Vitamins & Iron

8/8/2019 Vitamins & Iron

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Vitamin & IronPoisoning

Blaine (Jess) Benson, Pharm.D.

Director, NMPDIC

(505) 272-4261

[email protected]


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Prentation ObjectivesAt the completion of this presentation participants willbe able to:

1. Describe the pathophysiology and clinical manifestations

associated with poisoning from vitamins A, B complex, Cand D.

2. Identify triage values for poisoning from vitamins A and D.

3. Construct a treatment regimen for poisoning from vitaminA and vitamin D.

4. Describe the pathophysiology and clinical manifestationsassociated 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 anddescribe the rationale for each treatment element.


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Example CaseA 22-month-old boy was brought to a local hospitalEmergency Department with the complaint of bloodyemesis. Two hours earlier his parents had found an

empty bottle of ferrous sulfate 300 mg and estimatedthat he ingested approximately 50 tablets. Uponarrival his vital signs were normal but he was pale andpoorly responsive. Gastric lavage yielded two irontablets. An abdominal x-ray demonstrated at least 30

intact tablets in his stomach. He was transferred byhelicopter to a tertiary care facility and arrivedapproximately five hours after the ingestion.


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Iron Poisoning

3 hours post-ingestion


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Example Case (2)Temperature was 37.2C, heart rate 164 ,

respiratory rate 34, and blood pressure 90/40.

He was unresponsive and pale. His extremitieswere cool and mottled with decreased pulses.

There was bright red blood returning from his

nasogastric tube. A repeat abdominal film

showed


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Iron Poisoning

5 hours post ingestion


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Iron Poisoning

Etiology & Significance In the 1980s 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, sothey are found in homes with small children.


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Uses of Iron

Treatment of iron deficiency anemia

Supplemental intake of iron during pregnancy Multivitamin preparations


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Iron Salts

6633200Ferrous

Fumarate

3812325Ferrous

Gluconate

6520325Ferrous

Sulfate

Elem. Fe /

Tab (mg)

Elem. Fe

(%)

Strength

(mg)

Iron Salt


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Iron Salts

Salt % Elemental Iron

Ferrous sulfate 20Ferrous gluconate 12

Ferrous fumarate 33

Ferrous lactate 19

Ferrous chloride 28Ferrous ferrocholinate 13


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Available Forms Of Iron Oral

Tablets (regular and sustained release), capsules, elixirs,

suspensions, syrups, and drops

Prenatal products tend to contain 60 100 mg elementaliron per tablet.

Chewable multivitamins with iron tend to contain 15 18

mg elemental iron per tablet.

Parenteral

Iron dextran (ferric hydroxide complexed to dextran)


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Toxicity of Iron Toxic dose: 10-20 mg elemental iron

Fatal dose: 40-1600 mg/kg of elemental iron


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TissuesFerritin

Free

Iron

Hemosiderin

HemeEnzymes

Transferrin-Fe PlasmaRBCHgb

Macrophage

Degrading

Hgb FreeIron

Fe2+ AbsorbedSmall intestine

Fe excreted0.6 mg Daily

Blood Loss0.7 mg Fe Daily

in Menses

BilirubinExcreted


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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


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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


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Iron-Induced Acidosis Acidosis caused by generation of H+ from oxidation

of ferrous iron to ferric iron, the formation of ferrichydroxides:

Fe+2

Fe+3

+ H+

Fe+3 + 3H2O Fe(OH)3 + 3H+

In addition there is the interruption of the KrebsCycle 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


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Pathophysiology (3) Later effects

Free iron is delivered by way of the portal vein to the livercausing 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?


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Clinical Manifestations

Five Phases of Iron Poisoning Phase I - Gastric

Phase II - Latency

Phase III - Shock

Phase IV - Hepatic Injury

Phase V - GI scarring


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Phase I: Gastric

(0-6 hours post)

Vomiting (80%), lethargy (52%), explosive diarrhea(48%), asymptomatic (14%), coma/semi-coma

(5%), irritability (3%), seizures (1%), andhypovolemic shock.

LAB: increased serum iron (>300ug/dl)*, increasedWBC (>15,000), and increased BG (>150ug/dl),also, reversible coagulopathy (elevated PT andelevated PTT)


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Phase II: Latency

(6-24 hours post) Stabilization and subjective improvement.

Mild to moderate ingestions recover

completely at this stage.


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Phase III: Shock & Cyanosis

(12-48 hours post) Shock (distributive), vascular collapse,

refractory acidosis, with cyanosis and fever

Note: serum iron may be normal *


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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.


