COW – answer 1.1

COW

*CASE OF THE WEEK*

You are working your first overnight shift at your new job right out of residency. Part of your contract is to cover a smaller satellite facility with limited resources that takes a steep dive at night.

The triage nurse rolls by your station with a young woman in a wheelchair. The nurse is moving with purpose, which makes you a little nervous. The patient is bent over and holding her abdomen. She holds an emesis basin on her lap.  It looks like there is a small amount of blood present.

She seems sleepy but arousable and is unable to give much of meaningful history.

The nurse gets her in bed and points to her gravid uterus. She grimaces and puts the patient on the monitor.

Her husband arrives. He says that she has been depressed and withdrawn recently, not sure why. She texted him an ambiguous farewell message a few hours ago. He hands you an empty bottle of prenatal vitamins.  He says that she just bought this a couple of days ago and is concerned that she took all of them.

ROS: Postive for abdominal pain and hematemesis, decreased mental status

PMHx:

Unknown

PSHx

Unknown

Meds:

? prenatal vitamins

SHx

Unknown

FHx

Unknown

Physical Examination:

P 110  BP 95/60  RR 12  T 36.5

Fetal heart tones are 135 bpm via bedside ultrasound

General: Young woman, lying in bed, fetal position, sleepy but arousable

HEENT: PERRL, EOMI, MMM

Neck: supple, no LAD

Heart: Tachycardic, clear S1 and S2. No murmurs. No extra heart sounds

Lungs: clear

Abdomen: Gravid uterus, about 30 cm from pubic bone

Extremities: Thready pulses. No c/c/e

Neuro: Sleepy. Follows commands. MAE x 4. Normal reflexes at knees and ankles. No rigidity.

LABORATORIES:

Na 138

K 3.4

Cl 108

HCO3 16

Glucose 168

WBC 16K

Hgb 9.8

Hct 29

Plt 233K

VBG 7.28/25/152

QUESTION #1: You are concerned about overdose. What component of the prenatal vitamin is most concerning?

A. Vitamin A
B. Folinic acid
C. Calcium
D. Iron
E. ascorbic acid

ANSWER: D. Because hypervitaminosis A can cause both toxicity in the mother and the fetus, prenatal vitamins are specifically formulated with reduced amounts of vitamin A.  Iron toxicity is the most concerning component of prenatal vitamins in overdose.

QUESTION #2: Which is not an indication for deferroxamine?

A. 2 hour iron level >300
B. 4 hour iron level >500
C. Metabolic acidosis
D. Lethargy/AMS

ANSWER: A. Deferroxamine should be considered in patient looks ill, has repetitive vomiting, lethargy, hypotension, metabolic acidosis, and an iron level >500 ug/dL. 4-6 Hour levels are preferred, however, iron poisoning is a clinical diagnosis. Clinicians should not rely on a single measurement and a normal iron level does NOT rule out toxicity.

QUESTION #3: What are potential adverse reactions of deferroxamine?

A. Discolored urine
B. Hypotension
C. ALI/ARDS
D. Ototoxicity
E. A and B
F. B and C
G. All of the above

ANSWER: F.  Deferoxamine chelates free iron throughout the body and minimizing disruption of oxidative phosphorylation and improves metabolic acidosis. Interestingly, deferoxamine does not chelate a large amount of iron; however, the small amount of free iron it does chelate leads to significant clinical improvement. Chelation of iron creates ferrioxamine and is eliminated by the kidneys. Ferrioxamine SHOULD cause a reddish color of the urine (so-called vin-rose urine). Deferoxamine should be started, titrated up, and continued while the patient remains ill.  Hypotension is rate-related. Cases of ALI and ARDS are usually described in those with prolonged therapy (>36-72 h of therapy).

History:

  • In the 1990s iron was the leading cause of poisoning deaths, at least reported to the Poison Center, among children < 6.
  • Ironically, this paralleled an effort to be more vigilant in prescribing prenatal iron
  • FDA required warning labels, blister packaging and limits on the # of pills dispensed
  • The requirement of industry to use blister packs have been subsequently overturned.

