Iron toxicity: Difference between revisions
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*Biologically a component of hemoglobin, myoglobin, catalase, xanthine oxidase, etc | *Biologically a component of hemoglobin, myoglobin, catalase, xanthine oxidase, etc | ||
*Uptake highly regulated | *Uptake highly regulated | ||
*Amount of elemental iron ingested determines the risk, not the amount of iron salt<ref>The Royal Children's Hospital Melbourne Clinical Practice Guidelines. 2020. https://www.rch.org.au/clinicalguide/guideline_index/Iron_poisoning/</ref> | |||
{{Iron percentages table}} | {{Iron percentages table}} | ||
==Toxicity== | ===Toxicity=== | ||
''Toxicity determined by mg/kg of elemental iron ingested<ref name="ironoverview">Robotham JL, Lietman PS: Acute iron poisoning. A review. Am J Dis Child 1980; 134:875-879.</ref>'' | ''Toxicity determined by mg/kg of elemental iron ingested<ref name="ironoverview">Robotham JL, Lietman PS: Acute iron poisoning. A review. Am J Dis Child 1980; 134:875-879.</ref>'' | ||
{| {{table}} | {| {{table}} | ||
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==Clinical Features== | ==Clinical Features== | ||
*Absence of GI symptoms within 6hr of ingestion excludes significant iron ingestion (exception: enteric coated tablets) | *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. | *Significant iron toxicity can result in a severe [[lactic acidosis]] from hypoperfusion due to volume loss, vasodilation and negative inotropin effects. | ||
{| class="wikitable" | {| class="wikitable" | ||
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! scope="col" | '''Time Frame''' | ! scope="col" | '''Time Frame''' | ||
|- | |- | ||
| Stage 1||GI irritation: | | Stage 1||GI irritation: Nausea, vomiting, diarrhea, abdominal pain, hematemesis, hematochezia||30 mins-6 hours | ||
|- | |- | ||
| Stage 2: Latent|| | | Stage 2: Latent||GI symptoms may improve or resolve||6-24 hours | ||
|- | |- | ||
| Stage 3: Shock and metabolic acidosis||Metabolic acidosis, lactic acidosis, dehydration||6-72 hours | | Stage 3: Shock and metabolic acidosis||Metabolic acidosis, lactic acidosis, dehydration||6-72 hours | ||
|- | |- | ||
| Stage 4: Hepatotoxicity/ Hepatic necrosis||Hepatic failure||12-96 hours | | Stage 4: Hepatotoxicity/Hepatic necrosis||Hepatic failure with jaundice||12-96 hours | ||
|- | |- | ||
| Stage 5: Bowel obstruction||GI mucosa healing leads to scarring||2-8 weeks | | Stage 5: Bowel obstruction||GI mucosa healing leads to scarring||2-8 weeks | ||
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==Evaluation== | ==Evaluation== | ||
===Work-Up=== | ===Work-Up=== | ||
[[File:vin_rose.JPG| | [[File:vin_rose.JPG|thumb|Urine changes from rusty colored vin rose to clear.]] | ||
*Two large-bore peripheral IVs | |||
*CBC | *CBC | ||
*Chemistry - '''notice that this can appear like [[DKA]]''' | *Chemistry - '''notice that this can appear like [[DKA]]''' | ||
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**Used to follow efficacy of Fe chelation | **Used to follow efficacy of Fe chelation | ||
**Urine changes from rusty colored vin rose to clear | **Urine changes from rusty colored vin rose to clear | ||
*Urine pregnancy test | |||
*Type and Screen | *Type and Screen | ||
* | *XR KUB | ||
**In ambiguous cases consider abdominal xray as most Fe | **In ambiguous cases consider abdominal xray as most Fe tabletss are radioopaque<ref>The Royal Children's Hospital Melbourne Clinical Practice Guidelines. 2020. https://www.rch.org.au/clinicalguide/guideline_index/Iron_poisoning/</ref> | ||
**However, a normal XR KUB does not rule out significant ingestion, particularly if liquid iron or chewable vitamins with iron were ingested <ref>Everson GW, Oudjhane K, Young LW, Krenzelok EP. Effectiveness of abdominal radiographs in visualizing chewable iron supplements following overdose. Am J Emerg Med. 1989 Sep;7(5):459-63. doi: 10.1016/0735-6757(89)90245-3. PMID: 2757710.</ref> | |||
*EKG | |||
*A serum glucose > 150mg/dL and leukocyte count above 15,000 is 100% Sp and 50% Sn in predicting Fe levels > 300mcg/mL, but the absence cannot exclude iron toxicity <ref>Lacouture PG et al. Emergency assessment of severity in iron overdose by clinical and laboratory methods. J Pediatr 1981; 99:89-91.</ref> | |||
===Diagnosis=== | |||
=== | ''Serum iron concentration can guide treatment, but is not absolute in predicting or excluding toxicity.'' | ||
