A two year old boy is suspected of ingesting iron tablets.

a) List three clinical signs of iron poisoning.

b) List two investigations which would support the diagnosis of iron poisoning.

c) Which blood gas (a or b or c) would be most consistent with iron poisoning?  Justify your choice of answer.

 

a

b

c


pH

7.1

7.55

7.45

pCO2

34 mmHg (4.5 kPa)

30 mmHg (4.5 kPa)

34 mmHg (4.5 kPa)

pO2

75 mmHg (10 kPa)

90 mmHg (12 kPa)

70 mmHg (9.3 kPa)

BE

-18 mmol/L

+4 (mmol/L)

-0.1 mmo/L

d) List three treatments specific for iron poisoning and their mechanisms  of action.

e)  List one serious long term complication of iron poisoning.

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College Answer

a)          List three clinical signs of iron poisoning.

Clinical sign

Cause

Nausea / vomiting/ haematemesis

Acute gastritis, ischaemia

Diarrhoea

Abdominal pain

Melaena

Tachypnoea

Metabolic acidosis

Coma/ seizures

Shock/ hypotension

Myocardial depression

Oliguria

Capillary leak

Jaundice / coagulopathy

Hepatic necrosis

b)         List two investigations which would support the diagnosis of iron poisoning.

Iron Level > 300 microgm/dL, or 63 micromol/L

Abdominal XR:

Shows iron tablets

Blood gas

Metabolic acidosis

Hyperglycaemia

Coagulopathy

Interference with coagulation cascade/
hepatic failure

Deranged liver enzymes

From hepatic necrosis

Raised white cell count

c)         Which blood gas (a or b or c) would be most consistent with iron poisoning?  Justify your choice of answer.

 

a

b

c


pH

7.1

7.55

7.45

pCO2

34 mmHg (4.5 kPa)

30 mmHg (4.5 kPa)

34 mmHg (4.5 kPa)

pO2

75 mmHg (10 kPa)

90 mmHg (12 kPa)

70 mmHg (9.3 kPa)

BE

-18 mmol/L

+4 (mmol/L)

-0.1 mmo/L

Answer: Metabolic acidosis due to uncoupling of oxidative phosphorylation.

d)         List three treatments specific for iron poisoning and their mechanisms  of action.

Desferrioxamine

(Binds intravenous iron to form water soluble
ferrioxamine that is renally excreted)

Whole bowel irrigation

(Polyethylene glycol: works with minimal
complications, aim for clear rectal effluent and absence of tablets on AXR)

Exchange transfusion with plasmapheresis.

Surgical/ endoscopic removal of tablets

(If seen on AXR).

Treat coagulopathy

Treat hyperglycaemia

Aggressive volume resuscitation (as
capillary leak a feature)

Dialysis

But limited efficacy

Gastric Lavage with HCO3

(Controversial)

Note: Charcoal is ineffective.

e) List one serious long term complication of iron poisoning.

1. Bowel obstruction (esp gastric outlet)
2. GI strictures

Discussion

As this question closely resembles Question 8 from the second paper of 2013, I will not elaborate excessively.

a)

Feature Causes
   
Tachypnoea
  • Metabolic acidosis
Shock, circulatory collapse
  • Third space fluid losses
  • Blood and fluid loss from the ulcerated gut
  • Cardiotoxic effects, with cardiogenic shock
  • Vasodilation due to SIRS
Hypoglycaemia
  • Acute hepatotoxicity
Coma
  • Hypoglycaemia
  • Acute cerebral oedema due to liver failure
High anion gap metabolic acidosis
  • Lactic acidosis
  • Ketosis
  • Minor contribution from iron itself (conversion of  Fe3+ to Fe2+ produces a net loss of a cation, and therefore contributes to the decrease in the SID)
Hyperlactatemia
  • Acute hepatotoxicity and liver failure
  • Shock state
  • Direct mitochondrial toxicity
Renal failure
  • Shock state
  • mitochondrial (tubular) toxicity, ATN
Gastric ulceration
  • direct corrosive effect of the drug
Haemorrhage, melaena
  • from ulcerated gut surface

b)

  • Iron levels
  • ABG (demonstrating a mixed metabolic acidosis)

c)

  • Gas (a) most closely resembles lactic acidosis, as the base deficit and acidosis are significant.

d)

Decontamination

  • Activated charcoal has no role to play
  • Whole bowel irrigation - until effluent turns clear - is a good strategy; much of the toxicity is related to gut ulceration, and by diluting the iron in the gut lumen you may be able to ameliorate this direct corrosive effect, even if you don't manage to prevent toxic absorption.
  • Surgical removal of tablets - if a bezoar is clearly visible on the AXR

Enhanced elimination

  • Exhange transfusion: the removal of iron-poisoned blood is ery old-school, but it works (Movassaghi et al, 1969)
  • Haemodialysis can be considered to help remove the iron-desferrioxamine complexes, as they are renally excreted and there may not be enough renal function to remove this product. Otherwise, apart from correcting acidosis there is no role for dialysis.

Specific antidote

Supportive care

  • Intubation will likely be required to protect the airway not only from the decreased level of consciousness but also from the risks of aspiration associated with whole bowel lavage.
  • Mechanical ventilation will likely be with mandatory mode, to decrease the demands on the failing myocardium
  • Circulatory support should consist of simultaneous fluid resuscitation, inotrope and vasopressor infusions
  • Sedation should be rationalised, given that the patient is already in a coma before the sedation is given, and that the liver is doing little metabolically.
  • Correction of acidosis with bicarbonate may be indicated if catecholamine responsiveness is lost.
  • Electrolyte replacement -losses must be anticipated, the leaky gut and bowel lavage will result in potassium and phosphate depletion.
  • Haemodialysis may be required to maintain metabolic normality, as well as to remove ammonia which may accumulate due to the acute hepatocellular necrosis
  • Hypoglycaemia and ketosis will likely develop. The patient will need a dextrose infusion, as hepatic and skeletal muscle glycogen stores will be depleted.
  • Nutrition will likely be parenteral for some time, depending on the extent of gastric ulceration.
  • Coagulopathy will develop due to hepatocellular necrosis. Coagulation factor replacement will be required.

e)

Toxicity manifests in four stages, where the late Stage IV represents gastrointestinal scarring (4-6 weeks since ingestion) - gastric scarring and pyloric stricture are the specific features.

 

References

The Royal Childrens Hospital has a good set of guidelines for irone overdose.

Abhilash, Kundavaram PP, J. Jonathan Arul, and Divya Bala. "Fatal overdose of iron tablets in adults." Indian journal of critical care medicine: peer-reviewed, official publication of Indian Society of Critical Care Medicine 17.5 (2013): 311.

REISSMANN, KURT R., and THOMAS J. COLEMAN. "Acute Intestinal Iron Intoxication II. Metabolic, Respiratory and Circulatory Effects of Absorbed Iron Salts." Blood 10.1 (1955): 46-51.

REISSMANN, KURT R., et al. "Acute Intestinal Iron Intoxication I. Iron Absorption, Serum Iron and Autopsy Findings." Blood 10.1 (1955): 35-45.