The effect of anesthetic duration on kinetic and recovery characteristics of desflurane versus sevoflurane, and on the kinetic characteristics of compound A, in volunteers
The effect of anesthetic duration on kinetic and recovery characteristics of desflurane versus sevoflurane, and on the kinetic characteristics of compound A, in volunteers
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DOI：
10.1097/00000539-199802000-00037
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发表时间：
1998-02-01
影响因子：
5.7
通讯作者：
Weiskopf, RB
中科院分区：
文献类型：
--
作者：
Eger, EI;Gong, D;Weiskopf, RB
本研究记录了地氟烷（9.0%）与七氟烷（3.0%）的1.25最小肺泡麻醉浓度（MAC）在2 h（n = 7）和4 h（n = 9）的动力学差异，两者均以2 L/min的新鲜气体流入量给药。这些数据是我们先前对这些麻醉剂的g-h（n = 7）研究的扩展。在麻醉剂给药10分钟时，两种麻醉剂的平均吸入（F-1）和潮气末浓度（F-A）（F-I/F-A;更常用的F-A/F-I的倒数）均降至1.15以下，七氟烷与地氟烷之间的差异为1.0，几乎是地氟烷的两倍。在所有七氟烷给药期间，化合物A [CH 2F-O-（=CF2）CF 3）;一种由Baralyme（R）降解七氟烷产生的乙烯基醚]的F-A/F-I约等于0.8，平均吸入浓度约等于40 ppm。化合物A是令人感兴趣的，因为在约150 ppm-h时，它可以在大鼠和人类中诱导肾小球和肾小管损伤的生物化学和组织学证据。在消除过程中，化合物A的F-A/F-A0 F-A0（F-A0是麻醉剂给药期间的最后一次潮气末浓度）在麻醉2小时后突然降至0，在麻醉8小时后降至约0.1（F-A约为3 ppm）。相比之下，地氟烷和七氟烷的F-A/F-A0以传统的多指数方式降低，随着麻醉剂给药持续时间的增加，降低逐渐延迟。在任何给定的麻醉持续时间内，七氟烷的F-A/F-A0均超过地氟烷，客观和主观指标表明地氟烷的恢复更快。倍（平均值+/- SD）至指令初始响应（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）和定向使用地氟烷时的时间较短（2 h 12.7 +/- 1.6 vs 21.2 +/- 4.6 min，4 h 14.8 +/- 3.1 vs 25.3 +/- 6.5 min，8 h 19 +/- 4 vs 33 +/- 9 min）。根据数字符号替换试验、P-缺失试验和Trieger试验结果定义，地氟烷的回收率更快。七氟烷麻醉8小时后呕吐的发生率更高，但在较短的麻醉持续时间后没有发生。我们得出结论，对于每个麻醉持续时间，在麻醉给药期间，地氟烷的F-1更接近F-A，地氟烷麻醉后F-A/F-A0下降更快，客观指标表明地氟烷的恢复更快。最后，似乎在2小时和4小时给药后，所有摄取的化合物A都结合在体内。含义：无论麻醉持续时间如何，吸入麻醉剂地氟烷的消除和恢复均快于吸入麻醉剂七氟烷。七氟烷的毒性降解产物化合物A似乎与体内蛋白质不可逆地结合。
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 desflurane (9.0%) versus (on a separate occasion) sevoflurane (3.0%), both administered in a fresh gas inflow of 2 L/min, These data are extensions 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 difference from 1.0 nearly twice as great for sevoflurane as for desflurane. During all sevoflurane administrations, F-A/F-I for Compound A [CH2F-O-(=CF2) CF3); a vinyl ether resulting from the degradation of sevoflurane by Baralyme(R)] equaled approximately 0.8, and the average inspired concentration equaled approximately 40 ppm. Compound A is of interest because at approximately 150 ppm-h, it san Induce biochemical and histological evidence of glomerular and tubular injury in rats and humans. During elimination, F-A/F-A0 F-A0 for Compound A (F-A0 is the last end-tidal concentration during anesthetic administration) decreased 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, multiexponential manner, the decrease being increasingly delayed with increasing 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 desflurane. 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 digit symbol substitution test, P-deletion test, and Trieger test results was more rapid with desflurane. The incidence of vomiting tvas greater with sevoflurane after 8 h of anesthesia but not after shorter durations. 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 objective 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 sevoflurane. The toxic degradation product of sevoflurane, Compound A, seems to bind irreversibly to proteins in the body.