A wide variety of medications and substances can kill a toddler who ingests just a single dose. More than 1 million children ingest toxins in the United States every year, and more than 85% of the ingestions are unintentional. Most of the children are younger than 6 years.[1]
The intent of this article is not to guide treatment of poisoned children but rather to report toxic ingestions that proved fatal in small doses. The article addresses some types of toxic ingestions and those that may cause serious illness or injury, even in small quantities.[2]
Many of the involved toxins are common in the home or in household products. Ingestion of relatively small amounts of commonly used perfumes, cosmetics, cleaning solutions, alcoholic beverages, and other products may cause serious injury or death. Medications also are a common source of toxic ingestions in small quantities. If prior precautions are not taken, visits to the homes of friends or relatives (even grandparents) or visits from guests who bring medications into the home may result in tragedy.
Ingestion of a small number of common substances and drugs may be fatal in small doses. Most pediatric ingestions are benign. A formal risk assessment is required to allow clinical decision making on the need for resuscitation, treatment, decontamination, enhanced elimination, antidote requirement, and period of observation
The American Association of Poison Control Centers (AAPC) reported that in 2017, children younger than 6 years accounted for 956,871 of the 2,115,186 total exposures, but only 12 of the 1388 total fatalities.[3]
Pathophysiology varies according to the ingested substance. Children are particularly susceptible to injury from ingestion of small doses for the following reasons:
The following medications are of most concern:
The drugs of abuse that are potentially fatal include all amphetamines (including methamphetamine and MDMA) and opiates.
Non-pharmaceuticals that pose a risk of significant toxicity include the following:
The availability of non-pharmaceuticals in the community is extensive and any potential chemical ingestion requires a detailed review of the individual components. It is beyond the scope of this article to list every potential toxic ingestion. Included in the list below are case reports of fatalities associated with specific ingestions however expert assistance is required and the regional poison control center should be contacted for detailed risk assessment.
Tricyclic antidepressants: A dose of 10-20 mg/kg can be fatal.[4, 5, 6, 7] Toxicity is characterized by coma, seizures, hypotension, and ventricular arrhythmias. Case reports include the following:
Monoamine oxidase inhibitors: Fatal ingestions have occurred with 4-mg/kg to 6-mg/kg doses.[16] . Ingestions of one or two tablets of irreversible non-selective MAOIs maybe associated with toxicity.[17]
The antimalarial drugs chloroquine and hydroxychloroquine: Toxicity is characterized by rapid onset of hypokalemia, coma, seizures, and cardiorespiratory arrest within 1-3 hours. ECG changes include prolonged PR, QRS, and QT intervals and ventricular dysrhythmias.[18]
With chloroquine, a single 500-mg tablet can be fatal. Case reports include the following:
Cardiovascular drugs.
Calcium channel blocker toxicity includes severe cardiovascular collapse, which may be delayed 4-16 hours after ingestion with extended-release preparations. Verapamil and nifedipine are more likely to be associated with symptomatic toxicity. Potential ingestion of an extended-release preparation mandates a prolonged observation period (minimum of 12 hours up to 24 hours).[24]
Verapamil case reports include the following:
Nifedipine case reports include the following:
Beta-blockers: A literature review found no documented case of death or serious toxicity related to beta-blocker ingestion in pediatric patients younger than 6 years old.[31] Reported toxicity includes hypoglycemia,[31, 32] second-degree heart block,[32] and QRS widening and ventricular arrhythmias from sodium channel blockade; it also crosses the blood-brain barrier and may be associated with reduced Glasgow coma scale score and seizure activity.[33]
Clonidine: Ingestion of 0.1 mg/kg may cause bradycardia, hypotension, respiratory depression, and apnea. A retrospective review of the American Association of Poison Control Centers' National Poison Data System from January 2000 to December 2011 identified seven cardiac arrests and three deaths from clonidine.[34]
Lorcainide: Approximately 50 mg/kg can be fatal.[35]
Quinidine: Two 300-mg tablets can be fatal.
Disopyramide: A 2-year-old child ingested 600 mg and died 12 hours postingestion.[36]
Lidocaine: Ingestion of 1 oz of 2% viscous lidocaine solution was almost fatal in a 20-month-old girl.[37]
Opioids
Opioid analgesic agents may lead to significant CNS and respiratory depression.[38] Methadone is the most toxic opioid; a single dose can lead to fatalities in children. A literature review identified 21 fatalities associated with methadone ingestion (up to 2002) and 64 cases of significant CNS/respiratory depression.[38] Case reports include the following:
Codeine may be fatal to a toddler who ingests three 60-mg tablets.[40] Limited data suggests that children who ingested >5 mg/kg of codeine require up to 6 hours of observation in the ED.[38]
Fentanyl patches have caused death in opioid-naive patients who have chewed or sucked on the patches. This has led the FDA to release a statement on the risks to children and advice for safe disposal of patches. The release comments on 12 deaths associated with inadvertent fentanyl patch exposure.[41] Case reports include the following:
Toxicity from other opioids includes the following:
Hypoglycemic agents
Sulfonylureas. Ingestion of 1 or 2 tablets can lead to profound hypoglycemia and fatalities if not adequately treated.[46] All children with potential sulfonylurea ingestion should be observed in hospital with blood sugar levels taken for a minimum of 8 hours and potentially longer.[47] Symptomatic hypoglycemia may occur late.
