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Phencyclidine (PCP) intoxication in adults

Phencyclidine (PCP) intoxication in adults
Literature review current through: Jan 2024.
This topic last updated: Jun 20, 2022.

INTRODUCTION — Despite a fall in popularity since the 1970s, phencyclidine (PCP) continues to be used. Approximately 500 exposure cases involving PCP are reported to United States poison centers annually and that number appears to be stable [1]. Early identification and prompt symptomatic treatment are vital to avoid possible sequelae, including rhabdomyolysis and seizures.

The basic pharmacology, clinical manifestations, and management of PCP intoxication in adults is reviewed here. The management of PCP poisoning in children, ketamine and other sympathomimetic poisonings, and other issues related to the management of the poisoned patient are discussed separately. (See "Phencyclidine (PCP) intoxication in children and adolescents" and "Ketamine poisoning" and "General approach to drug poisoning in adults".)

PHARMACOLOGY AND CELLULAR TOXICOLOGY — PCP, or 1-(1-phenylcyclohexyl) piperidine hydrochloride, is a synthetic arylcycloalkylamine discovered in 1926 and a dissociative anesthetic. It is synthesized from piperidine and cyclohexanone [2]. It is a weak base with a pKa of 8.6 and is soluble in water and ethanol [3].

PCP is a stable white solid with a bitter taste. It is manufactured in many forms for recreational use, including powder, crystal, liquid, and tablets [4]. It has been sprinkled on leaves for ingestion, and there are reports of it being combined with embalming fluid to enable the drug's uniform distribution in cigarettes (often referred to as "wet," "illy," or "fry") [5]. Concentrations of the drug vary in PCP tablets (1 to 6 mg) and PCP-laced marijuana (1 to 10 mg) [6,7].

PCP has a number of analogs that may also be abused, including PHP (rolicyclidine, phenylcyclohexylpyrrolidine), PCE (N-ethyl-1-phenylcyclohexylamine), TCP (1-[1-(2-thienyl) cyclohexyl] piperidine), and PCC (1-piperidinocyclohexane-carbonitrile). PCC is commonly found in street grade PCP. PCC has the potential for increased toxicity due to the release of hydrogen cyanide when smoked [2], although acute cyanide toxicity is unlikely [8]. Another analog 3-Methoxyphencyclidine appears to cause similar effects [9] and has been implicated in several deaths [10-12]. There have been reports of less well-regulated designer drugs related to PCP with similar toxicity profiles including: methoxphenidine (a diarylethylamine) [13], and gacyclidine (a derivative of PCP or TCP) [14].

The dose of PCP varies depending upon the amount of active drug and the route. In general, symptoms first appear at 0.05 mg/kg. Alteration of body image has been reported at 0.1 mg/kg and 10 mg has been reported to cause catatonic stupor [15].

PCP is a noncompetitive antagonist of NMDA receptors [16]. It also stimulates sigma receptors and blocks the reuptake of biogenic amines. Stimulation of alpha adrenergic receptors is thought to be responsible for its sympathomimetic effects and cerebral vasospasm.

PCP has three primary sites of action in the central nervous system:

N-methyl-D-aspartate (NMDA) receptor complex – PCP has great affinity for NMDA receptor complexes in the hippocampus, neocortex, basal ganglia, and limbic system [16]. NMDA antagonism at these sites produces acute psychosis that mimics schizophrenia in humans and leads to excess excitatory neurotransmitter release (eg, glutamate, glycine, aspartate) that can cause agitation and seizures.

Dopamine, norepinephrine, and serotonin reuptake complex – PCP inhibits reuptake of dopamine, norepinephrine, and serotonin in neurons [17]. This action contributes to the adrenergic and dopaminergic effects of PCP intoxication.

Sigma receptor complex – PCP binding to the sigma receptor may explain, in part, the psychotic, anticholinergic, and movement abnormalities seen with intoxication [18].

