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Toxicology – a crash course in accidental overdoses

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Matthew (18 months) is brought into ED by his mum. He was found playing in his grandma’s handbag with what looked to be a pill in his mouth. Grandma has loads of meds in that handbag and it’s impossible for them to work out what is missing. What do you do?

What is different between adult toxicology and paediatric toxicology?

The anatomy is different. There is variation in weight, depending on the child to the toxic doses vary in a way that they don’t with adults. The body surface area is larger in young children, and the skin is thinner, so any skin absorption is higher. Children have smaller airways so constriction due to spasm is more of an issue, and also obstruction has a bigger impact on airflow (Poiseuilles law). Finally the volume distribution is different – children have a higher total body water.

The physiology is different. Children have a greater minute volume, which is important when it comes to inhaled substances such as carbon monoxide. Tachycardia increases the cardiac output rather than stroke volume so children can decompensate quickly. They can have immature kidney and liver function which affects elimination, and infants have lower liver glycogen stores so they become hypoglycaemic more easily. There is also increased blood brain barrier permeability, so there are greater toxic CNS effects, And finally remember that some drugs can cross the placenta and therefore there may be neonatal withdrawal syndrome.

Take a clear history

Get as much information as you can. See the packets yourself. Often there is uncertainty about the dose taken, so make sure you work out what the maximum dose could be. Often there is more than one child around so it’s not clear who took what –  assume the worst case scenario i.e. that one child took as much as was possible.

Get the specifics about the time, symptoms. If you are having trouble identifying which substance/berry/mushroom/flowers they took then use online resources, particularly the National Poisons Information Service.

Perform a good examination

Check the vital signs. This should include temperature – you can get hyperpyrexia in some substances e.g. ecstasy, cocaine or salicylates and you can get hypothermia with ethanol or barbiturates. Assess and note the GCS. Do a neurological exam with the rest of your systems exam. Look specifically at the eyes. skin, urine stools – think of specific toxidromes (e.g. opiates, salicylism, serotinergic, anticholinergic, antihistamines, deadly nightshade, cholinergic). Consider other potential causes of any symptoms described.

Do some basic investigations (where appropriate)

Consider a BM.

ECG (always do this if arrhythmia is known).

  • Sodium channel blockade – wide QRS
  • Potassium channel blocker, anti-psychotic overdose – long QT,
  • Calcium channel and beta blockers – heart block

Capillary blood gas.

  • TCA, salicylates (late sign), alcohol, metformin – high anion gap metabolic acidosis
  • Salicylates  – respiratory alkalosis
  • Sedatives – respiratory acidosis

Do paracetamol levels at 4 hours with paracetamol ingestion.

Imaging for foreign body

  • Radiopaque items – COINS (chloral, calcium, opiate, iron, neuroleptic, sustained release or coated)
  • Remember button batteries!

You can do drug levels for some ingestions – paracetamol, iron, alcohols, lithium, salicylate, theophylline, or anti-epileptics.

Bloods – LFT (delayed paracetamol), U&Es, INR (warfarin or delayed paracetamol)

Hourly obs in the department.

Know the one pill kills

Children pick up and eat plenty of random items, and Joe Rotella looked at non-toxic exposures here. But there are a few medications that we really do need to worry about. Those that can be fatal even after just ingesting a small amount.

Amphetamines (and ecstasy)

Amphetamines cause agitation, confusion, hyperthermia, and hypertension.

Calcium channel blockers

They cause delayed onset bradycardia, hypotension, conduction defect, and refractory shock. The potentially fatal dose is 15mg/kg. Calcium channel blockers decrease cardiac inotropy, may increase vasodilation, and, in overdose, can block insulin secretion. Long-acting calcium channel blocker effects may not appear for 18-24 hours, and therefore, children with ingestion should be admitted for 24 hours. Symptomatic patients should receive high-dose insulinaemia/euglycemia therapy of 1 unit/kg intravenous bolus and 1 unit/kg/hr intravenously with supplemental dextrose as needed (although it rarely is)

Chloroquine and hydroxychloroquine

Chloroquine causes coma, seizures, and cardiovascular collapse. The potentially fatal dose is 20mg/kg. The antimalarial quinine and the antiarrhythmic quinidine cause sodium-channel blockade, which leads to QRS widening and arrhythmias. There is a risk of hypokalemia-related QTc prolongation and torsades de pointes.

Quinine is found in minute amounts in tonic water.

