ORIGINAL CONTRIBUTION

Emergency Management of Acute Phencyclidine Intoxication Richard T. Rappolt, Sr, MD, ABMT San Francisco, California George R. Gay, MD, ABA, ABFP R. David Farris . San Diego, California

Phencyclidine (PCP) is a potent sympathomimetic and hallucinogenic dissociative anesthetic agent. As an abused street drug, it is most often smoked, thus allowing the user to titrate the dose. The clinical signs of PCP intoxication can be viewed in three dose-related stages, but waxing and waning of signs through the three stages is not uncommon. Treatment protocols for each stage address drug therapy and both clinical and psychological supportive measures. Rappolt RT Sr, Gay GR, Farris RD: Emergency management of acute phencyclidine intoxication. JACEP 8:68-76, February, 1979.

phencyclidine, poisoning; drug abuse, phencyclidine

INTRODUCTION It hit Haight-Ashbury in 1967 - PCP quickly acquired a reputation as a bummer drug. People named Strawberry were going around punching people named Wildflower. (T. Cahill, Rolling Stone, July 13, 1978.)

PCP, or phencyclidine (phenylcyclohexylpiperidine, an arylcycloakylamine), is a potent sympathomimetic and hallucinogenic dissociative anesthetic agent. Exhibiting high potency, with almost no respiratory depressant effect, at first it promised to be the long sought "perfect" intravenous anesthetic. First synthesized as Sernyl, beginning in 19571-3 it was studied as a nonnarcotic, nonbarbiturate anesthetic agent. Disturbing reports of psychologically distressing emergence and dysphoric postanesthetic reactions, however, brought an end to human testing in 1965. 4-9 In 1967, PCP was reintroduced as Sernylan and marketed as a veterinary anesthetic, used principally in primate research. 1° Since April of 1978, however, all legal manufacture and sale has been stopped and it is now classified as a controlled substance under class II of the Comprehensive Drug Abuse Prevention and Control Act of 1970.11 The structurally similar arylcycloakylamine anesthetic, ketamine (Ketalar), is marketed, however, and is in current clinical use in h u m a n subjects. Some patients report adverse reactions with this drug similar to those of PCP. 12 Phencyclidine was first seen as a street drug in San Francisco in 1967 where it was sold as the PeaCe Pill23 It is currently dealt as PCP, Angel Dust, Crystal, Hog, Kay J a y CKristal Joint"), the Pits or Rocket Fuel. 14-21 Often, too, because of its extreme potency, it is misrepresented as other "consciousness alPresented at the annual ACEP/EDNA Scientific Assembly in Houston, Texas, September, 1978. Address for reprints: Richard T. Rappolt, Sr, MD, 4104 Geary,Suite 403, San Francisco, California 94118. 8"2 (February) 1979

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t e r i n g " drugs, such as THC (tetrahydrocannabinol), cocaine, LSD, mescaline, psilocybin, etc.19, 2° It is easy to make in a kitchen laboratory. Piperidene p h o s p h a t e and cyclohexane are the main ingredients and it is, therefore, cheap. (One gram of PCP, ranging in purity from 10% to 100% may retail on the street for $60 to $75. From 10 to 50 mg may be snorted or rolled into a Kay Jay. To project a rough analogy, a joint of highest grade marijuana might retail for $15; a high grade Kay Jay would retail for $3.75.) 21 PCP is a white crystalline solid, readily soluble in both water and alcohol. It has a pKa of approximately 8.5.14 It can be self-administered by smoking something laced with the drug, by snorting it (insufflation), by oral ingestion, or occasionally by injection. The most favored route among chronic abusers is smoking, u s u a l l y rolled into a joint of marijuana or tobacco leaves. This and snorting Chorning," "snarfing") permits the user to titrate to some degree his level of intoxication.11,14, TM The onset is rapid, however, and profoundly incapacitating symptoms occur at relatively light levels of anesthesia. Oral ingestion of PCP is now rarely seen in the sophist i c a t e d drug user, a l t h o u g h this method may be employed in a suicide attempt. Excretion of PCP occurs in the urine, directly as the unchanged substance, with the glucuronides of its two known h y d r o x y l a t e d metabolites. 22-24 Urinary excretion is markedly pH dependent, with more than a 100-fold increase in excretion seen when the urine is acidified to 5.5 or lower. 14 The Clinical Reality

Even the mildly intoxicated PCP user presents a bizarre clinical picture. The PCP patient . . . [/s] sometimes 'zombielike' but quite often 'combative and hostile.' . . . A n orderly said that a lot o f patients come in after they punched out a window or something and that they liked to make animal sounds . . . . barking, growling, and gorilla-like s n o r t i n g . . . They seem to g a i n enormous strength, crazy strength. It takes a lot of people to hold them d o w n . . . You can hit them in the face, break their noses, and that should stop anyone. On PCP it might j u s t agitate them." (T. Cahill, Rolling Stone, July 13, 1978).

