DESCRIPTION

Iron is a commonly used oral medication and dietary supplement.

FORMS AND USES

• Iron (ferrous) fumarate 200 mg contains 66 mg elemental iron.
• Iron (ferrous) gluconate 325 mg contains 37 mg elemental iron.
• Iron (ferrous) sulfate 325 mg contains 65 mg elemental iron.
• A typical child's multivitamin tablet with iron contains 10 to 18 mg elemental iron; adult or prenatal multivitamins may contain up to 65 mg of iron.
• Iron dextran rarely causes iron toxicity.

TOXIC DOSE

Signs of toxicity begin to develop at doses above 20 mg/kg.

PATHOPHYSIOLOGY

• Initial toxicity is caused by direct irritation of the gastrointestinal mucosa.
• After absorption, the normal defense mechanisms are to bind iron tightly to serum proteins (e.g., transferrin, ferritin).
• In overdose, free iron exceeds defenses and produces widespread cellular injury.
• Mechanisms of cell toxicity include uncoupling of oxidative phosphorylation, free radical production, direct consumption of bicarbonate, direct depression of the myocardium, and disruption of production of coagulation proteins.

EPIDEMIOLOGY

• Poisoning is common.
• Toxic effects following exposure are typically mild to moderate.
• Death occurs as a result of large ingestions with delayed presentation.

CAUSES

• Acute overdose is usually suicidal in adults and accidental in children.
• The possibility of child neglect should be considered in patients under 1 year of age; suicide attempt in patients over 6 years of age.

WORKPLACE STANDARDS

No standards are available for iron.

PREGNANCY AND LACTATION

• US FDA Pregnancy Risk Category. Not categorized.
• Use of deferoxamine for iron poisoning improves maternal condition and thereby improves conditions for the fetus.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• WORKPLACE STANDARDS
• PREGNANCY AND LACTATION

DIFFERENTIAL DIAGNOSIS

• Other toxic causes of acute gastrointestinal injury include isopropyl alcohol, caustics, mushrooms, inorganic heavy metals, theophylline, and severe reactions to nonsteroidal antiinflammatory drugs and salicylates, among others.
• Other causes of anion gap metabolic acidosis are methanol, uremia, diabetic ketoacidosis, isoniazid, lactic acidosis, ethylene glycol, salicylate, toluene, and others.

SIGNS AND SYMPTOMS

• Initial symptoms are primarily vomiting, abdominal pain, diarrhea, and mild lethargy.
• In more severe cases, marked lethargy, anion gap metabolic acidosis, gastrointestinal bleeding, and shock will follow within hours.

Vital Signs

Tachycardia and tachypnea are common.

Cardiovascular

Hypotension and shock may develop in severe cases.

Pulmonary

• Hyperpnea to compensate for metabolic acidosis is common.
• Adult respiratory distress syndrome may develop in severe cases.

Gastrointestinal

• Early vomiting and diarrhea are common.
• Abdominal pain, hematemesis, and hematochezia occur early.

Hepatic

Mild to severe hepatic necrosis may occur in severe cases.

Renal

Renal failure may occur in association with shock or liver injury.

Hematologic

• Increased white blood cell count may occur early but is not a reliable marker for toxicity.
• Increased prothrombin time (PT) or international normalized ratio (INR) is common and may become severe.

Fluids and Electrolytes

• Increased anion gap acidosis may appear early in larger ingestions.
• Intravascular volume depletion is common and may become severe.

Neurologic

• Lethargy is common.
• Seizures and coma may occur in severe cases.

Endocrine

Hyperglycemia may occur early but is not a reliable marker for toxicity.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• The serum iron level should be determined 4 to 6 hours after ingestion if the patient is asymptomatic or upon arrival if the patient is symptomatic.
  • A level of less than 300 µg/dl is rarely symptomatic; 300 to 500 µg/dl is potentially toxic; over 500 µg/dl is usually treated with chelation.
  • The normal course of serum iron levels is to peak in the first few hours and then decline as iron is taken into cells.
  • A decreasing level does not assure improvement.
  • Serial levels are needed when tablets are found on abdominal radiographs.
  • Increasing levels should prompt further decontamination attempts.
  • Iron levels become uninterpretable after deferoxamine treatment.
• Serum electrolytes, BUN, and creatinine should be measured.
  • Tests should be determined at 4 to 6 hours after ingestion if the patient is asymptomatic or upon arrival if the patient is symptomatic.
  • Low serum bicarbonate or anion gap metabolic acidosis indicates clinically significant poisoning.

Recommended Tests

• Complete blood count (CBC) may be obtained to assess blood loss in symptomatic cases.
• ECG, serum acetaminophen and aspirin levels are determined in an overdose setting to detect occult overdose.
• Iron tablets may be visible on abdominal radiographs.
  • The radiograph is used to evaluate the effect of decontamination, but cannot rule out the continued presence of tablets.
  • Chewable tablets are usually not visible.

Not Recommended Tests

• The ratio of serum iron to total iron-binding capacity is not useful.
• The deferoxamine challenge test is no longer recommended to assess toxicity.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Hepatic
  • Renal
  • Hematologic
  • Fluids and Electrolytes
  • Neurologic
  • Endocrine
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests
  • Not Recommended Tests

• Treatment should focus on gastrointestinal decontamination, intensive supportive care, and administration of deferoxamine, if needed.
• Dose and time of exposure of elemental iron and possible coingestants should be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care provider should call the poison control center when:

• Gastrointestinal bleeding, acidosis, or hypotension is present, pills are seen on radiographs, or the patient worsens despite therapy.
• Signs and symptoms are not consistent with iron poisoning.
• Deferoxamine administration is needed.
• Coingestant, drug interaction, or underlying disease presents unusual challenges.

