Iron Poisoning

toxicology

1. Iron Poisoning By: Dr. Elham Khaled Mohammed

2. Physical Appearance: Metallic iron is silvery white in colour In fact it is an essential element and deficiency results in anaemia . Even if there is more than the required intake daily, the excess is excreted.

3. Iron poisoning is related in most instances to overdose of salts. One of the commonest is ferrous sulfate which occurs as bluish green crystals

4. Sources: Dietary Sources: The required daily amount of iron of 10–20 mg for adults is supplied through average diet. The required intake increases to 25–30 mg in pregnancy. The average daily intake for adults is 15 mg. Environmental Sources: Iron is found in 5.1% of the earth’s crust. It is the second most abundant metal, and the fourth most abundant element. It is believed that the earth’s core consists mainly of iron

5. Uses: Industrial uses: Biological uses – Iron is essential to life. It is a constituent of biological pigments such as haemoglobin , cytochromes and ferrichromes

6. Commonly used iron salts in therapeutics along with respective iron content are mentioned in Table 9.8. in Ref. The amount of iron in a particular iron salt (e.g. sulfate, gluconate , fumarate , etc.) is not the same.

7. The usual fatal dose corresponds to about 200 to 250 mg of elemental iron per kg of body weight. This can be calculated from the percentage of elemental iron in a particular preparation, e.g. a single 150 mg tablet of anhydrous ferrous sulfate which contains 37% of elemental iron will contain a total of 55 mg of elemental iron.

8. In practice, this can be as low as 60 mg of elemental iron/kg. Hence just a handful of these tablets (15 to 20 in number), can be lethal

9. Toxicokinetics : Iron poisoning occurs when serum iron level exceeds the total iron-binding capacity (TIBC), resulting in free circulating iron in the bloodstream

10. Free iron causes: Increased capillary permeability resulting in decreased plasma volume. Oxidation of ferrous to ferric iron releasing hydrogen ions. Subsequent hydration of ferric iron results in metabolic acidosis.

11. Inhibits mitochondrial function leading to hepatic damage, hypoglycaemia , and hypoprothrombinaemia . Inhibits thrombin-induced conversion of fibrinogen into fibrin. Has a direct corrosive action on the GI mucosa.

12. Stages of iron poisoning:

13. 1ST Stage: Develops within the first few hours after the ingestion. The direct irritative effects of iron on the gastrointestinal (GI) tract produce abdominal pain, vomiting,diarrhea . And hematemesis is not unusual. Severe gastrointestinal haemorrhagic necrosis with large losses of fluid and blood contribute to shock

14. 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 toxicity.

15. 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.

16. 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 patients. However, in the seriously poisoned, a metabolic acidosis is evolving. This may be compounded by a lack of adequate fluid resuscitation

17. 3rd Stage may appear early or develop hours after the second stage. Loss of adequate tissue perfusion and multi-organ failure: Shock occurs secondary to gastrointestinal haemorrhage , vomiting, vasodilatation, and reduced cardiac output (due to myocardial toxicity). – most deaths occur during this stage.

18. Multi-organ failure related to inadequate perfusion and direct toxicity ensues and results in: – Altered mental status / coma – Seizure – Acute renal failure – Metabolic Acidosis – Pulmonary oedema

19. 4th Stage develops 2 to 5 days after ingestion. It manifests as elevation of aminotransferase and may progress to hepatic failure. Patients may suffer from: – Hypoglycaemia – Coagulopathy and haemorrhage – Jaundice – Hepatic encephalopathy / coma

20. 5th Stage: which occurs 4 to 6 weeks after Ingestion, involves gastric outlet obstruction secondary to the corrosive effects of iron on the pyloric mucosa. However Actual obstruction is,, rare.

21. What do you do?

22. Take history of ingestion and decide: – 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

23. Investigations 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 .

24. Remember ! 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 intracellularly and not in the blood.

25. 1.Stomach wash with normal saline performed gently may be of benefit in massive ingestions. Desferrioxamine must not be used for lavage . 2. Activated charcoal is ineffective. 3. Magnesium hydroxide solution (1%) administered orally may help reduce absorption of iron by precipitating the formation of ferrous hydroxide

26. Magnesium hydroxide and calcium carbonate containing antacids may safely be used in therapeutic doses to help reduce iron absorption. 4. Correction of hypovolaemia , and metabolic acidosis.

27. 6. Chelation therapy: a. This is indicated in any of the following situations: More than one episode of vomiting or diarrhoea . Significant abdominal pain, hypovolaemia , or acidosis. Multiple radiopacities on abdominal radiograph. Serum iron level greater than 350 mcg/100 ml.

28. b. Chelation can be done either with desferrioxamine ( parenteral) or deferiprone (oral). – Dose ( desferrioxamine ): Liver transplantation is the only therapeutic avenue open in the presence of fulminant hepatic failure.

29. Adverse Effects: Sepsis: The use of desferrioxamine in iron-overdosed children has been associated with Yersinia enterocolitica septicaemia and mucormycosis . In such circumstances desferrioxamine may have provided the iron siderophore complex growth factor needed by the bacteria to induce overgrowth.

30. Visual Toxicity: Continuous intravenous administration of desferrioxamine , often in the presence of low iron stores, has produced visual toxicity (decreased visual acuity, night blindness, colour blindness, retinal pigmentary abnormalities). Visual toxicity has also been associated in patients with rheumatoid arthritis and chronic renal failure. The mechanism remains unclear.

31. Ototoxicity : In one study, some patients receiving desferrioxamine had abnormal audiograms, with a few requiring hearing aids. Risk factors include desferrioxamine dose, duration of therapy and the presence of a low serum ferritin .

32. Pulmonary Toxicity: A “pulmonary syndrome” has been associated with high dose IV (10 to 25 mg/kg/hr) desferrioxamine therapy for several days for acute and chronic iron overload patients. Features include severe tachypnoea , hypoxaemia , fever, eosinophilia , preceding urticaria , and pulmonary infiltrates

33. Summary:

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