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Official reprint from UpToDate®

www.uptodate.com ©2013 UpToDate®

AuthorsLarissa I Velez, MDJ Greene Shepherd, PharmDCollin S Goto, MD

Section EditorMichele Burns Ewald, MD

Deputy EditorJames F Wiley, II, MD, MPH

Approach to the child with occult toxic exposure

Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Jul 2013. | This topic last updated: Sep 6, 2012.

INTRODUCTION — In the United States, in 2002, there were approximately 2.4 million toxic exposures reported to the American

Association of Poison Control Centers Toxic Exposure Surveillance System (AAPCC-TESS) by 64 participating poison centers [1].

The true annual incidence of such exposures is unknown because of under-diagnosis and underreporting, but it was estimated to

be 4.6 million. Two-thirds of these exposures occurred in children younger than 20 years of age, one-half in children younger than

six years, and almost one-quarter in children younger than two years. Every physician who cares for children should be familiar

with the evaluation and management of poisoning.

The general approach and initial management of the child who is suspected to have ingested or inhaled an unknown poison is

reviewed here. Specific issues relating to management of common drug overdoses are discussed separately. (See appropriate

topic reviews).

CLINICAL PRESENTATION — The clinical presentation of occult ingestion varies depending upon the ingested substance and can

range from asymptomatic to critically ill. Occult toxic exposure should be considered in the differential diagnosis of children who

present with acute onset of multiorgan system dysfunction, altered mental status, respiratory or cardiac compromise, unexplained

metabolic acidosis, seizures, or a puzzling clinical picture [2,3]. The index of suspicion should be raised if the child is in the "at

risk" age group (one to four years of age) and/or has a previous history of ingestion [4].

Intentional etiologies for occult poisonings, including suicide attempts in older children and adolescents, and child abuse via forced

ingestion in young children, particularly those who are younger than one year of age, must not be overlooked [3]. (See "Suicidal

behavior in children and adolescents: Epidemiology and risk factors" and "Physical abuse in children: Epidemiology and clinical

manifestations" and "Munchausen syndrome by proxy (medical child abuse)".)

OVERVIEW OF APPROACH — The approach to the poisoned child begins with initial evaluation and stabilization followed by a

thorough evaluation to identify the agent(s) involved and assess the severity of exposure. The possibility of concomitant trauma or

illness must be recognized and addressed before initiation of decontamination [5,6]. (See "Classification of trauma in children".)

The tempo, sequence, methods, and priorities of management are dictated by the toxin(s) involved, the presenting and predicted

severity of poisoning, and the presenting phase of poisoning. Management usually begins with stabilization of the airway, breathing,

and circulation, and treatment of life- and/or limb-threatening trauma. It is then directed to the provision of supportive care,

prevention of poison absorption, and when appropriate, administration of antidotes and enhancement of elimination [7].

INITIAL EVALUATION AND STABILIZATION — Rapid evaluation of mental status, vital signs, and pupils enables classification of

the patient into a state of physiologic excitation (eg, central nervous system stimulation and increased temperature, pulse, blood

pressure, and respiration); depression (depressed mental status and decreased temperature, pulse, blood pressure, and

respiration); or mixed physiologic state. This initial characterization helps to direct initial stabilization efforts and provides a clue to

the etiologic agent (table 1) [7].

Airway — The airway of patients who have ingested an unknown substance must be monitored carefully. The patency of the

airway and gag reflex should be evaluated in patients who are sedated or obtunded. Even those who are awake and talking must be

monitored closely because their condition can deteriorate quickly. The position of the head should be optimized to maintain airway

patency. Endotracheal intubation should be performed in all patients in whom the airway is threatened. If intubation is necessary,

cervical spine stabilization must be maintained if trauma is suspected. (See "Emergent endotracheal intubation in children" and

"Rapid sequence intubation (RSI) in children" and "Pediatric cervical spine immobilization".)

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Breathing — After the airway is adequately secured, the quality of breathing must be evaluated. Poisoned patients may develop

respiratory failure for many reasons. Some toxins decrease the respiratory drive, whereas others impair muscle contraction; still

other toxins may directly damage the lung parenchyma or result in pulmonary edema. Any of these mechanisms may result in

hypoxia and/or hypercapnia (table 2). In a symptomatic or rapidly deteriorating patient, measurement of arterial blood gas should

be obtained. Supplemental oxygenation should be provided to maintain oxygen saturation >95 percent. Intubation and ventilation

are required in patients who cannot sustain adequate oxygenation or ventilation or who have severe acid-base disturbances. (See

"Emergent endotracheal intubation in children" and "Rapid sequence intubation (RSI) in children".)

Circulation — Intoxication by various drugs may cause blood pressure and heart rate abnormalities (table 3) and/or cardiac

conduction disturbances ranging from minor QT changes to a wide QRS complex form (table 4) [8-10]. Blood pressure

measurement and a 12-lead electrocardiogram (ECG) should be obtained in all patients who present with occult toxic exposure.

Continuous cardiac monitoring is often necessary.

The evaluation and management of circulatory compromise in patients with intoxication of unknown or multiple agents should occur

according to Advanced Cardiac Life Support (ACLS) or Pediatric Advanced Life Support (PALS) guidelines. (See "Assessment of

perfusion in pediatric resuscitation" and "Basic life support in infants and children" and "Primary drugs in pediatric resuscitation".)

The child should be evaluated for signs of shock, and because of the potential for rapid decompensation, at least one intravenous

(IV) line should be established in the stable patient and two large bore lines in the unstable or deteriorating patient. (See

"Physiology and classification of shock in children" and "Vascular (venous) access for pediatric resuscitation and other pediatric

emergencies".)

Altered mental status — Various drugs can cause mental status changes ranging from agitation to coma (table 5). Hypoxemia

and hypoglycemia are two common causes of altered mental status in the poisoned patient that should be promptly evaluated and

addressed during initial stabilization. In addition, administration of naloxone or thiamine should be considered in poisoned children

and adolescents who are thought to have opiate intoxication or thiamine deficiency, respectively. In contrast, the use of flumazenil

to reverse benzodiazepine ingestion is not routinely recommended because of potential serious adverse effects (eg, precipitation of

seizures) [11-13].

Hypoxemia – Rapid evaluation of oxygenation should be performed in all patients with altered mental status. This can be

performed with a bedside pulse oximeter and/or arterial blood gas measurement, which provides additional information about

the patient's ventilation and acid-base status and may, in turn, affect diagnosis and management. (See 'Ancillary studies'

below.) Pulse oximetry does not reflect oxyhemoglobin saturation in patients with carbon monoxide poisoning. If carbon

monoxide toxicity is a diagnostic consideration, the carboxyhemoglobin level should be measured by cooximetry using a

blood gas sample. (See "Carbon monoxide poisoning".)

Humidified oxygen should be administered to symptomatic poisoned children with altered mental status. Endotracheal

intubation is required in patients who cannot sustain adequate ventilation or oxygenation. (See "Emergent endotracheal

intubation in children" and "Rapid sequence intubation (RSI) in children".)

Hypoglycemia – Several drugs cause hypoglycemia (table 6); rapid assessment of blood glucose can be performed at the

bedside with a glucose strip [12]. A concentrated dextrose solution should be administered if blood glucose is low, the

accuracy of the result is questioned, or rapid assessment of blood glucose is not available [2,12]. The dose for dextrose is

0.25 g/kg administered intravenously or intraosseously. This is usually achieved with 2.5 mL/kg of 10 percent dextrose

solution since extravasation of higher concentrations of glucose will lead to severe tissue damage. (See "Approach to

hypoglycemia in infants and children", section on 'Glucose therapy'.)

Opiate intoxication – Administration of naloxone is indicated in patients who have depressed mental status, diminished

respirations, miotic pupils, or other circumstantial evidence of opiate intoxication [11,14,15]. The dose of naloxone varies

depending upon the age of the child and the clinical scenario. (See "Opioid intoxication in children and adolescents",

section on 'Naloxone'.)

Thiamine deficiency – The administration of thiamine should be considered in children and adolescents who may be

thiamine-deficient because of chronic disease, malnutrition, eating disorders, or alcoholism [2,12]. (See "Wernicke's

encephalopathy".) The notion that thiamine must be given before dextrose to avoid precipitating Wernicke's encephalopathy

is largely unsupported [12]. Uptake of thiamine into cells is slower than that of dextrose [16], and withholding dextrose until

the administration of thiamine is complete may prove detrimental to those with actual hypoglycemia.

Other considerations — Additional considerations in the initial stabilization of the child with an unknown toxic exposure include:

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Occult trauma – The patient should be completely undressed and examined to look for signs of occult trauma.

Decontamination – Gastrointestinal decontamination may be indicated as part of the initial stabilization in children who

have ingested a potentially life-threatening amount of poison (eg, iron) [3]. Ocular and/or dermal decontamination may be

necessary if coincident exposure occurred. (See "Decontamination of poisoned children".)

DIAGNOSIS OF POISONING — After the initial evaluation and stabilization, efforts should be focused on identification of agent(s)

involved, assessment of severity, and prediction of toxicity.

