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Abstract
Iron is a substance commonly found in the homes of many children, leading to a high potential for accidental ingestion. Without proper recognition and treatment, iron poisoning can be fatal. This article reviews the case of a toddler who presents to the pediatric intensive care unit with iron poisoning.
Ryan, a 2-year-old boy, is admitted to the pediatric intensive care unit (PICU) with hematemesis, diarrhea, and hypotension. He is also oozing blood from his peripheral intravenous (IV) line puncture sites. As the admitting nurse, you think about the possible causes of these symptoms. Would iron poisoning be on your list?
Young children with poisoning do not often require admission to the PICU,1 which makes it challenging for the PICU nurse to stay current in his or her knowledge about the vast number of drugs and substances that can cause toxicological symptoms in children. When children with severe iron poisoning present late after ingestion, the results may be fatal.2 In these cases, prompt and aggressive treatment is critically important. Therefore, the purpose of this article is to review the pathophysiology of acute iron poisoning in children and discuss the medications and interventions used in the treatment of iron poisoning.
INCIDENCE OF IRON POISONING IN THE UNITED STATES
More than 90% of poisonings occur in the home environment.1 Boys seem to be poisoned slightly more often than girls,1,3 and children younger than 6 years comprise most poison exposures.1 Although many children are exposed to poisons each year, very few of them die as a result.1
Iron is readily available both in prescription drugs and in over-the-counter formulations.2 Because iron may be viewed as a supplement, parents may not perceive it as a dangerous substance.4 It is well known that children who live in a house with either a pregnant woman or an infant are at a much higher risk of iron poisoning than other children.5,6 This increased risk is caused by the presence of iron supplements in the household that are used during pregnancy and in the postpartum period.
Historically, iron has been a significant cause of death among children who were accidentally poisoned. In the 1980s, iron caused more than 30% of the deaths in children who ingested drugs unintentionally.7 This trend continued in the early 1990s, prompting the US Food and Drug Administration (FDA) to require that all products containing more than 30 mg of iron be supplied in unit-dose packaging.4 Because pills in unit-dose packages must be opened individually before they can be ingested, it was hypothesized that the incidence of severe iron poisoning would decrease. Although the number of exposures did not decrease significantly, the number of deaths fell to almost zero.4 However, in October 2003, the US District Court ruled that the FDA did not have the authority to regulate how iron supplements are packaged, leaving the decision up to individual manufacturers.4
It may be too soon to know whether the US District Court's ruling will affect the rate of severe iron poisoning in the future. The most recent data from 20041 indicate that there were 2,017 iron exposures in children younger than 6 years and none of these exposures led to death. Poison control centers will continue to track reports of poisoning through the Toxic Exposure Surveillance System to provide data for analysis in the future.
RYAN'S STORY
Ryan is a 2-year-old boy who had been in his usual state of good health until late this morning, when his mother noticed that Ryan began vomiting and having diarrhea. She did not become concerned until Ryan began vomiting blood. Paramedics arrived and noted that Ryan appeared dehydrated and lethargic. A peripheral IV line was placed, and a normal saline fluid bolus of 20 mL/kg was begun. Ryan was transported to the pediatric emergency department.
Upon arriving at the emergency department, Ryan continued to require fluid boluses to manage his blood loss. Laboratory studies revealed increased prothrombin and activated partial thromboplastin times, as well as a significant metabolic acidosis on the arterial blood gas. His hematocrit was also low; thus, Ryan was typed and crossed for one unit of packed red blood cells and was sent to the PICU.
Ryan's father called as the boy was being admitted to the PICU and stated that, as he was packing up a bag with Ryan's clothes, he found an open bottle of prenatal vitamins with iron. The diagnosis has now become clear: Ryan was suffering from iron poisoning.