Disorientation, hallucination, extreme agitation, loss of motor control, nystagmus, drooling, vomiting 36/69

CLINICAL REGIMEN: PCP OVERDOSE: GENERAL

I.

what you can. vital signs continuously

HISTORY: Get

II. M O N I T O R QUENCE:

- - establish TEMPORAL SE-

Is Patient emerging or deepening? II1. ANALYSIS: Get blood, urine, gastric content in comatose patient, But DO NOT UNNECESSARILY INSTRUMENT THE "WALKING WOUNDED." IV. ASSESS level of intoxication: I CONSCIOUS?I I STAGE! ~

J

yes

~

no

t RESPONDS TODEEP PAIN? I [ STAGE II J'~-- yes

J

~

no

[ STAGE I1' I IF IN DOUBT, HOSPITALIZE. Fig. 1. G e n e r a l clinical r e g i m e n in t r e a t i n g suspected P C P overdose patient.

and diaphoresis create a frightening emergency department experience for the uninitiated health professional. The mildly intoxicated patient who is still upright will exhibit a ~slow, awkward, stiff-legged, almost tabetic, lurching gait. PCP has recently received much media attention, for example '~60 Minutes," which has focused on these early signs and upon PCP's rather marked psychotomimetic "behavioral toxicity."11,14,18, 2~-2s PCP has thus emerged in public consciousness as the newest '~drug t h r e a t " to the y o u t h of our nation. Yet, the development of effective medical mana g e m e n t of PCP overdoses has lagged behind these lurid headline articles, remaining at best piecemeal and inexact, largely empiric, and often lacking in sound sociologic and psychopharmacologic bases. Here we draw on a clinical experience in treating over 250 cases of PCP overdose at all stages of intoxication. A logical and proven step-bystep protocol is presented for recognition and proper treatment of PCP overdose (Figure 1) in the emergency department.

reabsorption of the alkalinized ~nonionized" PCP, with attendant recirculation and redistribution of the agent. Comatose patients may display rapid and seemingly unpredictable fluctuations in their clinical stage of intoxication. We prefer to observe the axiom of treating the pat i e n t as t h o u g h he were at the '~deepest" level of anesthesia indicated by any one sign. This will usually be the sign of coma. Also, a history may be unavailable or inaccurate. When first seen, patients may be disoriented, combative, or comatose. Patient and friends may believe that they have "invested in" some d r u g o t h e r t h a n PCP. Further, the diagnostic measurement of PCP in serum, urine, or gastric content requires chromatographic assay,23,29, 8° which may well be useful in retrospective analysis or longterm management, but which is impractical or impossible in the emergency situation. T r e a t m e n t must, therefore, rely on the physician's immediate clinical judgment.

RECOGNITION OF PCP INTOXICATION

It is very useful clinically to picture PCP intoxication in three progressive stages. Stage I is a low level overdose. The patient is conscious though very disoriented and may be violent and/or self-destructive. Stage II is a r e l a t i v e l y n o n t h r e a t e n i n g state of moderate dose where the pa-

The clinical signals of PCP i n t o x i c a t i o n are l a r g e l y doserelated. TM Waxing and w a n i n g of signs of intoxication are not uncommon though, and may well relate to the p h a r m a c o k i n e t i c s of enteric

JACEP

EVALUATION OF PCP INTOXICATION LEVEL AND THERAPY

8:2 (February) 1979

tient is unconscious, though not in immediate danger of death to the degree of a heavily dosed victim. Stage III is a state of heavy overdose. Adrenergic crisis 31 and s t a t u s epilepticus may be fatal, s~-34 Respiratory failure is a very late sequela. 1~,~4

I. REDUCE EXTERNAL STIMULI

Stage I Intoxication

II. AVOID INSTRUMENTATION

With the r a r e exception of the i n t e n t i o n a l oral overdose p a t i e n t , almost every case seen will fall into the low to low-moderate dose range (Figure 2). PCP has such potent initial effect on the sensory awareness and upon motor coordination t h a t the g r a d u a t e d m e t h o d of d r u g use - usually smoking - - incapacitates the u s e r before severe d e p t h of anesthesia is attained - - a life-protective servo-mechanism. Also, because of the absence of respiratory depression at this s t a g e (indeed r e s p i r a t i o n is augmen~ted), and because m a s s e t e r and neck strap-muscle spasm effectively create a "spastic open airway," an adequate airway and respiratory pattern is the rule r a t h e r than the exception. Initially obtain whatever history m a y be a v a i l a b l e . If s a m p l e s are available for future analysis (eg, a half-smoked joint), information gained from these may be helpful in r e t r o s p e c t i v e a n a l y s i s for possible ongoing therapy. Be prepared to imm e d i a t e l y i n s t i t u t e a l l efforts dir e c t e d t o w a r d life s y s t e m m a i n t e nance if m a s s i v e overdose is suspected (eg, oral, especially in the depressed or suicidal patient). I m m e d i a t e l y check v i t a l signs and monitor them continuously. Record a n d r e a c t a c c o r d i n g l y to a l l signs of sequential temporal change. Is the patient "emerging" or "deepening?" Not only must one assess the c l i n i c a l stage of i n t o x i c a t i o n , one must continually reassess and readjust therapy where indicated. U n l e s s a d e q u a t e f a c i l i t i e s for p r o l o n g e d o b s e r v a t i o n a r e imm e d i a t e l y a v a i l a b l e , eg, up to 12 hours, hospitalize. Done ~4 has noted t h a t in overdose cases in children with presenting PCP serum levels of 100 to 300 ng/ml - - coma or Stage II - - s e r u m half-life is one to t h r e e days. W h e n possible - - a n d especially in the comatose patient - - obtain samples of blood, urine, and gastric content for analysis. But, as a general rule, do not attempt mechanical instrumentation in Stage I. The psychologically disoriented p a t i e n t may misinterpret well-meant minist r a t i o n s . Also, the o v e r w h e l m i n g majority of patients brought to the

