Management of toxic exposure in children

Preventative strategies 

Most pediatric intoxications occur in the home. Approximately 15% of exposures occur outside the home, such as a day care center or a sitter's residence, including relatives [8], [9]. The substance ingested reflects the availability of the product [10]. Most of these ingestions are of a single household product, plant, food supplement, or medication. Most of these unintentional encounters result in mild or no symptoms, and significant morbidity or mortality is uncommon. Polypharmaceutic ingestion, with increased morbidity, is facilitated at homes of grandparents, who may inadequately shield their anticholinergic, antihypertensive, dysrhythmic, or psychoactive medications. In addition, access to illicit products manufactured at home or in clandestine laboratories may result in a more severe expression of toxicity [11].

Preventive strategies enacted by federal and state governments, organized physician groups, and individual clinicians have been enacted. Communal preventive strategies have decreased the incidence of poisoning. The 1960 passage of the Federal Hazardous Substance Labeling Act, which required proper labeling of products, was the first of these strategies. Child-resistant caps, mandated by the Poison Prevention Packaging Act of 1970, have significantly reduced morbidity and mortality from ingestions. Poison control center sticker trials, community programs, clinic- and office-based counseling also have had a measured impact. As a result, there has been a significant decline in the number of pediatric poisoning deaths: 216 in 1972 versus 25 in 1997 [2].

Individual clinicians have succeeded in the role of preventive health care. Emergency physicians (EPs) are not excused from preventive health practices, however. Secondary preventive efforts on the part of EPs regarding ingestions have the potential to improve the future health of children. After sensing the urgency, determining the need for monitoring, and early aggressive intervention when indicated, the EP should explore the social climate for any child brought for the evaluation of an ingestion. If the EP uncovers concerns and provides resources for socially isolated, medically, or psychologically ill parents, he or she may prevent a repeat ingestion [12], [13], [14], [15].

Patient history 

When not distracted by a patient's tenuous state, the EP benefits from a focused patient history. Information should be sought from emergency medical services, the accompanying caregiver, and, if potentially helpful, by telephone inquiry to others at the site of the incident. Obtaining a reliable history may be crucial to subsequent management.

Management of intoxication may be facilitated by identification of the substance. Knowing the agent ingested and understanding the pharmacology enables appropriate initial decision making. There are a limited number of pharmaceuticals, household products, and plants that are toxic for children (Box 1, Box 2). Knowing that an exposure includes a substance that is less toxic or nontoxic obviates immediate therapeutic interventions.

A second key element in decision making is the quantity of substance ingested. For many intoxicants, there may be a direct relationship with the volume consumed and the likelihood of adverse clinical manifestations. For various intoxicants, a minimum quantity (mg/kg) that leads to symptoms and the amount that leads to lethality in 50% of animals or children, or LD50, may be known. Predicting the amount consumed may be problematic [46]. For prescribed pills, projecting the amount missing may be possible by subtracting from the expected, remnant number. For liquids, a missing volume may be estimated. Unfortunately, pills or liquid may be unaccounted for when spilled at the scene. Also, there is no guarantee that the labeled content of the container was consistent with the pill or liquid that disappeared. An assessment of quantity consumed is facilitated if the ingestion was witnessed. The volume of a swallow is a function of body mass. The volume of a swallow is 0.27 mL/kg, or roughly 5 cc for a 2-year-old and 20 cc for an adolescent [16]. When two children have potentially coingested a substance, the mg/kg consumption should be calculated based on the principle that each child has taken all the substance and the other none.

The elapsed time since ingestion should provide insight as to the likelihood for deterioration for most pharmaceuticals and nonpharmaceuticals. Intoxication is unlikely if no clinical effects have occurred for those substances typically associated with prompt clinical change. Predicting clinical effects for substances with delayed manifestations, however, is not possible. In any case, the timing should be pursued. The elapsed time since ingestion may determine the use of charcoal, gastric emptying techniques, or specific antidotal therapy.