KINETICS — The absorption, peak serum concentration, and duration of effect vary with the route of PCP use. A retrospective study of 1000 patients found smoking to be the most common route (72 percent), usually via laced cigarettes or marijuana, followed by insufflation (13 percent), ingestion (12 percent), and intravenous (IV) injection (1.5 percent) [6]. Smoking, insufflation, and IV or intramuscular routes produce symptoms within two to five minutes, while oral ingestion produces symptoms in 30 to 60 minutes.

Smoking causes a rapid initial peak in plasma concentrations at five minutes and a second peak at 22 minutes. The second peak may be related to delayed absorption from the lungs. The mean half-life after smoking (24 hours) is similar to the IV route [7].

The peak effect following ingestion is approximately 90 minutes. The duration of action (one to three hours) is similar to the IV route [19]. PCP may undergo enterogastric recycling following oral doses [20]. Although not well absorbed in the stomach, PCP is actively secreted into the gastric fluid, where concentrations can reach 50 times that of the serum. It is then absorbed in the more alkaline small intestines.

IV injection of PCP produces an immediate effect. Following IV injection, the duration of action is one to two hours, despite the long terminal half-life (21 hours).

PCP has a large volume of distribution (6.2 L/kg) and is 65 percent protein bound [19]. The drug's high lipid solubility accounts for the ease with which it crosses the blood brain barrier and enters adipose tissue [16]. Cerebrospinal fluid (CSF) levels are reported to be four times serum levels due to the slightly more acidic pH of the CSF [21].

PCP displays first order kinetics with a half-life of 7 to 26 hours [22].

Elimination of PCP is principally by hepatic metabolism [19]. It is rapidly metabolized in the liver to hydroxylated derivatives and excreted in the urine primarily as a mono-4-hydroxypiperidine conjugate. These metabolites are thought to have minimal pharmacologic activity [3]. Approximately 5 to 10 percent is excreted unchanged in the urine [20]. A lower urine pH increases renal clearance, but this contributes little to overall elimination and may be dangerous. (See 'Enhanced elimination' below.)

CLINICAL FEATURES OF OVERDOSE

History — The diagnosis of PCP intoxication is made based upon the history and clinical evaluation. Unfortunately, a clear history is often unavailable as patients are frequently alone and exhibit alterations in mental status. Sometimes friends or emergency medical services personnel provide useful details. It can be helpful to know the street names for PCP, which include angel dust, embalming fluid, killer weed, peace pill, horse tranquilizer, and hog [23,24].

Severe poisoning can occur if a patient ingests large amounts of poorly packaged drug to avoid discovery by the authorities (body stuffing) or a break occurs in a container of concentrated drug that the patient has swallowed for the purpose of illicit transport (body packing). Co-ingestants are common with PCP use and may alter the clinical presentation or treatment. Marijuana cigarettes sometimes contain PCP [5]. (See "Internal concealment of drugs of abuse (body packing)".)

Physical examination

General findings — Physical examination should begin with an assessment of the patient's airway, breathing, circulation, and mental status. Although uncommon, patients with large PCP ingestions may present with profound CNS and respiratory depression requiring immediate endotracheal intubation. (See 'Management' below.)

PCP intoxication can produce a wide range of vital signs and physical findings depending upon the amount ingested, the route of administration, patient susceptibility, and the presence of co-ingestants (in one case series, 54 percent took another substance) [25]. Adrenergic stimulation is typical, but patients may exhibit central nervous system (CNS) stimulation or depression. Most patients are alert but experience hallucinations and demonstrate odd behavior and agitation similar to acute psychosis [6]. Patients may unexpectedly progress to coma, which may be prolonged. Because of this unpredictability, vital signs and clinical assessment should be repeated often until the patient has stabilized.

