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5.15.08 parikh

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methemoglobinemia...........

methemoglobinemia...........

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  • 1. METHEMOGLOBINEMIA Palak Parikh Morning Report May 16, 2008
  • 2. Methemoglobin Altered state of Hg in which the ferrous (Fe 2+) irons of heme are oxidized to the ferric (Fe 3+) state. Ferric hemes of methemoglobin are unable to bind oxygen. Oxygen dissociation curve is “left-shifted”, and oxygen delivery to the tissues is impaired.
  • 3. Oxygen Dissociation Curve
  • 4. Methemoglobinemia >1% of total Hg species is in the oxidized form. Due to imbalance due to either increased methemoglobin production or decreased methemoglobin reduction. High levels can lead to severe and irreversible tissue hypoxia and cell death.
  • 5. Methemoglobin Reduction toHemoglobin NADH-dependent reaction catalyzed by cytochrome b5 reductase (b5R) – only physiologically important pathway Alternate pathway uses an enzyme utilizing NADPH generated by G6PD in the hexose monophosphate shunt as a source of electrons.  Note: This pathway needs an electron acceptor or redox dye, such as methylene blue or flavin
  • 6. Reduction of Methemoglobin
  • 7. Causes of Methemoglobinemia Hereditary  Cytochrome b5 reductase deficiency  Hemoglobin M disease  Cytochrome b5 deficiency Acquired
  • 8. Agents that can causeMethemoglobinemia Aniline dyes  Local Anesthetic Benzene derivatives Agents  Benzocaine, Lidocaine, Chlorates Prilocaine Chloroquine  Metoclopramide Dapsone  Methylene Blue *** Nitrites  Paraquat  NTG, Nitric oxide  Primaquine Sulfonamides
  • 9. Blood in Methemoglobinemia Dark-red, chocolate, or brownish to blue in color Does not change in color w/ addition of oxygen, unlike deoxyhemoglobin
  • 10. Clinical Features ofMethemoglobinemia Cyanosis – detected when methemoglobin concentration exceeds 1.5 g/dL, or 8-12% of total hemoglobin. Early symptoms – headache, fatigue, dyspnea, lethargy At higher methemoglobin levels – respiratory depression, seizures, altered consciousness, shock, death Erythrocytosis – rare
  • 11. Diagnosis Standard – Co-oximeter  Interprets all readings in 630 nm range as methemoglobin (peak absorbance at 631 nm)  False positives if sulfhemoglobin and methylene blue present Confirmatory – Evelyn-Malloy method  Adds cyanide which binds to positively charged methemoglobin, eliminating peak at 630-635 nm in direct proportion to methemoglobin concentration  Subsequently adds ferricyanide to convert entire specimen to cyanomethemoglobin for measurement of total Hg concentration  Methemoglobin expressed as percentage of total concentration of Hg.
  • 12. Treatment of Methemoglobinemia Cytochrome b5r deficiency  indicated for cosmetic reasons only  methylene blue or ascorbic acid Acquired Methemoglobinemia  Discontinue offending agents – especially if dapsone or xylocaine-related med  Transfusion of pRBCs if anemic  Activated charcoal if overdose  Supplemental O2  Methylene Blue – if severe
  • 13. Methylene Blue Usually given only if methemoglobin level > 40-50% of total hemoglobin. Dose of 1 to 2 mg/kg IV over 5 minutes Dose may be repeated in 1 hr. Large (>7 mg/kg) cumulative doses can cause dyspnea, chest pain, and hemolysis Should not be used in a pt. with G6PD deficiency b/c it may further produce hemolysis.
  • 14. G6PD Deficiency Populations w/ High Incidence  African Americans  People of Mediterranean descent  Southeast Asians
  • 15. Severe Methemoglobinemia in G6PDDeficiency If Severe Methemoglonemia, can give:  Ascorbic acid (300 – 1000 mg/day PO in divided doses)  Risk of hemolysis in very high doses  Risk of kidney stone formation in high doses  Hyperbaric Oxygen  Exchange Transfusion
  • 16. HIV Patients Have lower glutathione levels in plasma and T lymphocytes, which may predispose them to clinically significant methemoglobinemia. May take primaquine or dapsone for PJP prophylaxis or treatment. If both drugs given within 1-2 days of each other, may increase risk of methemoglobinemia as half life of dapsone exceeds 30 hrs.
  • 17. Take-Home Points Methemoglobinemia is a condition in which >1% of total Hg species is in oxidized form (Fe 3+). Clinical Triad: Breathlessness, Cyanosis, Chocolate-colored blood. Dapsone and primaquine can cause methemoglobinemia, especially in HIV pts. Usually, if methemoglobin <40% of total Hg, can treat with O2, possibly pRBCs, and discontinuation of any offending agents. If methemoglobin >40% of total Hg, can give methylene blue (unless G6PD deficient).
  • 18. References Alexander, CM, et al. Principles of oximetry. Anesth Analg. 1989; 68:368. Curry, S. Methemoglobinemia. Annals of Emergency Medicine. 1982; 11:214-221. Darling, R., et al. The effect of methemoglobin on the equilibrium between oxygen and hemoglobin. American Journal of Physiology. 1942; 137:56. Evelyn, K, Malloy, H. Microdetermination of oxyhemoglobin, methemoglobin, and sulfhemoglobin in a single sample of blood. Journal of Biol Chem. 1938; 126:655. Goluboff, N. Methylene blue induced cyanosis and acute hemolytic anemia complicating the treatment of methemoglobinemia. Journal of Pediatrics. 1961; 58:86. Mansouri, A., et al. Concise review; methemoglobinemia. American Journal of Hematology. 1993; 42: 7-12. Prchal, Josef. Diagnosis and treatment of methemoglobinemia. UpToDate. 1/2008. Sin, Don, et al. Dapsone- and primaquine-induced methemoglobinemia in HIV- infected individuals. Journal of Acquired Immune Deficiency. 1996; 12:477-481.