Phencyclidine Toxicity

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Practice Essentials

Phencyclidine (PCP) is a hallucinogen—specifically, a dissociative anesthetic—that can produce a wide variety of physical and behavioral effects and has a high potential for abuse and dependence. Acute toxicity often resembling a psychotic episode. PCP is often taken in conjunction with other co-ingestants, including ethanol and marijuana. 

PCP is a white crystalline powder that is available in liquid, tablet, or powder forms. It can be snorted, ingested orally, or injected intravenously. It also can be smoked as a "joint" or "wet" ("embalming fluid") when sprinkled on cigarettes or applied to mint or marijuana leaves.[1]  Newer designer versions such as 3-MeO-PCP and 4-MeO PCP now exist.[2]

 

Background

Phencyclidine (PCP) was originally developed for use as a general anesthetic for surgery under the trade name Sernyl in the 1950s. Its use was discontinued in humans in 1965 because it often produced postanesthetic delirium with psychotic features, dysphoria, and occasionally extreme agitation. PCP under the name Sernylan was used as a veterinary anesthetic until 1978, after which time it became illegal to use altogether.

In the 1960s, people began illegally manufacturing phencyclidine in laboratories, and, by the late 1970s, it became a popular street drug. Common street names include angel dust, peace pill, crystal joint, hog, rocket fuel, KJ, elephant tranquilizer, supergrass, boat, tic-tac, zoom, wet, embalming fluid, and wack.

Pathophysiology

PCP, also known as 1-(1-phenylcyclohexyl-piperidine), is classified as a dissociative anesthetic. PCP acts mainly in the CNS, producing both stimulation and depression. Its sympathomimetic effects are thought to be due to weak reuptake inhibition of norepinephrine and dopamine. PCP also exerts some cholinergic and anticholinergic effects and has some other actions at nicotinic and opioid receptors.

The dissociative properties of PCP are believed to be due to its actions as a glutamate antagonist at the N -methyl-D-aspartate (NMDA) receptors. NMDA antagonists have been known to produce behavioral effects similar to those observed in schizophrenia, and they are used to induce an animal model of schizophrenia for research. PCP also affects the actions of dopamine, which may cause the psychomotor effects seen with PCP.

Clinical effects occur within minutes and usually last several hours. These symptoms may last up to 48 hours in the event of significant overdose. However, even more prolonged effects may be seen in chronic users either from enterohepatic recirculation or from delayed release of PCP from lipid stores. Because PCP is fat soluble, it accumulates in adipose tissue and the brain. Recurrent and fluctuating symptoms occur as PCP is remobilized from lipid stores, which can occur days, weeks, or months after the initial use.[3] The half-life of PCP is estimated at 17.4 hours; however, half-lives of 1-4 days have been reported.[4] PCP is primarily metabolized in the liver.

Epidemiology

The Drug Abuse Warning Network (DAWN) estimates that PCP-related emergency department (ED) visits increased more than 400% from 2005 to 2011 (from 14,825 to 75,538 visits). PCP-related ED visits doubled from 2009 to 2011. DAWN estimates from selected metropolitan areas show geographic variation in trends, with PCP-related ED visits increasing in some areas (New York City, Chicago) while remaining stable in others (Seattle, San Francisco, Phoenix).[5]

Of PCP-related ED visits in 2011, 72% involved PCP combined with other drugs; in about half, PCP was combined with illicit drugs (32% involved marijuana and 20% involved cocaine), and in about a quarter PCP was combined with pharmaceutical agents such as pain relievers (16%) and anti-anxiety and insomnia drugs (13%).

