Chemical and drug poisoning in children …

General Child Neurology

Updated 12.11.2024
Released 01.01.2012
Expires For CME 12.11.2027

Chemical and drug poisoning in children

Authors: Natalija Farrell PharmD, Johanna Caicedo MD

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Editor: Nina F Schor MD PhD

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Chemical and drug poisoning in children

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Introduction

Overview

Childhood poisoning often presents with delirium, seizures, and decreased consciousness, prompting neurologists to evaluate these cases. Ingestions in children under 5 years of age are typically accidental, stemming from exploratory behavior, whereas adolescents are more likely to engage in self-harm or recreational drug use. Many ingestions can be deceptively dangerous, making it crucial to recognize the signs of both common and severe poisonings and to treat them appropriately. This article will focus on common poisoning syndromes and toxins that affect the nervous system.

Physiology

Numerous mechanisms, including ingestion, inhalation, dermal contact, envenomation, and transplacental exposure may poison children. Pediatric patients ingest a higher dose per kilogram compared with adults who ingest the same amount of drug because of their small size.

Pediatric patients are more vulnerable to poisoning than adults due to differences in anatomy and physiology. Children have a higher body surface area-to-weight ratio, increased skin perfusion, and greater skin hydration, leading to increased dermal absorption and higher toxicity risks. They are also more susceptible to dehydration and insensible losses. Children have a higher respiratory rate and minute ventilation, meaning they inhale more toxins quickly, with carbon monoxide being a common and severe risk, particularly for younger children.

Children cannot maintain hyperpnea as long as adults due to their higher metabolic rate, and they desaturate faster during apnea or respiratory insufficiency, leading to worse outcomes in cases of poisoning that cause acidosis or respiratory depression. This can result in more pronounced acidemia, such as with salicylism or toxic alcohol poisoning. Additionally, children have limited glycogen stores, increasing the risk of fasting hypoglycemia from ethanol, beta-blockers, and other agents affecting glucose homeostasis.

Children have limited cardiovascular reserve under stress, relying heavily on heart rate to maintain cardiac output due to a reduced ability to increase stroke volume. Increased adrenergic tone helps sustain normal blood pressure until shock becomes severe. Consequently, a child with early circulatory failure may seem deceptively stable, with normal blood pressure but tachycardia. However, if a drug disrupts this delicate balance, such as calcium channel blockers or organophosphorus pesticides causing bradycardia, it can quickly lead to circulatory arrest, even in small doses (18).

Evaluation

HISTORY

When poisoning is suspected, a focused history should be obtained once the life-support phase is completed. For a child with known or suspected exposure, ask about the toxin, timing, and quantity ingested. However, young poisoned children often present with vague symptoms and no clear exposure history. Key indicators of occult poisoning include age (1 to 5 years), pica behavior, acute onset, multiple organ system dysfunction, altered sensorium, and an unusual clinical picture. Consider family and social factors, such as recent environmental changes, visits to homes with new or less child-proofed medications, family members with illnesses or new prescriptions, or high-risk situations like holiday gatherings or recent moves with accessible medications and products. Inconsistent history or concerning medical or family backgrounds may suggest malicious poisoning.

In evaluating a pediatric patient with a toxicological emergency, obtaining a detailed history is crucial to determine the exposure route. For pharmaceutical products, identify the xenobiotic, dose, dosage form (eg, tablet, capsule, patch, liquid), release mechanism (immediate or extended-release), and quantity ingested (74). For nonpharmaceutical exposures, packaging or ingredient lists can help identify toxic substances. Photographs of potentially consumed plants or mushrooms can be shared with experts for identification. Medical personnel or family members should provide pill bottles, containers, or medication lists to account for all potential exposures.

Timing is crucial in treating poisoning, as some gastrointestinal decontamination methods and antidotes are effective only within specific time windows after ingestion. After topical exposure, dermal decontamination may be necessary. Clinicians should also consider the exposure time and the xenobiotic's toxicokinetics when determining the observation period.

PHYSICAL EXAMINATION

Examine vital signs, capillary perfusion, and core temperature. Focus on central and autonomic nervous system findings, pupillary size and reactivity, and abnormalities in the skin, mucous membranes, and cardiorespiratory or gastrointestinal systems. Check for characteristic odors on breath or clothing. Toxidromes, such as those from opioids, sympathomimetics, cholinergics, and anticholinergics, are as indicative in children as in adults, though age-adjusted vital signs and developmental status should be considered. Examination findings suggestive of abuse or neglect may also raise the possibility of malicious poisoning.

TOXIDROMES

The specific xenobiotic ingested may often be unknown, particularly if children were unsupervised or the patient is unwilling to disclose information. In such cases, clinicians must rely on physical examination findings, vital signs, and laboratory data. Toxidromes, symptom clusters associated with certain drug classes (29), can aid in identifying single-drug exposures and predicting clinical outcomes. For multi-substance exposures, toxidromes can help rule out certain ingestions based on symptoms, though overlapping features of xenobiotics may complicate diagnosis (41; 18) (Table 2).

Table 2. Common Pediatric Toxidromes

	Vital Signs
	Heart rate	Blood pressure	Respiratory rate	Temp	Key physical examination findings	Examples
Sympathomimetic	↑	↑	↑	↑	Agitation, delirium, diaphoresis, tremor, myoclonus, fussiness, decreased sleep, crying	Cocaine, amphetamines, cathinones, pseudoephedrine
Opioid	↓	↓	↓	↓	Sedation, miosis, hyporeflexia, decreased bowel sounds, sleeping more than usual, poor eating	Morphine, oxycodone, fentanyl, heroin, methadone, buprenorphine
Sedative or hypnotic	↓	↓	—/↓	—/↓	Decreased level of consciousness, agitation, hyporeflexia, sleeping more than usual, poor eating, respiratory depression, particularly with high doses or combination with other respiratory depressants (eg, opioids)	Benzodiazepines, nonbenzodiazepine soporifics (eg, Z-drugs such as eszopiclone, zaleplon, zolpidem)
Anticholinergic	↑	↑*	—	↑	Delirium or hallucinations, flushed, dry mucous membranes, mydriasis, increased urinary retention, fussiness, decreased sleep, crying	Antihistamines, antipsychotics, tricyclic antidepressants, atropine, scopolamine
Cholinergic	↑/↓	—	—	—	Diarrhea, diaphoresis, seizures, involuntary urination, emesis, lacrimation, salivation, decreased sleep	Organophosphates, nerve agents
*Tricyclic antidepressants may reduce blood pressure and cause dysrhythmias. Information from: (41; 18; 54).

Sympathomimetic toxidrome

Sympathomimetics work by increasing adrenergic tone. Sympathomimetic toxicity is marked by hypertension, tachycardia, mydriasis, diaphoresis, agitation, and hyperactive bowel sounds. This pattern is commonly observed in adolescents using cocaine or amphetamines and can occur in younger children with accidental stimulant exposure.

Patients with sympathomimetic intoxication most commonly present with acute agitation that is often severe, and many patients require immediate intervention to limit self-injury.

Psychostimulant use, notably cocaine and methamphetamine, raises the risk of acute ischemic and hemorrhagic stroke. This elevated risk is multifactorial and related to acute blood pressure elevation, vasospasm, and thrombogenic platelet effects (09).

Chronic cocaine abuse is also associated with accelerated atherosclerosis through repeated endothelial damage, raising stroke risk in chronic users. Recent cocaine use has been associated with an increased risk of aneurysmal subarachnoid hemorrhage and higher rates of aneurysm rebleeding, delayed cerebral ischemia, and in-hospital mortality. Cocaine is a leading cause of drug-induced strokes (69), though amphetamines, phenylpropanolamine, phencyclidine, ephedrine, and pseudoephedrine also pose stroke risks (64).

Hyperthermia from sympathomimetics arises due to central thermoregulatory dysfunction, with additional contributions from heat exposure and increased heat production from agitation and motor activity. Uncontrolled hyperthermia significantly raises morbidity and mortality risks and can lead to rhabdomyolysis, liver failure, disseminated intravascular coagulation, and multiorgan failure. Therefore, it should be treated aggressively.

Seizures are seen in sympathomimetic overdose because of the lowered seizure threshold that occurs with acute ingestions. Seizures occur in patients with known seizure disorders and those without who may have a first-time seizure in the setting of sympathomimetic ingestion. Cocaine use is associated with a 1% to 2% incidence of seizures, usually single tonic-clonic events that often resolve without intervention. However, large doses (2 to 8 grams) can cause refractory seizures and be fatal. Treatment primarily involves sedation, and hypoglycemia must be addressed (48).

