Iron poisoning is commonly observed in children. First symptoms result from acute gastroenteritis and may be followed by hepatic and renal failure and shock.
Presentation
Pediatric patients may be presented before any symptoms develop if supervisors suspect an accidental ingestion of iron preparations. These patients may not develop any symptoms at all if the amount of ingested iron is less than 20 mg per kg.
Otherwise, patients usually present with (or develop) gastrointestinal symptoms such as nausea, vomitus, abdominal pain and diarrhea. Hematemesis and hemorrhagic diarrhea are particular suspicious of IP. Of note, adults suffering from IP may not report vomitus and abdominal pain.
Severe gastrointestinal symptoms may already be associated with hypotension, tachypnea, tachycardia, metabolic acidosis and strongly reduced awareness or coma. Subsequently, a quiescent period of up to 24 hours may be observed before severe metabolic acidosis, fever, convulsions, coagulopathy and shock may set in. It may take up to five days until jaundice and hypoglycemia reveal hepatic failure. Mucosal recovery may take an even longer time and may lead to pyloric stenosis or duodenal obstruction due to scarring.
The severity of the initial, gastrointestinal symptoms permits an estimation of the severity of intoxication. Without gastrointestinal symptoms, the aforementioned systemic complications will most likely not occur.
Entire Body System
- Gastric Lavage
Early decontamination of gut (gastric lavage/whole gut irrigation), desferrioxamine infusion (15 mg/kg/hour in saline), and aggressive management of shock, and organ failure preferably in a PICU are mainstay of management, and has improved the outcome [ncbi.nlm.nih.gov]
- Fatigue
Too little iron causes fatigue, reduced immunity, and anemia, which can be serious if untreated. But too much iron also causes a serious set of problems. [privatelabresults.com]
Heart failure can cause swelling of the legs, shortness of breath, trouble exercising, fatigue, fast or irregular heartbeat and nausea. [livestrong.com]
Nervous/muscular systems: Reduced work productivity, reduced physical fitness, weakness, fatigue, impaired cognitive function, reduced learning ability, increased distractibility, impaired reactivity and coordination. [drhoffman.com]
[…] support the previously hypothesized relation between household stressors and childhood poisoning. 20 The risk of iron poisoning followed a plausible temporal gradient, with a particularly high risk in the immediate postpartum period, when parents may be fatigued [cmaj.ca]
Gastrointestinal
- Abdominal Pain
Otherwise, patients usually present with (or develop) gastrointestinal symptoms such as nausea, vomitus, abdominal pain and diarrhea. Hematemesis and hemorrhagic diarrhea are particular suspicious of IP. [symptoma.com]
Scarring in either organ can cause crampy abdominal pain and vomiting. Severe scarring of the liver ( cirrhosis ) can develop later. [merckmanuals.com]
Iron causes two major effects Local - Gastrointestinal irritation Abdominal pain Nausea and vomiting Systemic - Cellular toxicity causing multi-organ failure Systemic toxicity may occur with doses greater than 60 mg/kg and is life-threatening with doses [kidshealthwa.com]
Scarring in either organ can cause crampy abdominal pain and vomiting. Severe scarring of the liver (cirrhosis) can develop later. [msdmanuals.com]
- Nausea
Otherwise, patients usually present with (or develop) gastrointestinal symptoms such as nausea, vomitus, abdominal pain and diarrhea. Hematemesis and hemorrhagic diarrhea are particular suspicious of IP. [symptoma.com]
Concentration 60 - 90 micromol/L and tablets visible on AXR or symptomatic (nausea, vomiting, diarrhoea, abdominal pain, haematemesis, fever). [rch.org.au]
Check with your doctor as soon as possible if any of the following side effects occur: More common Backache, groin, side, or muscle pain chest pain chills dizziness fainting fast heartbeat fever with increased sweating flushing headache metallic taste nausea [mayoclinic.org]
Within minutes or hours of swallowing iron tablets, nausea, vomiting, diarrhea, and gastrointestinal bleeding can occur. These problems can progress to shock, coma, seizures, and death. [emsaonline.com]
Nausea and vomiting are also common symptoms and bloody vomiting may occur. [en.wikipedia.org]
Psychiatrical
- Impulsivity
[…] does not necessarily result in child resistance and led them to recommend “the need to develop national and international standards for the child-resistance of unit-dose packs.” 4 (p313) Since intentional drug overdose as a suicidal gesture is often an impulsive [archpedi.ama-assn.org]
Workup
If supervisors present their children and report or suspect an accidental ingestion of prenatal vitamins or iron preparations, the overall content of possibly ingested tablets should be calculated in order to evaluate the probability of IP.