Theophylline
Symptoms of theophylline toxicity include vomiting, tremors, agitation and seizures. Metabolic changes include hyperglycemia, hypokalemia, hypophosphatemia, metabolic acidosis, and respiratory alkalosis. In addition, theophylline can cause significant arrhythmias.[48]
Ingestion of one 200-mg modified-release tablet will lead to toxicity in a 10-kg child. Ingestion of more than one tablet may be life threatening.[49] In one case report, an 8-kg child who ingested three tablets (445 mg) of theophylline presented with delayed seizures and tachycardia of 250 beats/min.[50]
Antipsychotic drugs
Life-threatening toxicity may include the following:
Miscellaneous drugs
Colchicine ingestion is potentially life-threatening. Effects are dose dependent, with doses of 0.5–0.8 mg/kg causing systemic toxicity. Doses >0.8 mg/kg lead to multi-organ failure and mortality approaches 100%. In a series of 23 cases of colchicine ingestion treated at a single pediatric intensive care unit (from November 1985 to March 2011), four patients had taken more than 0.8 mg/kg and three of them died.[53]
Iron ingestion can be life-threatening; 10 adult tablets may be fatal in a child. Children are more likely to consume more than one or two tablets of iron as the tablets are brightly colored, often sugar coated, and often considered harmless by care givers. Public education and changes in packaging has led to the reduction of significant toxicity from iron ingestion. Iron supplements were thought to be the primary cause of death in 16 pediatric patients over an 8-year period.[54]
Pseudoephedrine: A 2-year-old child was found dead after ingesting approximately seven 60-mg tablets.[36]
Topical preparations
Oil of Wintergreen (methyl salicylate): less than 5 mL (ie, 1 tsp) of oil of wintergreen is a potentially fatal dose, as it contains 7 g of salicylate. Case reports of fatal ingestions of oil of wintergreen include a 2-year-old boy who ingested 7.5 mL,[55] a 2-year-old girl who ingested 15 mL,[9] and another 2-year-old girl who ingested 10 mL.[25]
Benzocaine topical gels and liquids are contraindicated in children younger than 2 years due to a risk of methemoglobinemia. Small doses may lead to significant toxicity.
Camphor: Five milliliters (ie, 1 tsp) of 20% camphor oil or more than 50 mg/kg is a potentially lethal dose.[15] A 19-month-old child who ingested 5 mL of camphorated oil died 5 days postingestion.[56] Concentrations of 0.1 to 11% when used on unbroken skin is likely to be safe. Toxicity may be more likely to occur if the oil is used on broken skin or higher concentrations are used.
Dibucaine (Proctosedyl): A 8-month-old girl who ingested approximately half of a 30-g tube (ie, 150 mg, or 15 mg/kg) died 7 hours postingestion.[52] A 17-month-old girl ingested approximately 22.5 g of ointment, developed cardiorespiratory arrest, and died approximately 4 hours postingestion.[27]
Nicotine. Symptoms include vomiting, tachycardia, agitation and seizures. Toxicity can progress to lethal dysrhythmias and paralysis.[57]
A lethal dose of nicotine is estimated to be 1 mg/kg. Electronic cigarette (e-cigarette) solutions come in 5-20 ml vials with concentrations that vary from 8.5-22.2 mg/ml.[58] Epidemiological studies note an increase in exposures of children to e-cigarettes with 717 exposures in children < 5 years between June 2010 and September 2013.[59] Most patients experienced only minor effects. However, there is a real risk of significant toxic ingestion of nicotine in pediatric patients.
Ingestion of a single whole cigarette can be fatal. An 11-month-old girl was found dead at home. Autopsy revealed five undigested cigarettes and one tablet of diazepam.[12]
Amphetamines produce central and peripheral sympathomimetic effects. A single methamphetamine tablet may produce life-threatening toxicity. As methamphetamine abuse grows in the community, higher numbers of methamphetamine toxicity in pediatric patients occur.[60] In one review, the most common presenting complaint was agitation; two patients developed seizures.[60]
The substance 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) can be life-threatening. Status epilepticus from MDMA was reported in a 13-month-old boy.[61] Two other case reports of seizures and significant sympathomimetic effects have been reported.[62, 63] Para-methoxyamphetamine, which may be sold as MDMA, can significantly increase blood pressure, body temperature, and pulse rate.[64] Ingestion of a single tablet is potentially fatal.
Hallucinogen toxicity includes the following:
Alcohols have been involved in fatal poisonings, at the following doses:
Chemical agents
Pesticide and herbicide fatalities have included the following:
Rodenticides that can cause fatal toxicity include the following:
Other chemicals include the following:
Hydrocarbons
Plants and natural toxins
Most ingestions by children involve nontoxic substances. More than 1 million ingestions are believed to occur annually, most involving children younger than 7 years.