Both cause cinchonism, whose symptoms include blurred vision, hearing impairment, and flushing in mild cinchonism and deafness, blindness, and cardiac arrhythmias in severe poisoning. Treatment includes sodium bicarbonate when QRS is widened, replenishment of electrolytes, and supportive measures. Chloroquine toxicity is treated with the administration of diazepam 2 mg/kg.

Opioids

Opioids cause coma and respiratory depression. The potentially fatal dose of codeine is 10 mg/kg, and of hydrocodone is 1-5 mg/kg. Narcotics cause depression in mental status and directly act on the brain’s respiratory centre to depress respiration. A long-acting opioid like OxyContin® could have peak effects in a small child as long as 18-24 hours after ingestion. Therefore, ingestions should be treated with careful monitoring, supportive care, and administration of naloxone as needed.

Propranolol and sotolol

These cause coma, seizures, ventricular dysrhythmias, and hypoglycaemia. Beta-blockers will decrease heart rate but, fortunately, are unlikely to bring an otherwise healthy toddler’s heart rate below its intrinsic rate. Of greater concern is the development of hypoglycemia due to blockage of glycogenolysis and depression in mental status in the more lipid-soluble agents that cross the blood-brain barrier.

Propranolol is the most hydrophobic and lipid soluble, and so is the most worrisome of the beta-blocker ingestions. Symptomatic patients should be given glucagon (0.03-0.05 mg/kg), which goes through a “back door” of its own receptor, bypassing beta-receptors to stimulate cAMP cascade, leading to increased intracellular calcium for increased heart rate and contractility.

Sulfonylureas

These cause hypoglycaemia. The potentially fatal dose is 0.1 mg/kg. Oral hypoglycemics taken for type 2 diabetes stimulate insulin production, and clinically significant hypoglycaemia may occur up to 18-24 hours after ingestion. Treatment with sugar will prompt the pancreas to produce more insulin, creating a scenario where clinicians continue to “chase the tail” of the hypoglycaemia.

Ingestion of an oral hypoglycaemic in a non-diabetic child requires admission for glucose checks every 1-2 hours. Patients should eat regularly and those with glucose <70 mg/dL should receive the somatostatin analogue octreotide to inhibit insulin production.

Theophylline

These cause seizures, SVT, and vomiting.

Tricyclic antidepressants

These cause coma, seizures, hypotension, and ventricular dysrhythmia. The potentially fatal dose is 15 mg/kg. TCAs block fast sodium channels, leading to intraventricular conduction delay, widening of the QRS (with subsequent prolongation of QTc), and rightward axis deviation. The characteristic QRS >100 msec with a prominent terminal R in aVR (shown) is concerning and predictive of both ventricular arrhythmia onset and seizure activity.

A child who ingested a tricyclic antidepressant should be admitted for cardiac monitoring and serial ECGs. Any widening of the QRS > 100 msec should be treated with IV bicarbonate (1-2 mEq/kg/hr) to overcome sodium channel blockade.

Know the lethal non-drugs

Other substances are also potentially lethal but are not classed as drugs.

  • Organophosphate and carbamate insecticides – a single sip can cause cholinergic symptoms, seizures, and coma.
  • Paraquat/diquat – a sip can cause burns, multiorgan failure, or pulmonary fibrosis.
  • Hydrocarbons (solvents, eucalyptus oil, kerosene) – a sip can lead to coma, seizures, or aspiration pneumonia.
  • Camphor – 5ml of 100% can cause seizures, coma, hypotension.
    • The potentially fatal dose is 50mg/kg.
    • An overdose of camphor will result first in nausea and vomiting and can quickly progress to delirium, hallucinations, seizures, and cerebral oedema.
    • Camphor is used for its anti-itch, moth-repellent, cough suppressant, and muscle-soothing properties in products and is found in loads of products such as Tiger Balm,  Vicks, or VapoRub.
    • Treat any seizures with benzodiazepines and institute supportive measures.
  • Corrosives (sodium hydroxide, strong acids) can cause GI injury/perforation.
  • Naphthalene – one mothball can lead to methaemoglobinaemia and haemolysis.
  • Strychnine causes muscle spasms and respiratory failure.

 

General management

This will include observation and supportive care.

Seizures should be managed using benzodiazepines (avoid phenytoin as it has sodium channel-blocking properties, and this can make things worse)

Look for and treat secondary complications such as rhabdomyolysis, aspiration pneumonitis, or delirium.

Embrace the RRSIDEAD management principles – resuscitation, risk assessment, supportive care, investigations, decontamination, enhanced elimination, antidotes, and disposition.

