Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-24T17:20:24.319Z Has data issue: false hasContentIssue false

Release of S(+) enantiomers in breath samples after anaesthesia with isoflurane racemate

Published online by Cambridge University Press:  23 December 2004

H. A. Haeberle
Affiliation:
Tuebingen University Hospital, Department of Anaesthesiology and Intensive Care Medicine, Tuebingen, Germany
H. G. Wahl
Affiliation:
Philipps University Marburg, Department of Clinical Chemistry and Molecular Diagnostics, Marburg, Germany
G. Aigner
Affiliation:
Tuebingen University Hospital, Department of Anaesthesiology and Intensive Care Medicine, Tuebingen, Germany
K. Unertl
Affiliation:
Tuebingen University Hospital, Department of Anaesthesiology and Intensive Care Medicine, Tuebingen, Germany
H.-J. Dieterich
Affiliation:
Tuebingen University Hospital, Department of Anaesthesiology and Intensive Care Medicine, Tuebingen, Germany
Get access

Abstract

Summary

Background and objective: Isoflurane is a chiral volatile anaesthetic, routinely administered as racemate. It has a low metabolic rate and is mostly eliminated via respiration. In blood samples, S(+) enantiomers are found in greater proportion in the days immediately after administration of isoflurane racemate whereas the ratio in breath samples is unknown.

Methods: Breath and blood samples were drawn immediately after recovery and daily up to 19 days after operation from patients undergoing anaesthesia with isoflurane racemate. The percentage of isoflurane enantiomer was determined by gas chromatography mass spectrometry in blood and thermodesorption gas chromatography mass spectrometry in breath samples.

Results: In breath samples, there were significant differences in S(+) enantiomers at all time points compared to the racemate. During the early postoperative phase, the percentage of S(+) enantiomers were significantly enhanced whereas 5 days after surgery predominantly R(−) enantiomers (50.41%) were detected in the breath samples. Also in blood samples a statistical significant accumulation of the S(+) enantiomer was noted between days 1 and 5 compared to isoflurane racemate blood control. S(+) enantiomers were significantly higher in blood compared to breath samples and was most evident on the third day after surgery (51.43%).

Conclusions: During the first days after application of isoflurane racemate, the percentage of S(+) enantiomers are higher in breath and blood samples of patients. We suggest that resorbtion and/or redistribution of enantiomers are responsible for the different kinetics of isoflurane enantiomers.

