BACKGROUND: Defluorination of sevoflurane is catalysed by the hepatic enzyme cytochrome P450 2E1 (CYP2E1). Data about the ontogenesis (developmental variations in activity) of this enzyme suggest a low metabolism of sevoflurane during the first months of life. METHODS: To test this hypothesis, 45 children less than 48 months of age undergoingsevoflurane anaesthesia were enrolled in a prospective open clinical trial. The 24 h urine fluoride excretion was measured in five groups of children (A, <4 months; B, 4 to <8 months; C, 8-12 months; D, >12-24 months; and E, >24-48 months old). An index of sevoflurane metabolism (ISM) was calculated as the ratio of fluoride excretion, cumulative expiratory sevoflurane concentrations measured every minute during anaesthesia, and body surface area. ISM values were median (IQ 25-75%). RESULTS:ISM was lower in group A (n=9, 18.9 (11.2-29.5) than group C (n=11, 44.2 (37.5-53.5), P<0.05), group D (n=7, 52.6 (45.8-68.4), P<0.01) and group E (n=9, 53.6 (50.7-85), P<0.001). Median ISM expressed as a function of median age, exponentially increased with a rapid increase during the first months of life, followed by a slower increase after 10 months of age. CONCLUSION: These results suggest that, in children less than 48 months, sevoflurane metabolism parallels postnatal development of CYP2E1.
RCT Entities:
BACKGROUND: Defluorination of sevoflurane is catalysed by the hepatic enzyme cytochrome P450 2E1 (CYP2E1). Data about the ontogenesis (developmental variations in activity) of this enzyme suggest a low metabolism of sevoflurane during the first months of life. METHODS: To test this hypothesis, 45 children less than 48 months of age undergoing sevoflurane anaesthesia were enrolled in a prospective open clinical trial. The 24 h urine fluoride excretion was measured in five groups of children (A, <4 months; B, 4 to <8 months; C, 8-12 months; D, >12-24 months; and E, >24-48 months old). An index of sevoflurane metabolism (ISM) was calculated as the ratio of fluoride excretion, cumulative expiratory sevoflurane concentrations measured every minute during anaesthesia, and body surface area. ISM values were median (IQ 25-75%). RESULTS: ISM was lower in group A (n=9, 18.9 (11.2-29.5) than group C (n=11, 44.2 (37.5-53.5), P<0.05), group D (n=7, 52.6 (45.8-68.4), P<0.01) and group E (n=9, 53.6 (50.7-85), P<0.001). Median ISM expressed as a function of median age, exponentially increased with a rapid increase during the first months of life, followed by a slower increase after 10 months of age. CONCLUSION: These results suggest that, in children less than 48 months, sevoflurane metabolism parallels postnatal development of CYP2E1.