Acute Iron Toxicity - Clinical Toxicology PDF

IV- METAL TOXICITY (ACUTE IRON TOXICITY) At the end of this UNIT, students will be able to: List common sources of exposure to iron. Describe clinical picture of iron toxicity. List proper investigations of iron toxicity. Describe proper treatment for iron and lead toxicity. Keyw...

IV- METAL TOXICITY (ACUTE IRON TOXICITY) At the end of this UNIT, students will be able to: List common sources of exposure to iron. Describe clinical picture of iron toxicity. List proper investigations of iron toxicity. Describe proper treatment for iron and lead toxicity. Keywords & Terminology: Iron sources, Multiple Organs Failure, Blood Iron level, Deferoxamines. ACUTE IRON TOXICITY MANNER OF POISONING: Iron toxicity typically occur in children, 3-5 tablets may induce significant toxicity according to the amount of elemental iron contained in the ingested preparation. TOXIC ACTION: Saturated Transferrin: - Iron toxicity develops when serum iron concentrations exceed the iron binding capacity of transferrin “saturated transferrin” in blood. Circulating Free Iron: - The free circulating iron damages many organs by direct cellular toxicity, effects on vasculature and the release of vasodilating mediators. TOXICOKINETICS: Kinetics in overdose: Absorption: - In therapeutic dose: - Iron is absorbed poorly in therapeutic doses in the duodenum and jejunum. - In toxic dose: - However, with the development of gastrointestinal toxicity the extent and area of absorption is increased. Thus, the peak concentrations after iron poisoning occur later and the bioavailability is higher. Distribution: - Transferrin carrier: - Iron is transported in the blood by transferrin. When the binding sites on transferrin are saturated the unbound iron reacts with blood vessels and platelets. Elimination: - Iron loss: - There is no significant natural route of elimination other than by gastrointestinal cell loss and blood loss. | P a g e 34 CLINICAL PICTURE: Severe iron poisoning may proceed in FOUR phases: 1st GASTROINTESTINAL PHASE (GASTROINTESTINAL EFFECTS): - A severe hemorrhagic gastroenteritis occurs within few hours of ingestion. - Vomiting, colic and diarrhea are the main manifestations. - If fluid loss is significant there may be hypotension, and acidosis. nd 2 WINDOW PHASE: - During this period (about 4-12 hours post overdose), gastrointestinal symptoms improve. rd 3 MULTI-ORGAN FAILURE PHASE: - Subsequently systemic toxicity develops with pronounced effects on the following organs: GIT: Severe hemorrhagic gastroenteritis with occasional GI perforation. CNS: Lethargy, coma or convulsions. CVS: Intractable hypotension and pulmonary edema. Renal: Acute tubular necrosis and renal failure. Hepatic: Severe hepatic necrosis may occur with peak ALT/AST occurring 1-4 days post ingestion, this may be complicated by hypoglycemia. Metabolic: Severe lactic acidosis is common. Coagulopathy: An early and a late type of coagulopathy may occur; - The early type is probably due to a direct effect of iron on the coagulation cascade. - The late type is due to hepatic failure. 4th LATE COMPLICATIONS PHASE: - Patients with severe initial symptoms may develop gastric or pyloric scarring & obstruction INVESTIGATIONS: Blood Iron Level: To determine the need for specific treatment. Blood must be taken for iron concentrations prior to therapy with desferrioxamine. - 10 - 30 μmol /L: Normal Range. - 30 - 60 μmol /L: Unlike Significant Toxicity. - 60 - 90 μmol /L: Possible toxicity… Desferrioxamine is indicated in Symptomatic patients. - > 90 μmol /L: Frank toxicity…Desferrioxamine is indicated Irrespective of Clinical State. Abdominal X-ray: To identify radio-opaque tablets however their absence does not exclude iron overdose. Electrolytes, Arterial blood gases & Blood glucose level & Full blood count. Renal and Liver functions & Coagulation studies. DETERMINATION OF SEVERITY: Clinical Evaluation. Blood Iron Level. Dose of Ingested Elemental Iron: - < 10-20 mg/kg: Non toxic - 20-60 mg/kg: Potentially toxic - 60-120 mg/kg: Toxic but fatal outcome unlikely - 120 mg/kg: Potentially fatal | P a g e 35 TREATMENT: EMERGENCY AND SUPPORTIVE: Severe poisoning requires close monitoring (ABC, CVP line, regular electrolytes, blood gases and blood sugar monitoring) Volume replacement may be required (blood, fresh frozen plasma or crystalloids) Correction of acidosis. DECONTAMINATION: Activated Charcoal: - Not effective. - Iron is not adsorbed to charcoal. Gastric Lavage: - Limited value “Intact tablets may not pass via lavage tube”. Whole bowel irrigation: - The decontamination method of choice. - It is recommended for: - Ingestions >60 mg/kg confirmed on X-ray. - Un-dissolved tablets were detected on abdominal x-ray. - Sustained release or enteric coated iron tablets were reported. ANTIDOTE: DESFERRIOXAMINE: - Mechanism of Action: - It chelates ferric iron and causes redistribution of iron from tissue sites back into plasma. - The iron- desferrioxamine complex is renally eliminated. - Dose & Route: - Desferrioxamine is given intravenously at a rate of 15 mg/kg body weight/hour. - Reduce dose by 50% in severe renal impairment. - The urine will often (but not always) change to a vin rose color. - End Point of Therapy: - Treatment should be continued until serum iron concentrations fall below 60 micromol/ L and the urine (if it changed color) has returned to normal. - This normally takes 6-8 hours of treatment but may be longer in severe poisoning. - Side Effects: - Desferrioxamine infusion for greater than 24 hours may result in non-cardiogenic pulmonary edema. REFERENCES: o Olson, Kent R.; Anderson, Ilene B.; Benowitz, Neal L.; Blanc, Paul D.; Clark, Richard F.; Kearney, Thomas E.; Kim-Katz, Susan Y.; Wu, Alan H. B., Seventh Edition (Poisoning & Drug Overdose). McGraw-Hill Education. | P a g e 36