Comparison of Kinetics of Sevoflurane and Isoflurane in Humans

Abstract

The low solubility of sevoflurane in blood suggests that this agent should enter and leave the body more rapidly than isoflurane. However, the closeness of sevoflurane and isoflurane tissue/blood partition coefficients suggests that the rates of equilibration with and elimination from tissues should be similar. We tested both predictions, comparing sevoflurane with isoflurane and nitrous oxide in seven volunteers. We measured the rate at which the alveolar (end-tidal) (FA) concentration of nitrous oxide increased toward an inspired (FI) concentration of 65%-70%, then measured the concurrent rise in FA and mixed expired concentrations (FM) of sevoflurane and isoflurane at respective FI values of 1.0% sevoflurane and 0.6% isoflurane for 30 min. Minute ventilation (VE) was measured concurrently with the measurements of anesthetic concentrations. For the potent agents, we also measured VE, FA, and FM for 6-7 days of elimination. FA/FI values at 30 min of administration were as follows: nitrous oxide, 0.986 +/- 0.003 (mean +/- SD); sevoflurane, 0.850 +/- 0.018; and isoflurane, 0.733 +/- 0.027. FA/FA0 (FA0 = the last FA during administration) values after 5 min of elimination were as follows: sevoflurane, 0.157 +/- 0.020; isoflurane, 0.223 +/- 0.024. Recovery (volume of anesthetic recovered during elimination/volume taken up) of sevoflurane (101% +/- 7%) equaled recovery of isoflurane (101% +/- 6%). Time constants for a five-compartment mammillary model for sevoflurane were smaller than those for isoflurane for the lungs but were not different from isoflurane for the other compartments.(ABSTRACT TRUNCATED AT 250 WORDS)

Heterogeneity of human adipose blood flow

“…[4,5] that used identical methodology. The subjects average age, weight, height and calculated fat was 23 years, 72 kg and 182 cm (13.4% fat) for the sevoflurane study [5] and 25, 76 and 182 (15.4% fat) for the desflurane study [4]. Briefly, anesthesia was induced in healthy male volunteers using midazolam and/or thiopental and fentanyl and then 70% N 2 O was administered for 30 min and the ventilation was adjusted to produce normocapnea.…”

“…Briefly, anesthesia was induced in healthy male volunteers using midazolam and/or thiopental and fentanyl and then 70% N 2 O was administered for 30 min and the ventilation was adjusted to produce normocapnea. Then, the test anesthetics (either desflurane, isoflurane and halothane [4] or sevoflurane and isoflurane [5]) were administered for 30 minutes at a nearly constant inspired concentration along with 65% N 2 O. After 30 minutes, the volatile anesthetics were discontinued, maintaining the 65% N 2 O, and the washout was measured for 150 minutes, after which the N 2 O was discontinued, the endotrachial tube removed and gas samples were obtained through a mouthpiece and non-rebreathing valve.…”

“…al. [4,5]. In order to scale for differences in inspired concentration (constant during 30 minute uptake), all plots are in terms of P/P insp where P is the end tidal partial pressure.…”

“…This paper describes the PBPK modeling of a remarkable series of measurements of the pharmacokinetics of the volatile anesthetics isoflurane, sevoflurane and desflurane by Eger and colleagues [4,5]. They measured the ventilation rate and the inspired, mixed and end tidal gas concentration for 6 days following a 30 minute uptake in normal volunteers.…”

“…Experimental human data for these times periods are very limited (Table 1). The volatile anesthetic data of Eger and colleagues [4,5] used here probably represents the most accurate and extensive available data set.…”