The patient should be referred to a health-care facility when:

• More than 60 mg/kg elemental iron was ingested, or the patient is symptomatic.
• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Coingestant, drug interaction, or underlying disease presents unusual problems.

Admission Considerations

Inpatient treatment is warranted for patients with gastrointestinal bleeding, shock, or altered mental status; when gastrointestinal decontamination is unsuccessful; or if the patient is receiving deferoxamine.

DECONTAMINATION

Out of Hospital

Emesis should be induced with ipecac within 1 hour of ingestion for alert pediatric or adult patients or if more than 20 mg/kg was ingested (unless patient has already vomited).

In Hospital

• Emesis should be induced with ipecac for the pediatric patient who is too small to have effective lavage (unless the child has already vomited repeatedly).
• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients who present after a large ingestion or if signs of toxicity are present.
• Whole-bowel irrigation is used in patients with rising iron levels or with pills evident on KUB radiographs.
  • Adult dose is 1 to 2 L/h until rectal effluent is clear.
  • Pediatric dose is 25 ml/kg/h until rectal effluent is clear.
• Activated charcoal binds iron poorly but may be used if coingestion is suspected; if gastrointestinal bleeding is present, the use of charcoal should be avoided to allow endoscopy.
• Bicarbonate, phosphate, and milk of magnesia should not be used.

ANTIDOTES

Deferoxamine

• Indications. Treatment should be given to any patient with toxic effects (repeated vomiting or diarrhea, increased anion gap metabolic acidosis, gastrointestinal bleeding, altered mental status, or hypotension) or serum iron levels of more than 500 µg/dl on blood drawn 4 to 6 hours after ingestion.
• Contraindications. Renal insufficiency or oliguric renal failure are relative contraindications. The deferoxamine-iron complex may be dialyzed in patients with renal failure.
• Method of administration. The initial adult or pediatric dose is 15 mg/kg/h by continuous infusion. The rate may be titrated upward to 25 to 40 mg/kg/h based on the patients course (see SECTION III, Deferoxamine chapter, for further details.)
• Potential adverse effects
  • Rapid infusion may cause hypotension.
  • Anaphylactoid reactions occur rarely.

ADJUNCTIVE TREATMENT

• Hypotension
  • The patient should be given 10 to 20 ml/kg 0.9% saline intravenously and placed in the Trendelenburg position.
  • Larger volumes will often be needed.
  • Further fluid therapy should be guided by central pressure monitoring to avoid volume overload.
  • If hypotension does not respond to treatment, a vasopressor is administered.
    • The dose for dopamine is 2 to 5 µg/kg/min, titrated to effect; rates greater than 20 µg/kg/min are unlikely to provide further benefit.
    • If pressure does not respond, norepinephrine (0.1-0.2 µg/kg/min) may be added and titrated to effect.
    • High rates of infusion may cause tissue ischemia.
• Blood component therapy may be needed for the treatment of bleeding.
• An exchange transfusion should be considered for critically ill young children with high serum iron levels who deteriorate despite deferoxamine therapy.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
  • Deferoxamine
• ADJUNCTIVE TREATMENT

PATIENT MONITORING

• Iron level, CBC, serum electrolytes, and hemodynamic monitoring should be repeated frequently over the first few hours in patients with toxic effects to assess response to therapy.
• If abdominal radiographs reveal tablets, repeat radiographs are indicated to assess decontamination.

EXPECTED COURSE AND PROGNOSIS

• Most patients develop gastrointestinal effects, are treated with deferoxamine, and recover over 12 to 48 hours.
• In severe cases, effects develop rapidly and may lead to a course lasting several days and complicated by multiple effects of shock.
• In patients without shock or coma, mortality is less than 1%.
• Shock or coma predicts mortality of 50% with supportive treatment, 10% with supportive treatment and deferoxamine.
• Scarring from local corrosive effects may result in gastrointestinal obstruction 4 to 6 weeks after severe iron poisoning.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Asymptomatic patients with iron level less than 500 µg/ml, negative abdominal radiographs, and psychiatric evaluation may be discharged following decontamination and 4 to 6 hours of observation.
• From the hospital. Patients who receive deferoxamine may be discharged 4 hours after discontinuation of deferoxamine when they are asymptomatic, iron levels are decreasing, and serum bicarbonate level is normal.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

• Iron ingestion must be evaluated based on elemental iron content.
• An iron level drawn more than 8 hours after ingestion may be misleading because iron is now intracellular and therefore unmeasured.
• Indirect tests (such as for glucose) should not be substituted for iron level tests to exclude toxicity.

Poisoning by iron and its compounds.

See Also: SECTION II, Hypotension chapter; and SECTION III, Deferoxamine and Whole-Bowel Irrigation chapters.

RECOMMENDED READING

Curry S. Iron. In: Tintanalli JE, Krome RL, Ruiz E, eds. Emergency medicine. New York, McGraw Hill, 1992:598-601.

Gruber JE. Iron poisoning. In: Rosen P. Emergency medicine: concepts and clinical practice. St. Louis: Mosby, 1992:2593-2602.

Author: Kennon Heard

Reviewer: Richard C. Dart