Vital signs — Blood pressure elevation is reported in 32 to 57 percent of patients with PCP intoxication. Systolic blood pressure correlates with elevated plasma drug concentrations and is significantly higher than controls [26,27]. According to a large retrospective case series, hypertension resolves in less than four hours in 62 percent of cases but persists over 24 hours in 11 percent [6]. Spontaneous intracranial hemorrhage in association with uncontrolled hypertension has been reported [28-30].

Tachycardia occurs in 30 to 43 percent of patients with a positive urine PCP test [6,26]. In a case control study, tachycardia was more common in patients with confirmed PCP intoxication [27]. Patients may be hyperthermic (2.6 to 4 percent) or hypothermic (6.4 percent) depending upon the degree of psychomotor agitation and environmental conditions [6,31].

Neuropsychiatric findings — CNS signs and symptoms are common and vary widely. Patients may be alert with bizarre behavior, agitated or violent, or sedated and bordering on comatose. Furthermore, these symptoms may wax and wane over time. In case series, 46 to 52 percent of patients were alert and oriented upon arrival to the hospital, but most are alert and awake [6,25].

Psychomotor agitation occurs often, with observational data suggesting a rate between 34 and 64 percent [6,26]. Violence has been reported in 13 to 35 percent of patients and is more common in single drug exposures. According to a case series of 1000 confirmed PCP-intoxicated patients, 13 percent were involved in an altercation, of which 33 percent involved a gun or knife used to threaten others and 22 percent involved self-inflicted wounds [6]. Such violent behavior may be associated with delusions of super-human strength and diminished pain perception. Caregivers should be cautious when caring for agitated patients with possible PCP intoxication.

In the same case series, psychomotor symptoms related to PCP intoxication were grouped into major and minor patterns [6]. Major symptoms, including acute brain syndrome (defined below), psychosis, catatonia, and coma, were associated with a more severe course and poorer outcomes. Complications included trauma (16 percent of patients), rhabdomyolysis (2.2 percent), and aspiration pneumonia (1 percent). Minor symptoms included lethargy or stupor and combinations of bizarre behavior, violence, agitation, and euphoria in patients who were otherwise alert and oriented. Minor symptoms were usually associated with a less severe clinical course.

Acute brain syndrome, defined as disorientation combined with confusion, lack of judgment, inappropriate affect, or loss of memory, was the most common major symptom, reported in 37 percent of patients in one case series [32]. Psychosis was reported in 16.6 percent of patients in the aforementioned series, including 63 percent of patients without co-ingestants. A smaller case series reported a high rate of auditory hallucinations [31]. Visual and tactile hallucinations can also occur. Full recovery from psychosis may take weeks to months [33].

In the case series cited above, catatonia was found in 11.7 percent of patients [32]. In another series, approximately 6 percent of patients were reported to be wandering in public and 56 percent of them had disrobed [6]. Catatonia is typically of short duration with 85 percent of cases resolving by 24 hours [34].

Lethargy or stupor was reported in 3.8 percent of patients [32]. Coma was reported in 11 percent of patients, with the duration of unconsciousness ranging from 30 minutes to seven days. A smaller case series reported that 50 percent of patients developed a decreased level of consciousness at some time during their clinical course [26].

Horizontal, vertical, or rotatory nystagmus is common with reported rates ranging from 57 to 89 percent of cases (table 1) [6,27]. Other potential CNS effects include dystonic reactions, tardive dyskinesia, and athetosis, but these are rare. Symptoms such as ataxia, dysarthria, nausea, and vomiting may also occur.

Complications — Fatalities in the setting of PCP intoxication are uncommon and most are secondary to trauma. Other causes include hyperthermia, respiratory arrest, and intracranial hemorrhage.

Treating clinicians should be aware of the potential for multiple serious complications in patients with PCP intoxication. These occur most often with large ingestions and may include:

Rhabdomyolysis

Seizures

Hypoglycemia

Prolonged comatose state

Rhabdomyolysis developed in 2.2 percent of patients in one series of 1000 patients [32] and hemodialysis was necessary in 0.3 percent. In another case series, 40 percent of patients with PCP-associated rhabdomyolysis (defined as myoglobinuria and a creatine phosphokinase concentration above 16,000 IU/L) developed acute renal failure [35].

