Fluoride Action Network

Abstract

Occupational exposure to high concentrations of anesthetic gases (more than 500 ppm of nitrous oxide and more than 15 ppm of halothane and enflurane) can cause neurobehavioral effects in operating room personnel. Factors such as stress and work organization play an additional role in reducing performance capacities. It is still unclear whether these conditions may become the predominant factor in behavioral impairment when exposure to anesthetic gases is reduced; in addition, we wished to ascertain the extent of neurobehavioral and neuroendocrine effects at relatively low levels of exposure to such gases. Therefore the same group of 30 operating room personnel was examined with neurobehavioral tests during gaseous and nongaseous anesthesia. In this way, the neuropsychological performance was examined under the same stress conditions, but with different exposure levels to anesthetic gases. Serum cortisol was measured as an additional “biological stress indicator.” Prolactin secretion was examined to study possible interference of anesthetic gases with the dopaminergic system. The results were compared with those in a control group of 20 hospital workers from other departments, with similar characteristics in respect of age, sex, and education. During work with gaseous anesthesia, average airborne concentrations (geometric mean) of nitrous oxide were 50.9 ppm (SD 20.8) on the first day of the working week, and 54.2 ppm (SD 22.1) on the last day of the working week, whereas average urinary nitrous oxide (geometric mean) were 21.54 micrograms/l on the first day of the working week and 25.67 micrograms/l on the last day of the working week. The operating room workers showed slower reaction times at the end of the week with gaseous anesthesia, compared with workers using nongaseous anesthesia and the control group. At the same time they also showed increased secretion of prolactin, whereas cortisol remained unchanged. Therefore, it can be concluded that lower levels of exposure to anesthetic gases (and not only high exposure levels) cause an impairment of neurobehavioral performance, with the action of stress being less relevant. The mechanism of anesthetics’ neurotoxic action seems to be related to interference with the dopaminergic system.

*Original abstract online at https://link.springer.com/article/10.1007%2FBF00381630


 

Excerpt

Introduction

According to experimental and field studies, exposure to more than 500 ppm of nitrous oxide(N 2O) and more than 15 ppm of haJothane and enflurane can cause performance impairment in neurobehavioral exammations (Bruce and Bach 1975, 1976; Smith and Shirley 1978; Allison et al. 1979; Edling 1980; Mahoney et al. 1988. Control of exposure to anesthetic gases has received increased attention since the mid-1970s, when scavenging devices were fitted on anesthesia machines to vent the gases from the operating room. In the U.S. the National Institute for Occupational Safety andn Health (NIOSH) recommended in 1977 that exposure to N2O be limited to a time-weighted average (TWA) air concentration of 25 ppm, whereas the American Conference of Governmental Industrial Hygienists proposed a threshold limit value (TLV) of 50 ppm (ACGIH 1976). In 1989, the Italian Ministry of Health recommended a TLV-TWA of 100 and 50ppm, for already existing and for newly constructed operating rooms respectively (Ministero Sanita). The subsequent improvement of ventilation systems in workplaces led to a general decrease in exposure levels in most hospitals. Further neurobehav1oral field studies were subsequently conducted at concentration levels generally lower than 100 ppm of N 20, These studies showed that factors other than anesthetic gases, such as stress and work organization, may play an important role in determining performance impairment under these exposure conditions (Stollery 1988; Gilioii et al. 1992, Lucchini et al. 1995). Stress conditions activate the hypothalamic-adrenal system and cause hypersecretion of corticosteroids and catecholamines. When. in their daily activities, humans are subjected to mental, physical, or diverse environmental stresses, cortisol levels increase. These external stimuli provoke secretory peaks that interact with the physiological fluctuations due to circadian rhythm (Branderberger 1992; Tarui and Nakamura 1991; Lundberg et al. 1990). Therefore, serum cortisol can be used as a biological indicator or stress.

Recently, it was hypothesized that anesthetic gases have a similar mechanism of neurotoxic action to organic solvents. In fact. both substances might interfere with the dopaminergic system, which is very important in arousal and mood modulation. The tuberoinfundibular
system may be a specific target for these substances and/or their metabolites dissolved into the bloodstream, since it is not protected by the bloodbrain barrier. Moreover, the pituitary function can be selectively vulnerable and this effect is specifically shown by changes in prolactin (PRL) secretion, which is tonically modulated by the dopaminergic system (Mutti et at 1993).

Based on these observations, neurobehavioral functions, PRL secretion and serum cortisol were studied in operating room workers exposed to anesthetic gases at different times of the working week.

