Paediatric Toxicology Considerations

The presentation of a child to the emergency department (ED) by concerned parents after ingestion of a potential toxin is a frequent occurrence. About 40,000 ED attendances each year in England and Wales are as a result of suspected poisoning in children and about half of these children are admitted for treatment or observation [1]. Approximately 13% referrals were made to on call consultants in National Poisons Information Service regarding Paediatric toxicology [2].

The majority of paediatric ingestions involve accidental unintentional exposure to small doses of non-toxic or minimally toxic substances in children between the ages of one and five, and it can often be difficult to establish whether or not an actual ingestion has occurred. More than 80% of these ingestions occur in the home.

Incidence

The incidence of paediatric poisoning is partly determined by availability. Drugs appear second in frequency only to household products in the majority of episodes in children under the age of 5. In England and Wales 40% of cases of poisoning in children under the age of 15 relate to ingestion of pharmaceutical preparations. The most commonly ingested of these include iron, tricyclic antidepressants, benzodiazepines, paracetamol and oral contraceptive pills.

In the majority of accidental poisonings in children all that is required is parental reassurance, after a brief period of observation. Less than 1% of paediatric poisonings are clinically serious and death is rare [3]. In England and Wales, the most common cause of death from poisoning in children is in relation to carbon monoxide, but this will not be discussed further in this module.

Child protection

Although thankfully rare, the emergency physician must always consider the potential of child protection or safeguarding concerns for any paediatric toxicological presentation. Concerning features in the history and examination are discussed and key management points relating to paediatric poisons are demonstrated.

Child resistant containers

In general the mortality in paediatric poisoning cases appear to be steadily declining. This may be as a result of child-resistant containers (CRCs), first introduced in the UK in 1972 for junior preparations of aspirin and paracetamol and 1976 for adult versions, increased poison prevention efforts and safer pharmaceutical agents being prescribed to the general population, particularly anti-convulsants and anti-depressants. It should be remembered however, a significant proportion of children under the age of 5 are able to open the CRCs and these only have the potential to be an effective deterrent if the tablet in question is stored in them and not left loose.

Learning Bite

In August 2012 the Medicines and Healthcare Products Regulatory Agency (MHRA) introduced the Human Medicines Regulation that stated only those medications containing aspirin, paracetamol and greater than 24mg of elemental iron must be legally placed on the market in packaging that has been shown to be child resistant [4]. These drugs were chosen based on prevalence within the home and numbers of recorded toxic ingestions. It is now felt that although CRCs have a role to play in the prevention of accidental poisoning in children priority should be given to safe and appropriate storage of medicines.

Paediatric toxicology in the ED will encompass 4 distinct groups of patients:

Accidental poisoning

This is by far the most frequently occurring presentation in children and generally affects those under the age of 5. Boys of the age of 2 are the commonest group to be involved. This module focuses predominantly on this group. This often occurs when there is inadequate supervision of the child and psychosocial stress within a family (e.g. a new baby, maternal depression or substance misuse) can be an important factor, as well as personality traits of the child such as hyperactivity.

Deliberate self-poisoning

This is not covered in detail in this module but generally involves teenagers and reflects adult patterns of self-poisoning. Encompassed within this will be those teenagers and young adults that experiment with alcohol and recreational drugs. These teenagers will require assessment by age-appropriate psychiatric and social teams.

Iatrogenic poisoning

Differences in size, body surface area, and immaturity of metabolic pathways are just a few of the differences between children and adults that make prescribing for children more hazardous. Drug calculations always need to be double-checked.

Deliberate poisoning

Fabricated or induced illness by proxy (moving away from the term Munchausens by proxy) is rare, but must be considered in children presenting to medical services with an unclear constellation of symptoms in a situation where the doctors may, or may not, have social concerns for that child. A number of substances have been used including common salt, emetics and purgatives.

Learning Bite

Any toxicology presentation in a child or teenager requires investigation beyond the consequence of the exposure due to safeguarding, social and mental health issues.

There are certain anatomical, physiological and developmental differences between adults and children that influence paediatric toxicological presentations:

Anatomical differences

Body weight: This can vary considerably between children of different ages and nutritional status.

Body surface area (BSA): Children have a larger BSA than adults and will thus have a larger absorptive surface area for agents absorbed through the skin. BSA is also sometimes used to calculate drug dosages instead of body weight. In addition the skin of children is thinner and the keratinised epithelium less well developed.

