Links to 220.127.116.11 Iron Teaching Resources
Iron poisoning typically occurs in children. In children, the ingestion of 2-5 tablets may cause significant toxicity. Iron poisoning causes gastrointestinal toxicity followed by multiorgan failure. The specific antidote, desferrioxamine, should be used in patients with high iron concentrations before severe toxicity develops.
Elemental iron is the major source of toxicity. However iron is available in a large number of different salts. To calculate the mg of elemental iron in a preparation
Iron toxicity develops when serum iron concentrations exceed the iron binding capacity of transferrin in blood. The free circulating iron damages many organs by direct cellular toxicity, effects on vasculature and the release of vasodilating mediators:
1. Direct corrosive effect on the GIT
2. Metabolic acidosis
a. Conversion of Fe++ to Fe+++, binding to -OH and release of H+
b. Inhibition of mitochondrial respiration and lactic acid production
c. Decreased CO, vasodilatation, decreased peripheral perfusion and anoxia
d. Hypovolaemia secondary to; vomiting, diarrhoea, and GIT haemorrhage and third spacing
e. Hepatic failure
3. Cell death following lipid peroxidation due to production of free radicals
a. Initially due to direct iron inhibition of thrombin, then;
b. Secondary to hepatotoxicity and reduced production of factors II, VII, IX and X
Iron is absorbed poorly in therapeutic doses in the duodenum and jejunum. However, with the development of gastrointestinal toxicity the extent and area of absorption is increased. Thus, the peak concentrations after iron poisoning occur later and the bioavailability is higher.
Iron is transported in the blood by transferrin. When the binding sites on transferrin are saturated the unbound iron reacts with blood vessels and platelets.
There is no significant natural route of elimination other than by gastrointestinal cell loss and blood loss.
A severe iron poisoning leads to multiorgan failure. However, there are distinct phases:
Acute gastrointestinal toxicity (0.5–6 hours post ingestion)
A severe haemorrhagic gastroenteritis (nausea, vomiting, diarrhoea, corrosion, haematemesis) occurs within a few hours of ingestion. Vomiting occurs in virtually all patients with severe poisoning but is not a specific sign. If fluid loss is significant there may be hypotension, acidosis and central nervous system signs.
Latent or window period (4–12 hours post ingestion)
During this period gastrointestinal symptoms improve.
Metabolic acidosis/multiorgan failure (6–72 hours post ingestion)
Subsequently systemic toxicity develops with pronounced effects on the following organs:
Central nervous system
An early and a late type of coagulopathy may occur. The early type is probably due to a direct effect of iron on the coagulation cascade. It occurs rapidly and the aPTT is generally longer than the PT. It resolves rapidly when iron concentrations fall.
The late type is due to hepatic failure and a notable effect on the prothrombin time will not occur until after 24 hours. It may continue to get worse for several days, however, by analogy with paracetamol poisoning, it is likely that a PT that continues to rise after 3 to 4 days indicate a very poor prognosis.
GIT stricture formation (2–6 weeks post ingestion)
Patients should have the following investigations done urgently:
Iron concentrations are used to determine the need for specific treatment. Abdominal X-rays may identify radio-opaque tablets however their absence does not exclude iron overdose. A raised white cell count and hyperglycaemia commonly occur early in poisoning. Other tests serve as a baseline with which to determine subsequent toxicity. These tests (as well as blood gases and invasive blood pressure monitoring) need to be repeated regularly in patients who develop gastrointestinal or other toxicity.
Iron concentrations give a good guide to subsequent chances of toxicity and guide therapy. Blood must be taken for iron concentrations prior to therapy with desferrioxamine.
Example: Note that elemental quantity of iron in tablets needs calculation
This may be done using clinical state, dose ingested and/or iron concentrations.
Estimation of toxicity based on dose of elemental iron ingested:
Severe poisoning requires close monitoring (CVP line, arterial line, regular electrolytes, blood gases and blood sugar) and enthusiastic volume replacement. Patients may require blood transfusions, fresh frozen plasma and correction of acidosis.
Iron is well known to form drug concretions (pharmacobezoar) and/or become adherent to the gastric wall due to its corrosive effect. Activated charcoal is not effective as iron is not adsorbed by charcoal.
If persistent iron present on X-ray then consider:
X-ray review following decontamination procedures should be performed to ensure removal of drug from the GIT.
Mechanism of action
Desferrioxamine chelates ferric irons. Desferrioxamine causes redistribution of iron from tissue sites back into plasma and the iron desferrioxamine complex is renally eliminated. Indications for desferrioxamine are based on clinical symptoms and/or iron concentrations.
Desferrioxamine treatment should be started if:
This test is often unreliable and is therefore no longer recommended.
Desferrioxamine is given intravenously at a rate of 15 mg/kg body weight/hour. Reduce dose by 50% in severe renal impairment.
The urine will often, but not always, change to a vin rose colour.
Patients should receive an IV fluid bolus of 20 mL/kg normal saline before starting desferrioxamine to maintain intravascular volume and because the desferrioxamine-iron complex is renally cleared.
Treatment should be continued until serum iron concentrations fall below 60 micromol/L and the urine (if it changed colour) has returned to normal. This normally means 6-8 hours of treatment but may be substantially longer in severe poisoning. Use of desferrioxamine for greater than 24 hours may result in non-cardiogenic pulmonary oedema.
Patients with initial severe gastrointestinal toxicity may develop gastric and pyloric scarring and obstruction.