Like all heavy metal exposures an acute ingestion results in gastrointestinal irritation and then dose-related systemic toxicity potentially leading to death. Iron takes hours to reach from the GI tract to the intracellular space. This gives us the opportunity to prevent further absorption in large overdoses with decontamination and chelation.
Locally it is corrosive causing vomiting, diarrhoea, haematemasis and melaena with large GI fluid losses. Iron is a direct cellular toxin with major targets including the cardiovascular system and the liver. CNS toxicity results form the CVS instability and metabolic derangement. The coagulation cascaded is distributed and lactic acid forms from the liberation of hydrogen ions during the hydration of free ferric ions in the plasma.
- Absorption is normally finely regulated according to the body’s requirements, in overdose this mechanism is overwhelmed and bioavailability increases.
- Absorption of iron shifts intracellularly over a number of hours.
- Elimination is minimal in overdose.
- Hypovolaemia from GI losses:
- Give 10 – 20 ml/kg of IV crystalloid, if response is not adequate start noradrenaline [dose: 0.15mg/kg in 50ml D5W at 1-10ml/hr (0.05 – 0.5 mcg/kg/min)]. Ongoing fluid resuscitation is essential when there are ongoing losses and 3rd spacing.
- Iron overdose can be lethal and is based on the elemental iron in each drug preparation.
Ferrous or Ferric salt Calculation required for elemental iron Ferric Chloride Divide dose by 3.5 Ferrous Chloride Divide dose by 3 Ferrous Fumarate Divide dose by 3 Ferrous Gluconate Divide dose by 9 Ferrous Sulfate (dried) Divide dose by 3.3 Ferrous Sulfate Divide dose by 5
- >60 mg/kg of elemental iron can potentially lead to systemic toxicity.
- The risk assessment can be refined by abdominal X-rays to count the number of tablets (if the preparation is radio-opaque) and a 4 – 6 hour post ingestion level.
- Systemic toxicity does not occur without GI symptoms.
- Those presenting with systemic features of toxicity have a poor prognosis.
- Children: The dose ingested is usually less than that expected to cause systemic toxicity (60mg/kg)
Elemental Iron Dose Effect <20 mg/kg Asyptomatic 20 - 60 mg/kg Gastrointestinal symptoms >60 - 120 mg/kg Systemic toxicity anticipated >120 mg/kg Potentially lethal
- Although sometimes these phases merge and it should be just thought of a gastrointestinal phase and a systemic toxicity phase.
Time post-ingestion Clinical Features 0 - 6 hours Direct corrosive effect on the GI tract. Vomiting, diarrhoea and abdominal pain. Fluid losses may result in hypovolaemic shock 6 - 12 hours Increased iron absorption/distribution. Resolution of some symptoms making people suspect recovery. 12 - 48 hours Distribution of cellular metabolism - shock from vasodilatation and 3rd space losses, anion gap metabolic acidosis and hepatorenal failure. 2 - 5 days Acute hepatic failure with jaundice, coma, hypoglycaemia, coagulopathy and elevated aminotransferases. This phase is rare but has a high mortality. 2 - 6 weeks Delayed sequelae, including cirrhotic liver disease and GI fibrosis/strictures.
- Monitor fluid resuscitation and general supportive measure for any organ failure.
- Correct electrolyte abnormalities.
- Screening: 12 lead ECG, BSL, Paracetamol level
- FBC, EUC, LFTs, ABG (anion gap metabolic acidosis)
- Chest and abdominal X-rays (can confirm and monitor ingestion but be careful, some preparations are not radio-opaque – this is not a rule out test).
- Serum iron concentration usually peaks at 4 – 6 hours post ingestion. Levels > 90 micromol/L (500 microgram/dL) are thought to be predictive of systemic toxicity.
- If iron levels are not available a fall in the bicarbonate in conjunction with worsening symptoms is a good surrogate marker for systemic toxicity.
- Whole bowel irrigation with polyethylene glycol if the patient is cooperative and presents with >60mg/kg of elemental iron ingestion confirmed on X-ray.
- It requires one nurse – probably for the next 6 hours
- Place nasogastric tube and confirm with X-ray
- Administer PEG solution at 2L/hour by continuous infusion (children 25 ml/kg/hour)
- Given metoclopramide to reduce nausea and increase gastric emptying.
- Place the patient on a commode and continue until effluent is clear.
- Stop if there is abdominal distension or loss of bowel sounds.
- Serial abdominal X-rays can track the transit.
- If this is not possible it may be reasonable to remove the tablets via endoscope particularly when the ingestion maybe lethal.
- Not clinically useful
- Chelation is indicated when there is systemic toxicity (shock, metabolic acidosis, altered mental state) or a 4 – 6 hour iron level is >90 micromol/L (500 microgram/dL)
- Chelation with desferrioxamine is the agent of choice.
- Children who have ingested <40 mg/kg can be managed at home if asymptomatic. Larger ingestions require evaluation. Those who are asymptomatic at 6 hours maybe discharged.
- Any adult who has ingested <60 mg/kg can be observed for 6 hours and if asymptomatic can be medically cleared.
- Symptomatic patients require admission and those with systemic toxicity require chelation and an ICU admission.
References and Additional Resources:
- Chyka PA, Butler AY. Assessment of acute iron poisoning by laboratory and clinical observations. American Journal of Emergency Medicine 1993: 11(2):99-103.
- Murray L et al. Toxicology Handbook 3rd Edition. Elsevier Australia 2015. ISBN 9780729542241
- Pearn J, Nixon J, Ansford A, et al. Accidental poisoning in childhood: five year urban population study with 15 year analysis of fatality. British Medical Journal 1984; 288:44-46.
- Singhi SC, Baranwal AK, Jayashree M. Acute iron poisoning: Clinical picture, intensive care needs and outcome. Indian Pediatrics 2003: 40(12):1177-1182.
- Tenenbein M. Benefits of parenteral deferoxamine for acute iron poisoning. Journal of Toxicology – Clinical Toxicology 1996; 34(5):485-489.