Abstract
Sevoflurane is a comparatively recent addition to the range of inhalational anaesthetics which has been recently released for clinical use. In comparison to older inhalational agents such as isoflurane or halothane, the most important property of sevoflurane is its low solubility in the blood. This results in a more rapid uptake and induction than the ‘older’ inhalational agents, improved control of depth of anaesthesia and faster elimination and recovery. The more rapid pharmacokinetics are a result of the low blood/gas partition coefficient of 0.69. With an oil/gas partition coefficient of 47.2, the minimum alveolar concentration (MAC) of sevoflurane is 2.05%. Two to 5% of the drug taken up is metabolised by the liver. The pharmacokinetics of sevoflurane do not change in children, obese patients or patients with renal insufficiency.
The pharmacokinetics and pleasant odour of sevoflurane make mask induction feasible, which is an obvious advantage in paediatric anaesthesia. The hepatic metabolism of sevoflurane results in the formation of inorganic fluoride. Upon contact with alkaline CO2 absorbent, a small amount of sevoflurane is degraded and a metabolite (compound A) is formed and inhaled in trace amounts. Whether inorganic fluoride or compound A are nephrotoxic is presently a matter of controversy.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Wallin RF, Napoli MD, Regan BM. Laboratory investigation of a new series of inhalational anesthetic agents: the halomethyl polyfluoroisopropyl ethers. In: Frink BR, editor. Cellular biology and toxicity of anesthetics. Baltimore: Williams & Wikins, 1972: 285–95.
Wallin RF, Regan BM, Napoli MD, et al. Sevoflurane: a new inhalational anesthetic agent. Anesth Analg 1975; 54: 758–66.
Frink EJ, Brown BR. Sevoflurane. Baillieres Clin Anaesthesiol 1993; 7: 899–913.
Eger II EI. New inhaled anesthetics. Anesthesiology 1994; 80: 906–22.
Young CJ, Apfelbaum JL. Inhalational anesthetics: desflurane and sevoflurane. J Clin Anesth 1995; 7: 564–77.
Conzen P, Nuscheler M. New inhalational anesthetics [in German]. Anaesthesist 1996; 45: 674–93.
Patel SS, Goa KL. Sevoflurane: a review of its pharmacodynamic and pharmacokinetic properties and its clinical use in general anaesthesia. Drugs 1996; 51: 658–700.
Quasha AL, Eger II EI, Tinker JH. Determination and applications of MAC. Anesthesiology 1980; 53: 315–34.
Strum DP, Eger II EI. Partition coefficients for sevoflurane in human blood, saline, and olive oil. Anesth Analg 1987; 66: 654–6.
Scheller MS, Saidman LJ, Partridge BL. MAC of sevoflurane in humans and the New Zealand white rabbit. Can J Anaesth 1988; 35: 153–6.
Eger II EI. Partition coefficients of 1–653 in human blood, saline, and olive oil. Anesth Analg 1987; 66: 971–3.
Koblin DD, Eger II EI, Johnson BH, et al. Minimum alveolar concentrations and oil/gas partition coefficients of four anesthetic isomers. Anesthesiology 1981; 54: 314–7.
Koblin DD. Mechanisms of action. In: Miller RD, editor. Anesthesia. 4th ed. Vol 1. New York: Churchill Livingstone, 1994: 67–100.
Rampil IJ, Lockhart SH, Zwass MS, et al. Clinical characteristics of desflurane in surgical patients: minimum alveolar concentration. Anesthesiology 1991; 74: 429–33.
Stevens WC, Dolan WM, Gibbons RT, et al. Minimum alveolar concentrations (MAC) of isoflurane with and without nitrous oxide in patients of various ages. Anesthesiology 1975; 42: 197–200.
Gion H, Saidman LJ. The minimum alveolar concentration of enfluran in man. Anesthesiology 1971; 35: 361–4.
Saidman LJ, Eger II EI, Munson ES, et al. Minimum alveolar concentration of methoxyflurane, halothane, ether and cyclopropane in man: correlation with theories of anesthesia. Anesthesiology 1967; 28: 994–1002.
Hornbein TF, Eger II EI, Winter PM, et al. The minimum alveolar concentration of nitrous oxide in man. Anesth Analg 1982; 61: 553–6.