The route of exposure is also important for the patient and medical caretakers. Besides the most common route of oral toxic exposure, inhalation, ocular, or dermal contamination is possible. Patients who have been exposed to concentrated lipid-soluble compounds require skin decontamination. Special caution is necessary for organophosphate insecticides, which may be present in high enough quantities on skin, in sweat, and in bodily secretions of patients that serious sequelae can occur if proper protection of the staff is not accomplished.

A cause for the ingestion also must be pursued. Dismissing an ingestion as an accident in an “accident-prone” preschooler may lead to further injury or repeat ingestion. Multiple environmental factors can distract even a well-adjusted, supervisory figure; however, the EP should seek stressors, such as the following: ill health, including psychiatric disturbances; marital discontent and separation; spousal abuse; and unemployment or other financial burdens. If support is not offered to a dysfunctional family, a recurrence of ingestion or injury becomes more likely. Further inquiries should be driven by the age of the ingestor. The physician must determine if any discrepancy exists between the proffered history of ingestion with the developmental stage of the patient. Immobility and rudimentary hand-to-mouth coordination generally prevent self-poisoning by very young children and infants. Poisoning by an older sibling or parent should be considered for an ingestor who is younger than 1 year. For the elementary school child, the physician needs to inquire about academic underachievement and school avoidance, including truancy, as these events may reflect underlying pediatric psychopathology. Substance abuse, alcohol abuse, or feared pregnancy may precipitate an ingestion from the age of 9 through the teenage years. Failure to inquire about the possibility of suicide gesture or attempt may lead to inappropriate disposition and inadequate long-term support.

The pursuit of past medical history should include prior ingestions and injuries requiring medical attention, such as fractures or lacerations. Positive responses to these screening questions suggest that the current ingestion may reflect more than a chance occurrence [14].

Physical examination 

Physical signs of pediatric intoxication on admission to an emergency facility are highly variable. They depend on route of exposure, time and therapeutic intervention since exposure, extent of the exposure, type of product, and patient age.

As a rule, clinical consequences of a specific intoxication in the adult and pediatric populations are similar. The undesirable side effects and physical findings seen in adults from a class, product, or category of drug are also seen in children. Some of the impact of an intoxicant on a child may be subtle or, conversely, magnified as compared with adults because of peculiarities in metabolic degradation, pediatric anatomy, or physiology.

In pediatric patients, airway resistance is greater, cardiac output is very dependent on heart rate, and cardiovascular instability may be hidden by “normotensive” blood pressure readings. Young infants are very susceptible following ingestion to thermoregulatory problems, such as hypothermia and hyperthermia and including neuroleptic malignant syndrome [10]. In the first few years of life, mechanisms that typically distort a mental status (eg, hypoglycemia, electrolyte abnormality) or create focal findings may be masked by a reduced pediatric neurologic repertoire.

Neurologic symptoms 

The central and autonomic nervous system findings may be insidious (opioids, benzocaine, acetaminophen), abrupt (lidocaine, monocyclic and tricyclic antidepressants, theophylline, phenothiazines), transient (hydrocarbons), or fluctuate with alternating excitation and depression (imidazolines, phencyclidine, clonidine). The manifestations can arise directly from neurotoxicity (sympathomimetics, nicotine) or indirectly from hypoxia (oxidizing agents), hypoglycemia (alcohols, salicylates, hypoglycemics, β-blockers), electrolyte disturbance (theophylline, salicylates), hypoperfusion (iron, calcium channel blockers), or acidemia (salicylates, alcohols).

In adults, toxic substances tend to provoke a clearly defined nervous system alteration that is either excitatory or depressed. Toxic stimulation in an adult may be readily recognized. The poisoned adult may become restless, seem anxious or disoriented. On questioning the adult, his or her confusion may be readily apparent. Adults may be able to articulate abnormal sensations, such as paresthesias, difficulty in hearing, visual disturbances such as hallucinations, headache, dizziness, and other abnormal sensations. Cursory observation by the clinician may uncover generalized increased motor activity, motor excitation, or obvious dystonia.

