Ketamine as a Street Drug


Author: Charles Stewart, MD, FACEP

The Clinical setting

Your call is for an agitated 19 year old female at a large party.  Her companion states that your patient was searching for a k-hole and has been freaking out since she did the line of Lady K.  Your partner looks at you (Oh great wise soul that you are) and asks for an interpreter…What can you tell your partner about Lady K and its effects?

The Arylhexylamines (PCP and ketamine)

The prototype arylhexylamine is Phencyclidine [1-(1-phenylcycloheyl)piperidine hydrochloride] or PCP for short.  PCP is an arylcyclohexamine that was originally developed as an anesthetic agent (Sernyl).  A close analogue, Ketamine was discovered in 1962 by Parke Davis Labs.  The investigators were searching for PCP analogues with anesthetic properties.  Ketamine was further developed by the University of Michigan in 1965 during a search for safe anesthetic products.  It was widely used during the Vietnam War as a battlefield anesthetic.  Unfortunately, both phencyclidine and ketamine caused emergence agitation and thought disturbances.  PCP’s emergence agitation was somewhat more pronounced than that seen with the use of ketamine.

Phencyclidine was used as a veterinary anesthetic until 1979.  PCP was never approved for use in humans. Legal production of phencyclidine was discontinued in 1978.  PCP and several analogues are widely available on the street and easily and inexpensively synthesized.

The site of action of ketamine within the brain is not known.  It is hypothesized to act at multiple neurotransmitter sites including the dopaminergic system, the cholinergic, noradrenergic, serotoninergic, and the GABA transmitter systems.  Ketamine is not physically addictive.

Ketamine is still available, and is widely used for sedation, for intubation, and anesthesia.  It is extensively used by veterinarians as an anesthetic agent for veterinary surgery.  Ketamine is described as a “unique drug” because it has hypnotic (sleep producing) effects, analgesic, and amnesic effects. 

Ketamine as a medicine

Ketamine is quite useful in emergency medicine as the only available neuroleptic agent. [1]   Ketamine is often described as a dissociative anesthetic, where the higher cognitive functions are dissociated from the brainstem functions.  When properly used, the patient may appear to be awake, but is amnestic and unresponsive to pain. 

Ketamine has medical uses as a sedative/anesthetic agent for both intubation and sedation for procedures. Ketamine is still widely used as an anesthetic agent, particularly where the surgeon does not have an anesthesiologist to help him or her.  It is, arguably, the most widely used anesthetic agent in the world, with the greatest use in third world countries. [2]

In contrast to the other sedative agents, ketamine increases the cardiac output, pulse rate, blood pressure, myocardial oxygen consumption, cerebral blood flow, intraocular pressure, and possibly intracranial pressure. [3] Although it is a direct myocardial depressant, it causes a release of endogenous catecholamines resulting in the positive overall effects. Heart rate and blood pressure are usually maintained or increased because of centrally mediated sympathetic stimulation.   Indeed, ketamine may cause hypertension.  This effect is enhanced when other adrenergic agents are given, or the patient has been using cocaine.

There are two major advantages to the emergency department use of ketamine.  First, ketamine’ s release of endogenous catecholamines relaxes bronchial smooth muscle.  This makes ketamine useful for intubation of the COPD or asthmatic patient, as both a bronchodilator and a sedative. It is, perhaps, the sedative of choice in the asthmatic patient with respiratory failure. [4] [5]   The other major advantage of ketamine is in the setting of the hypovolemic patient, especially when the heart is directly involved, such as in pericardial tamponade or cardiogenic shock.  Ketamine provides the most cardiovascular and respiratory support of any agent. It should be readily available for the EMS provider who performs rapid sequence intubation.

Its onset of action is within 1 minute when given intravenously, and its duration of action ranges from 5 to 15 minutes. [6] [7]   Unless given extremely rapidly, apnea does not occur.  It is slower in action when given intramuscularly and will last longer.  This is advantageous when rapid control of the patient without venous access is needed.  The IV dose of ketamine for RSI in children is 2 mg/kg.  Some authorities feel that children who are sedated with ketamine should be also treated with atropine to reduce the secretions, but this opinion is not universal.

