TOXICOLOGY LABORATORY SCREENING

1 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. Qualitative screening is intended to identify

unknown substances involved in the toxic exposure. A benzodiazepine screen can

detect oxazepam, a common benzodiazepine metabolite, but will not detect

alprazolam and lorazepam as they are not metabolized to oxazepam. Opioid

screens may not detect synthetic opioids such as fentanyl and methadone.

Quantitative testing determines how much of a known drug is present and can help

determine the severity of toxicity and the need for aggressive interventions (e.g.,

hemodialysis).

Case 4-4 (Questions 1, 7)

TOXIDROMES

1 A toxidrome is a consistent constellation of signs and symptoms associated with

some specific classes of drugs. The most common toxidromes are those associated

with anticholinergic activity, increased sympathetic activity, and central nervous

system (CNS) stimulation or depression. Anticholinergic drugs increase heart rate

and body temperature, decrease GI motility, dilate pupils, and produce drowsiness

or delirium. Sympathomimetic drugs increase CNS activity, heart rate, body

temperature, and blood pressure. Opioids, sedatives, hypnotics, and antidepressants depress the CNS, but the specific class of CNS depressant often cannot be

easily identified.

Case 4-4 (Questions 1, 2, 5)

SALICYLATES

1 Acute ingestion of 150 to 300 mg/kg aspirin causes mild to moderate intoxication,

greater than 300 mg/kg indicates severe poisoning, and greater than 500 mg/kg is

potentially lethal. Symptoms of intoxication include vomiting, tinnitus, delirium,

tachypnea, metabolic acidosis, respiratory alkalosis, hypokalemia, irritability,

hallucinations, stupor, coma, hyperthermia, coagulopathy, and seizures. Salicylate

intoxication mimics other medical conditions and can be easily missed. Patients

with a chronic salicylate exposure, acidosis, or CNS symptoms and those who are

elderly are high-risk and should be considered for early dialysis.

Case 4-1 (Question 3),

Case 4-2 (Questions 1–6)

IRON

1 Acute elemental iron ingestions of less than 20 mg/kg are usually nontoxic; doses

of 20 to 60 mg/kg result in mild to moderate toxicity, and doses of greater than

60 mg/kg are potentially fatal. Symptoms of toxicity include nausea, vomiting,

diarrhea, abdominal pain, hematemesis, bloody stools, CNS depression,

hypotension, and shock. Patients with severe iron poisoning do not exhibit the

second stage of so-called recovery but continue to deteriorate.

Case 4-3 (Questions 2–14)

TRICYCLIC ANTIDEPRESSANTS

1 Severe toxicity has been associated with doses of 15 to 25 mg/kg. Symptoms

include tachycardia with prolongation of the PR, QTc, and QRS intervals, ST and

T-wave changes, acidosis, seizures, coma, hypotension, and adult respiratory

distress syndrome. A QRS segment greater than 100 milliseconds is commonly

seen in severe tricyclic antidepressant overdoses.

Case 4-4 (Questions 9–17)

ACETAMINOPHEN

1 Toxicity is associated with acute ingestions greater than 150 mg/kg or more than

7.5 g total in adults. Symptoms in patients with toxicity include vomiting, anorexia,

abdominal pain, malaise, and progression to characteristic centrilobular hepatic

necrosis. Acetaminophen-induced hepatotoxicity is universal by 36 hours after

ingestion, but patients who receive NAC within 8 to 10 hours after ingestion rarely

exhibit hepatotoxicity. There is no consensus as to the best route of NAC

administration, the optimal dosage regimen, or the optimal duration of therapy.

Case 4-5 (Questions 1–15)

67Managing Drug Overdoses and Poisonings Chapter 4

This chapter reviews common strategies for the evaluation and

management of drug overdoses and poisonings. Information for

the management of specific drug overdoses is best obtained from

a poison control center (reached by calling 1-800-222-1222 anywhere in the United States).

Epidemiologic Data

AMERICAN ASSOCIATION OF POISON CONTROL

CENTERS AND DRUG ABUSE WARNING NETWORK

Toxicity secondary to drug and chemical exposure commonly

occurs in children. The incidence of exposure to specific agents

and the severity of outcomes varies based on the population

studied (Table 4-1).1–3 The number of reported toxic exposures

in the United States in 2009 was approximately 2.48 million,

according to the American Association of Poison Control Centers

(AAPCC).3 In most cases, little or no toxicity was associated with

the exposure. Although 24.1% of patients received treatment at

a health care facility, only 6.1% reported moderate or severe

symptoms and 0.06% resulted in fatalities.