III. ESTABLISH CONTACT ART (Acceptance, Reassurance and Rest, Talkdown) Massage tense muscles

8"2 (February) 1979

STAGE I

Low overdose = 2-5 mg Probably smoking, snorting Serum level - - 25-90 ng/ml

IF POSSIBLE

IV. DIAZEPAM 10-30 mg po with cranberry juice V. ASCORBIC ACID 5-1.5 gm po VI. PROPRANOLOL 40-80 mg po AVOID activated charcoal, nasogastric tube at this stage. DO NOT give Ipecac to these convulsion-prone patients. Fig. 2. Protocol for treating low dose P C P intoxication.

emergency facility will be those who have t a k e n just "one toke over the line." While PCP was sometimes a good high, one that made you feel in tune with the music of the spheres, you had to watch those four ugly C's: combat, catatonia, convulsions, and coma. (T. Cahill, Rolling Stone, July 13, 1978)

U s u a l l y , Stage I p a t i e n t s will have ingested or inhaled about 2 mg to 5 mg of PCP, resulting in a serum c o n c e n t r a t i o n of 25 to 90 ng/ml. These p a t i e n t s ' biggest problem is " b e h a v i o r a l toxicity." PCP causes m a n y p e o p l e to b e h a v e i n d i s t i n guishably from primary schizophrenia. 27 Visual, auditory, and tactile illusions can occur. Somatic sensation is dissociated; patients lose track of their bodies to some extent and do n o t p e r c e i v e p a i n (the r e a s o n , of course, why phencyclidine was originally studied). As response to pain is lost, some patients may unwittingly seriously injure themselves. Caveat: Protect the PCP patient from himself.11,14 Perception to imminent ext e r n a l d a n g e r is i m p a i r e d and the user m a y fail to flee fires or avoid obvious accidents. Stage I p a t i e n t s are disoriented, and very frequently c o m b a t i v e and violent. Of t h e 20 deaths associated with PCP reported in the l i t e r a t u r e , 13 have been directly due to such behavioral toxicity; one was a provoked homicide. 11 Physiologic effects of PCP at low dose ( F i g u r e 2) i n c l u d e v i g o r o u s b r e a t h i n g and elevated h e a r t r a t e and blood pressure. These functions will remain intact with all but the most massive overdoses. "Knee-jerk-

JACEP

reflex" type cardiopulmonary resuscitation (CPR) efforts are, therefore, at the very least contraindicated in t h i s situation. O r o p h a r y n g e a l and b r o n c h i a l secretions are m a r k e d l y increased, creating a very moist and n o i s y s o u n d i n g a i r w a y . However, l a r y n g e a l and p h a r y n g e a l reflexes are also accentuated, and efforts to suction the airway may precipitate s p a s m . Avoid deep s u c t i o n i n g ; r a t h e r , remove secretions from the corners of the mouth and inner posterior cheek wells. In general, avoid all instrumentation at this stage. This includes the use of n a s o g a s t r i c tubes, u r i n a r y c a t h e t e r i z a t i o n , a n d a t t e m p t s at orotracheal intubation, s~ Other signs of Stage I intoxication include nystagmus, first horiz o n t a l t h e n v e r t i c a l , at first seen only with appropriate stimuli, later spontaneously. At deeper planes of Stage I, lid reflexes are lost and the eyes remain open in a blank stare. Also, deep tendon reflexes are noted to increase steadily, progressing to generalized spasticity with the appearance of cross-limb reflexes. Excessive salivation and drooling are noted, as are sweating and flushing. Hiccoughing is not uncommon. Rep e t i t i v e deglutition is seen as the premonitory sign to vomiting. Ataxia appears early, along with increasing generalized myoclonus and muscular spasticity. This very likely contributed to the high incidence (11) of the deaths due to drowning noted among t h e 13 " b e h a v i o r a l " d e a t h s reported. 11 Patients report an unusual

