Iron toxicity: Difference between revisions

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==Background==
==Background==
*Each 325mg ferrous sulfate tablet contains 65mg of elemental iron
*The toxicity is generally determined by the mg/kg of elemental iron ingested. The 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 the following elemental dose per kilograms:<ref name="ironoverview">Robotham JL, Lietman PS: Acute iron poisoning. A review. Am J Dis Child 1980; 134:875-879.</ref>
*Toxicity
{| {{table}}
**Mild: 10-20mg elemental iron/kg
| align="center" style="background:#f0f0f0;"|'''Mild:'''
**Moderate: 20-60mg/kg (approx 20-35 tablets)
| align="center" style="background:#f0f0f0;"|'''10-20mg/kg'''
**Severe: >60mg/kg
|-
| Moderate|| 20-60mg/kg
|-
| Severe||>60mg/kg
|}
*Absence of GI symptoms w/in 6hr of ingestion excludes significant iron ingestion
*Absence of GI symptoms w/in 6hr of ingestion excludes significant iron ingestion
*Significant iron toxicity can result in a severe lactic acidosis from hypopefusion due to volume loss, vasodilation and negative inotropin effects.
===Elemental Iron Percentages===
{| {{table}}
| align="center" style="background:#f0f0f0;"|'''Iron Preparation'''
| align="center" style="background:#f0f0f0;"|'''% of Elemental Iron'''
|-
| Ferrous Fumarate ||33%
|-
| Ferrous Sulfate ||20%
|-
| Ferrous Gluconate ||12%
|-
| Ferric pyrophosphate||30%
|-
| Ferroglycine sulfate||16%
|-
| Ferrous carbonate (anhydrous)||38%
|}


==Pathophysiology==
==Pathophysiology==
*GI tract irritant:
===Direct caustic injury to gastric mucosa<ref>Robotham JL, Lietman PS. Acute iron poisoning. A review. Am J Dis Child 1980; 134:875-879.</ref>===
**N/V, diarrhea, abdominal pain, bleeding
*Causing vomitting, diarrhea, abdominal pain, and bleeding
*Electron transport chain disruption:
===Impaired cellular metabolism===
**Lactic acidosis
*Inhibiting the electron transport chain causes lactic acidosis
*Portal vein iron delivery to liver:
*Direct hepatic, CNS, and cardiac toxicity
**Hepatotoxicity
*Cell membrane injury from lipid peroxidation<ref>Aisen P et al. Iron toxicosis. Int Rev Exp Pathol 1990. 31:1-46.</ref>
*Thrombin formation inhibition:
===Increased capillary permeability===
**Coagulopathy - direct effect on vitamin K clotting factors
*Hypotension
*Venodilation
===Portal vein iron delivery to liver===
*Hepatotoxicity
===Thrombin formation inhibition===
*Coagulopathy - direct effect on vitamin K clotting factors


==Clinical Features==
==Clinical Features==
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#UA
#UA
##Used to follow efficacy of Fe chelation (urine changes from rusty color to clear)
##Used to follow efficacy of Fe chelation (urine changes from rusty color to clear)
#T&S
#Type and Screen
#In ambiguous cases consider abd xray as most Fe tabs are radioopague
#In ambiguous cases consider abd xray as most Fe tabs are radioopague


==Diagnosis==
==Diagnosis==
*Serum Iron Concentration
Serum Iron concentration can guide treatment but are not absolute in predicting or excluding toxicity:
**Interpret w/ caution: low serum iron levels do not necessarily mean absence of toxicity
Peak serum iron level:
**Levels
*<300 mcg/dL: nontoxic or mild
***<300: nontoxic or mild
*300-500 mcg/dL: Significant GI symptoms and potential for systemic toxicity
***300-500: Significant GI symptoms and potential for systemic toxicity
*>500 mcg/dL: Moderate to severe systemic toxicity
***>500: Moderate to severe systemic toxicity
*>1000 mcg/dL: severe systemic toxicity and increased morbidity
***>1000: severe systemic toxicity and increased morbidity