Eger II EI. Uptake and distribution. In: Miller RD, editor. Anesthesia. 4th ed. Vol 1. New York: Churchill Livingstone, 1994: 101–24.
Malviya S, Lerman J. The blood/gas solubilities of sevoflurane, isoflurane, halothane, and serum constituent concentrations in neonates and adults. Anesthesiology 1990; 72: 793–6.
Targ AG, Yasuda N, Eger II EI. Solubility of 1–653, sevoflurane, isoflurane, and halothane in plastics and rubber composing a conventional anesthetic circuit. Anesth Analg 1989; 69: 218–25.
Munday IT, Ward PM, Foden ND, et al. Sevoflurane degradation by soda lime in a circle breathing system. Anaesthesia 1996; 51: 622–6.
Bito H, Ikeda K. Long-duration, low-flow sevoflurane anesthesia using two carbon dioxide absorbents. Anesthesiology 1994; 81: 340–5.
Liu J, Laster MJ, Eger II EI, et al. Absorption and degradation of sevoflurane and isoflurane in a conventional anesthetic circuit. Anesth Analg 1991; 72: 785–9.
Wong DT, Lerman J. Factors affecting the rate of disappearance of sevoflurane in Baralyme. Can J Anaesth 1992; 39: 366–9.
Cunningham DD, Huang S, Webster J, et al. Sevoflurane degradation to compound A in anaesthesia breathing systems. Br J Anaesth 1996; 77: 537–43.
Janshon GP, Dudziak R. Interaction of dry soda lime with enflurane and sevoflurane [in German]. Anaesthesist 1997; 46: 1050–3.
Wissing H, Kuhn I, Dudziak R. Heat production from reaction of inhalation anesthetics with dried soda lime [in German]. Anaesthesist 1997; 46: 1064–70.
Förster H, Dudziak R. Causes for the reaction between dry soda lime and the degradation products of inhalation anesthetics [in German]. Anaesthesist 1997; 46: 1054–63.
Förster H, Warnken UH, Asskali F. Different reactions of sevoflurane with individual components of soda lime [in German]. Anaesthesist 1997; 46: 1071–5.
Morio M, Fujii K, Satoh N, et al. Reaction of sevoflurane and its degradation products with soda lime. Anesthesiology 1992; 77: 1155–64.
Eger II EI, Ionescu P, Laster MJ, et al. Baralyme dehydration increases and soda lime dehydration decreases the concentration of compound A resulting from sevoflurane degradation in a standard anesthetic circuit. Anesth Analg 1997; 85: 892–8.
Gonsowski CT, Laster MJ, Eger II EI, et al. Toxicity of compound A in rats: effect of increasing duration of administration. Anesthesiology 1994; 80: 566–73.
Gonsowski CT, Laster MJ, Eger II EI, et al. Toxicity of compound A in rats: effect of a 3-hour administration. Anesthesiology 1994; 80: 556–65.
Kharasch ED, Thorning D, Garton K, et al. Role of renal cysteine conjugate β-lyase in the mechanism of compound A nephrotoxicity in rats. Anesthesiology 1997; 86: 160–71.
Keller KA, Callan C, Prokocimer P, et al. Inhalation toxicity study of a haloalkene degradant of sevoflurane, compound A (PIFE), in Sprague-Dawley Rats. Anesthesiology 1995; 83: 1220–32.
Bito H, Ikeda K. Renal and hepatic function in surgical patients after low-flow sevoflurane or isoflurane anesthesia. Anesth Analg 1996; 82: 173–6.
Bito H, Ikeda K. Plasma inorganic fluoride and intracircuit degradation product concentrations in long-duration, low-flow sevoflurane anesthesia. Anesth Analg 1994; 79: 946–51.
Bito H, Ikeda K. Closed-circuit anesthesia with sevoflurane in humans. Anesthesiology 1994; 80: 71–6.
Bito H, Ikeuchi Y, Ikeda K. Effects of low-flow sevoflurane anesthesia on renal function. Anesthesiology 1997; 86: 1231–7.
Frink EJ, Malan TP, Morgan SE, et al. Quantification of the degradation products of sevoflurane in two CO2 absorbants during low-flow anesthesia in surgical patients. Anesthesiology 1992; 77: 1064–9.