Seizures occur infrequently, with estimates ranging from 2.6 to 6 percent of cases [6,31,36]. Status epilepticus has been reported.

Prolonged psychiatric illness may stem from an underlying condition or drug effect. Psychiatric evaluation should be obtained after a period of observation confirms the patient is medically stable. A retrospective review performed at a psychiatric facility found that 20 patients with new-onset PCP-induced psychosis needed shorter hospitalizations (average 4.8 days; range 1 to 9) compared with 20 patients with new-onset functional psychosis (13.9 days; range 3 to 41) [37]. However, there are reports of patients with PCP-induced psychosis requiring up to four to six weeks for full recovery.

DIFFERENTIAL DIAGNOSIS — Due to the variable presentation of PCP intoxication, the differential diagnosis is considerable. Other toxicologic causes that should be entertained in cases of altered mental status, hallucinations, and excessive adrenergic activity include sympathomimetics, anticholinergic toxicity, other hallucinogens (LSD, mescaline, and psilocybin), ethanol or sedative hypnotic drug withdrawal, neuroleptic malignant syndrome (NMS), serotonin syndrome, and salicylate toxicity (table 2). (See "General approach to drug poisoning in adults" and "Evaluation of abnormal behavior in the emergency department" and "Methamphetamine: Acute intoxication" and "Anticholinergic poisoning" and "Intoxication from LSD and other common hallucinogens" and "Management of moderate and severe alcohol withdrawal syndromes" and "Serotonin syndrome (serotonin toxicity)" and "Salicylate (aspirin) poisoning: Clinical manifestations and evaluation".)

Medical illness must also be considered. Altered mental status and vital sign abnormalities should lead to careful evaluation for central nervous system infections (encephalitis, meningitis) and sepsis. Metabolic etiologies such as hypoglycemia, hyponatremia, hyperthyroidism, and hypoxia are easily assessed and should be investigated. Occult head trauma can cause acute changes in mental status. Patients without apparent medical or toxicologic illness who remain symptomatic should be evaluated for possible psychosis. (See "Clinical features and diagnosis of acute bacterial meningitis in adults" and "Diagnosis of delirium and confusional states".)

LABORATORY EVALUATION

General testing — Routine laboratory evaluation of the poisoned patient should include the following:

An electrocardiogram, to assess for cardiac conduction abnormalities

Fingerstick glucose, to rule out hypoglycemia as the cause of any alteration in mental status

Acetaminophen and salicylate concentrations (in patients with suspected self-harm ingestion), to rule out these common co-ingestions

Pregnancy test in women of childbearing age

Several other laboratory studies are indicated in the setting of PCP intoxication, including creatine kinase, urine myoglobin, and liver transaminases. Further testing is performed based upon clinical assessment. As examples, BUN and creatinine are obtained if rhabdomyolysis or other potential causes of renal failure are suspected, while a CT of the head and evaluation of cerebrospinal fluid may be needed in the setting of a persistently altered mental status.

The most common laboratory abnormalities associated with PCP intoxication include an elevated creatine kinase (70 percent), elevated liver transaminases (50 percent), hyperuricemia (24 percent), and hypoglycemia (22 percent) [6].

Testing for PCP — Serum and urine tests to determine PCP concentrations are available at some hospitals. However, the results of such tests are generally not available with sufficient speed to be of use during acute management.

Serum concentrations were once widely available, but with the decreased prevalence of PCP, most labs offer qualitative testing only. Qualitative testing is more helpful than quantitative concentrations since serum levels do not correlate well with brain concentrations or clinical toxicity [26,27]. Confirmatory testing using gas chromatography with mass spectroscopy is performed on rare occasions when definitive drug identification is needed [38].