If unable to obtain a serum iron level a glucose > 150 mg/dL and leukocyte count above 15000 is 100% specific and 50% sensitive in predicint=g levels > 300mcg/mL<ref>Lacouture PG et al. Emergency assessment of severity in iron overdose by clinical and laboratory methods. J Pediatr 1981; 99:89-91.</ref>
==Treatment==
==Treatment==
#Asymptomatic pt w/ ingestion of <20mg/kg only requires observation x6hr
===Observation x 6 hrs===
*Patients with asymptomatic ingestion of <20mg/kg only require observation x 6hr
#Volume resuscitation
#Volume resuscitation
#GI decontamination
===GI decontamination===
##Consider only for large overdose w/ visible pills in the stomach on x-ray
*Consider only for large overdose with visible pills in the stomach on x-ray
###Whole-bowel irrigation (polyethylene glycol)
*Whole-bowel irrigation (polyethylene glycol) will promote increased gastric emptying and avoid large bezoar formation<ref>Position paper: Whole bowel irrigation. J Toxicol Clin Toxicol 2004; 42:843-854.</ref>
####Children: 250-500mL/hr  
====Polyethylene glycol dosing====
####Adults: 2L/hr
'''Can be given orally or by NG tube'''
###Orogastric lavage
*20-40 mL/kg/hr in young children
##Charcoal is not effective
*2L/hr in adults
#Deferoxamine
Continue irrigation until the rectal effluent is clear
##Indications:
===[[Deferoxamine]]===
###Systemic toxicity
Deferoxamine chelates iron and creates a water-soluble compound ferrioxamine that is renally excreted and can be dialyzed.<ref name="ironoverview"></ref>
###Metabolic acidosis
====Indications====
###Progressive symptoms
#Systemic toxicity and iron level > 350 mcg/dL
###Serum iron level >500
#Metabolic acidosis
##Dosing:
#Progressive symptoms
###1000mg IV; start at 5mg/kg/hr, increase up to 15mg/kg/hr as tolerated
#Serum iron level >500 mcg/dL
###Subsequent doses are 500mg increments guided by clinical status of pt / urine color
====Dosing====
###Recommended amount during first 24hr is 360mg/kg or 6gm
#1000mg IV; start at 5mg/kg/hr, increase up to 15mg/kg/hr as tolerated for up to 24hrs
##Side effects:
#Subsequent doses are 500mg increments guided by clinical status of pt / urine color
###Hypotension (pre-existing hypotension is NOT a contraindication to therapy)
#Recommended amount during first 24hr is 360mg/kg not to exceed 6g.
###Contraindicated in renal failure patients not on HD
====Adverse effects====
###Long-term use: mucor/yersenia/mucosal infections, renal failure, sepsis
#[[Hypotension]] (pre-existing hypotension is NOT a contraindication to therapy)
###Can see "vin rose" urine
#[[ARDS]]
#Other therapies
#[[Yersinia enterocolitica]] sepsis<ref>Mazzoleni G. et al. Yersinia enterocolitica infection with ileal perforation associated with iron overload and
##Dialysis (removes deferoxamine-iron complex in renal failure pts)
deferoxamine therapy. Dig Dis Sci 1991; 36:1154-1160.</ref>
##Exchange transfusion
#Can see "vin rose" colored urine from chelated iron extretion
====Contraindications====
*Renal failure patients not on hemodialysis
===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<ref>Movassaghi N. et al. Comparison of exchange transfusion and deferoxamine in the treatment of acute iron poisoning. J Pediatr 1969; 75:604-608.</ref>
===Orogastric lavage===
*Does not remove large numbers of pills and may have serious adverse events
===[[Activated charcoal]]===
*Does not bind iron
 


==Disposition==
==Disposition==
*Discharge after 6hr obs for asymptomatic (or only vomited 1-2x) AND ingestion <20mg/kg
*Discharge after 6hr obs for asymptomatic (or only vomited 1-2x) AND ingestion <20mg/kg
*Admit to ICU if deferoxamine required
*Admit to ICU if deferoxamine required
*Psychiatric evaluation if intentional ingestion


==See Also==
==See Also==
Line 95: Line 137:


==Source==
==Source==
*Tintinalli
<references/>
 
[[Category:Tox]]
[[Category:Tox]]

Revision as of 14:45, 2 August 2015

Background

  • The toxicity is generally determined by the mg/kg of elemental iron ingested. The 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 the following elemental dose per kilograms:[1]
Mild: 10-20mg/kg
Moderate 20-60mg/kg
Severe >60mg/kg
  • Absence of GI symptoms w/in 6hr of ingestion excludes significant iron ingestion
  • Significant iron toxicity can result in a severe lactic acidosis from hypopefusion 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]

