quickly, accurately, and professionally in a reassuring manner.

Subsequent to telephone consultations, poison control center

staff should initiate follow-up calls to determine the effectiveness of the recommended treatment and the need for additional

evaluation or treatment.23,24

EFFECTIVE COMMUNICATION

Effective communication is essential to the assessment of potential poisonings. In most situations, the person seeking guidance

on the management of a potentially toxic exposure is the parent

of a small child who may have ingested a substance. The caller

is usually anxious about the child and may feel guilty about the

exposure. To calm the caller, the health care provider should

quickly reassure the parent that telephoning for help was appropriate and that the best assistance possible will be provided.24

If English is not the first language of the caller, or if there are

other communication barriers (e.g., panic), solutions must be

found to enhance outcomes. Most poison centers subscribe to

translation services or have bilingual staff to communicate with

non–English-speaking callers. Poison centers also have special

equipment to serve the hearing- and speech-impaired populations.

Once calm, effective communication is established, the health

care provider should first determine whether the patient is conscious and breathing and has a pulse. If life-threatening symptoms have occurred, the caller should call 9-1-1 for emergency

services. If the health care provider does not have the knowledge

or resources to provide poison information, he or she should

refer the caller to the closest poison control center. Information

on the location and phone number of the nearest poison control center can be found at http://www.aapcc.org or by calling

1-800-222-1222 in the United States.

GENERAL MANAGEMENT

Supportive Care and “ABCs”

Management of poisoned or overdosed patients is primarily based

on symptomatic and supportive care. Specific antidotes exist only

for a small percentage of the thousands of potential drugs and

chemicals that can cause a poisoning.

The first aspect of patient management should always be basic

support of airway, breathing, and circulation (the “ABCs”). The

assessment and treatment of the potentially poisoned patient

can be separated into seven primary functions: (a) gathering

history of exposure, (b) evaluating clinical presentation (i.e.,

“toxidromes”), (c) evaluating clinical laboratory patient data,

(d) removing the toxic source (e.g., irrigating eyes, decontaminating exposed skin), (e) considering antidotes and specific treatment, (f ) enhancing systemic clearance, and (g) monitoring

outcome.25–27

GATHERING HISTORY OF EXPOSURE

Comprehensive historical information about the toxic exposure

should be gathered from as many different sources as possible

(e.g., patient, family, friends, prehospital health care providers).

This information should be compared for consistency and evaluated relative to clinical findings and laboratory results. The

patient’s history of the exposure is often inaccurate and should be

confirmed with objective findings.25,26,28 For example, a patient

who presents to an ED with a supposed hydrocodone and carisoprodol overdose is expected to be lethargic or comatose. If the

patient arrives wide awake with tachycardia and agitation, the

caregiver should suspect exposure to other substances.

Specific information should be sought concerning the

patient’s state of consciousness, symptoms, probable intoxicant(s), and maximal amount and dosage form(s) of substance

ingested, as well as when the exposure occurred. Medications,

allergies, and prior medical problems also should be ascertained

to facilitate development of treatment plans (e.g., a history of

renal failure may indicate the need for hemodialysis to compensate for decreased renal drug clearance).25,26

EVALUATING CLINICAL PRESENTATION

AND TOXIDROMES

A thorough physical examination is needed to characterize the

signs and symptoms of overdose, and should be conducted serially to determine the evolution or resolution of the patient’s

intoxication. An evaluation of the presenting signs and symptoms can provide clues to the drug class causing the toxicity, confirm the historical data surrounding the toxic exposure, and suggest initial treatment.25,29–31 The patient may be asymptomatic

on presentation, even though a potentially severe exposure has

occurred, if absorption of the drug or toxic substance is incomplete or if the substance has not yet been metabolized to a toxic

substance.32–34

Characteristic toxidromes (i.e., a constellation of signs and

symptoms consistent with a syndrome) can be associated

with some specific classes of drugs.26,30,31 The most common

toxidromes are those associated with anticholinergic activity,

increased sympathetic activity, and central nervous system (CNS)

69Managing Drug Overdoses and Poisonings Chapter 4

stimulation or depression. Anticholinergic drugs can increase

heart rate and body temperature, decrease gastrointestinal (GI)

motility, dilate pupils, and produce drowsiness or delirium. Sympathomimetic drugs can increase CNS activity, heart rate, body

temperature, and blood pressure (BP). Opioids, sedatives, hypnotics, and antidepressants can depress the CNS, but the specific

class of CNS depressant often cannot be easily identified.