According to the Drug Abuse Warning Network (DAWN),

almost 2 million US emergency department (ED) visits involved

drug misuse or abuse in the year 2008. Of those cases, illicit drug

use was mentioned more than 2.7 million times because many

of the visits involved multiple drugs of abuse.4 These disparate

statistics from two national sources underscore the difficulty in

determining the true incidence of poisoning and overdoses.5

AGE-SPECIFIC DATA

Stratifying patients by age can be useful in assessing the likelihood of severe toxicity from an exposure. Most unintentional

ingestions by children 1 to 6 years of age occur because children

are curious, becoming more mobile, and beginning to explore

their surroundings, and they often put objects or substances into

their mouths.6 Of all reported poisonings, 38.9% occur in children younger than 3 years and 51.9% occur in children younger

than 6 years of age.3 According to AAPCC statistics, 11.26% of

pediatric (younger than 6 years of age) poisoning cases were

treated in a health care facility, and the remaining cases were

TABLE 4-1

Substances Most Commonly Involved in Poisoningsa

Children Adults Fatal Exposures (All Ages)

Personal care products Analgesics Sedatives/hypnotics/antipsychotics

Analgesics Sedatives/hypnotics/antipsychotics Cardiovascular agents

Cleaning substances Antidepressants Opioids

Topical products Cleaning substances Acetaminophen-containing products

Vitamins Cardiovascular agents Antidepressants

Antihistamines Alcohols Acetaminophen

Cough and cold products Bites, envenomations Alcohols

Pesticides Pesticides Stimulants and street drugs

Plants Antiepileptic agents Muscle relaxants

GI products Personal care products Cyclic antidepressants

Antimicrobials Antihistamines Antiepileptic agents

Arts and office supplies Hormones and hormone antagonists Fumes/gases/vapors

Alcohols Antimicrobials Aspirin

Hormones and hormone

antagonists

Chemicals Nonsteroidal anti-inflammatory drugs

Cardiovascular agents Fumes/gases/vapors Antihistamines

Hydrocarbons

a

Poisoning exposures are listed in order of frequency encountered.

GI, gastrointestinal.

Source: Bronstein AC et al. 2009 Annual report of the American Association of Poison Control Centers’ National Poison Data

System (NPDS): 27th Annual Report. Clin Toxicol (Phila). 2010;48:979.

managed at home.3 Severe toxicity in young children is relatively

uncommon as exposures usually involve the ingestion of relatively small amounts of a single substance.6,7 Of pediatric cases

reported to AAPCC, there were 769 (0.06%) life-threatening outcomes and 31 (0.00%) fatalities from a total of 1,290,784 pediatric

cases.3

AAPCC epidemiologic data also report medication errors,

which in the pediatric population commonly result from confusing units of measurement (e.g., teaspoons vs. milliliters or tablespoons vs. teaspoons), incorrect formulation or concentration

administered, dispensing cup errors, and incorrect formulation

or concentration dispensed from the pharmacy.3

In children older than 6 years of age, the reasons for toxic

exposure to medications are less clear.8 Adolescent children generally have poor knowledge of the toxicity of medications and

can overdose themselves unintentionally.6,9 The potential for

suicide attempts or intentional substance abuse should not be

ignored in older children. These intentional overdoses commonly

involve mixed exposures to illicit drugs, prescribed medications,

or ethanol, and are associated with more severe toxicity and death

than unintentional toxic exposures.

For many teens, using prescription drugs is not considered

dangerous as the drugs are not illegal like heroin or cocaine. In

a 2007 survey, 9.5% of adolescents 12 to 17 years of age said they

had used an illicit substance in the past month.10 The lifetime

use of opiates or opioids, other than heroin, in 12th graders has

doubled from 6.6% in 1991 to 13.2% in 2008.10

In geriatric patients, overdoses tend to have a greater potential

for severe adverse effects compared with overdoses in other age

groups.11 Although the elderly constitute 13% of the population,

they account for 33% of the drug use and 16% of the suicides.12

Patients age 65 or older take an average of 5.7 prescription medications along with 2 to 4 nonprescription drugs daily.11,12 In

2007, the suicide rate for people 65 years and older was 14.3 per

100,000 population compared with the national average of

11.3 per 100,000.13 The elderly are more likely to have underlying illnesses and often have access to a variety of potentially

dangerous medications. This results in higher rates of completed

suicides than in other age groups.11,12

68 Section 1 General Care

Information Resources

COMPUTERIZED DATABASES

A vast number of substances can be involved in a poisoning or

overdose. Reliable data about the contents of products, toxicities of substances, and treatment approaches need to be readily accessible. POISINDEX, a computerized database,14 provides

information on thousands of drugs by brand name, generic name,

and street name, as well as foreign drugs, chemicals, pesticides,

household products, personal care items, cleaning products, poisonous insects, poisonous snakes, and poisonous plants. Annual

subscriptions to POISINDEX, updated quarterly, are expensive

and are generally available only in large medical centers.15

PRINTED PUBLICATIONS

Textbooks and manuals also provide useful clinical information

about the presentation, assessment, and treatment of toxicities.

Goldfrank’s Toxicologic Emergencies16 and the pocket-size Poisoning & Drug Overdose17 are valuable, less-expensive alternatives to

computerized database programs. Books, however, are less useful than computerized databases because information must be

condensed and cannot be updated as frequently. Some drug package inserts also refer to treatment of acute toxicities; however,

the information can be inadequate or inappropriate.18,19

POISON CONTROL CENTERS

Poison control centers provide the most cost-effective and accurate information to health care providers and to the general

public.20,21 Poison centers are staffed by trained poison information specialists who have a pharmacy, nursing, or medical

background. Physician backup is provided 24 hours a day by

board-certified medical toxicologists. The nonphysician clinical

toxicologists, pharmacists, and nurses who staff poison control

centers are certified as specialists in poison information by the

AAPCC or as clinical toxicologists by the American Board of

Applied Toxicology.22

The poison information specialist must accurately and efficiently assess event-specific toxicity by telephone, without the

benefit of direct observation of the patient. The specialist must

communicate this assessment along with treatment information