70/37

but pleasant sensation while swimming, but with the loss of motor cont r o l and i m p a i r e d p e r c e p t i o n of danger, this may prove deadly. A major element of the effective treatment for a patient in Stage I is to reduce external stimuli whenever possible, as U s h e r t h e p a t i e n t to a quiet room, with m i n i m a l visual, a t ditory and tactile stimuli. Psychological support by e m e r g e n c y departm e n t personnel cannot be overemphasized. We have previously termed this ~The Science of A R T " - - t h a t is, Acceptance, R e d u c t i o n of s t i m u l i , R e s t and R e a s s u r a n c e , and T a l k down technique. 15 With a sincere: n o n p u n i t i v e , r e a s s u r i n g approach, the physician can help the PCP user re-enter reality. Establish voice cont a c t if at all possible. The patient may be a w a r e a l t h o u g h incapable of responding and, as patients in the classic Stage I of general anesthesia, they may well have hyperacusis. So s p e a k softly and r e a s s u r i n g l y . A gentle massag6 is also helpful, easing the tense muscles of the calves, upper arms and back. Foot massage is surprisingly effective. Pharmacologic i n t e r v e n t i o n at t h i s t i m e is b e s t i n i t i a t e d w i t h diazepam. This agent may serve to d r a m a t i c a l l y reverse somatosensory dissociation and will relieve muscle s p a s m a s well. ~5 D i a z e p a m is best used in judicious intravenous increm e n t a l dosages, u s u a l l y 2.5 mg at ten minute intervals, up to 25 mg t o t a l ( a l w a y s w i t h a s t r i c t eye on respirations, and with immediate res u s c i t a t i v e m e a s u r e s at hand). D i a z e p a m can also be g i v e n int r a m u s c u l a r l y in 5 mg increments (up to a total of 40 mg). Oral administration of 10 to 20 mg is possible in cooperative lowdose patients. Check their ability to voluntarily swallow with sips of clear liquids. Dramatic results may be seen within 30 to 45 minutes, With the oral route, we employ cranberry juice which is high in benzoic acid and contributes to an acid urine, and avoid orange juice which contributes to an alkaline urine. In the p a t i e n t who can t a k e medication po, we also give ascorbic acid 0.5 gm to 1.5 gm (by tablet or powdered in c r a n b e r r y juice). This greatly enhances u r i n a r y excretion of PCP24,15 Also, we routinely use propranolol, 40 to 80 mg, orally three times a day again given with cranberry juice. Propranolol specifically protects the p a t i e n t from p o s s i b l e a d r e n e r g i c crisis (or "dopaminergic storm"). In 38/71

addition to its adrenolytic cardiac effects, propranolo] also has been demo n s t r a t e d to cross the blood-brain barrier and to cause a central calmative effect. 15,36 Do not attempt to employ activ a t e d c h a r c o a l at S t a g e I. Also, Ipecac is contraindicated at all stages in t h e PCP overdosed, convulsionprone patient. Stage II Intoxication S t a g e II P C P i n t o x i c a t i o n is " m o d e r a t e " in severity (Figure 3). A p p r o x i m a t e l y 5 to 25 mg of PCP h a s been ingested/inhaled with a res u l t i n g Serum level of 100 to 300 ng/ml. This patient is clinically comatose but responsive to noxious or painful stimuli. Protective. oropharyngeal and glottic reflexes are still intact. Like the Stage I patient, this p a t i e n t has probably overdosed by smoking or inhalation. The initial steps outlined above for Stage I intoxication are, of course, indicated here also. Loosen the patient's clothing, use sponging, ice and fans to encourage heat dissipation and thus obviate possible hyperthermic crisis. In this stage, the patient will be u n a b l e to r e s p o n d to v e r b a l command. Therefore, institute cautious instrumentation where indicated. Caveat: Avoid deep o r o p h a r y n g e a l suctioning or a t t e m p t e d intubation except when a b s o l u t e l y necessary. Somatosensory pain is deadened. It is stimulation of the autonomic refley

system of the airway t h a t should be avoided. I n t r a m u s c u l a r diazepam, 10 to 30 mg, may restore the p a t i e n t to consciousness and orientation within 30 to 40 minutes and will definitely r e l i e v e a t t e n d a n t m u s c l e spasm. S i m i l a r l y , i n t r a v e n o u s l y administ e r e d d i a z e p a m , in 2.5 mg increments at five minute intervals to a maximum dose of 24 mg, may markedly improve the patient's condition within minutes. A continuous intravenous infusion of DsLR should be instituted via large bore cannula at this time. A s c o r b i c acid, 0.5 to 1.5 gin, s h o u l d be a d m i n i s t e r e d i n t r a v e nously in solution, slowly, over five to ten minutes. The a d r e n o l y t i c a g e n t , propranolol, is a sine qua non in our t r e a t m e n t of the Stage II patient: 1.0 mg is a d m i n i s t e r e d i n t r a v e n o u s l y every 30 minutes when the patient is stable. To regulate hypertensive or tachycardic %pikes, T M 1.0 mg increments are administered at one to five minute intervals to a maximum dose of 10 mg. Urinary bladder catheterization may be instituted here. PCP, as well a s any s y m p a t h o m i m e t i c intoxication, may be accompanied by acute urinary retentionY 7 We suggest conc o m i t a n t a d m i n i s t r a t i o n of furosem i d e 40 mg i n t r a v e n o u s l y at six hour intervals. This may effectively double PCP excretion with acidified urine. 14 Titration with ascorbic acid is directed towards a urinary pH of