Injecting amphetamines or cocaine can lead to endocarditis, septic emboli, and brain abscesses, potentially causing permanent neuronal changes and psychosis (16).

Anticholinergic toxidrome

The primary cause of the anticholinergic toxidrome is antagonism of muscarinic receptors. Clinicians should know the anticholinergic toxidrome, especially when a reliable history is unavailable. The mnemonic “red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, full as a flask” helps recall the classic signs: flushing, anhidrosis, dry mucous membranes, mydriasis, altered mental status, fever, and urinary retention. Decreased bowel sounds are also common. CNS effects can include delirium, hallucinations, agitation, restlessness, confusion, staccato speech, and picking at clothing or bedding, CNS effects may persist after peripheral features have resolved. Seizures and jerking movements may also occur although the mechanism is unclear (52). Morbidity and mortality result from cardiotoxicity, rhabdomyolysis, and status epilepticus. However, most patients will recover fully with rapid identification and aggressive therapy (15).

Numerous medications can produce anticholinergic toxicity (Table 3).

Table 3. Medications Producing Anticholinergic Toxicity

Amines

Atropine
Benztropine
Oxybutynin
Scopolamine
Glycopyrrolate
Ipratropium bromide
Trihexyphenidyl

Antihistamines

Diphenhydramine
Doxylamine
Pheniramine
Cetirizine
Hydroxyzine
Meclizine
Fexofenadine
Loratadine

Antidepressants

Amitriptyline
Clomipramine
Desipramine
Nortriptyline
Doxepin
Amoxapine

Antipsychotics

Chlorpromazine
Clozapine
Mesoridazine
Olanzapine
Promethazine
Quetiapine
Thioridazine

Serotonergic toxidrome

Serotonin is synthesized in presynaptic neurons through the decarboxylation and hydroxylation of L-tryptophan. Serotonin syndrome occurs due to excessive stimulation of 5-HT2A and 5-HT1A postsynaptic receptors. Within the presynaptic neuron, serotonin is metabolized by monoamine oxidase, and presynaptic serotonin receptors regulate its release and reuptake. The serotonergic system helps regulate wakefulness, thermoregulation, and vascular tone (50) (Table 4).

Table 4. Major Mechanisms of Common Substances and Medications That Modulate the Serotonergic System

Increased serotonin synthesis	Inhibit serotonin metabolism	Increased serotonin exocytosis	Increased 5-HT1 activation	5-HT2A antagonism	Reuptake inhibition
Tryptophan	MAO-I St. John's Wort Linezolid Tedizolid Methylene blue Procarbazine Syrian rue	Cocaine Ecstasy (MDMA) Dextromorphan	Buspirone Triptans Ergot derivatives Opiates LSD Mirtazapine Trazodone Lithium	Atypical antipsychotics Chlorpromazine	SSRI SNRI

Serotonin syndrome occurs when alterations in serotonergic transmission lead to clinical manifestations. This imbalance typically emerges within 24 hours of starting a new serotonergic agent, changing the dose of an existing one, or any factor affecting serotonergic metabolism. It can result from therapeutic medication use, illicit drugs, or intentional overdose. Various substances can precipitate serotonin toxicity through different mechanisms. Serotonin syndrome can present with a wide range of symptoms, not all of which may be present in every case. Vital signs typically show tachycardia and hypertension, often fluctuating due to autonomic instability. Hyperthermia may result from impaired temperature regulation. Physical examination findings may include altered mental status (eg, agitation), ocular clonus, dilated pupils, akathisia, tremor, deep tendon hyperreflexia, muscle clonus (inducible or spontaneous), muscle rigidity, positive Babinski signs, flushed skin, diaphoresis, and increased bowel activity. Neuromuscular symptoms, particularly hyperreflexia and muscle clonus, are often more pronounced in the lower extremities (67).

Diagnosis is primarily based on clinical findings, often using the Hunter Toxicity Criteria, which are the most accurate. A patient must have used a serotonergic agent and meet one of the following conditions: spontaneous clonus, inducible clonus with agitation or diaphoresis, ocular clonus with agitation or diaphoresis, tremor with hyperreflexia, hypertonia with temperature above 38°C and ocular clonus, or inducible clonus (13).

Severity varies. Mild serotonin syndrome may present with tachycardia, shivering, diaphoresis, mydriasis, intermittent tremor, or myoclonus. Moderate cases often feature hyperthermia, pronounced hyperreflexia or clonus, and mild agitation or confusion. Severe cases may include hyperthermia, pronounced rigidity (especially in the lower extremities), hypertension, or tachycardia and can rapidly progress to shock. Complications may involve renal failure, rhabdomyolysis, transaminitis, and disseminated intravascular coagulation, mainly due to hyperthermia and muscular rigidity (14). Typically, symptoms present within 6 hours of starting or increasing a pro-serotonergic drug, but mild cases may develop chronically.

Opioid toxidrome

There are three main opioid receptors: mu, delta, and kappa opioid receptors. All three receptor types are G protein-coupled receptors distributed primarily in the central nervous system, blocking ascending pain signals. However, these receptors also affect the immune system, the heart, and the gastrointestinal tract. Mu 2 receptors (OP3B) are localized to the periaqueductal gray matter, nucleus raphe magnus, medial thalamus, and medulla and are responsible for body analgesia and respiratory depression. Mu 2 activation diminishes chemoreceptor sensitivity to hypercapnia and decreases response to hypoxia, which may produce seizures (53).

Because of the mechanism of action of CNS depression, particularly the mu-opioid receptor in the pons, the most severe presentation of opioid overdose is apnea. In mild overdoses, the respiratory rate is slowed and tidal volumes are often decreased, with reduced response to hypercapnia (08).

Opioid toxicity in pediatric patients is still a leading cause of overdose-related fatalities among adolescents (45). Before the COVID-19 pandemic, there was an increase in pediatric exposures to methadone and buprenorphine (59; 24; 32). Regulatory changes during the pandemic have further increased the availability of these opioids in the home (34), potentially leading to more accidental exposures. The availability of liquid and sublingual formulations of these drugs can also exacerbate the risk of accidental ingestion.

Opiate toxicity is characterized by sedation, miosis, respiratory depression, peripheral vasodilation, hypotension, and decreased bowel motility. Multiple opiates have no direct pupillary effects, and meperidine and propoxyphene produce mydriasis (55; 53). Flushing and bronchospasm may occur secondary to histamine release. Anoxia-associated acute leukoencephalopathy carries a 23% mortality rate (39).

Complications of opiate abuse include endocarditis, cellulitis or abscesses of the extremities, epidural spinal abscesses, osteomyelitis, and myelopathy. Brain abscesses may complicate intravenous drug use of any type (39). Abscesses may raise intracranial pressure or serve as an irritating focus, producing seizures or strokes. Patients who are immobile due to acute toxicity are at risk for compartment syndrome, rhabdomyolysis, and peripheral nerve compression. Heroin use, in particular, is linked to the development of transverse myelopathy, neuropathy, spongiform leukoencephalopathy, seizures, and stroke (23).

Certain clinical manifestations warrant special mention. Propoxyphene causes cardiac sodium channel antagonism, leading to EKG changes mirroring those of tricyclic antidepressants. Seizures may occur secondary to hypoxia in the setting of an overdose of any opioid but are direct effects of meperidine, propoxyphene, and tramadol. Muscular rigidity has been reported with rapid administration of fentanyl.

Cholinergic toxidrome

Acetylcholinesterase breaks down acetylcholine in cholinergic synapses throughout the central, peripheral, and autonomic nervous systems. Inhibition of this enzyme leads to excessive acetylcholine accumulation and overstimulation of muscarinic and nicotinic receptors, resulting in acute cholinergic syndrome or crisis (28). Organophosphates irreversibly inhibit acetylcholinesterase, whereas carbamates typically cause reversible inhibition. Organophosphates are used in industrial settings and as pesticides, whereas carbamates include drugs like physostigmine, neostigmine, rivastigmine, meprobamate, and carisoprodol (68). Annually, nearly 3,000,000 people are exposed to these agents worldwide, and up to 300,000 die from poisoning. Organophosphorus poisoning is a leading cause of self-poisoning and suicide globally (31).