PATHOPHYSIOLOGY OF IRON POISONING
In large doses, iron directly damages cells by creating free radicals that cause injury to the cell.8 Once taken up into the cells, iron targets the mitochondria and interferes with aerobic cellular respiration, thereby producing a metabolic acidosis.2 The primary organ systems affected in iron poisoning include the gastrointestinal (GI) tract, the liver, and the cardiovascular system.8Figure 1 illustrates the pathophysiology of iron poisoning.
 | Figure 1. Pathophysiology of iron poisoning. |
Iron has a direct corrosive effect on the mucosa of the GI tract, leading to nausea and vomiting, diarrhea, melena, and hematemesis.8 These symptoms, which are often the presenting symptoms of iron poisoning, cause fluid losses from the GI tract, which leads to hypovolemia. Weeks after recovering from the exposure, the child may develop strictures that lead to obstruction; however, this occurs only rarely.8
The iron-rich blood of the GI tract passes into the liver via the portal vein. The hepatocytes are damaged by the iron, which leads to liver failure.8 Liver enzymes become increased, and coagulopathy develops, which increases the risk of bleeding and can further contribute to hypovolemia. Some children have permanent liver damage and may even require transplant.9
Iron directly damages the myocardial cells of the heart, which leads to decreased contractility and pump failure.9 In addition, iron causes direct vasodilatation, which leads to hypotension. Finally, iron damages the capillaries, which triggers capillary leak and allows fluid to third-space.9 This leads to further hypovolemia and hypotension.
Because of poor perfusion, children may also develop acute renal failure. Poor perfusion can also lead to central nervous system symptoms, ranging from mild lethargy to coma.2
As iron is taken up by individual cells throughout the body, it acts as an intracellular toxin and disrupts aerobic metabolism.9 As cells switch to anaerobic metabolism, metabolic acidosis results. Hypovolemia and hypotension, which lead to decreased tissue perfusion, can also contribute to metabolic acidosis. Left untreated, a shock state results, which leads to death.
DIAGNOSIS OF IRON POISONING
Diagnosing iron poisoning can be challenging, especially in young children who may not be able to tell an adult what they took.9 Therefore, diagnosis is based on symptoms, imaging studies, and laboratory analysis.
When there is a positive history of iron ingestion, it is important to estimate the amount of elemental iron ingested. Table 1 lists the iron content of common preparations. Ryan's father reads from the label on the prenatal vitamins that each tablet contains 60 mg of iron as ferrous fumarate. Table 1 states that ferrous fumarate is 33% elemental iron, so by multiplying 60 mg by 33%, we calculate that each tablet contains approximately 20 mg of elemental iron. Ryan's mother estimates that approximately one fourth of the bottle was left, meaning that Ryan could have ingested approximately 25 tablets. When we multiply 25 tablets by 20 mg of elemental iron in each tablet, we learn that Ryan could have ingested 500 mg of elemental iron. Ryan weighs 10 kg, so we divide the ingested amount by his weight and calculate that his potential exposure was 50 mg/kg.
 | TABLE 1 Iron Content of Common Preparations |
Typically, iron ingestions of less than 20 mg/kg have little risk of systemic toxicity and are usually limited to GI symptoms.8-10 Ingestions of 40 to 60 mg/kg carry a risk of severe toxicity, and ingestions of 200 to 250 mg/kg are potentially lethal.8,10 Based on this information, we predict that Ryan will have systemic symptoms from his ingestion.
Ryan underwent abdominal radiography to look for the presence of iron tablets in his GI tract. Because iron tablets are radiopaque, abdominal radiography may reveal undissolved tablets. However, pediatric multivitamins contain such a small amount of iron that they may not be revealed on x-ray film.8 Also, if liquid iron preparations were ingested, the x-ray film will usually be unrevealing. If iron tablets are noted on the x-ray film, then gastric lavage or whole-bowel irrigation may be helpful.9 Ryan's x-ray film shows undissolved tablets in the upper part of the duodenum, but none in the stomach.
