Iron Overdose

Reviewed and revised 23 May 2014

OVERVIEW

• Iron overdose can have local gastrointestinal effects as well as characteristic systemic toxicity (metabolic acidosis, liver failure, shock and multi-organ failure)
• Risk assessment is based on the amount of elemental iron ingested
• Iron does not bind to activated charcoal, but endoscopic/ surgical decontamination may be appropriate, and whole bowel irrigation has been used
• A specific antidote desferioxamine is available

MECHANISM OF TOXICITY

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, haemetemesis, melaena and fluid losses that may result in hypovolaemia.

Systemic effects:

• exact mechanisms are uncertain
• iron acts as a cellular toxin targeting 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

TOXICOKINETICS

• 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.

RISK ASSESSMENT

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

CLINICAL FEATURES

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, haemetemesis, 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

INVESTIGATIONS

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
• LFTs, Coags — hepatic failure
• UEC — renal failure

MANAGEMENT

Resuscitation as indicated with concurrent specific assessment and management of the toxidrome.

Resuscitation:

• ABCs
• Priority is early restoration of circulating volume
• Resuscitate with boluses of 10-20 mL/kg crystalloid to prevent shock from gastrointestinal losses, vasodilation and third spacing

Supportive care and monitoring

• Ongoing assessment of response to resuscitation and antidotes (see below)

Decontamination

• Iron not adsorbed by activated charcoal
• Whole bowel irrigation indicated for confirmed ingestions > 60 mg/kg (difficult and potentially hazardous in small children)
• Surgical or endoscopic removal of tablets if lethal ingestion (e.g. >120mg/kg) or WBI not feasible

Antidotes

• Desferrioxamine chelation therapy in cases of systemic toxicity (high serum 1iron level or metabolic acidosis on ABG) (see below)

Enhanced elimination

• nil

Disposition

• Ingestion of >40/mg/kg in children should be assessed at hospital
• 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 (ward, HDU, ICU depending on severity; ideally a paediatric center)
• 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
• Consider neglect in children
• Psychiatric assessment in adults

DESFERRIOXAMINE

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

Indications (may also be used in chronic iron overload)

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

Mechanism of action

• chelates free ferric and ferrous ions in the plasma resulting in water soluble complexes that can be renally excreted
• removes iron bound to transferrin and hemosiderin in the vascular compartment (does not effectively remove iron from stores in other compartments)
• ferrioxamine is excreted unchanged in the urine, which classically turns a vin rose colour (although this is not a reliable indicator of chelation)

Administration

• initial IV 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
• reconstitute the 500 mg powder with 5 mls sterile water and dilute to 100 mls with 5% glucose or normal saline

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)

Endpoints

• The infusion can be stopped when the patient is clinically stable and the serum iron level is <60 micromol/L
• usually about 56 hours therapy is sufficient, treatment >24 hours is rare

References and Links

LITFL

• Toxicology Conundrum 034 — The toddler with the Iron gut

Journal articles and Textbooks

• Chang TP, Rangan C. Iron poisoning: a literature-based review of epidemiology, diagnosis, and management. Pediatric emergency care. 27(10):978-85. 2011. [pubmed]
• Chyka PA, Butler AY. Assessment of acute iron poisoning by laboratory and clinical observations. The American journal of emergency medicine. 11(2):99-103. 1993. [pubmed]
• Murray, Lindsay, Daly, F, Little, M, Cadogan M. Toxicology handbook. 2nd ed. Sydney: Churchill Livingstone; 2010
• Singhi SC, Baranwal AK, M J. Acute iron poisoning: clinical picture, intensive care needs and outcome. Indian pediatrics. 40(12):1177-82. 2003. [pubmed]