AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Iron overdose has been one of the leading causes of death caused by toxicological agents in children younger than 6 years. Iron is used as a pediatric or prenatal vitamin supplement and for treatment of anemia. Iron is particularly tempting to young children because it appears similar to candy. Patients with anemias that require frequent blood transfusions also are at risk for developing chronic iron toxicity.

Pathophysiology

Iron toxicity can be classified as corrosive or cellular.

• Corrosive toxicity: Iron is an extremely corrosive substance to the GI tract. It acts on the mucosal tissues and manifests as hematemesis and diarrhea; patients may become hypovolemic because of fluid and blood loss.
• Cellular toxicity: The absorption of excessive quantities of ingested iron results in systemic iron toxicity. Severe overdose causes impaired oxidative phosphorylation and mitochondrial dysfunction, which can result in cellular death. The liver is one of the organs most affected by iron toxicity, but other organs such as the heart, kidneys, lungs, and the hematologic systems also may be impaired.

Individuals demonstrate signs of GI toxicity with ingestions of more than 20 mg/kg, but less than or equal to 40 mg/kg. Moderate-to-severe intoxication occurs when ingestion of elemental iron exceeds 40 mg/kg. Ingestions exceeding 60 mg/kg may be lethal.

Frequency

United States

More than 20,000 children accidentally ingested iron in 1995.

Mortality/Morbidity

Iron poisoning may result in mortality or short-term and long-term morbidity.

Age

Iron overdose is one of the leading causes of fatality from toxicological agents in children younger than 6 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Iron ingestions with GI symptoms such as vomiting and diarrhea (especially hemorrhagic)
• Hemorrhagic gastroenteritis, even in the absence of ingestion
• Hyperglycemia with metabolic acidosis during or following episodes of abdominal pain and gastroenteritis

Physical

Iron poisoning is often classified into 4 distinct stages. Understanding the course of poisoning is important, especially the second (recovery) stage, which may lure the physician into a false sense of security and result in premature and inappropriate discharge of a patient.

• Stage 1
• • Nausea and diarrhea, often accompanied by abdominal pain, characterize the gastrointestinal (GI) phase.
  • When the intoxication is severe, a hemorrhagic component is observed in conjunction with gastroenteritis.
  • The combination of fluid and blood loss, with additional third-spacing, may result in hypovolemia or shock.
  • Fatality occurs in a significant percentage of patients during this first phase.
• Stage 2
• • This stage is characterized by resolution of GI symptoms.
  • The patient appears to improve and recover.
  • This deceptive phase usually occurs 6-12 hours postingestion and may last as long as 24 hours.
  • Metabolic abnormalities during this phase may include hypotension, metabolic acidosis, and coagulopathy.
  • Some patients skip this phase and progress directly to stage 3.
• Stage 3
• • Stage 3 is characterized by metabolic acidosis.
  • It is hypothesized that high iron concentrations produce venous pooling and third-spacing of fluids.
  • Elevated liver enzymes and bilirubin are commonly observed with coagulopathy, indicative of hepatic dysfunction.
  • Hypoglycemia may accompany liver dysfunction.
  • The acidosis may indicate failure of other organs, such as the heart and kidneys.
• Stage 4
• • This stage is characterized by scarring of the healing GI tract. The stomach and/or intestines may be affected, resulting in gastric outlet or intestinal obstruction.
  • This phase usually is experienced weeks after a severe poisoning.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Sepsis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Measure steady-state serum iron levels at least 4 hours postingestion. Levels drawn more than 6 hours after ingestion may underestimate toxicity caused by ferritin binding and redistribution of iron.
• • Mild-to-moderate toxicity generally manifests at levels of 350-500 mcg/dL.
  • Hepatotoxicity usually is observed at levels higher than 500 mcg/dL.
  • Levels higher than 800 mcg/dL are associated with severe toxicity.
  • Samples drawn too early or too late postingestion may be unreliable.
  • In adults, hyperglycemia, leukocytosis, abdominal pain, and vomiting may be absent.
• Glucose
• • Glucose levels exceeding 150 mg/dL are common with severe iron toxicity.
  • Following glucose levels is important because hepatic dysfunction may cause hypoglycemia.
• Complete blood count
• • A white blood cell (WBC) count more than 15,000/mm³ is associated with severe iron poisoning.
  • A CBC is also helpful because anemia from blood loss may develop.
• Arterial blood gas (ABG) measurements are useful in determining the existence and severity of a metabolic acidosis.
• Coagulation studies are essential. Following the prothrombin time may be helpful.
• • Perform liver function tests (LFTs). Hepatic dysfunction is common in severe iron poisoning because the liver is the first organ outside of the GI tract to encounter iron.
• Electrolyte measurements and renal function tests assist in calculation of the anion gap and detection of electrolyte abnormalities and the presence of prerenal azotemia.
• Lipase and amylase levels may document occasional pancreatic injury.
• Obtain a pregnancy test in women of childbearing age.
• Determine type and cross-matching.
• Ferritin levels are helpful for chronic toxicity >1000 mcg/L.

