should be contacted at the obstetrician’s office.

Substance Identification

CASE 4-3, QUESTION 3: R.F.’s mother has been contacted

and has confirmed that the only green tablets in the house

are her prenatal iron supplements. She is close to the

75Managing Drug Overdoses and Poisonings Chapter 4

hospital and will await the arrival of her son. R.F. arrived

20 minutes later along with one green tablet and an

empty prescription container that was found by his older

brother. R.F. is still vomiting but is awake and alert with

a heart rate of 125 beats/minute, a respiratory rate of

28 breaths/minute, a temperature of 99.1◦F, and pulse

oximetry of 99%. How can the maximal potential severity

of this ingestion be estimated at this time?

R.F.’s vital signs, when corrected for age, are normal. Attention should now focus on identifying the ingested substance and

the maximal potential severity of the ingestion. Although this

case involves an unknown ingestion, with a possibility of being

a severe iron intoxication, the identity of the tablets still has not

been verified. Therefore, R.F. must be carefully assessed, and the

ingestion history reaffirmed.

All solid dosage prescription drugs are required by the US Food

and Drug Administration (FDA) to have identification markings. Reference books (e.g., Facts and Comparisons,91Physicians’

Desk Reference),92 computerized databases (e.g., IDENTIDEX),93

and the product manufacturers can assist in identifying solid

dosage forms. Websites such as http://www.pharmer.org94 and

http://www.drugs.com95 can also be useful in obtaining drug

identification information.

The imprint code markings on the green tablet brought to the

ED with R.F., the empty medication container, and the mother’s

assistance should be sufficient to correctly identify the tablet.

The identification of this green tablet will most likely establish the toxicity potential because most childhood ingestions

usually involve only one substance. Once the tablet has been

identified, the maximal number of tablets ingested should be

estimated.

The label on the empty medication container can provide

information on the identity and number of tablets dispensed.

The date the prescription was obtained, the number of estimated

doses taken, and the number currently remaining in the medication container can be used to approximate the maximal number

of tablets ingested.

R.F.’s vital signs and symptoms should be monitored at frequent intervals to evaluate whether his clinical status is consistent with expectations based on the suspected ingestion. Nausea, vomiting, diarrhea, and abdominal pain are commonly

encountered early in the course of iron intoxication.96–101 The

absence of symptoms, however, should not be interpreted as an

indication that a poisoning has not occurred, especially if the

patient is being evaluated within a short time after the presumed

ingestion.96,98–101

Evaluating Severity of Toxicity

CASE 4-3, QUESTION 4: R.F. weighs 22 pounds, appears

to be in no apparent distress, and has stopped vomiting.

About 30 mL of dark-colored vomitus was recovered, but

no tablets are seen, and testing demonstrates that no blood

is present in the vomitus. A maximum of 11 tablets was

ingested based on the bottle label and the mother’s recall.

What degree of toxicity should be expected in R.F.?

The potential severity of ingestion can be estimated for commonly ingested drugs such as acetaminophen,102 salicylates,75

iron,96 and TCAs103 because of well-established dose–toxicity

relationships. 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 more than 60 mg/kg

are severe and potentially fatal.97,99,101

The label on the prescription medication container, as well

as independent verification of the tablet by R.F.’s mother and

the tablet imprint, indicates that each tablet contained 300 mg

of ferrous sulfate in an enteric-coated formulation. Because

the dose–toxicity relationship of iron is based on the amount

of elemental iron ingested, knowledge of the specific iron salt

is important in calculating the ingested dose. Ferrous sulfate

contains 20% elemental iron, ferrous gluconate contains 12%,

and ferrous fumarate contains 33%.96,97,99,100 Therefore, each

300-mg ferrous sulfate tablet contains 60 mg of elemental iron.

R.F. ingested a maximum of 11 enteric-coated ferrous sulfate

300-mg tablets and he weighs 22 pounds (10 kg). His ingestion

of approximately 66 mg/kg (60 mg per tablet × 11 tablets =

660 mg total divided by 10-kg patient weight) of iron places him

at risk of severe toxicity. Although R.F.’s only symptom is vomiting at this time, absorption could be delayed because he ingested

an enteric-coated formulation.

