Urinary sevoflurane and hexafluoro-isopropanol as biomarkers of low-level occupational exposure to sevoflurane

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/l_urine (ND−18.5)(n=76) and total urinary hexafluoro-isopropanol (HFIP) 0.49 mg/l_urine (ND−6833.4) (n=75). A lower limit of detection (LOD) was achieved for urinary sevoflurane (0.03 μg/l_urine), 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/l_urine. 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/l_urine and 1.4 μg/l_urine for sevoflurane (corresponding to 2 ppm and 0.5 ppm, respectively), and 2.66 mg/l_urine and 0.82 mg/l_urine 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.