Imaging Studies

• A kidneys, ureters, bladder (KUB) film can determine if radiopacities are present; iron tablets are radiopaque for a few hours postingestion. However, the absence of radiopacities does not rule out a significant or lethal ingestion.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

• For patients who are hypovolemic, administer fluid boluses of 20 mL/kg of 0.9 isotonic sodium chloride solution or lactated Ringer (LR) solution.
• Provide oxygen to patients in shock.

Emergency Department Care

• Assume that symptomatic patients are hypovolemic. Administer vigorous isotonic crystalloid therapy (eg, 0.9 isotonic sodium chloride solution, LR solution) in 20 mL/kg boluses to attain and maintain hemodynamic stability.
• Gastric lavage with a large bore orogastric tube or administration of ipecac syrup may remove iron from the stomach. Ideally, these treatments should be performed 1-2 hours postingestion or even later if evidence of iron products in the stomach are observed on an x-ray. Each modality has its disadvantages.
• • Iron has a gelatinous texture and may be difficult to remove by lavage. Bezoar formation may occur.
  • The use of ipecac syrup is controversial. It may cause confusion regarding the etiology of vomiting (eg, from the iron toxicity or the emetic agent). Significant ingestions may cause hypotension and unstable vital signs. Therefore, only administer ipecac syrup in the prehospital setting (eg, if a child has ingested a significant amount of iron within the past 60 min).
• Perform whole-bowel irrigation in patients with a radiopacity on KUB until the radiopacity clears. Activated charcoal does not bind iron but should be utilized if co-ingestants are suspected.
• Oxygen should be supplemented.

Consultations

• Consultation with a toxicologist is recommended.
• Obtain a gastroenterology consultation for patients who have large iron bezoars.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce iron levels, prevent complications, and reduce morbidity.

Drug Category: Chelating agents

Chelation is the mainstay of therapy. It is indicated for serum iron levels >350 mcg/dL with evidence of toxicity or >500 mcg/dL regardless of signs or symptoms.

Drug Name	Deferasirox (Exjade)
Description	Tab for oral susp. Oral iron chelation agent demonstrated to reduce liver iron concentration in adults and children who receive repeated RBC transfusions. Binds iron with high affinity in a 2:1 ratio. Approved to treat chronic iron overload due to multiple blood transfusions. Treatment initiation recommended with evidence of chronic iron overload (ie, transfusion of about 100 mL/kg packed RBCs [about 20 U for 40-kg person] and serum ferritin level consistently >1000 mcg/L).
Adult Dose	Initial: 20 mg/kg PO qd on empty stomach 30 min ac Maintenance: Adjust dose by 5- to 10-mg/kg/d increments q3-6mo according to serum ferritin level trends; not to exceed 30 mg/kg/d Note: Dissolve tab completely in water, orange juice, or apple juice, then immediately drink susp; resuspend any remaining residue in small volume of liquid and swallow
Pediatric Dose	<2 years: Not established >2 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Data limited; do not take with aluminum-containing antacids
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Common adverse effects include diarrhea, nausea, abdominal pain, headache, pyrexia, cough, and rash; may increase serum creatinine and hepatic enzyme levels; decrease dose with persistent elevation of serum creatinine level; may cause auditory and visual disturbances; slight decreases in serum copper and zinc levels may occur; dissolve tab completely in water, orange juice, or apple juice and drink resulting susp immediately (do not swallow tab whole, do not chew or crush); measure serum ferritin levels monthly and adjust dose every 3-6 mo based on serum ferritin trends

