Biological Monitoring of Occupational Exposure to Nitrous Oxide, Sevoflurane, and Desflurane in Healthcare Workers: A Systematic Review

Anesthetic gases are widely used in healthcare settings. Biological monitoring has been applied to assess internal exposure, but the available evidence has never been comprehensively synthesized. This systematic review summarizes studies of occupational exposure to nitrous oxide, sevoflurane, and desflurane, evaluates reported relationships between airborne exposure and biological concentrations, and assesses biomarker suitability. Following PRISMA guidelines, PubMed and Scopus were searched for studies published in English or Italian from 1969 to 2026. Eligible biomarkers included nitrous oxide in blood, urine, or exhaled air, sevoflurane and hexafluoroisopropanol (HFIP) in urine, and desflurane in urine. Thirty-nine studies were included. More recent studies generally reported lower airborne and biomarker concentrations. Positive relationships between airborne and biological concentrations were reported. Regression-derived urinary nitrous oxide concentrations corresponding to 50 ppm airborne exposure ranged from 25 to 35 μg/L, clustering around 30 μg/L. At contemporary low exposures, unmetabolized urinary sevoflurane and desflurane were frequently below analytical detection limits, whereas HFIP remained measurable. Urinary nitrous oxide is the best-characterized biomarker. Urinary HFIP appears promising for low-level sevoflurane exposure, although between-study variability currently prevents definition of a biological guidance value. Evidence for urinary desflurane remains limited.