CNS changes can be the direct result of an ingested drug or

may be additive to other underlying CNS processes or medical

conditions.120 Many drug overdoses can produce different clinical manifestations at various times during the intoxication, and

different doses can produce different effects as well.30,68

Drugs with anticholinergic properties can produce disorientation, confusion, delirium, and visual hallucinations early in the

course of the intoxication; coma can become apparent as toxicity progresses. Generally, overdoses with anticholinergic drugs

do not produce true hallucinations, but rather pseudohallucinations. When a patient with an intact baseline mental status presents with psychosis, paranoia, or visual hallucinations,

CNS stimulants such as cocaine or amphetamines should be

considered.30,66

Drug intoxication–induced alterations in CNS function are

initially difficult to distinguish from those caused by underlying

psychiatric disorders, trauma, hypoxia, or metabolic disorders,

such as hepatic encephalopathy or hypoglycemia. However, with

the passage of time, decreased CNS function secondary to drug

toxicity is more likely to wax and wane in severity in contrast to

the more constant CNS depression that occurs with significant

trauma or metabolic disorders. Drug toxicity also rarely produces

focal neurologic findings. Changes in pupil size, reflexes, and vital

signs can provide insights into the pharmacologic class of drug

involved in the intoxication.26,30,31

CNS depression, seizures, disorientation, and other CNS

changes that are commonly associated with drugs likely to be

prescribed by psychiatrists should be evaluated carefully in T.C.

For example, T.C.’s pupil size would most likely be dilated if she

had ingested a TCA because of the anticholinergic effects of these

drugs. TCA intoxications can also cause myoclonic spasms.30

These spasms are often difficult to differentiate from seizure

activity caused by TCA overdoses, although the spasms are often

asymmetric and more persistent.121

CARDIOVASCULAR FUNCTION

Assessment of heart rate, rhythm, conduction, and measurements of hemodynamic function can also be used to help identify

the type of drug ingested. Overdoses of sympathomimetic drugs

usually increase heart rate. Overdoses of cardiac glycosides or

β-blockers can slow the heart rate. Although drugs can increase

or decrease heart rate directly, indirect cardiac effects (e.g., reflex

tachycardia in response to hypotension) also need to be considered. Abnormal heart rates produced by drug overdoses are

usually not treated unless hypotension or severe dysrhythmias

are precipitated.30,43

PULMONARY FUNCTION

Evaluating the rate and depth of respiration and the effectiveness

of gas exchange in an intoxicated patient can also help identify

drugs that might have been ingested. A decrease in respiratory

rate is commonly associated with the ingestion of CNS depressants. An increased respiratory rate and depth is generally associated with CNS stimulant toxicity. An increase in respiratory

rate can also be secondary to respiratory compensation for a

drug-induced metabolic acidosis.30 Aspiration of gastric contents

after vomiting is a common event in drug ingestions. Aspiration pneumonitis is the most common pulmonary abnormality

associated with significant intoxications.46 Noncardiogenic acute

pulmonary edema has been associated with drug overdoses of

salicylates81–84 (especially with chronic intoxications) and the use

of drugs of abuse (e.g., cocaine and heroin).122–129

TEMPERATURE REGULATION

Body temperature is an important and sometimes overlooked

parameter when assessing potential intoxications.30,43 Decreased

mental status is often associated with a loss of thermoregulation,

and this results in a body temperature that falls or increases

toward the ambient temperature. Increased body temperature

(hyperthermia) caused by overdoses of CNS stimulants (e.g.,

cocaine, amphetamines, ecstasy), salicylates, hallucinogens (e.g.,

phencyclidine), or anticholinergic drugs or plants (e.g., jimsonweed) can have serious consequences.30,32,43 Body temperature

should be measured rectally to obtain an accurate representation

of core body temperature.130

Hyperthermia caused by drug overdoses is commonly

encountered in hot, humid environments or when the intoxication is associated with physical exertion, increased muscle tone,

or seizures. In these patients, it is important to obtain renal function tests (e.g., BUN, serum creatinine) and a serum creatine

kinase measurement to determine whether rhabdomyolysis has

occurred secondary to breakdown of muscle tissue.30,43,130

GASTROINTESTINAL FUNCTION

The GI tract should be assessed for decreased motility because

drug absorption can be delayed or prolonged.30,131,132 When

this is the case, decontamination may be beneficial after an oral

ingestion even if a long time has elapsed since the ingestion. The

80 Section 1 General Care

presence of blood in either emesis or stool may signal ingestion

of a GI irritant or caustic substance.133

SKIN AND EXTREMITIES

The physical examination should include a thorough evaluation of the body surfaces. Look for causes of trauma that may

also explain the patient’s condition. Examination of the skin and

extremities can provide evidence of drug intoxication, especially

with IV or subcutaneous drug injection needle marks.30 Drugs

can be hidden in the rectum or vagina.30 Look for drug patches

(e.g., fentanyl) on hidden areas of the body such as the back of

the neck or scrotum. Fluid-filled bullae at gravity-dependent sites

that have been in contact with hard surfaces for a long time suggest prolonged coma.30 Muscle tone also should be assessed.30

