Iron

Iron toxicity may be severe and classically occurs over four phases:

• Phase 1: 0-6 hours
  Corrosive effect on the GI mucosa, leading to:
  • Nausea, vomiting
  • Fluid loss
• Phase 2: 6-12 hours
  Asymptomatic phase whilst iron shifts intracellularly.
• Phase 3: 12-48 hours
  Systemic iron toxicity caused by lipid peroxidation of mitochondrial membranes:
  • Multi-factorial shock
    • Distributive
      SIRS.
    • Cardiogenic
      Direct cardiac toxicity.
    • Hypovolaemic
      Third spacing and GI losses.
  • Hepatic necrosis
  • Acidosis
• Phase 4: 2-6 weeks
  Chronic GI strictures from scarring of mucosal erosions.

Epidemiology and Risk Factors

Pathophysiology

Aetiology

Clinical Manifestations

Phase 1:

• Nausea
• Vomiting
• Haematemesis
• Diarrhoea
• Melaena

Phase 3:

• Shock
  Multifactorial:
  • Vasodilatory
  • Cardiogenic
    Secondary to cardiac toxicity.
• Acidosis
  • HAGMA
    Multi-factorial lactic acidosis:
    • Generalised anaerobic metabolism due to mitochondrial toxicity
    • ↓ CO/cardiogenic shock
    • ↓ Hepatic lactate clearance
  • NAGMA
    Direct buffering of iron ions.
• Multi-organ failure
  • AKI
  • ALF

Investigations

Bedside:

• ABG
  • Acidosis
    Multifactorial:
    • HAGMA
      Lactic acidosis:
      • Hypovolaemia
        GI fluid losses.
      • Cardiogenic
        Myocardial toxicity.
      • Liver failure
    • NAGMA
      Ferric (Fe³⁺) iron and body water produce ferric hydroxide and a complimentary proton.

Laboratory:

• Blood
  • Serum iron
    Levels do not correlate with toxicity, but >90μmol/L is predictive of systemic toxicity.
    • Peak 4-6 hours following ingestion
    • ↓ Afterwards as iron moves intracellularly
  • Coag
  • UEC
  • LFT

Imaging:

• AXR
  • Confirm ingestion

Other:

Diagnostic Approach and DDx

Risk assessment is based on the amount of elemental iron ingested:

• Function of the:
  • Elemental iron content of the tablet
    
    • Varies depending if the tablet contains ferrous or ferric iron, and which anion it is bound with
    • Check the label
  • Number of tablets
    • History
    • Abdominal XR
• In general:
  • Asymptomatic: <20mg/kg
  • GI symptoms: 20-60mg/kg
  • Systemic: 60-120mg/kg
  • Lethal: >120mg/kg

The dose is divided by a constant to get the proportion of elemental iron in the tablet:

• Ferrous Sulfate (Dried): Dose/3.3
• Ferrous Sulfate (Heptahydrate): Dose/5
• Ferrous Gluconate: Dose/9
• Ferous Fumarate: Dose/3
• Ferric Chloride: Dose/3.5
• Ferrous Chloride: Dose/4

Management

• Remove tablets
  WBI or endoscopic removal.
• Give desferrioxamine
• Consider RRT

Resuscitation:

• C
  • Fluid resuscitation
    • GI losses
    • Distributive shock

Specific therapy:

Maximal licensed dose of desferioxamine is 80mg/kg/day, though severe toxicity will generally require more than this.

• Pharmacological
  • Desferrioxamine
    Chelates free iron ions in plasma, the water soluble complex is renally cleared.
    • Indicated for:
      • Shock
      • HAGMA
      • Altered mental state
      • Serum iron >90μmol/L
    • 15mg/kg/hr up to 40mg/kg/hr for severe toxicity
    • Requires cardiac monitoring due to risk of hypotension
    • Ceased when clinical stabile and serum ion <60μmol/L
• Procedural
• Physical
  • Whole bowel irrigation
    For all confirmed ingestions.
  • Endoscopic removal
    If WBI not feasible or potentially lethal ingestion.

Supportive care:

• A
  • Intubate for airway protection
• D
  • Low-dose sedation usually adequate
• F
  • RRT
    
    • For accompanying acidosis
    • ↑ Clearance of desferrioxamine-iron complexes in presence of AKI
  • Correct electrolytes

Disposition:

• If asymptomatic at 6 hours with a negative XR may be discharged
• Symptomatic patients should be admitted

Preventative:

Marginal and Ineffective Therapies

• Activated charcoal

Anaesthetic Considerations

Complications

• F
  • AKI
• E
  • Hypoglycaemia
    Liver failure.
• G
  • Hepatic failure
    Risk extends out to 5 days.
• H
  • Synthetic coagulopathy

Prognosis

Key Studies

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References

1. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.