Abstract
Objectives: Sevoflurane is an inhalation halogenated anaesthetic widely used in day and paediatric surgery. We were interested in evaluating biological markers of exposure to sevoflurane, which should improve the health surveillance of occupationally exposed personnel. Methods: A group of 36 subjects (13 male, 23 female) occupationally exposed to volatile anaesthetics in paediatric operating rooms was studied in a 2-week survey. Post-shift urine samples and specimens from passive samplers (for personal monitoring) were collected after 1.75−6 h morning exposure and analysed by headspace gas chromatography–mass spectrometry (GC–MS). Multiple determinations were assumed as independent values (in total, n=78: 24 from men, 54 from women; 25 from smokers, 53 from non-smokers). Results: Median sevoflurane external values were 0.13 parts per million (ppm) (range 0.03−18.82) (n=78), urinary sevoflurane 0.6 μg/lurine (ND−18.5)(n=76) and total urinary hexafluoro-isopropanol (HFIP) 0.49 mg/lurine (ND−6833.4) (n=75). A lower limit of detection (LOD) was achieved for urinary sevoflurane (0.03 μg/lurine), allowing quantitation of all but one of the samples; >25% of urine samples were unquantifiable by HFIP and were assigned a value equal to half the LOD of 0.10 mg/lurine. Urinary sevoflurane correlated well with breathing-zone data (r2=0.697 at log–log linear regression), whereas total urinary HFIP (r2=0.562 at log–log linear regression) seemed to be better described by a three-parameter logistic function and appeared to be influenced by smoking habits. Biological indices corresponding to National Institute for Occupational Safety and Health (NIOSH) exposure limits, calculated as means of linear regression slope and y intercept, were 3.9 μg/lurine and 1.4 μg/lurine for sevoflurane (corresponding to 2 ppm and 0.5 ppm, respectively), and 2.66 mg/lurine and 0.82 mg/lurine for HFIP. Conclusions: On the basis of our data, urinary unmodified, sevoflurane seems to be a more sensitive and reliable biomarker of short-term exposure to sevoflurane with respect to total urinary metabolite HFIP, which appears to be influenced by physiological and/or genetic individual traits, and seems to provide an estimate of integrated exposure.
Similar content being viewed by others
References
Accorsi A, Barbieri A, Raffi GB, et al (2001) Biomonitoring of exposure to nitrous oxide, sevoflurane, isoflurane and halothane by automated GC/MS headspace urinalysis. Int Arch Occup Environ Health 74:541–548
Accorsi A, Valenti S, Barbieri A, et al (2003a) Proposal for single and mixture biological exposure limits for sevoflurane and nitrous oxide at low occupational exposure levels. Int Arch Occup Environ Health 76:129–136
Accorsi A, Valenti S, Barbieri A, et al (2003b) Enflurane as an internal standard in monitoring halogenated volatile anesthetics by headspace gas chromatography–mass spectrometry. J Chromatogr A 985:259–264
American Conference of Governmental Industrial Hygienists (ACGIH) (2002) Threshold limit values (TLVs) for chemical substances and physical agents and biological exposure indices (BEIs). ACGIH Worldwide, Cincinnati
Bargellini A, Rovesti S, Barbieri A, et al (2001) Effects of chronic exposure to anesthetic gases on some immune parameters. Sci Tot Environ 270:149–156
Boivin JF (1997) Risk of spontaneous abortion in women occupationally exposed to anaesthetic gases: a meta-analysis. Occup Environ Med 54:541–548
Brodsky JB, Cohen EN (1985) Health experiences of operating room personnel. Anesthesiology 63:461–463
Byhahn C, Wilke HJ, Westpphal K (2001) Occupational exposure to volatile anaesthetics: epidemiology and approaches to reducing the problem. CNS Drugs 15:197–215
Cohen EN, Brown BW Jr, Bruce DL, et al (1975) A survey of anesthetic health hazards among dentists. J Am Dent Assoc 90:1291–1296
Eger EI II, Ionescu P, Gong D (1998) Circuit absorption of halothane, isoflurane, and sevoflurane. Anesth Analg 86:1070–1074
Frink EJ Jr, Malan TP, Morgan SE, et al (1992) Quantification of the degradation products of sevoflurane in two CO2 absorbants during low-flow anesthesia in surgical patients. Anesthesiology 77:1064–1069
Haufroid V, Gardinal S, Licot C, et al (2000) Biological monitoring of exposure to sevoflurane in operating room personnel by the measurement of hexafluoroisopropanol and fluoride in urine. Biomarkers 5:141–151