Increased tone or myoclonic spasms can be caused by some

drug overdoses (e.g., TCAs) and can produce rhabdomyolysis

or hyperthermia.30,130 Dry, hot, red skin may also be an indication of anticholinergic toxicity.30,43

In summary, an organ system assessment of T.C. can provide useful insights into the identity of drugs that might have

been ingested, the viability of organ function that might have

been adversely affected, and the treatment that should be

instituted.

Laboratory Tests

CASE 4-4, QUESTION 6: What laboratory tests should be

ordered for T.C.?

The laboratory assessment of an intoxicated patient should

be guided by the history of the events surrounding the ingestion,

clinical presentation, and past medical history.25,134 The status of

oxygenation, acid–base balance, and blood glucose concentration

must be determined, especially in patients with altered mental

status such as T.C.43 Oxygenation can be assessed initially by pulse

oximetry, and acid–base status by ABGs and serum electrolyte

concentrations.26,134,135 T.C. was given oxygen and a bolus of

IV fluid on her arrival at the ED. Paramedics administered glucose

during her transportation to the ED.

A medical history of organ dysfunction or medical disorders (e.g., diabetes, hypertension) that can damage organs of

elimination (e.g., kidney, liver) will also guide the need for

laboratory tests. A serum creatinine concentration and liver

function tests (e.g., aspartate aminotransferase [AST], alanine

aminotransferase [ALT]) should be ordered. Other more specific tests reflective of her past medical history can be ordered

subsequent to dialogue with her psychiatrist. A complete blood

cell count, complete chemistry panel, serum osmolality, and

other baseline laboratory tests should be obtained.30 Pregnancy

tests should be considered in female patients of childbearing age because unwanted pregnancies are common causes of

overdose.136,137

A baseline electrocardiogram (ECG) should be obtained when

exposure to a cardiotoxic drug is suspected or whenever the

cardiovascular or hemodynamic status is altered.26,29,43,135 A 12-

lead ECG should be ordered because T.C. is likely to have ingested

a psychotropic agent. Continuous cardiac monitoring should be

instituted because of the significant cardiotoxicity associated with

overdoses of these agents. Patients with severe TCA overdoses

frequently present with symptoms of coma, tachycardia with a

prolonged QRS segment, seizures, hypotension, and respiratory

depression.138–141

A chest radiograph is useful when the potential exists for either

direct pulmonary toxicity or aspiration.26,29 A chest radiograph

is indicated because T.C. had vomitus in her mouth and TCAs

are associated with the development of acute respiratory distress

syndrome and pulmonary edema.138,142,143

Qualitative Screening

CASE 4-4, QUESTION 7: Why should (or should not) T.C.’s

urine and blood be screened to assist in identifying the

ingested substance?

Toxicology laboratory testing can be used to identify the substances involved in a toxic exposure, to exclude substances, or

to measure the concentration of substances in serum or other

biological fluids.27,134,135 The identification and quantification of

compounds should be considered as two distinct types of toxicologic testing.27,144 Qualitative screening, intended to identify

unknown substances, must be able to identify which substance

or class of substances is involved in the toxic exposure. Quantitative testing is similar to therapeutic drug monitoring in that

the presence of the substance usually is known, and the question

being answered is how much is present.27

Screening various biological fluids suspected of having high

concentrations of a parent drug and its metabolites can identify

unknown substances. Urine is screened much more commonly

than blood, whereas gastric fluid is rarely evaluated. A urine drug

screen is preferred to a blood drug screen because urine generally

contains a higher concentration of a drug and its metabolites than

other body fluids.145

When reviewing the results of urine screening panels for drugs

and other substances, one must remember that the presence

of a substance in urine is not necessarily related to a concurrent toxicity. A positive result on a urine screening panel merely

indicates that the patient has ingested or has been exposed

to the substance, but it does not differentiate between toxic

and nontoxic doses. If a drug and its metabolites are eliminated slowly into the urine for a prolonged time, and if the

