Circulation 122,210 • Volume 32, No. 3 • February 2018   Issue PDF

Concern About the Use of Very Low Flow Sevoflurane Anesthesia

To the Editor:

I read with interest the article entitled “Low Flow and CO2 Absorbents” (APSF Newsletter October 2017, p.50). I was surprised to see a photograph of the flow meters of an anesthesia machine reading 0.2 liters per minute of oxygen and 0.2 liters per minute of air. I am concerned that a casual reader might conclude that these flow rates are safe to use in everyday practice. However, they barely provide enough oxygen for a normal adult requiring 3.4 mL/kg/min1 and do not offer any margin of safety. Furthermore, in advocating flow rates of 0.3 to 1.99 liters per minute, it is important to note that even a flow of 100% oxygen at the lowest figure (0.3 liters per minute) would not provide adequate oxygen for a patient weighing over 88 kg.

I was confused by the statements of Feldman and Hendrickx in the article regarding the dangers posed by compound A. On the one hand, they state without a reference: “The clinical relevance of compound A production remains to be demonstrated and should not be a primary consideration when selecting an absorbent. Indeed NaOH containing Ca(OH)2 absorbents are routinely used outside the U.S. during closed-circuit anesthesia without concern for, nor reports of, patient harm.” They then go on to state: “The ideal or best suited absorbent would be the lowest cost material that does not put the patient at risk from degradation of anesthetics.”

Because this article appears to advocate the use of extremely low flow anesthesia, it is important to note what the package insert2 for sevoflurane states on this subject: “While a level of Compound A exposure at which clinical nephrotoxicity might be expected to occur has not been established, it is prudent to consider all of the factors leading to Compound A exposure in humans, especially duration of exposure, fresh gas flow rate, and concentration of sevoflurane, USP. During sevoflurane, USP anesthesia the clinician should adjust inspired concentration and fresh gas flow rate to minimize exposure to Compound A. To minimize exposure to Compound A, sevoflurane exposure should not exceed 2 MAC∙hours at flow rates of 1 to < 2 L/min. Fresh gas flow rates of <1 L/min are not recommended.”

In my view, deviation from the package insert should be undertaken with extreme care and with a definite important goal in mind. A small potential savings of money during a particular case does not seem to qualify.


  1. Crone RK and O’Rourke PP: Pediatric and neonatal intensive care. In: Miller RD, ed. Anesthesia 3rd ed. Churchill Livingstone, Philadelphia 1990. P. 2221.
  2. Sevoflurane package insert: Accessed 10-14-17.

Mitchel B. Sosis, MS, MD, PhD
Holy Redeemer Hospital and Medical Center
Meadowbrook, PA

He has no conflicts of interest to declare.

In Response:

We appreciate the careful reading and thoughtful response by Dr. Sosis to our article entitled “Low Flow and CO2 Absorbents” which appeared in the last issue of the APSF Newsletter. The comments provide an opportunity for continued debate and clarification of our recommendations.

The first concern raised related to the photograph of flowmeters reading 0.2 L/min of oxygen and 0.2 L/min of air. The original question to the newsletter related to establishing a practice of very low flow anesthesia, as low as 0.3 L/min, so we wanted to address that scenario in our response. Oxygen consumption is indeed determined by patient size and for some patients, especially pediatric patients, 300 mls/min of oxygen may be sufficient or even excessive. Managing very low flow, or even closed circuit, anesthesia requires not only setting the fresh gas flow, but monitoring the oxygen concentration in the circuit to ensure that sufficient oxygen is being delivered. A functioning oxygen monitor is required as is vigilance by the clinician, but the technique can certainly be safe. Approaches to this technique have been described.1

With regard to Compound A, it is true that sevoflurane is used without restrictions on minimum flow rates throughout the world without concern for, or evidence of, clinically relevant toxicity. The literature examining this topic is extensive and does not support concern for significant patient harm related to Compound A exposure.2,3 FDA labeling recommendations may be helpful for minimizing Compound A exposure produced by CO2 absorbents with strong bases and the decision to comply with the FDA recommendation, when using those types of absorbents becomes a matter of clinical judgement as is true with all drug labeling. The FDA recommendations, however, pre-date the development of many currently available absorbents. Concern for toxicity has stimulated the production of absorbents which are not associated with Compound A production and can be used safely at any fresh gas flow rate.4 Based upon the literature, we believe that our recommendation to use absorbents without KOH and low concentrations of NaOH is sound, and supports the safe use of low flow or closed circuit anesthesia in the presence of sevoflurane. It is not our intent to endorse any particular absorbent product, but the chemical composition of these materials is readily available, and can help guide selection of the material that is best suited to individual practice.

Jeffrey Feldman, MD, MSE
Chair, APSF Committee on Technology Professor of Clinical Anesthesiology
Children’s Hospital of Philadelphia
Perelman School of Medicine
Philadelphia, PA

Jan Hendrickx, MD, PhD
Dept. of Anesthesiology/CCM
OLV Hospital
Aalst, Belgium

Dr. Feldman serves as a member of the Clinical Advisory Board, ClearLine MD, Boston, MA. Dr. Feldman has received consulting compensation from Draeger Medical, GE Medical, and Medtronic.

Dr. Hendrickx has received lecture support, consulting fees, equipment loans, or travel reimbursements from the following companies: AbbVie, Acertys, Aguettant, Air Liquide, Allied Healthcare, Armstrong Medical, Baxter, Draeger, evoked, GE, Hospithera, Heinen und Lowenstein, Intersurgical, Maquet, MDMS, MEDEC, Micropore, Molecular, MSD, NWS, Orion Pharma, Pall, Piramal, Philips, Quantium Medical, Sedana.


  1. Feldman JM. Managing fresh gas flow to reduce environmental contamination. Anesth Analg 2012;114:1093–101.
  2. Gentz B. Malan TP. Renal toxicity with sevoflurane. a storm in a teacup? Drugs2001;61:2155–2162.
  3. Eger EI. Compound A: does it matter? Can J Anesth 2001;48:427–430.
  4. Keijzer C. Compound A and carbon monoxide production from sevoflurane and seven different types of carbon dioxide absorbent in a patient model. Acta Anaesth Scand 2007;51:31–7.