Race and frequency of toxic ingestions appear to have no correlation. Toxic ingestions from a single dose occur most often as unintentional ingestions by young children aged 1-6 years.
Mortality and morbidity depend on the substance or drug ingested and the quantity relative to body weight (ie, mg/kg/dose).
Public education about the potentially fatal hazards posed by chemicals, medications, and common cleaning compounds is the key to prevention. Basic steps include the following:
Parents and the public should know how to contact the regional poison control center for suspected toxic ingestions.
For patient education information, see First Aid for Poisoning in Children and Child Safety Proofing.
Risk assessment is a specific and cognitive step taken in the assessment of all patients with possible ingestions. It involves a detailed history around the likely agent, the amount and timing of ingestion, and any current symptoms.
Some patients may present before developing significant symptoms. Other patients may present in an obtunded state and without a clear history of ingestion. Obtain collateral history from patients, family, paramedics, doctor, or pharmacist.
Elicit the following information:
Always assume a worst-case scenario. Assume all unaccounted for tablets have been taken. Do not account for spillage. Place the timing of ingestion at latest possible. If two children are involved, presume all the missing tablets were consumed by either child.
Physical examination findings are variable and depend on the specific agent and amount ingested. Findings may range from normal to obtundation or even cardiopulmonary arrest. Some examination results may offer subtle but specific clues regarding the type of ingestion. The recommended process is as follows:
Consider specific symptoms related to the ingestion or to the patient's preexisting medical conditions, if any. Order laboratory studies directed to the specific ingestion.
Have a low threshold for obtaining a electrocardiogram (ECG) in patients who have potentially ingested any toxin associated with sodium channel or potassium channel blockade or any cardiac medication, such as the following:
Radiography may help in specific ingestion cases. For example, in iron ingestion, radiopaque tablets may be visible in the GI tract. Other radiopaque substances include the following:
ECG changes in sodium channel blocker toxicity include widened QRS and right axis deviation of the terminal QRS. Sodium channel blockers include the following:
ECG changes in potassium channel toxicity include prolongation of the QT interval; plot the QT interval on a QT nomogram to identify patients at risk of developing torsade de pointes.Potassium channel blockers include the following:
ECG changes from calcium channel blocker and beta-blocker toxicity include the following:
Immediate care should include correction of any abnormalities of the ABCs (airway, breathing, circulation), plus two Ds: disability (ie, neurologic examination) and decontamination (ie, gastric decontamination, enhanced elimination, and antidote administration). ABC interventions should follow standard Pediatric Advanced Life Support (PALS) guidelines.
Previous advice to perform gastric decontamination for all serious ingestions is no longer recommended. Currently, gastric decontamination is recommended only for specific toxic ingestions, and for cases in which a formal risk-benefit analysis concludes that the probable benefits outweigh the risks.
The American Academy of Clinical Toxicology (AACT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) maintain updated position statements on gastric decontamination. Current recommendations cover the following[79] :
The position paper advises that use of single-dose activated charcoal may be considered if a patient has ingested, within the past hour, a potentially toxic amount of a substance known to be adsorbed to charcoal (eg, a calcium channel blocker).[80]
Principal risks of activated charcoal include pulmonary aspiration (with an unprotected airway), direct administration into lungs via misplaced nasogastric tube, impaired absorption of any oral antidotes, and distraction from resuscitation of the patient.[17] Thus, administration of activated charcoal is contraindicated unless the patient has an intact airway (with no risk of seizures or rapid decrease in level of consciousness) or a protected airway with confirmation of the nasogastric tube in the stomach
The dose of activated charcoal is 1 g/kg of body weight. Charcoal may be administered mixed with juice, soda, or ice cream.
Multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline. However, no controlled studies demonstrate that the enhanced elimination of those drugs provides clinical benefit.
The routine administration of ipecac at the site of ingestion or in the emergency department should definitely be avoided; in any case, ipecac is rapidly becoming unavailable[81]
Cathartics are not recommended as a method of gut decontamination[79]
Gastric lavage should not be performed routinely, if at all, for the treatment of poisoned patients; in the rare instances in which gastric lavage is indicated, it should only be performed by individuals with proper training and expertise[82]
Convincing evidence that WBI improves clinical outcome is lacking, but WBI can be considered for potentially toxic ingestions of sustained-release or enteric-coated drugs (particularly for patients who present later than 2 h after drug ingestion), and can be considered for substantial ingestions of iron, lithium, or potassium[83]
Always consult the regional poison control center. Locate the nearest US poison control center by contacting the American Association of Poison Control Centers at 1-800-222-1222. In addition to providing advice on management and specific treatment or antidotes, poison control centers have on-call toxicologists available for physician consultations. Data on toxic ingestions are compiled through reports to the poison control centers; these data improve treatment of future patients with similar ingestions.
The need for additional medical consultation depends on the nature of the ingestion and the toxicity of the substance.