Classic findings may not be present for all drugs within a therapeutic class. For example, opioids generally induce miosis, but

meperidine can produce mydriasis. Furthermore, the association

of symptoms with a particular class of toxic substances is difficult

when more than one substance has been ingested. Practitioners

should not focus only on the specific clinical findings associated

with a toxidrome. Rather, they should consider all subjective

and objective data gathered from the history of exposure, the

patient’s medical history, physical examination, and laboratory

findings.30

INTERPRETATION OF LABORATORY DATA

DRUG SCREENS

A urine drug screen can be useful in identifying the presence

of drugs and their metabolites in selected patients but is not

indicated in all cases of drug overdose. Urine drug screens can

be useful in a patient with coma of unknown etiology, when the

presented history is inconsistent with clinical findings, or when

more than one drug might have been ingested.35,36

PHARMACOKINETIC CONSIDERATIONS

The absorption, distribution, metabolism, and elimination of

drugs in the overdosed patient can be quite different than

when the drug is taken in usual therapeutic doses.32–34 The

expected pharmacodynamic and pharmacokinetic features of

drugs can be substantially altered by large drug overdoses, especially with drugs that exhibit dose-dependent pharmacokinetics.

The rate of drug absorption is generally slowed by large overdoses, and the time to reach peak serum drug concentrations

can be delayed.35,37 For example, peak serum concentrations of

phenytoin can be delayed for 2 to 7 days after an orally ingested

overdose.38,39 The volume of distribution of an overdosed drug

can be increased, and when usual metabolic pathways become

saturated, secondary clearance pathways can be important. For

example, large overdoses of acetaminophen saturate glutathione

mechanisms of metabolism, resulting in hepatotoxicity.40

When the pharmacokinetic parameters of an overdosed drug

are altered, serial plasma concentration measurements can better define the absorption, distribution, and clearance phases of

the ingested substance. Pharmacokinetic parameters that have

been derived from therapeutic doses should not be used to predict whether absorption is complete or to predict the expected

duration of intoxication caused by large overdoses.34,41,42

DECONTAMINATION

After the airway and the cardiopulmonary system are supported,

efforts should be directed toward removing the toxic substance

from the patient (i.e., decontamination).25,43 Decontamination

presumes that both the dose and the duration of toxin exposure are important in determining the extent of toxicity and that

prevention of continued exposure will decrease toxicity.32–34,43

This intuitive concept is clearly relevant to ocular, dermal, and

respiratory exposures, when local tissue damage is the primary

problem. Respiratory decontamination involves removing the

patient from the toxic environment and providing fresh air or

oxygen to the patient. Decontamination of skin and eyes involves

flushing the affected area with large volumes of water or saline

to physically remove the toxic substance from the surface.25,26

GASTROINTESTINAL DECONTAMINATION

Because most poisonings and overdoses result from oral ingestions, measures to decrease or prevent continued GI absorption

have commonly been used to limit the extent of exposure.25,26,40

GI decontamination should be considered if the ingestion is large

enough to produce potentially significant toxicity, or if the potential severity of the ingestion is unknown and the time since ingestion is less than1 hour. The following methods have historically

been used: (a) evacuation of gastric contents by emesis or gastric

lavage, (b) administration of activated charcoal as an adsorbent

to bind the toxic substance remaining in the GI tract, (c) use of

cathartics or whole bowel irrigation (WBI) to increase the rectal

elimination of unabsorbed drug, or (d) a combination of any of

these methods.44–49

For a PowerPoint presentation about GI

decontamination, go to http://thepoint.

lww.com/AT10e.

