Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals

Rachel Ash-Bernal, Robert Wise, Scott M Wright, Rachel Ash-Bernal, Robert Wise, Scott M Wright

Abstract

Methemoglobin is a form of hemoglobin that does not bind oxygen. When its concentration is elevated in red blood cells, functional anemia and tissue hypoxia may occur. We performed a retrospective case series to describe the cases of acquired methemoglobinemia (methemoglobin level >2%) detected and the clinical circumstances under which they occurred at 2 tertiary care hospitals and affiliated outpatient clinics over 28 months. We surveyed co-oximetry laboratory data to identify patients with methemoglobinemia. We reviewed these patients' medical records to extract the clinical information and context. One hundred thirty-eight cases of acquired methemoglobinemia were detected over the 28 months. There was no gender predisposition, and the condition occurred over a wide range of ages (patients aged 4 days to 86 years). Cases occurred in many areas of the hospital, including outpatient clinics. One fatality and 3 near-fatalities were directly attributable to methemoglobinemia. Dapsone was the most common etiology of acquired methemoglobinemia, accounting for 42% of all cases. The mean peak methemoglobin level among these individuals was 7.6%. In 5 of the patients with the most severely elevated levels, 20% benzocaine spray (Hurricaine Topical Anesthetic spray, Beutlich Pharmaceuticals, Waukegan, IL) was the etiology, associated with a mean peak methemoglobin level of 43.8%. Eleven pediatric patients developed methemoglobinemia either from exogenous exposure, such as drugs, or due to serious illness, such as gastrointestinal infections with dehydration. Almost all (94%) patients with methemoglobinemia were anemic. Drugs that cause acquired methemoglobinemia are ubiquitous in both the hospital and the outpatient setting. Acquired methemoglobinemia is a treatable condition that causes significant morbidity and even mortality. We hope that a heightened awareness of methemoglobinemia will result in improved recognition and treatment. Primary prevention efforts have the potential to reduce the morbidity and mortality associated with this condition.

Copyright 2004 Lippincott Williams & Wilkins

References

    1. Abdallah HY, Shah SA. Methemoglobinemia induced by topical benzocaine: a warning for the endoscopist. Endoscopy. 2002;34:730-734.
    1. Arens JF, Carrera AE. Methemoglobin levels following peridural anesthesia with prilocaine for vaginal deliveries. Anesth Analg. 1970;49:219-222.
    1. Barker S, Tremper K, Hyatt J. Effects of mehemoglobinemia on pulse oximetry and mixed venous oximetry. Anesthesiology. 1989;70:112-117.
    1. Benjamin E, Iberti TJ. Methemoglobinemia and respiratory failure. Anesthesiology. 1985;62:542-543.
    1. Beutler E. Glucose-6-phosphate dehydrogenase deficiency. N Engl J Med. 1991;324:169-174.
    1. Bojar RM, Rastegar H, Payne DD, Harkness SH, England MR, Stetz JJ, Weiner B, Cleveland RJ. Methemoglobinemia from intravenous nitroglycerin: a word of caution. Ann Thorac Surg. 1987;43:332-334.
    1. Bower PJ, Peterson JN. Methemoglobinemia after sodium nitroprusside therapy. N Engl J Med. 1975;293:865.
    1. Casey PB, Buckley BM, Vale JA. Methemoglobinemia following ingestion of a monolinuron/paraquat herbicide (Gramonol). J Toxicol Clin Toxicol. 1994;32:185-189.
    1. Chan TY. Food-borne nitrates and nitrites as a cause of methemoglobinemia. Southeast Asian J Trop Med Public Health. 1996;27:189-192.
    1. Christensen CM, Farrar HC, Kearns GL. Protracted methemoglobinemia after phenazopyridine overdose in an infant. J Clin Pharmacol. 1996;36:112-116.
    1. Cohen RJ, Sachs JR, Wicker DJ, Conrad ME. Methemoglobinemia provoked by malarial chemoprophylaxis in Vietnam. N Engl J Med. 1968;279:1127-1131.
    1. Coleman M, Coleman N. Drug-induced methaemoglobinemia. Treatment Issues in Drug Safety. 1996;14:394-405.
    1. Comly HH. Landmark article Sept 8, 1945: Cyanosis in infants caused by nitrates in well-water. By Hunter H. Comly. JAMA. 1987;257:2788-2792.