It is essential to identify potentially fatal agents and those with delayed clinical toxicity (table 7) as soon as possible so that

appropriate intervention can be undertaken. The most common fatal drug ingestions in children younger than six years of age

include prenatal iron supplements, antidepressants, cardiotoxic agents, and salicylates (table 8). In addition, a number of drugs

can be fatal if ingested by a toddler, even in small amounts (table 9) [17-20]. The most common fatal nondrug ingestions in children

younger than six years of age include hydrocarbons, alcohols, cosmetics, cleaning products, and pesticides [2,21,22]. (See

"Hydrocarbon poisoning".)

History — Obtaining an accurate history in an intoxicated patient is challenging, but crucial. The patient may be unwilling or unable

to provide the details of the history [23], and the personnel accompanying the patient to medical care may not know the details of

exposure (eg, agent, time, volume, immediate clinical effects). The patient's history should be confirmed and correlated whenever

possible with the signs, symptoms, and laboratory data expected from poisoning with the agent(s) implicated by history.

In the young child, the circumstances surrounding the ingestion can provide useful information (eg, location, activity just before

ingestion) [4,24]. Potential agents ingested in the kitchen, for example, may be different than those in the bathroom [4].

It is important to ask about exposure to the most commonly ingested agents in children younger than six years, which include

cosmetics and personal care products, cleaning products, analgesics, cough and cold preparations, topical agents, plants,

pesticides, and vitamins [1,22].

It is important to ask about recent illnesses and regular therapy with common medications. The overdosing of common medications

(eg, acetaminophen, ibuprofen) may result in chronic poisoning [2]. Among the 26 fatal toxic exposures in children younger than

six years of age in the United States in 2001, eight were caused by therapeutic errors (acetaminophen, aspirin, methadone,

morphine, oxycodone) [21]. (See "Management of acetaminophen (paracetamol) poisoning in children and adolescents" and

"Salicylate poisoning in children and adolescents".)

Information that is provided by an adolescent patient, particularly one with an intentional ingestion, may not be reliable [23,25,26].

Adolescents commonly present with ethanol or illicit drug intoxications. It is important to ask other household members about all

medications (prescription and over-the-counter), vitamin and mineral supplements (particularly prenatal vitamins), herbal remedies,

and folk remedies that are present in the home, as well as those that are used by recent visitors [11]. Adolescents may also be

exposed to occult toxins in the work or school environment (eg, alkaline corrosives, gases and fumes, cleaning agents, bleaches,

various drugs, acids, and hydrocarbons) [27].

Paramedics can provide important information about open containers, empty bottles, spilled contents, drug paraphernalia, or

suicide notes at the scene. If such items exist, the paramedics (or someone at the scene) should bring them to the hospital [11].

Unknown pills or chemicals may be identified by consultation with a regional poison control center (1-800-222-1222), computerized

poison identification system, or product manufacturer (eg, material data safety sheet).

It is also important to know about interventions in the prehospital setting (eg, administration of oxygen, intravenous fluid, dextrose,

or naloxone) since these may alter the patient's condition at the time of presentation.

Information about the quantity and timing of ingestion is helpful in making decisions about decontamination or the use of antidotes

(see below). Younger children tend to ingest small quantities of single agents. In one study of 66 children (age 1.5 to 4.5 years),

the volume of a "mouthful" was calculated by subtracting the volume of apple juice remaining in a cup after the child had taken one

sip from the original volume [28]. The mean volume of a mouthful was 9.3 mL (95% CI, 8-11 mL), with a range of 3.5 to 29 mL. In

contrast to younger children, older children and adolescents, in whom the ingestion is more likely intentional, ingest larger

quantities of multiple agents. In some cases, the only information that is available about the time of ingestion is the last time that

the patient was observed to be doing well.

Information from the past medical history is useful in the identification of available medications, possible coingestants, baseline

health status, and potential complicating factors (eg, G6PD deficiency). If the patient or family member cannot provide this

information, it may be obtained from medical records, pharmacy profiles, or Medic-Alert bracelets.

Information from the social history may be useful in determining the circumstances, intent, and/or agent of exposure. Unwitnessed,

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unintentional ingestions in young children tend to occur at times of decreased parental supervision (eg, when there are household

visitors or holiday parties) [2,3].

A history of illicit drug use in the patient or family members may provide a clue to the agent. Drug use in close family members has

been associated with unintentional (unsupervised) ingestion of illicit substances [29,30]. Drug use in older siblings may encourage

similar behavior in younger ones (eg, inhalant abuse). (See "Inhalant abuse in children and adolescents".)

Physical examination — The physical examination, particularly the evaluation of mental status and vital signs, should be

repeated frequently to determine the course of poisoning and the need for further intervention.

After the initial diagnostic evaluation and stabilization, other physical findings should be sought to further define a particular toxic

syndrome (toxidrome), to narrow the potential etiologies of poisoning (table 1), and to evaluate the possibility of child abuse. (See

"Physical abuse in children: Epidemiology and clinical manifestations".) The diagnosis may be assisted by [17]:

Temperature alterations (table 10)

Blood pressure and heart rate alterations (table 3)

Respiratory disturbances (table 11)

Pupillary findings (table 12)

Skin findings (table 13)

Neuromuscular abnormalities (table 14)

Mental status alterations (table 5)

Characteristic odors (table 15); these odors may not be detectable by all examiners

Other aspects of the physical examination may suggest particular agents or routes of exposure. Nosebleed may occur in

individuals who inhale cocaine or volatile substances. The latter may also cause facial rash, flushing, blisters, or a ring of paint

around the mouth and nose (the "huffer rash"). Wood's light (ultraviolet) examination of the patient's mouth or clothes may reveal

fluorescence if the patient has ingested antifreeze solution (eg, ethylene glycol), which commonly contains fluorescein dye (added

to help in the identification of radiator leaks) [31]. Needle tracks suggest intravenous drug use.

Discrepancies between the physical examination and the history may reflect an inaccurate ingestion history, a brief or prolonged

time interval between exposure and physical examination, or intentional poisoning.

Ancillary studies — The laboratory evaluation of the child with an unknown ingestion is performed to detect metabolic effects of

the poison that have both diagnostic and therapeutic implications. The laboratory evaluation should include the following (table 6

and table 16 and table 17 and table 18):

Rapid determination of blood glucose

Acid base status

Electrolytes

Blood urea nitrogen and creatinine

Serum osmolality (suspected ingestion of toxic alcohols or presence of anion gap acidosis)

Aspartate aminotransferase (AST) and Alanine aminotransferase (if acetaminophen ingestion suspected)

Quantitative acetaminophen serum concentration (suicidal intent or if suspected based on history)

Quantitative salicylate serum concentration (patients with respiratory alkalosis or metabolic acidosis)

Urine dipstick test

Urine pregnancy test (postmenarchal females)

Electrocardiogram

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Chocolate-colored blood that fails to turn pink after 10 minutes of exposure to air suggests methemoglobinemia, which may be

caused by a number of agents, including aniline dyes, benzocaine-containing teething products, dapsone, naphthalene, nitrites,

and pyridium (table 16) [4,23]. (See "Clinical features, diagnosis, and treatment of methemoglobinemia".)

It may be helpful to save samples of blood (10 mL, heparinized), urine (100 mL, first voided), vomitus, and gastric contents (first

lavage aspiration) for subsequent analysis [4]. Such samples should be appropriately labeled; they should be processed and stored

according to specific instructions supplied by the laboratory. Care should be taken to establish a chain of evidence for law

enforcement purposes if intentional poisoning or Munchausen by proxy are suspected (this includes proper sealing, labeling, and

storing of specimens to ensure that they cannot be tampered with). (See "Munchausen syndrome by proxy (medical child abuse)".)

Blood gas — Arterial or venous blood gas measurement offers a rapid evaluation of acid-base status (table 17), as well as

assessment of oxygenation (arterial blood gas only) and ventilation [32,33]. In a symptomatic or rapidly deteriorating patient, the

results of the arterial blood gas can be used to direct stabilization and supportive care while awaiting other laboratory results.

Cooximetry can be used to rapidly establish the diagnosis of carbon monoxide toxicity or methemoglobinemia.

Electrolytes — Measurement of serum electrolytes provides information about renal function, which is essential for the

elimination of some toxins, and further information about acid-base status (table 6). The electrolyte results can be used to calculate

the anion gap (Na – [Cl + HCO3]) [34-36], which helps to differentiate among the forms of metabolic acidosis (table 18) [37]. (See

"Approach to the child with metabolic acidosis".)

Serum osmolality — The serum osmolality (which must be calculated by freezing point depression) is essential for the

calculation of the osmolal gap. The osmolal gap is elevated in the presence of unmeasured osmotically active substances (table

19). The most important substances in the group are the toxic alcohols [38,39]. Calculation of the osmolal gap requires

simultaneous measurement of plasma osmolality, electrolytes, blood urea nitrogen (BUN), and creatinine [40,41]. (See "Serum

osmolal gap".)

Urinalysis — Urinalysis is necessary for evaluation of rhabdomyolysis, the prompt treatment of which may prevent renal failure.

(See "Clinical manifestations and diagnosis of rhabdomyolysis" and "Clinical features and diagnosis of heme pigment-induced

acute kidney injury (acute renal failure)" and "Prevention and treatment of heme pigment-induced acute kidney injury (acute renal

failure)".)

Examination of the urine can also be helpful in the diagnosis of ethylene glycol ingestion:

Microscopic examination of the urine may reveal calcium oxalate crystals (picture 1A-B), although the absence of

crystalluria does not preclude the presence of ethylene glycol ingestion. (See "Methanol and ethylene glycol poisoning".)

