Poisoning by Iron

Altaf Ansari
Beth Israel Medical Center

Iron Toxicity
5000 cases of Iron OD per year 20,000 cases of multivitamin with Iron per year Pills fruit flavored Animal shaped bottles of up to 250 Vitamins generally not considered toxic

Iron Toxicity

Relative toxicity of Iron depends on the total amount of elemental Iron

Elemental Iron Equivalents

Ferrous sulfate (anhydrous) Ferrous sulfate (hydrated) Ferrous gluconate Ferrous fumarate Ferrous chloride (anhydrous) Ferrous chloride (hydrated) Ferrous carbonate

37% 20% 12% 33% 44% 28% 12%

Dose Related Toxicity

<20mg/kg non toxic 20-60mg/kg moderately toxic >60 mg/kg severely toxic 180-300 mg/kg lethal 30-45 tablets in a 10 kg child is lethal

Question
15 years old girl presents to ED Suicidal gesture. Ingested 60 tablets of Ferrous sulfate 300mg C/O hematemesis and bloody diarrhea once Embarrassed and remorseful now Wishes to be discharged home with parents

Question

Vital signs: BP 96/62, HR 108/min, R 18/min, Temp 98.8 R Pulse Ox 98% RA Pain 2/10 Weight 50 Kg

Question
What to do? Ipecac orally. Arrange out patient psyche follow up. Initiate Deferoxamine therapy. Obtain abdominal radiographs. Gastric lavage with Sodium bicarbonate.

Answer
Ipecac Contra-indicated Out-patient Psych. Needs in patient ICU Deferoxamine. Abdominal radiographs indicated, not helpful if all Iron already absorbed. Gastric lavage with Bicarb. No data to show benefits

Why Deferoxamine?
Ferrous sulfate=20% elemental Iron Each tablet = 300mg Iron Each tab = 300mg X 20% = 60mg Elemental Iron 60 tablets of Ferrous sulfate 300mg each = 3600mg Elemental Iron 3600mg/50 Kg = 72 mg/Kg ingested

Toxicity by Peak Serum Iron Level

50-150 mcg/dl <350 mcg/dl 350-500 mcg/dl >500 mcg/dl lethal

normal none to mild toxicity moderately toxic severely toxic to

Risk of Coma by Peak Serum Iron Level

<500 mcg/dl 500-1000 mcg/dl >1000 mcg/dl

10% 25% 75%

Iron Metabolism
15mg ingested daily 10% of ingested Fe absorbed daily Increased ingestion=Increased absorption

Iron Metabolism
1 mg of Fe lost daily through GI mucosa, bile, skin and urine 2 mg of Fe maximum is lost daily even with Fe overload 16 mg of Fe menstrual loss per month 1.5 mg of Fe per day transferred to fetus

Pathophysiology of Fe Toxicity
Direct caustic effect on GI mucosa Direct myocardial depression Vasodilatation and increased capillary permeability Lactic acidosis, disrupts mitochondrial oxidative phosphorylation Catalyzes lipid peroxidation & free radicals

Stage 1

0-6 hours

Nausea,vomiting, diarrhea upper or lower GI bleeding Abdominal pain, perforation, peritonitis Hypotension, tachycardia, shock Hyperglycemia, leucocytosis, metabolic acidosis

Stage 2

2-48 hours

Apparent recovery GI symptoms subside False sense of security!!! Hyperglycemia, leucocytosis, acidosis persist

Stage 3

6-48 hours

Multiple organ dysfunction syndrome Cardiovascular collapse Cerebral edema Pulmonary edema Renal failure Severe metabolic acidosis, leucocytosis, elevated PT

Stage 4

2-6 days

Acute Hepatic Failure Jaundice Coma Abnormal LFTs, Elevated PT, Hypoglycemia

Stage 5

2-6 weeks

GI scarring Gastric outlet obstruction Intestinal obstruction

Diagnosis

Diagnosis of Fe poisoning should always be on clinical grounds!

Ancillary lab help

leucocytosis hyperglycemia, later hypoglycemia metabolic acidosis abnormal LFTs Elevated Lactate KUB before and after lavage Serum Fe level >350 mcg/dl

ED Diagnosis of Fe poisoning
Be persistent about History Obtain empty bottles and calculate amount of elemental Fe ingested Serum Fe level at presumed 4 hours, and a second level at 6-8 hours (sustained release?) Serum Fe level may be normal in Sage 3 Ancillary tests, and KUB

Treatment of Fe Toxicity
Consult Poison Control Early!!! Airway, breathing, circulation 2 large bore IVs, cardiac & pulse ox monitors,oxygen Initial labs including Type and Crossmatch

Gastric Emptying
Not neccessary if patient vomited and KUB negative Pills may clump together May erode mucosa and get embeded in sub mucosa Fe bezoars may require endoscopy or Gastrotomy

Fe Binding in GI Tract
No activated charcoal (Poor Fe binding) Gastric lavage with Bicarbonate, Phosphosoda or Deferoxamine not recommended

Decrease GI Transit time

No emetics or cathartics Whole Bowel Irrigation with Poly ethylene glycol or PEG-EL or Go-Lytely Given per NGT 1.5-2.0 liters per hour in adults 25 ml/kg/hr in children Continue for 5 hours or until Effluent=Infusate

Chelation Therapy, Deferoxamine

Specific Chelator of Ferric Iron Fe +Deferoxamine=Ferrioxamine Ferrioxamine excreted in urine Ferrioxamine also dialyzable Limits Fe entry into the cell Also chelates Intracellular Fe

Deferoxamine
100 mg of Deferoxamine binds with 8.5 mg of elemental Fe. May be given IM or IV IV is the preferred method of administration

Deferoxamine Challange Test

Give 50 mg/kg IM upto 1 gram Ferrioxamine gives vin rosecolor to urine Compare color of urine pre and post Deferoxamine If test Positive, start chelation If test Negative and no symptoms for 6 hrs, pt.may be discharged

Deferoxamine
Negative Deferoxamine test by itself does not rule out Fe toxicity All the Fe may be intracellular by now Dose: 15 mg/kg/ hour IV until urine returns to normal color or toxicity disappears

Indications for Deferoxamine

All symptomatic patients with more than 1 episode of vomiting or diarrhea All patients with abdominal pain, hypovolemia, acidosis, lethargy KUB with multiple opacities Even asymptomatic patients with SI 300500 mcg/dl Pregnancy is not a contra-indication

Deferoxamine , Adverse Reactions

Anaphlaxis, or anaphylactoid reactions Hypotension if given too fast Optic neuropathy, hearing loss Thrombocytopenia ARDS if given for >24 hrs

Deferoxamine, Adverse Reactions

Acute renal failure Yersenia Enterocolitis (growth factor) Mucormycosis, Pneumocystis (T cell depression) Deferoxamine + Compazine = Coma

Severe Iron Toxicity

Exchange transfusion Charcoal hemoperfusion Hemofiltration Hemodialysis after Deferoxamine Free radical Scavengers:vit C, vitE, Sulphdryl groups Liver transplant