The efficacy of GI decontamination varies, depending on

when the process is initiated relative to the time of ingestion,

dose ingested, and other factors. Furthermore, ipecac-induced

emesis, gastric lavage, cathartics, and activated charcoal are not

directly associated with improved patient outcomes.44–49

The most appropriate method for GI tract decontamination remains unclear because sound comparative data for different methods of GI decontamination are not available. Clinical research in healthy subjects, by necessity, must use nontoxic

doses of drugs. Studies using nontoxic doses are not applicable to

the overdose situation because alterations in GI absorption can

occur with large doses. In addition, low-dose studies generally

rely on pharmacokinetic end points such as peak plasma concentrations, area under the plasma concentration–time curve, or

quantity of drug recovered from the urine.44,45,47–49 In contrast,

clinical studies of GI decontamination methods in patients who

have ingested toxic doses of a substance use clinical outcomes

or a directional change in serum drug concentrations.44,45,48,49

These latter trials are not standardized with respect to the dose

ingested or to the time interval between drug ingestion and

GI decontamination.44–49

Ipecac-Induced Emesis and Gastric Lavage

Ipecac-induced emesis and gastric lavage primarily remove substances from the stomach. Their efficacy is affected significantly

by the time the ingested substance remains in the stomach. Gastric lavage and ipecac-induced emesis are most effective when

implemented before the substance moves past the stomach into

the intestine (usually within 1 hour).44,45

The commonly used adult gastric lavage tube (36F) has an

internal diameter too small to allow recovery of large tablet or

capsule fragments. An even smaller diameter lavage tube is used

for children.45 Gastric lavage may be useful only if large amounts

of a liquid substance were ingested and the patient arrived within

1 hour of the ingestion.45 However, patients usually arrive in

the ED more than an hour after ingestion, when absorption

of the toxin has most likely already occurred. As a result, the

efficacy of these procedures in overdose situations is minimal,

and no studies have confirmed that use of gastric lavage or ipecacinduced emesis improves the outcome of the patient.44,45,50 For

these reasons, ipecac is no longer used, and gastric lavage is used

only in rare, specific situations.

Activated Charcoal

In 1963, a review article concluded that activated charcoal was the

most valuable agent available for the treatment of poisoning.51

70 Section 1 General Care

This conclusion was based only on studies in fasting patients who

had nontoxic exposures. Nevertheless, data from those studies

were extrapolated to poisoned patients. Since then, activated

charcoal has become the preferred method of GI decontamination for the treatment of toxic ingestions.25,43,51–53

The goal of therapy is to decrease the absorption of the substance and reduce or prevent systemic toxicity.46 Unfortunately,

there are no satisfactorily designed clinical studies assessing benefit from the use of activated charcoal to guide the use of this

therapy. There is also no evidence that the administration of

activated charcoal improves clinical outcomes.46

The use of activated charcoal at a dose of 1 g/kg should be

considered when the patient has ingested a toxic substance that is

known to be absorbed by activated charcoal within 1 hour of the

ingestion. The potential for benefit is unknown if the activated

charcoal is given more than 1 hour after ingestion.46 It should

be noted that iron and lithium are not absorbed by activated

charcoal. Other forms of GI decontamination must be used to

remove those substances from the GI tract.46

Generally the use of activated charcoal is safe. Although there

are relatively few reports of adverse effects from the use of activated charcoal, there are numerous reports of complications,

usually involving aspiration. It is essential that the patient has an

intact or protected airway (intubation) before activated charcoal

is administered, especially in drowsy patients or patients who

may rapidly become obtunded.46

To see activated charcoal in a lung x-ray, go to

http://thepoint.lww.com/AT10e.