Cholinergic toxicity is marked by excessive muscarinic stimulation, presenting with miosis, bradycardia, bronchorrhea, urinary and fecal incontinence, and seizures. Severe airway secretions, bronchospasm, and respiratory muscle weakness can quickly lead to death (56; 19). Nicotinic symptoms may also occur, including muscle weakness that can progress to fasciculations and paralysis. Central nervous system effects include rapid loss of consciousness, seizures, and suppression of the medullary respiratory center (56).

Initially described by Wadia and colleagues and later by Senanayake and Karalliedde, intermediate syndrome typically occurs 24 to 96 hours after organophosphate exposure. It is characterized by cranial nerve palsies, weakness of neck flexors and proximal muscles, decreased deep tendon reflexes, and, ultimately, diaphragmatic weakness leading to type II respiratory failure. Dimethyl organophosphate compounds, such as methyl parathion and fenthion, are more frequently associated with intermediate syndrome than diethyl compounds. With adequate supportive care, which can involve prolonged mechanical ventilation, most patients have a complete resolution of neurologic dysfunction within 2 to 3 weeks (11). Etiology has not been elucidated but may be reflected in ineffective acetylcholinesterase reactivation (28).

Seizures are more common with organophosphate nerve agents like sarin and novichok. Some cases may show myocardial injury, indicated by a modest increase in troponin. Several organophosphates also affect neuropathy target esterase. Inhibition of neuropathy target esterase produces a breakdown of the myelin lining of nerve fibers, generating polyneuropathy (65) and organophosphate-induced delayed neuropathy, which usually appears after several weeks and leads to paralysis and phrenic nerve involvement, potentially causing respiratory failure.

Other important intoxications to consider

Cardiovascular drugs. Nonselective beta-blockers with alpha1-antagonist activity often cause peripheral vasodilation and hypotension. The lipophilic nature of propranolol can lead to CNS effects, including altered mental status and seizures, which are most common with propranolol toxicity (66).

Antidepressants. Tricyclic antidepressants, although not used as commonly as they were in the past, are still widely available, and new uses, such as the treatment of fibromyalgia, keep them on the market and in patients’ homes. Tricyclic antidepressant toxicity primarily manifests as cardiotoxicity. Although most unintentional pediatric tricyclic antidepressant exposures are asymptomatic, minor effects can occur with ingestions over 5 mg/kg (2.5 mg/kg for desipramine, nortriptyline, and trimipramine). Moderate to severe toxicity is likely with ingestions over 10 to 20 mg/kg. Diagnostic ECG findings include QRS prolongation greater than 100 milliseconds in lead aVR, alongside potential cardiac effects such as hypotension, tachycardia, and dysrhythmias. Additional symptoms may include seizures, agitation, coma, and anticholinergic effects like dry mouth and mydriasis (Beuhler 2010; 70; 76).

Bupropion, a unicyclic antidepressant with selective reuptake inhibition of dopamine, norepinephrine, and serotonin, also has peripheral alpha1-adrenergic agonism and possible sodium channel blockade. Significant symptoms are rare with ingestions below 10 mg/kg, but doses around 18.6 mg/kg are associated with symptomatic cases. Overdoses can lead to sinus tachycardia, nausea, hyperactivity, hallucinations, seizures, hypertension, and dysrhythmias, including cardiac arrest. Notably, overdoses in ages 13 to 18 years, with QTc greater than 500 milliseconds and tachycardia over 140 beats/minute, have a higher risk of seizures. Bupropion overdoses are more likely to cause seizures, hallucinations, and major outcomes compared to SSRIs and require more intensive interventions, such as cardiopulmonary resuscitation, intubation, vasopressors, and benzodiazepines. Compared to tricyclic antidepressant overdoses, bupropion is less likely to cause hypotension but still presents significant risks (70; 76).

Antimalarial. Chloroquine and hydroxychloroquine, used for malaria and autoimmune diseases, can cause severe toxicity, especially at high doses. These drugs inhibit sodium and potassium channels, leading to cardiac dysrhythmias, hypotension, and respiratory issues. CNS effects include drowsiness, coma, and seizures. Lethal doses are typically between 30 and 50 mg/kg. Management focuses on supportive care, including monitoring cardiac and respiratory function and treating seizures with benzodiazepines. There is no specific antidote, so treatment is symptomatic and supportive (26; 27).

Toxic alcohols. Toxic alcohols, including methanol, ethylene glycol, and isopropanol (ethanol is not covered here), are water-soluble, rapidly absorbed, and renally eliminated. Methanol is metabolized to formaldehyde and formic acid, whereas ethylene glycol is converted to glycolic acid and oxalic acid. Both alcohols' toxicities arise from these harmful metabolites. Methanol ingestion can lead to visual impairments, seizures, and central nervous system depression, whereas ethylene glycol can cause acute kidney injury and hypocalcemia. Clinical signs include an elevated osmolar gap initially and an anion gap metabolic acidosis later. Treatment should start empirically with fomepizole or ethanol based on clinical suspicion and osmol gap measurement, as toxic alcohol levels may take 24 to 48 hours to be reported (42; 62).

Camphor. Camphor is a terpenoid found in camphor trees and used for traditional medicine and as an ingredient in some mothballs. If ingested, it can cause coma, apnea, agitation, hyperreflexia, myoclonic jerks, and seizures. Deaths from respiratory failure and intractable seizures have been reported.

Salicylates. Salicylates, commonly found in medications like aspirin and topical pain relievers, can be highly toxic, especially in the form of wintergreen oil, which contains up to 1,400 mg of salicylate per milliliter. Salicylate toxicity typically presents with respiratory alkalosis due to respiratory center stimulation, followed by metabolic acidosis from mitochondrial poisoning. Severe cases can lead to death from acidosis, cerebral edema, and pulmonary edema.

Hydrocarbons. More than 28,000 cases of hydrocarbon exposure, primarily unintentional, are reported annually to United States poison centers, with over 28,000 cases. Children younger than 5 years account for most of nearly 14,000 annual pediatric cases. Although fatalities are rare, moderate effects requiring supportive care are common, especially following ingestion. Hydrocarbon ingestion, occurring in about 75% of cases in this age group, typically results from exploratory behavior with unsecured or improperly stored hydrocarbons. In adolescents and adults, exposure often stems from recreational inhalant misuse.

CNS depression often results from hydrocarbon exposure due to direct neuronal effects of specific agents or hypoxia from severe lung injury. Volatile hydrocarbons, such as aromatic and halogenated types, are highly lipid-soluble and absorbed through the lungs or gastrointestinal tract. They quickly diffuse into the CNS, where they affect neurotransmitter receptors, including the excitatory N-methyl-D-aspartate receptor and the inhibitory gamma-aminobutyric acid receptor. This interaction contributes to CNS depression. The euphoric effects of inhaling toluene and chlorinated hydrocarbons make them appealing for recreational use among older children and adolescents.

Cannabis. As of May 2022, recreational cannabis was legal in 19 states, with 37 states regulating cannabis for medical use. In Massachusetts, the incidence of Poison Control Center calls reporting pediatric cannabis exposures increased by 140% after legalization. Acute cannabis toxicity is frequently encountered in emergency departments due to the widespread availability and various forms of Cannabis sativa, including smoking, inhalation, and ingestion. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the primary cannabinoids associated with euphoria, hallucinations, and sedation. Synthetic cannabinoids, which have a higher affinity for CNS receptors and more potent euphoric effects, are harder to detect on drug tests. Symptoms of cannabis exposure can vary: adolescents may experience anxiety, tachycardia, and dysphoria, whereas severe cases can lead to cannabis-induced hyperemesis syndrome, characterized by persistent nausea, vomiting, and abdominal pain. In young children, high concentrations of THC in edibles can cause altered mental status, decreased muscle coordination, and, in severe cases, seizures. There is no antidote for cannabis intoxication. Management is symptomatic and includes observation for 8 to 12 hours or until mental status returns to baseline. Gut decontamination with activated charcoal is not effective. Respiratory depression, intubation, and ICU admission are more common following exposure to concentrated cannabis products, especially in young children (07; 46).

Laundry pods. Laundry detergent pods, introduced to the U.S. market in 2010, pose a significant risk, especially to young children. Between March 2012 and April 2013, exposures to these pods in children under 6 increased by over 600%, largely due to their candy-like appearance and bright colors. Fortunately, the incidence of morbidity and mortality has decreased since the implementation of product safety changes (60).

