ToxCard: Dexmedetomidine & Ketamine in Toxicologic Causes of Agitation

Authors: Jacob Leedekerken, MD (Emergency Medicine Resident, Carolinas Medical Center, Charlotte, NC); Kathryn T Kopec, DO (Emergency Medicine Attending, Medical Toxicologist, Carolinas Medical Center, Charlotte, NC) // Reviewed by: Cynthia Santos, MD, (@CynthiaSantosMD), Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)


A 22-year-old male presents to the emergency department (ED) via EMS acutely agitated following an unknown ingestion. He is currently yelling at staff and swinging wildly at security officers. Patient has not been responsive to verbal de-escalation. Vitals are unable to be obtained secondary to his agitation.


  1. Is ketamine or dexmedetomidine safe to use in acutely agitated patients secondary to toxicologic causes?
  2. What is the evidence on using ketamine or dexmedetomidine successfully in the toxicologic agitated patient?


The ideal pharmacologic agent for controlling agitated patients is often debated. Ketamine and dexmedetomidine are two newer drugs that are starting to be used more frequently in the management of agitation in the emergency department.


Dexmedetomidine is a highly selective alpha-2 adrenoreceptor agonist with sedative, anxiolytic, sympatholytic, and analgesic properties [1]. Sedative effects are secondary to the alpha-2 agonism in the locus coeruleus, whereas the analgesic effects stem from alpha-2 receptors in the central nervous system and spinal cord [2]. It was originally approved for less than 24-hour sedation of mechanically ventilated patients in the ICU and then subsequently for sedation of non-intubated patients prior to and/or during procedures [2]. However, off-label uses continue to expand given its advantageous properties.

Key Effects:

  • Sedative Effects:
    • Found to be non-inferior to midazolam and propofol for light/moderate sedation in mechanically ventilated patients in MIDEX and PRODEX trials [3].
    • Has demonstrated to have decreased the need for ventilation support by 20% and decreased ICU stay by roughly 14% [4].
    • Has ability to facilitate sedation without neurologic depression allowing for serial neurological exams if needed [5].
  • Cardiovascular Effects:
    • Bolus dose may induce hypertension
    • Often causes hypotension and bradycardia, however, with minimal clinical effects
      • Secondary to decreased catecholamine release and unopposed vagal activity [2]
    • The potential hypotension and bradycardia associated with dexmedetomidine has made it the agent of choice in cases with hypertension and tachycardia secondary to toxicological causes [6,7,8,9,10].
  • Respiratory Effects:
    • Minimal to no respiratory depression [2].


Ketamine is an NMDA receptor antagonist. It also causes nitric oxide synthase inhibition, limits reuptake of various neurotransmitters and binds to a variety of receptors including opioid receptors and muscarinic receptors [11]. Ketamine’s NMDA antagonism decreases glutamate excitatory transmission. This main mechanism of action along with its’ effects on other pathways has been shown to have promising clinical effects such as: producing a “dissociative” state, sedation, and analgesia. These effects occur without clinically significant effects regarding respiratory depression or hypotension.

Key Effects:

  • Sedative Effects:
    • Demonstrated successful use of acute agitation secondary to psychiatric disease or drug intoxication [12].
    • Has demonstrated a shorter time to sedation in comparison with midazolam, haloperidol, lorazepam, or a combination of benzodiazepine and haloperidol [13,14].
  • Cardiovascular Effects:
    • Increases in blood pressure and heart rate are frequently seen but rarely clinically significant [15,16].
  • Respiratory Effects: [15]
    • Not associated with respiratory depression
    • Potential use for bronchodilation/anxiolysis in asthma exacerbation
    • Low incidence of laryngospasm

Given the aforementioned effects of both ketamine and dexmedetomidine, it is understandable why they are both being used in the treatment of the agitated patient. Ketamine has been gaining popularity as a chemical sedative for acute, undifferentiated agitation and dexmedetomidine as an adjunct sedative. These agents have the potential to be ideal agents for agitation control in patient populations that have a high incidence of mental health disorders or overdose on respiratory depressants, such as opiates or benzodiazepines.


