Vitamin & Iron

Poisoning
Blaine (Jess) Benson, Pharm.D.
Director, NMPDIC
(505) 272-4261
Jebenson@salud.unm.edu
Prentation Objectives
At the completion of this presentation participants will
be able to:
1. Describe the pathophysiology and clinical manifestations
associated with poisoning from vitamins A, B complex, C
and D.
2. Identify triage values for poisoning from vitamins A and D.
3. Construct a treatment regimen for poisoning from vitamin
A and vitamin D.
4. Describe the pathophysiology and clinical manifestations
associated with iron poisoning.
5. Assess patient risk for iron poisoning based on dose,
laboratory findings, and patient risk factors.
6. Construct a treatment regimen for iron poisoning and
describe the rationale for each treatment element.
Example Case
A 22-month-old boy was brought to a local hospital
Emergency Department with the complaint of bloody
emesis. Two hours earlier his parents had found an
empty bottle of ferrous sulfate 300 mg and estimated
that he ingested approximately 50 tablets. Upon
arrival his vital signs were normal but he was pale and
poorly responsive. Gastric lavage yielded two iron
tablets. An abdominal x-ray demonstrated at least 30
intact tablets in his stomach. He was transferred by
helicopter to a tertiary care facility and arrived
approximately five hours after the ingestion.
Iron Poisoning
3 hours post-ingestion
Example Case (2)
Temperature was 37.2°C, heart rate 164 ,
respiratory rate 34, and blood pressure 90/40.
He was unresponsive and pale. His extremities
were cool and mottled with decreased pulses.
There was bright red blood returning from his
nasogastric tube. A repeat abdominal film
showed …
Iron Poisoning
5 hours post ingestion
Iron Poisoning
Etiology & Significance
 In the 1980’s iron was the most frequent medication
associated with pediatric poisoning fatality
 Poisonings occur commonly with these preparations
because:
 They are brightly colored, taste sweet, and are shaped like
favorite characters
 They are available in large quantities
 They are not considered harmful by many parents
 They are commonly used during and after pregnancy, so
they are found in homes with small children.
Uses of Iron

 Treatment of iron deficiency anemia

 Supplemental intake of iron during pregnancy
 Multivitamin preparations
Iron Salts
Iron Salt Strength Elem. Fe Elem. Fe /
(mg) (%) Tab (mg)
Ferrous 325 20 65
Sulfate
Ferrous 325 12 38
Gluconate
Ferrous 200 33 66
Fumarate
Iron Salts

Salt % Elemental Iron

Ferrous sulfate 20
Ferrous gluconate 12
Ferrous fumarate 33
Ferrous lactate 19
Ferrous chloride 28
Ferrous ferrocholinate 13
Available Forms Of Iron
 Oral
 Tablets (regular and sustained release), capsules, elixirs,
suspensions, syrups, and drops
 Prenatal products tend to contain 60 – 100 mg elemental
iron per tablet.
 Chewable multivitamins with iron tend to contain 15 – 18
mg elemental iron per tablet.
 Parenteral
 Iron dextran (ferric hydroxide complexed to dextran)
Toxicity of Iron
 Toxic dose: 10-20 mg elemental iron
 Fatal dose: 40-1600 mg/kg of elemental iron
Bilirubin
Tissues
Excreted Ferritin
Macrophage Hemosiderin