Eger II EI, Bowland T, Ionescu P, et al. Recovery and kinetic characteristics of desflurane and sevoflurane in volunteers after 8-h exposure, including kinetics of degradation products. Anesthesiology 1997; 87: 517–26.
Steffey EP, Laster MJ, Ionescu P, et al. Dehydration of Baralyme® increases compound A resulting from sevoflurane degradation in a standard anesthetic circuit used to anesthetize swine. Anesth Analg 1997; 85: 1382–6.
Fang ZX, Eger II EI, Laster MJ, et al. Carbon monoxide production from degradation of desflurane, enflurane, isoflurane, halothane, and sevoflurane by soda lime and Baralyme®. Anesth Analg 1995; 80: 1187–93.
Mapleson WW. Effect of age on MAC in humans: a meta-analysis. Br J Anaesth 1996; 76: 179–85.
Lerman J, Sikich N, Kleinman S, et al. The pharmacology of sevoflurane in infants and children. Anesthesiology 1994; 80: 814–24.
Katoh T, Ikeda K. Minimum alveolar concentration of sevoflurane in children. Br J Anaesth 1992; 68: 139–41.
Inomata S, Watanabe S, Taguchi M, et al. End-tidal sevoflurane concentration for tracheal intubation and minimum alveolar concentration in pediatric patients. Anesthesiology 1994; 80: 93–6.
Fragen RJ, Dunn KL. The minimum alveolar concentration (MAC) of sevoflurane with and without nitrous oxide in elderly versus young adults. J Clin Anesth 1996; 8: 352–6.
Katoh T, Ikeda K. The minimum alveolar concentration (MAC) of sevoflurane in humans. Anesthesiology 1987; 66: 301–3.
Kimura T, Watanabe S, Asakura N, et al. Determination of endtidal evoflurane concentration for tracheal intubation and minimum alveolar anesthetic concentration in adults. Anesth Analg 1994; 79: 378–81.
Stoelting RK, Longnecker DE, Eger II EI. Minimum alveolar concentrations in man on awakening from methoxyflurane, halothane, ether and fluroxene anesthesia: MAC awake. Anesthesiology 1970; 33: 5–9.
Katoh T, Suguro Y, Nakajima R, et al. Blood concentrations of sevoflurane and isoflurane on recovery from anaesthesia. Br J Anaesth 1992; 69: 259–62.
Yasuda N, Lockhart SH, Eger II EI, et al. Kinetics of desflurane, isoflurane, and halothane in humans. Anesthesiology 1991; 74: 489–98.
Yasuda N, Lockhart SH, Eger II EI, et al. Comparison of kinetics of sevoflurane and isoflurane in humans. Anesth Analg 1991; 72: 316–24.
Saito K, Takayasu T, Nishigami J, et al. Determination of the volatile anesthetics halothane, enflurane, isoflurane and sevoflurane in biological specimens by pulse-heating GC-MS. J Anal Toxicol 1995; 19: 115–9.
Shiraishi Y, Ikeda K. Uptake and biotransformation of sevoflurane in humans: a comparative study of sevoflurane with halothane, enflurane, and isoflurane. J Clin Anesth 1990; 2: 381–86.
Doi M, Ikeda K. Airway irritation produced by volatile anaesthetics during brief inhalation: comparison of halothane, enflurane, isoflurane and sevoflurane. Can J Anaesth 1993; 40: 122–6.
Baum VC, Yemen TA, Baum LD. Immediate 8% sevoflurane in children: a comparison with incremental sevoflurane and incremental halothane. Anesth Analg 1997; 85: 313–6.
Sigston PE, Jenkins AMC, Jackson EA, et al. Rapid inhalation induction in children: 8% sevoflurane compared with 5% halothane. Br J Anaesth 1997; 78: 362–5.
Yurino M, Kimura H. Vital capacity rapid inhalation induction technique: comparison of sevoflurane and halothane. Can J Anaesth 1993; 40: 440–3.
Yurino M, Kimura H. A comparison of vital capacity breath and tidal breathing techniques for induction of anaesthesia with high sevoflurane concentrations in nitrous oxide and oxygen. Anaesthesia 1995; 50: 308–11.
Nishiyama T, Nagase M, Tamai H, et al. Rapid induction with 7% sevoflurane inhalation: not the single-breath method. J Anesth 1995; 9: 36–9.
