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POISONINGS & INGESTIONS

757

cramping and vomiting. Emesis can be treated with

antiemetics and a slowed administration rate of the solution.

Hyperchloremia has been reported and requires repeated

serum chloride determinations during the procedure. It is

also important to note that activated charcoal, if indicated,

should be given before the initiation of whole bowel irriga-

tion. Repeat-dose activated charcoal is not effective when

given during whole bowel irrigation.

5. Ion trapping—Once a drug has been absorbed from the

GI tract, gut decontamination measures become relatively

ineffective. Ion trapping is a method to enhance elimination

of an already absorbed drug by “trapping” it in the urine.

Drugs that acidify urine (eg, salicylates) ionize in alkaline

urine and then cannot be reabsorbed by the kidney and are

therefore excreted. This treatment is most helpful in salicy-

late and phenobarbital ingestions.

The simplest method for ion trapping uses 1 L of 0.45%

saline solution to which 2 ampules of sodium bicarbonate

have been added. The solution is infused intravenously at a

rate of 150–250 mL/h. Urine pH is monitored, with the goal

being a pH of 7.0–8.0. Potassium deficits need to be replaced

because alkalinization of the urine is difficult to achieve in

the hypokalemic patient. Complications of urinary alkalin-

ization are volume overload and hypokalemia.

6. Hemodialysis and hemoperfusion—In some situa-

tions, hemodialysis or hemoperfusion may be required to

eliminate the toxin. Indications include patients refractory to

supportive care alone, those who have a potentially toxic

drug level or highly toxic dose of the ingestant, and those in

whom other routes of elimination are impaired (eg, by renal

failure). Few toxins are amenable to this type of therapy;

cases in which hemodialysis or hemoperfusion may be useful

are listed in Table 36–8.



Current Controversies & Unresolved Issues

Administration of activated charcoal has become the pri-

mary means for decontamination of the gut in most cases of

toxic ingestion. Gastric lavage was once a mainstay for

decontamination of the gut and removal of the ingested

agent. Recent studies, however, have shown little change in

outcome for most patients who undergo gastric lavage. In

addition, this method has the potential for causing serious

side effects such as aspiration. Gastric lavage should be lim-

ited to patients who ingest a potentially lethal amount of an

agent poorly adsorbed to charcoal or those who present less

than 1 hour after ingesting a potentially significant amount

of a toxic agent—and it should be done with care.

Ipecac, a central- and peripheral-acting agent used to

induce vomiting in patients with toxic ingestions, was once a

common method of gastric decontamination. However, this

agent is no more effective than gastric lavage, and vomiting

after ipecac can persist for several hours, precluding the use

of oral activated charcoal. Its use is contraindicated in caus-

tic and hydrocarbon ingestions and in infants under 6

months of age. At this point, syrup of ipecac has little, if any,

role in the management of toxic ingestions.

In the past, forced diuresis was recommended in the treat-

ment of several drug ingestions. Studies have shown that forced

diuresis does not enhance elimination significantly and that the

relatively large volumes of intravenous crystalloid needed can

lead to pulmonary edema, particularly in patients with cardiac

dysfunction. Forced diuresis is therefore no longer recom-

mended as a modality in treating drug ingestions.

Bateman DN: Gastric decontamination: A view for the millen-

nium. J Accid Emerg Med 1999;16:84–6. [PMID: 10191436]

Bond GR: The role of activated charcoal and gastric emptying in

gastrointestinal decontamination: A state-of-the-art review.

Ann Emerg Med. 2002;39:273–86. [PMID: 11867980]

Krenzelok EP, McGuigan M, Lheur P: Position statement: Ipecac

syrup. American Academy of Clinical Toxicology, European

Association of Poisons Centre and Clinical Toxicologists. J Toxicol

Clin Toxicol 1997;35:699–709. [PMID: 9482425]

Mokhlesi B et al: Adult toxicology in critical care: I. General

approach to the intoxicated patient. Chest 2003;123:577–92.

[PMID: 12576382]

Watson WA et al: 2004 Annual Report of the American Association

of Poison Control Centers Toxic Exposure Surveillance System.

Am J Emerg Med 2005;23:589–666. [PMID: 16140178]

Zimmerman JL: Poisonings and overdoses in the intensive care

unit: General and specific management issues. Crit Care Med

2003;31:2794-801. [PMID: 14668617]

MANAGEMENT OF SPECIFIC POISONINGS



Sedative-Hypnotic Overdose

ESSENTIALS OF DIAGNOSIS



Dysarthria.



Ataxia.



Emotional lability.



Altered sensorium.



Horizontal and vertical nystagmus.



Respiratory, cardiovascular, and renal failure.

Table 36–8. Poisons amenable to hemoperfusion or

hemodialysis.

Hemoperfusion Hemodialysis

Digitalis

Carbamazepine

Paraquat

Phenobarbital

Theophylline

Ethylene glycol

Methanol

Lithium

Salicylate

Theophylline

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CHAPTER 36

758

General Considerations

Sedative-hypnotic abuse is common, particularly among

patients who began using the drugs therapeutically for

sleep or as anxiolytics. Other patients may use these drugs

orally or intravenously because of the disinhibition and

euphoria they produce. In the past, short-acting barbitu-

rates such as amobarbital, pentobarbital, and secobarbital

were used commonly; these agents are used much less fre-

quently because benzodiazepines are now prescribed more

commonly. Their use is frequently combined with other

drugs or with alcohol.

Continued abuse of sedative-hypnotics is more likely to

cause mental and physical impairment when compared

with narcotics. When administered intravenously, the alka-

line barbiturate solutions cause sclerosis of the veins and

may result in profound ischemia if intraarterial injection

occurs.

Withdrawal from sedative-hypnotics produces a charac-

teristic syndrome that may be fatal. Although a period of ini-

tial improvement may occur after 8–16 hours of abstinence,

rapid deterioration with agitation, altered mental status, and

seizures frequently follows. ICU admission is mandatory for

any patient suspected of having barbiturate withdrawal

symptoms.

