THE EFFECT OF ANESTHETIC DURATION ON KINETIC AND RECOVERY CHARACTERISTICS OF DESFLURANE VERSUS SEVOFLURANE, AND ON THE KINETIC CHARACTERISTICS OF COMPOUND-A, IN VOLUNTEERS

This study documents the differences in kinetics of 2 h (n = 7) and 4 h (n = 9) of 1.25 minimum alveolar anesthetic concentration (MAC) of d esflurane (9.0%) versus (on a separate occasion) sevoflurane (3.0%), b oth administered in a fresh gas inflow of 2 L/min, These data are exte nsions of our previous g-h (n = 7) studies of these anesthetics. By 10 min of anesthetic administration, average inspired (F-1 and end-tidal concentration (F-A) (F-I/F-A; the inverse of the more commonly used F -A/F-I) decreased to less than 1.15 for both anesthetics, with the dif ference from 1.0 nearly twice as great for sevoflurane as for desflura ne. During all sevoflurane administrations, F-A/F-I for Compound A [CH 2F-O-(=CF2) CF3); a vinyl ether resulting from the degradation of sevo flurane by Baralyme(R)] equaled approximately 0.8, and the average ins pired concentration equaled approximately 40 ppm. Compound A is of int erest because at approximately 150 ppm-h, it san Induce biochemical an d histological evidence of glomerular and tubular injury in rats and h umans. During elimination, F-A/F-A0 F-A0 for Compound A (F-A0 is the l ast end-tidal concentration during anesthetic administration) decrease d abruptly to 0 after 2 h and),h of anesthesia and to approximately 0. 1 (F-A approximately 3 ppm) after 8 h of anesthesia. In contrast, F-A/ F-A0 for desflurane and sevoflurane decreased in a conventional, multi exponential manner, the decrease being increasingly delayed with incre asing duration of anesthetic administration. F-A/F-A0 for sevoflurane exceeded that for desflurane for any given duration of anesthesia, and objective and subjective measures indicated a faster recovery with de sflurane. Times (mean +/- SD) to initial response to command (2 h 10.9 +/- 1.2 vs 17.8 +/- 5.1 min, 4 h 11.3 +/- 2.1 vs 20.8 +/- 4.8 min, 8 h 14 +/- 4 vs 28 +/- 8 min) and orientation (2 h 12.7 +/- 1.6 vs 21.2 +/- 4.6 min, 4h 14.8 +/- 3.1 vs 25.3 +/- 6.5 min, 8 h 19 +/- 4 vs 33 /- 9 min) were shorter with desflurane. Recovery as defined by the dig it symbol substitution test, P-deletion test, and Trieger test results was more rapid with desflurane. The incidence of vomiting tvas greate r with sevoflurane after 8 h of anesthesia but not after shorter durat ions. We conclude that for each anesthetic duration, F-1 more closely approximates F-A with desflurane during anesthetic administration, F-A /F-A0 decreases more rapidly after anesthesia with desflurane, and obj ective measures indicate more rapid recovery with desflurane. Finally, it seems that after 2-h and 4-h administrations, all Compound A taken up is bound within the body. Implications: Regardless of the duration of anesthesia, elimination is faster and recovery is quicker for the inhaled anesthetic desflurane than far the inhaled anesthetic sevoflur ane. The toxic degradation product of sevoflurane, Compound A, seems t o bind irreversibly to proteins in the body.