The Drug-Induced Respiratory Disease Website
Known since the 1940s (PMID 18883450). Comprehensive list of causal drugs and chemicals available at PMID 1564446. Methemoglobin is the oxidized (Fe3+) species of hemoglobin (Fe2+). Patients present with slate-grey cyanosis, low SpO2, normal SaO2 and PaO2. Normally, methemoglobin is <1%. Levels above 40% can be life-threatening, producing pulmonary edema, cardiovascular collapse (PMID 17122537) CNS disturbances and death. Management includes i.v. methylene blue. A possible rebound increase in MeHb upon treatment requires close monitoring. Excess methylene blue can also produce methemoglobinemia. Guidelines: PMID 34467556.
Publications
Silent Hypoxia From Benzocaine-Induced Methemoglobinemia Following Transesophageal Echocardiogram.
Cureus 2025 Jul;17;e87109 — 2025 Jul — e87109
Occult Methemoglobinemia in a Medically-Complex 7-Year-Old Child and the Opportunity for Pharmacist Intervention in Pediatric Emergency Medicine.
The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG 2024 Dec;29;650-653 — 2024 Dec — 650-653
Case Report: An Uncommon Etiology of Vulvar Irritation and Swelling in an Adolescent Patient.
Journal of pediatric and adolescent gynecology 2022 Dec;35;715-717 — 2022 Dec — 715-717
Benzocaine-related methaemoglobinemia after transoesophageal echocardiography: a rare, life-threatening complication.
BMJ case reports 2021 Apr 23;14; — 2021 Apr 23
Topical Benzocaine and Methemoglobinemia.
American journal of therapeutics 2017 Sep/Oct;24;e596-e598 — 2017 Sep/Oct — e596-e598
An Uncommon Complication With Use of Topical Local Anesthetic Agents: Methemoglobinemia.
American journal of therapeutics 2016 Nov/Dec;23;e1968-e1969 — 2016 Nov/Dec — e1968-e1969
Nosocomial Methemoglobinemia Resulting from Self-Administration of Benzocaine Spray.
Case reports in anesthesiology 2015;2015;685304 — 2015 — 685304
An Atypical Case of Methemoglobinemia due to Self-Administered Benzocaine.
Case reports in emergency medicine 2015;2015;670979 — 2015 — 670979
Central cyanosis on a psychiatric unit treated at the Salford Royal Hospital.
Thorax 2014 Dec;69;1157-8 — 2014 Dec — 1157-8
Methemoglobinemia precipitated by benzocaine used during intubation.
Proceedings (Baylor University. Medical Center) 2014 Apr;27;133-5 — 2014 Apr — 133-5
Methemoglobinemia with the use of benzocaine spray for awake fiberoptic intubation.
Middle East journal of anaesthesiology 2013 Oct;22;337-40 — 2013 Oct — 337-40
Risk of acquired methemoglobinemia with different topical anesthetics during endoscopic procedures.
Local and regional anesthesia 2011;4;25-8 — 2011 — 25-8
Benzocaine induced methemoglobinemia: a potentially fatal complication of transesophageal echocardiography.
The Ochsner journal 2003;5;34-5 — 2003 — 34-5
Topical benzocaine-induced methemoglobinemia in the pediatric population.
Journal of pediatric health care : official publication of National Association of Pediatric Nurse Associates & Practitioners 2008 Nov-Dec;22;335-9; quiz 340-1 — 2008 Nov-Dec — 335-9; quiz 340-1
Intraoperative detection of methemoglobinemia in a patient given benzocaine spray to relieve discomfort from a nasogastric tube: a case report.
AANA journal 2008 Apr;76;99-102 — 2008 Apr — 99-102
Benzocaine and lidocaine induced methemoglobinemia after bronchoscopy: a case report.
Journal of medical case reports 2008 Jan 23;2;16 — 2008 Jan 23 — 16
Methemoglobinemia and benzocaine.
Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates 2007 Sep-Oct;30;342-5; quiz 346-7 — 2007 Sep-Oct — 342-5; quiz 346-7
Benzocaine-induced methemoglobinemia based on the Mayo Clinic experience from 28 478 transesophageal echocardiograms: incidence, outcomes, and predisposing factors.
Archives of internal medicine 2007 Oct 08;167;1977-82 — 2007 Oct 08 — 1977-82
Severe methemoglobinemia from topical anesthetic spray: case report, discussion and qualitative systematic review.
CJEM 2001 Jan;3;51-6 — 2001 Jan — 51-6
Methemoglobinemia-induced cardio-respiratory failure secondary to topical anesthesia.
American journal of therapeutics 2006 Nov-Dec;13;545-9 — 2006 Nov-Dec — 545-9
A rare side effect of transesophageal echocardiography: methemoglobinemia from topical benzocaine anesthesia.
European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology 2008 Mar;9;289-90 — 2008 Mar — 289-90
Benzocaine-induced methemoglobinemia.
Anesthesia progress 2005;52;136-9 — 2005 — 136-9
Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals.
Medicine 2004 Sep;83;265-73 — 2004 Sep — 265-73
Reported adverse event cases of methemoglobinemia associated with benzocaine products.
Archives of internal medicine 2004 Jun 14;164;1192-6 — 2004 Jun 14 — 1192-6
Critical rebound methemoglobinemia after methylene blue treatment: case report.
Pharmacotherapy 2004 Apr;24;538-40 — 2004 Apr — 538-40
Benzocaine-induced methemoglobinemia: a potentially fatal complication of transesophageal echocardiography.
Texas Heart Institute journal 2003;30;308-10 — 2003 — 308-10
Severe methemoglobinemia after transesophageal echocardiography.
American journal of therapeutics 2003 May-Jun;10;225-7 — 2003 May-Jun — 225-7
Severe methemoglobinemia on reexposure to benzocaine.
Journal of clinical anesthesia 2001 Mar;13;128-30 — 2001 Mar — 128-30
Unexpected cyanosis in the surgical patient.
Surgical endoscopy 2000 Jun;14;595 — 2000 Jun — 595
Benzocaine-induced methemoglobinemia: report of a severe reaction and review of the literature.
The Annals of pharmacotherapy 1994 May;28;643-9 — 1994 May — 643-9
Benzocaine-adultered street cocaine in association with methemoglobinemia.
Clinical chemistry 1992 Apr;38;596-7 — 1992 Apr — 596-7