Carpenter RL, Eger II EI, Johnson BH. Pharmacokinetics of inhaled anesthetics in humans: measurements during and after the simultaneous administration of enflurane, halothane, isoflurane, methoxyflurane, and nitrous oxide. Anesth Analg 1986; 65: 575–82.
Lockhart SH, Yasuda N, Peterson N, et al. Comparison of percutaneous losses of sevoflurane and isoflurane in humans. Anesth Analg 1991; 72: 212–5.
Carpenter RL, Eger II EI, Johnson BH, et al. Does the duration of anesthetic administration affect the pharmacokinetics or metabolism of inhaled anesthetics in humans? Anesth Analg 1987; 66: 1–8.
Eger II EI, Gong D, Koblin DD, et al. The effect of anaesthetic duration on kinetic and recovery characteristics of desflurane versus sevoflurane, and on the kinetic characteristics of Compound A, in volunteers. Anesth Analg 1998; 86: 414–21.
Eger II EI. Application of a mathematical model of gas uptake. In: Papper EM, Kitz RJ, editors. Uptake and distribution of anesthetic agents. New York: McGraw-Hill, 1963: 88.
Schwilden H, Tonner PH, Röpcke H. Predictability of inspiratory and endexpiratory concentrations of isoflurane and enflurane by pharmacokinetic models and interindividual variability [in German]. Anasth Intensivther Notf Med 1990; 25: 317–21.
Holady DA, Smith FR. Clinical characteristics and biotransformation of sevoflurane in healthy human volunteers. Anesthesiology 1981; 54: 100–6.
Landais A, Saint-Maurice C, Hamza J, et al. Sevoflurane elimination kinetics in children. Paediatr Anaesth 1995; 5: 297–301.
Funk W, Moldaschl L, Fujita Y, et al. Anaesthetic quality and serum-fluoride in children during inhalational induction and anaesthesia with sevoflurane or halothane [in German]. Anaesthesist 1996; 45: 22–30.
Wissing H, Kuhn I, Rietbrock S, et al. Die Pharmakokinetik von Sevofluran bei Säuglingen, Kindern und Erwachsenen unter klinischen Bedingungen [abstract]. Anästhesiol Intensivmed Notfallmed Schmerzther 1997; 32 Suppl. 1: S121.
Sarner JB, Levine M, Davis PJ, et al. Clinical characteristics of sevoflurane in children. Anesthesiology 1995; 82: 38–46.
Levine MF, Sarner J, Lerman J, et al. Plasma inorganic fluoride concentrations after sevoflurane anesthesia in children. Anesthesiology 1996; 84: 348–53.
Higuchi H, Satoh T, Arimura S, et al. Serum inorganic flouride levels in mildly obese patients during and after sevoflurane anesthesia. Anesth Analg 1993; 77: 1018–21.
Frink EJ, Malan TP, Brown EA, et al. Plasma inorganic fluoride levels with sevoflurane anesthesia in morbidly obese and nonobese patients. Anesth Analg 1993; 76: 1333–7.
Nishiyama T, Aibiki M, Hanaoka K. Inorganic flouride kinetics and renal tubular function after sevoflurane anesthesia in chronic renal failure patients receiving hemodialysis. Anesth Analg 1996; 83: 574–7.
Conzen PF, Nuscheler M, Melotte A, et al. Renal function and serum fluoride concentrations in patients with stable renal insufficiency after anesthesia with sevoflurane or enflurane. Anesth Analg 1995; 81: 569–75.
Kharasch ED. Biotransformation of sevoflurane. Anesth Analg 1995; 81 (6 Suppl.): S27–38.
Kharasch ED, Thummel KE. Identification of cytochrome P450 2E1 as the predominant enzyme catalyzing human liver microsomal defluorination of sevoflurane, isoflurane, and methoxyflurane. Anesthesiology 1993; 79: 795–807.
Kharasch ED, Armstrong AS, Gunn K, et al. Clinical sevoflurane metabolism and disposition: II. The role of cytochrome P450 2E1 in fluoride and hexofluoroisopropanol formation. Anesthesiology 1995; 82: 1379–88.
Kharasch ED, Karol MD, Lanni C, et al. Clinical sevoflurane metabolism and disposition: I. Sevoflurane and metabolite pharmacokinetics. Anesthesiology 1995; 82: 1369–78.