Airway calibre: The airway calibre of children is much smaller than that of adults. Due to Poiseuilles law any further reduction either due to constriction (bronchospasm) or obstruction (respiratory secretions or gastric contents) has a significant impact on air flow to the fourth power e.g. halving the radius will cause flow to fall to one sixteenth.

Body water: Children have proportionally greater total body water than adults and this will result in differing volumes of distribution.

Physiological differences

Ventilation: Children have a greater minute volume than adults and so are more susceptible to the effects of gases, vapours and aerosolised agents (carbon monoxide).

Cardiac output: Children increase their cardiac output predominantly by mounting a tachycardia and have limited capacity to increase their stroke volume. They can decompensate quickly if they lose fluid or become bradycardic, an important feature of organophosphorous compounds.

Renal and liver function: Immature renal and liver functioning in children predisposes them to impaired ability to eliminate, and detoxify, toxic substances, respectively.

Glycogen stores: Children have lower glycogen stores within the liver which predisposes them to early hypoglycaemia when they experience a physiological stress e.g. seizures or sepsis.

Blood brain barrier: Toxic agents have a greater potential to gain entry to the central nervous system as children have greater blood brain barrier permeability. In addition the central nervous system of children is still developing and thus at risk of injury from certain exposures (lead) and secondary brain injuries.

Neonates: Some agents (e.g. amphetamines, barbiturates, caffeine, cocaine, opioids and selective serotonin reuptake inhibitors) ingested by the mother in pregnancy will traverse the placenta and can lead to dependence in the foetus which may present as a withdrawal syndrome shortly after birth. Toxic agents may also be transferred by mother to baby in breast milk e.g. aspirin, cocaine and lithium [5].

Developmental considerations

Height: Children have access to, and their attention is drawn to, areas that adults may overlook (under the sink storage).

Developmental milestones: Children between the age of 1 and 5 are adventurous by nature. They will not always appreciate danger and will tend to copy their parents. This is of particular importance when medications are taken in their sight or termed sweets. Some toxic substances have bittering agents added to prevent accidental ingestion.

Learning Bite

When considering safeguarding or child protection concerns be sure that the mechanism of ingestion is consistent with that childs developmental age. Those ingestions under the age of 1 should be carefully assessed before being put down to an accidental ingestion.

History

It will be important to obtain a history from the care giver responsible for the child at the time of the ingestion. This needs to be combined with a systematic examination of the child with the aim of determining if a significant ingestion has occurred, of what substance, and what further investigation or management is required to allow an assessment of risk to be made.

What was ingested?

Ask for empty packets, unconsumed pills, berries, leaves or their descriptions. Aim to establish what potential toxins are contained within these.

What was the maximum possible amount ingested?

Weigh the child and calculate this on a mg/kg basis for medications or establish how many berries, leaves etc may have been eaten. Where more than one child or sibling is involved assume each has consumed the maximum amount in a worst case scenario.

What other toxins may have been available?

Enquire as to what prescription medications family members have within the household or what other household products were also present. This information is particularly important in suspected poisoning by an unknown substance. Consider plant or fungi ingestion in any acutely unwell child who has been outside.

When did the ingestion occur?

Aim to establish the time of ingestion (this may be a time frame of variable duration).

What symptoms have developed since then?

Ask specifically about coughing, choking, vomiting, diarrhoea, and reduced level of consciousness.

Could this be a deliberate ingestion?

Take all deliberate self-poisonings seriously. They will need a formal age-appropriate psychiatric assessment prior to discharge.

In general the vast majority of substances ingested are of insufficient volume to cause problems to even the smallest of child however there are a few important exceptions with regard to children less than 10kg in weight, often referred to as the one pill can kill list:

One pill can kill [6]

• Tricyclic antidepressants (dothiepin)
• Chloroquine and hydroxychloroquine
• Calcium channel blockers (diltiazem, verapamil)
• Opioids (oxycodone, methadone, morphine sulphate controlled release)
• Amphetamines (amphetamine, MDMA)
• Propranolol
• Theophylline
• Sulphonylureas (glicazide, glibenclamide)

Other toxic substances

• Camphor (present in VixVapoRub and Tiger Balm)
• Methylsalicylate (present in Oil of Winter Green)
• Toxic alcohols (methanol, ethylene glycol)
• Iron supplements
• Essential oils

Low risk ingestations

A number of common household substances and drugs can confidently be described as low toxicity and parents can be reassured. However, this does not mean that the circumstances of the ingestion should not be assessed. Full details can be found on Toxbase and a poster is available from NPIS. Common substances include the penicillins, oral contraception pill, silica gel (desiccating bags), glow sticks, slugs, snails and garden worms.

