(See also General Principles of Poisoning General Principles of Poisoning Poisoning is contact with a substance that results in toxicity. Symptoms vary, but certain common syndromes may suggest particular classes of poisons. Diagnosis is primarily clinical, but for... read more .)
Many commonly used over-the-counter (OTC) preparations contain iron. Of the many iron compounds used in OTC and prescription preparations, the most common are
Ferrous sulfate (20% elemental iron)
Ferrous gluconate (12% elemental iron)
Ferrous fumarate (33% elemental iron)
To children, iron tablets may look like candy. Prenatal multivitamins are the source of iron in most lethal iron ingestions among children. Children’s chewable multivitamins with iron usually have such small amounts that toxicity rarely occurs.
Pathophysiology of Iron Poisoning
Iron is toxic to the gastrointestinal system, cardiovascular system, and central nervous system. Specific mechanisms are unclear, but excess free iron is inserted into enzymatic processes and interferes with oxidative phosphorylation, causing metabolic acidosis Metabolic Acidosis Metabolic acidosis is primary reduction in bicarbonate (HCO3−), typically with compensatory reduction in carbon dioxide partial pressure (Pco2); pH may be markedly low or slightly... read more . Iron also catalyzes free radical formation, acts as an oxidizer, and, when plasma protein binding is saturated, combines with water to form iron hydroxide and free H+ ions, compounding the metabolic acidosis. Coagulopathy may appear early because of interference with the coagulation cascade and later because of liver injury.
Toxicity depends on the amount of elemental iron that has been ingested. Up to 20 mg/kg of elemental iron is not toxic, 20 to 60 mg/kg is mildly to moderately toxic, and > 60 mg/kg can cause severe symptoms and morbidity.
Symptoms and Signs of Iron Poisoning
Symptoms of iron poisoning occur in 5 stages (see table Stages of Iron Poisoning Stages of Iron Poisoning ); however, symptoms and their progression vary significantly. The severity of stage 1 symptoms usually reflects the overall severity of poisoning; late-stage symptoms develop only if stage 1 symptoms are moderate or severe. If no symptoms develop within the first 6 hours after ingestion, risk of serious toxicity is minimal. If shock and coma develop within the first 6 hours, the mortality rate is about 10%.
Diagnosis of Iron Poisoning
Determination of serum iron, electrolytes, and pH 3 to 4 hours after ingestion
Iron poisoning should be considered in mixed ingestions (because iron is ubiquitous) and in small children with access to iron and unexplained metabolic acidosis or severe or hemorrhagic gastroenteritis. Because children often share, siblings and playmates of small children who have ingested iron should be evaluated.
Abdominal x-ray is usually recommended to confirm ingestion; it detects intact iron tablets or iron concretions but misses chewed and dissolved tablets, liquid iron preparations, and iron in multivitamin preparations. Serum iron, electrolytes, and pH are determined 3 to 4 hours after ingestion. Toxicity is assumed if suspected ingestion is accompanied by any of the following:
Vomiting and abdominal pain
Serum iron levels > 350 mcg/dL (63 micromol/L)
Iron visible on x-ray
Unexplained metabolic acidosis
These iron levels may indicate toxicity; however, iron levels alone do not predict toxicity accurately. Total iron binding capacity is often inaccurate and not helpful in diagnosing serious poisoning and is not recommended. The most accurate approach is to serially measure levels of serum iron, bicarbonate, and pH (with calculation of the anion gap); these findings are then evaluated together, and results are correlated with the patient’s clinical status. For example, toxicity is suggested by increasing iron levels, elevated anion gap metabolic acidosis, worsening symptoms, or, more typically, some combination of these findings.
The deferoxamine challenge test is no longer recommended for evaluation of possible iron overdose because of poor sensitivity. In this test, deferoxamine, an iron chelating agent, was given intramuscularly, and serial urine samples were evaluated for the characteristic orange or reddish brown color (vin rosé urine) caused by excreted ferrioxamine).
Treatment of Iron Poisoning
For severe toxicity, IV deferoxamine
If radiopaque tablets are visible on abdominal x-ray, whole-bowel irrigation Whole-bowel irrigation Poisoning is contact with a substance that results in toxicity. Symptoms vary, but certain common syndromes may suggest particular classes of poisons. Diagnosis is primarily clinical, but for... read more with polyethylene glycol 1 to 2 L/h for adults or 25 to 40 mL/kg/h for children is done until no iron is visible on repeat abdominal x-ray. Administration via nasogastric tube may be necessary to deliver these large volumes and care must be taken to protect the airway; intubation may be necessary (see Tracheal Intubation Tracheal Intubation Most patients requiring an artificial airway can be managed with tracheal intubation, which can be Orotracheal (tube inserted through the mouth) Nasotracheal (tube inserted through the nose)... read more ). Gastric lavage is usually not helpful because vomiting tends to empty the stomach more efficiently. Activated charcoal does not adsorb iron and should be used only if other toxins also were ingested.
All patients with more than mild gastroenteritis are hospitalized. Patients with severe toxicity ( metabolic acidosis, Metabolic Acidosis Metabolic acidosis is primary reduction in bicarbonate (HCO3−), typically with compensatory reduction in carbon dioxide partial pressure (Pco2); pH may be markedly low or slightly... read more shock, severe gastroenteritis, or serum iron level > 500 mcg/dL [89.5 micromol/L]) are treated with IV deferoxamine to chelate free serum iron. Deferoxamine is infused at rates up to 15 mg/kg/h IV, titrated until hypotension occurs. Because both deferoxamine and iron poisoning can decrease blood pressure, patients receiving deferoxamine require IV hydration.
Iron toxicity, like some other hepatotoxins, can cause gastroenteritis followed by a quiescent phase, then shock and liver failure.
Suspect iron poisoning in mixed ingestions (because iron is ubiquitous) and in small children with access to iron and unexplained metabolic acidosis or severe or hemorrhagic gastroenteritis.
Suspect that toxicity is severe with increasing iron levels, metabolic acidosis, worsening symptoms, or a combination.
Do whole-bowel irrigation until an abdominal x-ray shows absence of radiopaque iron products.
Give IV deferoxamine to treat severe poisoning (eg, metabolic acidosis, shock, severe gastroenteritis, serum iron level > 500 mcg/dL [89.5 micromol/L]).
Drugs Mentioned In This Article
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