Urine examination by Wood's light (ultraviolet) may reveal fluorescence if the patient has ingested antifreeze solution, which

commonly contains fluorescein dye (added to help in the identification of radiator leaks) [31]. However, this finding is neither

sensitive nor specific for the diagnosis of ethylene glycol poisoning [42,43]. A negative control urine sample should be tested

simultaneously.

Electrocardiogram — Changes on electrocardiogram suggest poisoning by certain agents (table 4) and may indicate the need

for specific intervention (eg, sodium bicarbonate infusion (1 mEq/L)) for a widened QRS interval or ventricular arrhythmia.

Toxicology screens — The need for toxicology screening in patients with occult toxic exposure depends upon the clinical

scenario. Toxicology screening is rarely necessary in children who have an unintentional ingestion and are asymptomatic or have

clinical findings that are consistent with the history. It is indicated in children in whom the diagnosis of poisoning is uncertain, who

have coma of unknown etiology, where there is suspicion of child abuse or Munchausen syndrome by proxy, and in whom the

administration of an antidote depends upon the rapid identification of the toxic agent. Care should be taken to establish a chain of

evidence for law enforcement purposes if intentional poisoning or Munchausen by proxy are suspected (this includes proper

sealing, labeling, and storing of specimens to ensure that they cannot be tampered with). (See "Munchausen syndrome by proxy

(medical child abuse)".)

Urine screens provide qualitative data about the recent use of substances included in the screen. Urine screens usually test for a

limited number of substances (typically drugs of abuse). Positive and negative immunoassay screens for drugs do not absolutely

confirm or refute poisoning diagnoses and may need confirmation by gas chromatography-mass spectrophotometry (GC-MS).

False positives may occur if structurally similar substances cross-react with the assay (table 20). On the other hand, a negative

screen may reflect a drug concentration below the threshold limit of detection because the specimen was obtained before or after

peak concentration.

Qualitative screens are inexpensive and provide rapid results (usually within one hour). However, they provide no information about

timing or quantity of ingestion. The information obtained rarely affects clinical management, but may be useful in anticipating

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withdrawal and determining psychiatric disposition [10,44]. The spectrum of drugs included in the urine screen varies by institution;

clinicians should be familiar with the spectrum of drugs tested at their institution [45].

Serum testing provides quantitative data and is important in the diagnosis and management of ingestion of several drugs and

medications (table 21). As a general rule, drug concentrations should be ordered selectively depending upon the history, physical

examination findings, and clinical condition [10,46]. However, screening for acetaminophen and salicylates is strongly

recommended for patients with an uncertain history or intentional poisoning; few early signs may be present following lethal doses

of these agents, and specific treatments are available and highly effective if implemented early [47-49]. Quantitative testing may

also be considered for agents that have delayed clinical effects (table 7).

The interpretation of a single drug concentration for any drug must be made with caution because poisoning is a dynamic and

rapidly changing process. Intervention may be required despite serum concentrations in the therapeutic range. Results of these

tests should be considered in conjunction with the time of exposure. Levels that are obtained early in the course, while the drug is

still distributing throughout the body, are difficult to interpret properly. On the other hand, levels drawn very late after an exposure

may be deceivingly low.

Comprehensive qualitative toxic screening of urine, blood, or other body fluids is expensive and usually requires six hours for

results. Such testing rarely leads to changes in patient management and disposition, and is unlikely to affect patient outcome [50-

52]. In one retrospective study of comprehensive toxicology screens in 463 children younger than 19 years of age, 51 percent were

positive for exogenous toxins [50]. Among the positive screens, 97 percent were either suspected by history or physical

examination, present in the limited portion of the toxicology screen, or clinically insignificant; in the remaining 3 percent, patient

management was not altered as a result of the positive screen [50].

Nonetheless, such a comprehensive panel may be useful in patients who are critically ill or in whom the clinical picture does not fit

the stated history [2,23]. The spectrum of drugs included in the comprehensive drug screen varies by institution; clinicians should

be familiar with the spectrum of drugs tested at their institution [45].

Drugs and toxins that can cause coma or hypotension and are not detected by most drug screens include bromides, carbon

monoxide, chloral hydrate, clonidine, cyanide, organophosphates, tetrahydrozoline (in over-the-counter eye drops), beta blockers,

calcium-channel blockers, colchicine, digitalis, and iron [2,45].

Radiologic evaluation

Plain radiographs of the chest should be obtained in children and adolescents with inhalation exposures and those with respiratory

symptoms and signs (table 11 and table 22). Radiographs also may be obtained to search for concomitant injury and to confirm the

placement of endotracheal tubes, nasogastric tubes, and central lines [53]. In addition, certain radiopaque toxins, including

packets of illicit drugs smuggled internally by body packers, may be visualized by plain film radiographs (table 23 and image 1 and

image 2) [54]. (See "Internal concealment of drugs of abuse (body packing)".)

Computed tomography (CT) has little utility in the diagnosis of poisoning. However, CT of the head can be useful in identifying

injuries from or complications of poisoning such as intracranial hemorrhage (eg, in cocaine intoxication) or cerebral edema as a

complication of hypoxemia; abdominal CT can also be useful in the evaluation of body packers.

MANAGEMENT — Optimal management of the poisoned child depends upon the specific poison(s) involved, the presenting and

predicted severity of illness, and elapsed time between exposure and presentation. Supportive care is the mainstay of therapy,

which variably involves decontamination, antidotal therapy, and enhanced elimination techniques [11].

Supportive care — Supportive care is the most important aspect of treatment and, when coupled with decontamination, is usually

sufficient for complete recovery. Supportive care for toxic exposures is similar to that provided for other problems, but certain issues

are managed slightly differently:

Airway protection by endotracheal intubation should be performed early in the poisoned patient with depressed mental

status because of the high risk for aspiration and its associated complications, particularly when gastric decontamination is

necessary [55]. Endotracheal intubation with mechanical ventilation is also indicated for severe acid-base disturbances or

acute respiratory failure. In addition, mechanical ventilation may be necessary in patients who require sedation and/or

paralysis to limit the extent of complications such as hyperthermia, acidosis, and rhabdomyolysis.

Hypotension should be managed initially with intravenous fluids. Vasopressors are required when hypotension does not

resolve with volume expansion. Direct-acting vasopressors, such as norepinephrine, have been shown to be more effective

than indirect-acting agents, such as dopamine, when tricyclic antidepressants have been ingested [56,57]. (See "Tricyclic

antidepressant poisoning".)

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Hypertension in agitated patients is best treated initially with nonspecific sedatives such as a benzodiazepine [58]. When

hypertension necessitates specific therapy because of associated end-organ dysfunction, preferred treatments are

nitroprusside, esmolol, or phentolamine. The use of beta-blockers alone for patients with sympathetic hyperactivity (eg,

cocaine intoxication) is not recommended because it may result in unopposed alpha-adrenergic stimulation and intensified

vasoconstriction [58,59]. Short acting agents are generally preferred because they are easily titrated.

Ventricular tachycardias are usually treated with standard Advanced Cardiac Life Support (ACLS) or Pediatric Advanced Life

Support (PALS) recommendations: lidocaine, procainamide, amiodarone, and cardioversion or defibrillation. However, when

ventricular tachycardias occur in the context of intoxication with tricyclic antidepressants or other membrane-active agents,

sodium bicarbonate is the first-line therapy. Treatment with magnesium sulfate, overdrive pacing with isoproterenol, or a

temporary pacemaker may be effective in patients with drug-induced torsades de pointes and prolonged QT intervals on

electrocardiogram (ECG). Digoxin-poisoned patients with life-threatening tachyarrhythmias or bradyarrhythmias should be

treated with specific Fab fragments (Digibind). (See "Acquired long QT syndrome" and "Digitalis (cardiac glycoside)

poisoning".)

Bradyarrhythmias associated with hypotension should be treated in the standard fashion with atropine or temporary pacing.

However, in patients with calcium channel blocker or beta blocker intoxication, the administration of calcium and glucagon

may obviate the need for further measures [60-64]. (See "Calcium channel blocker poisoning" and "Major side effects of beta

blockers".)

Seizures are typically treated with benzodiazepines followed by barbiturates if necessary. Phenytoin may be effective in

controlling seizures caused by agents that stabilize neuronal membranes (eg, propranolol), but is not indicated in most

poisonings and is potentially harmful in seizures resulting from theophylline [64]. Seizures caused by certain agents may

require specific antidotes for their successful termination (eg, pyridoxine for isoniazid toxicity, glucose for hypoglycemic

agents). (See "Management of status epilepticus in children".)

Drug-associated agitation is usually treated with benzodiazepines, supplemented with high potency neuroleptics (eg,

haloperidol) as needed [65]. Agitation associated with certain toxidromes may be best treated with specific agents (eg,

physostigmine for the anticholinergic syndrome) [66]. (See appropriate topic reviews).

Decontamination — Following initial patient stabilization, patient decontamination is a priority. The sooner decontamination is

performed, the more effective it is at preventing poison absorption. Decontamination of poisoned children is discussed in detail

separately. (See "Decontamination of poisoned children".)

Activated charcoal has become the preferred method of GI decontamination in children. The use of activated charcoal is

controversial in the asymptomatic patient. If activated charcoal is to be administered, voluntary ingestion in the alert and

cooperative patient is preferred to nasogastric administration. (See "Decontamination of poisoned children", section on 'Activated

charcoal'.)

