We need you! Join our contributor community and become a WikEM editor through our open and transparent promotion process.
Iron toxicity
From WikEM
(Redirected from Iron (Fe))
Contents
Background
- Iron is the 4th most abundant atomic element in the earth's crust
- biologically a component of hemoglobin, myoglobin, catalase, xanthine oxidase, etc
- uptake highly regulated
Toxicity
- Toxicity determined by mg/kg of elemental iron
- Total amount of elemental iron ingested can calculated by multiplying the estimated number of tablets by the percentages of iron in the tablet preparation
- Clinical severity is based approximated by elemental dose per kilograms:[1]
| Severity | Dose (mg/kg) |
| Mild | 10-20 |
| Moderate | 20-60 |
| Severe | >60 |
- Absence of GI symptoms within 6hr of ingestion excludes significant iron ingestion (exception: enteric coated tablets)
- Significant iron toxicity can result in a severe lactic acidosis from hypoperfusion due to volume loss, vasodilation and negative inotropin effects.
Elemental Iron Percentages
| Iron Preparation | % of Elemental Iron |
| Ferrous Fumarate | 33% |
| Ferrous Sulfate | 20% |
| Ferrous Gluconate | 12% |
| Ferric pyrophosphate | 30% |
| Ferroglycine sulfate | 16% |
| Ferrous carbonate (anhydrous) | 38% |
Pathophysiology
- Direct caustic injury to gastric mucosa[2]
- occurs early, usually within several hours
- Causing vomiting, diarrhea, abdominal pain, and GI bleeding
- usually affects, the stomach, duodenum, colon rarely affected
- can lead to formation of gastric strictures 2-8 weeks post-ingestion
- Impaired cellular metabolism
- Inhibiting the electron transport chain causes lactic acidosis
- Direct hepatic, CNS, and cardiac toxicity (decreased CO and myocardial contractility)
- Cell membrane injury from lipid peroxidation[3]
- Increased capillary permeability
- Hypotension
- Venodilation
- hypovolemic shock
- Portal vein iron delivery to liver
- overwhelm storage capatcity of Ferritin
- Hepatotoxicity (cloudy swelling, periportal hepatic necrosis, elevated transaminases)
- destroys hepatic mitochondria, disrupts oxidative phosphorylation → worsening metabolic acidosis
- Thrombin formation inhibition
- Coagulopathy - direct effect on vitamin K clotting factors
Clinical Features
| Staging | Clinical Effect | Time Frame |
|---|---|---|
| Stage 1 | GI irritation: nausea and vomiting, abdominal pain, diarrhea | 30-60 mins |
| Stage 2: latent | reduced GI symptoms | 6-24 hours |
| Stage 3: shock and metabolic acidosis | metabolic acidosis, lactic acidosis, dehydration, coags, renal failure | 6-72 hours |
| Stage 4: hepatotox | hepatic failure | 12-96 hours |
| Stage 5: bowel obstruction | GI bowel scarring/healing | 2-8 weeks |
- Stage I: GI toxicity: nausea, vomiting, diarrhea, GI bleeding from local corrosive effects of iron on the gastric and intestinal mucosa
- Stage II: quiescent phase with resolution of GI symptoms and apparent clinical improvement
- controversy between toxicologists whether this stage exists in significant poisonings
- Stage III: systemic toxicity: shock and hypoperfusion
- Primarily hypovolemic shock and acidosis, myocardial dysfunction also contributes
- GI fluid losses, increase capillary permeability, decreased venous tone
- severe anion gap acidosis
- free radical damage to mitochondria disrupt oxidative phosphorylation which leads to lactic acidosis
- hepatotoxicity from iron delivery via portal blood flow
- Stage IV: clinical recovery, resolution of shock and acidosis usually by days 3-4
- Stage V: late onset of gastric and pyloric strictures (2-8 week later) [4]
Differential Diagnosis
Heavy metal toxicity
- Aluminum toxicity
- Antimony toxicity
- Arsenic toxicity
- Barium toxicity
- Bismuth toxicity
- Cadmium toxicity
- Chromium toxicity
- Cobalt toxicity
- Copper toxicity
- Gold toxicity
- Iron toxicity
- Lead toxicity
- Lithium toxicity
- Manganese toxicity
- Mercury toxicity
- Nickel toxicity
- Phosphorous toxicity