Examination

In an asymptomatic child presenting to the ED soon after an ingestion the physical examination is likely to be unremarkable but it may provide valuable information as to the nature of an unknown toxin.

As with any sick child, APLS principles [1] should be followed and a systematic ABCDE approach taken, paying special attention to the points below:

Carefully assess the vital signs

Take seriously observations that lie outside the normal range for the age of the child. Dont forget to measure the temperature (hyperpyrexia is associated with ingestion of ecstasy, cocaine and salicylates, whilst hypothermia suggests poisoning with ethanol or barbiturates).

Observe the mental status

There is a lack of supporting evidence to suggest the use of the Glasgow Coma Scale (GCS) in the prognosis or management of poisoned patients. In general the AVPU score is used in children.

Perform a thorough neurological examination

Neurological signs affecting one side of the body must not be attributed to a poisoning. Look for external signs of head injury or other evidence of non-accidental injury.

Examine the eyes, mucous membranes, skin, bowels and bladder

This information may be used to suggest a class of poisons that has been ingested to produce a specific toxidrome (or collection of signs and symptoms that class of toxins is known to cause). It must be noted however that often more than one substance has been ingested and rarely are the toxidromes so clear cut.

Exclude alternative causes

In addition, by examining the child the Emergency physician needs to exclude other organic conditions that may present in a similar fashion to poisonings. The reverse is true and the clinician should have a low threshold for considering a toxicological cause for a child’s presentation if a medical cause cannot be found.

Learning Bite

Significant toxidromes include opiate, sympathomimetic, salicylism, serotinergic, anticholinergic (tricyclic antidepressants, antihistamines, plant ingestions deadly nightshade) and cholinergic (organophosphorous and carbamate compounds). More details can be found in the Toxidrome module.

As most ingestions in children will be non-toxic, most cases will not require any investigations. In those that do, they tend to be basic bedside tests with the occasional use of analytical tests to detect significant levels of certain drugs in the blood. Rarely will blood, urine and other biological samples need to be sent for specific drug or chemical assays except in the cases where deliberate poisoning is considered, see below:

Bedside blood sugar measurement (BM)

This should be one of the first considerations in poisoned children as it is one of the deleterious effects of poisoning that is easily remedied and is mandatory in cases where the mental status is altered. If the first measurement is within normal limits and the patient remains well there is no evidence to advocate serial measurements unless the toxin ingested is known to cause hypoglycaemia or the child deteriorates [5].

ECG

Where the ingested substance is known to cause arrhythmias then a 12-lead ECG is mandatory, along with any child with altered mental status or abnormal heart rate or blood pressure. The interpreting clinician will need to be aware of normal differences between adult and paediatric ECGs.

Blood gas analysis

In children capillary blood gases are chosen in preference to arterial or venous sampling and can be used to assess acid-base balance and will provide valuable information for certain poisonings. Some machines will also allow a sodium to be checked. This measurement should be considered if deliberate poisoning is suspected.

Paracetamol

This will tend to be less commonly considered in Paediatric toxicology than in adults, and should not be routinely requested except where there is concern about access to paracetamol by the child. This tends to occur in relation to deliberate self-poisoning rather than accidental ingestions. In cases of deliberate self-harm, paracetamol levels should be considered routine as it is a common co-ingestant and any symptoms as a result of overdose tend to be delayed.

X-rays

These may be considered where there is suspicion of ingestion of radio-opaque substances or foreign bodies. A useful mnemonic is COINS [5]:

C	Chloral hydrate, calcium
O	Opiate or other drug packets
I	Iron and other metals
N	Neuroleptic agents
S	Sustained release or enteric coated preparations

Learning Bite

Button batteries rarely cause systemic toxicity but can result in localised mucosal ulceration with the inherent risk of gastrointestinal haemorrhage or perforation if they remain in the oesophagus or stomach. Once the battery has passed the pylorus it is unlikely to cause toxicity. When one or more magnets is ingested there is a risk of their becoming adherent with intervening bowel tissue which may become eroded and perforate or cause gastrointestinal bleeding. These will need endoscopic, if not surgical, removal.  See the Royal College of Emergency Medicine advice regarding button batteries as a cause of haematemesis in children.