STAGE II Moderate overdose = 5-25 mg Serum level - - 90-300 ng/ml

RECOGNIZED BY RESPONSE TO PAIN. I. PREVENT HYPERTHERMIC CRISIS Loosen clothing, use ice, sponges, fans, etc.

li. DIAZEPAM 10-30 mg IM OR 5-15 mg IV in 2.5 mg increments

II1. ASCORBIC ACID .5-1.5 gm in solution, slowly, over 5-10 minutes

IV. FUROSEMIDE 40 mg IV V. PROPRANOLOL 1.0 mg increments IV at 1-5 rain intervals (maximum dose = 10 mg)

Vl. AVOID S U C T I O N I N G NECESSARY.

OR I N T U B A T I O N

UNLESS ABSOLUTELY

IF patient is emerging after 1 hr, shift to Stage I treatments, but observe patient for at least 3 hours before release. Fig. 3. Protocol for treating moderate dose P C P intoxication.

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8:2 (February) 1979

5.5 or lower. We avoid the use of ammonium chloride, the traditional agent of choice to acidify urine, as inappropriate in the chronic drug user, since a m m o n i a b r e a k d o w n products place a burden on an often damaged hepatocellular complex2 ~ C o n t i n u i n g attention to temporal changes in the signs of the stage of intoxication is vital. If, after 30 to 45 minutes of observation and maintenance as described above, the patient is noticeably ~lightening" in depth of anesthesia, then the personal contact efforts of Stage I will prove rewarding. If, however, a prolonged, nonresponsive comatose state is noted, hospitalization is indicated.

STAGE III Heavy overdose = 25 mg plus Possible suicide - - probably po Serum = 300 ng/ml - - plus

COMATOSE, UNRESPONSIVE TO DEEP PAIN. HOSPITALIZE, MAINTAIN VITAL LIFE PROCESSES I. FLUIDS, IV - - Use DsLR, Push - - Use diuretic, esp, furosemide, 40 mg IV every 4-6 hrs - - Ascorbic acid, .5-1.5 gm IV every 4-6 hrs II. OROTRACHEAL INTUBATION BY AN EXPERT (Tracheostomy is rarely indicated.) III. LARGE BORE NASOGASTRIC TUBE Flush gastric contents (save for analysis). Instill 50 to 150 gm activated charcoal. IV. KEEP COOL BY SPONGING

Stage III Intoxication

Stage III, or '~high dose" PCP intoxication, is likely due to a dose of 25 mg or more, usually via oral ingestion, not uncommonly associated with a suicide attempt (Figure 4). In this stage, serum concentration of P C P will be in the 300+ ng/ml range.11, ~4,~s The clinical tip-off for identification of Stage III is a patient who is comatose and unresponsive to deep or surgical pain stimulus. Other signs are graphically illustrated. The tachypnea begun in Stage I increases steadily through Stage II, reaching 25% or greater over normal by mid-Stage II. (R.T. Rappolt, MD, and George R. Gay, MD, unpublished data.) In advanced Stage II, the accessory muscles of respiration show markedly increased effort. By Stage III periodic respiration may supervene. Apnea is a very later (terminal) sign. Protective airway reflexes begin to be obtunded in late Stage II and are lost. as the patient enters Stage III. This ominous event, coupled with increased respiration, continuing augmented orotracheal secretions and sustained vomiting, creates the problem of aspiration pneumonitis. Tachycardia and hypertension continue at 25% to over 100% above the expected norm, (R.T. Rappolt, MD, and George R. Gay, MD, unpublished data) and high output congestive heart failure and/or cerebrovascular accident may occur. Board-like muscle r i g i d i t y and g e n e r a l i z e d myoclonus increases, opisthotonos may be seen, and tonic-clonic seizure activity, at first i n t e r m i t t e n t and triggered by physical stimuli, progresses to a full-blown status epilepticus. At this point, the airway is truly lost and this event rapidly presages terminus. 33 8:2 (February) 1979

V. PROPRANOLOL Titrate hypertensive spikes with 1 mg IV every 1 rain (max 10 mg) VI. DIAZOXlDE Standing order for hypertensive crisis: 300 mg IV push VII. L U N G S - - PROTECTION Watch for pulmonary edema, aspiration pneumonitis. VIII. AVOID CHOLINERGICS eg, physostigmine; bronchial secretions already excessive. IX. SYMPTOMATICALLY CONTROL STATUS EPILEPTICUS IV anticonvulsants as necessary.

Fig. 4. Protocol for treating high dose PCP intoxication.