Degrading Free
Heme
Hgb Iron
Free Enzymes
Iron

Hgb Transferrin-Fe
Plasma
RBC
Blood Loss Fe2+ Absorbed Fe excreted
0.7 mg Fe Daily Small intestine 0.6 mg Daily
in Menses
Pathophysiology of Iron
Poisoning
 Cellular effects of iron
Fe+2 + H2O2 → Fe+3 + •OH + -OH
 Target organ damage
 GI Irritation => Vomiting (80%), Bloody diarrhea
 Damage to mucosal cells => Leukocytosis and fever
 Hemodynamic alterations
 Fluid shift from intravascular compartment to intracellular
space+bleeding => Hemoconcentration
 Results in decreased cardiac output and compensatory
increase in heart rate and systemic vascular resistance and
peripheral cyanosis
Pathophysiology (2)
 Target organ damage (continued)
 Venous pooling and increased blood viscosity =>
Hypotension
 Decreased brain perfusion/direct effect of iron =>
Lethargy
 Direct action of iron/ferritin => Vasodilitation =>
Shock
Iron-Induced Acidosis
 Acidosis caused by generation of H+ from oxidation
of ferrous iron to ferric iron, the formation of ferric
hydroxides:
Fe+2 → Fe+3 + H+
Fe+3 + 3H2O → Fe(OH)3 + 3H+
 In addition there is the interruption of the Krebs
Cycle due to:
 Lipid peroxidation of mitochondrial membranes by free iron
leading to interruption of the Krebs Cycle
 Excess iron acting as an electron sink to pull electrons from
the electron transport system
Pathophysiology (3)
 Later effects
 Free iron is delivered by way of the portal vein to the liver
causing damage and iron deposition in these area. The
result in severe cases is periportal liver damage
(opposed to the centrilobular necrosis seen with APAP).
 Hypoglycemia
 Fatty degeneration of renal cells => renal impairment
 Pulmonary hemorrhage/edema => mediated by ferrous
mediated peroxidation?
Clinical Manifestations
Five Phases of Iron Poisoning
 Phase I - Gastric
 Phase II - Latency
 Phase III - Shock
 Phase IV - Hepatic Injury
 Phase V - GI scarring
Phase I: Gastric
(0-6 hours post)

 Vomiting (80%), lethargy (52%), explosive diarrhea

(48%), asymptomatic (14%), coma/semi-coma
(5%), irritability (3%), seizures (1%), and
hypovolemic shock.

 LAB: increased serum iron (>300ug/dl)*, increased

WBC (>15,000), and increased BG (>150ug/dl),
also, reversible coagulopathy (elevated PT and
elevated PTT)
Phase II: Latency
(6-24 hours post)
 Stabilization and subjective improvement.
Mild to moderate ingestions recover
completely at this stage.
Phase III: Shock & Cyanosis
(12-48 hours post)
 Shock (distributive), vascular collapse,
refractory acidosis, with cyanosis and fever
 Note: serum iron may be normal *
Phase IV: Hepatic necrosis
(48-96 hours post)
 Shock (cardiogenic) and hepatic failure.
Complications of liver failure that can be seen
in this phase include hypoglycemia,
coagulopathy, cerebral edema,
hyperammonemia, sepsis, and pancreatitis.
Phase V: GI Scarring
(2-4 weeks post)
 Pyloric scarring and gastrointestinal
obstruction
Patient Assessment
 Orthostatic blood pressures
 Serum iron level (2 - 4 hours post)
 Symptomatic patients
blood glucose, electrolytes, CBC, ABG's, BUN,
creatinine, liver function tests, coagulation
studies, and abdominal radiograph
Significance of Serum Iron
Concentrations

Serum Iron Incidence of

(µg/100 mL) shock/coma
<500 8%
500-700 25%
>700 50%
Iron Poisoning Treatment
 Supportive care
 IV sodium bicarbonate for acidosis
 Early correction of hemodynamic abnormalities
with blood products and IV fluids
 Monitor fluid balance to avoid pulmonary
congestion and edema
Iron Poisoning Treatment (2)
 Prevent absorption
 Emesis or lavage or whole bowel irrigation.
Repeat X-ray after evacuation procedure.
 Oral complexation with sodium bicarbonate,
deferoxamine, magnesium hydroxide, or Fleets
Phosphosoda are ineffective and potentially
dangerous
 Emergency gastrostomy is occasionally
necessary
Iron Poisoning Treatment (3)
 Enhance elimination
 Exchange transfusion was used in pediatric
patients. This procedure is of questionable
efficacy and is associated with many
complications
Iron Poisoning Treatment (4)
 Provide antidote (Desferoxamine mesylate)
 Available Form
 Desferal mesylate 500 mg powder for injection

