No…No…No… Not in Your Mouth!!!

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NoNoNoNot in Your Mouth!!!

• A Toxicology Case Study

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Patient History

• 14-month-old girl
• At dinner time, her lips started to turn blue
  (cyanotic)
• Her parents took her to the hospital ER
• Physical exam revealed normal vital signs and
  alert patient
• Blood and urine specimens were collected for
  laboratory tests.

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Laboratory Results

• Capillary blood gas results

Note Although MetHgb is not normally reported
as part of the routine blood gas analysis
results, the instrument still measures
this parameter.
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What is Methemoglobin?

• Hemoglobin that has been oxidized from the
  ferrous state (Fe3) to the ferric state (Fe2)
• Decreases the ability of normal hemoglobin to
  release oxygen (O2)
• Thus, reduces the overall O2 delivery to tissues

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Causes of Methemoglobinemia

• Enzyme deficiencies
• NADH or NADPH methemoglobin reductase enzyme
  deficiency
• G6PD enzyme deficiency
• Mothball ingestion (with naphthalene)
• Nitrate ingestion (including well water)
• Adverse reactions to certain medications
• Phenacetin
• Benzocaine (found in teething gels)
• Dapsone

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Source of Patients Methemoglobinemia

• Mothball ingestion and well water exposure ruled
  out from parent report
• Parents initially hypothesized it might be from
  carpet cleaner
• The physician ordered a toxicology screen on her
  urine specimen to identify the substance causing
  the elevated methemoglobinemia.
• The screen revealed an unidentified substance so
  confirmatory testing was performed.

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Toxicology Screen
This test utilizes thin-layer chromatography to
identify over 700 substances in biological
fluids.
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Toxicology Screen
The resulting chromatogram is compared to
pictures in a library collection of over 700
known substances. The Medical Technologist
examines the color of each spot to make a
presumptive drug match. This technique takes
skill and practice.
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Confirmatory Testing

• Medical Technologist/Clinical Laboratory
  Scientist performing the confirmatory testing on
  a combined gas chromatography (GC) and mass
  spectrophotometry (MS) instrument.

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GC/MS results for patient
Suspect drug peak in patient sample
Gas Chromatogram
Normal cholesterol peak
Internal Standard run as a QC check
Mass spectrum that corresponds to suspected drug
peak above
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Comparison of patients mass spectrum to
database library for various chemicals

Patient mass spectrum
Database library mass spectrum for the drug
Dapsone that indicates a high quality match to
patient spectrum
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Explanation of GC/MS Findings

• The GC/MS analysis found a medication called
  Dapsone.
• The GC separates a mixture of components into
  individual pure compounds.
• The MS separates each pure substance into
  chemical fragments that are characteristic of
  its molecular structure.
• Thus, the various peaks on the MS spectrum
  determine the correct chemical identification.

Numbers and lines represent the various molecular
fragments of Dapsone detected by the mass
spectrophotometer.
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Pharmacology of Dapsone

• Dapsone is an oral antimicrobial used to treat
  leprosy and various skin disorders.
• Peak plasma levels in 4-8 hours after ingestion
• Normal dosage
• Adults 50-100 mg/day
• Children 1-2 mg/kg/day

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Dapsone Toxicity

• Toxic dose close to the therapeutic dose in both
  children and adults
• Severe poisonings documented after doses of 1 g
  in adults and 100 mg in children
• Signs Symptoms

• Tachycardia
• Hypotension
• Blurred vision
• Nausea

• Vomiting
• Methemoglobinemia
• Sulfhemoglobinemia
• Heinz Body Hemolytic Anemia

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What was the source of the Dapsone?

• Upon further review of days events, it was
  determined the child ingested her grandfather's
  medication that he had dropped on the carpet and
  couldnt find

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Treatment

• Methylene Blue IV
• methylene blue ? leukomethylene blue ? reduces
  methemoglobin ? hemoglobin

• Ketamine
• For sedation
• Ascorbic Acid (Vitamin C)
• Provides a reducing environment to
• allow the dye to act more efficiently
• Atropine
• Antidote for various toxic and
• anticholinesterase agents

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Subsequent Methemoglobin Levels
Normal range 0-2
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Childhood Poisoning

• 1.1 million calls about accidental poisoning in
  children 5 and under every year
• Every 30 seconds a child is poisoned
• Poisoning by medication leading cause of injury
  in 18-35 month olds
• More than 90 of poisonings occur at home

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Causes of Childhood Poisoning

• Inadequate storage of household products
• Confusion between candy
• Medication directions not
• followed correctly
• Dropping/misplacing
• medication
• Unsupervised children

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The Arsenic Hour

• Most calls to poison control centers occur
  between 4-10 p.m.
• Dinnertime is such a busy time of day children
  often left unsupervised

Results from Laboratory
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Case Summary

• 14-month-old girl presented with cyanosis and
  methemoglobinemia
• Confirmed by GC/MS to be Dapsone
• Given methylene blue and ascorbic acid
• Determined child ingested grandfather's medication

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References

• 1.      Agran, Phyllis F., MD, MPH, Anderson,
  Craig, DHSc, PhD, Winn, Diane, RN, MPH, Trent,
  Roger, PhD, Walton-Haynes, DDS, MPH, and Sharon
  Thayer, MPH. Rates of Pediatric Injuries by
  3-month Intervals for Children 0 to 3 years of
  age. Pediatrics 2003, 111 (6)683-692.
• 2.      Dart, Richard C., Hurlbut, Katherine M.,
  Yip, Luke and Edwin K. Kuffner. The 5 Minute
  Toxicology Consult. Philadelphia, PA Lippencott,
  Williams Wilkins, 2000 49-48, 88-89, 130-131,
  348-349.
• 3.      Leikin, J., MD and F. Paloucek, PharmD.
  Poisoning and Toxicology Handbook. Hudson, OH
  Lexi-Comp Inc., 2002 445-447.
• 4.      Olson, Kent R., MD, FACEP. Poisoning and
  Drug Overdose. Stamford, CT Appleton Lange,
  1999 152-154.
• 5.      Prasad, R., Das, B.P., Singh, R. and K.K.
  Sharma.Dapsone Induced Methemoglobinemia,
  Sulfhemoglobinemia and Hemolytic Anemia A Case
  Report with a Note on Treatment Strategies.
  Indian Journal of Pharmacology 2002, 34 283-285.
  
• 6.      Walker, Jon P., MD, Houston, Hugh, MD,
  Miller, Sandra, MD, and Gregory W. Rouan, MD.
  Acute Methemoglobinemia Secondary to Topical
  Benzocaine Spray. Advanced Studies in Medicine
  2003, 3 (1)45-48.
• 7.      http//www.inchem.org/documents/pims/pharm
  /dapsone.htm, 2003
• 8.      http//www.ntp-server.niehs.nih.gov/htdocs
  /LT-studies/TR020.html, 2003
• 9.      http//www.chkd.org, 2003
• 10.  http//www.yahoo.com, 2003
•  

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Credits

• This case was prepared by
• Ingrid Swanson, MT(ASCP)
• while she was a Medical Technology student in
  the
• 2004 Medical Technology Class at
• William Beaumont Hospital in Royal Oak, MI.