A1259974015YExkG

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New Zealand National Poisons Centre
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IRON OVERDOSE
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IRON

• In healthy adults 2 to 10 of dietary iron
  absorbed
• In iron deficiency states (including children) 80
  to 90 is absorbed
• In overdose, there is proportionally less of an
  ingested dose absorbed compared to a therapeutic
  dose, however, damage to intestinal mucosa can
  increase absorption
• Following absorption iron is bound to
  transferring and actively taken up by the liver
  during first pass. The remaining iron is
  transported by transferrin, primarily to the bone
  marrow.

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TOXIC MECHANISM

• In overdose total iron binding capacity is
  surpassed and free Ferric iron (Fe) is present
  in the blood
• Free protons are liberated leading to acidosis
• Fe3 3H2O ? FE(OH)3 3H
• Fe leads to production of the OH. radical, in
  turn causing lipid peroxidation and
• - Local tissue injury primarily the gut and
  liver
• Mitochondrial damage with loss of cellular
  aerobic respiration
• Free iron is a vasodilator
• Direct depression of coagulation factors

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SIGNS AND SYMPTOMS
Classic stages of iron poisoning Stage
I Gastrointestinal 30m to 6 hrs Stage
II Latent phase 2 to 4 hrs Stage III Shock
/ multiorgan failure / acidosis 2 to 24
hrs Stage IV Hepatotoxicity 12 to 24
hrs Stage V Gastrointestinal obstruction 1 to
7 wks
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STAGE I GASTROINTESTINAL
Initial symptoms are secondary to direct
irritant and corrosive effect of iron. In larger
overdoses, lipid peroxidation causes further
injury. Complaints include Epigastric
pain Nausea / vomiting Diarrhoea In more severe
cases Haematemesis Vasodilation Third
spacing Hypotension Metabolic acidosis may also
develop during this initial stage leading to the
latent phase being by-passed.
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STAGE II LATENT PHASE
A period where there is a deceptive apparent
improvement in the patients gastrointestinal
condition. It is often tempting to discharge such
patients. However, in the seriously poisoned, a
metabolic acidosis is evolving. This may be
compounded by a lack of adequate fluid
resuscitation.
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STAGE III SHOCK, MULITORGAN FAILURE, ACIDOSIS
Loss of adequate tissue perfusion and
multiorgan failure most deaths occur during this
stage. Shock occurs secondary to
gastrointestinal haemorrhage, vomiting,
third-spacing, vasodilation, and reduced cardiac
output (due to myocardial toxicity). Multiorgan
failure related to inadequate perfusion and
direct toxicity ensues and results in Altered
mental status / coma Seizure Acute renal
failure Pulmonary oedema
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STAGE IV HEPATOTOXICITY
Hepatic dysfunction is a poor prognostic sign.
Patients suffer related Hypoglycaemia Coagulopath
y and haemorrhage Jaundice Hepatic encephalopathy
/ coma
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STAGE V GASTROTINESTINAL OBSTRUCTION
In survivors mucosal injury may lead to the
formation of strictures. Though usually occurring
at the pylorus, they may be found throughout the
gastrointestinal tract. Actual obstruction is,
however, rare.
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DIAGNOSIS
History of ingestion Ingestions of 40 to 60
mg/kg should be medically assessed those above
60 mg/kg should be decontaminated. Investigation
Abdominal x-ray Serum iron concentration at 2 to
4 hours post-ingestion
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HISTORY OF INGESTION
Note that the elemental quantity of iron in
tablets needs calculation. 5 x Fergon tablets
(300 mg ferrous gluconate) ingested by a
child 5 x 300 mg / 10 kg 150 mg/kg In fact
only 11 (33 mg) of the tablet is elemental
iron 5 x 33 mg/10 kg 16.5 mg/kg
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DECONTAMINATION

• Activated charcoal will not bind iron, therefore
  it is necessary to administer whole bowel
  irrigation.
• Appropriate decontamination is recommended
• For ingestions greater than 60 mg/kg elemental
  iron
• Follow WBI with AXR to ensure removal of iron

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INTERVENTION CRITERIA
Less than 60 umol/L (335 ug/dL) Discharge into
the care of a responsible guardian if -
Asymptomatic, and - Iron not detected on
abdominal x-ray, and - Formulation ingested was
not sustained release or enteric-coated   Observe
and repeat iron serum concentration at 4 to 6
hours post-ingestion if - Patient symptomatic
(treatment may be indicated by severity), or -
Iron detected on abdominal x-ray, or - Sustained
release or enteric-coated formulation ingested
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INTERVENTION CRITERIA
60 to 90 umol/L (335 to 500 ug/dL) Observe and
repeat serum iron concentration at 4 to 6 hours
post-ingestion if - Asymptomatic, and - Iron not
detected on abdominal x-ray, and - Sustained
release or enteric-coated formulation
ingested   Admit for management if -
Symptomatic - Iron detected on abdominal x-ray
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INTERVENTION CRITERIA
Greater than 90 umol/L (500 ug/dL) Admit
regardless of symptoms for management, including
treatment with desferrioxamine
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CHELATION

• Indicated in all cases with signs of systemic
  intoxication and especially those with an high
  anion gap metabolic acidosis.
• Desferrioxamine
• 15 mg/kg/hr up to 80 mg/kg/d
• Continue until acidosis reversed and symptoms
  have resolved (do not rely on vin rosè coloured
  urine).
• Note
• Hypotension following too rapid infusion
• Renal failure in hypovolaemic patients
• Prolonged (gt24 hour) infusion associated with
  ARDS
• Interference with serum iron measurement

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SUPPORTIVE CARE
Cardiovascular Hypotension is a significant
problem and may be due to haemorrhage, third
spacing, vasodilation and compromised cardiac
output. Initially robust fluid replacement is
required. In severe cases invasive blood pressure
monitoring is warranted to guide management.
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SUPPORTIVE CARE
Acute Renal Failure Acute renal failure
generally occurs secondary to shock.
Haemodialysis should be employed increase removal
of iron-chelate, it will not remove iron
itself. Acute Liver Failure A poor prognostic
sign requires management of hypoglycaemia,
coagulopathy (factor replacement), and early
consultation with a liver unit.
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GIT
PLASMA
LABILE POOL
TISSUES
Fe
Fe
Fe-Trans
Fe
Fe
CNS Lungs Heart Liver Pancreas
Fe
Fe
Fe
Fe
Fe
Fe-Trans
Fe
Fe
Fe
Fe
Fe-Trans
Fe
Fe
Fe
Fe
Fe
Fe
Fe
Fe
Fe
CNS Lungs Heart Liver Pancreas
Fe
Fe-Trans
Fe
Fe
Fe
Fe-Trans
Fe
Fe
Fe-Trans
Fe
Fe
Fe