  • Causing vomitting, diarrhea, abdominal pain, and bleeding

Impaired cellular metabolism

  • Inhibiting the electron transport chain causes lactic acidosis
  • Direct hepatic, CNS, and cardiac toxicity
  • Cell membrane injury from lipid peroxidation[3]

Increased capillary permeability

  • Hypotension
  • Venodilation

Portal vein iron delivery to liver

  • Hepatotoxicity

Thrombin formation inhibition

  • Coagulopathy - direct effect on vitamin K clotting factors

Clinical Features

Iron Toxicity Stages
Stage Clinical Effect Time Frame
Stage 1 GI irritation: n/v, abd 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

Work-Up

  1. CBC
  2. Chemistry
    1. Anion gap metabolic acidosis
    2. Hyperglycemia
  3. Coags
  4. LFTs
  5. Iron levels
  6. UA
    1. Used to follow efficacy of Fe chelation (urine changes from rusty color to clear)
  7. Type and Screen
  8. In ambiguous cases consider abd xray as most Fe tabs are radioopague

Diagnosis

Serum Iron concentration can guide treatment but are not absolute in predicting or excluding toxicity: Peak serum iron level:

  • <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 > 150 mg/dL and leukocyte count above 15000 is 100% specific and 50% sensitive in predicint=g levels > 300mcg/mL[4]

Treatment

Observation x 6 hrs

  • Patients with asymptomatic ingestion of <20mg/kg only require observation x 6hr
  1. Volume resuscitation

GI decontamination

  • Consider only for large overdose with visible pills in the stomach on x-ray
  • Whole-bowel irrigation (polyethylene glycol) will promote increased gastric emptying and avoid large bezoar formation[5]

Polyethylene glycol dosing

Can be given orally or by NG tube

  • 20-40 mL/kg/hr in young children
  • 2L/hr in adults

Continue irrigation until the rectal effluent is clear

Deferoxamine

Deferoxamine chelates iron and creates a water-soluble compound ferrioxamine that is renally excreted and can be dialyzed.[1]

Indications

  1. Systemic toxicity and iron level > 350 mcg/dL
  2. Metabolic acidosis
  3. Progressive symptoms
  4. Serum iron level >500 mcg/dL

Dosing

  1. 1000mg IV; start at 5mg/kg/hr, increase up to 15mg/kg/hr as tolerated for up to 24hrs
  2. Subsequent doses are 500mg increments guided by clinical status of pt / urine color
  3. Recommended amount during first 24hr is 360mg/kg not to exceed 6g.

Adverse effects

  1. Hypotension (pre-existing hypotension is NOT a contraindication to therapy)
  2. ARDS
  3. Yersinia enterocolitica sepsis[6]
  4. Can see "vin rose" colored urine from chelated iron extretion

Contraindications

  • Renal failure patients not on hemodialysis

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]

Orogastric lavage

  • Does not remove large numbers of pills and may have serious adverse events

Activated charcoal

  • Does not bind iron


Disposition

  • Discharge after 6hr obs for asymptomatic (or only vomited 1-2x) AND ingestion <20mg/kg
  • Admit to ICU if deferoxamine required
  • Psychiatric evaluation if intentional ingestion

See Also

Toxidromes

Source

  1. ↑ 1.0 1.1 Robotham JL, Lietman PS: Acute iron poisoning. A review. Am J Dis Child 1980; 134:875-879.
  2. ↑ Robotham JL, Lietman PS. Acute iron poisoning. A review. Am J Dis Child 1980; 134:875-879.
  3. ↑ Aisen P et al. Iron toxicosis. Int Rev Exp Pathol 1990. 31:1-46.
  4. ↑ Lacouture PG et al. Emergency assessment of severity in iron overdose by clinical and laboratory methods. J Pediatr 1981; 99:89-91.
  5. ↑ Position paper: Whole bowel irrigation. J Toxicol Clin Toxicol 2004; 42:843-854.
  6. ↑ Mazzoleni G. et al. Yersinia enterocolitica infection with ileal perforation associated with iron overload and deferoxamine therapy. Dig Dis Sci 1991; 36:1154-1160.
  7. ↑ Movassaghi N. et al. Comparison of exchange transfusion and deferoxamine in the treatment of acute iron poisoning. J Pediatr 1969; 75:604-608.
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