Transcript No…No…No… Not in Your Mouth!!!

No…No…No…
Not in Your Mouth!!!
A Toxicology Case Study
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.
Laboratory Results
• Capillary blood gas results:
pH
pCO2
pO2
BE
HCO3
O2
Sat
TCO2
MetHgb
7.361
30.9
142
-7
17
98
18
28
Note:
Although MetHgb is not normally reported as part of the routine
blood gas analysis results, the instrument still measures this
parameter.
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
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
Source of Patient’s
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.
Toxicology Screen
This test utilizes thin-layer chromatography to
identify over 700 substances in biological fluids.
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.
Confirmatory Testing
• Medical
Technologist/Clinical
Laboratory Scientist
performing the
confirmatory testing on
a combined gas
chromatography (GC)
and mass
spectrophotometry
(MS) instrument.
GC/MS results for patient
Gas Chromatogram
Normal
cholesterol peak
Internal Standard
run as a QC check
Mass spectrum that
corresponds to suspected
drug peak above
Suspect drug
peak in patient
sample
Comparison of patient’s 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
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 it’s 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.
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
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
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 couldn’t find
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
Subsequent Methemoglobin
Levels
Date
Time
MetHgb %
July 3, 2003
0148
28.0
0430
27.0
0810
5.0
1402
11.0
2245
10.0
0608
7.0
1150
7.0
0837
3.0
July 4, 2003
July 5, 2003
Normal range = 0-2 %
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
Causes of Childhood Poisoning
Inadequate storage of household
products
Confusion between candy
Medication directions not
followed correctly
Dropping/misplacing
medication
Unsupervised children
“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
Ate Dinner
8:00 p.m
Arrived at
hospital
9:45 p.m.
1:00 a.m.
Results from
Laboratory
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
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
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.