Poisoning - Iron

Disclaimer These guidelines have been produced to guide clinical decision making for the medical, nursing and allied health staff of Perth Children’s Hospital. They are not strict protocols, and they do not replace the judgement of a senior clinician. Clinical common-sense should be applied at all times. These clinical guidelines should never be relied on as a substitute for proper assessment with respect to the particular circumstances of each case and the needs of each patient. Clinicians should also consider the local skill level available and their local area policies before following any guideline.  Read the full PCH Emergency Department disclaimer.

Aim 

To guide PCH Emergency Department (ED) staff with the assessment and management of iron poisoning in children.

This is a general approach to iron poisoning - for specific details, please contact Poisons Information: 13 11 26 or refer to the Toxicology and Toxinology – Therapeutic Guidelines (External website).

Background^1,2

Accidental iron ingestion is common in children but severe iron toxicity requiring chelation is rare.
Historically, iron toxicity was described in five stages; however, not all patients experience those stages, and the duration of each stage is imprecise and overlaps. Currently, iron toxicity is described as two overlapping stages with a pathophysiological basic i.e., gastrointestinal symptoms and systemic toxicity.

Iron causes two major effects¹

Local - Gastrointestinal irritation.

• Abdominal pain.
• Nausea and vomiting.

Systemic - Cellular toxicity causing multi-organ failure.

• Systemic toxicity may occur with doses greater than 60 mg/kg and is life-threatening with doses greater than 120 mg/kg of elemental iron.¹

Resuscitation and supportive care^3,4

• Priority is the restoration and ongoing replacement of adequate circulatory volume.
• Ongoing fluid replacement is essential in the face of continuing gastrointestinal and third-space losses.
• All patients with deliberate self-poisoning, regardless of the dose, should be referred to hospital for evaluation.

Ingested dose of elemental iron	Symptoms and management
< 20mg/kg	Patients usually remain asymptomatic Do not require decontamination or referral to hospital
20-40mg/kg	Patients often have mild gastrointestinal (GI) irritation manifested by transient abdominal discomfort and vomiting. One or two vomits are common and symptoms usually last less than 6 hours. Gastrointestinal decontamination is not required and minimally symptomatic patients (e.g., one or two vomits) do not require referral to hospital.
40-60mg/kg	Patients often have abdominal discomfort and vomiting but systemic toxicity is not expected. Symptoms usually resolve within 8 hours. Symptomatic patients will require referral to hospital for abdominal X-ray or a venous blood gas (to confirm that the dose is not larger than 60 mg/kg of elemental iron) and general supportive measures (intravenous fluids may be required). Systemic toxicity is not expected, and hospital admission is usually not required.
> 60-120 mg/kg	Patients have severe gastrointestinal symptoms and systemic toxicity may occur. Patients should be referred to hospital for evaluation and management. With appropriate management (which may include whole bowel irrigation +/- chelation) admission for greater than 24 hours is uncommon.
> 120mg/kg	Patients develop severe gastrointestinal symptoms and systemic toxicity that is potentially lethal. Early aggressive evaluation, whole bowel irrigation, meticulous fluid resuscitation, chelation and management in an intensive care unit will be required.

Nursing

• Record a full set of observations on the age appropriate Paediatric Acute Response and Recognition Observation Tool (PARROT), with additional information to be recorded on the Clinical Comments chart.
• Record a full set of neurological observations.
• Minimum of hourly observations should be recorded whilst in the emergency department.
• A baseline Electrocardiogram (ECG) should be performed on arrival. Continual cardiac monitoring should be done during desferrioxamine infusion.
• Consider topical local anaesthetic e.g., lidocaine (lignocaine) with prilocaine (EMLA^®) if an IV may be required.
• Strict, accurate fluid balance monitoring.
  • Note the urine may have a red discolouration in the event that a chelating agent is given.