Vomiting with aspiration of activated charcoal occurs in about

5% of patients who receive activated charcoal.46,53–55 The resulting pulmonary problems can be caused by aspiration of acidic

stomach contents or the charcoal. Decreased oxygenation can

occur immediately, or pulmonary effects can occur later.55–59

Adult respiratory distress syndrome has resulted after the unintentional instillation of charcoal into the lung.55 Aspiration of

charcoal can result in chronic lung disease or fatalities, whereas

the toxic exposure, for which the charcoal was administered, is

often not lethal or even serious.56,60

Cathartics

Historically, sorbitol (a cathartic) was often administered with

activated charcoal to enhance passage of the charcoal-substance

complex through the GI tract. However, decreased transit time

through the bowel has not been proven to decrease absorption

as drug absorption does not take place in the large bowel.47 Sorbitol is also associated with vomiting and aspiration.47 Hypernatremia can also develop subsequent to the administration of

repeat doses of activated charcoal with sorbitol.61,62 Currently,

most EDs use aqueous activated charcoal mixtures rather than

charcoal–sorbitol combinations. Because cathartics are not effective in reducing drug absorption or increasing patient outcome,

their use is no longer advised.47

Whole Bowel Irrigation

Whole bowel irrigation with a polyethylene glycol–balanced

electrolyte solution (e.g., Colyte, GoLYTELY) can successfully

remove substances from the entire GI tract in a period of

several hours. WBI is effective with ingestions of sustainedrelease dosage forms, as well as substances that form bezoars

(concretions of tablets or capsules), such as ferrous sulfate or

phenytoin.26,48,63 WBI is also indicated when the toxic agent is

not adsorbed by activated charcoal (e.g., body-packer packets,

lithium, iron, potassium).25,26,48,63 This method of GI decontamination takes much longer to complete and is associated

with poor patient compliance because large volumes of fluid

(2 L/hour for adults until the effluent is clear) need to be ingested

to be effective.63 A nasogastric (NG) tube can be inserted, and

the WBI fluid can be administered via NG tube so that lack of

patient compliance is no longer a factor.48

ANTIDOTES AND SPECIFIC TREATMENTS

An antidote is a drug that neutralizes or reverses the toxicity

of another substance. Some antidotes can displace a drug from

receptor sites (e.g., naloxone for opioids, flumazenil for benzodiazepines), and some can inhibit the formation of toxic metabolites (e.g., N-acetylcysteine [NAC] for acetaminophen, fomepizole for methanol).26,64,65 Some treatments are highly effective

for the management of individual drug overdoses but do not

meet the definition of an antidote. For example, sodium bicarbonate is used to treat the cardiotoxicity arising from tricyclic

antidepressant (TCA) overdoses, and benzodiazepines are used

to treat CNS toxicity associated with cocaine and amphetamine

overdoses.26,66–68 However, it is important to note that for antidotes to be effective, they must be readily available at the health

care facility in adequate doses to treat the patient in a timely

manner.69

ENHANCING SYSTEMIC CLEARANCE

Hemodialysis and manipulation of urine pH can enhance

the clearance of substances. Hemodialysis can successfully

treat some specific intoxications (e.g., methanol, ethylene glycol, aspirin, theophylline, lithium). Hemodialysis can also be

used in patients with severe acid–base disturbances or renal

dysfunction.50 Alkalinization of the urine can enhance the elimination of drugs such as aspirin and phenobarbital.70–72

MONITORING OUTCOME

Selecting the appropriate parameters and length of time to

monitor a patient who has been exposed to a toxic agent

requires knowledge of toxic effects and the time course of the

intoxication.36,37 Most patients who are at risk for moderate or

severe toxicity should be monitored in an intensive care unit

(ICU) with careful assessments of cardiac, pulmonary, and CNS

function.73,74

ASSESSMENT OF SALICYLATE

INGESTION

Gathering a History

CASE 4-1

QUESTION 1: M.O., the mother of a 3-year-old child, states

that her daughter, D.O., has ingested some aspirin tablets.

What additional information should be obtained from or

given to M.O. at this time?

Obtaining an initial assessment of the patient’s status is essential. The caller’s telephone number should be obtained in the

event that the call is disconnected, initial recommendations need

to be modified, or subsequent follow-up is needed. The health

care provider should ask for patient-specific information with

questions that are nonthreatening and nonjudgmental. The caller

should be reassured that calling for help was the right thing

to do.

