Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Filters applied. Clear all
. 1996 Jun;14(6):394-405.
doi: 10.2165/00002018-199614060-00005.

Drug-induced Methaemoglobinaemia. Treatment Issues


Drug-induced Methaemoglobinaemia. Treatment Issues

M D Coleman et al. Drug Saf. .


In normal erythrocytes, small quantities of methaemoglobin are formed constantly and are continuously reduced, almost entirely by the reduced nicotine adenine dinucleotide (NADH) diaphorase system, rather than the reduced nicotine adenine dinucleotide phosphate (NADPH) diaphorase system. Methaemoglobinaemias are usually the result of xenobiotics, either those that may directly oxidise haemoglobin or those that require metabolic activation to an oxidising species. The most clinically relevant direct methaemoglobin formers include local anaesthetics (such as benzocaine and, to a much lesser extent, prilocaine) as well as amyl nitrite and isobutyl nitrite, which have become drugs of abuse. Indirect, or metabolically activated, methaemoglobin formation by dapsone and primaquine may cause adverse reactions. The clinical consequences of methaemoglobinaemia are related to the blood level of methaemoglobin; dyspnoea, nausea and tachycardia occur at methaemoglobin levels of > or = 30%, while lethargy, stupor and deteriorating consciousness occur as methaemoglobin levels approach 55%. Higher levels may cause cardiac arrhythmias, circulatory failure and neurological depression, while levels of 70% are usually fatal. Cyanosis accompanied by a lack of responsiveness to 100% oxygen indicates a diagnosis of methaemoglobinaemia, which should be confirmed using a CO-oximeter. Pulse oximeters do not detect methaemoglobin and may give a misleading impression of patient oxygenation. Methaemoglobinaemia is treated with intravenous methylene blue (methyl-thioninium chloride; ;1 to 2 mg/kg of a 1% solution). If the patient does not respond, perhaps because of glucose-6-phosphate dehydrogenase (G6PD) deficiency or continued presence of toxin, admission to an intensive care unit and exchange transfusion may be required. Dapsone-mediated chronic methaemoglobin formation can be reduced by coadministration of cimetidine to aid patient tolerance. Increasing knowledge and awareness of drug-mediated acute methaemoglobinaemia among physicians should lead to prompt diagnosis and treatment of this potentially life-threatening condition.

Similar articles

See all similar articles

Cited by 46 articles

  • Methemoglobinemia: A Rare Entity Caused by Commonly Used Topical Anesthetic Agents, a Case Report.
    Rawla P, Pradeep Raj J. Rawla P, et al. J Hematol. 2017 Oct;6(4):87-89. doi: 10.14740/jh325w. Epub 2017 Sep 20. J Hematol. 2017. PMID: 32300399 Free PMC article.
  • Methemoglobin Modulation as an Intravascular Contrast Agent for Magnetic Resonance Imaging: Proof of Concept.
    McNally JS, Jaffey JA, Kim SE, Alexander MD, Shumway KL, Cohn LA, Parker DL, Day RW. McNally JS, et al. Front Vet Sci. 2019 Nov 26;6:416. doi: 10.3389/fvets.2019.00416. eCollection 2019. Front Vet Sci. 2019. PMID: 32039242 Free PMC article.
  • Lethal methemoglobinemia in the invasive brown treesnake after acetaminophen ingestion.
    Mathies T, Mauldin RE. Mathies T, et al. Sci Rep. 2020 Jan 21;10(1):845. doi: 10.1038/s41598-019-56216-1. Sci Rep. 2020. PMID: 31964901 Free PMC article.
  • Code Blue: Life-threatening Methemoglobinemia.
    Ponce Ríos JD, Yong R, Calner P. Ponce Ríos JD, et al. Clin Pract Cases Emerg Med. 2019 Mar 27;3(2):95-99. doi: 10.5811/cpcem.2019.3.41794. eCollection 2019 May. Clin Pract Cases Emerg Med. 2019. PMID: 31061960 Free PMC article.
  • Quantifying primaquine effectiveness and improving adherence: a round table discussion of the APMEN Vivax Working Group.
    Thriemer K, Bobogare A, Ley B, Gudo CS, Alam MS, Anstey NM, Ashley E, Baird JK, Gryseels C, Jambert E, Lacerda M, Laihad F, Marfurt J, Pasaribu AP, Poespoprodjo JR, Sutanto I, Taylor WR, van den Boogaard C, Battle KE, Dysoley L, Ghimire P, Hawley B, Hwang J, Khan WA, Mudin RNB, Sumiwi ME, Ahmed R, Aktaruzzaman MM, Awasthi KR, Bardaji A, Bell D, Boaz L, Burdam FH, Chandramohan D, Cheng Q, Chindawongsa K, Culpepper J, Das S, Deray R, Desai M, Domingo G, Duoquan W, Duparc S, Floranita R, Gerth-Guyette E, Howes RE, Hugo C, Jagoe G, Sariwati E, Jhora ST, Jinwei W, Karunajeewa H, Kenangalem E, Lal BK, Landuwulang C, Le Perru E, Lee SE, Makita LS, McCarthy J, Mekuria A, Mishra N, Naket E, Nambanya S, Nausien J, Duc TN, Thi TN, Noviyanti R, Pfeffer D, Qi G, Rahmalia A, Rogerson S, Samad I, Sattabongkot J, Satyagraha A, Shanks D, Sharma SN, Sibley CH, Sungkar A, Syafruddin D, Talukdar A, Tarning J, Ter Kuile F, Thapa S, Theodora M, Huy TT, Waramin E, Waramori G, Woyessa A, Wongsrichanalai C, Xa NX, Yeom JS, Hermawan L, Devine A, Nowak S, Jaya I, Supargiyono S, Grietens KP, Price RN. Thriemer K, et al. Malar J. 2018 Jun 20;17(1):241. doi: 10.1186/s12936-018-2380-8. Malar J. 2018. PMID: 29925430 Free PMC article.
See all "Cited by" articles


    1. Clin Pharmacol Ther. 1992 May;51(5):522-6 - PubMed
    1. Fundam Appl Toxicol. 1992 Feb;18(2):294-8 - PubMed
    1. Biochem J. 1992 Nov 15;288 ( Pt 1):303-7 - PubMed
    1. Lancet. 1978 Nov 11;2(8098):1043-4 - PubMed
    1. Ann Emerg Med. 1982 Apr;11(4):214-21 - PubMed

MeSH terms

LinkOut - more resources