Clinical Features

A. Symptoms and Signs—An overdose of these drugs results

in findings similar to those of intoxication with alcohol: ataxia,

altered sensorium, and dysarthria. Both horizontal and vertical

nystagmus may be present. When intoxication is severe, respira-

tory and cardiovascular compromise may occur. Ventilation is

usually slow and shallow, and pulmonary edema or pneumoni-

tis may develop. Centrally mediated vasomotor depression

results in a decrease in blood pressure. If perfusion is not main-

tained, renal failure may follow. Tissue hypoxia may develop as

a result of decreased respiratory function, and pupillary dilation

may be seen. Deep tendon reflexes also may be depressed.

B. Laboratory Findings—Routine laboratory studies should

include electrolytes and an arterial blood gas determination.

A sample of blood should be obtained and sent for barbitu-

rate concentration determination. Lethal levels vary widely

depending on patient factors and the presence of coinges-

tants. An acetaminophen level should be determined in case

this agent was coingested.

C. Imaging Studies—A chest x-ray is advisable to evaluate

the extent of atelectasis and pneumonitis present at the time

of admission.

Differential Diagnosis

Ingestions of nonbarbiturate sedatives such as chloral

hydrate, ethchlorvynol, glutethimide, methyprylon, and

methaqualone are the considerations when treating a barbi-

turate overdose. Coingestion of alcohol, benzodiazepines, or

opioids also must be considered.

Treatment

A. General Measures—When cardiovascular and respira-

tory parameters are normal and stable, supportive care gener-

ally is all that is required. However, when intoxication is

severe, hypoventilation and depressed cough and gag reflexes

are indications for intubation to protect the airway, prevent

aspiration, and allow for mechanical ventilation as needed.

B. Decontamination—Lavage generally should be consid-

ered if ingestion has been within the preceding 45 minutes.

Food in the stomach decreases absorption and may prolong

the time during which lavage is useful; however, if obtunda-

tion is a concern, the risks of lavage may not outweigh any

potential benefits of this procedure.

C. Diuresis—Although believed to be useful in the past,

forced diuresis is no longer felt to be useful. Sodium bicar-

bonate to alkalinize the urine prevents tubular reabsorption

of phenobarbital and supplemental potassium chloride

should be given to ensure alkalinization of the urine. Careful

serum electrolyte monitoring is mandatory.

D. Cardiovascular Support—Hypotension usually responds

to the administration of balanced salt solutions such as nor-

mal saline or lactated Ringer’s solution, although vasopres-

sors may be required. If large amounts of fluid are necessary

for resuscitation, fluid administration should be guided by

central venous or pulmonary artery catheter monitoring to

prevent pulmonary edema.

E. Hemodialysis—When renal failure occurs, hemodialysis

may be necessary. Most of the barbiturates are dialyzable,

although the short-acting forms have the lowest percentage

of removal.

Withdrawal

Withdrawal from sedative-hypnotics may be fatal. Symptoms

of withdrawal typically occur after 8–16 hours of abstinence

and include anxiety, tremulousness, weakness, and insomnia.

GI symptoms include abdominal cramping, anorexia, nau-

sea, and vomiting. As withdrawal progresses, neurologic

findings become predominant and are characterized by

twitching, coarse tremors, increased startle response, and

hyperactive deep tendon reflexes. After 2–3 days, grand mal

seizures may occur. As the seizures subside, improvement usu-

ally is noted, although some patients develop organic brain

syndrome with disorientation, visual and auditory hallucina-

tions, and delusions. Hyperthermia may lead to cardiovascular

collapse and death.

When withdrawal is suspected, the patient should be given

an intravenous dose of pentobarbital or phenobarbital based on

an estimate of the most recent consumption. This dose then can

be reduced by about 10% per day until the patient is drug-free.

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POISONINGS & INGESTIONS

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Mohammed Ebid AH, Abdel-Rahman HM: Pharmacokinetics of

phenobarbital during certain enhanced elimination modalities

to evaluate their clinical efficacy in management of drug over-

dose. Ther Drug Monit 2001; 23:209–16. [PMID: 11360027]

Palmer BF: Effectiveness of hemodialysis in the extracorporeal

therapy of phenobarbital overdose. Am J Kidney Dis

2000;36:640–3. [PMID: 10977799]



Opioids

ESSENTIALS OF DIAGNOSIS



Decreased level of consciousness.



Depressed respiration.



Miosis.



Pulmonary edema.

General Considerations

Narcotic abuse is a major problem worldwide. Although the

drugs of choice traditionally have been morphine and

heroin, the shorter-acting agents such as fentanyl have come

into vogue, especially among health care workers. Most nar-

cotics are administered intravenously because of the rapid

euphoria they produce. Methadone, a long-acting oral agent,

is used commonly in narcotic addiction treatment/mainte-

nance programs. Pentazocine is a synthetic analgesic with

both agonist and antagonist properties. When given to a

narcotic-dependent patient, pentazocine may cause with-

drawal symptoms. In high doses, it can cause visual halluci-

nations and dysphoria.

Immediate care of the narcotic overdose or withdrawal

patient focuses on resuscitation, stabilization, and use of

antidotes. Critical care of patients suffering from narcotic

overdose and withdrawal may include the treatment of con-

ditions caused by narcotic use and the sharing of injection

needles. These include pulmonary hypertension (presum-

ably from cotton fiber emboli), endocarditis (from bacterial

contamination), necrotizing fasciitis, and tetanus. Other

reported complications include hepatitis, AIDS, cutaneous

abscesses, and Guillain-Barré syndrome. Many patients will

use other intoxicants concurrently, such as alcohol or

cocaine, which complicates their care.

Clinical Features

A. Symptoms and Signs—Patients with opioid overdoses

present most commonly with decreased level of conscious-

ness, depressed respiration, and miotic pupils. In severe

cases, such as cases of attempted suicide, respiratory depres-

sion may be pronounced. Pulmonary edema may be seen,

particularly in heroin overdose. Other common findings

include hypo- or hyperthermia, emesis, hypoxia, hypoten-

sion, and depression of deep tendon reflexes.

B. Laboratory Findings—A blood sample should be sent for

toxicology screen and alcohol level and to check for other

CNS depressants. Routine electrolytes, a complete blood

count, and liver function tests should be obtained. In cases of

pulmonary edema, pulse oximetry and/or an arterial blood

gas analysis will help to assess severity. In patients with oral

opioid ingestions, an acetaminophen level should be deter-

mined. If the patient is febrile and uses opioids by injection

blood cultures should be sent.

