Ketamine and Phencyclidine

PCP is a noncompetitive N-Methyl-D-aspartate (NMDA) receptor antagonist and partial agonist at the dopamine2 (D2) receptor. The endogenous ligand for the NMDA receptor is glutamate, which is the major excitatory transmitter of the central nervous system. Blocking excitatory transmission broadly explains PCP's anesthetic effect.

Ketamine is as potent an NMDA receptor antagonist as PCP by the same mechanism of action. In contrast with PCP, it is not a D2 receptor partial agonist in humans, although animal studies suggested it might be.

The lack of dopamine agonism by ketamine may explain why PCP is associated with more hallucinations and dysphoria.

Ketamine is available in liquid or powder form. When used illicitly, the route of use of ketamine in powder form is typically snorting but it can be taken orally. The liquid form is given intravenously (IV), intramuscularly (IM), or subcutaneously.

PCP was once a common anesthetic, but is no longer legally manufactured. In illicit use, the route of use of PCP is being smoked on its own or used to lace marijuana or tobacco cigarettes. The hydrochloride salt is the form referred to as "angel dust" and is usually insufflated (snorted).

Acute effects generally fade rapidly and many patients regain normal consciousness in 45 minutes to several hours.

The effects of use are a giddy euphoria, often followed by bursts of anxiety or mood lability. At the doses of ketamine used for procedural sedation, nystagmus and tachycardia occur.

Signs of toxicity are a withdrawn state of depersonalization and disassociation. On its own, neither ketamine nor PCP impair the respiratory drive. The main concerns are injury to the patient or those around the patient because of unpredictable responses external stimuli.

With very high doses of either ketamine or PCP, acidosis, hyperthermia, tachycardia, arrhythmias, severe hypertension, seizures, and coma may occur; deaths are unusual. Ketamine may induce laryngospasm.

Emergence reaction is an adverse reaction to PCP and ketamine use seen during the recovery phase. It manifests with bizarre behavior, psychosis, confusion, hallucinations, vivid dreams, or the sensation of floating. Some symptoms may last for weeks.

• History and physical examination

• For PCP, urine drug test; ketamine is not detected on routine urine drug screening tests

• ECG, sometimes serial troponin testing

The clinical picture of a patient with nystagmus and tachycardia in a dissociated state is compelling enough to make a provisional diagnosis of ketamine or PCP use.

The clinician should also consider toxicity from dextromethorphan and synthetic cannabinoid receptor agonists. Dextromethorphan toxicity can be difficult to distinguish from ketamine or PCP toxicity. All 3 present with a dissociated state and nystagmus. Dextromethorphan is reported to be more associated with kaleidoscopic vision and rotatory nystagmus, but the sensitivity and specificity of those physical examination findings has not been established.

A general evaluation for patients with substance use should be performed, including serum glucose (use a rapid point-of-care test, if available); comprehensive metabolic panel, serums levels of other common substances that can alter consciousness (eg, alcohol, acetaminophen, salicylate), a urine drug screening test, urinalysis, and ECG.

For patients with an abnormal initial ECG or with chest pain, repeat ECGs or continuous cardiac monitoring should be performed as well as serial measurement of serum troponins.

Patients using PCP may present with violent or dangerous behavior, posing a danger to themselves or others. In addition, these patients may be impervious to pain and suffering from traumatic injuries. These patients may require sedation or paralysis with intubation to control their behavior and to allow examination for possible injuries.

Most routine urine drug screening tests detect PCP, but this test does not demonstrate the presence of a toxic level and the assay is neither sensitive nor specific. Common xenobiotics, including dextromethorphan, diphenhydramine, and ibuprofen cross-react with the assay and can give a false positive.

Ketamine is not detected on routine drug screening tests.

The definitive diagnosis of PCP or ketamine toxicity requires demonstrating that a toxic amount of the substance was present in the patient when the patient had concordant symptoms. In practice this level of certainty is difficult to achieve during an acute presentation. Serum tests for PCP or ketamine should be drawn with the understanding that results are unlikely to be available for weeks. As with many illicit substances, treatment must proceed under a provisional diagnosis while awaiting confirmation. The standard urine toxicology drug screen detects PCP. Despite its name, the urine toxicology screen should not be used to screen for PCP toxicity despite its name. It cross-reacts with many substances. Rather, it should be used to confirm a suspected exposure.

• Ketamine and phencyclidine are dissociative anesthetics that can cause a withdrawn state with depersonalization and disassociation.

• Use is associated with a risk of injury to the patient or others because of unpredictable responses external stimuli. Toxicity can include acidosis, hyperthermia, tachycardia, severe hypertension, seizures, and coma; ketamine can cause laryngospasm.

• Diagnose with history and physical examination and sometimes urine testing for PCP.

• Manage with monitoring, and sometimes benzodiazepines for agitation or seizures, or a paralytic (eg, succinylcholine) for laryngospasm.