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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

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No…No…No… Not in Your Mouth!!!

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  1. No…No…No…Not in Your Mouth!!! A Toxicology Case Study

  2. 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.

  3. pH pCO2 pO2 BE HCO3 O2 Sat TCO2 MetHgb 7.361 30.9 142 -7 17 98 18 28 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.

  4. 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

  5. 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

  6. 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.

  7. Toxicology Screen This test utilizes thin-layer chromatography to identify over 700 substances in biological fluids.

  8. 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.

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

  10. 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

  11. 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

  12. 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. Explanation of GC/MS Findings Numbers and lines represent the various molecular fragments of Dapsone detected by the mass spectrophotometer.

  13. 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

  14. 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

  15. 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

  16. 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

  17. Subsequent Methemoglobin Levels Normal range = 0-2 %

  18. 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

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

  20. “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

  21. 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

  22. 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

  23. 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.

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