The 2017 National Survey on Drug Use and Health, polling persons 12 years of age and older, found an an estimated 1.4 million people were current users of hallucinogens (LSD, PCP, peyote, mescaline, psilocybin mushrooms, MDMA or “Molly”, ketamine, DMT/AMT/“Foxy,” and Salvia divinorum). An estimated 114,000 adolescents aged 12 to 17 were current users of hallucinogens. (0.5%). Adults aged 18-25 represented the largest group currently using hallucinogens with and estimated 668,000 users (1.9%). Use among adults older than 25 was an estimated 0.3 percent, which represents 608,000 individuals.[6]

The 2012 Monitoring the Future Survey of high school seniors showed 1.6% using PCP once in their lifetime (down from 2.13% in 2011), 0.9% had used PCP at least once in the last year, and 0.5% had used PCP at least once in the last 30 days.[7]

Doses of 20 mg or more of PCP may cause prolonged coma, seizures, and even death. One death has been reported from an ingestion of 150-200 mg in an acute overdose. In 2017, the American Association of Poison Control Centers reported 220 single exposures to PCP with 16 major outcomes and 1 death.[8]

DAWN estimates that in 2011, 69% of PCP-related ED visits were made by males. Approximately 45% were made by persons aged 25 to 34 years. Persons aged 18 to 24 years accounted for 19% of visits, as did those aged 35 to 44.[5]

Prognosis

Morbidity and mortality are usually associated with rhabdomyolysis, renal failure, hypertensive crises, accidental trauma, and self-destructive behavior. The outcome in cases of PCP toxicity tends to be worse in patients who present with any of the following:

Chronic PCP toxicity results in cognitive deficits and mood disorders. Patients can develop speech impediments and also suffer from dysphoria, depression, anxiety, and psychosis.[9, 10]

Patient Education

For patient education information, see the First Aid and Injuries Center and Mental Health Center, as well as Drug Dependence & Abuse, Poisoning, Club Drugs, and Activated Charcoal. Further information is available on the following Web sites:

History

Because of the numerous routes of administration, variations in dosage, and possibility of co-ingestants, phencyclidine (PCP) produces a wide variety of physical and behavioral effects. Most commonly, witnesses may report agitation, bizarre actions, or violent behavior. Users of PCP often appear to be having a psychotic episode and may or may not report to the physician that they have taken the drug.

Physical Examination

In a study by McCarron et al that evaluated 1,000 patients presenting with acute phencyclidine (PCP) intoxication, clinical effects ranged from lethargy and coma to extreme agitation and psychosis.[11]

Common physical examination findings include the following:

Rare findings, usually only seen with high doses, include the following:

Other manifestations include the following:

Laboratory Studies

The diagnosis of phencyclidine (PCP) intoxication is a difficult one to make without a history of drug use from the patient. It should be considered in patients with bizarre behavior, hypertension, and nystagmus, or coma unresponsive to naloxone in a substance abuse case.

Exposure to PCP can be confirmed by qualitative urine toxicology screening. Serum screening for PCP is not useful clinically because the test is not readily available. In addition, quantitative serum PCP level does not correlate with the symptoms.

A fingerstick glucose test should be performed in all patients with altered mental status, as hypoglycemia can cause symptoms consistent with PCP intoxication. In addition, McCarron et al found that 20% of patients with acute PCP intoxication were hypoglycemic on presentation.[11]

No laboratory tests are specific for PCP intoxication, but, in addition to hypoglycemia, elevations in WBC count and BUN and creatinine levels may be seen. Serum creatine phosphokinase and urine myoglobin levels should also be measured to rule out rhabdomyolysis, especially in the patients with severe agitation.

Consider an arterial blood gas (ABG) measurement to assess for hypoxemia and metabolic acidosis in unresponsive patients.

Urine pregnancy tests are indicated for female patients of childbearing age.

Do not rely on the urine toxicology screen to diagnose acute PCP intoxication. Chronic PCP users can have positive test results for weeks after their last use. In addition, false-positive results for PCP have also been reported with many agents, including diphenhydramine (Benadryl) and dextromethorphan, agents in over-the-counter allergy and cough formulations that can produce clinical effects similar to PCP when taken in high doses.[12, 13] Other reported confounders include methadone, ibuprofen, chlorpromazine, and venlafaxine.[14] Consult the laboratory for a list of confounders. If contaminants are a concern, a gas chromatography–mass spectroscopy (GC-MS) confirmatory test can be ordered.