Risk assessment¹

• Vomiting and abdominal pain are common even after doses that are not associated with systemic toxicity.
• Systemic iron toxicity is characterised by:
  • shock
  • metabolic acidosis
  • hepatocellular injury
  • renal injury
  • gastrointestinal bleeding
• Risk assessment is based on the potential ingested dose of elemental iron and the observed evolving clinical features.
• The amount of elemental iron varies according to the form of iron, see Elemental Iron Equivalents table for common iron formulations.
  • In Australia the packaging usually states the elemental iron content (thus conversion is not required).
• If in doubt, consult the Poisons Information Centre (Telephone 13 11 26).

Elemental iron equivalents^1,5,7

Iron Formulation	Percentage Of Elemental Iron	Common Products	Elemental Iron Component
Ferrous sulfate	32%	325 mg tablet (Ferro-grad®) 250 mg tablet with folic acid (Ferro-grad F®)* 270 mg capsule with folic acid (Fefol®)*	105 mg 80 mg   87.4 mg
Ferrous gluconate	12%	207 mg capsule (Ferrous +C®)*	24 mg
Ferrous fumarate	33%	310 mg tablet with folic acid (Ferro-F®)* 200 mg tablet (Many brands including Ferro-tab®)	100 mg   65.7 mg
Iron polymaltose	27%	370 mg tablet (Maltofer®) 185 mg/5mL (Maltofer® Syrup®)	100 mg   50 mg per 5 ml
Ferrous sulfate heptahydrate	20%	150 mg per 5 mL liquid (Ferro-Liquid ®)	30 mg per 5 mL

**Fixed-dose combination products, consider the component of the other ingredients in the formulation although folate is not likely to cause toxicity.

Typical clinical course

• Symptoms are dose-dependent and range from mild GI upset to multi-organ failure.
• Significant toxicity follows predictable course with five clinical phases over time.

Phase	Onset post ingestion/duration	Clinical features
Phase 1 - Gastrointestinal	0.5-6 hours	Abdominal pain Vomiting Diarrhoea Large fluid losses may cause significant hypovolaemia, including metabolic acidosis, hypotension and dehydration
Phase 2 - Quiescent	6-12 hours	Progressive increase in iron absorption and distribution Improvement of gastrointestinal symptoms (sense of recovery)
Phase 3 - Cardiogenic shock and acidosis	24-48 hours	Progressive mitochondrial toxicity Hypotension Anion gap metabolic acidosis Vasodilatory shock (may develop from Phase 1) Potential multi-organ failure Coma
Phase 4 - Hepatic necrosis	2-5 days	Acute hepatic failure Jaundice Coagulopathy Hypoglycaemia Coma
Phase 5 - Bowel obstruction	2-6 days	Abdominal pain Vomiting Gastrointestinal fibrosis/strictures Cirrhotic liver disease

Investigations

Screening (in deliberate overdose)

• 12 lead ECG
• Blood glucose level
• Paracetamol level

Specific:

• Abdominal X-ray (quantity and confirmation of ingestion of radio-opaque iron tablets. X-ray may not show anything if a liquid or multivitamin preparation was ingested or in delayed presentations.).
• Serum iron level at 4-6 hours post ingestion.
• Blood gas
  • Bicarbonate is an indicator for metabolic acidosis (this may be used as a surrogate marker if iron levels are not available).

Suspected severe iron toxicity

• Full blood count
• Serum electrolyte, urea and creatinine concentrations
• Liver biochemistry
• Coagulation studies
• Blood glucose concentration
• Blood lactate concentration

Decontamination¹

• Indicated if the risk assessment suggests that the ingested dose is >60 mg/kg,
  AND
• patient has a normal mental status,
  AND
• there is evidence of iron tablets within the gastrointestinal tract (radio-opaque tablets are visible on X-ray, or presentation within 6 hours with clinical evidence of significant ingestion).
• Activated charcoal does not absorb iron.
• Whole bowel irrigation (WBI) with polyethylene glycol2 is the treatment of choice.
  • Commence nasogastric infusion at 25 mL/kg/hour.
  • Consultation with clinical toxicologist is recommended.
  • Preferred method for ingestions >60 mg/kg of elemental iron with evidence of tablet residue on abdominal X-ray and it has been less than 4 hours since ingestion.
  • Do not use in a patient at significant risk of pulmonary aspiration or with established ileus.
• Endoscopic removal may be indicated in patients with a potentially lethal iron ingestion (i.e., > 120 mg/kg of elemental iron) where whole bowel irrigation has failed or is impractical.

