The Perfluorocarbon Paradox: Historical Legacy and Residual Use of Isoflurane and Enflurane in Anesthesia Practice
Keywords:
anesthesia practice, desflurane, enflurane, isoflurane, perfluorocarbon, sevofluraneAbstract
This review article critically examines the paradoxical persistence of isoflurane and enflurane in anesthesia practice, despite well-documented concerns about their perfluorocarbon (PFC) composition and environmental impact. While these agents historically offered advantages in rapid induction, ease of administration, and cost-effectiveness, their continued use must now be weighed against newer, more environmentally sustainable alternatives such as sevoflurane and desflurane. Recent regulatory frameworks and updated studies emphasize the need to reduce volatile anesthetic emissions, as PFCs contribute significantly to global warming potential. Clinical considerations including enflurane’s association with epileptiform EEG activity have contributed to its withdrawal from most markets. By integrating historical perspectives, updated comparative pharmacology, and regulatory and environmental considerations, this article highlights multifaceted challenges and risk mitigation strategies, including engineering controls, administrative policies, and sustainable practice guidelines.
References
Council of the European Union, European Parliament. Regulation (EU) 2024/573 on fluorinated greenhouse gases, amending directive (EU) 2019/1937 and repealing regulation (EU) No 517/2014 [Internet]. 2024 [cited 2025 Jul 10]. Available from: https://www.europeansources.info/record/proposal-for-a-regulation-on-fluorinated-greenhouse-gases-amending-directive-eu-2019-1937-and-repealing-regulation-eu-no-517-2014/
Obcowska A, Racisz K, Duda J, et al. Environmental impact of anaesthetic gases-review of the most commonly discussed strategies. Med Srodow. 2025;28:1-5.
Samad K, Yousuf MS, Ullah H, Ahmed SS, Siddiqui KM, Latif A. Anesthesia and its environmental impact: approaches to minimize exposure to anesthetic gases and reduce waste. Med Gas Res. 2025;15:101-9.
Whalen FX, Bacon DR, Smith HM. Inhaled anesthetics: an historical overview. Best Pract Res Clin Anaesthesiol. 2005;19:323-30.
Varughese S, Ahmed R. Environmental and occupational considerations of anesthesia: a narrative review and update. Anesth Analg. 2021;133:826-35.
Čižmáriková R, Habala L, Markuliak M. General inhalational anesthetics-pharmacodynamics, pharmacokinetics and chiral properties. Ceska Slov Farm. 2021;70:7-17.
Parker NM. Comparative pharmacodynamics of inhaled anesthetics. In: Alaa AE, editor. Basic Anesthesia Review. 1st ed. New York: Oxford University Press; 2024. p. 180-2.
Perouansky M. Pearch RA, Hemmings HC, Franks NP. Inhaled anesthetics: mechanisms of action. In: Gropper MA, ed. Miller’s Anesthesia, 9th ed. Philadelphia: Elsevier, 2020:p444-61.
Ito BM, Sato S, Kufta CV, Tran D. Effect of isoflurane and enflurane on the electrocorticogram of epileptic patients. Neurology. 1988;38:924-8.
Flood P, Shafer SL, Berger AS. Inhaled anesthetics. In: Flood P, Rathmell JP, Urman RD, editors. Stoelting’ s pharmacology & physiology in anesthetic practice. 1st ed. Philadelphia: Wolters Kluwer; 2022.
Clare CA, Hatton GE, Shrestha N, et al. Intraoperative blood loss during induced abortion: a comparison of anesthetics. Anesthesiol Res Pract. 2018;2018:4051896.
Kakaei N, Amirian R, Azadi M, Mohammadi G, Izadi Z. Perfluorocarbons: a perspective of theranostic applications and challenges. Front Bioeng Biotechnol. 2023;11:1115254.
