Risk of topical anesthetic-induced methemoglobinemia: a 10-year retrospective case-control study

JAMA Intern Med. 2013 May 13;173(9):771-6. doi: 10.1001/jamainternmed.2013.75.


Importance: Methemoglobinemia is a rare but serious disorder, defined as an increase in oxidized hemoglobin resulting in a reduction of oxygen-carrying capacity. Although methemoglobinemia is a known complication of topical anesthetic use, few data exist on the incidence of and risk factors for this potentially life-threatening disorder.

Objective: To examine the incidence of and risk factors for procedure-related methemoglobinemia to identify patient populations at high risk for this complication.

Design and setting: Retrospective study in an academic research setting.

Participants: Medical records for all patients diagnosed as having methemoglobinemia during a 10-year period were reviewed.

Exposures: All cases of methemoglobinemia that occurred after the following procedures were included in the analysis: bronchoscopy, nasogastric tube placement, esophagogastroduodenoscopy, transesophageal echocardiography, and endoscopic retrograde cholangiopancreatography.

Main outcomes and measures: Comorbidities, demographics, concurrent laboratory values, and specific topical anesthetic used were recorded for all cases. Each case was compared with matched inpatient and outpatient cases.

Results: In total, 33 cases of methemoglobinemia were identified during the 10-year period among 94,694 total procedures. The mean (SD) methemoglobin concentration was 32.0% (12.4%). The methemoglobinemia prevalence rates were 0.160% for bronchoscopy, 0.005% for esophagogastroduodenoscopy, 0.250% for transesophageal echocardiogram, and 0.030% for endoscopic retrograde cholangiopancreatography. Hospitalization at the time of the procedure was a major risk factor for the development of methemoglobinemia (0.14 cases per 10,000 outpatient procedures vs 13.7 cases per 10,000 inpatient procedures, P < .001).

Conclusions and relevance: The overall prevalence of methemoglobinemia is low at 0.035%; however, an increased risk was seen in hospitalized patients and with benzocaine-based anesthetics. Given the potential severity of methemoglobinemia, the risks and benefits of the use of topical anesthetics should be carefully considered in inpatient populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anesthesia, Local / methods*
  • Anesthetics, Local / administration & dosage*
  • Anesthetics, Local / adverse effects*
  • Antidotes / therapeutic use
  • Benzocaine / administration & dosage
  • Benzocaine / adverse effects
  • Bronchoscopy
  • Case-Control Studies
  • Cholangiopancreatography, Endoscopic Retrograde
  • Comorbidity
  • Echocardiography, Transesophageal
  • Endoscopy, Digestive System
  • Female
  • Humans
  • Incidence
  • Inpatients / statistics & numerical data
  • Intubation, Gastrointestinal
  • Male
  • Massachusetts / epidemiology
  • Medical Records
  • Methemoglobinemia / chemically induced*
  • Methemoglobinemia / drug therapy
  • Methemoglobinemia / epidemiology*
  • Methylene Blue / therapeutic use
  • Middle Aged
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors


  • Anesthetics, Local
  • Antidotes
  • Methylene Blue
  • Benzocaine