The clinical benefit of gastric lavage has not been confirmed in controlled studies, and its routine use in the management of

poisoned patients is no longer recommended by the American Academy of Clinical Toxicology or the European Association of

Poisons Centres and Clinical Toxicologists. (See "Decontamination of poisoned children", section on 'Gastric lavage'.)

Whole bowel irrigation is another technique that may be considered for patients who have ingested large amounts of substances

that are not well bound to activated charcoal (table 24), sustained release preparations, and illicit drug packets [11]. (See

"Decontamination of poisoned children", section on 'Whole bowel irrigation'.)

Antidotes — Antidote administration is appropriate when there is a poisoning for which an antidote exists, the actual or predicted

severity of poisoning warrants its use, expected benefits of therapy outweigh its associated risk, and there are no

contraindications. Antidotes reduce or reverse poison effects by a variety of means. They may prevent absorption, bind and

neutralize poisons directly, antagonize end-organ effects, or inhibit conversion to more toxic metabolites. The pediatric doses for

antidotes recommended for stocking in hospitals that accept emergency admissions are listed in Table 2 (table 25A-B) [11,13].

The pharmacokinetics of the intoxicant and the antidote must be considered because the toxidrome may recur if the antidote is

eliminated more rapidly than the ingested substance, particularly if the antidote acts by antagonizing end-organ effects or inhibiting

conversion to toxic metabolites. As an example, somnolence and respiratory depression due to ingested opiates acutely reverse

with the administration of naloxone but recur in approximately one-third of cases because the elimination half-life of naloxone is

only 60 to 90 minutes [67,68]. (See "Opioid intoxication in children and adolescents".) Thus, in certain situations antidotes may

require repeated administration or continuous infusion.

The risks and benefits of antidote administration also must be carefully weighed in the setting of multiple drug ingestion. Many

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antidotes (eg, antivenom, chelating agents, N-acetylcysteine) may be used concurrently without adverse effects. However, notable

exceptions exist. When drugs that have opposite effects are taken at the same time, the reversal of one agent may unmask the

toxicity of another. As an example, in a patient who ingested diazepam and cocaine, the administration of flumazenil, the

benzodiazepine antidote, could lower the seizure threshold and increase the risk of serious complications. (See "Cocaine: Acute

intoxication".)

In addition, when drugs that have similar effects are co-ingested, the antidote may not seem to have any effect. This is a common

problem when opiates are ingested with large amounts of ethanol. In such circumstances, naloxone may be administered in such

large amounts that it results in opiate withdrawal. For this reason, naloxone should be administered at lower doses in patients in

whom there is a suspicion of opiate dependence. (See "Opioid withdrawal in adolescents".)

Diagnostic trial — In some cases, the clinical response to an antidote may suggest the etiology of poisoning [23]. Antidotes

should be used in selected clinical scenarios by clinicians who are experienced in their use, or after consultation with available

experts such as those at regional Poison Control Centers (1-800-222-1222). Examples include:

Improved alertness in response to flumazenil for benzodiazepine ingestion; flumazenil is contraindicated in drug ingestions

that may precipitate seizures and in patients with a known seizure disorder. It also may precipitate withdrawal in patients

with benzodiazepine dependence.

Improved alertness in response to glucose for insulin or oral hypoglycemic agent ingestion.

Improved alertness in response to physostigmine for anticholinergic agent ingestion; physostigmine is contraindicated in

tricyclic antidepressant overdoses. Physostigmine should not be administered to patients who have a widened QRS interval

on electrocardiogram.

Improved alertness in response to naloxone for opiate ingestion.

Improved clotting in response to protamine for heparin overdoses.

Abatement of dystonia in response to diphenhydramine for phenothiazine ingestion.

Enhanced elimination — Enhanced elimination techniques can be used for several drugs and toxins (table 26). Enhanced

elimination techniques are discussed in detail separately.

Disposition — Following initial evaluation, treatment, and a short period of observation, disposition of the patient is based upon the

observed and predicted severity of toxicity. Patients who develop only mild toxicity and who have only a low predicted severity can

be observed in the emergency department until they are asymptomatic. An observation period of six hours is usually adequate for

this purpose. All patients with intentional overdose require psychiatric assessment prior to discharge.

Other factors to consider in the disposition include whether the child's caregivers understand the potential for delayed

consequences of poisoning, have a means of transportation to return if necessary, and are able to provide adequate observation [3].

In addition, if suboptimal home environment contributed to the ingestion, consultation with a social worker may be indicated,

particularly if child neglect is being considered. (See "Child neglect and emotional abuse".)

Longer observation (or hospital admission) may be necessary for patients who are thought to have ingested substances with

delayed effects (table 7), sustained release preparations, or multiple agents. The duration of observation varies depending upon the

expected time of onset and duration of symptoms. The half-lives of drugs are calculated based upon therapeutic dosing; in the

overdose setting, the calculated half-life may be inaccurate and the duration of symptoms prolonged

The toxicity of agents varies depending upon whether the ingestion is acute or chronic, whether other substances have been

ingested, the time between ingestion and presentation, and the child's baseline health status. Thus, decisions regarding admission

should be based both on drug levels and the clinical scenario.

Patients with moderate observed toxicity or those who are at risk for such on the basis of history or initial laboratory data should be

admitted to an intermediate care floor or an appropriate observation unit for continued monitoring and treatment. Patients with

significant toxicity should be admitted to an ICU (table 27).

ADDITIONAL RESOURCES — Regional Poison Centers are available at all times for consultation on patients who are critically ill,

require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have clinical toxicologists

available for bedside consultation and/or inpatient care. Whenever available, these are invaluable resources to help in the diagnosis

and management of ingestions or overdoses. The World Health Organization provides a listing of international poison centers at its

website (www.who.int/gho/phe/chemical_safety/poisons_centres/en/index.html).

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Another helpful resource is the Cornell University Poisonous Plants Informational Database

(www.ansci.cornell.edu/plants/index.html).

SUMMARY AND RECOMMENDATIONS

Occult toxic exposure should be considered in the differential diagnosis of children who present with acute onset of

multiorgan system dysfunction, altered mental status, respiratory or cardiac compromise, unexplained metabolic acidosis,

seizures, or a puzzling clinical picture. The index of suspicion should be raised if the child is in the "at risk" age group (one

to four years of age) and/or has a previous history of poisoning. (See 'Clinical presentation' above.)

In older children and adolescents with occult poisoning suspect suicide attempts or recreational abuse of illicit or

prescription drugs. Child abuse via forced ingestion in young children also occurs, particularly in those who are younger than

one year of age. (See 'Clinical presentation' above.)

The approach to the poisoned child begins with initial evaluation and stabilization of airway, breathing, circulation, and

evaluation and treatment of disability while fully exposing the patient. (See 'Overview of approach' above and 'Initial evaluation

and stabilization' above.)

Hypoxemia and hypoglycemia are two common causes of altered mental status in the poisoned patient that should be

promptly evaluated and addressed during initial stabilization. (See 'Initial evaluation and stabilization' above.)

Administration of naloxone is indicated in patients who have depressed mental status, diminished respirations, miotic

pupils, or other circumstantial evidence of opioid intoxication. (See 'Altered mental status' above.)

History and physical examination are helpful in determining the type of poisoning in a significant number of children. (See

'Diagnosis of poisoning' above.)

Evaluation of mental status, vital signs, and pupils, along with assessment of skin and other findings (toxidrome recognition)

may provide clues to the type of poisoning and help guide empiric and directed treatment (table 1). (See 'Physical

examination' above.)

Key ancillary studies include rapid blood glucose, electrolytes with calculation of an anion gap, venous or arterial blood gas,

serum acetaminophen level, and electrocardiogram. Patients with respiratory alkalosis or metabolic acidosis and/or an

elevated anion gap also warrant measurement of a salicylate level and serum osmolality. (See 'Ancillary studies' above.)

Supportive care is the most important aspect of treatment and, when coupled with decontamination (when indicated), is

usually sufficient for complete recovery. (See 'Supportive care' above and 'Decontamination' above.)

Antidotes should be used in selected clinical scenarios by clinicians who are experienced in their use, or after consultation

with available experts such as those at regional Poison Control Centers (in the USA, 1-800-222-1222). The World Health

Organization provides a listing of international poison centers at its website

(www.who.int/gho/phe/chemical_safety/poisons_centres/en/index.html). (See 'Antidotes' above and 'Additional resources'

above.)

Use of UpToDate is subject to the Subscription and License Agreement.

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41. Hoffman RS, Smilkstein MJ, Howland MA, Goldfrank LR. Osmol gaps revisited: normal values and limitations. J Toxicol ClinToxicol 1993; 31:81.

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49. Sporer KA, Khayam-Bashi H. Acetaminophen and salicylate serum levels in patients with suicidal ingestion or altered mentalstatus. Am J Emerg Med 1996; 14:443.

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57. Buchman AL, Dauer J, Geiderman J. The use of vasoactive agents in the treatment of refractory hypotension seen in tricyclicantidepressant overdose. J Clin Psychopharmacol 1990; 10:409.

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59. Lange RA, Cigarroa RG, Flores ED, et al. Potentiation of cocaine-induced coronary vasoconstriction by beta-adrenergicblockade. Ann Intern Med 1990; 112:897.

