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Fluoride excretion in children after sevoflurane anaesthesia
C Lejus1, C Le Roux, E Legendre
1Department of Anaesthesiology, Hôtel Dieu, C.H.U. Nantes, France.
Insights
Sevoflurane metabolism in children under 48 months is low initially and increases with age. This developmental pattern of sevoflurane metabolism correlates with the postnatal maturation of the cytochrome P450 2E1 (CYP2E1) enzyme.
Area of Science:
- Anesthesiology
- Pharmacokinetics
- Pediatric Medicine
Background:
- Sevoflurane defluorination is catalyzed by cytochrome P450 2E1 (CYP2E1).
- Limited data suggests reduced CYP2E1 activity in early infancy, implying lower sevoflurane metabolism.
Purpose of the Study:
- To investigate the ontogenesis of sevoflurane metabolism in children under 48 months.
- To correlate sevoflurane metabolism with the developmental stages of CYP2E1.
Main Methods:
- Prospective open clinical trial involving 45 children under 48 months undergoing sevoflurane anesthesia.
- Measurement of 24-hour urinary fluoride excretion.
- Calculation of an index of sevoflurane metabolism (ISM) based on fluoride excretion, sevoflurane concentration, and body surface area.
Main Results:
- ISM was significantly lower in infants under 4 months compared to older children (P<0.05 to P<0.001).
- The ISM showed an exponential increase with age, with rapid growth in early months and slower progression after 10 months.
- Sevoflurane metabolism demonstrated a clear correlation with the age of the pediatric patients.
Conclusions:
- Sevoflurane metabolism in children under 48 months of age increases with postnatal development.
- The findings support the hypothesis that sevoflurane metabolism parallels the developmental maturation of CYP2E1 in early life.
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.