Case Based Pediatrics For Medical Students and Residents
Department of Pediatrics, University of Hawaii John A. Burns School of Medicine
Chapter XIV.11. Iron Overdose
Lynette L. Young, MD
August 2002

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A 2 year old boy presents to the emergency department with a chief complaint of blood-tinged vomiting. His mother was tending to her newborn infant when the patient climbed up and grabbed his mom's bottle of iron pills from the counter. He was able to open the bottle and thinking that the pills looked like candy, he ate them. His mother brought in her bottle of ferrous sulfate 325 mg (65 mg elemental iron) tablets. Counting the iron tablets in the bottle there is a maximum of 15 tablets missing (975 elemental Fe/12 kg = 81 mg/kg of elemental iron ingested).

Exam: VS T 36.9, P 120, R 30, BP 88/60, weight 12kg (10th percentile). He is alert, and being carried by mom. His skin is pink and warm with good perfusion and capillary refill. HEENT exam is negative. His oral mucosa is moist and there are no lesions. His neck is nontender. Heart regular rhythm and normal rate. Lungs are clear with good aeration. His abdomen is soft and slightly tender in the upper quadrants, with active bowel sound and no guarding. His distal pulses are strong and his distal extremities are warm. He is responding appropriately to mom.

An abdominal series reveals radiopaque tablets in the stomach and intestine.


Iron is a serious and potentially fatal ingestion. It used to be one of the leading causes of fatal poisonings in the pediatric age group. Toxicity is based on the amount of elemental iron ingested. The most common forms of iron include: ferrous sulfate (20% elemental iron), ferrous fumarate (33% elemental iron), and ferrous gluconate (12% elemental iron). Children's multivitamin with iron preparations contain 8 to 18 mg of elemental iron per chewable tablet. A common iron containing medication is a prenatal vitamin, which has 325 mg ferrous sulfate (65 mg elemental iron) per tablet.

Iron is absorbed in the intestine. The peak serum level ranges from 2 to 6 hours after ingestion of iron. Iron is absorbed in the ferrous (Fe++) form and is oxidized to the ferric from (Fe+++) within the cells. It is transported in the blood bound to transferrin. The iron binding capacity (transferrin level) is usually 300-500 mcg/dl (TIBC) and normal serum iron levels are 50-150 mcg/dl. There is usually no free iron circulating in the blood. The body has no specific way to excrete iron. Iron toxicity may result from the caustic/corrosive effect directly to the gastrointestinal mucosa. This may lead to perforation causing fluid loss from the gastrointestinal tract. Hypovolemia and shock may result. The second mechanism of toxicity is due to the presence of free iron in the circulation. Free iron may affect any organ including the kidneys, brain, lung, and heart. It builds up mainly in the liver. Free iron is found to concentrate in the mitochondria. Oxidative phosphorylation uncoupling is a mechanism for cellular toxicity. There are other unknown mechanisms for cellular injury. Lactic acidosis results from tissue hypoperfusion/cellular hypoxia. Free iron may also cause direct damage to the heart leading to decreased myocardial contractility (negative inotropic effect on the myocardium). Coagulopathies may occur from effects of iron on clotting factors.

There are four clinical phases of iron toxicity. In Phase I (0-6 hours), symptoms are due to the direct caustic/corrosive effect to the gastrointestinal mucosa. The patient may have symptoms of abdominal pain, vomiting (often with blood), and diarrhea. With severe iron poisoning, the patient may be lethargic or lapse into a coma. Shock and metabolic acidosis may result from blood and fluid loss and tissue hypoperfusion. Phase II (6-48 hours) is called the "honeymoon phase" or latent period. In this phase the gastrointestinal symptoms subside. There is an apparent improvement in symptoms. The patient may appear to be stabilized with appropriate therapy. Phase III (12 hours-5 days) is also known as the shock phase. There may be recurrence of gastrointestinal bleeding. Other symptoms in this clinical stage may include cyanosis, profound metabolic acidosis, coma, seizure, shock, and coagulopathy. The patient may have cardiac failure, renal failure, hepatic failure, and may go on to cardiovascular collapse and death. In Phase IV (2-6 weeks), the consequences of the corrosive effects of iron to the gastrointestinal mucosa may be evident. There may be scarring leading to strictures in the gastrointestinal tract. Obstruction may occur at the gastric outlet or small intestines.