Abdominal Radiographs

CASE 4-3, QUESTION 5: R.F. is expected to experience

potentially severe toxicity from his ingestion of iron. Why

would an abdominal radiograph be useful to verify the number of iron tablets that were actually ingested?

Radio-opaque substances (e.g., iron, enteric-coated tablets,

chloral hydrate, phenothiazines, heavy metals), theoretically, can

be visualized in the GI tract by an abdominal radiograph.104 The

ability of a radiograph to demonstrate the presence of a radiodense substance depends on the dosage form, concentration, and

molecular weight of the substance. The intact dosage form can

often be detected if the tablet has not already disintegrated or

dissolved.104

To see X-rays of iron in the GI tract, go to

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

Less than one-third of pediatric abdominal radiographs show

positive evidence of tablets or granules after iron poisoning.105

Children are more likely than adults to chew tablets rather than

swallow them whole, and false-negative results can occur even

when whole tablets have not already started to disintegrate. If the

tablets were chewed, an abdominal radiograph to verify the number of ingested iron tablets is not likely to be useful. However,

an abdominal radiograph after the completion of GI decontamination can help assess whether additional decontamination is

needed.104

Gastrointestinal Decontamination

CASE 4-3, QUESTION 6: Why would gastric lavage or activated charcoal not be indicated for the management of

R.F.’s iron ingestion?

When selecting a method of GI decontamination, consider the

substance ingested, maximal potential toxicity expected from the

drug dosage form, potential time course of toxicity, time elapsed

between ingestion and the initiation of treatment, symptoms,

and physical examination findings. Decontamination with activated charcoal is not indicated because R.F. has ingested iron

tablets, which are not adsorbed by activated charcoal.53,96,104

Gastric lavage would also not be effective because the removal

of large undissolved iron tablets from the stomach is limited by

76 Section 1 General Care

the small internal diameter of the gastric lavage tube, especially

in pediatric patients.104,105

Whole Bowel Irrigation

CASE 4-3, QUESTION 7: What other method of GI decontamination should be considered for R.F.?

Whole bowel irrigation with a polyethylene glycol electrolyte

solution can be considered in this case. WBI fluid can be administered orally or infused by NG tube at a rate of 1.5 to 2 L/hour for

adults and at a rate of 500 mL/hour for children.63,106 Although

the large volume of fluid to be ingested during a period of several

hours and the frequent association of nausea and vomiting often

result in poor patient compliance, R.F. is hospitalized and the

fluid can be infused by NG tube. WBI should be continued until

the rectal effluent is clear, which may take many hours.63,106,107

MONITORING EFFECTIVENESS OF TREATMENT

CASE 4-3, QUESTION 8: How should the effectiveness of

GI decontamination be assessed in the ED?

The simplest method of assessing GI decontamination is to

visually inspect the return fluid from the WBI for tablets or

tablet fragments. Increasing serum iron concentrations, deteriorating clinical status, or evidence of radiodense tablets in the GI

tract on abdominal radiograph would warrant more aggressive

treatment.97–99,105,107

Serum Iron Concentrations

CASE 4-3, QUESTION 9: At this time, R.F. has no evidence of

CNS or cardiovascular symptoms that can occur with toxic

iron ingestions. He did have one large dark-colored diarrheal stool that tested negative for blood. A serum iron concentration, obtained about 3 hours after the ingestion, was

470 mcg/dL (normal, 60–160 mcg/dL). What conclusions as

to severity or likely clinical outcome can be derived from

this serum iron concentration?

The serum iron concentration provides an indication as to

whether more aggressive therapy is needed.101,105,108 The higher

than normal serum iron concentration confirms the suspicion

that R.F. has ingested iron tablets despite both his current lack

of serious symptoms and the absence of tablet evidence in the

rectal effluent or by abdominal radiograph.

The time course of absorption is probably the most difficult

pharmacokinetic parameter to evaluate with toxic ingestions.

