Use of Ketamine for Acute Agitation in Behavioral Emergencies: A Systematic Review
Nahar Khalef Alkhaldi 1*, Khalid Saad Mobarak Alharbi 1, Abdullah ghazi Almutairi 1, Dalal Abdulhakim al Harbi 1, Awad Jzzaa Alshammari 1, Naif Ali Shalwah Alalawi 1, Abdulrhman Suliman Alturaif 1, Mesfer Hamed m. Almalki 1, Meshal Saleh d Alharbi 1, Fayez Mohammad Alshammari 1, Arwa Mohammad Emam 1, Khulud Nayyaf Alotaibi 1, Haya Naser Alkhanfari 1, Ghanadeer Abdullah Silsilah 1, Ahmed Nafal Alsalami 1, Yara Saleh Alghamdi 1
Journal of Angiotherapy 8 (7) 1-10 https://doi.org/10.25163/angiotherapy.8710334
Submitted: 25 May 2025 Revised: 12 July 2024 Published: 15 July 2024
Abstract
Background: Acute agitation in behavioral emergencies, stemming from psychiatric disorders, substance intoxication, or medical issues can be greatly concerning to health professionals working in emergency departments (EDs). Safe, rapid, effective sedation is crucial to providing a safe environment for both the patient and staff in the ED setting. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has gained increasing popularity in EDs as a treatment option because of its rapid onset of action, minimal respiratory depression, and cardiovascular stability. Aim: This narrative review aimed to bring together literature around ketamine's use for acute agitation in the ED, as well as the efficacy, safety, clinical applications, and challenges to implementation as it relates to dosing, routes of administration, and comparison with standard agents. Methods: This narrative review included 60 peer-reviewed articles published from 2010-2024 sourced from PubMed, Scopus, Web of Science and reference lists. The studies included randomized controlled trials (RCTs), observational studies, meta-analyses, and case series on adults (≥ 18 years) experiencing acute agitation with ED presentations. Results: Ketamine (4–5 mg/kg IM or 1–2 mg/kg IV) achieved sedation within 5–10 mins in 85–90% of cases, with improved efficacy over benzodiazepines and antipsychotics based on speed and consistency. Adverse events including hypoxia (10-12%) and psychomimetic effects (5-15%) were manageable. Ketamine performed well in substance induced agitation and agitation in patients with benzodiazepine histories. Conclusion: Ketamine is a efficacious and safe approach for acute agitation, especially in difficult cases. Written protocols, educational training, and ethical guidelines are needed for appropriated management.
Keywords: Ketamine, acute agitation, behavioral emergencies, emergency medicine, sedation.
References
Abbar, M., Demattei, C., El-Hage, W., Llorca, P. M., Samalin, L., Demaricourt, P., ... & Jollant, F. (2022). Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial. bmj, 376.
Allen, P. J., Johanson, K. E., Reveles, K. R., Neff, L. A., & Lock, A. E. (2023). Comparison of droperidol and midazolam versus haloperidol and lorazepam for acute agitation management in the emergency department. Annals of Pharmacotherapy, 57(12), 1367-1374.
Andrade, C. (2023). Ketamine for depression—Knowns, unknowns, possibilities, barriers, and opportunities. JAMA psychiatry, 80(12), 1189-1190.
Barbic, D., Andolfatto, G., Grunau, B., Scheuermeyer, F. X., MacEwan, W., Honer, W. G., ... & Barbic, S. P. (2018). Rapid agitation control with ketamine in the emergency department (RACKED): a randomized controlled trial protocol. Trials, 19(1), 651.
Bayrhammer-Savel, M., Ortner, M., Van Hout, M. C., & Komorowski, A. (2024). Psychiatric and legal considerations for ketamine treatment within prison settings. Frontiers in psychiatry, 15, 1316108.
Becker, S. H., & Forman, H. (2020). Implied consent in treating psychiatric emergencies. Frontiers in psychiatry, 11, 127.
Ben-Azu, B., Aderibigbe, A. O., Ajayi, A. M., & Iwalewa, E. O. (2016). Neuroprotective effects of the ethanol stem bark extracts of Terminalia ivorensis in ketamine-induced schizophrenia-like behaviors and oxidative damage in mice. Pharmaceutical Biology, 54(12), 2871-2879.
Burke, T. F., Mantena, S., Opondo, K., Orero, S., & Rogo, K. (2022). A ketamine package for use in emergency cesarean delivery when no anesthetist is available: an analysis of 401 consecutive operations. International Journal of Gynecology & Obstetrics, 158(2), 377-384.
Cadavid, A. M., Casas, F. D., Camelo, J. E., Tovar, A., Ramirez, C. D., Calle, E., & Visbal, K. (2023). Effect of Analgesic Low-Dose Ketamine Infusions on the Cardiovascular Response: A Retrospective Analysis. Pain Physician, 26(5), 495.