Most intoxicants that are excitatory in an adult create a similar physiology in the child, but the clinical expression may be more difficult to discern. Many cynical, adult-oriented EPs believe that “normal behavior” in a toddler includes restlessness, ineffectual motor activity, rapid task changing, and incomprehensible articulation. Wise physicians, however, who possess knowledge of age-dependent variations of norm may recognize an excitatory toxic ingestion from subtle findings that include increased motor tone, tremor, and self-injurious behavior, including repetitive picking of the skin or uncontrolled tongue thrusting. The inability to sit upright, grasp or transfer objects, outright refusal to stand and ambulate, or a broad-based gait may be more prominent in young patients and be more obvious than an ataxic dysarthric-producing ingestion in an adult. Repetitive twitching or jerking movements suggest muscular irritability or a dystonic equivalent in a child.

Intoxicants that depress the sensorium in adults produce the same effects in children. The clear progression from subjective sleepiness, apparent drowsiness, outright lethargy, to frank coma in adults is mirrored in school-aged and older children. In the preschool-aged population, the change in sensorium and motor tone are typically accelerated. Toddlers are much more prone to rapid obtundation.

The intoxicants classically leading to seizure in adults may also cause seizures in children [18] (Box 3). The seizure activity is more likely in a child than in an adult exposed to several products including nicotine, salicylates, camphor, and cocaine [19], [20]. In addition, children are uniquely predisposed to seizure as a neurotoxic reaction associated with oral ingestion of diethyltoluamide [21], camphor, ammonium fluoride, and lidocaine [22].

Vital signs 

In adults, specific toxic ingestion may be suspected from changes in vital signs. Various intoxicants produce characteristic alterations in temperature, heart rate, respiratory rate, and blood pressure. In the pediatric population, vital sign alterations with various intoxicants may also assist in diagnosis.

Opiates, sedative hypnotics, hypoglycemics, and alcohols classically cause hypothermia. Hypothermia with the pediatric ingestion from these substances may result from exposure or altered metabolic activity. Adult and pediatric hyperpyrexia is common following intoxication with amphetamines, anticholinergics, β-blockers, isoniazid, and sympathomimetics. Salicylate intoxication in the pediatric population consistently leads to hyperthermia. In children, the impact of cyclic antidepressants on temperature regulation is variable.

Anticholinergics, antihistamines, amphetamines, sympathomimetics, cyclic antidepressants, cyanide, propoxyphene, and theophylline create tachycardia. Lower doses on a mg/kg basis of iron create tachycardia in pediatric patients. Bradycardia with pediatric ingestion is similar to adults for sedative hypnotics, calcium channel blockers, clonidine, β-blockers, opiates, digitalis, nicotine, and alcohols.

An increased respiratory rate following ingestion may result from a toxin-induced metabolic acidosis, noncardiogenic pulmonary edema, or direct pulmonary insult. Pediatric patients appear to be more susceptible to pulmonary insult compared with adults following exposure to hydrocarbons, organophosphates, and salicylates. Bradypnea is more common in young patients following ingestion of acetone, barbiturates, ethanol, ibuprofen, nicotine, and sedative hypnotics. Following clonidine ingestion, respiratory depression, including apnea, are more pronounced in children [23].

Sedative hypnotics, heroin, and methadone disproportionately reduce blood pressure in children. Ace inhibitors, calcium channel blockers, digoxin, nitrites, β-blockers, imidazolines, cyclic antidepressants, theophylline, propoxyphene, and quinidine may produce profound hypotension. Sympathomimetics, amphetamines, phencyclidine, anticholinergics, nicotine, and cocaine raise blood pressure in children. Delayed hypertension may result from pediatric ingestion of thyroid supplements.

When a pill or a swallow can kill 

A small group of pharmaceutic and household products can create life-threatening effects when ingested in very small quantities [27]. Approximately 24 agents have the potential to be fatal to individuals with small body mass, such as a child younger than 2 years [22]. The pharmaceutic and household products capable of killing a toddler after consumption of 1 to 2 tablets or 1 to 2 tsp of a marketed-dose unit are listed in Box 4.

Gastrointestinal decontamination 

Gastrointestinal decontamination, a well-established toxicologic technique for asymptomatic and symptomatic patients, has fallen in disfavor. In asymptomatic adults, decontamination has been shown to be of no benefit [28]. In asymptomatic children, evidence of improved outcome following ingestion also has not been shown. Decontamination has been suggested, however, for the asymptomatic child who is at theoretic risk for significant toxicity [29]. If the pediatric patient has ingested a potentially life-threatening amount of a poison and decontamination can be undertaken promptly, orogastric lavage, activated charcoal, or whole bowel irrigation can be considered [30], [31], [32].