For example, drug concentrations can continue to rise after an

overdose despite GI decontamination.98,100,101,108 This prolongation of absorption time is further complicated when sustainedrelease or enteric-coated dosage formulations have been ingested

because the onset of symptoms is unpredictable.99

R.F.’s serum iron concentration of 470 mcg/dL suggests

a serious ingestion because peak serum iron concentrations

greater than 500 mcg/dL are usually predictive of significant

toxicity.98–101,105,108 This single serum iron concentration does

not provide information as to whether the serum concentration is rising or declining or when the serum iron concentration

will peak as a result of his iron ingestion.109 Iron tablets may

also clump together and form a bezoar. Bezoar formation can

result in prolonged absorption and delay the onset of toxicity.98,101

Samples for peak serum iron concentration should be obtained

4 to 6 hours after ingestion.99–101,108 Although R.F.’s serum iron

concentration was measured approximately 3 hours after ingestion, another serum iron measurement in 2 to 4 hours is needed

because he ingested an enteric-coated formulation.

Blood Glucose, White Blood Cell Count,

and Total Iron Binding Capacity

CASE 4-3, QUESTION 10: R.F. had WBI administered

through the NG tube for 4 hours until the rectal effluent was

clear. At this time, R.F. began to vomit numerous times and

became drowsy and fussy. A second serum iron concentration was ordered (i.e., 6 hours after ingestion). What other

laboratory tests could be helpful in assessing the potential

toxicity of iron in R.F.?

Blood glucose concentrations and white blood cell counts usually are increased when serum iron concentrations are greater

than 300 mcg/dL. A white blood cell count greater than 15,000/μL

and a blood glucose concentration greater than 150 mg/dL within

6 hours of ingestion generally suggest a greater likelihood of

severe iron intoxication.98 These tests provide supplemental confirmation of iron intoxication and may be useful in medical facilities in which serum iron concentrations cannot be obtained.

These laboratory tests are not routinely monitored in iron poisoning because of the poor sensitivity (about 50%).99 Treatment

should not be based on a white blood cell and glucose concentration alone.98–100,105 If a patient with severe iron toxicity presents

to a health care facility that cannot perform timely serum iron

levels, either the blood iron sample must be sent to a laboratory

that can do the testing quickly or the patient must be transferred

to a health care facility that can do serum iron testing for patient

monitoring.

It was once believed that if the serum iron concentration

exceeded the total iron binding capacity concentration, it would

indicate substantial iron toxicity. The correlation between the

total iron binding capacity concentration and iron toxicity, however, has not held up, and the total iron binding capacity test is

no longer used to monitor iron toxicity.101

Stages of Iron Toxicity

CASE 4-3, QUESTION 11: It is now 6 hours since R.F.

ingested the iron tablets. His second serum iron concentration is not yet available. He continues to be fussy and

drowsy but has missed his usual afternoon nap. He has several more episodes of vomiting. Why is R.F.’s relatively mild

course at this time not particularly reassuring?

The time between the ingestion of an overdose of drugs and

the development of severe toxicity can be delayed. It is unclear

why there may be an asymptomatic period, but it may be secondary to delayed absorption of the ingested drug, the time

required for the drug distribution, or the time needed to form

a toxic metabolite. Consequently, R.F. may still exhibit further

symptoms of severe toxicity. Four distinct stages of symptoms

can be encountered with iron toxicity.96–101

STAGE I

Stage I symptoms usually occur within 6 hours of ingestion.

During this time, nausea, vomiting, diarrhea, and abdominal pain

are encountered and are probably secondary to the erosive effects

of iron on the GI mucosa. The caustic effects of free iron can

cause bleeding as evidenced by blood in the vomitus and stool.

77Managing Drug Overdoses and Poisonings Chapter 4

In more severe intoxications, CNS and cardiovascular toxicity can

be present during stage I.98–101

STAGE II

The second stage of iron toxicity has been suggested as a period

of decreasing symptoms and an apparent improvement in the

clinical condition. This stage can last for up to 12 to 24 hours after

the ingestion and could be misinterpreted as resolving toxicity.