C. Imaging Studies—A chest x-ray should be obtained in

patients suspected to have pulmonary edema or other indi-

cations of pulmonary compromise. A head CT scan may be

useful in patients with depressed level of consciousness who

do not respond appropriately to naloxone to exclude the

presence of a mass lesion or intracranial bleed.

Treatment

A. General Measures—Most patients transferred to the

ICU will already have been stabilized and intravenous access

established. Patients should be reassessed on arrival to the

ICU because those with significant narcotic overdose are at

high risk for respiratory depression and airway compromise.

If indicated by either a low blood glucose determination or

in the obtunded patient in whom this measurement cannot

be made, 50 mL of 50% dextrose should be given intra-

venously along with 100 mg thiamine.

Mechanical ventilation may be required both for

decreased respiratory drive and for management of pul-

monary edema. Hypotension usually responds to volume

infusion and correction of hypoxia. Pulmonary edema

caused by narcotic overdose usually does not respond to the

customary regimen of diuretics and preload and afterload

reduction, and intubation is often required.

B. Decontamination—If the use of coingestants is sus-

pected, administration of activated charcoal is advisable; this

can be done either orally or via an nasogastric (NG) tube. If

there is a risk of aspiration, however, charcoal should be used

only if it has a high likelihood of improving the patient’s

outcome.

C. Narcotic Antagonists—Several narcotic antagonists have

been used—naloxone, naltrexone, nalmefine, nalorphine, and

levallorphan; the latter two also have agonist properties.

Although naltrexone is longer-acting than naloxone, its use in

the acute setting has been disappointing, and naloxone is the

drug of choice in this situation. An initial dose of 0.2–0.8 mg

should be administered intravenously for heroin and mor-

phine overdoses, titrating to response. When the abused drug

is codeine, pentazocine, or propoxyphene, an initial dose of

up to 2 mg naloxone may be required. When effective, an

improvement in respiration and mental status typically

occurs in less than 2 minutes, often in seconds. If no response

to a total dose of 2 mg is seen, the diagnosis of narcotic

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CHAPTER 36

760

overdose should be questioned. Because the half-life of nalox-

one is substantially shorter than that of most narcotic agents,

repeat dosing may be required to prevent recurrence of respi-

ratory and mental status depression. Continuous administra-

tion of naloxone intravenously may be required in some cases

to prevent relapse of respiratory depression.

D. Other Modalities—Because of the complications associ-

ated with narcotic abuse, additional therapy in the ICU may

be required for pulmonary edema, pneumonitis, cardiac

valvular compromise, or infectious complications. Overdosage

with meperidine may cause hyperactive reflexes and convul-

sions. Rhabdomyolysis may occur, particularly in patients

who have been obtunded for a significant amount of time; if

not treated, patients may develop renal failure from the myo-

globinuria seen in this condition.

Withdrawal

Withdrawal from narcotics produces autonomic distur-

bances, hyperexcitability, and personality changes character-

ized by drug-seeking behavior. Within the first 8 hours of

withdrawal, lacrimation, rhinorrhea, diaphoresis, and sneez-

ing are common. This is followed by nausea and vomiting,

diarrhea, and abdominal cramping. Patients may exhibit

tremors and twitching in association with myalgias.

Pilomotor erection produces the “cold turkey” appearance of

the skin. All the symptoms are relieved by the administration

of narcotic.

Clark NC, Lintzeris N, Muhleisen PJ: Severe opiate withdrawal in a

heroin user precipitated by a massive buprenorphine dose. Med

J Aust 2002;176:166–7. [PMID: 11913917]

Compton WM, Volkow ND: Major increases in opioid analgesic

abuse in the United States: Concerns and strategies. Drug

Alcohol Depend 2006;81:103–7. [PMID: 16023304]

Joranson DE, Ryan KM, Gilson AM, Dahl JL: Trends in medical use

and abuse of opioid analgesics. JAMA 2000;283:1710–4. [PMID:

10755497]

Paulozzi LJ: Opioid analgesic involvement in drug abuse deaths in

American metropolitan areas. Am J Public Health

2006;96:1755–7. [PMID: 17008568]

Sachdeva DK, Jolly BT: Tramadol overdose requiring prolonged

opioid antagonism. Am J Emerg Med 1997;15:217–8. [PMID:

9115538]



Sympathomimetics

ESSENTIALS OF DIAGNOSIS



Agitation, anxiety, hallucinations, psychosis.



Seizures.



Coma, stroke, encephalopathy.



Hypertension, tachycardia.

General Considerations

Sympathomimetics are a category of drugs that induce a

physiologic state similar to that caused by catecholamine

release. Many different prescription, over-the-counter, and

recreational or abuse drugs fall into this category.

Examples include amphetamine and its derivatives, over-

the-counter products for appetite control, cold remedies, and

stimulants (eg, phenylpropanolamine, caffeine, ephedrine, and

pseudoephedrine).

Overuse of sympathomimetics causes toxicity by induc-

ing excessive release of neurotransmitters, including epi-

nephrine and norepinephrine, and the subsequent α- and

β-adrenergic effects they produce. α-Adrenergic effects are

primarily vasoconstriction, diaphoresis, and dilated pupils;

-adrenergic effects lead to tachycardia, and β

-adrenergic

effects cause bronchodilation and vasodilation. The clini-

cal effects that result from any specific sympathomimetic

drug depend on the relative α- or β-adrenergic actions of

that drug (eg, phenylpropanolamine is an α-selective drug

that causes hypertension, diaphoresis, and mydriasis).

Duration of toxicity is usually limited; however, patients

may demonstrate prolonged toxicity if they ingest bags con-

taining the drug for illicit transport or if they use “Ice,” a

long-acting, smokable form of methamphetamine.

Clinical Features

A. Symptoms and Signs—Sympathomimetic toxicity

causes a toxic syndrome that includes primarily CNS and

cardiovascular effects (see Table 36–2). Both illicit drug users

and those who use excessive amounts of over-the-counter

medications (eg, diet aids, stimulants, and cold medications)

may present with sympathomimetic poisoning.