Higuchi H, Satoh T, Arimura S, et al (1993) Serum inorganic fluoride levels in mildly obese patients during and after sevoflurane anesthesia. Anesth Analg 77:1018–1021
Higuchi H, Sumikura H, Sumita S, et al (1995) Renal function in patients with high serum fluoride concentrations after prolonged sevoflurane anesthesia. Anesthesiology 83:449–458
Hobbhahn J, Wiesner G, Taeger K (1998) Occupational exposure and environmental pollution: the role of inhalation anesthetics with special consideration of sevoflurane (in German). Anaesthesist 47 [Suppl 1]:S77–S86
Hoerauf KH, Koller C, Taeger K, et al (1997) Occupational exposure to sevoflurane and nitrous oxide in operating room personnel. Int Arch Occup Environ Health 69:134–138
Hoerauf KH, Wiesner G, Schroegendorfer KF, et al (1999) Waste anesthetic gases induce sister chromatid exchange in lymphocytes of operating room personnel. Br J Anaesth 82:764–766
Ikeda M (1999) Solvents in urine as exposure markers. Toxicol Lett 108:99–106
Imbriani M, Zadra P, Negri S, et al (2001) Biological monitoring of occupational exposure to sevoflurane (in Italian). Med Lav 92:173–180
Kharasch ED, Jubert C (1999) Compound A uptake and metabolism to mercapturic acids and 3,3,3-trifluoro-2-fluoromethoxypropanoic acid during low-flow sevoflurane anesthesia: biomarkers for exposure, risk assessment, and interspecies comparison. Anesthesiology 91:1267–1278
Kharasch ED, Thummel KE (1993) Identification of cytochrome P450 2E1 as the predominant enzyme catalyzing human liver microsomal defluorination of sevoflurane, isoflurane, and methoxyflurane. Anesthesiology 79:795–807
Kharasch ED, Karol MD, Lanni C, et al (1995) Clinical sevoflurane metabolism and disposition. I. Sevoflurane and metabolite pharmacokinetics. Anesthesiology 82:1369–1378
Knill-Jones RP, Newman BJ, Spence AA (1975) Anesthetic practice and pregnancy: controlled survey of male anaesthetists in the United Kingdom. Lancet 2:807–809
Lieber CS (1997) Cytochrome P-4502E1: its physiological and pathological role. Physiol Rev 77:517–544
Lucchini R, Belotti L, Cassitto MG, et al (1997) Neurobehavioral functions in operating room personnel: a multicenter study (in Italian). Med Lav 88:396–405
Morio M, Fujii K, Satoh N, et al (1992) Reaction of sevoflurane and its degradation products with soda lime. Toxicity of the byproducts. Anesthesiology 77:1155–1164
National Institute for Occupational Safety and Health (NIOSH) (1977) Criteria for a recommended standard: occupational exposure to waste anesthetic gases and vapors. DHEW publication no. (NIOSH). US Department of Health, Education and Welfare, NIOSH, Cincinnati, pp 77–140. Available from http://www.cdc.gov/niosh/77–140.html
O’Keeffe NJ, Healy TE (1999) The role of new anesthetic agents. Pharmacol Ther 84:233–248
Poli D, Bergamaschi E, Manini P, et al (1999) Solid phase microextraction gas chromatographic–mass spectrometric method for the determination of inhalation anesthetics in urine. J Chromatogr B 732:115–125
Sarner JB, Levine M, Davis PJ, et al (1995) Clinical characteristics of sevoflurane in children: a comparison with halothane. Anesthesiology 82:38–46
Scapellato ML, Mastrangelo G, Maccà I, et al (2001) Occupational exposure to anesthetic gases and urinary excretion of D-glucaric acid. Biomarkers 6:294–301
STATA Corporation (2000) Intercooled STATA 7.0 for Windows 98. Texas
Tyther R, Halligan M, Wang J, et al (2001) Effects of chronic occupational exposure to anaesthetic gases on the rate of neutrophil apoptosis among anaesthetists. Eur J Anaesthesiol 19:604–608
Welborn LG, Hannallah RS, Norden JM, et al (1996) Comparison of emergence and recovery characteristics of sevoflurane, desflurane, and halothane in pediatric ambulatory patients. Anesth Analg 83:917–920
Acknowledgements
We would especially like to thank all the personnel of the operating rooms involved in the study for their helpful cooperation. We are grateful to Sergio Ghittori and Paola Zadra (University of Pavia), for their advice in setting up the analytical methods, and to Stefano Mattioli for assistance with the statistical analysis.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Accorsi, A., Morrone, B., Domenichini, I. et al. Urinary sevoflurane and hexafluoro-isopropanol as biomarkers of low-level occupational exposure to sevoflurane. Int Arch Occup Environ Health 78, 369–378 (2005). https://doi.org/10.1007/s00420-004-0580-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00420-004-0580-8