These pods contain highly concentrated detergent within a water-soluble membrane. The primary route of exposure is ingestion, though ocular exposure also occurs. Ingestions can lead to nausea, vomiting, and, in severe cases, lethargy, coma, respiratory distress, and pulmonary edema. Other less common symptoms of toxicity include coughing, choking, seizures, gastric burns, and respiratory arrest (61).

Dextromethorphan. Dextromethorphan is an over-the-counter cough suppressant and a selective sigma receptor agonist used in the U.S. since the 1950s. Dextromethorphan has a history of abuse for its hallucinogenic and dissociative effects, leading to its temporary removal from the market in the 1970s and subsequent reformulation into less palatable forms to deter misuse. Teenagers and young adults are the primary abusers via a practice known as "robotripping." Dextromethorphan toxicity can also result from the co-formulated substances in dextromethorphan-containing products, such as acetaminophen (hepatotoxicity), diphenhydramine (anticholinergic effects), ethanol (depressant effects), and pseudoephedrine (sympathomimetic effects) (20; 71).

Lead poisoning. Lead remains a common environmental toxin affecting children. Any detectable lead level is abnormal. Evidence shows that blood lead levels below 10 µg/dL are associated with adverse effects in infants and children. However, the U.S. Centers for Disease Control and Prevention reference value was lowered to 5 µg/dL in 2012 (37). Of the 32 jurisdictions that reported data to the CDC in 2014, prevalence data indicate that 76,680 U.S. children younger than 5 years had blood lead levels of 5 to 9 ug/dL (58).

Older children and adolescents experience fatigue, abdominal pain, back pain, myalgias, and paresthesias (33). Younger children exhibit problems with concentration, memory, and learning. Several meta-analyses have demonstrated that children’s IQ scores drop 2 to 3 points for every 10 ug/dL increase in blood lead level (79). Deficits in reading, mathematics, memory, language development, and motor skills are all documented sequelae of lead exposure (79). Typically, these sequelae are irreversible.

Acute lead poisoning in children may be secondary to ingestion or inhalation of volatilized lead. Symptoms of acute exposure include vomiting, apathy, bizarre behavior, loss of recently acquired developmental skills, and ataxia followed by seizures, delirium, and coma. Patients may develop devastating cerebral edema. It is important to note that “acute” presentations may be the culmination of the increasing body burden of lead secondary to ongoing exposure. Typically, children will have venous levels between 70 and 100 micrograms per deciliter when acute symptoms are present.

Lead alters fundamental nervous system functions, including calcium-modulated signaling, even in very low concentrations. Children exposed to lead are usually at a developmental age at which dendritic pruning occurs along with other crucial developmental events. The hippocampus is targeted, and learning and memory functions are significantly inhibited. Furthermore, lead exposure is responsible for peripheral neuropathy, which is thought to be related to Schwann cell dysfunction (53). Imaging studies of adults who had elevated blood lead levels in childhood show region-specific reductions in brain volume and changes in the microstructure of the brain.

Lead also has effects outside of the neurodevelopmental area. Hematologic effects include red cell fragility and lysis. Lead interferes with both ferrochelatase and delta amino levulinic acid, interfering with heme synthesis and causing anemia (79). Kidneys are common targets; hypertension is a frequent consequence. Delayed growth can also be a systemic consequence of lead exposure.

The risk of exposure to lead continues to be a major childhood hazard. Lead is in household dust, the soil, and lead pipes in some cities’ water supply, as well as lead paint and some ceramics. There is no safe level of lead (44; American Association of Poison Control Centers 2014; 03).

Elevation of whole blood lead level confirms the diagnosis. Although there is no safe or normal blood lead level, the CDC uses a 5 µg/dL blood level as the reference value (37).

Because there is no safe blood lead level, all children with a detectable lead level warrant education and an environmental investigation (63). Initial management requires identifying the lead source and removing the child from the exposure.

Venous blood levels are used to determine the necessity of chelation therapy. Chelation is not routinely recommended for children with blood lead levels less than 45 µg/dL. Although chelation with oral agents has been shown to reduce blood lead levels transiently, evidence has not found improved neurodevelopmental outcomes in children with blood lead levels less than 45 µg/dL who receive chelation. Even with chelation, the primary treatment for lead poisoning is removing the child from further lead exposure.

Asymptomatic children with blood lead levels of 45 µg/dL or greater should receive chelation therapy as soon as the blood lead level is confirmed with a venous lead level and only when the child is in a lead-safe environment (which may indicate hospitalization). The agent of choice is oral succimer. If the child cannot, for whatever reason, take succimer, then continuous infusion of calcium disodium edetate is suggested. Chelation should be performed in consultation with a toxicologist or other clinician experienced with chelating agents.

Symptomatic children with lead encephalopathy should be admitted to a pediatric intensive care unit to receive combined chelation therapy with dimercaprol and calcium disodium edetate. When inpatient chelation is complete, the child may be discharged if the clinical status has improved and the blood lead level is below 25 µg/dL. The child must be discharged to a lead-free environment, and the caretaker must have the discharge medication, such as succimer, and demonstrate knowledge of its administration. Close follow-up is necessary (63).

Synthetic cannabinoids. Synthetic cannabinoids are a growing group of chemicals designed to mimic THC's effects by acting on cannabinoid receptors. Unlike THC, most synthetic cannabinoids are undetectable in standard urine tests and are often altered to evade regulations. Synthetic cannabinoids are usually sprayed on plant material to be smoked, ingested, or vaporized.

Unlike marijuana, which contains compounds that temper THC's effects, synthetic cannabinoids are full agonists, binding more strongly to cannabinoid receptors. This can lead to severe toxic effects, including seizures, psychosis, kidney injury, and death. Synthetic cannabinoid users are more likely to require medical attention than cannabis users, with higher risks of agitation and cardiotoxicity. Physical symptoms include delayed pupil reactions, slurred speech, and excited delirium, with severe cases involving kidney injury, myocardial infarction, and status epilepticus. Treatment focuses on managing delirium and organ damage, with effects typically lasting about 8 hours (75; 17).

Benzodifurans: Bromo-Dragonfly, 2C-B-FLY, 3C-B-FLY. Benzodifurans, like Bromo-DragonFLY, 2C-B-FLY, and 3C-B-FLY, are potent hallucinogens that act through 5-HT2A agonism and serotonin release. Bromo-DragonFLY, the first of its kind, is an amphetamine derivative with a "dragonfly" shape, offering greater potency and a longer duration of action than other phenethylamines, with effects lasting up to 3 days.

These compounds can cause severe sympathomimetic toxicity, including tachycardia, hypertension, seizures, and prolonged vasoconstriction, which can lead to digit auto-amputation, renal failure, and even death. Overdose treatment involves supportive care, particularly with repeated doses of benzodiazepines for seizures, though vasoconstriction is often resistant to a wide variety of vasodilatory therapies (22; 17).

Diagnosis

In evaluating a child with unknown ingestion, the laboratory assessment should focus on identifying metabolic disturbances and guiding treatment (77). Key tests include:

	• Blood glucose. Rapid assessment to identify hypoglycemia or hyperglycemia.
	• Acid-base status. Using venous or arterial blood gas to assess metabolic acidosis or alkalosis.
	• Electrolytes. To evaluate for imbalances.
	• Blood urea nitrogen and creatinine. For assessing kidney function.
	• Serum osmolality. Particularly if toxic alcohol ingestion is suspected or there is a high anion gap.
	• AST and ALT. To evaluate liver function if acetaminophen toxicity is suspected.
	• Coagulation profile (PT, PTT, INR). In cases of abnormal bleeding or suspected anticoagulant or rodenticide ingestion.
	• Quantitative acetaminophen serum concentration. If overdose is suspected or there is suicidal intent.
	• Quantitative salicylate serum concentration. In patients with respiratory alkalosis or metabolic acidosis.
	• Urine dipstick test. To check for ketones and myoglobinuria.
	• Urine pregnancy test. For postmenarcheal females.
	• ECG. Changes on the electrocardiogram can indicate poisoning by certain agents and may require targeted interventions. For instance, sinus bradycardia and decreased AV node conduction (1st- to 3rd-degree heart block) may indicate a calcium channel or beta-adrenergic receptor blockade, and a widened QRS interval or ventricular arrhythmia may necessitate the administration of sodium bicarbonate infusion (1 mEq/kg). QT prolongation is a common effect of many drugs, and patients with this condition should be closely monitored with cardiac surveillance. Additionally, any other QT-prolonging medications, such as ondansetron, should be avoided to prevent further complications.
	• Toxicology screens. The need for toxicology screening in patients with occult toxic exposure depends on the clinical scenario. Toxicology screening is rarely necessary in children who have unintentional ingestion and are asymptomatic or have clinical findings that are consistent with the history. It is indicated in children with:
		- Uncertainty about the diagnosis of poisoning.
		- Coma of unknown etiology.
		- A potential need for an antidote that requires rapid identification of the toxic agent.
		- Suspicion of child abuse or Munchausen syndrome by proxy.