Elimination of poisons

Activated charcoal

Consider this if you are within one hour of ingestion and there are no concerns regarding protecting the airway. Remember that it does not absorb acids or alkalis, alcohols, metals or ionic compounds (e.g. iron, potassium, lithium), or hydrocarbons. The patient needs to have a normal GCS and be maintaining their own airway (or their airway is protected).

If you make a mistake with activated charcoal, it is not easily rectifiable, so be cautious about when to use it. The dose is 1g/kg, and you can mix it with ice cream or cola to encourage palatability.

Syrup of ipecacuanha

This has been used to induce emesis but is not recommended any more. Don’t do it!

Gastric lavage

Also, it is no longer commonly used.

Whole bowel irrigation

This is not very pleasant and is rarely performed. You could consider it if the ingested substance is slow- or extended-release and isn’t bound to charcoal. However, you need the patient to present and be treated before symptom onset. You should be confident that the ingestion is likely to end up with significant toxicity in spite of the use of any antidotes or supportive care.

Use polyethylene glycol – 30ml/kg/h until the effluent runs clear. This can be considered for iron (60mg/kg elemental iron), slow-release calcium channel blockers, or slow-release potassium chloride.

Any decision to decontaminate should be based on the benefits outweighing the risks, and it is not commonly done if the child is well. But if there is early toxicity, then consider it.

Enhanced elimination

This is rarely needed.

Multidose-activated charcoal can promote gut dialysis. It can be used with large ingestions of carbamazepine, phenobaritone, quinine, or theophylline. The dose is 1g/kg activated charcoal four hourly.

Alkalinisation of the urine in salicylate poisoning, or haemodialysis, promotes the ionisation of highly acidic drugs to stop its reabsorption across tubules and increase renal excretion. This can be considered with salicylates (although if severe, you will need to do urgent haemodialysis rather than alkalinisation) or phenobarbitone. The dose is 1-2 mmol/kg NaHCO3 stat and then you can infuse further doses over the next 1-2 hours. You are aiming for a urinary pH>7.5.

Haemodialysis is good for water-soluble toxins,  which are low molecular weight, not protein bound, and have a small volume of distribution. This would need ICU input.

Specific toxins – iron

Iron supplements are available in different formulations – the important thing to consider is the amount of elemental iron ingested, not the amount of iron salt.

Ingestion of >40 mg/kg of elemental iron is significant (or if an unknown quantity has been ingested or the child is symptomatic)

Symptoms in the initial period can include nausea, vomiting, diarrhoea, abdominal pain, hypotension, haematemesis, and fever.  In severe iron poisoning, there can be a latent period (6-24 hours) where the initial symptoms seem to subside, but later systemic toxicity occurs with organ failure.

Later symptoms usually appear at 6-24 hours and last 12-24 hours. These include cardiovascular symptoms, e.g. tachycardia, vasoconstriction, hypotension, and shock, or metabolic symptoms, e.g. metabolic acidosis.

Multiple organ failure can occur >48 hours after ingestion.

Management

If the child is asymptomatic but has ingested tablets, then do an abdominal x-ray, and if it’s negative, then no further observation is required. If an unknown amount or >40 mg/kg has been ingested, measure the serum iron concentrations four hourly until it starts to fall.

All symptomatic children should have an abdominal x-ray (if tablet ingestion), a blood gas (acidosis), and a glucose (hyperglycaemia). Serum iron concentration should be performed immediately and repeated 4-6 hours after the ingestion (peak concentration). With slow-release or enteric-coated tablets, concentrations should be repeated at 6-8 hours due to the possibility of delayed absorption. Once desferrioxamine has been started, iron concentrations are inaccurate at most labs (but check with your own).

Do bloods – FBC, U+Es, LFTs, clotting, and a group and save.

Resuscitation

Provide supportive treatment to maintain adequate blood pressure and electrolyte balance, e.g. fluid bolus (20 mL/kg) for hypovolaemia or hypotension and potassium/glucose administration as necessary.

Decontamination

Activated charcoal does not bind to iron and is not indicated. The decontamination of choice is whole bowel irrigation, and this should be considered if the x-ray reveals tablets ingested and it’s a significant dose.

Antidote – desferrioxamine

Desferrioxamine is a chelating agent that forms a water-soluble desferrioxamine-iron complex. This should always be used in conjunction with advice from a toxicologist.