A patient who has ingested less than 20 mg/kg of elemental iron and is asymptomatic can be observed. If the patient remains asymptomatic 4-8 hours after ingestion, he/she can be discharged to home. A serum iron level should be obtained on arrival to the emergency department if the patient is symptomatic or has ingested >60 mg/kg of elemental iron. A serum iron level should be drawn 4-6 hours post-ingestion if the patient is asymptomatic and has ingested 20-60 mg/kg or an unknown amount of elemental iron. With a serum iron level of less than 300 mcg/dl, the patient is usually asymptomatic. There is potentially moderate toxicity with an iron level between 300 to 500 mcg/dl. Serum iron levels greater than 500 mcg/dl fall in the severe toxicity range. If the iron tablet is enteric-coated or a sustained-released tablet, the absorption may be delayed and a second level drawn 6-8 hours after ingestion should be considered. The serum iron level may not be reliable if deferoxamine has been given. Other laboratory tests that are recommended are serum electrolytes, BUN, and creatinine. A baseline CBC can be drawn. An abdominal radiograph to look for radiopaque iron pills may be helpful. There are several tests previously used in iron poisoning which are no longer recommended. These include the total iron binding capacity (TIBC) (1) and the deferoxamine challenge test. They are not good predictors of toxicity. Also, previously recommended white blood cell count >15,000/mcL and blood sugar level of >150 mg/dL should not be used to predict the severity of iron overdose (2).

For patients with serious iron ingestion, treatment should include gastric decontamination, intensive supportive therapy, and deferoxamine administration. Gastric lavage should be done for patients with a large ingestion or if they are symptomatic. Whole bowel irrigation (WBI) is recommended if there are iron pills seen on X-ray and for any significant ingestion. The pediatric dose is 25-40 ml/kg/h up to a maximum of 500 ml/h. The dose in adolescents and adults is 1.5 to 2 L/h (3). This is continued for 4-6 hours or until the rectal effluent is clear. There are no studies to prove the effectiveness of whole-bowel irrigation in iron poisoning. A follow-up radiograph may be indicated. Activated charcoal does not bind iron well, but it can be considered if there is a co-ingestion.

Supportive treatment may include intravenous crystalloid fluids to treat shock. Dopamine and norepinephrine can be used if the hypotension persists. Blood component therapy may be needed for those patients with blood loss. Exchange transfusion is sometimes considered in young patients who worsen despite deferoxamine therapy although its effectiveness is questionable.

Deferoxamine chelates the ferric ion (Fe+++). It is given intravenously to patients who are symptomatic with vomiting, diarrhea, increased anion gap metabolic acidosis, gastrointestinal bleeding, lethargy, or hypotension. Deferoxamine therapy is also recommended if the serum iron level is greater than 500 mcg/dl. The iron-deferoxamine complex (ferrioxamine) is water-soluble and is excreted in the urine. It may cause the urine to be pinkish-orange ("vin-rose"). The initial dose of deferoxamine is 15 mg/kg/h. The rate may be increased up to 25 to 40 mg/kg/h. Rapid infusion of deferoxamine may cause hypotension.

Mortality is low in iron poisoning patients if they do not have shock or coma. With supportive treatment of patients with shock or coma, the mortality rate is about 50%. If deferoxamine treatment is added, the mortality rate drops to 10%. Patients may be discharged home from the emergency department after 4-6 hours of observation if they are asymptomatic, have serum iron levels less than 300 to 500 mcg/dl, and have a negative abdominal X-ray. A psychiatric evaluation is needed if it was an intentional ingestion.