Treatment

Children with significant ocular or dermal contamination require prompt topical decontamination based on the substance involved and clinical situation. Gastrointestinal decontamination practices have shifted, with most poisoned patients managed effectively in the emergency department without such interventions. Gastric emptying with syrup of ipecac is no longer recommended, and gastric lavage is rarely used except in cases of high-lethality ingestions within 30 to 60 minutes due to its complexity and risk of complications in young children (10).

Single-dose activated charcoal is no longer routinely used but may be considered if the patient presents soon after ingestion of substances that bind to activated charcoal and supportive or antidotal treatments are insufficient. Activated charcoal is contraindicated for caustics and hydrocarbons due to the risk of mucosal injury and pulmonary aspiration. When used, the pediatric dose is generally 1 g/kg, often mixed in a fruit-flavored drink to improve acceptance. However, activated charcoal administration can induce vomiting in about 20% of children, and use of a nasogastric tube is associated with risks such as inadvertent tracheal placement, especially in obtunded or uncooperative children.

Activated charcoal is often recommended to be administered within 1 hour of ingestion, but this guideline is based on outdated data from before the development of extended-release medications. Factors such as anticholinergic agents (eg, diphenhydramine) that slow gastric motility and drugs like salicylates and bupropion, which can form concretions or pharmacobezoars, can delay the dissolution and absorption of ingested substances. Therefore, activated charcoal can still be beneficial beyond the 1-hour window if there is ongoing absorption and it is deemed appropriate based on the clinical context (Table 5).

Table 5. Gastrointestinal Decontamination Strategies

	Dosing	Role in Therapy	Contraindications or Warnings
Single-dose activated charcoal (adsorption)	• Dosing of 0.5-1 g/kg is recommended by some sources. • Infants: < 1 year oral, nasogastric: 10-25 g • Children: 1-12 years oral, nasogastric: 25-50 g • Adolescents: oral, nasogastric: 25-100 g. • Palatability may be increased by mixing in cola or chocolate milk or adding cherry flavoring.	• Within approximately 1 hour of xenobiotic ingestion. • Multidose activated charcoal may be considered for initial gastrointestinal decontamination and enhanced elimination in life-threatening ingestions of carbamazepine, dapsone, phenobarbital, quinine, or theophylline.	• Gastrointestinal discontinuity or perforation • Anticipated need for endoscopic visualization • Risk of aspiration in altered mental status or airway compromise • Formulations containing sorbitol are not recommended because of the risk of severe dehydration and electrolyte imbalances. • Activated charcoal containing sorbitol should be limited to a one-time dose if used.
Whole-bowel irrigation (flush out the gastrointestinal tract)	• Polyethylene glycol + electrolyte solution • Children: oral, nasogastric: 500 mL/hr or 25 mL/kg/hr • Adolescents: oral, nasogastric: 1-2 L/hr Continued for 4-6 hours or until clear rectal effluent	• Not routinely recommended • Consider in potentially toxic ingestions of sustained-release products, bezoars, or extended-release products • Xenobiotic not adsorbed by activated charcoal (eg, iron, lithium) • Passage of illicit drugs in body “stuffers” or “packers” or other foreign bodies.	• Nausea or vomiting gastrointestinal discontinuity or perforation • Hemodynamic instability
Gastric lavage (gastric irrigation)	• Not routinely recommended. For more information, see (10).	• Not routinely recommended because of its association with life-threatening complications (eg, aspiration pneumonitis or pneumonia, esophageal or gastric perforation, fluid or electrolyte imbalances).	• Craniofacial abnormalities • Concomitant head trauma gastrointestinal discontinuity or perforation • Risk of aspiration in altered mental status or airway compromise
Information from: (05; 21; 10).

Although supportive care is usually appropriate and sufficient, several xenobiotics have preferred antidotes to be considered when appropriate in certain cases.

Antidote administration is appropriate when an antidote exists for a poisoning, the actual or predicted severity of the poisoning warrants its use, the 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 drug conversion to more toxic metabolites (Table 6).

Table 6. Recommended Antidotes in Pediatric Poisonings

Antidote	Poisoning indication	Pediatric dose
N-acetylcysteine	Acetaminophen	• Oral loading dose: 140 mg/kg orally • Oral maintenance doses: 70 mg/kg every 4 hours for 17 doses • Intravenous administration: - 150 mg/kg over 1 hour (loading dose) - 50 mg/kg intravenously over 4 hours - 100 mg/kg intravenously over 16 hours
Atropine	Carbamate insecticide Organophosphate insecticide	• 0.02 mg/kg intravenously bolus (0.1 mg minimum dose; maximum single dose 0.5 mg for children and 1.0 mg for adolescents) repeat doses titrated to effect
	Carbamate insecticide Organophosphate insecticide
Crotalid antivenin	Crotalid snakes	• Four to six vials (more if severe)
Calcium gluconate and calcium chloride (10%)	Calcium channel blocker Hydrogen fluoride	• Gluconate: 100 to 200 mg/kg intravenous • Chloride: 20 to 30 mg/kg intravenous • Repeat doses and intravenous infusions are common
	Calcium channel blocker Hydrogen fluoride
Cyanide antidote kit (may contain sodium nitrite 3%, sodium thiosulfate, or hydroxocobalamin)	Cyanide	• Sodium thiosulfate: 400 mg/kg intravenous (maximum 12.5 grams) • Hydroxocobalamin: 70 mg/kg intravenous (maximum 5 grams) • Sodium nitrite: 6 mg/kg by slow intravenous infusion (maximum 300 mg, only give if not contraindicated and hydroxocobalamin is not available)
Deferoxamine	Iron	• 5 to 15 mg/kg per hour intravenous infusion, titrated to effect
Digoxin immune Fab	Digoxin Digitoxin Natural products (eg, plants, toads)	• Empiric dosing: 10 to 20 vials intravenous bolus for life-threatening toxicity; see package insert for other dosing regimens.


Dimercaprol (BAL, British antilewisite)	Acute arsenic Inorganic mercury Lead (with encephalopathy)	• 2.5 to 4 mg/kg intramuscular


Ethanol (10%)	Methanol Ethylene glycol	• Loading dose 10 mg/kg intravenously or orally, followed by maintenance dose 1 to 2 mL/kg per hour intravenously or orally
	Methanol Ethylene glycol
Fomepizole (4-methylpyrazole)	Methanol Ethylene glycol	• 15 mg intravenous bolus, then 10 mg/kg intravenous every 12 hours for four doses; after these, increase dose back to 15 mg/kg
	Methanol Ethylene glycol
Glucagon	Beta-adrenergic antagonist Calcium channel blocker	• 0.15 mg/kg intravenous bolus followed by 0.1 mg/kg per hour intravenous infusion titrated to effect
	Beta-adrenergic antagonist Calcium channel blocker
Methylene blue	Methemoglobinemia	• 1 to 2 mg/kg slow intravenous infusion, repeat doses are common
Naloxone	Acute opioid poisoning	• 0.4 to 2 mg intravenous, titrated to effect
Pralidoxime chloride (PAM)	Organophosphate insecticide	• 20 to 40 mg/kg slow intravenous infusion, followed by 5 to 10 mg/kg per hour continuous infusion or 20 mg/kg every 4 hours
Pyridoxine	Isoniazid	• 1 gm per gram ingested or empiric dosing 75 mg/kg intravenous bolus up to 5 g
Sodium bicarbonate	Tricyclic antidepressant Cocaine Salicylates	• 1 to 2 mEq/kg intravenous bolus, titrate repeat boluses to QRS duration do not exceed arterial pH 7.55)

		• 150 mEq + 40 mEq KCl in 1 L of D5W infused to maintain urine output at 1 to 2 mL/kg per hour and a urine pH of approximately 7.5
Data from (04; 25; 40).