The United States National Institute on Drug Abuse (NIDA) guidelines for federal workplace drug testing uses a cutoff urine PCP concentration of 25 ng/mL. Urine toxicology screens may remain positive for several weeks. In one series of chronic users, urine screens remained positive for an average of 14 days [39]. CSF testing has been reported in two cases with concentrations one to four times the serum levels [21].

Multiple causes of false positive urine tests have been reported and the potential adverse medicolegal consequences of such results are profound. Drugs capable of causing a false positive urine test include ketamine [40], dextromethorphan [38,41], diphenhydramine [42], venlafaxine [43], and tramadol [44,45]. In addition, there is evidence to suggest that alprazolam, clonazepam, carvedilol, and lamotrigine may cross react as well [46,47]. Because the cross-reactivity of tests varies among manufacturers, the best information is available from the test manual.

MANAGEMENT

Airway, breathing, and circulation — Initial stabilization including a rapid assessment of the airway, breathing, and circulation is important. Airway protection with endotracheal intubation and mechanical ventilation was necessary in 1.2 percent of patients in one large case series [32]. Theoretically, succinylcholine may exacerbate rhabdomyolysis-related hyperkalemia.

Some clinicians believe that PCP intoxication may increase airway secretions and the risk of laryngospasm, but such cases are likely to be extremely uncommon.

Patients with potentially life-threatening clinical findings (eg, stupor, hyperthermia) are placed on a cardiac monitor, given supplemental oxygen, and have intravenous access established. Abnormal vital signs are addressed immediately, and advanced life support measures are instituted as needed. Further acute interventions are based upon clinical findings, as quantitative testing for PCP is generally unavailable and unhelpful. (See "General approach to drug poisoning in adults" and "Advanced cardiac life support (ACLS) in adults".)

Sedation — Rapid control of psychomotor agitation is the cornerstone of successful management. Physical restraints may be necessary initially and several staff members are often needed to control patients agitated from PCP. Thereafter, chemical sedation is essential to control agitation, prevent or treat hyperthermia, perform a thorough physical examination, and obtain necessary studies.

Little evidence exists to guide the use of sedatives in the management of PCP intoxication. Based upon observational reports and broad clinical experience, we believe benzodiazepines are the preferred agents to achieve chemical sedation. We treat severely agitated patients immediately with benzodiazepines (eg, lorazepam 4 mg intravenously [IV] or midazolam 5 mg IV, or intramuscularly [IM] if IV access is not available). These doses can be repeated every five to ten minutes based upon patient response.

Butyrophenones (eg, droperidol 5 mg or haloperidol 5 to 10 mg) may be used as adjunctive therapy when benzodiazepines do not adequately control symptoms [48]. These doses may be repeated. Some clinicians prefer to avoid butyrophenones because they are purported to lower the seizure threshold and impair heat dissipation in hyperthermic patients. However, there are no high-quality studies in humans to support such claims.

In the rare case of severe refractory psychomotor agitation or status epilepticus, treatment with a barbiturate or a propofol infusion may be necessary. Endotracheal intubation and mechanical ventilation are commonly required in such instances.

We treat mildly or moderately intoxicated patients with benzodiazepines and a quiet environment. Lorazepam 1 to 2 mg IV or midazolam 2 to 5 mg IV may be adequate, and should be repeated as needed. Small observational studies suggest that sensory deprivation (dark, quiet room; hands covered) may decrease agitation [49].

Treatment of complications — Once adequate sedation is achieved, the patient with PCP intoxication should be carefully examined for secondary injuries. PCP intoxication often leads to bizarre behavior, hallucinations, delusions of physical prowess, and a diminished perception of pain. As a result, PCP abuse is often associated with trauma. A large case series reported injuries in 13 percent of patients, 22 percent of which were self-inflicted [6].

