- Robert J Hoffman, MD
Robert J Hoffman, MD
- Research Director, Department of Emergency Medicine
- Beth Israel Medical Center
Ketamine was synthesized in 1962 by Parke Davis and first used in humans in 1965 [1,2]. The United States military used ketamine as a field anesthetic during the Vietnam War, and the agent gradually gained popularity for use in brief surgical procedures as both an induction and maintenance agent for general anesthesia.
By the 1970s, ketamine became a widely used recreational drug, with street names such as K, Special K, Kitkat, Vitamine K, Ket, and Super K. Ketamine abuse is closely associated worldwide with the use of other "club drugs" including "ecstasy" (3,4-methylenedioxymethamphetamine or MDMA), gamma hydroxybutyrate (GHB), and methamphetamine, often in the setting of large dance parties (sometimes referred to as raves) .
Ketamine is produced by a complicated, multistep synthesis that essentially precludes clandestine drug production. Most if not all ketamine sold illicitly in the United States is obtained by diversion of legitimate supplies.
This topic review will discuss the presentation and treatment of ketamine intoxication, as well as poisoning with ketamine analogues, including methoxketamine, methoxetamine, tiletamine, xylazine, and similar substances. A summary table to facilitate emergent management is provided (table 1). Discussions of the use of ketamine for procedural sedation and induction for rapid sequence intubation (RSI) are found elsewhere. (See "Procedural sedation in adults", section on 'Ketamine' and "Sedation or induction agents for rapid sequence intubation in adults", section on 'Ketamine' and "Pharmacologic agents for pediatric procedural sedation outside of the operating room", section on 'Ketamine'.)
Ketamine is an arylcycloalkylamine that is structurally related to phencyclidine (PCP). Ketamine is a dissociative anesthetic and hallucinogen. It acts primarily as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, but also possesses some opioid receptor activity and sympathomimetic properties. The latter results in enhanced central and peripheral monoaminergic transmission and inhibition of central and peripheral cholinergic transmission . The primary site of ketamine's CNS activity appears to be the thalamocortical projection system, where it causes depression of certain cortical and thalamic functions and stimulation of parts of the limbic system .
- Corssen G, Domino EF. Dissociative anesthesia: further pharmacologic studies and first clinical experience with the phencyclidine derivative CI-581. Anesth Analg 1966; 45:29.
- Miller RD. Miller's Anesthesia, 6th, Elsevier Churchill Livingstone, New York 2005.
- Weir E. Raves: a review of the culture, the drugs and the prevention of harm. CMAJ 2000; 162:1843.
- Adams HA. [Mechanisms of action of ketamine]. Anaesthesiol Reanim 1998; 23:60.
- Miyasaka M, Domino EF. Neural mechanisms of ketamine-induced anesthesia. Int J Neuropharmacol 1968; 7:557.
- Kohrs R, Durieux ME. Ketamine: teaching an old drug new tricks. Anesth Analg 1998; 87:1186.
- Report on the Risk Assessment of Ketamine in the Framework of the Joint action on New Synthetic Drugs, European monitoring Centre for Drugs and Drug Addiction, September 2000.
- Ward J, Rhyee S, Plansky J, Boyer E. Methoxetamine: a novel ketamine analog and growing health-care concern. Clin Toxicol (Phila) 2011; 49:874.
- Shields JE, Dargan PI, Wood DM, et al. Methoxetamine associated reversible cerebellar toxicity: three cases with analytical confirmation. Clin Toxicol (Phila) 2012; 50:438.
- Hill SL, Harbon SC, Coulson J, et al. Methoxetamine toxicity reported to the National Poisons Information Service: clinical characteristics and patterns of enquiries (including the period of the introduction of the UK's first Temporary Class Drug Order). Emerg Med J 2014; 31:45.
- Corazza O, Assi S, Schifano F. From "Special K" to "Special M": the evolution of the recreational use of ketamine and methoxetamine. CNS Neurosci Ther 2013; 19:454.
- Wikström M, Thelander G, Dahlgren M, Kronstrand R. An accidental fatal intoxication with methoxetamine. J Anal Toxicol 2013; 37:43.
- Reyes JC, Negrón JL, Colón HM, et al. The emerging of xylazine as a new drug of abuse and its health consequences among drug users in Puerto Rico. J Urban Health 2012; 89:519.
- Ng SH, Tse ML, Ng HW, Lau FL. Emergency department presentation of ketamine abusers in Hong Kong: a review of 233 cases. Hong Kong Med J 2010; 16:6.
- Reich DL, Silvay G. Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesth 1989; 36:186.
