You’re working a busy shift in the peds ED among a seemingly endless cycle of various permutations of fevers, cough, abdominal pain, vomiting, diarrhea, when another kid pops up on the board: “vomiting, abdominal pain.” Fantastic. You go over to the kid and find a 4-year-old male with no significant past medical or birth history. Immunizations are UTD, and he is generally healthy. As per mom, he was in his usual state of health when he suddenly started to complain of generalized abdominal pain with multiple episodes of bloody vomiting and diarrhea for the last 3 hours. There have been no fevers, prior similar episodes, sick contacts, recent travel, recent antibiotics, or sketchy foods that the mom can recall. The kid mentions having eaten some candy earlier but won’t say from where he got it. The mom isn’t sure about that but mentions he may have gotten it from one of his older siblings, and in their family, the boys don’t snitch on each other. Physical exam demonstrates a boy in pain holding his abdomen who is afebrile, tachycardic, and somewhat toxic-appearing. It’s difficult to get a proper physical exam, but he seems to have generalized abdominal tenderness. Hmmm, this kid looks a little too sick than your run of the mill food-borne gastroenteritis. Maybe intussusception, inflammatory bowel disease, or foreign body??
What was it about that “candy”? The kid admits to getting the candy out of the mom’s purse. The mom gives a loud, “Huh? Say what, now??” And lo and behold, in the purse you find…
Introduction and Brief Pathophysiology
Prior to 1990, iron toxicity used to be one of the major causes of toxicological deaths in children younger than 6 years. This was due to many factors including the medication’s resemblance to candy, presumed safety of iron-containing supplements, and simply not knowing that iron can be present in various multivitamin preparations in somewhat significant amounts (up to 100mg of elemental iron).1 Since then, public health efforts have increased awareness and education, and federal packaging regulations had mandated unit-dose packaging for meds containing >= 30mg elemental iron per dose. This has helped to significantly reduce the incidence of iron poisoning.2,3 Nevertheless, as EM docs, we have to be ready for anything that comes through those doors, so let’s take a further look into iron toxicity.
*Note: The federal regulations for unit-dose packaging has since been lifted by the FDA.4
Medications that resemble candy. Image Source: http://allparenting.com/my-family/articles/971239/watch-out-these-drugs-look-like-candy
How does iron toxicity present?
Described in textbooks as early as the 1950s,6 acute iron toxicity classically presents in 4-5 phases:
|1) Local/GI Toxicity||0.5-6h||Nausea, vomiting, diarrhea, GI bleeding||Redox reactions + free-radicals = damage to GI mucosa and increased passive absorption of Fe|
|2) Latent Period||6-24h||Improving GI symptoms from phase I; however, progressive organ cellular toxicity and organ damage, metabolic acidosis||This phase is not always present|
|3) Systemic Toxicity||12-24h||Hemodynamic instability, shock, coagulopathy/DIC, metabolic acidosis||1) Negative inotropy
2) Decreased plasma volume
3) Inhibition of thrombin/coagulation cascade
a) lactic acid due to shock
b) Inhibition of oxidative phosphorylation (protons normally used to form H2O are released)
c) Ferric hydroxide formation (Fe3++3H2O -> Fe(OH)3 + 3H+)
|4) Hepatotoxicity||<48h||Hepatic failure||Liver receives absorbed ions, iron from portal system, free-radical formation causes oxidative damage|
|5) Aftermath||3-6 weeks||Intestinal obstruction||Caused by strictures, fistulas, scars; gastric outlet obstruction most common|
Table source: 1,8
ABCs, IV access, monitor. What was the question? Oh right, more specifics…
Calculate ingested dose of elemental iron (if possible)= [Amount of elemental iron in ingested formulation (refer to table below) x number of pills ingested]/weight in kg. As a GENERAL rule, the amount of ingested elemental iron can be risk stratified as follows:
– 20 mg/kg: mild symptoms start (nausea, vomiting, abdominal pain)1
– 40 mg/kg: cutoff of whether or not patient can be monitored at home or should be evaluated at a health care facility (as recommended by the American Association of Poison Control Centers). *If severe or persistent symptoms are present or the ingestion was intentional, this cutoff does not apply – the patient should be evaluated at a medical facility regardless of calculated ingested amount.6
– 60 mg/kg: severe toxicity1
Table Source: 6
Serum Iron Level is useful for diagnosis; should be measured at 4 hours after ingestion as peak levels occur at 4-6 hours after ingestion.1
<300 mcg/dL: less than upper range of body’s TIBC –> unlikely to be clinically significant1
>500 mcg/dL: moderate to severe toxicity8 – chelation therapy indicated7
>1000mcg/dL: severe toxicity, significant mortality8
CMP, Coags, VBG, Lactate may be helpful to assess for metabolic acidosis, coagulopathy, electrolyte imbalance, etc.
Also Not Absolutely Necessary But Can Be Helpful…
WBC, glucose may both be elevated in iron overdose, but these tests are neither sensitive nor specific.1 According to Goldfrank’s, one study found that WBC level of >15K or serum glucose of > 150 was found to be predictive of significant elevated iron concentration, but the results have not been replicated.14 It is important to remember normal WBC and glucose does not exclude toxicity.13
TIBC was once theorized to be helpful but has not proven to be reliable.1
KUB may be helpful for diagnosis and indicate need for whole bowel irrigation (WBI). See below. A negative KUB does NOT exclude iron ingestion or risk of toxicity.