Association of state and territorial solid waste management officials. Perfluorinated chemicals (PFCs): perfluorooctanoic acid (PFOA) & perfluorooctane sulfonate (PFOS) [Internet]. Remediation and Reuse Focus Group Federal Facilities Research Center 2015 [cited 2024 Aug 12]. Available from: https://clu-in.org/download/contaminantfocus/pops/POPs-ASTSWMO-PFCs-2015.pdf
Nocentini G, MacLaren G, Bartlett R, et al. Perfluorocarbons in research and clinical practice: a narrative review. ASAIO J. 2023;69:1039-48.
Olika MK, Dessalegn ZM, Mekonin GT, et al. Effect of inhalational anesthetics exposure on reproductive outcomes and its predictors among healthcare personnel in Jimma zone public hospitals: a comparative cross-sectional study. Int J Womens Health. 2022;14:1555-68.
Krafft PK, Riess JG. Therapeutic oxygen delivery by perfluorocarbon-based colloids. Adv Colloid Interface Sci. 2021;294:102407.
Lee YJ. Potential health effects of emerging environmental contaminants perfluoroalkyl compounds. Yeungnam Univ J Med. 2018;35:156-64.
Coburn J. Lessons learned from DuPont’s role in PFOA exposure [Internet]. IEEE international symposium on ethics in engineering, science and technology (ETHICS) ethics in engineering, science and technology (ETHICS) 2021 [cited 2024 Aug 15]. Available from: https://ieeexplore.ieee.org/document/9632788/metrics#metrics
Bogdan AR, Johnson SF, Goeden H. Estimation of serum PFOA concentrations from drinking and non–drinking water exposures. Environ Health Perspect. 2023;131:67701.
Bonato M, Corrà F, Bellio M, et al. PFAS environmental pollution and antioxidant responses: an overview of the impact on human field. Int J Environ Res Public Health. 2020;17:8020.
Paris-Davila P, Gaines LGT, Lucas K, Nylander-French LA. Occupational exposures to airborne per-and polyfluoroalkyl substances (PFAS)-a review. Am J Ind Med. 2023;66:393-410.
McGain F, Sheridan N, Wickramarachchi K, Yates S, Chan B, McAlister S. Carbon footprint of general, regional, and combined anesthesia for total knee replacements. Anesthesiology. 2021;135:976-91.
Environment Protection Agency. Past PFOA and PFOS health effects science documents. [Internet]. 2024 [cited 2025 Jul 10]. Available from: https://www.epa.gov/sdwa/past-pfoa-and-pfos-health-effects-science-documents
Novo C. From contamination to accountability: Europe’s drive to regulate PFAS and protect water resources. [Internet]. 2025 [cited 2025 Jul 10]. Available from: https://smartwatermagazine.com/news/smart-water-magazine/contamination-accountability-europes-drive-regulate-pfas-and-protect-water
Beard JW, Kennedy RR, Philip JH, et al. Environmental and economic impacts of end-tidal control of volatile anesthetics: a scoping review and analysis. Open Anesthesia J. 2025;19:e25896458355905.
EPPA SA/NV. SOCIO-Economic analysis of the potential restriction of the per-and polyfluoroalkyl substances (PFAS) used in the production, packaging and delivery of human medicinal products. [Internet]. 2023 [cited 2025 Jul 10]. Available from: https://www.efpia.eu/media/52ipvgfi/annex-1-efpia_sea_pfas_final.pdf
Gonzalez-Pizarro P, Brazzi L, Koch S, et al. European Society of Anaesthesiology and Intensive Care consensus document on sustainability: 4 scopes to achieve a more sustainable practice. Eur J Anaesthesiol. 2024;41:260-77.
Environment Protection Agency. International actions - the Montreal protocol on substances that deplete the ozone layer. [Internet]. 2025 [cited 2025 Jul 10]. Available from: https://www.epa.gov/ozone-layer-protection/international-actions-montreal-protocol-substances-deplete-ozone-layer
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