Iron poisoning
| Iron poisoning | |
|---|---|
| Other names: Iron toxicity | |
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| Iron supplement from the late 19th and early 20th century | |
 | |
| Specialty | Emergency medicine |
| Symptoms | Initial: Vomiting, diarrhea, abdominal pain, drowsiness[1] Later: Liver problems, fever, bleeding, metabolic acidosis[1] |
| Complications | Liver cirrhosis, intestinal problems[1] |
| Usual onset | Within 6 hrs[2] |
| Causes | >20 mg/kg elemental iron (>60 mg/kg severe)[3] |
| Diagnostic method | Based on symptoms, history of events, blood iron levels[1][4] |
| Treatment | Whole bowel irrigation, deferoxamine, hemodialysis[1][4] |
| Frequency | Relatively common[1] |
Iron poisoning occurs from excess iron supplements resulting in acute toxicity. Symptoms in the first 6 hours may include vomiting, diarrhea, abdominal pain, and drowsiness.[1] In severe cases there may be fast breathing, low blood pressure, seizures, or coma.[1] Often people then briefly improve, after which liver problems, fever, bleeding, and metabolic acidosis may occur.[1] It is at this point that people may die and among those who recover liver cirrhosis may occur.[1]
Iron supplements are available over the counter as a single entity iron salt or in combination with vitamin supplements such as prenatal vitamins.[4] Overdoses may be unintentional, predominantly occurring in young children, or intentional, as a suicide attempts in older people.[4] The diagnosis is typically based on symptoms, history of events, and blood iron levels.[1][4] Occasionally X-rays may be used to see pills in the intestines.[1]
Initial efforts may include whole bowel irrigation.[1] In those with severe symptoms or high iron levels treatment with deferoxamine in hospital is required.[1] Occasionally hemodialysis or surgery may be useful.[4] If no symptoms are present within 6 hours of ingestion, no specific treatment is generally required.[2]
Iron poisoning is relatively common.[1] In children it is a common reason for death from overdose.[3] In severe poisoning the risk of death is about 10%.[3] As a response, in 1997 the US Food and Drug Administration (FDA) implemented regulations requiring warning labels and unit dose packaging for products containing more than 30 mg of elemental iron per dose.[5]
Signs and symptoms
Manifestation of iron poisoning may vary depending on the amount of iron ingested by the individual and is further classified by five stages based on timing of signs and symptoms. In mild to moderate cases, individuals may be asymptomatic or only experience mild gastrointestinal symptoms that resolve within six hours.[6] In serious cases, individuals may present with systemic signs and symptoms and require treatment. Clinical presentation of iron poisoning in the absence of treatment progresses in five stages: the gastrointestinal phase, latent phase, metabolic acidosis and shock phase, hepatotoxicity phase, and bowel obstruction due to scarring.[7]
| Stage | Phase | Time post-ingestion | Symptoms |
|---|---|---|---|
| 1 | Gastrointestinal | 30 minutes to 6 hours | Abdominal pain, diarrhea, vomiting, black stool |
| 2 | Latent | 6 to 24 hours | None |
| 3 | Metabolic Acidosis and Shock | 6 to 72 hours | Hypovolemic shock, low blood pressure, rapid breathing, shortness of breath, tachycardia |
| 4 | Hepatotoxicity | 12 to 96 hours | Acute liver failure |
| 5 | Bowel Obstruction | 2 to 8 weeks | Vomiting, obstruction of small intestine preventing passage of food (due to scarring) |
The first indication of iron poisoning occurs within the first six hours post-ingestion and involves gastrointestinal symptoms including abdominal pain accompanied by nausea and vomiting with or without blood. Due to the disintegration of iron tablets, the stool may appear as black or dark green or gray.[8] After the first stage, gastrointestinal symptoms appear to resolve in the latent phase and individuals may show signs of improvement.[7] Following this stage, the iron begins to affect the cells of the body's organs which manifests as numerous systemic signs and symptoms developing after 6 to 72 hours, in the metabolic acidosis phase. Individuals may present with signs of cardiogenic shock indicated by low blood pressure, rapid heart rate and severe shortness of breath.[6] Hypovolemic shock occurs due to loss of blood from the gastrointestinal bleeding caused by the iron. During this phase, metabolic acidosis may also develop damaging internal organs such as the brain and liver.[8] In the fourth stage taking place 12 to 96 hours after ingestion, liver toxicity and failure occurs as the cells begin to die. In the last stage of iron poisoning following 2 to 8 weeks after ingestion, scarring of the gastrointestinal mucosal lining resulting in bowel obstruction.[4]
Cause
Toxic dose
Iron poisoning can occur when doses of 20 to 60 mg/kg or more of elemental iron is ingested with most cases reporting primarily gastrointestinal symptoms.[8] Systemic signs and symptoms shown in serious toxicity occur at higher doses exceeding 60 mg/kg.[6] Ingesting above 120 mg/kg may be fatal.[8] The therapeutic dose for iron deficiency anemia is 3–6 mg/kg/day. Individuals who have ingested less than 20 mg/kg of elemental iron typically do not exhibit symptoms.[8] It is unlikely to get iron poisoning from diet alone with iron supplements being the cause of overdose. The amount of elemental iron in an iron supplement can be calculate based on the percentage it constitutes for per tablet.