Qualitative urine toxicology screen

As most accidental paediatric poisonings will not involve the drugs which are screened for by standard bedside urine testing strips then this will not play a role in investigation, or alter management, of these patients. Even in the older paediatric population who may experiment with recreational drugs or abuse prescription drugs of other family members tox screens have not been shown to improve patient outcome or change management of poisoned patients in various studies examining their use in the ED setting [5].

The important caveat to this, however, is where there is a suspicion of the deliberate poisoning of a child. In that situation, samples of biological substances such as blood, urine and gastric aspirates will need to be sent for qualitative analysis. For forensic purposes a positive sample will need confirmation using a second methodology. Samples sent from the ED may be used as evidence in subsequent legal action and thus consideration should be paid to ensuring a chain of custody for such samples (follow your local departmental policy).

After undertaking a thorough history and examination of a poisoned child the Emergency physician will need to make a risk assessment of the likely exposure and the probable course of toxicity.

As a rule, as in adults, management is largely supportive in nature. The vast majority of ingestions in children will be of low or non-toxic substances. Details of these can be found on the Toxbase website (see poster). Reassurance can be given to parents if their child has ingested a substance on this list with advice to observe their child at home and to return if symptoms such as vomiting, rash or altered conscious level were to develop.

For other agents that Toxbase specifies as requiring further management this will fall under two headings, general and specific. Where you are unsure as to the most appropriate management of a child who has been poisoned, expert advice is available 24 hours a day, 7 days a week through the National Poisons Information Service and should be consulted.

Unknown ingestion

Where parents have provided a description of a particular tablet, leaf, berry etc or have a sample of that ingested there are various resources available to identify said substance. By contacting the Poisons Information Service (NPIS) they have access to TICTAC a comprehensive drug identification database. Links with the Royal Botanic Gardens at Kew similarly exist to help identify unknown plants.

General management

The cornerstone of effective management in paediatric poisoning cases is good supportive care and appropriate observation. Supportive care will aim to normalise abnormal clinical observations to ensure normothermia, euglycaemia, euvolaemia (with normalisation of acid-base balance and electrolyte abnormalities) and prompt management of seizures. First line treatment for drug-induced seizures will be benzodiazepines. Phenytoin, with its sodium channel blocking properties, should be avoided as it may exacerbate the problem. Be aware of potential secondary complications such as rhabdomyolysis, aspiration pneumonitis and persistent delirium.

Gut decontamination is covered fully in another session but includes activated charcoal in a small number of cases where a potentially toxic amount of a well charcoal-adsorbed poison has been ingested within the last one hour, in a child in whom there are no concerns regarding their ability to protect their own airway.

Induced emesis (ie syrup of ipecacuanha) is no longer recommended in any circumstance [9]. Gastric lavage is still mentioned however the appropriate expertise most be sought and the patients airway secured; this is unlikely to be achieved in the first hour post ingestion. Whole bowel irrigation remains a possibility for some slow release preparations but is reliant on patient compliance.

Activated charcoal can be mixed with a cola-type drink to make it more palatable without reducing its effectiveness [8].

Specific therapies

Antidotes

These are used in poisonings by a limited number of toxins but are rarely required in paediatric poisonings. Obtaining an antidote and its use should not distract from appropriate supportive care. Be aware of the changes to paracetamol overdose management implemented in 2012 following a review by the Commission on Human Medicines. Weight based tables are now available to guide dosage and administration of intravenous acetylcysteine [10].

Elimination for aspirin toxicity

This may include alkalinisation of the urine in severe salicylate poisoning as well as more invasive elimination methods including haemodialysis. Refer to Toxbase advice for specific poisonings.

Disposition

As mentioned above, most children will be able to be discharged home once fully assessed and the causative agent deemed low or non-toxic. Other ingestions may determine a longer period of observation in a healthcare facility with the ability to manage the child if they were to deteriorate. All however should be assessed for social, mental health and safeguarding risks.

Child protection and safeguarding concerns

Whether the child concerned is at risk of further harm on discharge from the ED must be considered in any poisoning case. Deliberate poisonings (including Munchausens by proxy) are thankfully rare but your index of suspicion should be higher in children under the age of 1 or where the story relating to the ingestion of said substance does not fit with the developmental milestones that child has reached. Often deliberate poisonings may not present as this and may include failure to thrive, chronic problems or a non-specific acute presentation.

