Inverse relationship between age-dependent erythrocyte activity of methaemoglobin reductase and prilocaine-induced methaemoglobinaemia during infancy

Br J Anaesth. 1990 Jan;64(1):72-6. doi: 10.1093/bja/64.1.72.


We have measured plasma concentrations of local anaesthetics, and the substance fraction of methaemoglobin (MetHb), in infants less than 3 months of age, after application of a lignocaine-prilocaine cream (EMLA). A total of EMLA 2 g was applied over four different skin areas, totalling 16 cm2, for 4 h before anaesthesia for a minor surgical procedure. Sampling was carried out before and 4, 8 and 12 h after application. Maximum MetHb values (median = 2.24%) were obtained usually at 8 h and were significantly (P less than 0.001) higher than before application (median 1.32%). The plasma concentrations of local anaesthetics were low (maximum values: prilocaine 78 ng ml-1, lignocaine 412 ng ml-1). The activity of erythrocyte MetHb reductase (cytochrome b5 reductase) was analysed. Data from a previously studied group of infants aged 3-12 months were included also. Enzyme activity did not reach adult levels until after the age of 3 months. It showed a good inverse correlation with the maximum MetHb values after application of EMLA. Although the MetHb concentrations in the infants younger than 3 months were small, the enzyme capacity may be overloaded when EMLA is administered at the same time as other MetHb-inducing agents. It is concluded that the use of EMLA should be restricted in this age group.

MeSH terms

  • Age Factors
  • Anesthetics, Local / pharmacology*
  • Cytochrome-B(5) Reductase / blood*
  • Drug Combinations / pharmacology
  • Erythrocytes / enzymology*
  • Female
  • Humans
  • Infant
  • Lidocaine / blood
  • Lidocaine / pharmacology*
  • Lidocaine, Prilocaine Drug Combination
  • Male
  • Methemoglobinemia / chemically induced*
  • NADH, NADPH Oxidoreductases / blood*
  • Prilocaine / blood
  • Prilocaine / pharmacology*


  • Anesthetics, Local
  • Drug Combinations
  • Lidocaine, Prilocaine Drug Combination
  • Prilocaine
  • Lidocaine
  • NADH, NADPH Oxidoreductases
  • Cytochrome-B(5) Reductase