CNS toxicity is manifested as agitation, anxiety, delusions,

hallucinations, paranoia, and seizures. Sympathomimetics

may cause a psychotic state indistinguishable from that seen

in schizophrenia; although almost always temporary, this

psychosis may take weeks to months to resolve. Less common

but more severe effects include coma, strokes (ischemic and

hemorrhagic), hypertensive encephalopathy, and focal neu-

rologic deficits.

Cardiovascular effects include hypertension and sinus

tachycardia. Hypertension may be of rapid onset and severe.

Because these patients often do not have underlying hyper-

tension, they have no CNS autoregulation at these exces-

sively high blood pressures. As a result, they are much more

likely to suffer serious CNS sequelae such as hemorrhagic

strokes or encephalopathy from acute hypertension. Sinus

bradycardia or atrioventricular block occurs mainly after

ingestion of drugs with primarily α-agonist properties.

Patients may suffer tachydysrhythmias, cardiac ischemia,

and rarely, infarction.

Other findings include rhabdomyolysis with or without

renal failure, diarrhea, intestinal cramping, and hyperther-

mia. Pupils typically are dilated if the patient ingests an agent



POISONINGS & INGESTIONS

761

with α-adrenergic properties; by the same mechanism, these

patients also may be diaphoretic.

B. Laboratory Findings—Laboratory abnormalities are

variable and not diagnostic. Toxicology screening may be

positive for sympathomimetic drugs, but it is by no means

comprehensive of the wide array of available agents; there-

fore, a negative screen does not exclude sympathomimetic

toxicity. Leukocytosis is common as a result of demargina-

tion caused by catecholamine stimulation. Patients should

have a creatine kinase (CK) determination to evaluate for

rhabdomyolysis. Serum electrolytes (especially potassium)

and blood pH should be tested.

C. Imaging Studies—CT scanning is indicated in patients

with altered mental status or seizures.

Differential Diagnosis

Thyrotoxicosis may present in a manner identical to sympa-

thomimetic overdose. A history of thyroid disease is sugges-

tive of the diagnosis, as is the presence of goiter or physical

findings suggestive of hyperthyroidism. CNS infections may

cause similar clinical findings. Drug withdrawal (eg, ethanol

and benzodiazepines) also presents with agitation and car-

diovascular abnormalities. Similar clinical findings result

from toxic effects of theophylline, tricyclic and SSRI antide-

pressants, anticholinergics, isoniazid, phencyclidine, and

salicylates, and from interaction between monoamine oxi-

dase inhibitors and other drugs. The agitation and paranoia

seen in these patients may mimic psychiatric disorders such

as schizophrenia.

Treatment

A. General Measures—After initial assessment and stabi-

lization, treatment should be individualized to the drug

involved and the toxic clinical effects manifest. If the drug

was ingested, gastric lavage should be considered if presenta-

tion is within 1 hour of ingestion or if the patient is trans-

porting the drugs as a body packer. Care must be taken to

protect the airway because these patients may seize as a result

of their ingestion. Activated charcoal should be administered

to all patients with an oral ingestion. Repeat-dose activated

charcoal is helpful in enhancing caffeine elimination. Forced

diuresis, hemodialysis, and hemoperfusion are not helpful in

these poisonings.

B. Hypertension—Hypertension is a medical emergency in

these patients because of the risk of hemorrhage or

encephalopathy. Patients with evidence of end-organ dys-

function from hypertension (eg, headache, renal compro-

mise, cardiac ischemia, and heart failure) should be treated

with antihypertensive agents. Nitroprusside is a good choice

because it is easily titratable and doses can be adjusted rap-

idly. Phentolamine may be used in patients who overdose on

pure α-agonists such as phenylpropanolamine. Although

nifedipine is a potent antihypertensive agent, it is not easily

titrated, and cases of prolonged hypotension from its use

have been reported. Labetalol may be a good choice in

patients with significant tachycardia.

C. Arrhythmias—Sinus tachycardia rarely requires interven-

tion. Supraventricular tachycardia is usually benign; how-

ever, when the patient suffers compromise from the rapid

ventricular response, verapamil or adenosine may be used to

control the rhythm. Esmolol may be used to treat both

supraventricular tachycardia and ventricular dysrhythmias.

Esmolol and other β-adrenergic blockers may worsen hyper-

tension because of unopposed α-adrenergic activity.

D. Seizures—Seizures and agitation should be treated with

benzodiazepines. Status epilepticus may develop and may

require treatment with phenobarbital and phenytoin. If these

medications are ineffective, paralysis may be required to pre-

vent rhabdomyolysis, acidosis, and hyperthermia.

Continuous electroencephalographic monitoring is required

in these patients because they may continue to have electri-

cal seizure activity despite chemical paralysis.

E. Psychosis—Benzodiazepines may be used to treat psy-

chosis associated with sympathomimetic overdoses.

Although neuroleptics have been used in the past, they can

lower the seizure threshold and alter thermoregulation; their

use probably should be avoided in this situation.

F. Myocardial Ischemia—Although actual myocardial

infarction is rare, patients with angina pectoris should be

managed with aspirin, nitrates, and heart rate control.

Patients usually respond to this treatment and should be

monitored for elevation of cardiac enzymes or changes in the

ECG consistent with myocardial infarction.

G. Hyperthermia—Hyperthermia can be severe and life-

threatening. When present, aggressive treatment is war-

ranted. Patients with agitation or seizures should receive

benzodiazepines. Antipyretics are rarely helpful. All clothing

should be removed and patients sprayed with a mist of water

or covered with damp sheets to increase evaporation, and a

fan is helpful. Those with excessive agitation or seizures who

do not respond to benzodiazepines may need paralysis to

control heat production.

Derlet RW, Horowitz BZ: Cardiotoxic drugs. Emerg Med Clin

North Am 1995;13:771–91. [PMID: 7588189]

Guharoy R et al: Methamphetamine overdose: Experience with six

cases. Vet Hum Toxicol 1999;41:28–30. [PMID: 9949482]

Holstege CP, Eldridge DL, Rowden AK: ECG manifestations: the

poisoned patient. Emerg Med Clin North Am 2006;24:159–77.

[PMID: 16308118]

Swalwell CI, Davis GG: Methamphetamine as a risk factor for

acute aortic dissection. J Forensic Sci 1999;44:23–6. [PMID:

9987866]



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762



Phencyclidine

ESSENTIALS OF DIAGNOSIS



Nystagmus.