    1. Cummings MH, Day S, Norton S, Cook G, Alexander WD. Petrol octane booster and methaemoglobinaemia. J Intern Med. 1994;235:279-280.
    1. Dinneen SF, Mohr DN, Fairbanks VF. Methemoglobinemia from topically applied anesthetic spray. Mayo Clin Proc. 1994;69:886-888.
    1. Disanto A, Wagner J. Pharmacokinetics of highly ionized drugs II: Methylene blue-absorption, metabolism and excretion in man and dog after oral absorption. J Pharm Sci. 1972;61:1086-1090.
    1. Douglas WW, Fairbanks VF. Methemoglobinemia induced by a topical anesthetic spray (Cetacaine). Chest. 1977;71:587-591.
    1. Dudley MJ, Solomon T. A case of methaemoglobinaemia. Arch Emerg Med. 1993;10:117-119.
    1. Elsner P, Dummer R. Signs of methaemoglobinaemia after topical application of EMLA cream in an infant with haemangioma. Dermatology. 1997;195:153-154.
    1. Eltzschig H, Rohrbach M, Schroeder TH. Methaemoglobinaemia after peribulbar blockade: an unusual complication in ophthalmic surgery. Br J Ophthalmol. 2000;84:442.
    1. Fairbanks V. Blue gods, blue oil and blue people. Mayo Clin Proc. 1994;69:889-892.
    1. Ferraro L, Zeichner S, Greenblott G, Groeger JS. Cetacaine-induced acute methemoglobinemia. Anesthesiology. 1988;69:614-615.
    1. Ferraro-Borgida MJ, Mulhern SA, DeMeo MO, Bayer MJ. Methemoglobinemia from perineal application of an anesthetic cream. Ann Emerg Med. 1996;27:785-788.
    1. Finan A, Keenan P, Donovan FO, Mayne P, Murphy J. Methaemoglobinaemia associated with sodium nitrite in three siblings. BMJ. 1998;317:1138-1139.
    1. Finch C. Methemoglobinemia and sulfehemoglobin. N Engl J Med. 1948;239:470.
    1. Finch C. Treatment of intracellular methemoglobinemia. Bull N Engl Med Center. 1947;6:241-245.
    1. Friedman PM, Mafong EA, Friedman ES, Geronemus RG. Topical anesthetics update: EMLA and beyond. Dermatol Surg. 2001;27:1019-1026.
    1. Gentile DA. Severe methemoglobinemia induced by a topical teething preparation. Pediatr Emerg Care. 1987;3:176-178.
    1. Gold NA, Bithoney WG. Methemoglobinemia due to ingestion of at most three pills of pyridium in a 2-year-old: case report and review. J Emerg Med. 2003;25:143-148.
    1. Gosnold JK, Johnson GS. Methaemoglobinaemia as a result of sodium nitrate poisoning. Arch Emerg Med. 1993;10:260-261.
    1. Grum DF, Rice TW. Methemoglobinemia from topical benzocaine. Cleve Clin J Med. 1990;57:357-359.
    1. Gunaratnam NT, Vazquez-Sequeiros E, Gostout CJ, Alexander GL. Methemoglobinemia related to topical benzocaine use: is it time to reconsider the empiric use of topical anesthesia before sedated EGD? Gastrointest Endosc. 2000;52:692-693.
    1. Harrison MR. Toxic methaemoglobinaemia. A case of acute nitrobenzene and aniline poisoning treated by exchange transfusion. Anaesthesia. 1977;32:270-272.
    1. Harvey JW, Keitt AS. Studies of the efficacy and potential hazards of methylene blue therapy in aniline-induced methaemoglobinaemia. Br J Haematol. 1983;54:29-41.
    1. Haynes JM. Acquired methemoglobinemia following benzocaine anesthesia of the pharynx. Am J Crit Care. 2000;9:199-201.
    1. Hebbel R, Eaton JW, Balasingam M, Steinberg MH. Spontaneous oxygen radical generation by sickle erythrocytes. J Clin Invest. 1982;70:1253-1259.
    1. Henretig FM, Gribetz B, Kearney T, Lacouture P, Lovejoy FH. Interpretation of color change in blood with varying degree of methemoglobinemia. J Toxicol Clin Toxicol. 1988;26:293-301.