All immediate efforts here must be directed to m a n a g e m e n t of the a i r w a y and control of the status. Intravenous phenobarbital (and perhaps phenytein) should be employed and continued throughout this crisis and for sometime thereafter. Corneal reflex has been lost in mid-Stage II, and the roving eyes CGroucho eyes") of Stage II are now beginning to dilate and exhibit hippus p h e n o m e n o n . Fixed, dilated pupils are a sign of dangerously deep intoxication. Adrenergic crisis may c r e a t e not only l i f e - t h r e a t e n i n g spikes of blood pressure and pulse rate, ~1 but a concomitant malignant hyperthermic reaction. The t r e a t m e n t of this patient must be the most immediate, skilled, and intelligent. All efforts must be addressed to the maintenance of vital life processes. Initiate intravenous therapy as outlined above. Push fluids and use the diuretic effect of furosemide (40 mg intravenously, every 6 hours). Insert a urinary catheter and monitor urine output. The limited but rather elegant work by Done 14 has shown that, at a urine pH of 4.5, urine to s e r u m PCP c o n c e n t r a t i o n ratios

JACEP

reach 200, supposedly due to a simple "ion trapping" effect. We suggest that urine pH be maintained at 5.0 to 5.5 by periodic intravenous infusion of ascorbic acid, 0.5 to 1.5 gm, every 4 to 6 hours - - or as required. Orotracheal intubation should be carried out only by an expert, and only in a controlled situation, such as the operating room. Tracheostomy is rarely, if ever, indicated. Controlled or assisted respiration will not be necessary except in the extreme case. Vigorous tracheo-bronchial toilet is fully indicated here. Protect the lungs! Watch for pulmonary edema, a late sequela, as well as for aspiration pneumonitis. Avoid the use of cholinergic agents such as physostigmine as they may increase already excessive orotracheo-bronchial secretions. Pass a large bore gastric tube and flush the gastric contents. (Save them for analysis.) Done TM suggests that ion trapping of PCP occurs in a h i g h l y acid gastric content. He further suggests periodic lavage with a solution of hydrochloric acid to m a i n t a i n a gastric pH of 2.0.14 Caveat: If continuous gastric drainage is employed, be aware of the po72/39

tential of attendant alkalosis and adjust the pH downward as suggested by Done. Our protocol consists of an initial gastric lavage w i t h n o r m a l saline, immediately followed by installation of 150 gm activated charcoal. The charcoal has a cathartic effect, causing a rapid gastrointestinal transit. We then titrate the patient parenterally with ascorbic acid to achieve a urine pH of 5.5 or lower. In attempts to clear the system of PCP, peritoneal dialysis, with and without serum albumin added, has proved relatively ineffective. 14 In light of the rather exceptional results obtained in enhancing PCP excretion by the acidification of the urine, however, the major thrust of our clinical efforts should be directed here. A prolonged coma, with waxing and waning of signs of "lightening" and '~deepening" is often seen in the massively overdosed PCP reaction. PCP has a serum half-life of almost four days. 14 Even with rapid urinary elimination, we can expect to see lingering signs of mild intoxication for several days after the patient has emerged from coma. 14 Serial samples of blood, urine, and gastric content should be obtained throughout hospitalization for spectrophotometric assay. Strict attention should be paid to the patient's core temperature, and ice and sponging used when necessary. Hypertensive spikes should be controlled by t i t r a t i o n with intravenous propranolol, i mg every 1 minute as necessary to a maximum of 10 rag. A s t a n d i n g order for diazoxide should be written as well. EMERGENCE PHENOMENA

The PCP-overdose therapist is well advised to consider that as a patient emerges from one level of intoxication to the next lighter level, he will display the signs and symptoms of that stage and be subject to the concomitant dangers.25, ~s For example, a patient emerging from Stage II may easily become violent or selfdestructive in Stage I. Two distinct but often overlapping multiple symptom complexes are frequently seen in the emerging/ recovering patient: The Anxiety/Depression/Confusional State, and the more severe, life-threatening, dopaminergic storm (Figures 5 and 6). The Anxiety/Depression/Confusional State is seen in the immediate emergence period. Symptoms may 40/73

ANXIETY-DEPRESSION CONFUSION OF EMERGENCE Different in each person Chronic users present less problem DIAZEPAM 10 mg po qid or tid - - one week, and/or HALOPERIDOL. 5 mg po qid - - one week, with DIPHENHYDRAMINE 25 mg II. ASCORBIC ACID .5 gm po qid - - one week Ul. FUROSEMIDE 40 mg po qid - - one week IV. PROPRANOL.OL 40 mg po tid - - one week In hospitalized patients, substitute appropriate IM or tV dosages. Haloperidol may be replaced by droperidoi, a potent neuroieptic, 2.5 mg IV every 6 hrs. AVOID CITRUS JUICES (which alkalinize the urine) AVOID METHYL. XANTHINES (coffee, tea, chocolate, coke)

Fig. 5. Protocol for treating anxiety/depression, confusion state in patient emerging from PCP intoxication. DOPAMINERGIC STORM A POSTINGESTIONAL SEQUEL.A 72-96 hr following Stage II or III OD when patient otherwise appears to be recovering, he/she may develop: (A) HYPERTENSIVE CRISIS encephalopathy and possible CVA. (B) MAL.IGNANT-TYPE HYPERTHERMIA Usually occurs in younger patients. May be preceded by: throbbing headache agitated b e h a v i o r - "de novo psychosis" - - nothing. PROTECT by maintenance of PROPRANOL.OL, 40 mg po tid - - one week. - - direct hypertensive lytic effect. crosses blood brain barrier, central calmative effect.