Ketamine also increases salivary and bronchial secretions. [8]  Secretions can be decreased with atropine 0.01 mg/kg (minimum dose 0.15 mg) or glycopyrrolate 0.005 mg/kg.  A usual dose of glycopyrrolate is 0.2 or 0.4 mg.

Ketamine causes awakening (emergence) hallucinations that many adults find quite unpleasant. [9]   These emergence reactions occur in up to 50% of adults but are rare in children under 10 years of age. [10]   If the drug is being used as a pure sedative as an adjunct for a painful procedure, this may be of some concern.  It is widely taught that the emergence reaction may be abolished with concomitant use of a benzodiazepine. Randomized, double-blinded studies in ketamine induced sedation with and without benzodiazepines have not shown this to be true. [11] [12]

The disadvantages of ketamine are few. It may result in worsening hypotension if given to patients who are either sympathetically depleted or those who have severe coronary artery disease and may not tolerate increased myocardial oxygen consumption. Administration of any sedative agent in this setting is hazardous.

Ketamine should be used with extreme caution in hypertensive patients (increases blood pressure) and those with open eye injuries and glaucoma (due to increased intraocular pressure).  Ketamine may be an appropriate drug for the hypotensive unstable patient, however.

The biggest concern over the use of ketamine is its potential to affect ICP secondary to its ability to increase cerebral blood flow by 30% to 60%.  It is currently contraindicated in head injury (due to both increased oxygen consumption and increased intracranial pressure associated with ketamine). [13]   This contraindication is being reviewed and may be revised.

Even though the cerebral metabolic rate is increased with ketamine, cerebral blood flow is probably sufficient to meet demand. Evidence is accumulating that this increase in cerebral blood flow does not increase ICP. [14]   In fact, there is growing evidence that ketamine is neuroprotective in head trauma. [15]   As noted above there is reluctance to use ketamine when the patient has head injury.   Ketamine may be useful when induction is needed in a profoundly hypotensive patient: any reduction in mean arterial pressure is more likely to worsen cerebral ischemia than will a transient rise in ICP.

Ketamine as a recreational drug

Ketamine has now gained in popularity as an illicit hallucinogen.  It is being used by many as a “club drug” and distributed at parties and “raves.”  According to the Drug Enforcement Administration, ketamine is an emerging drug on both coasts, Florida, and Georgia.  It is particularly popular in the New York – New Jersey area, San Diego, DC, and Miami. In 1999, ketamine was made a schedule III narcotic by the DEA. Much of the illicit supply is stolen from hospitals and veterinary clinics.

Ketamine is known on the street as K, Ket, Special K, Vitamin K, Lady K, Kit Kat, Keller, kelly’s day, Green, Blind squid, Cat valium, purple, Special 1a coke, super acid, and Super C.   The trade names are Ketalar and Ketaset. The experience is often called tripping, k-ing, or entering the k-hole.

Ketamine is a liquid, but can be dried and made into a tablet or powder.  Ketamine can be snorted, swallowed, injected intravenously, and injected IM. The most potent ways of using it are IM and IV. 

Because of the fine white powder that results when it is dried, ketamine is often mistaken for cocaine or crystal methamphetamine.  It may be sold as MDMA or ecstasy.  It may be mixed with other drugs such as ephedrine or caffeine to dilute the powder.  PCP is often substituted for ketamine and will have much the same effect in equivalent doses.

Part of PCP’s popularity is because it is easy and cheap to manufacture.  All the budding sidewalk pharmaceutical company needs is a porcelain bowl, a handful of nickels to catalyze the reaction, L-tryptophan, and piperazine.  The cost of manufacturing a single dose of PCP is somewhat less than ten cents.  It can sell on the street for fifty dollars or more, when marketed as ketamine.

Since PCP is inexpensive and easy to manufacture, sidewalk pharmaceutical representatives will often market PCP as ketamine. Remember that you can't rely too much on the history.  The street-wise clinician will suspect PCP intoxication in any patient who admits to using other drugs.

Ketamine is used for the dissociative state.  The specific effects that the drug user wishes to obtain from ketamine is the mild dreamy feeling of the low dose.  Users report feeling “floating outside of their bodies.”  The experience is described as quite like taking PCP (author – this stands to reason, since they are quite similar chemically.) 