Enhanced elimination

Enhanced elimination of toxins can be crucial in specific poisonings. Urinary alkalinization is a key therapy for moderate to severe salicylate intoxication. Multiple-dose activated charcoal can increase the clearance of toxins like barbiturates, salicylates, carbamazepine, and theophylline through intestinal dialysis. Despite its potential benefits, multiple-dose activated charcoal can lead to complications such as vomiting, aspiration, and intestinal obstruction, and its clinical benefits are not always clear. Historically, multiple-dose activated charcoal was useful for managing mild to moderate theophylline toxicity, but its use is now rare in children. It may still be considered for severe salicylate or carbamazepine poisonings.

For cases with high serum concentrations of highly toxic substances, extracorporeal toxin removal methods like high-flux hemodialysis are employed to prevent severe organ damage or system collapse. Hemodialysis is effective for removing solutes and toxins with low molecular weight, minimal protein binding, and low volume of distribution, such as salicylates, toxic alcohols, lithium, and theophylline. Hemodialysis can also be lifesaving for managing metabolic disturbances and electrolyte imbalances, even if toxin removal is not substantial, as seen in metformin-associated lactic acidosis (18; 77).

Treatment consideration based on toxidromes

Sympathomimetic. Patients should be placed in a calm atmosphere. Hyperthermic patients require aggressive cooling using ice packs and conventional cooling measures. Patients with focal neurologic deficits require imaging. Physical restraints predispose to metabolic acidosis and rhabdomyolysis and should be avoided. Haloperidol interferes with heat dissipation and lowers the seizure threshold; therefore, it should also be avoided (02; 36). Benzodiazepines are the first-line agent. Beta-blockers should also be avoided for fear of unopposed alpha-agonist effects. There is no antidotal therapy for sympathomimetic exposure.

Anticholinergic. Supportive care and benzodiazepines are indicated for mild to moderate toxicity. As with sympathomimetic agents, haloperidol should be avoided (72).

Physostigmine is indicated for patients who have both peripheral and moderate central anticholinergic toxicity, ie, moderate to severe agitation or delirium. It should not be given if a condition other than pure anticholinergic poisoning is suspected, ie, tricyclic antidepressant overdose (73). Physostigmine should be administered in a monitored setting. Physostigmine may produce secretions, inhibition of vascular smooth muscle, fasciculations, weakness, and paralysis (72).

The dose of physostigmine is 0.5 to 2 mg in adolescents and adults and 0.02 mg/kg in children, up to a maximum of 0.5 mg per dose. Atropine should be available. Physostigmine should be infused over 5 minutes. Overly rapid administration may result in cholinergic symptoms or seizures. Given the brief duration of action (half-life is approximately 15 minutes), repeat dosing is often necessary (73).

Serotonergic. Initial management requires the identification and withdrawal of the offending agent. Mild or moderate serotonin syndrome will typically resolve in 24 hours. More severe cases will require the administration of intravenous fluids and administration of benzodiazepines to control agitation. Correction of hypotension or hypertension should be achieved with short-acting agents, given the characteristic autonomic instability (06). Dopamine is metabolized to epinephrine and norepinephrine by monoamine oxidase and, therefore, should be avoided. Hyperthermia and rigidity not readily controlled with cooling and sedation will require intubation and pharmacologic paralysis. Succinylcholine should be avoided, given the risk of hyperkalemia. Typically, hyperthermia resolves rapidly following paralysis.

Specific antidotal therapy includes cyproheptadine, a histamine-1 receptor antagonist with nonspecific 5-HT1A and 5-HT2A antagonistic properties and weak anticholinergic activity. Cyproheptadine is indicated if benzodiazepines and supportive care fail to improve agitation and normalize vital signs. The initial recommended dose is 12 mg, followed by 2 mg every 2 hours until symptoms are controlled. Cyproheptadine is not available in a parenteral form; the oral form may be crushed and given through a nasogastric or orogastric tube if necessary. Antipsychotic agents such as olanzapine and chlorpromazine have been considered for antidotal treatment; however, given their unproven efficacy, their use is not recommended (13).

Opiate. For mild cases, supportive care may suffice. Patients who are exhibiting significant respiratory depression require opiate antagonism with naloxone. Naloxone is an opiate receptor antagonist with a rapid onset of action. Children and adolescents with suspected opioid toxicity should receive naloxone rather than supportive care alone. Children under 20 kg should receive a dose of 0.1 mg/kg up to a maximum of 2 g per dose. Children over 20 kg can receive a dose of 2 g. Adolescents with suspected opioid addiction should receive lower doses of naloxone, similar to the adult treatment strategy, to avoid precipitating opioid withdrawal (80). Careful investigation of the chronic sequelae of opiate abuse should occur, and infectious or other complications may be addressed as they are identified (78).

The triad of respiratory depression, CNS depression, and miosis with a relatively acute onset strongly suggests opioid toxicity and requires immediate naloxone administration and ventilatory support. Delay of therapy for routine urine drug testing is not recommended. The standard naloxone dose is 0.1 mg/kg, but lower doses may be used to avoid withdrawal in patients on chronic opioid therapy. Naloxone can be given intravenously, intraosseously, endotracheally, intranasally, intramuscularly, or subcutaneously. Intravenous administration acts within 5 minutes, but if intravenous access is not available, other routes should be used to avoid delaying treatment (12). Over 50% of patients respond partially to naloxone (74; 38). Early discharge before adequate opioid clearance may result in re-sedation. For patients needing multiple naloxone doses, consider starting a naloxone infusion at half the required hourly dose (eg, 1 mg/hour if 2 mg was administered).

Cholinergic. Patients with environmental exposure to organophosphates require aggressive decontamination, including full removal of clothing and vigorous washing of the body with soap and water (19). Water itself can help deactivate some nerve agents. If less than 1 hour has passed following ingestion, activated charcoal can be given (1 g/kg with a maximum dose of 50 g). Patients with markedly depressed mental status require 100% oxygen and immediate endotracheal intubation (11; 01).

Atropine antagonizes the effect of acetylcholine. Atropine is indicated in the setting of any clinical signs of toxicity (0.05 mg/kg boluses in children or 1 mg boluses in adolescents). Patients with mild toxicity may require only 1 to 2 mg, whereas more severe cases may require hundreds of milligrams over several days. Boluses may be repeated every 3 to 5 minutes until pulmonary muscarinic signs and symptoms are alleviated (11).

Pralidoxime and other oximes are cholinesterase-reactivating agents that effectively treat both muscarinic and nicotinic symptoms. It must be administered concurrently with atropine to prevent worsening symptoms due to transient oxime-induced acetylcholinesterase inhibition. Pralidoxime can be given to patients with evidence of cholinergic toxicity or neuromuscular dysfunction or with exposures to organophosphorus agents known to cause delayed neurotoxicity. Children can be given 25 to 50 mg/kg boluses based on the severity of treatment. It should be administered slowly over 30 minutes. Rapid administration has been associated with cardiac arrest. A continuous infusion of 10 to 20 mg/kg/hr for children can be given after the bolus dose (11).

Seizure activity may be effectively managed with benzodiazepines (57).