Fig. 6. Protocol for treating dopaminergic storm sequela in patient emerging from PCP intoxication. range from slight depression and withdrawal, to catatonic stupor, to inappropriate and violent destructive behavior. 3s Outpatient Treatment

For the outpatient, the following regimen has demonstrated clinical efficacy. For anxiety and sedation, diazepam, 10 rag, is prescribed orally three or four times a day for one week. The butyrophenone haloperidol has been demonstrated to be particularly efficacious in a b a t i n g postingestion psychotomimetic phenomena taken orally, 5 mg four times a day for one week. We concurrently prescribe diphenhydramine, 25 mg, to block any undesired extrapyramidal effects.

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Also, we prescribe ascorbic acid to be taken orally in a dosage of 0.5 gm four times a day for one week. To insure u r i n a r y wash out, we also prescribe f u r o s e m i d e 40 mg four times a day for one week. And, most importantly, to protect the r e c o v e r i n g victim's card i o v a s c u l a r status, we prescribe propranolol to be taken orally in the dosage of 40 mg three times a day for one week. A potentially life-threatening postingestion sequela is a true adr e n e r g i c crisis, or dopaminergic storm, which may appear 72 to 96 hours following PCP overdose, usually of Stage II or III, when the patient seems to be recovering. This may present as a hypertensive crisis with encephalopathy and possible cerebrovascular accident (CVA). A 8:2 (February) 1979

m a l i g n a n t hyperthermic crisis may also supervene. This possibly lethal l a t e effect may be avoided by the maintenance of p r o p r a n o l o l 40 mg o r a l l y t h r e e times a day for at least seven days. Aside from the direct hypertensive lytic effect, p r o p r a n o l o l h a s been d e m o n s t r a t e d to cross t h e bloodbrain b a r r i e r and, acting on the dopaminergic receptor sites of the limbic and mesolimbic system, to produce a c e n t r a l c a l m a t i v e effect as well. 86 For acutely ill, hospitalized pat i e n t s , a d j u s t m e n t can e a s i l y be made to provide the diazepam, prop r a n o l o l , a s c o r b i c acid a n d furosemide by i n t r a m u s c u l a r or i n t r a venous route as appropriate. In such situations, haloperidol may be replaced by the potent neuroleptic, droperidol, in an intramuscular or intravenous dosage of 2.5 mg every six hours. "~

CASE STUDIES Two case histories demonstrate signs and symptoms of Stage ]1 and Stage I PCP intoxication and outline appropriate therapy in each case. C a s e N u m b e r One. A 58-yearold m a n smoked a "large" Kay J a y prepared from a $75/gm purchase of "high grade" PCP by his son. The patient was a socially prominent man of large habitus (6 ft, 220 lbs) who took daily medication for mild hypertension. He reportedly drank at least three cocktails per day, was a heavy smoker, but was previously naive to illicit drug use. One of the a u t h o r s was summoned to the patient's home by his worried son approximately one hour after the drug use. The p a t i e n t exhibited a blank stare and was unres p o n s i v e to v e r b a l s t i m u l u s b u t maintained an upright posture, rocking back and forth in a rocking chair in stereotypical repetitive manner. Blood pressure was 202/100 mm Hg. P u l s e r a t e was t l 4 / m i n u t e a n d bounding; respiratory rate was 28/ minute. Stertorous b r e a t h i n g with deep g u t t u r a l phonation was noted. He was drooling copiously and appeared to gag on his saliva at times. He was flushed and diaphoretic. His pupils were 3 mm and sluggishly reactive to light. His eyes were '~roving." He had been made to drink one large glass of cranberry juice with 1.5 gm of ascorbic acid (crushed tablets) a few m i n u t e s before per instruction by phone to his son. Fifteen minutes after being first