testing methodology detects small concentrations of the substance, urine drug screening could identify the presence of a

substance days, weeks, or even months after the exposure (e.g.,

marijuana).27,135

It is important to know which drugs or substances are tested

at a given laboratory. Many laboratories restrict the number of

drugs for which they test because 15 drugs account for more

than 90% of all drug overdoses.35 Some urine toxicology screens

only detect common drugs of abuse (e.g., amphetamines, barbiturates, benzodiazepines, cocaine, marijuana, opioids).135 Some

drugs of abuse are not detected on routine drug screening (e.g.,

gamma hydroxybutyrate, ketamine, flunitrazepam).27 Some

analyses detect only antibodies to drug metabolites. For example,

a benzodiazepine screen detects oxazepam, a common benzodiazepine metabolite. However, alprazolam and lorazepam are

not metabolized to oxazepam and will not be detected in a urine

screen. Likewise, an opioid screen may not detect the synthetic

opioids such as fentanyl and methadone.135

Results of qualitative toxicology screening tests are difficult

to interpret. False negatives, false positives, cross-reactivity with

related drugs, chronicity of exposure, and length of time since

last exposure all complicate results.113,114,135 Urine toxicology

screen results rarely change clinical management of the patient.

Monitoring mental, cardiovascular, and respiratory status and

other laboratory parameters provide better clues than the results

of a urine toxicology screen.26,27,134,135,144

Toxicology screening can be appropriate when the history

of a suspected toxic exposure is unavailable, inaccurate, or

81Managing Drug Overdoses and Poisonings Chapter 4

inconsistent with the clinical findings.27 However, it is important to know which drugs are detected on a given toxicology

screen.135 A comprehensive qualitative urine drug screen can be

considered for T.C. because information about the substance(s)

she ingested is not yet known.

Quantitative Testing

CASE 4-4, QUESTION 8: Why should a quantitative toxicology laboratory test be ordered (or not ordered) for T.C. as

well?

After a qualitative urine analysis for drugs, a quantitative analysis of drug concentration in blood can help determine the severity of toxicity and the need for aggressive interventions (e.g.,

hemodialysis).27,36,135,144 Quantitative tests are especially useful

when assessing the potential toxicity of drugs with delayed clinical toxicity or when the toxicity primarily is caused by metabolites (e.g., ethylene glycol, methanol). The concentration of a

drug in serum is sometimes much more predictive of end-organ

damage than clinical findings (e.g., acetaminophen effect on the

liver).

Quantifying the amount of drug in serum is useful when (a)

the concentration of the substance correlates with toxic effects,

(b) the turnaround time for results is rapid, and (c) treatment

can be guided by the serum concentration.35,134,144 To aid in

the care of poisoned patients, stat quantitative serum concentrations of acetaminophen, carbamazepine, carboxyhemoglobin,

digoxin, ethanol, ethylene glycol, iron, lithium, methanol, methemoglobin, phenobarbital, salicylates, and theophylline should be

available at laboratories of large health care facilities.26,27,36,134,144

When blood samples are collected to quantitate potentially

intoxicating substances, as much information as possible should

be obtained about the time course of events to determine

whether absorption and distribution of the substance is complete.

Serial samples may be needed to determine whether significant

absorption is still occurring.32,33 In contrast to the interpretation

of therapeutic serum concentrations of chronically administered

drugs, the serum concentration of a substance ingested in an

overdose is not likely to be at steady state.

Quantitative toxicologic testing will not benefit T.C. at this

point in time because the identity of the ingested substance is

unknown. Nevertheless, a serum ethanol concentration could

be useful in this case because alcohol is often ingested concurrently in overdose situations.134 Most poison centers also recommend obtaining a quantitative acetaminophen level on all

intentional ingestions because serious hepatotoxicity can occur

if acetaminophen ingestion is missed.27,134,135

Assessment

CASE 4-4, QUESTION 9: T.C.’s clinical status has not

changed in the past 10 minutes. A urine toxicology screen,

blood acetaminophen, blood alcohol, and ABGs have been

ordered. The 12-lead ECG shows a prolonged QRS interval of 0.14 seconds (normal, <0.1 seconds). No antidotes

have been administered. T.C.’s physical examination did not

detect any evidence of trauma to her head. Her pupils

were dilated and slowly responsive to light, and her bowel

sounds were hypoactive. What conclusions can be made

at this time with regard to the likely substance ingested

by T.C.?