Higher doses produce a hallucinogenic effect and the “out of body experience” is very strong. This experience is often referred to as entering a “K-hole” and has been compared to a near death experience – (although the author was unable to find anybody who actually has both had a near death experience and has used or uses ketamine.)  Many users find this out of body experience spiritually significant, while others find it quite frightening.  In higher doses, the drug induces coma.

Ketamine may relieve tension and anxiety in users.  It intensifies colors and sounds, and is purported to be a mild sexual stimulant.

Since ketamine is an anesthetic, the user feels no pain and may have an exaggerated sense of strength. 

The effects of a ketamine high usually last about an hour if used orally, 45-60 minutes if snorted, and 30-45 minutes when injected.  The k-trip can last as long as 4-6 hours.  The senses, judgment, and coordination may be affected for up to 24 hours after use.

Long-term effects include tolerance, physical and psychological dependence.  Flashbacks occur after use of this drug and are not predictable.  Two psychological difficulties which seem common for regular users of ketamine include paranoia and egocentrism.  There are multiple reports of users who start to see patterns and coincidences in the world around them that (to them, at least) seem to indicate that they are somehow more important to the world than other people.

Individuals who use it regularly may find it difficult to stop. Effects of chronic use of ketamine may take several months to wear off completely.

There is little medical experience with high doses of ketamine.  We don’t even know the minimal toxic or the lethal dose in humans.  Large doses can produce vomiting, convulsions, respiratory depression, and hypotension. Only 9 cases of inadvertent overdose were identified in the literature (all IV and ranging from 25 to 50 mg/kg). [16]   Respiratory depression was uniformly seen and led to death in one case (a two month old with concomitant critical illness).  Assisted ventilations were required in another three cases. Recovery was prolonged with high doses, but uneventful.   Respiratory depression occurs at the time of peak concentration of the drug in the CNS. Intramuscular administration of ketamine has resulted in only one published case of a brief period of apnea with no sequelae. [17]

Since ketamine is known to cause apnea when administered by rapid IV injection, the prehospital clinician should be aware of this complication. At least one death has been recorded where an individual took a bath after using ketamine and drowned.

Treatment

Ketamine can cause broad behavioral and mood changes that last about 1-2 hours.  If these patients are quiet, without seizures, without agitation, and without hypotension, gentle supportive care is the only treatment needed. Provoking the ketamine user with questions or physical contact can cause them to be both hyperactive and insensitive to pain (remember - it was first developed as an anesthetic!)  If the patient has normal vital signs, quiet observation is usually appropriate.  Cranberry juice or ascorbic acid to acidify the urine and help eliminate the drug may be appropriate and certainly wouldn’t do any harm.

If the patient becomes hostile or agitated, diazepam or haloperidol may be required.  Benzodiazepines have been shown in multiple studies not to reduce the incidence of dreams, hallucinations, and illusions associated with licit ketamine use in children. [18] [19]   There is no reason why they should be expected to decrease the emergence phenomenon in the illicit overdose of ketamine in adolescents and adults.  Indeed, benzodiazepines may suppress ketamine metabolism through competition for hepatic metabolism and may prolong ketamine recovery time. [20]

Hypotension should be treated with fluids.  Seizures may be treated with benzodiazepines in usual doses and routes.  Patients should be protected from harming themselves. If the patient has difficulty with maintenance of the airway, then intubation should be considered.

Droperidol has been advocated for treatment of the vomiting associated with high doses of ketamine.

For extreme violence or agitation, consider mummification restraints.  Four point restraints tend to be broken or to cause muscle damage to the patient.  This may be easier to conceive of than to perform in a struggling and agitated patient!

Any patient with a temperature of 101F or more should be aggressively treated with cooling.  Consider rhabdomyolysis imminent in these patients.

As with all overdoses, presume that ketamine was not the only substance taken.  Ketamine will not be detected by the common urine screening tests in both workplace and routine emergency room drug screenings. There are, however, a number of different specific assays both for the parent compound and various metabolites. The drug is detectable for about 48 hours after use.  Those labs that usually measure ketamine are often reference labs with long wait times. Ketamine has been used as a “date rape” drug.  Ketamine can be detected by the ToxiLab system.

Although laboratory tests for ketamine are not useful for management of the overdose, the laboratory should not be neglected. Ensure that the following laboratory tests are obtained: Glucose, CPK, Liver enzymes, and uric acid.  An increase in CPK, uric acid, SGOT, and SGPT may be a good clue to look for rhabdomyolysis.