Pediatric patients presenting with severe gastrointestinal symptoms, hematemesis or hemorrhagic diarrhea and metabolic acidosis of unknown origin are suspicious for IP. Abdominal X-rays may help to detect intact tablets or highly concentrated iron preparations, but other formulations may not be visible.
Analyses of blood samples may reveal altered serum ion levels (> 350 μg/dl or > 64 μmol/l) and metabolic acidosis. Furthermore, water and electrolyte balances as well as glucose levels, hepatic and renal functions should be checked. Blood screens may, however, not yield concluding results when drawn before three hours after iron ingestion. Samples obtained more than six hours after ingestion may yield low serum ion levels due to iron redistribution and thus cause an underestimation of the severity of the case. It is therefore recommended to revise serum ion and bicarbonate levels as well as blood pH repeatedly until alterations can be detected or six hours have passed without any symptoms.
Care should be taken when estimating the severity of IP solely based on serum ion levels. Such estimates are generally not helpful because iron binding capacity varies with hepatic function and other conditions. Any prognosis needs to consider the overall condition of the patient, disease progress or recovery and the development of laboratory results over time.
A hemogram should also be realized. Alterations associated with IP would be anemia and leukocytosis (> 15,000 cells/μl).
Treatment
An intravenous access should be established in all patients with acute IP. Bolus infusions with physiological saline or lactated Ringers solution (20 ml per kg) are usually advisable. Further fluid substitution and corrections of electrolyte imbalances may be required if blood screens reveal the corresponding deficits.
Within less than one hour of iron ingestion, patients may benefit from inducing vomitus in order to decontaminate their stomach. This measure will not be helpful if realized at later points in time or in patients that already present gastrointestinal symptoms. Emetics are contraindicated in patients with reduced awareness due to the increased risk for aspiration and aspiration pneumonia [6].
If less than two hours have passed since iron ingestion or if iron preparations could be detected inside the stomach in abdominal radiographic images, further intoxication may be prevented by gastric lavage with a large-bore orogastric tube. However, iron preparations may not be easily removed. In determined cases, laparoscopic or endoscopic removal of iron bezoars may be indicated [7] [8]. In order to rinse the complete gastrointestinal tract, whole-bowel irrigation may be an adequate measure.
Further methods to reduce iron levels include the application of chelators such as deferoxamine. Deferoxamine should be intravenously administered to patients whose serum iron levels are elevated and to those who show severe gastrointestinal symptoms, metabolic acidosis or shock. Asymptomatic patients should receive deferoxamine perorally. Chelated iron will be excreted by the kidneys, which is another reason for aggressive fluid therapy.
When all measures to reduce iron loads have been taken, treatment focuses on the prevention of complications. Hemodynamic, hepatic and renal failure have to be avoided if at all possible. In this line, exchange transfusions may be helpful [9]. Severe IP may require oxygen supplementation or hemodialysis [10].
Patients suffering from chronic IP will obviously not benefit from gastric lavage or similar measures. They should be treated with fluid therapy and iron chelators. In such patients, deferasirox may pose an alternative to deferoxamine. This drug is approved to treat chronic iron overload. With deferasirox, chelated iron and drug metabolites will be excreted via bile and bowel.