This stage may represent the time needed for the absorbed iron

to distribute throughout the body before systemic symptoms

develop.96 Alternatively, this stage might merely reflect patients

who did not receive treatment early in the course of intoxication

and appeared to be well before systemic effects developed. In

most severe cases, stage II is not encountered and the patient’s

condition continues to progressively deteriorate.98–101

STAGE III

Stage III generally occurs 12 to 48 hours after iron ingestion and is characterized by CNS toxicity (e.g., lethargy, coma,

seizures) and cardiovascular toxicity (e.g., hypotension, shock,

pulmonary edema). Metabolic acidosis, hypoglycemia, hepatic

necrosis, renal damage, and coagulopathy can be experienced at

this stage.98–101

STAGE IV

The final stage is apparent 4 to 6 weeks after acute iron ingestion

and consists of late-appearing GI tract sequelae that are secondary to the initial local toxicity. In this stage, prior tissue damage

can progress to gastric scarring and strictures at the pylorus,

resulting in permanent abnormalities of GI function.98–101

Patients can present to the health care facility in any stage of

iron toxicity and can have a fatal outcome in any stage. Assigning

a stage of toxicity should not be based on time since ingestion,

but instead should be based on clinical symptoms.100

Deferoxamine Chelation

CASE 4-3, QUESTION 12: The clinical laboratory has

reported that the second serum iron concentration that was

obtained 6 hours after ingestion from R.F. has increased

from 470 to 553 mcg/dL. The child has continued to vomit.

R.F.’s mother states that the child looks “pale” to her. What

criteria are most important in determining whether the antidote deferoxamine should be administered to R.F.?

Deferoxamine (Desferal) chelates iron by binding ferric ions

in plasma to form the iron complex ferrioxamine.99 Deferoxamine prevents iron toxicity at a cellular level by removing iron

from mitochondria.97 Unfortunately, deferoxamine is not a very

effective antidote as a relatively small amount of iron is bound

(approximately 9 mg of iron to 100 mg of deferoxamine).109,110

The iron–deferoxamine complex primarily is excreted renally as

ferrioxamine.97,99,100 Renal elimination of the ferrioxamine usually results in a pinkish-orange urine, often described as “vin

rose.”97,99,100 Deferoxamine therapy should be initiated when

serum iron concentrations exceed 500 mcg/dL and when symptoms of iron toxicity (e.g., GI symptoms, hemorrhage, coma,

shock, seizures) are present.97–100 R.F. is experiencing symptoms,

he presumably ingested up to 66 mg/kg of elemental iron, and

iron absorption appears to be ongoing based on the increase in

his serum iron concentration. Therefore, R.F. should be treated

with deferoxamine.

DEFEROXAMINE DOSE

CASE 4-3, QUESTION 13: What dose of deferoxamine

should be prescribed for R.F., and how should it be administered?

Deferoxamine is most effective when administered intravenously as a constant infusion owing to its short half-life

(76 ± 10 minutes).98,100,109 Clinically, a slow IV infusion is

preferred instead of intramuscular administration because the

IV dose can be better controlled, is less painful, and is better absorbed than an intramuscularly administered dose.100–101

Deferoxamine at a dose of 15 mg/kg/hour is usually administered

in a continuous IV infusion. However, doses up to 45 mg/kg/hour

have been used in patients with severe iron poisoning.98–101,109

Hypotension can result from administering IV boluses of deferoxamine too rapidly.97,99,101,109,110 According to the manufacturer,

the total deferoxamine dose should not exceed 6 g every 24 hours

when administered to adults or children, but adverse effects have

 patient usually presents with a partially compensated respiratory alkalosis.72,78,79,81 Hypokalemia can result from increased

GI and renal losses of potassium, as well as from systemic

alkalosis.72,79,80

Although marked metabolic and neurologic abnormalities

are most commonly observed in young children with advanced

salicylate intoxication, adolescents or adults acutely poisoned

with a large dose of salicylates can exhibit these symptoms as

well.72,78,79 Acute salicylism in a young child often takes a more

severe course than that typically seen in adults. After acute ingestion, children quickly pass through the phase of pure respiratory

alkalosis. Renal bicarbonate loss secondary to respiratory alkalosis reduces the buffering capacity more profoundly in a child

and facilitates the development of metabolic acidosis.72,77,79,81

Salicylates have toxic effects on several biochemical pathways

that contribute to metabolic acidosis and other symptoms.72,79–81

Mitochondrial oxidative phosphorylation is uncoupled and

results in an impaired ability to generate high-energy phosphates, increased oxygen use and carbon dioxide production,

increased heat production and hyperpyrexia, increased tissue glycolysis, and increased peripheral demand for glucose. Salicylates

also inhibit key dehydrogenase enzymes within the Krebs cycle,

resulting in increased levels of pyruvate and lactate. The increased

demand for peripheral glucose causes increased glycogenolysis, gluconeogenesis, lipolysis, and free fatty acid metabolism.