    1. Hornfeldt CS, Rabe WH III. Nitroethane poisoning from an artificial fingernail remover. J Toxicol Clin Toxicol. 1994;32:321-324.
    1. Hovenga S, Koenders ME, van der Werf TS, Moshage H, Zijlstra JG. Methaemoglobinaemia after inhalation of nitric oxide for treatment of hydrochlorothiazide-induced pulmonary oedema. Lancet. 1996;348:1035-1036.
    1. Humphreys SD, Routledge PA. The toxicology of silver nitrate. Adverse Drug React Toxicol Rev. 1998;17:115-143.
    1. Jackson SH, Barker SJ. Methemoglobinemia in a patient receiving flutamide. Anesthesiology. 1995;82:1065-1067.
    1. Jaffe E. Methemoglobin pathophysiology. Prog Clin Biol Res. 1981;51:133-151.
    1. Jaffe E. Methemogloginemia. Clin Haematol. 1981;10:99-122.
    1. Jaffe E, Hsin-Soon H. DPNH-Methemoglobin reductase deficiency and hereditary methemoglobinemia. Semin Hematol. 1971;8:417-437.
    1. Jaffe ER. Enzymopenic hereditary methemoglobinemia: a clinical/biochemical classification. Blood Cells. 1986;12:81-90.
    1. Jaffe ER. Is it bad to be blue? N Engl J Med. 1969;281:957-958.
    1. Jolly BT, Monico EP, McDevitt B. Methemoglobinemia in an infant: case report and review of the literature. Pediatr Emerg Care. 1995;11:294-297.
    1. Kantor GS. Primaquine-induced methemoglobinemia during treatment of Pneumocystis carinii pneumonia. N Engl J Med. 1992;327:1461.
    1. Katsumata Y, Aoki M, Oya M, Suzuki O, Yada S. Simultaneous determination of carboxyhemoglobin and methemoglobin in victims of carbon monoxide poisoning. J Forensic Sci. 1980;25:546-549.
    1. Kearns GL, Fiser DH. Metoclopramide-induced methemoglobinemia. Pediatrics. 1988;82:364-366.
    1. Khan AM, Singh NT, Bilgrami S. Flutamide induced methemoglobinemia. J Urol. 1997;157:1363.
    1. Kotler RL, Hansen-Flaschen J, Casey MP. Severe methaemoglobinaemia after flexible fibreoptic bronchoscopy. Thorax. 1989;44:234-235.
    1. Kouides PA, Abboud CN, Fairbanks VF. Flutamide-induced cyanosis refractory to methylene blue therapy. Br J Haematol. 1996;94:73-75.
    1. Krafte-Jacobs B, Brilli R, Szabo C, Denenberg A, Moore L, Salzman AL. Circulating methemoglobin and nitrite/nitrate concentrations as indicators of nitric oxide overproduction in critically ill children with septic shock. Crit Care Med. 1997;25:1588-1593.
    1. Kumar A, Chawla R, Ahuja S, Girdhar KK, Bhattacharya A. Nitrobenzene poisoning and spurious pulse oximetry. Anaesthesia. 1990;45:949-951.
    1. Kuschner WG, Chitkara RK, Canfield J Jr, Poblete-Coleman LM, Cunningham BA, Sarinas PS. Benzocaine-associated methemoglobinemia following bronchoscopy in a healthy research participant. Respir Care. 2000;45:953-956.
    1. Laney RF, Hoffman RS. Methemoglobinemia secondary to automobile exhaust fumes. Am J Emerg Med. 1992;10:426-428.
    1. Lang PG Jr. Sulfones and sulfonamides in dermatology today. J Am Acad Dermatol. 1979;1:479-492.
    1. Ludwig SC. Acute toxic methemoglobinemia following dental analgesia. Ann Emerg Med. 1981;10:265-266.
    1. Luk G, Riggs D, Luque M. Severe methemoglobinemia in a 3-week-old infant with a urinary tract infection. Crit Care Med. 1991;19:1325-1327.
    1. Lukens JN. Landmark perspective: the legacy of well-water methemoglobinemia. JAMA. 1987;257:2793-2795.
    1. Malatinsky J, Kadlic T, Kovacik V. Acute poisoning by higher nitrogen oxides. Anesth Analg. 1973;52:94-99.
    1. Mandrell BN, McCormick JN. Dapsone-induced methemoglobinemia in pediatric oncology patients: case examples. J Pediatr Oncol Nurs. 2001;18:224-228.