Prognosis
Prognosis of IP depends on the ingested amount of iron and on the overall condition of the patient. Since earliest symptoms of IP result from an acute gastroenteritis, the absence of such symptoms allows for the conclusion that no severe intoxication has taken place. If gastrointestinal symptoms do not develop within six hours of ingestion, they are unlikely to occur at all. Doses of less than 20 mg per kg are considered non-toxic and symptoms should not be expected if the amount of ingested iron is below this limit. Severe consequences may arise from ingestion of more than 60 mg per kg, with 250 mg per kg being possibly lethal.
Severe symptoms associated with IP and a less favorable prognosis include esophagitis [5], gastrointestinal perforation and sepsis, hepatic and renal failure, myocardial dysfunction and cardiogenic shock, anemia, coagulopathy, CNS depression and coma.
Etiology
While some IP occur due to accidental excess oral iron substitution in adults, the vast majority of cases affects children. Possibly toxic iron sources are ferrous sulfate tablets and prenatal vitamins including iron preparations that contain high amounts of elemental iron (approximately 60 mg per tablet). This type of tablets is usually sugar-coated and brightly-colored, thus appears like candy and is very attractive to children [1] [2].
Epidemiology
Children aged less than six account for the majority of IP cases. In this age group, about 16,000 cases are registered annually in the United States [3] [4].
Most children suffering from IP develop only mild symptoms. With regards to cases of sole iron exposure, less than 0.5% were classified as severe intoxications, no deaths have been registered. The percentage of severe intoxications due to unsupervised vitamin intake is even less.
It has been suggested to classify up to 20 mg per kg of elemental iron as non-toxic, doses of up to 60 mg per kg as toxic and higher doses as severely toxic. Severe symptoms and possibly mortality may develop after severe intoxications with more than 60 mg per kg of iron.
Pathophysiology
IP is associated with corrosive damage to the mucosa of the gastrointestinal tract and interferes with metabolic processes upon absorption.
Mucosal damage is responsible for symptoms of acute gastroenteritis, e.g., nausea, vomiting, hematemesis, abdominal pain and diarrhea. Subsequently, water and electrolyte imbalances may cause further problems.
Once absorbed via the intestinal mucosa, iron ions may reach further organ systems and mediate further damage. Liver and kidneys are particularly susceptible to IP, but the cardiovascular system as well as the central nervous system may also be significantly damaged. It has been suggested that iron interferes with enzyme activity, hinders oxidative phosphorylation and therefore causes mitochrondrial dysfunction which leads to severe lactic acidosis and cell death.
These processes result in hypovolemia and severe metabolic acidosis. Additionally, iron mediates vasodilative and negative inotropic effects that aggravate hemodynamic problems and may lead to shock.
Of note, prolonged exposure to excessive amounts of iron may result in hepatic, renal or myocardial siderosis.
Prevention
Parents and supervisors should be aware of the risk associated with accidental iron ingestion. Any medication should be kept out of reach of children.
If iron intake is suspected, children should be examined as soon as possible in order to permit the removal of iron sources before these are absorbed in the intestine.
Summary
Iron poisoning (IP) generally occurs due to accidental ingestion of iron preparations by young children. The severity of IP mainly depends on the overall amount of ingested iron and the general condition of the patient. More than 20 mg per kg are considered to be toxic and if the patient ingested more than 60 mg per kg, severe symptoms are to be expected.
IP initially manifests as acute gastroenteritis and patients may present with nausea, vomitus, abdominal pain and diarrhea. In severe cases, hematemesis and hemorrhagic diarrhea are observed. Fever, convulsions, shock, hepatic and renal failure may occur with a certain delay to gastrointestinal symptoms. The severity of the latter may indicate the overall severity of IP. If gastrointestinal symptoms do not develop, it is unlikely for more severe complications to occur.
If accidental ingestion of iron is detected early on, therapeutic measures can be taken to remove its source from the gastrointestinal tract and to avoid further absorption. Otherwise, fluid therapy, corrections of acid-base and electrolyte balances as well as the application of chelators are the mainstays of treatment.