References

01: Aman S, Paul S, Chowdhury FR. Management of organophosphorus poisoning: standard treatment and beyond. Crit Care Clin 2021;37(3):673-86. PMID 34053713
02: Amann BL, Pogarell O, Mergl R, et al. EEG abnormalities associated with antipsychotics: a comparison of quetiapine, olanzapine, haloperidol and healthy subjects. Hum Psychopharmacol 2003;18(8):641-6. PMID 14696024
03: American Academy of Pediatrics. Lead exposures in children. Health Initiatives. Available at: http://www.aap.org/. Accessed February 4, 2016.
04: Anonymous. Clinical policy for the initial approach to patients presenting with acute toxic ingestion or dermal or inhalation exposure. Ann Emerg Med 1999;33(6):735-61. PMID 10339698
05: Anonymous. Position paper: whole bowel irrigation. J Toxicol Clin Toxicol 2004;42(6):843-54. PMID 15533024
06: Arnold DH. Consultation with the specialist: the central serotonin syndrome: paradigm for psychotherapeutic misadventure. Pediatr Rev 2002;23(12):427-32. PMID 12456895
07: Assaf RR, Young KD. Trends in pediatric recreational drug use and ingestions. Adv Pediatr 2021;68:261-81. PMID 34243857
08: Azevedo K, Johnson M, Wassermann M, Evans-Wall J. Drugs of abuse-opioids, sedatives, hypnotics. Crit Care Clin 2021;37(3):501-16. PMID 34053703
09: Bachi K, Mani V, Jeyachandran D, Fayad ZA, Goldstein RZ, Alia-Klein N. Vascular disease in cocaine addiction. Atherosclerosis 2017;262:154-62. PMID 28363516
10: Benson BE, Hoppu K, Troutman WG, et al. Position paper update: gastric lavage for gastrointestinal decontamination. Clin Toxicol (Phila) 2013;51(3):140-6. PMID 23418938
11: Bird S, Traub SJ, Grayzel J. Organophosphate and carbamate poisoning. In: Post TW, editor. UpToDate. Waltham, MA: UpToDate, 2020.
12: Boyer EW, McCance-Katz EF, Marcus S. Methadone and buprenorphine toxicity in children. Am J Addict 2010;19(1):89-95. PMID 20132125
13: Boyer EW, Shannon M. Serotonin syndrome (serotonin toxicity). In: Post TW, editor. UpToDate. Waltham, MA: UpToDate, 2020.
14: Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352(11):1112-20. PMID 15784664
15: Broderick ED, Metheny H, Crosby B. Anticholinergic toxicity. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2023. PMID 30521219
16: Brown H, Pollard KA. Drugs of abuse: sympathomimetics. Crit Care Clin 2021;37(3):487-99. PMID 34053702
17: Caffrey CR, Lank PM. When good times go bad: managing “legal high” complications in the emergency department. Open Access Emerg Med 2017;10:9-23. PMID 29302196
18: Calello DP, Henretig FM. Pediatric toxicology: specialized approach to the poisoned child. Emerg Med Clin North Am 2014;32(1):29-52. PMID 24275168
19: Cannard K. The acute treatment of nerve agent exposure. J Neurol Sci 2006;249(1):86-94. PMID 16945386
20: Chyka PA, Erdman AR, Manoguerra AS, et al. Dextromethorphan poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila) 2007;45(6):662-77. PMID 17849242
21: Chyka PA, Seger D, Krenzelok EP, et al. Position paper: single-dose activated charcoal. Clin Toxicol (Phila) 2005;43(2):61-87. PMID 15822758
22: Coppola M, Mondola R. Bromo-DragonFly: chemistry, pharmacology and toxicology of a benzodifuran derivative producing LSD-like effects. J Add Res Ther 2012;3(4):133.
23: Dabby R, Djaldetti R, Gilad R, et al. Acute heroin-related neuropathy. J Peripher Nerv Syst 2006;11(4):304-9. PMID 17117938
24: Darracq MA, Thornton SL. Respiratory depression following medications for opioid use disorder (MOUD)-approved buprenorphine product oral exposures; National Poison Database System 2003-2019. Clin Toxicol (Phila) 2021;59(4):303-12. PMID 32894033
25: Dart RC, Goldfrank LR, Chyka PA, et al. Combined evidence-based literature analysis and consensus guidelines for stocking of emergency antidotes in the United States. Ann Emerg Med 2000;36(2):126-32. PMID 10918103
26: Della Porta A, Bornstein K, Coye A, Montrief T, Long B, Parris MA. Acute chloroquine and hydroxychloroquine toxicity: a review for emergency clinicians. Am J Emerg Med 2020;38(10):2209-17. PMID 33071096
27: Doyno C, Sobieraj DM, Baker WL. Toxicity of chloroquine and hydroxychloroquine following therapeutic use or overdose. Clin Toxicol (Phila) 2021;59(1):12-23. PMID 32960100
28: Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet 2008;371(9612):597-607. PMID 17706760
29: Erickson TB, Thompson TM, Lu JJ. The approach to the patient with an unknown overdose. Emerg Med Clin North Am 2007;25(2):249-81. PMID 17482020
30: Even KM, Armsby CC, Bateman ST. Poisonings requiring admission to the pediatric intensive care unit: a 5-year review. Clin Toxicol (Phila) 2014;52(5):519-24. PMID 24738737
31: Eyer P. The role of oximes in the management of organophosphorus pesticide poisoning. Toxicol Rev 2003;22(3):165-90. PMID 15181665
32: Farnaghi F, Gholami N, Hassanian-Moghaddam H, McDonald R, Zamanzadeh R, Zamani N. Unintentional buprenorphine and methadone poisoning in children: a matched observational study. Clin Toxicol (Phila) 2021;59(8):727-33. PMID 33475438
33: Fonte R, Agosti A, Scafa F, Candura SM. Anaemia and abdominal pain due to occupational lead poisoning. Haematologica 2007;92(2):e13-4. PMID 17405745
34: Goldsamt LA, Rosenblum A, Appel P, Paris P, Nazia N. The impact of COVID-19 on opioid treatment programs in the United States. Drug Alcohol Depend 20211;228:109049. PMID 34600258
35: Gummin DD, Mowry JB, Beuhler MC, et al. 2022 Annual Report of the National Poison Data System® (NPDS) from America's Poison Centers®: 40th Annual Report. Clin Toxicol (Phila) 2023;61(10):717-939. PMID 38084513
36: Hatzipetros T, Raudensky JG, Soghomonian JJ, Yamamoto BK. Haloperidol treatment after high-dose methamphetamine administration is excitotoxic to GABA cells in the substantia nigra pars reticulata. J Neurosci 2007;27(22):5895-902. PMID 17537960
37: Hauptman M, Bruccoleri R, Woolf AD. An update on childhood lead poisoning. Clin Pediatr Emerg Med 2017;18(3):181-92. PMID 29056870
38: Hayes BD, Klein-Schwartz W, Doyon S. Toxicity of buprenorphine overdoses in children. Pediatrics 2008;121(4):e782-6. PMID 18381506
39: Hill MD, Cooper PW, Perry JR. Chasing the dragon--neurological toxicity associated with inhalation of heroin vapour:case report. CMAJ 2000;162(2):236-8. PMID 10674060
40: Hoffman RS, Howland MA, Lewin NA, Nelson LS, Goldfrank LR. Goldfrank’s toxicologic emergencies. 10th ed. New York: McGraw-Hill, 2015.
41: Holstege CP, Borek HA. Toxidromes. Crit Care Clin 2012;28(4):479-98. PMID 22998986
42: Hoyte C, Schimmel J, Hadianfar A, Banerji S, Nakhaee S, Mehrpour O. Toxic alcohol poisoning characteristics and treatments from 2000 to 2017 at a United States regional poison center. Daru 2021;29(2):367-76. PMID 34709587
43: Koren G, Nachmani A. Drugs that can kill a toddler with one tablet or teaspoonful: a 2018 updated list. Clin Drug Investig 2019;39(2):217-20. PMID 30443871
44: Lanphear BP, Hornung R, Khoury J, et al. Low-level environmental lead exposure and children’s intellectual function: an international pooled analysis. Environ Health Perspect 2005;113(7):894-9. PMID 16002379
45: Lim JK, Earlywine JJ, Bagley SM, Marshall BD, Hadland SE. Polysubstance involvement in opioid overdose deaths in adolescents and young adults, 1999-2018. JAMA Pediatr 2021;175(2):194-6. PMID 33226412
46: Lin A, O'Connor M, Behnam R, Hatef C, Milanaik R. Edible marijuana products and potential risks for pediatric populations. Curr Opin Pediatr 2022;34(3):279-87. PMID 35634702
47: Madden MA. Pediatric toxicology: emerging trends. J Pediatr Intensive Care 2015;4(2):103-10. PMID 31110859
48: Majlesi N, Shih R, Fiesseler FW, Hung O, Debellonio R. Cocaine-associated seizures and incidence of status epilepticus. West J Emerg Med 2010;11(2):157-60. PMID 20823966
49: Matteucci MJ. One pill can kill: assessing the potential for fatal poisonings in children. Pediatr Ann 2005;34(12):964-8. PMID 16419734
50: Mohammad-Zadeh LF, Moses L, Gwaltney-Brant SM. Serotonin: a review. J Vet Pharmacol Ther 2008;31(3):187-99. PMID 18471139
51: Mowry JM, Spyker DA, Brooks DE, McMillian N, Schauben JL. Clinical toxicology 2015. Available at: http://www.tandfonline.com/. Accessed November 2015.
52: Muench J, Hamer AM. Adverse effects of antipsychotic medications. Am Fam Physician 2010;81(5):617-22. PMID 20187598
53: Nelson LS, Olsen D. Opioids. In: Nelson LS, Olsen D, et al, editors. Goldfrank’s toxicologic emergencies. 10th ed. New York: McGraw-Hill, 2015:492-509.
54: Nelson LS, Howland M, Lewin NA, et al. Initial evaluation of the patient: vital signs and toxic syndromes. In: Nelson LS, Howland M, Lewin NA, et al., editors. Goldfrank’s Toxicologic Emergencies, 11th ed. McGraw-Hill, 2019.
55: Nelson LS, Perrone J. Curbing the opioid epidemic in the United States: the risk, evaluation and mitigation strategy (REMS). JAMA 2012;308(5):457-8. PMID 22851109
56: Newmark J. Therapy for nerve agent poisoning. Arch Neurol 2004;61(5):649-52. PMID 15148139
57: Olsen KR. Poisoning and drug overdose. 6th ed. McGraw-Hill Education, 2012.
58: Raymond J, Brown MJ. Childhood blood lead levels in children aged <5 years—United States, 2009-2014. MMWR Surveill Summ 2017;66(3):1-10. PMID 28103215
59: Rege SV, Ngo DA, Ait-Daoud N, Rizer J, Sharma S, Holstege CP. Epidemiology of pediatric buprenorphine and methadone exposures reported to the poison centers. Ann Epidemiol 2020;42:50-7.e2. PMID 31992493
60: Reynolds KM, Burnham RI, Delva-Clark H, Green JL, Dart RC. Impact of product safety changes on accidental exposures to liquid laundry packets in children. Clin Toxicol (Phila) 2021;59(5):392-9. PMID 32960108
61: Rocka A, Piędel F, Madras D, Krawiec P, Pac-Kożuchowska E. Dark side of laundry pods: analysis of exposure to laundry detergent capsules in children. J Paediatr Child Health 2021;57(12):1912-6. PMID 34129255
62: Ross JA, Borek HA, Holstege CP, King JD. Toxic alcohol poisoning. Emerg Med Clin North Am 2022;40(2):327-41. PMID 35461626
63: Sample JA. Childhood lead poisoning: management. In: Post TW, editor. Waltham, MA: UpToDate, 2020.
64: Sanchez-Ramos J. Neurologic complications of psychomotor stimulant abuse. Int Rev Neurobiol 2015;120:131-60. PMID 26070756
65: Shannon MW, Borron SW, Burns MJ, Haddad LM, Winchester JF. Haddad and Winchester's clinical management of poisoning and drug overdose. 4th ed. Philadelphia: Saunders/Elsevier, 2007.
66: Shepherd G. Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers. Am J Health Syst Pharm 2006;63(19):1828-35. PMID 16990629
67: Simon LV, Torrico TJ, Keenaghan M. Serotonin syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2024.
68: Solomon GM, Moodley J. Acute chlorpyrifos poisoning in pregnancy: a case report. Clin Toxicol (Phila) 2007;45(4):416-9. PMID 17486485
69: Sordo L, Indave BI, Barrio G, Degenhardt L, de la Fuente L, Bravo MJ. Cocaine use and risk of stroke: a systematic review. Drug Alcohol Depend 2014;142:1-13. PMID 25066468
70: Spiller HA, Bosse GM, Beuhler M, Gray T, Baker SD. Unintentional ingestion of bupropion in children. J Emerg Med 2010;38(3):332-6. PMID 18657932
71: Stanciu CN, Penders TM, Rouse EM. Recreational use of dextromethorphan, "Robotripping": a brief review. Am J Addict 2016;25(5):374-7. PMID 27288091
72: Su M. Anticholinergic poisoning. In: Erickson TB, Ahrens WR, Aks SE, et al., eds. Pediatric Toxicology. McGraw-Hill, 2005.
73: Su M, Goldman M. Anticholinergic poisoning. In: Post TW, editor. Waltham, MA: UpToDate, 2020.
74: Toce MS, Burns MM, O'Donnell KA. Clinical effects of unintentional pediatric buprenorphine exposures: experience at a single tertiary care center. Clin Toxicol (Phila) 2017;55(1):12-17. PMID 27756148
75: Trecki J, Gerona RR, Schwartz MD. Synthetic cannabinoid-related illnesses and deaths. N Engl J Med 2015;373(2):103-7. PMID 26154784
76: Overberg A, Morton S, Wagner E, et al. Toxicity of bupropion overdose compared with selective serotonin reuptake inhibitors. Pediatrics 2019;144:e20183295. PMID 31278211
77: Velez LI. Approach to the child with occult toxic exposure. In: UpToDate, Connor RF, editor. Wolters Kluwer, 2024.
78: Wong J. Naloxone and nalmefene. In: Olsen KR, ed. 2012 Poisoning and drug overdose. 6th ed. McGraw-Hill, 2012.
79: Woolf AD, Goldman R, Bellinger DC. Update on the clinical management of childhood lead poisoning. Pediatr Clin North Am 2007;54(2):271-94. PMID 17448360
80: Yin S. Opioid intoxication in children and adolescents. In: Post TW, ed. Waltham, MA: UpToDate, 2020.
81: References especially recommended by the author or editor for general reading.