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Topic 6496 Version 9.0

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GRAPHICS

Poisoning syndromes (toxidromes)

Toxidrome Mental status Pupils Vital signsOther

manifestationsExamples of toxic

agents

Sympathomimetic Hyperalert,agitation,hallucinations,paranoia

Mydriasis Hyperthermia,tachycardia,hypertension,widened pulsepressure,tachypnea,hyperpnea

Diaphoresis,tremors,hyperreflexia,seizures

Cocaine,amphetamines,cathinones,ephedrine,pseudoephedrine,phenylpropanolamine,theophylline, caffeine

Anticholinergic Hypervigilance,agitation,hallucinations,delirium withmumbling speech,coma

Mydriasis Hyperthermia,tachycardia,hypertension,tachypnea

Dry flushed skin,dry mucousmembranes,decreased bowelsounds, urinaryretention,myoclonus,choreoathetosis,picking behavior,seizures (rare)

Antihistamines,tricyclicantidepressants,cyclobenzaprine,orphenadrine,antiparkinson agents,antispasmodics,phenothiazines,atropine,scopolamine,belladonna alkaloids(eg, Jimson Weed)

Hallucinogenic Hallucinations,perceptualdistortions,depersonalization,synesthesia,agitation

Mydriasis(usually)

Hyperthermia,tachycardia,hypertension,tachypnea

Nystagmus Phencyclidine, LSD,mescaline, psilocybin,designeramphetamines (eg,MDMA, MDEA)

Opioid CNS depression,coma

Miosis Hypothermia,bradycardia,hypotension,apnea,bradypnea

Hyporeflexia,pulmonary edema,needle marks

Opiates (eg, heroin,morphine,methadone,oxycodone,hydromorphone),diphenoxylate

Sedative-hypnotic

CNS depression,confusion, stupor,coma

Miosis(usually)

Hypothermia,bradycardia,hypotension,apnea,bradypnea

Hyporeflexia Benzodiazepines,barbiturates,carisoprodol,meprobamate,glutethimide,alcohols, zolpidem

Cholinergic Confusion, coma Miosis Bradycardia,hypertensionorhypotension,tachypnea orbradypnea

Salivation, urinaryand fecalincontinence,diarrhea, emesis,diaphoresis,lacrimation, GIcramps,bronchoconstriction,musclefasciculations andweakness, seizures

Organophosphateand carbamateinsecticides, nerveagents, nicotine,pilocarpine,physostigmine,edrophonium,bethanechol,urecholine

Serotoninsyndrome

Confusion,agitation, coma

Mydriasis Hyperthermia,tachycardia,hypertension,tachypnea

Tremor, myoclonus,hyperreflexia,clonus, diaphoresis,flushing, trismus,rigidity, diarrhea

MAOIs alone or with:SSRIs, meperidine,dextromethorphan,TCAs, L-tryptophan

CNS: central nervous system.

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Drugs and toxins that cause hypoxia/hypoxemia

By CNS depression

Opiates

Barbiturates

Ethanol, ethylene glycol, methanol, isopropylalcohol

Sedative-hypnotics (usually if co-ingested withanother CNS depressant)

Tricyclic antidepressants

Clonidine

By impairing oxygen diffusion

Opiates

Salicylates

Hydrocarbons (aspiration pneumonitis)

Paraquat

Smoke inhalation

Phosgene and chlorine

By complications

Any CNS depressant can result in aspiration.

By paralysis of the ventilatory muscles

Neuromuscular blockers (pancuronium, vecuronium,succinylcholine, etc.)

Organophosphates and carbamates

Snakebites

Tetanus toxin

Strychnine

Botulinum toxin

Simple asphyxiants (Displace oxygen in thelungs)

Methane

Propane

Nitrogen

Carbon dioxide

Cellular asphyxiants (Inability to deliver orutilize oxygen by the cell)

Carbon monoxide

Cyanide

Hydrogen sulfide

Methemoglobinemia

Sulfhemoglobinemia

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Drug- and toxin-induced changes in blood pressure and pulse

Hypertension withtachycardia

Sympathomimetics

Amphetamines

Cocaine

Ephedrine

Pseudoephedrine

Theophylline

Caffeine

Methylphenidate

Cathinones

Anticholinergics

Antihistamines

TCAs (early)

Phenothiazines (some)

Antiparkinson agents

Muscle relaxants

Clozapine

Central hallucinogens

Designer amphetamines

Lysergic aciddiethylamide (LSD)

Phencyclidine (PCP)

Synthetic cannabinoids

Envenomations

Black widow spider bite

Scorpion stings

Drug withdrawal states

MAOIs (foods withtyramine)

Nicotine

Cholinergic agents(sometimes)

Organophosphates

Carbamates

Thyroid hormone

Hypertension withbradycardia

Alpha-adrenergicagonists

Phenylpropanolamine

Phenylephrine

Phentermine

Ergot alkaloids

Sumatriptan

Clonidine (early)

Guanfacine

Imidazolines

Tetrahydrozoline

Oxymetazoline

Cholinergic agents

Organophosphates

Carbamates

Steroid hormones

Glucocorticoids

Mineralocorticoids

Estrogen

Progesterone

Androgens

Yohimbine

Heavy metals

Lead

Disulfiram reaction(early)

Hypotension withtachycardia

Beta-adrenergicagonists

Theophylline

Albuterol

Isoproterenol

Terbutaline

Caffeine

Disulfiram reaction(late)

Toxic alcohols

Isopropyl alcohol

Carbon monoxide

Alpha-adrenergicantagonists

Phenothiazines

TCAs

Hydralazine

Heavy metals (acute)

Iron

Arsenic

Colchicine

Nitrates

Sodium nitroprusside

Hypotension withbradycardia

Beta-blockers

Calcium-channelblockers

Cardiac glycosides

Digoxin

Digitalis purpurea

Oleander

Red squill

Bufotenin

Clonidine

Alpha-methyldopa

Cyanide

Carbon monoxide (late)

Opiates

Sedative-hypnotics

Barbiturates

Benzodiazepines

Cholinergics

Organophosphates

Carbamates

Antiarrhythmics

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Drug- and toxin-induced electrocardiographic abnormalities

Bradycardia/AVblockade

Beta blockers

Calcium channelblockers

Cardiac glycosides

Digoxin

Digitoxin

Red squill

Digitalis lanata

Digitalis purpurea

Bufotenin

Oleander

Alpha-adrenergicagonists

Phenylpropanolamine

Clonidine

Imidazolines

Cholinergics

Organophosphates

Carbamates

Opioids

Sedative-hypnotics

Magnesium

Supraventriculartachycardia

Sympathomimetics

Amphetamines

Cocaine

Theophylline

Caffeine

Methylphenidate

Ephedrine

Pseudoephedrine

Albuterol

Dobutamine

Epinephrine

Dopamine

Anticholinergics

Antihistamines

TCAs

Phenothiazines

Clozapine

Atropine

Scopolamine

Thyroid hormone

Cellular asphyxiants

Carbon monoxide

Drug withdrawal states

Ventriculartachycardia

Sympathomimetics

Cocaine

Amphetamines

Theophylline

Antidepressants

TCAs

Antipsychotics

Phenothiazines

Chlorinatedhydrocarbons

Chloral hydrate

Solvents

Fluoride

Cardiac glycosides

Potassium

QRS and QTintervalprolongation

Antidepressants

Antipsychotics

Antihistamines

Diphenhydramine

Astemizole

Terfenadine

Antiarrhythmics

Quinidine

Disopyramide

Procainamide

Propafenone

Flecainide, encainide

Amiodarone

Calcium channelblockers (rare)

Beta blockers (rare)

Propoxyphene

Organophosphateinsecticides

Antimicrobials

Amantadine

Azithromycin

Chloroquine

Erythromycin

Pentamidine

Quinine

Quinolones (eg,ciprofloxacin)

Arsenic

Thallium

Fluoride

Citrate

Lithium

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Drug- and toxin-induced mental status alterations

Central nervous system depression

Anticholinergics

Antihistamines

Belladonna alkaloids

Phenothiazines

Antidepressants

Cyclic antidepressants

Selective serotonin reuptake inhibitors

Monoamine oxidase inhibitors

Antipsychotics

Simple asphyxiants

Carbon dioxide

Inert gases

Cellular asphyxiants

Carbon monoxide

Cyanide

Hydrogen sulfide

Methemoglobinemia

Lithium

Cholinergics

Organophosphates

Carbamates

Sympatholytics

Beta blockers

Clonidine

Sedative-hypnotics

Benzodiazepines

Barbiturates

Muscle relaxants

Hypoglycemic agents

Heavy metals

Opiates

Antiepileptics

Mushrooms

Salicylates

Gamma-hydroxybutyrate

Volatile inhalants

Alcohols

Agitation

Amantadine

Sympathomimetics

Amphetamines

Cocaine

Caffeine

Phenylpropanolamine

Theophylline

Cathinones

Anticholinergics

Antihistamines

Atropine

Scopolamine

Antiparkinson agents

Antispasmodics

Muscle relaxants

Plants containing belladonna alkaloids

Phenothiazines

Tricyclic antidepressants

Salicylates

Central hallucinogens

Lysergic acid diethylamide (LSD)

Phencyclidine

Mescaline

Psilocybin

Ketamine

Designer amphetamines

Synthetic cannabinoids

Drug withdrawal states

Lithium

Carbon monoxide

Hypoglycemic agents

Heavy metals

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Drug- and toxin-induced electrolyte abnormalities