    1. Mansuouri A, Lurie A. Concise review: methemoglobinemia. Am J Hematol. 1993;42:7-12.
    1. Margulies DR, Manookian CM. Methemoglobinemia as a cause of respiratory failure. J Trauma. 2002;52:796-797.
    1. Mary AM, Bhupalam L. Metoclopramide-induced methemoglobinemia in an adult. J Ky Med Assoc. 2000;98:245-247.
    1. May RB. An infant with sepsis and methemoglobinemia. J Emerg Med. 1985;3:261-264.
    1. McGrath PD, Moloney JF, Riker RR. Benzocaine-induced methemoglobinemia complicating transesophageal echocardiography: a case report. Echocardiography. 1998;15:389-392.
    1. Medina I, Mills J, Leoung G, Hopewell PC, Lee B, Modin G, Benowitz N, Wofsy CB. Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone. N Engl J Med. 1990;323:776-782.
    1. Modarai B, Kapadia YK, Kerins M, Terris J. Methylene blue: a treatment for severe methaemoglobinaemia secondary to misuse of amyl nitrite. Emerg Med J. 2002;19:270-271.
    1. Morse DL, Baker EL Jr, Kimbrough RD, Wisseman CL III. Propanil-chloracne and methomyl toxicity in workers of a pesticide manufacturing plant. Clin Toxicol. 1979;15:13-21.
    1. Nathan DM, Siegel AJ, Bunn HF. Acute methemoglobinemia and hemolytic anemia with phenazopyridine: possible relation to acute renal failure. Arch Intern Med. 1977;137:1636-1638.
    1. O'Donohue WJ Jr, Moss LM, Angelillo VA. Acute methemoglobinemia induced by topical benzocaine and lidocaine. Arch Intern Med. 1980;140:1508-1509.
    1. O'Grady J, Jarecsni E. Sodium chlorate poisoning. Br J Clin Pract. 1971;25:38-39.
    1. Ohashi K, Yukioka H, Hayashi M, Asada A. Elevated methemoglobin in patients with sepsis. Acta Anaesthesiol Scand. 1998;42:713-716.
    1. Osterhoudt KC, Wiley CC, Dudley R, Sheen S, Henretig FM. Rebound severe methemoglobinemia from ingestion of a nitroethane artificial-fingernail remover. J Pediatr. 1995;126:819-821.
    1. Pierce JM, Nielsen MS. Acute acquired methaemoglobinaemia after amyl nitrite poisoning. BMJ. 1989;298:1566.
    1. Plotkin JS, Buell JF, Njoku MJ, Wilson S, Kuo PC, Bartlett ST, Howell C, Johnson LB. Methemoglobinemia associated with dapsone treatment in solid organ transplant recipients: a two-case report and review. Liver Transpl Surg. 1997;3:149-152.
    1. Pollack ES, Pollack CV Jr. Incidence of subclinical methemoglobinemia in infants with diarrhea. Ann Emerg Med. 1994;24:652-656.
    1. Pounder RE, Craven ER, Henthorn JS, Bannatyne JM. Red cell abnormalities associated with sulphasalazine maintenance therapy for ulcerative colitis. Gut. 1975;16:181-186.
    1. Price AH, Fletcher KA. Ethnic differences in the reactions to drugs and xenobiotics. The metabolism and toxicity of primaquine. Prog Clin Biol Res. 1986;214:261-278.
    1. Rehman H. Methemoglobinemia. West J Med. 2001;175:193-196.
    1. Robicsek F. Acute methemoglobinemia during cardiopulmonary bypass caused by intravenous nitroglycerin infusion. J Thorac Cardiovasc Surg. 1985;90:931-934.
    1. Rodriguez L, Smolik I, Zhehlik A. Benzocaine-induced methemoglobinemia: report of a severe reaction and review of the literature. Ann Pharmacother. 1994;28:643-649.
    1. Roigas H, Zoellner E, Jacobasch G, Shultze M, Rapport S. Regulatory factors in methylene blue catalysis in erythrocytes. Eur J Biochem. 1970;12:24-30.
