Basics
Description
- Peak concentrations are 2-4 hr postingestion
- Serum concentrations not reliable if obtained >4-6 hr after ingestion:
- Enteric coated or sustained release-warrants serial levels
- Postabsorption: Iron redistributes into tissues, and fall in serum iron occurs as free iron shifts intracellularly resulting in cellular injury
- Injury patterns:
- Corrosive injury to intestinal mucosa may result in profound fluid loss (shock), hemorrhage, and perforation
- Liver receives largest load of iron because of portal venous circulation-(hemorrhagic periportal necrosis)
- Free iron:
- Concentrates in mitochondria, disrupting oxidative phosphorylation; catalyzes lipid peroxidation and free radical formation, resulting in cell death; increases anaerobic metabolism and acidosis
- Causes myocardial depression, venodilation, and cerebral edema
- Hydration of ferric form liberates 3 protons, resulting in acidemia
Etiology
Elemental iron ingestion:
- Nontoxic <20 mg/kg
- Moderate to severe >40 mg/kg
- Lethality possible >60 mg/kg
- Elemental iron equivalents:
- Ferrous sulfate, 20% (325 mg = 65 mg Fe)
- Ferrous gluconate, 12%
- Ferrous fumarate, 33%
- Prenatal vitamins vary from 60-90 mg elemental iron per tablet
- Childrens vitamins may contain 5-18 mg elemental iron per tablet
- Historically notorious for the highest mortality rate among pediatric accidental exposures (adult iron products)
- Children's chewable iron products have been shown to be safe
Diagnosis
Signs and Symptoms
- Classically divided into 5 stages:
- Stage 1: GI (0.5-6 hr):
- Abdominal pain
- Vomiting
- Diarrhea
- Hematemesis
- Hematochezia
- Stage 2: Latent/quiescent (6-24 hr):
- Resolution of GI symptoms
- Deceptive phase (ongoing injury?)
- Possible hypotension and acidosis
- Stage 3: Shock and organ failure (6-72 hr):
- Hypoperfusion
- Metabolic acidosis
- Coma
- Coagulopathy
- Stage 4: Hepatic failure (2-3 days):
- Coagulopathy
- Hypoglycemia
- Jaundice
- Elevated LFTs (transaminases) and bilirubin
- Stage 5: Obstruction (2-4 wk):
- Gastric outlet and small bowel obstruction
- Abdominal pain, vomiting
- Patient may present in or skip any of the 5 stages
- If onset of stage 1 does not occur within 6 hr, likely not significant ingestion
Essential Workup
Acute iron poisoning is a clinical diagnosis, regardless of lab results
Diagnosis Tests & Interpretation
Lab
- Serum iron levels (mg/dL):
- Peak absorption 2-6 hr
- 4 hr is most common time for peak
- Delayed peak with enteric coated/sustained release
- Electrolytes, BUN/creatinine, glucose:
- Anion gap metabolic acidosis
- Hyperglycemia early
- Hypoglycemia late
- Arterial blood gas:
- CBC:
- Anemia with significant hemorrhage
- Leukocytosis
- Liver function
- Coagulation profile
- Lactate
- Type and screen if hemorrhage
- Total iron-binding capacity is not useful and not recommended
Imaging
Abdominal radiograph check for:
- Tablets (childrens chewables rarely visible)
- Absence of pill fragment interpretation:
- Patient did not ingest iron
- Iron was in solution or has already dissolved
- Patient ingested pediatric multivitamin product
- Absence of radiopacities does not rule out significant or lethal ingestion
- Perforation
Differential Diagnosis
- Sepsis
- Acetaminophen toxicity
- Toxic ingestions causing anion gap acidosis:
- Salicylate
- Cyanide
- Methanol
- Ethylene glycol
- Mushrooms
- Heavy metals
- Theophylline toxicity
- GI bleed from other causes (alcoholic liver disease)
Treatment
Pre-Hospital
Collect prescription bottles/medications for identification in the ED
Initial Stabilization/Therapy
- ABCs:
- Intubate if profoundly unstable
- Venous access and fluids for hypotension
- Cardiac monitor and pulse oximetry
- Naloxone, thiamine, dextrose (or Accu-Chek) as indicated for altered mental status
Ed Treatment/Procedures
- Decontamination:
- Poorly adsorbed by activated charcoal
- Gastric lavage has not been shown to change outcome
- NaHCO3, phospho soda, and oral deferoxamine are not recommended
- If pill fragments are visualized on x-ray, or history of significant ingestion:
- Consider whole bowel irrigation (with NG GoLytely: Peds: 10-15 mL/kg/h; adult: 1-2 L/h) while monitoring progression with radiograph (KUB).