Hypertension.



Tachycardia.



Agitation, psychosis, violent behavior.



Seizures.

General Considerations

Phencyclidine (PCP), pharmacologically related to ketamine,

is an illicit hallucinogen used as a recreational drug. The

usual method of consumption is by smoking cigarettes that

have been soaked in a solution of PCP. PCP also can be used

via the intranasal route or by ingestion. Some patients have

become intoxicated from percutaneous exposure by han-

dling the drug. Absorption is rapid by any route; effects are

seen within a few minutes to half an hour. The drug is highly

lipid-soluble, and inconstant release from adipose tissue may

lead to waxing and waning findings that are predominantly

due to CNS effects. Metabolism is primarily in the liver. The

half-life varies from 7 hours to over 3 days.

Clinical Features

The clinical presentation of PCP intoxication is extremely

variable, ranging from confusion to agitation. Alterations in

mental status are erratic, and violent behavior often occa-

sions transport to a hospital. Concurrent use of other drugs

of abuse is common, and the treating physician must be

aware of this possibility when evaluating these patients. In

addition, phencyclidine is an analgesic agent. These patients

may suffer significant traumatic injuries with minimal find-

ings on examination.

A. Symptoms and Signs—The most common findings

(>50% of patients) are nystagmus (horizontal, vertical, or

rotatory) and hypertension. Although hypertension is com-

mon, medical complications are rare. Tachycardia is also

common, but rates over 130 beats/min are unusual. The level

of consciousness may vary from comatose to agitated to fully

alert. Mental status may wax and wane, and unpredictable

and precipitous violent outbursts may occur. These patients

may require physical and chemical restraints to prevent them

from hurting themselves or the medical personnel caring for

them. Hallucinations, frank psychosis, and seizures are com-

mon. Most symptoms resolve spontaneously within hours;

however, some patients may remain symptomatic for several

days or even a week. The psychosis may last months, and in

these cases, recovery may be gradual. Rhabdomyolysis is a

relatively common complication of PCP intoxication and

may lead to renal failure in up to 2.5% of cases.

B. Laboratory Findings—Urine for PCP level may be sent to

confirm the diagnosis. Quantitative levels are not necessary

and do not correlate with clinical effects. If patients who

appear to be PCP-intoxicated have negative urine results,

they need to be evaluated for other causes of their symptoms

(see “Differential Diagnosis” below).

Elevated creatine kinase levels are found in up to 70% of

cases and can occur even in the absence of excessive muscle

activity. Although usually positive for blood, initial urine

dipstick may be negative despite a significant elevation in

CK, so all patients with PCP intoxication should have a

serum sample sent for CK measurement.

C. Concealed Injuries—Because PCP has anesthetic proper-

ties, patients may suffer significant trauma in the prehospital

setting that may not be manifested in the usual fashion. All

patients should undergo a thorough physical evaluation for

trauma and be reevaluated several times during the hospital

stay, particularly as their mental status improves.

Differential Diagnosis

Lethargic patients may have consumed other intoxicants,

including sedative-hypnotic drugs or barbiturates. Patients

who are agitated or violent must be evaluated for possible

sympathomimetic use or a withdrawal syndrome. Other

causes include head trauma, infection (eg, meningitis or

encephalitis), metabolic derangements, and psychiatric

disorders.

Treatment

A. Decontamination—Gastric lavage is rarely indicated

because PCP is typically inhaled. If patients ingest the agent,

activated charcoal should be used.

B. Supportive Measures—Most patients respond to mini-

mal measures such as being placed in a quiet, darkened room

with minimal stimulation. Benzodiazepines may be useful to

decrease agitation. In some cases, however, specific treatment

measures may be necessary.

Patients with hypertension or tachycardia rarely need

intervention for these problems; end-organ dysfunction

should be managed in the usual manner. Hyperthermia

requires treatment with antipyretics and cooling measures as

necessary. Seizures should be treated with benzodiazepines.

If the patient develops refractory seizures, phenytoin may be

used, but neuromuscular blockade may be required to pre-

vent acidosis, hyperkalemia, and rhabdomyolysis.

Continuous electroencephalographic monitoring is required

in this situation.

In the past, urinary acidification was advocated to cause

urinary ion trapping of the drug and enhance elimination.

Because only a small amount of the drug is excreted

unchanged in the urine, and because induction of aciduria is

difficult to achieve and may lead to renal dysfunction owing

to rhabdomyolysis, this treatment is no longer recommended.



POISONINGS & INGESTIONS

763

C. Hydration—If serum CK is elevated, vigorous hydration is

required, and intravenous crystalloid is the mainstay of ther-

apy. Normal saline should be used until the patient is

volume-repleted and has a good urine outflow; the goal is a

urine output of 150 mL/h. Adequate urine output is the

mainstay of therapy, but additional therapy with intravenous

mannitol and bicarbonate also may be used. Follow serial CK

levels to ensure that levels decrease. BUN and creatinine lev-

els should be measured to monitor renal function, and potas-

sium levels and blood gases should be followed to evaluate

hyperkalemia and acidosis.

D. Restraints and Sedation—Patients who are agitated or

violent may require physical or chemical restraints. The use

of physical restraints alone may exacerbate rhabdomyolysis

as the patient fights against the restraints. Restrained patients

should be placed in a quiet room to avoid stimulation.

Benzodiazepines or haloperidol may be used for sedation.

Brust JC: Acute neurologic complications of drug and alcohol

abuse. Neurol Clin 1998;16:503–19. [PMID: 9537972]

Greydanus DE, Patel DR: The adolescent and substance abuse:

Current concepts. Dis Mon 2005;51:392–431. [PMID: 16316792]

Haroz R, Greenberg MI: Emerging drugs of abuse. Med Clin North

Am 2005;89:1259–76. [PMID: 16227062]

Leshner AI: Hallucinogens and dissociative drugs including LSD,

PCP, ketamine, dextromethorphan. National Institute on Drug

Abuse Research Report Series. NIH Pub. No. 01-4209.

Washington: NIH, 2001.

Mokhlesi B, Garimella PS, Joffe A et al: Street drug abuse leading

to critical illness. Intensive Care Med 2004;30:1526–36. [PMID:

14999443]

Wills B, Erickson T: Drug- and toxin-associated seizures. Med Clin

North Am 2005;89:1297–321. [PMID: 16227064]



Cocaine

ESSENTIALS OF DIAGNOSIS



Hypertension.