Type
Original Article
Copyright
2004 European Society of Anaesthesiology

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Calvey TN. Chirality and the mode of action of anaesthetics. Eur J Anaesthesiol 1999; 16: 275277.Google Scholar
Hall AC, Lieb WR, Franks NP. Stereoselective and non-stereoselective actions of isoflurane on the GABAA receptor. Br J Pharmacol 1994; 112: 906910.Google Scholar
Oz M, Tchugunova Y, Dinc M, Dunn SM. Effects of isoflurane on voltage-dependent calcium fluxes in rabbit T-tubule membranes: comparison with alcohols. Arch Biochem Biophys 2002; 398: 275283.Google Scholar
Moody EJ, Harris BD, Skolnick P. Stereospecific actions of the inhalation anesthetic isoflurane at the GABAA receptor complex. Brain Res 1993; 615: 101106.Google Scholar
Franks NP, Lieb WR. Stereospecific effects of inhalational general anesthetic optical isomers on nerve ion channels. Science 1991; 254: 427430.Google Scholar
Harris BD, Moody EJ, Basile AS, Skolnick P. Volatile anesthetics bidirectionally and stereospecifically modulate ligand binding to GABA receptors. Eur J Pharmacol 1994; 267: 269274.Google Scholar
Jones MV, Harrison NL. Effects of volatile anesthetics on the kinetics of inhibitory postsynaptic currents in cultured rat hippocampal neurons. J Neurophysiol 1993; 70: 13391349.Google Scholar
Quinlan JJ, Firestone S, Firestone LL. Isoflurane's enhancement of chloride flux through rat brain gamma-aminobutyric acid type A receptors is stereoselective. Anesthesiology 1995; 83: 611615.Google Scholar
Lysko GS, Robinson JL, Casto R, Ferrone RA. The stereospecific effects of isoflurane isomers in vivo. Eur J Pharmacol 1994; 263: 2529.Google Scholar
Dickinson R, White I, Lieb WR, Franks NP. Stereoselective loss of righting reflex in rats by isoflurane. Anesthesiology 2000; 93: 837843.Google Scholar
Eger EI, Koblin DD, Laster MJ, et al. Minimum alveolar anesthetic concentration values for the enantiomers of isoflurane differ minimally. Anesth Analg 1997; 85: 188192.Google Scholar
Schmidt R, Wahl HG, Haberle H, Dieterich HJ, Schurig V. Headspace gas chromatography-mass spectrometry analysis of isoflurane enantiomers in blood samples after anesthesia with the racemic mixture. Chirality 1999; 11: 206211.Google Scholar
Haeberle HA, Wahl HG, Jakubetz H, et al. Accumulation of S(+) enantiomer in human beings after general anaesthesia with isoflurane racemate. Eur J Anaesthesiol 2002; 19: 641646.Google Scholar
Eger IIEI. The pharmacology of isoflurane. Br J Anaesth 1984; 56 (Suppl. 1): 71S99S.Google Scholar
Wahl HG, Haberle H, Schmidt R, Dieterich HJ, Liebich HM. Analysis of Isoflurane Enantiomers in Human Breath Thermodesorption Gas Chromatography Mass Spectrometry. 23rd International Symposium on Capillary Chromatography 2000.
Harris B, Moody E, Skolnick P. Isoflurane anesthesia is stereoselective. Eur J Pharmacol 1992; 217: 215216.Google Scholar
Lerou JG, Dirksen R, Beneken Kolmer HH, Booij LH. A system model for closed-circuit inhalation anesthesia. I. Computer study. Anesthesiology 1991; 75: 345355.Google Scholar
Lerou JG, Booij LH. Model-based administration of inhalation anaesthesia. 2. Exploring the system model. Br J Anaesth 2001; 86: 2937.Google Scholar
Lerou JG, Booij LH. Model-based administration of inhalation anaesthesia. 3. Validating the system model. Br J Anaesth 2002; 88: 2437.Google Scholar
Lerou JG, Verheijen R, Booij LH. Model-based administration of inhalation anaesthesia. 4. Applying the system model. Br J Anaesth 2002; 88: 175183.Google Scholar
Yasuda N, Lockhart SH, Eger II EI, et al. Kinetics of desflurane, isoflurane, and halothane in humans. Anesthesiology 1991; 74: 489498.Google Scholar
Eger II EI, Johnson BH. Rates of awakening from anesthesia with I-653, halothane, isoflurane and sevoflurane: a test of the effect of anesthetic concentration and duration in rats. Anesth Analg 1987; 66: 977982.Google Scholar
Stoelting RK, Eger IIEI. The effects of ventilation and anesthetic solubility on recovery from anesthesia: an in vivo and analog analysis before and after equilibrium. Anesthesiology 1969; 30: 290296.Google Scholar
Xu Y, Tang P, Firestone L, Zhang TT. 19F nuclear magnetic resonance investigation of stereoselective binding of isoflurane to bovine serum albumin. Biophys J 1996; 70: 532538.Google Scholar
Xu Y, Seto T, Tang P, Firestone L. NMR study of volatile anesthetic binding to nicotinic acetylcholine receptors. Biophys J 2000; 78: 746751.Google Scholar
Eckenhoff RG. Do specific or nonspecific interactions with proteins underlie inhalational anesthetic action? Mol Pharmacol 1998; 54: 610615.Google Scholar
Pohorecki R, Howard BJ, Matsushita M, Stemmer PM, Becker GL, Landers DF. Isoflurane isomers differ in preservation of ATP in anoxic rat hepatocytes. J Pharmacol Exp Ther 1994; 268: 625628.Google Scholar
Bradshaw JJ, Ivanetich KM. Isoflurane: a comparison of its metabolism by human and rat hepatic cytochrome P-450. Anesth Analg 1984; 63: 805813.Google Scholar
Garton KJ, Yuen P, Meinwald J, Thummel KE, Kharasch ED. Stereoselective metabolism of enflurane by human liver cytochrome P450 2E1. Drug Metab Dispos 1995; 23: 14261430.Google Scholar