Phencyclidine Toxicity

Etiology

PCP toxicity is caused by the use and abuse of phencyclidine.[2][3][4]

Epidemiology

There were 75,538 emergency department visits in 2011 due to PCP, according to the Drug Abuse Warning Network. This was up 400% from 2005 (14,825). Seventy-two percent of PCP-related emergency department visits in 2011 involved PCP used in combination with other drugs such as marijuana, cocaine, analgesics, and anxiolytics. The majority of emergency department visits due to PCP in 2011 involved male patients (69%). Forty-five percent were patients who were 25 to 34 years old. Patients who were aged 18 to 24 years old and 35 to 44 years old accounted for 19% of emergency department visits each. According to the American Association of Poison Control Centers, there were two deaths from PCP in 2012.  

Pathophysiology

PCP is available as a powder, crystal, liquid, and tablet. It produces both stimulation and depression of the CNS. PCP is a non-competitive antagonist to the NMDA receptor, which causes analgesia, anesthesia, cognitive defects, and psychosis. PCP blocks the uptake of dopamine and norepinephrine, leading to sympathomimetic effects such as hypertension, tachycardia, bronchodilation, and agitation. PCP can also cause sedation, muscarinic, and nicotinic signs by binding to acetylcholine receptors and GABA receptors. Sigma receptor stimulation by PCP causes lethargy and coma.[5][6][7]

Toxicokinetics

PCP, also known as 1-(1-phenylcyclohexyl-piperidine), is a synthetic arycycloalkylamine created from piperidine and cyclohexanone. It has a volume distribution of 6.2 L/kg and a pH between 8.6 and 9.4. It is soluble in water and ethanol. PCP begins to cause symptoms at a dose of 0.05mg/kg, and a dose of 20 mg or more can cause seizures, coma, and death. It is mainly metabolized by the liver, and 10% is excreted in the kidneys. Inhalation (the most common route of administration) and intravenous routes of administration produce symptoms in 2 to 5 minutes. Oral ingestion produces symptoms in 30 to 60 minutes. The half-life is estimated to be 21 hours, but symptoms can last from several hours up to 48 hours, depending on the dose. Recurrent, fluctuating symptoms can occur because PCP is fat-soluble and can be released from lipid stores and adipose tissue that can occur days to months after the initial use.

History and Physical

Depending on the dose, administration route, and coingestants, PCP can cause a wide spectrum of clinical effects, from coma to extreme agitation or psychosis. Many times, patients are unable to give a clear history, so it is imperative to attempt to obtain a history from emergency medical personnel, family, friends, and witnesses. Familiarity with the street names for PCP can be helpful as well.

• General - ranging from coma to severe agitation, hyperthermia, hypoxia
• HEENT– Nystagmus, horizontal, vertical, rotary (60%- 90%), mydriasis (6%), miosis (2%)
• Cardiovascular – hypertension (60%), tachycardia (30%)
• Neurological – mild to severe agitation, confusion, hallucinations, delusions, violent behavior, seizures, muscle rigidity, ataxia, coma
• Trauma - thorough examination for evidence of trauma should be completed as injuries secondary to PCP intoxication can occur due to agitation, hallucinations, diminished perception of pain, and delusions of increased physical ability

Evaluation

The evaluation should include the following:

• Serum PCP level -  not available at many hospitals
• Fingerstick blood glucose - present in 22% of cases of PCP toxicity
• Complete blood count–leukocytosis can be seen
• Electrolyte panel–BUN and creatinine can be elevated
• Creatine kinase– elevated it in 70% of cases with PCP toxicity
• Acetaminophen and salicylate levels–to evaluate for other coingestions
• Electrocardiogram – to evaluation for conduction abnormalities
• Consider CT head – to rule out other causes of altered mental status
• Consider cerebral spinal fluid evaluation – to rule out CNS infection
• Urine toxicology screen – can be helpful to identify coingestions, but may not be helpful to identify acute PCP intoxication because chronic PCP users can have a positive test weeks after their last use. False positives occur for PCP with methadone, ibuprofen, venlafaxine, and chlorpromazine use
• Liver function test – elevated in 50% of cases with PCP toxicity
• Urinalysis -  elevated myoglobin levels
• Imaging studies-  should be performed when there is a concern for trauma secondary to PCP intoxication

Treatment / Management

Most patients survive PCP intoxication with supportive care. Airway, breathing, circulation, and hemodynamic monitoring are essential to the care of patients with PCP toxicity. Intubation with ventilatory support may be required for airway protection.

Gastrointestinal decontamination is generally unnecessary in PCP ingestions; however, activated charcoal may be beneficial with massive ingestion of PCP or a dangerous coingestion. Activated charcoal therapy should only be started within one hour from the time of ingestion. The activated charcoal dose is 1 g/kg, with a maximum dose of 50 g.

Sedation with medication and physical restraints may be required to control agitation, violent behavior, and psychosis due to PCP intoxication. Placing the patient in a calm environment such as a quiet room with the lights dimmed may be helpful. Benzodiazepines are the preferred medication for chemical sedation in patients with PCP toxicity. Lorazepam 2 to 4 mg intravenous (IV) or intramuscular (IM), or diazepam 5 to 10 mg IV or IM are recommended. Repeated doses every 10 minutes may be required for adequate sedation. Benzodiazepines are also the first-line treatment for PCP-induced hypertension and seizures. Hyperthermia from PCP toxicity is due to psychomotor agitation and can be successfully treated with benzodiazepines as well.

Patients with mild symptoms can be discharged one to 2 hours after they become symptom-free and have no other medical complications or behavioral issues that need to be addressed. Patients with severe symptoms or medical complications should be admitted to a monitored bed. Patients who are asymptomatic who present to the emergency department after PCP use should be observed for at least 6 hours before being discharged. Psychiatric evaluation should be considered in patients whose medical symptoms/complications have resolved but required further management of behavioral issues.

Differential Diagnosis

• Alcohol intoxication
• Amphetamine intoxication
• Anticholinergic poisoning
• Bipolar disorder
• Brain neoplasms
• Cocaine toxicity
• Diphenhydramine toxicity
• Delirium tremors
• Encephalitis
• Hyperthyroidism
• Hypoglycemia
• Hyponatremia
• Hypoxia
• Lysergic acid diethylamide (LSD) toxicity
• Malignant hyperthermia
• MDMA toxicity
• Neuroleptic malignant syndrome
• Serotonin syndrome
• Salicylate poisoning
• Toxic alcohol poisoning
• Trauma  (self-induced or accidental)
• Meningitis/encephalitis
• Schizophrenia
• Sepsis
• SSRI toxicity

Complications

• Hypoglycemia
• Seizures
• Myocardial infarction
• Rhabdomyolysis
• Coma
• Intraparenchymal hemorrhage
• Subarachnoid hemorrhage