Hyperkalemia

Cardiac glycosides

Fluoride

Hypokalemia

Beta-adrenergic agonists

Albuterol

Theophylline

Epinephrine

Methylphenidate

Caffeine

Diuretics

Toluene

Barium

Hypocalcemia

Ethylene glycol

Oxalate

Fluoride

Hyperglycemia

Beta-adrenergic agonists

Albuterol

Theophylline

Epinephrine

Caffeine

Calcium channel blockers

Iron

Vacor (rodenticide)

Hypoglycemia

Ackee fruit (unripe)

Beta blockers

Insulin

Oral hypoglycemic agents

Ethanol

Quinine

Salicylate

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Toxic time bombs (delayed clinical toxicity)

Acetaminophen

Pennyroyal oil

Carbon tetrachloride

Mushrooms

Amanita (amatoxin)

Lepiota (amatoxin)

Gyromitra (gyromitrin)

Cortinarius (orellanine/orelline)

Toxic alcohols

Ethylene glycol

Methanol

Sustained-release preparations

Calcium-channel blockers

Beta-blockers

Lithium

Theophylline

Enteric-coated preparations

Aspirin

Monoamine oxidase inhibitors

Drug packet ingestion (heroin, cocaine)

Oral hypoglycemic agents

Diphenoxylate

Methylene chloride

Paraquat/diquat

Cyanogenic glycosides

Flouride

Warfarin/superwarfarin

Brodifacoum

Neurotoxic snake envenomation

Antimetabolites

Colchicine

Methotrexate

Alkylating agents

Fat-soluble organophosphate insecticides

Ergotamines

Heavy metals

Lead

Thallium

Mercury

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Agents causing fatal poisonings among children younger than six years of age*

Analgesic drugs

Fumes, gases, vapors (eg, carbon monxide)

Cough and cold preparations

Insecticides and pesticides

Antidepressant drugs

Cardiovascular drugs

Cosmetics and personal care products

Hydrocarbons

Stimulants and illicit drugs

* Excluding bites and envenomations.Data from: Annual Reports of the American Association of Poison Control Centers Toxic Exposure SurveillanceSystem.

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Medications and toxins potentially fatal to toddler in one or two doses

DrugEstimated

minimum fataldose

Major effects

Benzocaine (eg, Orajel®) <20 mg/kg Methemoglobinemia, seizures

Beta blockers Unclear Seizures, hypoglycemia, bradycardia,hypotension

Calcium antagonists <40 mg/kg Bradycardia, hypotension

Camphor Approximately 50mg/kg

Seizures, CNS depression, respiratorydepression

Chloroquine <30 mg/kg Seizures, arrhythmias

Clonidine Unclear Bradycardia, hypotension, CNS depression

Diphenyoxylate (eg, Lomotil®) 1.2 mg/kg CNS depression, respiratory depression

Imidazoline-derivedsympathomimetics (eg, Visine®,Afrin®)

Unclear Lethargy, miosis, hypotension, bradycardia,respiratory depression, shock

Lindane Approximately 6mg/kg

Seizures, CNS depression

Methadone Approximately 5mg/kg

CNS depression, respiratory depression

Methyl salicylate Approximately 200mg/kg

Seizures, acidosis, cardiovascular collapse

Opioids (eg, methadone, long-acting morphine)

Unknown Miosis, CNS depression, respiratorydepression

Phenothiazines Approximately 20mg/kg

Seizures, arrhythmias, CNS depression

Phenylpropanolamine Unclear Arrhythmia, intracranial bleed

Quinidine Approximately 50mg/kg

Seizures, arrhythmia, CNS depression

Quinine Approximately 80mg/kg

Seizures, arrhythmias, retinal injury

Sulfonylureas <1 mg/kg Hypoglycemia

Theophylline Approximately 50mg/kg

Seizures, arrhythmias

Tricyclic antidepressants Approximately 15mg/kg

Seizures, arrhythmias, hypotension

Toxic alcohols (eg, methanol,ethylene glycol)

0.3 mL/kg CNS depression

Adapted from:1. Osterhoudt KC. The toxic toddler: drugs that can kill in small doses. Contemp Pediatr 2000; 17:73.2. Liebelt EL, Shannon MW. Small doses, big problems: a selected review of highly toxic common medications.

Pediatr Emerg Care 1993; 9:292.3. Koren G. Medications which can kill a toddler with one tablet or teaspoonful. J Toxicol Clin Toxicol 1993; 31:407.4. Henry K, Harris CR. Deadly ingestions. Pediatr Clin North Am 2006; 53:293.5. Michael JB, Sztajnkrycer MD. Deadly pediatric poisons: nine common agents that kill at low doses. Emerg Med

Clin North Am 2004; 22:1019.

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Drug- and toxin-induced temperature abnormalities

Hyperthermia

Increased heat production

Muscular hyperactivity/rigidity

Sympathomimetics

Cocaine

Amphetamines

Phenylpropanolamine

Ephedrine

Cathinones

Anticholinergics

Drug withdrawal states

Lithium

Central hallucinogens

Phencyclidine

Lysergic acid diethylamide (LSD)

Designer amphetamines (MDMA, MDEA)

Synthetic cannabinoids

Drugs causing recurrent seizures

Isoniazid

Theophylline

Strychnine

Neuroleptic malignant syndrome

Serotonin syndrome

MAO inhibitors

Malignant hyperthermia

Impaired heat dissipation

Impaired sweating

Anticholinergic agents

Antihistamines

Phenothiazines

Tricyclic antidepressants

Increased metabolic rate

Uncoupled oxidative phosphorylation

Salicylates

Dinitrophenol, pentachlorophenol

Thyroid hormone

Hypersensitivity reactions

Metal fume fever

Polymer fume fever

Hypothermia

Opioids

Sedative-hypnotics

Benzodiazepines

Barbiturates

Alcohols

Sympatholytics

Beta blockers

Clonidine

Alpha-adrenergic antagonists

Hypoglycemic agents

Antipsychotics

General anesthetic agents

Carbon monoxide

Drugs which cause flaccid coma

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Drugs and toxins associated with respiratory dysfunction

Tachypnea/hyperventilation

Sympathomimetics

Amphetamines

Cocaine

Caffeine

Theophylline

Nicotine

Cathinones

Central hallucinogens

Lysergic acid diethylamide (LSD)

Phencyclidine

Designer amphetamines

Synthetic cannabinoids

Anticholinergics

Drug withdrawal states

Salicylates

Dinitrophenol, pentacholorphenol

Drug-associated hepatic failure

Acetaminophen

Amanita mushrooms

Cellular asphyxiants

Carbon monoxide

Cyanide

Hydrogen sulfide

Methemoglobinemia

Toxins that induce pulmonary edema

Opioids

Pulmonary irritants

Drugs that induce metabolic acidosis (respiratorycompensation)

Methanol

Ethylene glycol

Alcoholic ketoacidosis

Iron

Isoniazid

Bradypnea/hypoventilation

CNS depressants

Opioids

Sedative-hypnotics

Alcohols

Antidepressants

Antipsychotics

Sympatholytics

Volatile inhalants (solvents)

Cholinergics

Muscle relaxants

Antiepileptics

Respiratory muscle failure

Botulism

Carbamates

Neurotoxic snake envenomation

Neuromuscular blocking agents

Organophosphates

Paralytic shellfish poisoning (saxitoxin)

Puffer fish poisoning (tetrodotoxin)

Strychnine

Tetanus

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Drug- and toxin-induced ocular abnormalities

Mydriasis

Sympathomimetics

Cocaine

Caffeine

Ephedrine

Amphetamines

Methylphenidate

Cathinones

Anticholinergics

Atropine

Scopolamine

TCAs

Antihistamines

Antiparkinson agents

Muscle relaxants

Antispasmodics

Phenothiazines (some)

Plants (with belladonna alkaloids)

Hallucinogens

LSD

Mescaline

Psilocybin

Designer amphetamines

Miscellaneous

Glutethimide

MAOIs

Nicotine

Serotonin syndrome

Drug withdrawal states

Miosis

Opioids

Heroin

Morphine

Hydromorphone

Oxycodone

Hydrocodone

Codeine

Propoxyphene

Sedative-hypnotics

Barbiturates

Benzodiazepines

Alcohols (with deep coma)

Zolpidem and related medications

Cholinergics

Nerve agents

Organophosphate insecticides

Carbamate insecticides

Pilocarpine

Edrophonium

Physostigmine

Sympatholytics

Clonidine

Oxymetazoline

Tetrahydrazoline

Antipsychotics

Miscellaneous

Phencyclidine

Nystagmus

Barbiturates

Carbamazepine

Phencyclidine

Phenytoin

Lithium

Ethanol

Toxic alcohols

Organophosphates

Scorpion stings

Strychnine

MAOIs

Serotonin syndrome

Ketamine

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Drug- and toxin-induced skin abnormalities

Red and flushed

Anticholinergic agents

Antihistamines

TCAs

Atropine

Scopolamine

Belladonna alkaloids

Phenothiazines

Boric acid

Disulfiram reaction

Disulfiram/ethanol

Cephalosporins/ethanol

Solvents/ethanol

Coprinusmushrooms/ethanol

Monosodium glutamate

Scombroid fishpoisoning

Rifampin

Carbon monoxide (rare)

