Statement on the Use of Low Gas Flows for Sevoflurane
Developed by: Committee on Equipment and Facilities
Original Approval: October 18, 2023
The U.S. Food and Drug Administration (FDA)-approved labeling by the manufacturer indicating a minimum fresh gas flow (FGF) for sevoflurane is dated and not supported by current research. However, the package insert continues to influence the behavior of anesthesia professionals, who may be reluctant to use off-label FGF settings when administering sevoflurane.1 The FDA-approved package insert for sevoflurane currently recommends “sevoflurane exposure should not exceed 2 [minimum alveolar concentration] hours at flow rates of 1 to < 2 L/min. Fresh gas flow rates < 1 L/min are not recommended.”2 This FDA warning leads to excess sevoflurane delivery beyond what is needed for the desired clinical effect and contributes to avoidable expense and environmental pollution. The use of low FGF with sevoflurane has been extensively studied, is a safe practice, and has economic and environmental benefits.3–8 The ASA has evaluated current scientific studies and concludes there is no reasonable evidence to support a lower limit of fresh gas flow when using sevoflurane. Therefore, the ASA supports the use of low fresh gas flows when sevoflurane is administered.
The FDA recommendation against the use of the volatile anesthetic sevoflurane with FGF of < 2 L/min cites studies performed in animal models.2,9,10 However, extensive research has found no evidence of harm in humans due to sevoflurane use with low FGF.7,8,11–15 Notably, countries of the European Union never introduced minimal FGF restrictions and routinely use low FGF in practice. Furthermore, purposeful selection of CO2 absorbent can eliminate any remaining safety concerns surrounding low flow sevoflurane.
The manufacturer label for sevoflurane cites studies in animal models that showed evidence of renal toxicity due to exposure to Compound A (fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether), a degradant formed by the reaction of sevoflurane with strong bases (NaOH, KOH) in some CO2 absorbents.9,10 These findings have not been replicated in humans, however.7,8,11–15 Furthermore, some CO2 absorbents currently on the market were designed to have a limited concentration of strong base (<2% NaOH or KOH) or eliminate NaOH/KOH entirely, reducing Compound A production to negligible amounts even when using low FGF.16–18 Low-alkalinity absorbent technologies are formulated to optimize CO2 absorption while minimizing Compound A production. Thus, potential concerns about Compound A toxicity can be addressed with the purposeful selection of CO2 absorbent. Chemical compositions of CO2 absorbents, including the percentage of NaOH or KOH, can be obtained from the manufacturer.
The anesthesia professional should determine the optimal low flow rate to avoid unnecessary waste, costs, and pollution, while ensuring safe and effective care for the patient. While there is no scientific evidence to support a specific lower limit of fresh gas flow when using sevoflurane, or any inhaled anesthetic, equipment capabilities can influence the minimum safe FGF. Equipment features favoring lower FGF include return of gas sampled for CO2 and agent concentration monitoring to the breathing circuit and a circuit with minimal intrinsic leak.
Most adult patients under anesthesia can be managed with a FGF of 0.5 L/min without adding significant burden to the anesthesia professional. With vigilance, flows can often be decreased further to approach “closed-circuit” conditions, where the anesthetic and fresh gas supplied equal the amounts consumed by the patient.17 Since the closed-circuit FGF threshold in adults is typically less than 0.5 L/min, any amount of gas flow above that threshold results in excessive anesthetic lost through the waste anesthetic gas (WAG) management system. Sevoflurane is a potent greenhouse gas, contributing to climate change and the associated negative impacts on human health. As volatile anesthetics are costly environmental pollutants, anesthetic waste should be minimized by reducing FGF whenever possible.6,19–22
It is important to understand the tools and concepts underlying low flow sevoflurane for safe and effective administration. Provider-targeted education on low flow sevoflurane use will increase comfort in reducing FGF and minimizing pollution due to your practice. ASA offers a course developed by the Anesthesia Patient Safety Foundation on low-flow anesthesia which can be accessed free of charge by any anesthesia professional. Continuing education credits are offered including safety credits for those involved in the MOCA process. (See apsf.org/tei/lfa.)
- McGain F, Bishop JR, Elliot-Jones LM, Story DA, Imberger GLL. A survey of the choice of general anaesthetic agents in Australia and New Zealand. Anaesth Intensive Care. 2019;47(3):235-241. doi:10.1177/0310057X19836104
- Abbvie Ltd. Ultane (sevoflurane) package insert. https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/020478s016lbl.pdf. Published 2003. Accessed January 4, 2023.
