Yasuda N, Lockhart S H, Eger E I, Weiskopf R B, Johnson B H, Freire B A, Fassoulaki A
Department of Anesthesia, University of California, San Francisco 94143-0464.
Anesthesiology. 1991 Mar;74(3):489-98. doi: 10.1097/00000542-199103000-00017.
The low solubility of desflurane in blood and tissues suggests that the partial pressures of this agent in blood and tissues should approach the inspired partial pressure more rapidly than would the blood and tissue partial pressures of other potent inhaled anesthetics. We tested this prediction, comparing the pharmacokinetics of desflurane with those of isoflurane, halothane, and nitrous oxide in eight volunteers. We measured the rate at which the alveolar (endtidal) (FA) concentration of nitrous oxide increased towards an inspired (FI) concentration of 65-70%, and then measured the concurrent increase in FA and mixed expired concentrations (FM) of desflurane, isoflurane, and halothane at respective FI values of 2.0%, 0.4%, 0.2%. Minute ventilation (VE) was measured concurrently with the measurements of anesthetic concentrations. The potent vapors were administered for 30 min; administration of nitrous oxide continued throughout the period of anesthesia. For the potent agents, we also measured VE, FA, and FM for 5-7 days of elimination. We used FA/FI and FA/FA0 (FA0 = the last FA during the administration of each anesthetic) to define the rate of increase of anesthetic in the lungs and the rate of elimination of anesthetic, respectively. FA/FI values at 30 min of administration were: (mean +/- SD) nitrous oxide 0.99 +/- 0.01, desflurane 0.90 +/- 0.01, isoflurane 0.73 +/- 0.03, and halothane 0.58 +/- 0.04. FA/FA0 values after 5 min of elimination were: desflurane 0.14 +/- 0.02, isoflurane 0.22 +/- 0.02, and halothane 0.25 +/- 0.02. Recovery (volume of anesthetic recovered during elimination per volume taken up) of desflurane (105 +/- 25%) equalled recovery of isoflurane (102 +/- 13%) and exceeded recovery of halothane (64 +/- 9%). Time constants for a five-compartment mammillary model for halothane and isoflurane differed for the lungs, fat group, and hepatic metabolism, and exceeded those for desflurane for all compartments. In summary, we found that FA/FI of desflurane increases more rapidly and that FA/FA0 decreases more rapidly in humans than do these variables with other available potent anesthetics. We also found that desflurane resists biodegradation in humans and so may have little or no toxic potential.
地氟烷在血液和组织中的低溶解度表明，与其他强效吸入麻醉药相比，该药物在血液和组织中的分压应能更快地接近吸入分压。我们对这一预测进行了测试，在8名志愿者中比较了地氟烷与异氟烷、氟烷和氧化亚氮的药代动力学。我们测量了氧化亚氮肺泡（呼气末）（FA）浓度朝着65 - 70%的吸入（FI）浓度增加的速率，然后在各自2.0%、0.4%、0.2%的FI值下测量了地氟烷、异氟烷和氟烷的FA和混合呼出浓度（FM）的同时增加。在测量麻醉药浓度的同时测量分钟通气量（VE）。强效挥发性麻醉药给药30分钟；在整个麻醉期间持续给予氧化亚氮。对于强效麻醉药，我们还在消除的5 - 7天内测量了VE、FA和FM。我们使用FA/FI和FA/FA0（FA0 = 每种麻醉药给药期间的最后一个FA）分别定义麻醉药在肺中的增加速率和麻醉药的消除速率。给药30分钟时的FA/FI值为：（均值±标准差）氧化亚氮0.99±0.01，地氟烷0.90±0.01，异氟烷0.73±0.03，氟烷0.58±0.04。消除5分钟后的FA/FA0值为：地氟烷0.14±0.02，异氟烷0.22±0.02，氟烷0.25±0.02。地氟烷的回收率（消除期间回收的麻醉药体积与摄取的体积之比）（105±25%）等于异氟烷的回收率（102±13%）且超过氟烷的回收率（64±9%）。氟烷和异氟烷的五室乳头模型的时间常数在肺、脂肪组和肝代谢方面有所不同，且所有隔室的时间常数均超过地氟烷的时间常数。总之，我们发现与其他可用的强效麻醉药相比，地氟烷的FA/FI增加得更快，FA/FA0下降得更快。我们还发现地氟烷在人体中抗生物降解，因此可能几乎没有或没有毒性潜力。