Citrome, L., Correll, C. U., San, L., Zeller, S. L., Madden, S., Gutierrez, J., ... & Rabinowicz, A. L. (2024). Alternative Approaches for Addressing Acute Agitation in Schizophrenia and Bipolar Disorder. The Primary Care Companion for CNS Disorders, 26(1), 51278.
Cole, J. B., Klein, L. R., Nystrom, P. C., Moore, J. C., Driver, B. E., Fryza, B. J., ... & Ho, J. D. (2018). A prospective study of ketamine as primary therapy for prehospital profound agitation. The American Journal of Emergency Medicine, 36(5), 789-796.
Cooper, M. D., Rosenblat, J. D., Cha, D. S., Lee, Y., Kakar, R., & McIntyre, R. S. (2017). Strategies to mitigate dissociative and psychotomimetic effects of ketamine in the treatment of major depressive episodes: a narrative review. The World Journal of Biological Psychiatry, 18(6), 410-423.
DeWilde, K. E., Levitch, C. F., Murrough, J. W., Mathew, S. J., & Iosifescu, D. V. (2015). The promise of ketamine for treatment-resistant depression: current evidence and future directions. Annals of the New York Academy of Sciences, 1345(1), 47-58.
Dong, H., Yang, C., Shen, Y., Liu, L., Liu, M., & Hao, W. (2019). Effects of ketamine use on psychotic disorders and symptoms in male, methamphetamine-dependent subjects. The American Journal of Drug and Alcohol Abuse, 45(3), 276-284.
Garriga, M., Pacchiarotti, I., Kasper, S., Zeller, S. L., Allen, M. H., Vazquez, G., ... & Vieta, E. (2016). Assessment and management of agitation in psychiatry: expert consensus. The world journal of biological psychiatry, 17(2), 86-128.
Green, S. M., Mason, K. P., & Krauss, B. S. (2016). Ketamine and propofol sedation by emergency medicine specialists: mainstream or menace?. BJA: British Journal of Anaesthesia, 116(4), 449-451.
Green, S. M., Roback, M. G., Kennedy, R. M., & Krauss, B. (2011). Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Annals of emergency medicine, 57(5), 449-461.
Hopper, A. B., Vilke, G. M., Castillo, E. M., Campillo, A., Davie, T., & Wilson, M. P. (2015). Ketamine use for acute agitation in the emergency department. The Journal of emergency medicine, 48(6), 712-719.
Hosseindoost, S., Zabetpoor, M. J., Ghazi, S. F., Orandi, A., & Pestei, K. (2023). Comparison of Ketamine to Haloperidol for Preventing Delirium in ICU Elderly Patients. depression, 10, 12.
Huang, M. C., Chen, C. H., Liu, T. H., Chung, A. N., Liu, Y. L., Quednow, B. B., & Bavato, F. (2023). Comorbidity of ketamine dependence with major depressive disorder increases the vulnerability to neuroaxonal pathology. Journal of psychiatric research, 158, 360-364.
Isbister, G. K., Calver, L. A., Downes, M. A., & Page, C. B. (2016). Ketamine as rescue treatment for difficult-to-sedate severe acute behavioral disturbance in the emergency department. Annals of emergency medicine, 67(5), 581-587.
Klein, L. R., Cole, J. B., Driver, B. E., Battista, C., Jelinek, R., & Martel, M. L. (2018). Unsuspected critical illness among emergency department patients presenting for acute alcohol intoxication. Annals of Emergency Medicine, 71(3), 279-288.
Larkin, G. L., & Beautrais, A. L. (2011). A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department. International Journal of Neuropsychopharmacology, 14(8), 1127-1131.
Mankowitz, S. L., Regenberg, P., Kaldan, J., & Cole, J. B. (2018). Ketamine for rapid sedation of agitated patients in the prehospital and emergency department settings: a systematic review and proportional meta-analysis. The Journal of Emergency Medicine, 55(5), 670-681.
Riddell, J. M., Trummel, J. M., & Onakpoya, I. J. (2019). Low-dose ketamine in painful orthopaedic surgery: a systematic review and meta-analysis. British Journal of Anaesthesia, 123(3), 325-334.
Riddell, J., Tran, A., Bengiamin, R., Hendey, G. W., & Armenian, P. (2017). Ketamine as a first-line treatment for severely agitated emergency department patients. The American Journal of Emergency Medicine, 35(7), 1000-1004.
Sheikh, S., & Hendry, P. (2018). The expanding role of ketamine in the emergency department. Drugs, 78(7), 727-735.
Smith-Apeldoorn, S. Y., Veraart, J. K., Spijker, J., Kamphuis, J., & Schoevers, R. A. (2022). Maintenance ketamine treatment for depression: a systematic review of efficacy, safety, and tolerability. The Lancet Psychiatry, 9(11), 907-921.
Strayer, R. J., & Nelson, L. S. (2008). Adverse events associated with ketamine for procedural sedation in adults. The American journal of emergency medicine, 26(9), 985-1028.
Zeller, S. L., & Citrome, L. (2016). Managing agitation associated with schizophrenia and bipolar disorder in the emergency setting. Western Journal of Emergency Medicine, 17(2), 165.