- Martindale: The Complete Drug Reference, 34th, Sweetman S. (Ed), Pharmaceutical Press, London 2005.
- Green SM, Li J. Ketamine in adults: what emergency physicians need to know about patient selection and emergence reactions. Acad Emerg Med 2000; 7:278.
- Garfield JM, Garfield FB, Stone JG, et al. A comparison of psychologic responses to ketamine and thiopental--nitrous oxide--halothane anesthesia. Anesthesiology 1972; 36:329.
- Lahti AC, Weiler MA, Tamara Michaelidis BA, et al. Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology 2001; 25:455.
- Green SM, Sherwin TS. Incidence and severity of recovery agitation after ketamine sedation in young adults. Am J Emerg Med 2005; 23:142.
- Lalonde BR, Wallage HR. Postmortem blood ketamine distribution in two fatalities. J Anal Toxicol 2004; 28:71.
- Green SM, Clark R, Hostetler MA, et al. Inadvertent ketamine overdose in children: clinical manifestations and outcome. Ann Emerg Med 1999; 34:492.
- Dillon JB. Clinical experience with repeated ketamine administration for procedures requiring anesthesia. In: Ketamine, Kreuscher H. (Ed), Spring-Verlag, Berlin 1969.
- Smith JA, Santer LJ. Respiratory arrest following intramuscular ketamine injection in a 4-year-old child. Ann Emerg Med 1993; 22:613.
- Green SM, Rothrock SG, Lynch EL, et al. Intramuscular ketamine for pediatric sedation in the emergency department: safety profile in 1,022 cases. Ann Emerg Med 1998; 31:688.
- Murphy JL Jr. Hypertension and pulmonary oedema associated with ketamine administration in a patient with a history of substance abuse. Can J Anaesth 1993; 40:160.
- Pandey CK, Mathur N, Singh N, Chandola HC. Fulminant pulmonary edema after intramuscular ketamine. Can J Anaesth 2000; 47:894.
- Weiner AL, Vieira L, McKay CA, Bayer MJ. Ketamine abusers presenting to the emergency department: a case series. J Emerg Med 2000; 18:447.
- Shahani R, Streutker C, Dickson B, Stewart RJ. Ketamine-associated ulcerative cystitis: a new clinical entity. Urology 2007; 69:810.
- Middela S, Pearce I. Ketamine-induced vesicopathy: a literature review. Int J Clin Pract 2011; 65:27.
- Gray T, Dass M. Ketamine cystitis: an emerging diagnostic and therapeutic challenge. Br J Hosp Med (Lond) 2012; 73:576.
- Wood DM, Nicolaou M, Dargan PI. Epidemiology of recreational drug toxicity in a nightclub environment. Subst Use Misuse 2009; 44:1495.
- Gill JR, Stajíc M. Ketamine in non-hospital and hospital deaths in New York City. J Forensic Sci 2000; 45:655.
- Hsu HR, Mei YY, Wu CY, et al. Behavioural and toxic interaction profile of ketamine in combination with caffeine. Basic Clin Pharmacol Toxicol 2009; 104:379.
- Pruitt JW, Goldwasser MS, Sabol SR, Prstojevich SJ. Intramuscular ketamine, midazolam, and glycopyrrolate for pediatric sedation in the emergency department. J Oral Maxillofac Surg 1995; 53:13.
- Toft P, Rømer UD. Glycopyrrolate compared with atropine in association with ketamine anaesthesia. Acta Anaesthesiol Scand 1987; 31:438.
- Chudnofsky CR, Weber JE, Stoyanoff PJ, et al. A combination of midazolam and ketamine for procedural sedation and analgesia in adult emergency department patients. Acad Emerg Med 2000; 7:228.
- KINETICS AND METABOLISM
- DOSAGES AND FORMULATIONS
- CLINICAL PRESENTATION
- Vital signs
- Central nervous system (CNS) effects
- Respiratory and airway effects
- Cardiovascular effects
- Ocular effects
- Other effects from chronic abuse
- Presentation after iatrogenic administration
- Presentation after illicit use
- DIFFERENTIAL DIAGNOSIS
- LABORATORY EVALUATION
- Airway and breathing support
- - Laryngospasm
- - Respiratory depression
- - Salivation
- Cardiovascular support
- Supportive care
- Psychomotor agitation, muscle rigidity, hallucination
- Gastrointestinal decontamination
- Enhanced elimination
- PEDIATRIC CONSIDERATIONS
- ADDITIONAL RESOURCES
- SUMMARY AND RECOMMENDATIONS
- Presentation and evaluation