Pale anddiaphoretic

Sympathomimetics

Cocaine

Amphetamines

Theophylline

Caffeine

Ephedrine

Phenylpropanolamine

Cathinones

Cholinergic agents

Organophosphates

Carbamates

Nerve agents

Central hallucinogens

Lysergic aciddiethylamide (LSD)

Phencyclidine

Mescaline

Psilocybin

Designer amphetamines

Synthetic cannabinoids

Arsenic

Salicylates

Cyanotic

Methemoglobinemia

Sulfhemoglobinemia

Hypoxemia

Desquamation

Stevens-Johnsonsyndrome

Toxic epidermalnecrolysis

Boric acid

Heavy metals

Arsenic

Mercury

Thallium

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Drug- and toxin-induced movement disorders

Seizures

Propranolol

Insecticides (eg,organophosphates, carbamates)

Lidocaine and other localanesthetics

Sympathomimetics

Cocaine

Amphetamines

Theophylline

Caffeine

Nicotine

Drug withdrawal states

Antidepressants

TCAs

Bupropion

Citalopram

Escitalopram

Fluvoxamine

Venlafaxine

Amoxapine

Maprotiline

Antipsychotics

Phenothiazines

Clozapine

Salicylates

Camphor

Isoniazid

Chemical nerve agents (eg,soman, VX)

Lithium

Hypoglycemic agents

Cyanide

Carbon monoxide

Meperidine

Propoxyphene

Orphenadrine

Antihistamines (rare)

Lindane

Gyromitra-containing mushrooms

Heavy metals

Antimicrobials

Imipenem

Tremors/myoclonus

Lithium

Antipsychotics

Sympathomimetics

Cocaine

Theophylline

Amphetamines

Caffeine

Albuterol

Methylphenidate

Cathinones

Anticholinergics

Antihistamines

TCAs

Drug Withdrawal states

Heavy metals

Rigidity/parkinsonism

Antipsychotics (neuroleptics)

Metoclopramide

Amoxapine

Carbon monoxide (delayed)

Methanol

Ethylene glycol

Phencyclidine

MAOIs

Serotonin syndrome

Black widow spider bite

Lithium

Methaqualone

MPTP (designer meperidine)

Manganese

Strychnine

Carbon disulfide

Cyanide

Malignant hyperthermia

Neuroleptic malignant syndrome

Postanoxic injury from any agent

Choreoathetosis

Anticholinergics

TCAs

Antihistamines

Antiepileptics

Phenytoin

Carbamazepine

Weakness/paralysis

Barium (hypokalemia)

Magnesium

Solvent abuse

Toluene

Gasoline

Heavy metals

Mercury

Thallium

Insecticides

Organophosphates

Carbamates

Nicotine

Botulism

Neurotoxic snake envenomation

Tick paralysis

Seafood poisoning

Paralytic shellfish

Pufferfish (fugu)

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Penicillins

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Drug- and toxin-associated odors

Odor Agent(s)

Acetone (fruity) Ethanol, isopropyl alcohol, chloroform, salicylates

Bitter almonds Cyanide

Garlic Arsenic, organophosphates, phosphorus, thallium, selenium

Mothballs Naphthalene, paradichlorobenzene

Kerosene (petroleum distillate) Organophosphates, parathion

Freshly mown hay Phosgene

Rotten eggs Hydrogen sulfide

Wintergreen Methyl salicylate

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Laboratory abnormalities associated with certain toxins or drugs

Rhabdomyolysis

Sympathomimetics

Cocaine

Amphetamines

Cathinones

Anticholinergics

Central hallucinogens

Phencyclidine

LSD

Designer amphetamine

Synthetic cannabinoids

Neuroleptics (NMS)

Malignant hyperthermia

Serotonin syndrome

Ethanol

Toluene

Isoniazid

Strychnine

Antidepressants

Sedative-hypnotics

Snake bite

Tetanus

Opioids

Toxic alcohols

Cellular asphyxiants

Corticosteroids

Any agent that causes extremeagitation, hyperthermia,seizures, prolonged coma

Hepatotoxicity

Acetaminophen

Ethanol

Amanita mushrooms

Isoniazid

Phenytoin

Halogenated hydrocarbons

Carbon tetrachloride

Heavy metals

Iron

Gyromitra mushrooms

Paraquat

Phenylbutazone

Phosphorus (yellow)

Methotrexate

Rifampin

Oral contraceptives

Vinyl chloride

Androgens

Alpha-methyldopa

Halothane

Valproic acid

Tetracycline

Erythromycin estolate

Dimethylformamide

Allopurinol

Sulfonamides

Pennyroyal oil

Salicylates

Chlorpromazine

Troglitazone

Pyrrolizidine alkaloids (plants)

Nitrofurantoin

Methemoglobinemia

Nitrates

Nitroglycerin

Well water

Silver nitrate

Nitrites

Amyl nitrite

(Iso)butyl nitrite

Trinitrotoluene

Aniline dyes

Phenazopyridine

Chlorates

Dapsone

Hydrazines

Local anesthetics

Benzocaine

Lidocaine

Prilocaine

Phenacetin

Toluidine

Toluenediamine

Sulfonamides

Aromatic amines

Nitrobenzene

Chloroquine

Primaquine

Naphthalene

Nitroprusside

Chlorobenzene

Nitrous gases (arc welders)

Metoclopramide

Phenols

Pyridine

Arsine

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Agents that result in acid-base disturbances*

Acid-base disturbances Drug or toxin

Respiratory alkalosis Aspirin (early)

Metabolic acidosis Methanol (delayed)

Paraldehyde, phenformin

Iron, isoniazid

Lactate (cyanide, carbon monoxide, theophylline,methemoglobin inducers)

Ethanol

Ethylene glycol (delayed)

Salicylates

Toluene

Ibuprofen

Metformin

Respiratory acidosis Barbiturates

Opiates

Combinations of sedative-hypnotics

Neuromuscular blocking agents

Metabolic alkalosis Diuretics

Milk alkali syndrome

Combined respiratory alkalosis andmetabolic acidosis

Aspirin

Adapted from Fulop, M. J Emerg Med 1998; 16:97; and Rutecki, GW, Whittier, FC. Consultant 1991; 44.

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Drug- and toxin-induced alterations in the anion gap

Increased anion gap withmetabolic acidosis(>13 meq/L)*

Methanol

Ethylene glycol

Ethanol (alcoholic ketoacidosis)

Salicylates

Isoniazid

Iron

Glycol ethers

NSAID

Ketoprofen

Naproxen

Phenylbutazone

Sympathomimetics

Cocaine

Theophylline

Caffeine

Cathinones

Albuterol

Increased anion gap withmetabolic acidosis(>13 meq/L) (cont)

Salicylates

Dinitrophenol

Inorganic acid

Metformin

Phenformin

Paraldehyde

Formaldehyde

Toluene

Sulfur (elemental)

Colchicine

Fluroacetate

Cellular asphyxiants

Carbon monoxide

Cyanide

Hydrogen sulfide

Methemoglobinemia

Propylene glycol

Benzyl alcohol

Phenol

Strychnine

Vacor

Decreased anion gap(<6 meq/L)

Hypermagnesemia

Hypercalcemia

Bromide

Nitrates

Lithium

Iodide

Spironolactone

Ammonium chloride

Acetazolamide

* Any poison causing seizure, hypoxemia, shock (hypotension), cellular anoxia, or rhabdomyolysis will result in ahigh anion gap metabolic acidosis from increased serum lactic acid concentrations.

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Increased osmolal and oxygen saturation gaps

Increased osmolal gap (normal 5 ± 7[SD] m0sm/L)

Acetone

Ethanol

Ethylene glycol

Glycerol

Hypermagnesemia (>9.5 mEq/L)

Isopropyl alcohol

Mannitol

Methanol

Propylene glycol

Benzyl alcohol

Sorbitol

Ethyl ethers

Glycol ethers

Increased oxygen saturation gap (>5percent difference)

Carbon monoxide

Cyanide

Sulfhemoglobinemia

Hydrogen sulfide

Methemoglobin

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Urinary calcium oxalate monohydrate crystals underpolarized light

Urine sediment viewed under polarized light showing coarse,needle-shaped calcium oxalate monohydrate crystals. Thesecrystals have a similar appearance to hippurate crystals.Courtesy of W Merrill Hicks, MD.

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Calcium oxalate crystals in the urine

Urine sediment showing both dumbbell-shaped calcium oxalatemonohydrate (long arrow) and envelope-shaped calcium oxalatedihydrate (short arrows) crystals. Although not shown, themonohydrate crystals may also have a needle-shapedappearance. The formation of calcium oxalate crystals isindependent of the urine pH.Courtesy of Frances Andrus, BA, Victoria Hospital, London, Ontario.

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Urine testing for drugs of abuse

Drug Duration of detectability in urineDrugs causing false positive

preliminary urine screens

Amphetamines 2 to 3 days Ephedrine, pseudoephedrine,phenylephrine, selegiline, chlorpromazine,trazodone, bupropion, desipramine,amantadine, ranitidine

Cocaine 2 to 3 days Topical anesthetics containing cocaine

Marijuana 1 to 7 days (light use); 1 month withchronic moderate to heavy use

Ibuprofen, naproxyn, dronabinol, efavirenz,hemp seed oil

Opiates 1 to 3 days Rifampin, fluoroquinolones, poppy seeds,quinine in tonic water

Phencyclidine 7 to 14 days Ketamine, dextromethorphan

Adapted from: The Medical Letter 2002; 44:71.