71Managing Drug Overdoses and Poisonings Chapter 4

Evaluating Clinical Presentation

CASE 4-1, QUESTION 2: On further questioning, M.O.

states that D.O. is crying and complaining of a stomachache.

Otherwise, the child appears to be acting normally. D.O.

was found sitting on the bathroom floor with an aspirin

bottle in her hand and some partially chewed tablets on

the floor next to her. M.O. states that the child had the

same look on her face that she has when she eats things

that she does not like. M.O. reports that she can see white

tablet material gummed on the child’s teeth. The mother

was gone no more than 5 minutes and had asked her 5- and

6-year-old sons to watch their sister. What additional information is needed to correctly assess the potential for

toxicity in D.O.?

To determine the potential toxicity for an unintentional ingestion, it is important to assess the presence of symptoms and to

identify the substance ingested. Inquiries should begin with openended questions to determine the facts that the caller is certain of

versus what may have been assumed. The answers usually point

to more specific information that is needed to accurately assess

the exposure.23

D.O.’s symptoms presently are not life-threatening. Her

behavior is consistent with being scared in response to the

mother’s anxiety. Once it has been established that the child does

not need immediate life-saving treatment, the caller is generally

more willing and able to answer additional questions.

M.O. already has provided information about the child’s

symptoms. More information is needed to determine the identity of the ingested substance, the time of ingestion, the brand of

aspirin (to ensure that the product is not an aspirin-combination

or even an aspirin-free formulation), the dosage form, the number of dosage units in a full container, and the number of remaining dosage units in the container. The parent should be careful to

look for tablets under beds, rugs, or other locations out of sight

(e.g., wastepaper baskets, toilets, pet food dishes, pockets). The

dosage forms in the container should be identical in appearance,

and the contents should be what are stated on the label. Information concerning the child’s weight and health status, as well

as whether the child is taking other medications, is also important. The child’s weight is useful in determining the maximum

milligram per kilogram dose of aspirin that was ingested.

When more than one child is present during an ingestion,

the caller should be questioned as to whether other children also

could have participated in the ingestion. In this situation, the

children could have shared equally in the missing medication,

all of the drug could have been fed to one child, or all of the

drug could have been ingested by the oldest or most aggressive

child. When it is unclear how much is missing among a group

of children, each child should be evaluated and managed as if

he or she may have ingested the total missing quantity.

Triage of Call

CASE 4-1, QUESTION 3: M.O. has now determined that a

total of five tablets each containing 325 mg per tablet of

aspirin are missing from the bottle. Because M.O. recalls

having taken two aspirin tablets from this bottle, it is not

likely that her daughter took more than three tablets. M.O.

states that D.O. weighs 36 pounds. What treatment is

needed for this child?

The maximal dose of aspirin ingested by this child is likely to

be much less than the minimal dose required to cause significant

symptoms based on her weight for her age (i.e., 36 pounds or

approximately 16 kg). A dose of 150 mg/kg of aspirin is the smallest dose at which treatment or assessment at a health care facility

is necessary.72,75 D.O. is likely to have ingested a maximum of

975 mg of aspirin (i.e., three 325-mg tablets), which is about

60 mg/kg (975 mg divided by 16 kg). If this child is healthy, takes

no medications, and is not allergic to aspirin, the child does not

require any treatment. With this history of ingestion, the only

adverse effect that might occur is some mild nausea. Providing

information to the mother that her child had not ingested a toxic

or dangerous amount will be reassuring.

For many years, aspirin was the most common cause of unintentional poisoning and poisoning deaths among children.75–77

However, safety closure packaging and reduction of the total

aspirin content in a full bottle of children’s aspirin to approximately 3 g has steadily reduced the frequency of pediatric aspirin

poisoning and deaths.76–78 Although acute aspirin poisoning

remains a problem, the largest percentage of life-threatening

intoxications now results from therapeutic overdose.72 Therapeutic overdoses occur when a dose is given too frequently,

when both parents unknowingly dose the child with the drug, or

when too large a dose is given. Therapeutic overdoses are especially problematic when excessive doses are given for a prolonged

period and the drug is able to accumulate.72

Outcome for M.O.