References

  1. Allison RH, Shirley AW, Smith G (1979) Threshold concentration of nitrous oxide affecting psychomotor performance. Br J Anaesth 51:177. Google Scholar

  2. American Conference of Governmental Industrial Hygienists (1976) TLVs. Threshold limit values for chemical substances and physical agents in the workroom environment with intended changes. ACGIH, Cincinnati, Ohio p 52. Google Scholar

  3. Arflni G, Mutti A, Vescovi PP, Ferroni C, Ferrari M, Giardi C, Passeri M, Franchini I (1987) Impaired dopaminergic modulation of pituitary secretion in workers occupationally exposed to styrene: further evidence from PRL response to TRH stimulation. J Occup Med 29:826–830. PubMed  Google Scholar

  4. Brandenberger G (1992) Evaluation of the effects of an environmental stress on plasma cortisol: methodological aspects (in French). Trav Hum 55:211–218. Google Scholar

  5. Bruce DL, Bach MJ (1975) Psychological studies of human performance as affected by traces of enflurane and nitrous oxide. Anesthesiology 42:194. PubMed  Google Scholar

  6. Bruce DL, Back MJ (1976) Effects of trace anaesthetic gases on behavioral performance of volunteers. Br J Anaesth 48:871. PubMed  Google Scholar

  7. Cohen EN, Trudel JR, Emunds HN, Watson E (1975) Urinary metabolites of halothane in man. Anesthesiology 43:382–385. Google Scholar

  8. Dahlgren BE (1979) Fluoride concentrations in urine of delivery ward personnel following exposure to low concentrations of methoxyfluorane. J Occup Med 21:624–626. Google Scholar

  9. Davenport HT, Halsey MJ, Wardley-Smith B, Bateman PE (1980) Occupational exposure to anaesthetic gases in 20 hospitals. Anaesthesia 35:354–359. Google Scholar

  10. Edling C (1980) Anesthetic gases as an occupational hazard-a review. Scand J Work Environ Health 6:85–93. PubMed  Google Scholar

  11. Gamberale F (1985) Use of behavioral performance tests in the assessment of solvent toxicity. Scand J Work Environ Health, Suppl 1:65–74. Google Scholar

  12. Gamberale F, Iregren A, Kjellberg A (1990) SPES: assessing the effects of the work environment on man with computerized performance testing. In: Karkowski W, Genaidy AM, Asfour SS (eds) Computer aided ergonomics: a research guide. Taylor & Francis, London, pp 381–396.Google Scholar

  13. Gilioli R, Belotti L, Camerino D, Cassitto MG, Girelli R, Lucchini R, Margonari M, Micheloni G, Villa L (1992) Neurobehavioral effects from inhalation anesthetics: a critical review (in Italian) G Ital Med Lav 14:35–41. Google Scholar

  14. Holaday DA, Fiserova-Bergerova V (1979) Fate of fluorinated metabolites of inhalation anesthetics in man. Drug Metab Rev 9:61–72. PubMed  Google Scholar

  15. Imbriani M, Ghittori S, Pezzagno G, Capodaglio E (1988) Nitrous oxide (NZO) in urine as biological index of exposure in operating room personnel. Appl Ind Hyg 8:223–227. Google Scholar

  16. Lucchini R, Toffoletto F, Camerino D, Fazioli R, Ghittori S, Gilioli R, Signorini A, Alessio L (1995) Neurobehavioral functions in operating room personnel exposed to anesthetic gases. Med Lav 86:27–33. PubMed  Google Scholar

  17. Lundberg U, Melin B, Fredrikson M (1990) Comparison of neuroendocrine measurements under laboratory and naturalistic conditions. Pharmacol Biochem Behav 37:697–702. Google Scholar

  18. Mahoney FC, Moore PA, Baker EL, Letz R (1988) Experimental nitrous oxide exposure as a model system for evaluating neurobehavioral tests. Toxicology 49:449–457. Google Scholar

  19. Ministero della Sanità (1989) Linee guida per ridurre l’inquinamento ambientale da anestetici. Circolare no. 5 del 14/3/1989

  20. Mutti A, Franchini I (1987) Toxicity of metabolites to dopaminergic systems and the behavioral effects of organic solvents. Br J Ind Med 44:721–723. Google Scholar

  21. Mutti A, Alinovi R, Bacchini A, Bergamaschi E, Biagni C, Smargiassi A, Cavazzini A, Franchini I (1993) Mechanism and markers of styrene-induced behavioral and neuroendocrine changes. In: Lotti M, Manno M (eds) Mechanism of toxicity and their relevance in industrial toxicology. SGE, Padova, Italy, pp 127–137. Google Scholar

  22. NIOSH (1977) Criteria for a recommended standard: occupational exposure to waste anesthetic gases and vapors. Publication no. 77-140, US DHEW, Cincinnati, Ohio. Google Scholar

  23. Sharer NM, Nunn JF, Royston JP, Chanarin I (1983) Effects of chronic exposure to nitrous oxide on methionine synthetase activity. Br J Anaesth 55:693–701. Google Scholar

  24. Smith G, Shirley AW (1978) A review of the effects of trace concentrations of anaesthetics on performance. Br J Anaesth 50:701–711. Google Scholar

  25. Stollery BT, Broadbent DE, Lee WR, Keen RI, Healey TEJ, Beatty P (1988) Mood and cognitive function in anesthetists working in actively scavenged operating theaters. Br J Anaesth 61:446–455. PubMed  Google Scholar

  26. Tarui H, Nakamura A (1991) Hormonal response of pilots flying high-performance aircraft during seven repetitive flight missions. Aviat Space Environ Med 62:1127–1131. Google Scholar

  27. Vieira E, Cleaton-Jones P, Moyes D (1983) Effects of low concentrations of nitrous oxide on the developing rat fetus. Br J Anaesth 55:67–69. PubMed  Google Scholar