8:2 (February) 1979

seen, his blood pressure was 200/120 mm Hg. Pulse rate was 160/minute and r e s p i r a t i o n s were labored and noisy at 28 to 30/minute. His hands were flexed over his chest, and his entire posture seemed "stiffer." Secretions were suctioned from his mouth, and at this point he could no longer voluntarily swallow. Moist rales and heavy rhonchi were heard over both upper lung quadrants. P r o p r a n o l o l was a d m i n i s t e r e d i n t r a v e n o u s l y in 1 mg boluses. A t o t a l of 6 mg over a t e n - m i n u t e p e r i o d w a s g i v e n w h i l e his v i t a l signs were continually monitored. After 6 mg of propranolol, blood pressure was 184/120 mm Hg, pulse rate was 100/minute, and r e s p i r a tions were 24/minute. His posture relaxed somewhat and his upper airway appeared less obstructed. He was transported by ambulance to an intensive care ward. At the time of admission, his blood pressure was 106/ 90 mm Hg, his pulse rate 90/minute, and his respirations 18/minute. Three hours after being first seen he appeared to be aware of his surroundings, and responded to verbal s t i m u l i w i t h g r u n t e d monosyllables. Over the next two days he was treated with the following oral medications: propranolol, 80 mg, three times a day; ascorbic acid 1.0 gm four times a day and furosemide, 40 mg three times a day. A p p a r e n t l y c o m p l e t e l y recovered, he was discharged with the following medications: propranolol, 40 mg three times a day; haloperidol, 5 mg four times a day; diphenhydramine, 25 mg three times a day; ascorbic acid 1 gm four times a day (to be taken with cranberry juice), and furosemide, 40 mg per day. T h e s e m e d i c a t i o n s were continued for seven days. Recovery was uneventful. C a s e N u m b e r Two. One of the a u t h o r s was called to see a 13-yearold C h i c a n a from t h e S o u t h S a n Francisco Bay area who had smoked a "duster" at a rock concert, one of 13 people seen t h a t day for similar comp l a i n t s . She was of slight h a b i t u s and reportedly had just inhaled "only a few tokes." Available history indicated t h a t she was not new to this form of recreational drug use. The p a t i e n t arrived by stretcher at a medical field tent. She was comatese and her posture was a boards t i f f e x t e n s o r r i g i d i t y . H e r ext r e m i t i e s showed a t o n i c - c l o n i c spasticity, accentuated by stimulus ( m o v e m e n t of the s t r e t c h e r , loud

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noises). Her eyes were open and staring, nonblinking. The pupils were 2 mm with only a sluggish light reflex. Her blood pressure was 140/90 ram Hg, pulse rate l l 0 / m i n u t e , and respirations, 24/minute. She responded to deep pain stimulus by generalized withdrawal. She was moved to a quiet area, and counselors proceeded to gently t a l k to her and to massage the muscles of her legs, upper back and arms. At 15 minutes, her muscle spasms appeared much diminished but she was still unresponsive to voice. Vital signs were unchanged. Diazepam, 20 mg, w a s injected i n t r a m u s c u l a r l y into the right deltoid. A t 30 m i n u t e s she a p p e a r e d visibly more relaxed and responded to verbal stimuli. At t h a t time her blood pressure was 110/70 mm Hg, pulse rate was 80/minute, and respirations, 16/minute. Within 15 minutes later, she was sitting up, app e a r e d weak but with v o l u n t a r y m u s c u l a r control, and was sipping water and conversing. One hour after a d m i s s i o n she was r e l e a s e d to t h e c a r e of h e r friends and walked out unassisted. Several hours later she was seen in the crowd, a n i m a t e d and enjoying the music.

CONCLUSION Several points of practical clinical a p p l i c a b i l i t y s h o u l d be reemphasized here for the recognition of the stages of PCP intoxication and proper emergency medical intervention (Figure 7). First, at this time P C P is a drug of choice in our inner urban ghettoes b u t its use spills over into almost e v e r y social sphere. The i n i t i a t e d PCP user will, through titration to a light plane of Stage I, seldom come to the e m e r g e n c y d e p a r t m e n t . Those who are seen may exhibit the disinhibited behavioral toxicity which often calls these low-overdosed individuals to the attention of the law. Secondly, heavy overdose is seldom seen in the PCP smoker due to the fail-safe servo-mechanism of intoxication previously mentioned. The vast majority of PCP intoxications seen in the emergency d e p a r t m e n t then, will be the low-overdose, Stage I. Also, even in the rare heavy overdose victim, the clinical course will v e r y r a r e l y p r o g r e s s to t e r m i n u s w i t h proper clinical m a n a g e m e n t . R e s p i r a t i o n is s t i m u l a t e d r a t h e r than depressed; the airway is usually patent.

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STAOESOF (PEP) PItE~C¥CLLDIHE IHTOXlCAT|OH

! a.) Rapid onset of speech impairment, with perceptual distortions, change in affect. Vivid visual, auditory and occasional tactile hallucinations. Paranoid ideation (may be violent, suicidal, or homicidal). b.) Voluntary control lost quite early c.) Frozen, or "Spastic Open Airway" d.) At first on stimulus, then at rest. e.) Injudicious instrumentation, e.g. suctioning, attempted intubation may precipitate severe laryngospasm. f.) Potentially deadly point where increased respiratory effort, sustained vomiting, and lack of protective reflexes coincide.

Fig. 7. Protocol for PCP intoxication management. A pitfall to avoid is overjudicious i n s t r u m e n t a t i o n of the airway which may cause severe laryngospasm and airway compromise. Adrenergic crisis m a y occur and p r e c i p i t a t e h i g h o u t p u t congestive h e a r t failure, a CVA, or a m a l i g n a n t b y p e r t h e r m i c crisis. Muscular rigidity m a y progress to seizures and stat u s epilepticus. Proper medical approach can obviate these sequelae. We hope e m e r g e n c y physicians will benefit from this graphic, quickly learned, practical and highly effective a n d safe, d i a g n o s t i c a n d therapeutic algorithm. REFERENCES

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