Of note, adults are more likely to be affected by chronic IP that may result from repeated blood transfusions. Gastrointestinal symptoms are not to be expected in these cases. Therefore, therapeutic measures aiming at the reduction of the gastrointestinal iron load are not applied in these patients.
Patient Information
Iron poisoning (IP) frequently occurs in young children that accidentally ingest prenatal vitamins or other formulations containing iron. These are frequently prescribed to treat anemia. Different iron preparations pose distinct risks because their iron content may differ significantly.
Several thousand cases of IP are registered annually in the United States. Although most cases proceed asymptomatically or with only mild symptoms, high amounts of iron may cause severe damage to the gastrointestinal tract, to liver, kidneys and the cardiovascular system and even be lethal.
Direct corrosive action mediated by the recently ingested iron accounts for the initial symptoms of acute IP, i.e., for nausea, vomitus, abdominal pain and diarrhea. In severe cases, vomitus and diarrhea contain blood. During this stage of the disease, measures can be taken to remove tablets containing iron from the child's stomach. This may help to prevent iron absorption and thus iron-mediated damage to other organ system.
Once iron is absorbed in the small intestine, it reaches the liver, the heart and the kidneys. Severely intoxicated children may go into shock after the initial gastrointestinal symptoms subsided. Liver and kidney failure may develop several days after the accidental ingestion of iron. In order to prevent these conditions, physicians administer iron chelators. These substances bind iron and promote its excretion.
IP is diagnosed based on clinical history, the results of clinical examination and laboratory results. In this context, blood screens are particularly important to measure serum ion levels. Also, complications affecting other organ systems may be assessed by analyses of blood samples. The above mentioned therapeutic measures are usually supplemented with fluid therapy.
Prognosis is good if the amount of ingested iron does not exceed certain limits, if IP is detected early and if severe complications can be avoided.
In order to prevent IP, any medication should be kept out of reach of children.
References
- Morris CC. Pediatric iron poisonings in the United States. South Med J. 2000; 93(4):352-358.
- Juurlink DN, Tenenbein M, Koren G, Redelmeier DA. Iron poisoning in young children: association with the birth of a sibling. Cmaj. 2003; 168(12):1539-1542.
- Bronstein AC, Spyker DA, Cantilena LR, Jr., Green JL, Rumack BH, Dart RC. 2010 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 28th Annual Report. Clin Toxicol (Phila). 2011; 49(10):910-941.
- Mowry JB, Spyker DA, Cantilena LR, Jr., Bailey JE, Ford M. 2012 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 30th Annual Report. Clin Toxicol (Phila). 2013; 51(10):949-1229.
- Cerezo A, Costan G, Gonzale A, et al. [Severe esophagitis due to overdose of iron tablets]. Gastroenterol Hepatol. 2008; 31(8):551-552.
- Höjer J, Troutman WG, Hoppu K, et al. Position paper update: ipecac syrup for gastrointestinal decontamination. Clin Toxicol (Phila). 2013; 51(3):134-139.
- Ng HW, Tse ML, Lau FL, Chu W. Endoscopic removal of iron bezoar following acute overdose. Clin Toxicol (Phila). 2008; 46(9):913-915.
- Haider F, De Carli C, Dhanani S, Sweeney B. Emergency laparoscopic-assisted gastrotomy for the treatment of an iron bezoar. J Laparoendosc Adv Surg Tech A. 2009; 19 Suppl 1:S141-143.
- Carlsson M, Cortes D, Jepsen S, Kanstrup T. Severe iron intoxication treated with exchange transfusion. Arch Dis Child. 2008; 93(4):321-322.
- Gumber MR, Kute VB, Shah PR, et al. Successful treatment of severe iron intoxication with gastrointestinal decontamination, deferoxamine, and hemodialysis. Ren Fail. 2013; 35(5):729-731.