Tachycardia and other dysrhythmias.



Headache.



Myocardial infarction.



Transient ischemic attacks, stroke.



Seizures.

General Considerations

Cocaine is available as cocaine hydrochloride, a water-soluble

crystalline salt that can be used intranasally or dissolved and

injected intravenously. Cocaine is also available in an alkaloid

form that is not water-soluble and can be smoked in a free-

base form or mixed with baking soda and water and smoked

as the “crack” form. Absorption from all sites is rapid. The

half-life varies with the route of administration; intravenous

use or smoking leads to a half-life of 60–90 minutes, whereas

intranasal or oral use has a half-life of several hours.

Cocaine has several effects. It causes CNS release of neu-

rotransmitters, including dopamine; acts as a local anes-

thetic; blocks neuronal catecholamine reuptake; and inhibits

serotonin reuptake. The end result of these mechanisms is a

spectrum of clinical findings primarily involving the central

nervous and cardiovascular systems. Respiratory and meta-

bolic effects also may be noted.

Clinical Features

A. Symptoms and Signs—Hypertension occurs frequently

and can be severe. It can lead to intracranial bleeding, aortic

dissection, and cardiac ischemia. Tachycardia is also com-

mon, as are dysrhythmias, including atrial fibrillation, atrial

tachycardia, ventricular tachycardia, and rarely, asystole.

Cocaine is a potent vasoconstrictor that may result in

organ ischemia. Myocardial infarction, bowel ischemia, renal

infarction, and limb ischemia all have been reported. A com-

bination of vasospasm, enhanced platelet aggregation, and

enhanced workload caused by an excessive demand for oxy-

gen produces end-organ dysfunction. In addition to organ

ischemia, cocaine can cause a myocarditis manifested by ele-

vated CK-MB enzymes and diffuse ST-segment elevations or

T-wave inversions on ECG.

There are many CNS manifestations of cocaine toxicity.

Headache is common in chronic abusers. In patients who

develop CNS complications owing to cocaine, cerebral

infarction occurs in about one-fourth, subarachnoid hemor-

rhage in another one-fourth, and intraparenchymal hemor-

rhage in the remainder.

Patients who abuse cocaine also may present with

depressed mental status or frank coma, a condition known as

cocaine abstinence syndrome. This phenomenon is likely due

to CNS depletion of neurotransmitters. These patients char-

acteristically have been using large amounts of cocaine for

over a week and present either after a seizure or when they

are found obtunded. They may be frankly comatose or

extremely difficult to arouse, often prompting extensive

medical evaluation of their altered mental status. Typically,

they awaken completely within 24 hours.

Seizures occur in up to 2% of cocaine abusers, and

although they usually occur soon after cocaine use, they may

not present until several hours later. Transient ischemic

attacks have been described and may lead to stroke; cocaine

use should be considered in the differential diagnosis of a

young patient with a stroke. Strokes are independent of the

route of administration and may occur as late as 24 hours

after use. They can present in first-time users but are more

common in chronic abusers.

Pulmonary complications include pneumothorax and

pneumomediastinum in patients who smoke or snort

cocaine. Pulmonary edema is rare in most cases of cocaine



CHAPTER 36

764

toxicity but is a common finding in patients who die of

cocaine intoxication.

Rhabdomyolysis may occur with excess muscle activity

and hyperthermia. Hyperthermia, when present, is often

severe.

B. Laboratory Findings—Laboratory evaluation of patients

with serious intoxication should include an ECG and meas-

urements of serum electrolytes, total CK levels, and a urine

test for myoglobin. Blood for cardiac markers may be indi-

cated by the patient’s clinical presentation. Toxicology

screens for cocaine may focus the diagnosis.

C. Imaging Studies—CT head scanning should be per-

formed in any patient with a concerning headache or in

those with neurologic findings or altered mental status. Plain

films of the abdomen may reveal packets in the intestines of

patients who swallow containers of the drug for the purpose

of transport (“body packers”).

Differential Diagnosis

Other stimulants, including sympathomimetics, SSRIs, theo-

phylline, phencyclidine, and anticholinergic drugs, can cause

a similar clinical picture. Withdrawal from ethanol or benzo-

diazepines may present similarly, as can thyrotoxicosis and

CNS infection. Psychiatric disorders are also in the differen-

tial diagnosis.

Treatment

A. Supportive Measures—Basic supportive measures such

as intravenous access, fluid administration, and supplemen-

tal oxygen should be initiated as indicated by the clinical sit-

uation. Gastric decontamination is not indicated in most

cases; however, patients who have ingested packets of the

drug are candidates for whole bowel irrigation.

B. Hyperthermia—When hyperthermia is present, the

patient should be undressed completely and sprayed with a

cool mist or draped with a wet sheet. A fan can be used to

facilitate evaporation. Ice packs should be placed at the neck,

axillae, and groin. Care should be taken not to overcool the

patient. Antipyretic agents are not effective.

C. Seizures—Initial treatment of agitation and seizures

should be with benzodiazepines. Neuroleptics may be effec-

tive, but since they lower the seizure threshold, their use is

discouraged. Seizures refractory to benzodiazepines can be

treated with phenobarbital or phenytoin. Status epilepticus

unresponsive to this therapy should be treated with pharma-

cologic paralysis and mechanical ventilation; continuous

EEG monitoring is necessary in these cases to ensure that the

paralyzed patient is not seizing.

D. Hypertension—Mild hypertension usually does not require

intervention. Severe hypertension or labile hypertension

should be treated with intravenous nitroprusside. Labetalol is

another alternative, especially in the tachycardiac patient.

Tachydysrhythmias that require treatment may respond to β-

blockers such as esmolol or metoprolol, but the patient must

be observed carefully for the development of worsening hyper-

tension from the unopposed α-adrenergic stimulation and β-

adrenergic blockade. Concurrent use of nitroprusside with

β-blockers is often necessary. Patients suspected of having a

myocardial infarction should receive standard therapy, but may

or may not have classic arteriosclerotic coronary artery disease.

E. Rhabdomyolysis—Rhabdomyolysis should be treated

with isotonic fluids to ensure a urine output of over 150 mL/h.