Other major potential complications of PCP intoxication include hyperthermia, seizures, rhabdomyolysis, and hypertension. Hyperthermia typically improves with adequate sedation, but external cooling and, in a small number of severe refractory cases, even paralysis and mechanical ventilation may be necessary. Hypertension is typically transient and rarely requires pharmacologic intervention beyond sedation. Refractory hypertension can be treated with short acting agents such as nitroglycerin or nitroprusside that can be titrated to effect. Cardiac monitoring and frequent reexamination are essential in patients with any significant complication. (See "Severe nonexertional hyperthermia (classic heat stroke) in adults" and "Convulsive status epilepticus in adults: Classification, clinical features, and diagnosis" and "Evaluation and treatment of hypertensive emergencies in adults" and "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)".)

Animal studies suggest that antipsychotic medications can block PCP mediated behavioral effects [50]. Clinical trials in humans are needed before this approach can be recommended.

Decontamination — Most patients survive PCP intoxication uneventfully with supportive care; decontamination is generally unnecessary in isolated ingestions. However, decontamination with activated charcoal (AC) may be useful if a massive ingestion or a potentially dangerous co-ingestant is present and treatment is started within one hour of ingestion. Patients who ingest large amounts of PCP to avoid police detection (body stuffers) or to transport drug for distribution (body packers) may sustain massive ingestions. Any potential benefit from AC must be weighed against the risk of aspiration, especially given the potential for altered mental status and seizures with severe PCP intoxication. AC is given in a dose of 1 g/kg (maximum 50 g).

We do NOT typically use multidose activated charcoal (MDAC) in patients with PCP intoxication. MDAC provides a theoretical benefit because of the extensive enterohepatic recirculation of PCP. Dogs treated with AC following oral doses of PCP demonstrated decreased duration of anesthesia, seizures, and death [51]. Giving rats activated charcoal following an oral dose of PCP significantly elevated the lethal dose (LD50) of PCP [51]. However, there is no evidence of clinical benefit in humans, and the potential for aspiration exists whenever AC is given.

We do not suggest the use of nasogastric suction in patients with PCP intoxication. Nasogastric suction is theoretically beneficial when performed soon after ingestion due to the high concentration of PCP in the stomach's acidic environment. However, it has no proven benefit and may cause electrolyte abnormalities, aspiration, and unwanted difficulty in agitated patients.

Whole bowel irrigation is not routinely recommended. It should only be used in patients who have ingested potentially lethal amounts of PCP, as may occur with body stuffers or body packers. (See "Internal concealment of drugs of abuse (body packing)".)

Enhanced elimination — Neither urine acidification nor charcoal hemoperfusion should be used in the treatment of PCP intoxication.

Although some toxicologists have proposed urinary acidification as a means of increasing PCP clearance [20], this process increases total drug clearance by only one percent [4,7]. Moreover, acidification increases the potential for systemic acidosis, worsening rhabdomyolysis and renal damage, and precipitation of uric acid leading to nephrolithiasis [52].

In a study of dogs loaded with 5 mg/kg of PCP, charcoal hemoperfusion failed to reduce the number of seizures, duration of coma, or tissue concentration compared with control animals [53]. Only 2 percent of the parent compound was recovered. The authors concluded that PCP's high volume of distribution, high lipid solubility, and low plasma concentration make removal by hemoperfusion ineffective.

DISPOSITION — Due to the variable course of PCP toxicity, even patients without severe symptoms or complications benefit from some period of observation. Patients presenting early following an ingestion may be asymptomatic initially but should be observed for at least six hours. Patients with mild symptoms presenting a few hours after the onset of intoxication generally recover within several hours. Such patients may be discharged provided the effects of intoxication have resolved and the patient remains symptom-free during a brief (one to two hours) period of observation. In a case series of 184 patients, 83 percent went home, 8 percent were admitted, and the rest were transferred to a crisis center [25].