A high serum iron level, in addition to clinical symptoms, can solidify the diagnosis of iron poisoning. However, in a child who is symptomatic, one should not wait for an iron level before starting treatment.8Table 2 lists the significance of serum iron levels in children with iron poisoning. Iron levels peak between 4 and 6 hours after ingestion.8,9 Typically, serum iron levels are measured when the child presents and every 1 to 2 hours thereafter.8 When the serum iron level begins to decrease, it is not necessary to keep tracking it.8 By this time, the iron in the bloodstream has entered the cells and the blood level does not change the treatment plan.
 | TABLE 2 Serum Iron Levels in Children With Iron Poisoning |
A blood gas usually reveals a metabolic acidosis, and the lactate concentration may be increased. Other laboratory studies include a complete blood cell count, liver and renal function tests, electrolytes, and coagulation studies. In the past, total iron binding capacity was used as a marker of toxicity, but it has not been found to be reliable and is not recommended.8,9
Six hours after ingestion, Ryan's serum iron level is 545 mcg/dL, indicating a likelihood for systemic toxicity. His other laboratory studies show a metabolic acidosis on the blood gas, coagulopathy, anemia, and increased liver function tests.
TREATMENT IN THE PICU
Table 3 summarizes the key points of iron poisoning treatment in the PICU. Initial management includes providing airway and ventilatory support and oxygen if needed. The child should be placed on a cardiac monitor, and good IV access should be secured.8 Some clinicians opt to place a central line to monitor central venous pressures and guide fluid replacement.9,10 Fluid losses are replaced with either normal saline or lactated Ringer solution, and a blood transfusion may be necessary to treat anemia. Intravenous sodium bicarbonate may be used to treat acidosis.10 Children may also require inotropes to maintain cardiac output. Adequate urine output (>1 mL kg-1 h-1) should also be maintained.
 | TABLE 3 Key Points of Iron Poisoning Treatment in the PICU |
Ryan was placed on a cardiac monitor upon arrival at the PICU. His oxygen saturation was 97%, and he showed no signs of respiratory distress. A central line was placed to improve IV access and to monitor his central venous pressure. Despite fluid boluses and blood transfusions, Ryan remained hypotensive and continued to have fluid losses from his GI tract. Dopamine was begun at 10 mcg kg-1 min-1, which improved Ryan's blood pressure. Sodium bicarbonate was administered to treat his metabolic acidosis. A Foley catheter was placed to monitor urine output, which was 2 mL kg-1 h-1.
Gastric lavage can be a risky procedure in children because of the risk of aspiration, and it has not been shown to improve the overall outcome.8 Also, it can be difficult to place a tube that is large enough for undissolved tablets to pass through the lumen of the tube. Therefore, the role of gastric lavage is limited to children who present within an hour of ingestion8,10 and have ingested more than 20 mg/kg of iron.9 If gastric lavage is attempted, tap water or normal saline is the recommended solution,10 and a post-lavage abdominal x-ray film should be obtained after the procedure to look for further tablets or fragments of tablets.9 Because Ryan's abdominal x-ray film indicated that the tablets were beyond the pyloric sphincter and more than 1 hour had passed since the ingestion occurred, gastric lavage was not indicated.
Whole-bowel irrigation is used to flush the contents of the bowel out of the body. This intervention may be useful in patients with iron poisoning, especially children who are symptomatic or who have tablets in the bowel that are visible on x-ray film.8 A nasogastric tube is placed and a polyethylene glycol-balanced electrolyte solution, such as Golytely, is begun.8-10 A balanced electrolyte solution is favored to prevent fluid and electrolyte shifts across the bowel wall.9,10 The recommended rate of infusion is 15 to 40 mL kg-1 h-1 until the effluent is clear and tablets are no longer visible on x-ray film.10
Because iron tablets were visible on Ryan's abdominal x-ray film, whole-bowel irrigation was begun. A nasogastric tube was placed, and an infusion of Golytely was begun. The infusion was discontinued after the effluent was clear, and a follow-up radiograph showed that there were no visible tablets in the bowel.