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All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

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Natalija Farrell PharmD

Dr. Farrell of Boston Medical Center has no relevant financial relationships to disclose.
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Nina F Schor MD PhD

Dr. Schor of the University of Rochester School of Medicine and Dentistry has no relevant financial relationships to disclose.
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Former Authors

Russell Berger MD
Steven D Salhanick MD
Ruth A Lawrence MD
Kristina Stang BS
Stephen L Nelson Jr MD PhD

ICD & OMIM codes

ICD-10: Abnormal lead level in blood: R78.71

Poisoning by other parasympathomimetics [cholinergics], accidental (unintentional): T44.1X1

Poisoning by other parasympatholytics [anticholinergics and antimuscarinics] and spasmolytics, accidental (unintentional): T44.3X1

Poisoning by, adverse effect of and underdosing of other and unspecified antidepressants: T43.2

Poisoning by, adverse effect of and underdosing of tricyclic and tetracyclic antidepressants: T43.0

Poisoning by, adverse effect of and underdosing of monoamine-oxidase-inhibitor antidepressants: T43.1

Poisoning by, adverse effect of and underdosing of phenothiazine antipsychotics and neuroleptics: T43.3

Poisoning by, adverse effect of and underdosing of butyrophenone and thiothixene neuroleptics: T43.4

Poisoning by, adverse effect of and underdosing of other and unspecified antipsychotics and neuroleptics: T43.5

Poisoning by, adverse effect of and underdosing of psychostimulants: T43.6

Poisoning by, adverse effect of and underdosing of other psychotropic drugs: T43.8

Poisoning by, adverse effect of and underdosing of unspecified psychotropic drug: T43.9
ICD-11: Harmful effects of or exposure to noxious substances, chiefly nonmedicinal as to source, not elsewhere classified: NE61

Harmful effects of drugs, medicaments or biological substances, not elsewhere classified: NE60

Unintentional exposure to or harmful effects of opioids or related analgesics: PB20

Unintentional exposure to or harmful effects of sedative hypnotic drugs or other CNS depressants: PB21

Unintentional exposure to or harmful effects of psychostimulants: PB22

Unintentional exposure to or harmful effects of cannabinoids or hallucinogens: PB23

Unintentional exposure to or harmful effects of analgesics, antipyretics or nonsteroidal anti-inflammatory drugs: PB24

Unintentional exposure to or harmful effects of antidepressants: PB25

Unintentional exposure to or harmful effects of antipsychotics: PB26

Unintentional exposure to or harmful effects of antiepileptics or antiparkinsonism drugs: PB27

Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance: PB28

Unintentional exposure to or harmful effects of multiple drugs, medicaments or biological substances: PB29

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Chemical and drug poisoning in children

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Chemical and drug poisoning in children

Cite this article

Introduction

Overview

Epidemiology

Physiology

“One pill can kill”

Table 1. Notable One-Pill-Can-Kill Medications or Classes

Evaluation

HISTORY

PHYSICAL EXAMINATION

TOXIDROMES

Table 2. Common Pediatric Toxidromes

Sympathomimetic toxidrome

Anticholinergic toxidrome

Table 3. Medications Producing Anticholinergic Toxicity

Serotonergic toxidrome

Table 4. Major Mechanisms of Common Substances and Medications That Modulate the Serotonergic System

Opioid toxidrome

Cholinergic toxidrome

Other important intoxications to consider

Diagnosis

Treatment

Table 5. Gastrointestinal Decontamination Strategies

Table 6. Recommended Antidotes in Pediatric Poisonings

Enhanced elimination

Treatment consideration based on toxidromes

References

Contributors

Authors

Editor

Former Authors

ICD & OMIM codes

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