Pharmacology

  • Because iron is a transition metal, it can accept and donate electrons relatively easily and this feature is utilized in many biochemical process, most notably in the electron transport chain, myoglobin and hemoglobin.
  • The body cannot actively excrete iron, therefore, total body iron is regulated by absorption.
  • In iron-deficient states, iron uptake by the duodenum can increase to 95%.
  • In therapeutic dosing, certain functions are saturated and further uptake is limited, however, in overdose, oxidation and disruption of the GI mucosa allows iron to be absorbed by its concentration gradient.
  • Toxicity depends on the amount of ELEMENTAL IRON anticipated to be absorbed.
  • Calculating the amount of elemental iron in a given supplement depends on the molecular weight of the compound. See the table below for the percent elemental iron per formulation (Adapted from Goldfrank’s Chapter 40, table 40-1).
Formulation % elemental iron
Ferrous chloride 28
Ferrous fumarate 33
Ferrous gluconate 12
Ferrous lactate 19
Ferrous sulfate 20
  • Chewable vitamins tend to have lower concentration of elemental iron (10-18 mg) per tablet when compared to prenatal vitamins (65 mg) and, accordingly, fatalities have not been reported.

Pathophysiology:

  • Iron generates oxidative stress via the Fenton reaction and the Haber-Weiss cycle.

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  • These reactive oxygen species oxidize membrane lipids and damage GI epithelium.
  • Once absorbed, iron binds to circulating proteins, mainly transferrin
  • Once saturated, “free” iron is free to distribute to the various organs.

Free iron leads to metabolic acidosis by two main mechanisms:

  1. Disruption of ox-phos (buffer lost, usual H+ not incorportated into ATP)
  2. Ferric iron + 3H2O à Fe(OH)3 + 3 H+

Clinical Manifestations:

  • AS A MEMORY TOOL ONLY, you can think about the clinical manifestations in 5 stages:

Stage 1: GI distress from local tissue damage in the gut. Gi bleeding, bowel necrosis and hemodynamic instability.  Without vomiting in the first 6 hours, UNLIKELY TO GET SICK

Stage 2: “latent stage”.  GI symptoms have resolved  but develop AMS, metabolic acidosis,  and tachycardia.  THEY WILL APPEAR ILL.

Stage 3: “Shock stage” Coagulopathy, seizures, coma.

Stage 4: Hepatic failure

Stage 5: Chronic issues: GI scarring and stricture

Testing:

  • NOT ALL FORMULATION ARE RADIOPAQUE
  • Liquid and chewable formulations often will not show up on plain radiography
  • Follow electrolytes, ABG or VBG, lactate, coags, WBC (may suggest toxicity), APAP/Salicylate, EKG

DIAGNOSIS:

  • Diagnosis remains clinical
  • Peak iron levels are thought to occur between 2-6 hours post ingestion
  • Serum [Fe] 300-500 à GI and moderate systemic toxicity
  • Serum [Fe] 500-1000 à severe systemic toxicity and shock
  • Serum [Fe] >1000 à high likelihood of death
  • MUST FOLLOW SEQUENTIAL LEVELS, NOT A RULE OUT TEST
  • TIBC (total iron binding capacity) and ferritin are not useful, may lead to confusion, and not recommended

MANAGEMENT:

  • ABCs
  • IV fluids
  • Whole bowel irrigation
  • For patients with retained iron despite WBI may require EGD and/or surgical removal
  • Antidotal therapy

DEFEROXAMINE

  • Deferoxamine + Fe3+ à ferioxamine à Excreted by kidneys
  • Consider treatment if patient looks ill, has repetitive vomiting, lethargy, hypotension, metabolic acidosis, iron level >500 ug/dL
  • Intravenous administration should be increased to 15mg/kg/h.
  • Continue therapy until patient is clinically well.
  • Could consider dialyzing at the same time (animal studies exist)
  • ADVERSE EFFECTS:
  • Hypotension is rate-limiting factor
  • ALI and ARDS
  • PREGNANCY IS NOT A CONTRAINDICATION

Dispo:

  • AAPC guidelines are as follows
  • >40 mg/kg adult formulation or severe or persistent symptoms (alterations in level of consciousness, hematemesis, and bloody diarrhea, persistent vomiting), refer to ED (use pre-pregnancy weight for pregnant women)
  • All children’s chewable vitamins manage at home unless persist vomiting/diarrhea warrant IV fluids
  • All patients with carbonyl iron or polysaccharide-iron complex remain at home
  • Observe for six hours; if asymptomatic à home
  • Otherwise, admit

For pregnant patients: TREAT MOTHER as above.

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