It is widely believed that iron does not bind to activated charcoal.8 Some investigators have challenged that idea and have experimented with iron binding with activated charcoal,12 activated charcoal with deferoxamine,12 and sodium bicarbonate.13 However, these studies have been done on either healthy adult volunteers12 or animal models,13 and further research is needed before recommending activated charcoal in pediatric iron poisoning. For now, activated charcoal is only indicated if there is reason to believe that the child has ingested additional toxins that can adsorbed by charcoal.8
As shown in Figure 2, deferoxamine binds with free iron to create a ferrioxamine complex, which is excreted by the kidneys in the urine. This complex turns the urine a reddish-brown, or "vin rose," color.8 However, in one study,6 up to one third of children with iron poisoning did not have any color change in their urine when deferoxamine was administered. If a color change does occur, the color of the urine should be noted while deferoxamine therapy continues. When the urine returns to a clear yellow color, deferoxamine may then be discontinued.9
 | Figure 2. Chelation of iron with deferoxamine. |
Deferoxamine therapy is indicated for children with systemic signs of iron poisoning,8 and children who only have GI symptoms do not usually need chelation therapy. Deferoxamine is administered as a continuous IV infusion at a rate of 15 mg kg-1 h-1.8-10 If the infusion is administered at a faster rate, then hypotension often occurs.8,9 The maximum daily dose is 360 mg kg-1 d-1, with a total limit of 6 g.10 Children who require deferoxamine infusions for more than 3 days have an increased risk of developing acute respiratory distress syndrome.14 Also, the ferrioxamine complex acts as a medium of growth for Yersinia enterocolitica; thus, children may require sepsis prophylaxis after chelation therapy.8 Intramuscular administration of deferoxamine has been used in the past, but absorption tends to be erratic, especially in children with poor perfusion.8,9 In symptomatic patients, deferoxamine should be started as soon as possible after iron poisoning is suspected, and it is not necessary to wait for a serum iron level before beginning the drug.8 Maintenance of adequate urine output is critical to allow the ferrioxamine complex to clear the body.8
Ryan was started on IV deferoxamine in the PICU, and his urine changed to a reddish-brown color shortly after the infusion was begun. Deferoxamine was continued for approximately 20 hours, when the urine changed back to a clear yellow color. By this point, his metabolic acidosis had resolved and fluid losses from the GI tract were minimal.
Iron cannot be dialyzed, but the ferrioxamine complex can be removed by hemodialysis.8 Thus, hemodialysis (or other renal replacement therapies) may be used to support a child in acute renal failure or to remove the ferrioxamine complex if urine output is inadequate. Because Ryan had adequate urine output and no signs of acute renal failure, dialysis was not indicated.
OUTCOME OF RYAN'S STORY
Ryan was transferred from the PICU to the acute care unit after the deferoxamine was discontinued, the metabolic acidosis had resolved, and his hemodynamic status was stable. In the acute care unit, his diet was advanced and his IV fluids were discontinued. Ryan is at risk of strictures developing along the GI tract, which can occur 1 to 7 weeks after ingestion.8 Before discharge, his parents were counseled regarding the signs of GI obstruction, including abdominal pain, distention, and vomiting. In addition, his parents received instruction on poison prevention. Ryan will also be monitored by a pediatric gastroenterologist for mild liver failure, which resulted from the iron ingestion.
SUMMARY
Without proper recognition and treatment, severe iron poisoning can be fatal. Most exposures occur in children younger than 6 years. Priorities for management in the PICU include fluid resuscitation, GI decontamination, chelation therapy with deferoxamine, and maintenance of good hemodynamics and urine output. A thorough understanding of the pathophysiology and treatment of iron poisoning will help the PICU nurse provide effective nursing care when children like Ryan present to the PICU.
References
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