 Mechanism
 Specific chelator for iron. Binds free iron to form
ferrioxamine (vin rose colored complex). Theoretically, 100
mg of deferoxamine binds 9.35 mg of Fe+3.
 Indications
 Patients showing signs of serious intoxication (shock,
metabolic acidosis, coma), or
 Patients with serum iron concentrations ≥500 µg/dL
Iron Poisoning Treatment (5)
 Deferoxamine (continued)
 Dose
 ≤15 mg/kg/hr IV, not to exceed 6 grams per day
 Side effects
 Hypotension with rapid injection
 Anaphylactoid reaction with rapid injection
 Hypotension associated with ferrioxamine accumulation in
patients with renal impairment (require dialysis)
 Fever, dysuria, leg cramps, rashes, and puritis.
 Acute respiratory distress syndrome with infusion durations
of greater than 24 hours
 Sepsis from siderophores (Yersinia enterocolitica
Iron Poisoning Treatment (6)
 Deferoxamine (continued)
 Endpoints
 Return of urine color from vin-rose to amber
 Dissipation of symptoms (acidosis, shock)
 Serum iron of ≤350 µg/dL
Vitamin A
 Available forms
 Food: Either preformed vitamin A (liver) or as carotenoids
(carrots).
 Vitamin Preparations: Multiple vitamins typically contain
5000 IU per dose
 Poisoning Manifestations
 Acute: Nausea, vomiting diarrhea, headache, drowsiness
irritability, and blurred vision. This is followed in 24-72
hours by extensive desquamation.
 Chronic: Bone abnormalities (asynchronous growth,
exostoses , metaphyseal flares, epiphyseal premature
closures), hepatotoxicity, intracranial hypertension (blurred
vision, headaches, diplopia), hypercalcemia
Vitamin A
 Toxic Dose
 Acute Toxic Dose: >25,000 IU/kg
 Chronic Toxic Dose: 25,000-50,000 IU/day for as few as 30
days
 Treatment
 Supportive Care
 Increased intracranial pressure
 Daily lumbar puncture, 40 mg IV furosemide, 1 gram/kg of
mannitol, 250 mg acetazolamide QID, a short course of
prednisone
 Hypercalcemia
 Loop diuretics, IV fluids and prednisone (20 mg/day)
 Preventing absorption
 Activated charcoal, lavage, or ipecac syrup
Vitamin B3 (Niacin)
 Available forms
 Multiple vitamins typically contain 20-30 mg per dose
 Poisoning Manifestations
 Nausea, gastritis, and diarrhea. Severe flushing and
pruritus (prostaglandin mediated histamine release).
Chronic high dose associated with hyperuricemia, glucose
intolerance, and hepatotoxicity.
 Toxic Dose
 Acute Toxic Dose: 100 mg
 Chronic Toxic Dose: 750 mg/day for several months
 Treatment
 Pre-treatment with aspirin
Vitamin B6 (Pryridoxine)
 Available forms
 Multiple vitamins typically contain 1-6 mg per dose. Also
available in 50-500 mg tablets and solution for injection
(100 mg/mL).
 Poisoning Manifestations
 Peripheral neuropathy (loss of proprioception and pain,
temperature, and vibratory sensations; loss of tendon
reflexes)
 Toxic Dose
 Acute Toxic Dose: 132 – 183 gram
 Chronic Toxic Dose: 2-5 gram/day for several months
 Treatment: Prevent absorption for massive
ingestions
Vitamin C (Ascorbic Acid)
 Available forms
 Multiple vitamins typically contain 60 – 300 mg per dose.
Tablets, capsules and solutions for injection are also
available.
 Poisoning Manifestations
 Chronic high dose associated with diarrhea and urinary
nepholithiasis. Massive acute dose is associated with
nephropathy and renal failure.
 Toxic Dose
 Acute Toxic Dose: 40-50 grams IV
 Chronic Toxic Dose: 2 grams/day for several months
 Treatment: Hemodialysis if patients develop renal
failure/insufficiency
Vitamin D (Cholecalciferol)
 Available forms
 Manufactured in the skin from cholesterol after exposure to
sunlight.
 Multiple vitamins typically contain 400 IU per dose
 Some rodenticides contain cholecalciferol as the active
ingredient
 Poisoning Manifestations
 Hypercalcemia, hypercalcuria, muscle weakness,
headache, nausea, vomiting, bone pain, proteinuria, renal
compromise, hypertension, and cardiac arrhythmias.
 Toxic Dose
 Chronic Toxic Dose: 5,000-25,000 IU/day for several
weeks
Vitamin D
 Treatment
 Supportive Care
 Hypercalcemia
Loop diuretics, IV fluids and prednisone (20 mg/day)
 Preventing absorption
 Activated charcoal, lavage, or ipecac syrup
 Antidotes
 Calcitonin-salmon: 4-8 MRS units/kg every 6 hours
 or, pamodrinate 60-90 mg, IV over 2-24 hours for corrected
serum calcium of 12-13 mg/dL
Case Discussion
This case illustrates a near-fatal iron poisoning. The
patient was treated with deferoxamine for three days
(until his urine was no longer red-orange). He
developed adult respiratory distress syndrome
(presumably from the deferoxamine) on day four and
was mechanically ventilated for six days. A gastric
outlet obstruction was detected two weeks post
exposure. This was treated surgically. He recovered
completely and left the hospital four weeks after the
exposure.
SOAP Note - Subjective
 A 12kg, 22-month-old boy was brought to a local hospital
Emergency Department with the complaint of bloody emesis.
Two hours earlier his parents had found an empty bottle of
ferrous sulfate 300 mg and estimated that he ingested
approximately 50 tablets. Upon arrival his vital signs were
normal but he was pale and poorly responsive. Gastric
lavage yielded two iron tablets. An abdominal x-ray
demonstrated at least 30 intact tablets in his stomach. He
was flown by helicopter to our hospital approximately five
hours after the ingestion. He continues to appear pale and
poorly responsive. He as cool, mottled extremities with
decreased peripeheral pulses. He has bright red blood
draining from his nasogastric tube.
SOAP Note - Objective
 HR 164, BP 90/40, RR 34, T 37.2C
 Electrolytes: Na 126 , K 3.2 , Cl 91, CO2 11
 Arterial Blood Gases: pH 7.09, PCO2 3.6 27
mm Hg, PO2 180 mm Hg, bicarb 8 mmol/L,
BE -20.6 mmol/L
SOAP Note - Assessment
 Severe iron poisoning. By history the patient
ingested 250 mg/kg elemental iron. The fatal
dose is 60-100 mg/kg elemental iron. The
patient is displaying signs and symptoms
consistent with the first phase of severe iron
poisoning (vomiting, hematemesis, shock,
metabolic acidosis with an anion gap (24),
gastric hemorrhage). The patient is likely
suffering from hypovolemic shock presently.
SOAP Note - Plan
 Supportive care
 IV sodium bicarbonate for acidosis:
HCO3 deficit (mEq) = 0.5 X lean body weight (kg)
X (desired [HCO3] – measured [HCO3]). For this
patient, 0.5 X 12 kg X (20-8) = 72 mEq.
 Correction of hemodynamic abnormalities with
blood products and IV fluids
 Initial Treatment: Two 20 mL/kg boluses of Lactated
Ringer’s within 30 minute, then consider inotrope or
vasopressor.
 Vasopressor: Dopamine 5-15 mcg/kg/min
SOAP Note - Plan (2)
 Prevent further absorption
 Elected not start WBI because patient has active GI
bleeding.
 Provide antidote
 Deferoxamine 15 mg/kg/hour IV through continuous
infusion. (Rationale: Chelate free iron) Endpoints: Return
of urine color from vin-rose to amber, dissipation of
symptoms, (acidosis, shock), and serum iron of ≤350 µg/dL
 Labs:
 Serum iron (clarify risk), CBC, Hct and Hgb (active
bleeding), ABG’s (response to bicarbonate therapy and
monitoring for alkalosis), electrolytes (monitor for
hypokalemia, and hypocalcemia after bicarbonate therapy)
Interpreting Blood Gases
Condition pH PO2 PCO2 HCO3