Enhanced elimination

• Not clinically useful.

Antidote^1,4

• Desferrioxamine (chelating agent)⁵ is the antidote for systemic iron poisoning.
• The decision to administer desferrioxamine is based on the presence of toxicity (shock, metabolic acidosis, altered mental status) or predicted by a serum iron level > 90 micromol/L (500 microgram/dL) at 4-6 hours post ingestion.
• Clinical Toxicologist should be contacted if administration of desferrioxamine is considered.
• Specific dosage and administration details should be obtained from the Toxicology Handbook.

Disposition⁴

•  Children who have ingested < 40 mg/kg elemental iron may be managed at home provided they remain asymptomatic.
• Larger or symptomatic ingestions are evaluated in hospital. The child who remains asymptomatic at 6 hours and has an abdominal X-ray negative for iron may be safely discharged.
• All patients who have deliberately self-poisoned with iron are evaluated in hospital. If the history suggests ingestion of < 60 mg/kg of elemental iron and they remain asymptomatic at 6 hours, they can be medically cleared. Psychiatric input is likely needed for a deliberate potentially lethal overdose.
• Symptomatic patients requiring intravenous fluid therapy or WBI require admission to a medical ward.
• Those presenting with established systemic iron toxicity or requiring intravenous chelation therapy are admitted to intensive care.
• In cases where serum iron levels are not easily accessible, declining serum bicarbonate levels or rising lactate levels serve as effective alternative indicators of systemic iron poisoning. When combined with worsening clinical symptoms, these markers warrant the administration of desferrioxamine.

References and related external legislation, policies, and guidelines

1. Toxicology and Toxinology – Iron Poisoning -Therapeutic Guidelines (External website).
2. AMH Children’s Dosing Companion (2024) Australian Medicines Handbook Pty Ltd 2021, [Internet] Macrogol laxatives; [Modified: January 2022. Cited: 16 February 2022] Available from: Macrogol laxatives - AMH Children's Dosing Companion (health.wa.gov.au)
3. Therapeutic Guidelines (2020), [Internet] Iron Poisoning [cited: 27 February 2024]. Available from: Topic | Therapeutic Guidelines (health.wa.gov.au)
4. The Toxicology Handbook (2022), 4th edition. Iron [Cited: 27 February 2024]
5. AMH Children’s Dosing Companion (2024) Australian Medicines Handbook Pty Ltd 2021, [Internet] Desferrioxamine; [Modified: January 2022. Cited: 16 February 2022] Available from: Desferrioxamine - AMH Children's Dosing Companion (health.wa.gov.au)
6. Toxinz Poisons Information (2013) National Poisons Centre, New Zealand. Online – http://www.toxinz.com
7. MIMSOnline February 2024. Cited 15 October 2024]

Related CAHS internal policies, procedures and guidelines

• Hypoglycaemia - ED Guidelines
• Poisoning – Paracetamol - ED Guidelines
• Poisoning Overview - ED Guidelines
• Poisoning - Salicylates - ED Guideline
• Poisoning – Tricyclic Antidepressants - ED Guideline
• Poisoning – Hypoglycaemic Agent – ED Guideline

Useful resources (including related forms)

• Poisons Information Service Western Australia: 13 11 26 (24-hour service).
• The Toxicology Handbook Fourth Edition – External website

Endorsed by:	Executive Director, Medical Services	Date:	Oct 2024
		Review date:	Jul 2027

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