- Platinum toxicity
- Selenium toxicity
- Silver toxicity
- Thallium toxicity
- Tin toxicity
- Zinc toxicity
CAT MUDPILERS
- C-Cyanide
- A-ASA, Alcohol
- T-Toluene
- M-Methanol, Metformin
- U-Uremia
- D-DKA
- P-Paraldehyde, Post-ictal lactic acidosis (transient, 60-90 min), Phenformin (withdrawn in 1970s)
- I-Iron, INH, Inhalents, Inborn Errors
- L-Lactic Acidosis
- E-Ethylene glycol, Ethanol
- R-Rhabdomyolysis
- S-Salicylates, Solvents, Starvation
Evaluation
Work-Up
- CBC
- Chemistry - notice that this can appear like DKA
- Anion gap metabolic acidosis
- Hyperglycemia
- Coags
- LFTs
- Iron levels
- Urinalysis
- Used to follow efficacy of Fe chelation
- Urine changes from rusty colored vin rose to clear
- Type and Screen
- Xr KUB
- In ambiguous cases consider abdominal xray as most Fe tabs are radioopaque
Serum Iron Concentration
Serum iron concentration can guide treatment but are not absolute in predicting or excluding toxicity
Peak serum iron level (usually around 4hrs post ingestion although very high doses may lead to delayed peak):
- <300 mcg/dL: nontoxic or mild
- 300-500 mcg/dL: Significant GI symptoms and potential for systemic toxicity
- >500 mcg/dL: Moderate to severe systemic toxicity
- >1000 mcg/dL: severe systemic toxicity and increased morbidity
If unable to obtain a serum iron level a glucose > 150mg/dL and leukocyte count above 15000 is 100% specific and 50% sensitive in predicint=g levels > 300mcg/mL[5]
Management
Observation x 6 hrs
- Patients with asymptomatic ingestion of <20mg/kg only require observation x 6hr
- Volume resuscitation
Whole bowel irrigation
- Consider only for large overdose with visible pills in the stomach on x-ray
- Promotes increased gastric emptying and avoids large bezoar formation[6]
Deferoxamine
- Systemic toxicity and iron level > 350 mcg/dL
- Metabolic acidosis
- Progressive symptoms
- Serum iron level >500 mcg/dL
- large #of pills on KUB
- estimated dose > 60mg/kg Fe2+
- Administered IV or IM because of poor oral absorption
- one mole of Deferoxamine (100mg) bind one mole of iron (9mg) to form ferrioxamine
- vin-rose urine (ferrioxamine is a reddish compound)
- 15mg/kg/hr (determined empirically and never clinically tested), max 35mg/kg/hr
- can start slower at 8mg/kg/hr if concern for hypotension and uptitrate
- can give 90mg/kg IM if unable to obtain IV however IVF is critical so IV access should be established ASAP
- can cause hypotension
- may cause flushing (anaphylactoid reaction)
- rarely causes ARDS - associated with prolonged use
- probably safe to use in pregnancy (give if obvious signs of shock/toxicity)
Hemodialysis
- Not effective in removing iron due to large volumes of distribution
- Dialysis can removes deferoxamine-iron complex in renal failure patients
Exchange transfusion
- Minimal evidence but has been described in larger overdoses[7]
Not Indicated
Orogastric lavage
- Does not remove large numbers of pills and may have serious adverse events
Activated charcoal
- Does not bind iron
Poison Control
1-800-222-1222 (United States)
Disposition
- Discharge after 6hr observation for asymptomatic (or only vomited 1-2x) AND ingestion <20mg/kg
- Admit to ICU if deferoxamine required
- Psychiatric evaluation if intentional ingestion
See Also
References
- ↑ Robotham JL, Lietman PS: Acute iron poisoning. A review. Am J Dis Child 1980; 134:875-879.
- ↑ Robotham JL, Lietman PS. Acute iron poisoning. A review. Am J Dis Child 1980; 134:875-879.
- ↑ Aisen P et al. Iron toxicosis. Int Rev Exp Pathol 1990. 31:1-46.
- ↑ Fine, J. Iron Poisoning. Curr Probl Pediatr, Vol 30, Iss 3, p 71-90, March 2000
- ↑ Lacouture PG et al. Emergency assessment of severity in iron overdose by clinical and laboratory methods. J Pediatr 1981; 99:89-91.
- ↑ Position paper: Whole bowel irrigation. J Toxicol Clin Toxicol 2004; 42:843-854.
- ↑ Movassaghi N. et al. Comparison of exchange transfusion and deferoxamine in the treatment of acute iron poisoning. J Pediatr 1969; 75:604-608.