The addition of mannitol or alkalinization also may be

useful.

Camus P et al: Drug-induced and iatrogenic infiltrative lung dis-

ease. Clin Chest Med 2004;25:479–519. [PMID: 15331188]

Feldman JA et al: Acute cardiac ischemia in patients with cocaine-

associated complaints: Results of a multicenter trial. Ann Emerg

Med 2000;36:469–76. [PMID: 11054201]

Hollander JE, Henry TD: Evaluation and management of the

patient who has cocaine-associated chest pain. Cardiol Clin

2006;24:103–14. [PMID: 16326260]

Kleerup EC et al: Chronic and acute effects of “crack” cocaine on

diffusing capacity, membrane diffusion, and pulmonary capil-

lary blood volume in the lung. Chest 2002;122:629–38. [PMID:

12171843]

Miller MB: Arrhythmias associated with drug toxicity. Emerg Med

Clin North Am 1998;16:405–17. [PMID: 9621850]

Shanti CM, Lucas CE: Cocaine and the critical care challenge. Crit

Care Med 2003;31:1851–9. [PMID: 12794430]



Tricyclic Antidepressants

ESSENTIALS OF DIAGNOSIS



Tachycardia, arrhythmias.



Seizures.



Sensorium may range from awake and alert to comatose.



Mydriasis.



Dry skin.



Ileus.



Urinary retention.

General Considerations

Tricyclic antidepressants (TCAs) such as amitriptyline, doxepin,

and trimipramine work therapeutically by blocking reuptake

of norepinephrine into adrenergic nerves, but they also have

significant toxic effects related to their anticholinergic

and α-adrenergic blocking properties. When ingested, they

are absorbed rapidly; in overdose situations, owing to the slowed

intestinal motility from the anticholinergic effects, absorption

may be prolonged, increasing the half-life to as much as 3–4 days.



POISONINGS & INGESTIONS

765

Clinical Features

A. Signs and Symptoms—Patients with TCA overdose may

deteriorate rapidly, progressing from awake with normal

vital signs to having seizures or cardiac arrest within less than

an hour of significant ingestion. Mental status may range

from awake and alert to having seizures to frankly comatose.

Patients with suspected TCA ingestion need immediate

medical evaluation and close observation. Evaluation often

reveals both central and peripheral anticholinergic effects:

tachycardia, mydriasis, dry skin, urinary retention, ileus, ele-

vated temperature (usually mild), altered mental status (eg, agi-

tation, anxiety, delirium, and coma), seizures, and occasionally,

respiratory depression. Cardiovascular effects are usually the

cause of death and can include sinus tachycardia, dysrhyth-

mias, atrioventricular blockade, and hypotension (decreased

contractility and α-adrenergic blockade). This ingestion

should be suspected in any patient who presents with seizures,

anticholinergic signs (including coma), and cardiovascular

abnormalities, particularly if the ECG is abnormal.

B. Electrocardiography—The single most valuable initial test

in patients suspected of having a TCA overdose is the ECG.

Common findings include sinus tachycardia, PR-interval and

QT-segment prolongation, and nonspecific ST-segment

changes. QRS complex prolongation suggests a serious over-

dose. Rightward and superior terminal QRS forces (a wide,

prominent S wave in leads I, aVF, and V

, with a prominent R

wave in aVR) are very suggestive of TCA overdose.

C. Laboratory Findings—General laboratory evaluation is

rarely helpful. Drug levels correlate poorly with toxic effects

and can vary widely in an individual patient.

D. Imaging Studies—Since some TCAs are radiopaque, a

plain film of the abdomen may show tablets in the stomach

or intestines.

Differential Diagnosis

The combination of altered mental status, seizures, and car-

diovascular abnormalities suggests several diagnoses.

Toxicologic causes include phenothiazines, anticholinergics,

and theophylline; less commonly, β-blockers, calcium chan-

nel blockers, and local anesthetic drug overdose (eg, lido-

caine) can cause these findings. Nontoxicologic causes

include meningitis, sepsis, hypoglycemia (severe), anaphy-

laxis, and head trauma.

Treatment

A. Initial Management—General measures aimed at stabi-

lization, monitoring, and intravenous access should be insti-

tuted rapidly. A urinary catheter should be placed to monitor

urine output and provide easy determination of urine pH.

Syrup of ipecac should be avoided because these patients may

deteriorate rapidly and become obtunded before vomiting

begins, placing them at risk for aspiration. Gastric lavage should

be considered in patients presenting within 1 hour of ingestion

of a large amount of TCAs. If gastric lavage is performed,

suction and airway management equipment must be readily

available in the event the patient develops seizures. Activated

charcoal, 100 g, should be placed down the lavage tube (if

used) or given to the patient via NG tube. There is some evi-

dence that a repeated-dose activated charcoal regimen (every

2–4 hours) may be helpful in significant ingestions.

TCA overdose patients need to be admitted to the ICU if

they have any of the following: persistent tachycardia (>120

beats/min); dysrhythmias, including premature ventricular

contractions; QRS >100 ms; hypotension; or evidence of

CNS toxicity. Patients admitted should be monitored until

they are free of toxicity for 24 hours. Patients who present

with none of the preceding and do not develop any of the

listed admission criteria after 6 hours of observation may be

discharged; a psychiatric evaluation before discharge is pru-

dent and is mandatory in cases of attempted suicide.

B. Bicarbonate Therapy—Alkalinization of the blood is a

mainstay in the therapy of TCA ingestion. It effectively treats

most of the major adverse effects of the drug, including

hypotension, cardiac conduction abnormalities, and dys-

rhythmias. Alkalinization has varying efficacy in the treat-

ment of seizures and coma. Optimal blood pH is 7.50, and

the urine pH should be over 7.0. Alkalinization is achieved by

intravenous sodium bicarbonate therapy; in intubated

patients, transient hyperventilation will alkalinize the blood

until intravenous therapy can be initiated.

Supportive care and alkalinization therapy usually are ade-

quate to manage patients with TCA overdose. In some cases,

additional measures will be needed to stabilize the patient.