Follow-up telephone consultation on toxic ingestions is important to identify children who unexpectedly develop symptoms

that might need to be treated. A telephone call to M.O. 6 to

24 hours after her initial call would be appropriate to follow up

on the child. On a call back to M.O., the parent stated that she gave

D.O. lunch at the appropriate time. D.O. then watched cartoons,

took her usual nap, and remained asymptomatic.

Acute and Chronic Salicylism

SIGNS AND SYMPTOMS

CASE 4-2

QUESTION 1: V.K., a 65-year-old, 55-kg woman with a history of chronic headaches, has taken 10 to 12 aspirin tablets

daily for several months. On the evening of admission, she

became lethargic, disoriented, and combative. Additional

history revealed that she ingested up to 100 aspirin tablets

on the morning of admission (about 10 hours earlier) in

a suicide attempt. She complained of ringing in her ears,

nausea, and three episodes of vomiting. Vital signs were

BP 140/90 mm Hg, pulse 110 beats/minute, respirations

36 breaths/minute, and temperature 102.5◦F. V.K.’s laboratory data obtained on admission were as follows:

Serum sodium (Na), 148 mEq/L

Potassium (K), 2.8 mEq/L

Chloride (Cl), 105 mEq/L

Bicarbonate, 10 mEq/L

Glucose, 60 mg/dL

Blood urea nitrogen (BUN), 35 mg/dL

Creatinine, 2.2 mg/dL

Arterial blood gas (ABG) values (room air) were as follows: pH, 7.25; PCO2, 20 mm Hg; and PO2, 95 mm Hg.

A serum salicylate concentration measured approximately

12 hours after the acute ingestion was 88 mg/dL. Her

hemoglobin was 9.6 g/dL with a hematocrit of 28.9% and a

prothrombin time (PT) of 16.4 seconds. Is V.K. at high risk

because of her ingestion?

72 Section 1 General Care

The symptoms and severity of salicylate intoxication depend

on the dose consumed; the patient’s age; and whether the ingestion was acute, chronic, or a combination of the two.77,79,80 This

case illustrates an acute ingestion in someone who has also chronically ingested aspirin. Acute ingestion of 150 to 300 mg/kg of

aspirin is likely to produce mild to moderate intoxication, greater

than 300 mg/kg indicates severe poisoning, and greater than

500 mg/kg is potentially lethal.72,75 V.K., who ingested approximately 600 mg/kg, has taken a potentially lethal dose. Chronic salicylate intoxication is usually associated with ingestion of greater

than 100 mg/kg/day for more than 2 days.72,75 V.K. has been taking

70 mg/kg/day for her headaches in addition to her acute ingestion. V.K. demonstrates many of the findings typical of severe

acute salicylism (see Pathophysiology of Salicylate Intoxication

and Assessment of Toxicity sections). V.K.’s prognosis is potentially poor because she is elderly and has taken a potentially lethal

overdose of aspirin.

Pathophysiology of Salicylate

Intoxication

CASE 4-2, QUESTION 2: Describe the pathophysiology and

clinical features of acute and chronic salicylism.

Toxicity from salicylate exposure results in direct irritation of the GI tract, direct stimulation of the CNS respiratory center, stimulation of the metabolic rate, lipid and

carbohydrate metabolism disturbances, and interference with

hemostasis.72,75,77,79,80 Toxic doses of salicylate directly stimulate the medullary respiratory center leading to nausea, vomiting, tinnitus, delirium, tachypnea, seizures, and coma, and

influence several key metabolic pathways.72,77–81 Direct stimulation of the respiratory drive increases the rate and depth

of ventilation, which can result in primary respiratory alkalosis. The respiratory alkalosis causes increased renal excretion

of bicarbonate, resulting in decreased buffering capacity. The