The latter results in enhanced formation of keto acids and

ketoacidosis.77,81

The patient may become severely volume depleted through

several mechanisms.72,79,81 Hyperthermia and hyperventilation

produce increased insensible water loss, vomiting may promote

GI fluid losses, and the solute load caused by altered glucose

metabolism results in an osmotic diuresis. Depending on the

patient’s acid–base balance and net fluid and electrolyte intake

and output, serum sodium and potassium concentrations may be

normal, elevated, or decreased. Hypernatremia and hypokalemia

are most common.77,79

Blood glucose concentration is usually normal or slightly

elevated, although hypoglycemia may accompany chronic salicylism (e.g., as illustrated by V.K.) or occur late in acute intoxication. CNS glucose levels can be markedly reduced in the presence

of normal blood glucose concentrations because increased CNS

glucose utilization to generate high-energy phosphate exceeds

the rate at which glucose can be supplied.72,77,79,81

Other manifestations of severe acute salicylism include a

variety of neurologic signs and symptoms: disorientation, irritability, hallucinations, lethargy, stupor, coma, and seizures.73,77

Hyperthermia may be marked and can result in the inappropriate administration of aspirin as an antipyretic. Coagulopathy

can occur because of impaired platelet function, hypoprothrombinemia, reduced factor VII production, and increased capillary

fragility, especially when aspirin is taken chronically.79–81 Pulmonary edema and acute renal failure also can occur, but the

former occurs more commonly after chronic intoxication.79,81,82

Chronic salicylism symptoms are similar to acute intoxications. However, patients with chronic exposures may have fewer

GI symptoms but generally appear more ill and have more CNS

symptoms.75,83 In both adults and children, the principal signs

of chronic salicylism are a partially compensated metabolic acidosis, increased anion gap, ketosis, dehydration, electrolyte loss,

hyperventilation, tremors, agitation, confusion, stupor, memory deficits, renal failure, and seizures.77,79,80,84 The severity of

CNS manifestations is related to the cerebrospinal fluid (CSF)

salicylate concentration.78,79 CSF concentrations may increase

in the presence of systemic acidosis because a greater fraction

of salicylate is not ionized and can cross the blood–brain barrier. Therefore, metabolic acidosis is especially dangerous in a

salicylate-intoxicated patient.77,79

Unless the history of salicylate intake is specifically sought,

the problem may not be immediately apparent, especially in

the elderly in whom such findings are likely to be attributed to

other causes (e.g., encephalitis, meningitis, diabetic ketoacidosis,

myocardial infarction).27,79,83 Delay in diagnosis has been associated with increased mortality.27,72,79,83 Unfortunately, plasma

salicylate concentrations do not correlate well with the degree of

poisoning in chronically intoxicated patients. It is more important to treat the patient according to the clinical status rather

than his or her salicylate concentration.72 Death in patients with

salicylism, whether acute or chronic, results from CNS or cardiac

dysfunction, or pulmonary edema.77,79,83

ASSESSMENT OF TOXICITY

CASE 4-2, QUESTION 3: What signs, symptoms, and laboratory values in V.K. are consistent with salicylate intoxication?

V.K. demonstrates many of the findings typical of severe

acute salicylism. Hyperventilation has resulted from the direct

respiratory stimulant effects of salicylate and as compensation

for her metabolic acidosis (Pco2, 20 mm Hg; pH, 7.25; serum

bicarbonate, 10 mEq/L; respiratory rate, 36 breaths/minute).

Hypokalemia (2.8 mEq/L) in the presence of metabolic acidosis represents severe potassium depletion because of increased

renal and possibly GI losses. Hyperpyrexia caused by salicylate

is present in V.K., although an infectious cause must also be considered. Her neurologic symptoms of lethargy, disorientation,

and combativeness, as well as tinnitus, nausea, and vomiting,

are commonly seen in severe salicylate intoxication. In addition,

73Managing Drug Overdoses and Poisonings Chapter 4

being elderly and taking a lethal amount of aspirin bodes ill for

this patient’s outcome.