Imaging Studies

No imaging studies are necessary for the evaluation of acute PCP intoxication. Consider a CT scan of the head to rule out an intracranial cause for altered mental status. Consider specific imaging to evaluate traumatic injuries associated with PCP intoxication.

Procedures

For patients who are unable to protect their airway or have evidence of respiratory compromise, endotracheal intubation and mechanical ventilation may be needed.

Consider lumbar puncture in patients with altered mental status and fever in whom the diagnosis is unclear.

Prehospital Care

Evaluate and stabilize the patient's airway, breathing, and circulation (ABCs) including cervical spine immobilization if traumatic injury is suspected.

Physical restraints may be required to prevent self-injury and to protect the medical staff. These patients should be monitored closely due to several death reports of PCP-intoxicated patients while being physically restrained.

Chemical restraints may also be used. Establish intravenous access and administer benzodiazepines for patients with severe agitation. Intramuscular benzodiazepines are an alternative if intravenous access is unobtainable.

Emergency Department Care

After addressing and stabilizing the ABCs, treatment of PCP intoxication starts with initial supportive measures (IV, O2, cardiac monitor). ECG may be indicated to assess for dysrhythmias. Obtain a fingerstick to rule out hypoglycemia. Place patients in a dark, quiet room under continuous observation to minimize environmental stimuli.

Consider activated charcoal for oral ingestions and co-ingestions. Multiple doses of charcoal may be beneficial in the case of large overdose. Only one dose of sorbitol should be given, usually with the initial dose. Clinicians should be aware that inappropriate administration of activated charcoal can convert relatively benign exposure (eg, mild PCP intoxication) into a very serious condition (eg, aspiration pneumonia).

Extreme violent psychotic behavior requires sedation with parenteral benzodiazepines. Seizures should be treated with benzodiazepines. Haloperidol should be reserved for patients with mild, predominately psychotic symptoms, with normal vital signs. Butyrophenones (haloperidol, droperidol) and phenothiazines (eg, chlorpromazine) should be avoided in moderate and severe intoxications because they can lower seizure threshold, cause dystonic reactions, induce hypotension, and worsen anticholinergic symptoms, including hyperthermia.

Hyperthermia may be treated by conventional cooling methods.

Rhabdomyolysis is treated with intravenous hydration, urine alkalinization, and osmotic/diuretic agents. Possible caveat: There is a theoretical, but clinically unproven, concept of increased PCP reabsorption secondary to the urine alkalinization.

For hypertensive emergencies, try to control agitation first with parenteral benzodiazepines. For persistent hypertension, intravenous nitroprusside is the agent of choice. Because of the theoretical concept of unopposed alpha effect (worsening of hypertension) and the availability of other antihypertensive agents (eg, calcium-channel blockers, intravenous nitroglycerin), pure beta-blockade should be avoided. Even labetalol, which has both alpha- (weak) and beta-blocking abilities, can be given only after alpha-blockade with phentolamine is achieved.

Acute PCP toxicity can usually be managed conservatively with an observation period of a few hours. More serious ingestions may require admission to an intensive care unit for days to weeks.

Any patient with evidence of unrelenting agitation, hypertensive crisis, hyperthermia, seizures, respiratory depression, rhabdomyolysis, or severe traumatic injuries should be admitted to the hospital, and possibly to an intensive care setting if indicated.

Consider a psychiatric evaluation for substance abuse counseling and/or suicidal ideations. Consider referral to a drug rehabilitation program. Repeated use of PCP can result in addiction, and abrupt discontinuation of the drug can produce withdrawal symptoms, including craving, confusion, and depression.

