Methemoglobinemia related to local anesthetics: a summary of 242 episodes

Anesth Analg. 2009 Mar;108(3):837-45. doi: 10.1213/ane.0b013e318187c4b1.


Background: The purpose of this article is to summarize all episodes of local anesthetic-related methemoglobinemia found in the medical literature.

Methods: I performed a search of the American National Library of Medicine's PubMed with the following key words: "local anesthetic" and "methemoglobinemia."

Results: Two-hundred-forty-two episodes (40.1% published in year 2000 or after) were found. Chocolate-colored blood suggests methemoglobinemia but other colors may be found. A discrepancy between the pulse oximeter saturation (< or = 90%) and the arterial oxygen partial pressure (> or = 70 mm Hg) was present in 91.8% of the episodes. The difference between oxygen saturation measured by pulse oximetry and co-oximetry varied from -6.2% to 44.7%. Plain prilocaine may induce clinically symptomatic methemoglobinemia in children older than 6 mo at doses exceeding 2.5 mg/kg. In adults, the dose of prilocaine should be kept lower than 5.0 mg/kg, which is reduced to 3.2 mg/kg in the presence of renal insufficiency and to 1.3 mg/kg if other oxidizing drugs are used concurrently. A single spray of benzocaine may induce methemoglobinemia. Clinical symptoms may be observed at relatively low methemoglobin values, including coma at 32.2 and 29.1% in children and adults, respectively. Rebound methemoglobinemia (benzocaine on mucous membranes) with methemoglobin values as high as 59.9% may occur up to 18 h after methylene blue administration. Complications of methemoglobinemia include hypoxic encephalopathy, myocardial infarction, and death.

Conclusion: Benzocaine should no longer be used. Prilocaine should not be used in children younger than 6-mo-old, in pregnant women, or in patients taking other oxidizing drugs. The dose should be limited to 2.5 mg/kg.

Publication types

  • Meta-Analysis

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Anemia / complications
  • Anesthetics, Local / adverse effects*
  • Benzocaine / adverse effects
  • Child
  • Child, Preschool
  • Cocaine / adverse effects
  • Female
  • Hemoglobins / metabolism
  • Humans
  • Infant
  • Lidocaine / adverse effects
  • Male
  • Methemoglobinemia / blood
  • Methemoglobinemia / chemically induced*
  • Methemoglobinemia / epidemiology
  • Middle Aged
  • Pregnancy
  • Prilocaine / adverse effects
  • Tetracaine / adverse effects
  • Young Adult


  • Anesthetics, Local
  • Hemoglobins
  • Prilocaine
  • Tetracaine
  • Lidocaine
  • Cocaine
  • Benzocaine