LABORATORY EVALUATION

CASE 4-2, QUESTION 4: What objective evaluations should

be assessed in a patient with presumed salicylate intoxication?

V.K.’s workup illustrates a thorough initial patient evaluation.

Laboratory evaluation should include ABG values, serum electrolytes, BUN, serum creatinine, blood glucose, and a complete

blood cell count.77,79,80 Urine should be tested for specific gravity

and pH.77 In symptomatic patients, a PT or international normalized ratio (INR) and partial thromboplastin times are useful

to assess the presence of salicylate-induced coagulopathy. Vitals

signs should be monitored for an increased respiratory rate and

hyperpyrexia.78,79 Physical examination should include an evaluation of chest radiograph, cardiopulmonary and neurologic function, and measurement of urine output.79

A salicylate blood concentration should be obtained 6 hours

after an acute ingestion at a known time, immediately and

6 hours after an acute ingestion at an unknown time, and immediately and every 2 to 6 hours in symptomatic patients.27,68,77,79,85

Serum salicylate concentrations should be reassessed every 4 to

6 hours to verify that the original concentration represented a

peak level and that the salicylate level is decreasing rather than

increasing.27,72,77,80,82 Obtaining the units of measurement on

salicylate serum concentrations is essential because different laboratories report concentrations in different units (e.g., mg/dL,

mcg/mL, mmol/L). An incorrect interpretation of the salicylate

unit of measurement can result in overestimates or underestimates of the severity.27

Historically, the Done nomogram was used to determine the

degree of toxicity from a known single acute salicylate ingestion by plotting the serum salicylate concentration by time since

the ingestion.86 However, clinical symptoms and laboratory findings are more useful in identifying the degree of acute intoxication, assessing patient prognosis, and guiding therapy.85 In case

of chronic ingestions, the nomogram is not useful, and other

parameters such as acid–base and electrolyte balance should be

used to determine severity of the case.72,77

The Done nomogram is also not useful in certain situations

such as ingestion of enteric-coated or sustained-release salicylate

products, when the time of ingestion is unknown, or when the

patient is acidemic or has renal failure.77,79,80,85–87 The nomogram is also less useful when salicylate serum concentrations

are measured more than 12 hours after ingestion. Serum concentrations obtained less than 6 hours after ingestion in acute

ingestion situations are also difficult to interpret because the

drug level has not yet peaked and can result in an underestimation of the eventual degree of intoxication.72,77,84,87 Salicylate

concentrations can continue to rise for approximately 24 hours

if a large amount has been taken or if enteric-coated tablets have

been ingested. Enteric-coated tablets can clump together, forming a bezoar that slowly releases drug into the gut.79,85 Because

of these difficulties in interpreting salicylate concentrations, the

Done nomogram is no longer used.27

MANAGEMENT

CASE 4-2, QUESTION 5: What would be a reasonable management plan for V.K.?

Management of salicylate intoxication depends on the degree

of acid–base and electrolyte disturbances.72,77,79 Activated charcoal is not indicated for V.K. because the ingestion occurred

approximately 10 hours ago and she has a somewhat altered

mental status.46 The risk of aspiration is greater than the value

of possibly adsorbing any remaining aspirin from the GI tract. In

addition, V.K. already has symptoms of salicylate poisoning, indicating that the aspirin has already been absorbed. Others might

argue that if she ingested 100 tablets, some of the drug may still

be present in the GI tract and giving activated charcoal late may

bind some of the drug still present.