Consultations

Consult with a board-certified medical toxicologist or a local poison control center for further recommendations.

Medication Summary

The goals of pharmacotherapy are to relieve the toxic effects of PCP, reduce morbidity, and prevent complications.

Activated charcoal (Liqui-Char)

Clinical Context:  Because PCP undergoes enterohepatic recirculation, may be indicted if clinically feasible. Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.

Class Summary

These agents prevent further absorption of adsorbable toxins from the GI tract. They are most beneficial if administered within 1-2 h of ingestion.

Diazepam (Valium)

Clinical Context:  Enhances GABA transmission. Appears to act on part of the limbic system, the thalamus and hypothalamus, to induce a calming effect. Rapidly distributes to other body fat stores. Twenty minutes after initial IV infusion, serum concentration drops to 20% of Cmax.

Individualize dosage and increase cautiously to avoid adverse effects.

Lorazepam (Ativan)

Clinical Context:  Short-acting anxiolytic with relatively long half-life.

Increases transmission of GABA, a major inhibitory neurotransmitter in the brain.

May be used IV and is well absorbed after IM injection. Onset of action occurs within min of an injection, and effects peak 15-20 min after injection. Duration of action is 6-8 h. No active metabolites exist.

Midazolam (Versed)

Clinical Context:  Used as alternative in termination of refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Thus, clinician must wait 2 min to fully evaluate sedative effects before initiating procedure or repeating dose. Has twice the affinity for benzodiazepine receptors than diazepam. May be administered IM if unable to obtain vascular access.

Class Summary

Indications include agitation, violent behavior, psychosis, seizures, and muscular rigidity.

Nitroprusside (Nitropress)

Clinical Context:  Produces vasodilation and increases inotropic activity of the heart. At higher dosages, may exacerbate myocardial ischemia by increasing the heart rate.

Class Summary

These agents are used for blood pressure control in hypertensive crises to minimize end-organ damage.

Haloperidol (Haldol)

Clinical Context:  Butyrophenone noted for high potency and low potential for causing orthostasis. Downside is high potential for EPS and dystonia. Lowers seizure threshold and worsens anticholinergic symptoms, including hyperthermia. Should be reserved only for mild PCP intoxications with predominantly psychotic features and normal vital signs.

Parenteral dosage form may be admixed with 2 mg lorazepam for better anxiolytic effects.

Class Summary

These agents are used for acute psychosis when no contraindications are present.

Author

Patrick L West, MD, Clinical Instructor, Medical Toxicology Fellow, Department of Emergency Medicine, Oregon Health and Sciences University; Staff Physician, Department of Emergency Medicine, Portland Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Nathanael J McKeown, DO, Assistant Professor, Department of Emergency Medicine, Oregon Health and Science University School of Medicine; Medical Toxicologist, Oregon Poison Center; Attending Physician, Emergency Medicine, Portland Veteran Affairs Medical Center

Disclosure: Nothing to disclose.

Robert S Helman, MD, Director, Premier Care of Great Neck Urgent Care Center

Disclosure: Nothing to disclose.

Specialty Editors

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

Disclosure: Nothing to disclose.

Fred Harchelroad, MD, FACMT, FAAEM, FACEP, Attending Physician in Emergency Medicine and Medical Toxicology, Excela Health System

Disclosure: Nothing to disclose.

Chief Editor

Michael A Miller, MD, Clinical Professor of Emergency Medicine, Medical Toxicologist, Department of Emergency Medicine, Texas A&M Health Sciences Center; CHRISTUS Spohn Emergency Medicine Residency Program

Disclosure: Nothing to disclose.

Additional Contributors

Lance W Kreplick, MD, FAAEM, MMM, UHM, Staff Physician for Occupational Health and Rehabilitation, Company Care Occupational Health Services; President and Chief Executive Officer, QED Medical Solutions, LLC

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Nicole S Johnson, MD, and Mark A Silverberg, MD, to the development and writing of this article.

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