- Kennedy RR, Hendrickx JFA, Feldman JM. There are no dragons: Low-flow anaesthesia with sevoflurane is safe. Anaesth Intensive Care. 2019;47(3):223-225. doi:10.1177/0310057X19843304
- Feldman JM. Managing fresh gas flow to reduce environmental contamination. Anesth Analg. 2012;114(5):1093-1101. doi:10.1213/ANE.0b013e31824eee0d
- Baum JA. Low-flow anesthesia : Theory , practice , technical preconditions , advantages , and foreign gas accumulation. J Anesth. 1999;13:166-174.
- Varughese S, Ahmed R. Environmental and Occupational Considerations of Anesthesia: A Narrative Review and Update. Anesth Analg. 2021;133(4):826-835. doi:10.1213/ANE.0000000000005504
- Bito H, Ikeuchi Y, Ikeda K. Effects of low-flow sevoflurane anesthesia on renal function. Anesthesiology. 1997;86(6):1231-1237.
- Kharasch ED, Frink EJ, Zager R, Bowdle TA, Artru A, Nogami W. Assessment of low-flow sevoflurane and isoflurane effects on renal function using sensitive markers of tubular toxicity. Anesthesiology. 1997;86(6):1238-1253.
- Morio M, Fujii K, Satoh N, et al. Reaction of sevoflurane and its degredation products with soda lime. Anesthesiology. 1992;77(6):1155-1164.
- Keller K, Callan C, Prokocimer P, et al. Inhalation toxicity study of haloalkene degradent of sevoflurane, Compound A (PIFE), in Sprague-Dawley rats. Anesthesiology. 1995;83(6):1220-1232.
- Sondekoppam R V., Narsingani KH, Schimmel TA, McConnell BM, Buro K, Özelsel TJP. The impact of sevoflurane anesthesia on postoperative renal function: a systematic review and meta-analysis of randomized-controlled trials. Can J Anesth. 2020;67(11):1595-1623. doi:10.1007/s12630-020-01791-5
- Xing N, Wei X, Chang Y, Du Y, Zhang W. Effects of low-flow sevoflurane anesthesia on renal function in low birth weight infants. BMC Anesthesiol. 2015;15(1):1-5. doi:10.1186/1471-2253-15-6
- Kharasch ED, Frink EJ, Artru A, Michalowski P, Rooke GA, Nogami W. Long-duration low-flow sevoflurane and isoflurane effects on postoperative renal and hepatic function. Anesth Analg. 2001;93(6):1511-1520. doi:10.1097/00000539-200112000-00036
- Duymaz G, Yağar S, Özgök A. Comparison of Effects of Low-Flow Sevoflurane and Low-Flow Desflurane Anaesthesia on Renal Functions Using Cystatin C. Turk J Anaesthesiol Reanim. 2017;45(2):93-97. doi:10.5152/TJAR.2017.72325
- Lineburger EB, Módolo NSP, Braz LG, do Nascimento P. Minimal fresh gas flow sevoflurane anesthesia and postoperative acute kidney injury in on-pump cardiac surgery: a randomized comparative trial. Brazilian J Anesthesiol (English Ed. 2022). doi:10.1016/j.bjane.2021.11.004
- Kobayashi S, Bito H, Morita K, Katoh T, Sato S. Amsorb Plus and Drägersorb Free, two new-generation carbon dioxide absorbents that produce a low compound A concentration while providing sufficient CO2 absorption capacity in simulated sevoflurane anesthesia. J Anesth. 2004;18(4):277-281. doi:10.1007/s00540-004-0253-5
- Feldman JM, Hendrickx J, Kennedy RR. Carbon Dioxide Absorption during Inhalation Anesthesia: A Modern Practice. Anesth Analg. 2021;132(4):993-1002. doi:10.1213/ANE.0000000000005137
- Olympio MA. Carbon Dioxide Absorbent Desiccation Safety Conference Convened by APSF. APSF Newsletter. 2005:25-44.
- Sherman JD, Ryan S. Ecological Responsibility in Anesthesia Practice. Int Anesthesiol Clin. 2010;48(3):139-151.
- Eckelman MJ, Sherman J. Environmental impacts of the U.S. health care system and effects on public health. PLoS One. 2016;11(6):1-14. doi:10.1371/journal.pone.0157014
- McGain F, Muret J, Lawson C, Sherman JD. Environmental sustainability in anaesthesia and critical care. Br J Anaesth. 2020;125(5):680-692. doi:10.1016/j.bja.2020.06.055
- Yasny JS, White J. Environmental implications of anesthetic gases. Anesth Prog. 2012;59(4):154-158. doi:10.2344/0003-3006-59.4.154