Orogastric lavage may be useful for a substance known to delay gastric emptying or to form a concretion. It is an acceptable method for urgent removal of a solid or liquid substance for a child with an adequate gag reflex, where the airway need not necessarily be protected. The child should be placed in the Trendelenburg left-lateral decubitus position and monitored during tube passage. The largest bore possible should be used. A 16- to 28-French (F) tube should be used in a child, and at least a 36-F tube should be used in an adolescent. After tube placement is confirmed, normal saline is introduced in 50 to 100 cc aliquots in young children and up to 200 cc in adolescents [33]. Fluid is withdrawn by either aspiration or by gravity drainage. Lavage performed in this fashion has been shown to decrease the mean serum bioavailability of specific toxins [34]. Two points are important: recovery of all accounted-for intact tablets does not ensure that some quantity of drug has already been absorbed [35]. Second, lavage continued until the effluent is clear does not ensure that all of the gastric intoxicant has been retrieved. Toxic overdoses that may benefit from lavage include tricyclic antidepressants, calcium channel agonists, or toxins that are not bound by charcoal, such as iron, lithium, and alcohols. If activated charcoal also is to be administered, it should be infused after the last effluent is acquired [36].

Activated charcoal may be given after gastric evacuation. The greatest benefit occurs when it is administered within an hour of ingestion. There are insufficient data to support or exclude its use 1 hour after ingestion [30]. The recommended dose of charcoal is 1 g/kg in children up to the age of 1 year, 25 to 50 g in children aged 1 to 12 years, and 25 to 100 g in adolescents [29]. Activated charcoal may also be administered without gastric emptying procedures. Charcoal may be given by nasogastric tube or offered as a flavored slurry. The addition of chocolate milk, cola, or cherry-flavored syrup improves both the taste and ease of swallowing for children [37].

Whole bowel irrigation has greatest utility for potentially toxic ingestions of sustained-release or modified-release pharmaceuticals (eg, calcium channel antagonist) that have delayed absorption [38]. Whole bowel irrigation has been shown to be effective when initiated within 4 hours after the ingestion of enteric-coated aspirin [39]. Whole bowel irrigation may enhance passage of whole pill fragments that have passed beyond the pylorus (eg, radiographically documented iron tablets). Whole bowel irrigation may also be the preferred route of decontamination for medications that are not absorbed by charcoal. A polyethylene glycol electrolyte solution is offered by mouth or, when declined, by nasogastric tube. For children up to age 6, the recommended rate is 0.5 L/hour; for children aged 6 to 12 years, 1 L/hour; and for children older than 12 years, the recommended rate is 1.5 to 2 L/hour [32].

Enhanced elimination 

Supportive care that sufficiently sustains vital functions in pediatric patients can be provided while the clinician awaits the normal process of drug elimination. In certain circumstances, efforts to adsorb and increase the enteric or renal excretion of a drug may improve patient outcome. Two methods that can improve recovery, and which may be begun in an emergency setting, are multiple dosing of activated charcoal and urinary alkalization.

There have been several reports on the use of multiple-dose activated charcoal in the pediatric population. An accelerated rate of drug clearance has been shown for many drugs with enterohepatic recirculation [40]. The current recommendations include its use for life-threatening ingestions of carbamazepine, dapsone, phenobarbital, quinine, digoxin, and sustained-release preparations [10], [41]. A dose of 5 to 10 g every 3 to 4 hours is recommended [40]. Multiple doses should be administered only if the patient has an intact gag reflex, a protected airway, and no evidence of adynamic ileus or mechanical bowel obstruction.

