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8/10/13 Approach to the child with occult toxic exposure
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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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46. Osterloh JD. Utility and reliability of emergency toxicologic testing. Emerg Med Clin North Am 1990; 8:693.
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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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54. Florez MV, Evans JM, Daly TR. The radiodensity of medications seen on x-ray films. Mayo Clin Proc 1998; 73:516.
55. Roy TM, Ossorio MA, Cipolla LM, et al. Pulmonary complications after tricyclic antidepressant overdose. Chest 1989;96:852.
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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