- Caution with GI bleed
- Endoscopy or gastrotomy can remove bezoar formation after massive ingestions (>240 mg/kg)
- Chelation with deferoxamine (DFO):
- DFO is a highly specific chelator of parenteral iron
- IV infusion results in more constant DFO levels and is route of choice:
- Administer as soon as possible (<24 hr)
- Administration techniques:
- Increase IV infusion rate to 15 mg/kg/h over 20 min, monitoring for hypotension
- Decrease infusion rate if hypotension
- Infusion rates as high as 45 mg/kg/h have been tolerated
- Disregard manufacturers recommendation of max. daily doses of 6 g in serious iron exposures
- IM DFO challenge test is not advocated
- Interpret serum levels cautiously:
- Time since ingestion must be considered: Treatment may be indicated in patient who presents late, after distribution stage (>8 hr postingestion), with serum iron level <350 mg/dL
- If serum iron levels are not readily available, base treatment decisions on clinical status
- Length of infusion (controversial):
- DFO-iron complex causes urine to turn vin rose color; this suggests continuing infusion until urine returns to normal
- Resolution of signs and symptoms of significant toxicity is criterion for discontinuing DFO
- Prolonged DFO therapy >24-48 hr may precipitate adult respiratory distress syndrome
- In severe cases with continued signs and symptoms, infusion may be continued cautiously at lower dose
- Controversies:
- Safety of DFO infusions given for >24 hr
- Maximal infusion rates and total amount
- Serum iron concentration warranting treatment
- Endpoint of treatment (best endpoint is resolution of poisoning, i.e., acidemia)
- Role of extracorporeal elimination
- Contact regional poison center for moderate to severe iron exposures
Medication
- Dextrose: D50W 1 amp (50 mL or 25 g; peds: D25W 2-4 mL/kg) IV
- Naloxone (Narcan): 2 mg (peds: 0.1 mg/kg) IV or IM initial dose
- Thiamine (vitamin B1): 100 mg (peds: 50 mg) IV or IM
Follow-Up
Disposition
Admission Criteria
- GI symptoms or dehydration
- Altered mental status
- Hypotension, lethargy, metabolic acidosis, or shock
- Serum iron >500 mg/dL
- Serum iron >350 mg/dL and pills seen on KUB
- Rising serum iron levels
- Patients treated with deferoxamine
- ICU admission for coma, shock, metabolic acidosis, or iron levels >1,000 mg/dL
Discharge Criteria
- Asymptomatic with negative radiograph
- Minimal to no symptoms after 6-hr observation
- Mild GI symptoms that have resolved without evidence of metabolic acidosis and serum iron <350 mg/dL
Issues for Referral
Contact regional poison center for mild to moderate toxicity
Follow-Up Recommendations
- Follow-up after discharge may be indicated in patients who are at risk of developing gastric outlet obstruction
- Psychiatric referral for patients with intentional overdose
Pearls and Pitfalls
- DFO may be indicated in patients who present late, after distribution stage (>8 hr postingestion), or with serum iron level <350 mg/dL and signs of intracellular poisoning (e.g., anion gap metabolic acidosis)
- Resolution of GI symptoms does not indicate that there is no ongoing toxicity that may progress over time
Additional Reading
- Bryant SM, Leikin J. Iron. In: Brent J, Wallace KL, Burkhart KK, et al., eds. Critical Care Toxicology. St. Louis, MO: Mosby; 2005.
- Chang TP, Rangan C. Iron poisoning: A literature-based review of epidemiology, diagnosis, and management. Pediatr Emerg Care. 2011;27:978-985.
- Tenenbein M. Unit-dose packaging of iron supplements and reduction of iron poisoning in young children. Arch Pediatr Adolesc Med. 2005;159:557-560.
Codes
ICD9
964.0 Poisoning by iron and its compounds
ICD10
- T45.4X1A Poisoning by iron and its compounds, accidental, init
- T45.4X4A Poisoning by iron and its compounds, undetermined, init
SNOMED
- 445902007 Poisoning by iron (disorder)
- 216802005 Accidental poisoning by iron compounds (disorder)