IRON POISONING Poisoning presentation.pptx

Iron Poisoning

1. IRON POISONING:

2. Introduction: Iron supplements are widely available, particularly in homes with small children and young women. Women of child bearing age are seen to be more susceptible to intentional overdose due to impact of maternal stress. Attractiveness of bright red coloured sugar coated tablets and improper storage of iron makes children susceptible to accidental ingestion.

3. Pharmacology: Excess iron in overdose may saturate the body’s mechanisms for iron homeostasis, allowing for unbound iron to cause organ toxicity. Due to its reactivity with oxygen, iron is always bound to a carrier molecule under normal circumstances. These include Transferrin ( Serum protein), Ferritin (Intracellular Storage), Iron containing proteins (Haemoglobin, Myoglobin, Cytochromes). Body cannot directly excrete iron, regulation depends on GI uptake and limitation of absorption by sloughing of mucosal cells containing surplus iron . Oral bioavailability depends on formulation ingested along with body iron stores (increased with iron deficiency) and ingestion with food or fasting (increased In fasting state).

4. CONT: Ferrous iron is transported into enterocytes of GI tract , oxidized to ferric iron , which binds with transferrin and transported from the enterocytes into the circulation throughout the body. Iron is stored in the body in the form of ferritin (in adults , about 0.5-1 gram), and hemosiderin, primarily in the bone marrow , spleen ,liver.

5. Pathophysiology: Iron, a transitional metal, is a potent catalyst for production of free radicals. Through this, it causes gastric irritation, causing vomiting, diarrhoea, abdominal pain, mucosal ulceration, bleeding soon after significant ingestion. Free iron disrupts critical cellular processes and induces acidosis and widespread organ toxicity. In acute poisoning, with the appearance of free iron, a multifactorial metabolic acidosis with elevated lactate appears due to inhibition of oxidative phosphorylation by disruption of mitochondrial electron transport chain, production of toxic hydroxyl free radicals, induction of membrane lipid peroxidation. Hypotension might occur.

6. CONT: Hepatotoxicity occurs as portal blood supply delivers a large amount of iron to the liver. Coagulopathy might occur through inhibition of thrombin formation and the effect of thrombin on fibrinogen. Myocardial and vascular dysfunction result from vasodilation , negative inotropic effect, direct myocardial iron deposition. Moderate Toxicity: 20 to 60 miligrams /Kg,(of elemental iron) Severe Toxicity:>60 miligrams /Kg.(of elemental iron). Exceptions: Chelated iron and carbonyl iron… Toxicity is less as Chelator ligand and carbonyl compound limits the redox reaction.

7. Clinical Features: Five stages are traditionally described but can be considered to manifest as 2 stages: Local GI toxicity and Systemic Toxicity. Stage 1: Abdominal pain, vomiting, diarrhoea. –Vomiting most consistent sign… absence of GI symptoms within 6 hrs of ingestion essentially excludes a significant iron ingestion. Stage 2: A/K/A Latent Stage. 6 to 24 hrs when there is resolution of symptoms… Falsely can be thought of as remission… can be differentiated by systemic deterioration,,, worsening metabolic acidosis, altered lab reports. Stage 3: Systemic toxicity…shock and lactic acidosis… iron induced coagulopathy may worsen bleeding and hypovolemia… Renal failure, Cardiomyopathy, failure of other critical organs may occur.

8. CONT: Stage 4: Hepatic stage, develops 4-5 days following ingestion… results from iron uptake by reticuloendothelial system with local lipid peroxidation… Manifests as elevation of aminotransferase levels and may progress to acute fulminant hepatic failure. Stage 5: Delayed sequelae… gastric outlet obstruction…these are rare and occurs after 4-6 weeks.

9. Lab Diagnosis: Largely clinical diagnosis. General condition can be found out with routine examinations. ABG very important in case of moderate to severe toxicity with respiratory compromise. In general, Serum iron levels measures within 4-6 hrs after an acute ingestion correlate with severity of toxicity. Imaging: Standard ferrous sulfate tablets and reduced iron are radiopaque and frequently visible on routine radiographs.. May help guide GI decontamination.

10. Treatment: Patients with clinical toxicity should be first stabilized with attention to airway, breathing, circulation; after which GI decontamination and deferoxamine therapy can proceed. Aggressive fluid resuscitation might be needed. Coagulopathy should be treated with Parenteral Vitamin K and /or Fresh frozen plasma. Do not give Ipecac syrup, activated charcoal, cathartics, oral sodium bicarbonate. Whole bowel irrigation with polyethylene glycol solution maybe effective in case of large ingestion. 250-500 ml/hr in children, 2 Lit/hr in adults by nasogastric tube may clear GI Tract.

11. CONT: Endoscopy can remove large iron loads or iron containing gastric bezoar. DEFEROXAMINE: Chelating agent derived from Streptomyces Pilosus . It binds free iron, iron from plasma, iron from inside cells, mitochondria but not iron bound to organic molecules. 100 miligrams of deferoxamine bind to 9 miligrams of elemental iron. Upon Binding , it forms the complex ferrioxamine , which is renally excreted. INDICATION: Iron poisoned patients with systemic toxicity, persistent emesis, metabolic acidosis, progressive toxicity, serum iron levels predictive of moderate to severe toxicity. DOSE: 1gm initially given IV( in children: 50 mg/kg). ---Start infusion at 5 mg/kg/hr to avoid rate related hypotension… can be titrated to 15 mg/kg/hr as tolerated.

12. CONT: Recommended doses are 360 mg/kg or 6 grams in adults during the first 24 hrs, typically ordered as 500 mg infusions over 4-8 hrs. Amounts larger than this or administered longer than this a/w complications including renal failure and pulmonary toxicity. As ferrioxamine is excreted , the urine colour changes to “VIN ROSE” , typically brown or rusty hue. Disappearance of this colour indicates no more free iron is available to be complexed. False negative results , colour change latency, difficulty in visualizing colour may limit the utility of this test. Clinical recovery of the patient is the most important factor in guiding deferoxamine therapy. Oral Chelators: Deferasirox and Deferiprone… Effective when taken simultaneously or within 1 hr of iron ingestion.