Phencyclidine Intoxication and Phencyclidine Intoxication Delirium

Diagnosis and Clinical Features. The cornerstone of diagnosis of PCP intoxication (Table 11.11-3) is a history of PCP use, detection of PCP in body fluids, or both. A number of assays for PCP are available; however, for several reasons, it can be dangerous to rely on them. First, the combination of PCP’s lipophilicity, long duration of action, and pKa predicts that prominent clinical effects may be present in the absence of measurable concentrations of PCP in blood or CSF. This is particularly true for acute psychotic reactions, which have been observed at serum PCP concentrations undetectable by most assay systems. A positive assay for PCP should generally be used only qualitatively; it is particularly important not to assume that a low measured concentration predicts an uneventful recovery. pKa considerations in relation to varying urinary and intestinal pH and enterohepatic recirculation indicate that concentrations can be expected to fluctuate. Clinical indications of significant neuronal hyperexcitability, hypertension, hyperthermia, or other physiological dysregulation should be interpreted as indicating a possible

Table 11.11-3.

DSM-IV-TRDiagnostic Criteria for Phencyclidine Intoxication

A.  Recent use of phencyclidine (or a related substance).

B.  Clinically significant maladaptive behavioral changes (e. g., belligerence, assaultiveness, impulsiveness, unpredictability, psychomotor agitation, impaired judgment, or impaired social or occupational functioning) that developed during, or shortly after, phencyclidine use.

C.  Within an hour (less when smoked, snorted, or used intravenously), two (or more) of the following signs:

(1)  Vertical or horizontal nystagmus

(2)  Hypertension or tachycardia

(3)  Numbness or diminished responsiveness to pain

(4)  Ataxia

(5)  Dysarthria

(6)  Muscle rigidity

(7)  Seizures or coma

(8)  Hyperacusis

D.  The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder.

Specify if:

With perceptual disturbances

From American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Washington, DC: American Psychiatric Association; 2000, with permission.

FIGURE11.11-2. Dose range of phencyclidine (PCP) effects. The relation of dose, serum concentration, molecular target sites, and clinical effects is shown. The shaded area represents clinically relevant interactions. ABS, acute brain syndrome; ACh, acetylcholine; BDZ, benzodiazepine; DA, dopamine; GABA, y - aminobutyric acid; 5-HT, serotonin; I. V., intravenous; NE, norepinephrine; NMDA, N-methyl-D-aspartate. (From Javitt DC, Zukin SR: Recent advances in the phencyclidine model of schizophrenia. Am JPsychiatry. 1991;148:1301, with permission.)


Impending medical emergency. Reliance on history may also yield many false negatives, because PCP may have been misrepresented as another drug or used as an adulterant by the dealer. As PCP levels fluctuate, various mixtures of symptoms of intoxication, delirium, and psychosis are seen.

The diagnosis of ketamine abuse must be made, for the most part, without recourse to urine testing. Rapid screening assays are not generally available. Furthermore, ketamine cross-reacts unreliably with immunoassays for PCP. As with PCP, a history of ingestion is critical to making the diagnosis. Typical street doses are in the range of 100 to 200 mg. The most common complaints of ketamine abusers who present themselves to the emergency department are anxiety, chest pain, and palpitations. The most common physical manifestation of ketamine intoxication is tachycardia. Nystagmus is seen in only a minority of cases but is rotary in character when it does occur.

Physiological Bases of Intoxication, Delirium, and Medical Complications. The range of clinical effects of PCP can be correlated with dose, serum PCP concentration, and interaction with several molecular target sites (Fig. 11.11-2). The CNS NMDA receptor complex would be the only system affected significantly at low PCP doses. Serum PCP concentrations as large as approximately .1 pmol correspond to a clinical state manifesting psychotomimetic symptoms and impaired cognition without physiological disturbances of vital functions other than nystagmus, hypertension, tachycardia, dysarthria, or hyperacusis. Serum concentrations just greater than approximately.1 p mol correspond to a state of delirium and, at approximately.3 pmol, to incipient dissociative anesthesia, with prominent numbness or diminished responsiveness to pain. At still higher doses, as additional types of receptors are occupied, acute brain syndrome accompanied by prominent neurological and cardiovascular complications is seen. Deaths from hyperthermia, status epilepticus, and hypertensive crisis have been reported. At high doses, PCP exerts direct excitatory effects on skeletal muscle endplates. These effects may underlie the many reports of superhuman strength from the late 1970s. Together with the behavioral effects of high-dose PCP, these effects probably account for muscle trauma, which, in a number of patients, has resulted in rhabdomyolysis, myoglobinuria, and renal failure. Serum concentrations of 1.0 p mol and greater are associated with coma and death. PCP-induced delirium and coma result from the combination of noncompetitive inhibition of the PCP-NMDA receptor, blockade of the reuptake sites for catecholamines and indolamines, and blockade of sodium and potassium channels and nicotinic and muscarinic cholinergic receptors.

Ketamine, because of its lower potency, shorter half-life, and decreased propensity to interact with non-NMDA binding sites, has much lower associated morbidity and mortality. Death due to uncomplicated ketamine intoxication is rare. For example, in a review of all ketamine-associated deaths in New York City between 1997 and 1999, there were no instances of fatal intoxication due to ketamine alone. In virtually all cases of fatality, ketamine was combined with other drugs, particularly opiates, with cause of death being multidrug intoxication.

