: 121–127.

[7] Wong AH, Ray JM, Cramer LD, Brashear TK, Eixenberger C, McVaney C, et al. Design and implementation of an agitation code response team in the emergency department. Annals of Emergency Medicine. 2022; 79: 453–464.

[8] Hopper AB, Vilke GM, Castillo EM, Campillo A, Davie T, Wilson MP. Ketamine use for acute agitation in the emergency department. The Journal of Emergency Medicine. 2015; 48: 712–719.

[9] Jamal SM, Fathil SM, Nidzwani MM, Ismail AK, Yatim FM. Intravenous ketamine is as effective as midazolam/fentanyl for procedural sedation and analgesia in the emergency department. The Medical journal of Malaysia. 2011; 66: 231–233.

[10] Sih K, Campbell SG, Talion JM, Magee K, Zed PJ. Ketamine in adult emergency medicine: controversies and recent advances. Annals of Pharmacotherapy. 2011; 45: 1525–1534.

[11] Burnett A, Panchal D, Peterson B, Ernest E, Griffith K, Frascone RJ, et al. The administration of prehospital ketamine for chemical restraint does not prolong on-scene times compared to Haloperidol based sedation. Australasian Journal of Paramedicine. 2015; 12: 1–7.

[12] Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Annals of Emergency Medicine. 2011; 57: 449–461.

[13] Goddard K, Sampson C, Bedy S, Ghadban R, Stilley J. Effect of ketamine on cardiovascular function during procedural sedation of adults. Cureus. 2021; 13: e14228.

[14] Riddell J, Tran A, Bengiamin R, Hendey GW, Armenian P. Ketamine as a first-line treatment for severely agitated emergency department patients. The American Journal of Emergency Medicine. 2017; 35: 1000–1004.

[15] Kurdi M, Theerth K, Deva R. Ketamine: current applications in anesthesia, pain, and critical care. Anesthesia: Essays and Researches. 2014; 8: 283.

[16] Sullivan N, Chen C, Siegel R, Ma Y, Pourmand A, Montano N, et al. Ketamine for emergency sedation of agitated patients: a systematic review and meta-analysis. The American Journal of Emergency Medicine. 2020; 38: 655–661.

[17] Lin J, Figuerado Y, Montgomery A, Lee J, Cannis M, Norton VC, et al. Efficacy of ketamine for initial control of acute agitation in the emergency department: a randomized study. The American Journal of Emergency Medicine. 2021; 44: 306–311.

[18] Sheikh S, Hendry P. The expanding role of ketamine in the emergency department. Drugs. 2018; 78: 727–735.

[19] Kim HK, Leonard JB, Corwell BN, Connors NJ. Safety and efficacy of pharmacologic agents used for rapid tranquilization of emergency department patients with acute agitation or excited delirium. Expert Opinion on Drug Safety. 2021; 20: 123–138.

[20] Gottlieb M, Long B, Koyfman A. Approach to the agitated emergency department patient. The Journal of Emergency Medicine. 2018; 54: 447–457.

[21] Mo H, Campbell MJ, Fertel BS, Lam SW, Wells EJ, Casserly E, et al. Ketamine safety and use in the emergency department for pain and agitation/delirium: a health system experience. Western Journal of Emergency Medicine. 2020; 21: 272–281.

[22] Yildiz A. Pharmacological management of agitation in emergency settings. Emergency Medicine Journal. 2003; 20: 339–346.

[23] Wilson M, Pepper D, Currier G, Holloman G, Feifel D. The psychopharmacology of agitation: consensus statement of the American Association for emergency psychiatry project BETA psychopharmacology workgroup. Western Journal of Emergency Medicine. 2012; 13: 26–34.

[24] Barbic D, Andolfatto G, Grunau B, Scheuermeyer FX, Macewan B, Qian H, et al. Rapid agitation control with ketamine in the emergency department: a blinded, randomized controlled trial. Annals of Emergency Medicine. 2021; 78: 788–795.

[25] Roppolo LP, Morris DW, Khan F, Downs R, Metzger J, Carder T, et al. Improving the management of acutely agitated patients in the emergency department through implementation of Project BETA (Best Practices in the Evaluation and Treatment of Agitation). Journal of the American College of Emergency Physicians Open. 2020; 1: 898–907.

[26] O’Brien ME, Fuh L, Raja AS, White BA, Yun BJ, Hayes BD. Reduced-dose intramuscular ketamine for severe agitation in an academic emergency department. Clinical Toxicology. 2020; 58: 294–298.

[27] Aghili M, AkhavanHejazi H, Naderpour Z, Vahidi E, Saeedi M. Haloperidol-Midazolam vs. Haloperidol-Ketamine in controlling the agitation of delirious patients; a randomized clinical trial. Archives of Academic Emergency Medicine. 2023; 11: e61.

[28] Szarmach J, Cubała WJ, Włodarczyk A, Wiglusz MS. Short-term ketamine administration in treatment-resistant depression: focus on cardiovascular safety. Psychiatria Danubina. 2019; 31: 585–590.

[29] Heydari F, Gholamian A, Zamani M, Majidinejad S. Effect of intramuscular ketamine versus haloperidol on short-term control of severe agitated patients in emergency department; a randomized clinical trial. Bulletin of Emergency and Trauma. 2018; 6: 292–299.

[30] Keseg D, Cortez E, Rund D, Caterino J. The use of prehospital ketamine for control of agitation in a metropolitan firefighter-based EMS system. Prehospital Emergency Care. 2015; 19: 110–115.

[31] 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. The American Journal of Emergency Medicine. 2018; 36: 789–796.

[32] Isbister GK, Calver LA, Downes MA, Page CB. Ketamine as rescue treatment for difficult-to-sedate severe acute behavioral disturbance in the emergency department. Annals of Emergency Medicine. 2016; 67: 581–587.e1.

[33] Scheppke K, Braghiroli J, Shalaby M, Chait R. Prehospital use of IM ketamine for sedation of violent and agitated patients. Western Journal of Emergency Medicine. 2014; 15: 736–741.

[34] Hollis GJ, Keene TM, Ardlie RM, Caldicott DG, Stapleton SG. Prehospital ketamine use by paramedics in the Australian Capital Territory: a 12 month retrospective analysis. Emergency Medicine Australasia. 2017; 29: 89–95.

[35] Gangathimmaiah V, Le Cong M, Wilson M, Hooper K, Perry A, Burman L, et al. Ketamine sedation for patients with acute behavioral disturbance during aeromedical retrieval: a retrospective chart review. Air Medical Journal. 2017; 36: 311–314.