1) In suspected iron overdose, you should involve your local Poison Control Center, (1-800-222-1222).
2) Supportive Care/Fluids – There may be fluid losses (vomiting, diarrhea) so replete with isotonic fluids, such as normal saline or lactated ringers.
3) GI decontamination – This is recommended for early presentation of massive ingestion or if pill fragments are seen on XR. However, it is not worthwhile if patient is already vomiting. Give polyethylene-glycol electrolyte solution (GoLytely) via NG tube at 500 ml/h (9mo-6y), 1000ml/h (6-12yr), 2000ml/h (>=13yr) until clear rectal effluent is achieved.9 Activated charcoal is not considered useful in these poisonings.
4) Deferoxamine (DFO) is a chelator of free iron.
– Serum iron > 500 ug/dL
– Significant clinical manifestations
– Significant metabolic acidosis
IM: 50mg/kg q6hr, max 6g/24h
IV: max rate 15mg/kg/hr for 1 hour then lowered to 125 mg/h
– IV is more effective than IM
No clear guidelines of rate and duration of DFO. Expert consultation is recommended (i.e call your local Poison Control Center early at 800-222-1222).1
Major potential adverse effects
– Hypotension, renal failure, acute respiratory distress, sepsis due to Yersinia1,8
5) Other interventions that have helped in case studies in the past, but there are no clear indications or guidelines:
– Endoscopic removal of iron bezoar10
– Emergency gastrotomy has found iron embedded in gastric mucosa11
– Exchange transfusion/Plasmapheresis12
6) Interventions that are NOT proven to work and/or are not recommended:
Oral complexers, activated charcoal, cathartics, calcium EDTA, oral sodium bicarbonate, oral phosphates, sodium bisphosphonate, magnesium hydroxide, gastric lavage, hemodialysis/hemofiltration1
Discharge if asymptomatic after 6 hours of ingestion, ingested elemental iron is < 40mg/kg, or if 4-6 hour serum iron level < 300 mcg/dL.
Otherwise, admit to regular floor or PICU depending on level of toxicity and severity of symptoms
Written By: Dr. Peter Song, PGY-2 Emergency Medicine at SUNY Downstate
Edited By: Dr. Caitlin Feeks, 2nd year PEM Fellow; Dr. Wiener, Associate Professor of Emergency Medicine and Medical Toxicology at SUNY Downstate; Dr. DeSouza, Associate Professor of Emergency Medicine at SUNY Downstate
- Chang TP1, Rangan C. Iron poisoning: a literature-based review of epidemiology, diagnosis, and management. Pediatr Emerg Care. 2011 Oct; 27(10):978-85. doi: 10.1097/PEC.0b013e3182302604.
- Tenenbein M1. Unit-dose packaging of iron supplements and reduction of iron poisoning in young children. Arch Pediatr Adolesc Med. 2005 Jun; 159(6):557-60.
- Broderick M1, Dodd-Butera T, Wahl P. A program to prevent iron poisoning using public health nurses in a county health department. Public Health Nurs. 2002 May-Jun;19(3):179-83.
- Food and Drug Administration, HHS. Iron-containing supplements and drugs; label warning statements and unit-dose packaging requirements; removal of regulations for unit-dose packaging requirements for dietary supplements and drugs. Final rule; removal of regulatory provisions in response to court order. Fed Regist. 2003 Oct 17;68(201):59714-5.
- Wallerstein RO, Mettier SR. Iron in Clinical Medicine. University of California Press, 1958. pp 93-103
- Manoguerra AS1, Erdman AR, et al. Iron ingestion: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2005;43(6):553-70.
- Leikin S, Vossough P, Mochir-Fatemi F. Chelation therapy in acute iron poisoning. J Pediatr. 1967;71:425Y430.
- Fine JS, Iron poisoning. Curr Probl Pediatr. 2000 Mar;30(3):71-90.
- Bouchard N. Current Guidelines For Gastrointestinal Decontamination In The Emergency Department. EM Practice Guidelines Update: 2010 Aug; 2(8): 8
- Ng HW, Tse ML, Lau FL, et al. Endoscopic removal of iron bezoar following acute overdose. Clin Toxicol. 2008;17:1Y3.
- Peterson CD, Fifield GC. Emergency gastrotomy for acute iron poisoning. Ann Emerg Med. 1980 May;9(5):262-4.
- Carlsson M, Cortes D, Jepsen S, et al. Severe iron intoxication treated with exchange transfusion. Arch Dis Child. 2008;93:321Y322.
- Goldfrank, LR et al. Goldfrank’s Toxicological Emergencies. Chapter 46: Iron. 10th McGraw-Hill Education; 2015.
- Lacouture PG, Wason S, Temple AR, et al; Emergency Assessment of severity in iron ovverdose by clinical and laboratory methods. J Pediatrics. 1981;99:89-91.