''Serum iron concentration can guide treatment but | |||
{| {{table}} | {| {{table}} | ||
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==Management== | ==Management== | ||
===Observation | ===Observation=== | ||
*Patients with asymptomatic ingestion of <20mg/kg only require observation | *Patients with asymptomatic ingestion of < 20mg/kg of elemental iron may only require observation for 6 hours | ||
*Volume resuscitation | *Volume resuscitation | ||
===Orogastric Lavage=== | |||
*Unclear benefit. Risk of aspiration, perforation, laryngospasm | |||
*Intubate prior to procedure if patient not protecting airway | |||
*Indication: Normal saline via large orogastric tube for moderate to severe iron poisoning if there are still many iron tablets (20-30) in abdominal radiograph may be beneficial | |||
===[[Whole bowel irrigation]]=== | ===[[Whole bowel irrigation]]=== | ||
* | *Indicated for large ingestion | ||
*Administer polyethylene glycol solution at 2 L/hr in adults and 250-500 mL/hr in children | |||
*Do not base only on radioopaque evidence of iron pills as not all formulations are readily visible on XR | *Do not base only on radioopaque evidence of iron pills as not all formulations are readily visible on XR | ||
*Orogastric lavage only is not likely to be successful after iron tablets have moved past the pylorus | *Orogastric lavage only is not likely to be successful after iron tablets have moved past the pylorus | ||
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**One mole of Deferoxamine (100mg) binds one mole of iron (9mg) to form ferrioxamine | **One mole of Deferoxamine (100mg) binds one mole of iron (9mg) to form ferrioxamine | ||
**Results in vin-rose urine (ferrioxamine is a reddish compound) | **Results in vin-rose urine (ferrioxamine is a reddish compound) | ||
* | *Dose | ||
** | **5-15 mg/kg/hr, max of 35 mg/kg/hr or 6g total per day | ||
**Can give 90 mg/kg IM if unable to obtain IV | **Start slower at 5-8 mg/kg/hr if hypotensive and uptitrate as tolerated | ||
**Titrate up for worsening metabolic acidosis, progressive organ failure, persistent vin rosé urine (ongoing choleation) | |||
**Can give 90 mg/kg IM if unable to obtain IV, but must establish IV ASAP given patient will need fluid resuscitation | |||
*Adverse reactions | *Adverse reactions | ||
**Hypotension | **Hypotension | ||
**May cause flushing (anaphylactoid reaction) | **May cause flushing (anaphylactoid reaction) | ||
**Rarely causes ARDS - associated with prolonged use | **Rarely causes ARDS - associated with prolonged use | ||
** | **Safe in pregnancy (give if obvious signs of shock/toxicity) | ||
===Hemodialysis=== | ===Hemodialysis=== | ||
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===Not Indicated=== | ===Not Indicated=== | ||
====[[Activated charcoal]]==== | ====[[Activated charcoal]]==== | ||
*Does not | *Does not absorb significant amounts if iron and is not recommended | ||
===Poison Control=== | ===Poison Control=== | ||
1-800-222-1222 (United States) | *1-800-222-1222 (United States) | ||
==Disposition== | ==Disposition== | ||
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==See Also== | ==See Also== | ||
[[Toxidromes]] | *[[Toxidromes]] | ||
*[[Hemochromatosis]] | |||
==External Links== | |||
*Example clinical practice guideline: https://www.rch.org.au/clinicalguide/guideline_index/Iron_poisoning/ | |||
==References== | ==References== | ||
<references/> | <references/> | ||
[[Category:Toxicology]] | [[Category:Toxicology]] |
Latest revision as of 18:50, 8 August 2023
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
- Amount of elemental iron ingested determines the risk, not the amount of iron salt[1]
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% |
Toxicity
Toxicity determined by mg/kg of elemental iron ingested[2]
Severity | Elemental Iron Dose (mg/kg)^ |
Mild | 10-20 |
Moderate | 20-60 |
Severe | >60 |
^Total amount of elemental iron ingested calculated by multiplying estimated number of tablets by the percentages of iron in the tablet preparation (see above)
Pathophysiology
- Direct caustic injury to gastric mucosa[3]
- 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[4]
- Increased capillary permeability
- Hypotension
- Venodilation
- Hypovolemic shock
- Portal vein iron delivery to liver
- Overwhelm storage capacity 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
- 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.