    1. Rosove MH, Harwig SS, Ahmed RA. Dapsone and Heinz bodies. Arch Dermatol. 1985;121:25.
    1. Ruf B, Pohle HD. Clindamycin/primaquine for Pneumocystis carinii pneumonia. Lancet. 1989;2:626-627.
    1. Sandza JG Jr, Roberts RW, Shaw RC, Connors JP. Symptomatic methemoglobinemia with a commonly used topical anesthetic, Cetacaine. Ann Thorac Surg. 1980;30:187-190.
    1. Schott AM, Vial T, Gozzo I, Chareyre S, Delmas PD. Flutamide-induced methemoglobinemia. DICP. 1991;25:600-601.
    1. Seibert RW, Seibert JJ. Infantile methemoglobinemia induced by a topical anesthetic, Cetacaine. Laryngoscope. 1984;94:816-817.
    1. Severinghaus JW, Xu FD, Spellman MJ Jr. Benzocaine and methemoglobin: recommended actions. Anesthesiology. 1991;74:385-387.
    1. Shepherd G, Grover J, Klein-Schwartz W. Prolonged formation of methemoglobin following nitroethane ingestion. J Toxicol Clin Toxicol. 1998;36:613-616.
    1. Sietsma A, Naughton MA, Harley JD. "Blue soldiers". Med J Aust. 1968;2:811.
    1. Sin DD, Shafran SD. Dapsone- and primaquine-induced methemoglobinemia in HIV-infected individuals. J Acquir Immune Defic Syndr Hum Retrovirol. 1996;12:477-481.
    1. Singh RK, Kambe JC, Andrews LK, Russell JC. Benzocaine-induced methemoglobinemia accompanying adult respiratory distress syndrome and sepsis syndrome: case report. J Trauma. 2001;50:1153-1157.
    1. Smith MA, Shah NR, Lobel JS, Hamilton W. Methemoglobinemia and hemolytic anemia associated with Campylobacter jejuni enteritis. Am J Pediatr Hematol Oncol. 1988;10:35-38.
    1. Smith RP, Carleton RA. Letter: Nitroprusside and methemoglobinemia. N Engl J Med. 1976;294:502-503.
    1. Steffen C, Seitz R. Severe chlorate poisoning: report of a case. Arch Toxicol. 1981;48:281-288.
    1. Stoiber TR. Toxic methemoglobinemia complicating transesophageal echocardiography. Echocardiography. 1999;16:383-385.
    1. Taddio A, Stevens B, Craig K, Rastogi P, Ben-David S, Shennan A, Mulligan P, Koren G. Efficacy and safety of lidocaine-prilocaine cream for pain during circumcision. N Engl J Med. 1997;336:1197-1201.
    1. Tremper K, Barker S. Using pulse oximetry when dyshemoglobin levels are high. J Crit Illn. 1988;1:103-107.
    1. Tush GM, Kuhn RJ. Methemoglobinemia induced by an over-the-counter medication. Ann Pharmacother. 1996;30:1251-1254.
    1. Udeh C, Bittikofer J, Sum-Ping ST. Severe methemoglobinemia on reexposure to benzocaine. J Clin Anesth. 2001;13:128-130.
    1. Uetrecht J. Dapsone and sulfapyridine. Clin Dermatol. 1989;7:111-120.
    1. Vessely MB, Zitsch RP III. Topical anesthetic-induced methemoglobinemia: a case report and review of the literature. Otolaryngol Head Neck Surg. 1993;108:763-767.
    1. Viallon A, Page Y, Bertrand JC. Methemoglobinemia due to riluzole. N Engl J Med. 2000;343:665-666.
    1. Wagner A, Marosi C, Binder M, Roggla G, Staudinger T, Keil F, Locker GJ, Frass M. Fatal poisoning due to dapsone in a patient with grossly elevated methaemoglobin levels. Br J Dermatol. 1995;133:816-817.
    1. Ward KE, McCarthy MW. Dapsone-induced methemoglobinemia. Ann Pharmacother. 1998;32:549-553.
    1. Warren RE, Van de Mark TB, Weinberg S. Methemoglobinemia induced by high doses of prilocaine. Oral Surg Oral Med Oral Pathol. 1974;37:866-871.
    1. Wright R, Lewander W, Woolf A. Methemoglobinemia: etiology, pharmacology, and clinical management. Ann Emerg Med. 1999;34:646-656.

Source: PubMed

3
Abonnieren