What research has been published on the use of ketamine or dexmedetomidine in regard to their benefit or safety in agitated patients from toxicological causes?


Dexmedetomidine has demonstrated safety and agitation control in cases of cocaine [17], methamphetamines [18], dextromethorphan [7], MDMA [7], methylphenidate [9], serotonin toxicity [6,19,20], anticholinergic toxicity [8,21] and alcohol/opioid withdrawal [22,23,24]. Dexmedetomidine was used as a sedative adjunct in these cases and assisted with resolution of hypertension, tachycardia, and hyperthermia. No adverse effects, such as respiratory depression, were noted.


There are limited studies specifically looking at the use of ketamine for toxicologic emergencies, however, there are multiple studies of its successful use in the acute undifferentiated agitated patient. It has also been documented as an adjunct for the treatment of alcohol withdrawal syndrome (AWS).

  • A 2018 systematic review of ketamine’s use in agitated patients found that 40.4% of patients had a discharge diagnosis of substance use [15].
  • Multiple studies in adolescents and adults have demonstrated effectiveness and faster control of agitation with ketamine [12,13,14].
  • Associated with reduced GABA agonist requirements, shorter ICU stays, and lower incidence of intubation in ICU patients diagnosed with delirium tremens [25].

Key Points:


  • Selective alpha-2 adrenoreceptor agonist with sedative, anxiolytic, sympatholytic, and analgesic properties.
  • Potential adjunctive therapy for control of agitation from toxicological syndromes secondary to its respiratory sparring sedation and sympatholytic properties.
  • Major adverse effects are bradycardia and hypotension, which can be actually be beneficial in severe agitation.


  • NMDA receptor antagonist
  • Use in AWS has potential advantages including reduction of GABA agonists, ICU length of stay, and decreased intubations.
  • Beneficial for acute agitation given its quick onset of sedation compared to commonly used sedatives such as: midazolam, haloperidol, and lorazepam.
  • Adverse effects: hypersalivation, emergence delirium/hallucinations, and nausea/vomiting.

References/Further Reading:

  1. Virtanen R, Savola JM, Saano V, Nyman L. Characterization of the selectivity, specificity and potency of medetomidine as an alpha 2-adrenoceptor agonist. Eur J Pharmacol. 1988;150:9–14.
  2. Weerink, M., Struys, M., Hannivoort, L. N., Barends, C., Absalom, A. R., & Colin, P. (2017). Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clinical pharmacokinetics, 56(8), 893–913. doi:10.1007/s40262-017-0507-7
  3. Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA 2012;307:1151-60. 10.1001/jama.2012.304
  4. Chen K, Lu       Z, Xin YC, Cai Y, Chen       Y, Pan SM. Alpha‐2 agonists for long‐term sedation during mechanical ventilation in critically ill patients. Cochrane Database of Systematic Reviews 2015, Issue 1. Art. No.: CD010269. DOI: 10.1002/14651858.CD010269.pub2.
  5. Tang, J.F., Chen, PL., Tang, E.J. et al. Dexmedetomidine Controls Agitation and Facilitates Reliable, Serial Neurological Examinations in a Non-Intubated Patient with Traumatic Brain Injury. Neurocrit Care (2011) 15: 175.
  6. Rushton, W. F., & Charlton, N. P. (2014). Dexmedetomidine in the Treatment of Serotonin Syndrome. Annals of Pharmacotherapy, 48(12), 1651–1654.
  7. Tobias JD. Dexmedetomidine to control agitation and delirium from toxic ingestions in adolescents. J Pediatr Pharmacol Ther. 2010;15(1):43–48.
  8. Cowan K, Landman RA, Saini A. Dexmedetomidine as an Adjunct to Treat Anticholinergic Toxidrome in Children. Glob Pediatr Health. 2017;4:2333794X17704764. Published 2017 Apr 24. doi:10.1177/2333794X17704764
  9. Bagdure DN, Bhoite GR, Reiter PD, Dobyns EL. Dexmedetomidine in a child with methylphenidate intoxication. Ind J Pediatr. 2013;80(4):343–344.
  10. Mohorn, P. L., Vakkalanka, J. P., Rushton, W., Hardison, L., Woloszyn, A., Holstege, C., & Corbett, S. M. (2014). Evaluation of dexmedetomidine therapy for sedation in patients with toxicological events at an academic medical center. Clinical Toxicology, 52(5), 525–530. doi: 10.3109/15563650.2014.913175
  11. J. Sleigh, M. Harvey, L. Voss, B. Denny. Ketamine – more mechanisms of action than just NMDA blockade. Trends Anaesth Crit Care, 4 (2014), pp. 76-81
  12. Kowalski JM, Kopec KT, Lavelle J, et al. A novel agent for management of agitated delirium: a case series of ketamine utilization in the pediatric emergency department. Pediatr Emerg Care. 2015 Oct 13.
  13. Cole JB, Moore JC, Nystrom PC, et al. A prospective study of ketamine versus haloperidol for severe prehospital agitation. Clin Toxicol 2016;54(7):556–62. PMID: 27102743
  14. 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 Jul;35(7):1000-1004. PMID: 28237385
  15. 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. doi: 10.1016/j.jemermed.2018.07.017
  16. A.B. Hopper, G.M. Vilke, E.M. Castillo, A. Campillo, T. Davie, M.P. Wilson. Ketamine use for acute agitation in the emergency department. J Emerg Med, 48 (2015), pp. 712-719
  17. Menon, D. V., Wang, Z., Fadel, P. J., Arbique, D., Leonard, D., Li, J.-L., … Vongpatanasin, W. (2007). Central Sympatholysis as a Novel Countermeasure for Cocaine-Induced Sympathetic Activation and Vasoconstriction in Humans. Journal of the American College of Cardiology, 50(7), 626–633. doi: 10.1016/j.jacc.2007.03.060
  18. Lam, R.P., Yip, W.L., Wan, C.K., & Tsui, M.S. (2017). Dexmedetomidine use in the ED for control of methamphetamine-induced agitation. The American journal of emergency medicine, 35 4, 665.e1-665.e4 .
  19. D’Orazi, F., & Mansour, M. (2015). Treatment of Refractory Serotonin Syndrome with Dexmedetomidine. Journal Of Nature And Science (JNSCI), 1(2), e47. Retrieved from
  20. Akingbola O.A., Singh D. Dexmedetomidine to treat lisdexamfetamine overdose and serotonin toxidrome in a 6-year-old girl. Am. J. Crit. Care. 2012;21:456–459.
  21. Walker A, Delle Donne A, Douglas E, Spicer K, Pluim T. Novel use of dexmedetomidine for the treatment of anticholinergic toxidrome. J Med Toxicol. 2014;10(4):406–410. doi:10.1007/s13181-014-0408-1
  22. Wong, G. T. and Irwin, M. G. (2013), Poisoning with illicit substances: toxicology for the anaesthetist. Anaesthesia, 68: 117-124. doi:10.1111/anae.12053
  23. Guirguis, E., Richardson, J., Kuhn, T., & Fahmy, A. (2017). Treatment of Severe Alcohol Withdrawal: A Focus on Adjunctive Agents. The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians, 33(5), 204–212. doi:10.1177/8755122517714491
  24. Foertsch, M. J., Winter, J. B., Rhoades, A. G., Martin, L. T., Droege, C. A., & Ernst, N. E. (2019). Recognition, Assessment, and Pharmacotherapeutic Treatment of Alcohol Withdrawal Syndrome in the Intensive Care Unit. Critical Care Nursing Quarterly, 42(1), 12–29. doi: 10.1097/cnq.0000000000000233
  25. Pizon, A. F., Lynch, M. J., Benedict, N. J., Yanta, J. H., Frisch, A., Menke, N. B., … Kane-Gill, S. L. (2018). Adjunct Ketamine Use in the Management of Severe Ethanol Withdrawal. Critical Care Medicine, 46(8). doi: 10.1097/ccm.0000000000003204



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