V.K.’s hypokalemia, acidosis, and hypoglycemia must be corrected, and is probably best accomplished through the administration of intravenous (IV) hypotonic saline–dextrose solutions

combined with potassium supplementation. This solution is

administered at a rate that replaces the patient’s deficits and keeps

pace with continued losses.72,77,79–81 Care should be taken to

avoid overzealous fluid therapy, which can predispose the patient

to cerebral or pulmonary edema.79,81 Administration of an IV

dextrose bolus is also indicated because V.K. is hypoglycemic (60

mg/dL).77,79,81

SODIUM BICARBONATE

It is important to correct V.K.’s acidosis because acidosis will

increase CSF salicylate concentrations.78,79 Correction of acidosis

can be accomplished by adding sodium bicarbonate to her IV

fluids.72,77–80 V.K.’s serum sodium and potassium concentrations

should be monitored closely as adding potassium to IV fluids

will mostly likely be required.86 Providing adequate ventilation

to prevent respiratory alkalosis is essential. With a respiratory

rate of 36 breaths/minute, placing the patient on a ventilator

to assist with breathing might be considered. However, forced

mechanical ventilation can interfere with the patient’s need to

compensate to maintain the serum pH. Patients on ventilators

can become severely acidotic, which can result in death because

of an inability to compensate adequately.77,88

SEIZURES

Seizures are not evident in V.K. but can be encountered in cases

of severe salicylate poisoning. Seizures generally carry a poor

prognosis and are indicative of severe salicylate intoxication that

requires hemodialysis.77 Other treatable causes of seizures (e.g.,

marked alkalosis, hypoglycemia, hyponatremia) can be present

in individuals such as V.K. and should be ruled out. If seizures

occur, benzodiazepines are the drugs of choice for treatment.77

COAGULOPATHY AND HYPERTHERMIA

Coagulopathy generally responds to vitamin K1, which should

be given if the PT or INR is prolonged.77 GI bleeding or other

hemorrhage can occur but is not common.77,79,80 Mild hyperthermia usually does not require therapy, but cooling fans and

mist may be required for extremely elevated temperatures.77,81

PULMONARY EDEMA

Noncardiogenic pulmonary edema commonly occurs in salicylate intoxications, especially when the overdose is attributable to

chronic ingestions.77,79,82 Pulmonary edema is associated with a

high incidence of neurologic symptoms in patients and can occur

even without fluid overload.79,82 Increased alveolar capillary

membrane permeability, prostaglandin effects, and a metabolic

interaction with platelets releasing membrane permeability substances are the primary mechanisms for the cause of pulmonary

edema associated with salicylate overdose. Treatment is aimed

at reducing salicylate levels via alkalinization or hemodialysis.82

ALKALINIZATION

CASE 4-2, QUESTION 6: What measures will enhance salicylate elimination? Which of these may be indicated in V.K.?

74 Section 1 General Care

Alkalinization of the urine and hemodialysis can enhance the

excretion of salicylate in overdose situations.72,78 Hemodialysis is preferred because it can also correct fluid and electrolyte

imbalances.79,82,83 Sodium bicarbonate is recommended for alkalinization to increase the arterial pH with the goal of minimizing

salicylate transport into the CNS.78,79,81

Although large doses of sodium bicarbonate can enhance

the renal elimination of the weak acid and shorten its half-life,

this treatment does not favorably influence the morbidity or

mortality of patients with salicylism. Alkalinization with forced

fluid diuresis can also place the patient at risk for sodium and

fluid retention, as well as pulmonary edema if too much fluid

is given too quickly.77,79,80,82 Whether the urine can be adequately alkalinized (pH >7) in severely intoxicated pediatric

patients has been questioned because of the large acid load

that is excreted.72,77,78 Nevertheless, urine alkalinization with

sodium bicarbonate should be attempted in severely salicylateintoxicated adult patients such as V.K.

Potassium replacement in patients receiving alkalinization is

essential.77,79,81 These patients may require large amounts of

potassium supplementation as a result of renal wasting of potassium. The risk for pulmonary edema can be minimized if this is

done without forcing fluids.77,79–81

Hemodialysis should be considered in patients who show progression of severe salicylate intoxication and seizure activity, renal

failure, or plasma salicylate concentrations in the potentially fatal

range.72,79,80,82,84 Patients with a chronic exposure, acidosis, or

CNS symptoms and those who are elderly or ill are high-risk

patients and should be considered for early dialysis.79,84 Because

V.K. has many of the risk factors, she is a candidate for emergent

hemodialysis.

CLINICAL OUTCOME OF PATIENT V.K.

