In healthy adults ~ 2 to 10% of dietary iron absorbed
• In iron deficiency states (including children) 80 to 90% is
• 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.
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
Stages of iron poisoning
Gastrointestinal 30m to 6 hrs
Latent phase 2 to 4 hrs
Shock / multiorgan failure / acidosis 2 to 24 hrs
Hepatotoxicity 12 to 24 hrs
Gastrointestinal obstruction 1 to 7 wks
– Develops within the first few hours after the
ingestion. The direct irritative effects of iron on
the gastrointestinal (GI) tract produce abdominal
pain, vomiting, and diarrhea. Hematemesis is not
– Vomiting is the clinical sign most consistently
associated with acute iron toxicity. The absence
of these symptoms within 6 hours of ingestion
essentially excludes a diagnosis of significant iron
2nd Stage (Latent Stage)
– which may continue for up to 24 hours after
ingestion, the patient’s GI symptoms may resolve,
thereby producing a false sense of security despite
toxic amounts of iron being absorbed into the body.
– Patients may not be symptomatic but still appear ill
and may have abnormal vital signs and evidence of
poor tissue perfusion because of ongoing volume
loss and worsening metabolic acidosis.
Watch Out Latent Phase !!!
A period where there is a deceptive apparent
improvement in the patient’s gastrointestinal
condition. It is often tempting to discharge such
However, in the seriously poisoned, a metabolic
acidosis is evolving. This may be compounded
by a lack of adequate fluid resuscitation.
may appear early or develop hours after the second stage.
Loss of adequate tissue perfusion and multi-organ failure:
– most deaths occur during this stage.
Shock occurs secondary to gastrointestinal haemorrhage, vomiting, third-
spacing, vasodilatation, and reduced cardiac output (due to myocardial
Multi-organ failure related to inadequate perfusion and direct toxicity ensues
and results in:
– Altered mental status / coma
– Acute renal failure
– Metabolic Acidosis
– Pulmonary oedema
develops 2 to 5 days after ingestion. It
manifests as elevation of aminotransferase and
may progress to hepatic failure.
Patients may suffer from:
– Coagulopathy and haemorrhage
– Hepatic encephalopathy / coma
– which occurs 4 to 6 weeks after Ingestion, involves
gastric outlet obstruction secondary to the corrosive
effects of iron on the pyloric mucosa.
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.
Diagnosis & Differentials
The diagnosis of iron poisoning is based on the clinical
picture and the history provided by the patient,
significant others, or out-of-hospital care providers.
Toxic effects have been reported after oral doses as
low as 10 to 20 mg/kg elemental iron.
Moderate toxicity occurs at doses of 20 to 60 mg/kg
elemental iron, and severe toxicity can be expected
after doses larger than 60 mg/kg elemental iron.
What do you do?
Take history of ingestion and decide:
– Ingestions of 40 to 60 mg/kg should be medically
assessed; those above 60 mg/kg should be
– Abdominal x-ray
– Serum iron concentration at 2 to 4 hours post-ingestion
Laboratory work should be sent for
– Serum electrolytes, blood urea nitrogen
– Serum glucose, coagulation studies
– Complete blood count
– Hepatic enzymes & serum iron level.
It is crucial to note that the determination of a single
serum iron level does not reflect
– what iron levels have been previously
– what directions they are going
– the degree of iron toxicity in the tissues.
A single low serum level does not exclude the
diagnosis of iron toxicity because there are
variable times to peak level after ingestion of
different iron preparations.
Serum iron levels have limited use in directing
management because excess iron is toxic intra-
cellularly and not in the blood.
In general, serum levels between 300 and 500
µg/dL correlate with mild systemic toxicity and
iron levels between 500 and 1,000 µg/dL are
associated with significant morbidity. The total
iron-binding capacity (TIBC) is currently thought
to have little value in the assessment of iron-
poisoned patients because it becomes falsely
elevated in the presence of elevated serum iron
levels or desferoxamine.
A plain radiograph of the kidneys, ureters, and
bladder may show iron in the GI tract; however,
many iron preparations are not routinely
detected, so negative radiographs do not
exclude iron ingestion.
Patients who have remained asymptomatic for 6 hours
after ingestion of iron and who have a normal physical
examination do not require medical treatment for iron
Patients whose symptoms resolve after a short period
and who have normal vital signs usually have mild
toxicity and require only supportive care.
– This subset of patients still requires an observation period.
Less than 60 umol/L (335 ug/dL)
– - Asymptomatic, and
– - Iron not detected on abdominal x-ray, and
– - Formulation ingested was not sustained release or enteric-
Observe and repeat iron serum concentration at 4 to 6 hours
– - Patient symptomatic (treatment may be indicated by
– - Iron detected on abdominal x-ray, or
– - Sustained release or enteric-coated formulation ingested
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
Admit for management if:
– Iron detected on abdominal x-ray
Greater than 90 umol/L (500 ug/dL)
Admit regardless of symptoms for management,
including treatment with desferrioxamine
– Patients should receive supplemental oxygen, be
placed on a cardiac monitor, and have 2 large-bore
intravenous (IV) lines established.
– Patients should receive vigorous IV crystalloid
infusion to help correct hypovolemia and tissue
– Patients who present within 2 hours of ingestion
should undergo gastric lavage.
– Activated charcoal does not bind iron, and its use is not
– Whole bowel irrigation with polyethylene glycol
solution has been demonstrated to be efficacious.
Administration of 250 to 500 mL/h in children and 2L/h
in adults via nasogastric tube may clear the GI tract of
iron pills before absorption occurs.
– Antiemetics such as promethazine (25 mg intramuscularly
[IM] in adults; 0.25-0.5mg/kg IM in pediatric patients) or
ondansetron (4 mg IV in adults; 0.1mg/kg to a maximum
dose of 4 mg in adults;0.1 mg/kg to a maximum dose of 4
4mg in pediatric patients) should be administered.
– Coagulopathy should be corrected with vitamin K1 (5-25
mg. subcutaneously (SQ) and fresh-frozen plasma 10-25
mL/kg in adults; 10 ml/kg in pediatric patients). Blood
should be typed and screened or cross matched, as
– Deferoxamine is a chelating agent that can remove
iron from tissues and free iron from plasma.
Deferoxamine combines with iron to form water
soluble ferrioxamine, which is excreted in the urine.
Deferoxamine is safe to administer to children and
– Patients with mild iron toxicity may be treated with
deferoxamine 90 mg/kg IM, up to 1 g in children and
2 g in adults. The dose may be repeated every 4 to 6
hours, as clinically indicated.
Indicated in all cases with signs of systemic intoxication and
especially those with an high anion gap metabolic acidosis.
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).
• Hypotension following too rapid infusion
• Renal failure in hypovolaemic patients
• Prolonged (>24 hour) infusion associated with ARDS
• Interference with serum iron measurement
– Hypotension is a significant problem and may be
due to haemorrhage, third spacing, vasodilatation
and compromised cardiac output.
– Initially robust fluid replacement is required.
– In severe cases invasive blood pressure monitoring
is warranted to guide therapy.
Acute Renal Failure
– Acute renal failure generally occurs secondary to
– Haemodialysis should be employed increase
removal of iron-chelate, it will not remove iron
Acute Liver Failure
– A poor prognostic sign:
– requires management of
coagulopathy (factor replacement)
early consultation with a liver unit.