NEUROLOGICAL MANIFESTATIONS. The vast majority of PCP-intoxicated patients manifest horizontal, vertical, or rotatory nystagmus, which can help distinguish PCP intoxication from a naturally occurring psychotic state. Neuronal hyperexcitability is dose dependent, ranging from increased deep tendon reflexes, to opisthotonos, to focal or generalized seizures, or to status epilepticus. Focal neurological findings may arise from cerebral vasoconstriction. Coma can occur at any point during intoxication. Rotary nystagmus may also be seen during ketamine intoxication but is less common. The absence of nystagmus therefore cannot be used to exclude a diagnosis of ketamine intoxication.

BEHAVIORAL MANIFESTATIONS. Clinically urgent short-term behavioral complications of PCP abuse stem from behavioral disin-hibition, which can be coupled with severe agitation, panic, rage, and aggression. The disruption of sensory input by PCP can cause unpredictable, exaggerated, distorted, or violent reactions to environmental stimuli. Such reactions are more common with somewhat higher doses, at which some delirium, as well as neurological symptoms and other medical complications, is observed. The behavioral manifestations can severely compromise the clinician’s ability to treat the medical complications.

CARDIOVASCUIAR MANIFESTATIONS.  PCP-induced hyperten

Sion is dose dependent. Mild hypertension is seen in all patients with PCP intoxication. With increasing PCP dose, the panoply of sympathomimetic responses is seen; hypertensive crisis is common in association with high doses and may lead to cerebral hemorrhage. Tachycardia and mild hypertension are also seen with ketamine but are substantially less severe and unlikely to be life threatening.

AUTONOMIC MANIFESTATIONS.  Severe hyperthermia has been

Observed and can be delayed, fatal, or both. The anticholinergic properties of PCP can evoke the full spectrum of atropine-like toxicity in a dose-dependent manner and can be managed accordingly.

Diffe rential D iagnosis.  Even when PCP is detected in body

Fluids, remember that PCP is frequently taken in combination with another drug or drugs. Depending on the analytical method used, an assay for PCP may fail to detect an intoxicating concentration of PCP. Although not conclusive or totally specific for PCP intoxication, the constellation of nystagmus, ataxia, and mild hypertension is typically observed even in mild, low-dose PCP intoxication.

Treatment.  Treatment of PCP intoxication aims to reduce sys

Temic PCP levels and to address significant medical, behavioral, and psychiatric issues. For intoxication and PCP-induced psychotic disorder, although resolution of current symptoms and signs is paramount, the long-term goal of treatment is prevention of relapse to PCP use. PCP levels may fluctuate over many hours or even days, especially after oral administration. Therefore, a prolonged period of clinical observation is mandatory before concluding that no serious or life-threatening complications will ensue.

Trapping of ionized PCP in the stomach has led to the suggestion of continuous nasogastric suction as a treatment for PCP intoxication. However, this strategy can be needlessly intrusive and can induce electrolyte imbalances. Administration of activated charcoal is safer, and it binds PCP and diminishes toxic effects of PCP in animals.

Trapping of ionized PCP in urine has led to the suggestion of urinary acidification as an aid to drug elimination. However, this strategy may be ineffective and is potentially dangerous. Only a small portion of PCP is excreted in urine, metabolic acidosis itself carries significant risks, and acidic urine can increase the risk of renal failure secondary to rhabdomyolysis. Because of the extremely large volume of distribution of PCP, neither hemodialysis nor hemoperfusion can significantly promote drug clearance.

No drug is known to function as a direct PCP antagonist. Any compound binding to the PCP receptor, which is located within the ion channel of the NMDA receptor, would block NMDA receptor-mediated ion fluxes as does PCP itself. NMDA receptor mechanisms predict that pharmacological strategies promoting NMDA receptor activation (e. g., administration of a glycine site agonist drug) would promote rapid dissociation of PCP from its binding sites. However, no clinical trials of NMDA agonists for PCP or ketamine intoxication in humans have been carried out to date. Therefore, treatment must be supportive and directed at specific symptoms and signs of toxicity. Classical measures should be used for medical crises, including seizures, hypothermia, and hypertensive crisis.

Because PCP disrupts sensory input, environmental stimuli can cause unpredictable, exaggerated, distorted, or violent reactions. A cornerstone of treatment is therefore minimization of sensory inputs to PCP-intoxicated patients. Patients should be evaluated and treated in as quiet and isolated an environment as possible. Precautionary physical restraint is recommended by some authorities, with the risk of rhabdomyolysis from struggle against the restraints balanced by the avoidance of violent or disruptive behavior. Pharmacological sedation can be accomplished with oral or IM antipsychotics or benzodiazepines; there is no convincing evidence that either class of compounds is clinically superior. Because of the anticholinergic actions of PCP at high doses, neuroleptics with potent intrinsic anticholinergic properties should be avoided.

Course and Prognosis. Complete recovery from PCP intoxication is the rule in the absence of major medical complications. However, many patients relapse to PCP use immediately after discharge from treatment, even after severe PCP-related complications. Intoxication usually occurs in the context of abuse, dependence, or both. Unfortunately, no specific behavioral treatments for PCP abuse and dependence have been described. Case reports indicate successful responses to residential and intensive outpatient treatment regimens with long-term follow-up, including urine monitoring with or without contingency contracting.

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