Forced diuresis in association with alkalinization of the urine can enhance elimination of salicylates and phenobarbital. The method can be employed when the patient has a potentially life-threatening amount of either drug, is hemodynamically stable, has normal renal function, and has no evidence of cerebral or pulmonary edema. The goal is to keep the urinary pH at greater than 7.5. This can be accomplished by intermittently providing 1 to 2 mEq/kg of sodium bicarbonate intravenously over a 1 to 2 hour time frame [33]. An alternative method is to provide a renewable, continuous intravenous infusion of sodium bicarbonate every 4 hours based on clinical and laboratory reassessment. The following formula is used:

Antidotes 

Antidote administration may supplement supportive care and, in certain circumstances, prevent or reverse toxicity. The benefit of an antidote is derived from its mechanism of action. Some antidotes displace an intoxicant from a site of action. Some examples are oxygen for carbon monoxide, naloxone for opiates, and vitamin K preparations for oral anticoagulants. An antidote also may act in competition at a receptor site, such as atropine with acetylcholine. Other antidotes, such as N-acetylcysteine, restore function by repair or by bypassing the production of toxic metabolites. Several antidotes hasten the excretion of a detoxification complex. Examples include deferoxamine-ferric iron and cyanmethemoglobin.

The acute intoxications for which antidotes are a proven benefit are few. Much of the information has been derived from studies on adults; however, there is reasonable strength of evidence for pediatric recommendations [42]. Table 2selectively lists antidotes for pediatric intoxications.

Table 2. Selected pediatric antidotes for acute intoxication

	Toxin	Trigger for use	Antidote	Administration
	Acetaminophen
	Liquid	>225–250 mg/L at 2 h [46]	N-acetylcysteine	Oral, IV [48] (pending FDA approval), 140 mg/kg;
	Pills	>150–200 mg/L at 4 h		70 mg/kg q 4 h, at least 36 h [51]
	Anticholinergics	Confirm cause of altered mental status	Physostigmine	IV, 0.02 mg/kg over 5–10 min [11]
	Benzodiazepines	Confirm cause of altered mental status	Flumazenil	IV, 0.005–0.01 mg/kg at 0.2 mg/min rate; maximum 1 mg [50]
	β-blockers	Cardiovascular toxicity	Glucagon	IV, 0.15 mg/kg bolus; 0.1 mg/kg/h maintenance
	Calcium channel blockers	Cardiovascular toxicity	10% Calcium chloride solution	1–2 cc/kg over 5 min; repeat every 10–20 min
	Cyanide	Any manifestations	3% Sodium nitrite solution and	IV, 0.2–0.3 cc/kg over 5 min; maximum 10 cc
			25% sodium thiosulfate solution	IV, 1–2 cc/kg over 1–2 min
	Ethylene glycol, methanol	Acidemia; >20 mg/dL ethylene glycol	10% Ethanol or	IV, 10 cc/kg; continuous 1.5 cc/kg/h
			fomepizole	IV, 15 mg/kg bolus; 10 mg/kg
				q 12 h × 4, 15 mg/kg q 12 h thereafter [38]
	Iron	Serum iron >TIBC, or	Deferoxamine	IM, 90 mg/kg; maximum 1 g, or
		350–500 mcg/dL		IV, 10–15 mg/kg/h
	Isoniazid	Neurotoxicity; >40 mg/kg ingestion	Pyridoxine	IV, 75 mg/kg bolus; maximum 5 g [49]
	Opioids	CNS depression	Naloxone	0.1–0.4 mg/kg bolus; 0.16 mg/kg/h continuous
	Organophosphate	Nicotinic, muscarinic or CNS manifestations	Atropine and pralidoxime	IV, 0.05–0.1 mg/kg; repeat as necessary
				25–50 mg/kg over 15–30 min; continuous 10–20 mg/kg/h up to 500 mg/h [47]
	Oxidants	Methemoglobinemia, >20%–30%	1% Methylene blue solution	1–2 mg/kg over 5 min; repeat 1 mg/kg [52]
	Sulfonylureas	Hypoglycemia	Octreotide	Subcut 1 mcg/kg every 12 h;
				IV, 15 ng/kg/min [28]

Abbreviations: CNS, central nervous system; IM, intramuscular; IV, intravenous. Adapted from American College of Emergency Physicians. Clinical policy for the initial approach to patients presenting with acute toxic ingestion or dermal or inhalation exposure. Ann Emerg Med 1999;33:735–61.