Wandel C, Neff S, Keppler G, et al. The relationship between cytochrome P4502E1 activity and plasma fluoride levels after sevoflurane anesthesia in humans. Anesth Analg 1997; 85: 924–30.
Mazze RI, Shue GL, Jackson SH. Renal dysfunction associated with methoxyflurane anesthesia: a randomized, prospective clinical evaluation. JAMA 1971; 216: 278–88.
Cousins MJ, Mazze RI. Methoxyflurane nephrotoxicity. A study of dose response in man. JAMA 1973; 225: 1611–6.
Cittanova ML, Lelongt B, Verpönt MC, et al. Fluoride ion toxicity in human kidney collecting duct cells. Anesthesiology 1996; 84: 428–35.
Kharasch ED, Hankins DC, Thummel KE. Human kidney methoxyflurane and sevoflurane metabolism. Anesthesiology 1995; 82: 689–99.
Malan Jr TP. Sevoflurane and renal function. Anesth Analg 1995; 81 (6 Suppl.): S39–45.
Higuchi H, Sumikura H, Sumita S, et al. Renal function in patients with high serum fluoride concentrations after prolonged sevoflurane anesthesia. Anesthesiology 1995; 83: 449–58.
Goldberg ME, Cantillo J, Larijani GE, et al. Sevoflurane versus isoflurane for maintenance of anesthesia: are serum inorganic fluoride ion concentrations of concern? Anesth Analg 1996; 82: 1268–72.
Frink EJ, Malan TP, Isner RJ, et al. Renal concentrating function with prolonged sevoflurane or enflurane anesthesia in volunteers. Anesthesiology 1994; 80: 1019–25.
Ebert TJ, Frink Jr EJ, Kharasch ED. Absence of biochemical evidence for renal and hepatic dysfunction after 8 hours of 1.25 minimum alveolar concentration sevoflurane anesthesia in volunteers. Anesthesiology 1998; 88: 601–10.
Kharasch ED, Frink EJ, Zager R, et al. Assessment of low-flow sevoflurane and isoflurane effects on renal function using sensitive markers of tubular toxicity. Anesthesiology 1997; 86: 1238–53.
Frink Jr EJ, Green Jr WB, Brown EA, et al. Compound A concentrations during sevoflurane anesthesia in children. Anesthesiology 1996; 84: 566–71.
Eger II EI, Koblin DD, Bowland T, et al. Nephrotoxicity of sevoflurane versus desflurane anesthesia in volunteers. Anesth Analg 1997; 84: 160–8.
Eger II EI, Gong D, Koblin DD, et al. Dose-related biochemical markers of renal injury after sevoflurane versus desflurane anesthesia in volunteers. Anesth Analg 1997; 85: 1154–63.
Eger II EI, Ionescu P, Laster MJ, et al. Quantitative differences in the production and toxicity of CF2=BrCl versus CH2F-O-C(=CF2)(CF3) (Compound A): the safety of halothane does not indicate the safety of sevoflurane. Anesth Analg 1997; 85: 1164–70.
Frink Jr EJ. The hepatic effects of sevoflurane. Anesth Analg 1995; 81 (6 Suppl.): S46–50.
Stanski DR. Monitoring depth of anesthesia. In: Miller RD, editor. Anesthesia. 4th ed. Vol 1. New York: Churchill Livingstone, 1994: 1127–59.
Prys-Roberts C. Anaesthesia: a practical or impractical construct [editorial]? Br J Anaesth 1987; 59: 1341–5.
Frink Jr EJ, Malan TP, Atlas M, et al. Clinical comparison of sevoflurane and isoflurane in healthy patients. Anesth Analg 1992; 74: 241–5.
Lerman J, Davis PJ, Welborn LG, et al. Induction, recovery, and safety characteristics of sevoflurane in children undergoing ambulatory surgery. Anesthesiology 1996; 84: 1332–40.
Greenspun JC, Hannallah RS, Welborn LG, et al. Comparison of sevoflurane and halothane anesthesia in children undergoing outpatient ear, nose, and throat surgery. J Clin Anesth 1995; 7: 398–402.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Behne, M., Wilke, HJ. & Harder, S. Clinical Pharmacokinetics of Sevoflurane. Clin Pharmacokinet 36, 13–26 (1999). https://doi.org/10.2165/00003088-199936010-00002
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-199936010-00002