Those with severe agitation, delirium, or seizures may require

benzodiazepines or barbiturates for control. Dysrhythmias

refractory to alkalinization can be treated with lidocaine or

cardioversion. Class Ia antiarrhythmic agents should be

avoided in this patient population because they can exacerbate

dysrhythmias. Hypotension that does not respond to alkalin-

ization can be managed with fluid boluses or with vasopres-

sors; since the hypotension is often due to α-adrenergic

blockade, α-adrenergic agonists (eg, phenylephrine or

methoxamine) are a good choice. Dopamine may be ineffec-

tive or may exacerbate hypotension owing to its β-agonist

effects (peripheral β

-adrenergic stimulation produces vasodi-

lation). Hemodialysis and hemoperfusion are relatively inef-

fective in these patients because the TCAs are highly

protein-bound and not easily removed by these measures.

Current Controversies and Unresolved Issues

In the past, physostigmine was recommended for treatment

of TCA overdose. As an acetylcholinesterase inhibitor,

physostigmine increases acetylcholine availability at receptor

sites and reverses central and peripheral anticholinergic

effects. It has not been proven to be effective in treating

hypotension, ventricular dysrhythmias, and conduction dis-

turbances, which are the major causes of fatal toxicity in TCA

overdoses. Significant adverse effects such as atrioventricular



CHAPTER 36

766

blockade, bradycardia, and asystole may occur with

physostigmine. Therefore, use of physostigmine is not rec-

ommended in the treatment of TCA overdose.

Kerr GW, McGuffie AC, Wilkie S: Tricyclic antidepressant over-

dose: A review. Emerg Med J 2001;18:236–41. [PMID:

11435353]

Liebelt EL et al: Serial electrocardiogram changes in acute tricyclic

antidepressant overdoses. Crit Care Med 1997;25:1721–6.

[PMID: 9377889]

Liebelt EL, Francis PD, Woolf AD: ECG lead aVR versus QRS inter-

val in predicting seizures and arrhythmias in acute tricyclic

antidepressant toxicity. Ann Emerg Med 1995;26:195–201.

[PMID: 7618783]

O’Connor N et al: Prolonged clinical effects in modified-release

amitriptyline poisoning. Clin Toxicol (Phila) 2006;44:77–80.

[PMID: 16496498]

Seger DL et al: Variability of recommendations for serum alkalin-

ization in tricyclic antidepressant overdose: A survey of U.S.

poison center medical directors. J Toxicol Clin Toxicol

2003;41:331–8. [PMID: 12870873]

Thanacoody HK, Thomas SH: Tricyclic antidepressant poisoning:

Cardiovascular toxicity. Toxicol Rev 2005;24:205–14. [PMID:

16390222]

Woolf AD et al: Tricyclic antidepressant poisoning: An evidence-

based consensus guideline for out-of-hospital management.

Clin Toxicol (Phila) 2007;45:203–33. [PMID: 17453872]



Serotonin Syndrome

ESSENTIALS OF DIAGNOSIS



Coma, somnolence, confusion, agitation, or seizures.



Autonomic instability, including fever, diaphoresis,

tachycardia, hyper- or hypotension, mydriasis.



Clonus (may be spontaneous), especially ocular clonus,

rigidity, hyperreflexia.



History of use of serotonin-based antidepressants or

other drugs associated with serotonin release.

General Considerations

The serotonin syndrome historically has been associated with

cocaine, amphetamines, and other drugs that cause increased

release of serotonin, such as a drug of abuse, 3,4–methylene-

dioxymethamphetamine (MDMA or “ecstasy”), or dex-

tromethorphan, bromocriptine, and linezolid. With the

increased use of selective serotonin reuptake inhibitors

(SSRIs) as antidepressants, overdose of these agents is respon-

sible for a number of cases of serotonin syndrome.

Clinical Features

A. Symptoms and Signs—The serotonin syndrome shares

many symptoms and signs with overdose of sympath-

omimetics (eg, tachycardia and mydriasis) and with the

neuroleptic malignant syndrome (eg, rigidity, hyperthermia,

and alterations of mental status). In fact, distinguishing sero-

tonin syndrome from these may be difficult. Most cases of

serotonin syndrome are mild and self-limited, but severe

complications can include diaphroresis with severe fluid loss,

rhabodomyolysis, marked hyperthermia, and death.

Diagnostic criteria have been proposed, but these are some-

what nonspecific.

B. Laboratory Findings—Laboratory evaluation in patients

with serious intoxication should include an ECG and meas-

urements of serum electrolytes, total CK levels, and urinary

myoglobin. There are no specific tests for this syndrome,

although toxicology studies may demonstrate the presence of

concomitant cocaine, amphetamines, or other drugs.

Differential Diagnosis

The differential diagnosis includes sympathomimetic over-

dose, including amphetamines and cocaine, both of which

also can trigger the serotonin syndrome. A more confusing

clinical picture is the neuroleptic malignant syndrome, in

which muscular rigidity, altered mental status, and hyper-

thermia are key features. Some authors have suggested that

dilated pupils with clonus and hyperreflexia rather than

severe muscle rigidity make it more likely to be the serotonin

syndrome. A key differential feature is evidence of an over-

dose of an SSRI or other drug. While neuroleptic malignant

syndrome may occur at any time after a neuroleptic is pre-

scribed, it is not more likely after an overdose. Other possible

syndromes include thyroid storm and withdrawal from ben-

zodiazepines or ethanol.

Treatment

A. Supportive Measures—Basic supportive measures such

as intravenous fluid administration and supplemental oxy-

gen should be initiated as indicated by the clinical situation.

When hyperthermia is present, the patient should be

undressed completely and sprayed with a cool mist or draped

with a wet sheet. A fan can be used to facilitate evaporation.

Ice packs should be placed at the neck, axillae, and groin.

Care should be taken not to overcool the patient. Antipyretic

agents are not effective.

B. Specific Treatment—Potential drugs precipitating the

serotonin syndrome should be discontinued. Benzodiazepines

generally are considered useful for the serotonin syndrome.

They are anticonvulsants, are not associated with serotonin

release, and are anxiolytic and sedating. Dantrolene uncou-

ples excitation-contract in skeletal muscles and has been

used in malignant hyperthermia, neuroleptic malignant

syndrome, and serotonin syndrome. There are case reports

of benefit from dantrolene in serotonin syndrome but no

controlled trials.

C. Current Controversies—A number of authors have com-

mented on the approach when it is not clear whether a