Any patient with significant complications (eg, rhabdomyolysis, coma, status epilepticus) or severe symptoms (eg, uncontrolled hypertension, hyperthermia) should be admitted to an intensive care setting. Patients with less severe but persistent symptoms should be admitted to an appropriate ward for further monitoring and treatment.

Psychiatric evaluation should be obtained where appropriate, once medical problems have been addressed. Chronic abusers may benefit from treatment for substance abuse. (See "Substance use disorders: Clinical assessment".)

FUTURE CONSIDERATIONS — Supportive care remains the cornerstone of the management of PCP toxicity. However, the use of monoclonal antibodies to reverse toxicity is being studied and may provide an alternative approach in the future [54,55]. Monoclonal anti-phencyclidine Fab antibody fragments successfully reversed PCP-induced locomotor effects in a rat model [54]. These antibodies are not able to cross the blood brain barrier and directly reverse receptor binding. However, the antibodies decrease the concentration of free PCP and alter its pharmacokinetics.

PEDIATRIC CONSIDERATIONS — The clinical presentation of PCP intoxication is different in infants and young children than in adolescents or adults. The diagnosis and management of children with PCP intoxication is reviewed separately. (See "Phencyclidine (PCP) intoxication in children and adolescents".)

ADDITIONAL RESOURCES

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment" and "Society guideline links: Treatment of acute poisoning caused by recreational drug or alcohol use".)

SUMMARY AND RECOMMENDATIONS

Pharmacology and kinetics – Phencyclidine (PCP) is a dissociative anesthetic that is abused primarily for its hallucinatory effects. Significant toxicity is rare but potentially serious. The drug's onset of action is rapid, but the duration of action is generally brief (one to four hours). (See 'Pharmacology and cellular toxicology' above and 'Kinetics' above.)

Clinical presentation – Symptoms and signs of PCP intoxication vary depending upon the route of exposure, dose, and co-ingestants, and may include altered mental status (from comatose to profound psychomotor agitation), hallucinations, hypertension, tachycardia, and multidirectional nystagmus. Severe complications may include traumatic injuries, rhabdomyolysis, hyperthermia, and seizures. (See 'Clinical features of overdose' above.)

Differential diagnosis – Due to the variable presentation of PCP intoxication, the differential diagnosis is vast. (See 'Differential diagnosis' above.)

Laboratory testing for PCP – Quantitative drug concentrations have little role in the management of acute toxicity. Qualitative testing is available, but false positives are frequent. Results may remain positive for weeks. (See 'Testing for PCP' above.)

Control of agitation – Rapid control of psychomotor agitation is the cornerstone of successful management. Physical restraints may be necessary initially and several staff members are often needed to control patients agitated from PCP. Chemical sedation should be administered as rapidly as possible. Decontamination and other aspects of management are discussed above. (See 'Management' above.)

In patients with PCP-related psychomotor agitation who require sedation, we suggest the use of benzodiazepines (Grade 2C). We treat severely agitated patients immediately with intravenous (IV) benzodiazepines (lorazepam 4 mg IV or diazepam 5 to 10 mg IV). These doses can be repeated every eight to ten minutes based upon patient response. In severely intoxicated patients, intramuscular (IM) injection may be used initially if IV access is unavailable. Midazolam (5 mg IM) may be used in such situations. (See 'Sedation' above.)

We treat mildly or moderately intoxicated patients with benzodiazepines and a quiet environment. Lorazepam 1 to 2 mg IV or diazepam 2 to 5 mg IV may be adequate, and may be repeated as needed. (See 'Sedation' above.)

Disposition – Patients with significant symptoms should be admitted to a monitored setting. Due to the relatively short duration of action, patients with mild symptoms are candidates for a period of observation and discharge. Patients whose medical symptoms resolve but have persistent behavioral issues should undergo a psychiatric evaluation. (See 'Disposition' above.)

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Topic 313 Version 26.0

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