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Phase V: GI Scarring

(2-4 weeks post)

Pyloric scarring and gastrointestinal

obstruction


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Patient Assessment

Orthostatic blood pressures

Serum iron level (2 - 4 hours post)

Symptomatic patientsblood glucose, electrolytes, CBC, ABG's, BUN,

creatinine, liver function tests, coagulation

studies, and abdominal radiograph


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Significance of Serum Iron

Concentrations

50%>700

25%500-700

8%


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Iron Poisoning Treatment

Supportive care

IV sodium bicarbonate for acidosis

Early correction of hemodynamic abnormalitieswith blood products and IV fluids

Monitor fluid balance to avoid pulmonary

congestion and edema


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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 FleetsPhosphosoda are ineffective and potentiallydangerous

Emergency gastrostomy is occasionallynecessary


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Enhance elimination

Exchange transfusion was used in pediatric

patients. This procedure is of questionable

efficacy and is associated with many

complications


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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 g/dL


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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 inpatients 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


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Deferoxamine (continued)

Endpoints

Return of urine color from vin-rose to amber

Dissipation of symptoms (acidosis, shock)

Serum iron of350 g/dL


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Vitamin A

Available forms Food: Either preformed vitamin A (liver) or as carotenoids

(carrots).

Vitamin Preparations: Multiple vitamins typically contain5000 IU per dose

Poisoning Manifestations Acute: Nausea, vomiting diarrhea, headache, drowsiness

irritability, and blurred vision. This is followed in 24-72hours by extensive desquamation.

Chronic: Bone abnormalities (asynchronous growth,exostoses , metaphyseal flares, epiphyseal prematureclosures), hepatotoxicity, intracranial hypertension (blurredvision, headaches, diplopia), hypercalcemia


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Vitamin A

Toxic Dose Acute Toxic Dose: >25,000 IU/kg

Chronic Toxic Dose: 25,000-50,000 IU/day for as few as 30days

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


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Vitamin B3

(Niacin)

Available forms Multiple vitamins typically contain 20-30 mg per dose

Poisoning Manifestations

Nausea, gastritis, and diarrhea. Severe flushing andpruritus (prostaglandin mediated histamine release).Chronic high dose associated with hyperuricemia, glucoseintolerance, and hepatotoxicity.

Toxic Dose

Acute Toxic Dose: 100 mg Chronic Toxic Dose: 750 mg/day for several months

Treatment Pre-treatment with aspirin


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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 tendonreflexes)

Toxic Dose Acute Toxic Dose: 132 183 gram

Chronic Toxic Dose: 2-5 gram/day for several months

Treatment: Prevent absorption for massiveingestions


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Vitamin C (Ascorbic Acid)

Available forms Multiple vitamins typically contain 60 300 mg per dose.

Tablets, capsules and solutions for injection are alsoavailable.

Poisoning Manifestations Chronic high dose associated with diarrhea and urinary

nepholithiasis. Massive acute dose is associated withnephropathy 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 renalfailure/insufficiency


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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, renalcompromise, hypertension, and cardiac arrhythmias.

Toxic Dose Chronic Toxic Dose: 5,000-25,000 IU/day for several

weeks


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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 correctedserum calcium of 12-13 mg/dL


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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 recoveredcompletely and left the hospital four weeks after the

exposure.


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SOAP Note - Subjective

A 12kg, 22-month-old boy was brought to a local hospitalEmergency Department with the complaint of bloody emesis.Two hours earlier his parents had found an empty bottle offerrous sulfate 300 mg and estimated that he ingested

approximately 50 tablets. Upon arrival his vital signs werenormal but he was pale and poorly responsive. Gastriclavage yielded two iron tablets. An abdominal x-raydemonstrated at least 30 intact tablets in his stomach. Hewas flown by helicopter to our hospital approximately fivehours after the ingestion. He continues to appear pale and

poorly responsive. He as cool, mottled extremities withdecreased peripeheral pulses. He has bright red blooddraining from his nasogastric tube.


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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 27mm Hg, PO2 180 mm Hg, bicarb 8 mmol/L,

BE -20.6 mmol/L


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SOAP Note - Assessment

Severe iron poisoning. By history the patientingested 250 mg/kg elemental iron. The fataldose is 60-100 mg/kg elemental iron. The

patient is displaying signs and symptomsconsistent with the first phase of severe ironpoisoning (vomiting, hematemesis, shock,metabolic acidosis with an anion gap (24),

gastric hemorrhage). The patient is likelysuffering from hypovolemic shock presently.


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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 thispatient, 0.5 X 12 kg X (20-8) = 72 mEq.

Correction of hemodynamic abnormalities withblood products and IV fluids

Initial Treatment: Two 20 mL/kg boluses of Lactated

Ringers within 30 minute, then consider inotrope orvasopressor.

Vasopressor: Dopamine 5-15 mcg/kg/min


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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: Returnof urine color from vin-rose to amber, dissipation ofsymptoms, (acidosis, shock), and serum iron of350 g/dL

Labs: Serum iron (clarify risk), CBC, Hct and Hgb (active

bleeding), ABGs (response to bicarbonate therapy andmonitoring for alkalosis), electrolytes (monitor forhypokalemia, and hypocalcemia after bicarbonate therapy)


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Interpreting Blood Gases

NRespiratory Alkalosis

NNMetabolic Alkalosis

NRespiratory acidosis

NNMetabolic acidosis

18-2435-4590-1007.35-

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Normal

HCO3PCO2PO2pHCondition


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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


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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


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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


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Blood Pressure Maintenance

Systemic Arterial Pressure =

Cardiac Output X Systemic Vascular Resistance

Heart Rate X Stroke Volume

Preload Myocardial Contractility


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Inotropes & Vasopressors

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Vitamins & Iron