- Ferrous sulfate contains 20% elemental iron per mg of mineral salt
- Ferrous gluconate contains 12% elemental iron per mg of mineral salt
- Ferrous fumarate contains 33% elemental iron per mg of mineral salt
For example, a 300 mg tablet of ferrous fumarate will contain 100 mg of elemental iron or 33%.
Pathophysiology
Iron is essential for the production of hemoglobin in red blood cells which is responsible for transporting oxygen throughout the body. In normal physiologic conditions, nonionic forms of iron (Fe°) are converted into ferrous iron (Fe2+) by gastric acid in the stomach. Ferrous iron is then absorbed in the small intestine where it is oxidized into its ferric iron (Fe3+) form before being released into the bloodstream.[8] Free iron in the blood is toxic to the body as it disrupts normal cell function, damaging organs such as the liver, stomach, and cardiovascular system.[8] The human body has protective mechanisms in place to prevent excess free ferric iron from circulating the body. When being transported throughout the body, iron is bound to an iron transporting protein called transferrin to prevent iron from being absorbed into different cells.[9] Any excess iron is stored as ferritin in the liver.[9] In the event of iron overdose, iron stores become oversaturated and the body's protective mechanisms fail resulting in excess free circulating iron.[9]
Diagnosis
Iron toxicity is primarily a clinical diagnosis that involves getting a detailed patient history and physical examination of the individuals signs and symptoms. Information such as how much iron was ingested and the timing should be gathered to assess the level of toxicity. Signs for severe iron poisoning should be evaluated such as any confusion or extreme lethargy, increased heart rates, low blood pressure for adults.[8] In children, signs of shock can be noted with behavioral changes such as decreased responsiveness, crying, and inability to focus.[10] Persistent vomiting is often associated with iron poisoning and also used to determine severity of iron poisoning. Laboratory tests such as measuring the peak serum iron level after 4 to 6 hours of ingestion can be useful in determining the severity of iron toxicity.[8] In general, levels below 350mcg/dL are associated with more mild iron poisoning while upper levels above 500mcg/dL are associated with more severe iron poisoning.[4] Measuring electrolyte levels, kidney function, serum glucose, liver function tests (enzymes and bilirubin), complete blood count, clotting time via prothrombin and partial thromboplastin time, anion gap for metabolic acidosis, should be conducted for clinical monitoring and confirmation of iron poisoning.[4][2][8]
The deferoxamine challenge test is a diagnostic test for confirming iron poisoning, however it is no longer recommended for diagnostic purposes due to concerns regarding the accuracy.[4] Deferoxamine can be administered intramuscularly as a single dose where it then binds to free iron in the blood and is excreted into the urine turning it to a "brick orange" or pink/red/orange color.[8][11] Radiographs are no longer used for diagnosis due to the lack of connection between severity of iron toxicity and the presence of radiopaque iron tablets in the stomach on X-rays.[4] This method also requires that the ingested tablet to be radiopaque which most iron preparations are not.[4]
Treatment
Management of acute iron poisoning involves providing a patient with respiratory support and intravenous deferoxamine. Patients exhibiting severe symptoms in the gastrointestinal phase should receive volume resuscitation to prevent hypovolemic shock from the loss of blood volume.[8] Normal saline is administered intravenously to maintain adequate volume of fluid in the body. Deferoxamine is a drug that is used in cases of serious iron poisoning. It is a chelating agent and binds to free iron in the body in order to be eliminated by the kidneys into urine.[11] Dosing of deferoxamine should be determined through consultation with a toxicologist but is typically continuously infused at 15 mg/kg to 35 mg/kg per hour and not exceeding the maximum daily dose of 6 grams for adults.[4] In pediatric patients, doses should not exceed 15 mg/kg per hour.[8] recommended duration of treatment is until symptoms have resolved which is usually 24 hours.[4] In non-fatal cases of iron poisoning where there is liver failure, liver transplantation may be necessary.[8]
Treatment of iron poisoning should be based on clinical presentation, peak serum iron levels and other laboratory results. As a general guideline, patients who have ingested lower doses of elemental iron, have a peak serum iron level less than 500mcg/dL and are asymptomatic or only exhibit mild gastrointestinal symptoms typically do not require treatment and should be monitored for 6 hours after ingestion.[2][8] In cases where high doses of elemental iron have been ingested and the patient is exhibiting signs and symptoms of severe systemic iron poisoning, supportive care measures like volume resuscitation and deferoxamine should be initiated immediately.[8] A quick response to iron poisoning can significantly improve clinical outcomes.