Drug Category: GI decontaminants

Because adsorption to activated charcoal is minimal, whole bowel irrigation is the GI decontamination method of choice.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Treat patients who are symptomatic with deferoxamine, regardless of iron level.
• Admit patients who have been hemodynamically unstable to an intensive care unit.
• Whole bowel irrigation may be of benefit.
• Other modalities that may be essential include mechanical ventilation and blood product transfusions.
• Aggressive hydration aids in eliminating chelated iron by maintaining an appropriate urine output.

Further Outpatient Care

• Asymptomatic patients with serum iron levels less than 300-350 mcg/dL may be discharged.

Transfer

• Transfer patients if intensive care facilities or deferoxamine is not available locally.

Deterrence/Prevention

• Safekeeping of all medications, not just iron pills, from young children is important.

Complications

• Hepatic necrosis
• Myocardial dysfunction
• Cardiogenic shock
• CNS depression
• Coma
• Convulsion
• Anemia
• Coagulopathy
• Sepsis (Yersinia infection)
• Adult respiratory distress syndrome (ARDS)
• Gastrointestinal perforation
• Intestinal stricture formation

Prognosis

• Persistently symptomatic patients with serum iron levels higher than 350 mcg/dL should be admitted.
• Patients with serum iron levels higher than 1000 mcg/dL should be in a facility that can provide age-appropriate intensive care.

Patient Education

• Common medicines and vitamins may be lethal.
• All medicines should be kept out of reach of children.
• For excellent patient education resources, visit eMedicine's Poisoning - First Aid and Emergency Center. Also, see eMedicine's patient education articles Iron Poisoning and Poison Proofing Your Home.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Discharging a stage 2 patient may lead to serious morbidity. Patients in stage 2 may appear well but still have the potential of cardiovascular collapse.
• Obtaining a "normal" or low iron level more than 6 hours after an ingestion may be misleading. Redistribution of iron in tissues is the reason that the level is low. Toxicity is still possible. Treat the patient, not the numbers.

Special Concerns

• Pregnancy: The lethal potential of severe intoxication without treatment of deferoxamine far outweighs the risk to the fetus.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Alymara V, Bourantas D, Chaidos A. Effectiveness and safety of combined iron-chelation therapy with deferoxamine and deferiprone. Hematol J. 2004;5(6):475-9. [Medline].
• Bosse GM. Conservative management of patients with moderately elevated serum iron levels. J Toxicol Clin Toxicol. 1995;33(2):135-40. [Medline].
• Cheney K, Gumbiner C, Benson B, Tenenbein M. Survival after a severe iron poisoning treated with intermittent infusions of deferoxamine. J Toxicol Clin Toxicol. 1995;33(1):61-6. [Medline].
• Hershko CM, Link GM, Konijn AM. Iron chelation therapy. Curr Hematol Rep. Mar 2005;4(2):110-6. [Medline].
• McGuigan MA. Acute iron poisoning. Pediatr Ann. Jan 1996;25(1):33-8. [Medline].
• Mills KC, Curry SC. Acute iron poisoning. Emerg Med Clin North Am. May 1994;12(2):397-413. [Medline].
• Morse SB, Hardwick WE Jr, King WD. Fatal iron intoxication in an infant. South Med J. Oct 1997;90(10):1043-7. [Medline].
• 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. Sep 1996;14(5):454-5. [Medline].
• Tenenbein M. Benefits of parenteral deferoxamine for acute iron poisoning. J Toxicol Clin Toxicol. 1996;34(5):485-9. [Medline].

Article Last Updated: Jan 8, 2007