The toddler with the Iron gut

An ingestion of 50mg/kg is expected to cause gastrointestinal symptoms, but not systemic toxicity.

Risk assessment according to dose is:

• <20mg/kg –– asymptomatic
• 20-60mg/kg –– GI symptoms only
• 60-120mg/kg –– potential for systemic toxicity
• >120mg/kg –– potentially lethal

Note that this is based on the amount of elemental iron ingested. This varies considerably between different types of iron tablets, depending on the type of ferrous or ferric salt:

• ferrous sulfate (dried) — divide dose by 3.3
• ferrous sulfate (heptahydrate) — divide dose by 5
• ferrous gluconate — divide dose by 9
• ferous fumarate — divide dose by 3
• ferric chloride — divide dose by 3.5
• ferrous chloride — divide dose by 4

Iron has local gastrointestinal effects followed by systemic effects (that do not occur without preceding GI toxicity following iron ingestion)

Local effects:

• corrosive injury to the gastrointestinal mucosa resulting in vomiting, diarrhoea, hemetemesis, melena and fluid losses that may result in hypovolemia.

Systemic effects:

• Although the exact mechanisms are uncertain, iron acts as a cellular toxin targetting the cardiovascular system and the liver, with secondary CNS effects, metabolic acidosis due to hyperlactemia and free proton production from the hydration of free ferric ions, and coagulopathy.

In overdose the finely tuned mechanisms that normally regulate gastrointestinal absorption of iron are overwhelmed and bioavailability is greatly increased. Once iron is absorbed into the systemic circulation iron is is gradually moved intracellularly over 6 to 12 hours. Elimination is minimal.

Iron poisoning classically follows 5 stages, although the stages usually overlap, reflecting the two important phases of toxicity: gastrointestinal and systemic.

Classic stages and time course of iron toxicity:

• 0-6 hours –– vomiting, diarrhoea, hemetemesis, melena, abdominal pain. Significant fluid loseses may lead to hypovolemic shock
• 6-12 hours –– gastrointestinal symptoms wane and the patient appears to be getting better. During this time iron shifts intracellularly from the circulation
• 12-48 hours –– Cellular toxicity becomes manifest as vasodilative shock and third-spacing, high anion gap metabolic acidosis (HAGMA) and hepatorenal failure
• 2-5 days –– acute heaptic failure, although rare mortality is high
• 2-6 weeks –– chronic sequelae occur in survivors –– cirrhosis and gastrointestinal scarring and strictures

In addition to the usual screening tests in suspected tox cases (BSL, ECG, paracetamol level) the following specific tests can be useful:

• serum iron concentration
  • peak levels occur 4-6 hours following iron ingestion
  • after 6 hours iron levels fall due to intracellular shift
  • levels do not clearly correlate with clinical toxicity, but > 90 micromol/L (500 mcg/dL) is generally considered predictive of systemic toxicity (equivalent to >60mg/kg)
• blood gas
  • the presence of HAGMA is a useful marker of systemic toxicity
  • in the absence of iron levels a serum bicarbonate level can be used as a surrogate marker
• abdominal X-ray — can be used to confirm ingestion

Desferrioxamine chelation therapy is an option for severe iron toxicity – the indications, duration and end-points of therapy are controversial.

Indications:

• level >90 micromol/L at 4-6 hours post-ingestion
• evidence of systemic toxicity
  • shock
  • metabolic acidosis
  • altered mental status

Administration:

• initial infusion rate of 15 mg/kg/h, reduced if hypotension occurs, may be titrated up to 40mg/kg/h in severe toxicity
• cardiac monitoring is mandatory
• desferrioxamine is is made as a 5 mg/mL solution by reconsituting 500mg in 5 mL sterile water then diluting up to 100 mL with normal saline or 5% glucose.

Adverse effects:

• hypersensitivity
• hypotension (with rapid or high-dose IV administration)
• ARDS (with infusions >24h)
• toxic retinopathy
• Yersinia sepsis (the ferrioxamine complex is a siderophore that promotes growth)

The infusion can be stopped when the patient is clinically stable and the serum iron level is <60 micromol/L. Ferrioxamine is excreted unchanged in the urine, which classically turns a vin rose colour.

Fluid resuscitation

Resuscitate with boluses of 10-20 mL/kg crystalloid to prevent shock from gastrointestinal losses, vasodilation and third spacing.

Decontamination is not indicated in this cases systemic toxicity is not expected based on risk assessment

Iron – like other metals – does not bind to activated charcoal but whole bowel irrigation can be used for abdominal x-ray confirmed ingestions of >60 mg/kg. In potentially lethal ingestions (e.g. >120 mg/kg) surgical or endoscopic removal of iron are options.

No

Ingestions of >40/mg/kg in children should be assessed at hospital. Then:

• Those asymptomatic at 6 hours with a negative abdominal x-ray can be discharged home.
• Those with symptoms are admitted to hospital and may require IV fluids.
• Patients with the potential for systemic toxicity may be best managed at larger hospitals where iron levels can be measured and iron chelation therapy administered if needed.

In hospitals where serum iron levels are unavailable a serum bicarbonate can be used as a surrogate marker of systemic toxicity.

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• Tenenbein M (1996). Benefits of parenteral deferoxamine for acute iron poisoning. Journal of Toxicology – Clinical Toxicology, 34 (5), 485-9 PMID: 8800185
• Cohen AR (2007). Pediatric iron overload. Clinical Advances in Hematology & Oncology, 5 (8), 601-2 PMID: 17982399
  Howland MA (1996). Risks of parenteral deferoxamine for acute iron poisoning. Journal of Toxicology – Clinical Toxicology, 34 (5), 491-7 PMID: 8800186
• Madiwale T,  Liebelt E (2006). Iron: not a benign therapeutic drug. Current Opinion in Pediatrics, 18 (2), 174-9 PMID: 16601499
• Manoguerra AS, et al (2005). Iron ingestion: an evidence-based consensus guideline for out-of-hospital management. Clinical Toxicology, 43 (6), 553-70 PMID: 16255338