A repeat salicylate level 6 hours later (18 hours after ingestion)

had increased to 93 mg/dL. Her chemistry panel revealed serum

sodium, 144 mEq/L; potassium, 2.1 mEq/L; chloride, 100 mEq/L;

bicarbonate, 9 mEq/L; glucose, 78 mg/dL; creatinine, 4.8 mg/dL;

and BUN, 42 mg/dL. Her hemoglobin was now 8.5 g/dL with a

hematocrit of 23% and a PT of 16.6 seconds. V.K.’s pH on blood

gases remained in the 7.2 to 7.3 range. Urinary alkalinization was

attempted with a high-dose IV sodium bicarbonate infusion in

an attempt to reach a urine pH of 7.5. However, her urine pH

never increased above pH 5.6. V.K. became fluid overloaded and

exhibited dyspnea. She was placed on a ventilator with worsening of her symptoms. A chest radiograph showed pulmonary

edema. V.K. became confused and agitated, pulling at her IV

lines and trying to get out of bed. Nephrology was consulted

to provide emergent hemodialysis to correct the acidosis, electrolyte abnormalities, and fluid overload. As the catheter was

being placed, the patient had a tonic-clonic seizure. Lorazepam

2 mg IV was administered and the seizure stopped. At this time,

the patient was unresponsive. The NG tube revealed the presence of copious amounts of bright red blood. She was rushed to

surgery for an emergency laparotomy. On the way to the operating room, she had another seizure, went into respiratory arrest,

coded, and could not be resuscitated.

ASSESSMENT OF IRON INGESTION

Gathering History and Communications

CASE 4-3

QUESTION 1: The grandmother of R.F., a 20-month-old boy,

calls the ED because her grandson is vomiting and appears

to have been playing with some green tablets. The child

was left alone in his room for about 15 minutes to take a

nap. Why might the consultation with this grandmother be

expected to be more difficult than the consultation in Case

4-1, Question 1?

Phone calls to a health care provider, a health care facility,

or a poison control center from individuals other than the parent are usually more difficult to manage as the caller may not

be able to provide all patient-specific information needed (e.g.,

patient weight, chronic medications) to accurately assess the drug

ingestion. Additional information is often needed from a parent.

Furthermore, nonparent callers tend to be more upset about

an unintentional ingestion and may have more difficulty than a

parent in taking decisive action.

Triage of Call

CASE 4-3, QUESTION 2: Despite additional questioning,

R.F.’s grandmother cannot identify the tablets and cannot

find any labeling or empty medicine containers that could

help in the tablet identification. R.F. is still vomiting, and

some of the vomitus is green-colored like the tablets. There

are three children in the household and two adults who take

medications for various chronic illnesses. According to the

grandmother, R.F. is healthy, and no one else in the household currently has the “flu” or other GI illness. The child’s

mother gave birth 3 weeks ago and is now at her obstetrician’s office for a postnatal visit. What recommendations

could be provided to R.F.’s grandmother at this time?

With this history, the practitioner should consider whether

the information presented by R.F.’s grandmother is consistent

with a drug ingestion and whether this incident is likely to

be associated with a significant adverse outcome. Most 2-yearold children experience limited toxicity with unintentional drug

ingestions because only a relatively small amount of substance is usually ingested.6,7 Nevertheless, some substances

(e.g., methanol, ethylene glycol, nicotine, caustic substances,

camphor, chloroquine, clonidine, diphenoxylate-atropine, theophylline, oral hypoglycemic agents, calcium-channel blockers,

TCAs) can produce significant toxicity when only small amounts

are ingested.7,89,90

Although the history of drug ingestion in R.F. is somewhat

vague, the description of a green tablet, the vomiting of green

material, and the recent pregnancy of his mother suggest possible ingestion of prenatal iron tablets. Because this exposure

would be categorized as an unknown toxicity with a realistic

potential for severe toxicity if iron tablets were ingested, R.F.

should be brought to the ED for evaluation. Depending on the

distance to the hospital and the anxiety level of the grandmother,

the practitioner might want to instruct the grandmother to call

for emergency medical services transportation. She should be

instructed to take the green tablets to the ED along with the

child so the tablets can be identified. Other medications that are

in the house should also be taken to the ED, and the mother