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severely altered mental status and became comatose, not

responding even to painful stimuli. She suddenly experienced a tonic-clonic seizure, which lasted about 2 minutes

and terminated spontaneously. Should anticonvulsant therapy be initiated for T.C. at this time?

CNS toxicity is common in TCA overdoses. Symptoms include agitation, hallucinations, coma, myoclonus, and

seizures.121,138–141 Seizures can cause significant increases in acidosis and increase cardiotoxicity. Seizures are often seen immediately before cardiopulmonary arrest. Because of the severe consequences of prolonged seizures, aggressive drug treatment with

rapid onset of action is indicated, and benzodiazepines are the

drugs of choice to treat these seizures.138,141

83Managing Drug Overdoses and Poisonings Chapter 4

Drug overdose–induced grand mal seizures are most commonly single seizures that terminate before drug therapy can

be administered.140 Seizure activity is not expected to persist,

so instituting long-term anticonvulsant therapy is not indicated.

However, if her seizure did not stop within 1 to 2 minutes, a

benzodiazepine would have been indicated.121,138,140 The onset

of action of phenobarbital is too delayed for managing acute

seizures, and phenytoin is usually ineffective in treating drug

toxicity–related seizures.121 After a seizure, the patient may

become more acidotic and hypotensive.141 Blood gases, creatine kinase, and ECG changes should be monitored immediately

after a seizure.

Interpretation of Urine Screens

CASE 4-4, QUESTION 16: T.C.’s BP fell to 88/42 mm Hg, and

dopamine was started. Her pH on repeat ABGs was 7.26.

T.C.’s ECG normalized after the administration of 150 mL

of sodium bicarbonate by IV bolus. After dopamine, her BP

increased to 102/68 mm Hg, and seizure activity ceased.

The urine drug screen results were positive for amitriptyline and nortriptyline. Acetaminophen and alcohol were not

detected in her blood. Does the presence of nortriptyline

indicate that T.C. has ingested other drugs in addition to

her amitriptyline?

Nortriptyline is a metabolite of amitriptyline and, therefore,

was identified on the urine drug screen. Metabolites, as well as

the parent compound, are often identified on comprehensive

urine drug screens.135

Duration of Hospitalization

CASE 4-4, QUESTION 17: How long should T.C. be monitored?

T.C. should be admitted to the ICU and monitored until all

evidence of CNS and cardiovascular toxicity has been reversed.121

There is some controversy over how long symptomatic patients

should be observed. Some believe symptomatic patients need cardiac monitoring for 24 hours after ingestion.140 Others believe

TCA overdose patients need to be monitored until they are symptomfree for 24 hours because of a few reports of late development of symptoms.141 However, 98% of signs of cardiotoxicity and arrhythmias are seen within the first 24 hours after

TCA ingestion.121,139 Because the incidence of late-occurring

symptoms is rare, most patients are discharged after they are

fully awake.138 After the toxicity has completely resolved, T.C.

should be evaluated by a psychiatrist to determine whether

she should be admitted for inpatient treatment of her suicidal

ideation.138–140

Outcome of Patient T.C.

T.C. had no further seizure activity. She remained on a dopamine

infusion for 8 hours and required several more boluses of IV

sodium bicarbonate. The next afternoon, she started to awaken

with her family at the bedside. She was tearful and expressed

regret that her suicide attempt was not successful. She repeatedly

told her family that they would be better off without her. Her

psychiatrist saw her, and arrangements were made to transfer

her to an in-patient psychiatric hospital once she was medically

cleared.

ASSESSMENT OF ACETAMINOPHEN

INGESTION

Mechanism of Hepatotoxicity

CASE 4-5

QUESTION 1: L.P., a 23-year-old woman who is about

32 weeks pregnant, presents to the ED 5 hours after ingesting 50 acetaminophen 500-mg tablets. She is depressed and

hoped to end her pregnancy by ingesting acetaminophen.

Her pregnancy was unplanned, and she has received no

prenatal care. L.P. has vomited spontaneously four times

since the ingestion and is complaining of abdominal pain;

her heart rate is 100 beats/minute, BP is 100/70 mm Hg,

and temperature is 97.5◦F. L.P. does not have any chronic

diseases, and the remainder of her medical history is unremarkable. How does an overdose of acetaminophen cause

toxicity?

Acetaminophen is metabolized in the liver by glucuronidation

and sulfation. The mixed-function oxidase system cytochrome

P-450 (CYP) 2E1 metabolizes a portion of the acetaminophen

to the highly reactive metabolite N-acetyl-p-benzoquinoneimine

(NAPQI). In therapeutic doses, this metabolite is detoxified in

the liver by glutathione. At toxic serum acetaminophen concentrations, the glucuronidation and sulfation metabolic pathways

become saturated. Usually, NAPQI is detoxified by conjugation

with glutathione, but increased amounts of the toxic metabolite

deplete hepatic glutathione stores. When glutathione stores are

decreased to about 30% of normal, the toxic metabolite binds

to liver cells, resulting in the characteristic centrilobular hepatic

necrosis seen in acetaminophen overdoses.154–157

For a diagram that shows the mechanism of

acetaminophen poisoning and treatment, go

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

Complication of Pregnancy

CASE 4-5, QUESTION 2: How does L.P.’s pregnancy change

the management of her acetaminophen ingestion?

Pregnancy does not alter the initial approach to the assessment or treatment of potentially toxic ingestions, and assessment should focus initially on the mother.158,159 Overdoses

during pregnancy are often associated with attempted abortions,

depression, prior loss of a child or children, potential loss of

a lover, or economic reasons.136,137,158,159 Intentional ingestions

of analgesics, prenatal vitamins, iron, psychotropic agents, and

antibiotics account for 74% of the overdoses during pregnancy.

The fetus is at risk when the mother overdoses on

acetaminophen because acetaminophen crosses the placenta.

The fetal liver can oxidize acetaminophen to its hepatotoxic

metabolite by 14 weeks of gestation.154 However, the fetal liver

has only about 10% of the capability of the adult liver to metabolize acetaminophen. The fetal liver can conjugate acetaminophen

with both glutathione and sulfate, but detoxification by glutathione conjugation appears to be decreased.160,161

In studies of maternal acetaminophen toxicity, most of the

pregnant women survived without damage to themselves or

their babies. However, there were also maternal and fetal deaths

as a result of the overdoses.160,162,163 Acetaminophen overdoses

during pregnancy did not appear to increase the risk for birth

84 Section 1 General Care

defects or adverse pregnancy outcome unless the mother suffered severe toxicity, emphasizing the need to treat the mother

promptly.154,160,163

Gastrointestinal Decontamination

CASE 4-5, QUESTION 3: What GI decontamination should

be initiated for L.P.?