A much more common situation is that of accidental ingestion as a result of inappropriate supervision at home. Of children under the age of 6 who present to the ED with an ingestion of a toxin, 30% will represent to the ED with a further episode [11]. It is not just the child themselves that is at potential harm but also their siblings or other children in the household. This may be a symptom of a family network requiring extra support. Provide poison prevention advice and education to these parents and arrange further follow-up in the form of a health visitor or school nurse referral.

Where children have been placed at more significant risk or there are concerns about deliberate poisoning then the case will need to be discussed with the Lead for Child Protection before the child leaves the ED. Follow local safeguarding policies and ensure good documentation in the notes. To safeguard children it is important that health services share information.

• Not taking a thorough history: It is vital to establish what agent might have been ingested, how much, when and what has happened subsequently.  These details alone will determine your management in the majority of toxicology presentations to the Paediatric ED.
• Not being aware of those drugs on the “one pill can kill” list: Whilst the vast majority of ingestions in children are minor and require no specific intervention certain drugs if ingested by a baby or small child (<10kg) may prove fatal.
• Not seeking expert help: Children are not small adults and there can be significant differences between children and adults with regard to anatomy, physiology and developmental differences.  If in doubt, call the National Poisons Information Service. Although you may feel comfortable managing a child with a specific ingestion, obtaining Toxbase information can assist other healthcare professionals involved in that child’s care as well as contributing to epidemiological data with regard to paediatric poisonings.
• Being distracted by the use of antidotes: Good supportive care is the key to achieving good outcomes in the poisoned patient. Antidotes play a very limited role and should only supplement good basic care.
• Blind use of screening toxicology urine analysis: Assessment for signs and symptoms of a particular toxidrome generally proves more clinically useful than urinary toxicology screening tests. Results from these screens are not qualitative and thus it is not possible to determine if a positive test relates to a current toxic ingestion or previous exposure with detectable, but clinically insignificant, drug levels.
• Failing to identify potential safeguarding concerns: A significant proportion of children who present with ingestion of a toxin will return to the ED with a subsequent episode. This may be a symptom of a family network requiring extra support. On very rare occasions the child may have been deliberately poisoned. Be alert to these possibilities and where you have concerns follow local safeguarding policies and ensure clear documentation in the notes.

1. Samuels M, Wieteska S (eds). Advanced Paediatric Life Support: A Practical Approach to Emergencies, 6th Edition. Advanced Life Support Group. Wiley-Blackwell Ltd, 2016. Appendix E: General Approach to poisoning and envenomation.
2. National Poisons Information Service – Annual Report 2021-2022. Commissioned by the Public health England on behalf of UK health departments. Published November 2022.
3. Gummin DD, Mowry JB, Beuhler MC, et al. 2020 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 38th Annual Report. Clin Toxicol (Phila). 2021 Dec;59(12):1282-1501.
4. Medicines and Healthcare products Regulatory Agency (MHRA) Human Medicines Regulations (SI 21012/1916) Child Resistant Packaging for medicines. Gov.UK. Last updated 31 December 2020.
5. Hoffman J, et al. Paediatric Toxicology Update: Rational Management of Paediatric Exposures and Poisonings. Emerg Med Pract 2007;9(4).
6. McCoubrie D, Murray L, Daly FF, Little M. Toxicology case of the month: ingestion of two unidentified tablets by a toddler. Emerg Med J. 2006 Sep;23(9):718-20.
7. TICTAC Visual ID System for healthcare.
8. Cheng A, Ratnapalan S. Improving the palatability of activated charcoal in pediatric patients. Pediatr Emerg Care. 2007 Jun;23(6):384-6.
9. Krenzelok EP, McGuigan M, Lheur P. Position statement: ipecac syrup. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol. 1997;35(7):699-709.
10. National Institute for Health and Care Excellence (NICE). Acetylcysteine. BNF.
11. Greene SL, Dargan PI, Jones AL. Acute poisoning: understanding 90% of cases in a nutshell. Postgrad Med J. 2005 Apr;81(954):204-16.
12. Cameron P, et al. (eds). Textbook of Paediatric Emergency Medicine. 3rd edn. Elsevier, 2018.
13. Paracetamol poisoning – management proforma for children. Leicester Royal Infirmary, June 2020.