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Iron poisoning is a clinical diagnosis. Signs and symptoms consistent with iron poisoning should guide treatment, rather than serum iron concentrations alone (Figure 198-1). Patients who are asymptomatic on ED arrival, have not ingested a potentially toxic amount, and have normal findings on physical examination can be observed and do not require specific medical treatment. Patients who vomit once or twice from the gastric irritant effects of iron but who are otherwise asymptomatic can also be observed and may require no specific treatment.
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Patients with clinical toxicity should first be stabilized with attention to airway, breathing, and circulation, after which GI decontamination and chelation therapy with deferoxamine may proceed.2,18 Antiemetics such as metoclopramide or ondansetron should be used for repetitive vomiting. Patients with persistent vomiting and abnormal vital sign values or other signs of poor perfusion or shock should undergo aggressive fluid resuscitation and treatment with deferoxamine. Coagulopathy should be treated with parenteral vitamin K1 and/or fresh frozen plasma, as indicated. Significant blood loss may require transfusion.
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Do not use ipecac syrup because it may obscure the initial signs of clinical toxicity and is not proven to be more effective at gastric emptying than is iron-induced vomiting.19 Do not give activated charcoal, cathartics, oral sodium bicarbonate, or phosphosoda. Activated charcoal does not adsorb significant amounts of iron in an overdose to prevent toxicity, and its use may complicate endoscopy if that becomes necessary.19 Cathartics should not be given. Orogastric lavage may not be effective if the ingested tablets are large or if several hours have elapsed since ingestion, but it may be useful in rare cases if performed shortly after large ingestion, prior to significant vomiting, or if a modified-release formulation was ingested.2,20 There are no data to support the efficacy of oral sodium bicarbonate or phosphosoda in forming insoluble iron salts and preventing absorption.2,19
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Radiopaque tablets visible on radiography indicate potential for progressive toxicity and can guide decontamination measures (Figure 198-2). Whole-bowel irrigation with a polyethylene glycol solution is effective in children with large iron ingestions.2,21 Administration of 250 to 500 mL/h in children or 2 L/h in adults by nasogastric tube may clear the GI tract of iron pills before absorption can occur.21 Endoscopy can remove large iron loads or an iron-containing gastric bezoar.22,23 Laparoscopic gastrotomy may be a rare option for removal of an iron-containing gastric bezoar in profoundly ill patients when other measures are unsuccessful or impractical.24
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Deferoxamine is chelating agent derived from Streptomyces pilosus used to treat iron toxicity. Deferoxamine binds free iron, iron from plasma, and iron from inside cells and mitochondria, but not iron bound to organic molecules. Upon binding, it forms the complex ferrioxamine, which is renally excreted. Deferoxamine can be safely administered to children and pregnant women.3 Although deferoxamine binds a small amount of iron (9 milligrams of elemental iron for each 100 milligrams of deferoxamine) and thus chelates only a small fraction of the total amount of iron ingested, removing this small but critical amount of iron often proves clinically effective in restoring cellular function. Deferoxamine may work by other mechanisms in addition to binding excess iron, and complete binding of ingested iron is not the goal of therapy.
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Administration of deferoxamine is indicated in the iron-poisoned patient with systemic toxicity, persistent emesis, metabolic acidosis, progressive symptoms, or a serum iron level predictive of moderate to severe toxicity (Figure 198-1).2,18 The manufacturer recommends IM administration for all patients not in shock,25 but most toxicologists advise IV administration rather than IM administration because of the unreliability of IM absorption and enhanced iron excretion following IV administration.2,18
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The initial deferoxamine adult dose is 1000 milligrams (children 50 milligrams/kg) IV. Begin the infusion slowly, starting at 5 milligrams/kg per hour to avoid producing a rate-related drop in blood pressure. Aggressive volume resuscitation may be required in the volume-depleted, hypotensive, iron-toxic patient who is in need of deferoxamine. Hypotension is not a contraindication to IV deferoxamine administration.
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The infusion rate of deferoxamine IV can be increased up to 15 milligrams/kg per hour as tolerated. The recommended amount of deferoxamine for an acute iron overdose is a total of 360 milligrams/kg or 6 grams in an adult during the first 24 hours, typically ordered as 500-milligram infusions over 4 to 8 hours after the initial 1000-milligram dose.18,25 Amounts larger than this are associated with complications, including mucormycosis, renal insufficiency or failure,26 pulmonary toxicity,27 and sepsis from Yersinia enterocolitica, which may be related to duration of therapy.
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As ferrioxamine is excreted, the urine color changes to what is classically called "vin rosé" but is more typically a brown or rusty hue.28 Theoretically, the disappearance of the "vin rosé" color means that the patient no longer has significant toxicity because there is no more free iron available to be complexed with deferoxamine and excreted. False-negative results, color-change latency, and difficulty in visualizing a color change can limit the utility of this test.18
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There is uncertainty regarding the duration of deferoxamine therapy.2,18,25 Recommended endpoints include clinical recovery and normal iron levels, measurement of normal iron-to-creatinine ratios, and clinical recovery with normal iron level in conjunction with normal urine color. Clinical recovery of the patient is probably the most important factor guiding the decision to terminate therapy because measured iron levels are artificially depressed by the presence of deferoxamine and urine color change can be unreliable. Continue deferoxamine therapy in patients who continue to exhibit severe iron toxicity after 24 hours of treatment, using a decreased rate to avoid the associated risks mentioned earlier.
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Oral iron chelators—deferiprone and deferasirox—reduce iron absorption when administered simultaneously or within 1 hour of iron ingestion.29 However, there is no evidence of benefit in human overdoses, and oral chelation therapy would theoretically be of use only when taken promptly after the iron ingestion; thus their use is limited by the time to presentation for treatment and the significant vomiting expected with clinical iron toxicity. Oral iron chelating agents should NOT replace intravenous deferoxamine when chelation is indicated in clinical iron toxicity.
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Although hemodialysis and hemofiltration do not remove iron, such treatment may be necessary to remove the deferoxamine–iron complex in patients with renal failure who are unable to excrete the complex in their urine.18,30,31 Severe iron poisoning can be treated with exchange transfusion in addition to deferoxamine therapy.32