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 "Iron Poisoning - Injuries and Poisoning". Merck Manuals Consumer Version. Archived from the original on 23 November 2023. Retrieved 27 November 2023.
- ↑ 2.0 2.1 2.2 2.3 Manoguerra, Anthony S.; Erdman, Andrew R.; Booze, Lisa L.; Christianson, Gwenn; Wax, Paul M.; Scharman, Elizabeth J.; Woolf, Alan D.; Chyka, Peter A.; Keyes, Daniel C.; Olson, Kent R.; Caravati, E. Martin (2005-01-01). "Iron Ingestion: an Evidence-Based Consensus Guideline for Out-of-Hospital Management". Clinical Toxicology. 43 (6): 553–570. doi:10.1081/CLT-200068842. ISSN 1556-3650. PMID 16255338.
- ↑ 3.0 3.1 3.2 "Iron Poisoning - Injuries; Poisoning". Merck Manuals Professional Edition. Archived from the original on 28 November 2023. Retrieved 27 November 2023.
- ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 Yuen, Ho-Wang; Becker, Wenxia (2020), "Iron Toxicity", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 29083637, archived from the original on 2022-05-17, retrieved 2020-12-30
- ↑ Tenenbein, Milton (1 June 2005). "Unit-Dose Packaging of Iron Supplements and Reduction of Iron Poisoning in Young Children". Archives of Pediatrics & Adolescent Medicine. 159 (6): 557–560. doi:10.1001/archpedi.159.6.557. ISSN 1072-4710. Archived from the original on 8 February 2012. Retrieved 28 November 2023.
- ↑ 6.0 6.1 6.2 Chang, Todd Pou-Yen; Rangan, Cyrus (October 2011). "Iron poisoning: a literature-based review of epidemiology, diagnosis, and management". Pediatric Emergency Care. 27 (10): 978–985. doi:10.1097/PEC.0b013e3182302604. ISSN 1535-1815. PMID 21975503. S2CID 29833860. Archived from the original on 2023-09-06. Retrieved 2023-09-27.
- ↑ 7.0 7.1 "Iron Poisoning - Injuries and Poisoning". MSD Manual Consumer Version. Archived from the original on 2021-11-17. Retrieved 2020-12-30.
- ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 8.10 8.11 8.12 8.13 8.14 8.15 8.16 UpToDate. "Acute Iron Poisoning". www.uptodate.com. Archived from the original on 2022-07-14. Retrieved 2020-12-31.
- ↑ 9.0 9.1 9.2 Robotham, James L. (September 1980). "Acute Iron Poisoning: A Review". JAMA Pediatrics. 134 (9): 875–879. doi:10.1001/archpedi.1980.02130210059016. PMID 6998282. Archived from the original on 2023-11-10. Retrieved 2023-09-27.
- ↑ Waltzman, Mark. "Initial Evaluation of Shock in Children". www.uptodate.com. Archived from the original on 2021-04-27. Retrieved 2021-04-27.
- ↑ 11.0 11.1 Lexicomp. "Deferoxamine: Drug Information". www.uptodate.com. Archived from the original on 2021-04-27. Retrieved 2021-04-27.
External links
- Iron poisoning Archived 2012-02-04 at the Wayback Machine in General Practice Notebook
- Iron Poisoning Archived 2012-04-12 at the Wayback Machine at WebMD
- Iron Poisoning Archived 2014-03-31 at the Wayback Machine Merck Manual