Staging | Clinical Effect | Time Frame |
---|---|---|
Stage 1 | GI irritation: Nausea, vomiting, diarrhea, abdominal pain, hematemesis, hematochezia | 30 mins-6 hours |
Stage 2: Latent | GI symptoms may improve or resolve | 6-24 hours |
Stage 3: Shock and metabolic acidosis | Metabolic acidosis, lactic acidosis, dehydration | 6-72 hours |
Stage 4: Hepatotoxicity/Hepatic necrosis | Hepatic failure with jaundice | 12-96 hours |
Stage 5: Bowel obstruction | GI mucosa healing leads to scarring | 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) [5]
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
- Phosphorus 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, Inhalants, Inborn Errors
- L-Lactic Acidosis
- E-Ethylene glycol, Ethanol
- R-Rhabdomyolysis
- S-Salicylates, Solvents, Starvation
Hyperglycemia
- Physiologic stress response (rarely causes glucose >200 mg/dL)
- Diabetes mellitus (main)
- Hemochromatosis
- Iron toxicity
- Sepsis
Evaluation
Work-Up
- Two large-bore peripheral IVs
- 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
- Urine pregnancy test
- Type and Screen
- XR KUB
- EKG
- A serum glucose > 150mg/dL and leukocyte count above 15,000 is 100% Sp and 50% Sn in predicting Fe levels > 300mcg/mL, but the absence cannot exclude iron toxicity [8]
Diagnosis
Serum iron concentration can guide treatment, but is not absolute in predicting or excluding toxicity.
Peak Serum Iron Level (mcg/dL)^ | Category |
<300 | Nontoxic or mild |
300-500 | Significant GI symptoms and potential for systemic toxicity |
>500 | Moderate to severe systemic toxicity |
>1000 | Severe systemic toxicity and increased morbidity |
^usually around 4hrs post ingestion although very high doses may lead to delayed peak
Management
Observation
- Patients with asymptomatic ingestion of < 20mg/kg of elemental iron may only require observation for 6 hours
- Volume resuscitation
Orogastric Lavage
- Unclear benefit. Risk of aspiration, perforation, laryngospasm
- Intubate prior to procedure if patient not protecting airway
- Indication: Normal saline via large orogastric tube for moderate to severe iron poisoning if there are still many iron tablets (20-30) in abdominal radiograph may be beneficial
Whole bowel irrigation
- Indicated for large ingestion
- Administer polyethylene glycol solution at 2 L/hr in adults and 250-500 mL/hr in children
- Do not base only on radioopaque evidence of iron pills as not all formulations are readily visible on XR
- Orogastric lavage only is not likely to be successful after iron tablets have moved past the pylorus
- Supported by case reports and uncontrolled case series, but rationale behind it makes it largely supported by toxicologists[9]
- Promotes increased gastric emptying and avoids large bezoar formation[10]
Deferoxamine
- Indications
- Pregnancy
- Systemic toxicity and iron level > 350 mcg/dL
- Iron level >500mcg/dL
- Metabolic acidosis
- Altered Mental Status
- Progressive symptoms, including shock, coma, seizures, refractory GI symptoms
- Large number of pills on KUB
- Estimated dose > 60mg/kg Fe2+
- Administered IV due to poor oral absorption
- One mole of Deferoxamine (100mg) binds one mole of iron (9mg) to form ferrioxamine
- Results in vin-rose urine (ferrioxamine is a reddish compound)
- Dose
- 5-15 mg/kg/hr, max of 35 mg/kg/hr or 6g total per day
- Start slower at 5-8 mg/kg/hr if hypotensive and uptitrate as tolerated
- Titrate up for worsening metabolic acidosis, progressive organ failure, persistent vin rosé urine (ongoing choleation)
- Can give 90 mg/kg IM if unable to obtain IV, but must establish IV ASAP given patient will need fluid resuscitation
- Adverse reactions
- Hypotension
- May cause flushing (anaphylactoid reaction)
- Rarely causes ARDS - associated with prolonged use
- Safe 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[11]
Not Indicated
Activated charcoal
- Does not absorb significant amounts if iron and is not recommended
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
External Links
- Example clinical practice guideline: https://www.rch.org.au/clinicalguide/guideline_index/Iron_poisoning/
References
- ↑ The Royal Children's Hospital Melbourne Clinical Practice Guidelines. 2020. https://www.rch.org.au/clinicalguide/guideline_index/Iron_poisoning/
- ↑ 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
- ↑ The Royal Children's Hospital Melbourne Clinical Practice Guidelines. 2020. https://www.rch.org.au/clinicalguide/guideline_index/Iron_poisoning/
- ↑ Everson GW, Oudjhane K, Young LW, Krenzelok EP. Effectiveness of abdominal radiographs in visualizing chewable iron supplements following overdose. Am J Emerg Med. 1989 Sep;7(5):459-63. doi: 10.1016/0735-6757(89)90245-3. PMID: 2757710.
- ↑ Lacouture PG et al. Emergency assessment of severity in iron overdose by clinical and laboratory methods. J Pediatr 1981; 99:89-91.
- ↑ Hoffman RS et al. Goldfrank's Toxicologic Emergencies. 10th Ed. Pg 618-219. McGraw Hill, 2015.
- ↑ 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.