Questions

1. True or False: Charcoal is effective in binding iron and should be given in significant iron ingestions.

2. A 3 year old female (15 kg) ingested 15 of her mom's prenatal (325 mg ferrous sulfate) iron tablet. How much elemental iron per kilogram did she take?
. . . . . a. 15 mg/kg
. . . . . b. 25 mg/kg
. . . . . c. 45 mg/kg
. . . . . d. 65 mg/kg
. . . . . e. 85 mg/kg

3. Deferoxamine chelates the:
. . . . . a. Ferrous ion (Fe++).
. . . . . b. Ferric ion (Fe+++).

4. The two basic mechanisms of iron toxicity include:
. . . . . a. Direct corrosive effect on the gastrointestinal mucosa.
. . . . . b. Formation of a toxic metabolite.
. . . . . c. Binding to the protein transferrin.
. . . . . d. Toxic effect of the free ion.

5. Gastrointestinal symptoms may improve in which clinical (latent) stage of iron poisoning?
. . . . . a. Phase I
. . . . . b. Phase II
. . . . . c. Phase III
. . . . . d. Phase IV
. . . . . e. Phase V

6. True or False: Total iron binding capacity (TIBC) is a reliable predictor of toxicity in iron poisoning?

7. The whole bowel irrigation rate in children is?
. . . . . a. 5 ml/kg/h.
. . . . . b. 25 ml/kg/h.
. . . . . c. 75 ml/kg/h.
. . . . . d. 100 ml/kg/h.

8. The deferoxamine infusion rate should initially be started at:
. . . . . a. 15 mg/kg/h.
. . . . . b. 25 mg/kg/h.
. . . . . c. 40 mg/kg/h.
. . . . . d. 50 mg/kg/h.


References

1. Tenenbein M, Yatscoff RW. The total iron-binding capacity in iron poisoning - Is it useful? Am J Dis Child 1991;45:437-439.

2. Palatnick W, Tenenbein M. Leukocytosis, hyperglycemia, vomiting, and positive X-rays are not indicators of severity of iron overdose in adults. Am J Emerg Med 1996;14:454-455.

3. Velez LI, Delaney KA. Chapter 151 - Heavy Metals. In: Marx JA (ed). Emergency Medicine Concepts and Clinical Practice, fifth edition. 1992, St. Louis: Mosby Year Book, pp. 2151-2152.

4. Osterhoudt KC, Shannon M, Henretig FM. Chapter 88 - Toxicologic Emergencies. In: Fleisher GR, Ludwig S (eds). Textbook of Pediatric Emergency Medicine, fourth edition. 2000, Baltimore: Lippincott Williams & Wilkins, pp. 914-917.

5. Wasserman GS. Chapter 40 - Specific Toxins. In: Barkin RM (ed). Pediatric Emergency Medicine Concepts and Clinical Practice. 1997, St. Louis: Mosby Year Book, pp. 555-556.

6. Dart RC (ed). The 5 Minute Toxicology Consult. 2000, Baltimore: Lippincott Williams & Wilkins, pp. 446-447.

7. Woo OF. Iron. In: Olsen KR (ed). Poisoning & Drug Overdose, third edition. 1999, Stamford: Appleton & Lange, pp. 192-194.

8. Perrone J. Chapter 35 Iron. In Goldfrank LR, Flomenbaum NE, Lewin NA, Weisman RS, Howland MA, Hoffman RS (eds). Goldfrank's Toxicologic Emergencies, sixth edition. 1998, Stamford: Appleton & Lange; pp. 619-627.

9. Fine JS. Iron poisoning. Curr Probl Pediatr 2000;30:71-90.


Answers to questions

1. False

2. d

3. b

4. a & d

5. b

6. False

7. b

8. a


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