Consider desferrioxamine if serum iron concentrations >90 micromol/L; concentrations are  60-90 micromol/L and tablets are visible on the x-ray or the patient is symptomatic (nausea, vomiting, diarrhoea, abdominal pain, haematemesis, or fever); the child has significant symptoms of altered conscious state, hypotension, tachycardia, tachypnoea, or worsening symptoms irrespective of ingested dose or serum iron concentration. Do not wait for the iron levels to return if the patient has an altered conscious state, shock, severe acidosis (pH <7.1), or worsening symptoms.

The dose is 15mg/kg/hr (IV), and the rate is reduced after 4-6 hours so that the total intravenous dose does not exceed 80mg/kg/24 hours. Treatment in significant poisoning is usually for 12 -16 hours, but essentially until the child is asymptomatic, the anion-gap acidosis is resolved, and the serum iron concentration is <60 micromol/L. Desferrioxamine-iron complex is renally excreted, so be careful if the patient develops oliguria, as this can be dangerous

Specific toxins – essential oils

Essential oils are common in most households, e.g. lavender, tea tree, nutmeg, sage, or peppermint. Toxicity can occur from the essential oil itself or from the hydrocarbons or emulsifiers that have been added. Essential oil concentrations range from 1-20%, and volumes of 2-3 mL have been associated with toxicity in children. The most common symptoms are mucous membrane irritation and gastrointestinal symptoms with possible CNS depression.

Asymptomatic children with likely small ingestions do not usually require investigation. If there are signs of aspiration pneumonitis, a chest x-ray and blood gas would be helpful. Do U+Es and LFTs in patients with significant symptoms or large ingestion?

Management

A pneumonitis is managed supportively, and prophylactic antibiotics are not indicated unless there is objective evidence of bacterial infection. Charcoal is contraindicated due to the risk of aspiration, so do not give this. NAC can be considered for significant clove oil poisoning.

For asymptomatic children where there are concerns regarding significant exposure (>5 mL), observe them for 4 hours post-exposure. Symptomatic patients should be admitted for a longer period of observation +/- supportive care.

What should you do when you don’t know what they’ve taken?

As I mentioned above, it is a frequent occurrence that the family is unsure about exactly what has been taken and how much. Be sensible and get a realistic assessment of the worst-case scenario regarding the volume/nature of the ingestion.

If in doubt, observe for 12 hours minimum. Monitor the obs and neurology during that time, and if there are any unusual obs, then do cardiac monitoring. Get IV access only if there are signs of toxicity. Do a BSL and ECG initially as a baseline.

Use common sense, and don’t discharge the child in the middle of the night if there is uncertainty.

Safeguarding

Safeguarding is a crucial part of paeds tox – and is easily overlooked.

Consider the developmental stage and height of the child – were the medications/substances kept appropriately out of reach, or were they left lying in an accessible place?

Consider if there was adequate supervision. Was the child left unattended, and that’s why they were able to access the medications/cupboard/handbag without anyone noticing?

Consider fabricated or induced illness if the story doesn’t seem to fit (although this is a difficult diagnosis to make).

Place priority on the safe storage of medications and involve the safeguarding teams where appropriate. 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. Child-resistant containers do have a role to play in preventing accidental poisoning, but the priority is for families to ensure safe storage.

Grandma sent through pictures of all the medications in her bag. There were no ‘one pill kills’, and it was mainly vitamin supplements. On reflection, Grandma didn’t think anything was missing. Matthew remained well in the department and was asymptomatic, so he was discharged.

References

https://lifeinthefastlane.com/toxicology-conundrum-029/

https://www.starship.org.nz/for-health-professionals/starship-clinical-guidelines/p/poisoning-management-of-childhood/

https://kidshealthwa.com/guidelines/poisoning-overview/

https://www.rch.org.au/clinicalguide/guideline_index/High_risk_-_low_dose_paediatric_ingestions/

https://reference.medscape.com/features/slideshow/deadly-ingestions

https://www.rch.org.au/clinicalguide/guideline_index/Iron_poisoning/

https://www.rch.org.au/clinicalguide/guideline_index/Essential_Oil_Poisoning/

Author

  • Tessa Davis is a Consultant in Paediatric Emergency Medicine at the Royal London Hospital and a Senior Lecturer at Queen Mary University of London.

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2 thoughts on “Toxicology – a crash course in accidental overdoses”

  1. Great post! Tessa could I just confirm that the dose for diazepam is to 2mg/kg bolus or over 24 hours, I thought the dose is a bolus of 0.5mg/kg and 1 mg/kg over 24 hours. Is there evidence it is better than propofol?

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