Normal 7.35- 90-100 35-45 18-24

7.45

Metabolic acidosis ↓ N N ↓

Respiratory acidosis ↓ ↓ ↑ N

Metabolic Alkalosis ↑ N N ↑

Respiratory Alkalosis ↑ ↑ ↓ N
Calculating An Anion Gap

Cationsmeas+Cationsunmeas=Anionsmeas +Anionsunmeas

Cationsmeas- Anionsmeas = Anionsunmeas- Cationsunmeas

(Na) - (Cl + HCO3) = Anion Gap

(142) - (104 + 27) = 11

Normal Anion Gap = 8-12

Example: Metabolic Acidosis
With Anion Gap
Cationsmeas+Cationsunmeas=Anionsmeas +Anionsunmeas

Cationsmeas- ↓Anionsmeas =↑ Anionsunms- Cationsunme

(Na) - (Cl + HCO3) = Anion Gap

(138) - (100 + 17) = 21

Anion Gap = 21
Anion Gap Metabolic Acidosis
M ethanol
U remia
D iabetic ketoacidosis
P araldehyde, phenformin
I soniazid, iron, ibuprofen
L actic acidosis
E thylene glycol
C arbon monoxide, CN, and caffeine
A lcoholic ketoacidosis, albuterol, aspirin
T heophylline, toluene
Blood Pressure Maintenance

Systemic Arterial Pressure =

Cardiac Output X Systemic Vascular Resistance

Heart Rate X Stroke Volume

Preload Myocardial Contractility

Inotropes & Vasopressors