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Commonly available serum quantitative levels

Drug or toxin Toxic level

Acetaminophen >150 mg/L at 4 hours (if later, plot on nomogram)

Salicylate >30 mg/dL or 300 mg/L

Theophylline >20 mcmol/L

Phenobarbital >50 mg/L

Carbamazepine >12 mg/L

Phenytoin >20 mg/L

Valproic acid >150 mg/L

Digoxin >2.0 ng/L (distribution takes approx. 6 hours)

Ethanol >100 mg/dL

Ethylene glycol >20 mg/dL

Methanol >20 mg/dL

Carboxyhemoglobin >10 percent

Methemoglobin >15 percent

Lithium >2.0 meq/L

Iron >500 mcg/dL

Lead >25 mg/dL

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Agents associated with noncardiogenic pulmonary edema

Irritant gases

Ammonia

Chlorine

Hydrogen sulfide

Nitrogen oxides

Phosgene

Smoke

Sulfur dioxide

Metal oxides

Acid and alkaline gases

Aldehydes

Isocyanates

Polymers

Volatile inhalants (hydrocarbons)

Gasoline

Kerosene

Butane

Beryllium

Opiates

Heroin

Methadone

Sedative-hypnotics

Ethchlorvynol

Cellular asphyxiants

Cyanide

Carbon monoxide

Salicylates

Organophosphates

Phencyclidine

Paraquat

Ethylene glycol

Heavy metals

Sympathomimetics

Beta blockers

Calcium-channel blockers

Any agent that causes prolonged hypoxia or hypotension may result in the acute respiratorydistress syndrome.

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Agents possibly radiopaque on plain x-ray

C Chlorinated hydrocarbons (eg, chloral hydrate, carbon tetrachloride)

Calcium salts (eg, calcium carbonate)

Crack vials

H Heavy metals (eg, iron, arsenic, mercury, thallium, lead)

I Iodinated compounds (eg, thyroxine)

P Psychotropics (eg, phenothiazines, lithium, cyclic antidepressants)

Packets of drugs (eg, cocaine and heroin "body packers")

Play-Doh

Potassium salts

E Enteric-coated tablets (eg, aspirin)

S Salicylates

Sodium salts

Sustained-release preparations

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Abdominal radiograph in iron overdose

Abdominal radiograph showing radiopaque iron (ferrous sulfate)tablets visualized in the stomach of an intentional overdosepatient (arrow).Courtesy of Michael J Burns, MD.

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Drug packet ingestion

Abdominal radiograph showing radiopaque drug packets ingestedby a "body packer."Courtesy of Michael J Burns, MD.

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Agents for which activated charcoal is not recommended

Heavy metals

Arsenic

Lead

Mercury

Iron

Zinc

Cadmium

Inorganic ions

Lithium

Sodium

Calcium

Potassium

Magnesium

Fluoride

Iodide

Boric acid

Corrosives

Acids

Alkali

Hydrocarbons

Alkanes

Alkenes

Alkyl halides

Aromatic hydrocarbons

Alcohols

Acetone

Ethanol

Ethylene glycol

Isopropanol

Methanol

Essential oils

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Recommended antidotes in pediatric poisonings

AntidotePoisoningindication

Pediatric dose

N-acetylcysteine AcetaminophenOral Loading dose: 140 mg/kg orally; oralmaintenance doses: 70 mg/kg every four hours for17 doses

Intravenous (IV) administration: 150mg/kg over 1hour (loading dose); 50 mg/kg IV over 4 hours;100 mg/kg IV over 16 hours

Atropine Carbamateinsecticide

0.02 mg/kg IV bolus (0.1 mg minimum dose;maximum single dose 0.5 mg for children and 1.0mg for adolescents) repeat doses titrated to effect

Organophosphateinsecticide

Crotalid antivenin Crotalid snakes 4 to 6 vials (more if severe)

Calcium gluconate and calciumchloride (10 percent)

Calcium channelblocker

Gluconate: 100 to 200 mg/kg IV Chloride: 20 to 30mg/kg IV repeat doses and IV infusions arecommon

Hydrogen fluoride(HF)

Cyanide antidote kit (maycontain sodium nitrite 3 percent,sodium thiosulfate, and/orhydroxocobalamin)

CyanideSodium thiosulfate: 400 mg/kg IV (maximum 12.5grams)

Hydroxocobalamin: 70 mg/kg IV (maximum 5grams)

Sodium nitrite: 6 mg/kg by slow IV infusion(maximum 300 mg, only give if not contraindicatedand hydroxocobolamin is not available), refer toUpToDate topics on cyanide poisoning

Deferoxamine Iron 5 to 15 mg/kg per hour IV infusion, titrated toeffect

Digoxin immune Fab Digoxin Empiric dosing: 10 to 20 vials IV bolus fo life-threatening toxicity; see package insert for otherdosing regimensDigitoxin

Natural product(eg, plants,toads)

Dimercaprol (BAL, Britishantilewisite)

Acute arsenic 2.5 to 4 mg/kg IM

Inorganic mercury

Lead (withencephalopathy)

Data from: Dart, RC, Goldfrank, LR, Chyka, PA, Lotzer, D. Combined evidence-based literature analysis and consensusguidelines for stocking of emergency antidotes in the United States. Ann Emerg Med 2000; 36:126 and Clinical policyfor the initial approach to patients presenting with acute toxic ingestion or dermal or inhalation exposure. Ann EmergMed 1999; 33:735.

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Recommended antidotes in pediatric poisonings (continued)

AntidotePoisoningindication

Pediatric dose

Ethanol (10percent)

Methanol Loading dose 10 mg/kg IV or PO, followed by maintenance dose 1to 2 mL/kg per hour IV or PO

Ethylene glycol

Fomepizole (4-methylpyrazole)

Methanol 15 mg IV bolus, then 10 mg/kg IV every 12 hours for four doses;after these, increase dose back to 15 mg/kg

Ethylene glycol

Glucagon Beta-adrenergicantagonist

0.15 mg/kg IV bolus followed by 0.1 mg/kg per hour IV infusiontitrated to effect

Calcium channelblocker

Methylene blue Methemoglobinemia 1 to 2 mg/kg slow IV infusion, repeat doses are common

Naloxone Acute opioidpoisoning

0.4 to 2 mg IV, titrated to effect

Pralidoximechloride (PAM)

Organophosphateinsecticide

20 to 40 mg/kg slow IV infusion, followed by 5 to 10 mg/kg perhour continuous infusion or 20 mg/kg every four hours

Pyridoxine Isoniazid (INH) 1 gm per gram ingested or empiric dosing 75 mg/kg IV bolus up to5 g

Sodiumbicarbonate

Tricyclicantidepressant

1 to 2 mEq/kg IV bolus, titrate repeat boluses to QRS duration donot exceed arterial pH 7.55)

Cocaine

Salicylates 150 mEq + 40 mEq KCl in 1L of D5W infused to maintain urineoutput at 1 to 2 mL/kg per hour and a urine pH approximately 7.5

Adapted from Dart, RC, Goldfrank, LR, Chyka, PA, Lotzer, D. Combined evidence-based literature analysis andconsensus guidelines for stocking of emergency antidotes in the United States. Ann Emerg Med 2000; 36:126 andClinical policy for the initial approach to patients presenting with acute toxic ingestion or dermal or inhalationexposure. Ann Emerg Med 1999; 33:735.

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Intoxications in which enhanced elimination techniques may be used

Ion Trapping

Aspirin

Phenobarbital

Multi-dose Charcoal

Phenobarbital

Dapsone

Aspirin

Quinine/quinidine

Theophylline

Carbamazepine

Hemodialysis

Ethylene glycol

Methanol

Isopropyl alcohol

Ethanol

Aspirin

Theophylline

Phenobarbital

Lithium

Hemoperfusion

Theophylline

Chelation

Iron

Mercury

Lead

Arsenic

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Criteria for ICU admission of poisoned patient

CNS depression, including significant lethargy, coma (Glasgow coma scale ≤6)

Agitation requiring chemical or physical restraint

Respiratory depression (PCO2 >45 mmHg), hypoxia or respiratory failure (ARDS), and/or endotrachealintubation

Hypotension (SBP ≤80 mmHg)

Seizures that are prolonged or recurring

Second or third degree AV block on ECG

Nonsinus cardiac rhythm on ECG

Significant acid-base disturbances (eg, metabolic acidosis with pH ≤7.2)

Significant metabolic abnormalities requiring close monitoring or aggressive correction

Extremes of temperature (eg, hyperthermia with T >104°F)

Poisoning with a "toxic time bomb"

Ingested drug packets, sustained-release preparations

Quantitative level of drug which predicts unfavorable outcome

Need for invasive hemodynamic monitoring (eg, pulmonary artery catheter or arterial line) or cardiac pacing

Need for whole bowel irrigation to enhance GI elimination of poison

Need for emergency hemodialysis, hemoperfusion, hemofiltration

Need for emergency antidote which requires close monitoring (eg, crotalid antivenin, Digibind,physostigmine, naloxone drip)

Ischemic chest pain from toxin (eg, cocaine, carbon monoxide)

TCA or other drug exposure with QRS >120 msec or QTc >500 msec