References

[1] Stoelting RK. Nonbarbiturate induction agents. In Stoelting RK (ed). Pharmacology and physiology in anesthetic practice, 2d ed. Philadelphia: JB Lippincott, 1991:134.

[2] World Federation of Societies of Anesthesiologists. Administering a ketamine anaesthetic. http://www.nda.ox.ac.uk/wfsa/html/u04/u04_011.htm

[3] Green LM, Nakamura R, Johnson NE. Ketamine sedation for pediatric procedures: Parts I and II. Ann Emerg Med 1990;19:1024-1046.

[4] Tobias JD.  Airway management for pediatric emergencies.  Pediatric Ann 1996;25:317-328.

[5] Nichols DG.  Emergency management of status asthmaticus in children. Ped Annals 1996;25:394-403.

[6] L’Hommedieu CS.  The use of ketamine for the emergency intubation of patients with status asthmaticus.  Ann Emerg Med 1987;16:568-571.

[7] White PF, Way WL, Trevor AJ.  Ketamine: its pharmacology and therapeutic uses.  Anesthesiology 1982;56:119-136.

[8] Epstein FB.  Ketamine dissociative sedation in pediatric emergency medical practice.  Am J Emerg Med 1993;11:180-182

[9] Cartwright PD, Pingel SM. Midazolam and diazepam in ketamine anesthesia. Anaesthesia 1984;59:439.

[10] Jankiewizc AM, Nowakowski P.  Ketamine and succinylcholine for emergency intubation of pediatric patients.  DICP 1991;25:475-476.

[11] Sherwin TS, Green SM, et al.  Does adjunctive midazolam reduce recovery agitation after ketamine sedation for pediatric procedures? A randomized, double-blind, placebo-controlled trial.  Ann Emerg Med 2000;35:229-238.

[12] Wathen JE, Roback MG, Mackenzie T, Bothner JP.  Does midazolam alter the clinical effects of intravenous ketamine sedation in children?  A double-blind, randomized, controlled emergency department study.  Ann Emerg Med. 2000;36:579-588.

[13] Hougaard K, Hansen A, Brodersen P.  The effect of ketamine on regional cerebral blood flow in man. Anesthesiology 1974;41:562-567.

[14] Rodriguez A, Sanchez L. Intravenous ketamine does not increase intracranial pressure in neurosurgical patients with normal or increased ICP [abstract]. Crit Care Med 1994;24:A57.

[15] Smith DH, Okiyama K, Gennarelli TA, McIntosh TK. Magnesium and ketamine attenuate cognitive dysfunction following experimental brain injury. Neurosci Lett 1993;157:211.

[16] Green SM, Clark R, Hostetler MA, et al.  Inadvertent ketamine overdose in children: clinical manifestation and outcome.  Ann Emerg Med 1999;34:492-497.

[17] Green SM, Rothrock SG.  Transient apnea with intramuscular ketamine.  Am J Emerg Med 1997;15:441. OP CIT.

[18] Sherwin TS, Green SM, et al.  Does adjunctive midazolam reduce recovery agitation after ketamine sedation for pediatric procedures? A randomized, double-blind, placebo-controlled trial.  Ann Emerg Med 2000;35:229-238.

[19] Wathen JE, Roback MG, Mackenzie T, Bothner JP.  Does midazolam alter the clinical effects of intravenous ketamine sedation in children?  A double-blind, randomized, controlled emergency department study.  Ann Emerg Med. 2000;36:579-588.

[20] Green SM, Rothrock SG, Lynch EL, et al.  Intramuscular ketamine for pediatric sedation in the emergency department: Safety profile in 1022 cases.  Ann Emerg Med 1998;31:688-697.


About The Author: Dr. Stewart is an emergency physician in private practice in Colorado Springs. He is also an Associate Clinical Professor of Emergency Medicine at the University of Rochester. He is the author of over 120 articles and three books, including Environmental Emergencies, published by Williams and Wilkins in 1990. He served as an oral examiner for the American Board of Emergency Medicine. He is the Medical Editorial Consultant for EMS Magazine and has been a medical advisory board member for the EMS association of Colorado for many years.